• Adolescents’ experiences of fluctuating pain in musculoskeletal disorders: a qualitative systematic review and thematic synthesis

      Khanom, Sonia; orcid: 0000-0002-9869-2476; email: sonia.khanom@postgrad.manchester.ac.uk; McDonagh, Janet E.; Briggs, Michelle; Bakir, Ebru; McBeth, John (BioMed Central, 2020-10-02)
      Abstract: Background: Adolescents with chronic musculoskeletal pain experience daily fluctuations in pain. Although not all fluctuations are bothersome, pain flares are a distinct type of symptom fluctuation with greater impact. Since literature on the experience of pain flares is non-existent, the aim of this review was to (i) synthesise the qualitative literature on adolescents’ experiences of fluctuating pain in musculoskeletal disorders in order to (ii) identify knowledge gaps to inform future research on pain flares. Methods: Electronic databases (CINAHL, MEDLINE, EMBASE, PsycINFO), grey literature and reference lists were searched from inception to June 2018 for qualitative studies reporting adolescents’ experiences of pain. Comprehensiveness of reporting was assessed using the Consolidated Criteria for Reporting Qualitative Health Research. Studies were analysed using thematic synthesis. Results: Of the 3787 records identified, 32 studies (n = 536) were included. Principal findings were synthesised under three key themes: 1) symptom experience, 2) disruption and loss, and 3) regaining control. The first theme (symptom experience) describes adolescent’s perception and interpretation of pain fluctuations. The second theme (disruption and loss) describes the physical, social and emotional constraints faced as a result of changes in pain. The third theme (regaining control) describes coping strategies used to resist and accommodate unpredictable phases of pain. Each theme was experienced differently depending on adolescents’ characteristics such as their developmental status, pain condition, and the duration of the pain experience. Conclusions: Adolescents with chronic musculoskeletal pain live with a daily background level of symptoms which frequently fluctuate and are associated with functional and emotional difficulties. It was not clear whether these symptoms and challenges were experienced as part of ‘typical’ fluctuations in pain, or whether they reflect symptom exacerbations classified as ‘flares’. Further research is needed to explore the frequency and characteristics of pain flares, and how they differ from their typical fluctuations in pain. The review also highlights areas relating to the pain experience, symptom management and health service provision that require further exploration to support more personalised, tailored care for adolescents with chronic musculoskeletal pain.
    • Assessing the relation between alcohol consumption and risk of disease and mortality

      Alam, Benyamin; orcid: 0000-0002-6349-2650; email: benyamin.alam@student.manchester.ac.uk; Anwar, Mehreen; Bareli, Leonardo; Chowdhury, Shamia (BioMed Central, 2021-06-28)
    • Benefits and harms of Risperidone and Paliperidone for treatment of patients with schizophrenia or bipolar disorder: a meta-analysis involving individual participant data and clinical study reports

