Publications by authors named "Susan M Smith"

284 Publications

The inverse care law and the potential of primary care in deprived areas.

Lancet 2021 Feb;397(10276):775-776

Institute of Health and Wellbeing, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 9LX, UK. Electronic address:

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http://dx.doi.org/10.1016/S0140-6736(21)00317-2DOI Listing
February 2021

A micro costing analysis of the development of a primary care intervention to improve the uptake of diabetic retinopathy screening.

Implement Sci 2021 Feb 10;16(1):17. Epub 2021 Feb 10.

School of Public Health, College of Medicine & Health, University College Cork, Western Gateway Building, Western Rd., Cork, Ireland.

Background: The application of economic analysis within implementation science is still developing and the cost of intervention development, which differs markedly from the costs of initial implementation and maintenance, is often overlooked. Our aim was to retrospectively cost the development of a multifaceted intervention in primary care to improve attendance at diabetic retinopathy screening.

Methods: A retrospective micro costing of developing the intervention from the research funder perspective was conducted. It was based on a systematic intervention development process involving analysis of existing audit data and interviews with patients and healthcare professionals (HCPs), conducting consensus meetings with patients and HCPs, and using these data together with a rapid review of the effectiveness of interventions, to inform the final intervention. Both direct (non-personnel, e.g. travel, stationary, room hire) and indirect (personnel) costs were included. Data sources included researcher time logs, payroll data, salary scales, an online financial management system, invoices and purchase orders. Personnel involved in the intervention development were consulted to determine the activities they conducted and the duration of their involvement. Sensitivity and scenario analyses were conducted to estimate uncertainty around parameters and scope.

Results: The total cost of intervention development (July 2014-January 2019) was €40,485 of which 78% were indirect (personnel) costs (€31,451). In total, personnel contributed 1368 h to intervention development. Highest cost activities were the patient interviews, and consensus process, contributing 23% and 34% of the total cost. Varying estimated time spent on intervention development activities by + 10% increased total intervention development cost by 6% to €42,982.

Conclusions: Our results highlight that intervention development requires a significant amount of human capital input, combining research experience, patient and public experience, and expert knowledge in relevant fields. The time committed to intervention development is critical but has a significant opportunity cost. With limited resources for research on developing and implementing interventions, capturing intervention development costs and incorporating them as part of assessment of cost-effective interventions, could inform research priority and resource allocation decisions.
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http://dx.doi.org/10.1186/s13012-021-01085-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877098PMC
February 2021

Global metabolomic profiling reveals hepatic biosignatures that reflect the unique metabolic needs of late-term mother and fetus.

Metabolomics 2021 02 7;17(2):23. Epub 2021 Feb 7.

UNC Nutrition Research Institute, University of North Carolina at Chapel Hill, 500 Laureate Way, Kannapolis, NC, 28081, USA.

Objective: Gestational disorders including preeclampsia, growth restriction and diabetes are characterized, in part, by altered metabolic interactions between mother and fetus. Understanding their functional relevance requires metabolic characterization under normotypic conditions.

Methods: We performed untargeted metabolomics on livers of pregnant, late-term C57Bl/6J mice (N = 9 dams) and their fetuses (pooling 4 fetuses/litter), using UPLC-MS/MS.

Results: Multivariate analysis of 730 hepatic metabolites revealed that maternal and fetal metabolite profiles were highly compartmentalized, and were significantly more similar within fetuses (ρ = 0.81), or within dams (ρ = 0.79), than within each maternal-fetal dyad (ρ = - 0.76), suggesting that fetal hepatic metabolism is under distinct and equally tight metabolic control compared with its respective dam. The metabolite profiles were consistent with known differences in maternal-fetal metabolism. The reduced fetal glucose reflected its limited capacity for gluconeogenesis and dependence upon maternal plasma glucose pools. The fetal decreases in essential amino acids and elevations in their alpha-keto acid carnitine conjugates reflects their importance as secondary fuel sources to meet fetal energy demands. Whereas, contrasting elevations in fetal serine, glycine, aspartate, and glutamate reflects their contributions to endogenous nucleotide synthesis and fetal growth. Finally, the elevated maternal hepatic lipids and glycerol were consistent with a catabolic state that spares glucose to meet competing maternal-fetal energy demands.

Conclusions: The metabolite profile of the late-term mouse dam and fetus is consistent with prior, non-rodent analyses utilizing plasma and urine. These data position mouse as a suitable model for mechanistic investigation into how maternal-fetal metabolism adapts (or not) to gestational stressors.
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http://dx.doi.org/10.1007/s11306-021-01773-8DOI Listing
February 2021

Link workers providing social prescribing and health and social care coordination for people with multimorbidity in socially deprived areas (the LinkMM trial): protocol for a pragmatic randomised controlled trial.

BMJ Open 2021 Feb 1;11(2):e041809. Epub 2021 Feb 1.

Department of General Practice, HRB Centre for Primary Care Research, Royal College of Surgeons, Dublin, Ireland.

Introduction: Link workers are non-health or social care professionals based in primary care who support people to develop and achieve a personalised set of health and social goals by engaging with community resources. Link workers have been piloted in areas of deprivation, but there remains insufficient evidence to support their effectiveness. Multimorbidity is increasing in prevalence, but there are limited evidence-based interventions. This paper presents the protocol for a randomised controlled trial (RCT) that will test the effectiveness of link workers based in general practices in deprived areas in improving health outcomes for people with multimorbidity.

Methods And Analysis: The protocol presents the proposed pragmatic RCT, involving 10 general practitioner (GP) practices and 600 patients. Eligible participants will be community dwelling adults with multimorbidity (≥two chronic conditions) identified as being suitable for referral to a practice-based link worker. Following baseline data collection, the patients will be randomised into intervention group that will meet the link worker over a1-month period, or a 'wait list' control that will receive usual GP care. Primary outcomes are health-related quality of life as assessed by EQ-5D-5L and mental health assessed by Hospital Anxiety and Depression Scale. Secondary outcomes are based on the core outcome set for multimorbidity. Data will be collected at baseline and on intervention completion at 1 month using questionnaires self-completed by participants and GP records. Parallel process and economic analyses will be conducted to explore participants' experiences and examine cost-effectiveness of the link worker intervention.

Ethics And Dissemination: Ethical approval has been granted by the Irish College of General Practitioners Ethics Committee. The findings will be published in peer-reviewed journals.

Trial Registration Number: ISRCTN10287737;Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2020-041809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852975PMC
February 2021

Interventions for improving outcomes in patients with multimorbidity in primary care and community settings.

Cochrane Database Syst Rev 2021 01 15;1:CD006560. Epub 2021 Jan 15.

Department of Family Medicine, University of Sherbrooke, Quebec, Canada.

Background: Many people with chronic disease have more than one chronic condition, which is referred to as multimorbidity. The term comorbidity is also used but this is now taken to mean that there is a defined index condition with other linked conditions, for example diabetes and cardiovascular disease. It is also used when there are combinations of defined conditions that commonly co-exist, for example diabetes and depression. While this is not a new phenomenon, there is greater recognition of its impact and the importance of improving outcomes for individuals affected. Research in the area to date has focused mainly on descriptive epidemiology and impact assessment. There has been limited exploration of the effectiveness of interventions to improve outcomes for people with multimorbidity.