      Hodkinson, Alexander; orcid: 0000-0003-2063-0977; email: alexander.hodkinson@manchester.ac.uk; Heneghan, Carl; Mahtani, Kamal R.; Kontopantelis, Evangelos; Panagioti, Maria (BioMed Central, 2021-08-25)
      Abstract: Background: Schizophrenia and bipolar disorder are severe mental illnesses which are highly prevalent worldwide. Risperidone and Paliperidone are treatments for either illnesses, but their efficacy compared to other antipsychotics and growing reports of hormonal imbalances continue to raise concerns. As existing evidence on both antipsychotics are solely based on aggregate data, we aimed to assess the benefits and harms of Risperidone and Paliperidone in the treatment of patients with schizophrenia or bipolar disorder, using individual participant data (IPD), clinical study reports (CSRs) and publicly available sources (journal publications and trial registries). Methods: We searched MEDLINE, Central, EMBASE and PsycINFO until December 2020 for randomised placebo-controlled trials of Risperidone, Paliperidone or Paliperidone palmitate in patients with schizophrenia or bipolar disorder. We obtained IPD and CSRs from the Yale University Open Data Access project. The primary outcome Positive and Negative Syndrome Scale (PANSS) score was analysed using one-stage IPD meta-analysis. Random-effect meta-analysis of harm outcomes involved methods for coping with rare events. Effect-sizes were compared across all available data sources using the ratio of means or relative risk. We registered our review on PROSPERO, CRD42019140556. Results: Of the 35 studies, IPD meta-analysis involving 22 (63%) studies showed a significant clinical reduction in the PANSS in patients receiving Risperidone (mean difference − 5.83, 95% CI − 10.79 to − 0.87, I2 = 8.5%, n = 4 studies, 1131 participants), Paliperidone (− 6.01, 95% CI − 8.7 to − 3.32, I2 = 4.3%, n = 13, 3821) and Paliperidone palmitate (− 7.89, 95% CI − 12.1 to − 3.69, I2 = 2.9%, n = 5, 2209). CSRs reported nearly two times more adverse events (4434 vs. 2296 publication, relative difference (RD) = 1.93, 95% CI 1.86 to 2.00) and almost 8 times more serious adverse events (650 vs. 82; RD = 7.93, 95% CI 6.32 to 9.95) than the journal publications. Meta-analyses of individual harms from CSRs revealed a significant increased risk among several outcomes including extrapyramidal disorder, tardive dyskinesia and increased weight. But the ratio of relative risk between the different data sources was not significant. Three treatment-related gynecomastia events occurred, and these were considered mild to moderate in severity. Conclusion: IPD meta-analysis conclude that Risperidone and Paliperidone antipsychotics had a small beneficial effect on reducing PANSS score over 9 weeks, which is more conservative than estimates from reviews based on journal publications. CSRs also contained significantly more data on harms that were unavailable in journal publications or trial registries. Sharing of IPD and CSRs are necessary when performing meta-analysis on the efficacy and safety of antipsychotics.
    • Blast cells surviving acute myeloid leukemia induction therapy are in cycle with a signature of FOXM1 activity

      Williams, Mark S.; email: mark.williams-4@manchester.ac.uk; Basma, Naseer J.; Amaral, Fabio M. R.; Wiseman, Daniel H.; Somervaille, Tim C. P.; orcid: 0000-0002-9188-4379; email: tim.somervaille@cruk.manchester.ac.uk (BioMed Central, 2021-10-28)
      Abstract: Background: Disease relapse remains common following treatment of acute myeloid leukemia (AML) and is due to chemoresistance of leukemia cells with disease repopulating potential. To date, attempts to define the characteristics of in vivo resistant blasts have focused on comparisons between leukemic cells at presentation and relapse. However, further treatment responses are often seen following relapse, suggesting that most blasts remain chemosensitive. We sought to characterise in vivo chemoresistant blasts by studying the transcriptional and genetic features of blasts from before and shortly after induction chemotherapy using paired samples from six patients with primary refractory AML. Methods: Leukemic blasts were isolated by fluorescence-activated cell sorting. Fluorescence in situ hybridization (FISH), targeted genetic sequencing and detailed immunophenotypic analysis were used to confirm that sorted cells were leukemic. Sorted blasts were subjected to RNA sequencing. Lentiviral vectors expressing short hairpin RNAs were used to assess the effect of FOXM1 knockdown on colony forming capacity, proliferative capacity and apoptosis in cell lines, primary AML cells and CD34+ cells from healthy donors. Results: Molecular genetic analysis revealed early clonal selection occurring after induction chemotherapy. Immunophenotypic characterisation found leukemia-associated immunophenotypes in all cases that persisted following treatment. Despite the genetic heterogeneity of the leukemias studied, transcriptional analysis found concerted changes in gene expression in resistant blasts. Remarkably, the gene expression signature suggested that post-chemotherapy blasts were more proliferative than those at presentation. Resistant blasts also appeared less differentiated and expressed leukemia stem cell (LSC) maintenance genes. However, the proportion of immunophenotypically defined LSCs appeared to decrease following treatment, with implications for the targeting of these cells on the basis of cell surface antigen expression. The refractory gene signature was highly enriched with targets of the transcription factor FOXM1. shRNA knockdown experiments demonstrated that the viability of primary AML cells, but not normal CD34+ cells, depended on FOXM1 expression. Conclusions: We found that chemorefractory blasts from leukemias with varied genetic backgrounds expressed a common transcriptional program. In contrast to the notion that LSC quiescence confers resistance to chemotherapy we find that refractory blasts are both actively proliferating and enriched with LSC maintenance genes. Using primary patient material from a relevant clinical context we also provide further support for the role of FOXM1 in chemotherapy resistance, proliferation and stem cell function in AML.
    • Brief Engagement and Acceptance Coaching for Hospice Settings (the BEACHeS study): results from a Phase I study of acceptability and initial effectiveness in people with non-curative cancer