Objectives: To determine the effectiveness of health-service or patient-oriented interventions designed to improve outcomes in people with multimorbidity in primary care and community settings. Multimorbidity was defined as two or more chronic conditions in the same individual.

Search Methods: We searched MEDLINE, EMBASE, CINAHL and seven other databases to 28 September 2015. We also searched grey literature and consulted experts in the field for completed or ongoing studies.

Selection Criteria: Two review authors independently screened and selected studies for inclusion. We considered randomised controlled trials (RCTs), non-randomised clinical trials (NRCTs), controlled before-after studies (CBAs), and interrupted time series analyses (ITS) evaluating interventions to improve outcomes for people with multimorbidity in primary care and community settings. Multimorbidity was defined as two or more chronic conditions in the same individual. This includes studies where participants can have combinations of any condition or have combinations of pre-specified common conditions (comorbidity), for example, hypertension and cardiovascular disease. The comparison was usual care as delivered in that setting.

Data Collection And Analysis: Two review authors independently extracted data from the included studies, evaluated study quality, and judged the certainty of the evidence using the GRADE approach. We conducted a meta-analysis of the results where possible and carried out a narrative synthesis for the remainder of the results. We present the results in a 'Summary of findings' table and tabular format to show effect sizes across all outcome types.

Main Results: We identified 17 RCTs examining a range of complex interventions for people with multimorbidity. Nine studies focused on defined comorbid conditions with an emphasis on depression, diabetes and cardiovascular disease. The remaining studies focused on multimorbidity, generally in older people. In 11 studies, the predominant intervention element was a change to the organisation of care delivery, usually through case management or enhanced multidisciplinary team work. In six studies, the interventions were predominantly patient-oriented, for example, educational or self-management support-type interventions delivered directly to participants. Overall our confidence in the results regarding the effectiveness of interventions ranged from low to high certainty. There was little or no difference in clinical outcomes (based on moderate certainty evidence). Mental health outcomes improved (based on high certainty evidence) and there were modest reductions in mean depression scores for the comorbidity studies that targeted participants with depression (standardized mean difference (SMD) -0.41, 95% confidence interval (CI) -0.63 to -0.2). There was probably a small improvement in patient-reported outcomes (moderate certainty evidence). The intervention may make little or no difference to health service use (low certainty evidence), may slightly improve medication adherence (low certainty evidence), probably slightly improves patient-related health behaviours (moderate certainty evidence), and probably improves provider behaviour in terms of prescribing behaviour and quality of care (moderate certainty evidence). Cost data were limited.

Authors' Conclusions: This review identifies the emerging evidence to support policy for the management of people with multimorbidity and common comorbidities in primary care and community settings. There are remaining uncertainties about the effectiveness of interventions for people with multimorbidity in general due to the relatively small number of RCTs conducted in this area to date, with mixed findings overall. It is possible that the findings may change with the inclusion of large ongoing well-organised trials in future updates. The results suggest an improvement in health outcomes if interventions can be targeted at risk factors such as depression in people with co-morbidity.
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http://dx.doi.org/10.1002/14651858.CD006560.pub4DOI Listing
January 2021

An enriched biosignature of gut microbiota-dependent metabolites characterizes maternal plasma in a mouse model of fetal alcohol spectrum disorder.

Sci Rep 2021 Jan 8;11(1):248. Epub 2021 Jan 8.

Department of Nutrition, UNC Nutrition Research Institute, University of North Carolina at Chapel Hill, 500 Laureate Way, Kannapolis, NC, 28082, USA.

Prenatal alcohol exposure (PAE) causes permanent cognitive disability. The enteric microbiome generates microbial-dependent products (MDPs) that may contribute to disorders including autism, depression, and anxiety; it is unknown whether similar alterations occur in PAE. Using a mouse PAE model, we performed untargeted metabolome analyses upon the maternal-fetal dyad at gestational day 17.5. Hierarchical clustering by principal component analysis and Pearson's correlation of maternal plasma (813 metabolites) both identified MDPs as significant predictors for PAE. The majority were phenolic acids enriched in PAE. Correlational network analyses revealed that alcohol altered plasma MDP-metabolite relationships, and alcohol-exposed maternal plasma was characterized by a subnetwork dominated by phenolic acids. Twenty-nine MDPs were detected in fetal liver and sixteen in fetal brain, where their impact is unknown. Several of these, including 4-ethylphenylsulfate, oxindole, indolepropionate, p-cresol sulfate, catechol sulfate, and salicylate, are implicated in other neurological disorders. We conclude that MDPs constitute a characteristic biosignature that distinguishes PAE. These MDPs are abundant in human plasma, where they influence physiology and disease. Their altered abundance here may reflect alcohol's known effects on microbiota composition and gut permeability. We propose that the maternal microbiome and its MDPs are a previously unrecognized influence upon the pathologies that typify PAE.
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http://dx.doi.org/10.1038/s41598-020-80093-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794323PMC
January 2021

Effectiveness of link workers providing social prescribing on health outcomes and costs for adult patients in primary care and community settings. A protocol for a systematic review of the literature.

HRB Open Res 2019 17;2:21. Epub 2020 Nov 17.

Department of General Practice, Royal College of Surgeons in Ireland, Dublin, Ireland.

The use of link workers for social prescribing and health and social care coordination is increasing, but there is insufficient data to demonstrate their effectiveness or for whom they work best. Multimorbidity is increasing in prevalence and affects those living in deprived areas ten years earlier than affluent areas. This systematic review aims to examine the evidence for the effectiveness and costs of link workers in improving health outcomes. We will also look for evidence for the use of link workers specifically for people living with multimorbidity and in deprived areas. Databases of published and grey literature will be searched for randomised and non-randomised controlled trials examining use of link workers based in primary care for community dwelling adults compared to usual care. Primary outcomes will be health related quality of life and mental health. Data on costs will be extracted. Studies will be selected for inclusion by title and abstract review by two reviewers. A Preferred Reporting Items for Systematic Reviews (PRISMA) flow diagram will document the selection process. A standardised form will be used to extract data. Data quality will be assessed using the Cochrane Risk of Bias tool for randomised controlled trials, a narrative synthesis will be completed and the GRADE assessment tool used to comment on evidence quality. A meta-analysis of effect size of primary outcomes and subgroup analysis for multimorbidity and social deprivation will be performed if there are sufficient comparable data. This systematic review will give an important overview of the evidence for the use of link workers providing social prescribing and health and social care coordination in primary care. This will help inform intervention development and guide policy makers on whether these interventions are cost effective and which groups stand to benefit most. CRD42019134737 (04/07/2019).
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http://dx.doi.org/10.12688/hrbopenres.12936.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745185PMC
November 2020

The experience of financial burden for people with multimorbidity: A systematic review of qualitative research.