      Hulbert-Williams, Nicholas J.; email: n.hulbertwilliams@chester.ac.uk; Norwood, Sabrina F.; Gillanders, David; Finucane, Anne M.; Spiller, Juliet; Strachan, Jenny; Millington, Susan; Kreft, Joseph; Swash, Brooke (BioMed Central, 2021-06-25)
      Abstract: Objectives: Transitioning into palliative care is psychologically demanding for people with advanced cancer, and there is a need for acceptable and effective interventions to support this. We aimed to develop and pilot test a brief Acceptance and Commitment Therapy (ACT) based intervention to improve quality of life and distress. Methods: Our mixed-method design included: (i) quantitative effectiveness testing using Single Case Experimental Design (SCED), (ii) qualitative interviews with participants, and (iii) focus groups with hospice staff. The five-session, in-person intervention was delivered to 10 participants; five completed at least 80%. Results: At baseline, participants reported poor quality of life but low distress. Most experienced substantial physical health deterioration during the study. SCED analysis methods did not show conclusively significant effects, but there was some indication that outcome improvement followed changes in expected intervention processes variables. Quantitative and qualitative data together demonstrates acceptability, perceived effectiveness and safety of the intervention. Qualitative interviews and focus groups were also used to gain feedback on intervention content and to make design recommendations to maximise success of later feasibility trials. Conclusions: This study adds to the growing evidence base for ACT in people with advanced cancer. A number of potential intervention mechanisms, for example a distress-buffering hypothesis, are raised by our data and these should be addressed in future research using randomised controlled trial designs. Our methodological recommendations—including recruiting non-cancer diagnoses, and earlier in the treatment trajectory—likely apply more broadly to the delivery of psychological intervention in the palliative care setting. This study was pre-registered on the Open Science Framework (Ref: 46,033) and retrospectively registered on the ISRCTN registry (Ref: ISRCTN12084782).
    • Can we achieve better recruitment by providing better information? Meta-analysis of ‘studies within a trial’ (SWATs) of optimised participant information sheets

      Madurasinghe, Vichithranie W.; Bower, Peter; orcid: 0000-0001-9558-3349; email: peter.bower@manchester.ac.uk; Eldridge, Sandra; Collier, David; Graffy, Jonathan; Treweek, Shaun; Knapp, Peter; Parker, Adwoa; Rick, Jo; Salisbury, Chris; et al. (BioMed Central, 2021-09-23)
      Abstract: Background: The information given to people considering taking part in a trial needs to be easy to understand if those people are to become, and then remain, trial participants. However, there is a tension between providing comprehensive information and providing information that is comprehensible. User-testing is one method of developing better participant information, and there is evidence that user-tested information is better at informing participants about key issues relating to trials. However, it is not clear if user-testing also leads to changes in the rates of recruitment in trials, compared to standard trial information. As part of a programme of research, we embedded ‘studies within a trial’ (SWATs) across multiple ongoing trials to see if user-tested materials led to better rates of recruitment. Methods: Seven ‘host’ trials included a SWAT evaluation and randomised their participants to receive routine information sheets generated by the research teams, or information sheets optimised through user-testing. We collected data on trial recruitment and analysed the results across these trials using random effects meta-analysis, with the primary outcome defined as the proportion of participants randomised in a host trial following an invitation to take part. Results: Six SWATs (n=27,805) provided data on recruitment. Optimised participant information sheets likely result in little or no difference in recruitment rates (7.2% versus 6.8%, pooled odds ratio = 1.03, 95% CI 0.90 to 1.19, p-value = 0.63, I2 = 0%). Conclusions: Participant information sheets developed through user testing did not improve recruitment rates. The programme of work showed that co-ordinated testing of recruitment strategies using SWATs is feasible and can provide both definitive and timely evidence on the effectiveness of recruitment strategies. Trial registration: Healthlines Depression (ISRCTN14172341) Healthlines CVD (ISRCTN27508731) CASPER (ISRCTN02202951) ISDR (ISRCTN87561257) ECLS (NCT01925625) REFORM (ISRCTN68240461) HeLP Diabetes (ISRCTN02123133)
    • Canine Genetics and Epidemiology is now Canine Medicine and Genetics