Health Expect 2020 Dec 2. Epub 2020 Dec 2.

HRB Centre for Primary Care, Royal College of Surgeons in Ireland, Dublin, Ireland.

Background: Multimorbidity prevalence is increasing globally. People with multimorbidity have higher health care costs, which can create a financial burden.

Objective: To synthesize qualitative research exploring experience of financial burden for people with multimorbidity.

Search Strategy: Six databases were searched in May 2019. A grey literature search and backward and forward citation checking were also conducted.

Inclusion Criteria: Studies were included if they used a qualitative design, conducted primary data collection, included references to financial burden and had at least one community-dwelling adult participant with two or more chronic conditions.

Data Extraction And Synthesis: Screening and critical appraisal were conducted by two reviewers independently. One reviewer extracted data from the results section; this was checked by a second reviewer. GRADE-CERQual was used to summarize the certainty of the evidence. Data were analysed using thematic synthesis.

Main Results: Forty-six studies from six continents were included. Four themes were generated: the high costs people with multimorbidity experience, the coping strategies they use to manage these costs, and the negative effect of both these on their well-being. Health insurance and government supports determine the manageability and level of costs experienced.

Discussion: Financial burden has a negative effect on people with multimorbidity. Continuity of care and an awareness of the impact of financial burden of multimorbidity amongst policymakers and health care providers may partially address the issue.

Patient Or Public Contribution: Results were presented to a panel of people with multimorbidity to check whether the language and themes 'resonated' with their experiences.
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http://dx.doi.org/10.1111/hex.13166DOI Listing
December 2020

Airborne transmission of SARS-CoV-2 via aerosols.

Rev Med Virol 2020 Oct 26:e2184. Epub 2020 Oct 26.

Health Technology Assessment Directorate, Health Information and Quality Authority, Dublin, Ireland.

A key consideration in the Covid-19 pandemic is the dominant modes of transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The objective of this review was to synthesise the evidence for the potential airborne transmission of SARS-CoV-2 via aerosols. Systematic literature searches were conducted in PubMed, Embase, Europe PMC and National Health Service UK evidence up to 27 July 2020. A protocol was published and Cochrane guidance for rapid review methodology was adhered to throughout. Twenty-eight studies were identified. Seven out of eight epidemiological studies suggest aerosol transmission may occur, with enclosed environments and poor ventilation noted as possible contextual factors. Ten of the 16 air sampling studies detected SARS-CoV-2 ribonucleic acid; however, only three of these studies attempted to culture the virus with one being successful in a limited number of samples. Two of four virological studies using artificially generated aerosols indicated that SARS-CoV-2 is viable in aerosols. The results of this review indicate there is inconclusive evidence regarding the viability and infectivity of SARS-CoV-2 in aerosols. Epidemiological studies suggest possible transmission, with contextual factors noted. Viral particles have been detected in air sampling studies with some evidence of clinical infectivity, and virological studies indicate these particles may represent live virus, adding further plausibility. However, there is uncertainty as to the nature and impact of aerosol transmission of SARS-CoV-2, and its relative contribution to the Covid-19 pandemic compared with other modes of transmission.
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http://dx.doi.org/10.1002/rmv.2184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645866PMC
October 2020

Alternative clinical specimens for the detection of SARS-CoV-2: A rapid review.

Rev Med Virol 2020 Oct 22. Epub 2020 Oct 22.

Health Technology Assessment Directorate, Health Information and Quality Authority, Dublin, Ireland.

The collection of nasopharyngeal swabs to test for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an invasive technique with implications for patients and clinicians. Alternative clinical specimens from the upper respiratory tract may offer benefits in terms of collection, comfort and infection risk. The objective of this review was to synthesise the evidence for detection of SARS-CoV-2 ribonucleic acid (RNA) using reverse transcription polymerase chain reaction (RT-PCR) tested saliva or nasal specimens compared with RT-PCR tested nasopharyngeal specimens. Searches were conducted in PubMed, Embase, Europe PMC and NHS evidence from December 2019 to 20 July 2020. Eighteen studies were identified; 12 for saliva, four for nasal and two included both specimen types. For saliva-based studies, the proportion of saliva samples testing positive relative to all positive samples in each study ranged from 82.9% to 100%; detection in nasopharyngeal specimens ranged from 76.7% to 100%; positive agreement between specimens for overall detection ranged from 65.4% to 100%. For nasal-based studies, the proportion of nasal swabs testing positive relative to all positive samples in each study ranged from 81.9% to 100%; detection in nasopharyngeal specimens ranged from 70% to 100%; positive agreement between specimens for overall detection ranged from 62.3% to 100%. The results indicate an inconsistency in the detection of SARS-CoV-2 RNA in the specimen types included, often with neither the index nor the reference of interest detecting all known cases. Depending on the test environment, these clinical specimens may offer a viable alternative to standard. However, at present the evidence is limited, of variable quality, and relatively inconsistent.
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http://dx.doi.org/10.1002/rmv.2185DOI Listing
October 2020

The duration of infectiousness of individuals infected with SARS-CoV-2.

J Infect 2020 12 10;81(6):847-856. Epub 2020 Oct 10.

Health Information and Quality Authority, Smithfield, Dublin 7, Ireland.

Objectives: To summarise the evidence on the duration of infectiousness of individuals in whom SARS-CoV-2 ribonucleic acid is detected.

Methods: A rapid review was undertaken in PubMed, Europe PubMed Central and EMBASE from 1 January 2020 to 26 August 2020.

Results: We identified 15 relevant studies, including 13 virus culture and 2 contact tracing studies. For 5 virus culture studies, the last day on which SARS-CoV-2 was isolated occurred within 10 days of symptom onset. For another 5 studies, SARS-CoV-2 was isolated beyond day 10 for approximately 3% of included patients. The remaining 3 virus culture studies included patients with severe or critical disease; SARS-CoV-2 was isolated up to day 32 in one study. Two studies identified immunocompromised patients from whom SARS-CoV-2 was isolated for up to 20 days. Both contact tracing studies, when close contacts were first exposed greater than 5 days after symptom onset in the index case, found no evidence of laboratory-confirmed onward transmission of SARS-CoV-2.

Conclusion: COVID-19 patients with mild-to-moderate illness are highly unlikely to be infectious beyond 10 days of symptoms. However, evidence from a limited number of studies indicates that patients with severe-to-critical illness or who are immunocompromised, may shed infectious virus for longer.
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http://dx.doi.org/10.1016/j.jinf.2020.10.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547320PMC
December 2020

Diet-induced obesity in genetically diverse collaborative cross mouse founder strains reveals diverse phenotype response and amelioration by quercetin treatment in 129S1/SvImJ, PWK/EiJ, CAST/PhJ, and WSB/EiJ mice.

J Nutr Biochem 2021 Jan 8;87:108521. Epub 2020 Oct 8.

Department of Food, Bioprocessing and Nutrition Sciences, Plants for Human Health Institute, North Carolina State University, Kannapolis, North Carolina, USA. Electronic address:

Significant evidence suggests protective effects of flavonoids against obesity in animal models, but these often do not translate to humans. One explanation for this disconnect is use of a few mouse strains (notably C57BL/6 J) in obesity studies. Obesity is a multifactorial disease. The underlying causes are not fully replicated by the high-fat C57BL/6 J model, despite phenotypic similarities. Furthermore, the impact of genetic factors on the activities of flavonoids is unknown. This study was designed to explore how diverse mouse strains respond to diet-induced obesity when fed a representative flavonoid. A subset of Collaborative Cross founder strains (males and females) were placed on dietary treatments (low-fat, high-fat, high-fat with quercetin, high-fat with quercetin and antibiotics) longitudinally. Diverse responses were observed across strains and sexes. Quercetin appeared to moderately blunt weight gain in male C57 and both sexes of 129S1/SvImJ mice, and slightly increased weight gain in female C57 mice. Surprisingly, quercetin dramatically blunted weight gain in male, but not female, PWK/PhJ mice. For female mice, quercetin blunted weight gain (relative to the high-fat phase) in CAST/PhJ, PWK/EiJ and WSB/EiJ mice compared to C57. Antibiotics did not generally result in loss of protective effects of quercetin. This highlights complex interactions between genetic factors, sex, obesity stimuli, and flavonoid intake, and the need to move away from single inbred mouse models to enhance translatability to diverse humans. These data justify use of genetically diverse Collaborative Cross and Diversity Outbred models which are emerging as invaluable tools in the field of personalized nutrition.
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http://dx.doi.org/10.1016/j.jnutbio.2020.108521DOI Listing
January 2021

Corrigendum to "Benefits and harms of exercise therapy in people with multimorbidity: A systematic review and meta-analysis of randomised controlled trials" [Ageing Res. Rev. 63C (2020) 101166].

Ageing Res Rev 2020 Dec 7;64:101190. Epub 2020 Oct 7.

Research Unit for Musculoskeletal Function and Physiotherapy, Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, 5230 Odense M, Denmark; Department of Physiotherapy and Occupational Therapy, Næstved-Slagelse-Ringsted Hospitals, Region Zealand, 4200 Slagelse, Denmark.

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http://dx.doi.org/10.1016/j.arr.2020.101190DOI Listing
December 2020

The evolution of an evidence based intervention designed to improve prescribing and reduce polypharmacy in older people with multimorbidity and significant polypharmacy in primary care (SPPiRE).

J Comorb 2020 Jan-Dec;10:2235042X20946243. Epub 2020 Sep 14.

HRB Centre for Primary Care Research and RCSI Department of General Practice, Royal College of Surgeons in Ireland, Dublin, Ireland.

Introduction: By the time an intervention is ready for evaluation in a definitive RCT the context of the evidence base may have evolved. To avoid research waste, it is imperative that intervention design and evaluation is an adaptive process incorporating emerging evidence and novel concepts. The aim of this study is to describe changes that were made to an evidence based intervention at the protocol stage of the definitive RCT to incorporate emerging evidence.

Methods: The original evidence based intervention, a GP delivered web guided medication review, was modified in a five step process:Identification of core components of the original intervention.Literature review.Modification of the intervention.Pilot study.Final refinements. A framework, developed in public health research, was utilised to describe the modification process.

Results: The population under investigation changed from older people with a potentially inappropriate prescription (PIP) to older people with significant polypharmacy, a proxy marker for complex multimorbidity. An assessment of treatment priorities and brown bag medication review, with a focus on deprescribing were incorporated into the original intervention. The number of repeat medicines was added as a primary outcome measure as were additional secondary patient reported outcome measures to assess treatment burden and attitudes towards deprescribing.

Conclusions: A framework was used to systematically describe how and why the original intervention was modified, allowing the new intervention to build upon an effective and robustly developed intervention but also to be relevant in the context of the current evidence base.
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http://dx.doi.org/10.1177/2235042X20946243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493276PMC
September 2020

Immune response following infection with SARS-CoV-2 and other coronaviruses: A rapid review.

Rev Med Virol 2020 Sep 23:e2162. Epub 2020 Sep 23.

Health Technology Assessment Directorate, Health Information and Quality Authority, Dublin 7, Ireland.

In this review, we systematically searched and summarized the evidence on the immune response and reinfection rate following SARS-CoV-2 infection. We also retrieved studies on SARS-CoV and MERS-CoV to assess the long-term duration of antibody responses. A protocol based on Cochrane rapid review methodology was adhered to and databases were searched from 1/1/2000 until 26/5/2020. Of 4744 citations retrieved, 102 studies met our inclusion criteria. Seventy-four studies were retrieved on SARS-CoV-2. While the rate and timing of IgM and IgG seroconversion were inconsistent across studies, most seroconverted for IgG within 2 weeks and 100% (N = 62) within 4 weeks. IgG was still detected at the end of follow-up (49-65 days) in all patients (N = 24). Neutralizing antibodies were detected in 92%-100% of patients (up to 53 days). It is not clear if reinfection with SARS-CoV-2 is possible, with studies more suggestive of intermittent detection of residual RNA. Twenty-five studies were retrieved on SARS-CoV. In general, SARS-CoV-specific IgG was maintained for 1-2 years post-infection and declined thereafter, although one study detected IgG up to 12 years post-infection. Neutralizing antibodies were detected up to 17 years in another study. Three studies on MERS-CoV reported that IgG may be detected up to 2 years. In conclusion, limited early data suggest that most patients seroconvert for SARS-CoV-2-specific IgG within 2 weeks. While the long-term duration of antibody responses is unknown, evidence from SARS-CoV studies suggest SARS-CoV-specific IgG is sustained for 1-2 years and declines thereafter.
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http://dx.doi.org/10.1002/rmv.2162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536965PMC
September 2020

Engineered high-affinity zinc binding site reveals gating configurations of a human proton channel.

J Gen Physiol 2020 10;152(10)

Department of Physiology & Biophysics, Rush University, Chicago IL.

The voltage-gated proton channel (HV1) is a voltage sensor that also conducts protons. The singular ability of protons to penetrate proteins complicates distinguishing closed and open channels. When we replaced valine with histidine at position 116 in the external vestibule of hHV1, current was potently inhibited by externally applied Zn2+ in a construct lacking the two His that bind Zn2+ in WT channels. High-affinity binding with profound effects at 10 nM Zn2+ at pHo 7 suggests additional groups contribute. We hypothesized that Asp185, which faces position 116 in our closed-state model, contributes to Zn2+ chelation. Confirming this prediction, V116H/D185N abolished Zn2+ binding. Studied in a C-terminal truncated monomeric construct, V116H channels activated rapidly. Anomalously, Zn2+ slowed activation, producing a time constant independent of both voltage and Zn2+ concentration. We hypothesized that slow turn-on of H+ current in the presence of Zn2+ reflects the rate of Zn2+ unbinding from the channel, analogous to drug-receptor dissociation reactions. This behavior in turn suggests that the affinity for Zn2+ is greater in the closed state of hHV1. Supporting this hypothesis, pulse pairs revealed a rapid component of activation whose amplitude decreased after longer intervals at negative voltages as closed channels bound Zn2+. The lower affinity of Zn2+ in open channels is consistent with the idea that structural rearrangements within the transmembrane region bring Arg205 near position 116, electrostatically expelling Zn2+. This phenomenon provides direct evidence that Asp185 opposes position 116 in closed channels and that Arg205 moves between them when the channel opens.
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http://dx.doi.org/10.1085/jgp.202012664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537347PMC
October 2020

Benefits and harms of exercise therapy in people with multimorbidity: A systematic review and meta-analysis of randomised controlled trials.