      Ollier, William; email: Bill.Ollier@manchester.ac.uk; Gaschen, Frédéric; email: fgaschen@lsu.edu; Kennedy, Lorna (BioMed Central, 2020-07-27)
    • Children and young people’s experiences of completing mental health and wellbeing measures for research: learning from two school-based pilot projects

      Demkowicz, Ola; orcid: 0000-0001-9204-0912; email: ola.demkowicz@manchester.ac.uk; Ashworth, Emma; Mansfield, Rosie; Stapley, Emily; Miles, Helena; Hayes, Daniel; Burrell, Kim; Moore, Anna; Deighton, Jessica (BioMed Central, 2020-09-16)
      Abstract: Background: In recent years there has been growing interest in child and adolescent mental health and wellbeing, alongside increasing emphasis on schools as a crucial site for research and intervention. This has coincided with an increased use of self-report mental health and wellbeing measures in research with this population, including in school-based research projects. We set out to explore the way that children and young people perceive and experience completing mental health and wellbeing measures, with a specific focus on completion in a school context, in order to inform future measure and research design. Methods: We conducted semi-structured interviews and focus groups with 133 participants aged 8–16 years following their completion of mental health and wellbeing measures as part of school-based research programmes, using thematic analysis to identify patterns of experience. Findings: We identified six themes: Reflecting on emotions during completion; the importance of anonymity; understanding what is going to happen; ease of responding to items; level of demand; and interacting with the measure format. Conclusions: Our findings offer greater insight into children and young people’s perceptions and experiences in reporting on their mental health and wellbeing. Such understanding can be used to support more ethical and robust data collection procedures in child and adolescent mental health research, both for data quality and ethical purposes. We offer several practical recommendations for researchers, including facilitating this in a school context.
    • Chronic anticoagulation is not associated with a reduced risk of acute kidney injury in hospitalised Covid-19 patients

      Parker, Kathrine; email: Kathrine.parker@postgrad.manchester.ac.uk; Hamilton, Patrick; Hanumapura, Prasanna; Castelino, Laveena; Murphy, Michelle; Challiner, Rachael; Thachil, Jecko; Ebah, Leonard (BioMed Central, 2021-06-16)
      Abstract: Background: Coronavirus-19 (COVID-19) has been declared a global pandemic by the World Health Organisation. Severe disease typically presents with respiratory failure but Acute Kidney Injury (AKI) and a hypercoagulable state can also occur. Early reports suggest that thrombosis may be linked with AKI. We studied the development of AKI and outcomes of patients with COVID-19 taking chronic anticoagulation therapy. Methods: Electronic records were reviewed for all adult patients admitted to Manchester University Foundation Trust Hospitals between March 10 and April 302,020 with a diagnosis of COVID-19. Patients with end-stage kidney disease were excluded. AKI was classified as per KDIGO criteria. Results: Of the 1032 patients with COVID-19 studied,164 (15.9%) were taking anticoagulant therapy prior to admission. There were similar rates of AKI between those on anticoagulants and those not anticoagulated (23.8% versus 19.7%) with no difference in the severity of AKI or requirement of renal replacement therapy between groups (1.2% versus 3.5%). Risk factors for AKI included hypertension, pre-existing renal disease and male sex. There was a higher mortality in those taking anticoagulant therapy (40.2% versus 30%). Patients taking anticoagulants were less likely to be admitted to the Intensive Care Unit (8.5% versus 17.4%) and to receive mechanical ventilation (42.9% versus 78.1%). Conclusion: Patients on chronic anticoagulant therapy did not have a reduced incidence or severity of AKI suggesting that AKI is unlikely to be thrombotic in nature. Therapeutic anticoagulation is currently still under investigation in randomised controlled studies to determine whether it has a potential role in COVID-19 treatment.
    • Clinical, humanistic, and economic burden of severe haemophilia B in adults receiving factor IX prophylaxis: findings from the CHESS II real-world burden of illness study in Europe