Ageing Res Rev 2020 11 5;63:101166. Epub 2020 Sep 5.

Research Unit for Musculoskeletal Function and Physiotherapy, Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, 5230, Odense M, Denmark; Department of Physiotherapy and Occupational Therapy, Næstved-Slagelse-Ringsted Hospitals, Region Zealand, 4200, Slagelse, Denmark.

Objectives: To investigate the benefits and harms of exercise therapy on physical and psychosocial health in people with multimorbidity.

Design: Systematic review of randomised controlled trials (RCTs). Data sources MEDLINE, EMBASE, CENTRAL and CINAHL from 1990 to April 20th, 2020 and Cochrane reviews on the effect of exercise therapy for each of the aforementioned conditions, reference lists of the included studies, the WHO registry and citation tracking on included studies in Web of Science.

Eligibility Criteria For Study Selection: RCTs investigating the benefit of exercise therapy in people with multimorbidity, defined as two or more of the following conditions: osteoarthritis (of the knee or hip), hypertension, type 2 diabetes, depression, heart failure, ischemic heart disease, and chronic obstructive pulmonary disease on at least one of the following outcomes: Health-related quality of life (HRQoL), physical function, depression or anxiety.

Summary And Quality Of The Evidence: Meta-analyses using a random-effects model to assess the benefit of exercise therapy and the risk of non-serious and serious adverse events according to the Food and Drug Administration definition. Meta-regression analyses to investigate the impact of pre-specified mediators of effect estimates. Cochrane 'Risk of Bias Tool' 2.0 and the GRADE assessment to evaluate the overall quality of evidence.

Results: Twenty-three RCTs with 3363 people, testing an exercise therapy intervention (mean duration 13.0 weeks, SD 4.0) showed that exercise therapy improved HRQoL (standardised mean difference (SMD) 0.37, 95 % CI 0.14 to 0.61) and objectively measured physical function (SMD 0.33, 95 % CI 0.17 to 0.49), and reduced depression symptoms (SMD -0.80, 95 % CI -1.21 to -0.40) and anxiety symptoms (SMD -0.49, 95 % CI -0.99 to 0.01). Exercise therapy was not associated with an increased risk of non-serious adverse events (risk ratio 0.96, 95 % CI 0.53-1.76). By contrast, exercise therapy was associated with a reduced risk of serious adverse events (risk ratio 0.62, 95 % CI 0.49 to 0.78). Meta-regression showed that increasing age was associated with lower effect sizes for HRQoL and greater baseline depression severity was associated with greater reduction of depression symptoms. The overall quality of evidence for all the outcomes was downgraded to low, mainly due to risk of bias, inconsistency and indirectness.

Conclusions: Exercise therapy appears to be safe and to have a beneficial effect on physical and psychosocial health in people with multimorbidity. Although the evidence supporting this was of low quality, it highlights the potential of exercise therapy in the management and care of this population.
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http://dx.doi.org/10.1016/j.arr.2020.101166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116122PMC
November 2020

Protocol for the development of a core outcome set for reporting outcomes of management of velopharyngeal dysfunction.

BMJ Open 2020 08 13;10(8):e036824. Epub 2020 Aug 13.

Department of Plastic Surgery, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.

Introduction: Velopharyngeal dysfunction (VPD) is present in up to 40% of patients following cleft palate repair. Children with VPD display hypernasal speech, nasal air emission and are at a high risk for developing articulation disorders. The overall result is decreased intelligibility and acceptability of speech, as well as significant functional and social impairments. Although there are several surgical approaches for the management of children with VPD, standard treatment protocols have not been well defined. There is a need for a core outcome set (COS) to reduce outcome reporting bias and heterogeneity across studies of VPD. The COS-VPD Initiative is an international effort to establish a COS for the reporting of studies of the management of VPD.

Methods And Analysis: The study has been developed according to the Core Outcome Set-STAandards for Development standards for the design of a COS study and will be carried out according to the guidance of the Core Outcome Measures in Effectiveness Trials (COMET) initiative. A long list of clinical and patient-reported outcomes will be identified from a systematic review of the literature. A two-stage Delphi consensus process will be used to refine this list into a COS. An international panel of key stakeholders including patients, parents and multidisciplinary clinical and academic experts will be invited to participate in this process. Consensus criteria will be specified a priori and the steering group will ratify the final COS.

Ethics And Dissemination: The study has ethical approval through Children's Health Ireland at Crumlin Research and Ethics Committee, Ref: GEN/683/18. The study is registered with the COMET Initiative (http://www.cometinitiative.org/studies/details/1146?result=true). The COS will be disseminated by publication in the peer-reviewed literature, presentation at international research meetings and distribution to patient-representative organisations. This will facilitate the application of the COS in future studies of the management of VPD.
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http://dx.doi.org/10.1136/bmjopen-2020-036824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430341PMC
August 2020

Correction to: Development of an intervention to facilitate implementation and uptake of diabetic retinopathy screening.

Implement Sci 2020 Jul 30;15(1):61. Epub 2020 Jul 30.

School of Public Health, University College Cork, Western Gateway Building, Western Rd, Cork, Ireland.

An amendment to this paper has been published and can be accessed via the original article.
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http://dx.doi.org/10.1186/s13012-020-01026-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393863PMC
July 2020

A qualitative exploration of the prescribing and use of statins in asymptomatic people in Ireland: A case of medicalisation, biomedicalisation and pharmaceuticalisation.

Health (London) 2020 Jul 27:1363459320946067. Epub 2020 Jul 27.

J.E. Cairnes School of Business and Economics, National University of Ireland Galway, Ireland.

There has been a notable increase in the use of statins in people without cardiovascular disease but who may be at risk in the future. The majority of statin users now fall into this category but little research has focused exclusively on this group. Debate has ensued regarding medicating asymptomatic people, and processes described variously as medicalisation, biomedicalisation and pharmaceuticalisation are used to explain how this happens. These overlapping and interrelated processes require issues to be 'problemised' as medical problems requiring medical solutions given the prevailing understandings of health, risk and disease. However, current understandings of risk and disease are not simply the result of technological and scientific advances, they are also socially constructed. We interviewed members of the public, GPs and others, and found that rather than high cholesterol being seen as one of several risk factors that contributes to heart disease, it tended to be promoted simplistically to the status of a disease needing treatment of itself. Statins were justified by those taking them as different to 'unnecessary medicines'. However, some participants demonstrated resistance to statins, worried about over-medicalisation and deviated from accepted practices, indicating a complex 'muddling through' in the face of uncertainty.
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http://dx.doi.org/10.1177/1363459320946067DOI Listing
July 2020

An interaction between fetal sex and placental weight and efficiency predicts intrauterine growth in response to maternal protein insufficiency and gestational exposure window in a mouse model of FASD.

Biol Sex Differ 2020 07 20;11(1):40. Epub 2020 Jul 20.

Nutrition Research Institute, Department of Nutrition, University of North Carolina at Chapel Hill, Room #3104, 500 Laureate Way, Kannapolis, NC, 28081, USA.

Background: Individuals exposed to gestational stressors such as alcohol exhibit a spectrum of growth patterns, suggesting individualized responses to the stressors. We hypothesized that intrauterine growth responses to gestational alcohol are modified not only by the stressor's severity but by fetal sex and the placenta's adaptive capacity.

Methods: Pregnant C57BL/6J mice were assigned to one of three groups. Group 1 consumed a normal protein diet (18% protein by weight) and received 4.5 g alcohol/kg body weight (NP-Alc-8) or isocaloric maltodextrin (NP-MD-8) daily from embryonic day (E) 8.5-E17.5. Group 2 consumed the same diet but received alcohol (NP-Alc-13) or maltodextrin (NP-MD-13) daily from E13.5-E17.5. Group 3 consumed the same diet but containing a lower protein content (12% protein by weight) from E0.5 and also received alcohol (LP-Alc-8) or maltodextrin (LP-MD-8) daily from E8.5-E17.5. Maternal, placental, and fetal outcomes were assessed on E17.5 using 2-way ANOVA or mixed linear model.

Results: We found that intrauterine growth differed in the alcohol-exposed fetuses depending on sex and insult severity. Both NP-Alc-8 (vs. NP-MD-8) males and females had lower body weight and asymmetrical growth, but only NP-Alc-8 females had lower placental weight (P < 0.05). NP-Alc-13 (vs. NP-MD-13) females, but not their male littermates, had lower body weight (P = 0.019). Alcohol exposure beginning from E8.5 (vs. E13.5) decreased the ratio of fetal liver-to-body weight and increased the ratio of fetal brain-to-liver weight in both sexes (P < 0.05). LP-Alc-8 (vs. NP-MD-8) group had smaller litter size (P = 0.048), but the survivors had normal placental and body weight at E17.5. Nevertheless, LP-Alc-8 fetuses still showed asymmetrical growth. Correlation analyses reveal a relationship between litter size and placental outcomes, which were related to fetal outcomes in a sex-dependent manner, suggesting that the placenta may mediate the consequence of LP-Alc-altered litter size on fetal development.

Conclusions: Our data indicate that the placenta is strongly involved in the fetal stress response and adapts in a sex-dependent fashion to support fetal development under the alcohol stressor. These variables may further influence the spectrum of intrauterine growth outcomes observed in those diagnosed with fetal alcohol spectrum disorder.
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http://dx.doi.org/10.1186/s13293-020-00320-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372829PMC
July 2020

Interdomain Flexibility within NADPH Oxidase Suggested by SANS Using LMNG Stealth Carrier.

Biophys J 2020 08 3;119(3):605-618. Epub 2020 Jul 3.

University Grenoble Alpes, CNRS, CEA, Institut de Biologie Structurale, Grenoble, France. Electronic address:

Small angle neutron scattering (SANS) provides a method to obtain important low-resolution information for integral membrane proteins (IMPs), challenging targets for structural determination. Specific deuteration furnishes a "stealth" carrier for the solubilized IMP. We used SANS to determine a structural envelope of SpNOX, the Streptococcus pneumoniae NADPH oxidase (NOX), a prokaryotic model system for exploring structure and function of eukaryotic NOXes. SpNOX was solubilized in the detergent lauryl maltose neopentyl glycol, which provides optimal SpNOX stability and activity. Using deuterated solvent and protein, the lauryl maltose neopentyl glycol was experimentally undetected in SANS. This affords a cost-effective SANS approach for obtaining novel structural information on IMPs. Combining SANS data with molecular modeling provided a first, to our knowledge, structural characterization of an entire NOX enzyme. It revealed a distinctly less compact structure than that predicted from the docking of homologous crystal structures of the separate transmembrane and dehydrogenase domains, consistent with a flexible linker connecting the two domains.
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http://dx.doi.org/10.1016/j.bpj.2020.06.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399496PMC
August 2020

Comparison of Student Pharmacists' Clinical Interventions by Semester During APPE Internal Medicine and Critical Care Rotations.

J Pharm Pract 2020 Jul 10:897190020938204. Epub 2020 Jul 10.

Levine College of Health Sciences, Wingate University School of Pharmacy, NC, USA.

Background: Students contribute to health care through clinical interventions made during rotations. Previous studies assessed student interventions through cost savings instead of student progression throughout the year.

Objective: The purpose of this project is to assess clinical interventions made by student pharmacists completing internal medicine and critical care rotations during their Advanced Pharmacy Practice Experiences (APPE) year to determine whether there is a difference in the number and type of interventions between three 3-block rotations, rotation type, and participation in a concentrated learning experience.

Methods: Student clinical interventions from 2013 to 2018 were collected. Interventions were organized into categories and subcategories. The primary end point was the difference in the number of interventions between rotation blocks 1 to 3, 4 to 6, and 7 to 9. Secondary objectives compared interventions based on rotation type and participation in a concentrated learning experience. Descriptive statistics and Fisher's exact tests were conducted.

Results: A total of 848 interventions were analyzed. Average student interventions were 39 in blocks 1 to 3, 18 in blocks 4 to 6, and 62 in blocks 7 to 9. Interventions were significantly above the median for students in blocks 1 to 3 and blocks 7 to 9 compared to blocks 4 to 6 ( = .048 and = .036), respectively. Interventions were significantly above the median for students completing critical care rotations ( = .03). No significant difference was noted in the number of interventions above the median based on participation in a concentrated learning experience ( = .34).

Conclusions: Although a difference exists in the number of interventions made during 3 semesters, more research is needed to assess the relationship of rotation block, student program, and rotation type to intervention number.
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http://dx.doi.org/10.1177/0897190020938204DOI Listing
July 2020

SARS-CoV-2 detection, viral load and infectivity over the course of an infection.

J Infect 2020 09 29;81(3):357-371. Epub 2020 Jun 29.

Health Information and Quality Authority, Smithfield, Dublin 7, Ireland.

Objectives: To summarise the evidence on the detection pattern and viral load of SARS-CoV-2 over the course of an infection (including any asymptomatic or pre-symptomatic phase), and the duration of infectivity.

Methods: A systematic literature search was undertaken in PubMed, Europe PubMed Central and EMBASE from 30 December 2019 to 12 May 2020.