      Burke, Tom; Asghar, Sohaib; orcid: 0000-0001-8276-0131; O’Hara, Jamie; Chuang, Margaret; Sawyer, Eileen K.; Li, Nanxin; email: n.li@uniqure.com (BioMed Central, 2021-12-20)
      Abstract: Background: Real-world studies of the burden of severe haemophilia B in the context of recent therapeutic advances such as extended half-life (EHL) factor IX (FIX) products are limited. We analysed data from the recent CHESS II study to better understand the clinical, humanistic, and economic burden of severe haemophilia B in Europe. Data from male adults with severe haemophilia B receiving prophylaxis were analysed from the retrospective cross-sectional CHESS II study conducted in Germany, France, Italy, Spain and the United Kingdom. Inhibitors were exclusionary. Patients and physicians completed questionnaires on bleeding, joint status, quality of life, and haemophilia-related direct and indirect costs (2019–2020). All outcomes were summarised using descriptive statistics. Results: A total of 75 CHESS II patients were eligible and included; 40 patients (53%) provided self-reported outcomes. Mean age was 36.2 years. Approximately half the patients were receiving EHL versus standard half-life (SHL) prophylaxis (44% vs 56%). Most patients reported mild or moderate chronic pain (76%) and had ≥ 2 bleeding events per year (70%), with a mean annualised bleed rate of 2.4. Mean annual total haemophilia-related direct medical cost per patient was €235,723, driven by FIX costs (€232,328 overall, n = 40; €186,528 for SHL, €290,620 for EHL). Mean annual indirect costs (€8,973) were driven by early retirement or work stoppage due to haemophilia. Mean quality of life (EQ-5D) score was 0.67. Conclusions: These data document a substantial, persistent real-world burden of severe haemophilia B in Europe. Unmet needs persist for these patients, their caregivers, and society.
    • Clinical, humanistic, and economic burden of severe hemophilia B in the United States: Results from the CHESS US and CHESS US+ population surveys

      Burke, Tom; Asghar, Sohaib; orcid: 0000-0001-8276-0131; O’Hara, Jamie; Sawyer, Eileen K.; Li, Nanxin; email: n.li@uniqure.com (BioMed Central, 2021-03-20)
      Abstract: Background: Hemophilia B is a rare congenital bleeding disorder that has a significant negative impact on patients’ functionality and health-related quality of life. The standard of care for severe hemophilia B in the United States is prophylactic factor IX replacement therapy, which incurs substantial costs for this lifelong condition. Accurate estimates of the burden of hemophilia B are important for population health management and policy decisions, but have only recently accounted for current management strategies. The ‘Cost of Severe Hemophilia across the US: a Socioeconomic Survey’ (CHESS US) is a cross-sectional database of medical record abstractions and physician-reported information, completed by hematologists and care providers. CHESS US+ is a complementary database of completed questionnaires from patients with hemophilia. Together, CHESS US and CHESS US+ provide contemporary, comprehensive information on the burden of severe hemophilia from the provider and patient perspectives. We used the CHESS US and CHESS US+ data to analyze the clinical, humanistic, and economic burden of hemophilia B for patients treated with factor IX prophylaxis between 2017 and 2019 in the US. Results: We conducted analysis to assess clinical burden and direct medical costs from 44 patient records in CHESS US, and of direct non-medical costs, indirect costs, and humanistic burden (using the EQ-5D-5L) from 57 patients in CHESS US+. The mean annual bleed rate was 1.73 (standard deviation, 1.39); approximately 9% of patients experienced a bleed-related hospitalization during the 12-month study period. Nearly all patients (85%) reported chronic pain, and the mean EQ-5D-5L utility value was 0.76 (0.24). The mean annual direct medical cost was $614,886, driven by factor IX treatment (mean annual cost, $611,971). Subgroup analyses showed mean annual costs of $397,491 and $788,491 for standard and extended half-life factor IX treatment, respectively. The mean annual non-medical direct costs and indirect costs of hemophilia B were $2,371 and $6,931. Conclusions: This analysis of patient records and patient-reported outcomes from CHESS US and CHESS US+ provides updated information on the considerable clinical, humanistic, and economic burden of hemophilia B in the US. Substantial unmet needs remain to improve patient care with sustainable population health strategies.
    • Co-expression of C9orf72 related dipeptide-repeats over 1000 repeat units reveals age- and combination-specific phenotypic profiles in Drosophila