Results: We identified 113 studies conducted in 17 countries. The evidence from upper respiratory tract samples suggests that the viral load of SARS-CoV-2 peaks around symptom onset or a few days thereafter, and becomes undetectable about two weeks after symptom onset; however, viral loads from sputum samples may be higher, peak later and persist for longer. There is evidence of prolonged virus detection in stool samples, with unclear clinical significance. No study was found that definitively measured the duration of infectivity; however, patients may not be infectious for the entire duration of virus detection, as the presence of viral ribonucleic acid may not represent transmissible live virus.

Conclusion: There is a relatively consistent trajectory of SARS-CoV-2 viral load over the course of COVID-19 from respiratory tract samples, however the duration of infectivity remains uncertain.
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http://dx.doi.org/10.1016/j.jinf.2020.06.067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323671PMC
September 2020

The experience of financial burden for patients with multimorbidity: A protocol for a systematic review of qualitative research.

HRB Open Res 2019 26;2:16. Epub 2020 Mar 26.

HRB Centre for Primary Care, Royal College of Surgeons in Ireland, Dublin, Ireland.

Multimorbidity is increasingly important due to its high disease burden, prevalence and related high healthcare utilisation. For patients, there is also a high financial burden due to direct and indirect costs arising from their multimorbidity. It is unclear how this financial burden affects patients. This study aims to synthesise qualitative evidence exploring the experience of financial burden from the perspective of patients with multimorbidity. The review will be reported using the ENTREQ guidelines. A systematic search of Lilacs, PubMed, CINAHL, EMBASE, PsycINFO, and Applied Social Sciences Index and Abstracts will be conducted using a predefined search strategy. A search of fourteen pre-specified websites will be conducted for grey literature. Forward and backward citation checking of included studies will be conducted also. Studies will be included if they contain primary qualitative research and reference the experience of financial burden from the perspective of adult (≥ 18 years) community dwelling patients with multimorbidity. Studies from any country and in any language will be included. Titles and abstracts of search results will be screened; if a study appears relevant, then full-texts will be screened for eligibility. Study characteristics of included articles will be extracted. Study quality will be evaluated using the critical appraisal skills programme (CASP) checklist for qualitative research. These three processes will be carried out by two reviewers independently. Thematic-synthesis will be used to analyse data. This will be carried out by one reviewer and cross-checked by a second reviewer. The GRADE CERQual approach will be used to assess the overall confidence in the evidence. This review will identify evidence on the experiences of financial burden for patients with multimorbidity and forms part of a project to support consideration of financial burden for patients in the development of clinical guidelines in Ireland.  CRD42019135284.
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http://dx.doi.org/10.12688/hrbopenres.12915.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309055PMC
March 2020

Evaluation of the General Practice Pharmacist (GPP) intervention to optimise prescribing in Irish primary care: a non-randomised pilot study.

BMJ Open 2020 06 28;10(6):e035087. Epub 2020 Jun 28.

HRB Centre for Primary Care Research, Department of General Practice, Royal College of Surgeons in Ireland, Dublin, Ireland

Objective: Limited evidence suggests integration of pharmacists into the general practice team could improve medicines management for patients, particularly those with multimorbidity and polypharmacy. This study aimed to develop and assess the feasibility of an intervention involving pharmacists, working within general practices, to optimise prescribing in Ireland.

Design: Non-randomised pilot study.

Setting: Primary care in Ireland.

Participants: Four general practices, purposively sampled and recruited to reflect a range of practice sizes and demographic profiles.

Intervention: A pharmacist joined the practice team for 6 months (10 hours/week) and undertook medication reviews (face to face or chart based) for adult patients, provided prescribing advice, supported clinical audits and facilitated practice-based education.

Outcome Measures: Anonymised practice-level medication (eg, medication changes) and cost data were collected. Patient-reported outcome measure (PROM) data were collected on a subset of older adults (aged ≥65 years) with polypharmacy using patient questionnaires, before and 6 weeks after medication review by the pharmacist.

Results: Across four practices, 786 patients were identified as having 1521 prescribing issues by the pharmacists. Issues relating to deprescribing medications were addressed most often by the prescriber (59.8%), compared with cost-related issues (5.8%). Medication changes made during the study equated to approximately €57 000 in cost savings assuming they persisted for 12 months. Ninety-six patients aged ≥65 years with polypharmacy were recruited from the four practices for PROM data collection and 64 (66.7%) were followed up. There were no changes in patients' treatment burden or attitudes to deprescribing following medication review, and there were conflicting changes in patients' self-reported quality of life.

Conclusions: This non-randomised pilot study demonstrated that an intervention involving pharmacists, working within general practices is feasible to implement and has potential to improve prescribing quality. This study provides rationale to conduct a randomised controlled trial to evaluate the clinical and cost-effectiveness of this intervention.
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http://dx.doi.org/10.1136/bmjopen-2019-035087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322285PMC
June 2020

Quality, scope and reporting standards of randomised controlled trials in Irish Health Research: an observational study.

Trials 2020 Jun 8;21(1):494. Epub 2020 Jun 8.

HRB Centre for Primary Care Research, Department of General Practice, Royal College of Surgeons in Ireland, 123 St Stephens Green, Dublin 2, Ireland.

Background: Despite efforts to improve the accuracy and transparency of the design, conduct, and reporting of randomised controlled trials (RCTs), deficiencies remain. Such deficiencies contribute to significant, avoidable waste of health research investment and impede reproducibility. This study aimed to synthesise and critically analyse changes over time in the conduct and reporting of internationally published evidence on patient and/or population health-oriented RCTs conducted in one country.

Methods: This observational study drew on systematic review methods. We searched six databases for published RCTs (database inception to December 2018) where ≥ 80% of participants were recruited in the Republic of Ireland. RCTs of interventions targeted at patients, providers and/or policy makers intended to improve health, healthcare or health research were included. For each study, screening, data extraction and methodological quality appraisal were conducted by one member of the author team.

Results: From 17,560 titles and abstracts, 752 unique RCTs were published in 745 papers between 1968 and 2018, with a steady year-on-year increase since 1968. The number of participants was in the range of 2-8628. The majority were parallel design (86%) and classified as treatment evaluation. Of the 418 RCTs published since the introduction of mandatory clinical trial registration by the International Committee of Medical Journal Editors in 2005, 32% (n = 134) provided a trial registration number. This increased to 47% when taking studies published between 2013 and 2018 (n = 232). Since the 1996 publication of the CONSORT statement, 16% of included RCTs made specific reference to a standardised reporting guideline and this increased to 31% for more recent studies published between 2013 and 2018. Overall, 7% (n = 53) of studies referred to a published study protocol, increasing to 20% for studies published between 2013 and 2018.

Conclusion: Evidence from this single-country study of RCTs published in the international literature suggests that both the number overall, the number registered and the number referencing reporting guidelines have increased steadily over time. Despite widespread endorsement of reporting standards, reporting of RCTs remains suboptimal in domains such as compliance with the CONSORT statement and prospective trial registration. Researchers, funders and journal editors, nationally and internationally, should continue to focus on improving reporting and examining avoidable waste of health research investment.
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http://dx.doi.org/10.1186/s13063-020-04396-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278139PMC
June 2020

Development of an intervention to facilitate implementation and uptake of diabetic retinopathy screening.

Implement Sci 2020 05 19;15(1):34. Epub 2020 May 19.

School of Public Health, University College Cork, Western Gateway Building, Western Rd, Cork, Ireland.

Background: 'Implementation interventions' refer to methods used to enhance the adoption and implementation of clinical interventions such as diabetic retinopathy screening (DRS). DRS is effective, yet uptake is often suboptimal. Despite most routine management taking place in primary care and the central role of health care professionals (HCP) in referring to DRS, few interventions have been developed for primary care. We aimed to develop a multifaceted intervention targeting both professionals and patients to improve DRS uptake as an example of a systematic development process combining theory, stakeholder involvement, and evidence.

Methods: First, we identified target behaviours through an audit in primary care of screening attendance. Second, we interviewed patients (n = 47) and HCP (n = 30), to identify determinants of uptake using the Theoretical Domains Framework, mapping these to behaviour change techniques (BCTs) to develop intervention content. Thirdly, we conducted semi-structured consensus groups with stakeholders, specifically users of the intervention, i.e. patients (n = 15) and HCPs (n = 16), regarding the feasibility, acceptability, and local relevance of selected BCTs and potential delivery modes. We consulted representatives from the national DRS programme to check intervention 'fit' with existing processes. We applied the APEASE criteria (affordability, practicability, effectiveness, acceptability, side effects, and equity) to select the final intervention components, drawing on findings from the previous steps, and a rapid evidence review of operationalised BCT effectiveness.

Results: We identified potentially modifiable target behaviours at the patient (consent, attendance) and professional (registration) level. Patient barriers to consent/attendance included confusion between screening and routine eye checks, and fear of a negative result. Enablers included a recommendation from friends/family or professionals and recognising screening importance. Professional barriers to registration included the time to register patients and a lack of readily available information on uptake in their local area/practice. Most operationalised BCTs were acceptable to patients and HCPs while the response to feasibility varied. After considering APEASE, the core intervention, incorporating a range of BCTs, involved audit/feedback, electronic prompts targeting professionals, HCP-endorsed reminders (face-to-face, by phone and letter), and an information leaflet for patients.

Conclusions: Using the example of an intervention to improve DRS uptake, this study illustrates an approach to integrate theory with user involvement. This process highlighted tensions between theory-informed and stakeholder suggestions, and the need to apply the Theoretical Domains Framework (TDF)/BCT structure flexibly. The final intervention draws on the trusted professional-patient relationship, leveraging existing services to enhance implementation of the DRS programme. Intervention feasibility in primary care will be evaluated in a randomised cluster pilot trial.
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http://dx.doi.org/10.1186/s13012-020-00982-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236930PMC
May 2020

The benefits and harms of therapeutic exercise on physical and psychosocial outcomes in people with multimorbidity: Protocol for a systematic review.

J Comorb 2020 Jan-Dec;10:2235042X20920458. Epub 2020 May 12.

Research Unit for Musculoskeletal Function and Physiotherapy, Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense M, Denmark.

Aim: The aim of this study is to investigate the benefits and harms of therapeutic exercise in people with multimorbidity defined as the combination of two or more of the following conditions: knee and hip osteoarthritis, hypertension, diabetes type 2, depression, heart failure, ischaemic heart disease and chronic obstructive pulmonary disease, by performing a systematic review of randomized controlled trials (RCTs).

Methods: This study will be performed according to the recommendations from the Cochrane Collaboration and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We will search for RCTs investigating the effect of therapeutic exercise in multimorbidity, as defined above, in MEDLINE, EMBASE, CENTRAL and CINAHL from 1990. Cochrane reviews on the effect of therapeutic exercise for each of the aforementioned conditions and references of the included studies will be checked for eligible studies and citation tracking will be performed in Web of Science. We will assess the risk of bias of the included studies using the Cochrane 'Risk of Bias Tool' 2.0 and the Grading of Recommendations Assessment, Development and Evaluation assessment for judging the overall quality of evidence. Meta-analyses will be performed, if possible, using a random-effects model as heterogeneity is expected due to differences in interventions and participant characteristics and outcome measures. Subgroup and meta-regression analyses will be performed to explore potential predictors of outcomes.

Dissemination: The results of this systematic review will be published in a peer-review journal, presented at national and international conferences and made available to end users via infographics, podcasts, press releases and videos.
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http://dx.doi.org/10.1177/2235042X20920458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218324PMC
May 2020

Feasibility of an implementation intervention to increase attendance at diabetic retinopathy screening: protocol for a cluster randomised pilot trial.

Pilot Feasibility Stud 2020 12;6:64. Epub 2020 May 12.

1School of Public Health, University College Cork, Western Gateway Building, Western Rd, Cork, Ireland.

Background: Diabetic retinopathy screening (DRS) leads to the earlier detection of retinopathy and treatment that can prevent or delay the development of diabetes-related blindness. However, uptake continues to be sub-optimal in many countries, including Ireland. Routine management of type 2 diabetes largely takes place in primary care. As such, there may be an opportunity in primary care to introduce interventions to improve DRS uptake. However, few studies test the feasibility of interventions to enhance DRS uptake in this context. Our aim is to investigate the feasibility of an implementation intervention (IDEAs (Improving Diabetes Eye screening Attendance)) delivered in general practice to improve the uptake of the national DRS programme, RetinaScreen.

Methods: The IDEAs study is a cluster randomised pilot trial with an embedded process evaluation and economic evaluation. Following stratification by practice size, eight general practices (clusters) will be randomly allocated to intervention ( = 4) or wait-list control groups ( = 4). The intervention will be delivered for 6 months, after which, it will be administered to wait-list control practices. The intervention is multi-faceted and comprises provider-level components (training, audit and feedback, health care professional prompt, reimbursement) and patient-level components (GP-endorsed reminder with information leaflet delivered opportunistically face-to-face, and systematically by phone and letter). Patient inclusion criteria are type 1 or type 2 diabetes and DRS programme non-attendance. A multi-method approach will be used to determine screening uptake, evaluate the trial and study procedures and examine the acceptability and feasibility of the intervention from staff and patient perspectives. Quantitative and qualitative data will be collected on intervention uptake and delivery, research processes and outcomes. Data will be collected at the practice, health professional and patient level. A partial economic evaluation will be conducted to estimate the cost of delivering the implementation intervention in general practice. Formal continuation criteria will be used to determine whether IDEAs should progress to a definitive trial.

Discussion: Findings will determine whether IDEAsis feasible and acceptable and will be used to refine the intervention and study procedures. A definitive trial will determine whether IDEAs is a cost-effective intervention to improve DRS uptake and reduce diabetes-related blindness.

Trial Registration: ClinicalTrials.gov NCT03901898. Registered 3rd April 2019.
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http://dx.doi.org/10.1186/s40814-020-00608-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216495PMC
May 2020