      West, Ryan J. H.; orcid: 0000-0001-9873-2258; email: r.j.west@sheffield.ac.uk; Sharpe, Joanne L.; Voelzmann, André; Munro, Anna L.; Hahn, Ines; Baines, Richard A.; Pickering-Brown, Stuart; email: SPB@Manchester.ac.uk (BioMed Central, 2020-09-07)
      Abstract: A large intronic hexanucleotide repeat expansion (GGGGCC) within the C9orf72 (C9orf72-SMCR8 Complex Subunit) locus is the most prevalent genetic cause of both Frontotemporal Dementia (FTD) and Motor Neuron Disease (MND). In patients this expansion is typically hundreds to thousands of repeat units in length. Repeat associated non-AUG translation of the expansion leads to the formation of toxic, pathological Dipeptide-Repeat Proteins (DPRs). To date there remains a lack of in vivo models expressing C9orf72 related DPRs with a repeat length of more than a few hundred repeats. As such our understanding of how physiologically relevant repeat length DPRs effect the nervous system in an ageing in vivo system remains limited. In this study we generated Drosophila models expressing DPRs over 1000 repeat units in length, a known pathological length in humans. Using these models, we demonstrate each DPR exhibits a unique, age-dependent, phenotypic and pathological profile. Furthermore, we show co-expression of specific DPR combinations leads to distinct, age-dependent, phenotypes not observed through expression of single DPRs. We propose these models represent a unique, in vivo, tool for dissecting the molecular mechanisms implicated in disease pathology, opening up new avenues in the study of both MND and FTD.
    • Comparison of the impact of two national health and social care integration programmes on emergency hospital admissions

      Morciano, Marcello; orcid: 0000-0002-0009-5201; email: marcello.morciano@manchester.ac.uk; Checkland, Katherine; orcid: 0000-0002-9961-5317; Durand, Mary Alison; orcid: 0000-0003-2205-4002; Sutton, Matt; orcid: 0000-0002-6635-2127; Mays, Nicholas; orcid: 0000-0001-9808-8466 (BioMed Central, 2021-07-12)
      Abstract: Background: Policy-makers expect that integration of health and social care will improve user and carer experience and reduce avoidable hospital use. [We] evaluate the impact on emergency hospital admissions of two large nationally-initiated service integration programmes in England: the Pioneer (November 2013 to March 2018) and Vanguard (January 2015 to March 2018) programmes. The latter had far greater financial and expert support from central agencies. Methods: Of the 206 Clinical Commissioning Groups (CCGs) in England, 51(25%) were involved in the Pioneer programme only, 22(11%) were involved in the Vanguard programme only and 13(6%) were involved in both programmes. We used quasi-experimental methods to compare monthly counts of emergency admissions between four groups of CCGs, before and after the introduction of the two programmes. Results: CCGs involved in the programmes had higher monthly hospital emergency admission rates than non-participants prior to their introduction [7.9 (95% CI:7.8–8.1) versus 7.5 (CI: 7.4–7.6) per 1000 population]. From 2013 to 2018, there was a 12% (95% CI:9.5–13.6%) increase in emergency admissions in CCGs not involved in either programme while emergency admissions in CCGs in the Pioneer and Vanguard programmes increased by 6.4% (95% CI: 3.8–9.0%) and 8.8% (95% CI:4.5–13.1%), respectively. CCGs involved in both initiatives experienced a smaller increase of 3.5% (95% CI:-0.3–7.2%). The slowdown largely occurred in the final year of both programmes. Conclusions: Health and social care integration programmes can mitigate but not prevent rises in emergency admissions over the longer-term. Greater financial and expert support from national agencies and involvement in multiple integration initiatives can have cumulative effects.
    • Comparison of the impact of two national health and social care integration programmes on emergency hospital admissions

      Morciano, Marcello; orcid: 0000-0002-0009-5201; email: marcello.morciano@manchester.ac.uk; Checkland, Katherine; orcid: 0000-0002-9961-5317; Durand, Mary Alison; orcid: 0000-0003-2205-4002; Sutton, Matt; orcid: 0000-0002-6635-2127; Mays, Nicholas; orcid: 0000-0001-9808-8466 (BioMed Central, 2021-07-12)
      Abstract: Background: Policy-makers expect that integration of health and social care will improve user and carer experience and reduce avoidable hospital use. We evaluate the impact on emergency hospital admissions of two large nationally-initiated service integration programmes in England: the Pioneer (November 2013 to March 2018) and Vanguard (January 2015 to March 2018) programmes. The latter had far greater financial and expert support from central agencies. Methods: Of the 206 Clinical Commissioning Groups (CCGs) in England, 51(25%) were involved in the Pioneer programme only, 22(11%) were involved in the Vanguard programme only and 13(6%) were involved in both programmes. We used quasi-experimental methods to compare monthly counts of emergency admissions between four groups of CCGs, before and after the introduction of the two programmes. Results: CCGs involved in the programmes had higher monthly hospital emergency admission rates than non-participants prior to their introduction [7.9 (95% CI:7.8–8.1) versus 7.5 (CI:7.4–7.6) per 1000 population]. From 2013 to 2018, there was a 12% (95% CI:9.5–13.6%) increase in emergency admissions in CCGs not involved in either programme while emergency admissions in CCGs in the Pioneer and Vanguard programmes increased by 6.4% (95% CI: 3.8–9.0%) and 8.8% (95% CI:4.5–13.1%), respectively. CCGs involved in both initiatives experienced a smaller increase of 3.5% (95% CI:-0.3–7.2%). The slowdown largely occurred in the final year of both programmes. Conclusions: Health and social care integration programmes can mitigate but not prevent rises in emergency admissions over the longer-term. Greater financial and expert support from national agencies and involvement in multiple integration initiatives can have cumulative effects.
    • Correction to: Factors determining ultra-short-term survival and the commencement of active treatment in high-grade serous ovarian cancer: a case comparison study

      Hawarden, Amy; Russell, Bryn; Gee, Mary Ellen; Kayali, Fatima; Clamp, Andrew; Crosbie, Emma Jayne; Edmondson, Richard John; email: richard.edmondson@manchester.ac.uk (BioMed Central, 2021-05-26)
    • Correction to: Quality of life improved for patients after starting dialysis but is impaired, initially, for their partners: a multi-centre, longitudinal study

      Moore, Currie; email: currie.moore@postgrad.manchester.ac.uk; Carter, Lesley-Anne; Mitra, Sandip; Skevington, Suzanne; Wearden, Alison (BioMed Central, 2020-07-06)
      An amendment to this paper has been published and can be accessed via the original article.
    • Correction to: Symptoms in first-degree relatives of patients with rheumatoid arthritis: evaluation of cross-sectional data from the symptoms in persons at risk of rheumatoid arthritis (SPARRA) questionnaire in the Preclinical EValuation of Novel Targets in RA (PREVeNT-RA) Cohort

      Costello, R. E.; Humphreys, J. H.; Sergeant, J. C.; Haris, M.; Stirling, F.; Raza, K.; van Schaardenburg, D.; Bruce, Ian N.; email: ian.bruce@manchester.ac.uk (BioMed Central, 2021-10-19)
      An amendment to this paper has been published and can be accessed via the original article.
    • Correction to: The LUCID study: living with ulcerative colitis; identifying the socioeconomic burden in Europe

      Ruiz-Casas, Leonardo; Evans, Jonathan; orcid: 0000-0002-3490-7191; email: jonathan.evans@hcdeconomics.com; Rose, Alison; Pedra, Gabriel Ghizzi; Lobo, Alan; Finnegan, Alan; Hayee, Bu; Peyrin-Biroulet, Laurent; Sturm, Andreas; Burisch, Johan; et al. (BioMed Central, 2021-12-15)
    • Correction to: The role of real-world data in the development of treatment guidelines: a case study on guideline developers’ opinions about using observational data on antibiotic prescribing in primary care

      Steels, Stephanie; email: Stephanie.Steels@manchester.ac.uk; Van der Zande, Marieke; van Staa, Tjeerd Pieter (BioMed Central, 2020-05-26)
      An amendment to this paper has been published and can be accessed via the original article.