• 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.
    • 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 (2021-08-25)
      <h4>Background</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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, I<sup>2</sup> = 8.5%, n = 4 studies, 1131 participants), Paliperidone (- 6.01, 95% CI - 8.7 to - 3.32, I<sup>2</sup> = 4.3%, n = 13, 3821) and Paliperidone palmitate (- 7.89, 95% CI - 12.1 to - 3.69, I<sup>2</sup> = 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.<h4>Conclusion</h4>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.
    • Conceptual Model of Hearing Health Inequalities (HHI Model): A Critical Interpretive Synthesis

      Tsimpida, Dialechti; orcid: 0000-0002-3709-5651; email: dialechti.tsimpida@manchester.ac.uk; Kontopantelis, Evangelos; Ashcroft, Darren M.; Panagioti, Maria (SAGE Publications, 2021-05-28)
      Hearing loss is a major health challenge that can have severe physical, social, cognitive, economic, and emotional consequences on people’s quality of life. Currently, the modifiable factors linked to socioeconomic inequalities in hearing health are poorly understood. Therefore, an online database search (PubMed, Scopus, and Psych) was conducted to identify literature that relates hearing loss to health inequalities as a determinant or health outcome. A total of 53 studies were selected to thematically summarize the existing literature, using a critical interpretive synthesis method, where the subjectivity of the researcher is intimately involved in providing new insights with explanatory power. The evidence provided by the literature can be summarized under four key themes: (a) There might be a vicious cycle between hearing loss and socioeconomic inequalities and lifestyle factors, (b) socioeconomic position may interact with less healthy lifestyles, which are harmful to hearing ability, (c) increasing health literacy could improve the diagnosis and prognosis of hearing loss and prevent the adverse consequences of hearing loss on people’s health, and (d) people with hearing loss might be vulnerable to receiving low-quality and less safe health care. This study uses elements from theoretical models of health inequalities to formulate a highly interpretive conceptual model for examining hearing health inequalities. This model depicts the specific mechanisms of hearing health and their evolution over time. There are many modifiable determinants of hearing loss, in several stages across an individual’s life span; tackling socioeconomic inequalities throughout the life-course could improve the population’s health, maximizing the opportunity for healthy aging.
    • Concordance and timing in recording cancer events in primary care, hospital and mortality records for patients with and without psoriasis: A population-based cohort study

      editor: Ramagopalan, Sreeram V.; Trafford, Alex M.; orcid: 0000-0001-8145-8133; email: alex.trafford@postgrad.manchester.ac.uk; Parisi, Rosa; Rutter, Martin K.; Kontopantelis, Evangelos; Griffiths, Christopher E. M.; Ashcroft, Darren M.; orcid: 0000-0002-2958-915X; on behalf of the Global Psoriasis Atlas (GPA) (Public Library of Science, 2021-07-19)
      Background: The association between psoriasis and the risk of cancer has been investigated in numerous studies utilising electronic health records (EHRs), with conflicting results in the extent of the association. Objectives: To assess concordance and timing of cancer recording between primary care, hospital and death registration data for people with and without psoriasis. Methods: Cohort studies delineated using primary care EHRs from the Clinical Practice Research Datalink (CPRD) GOLD and Aurum databases, with linkage to hospital episode statistics (HES), Office for National Statistics (ONS) mortality data and indices of multiple deprivation (IMD). People with psoriasis were matched to those without psoriasis by age, sex and general practice. Cancer recording between databases was investigated by proportion concordant, that being the presence of cancer record in both source and comparator datasets. Delay in recording cancer diagnoses between CPRD and HES records and predictors of discordance were also assessed. Results: 58,904 people with psoriasis and 350,592 comparison patients were included using CPRD GOLD; whereas 213,400 people with psoriasis and 1,268,998 comparison patients were included in CPRD Aurum. For all cancer records (excluding keratinocyte), concordance between CPRD and HES was greater than 80%. Concordance for same-site cancer records was markedly lower (<68% GOLD-linked data; <72% Aurum-linked data). Concordance of non-Hodgkin lymphoma and liver cancer recording between CPRD and HES was lower for people with psoriasis compared to those without. Conclusions: Concordance between CPRD and HES is poor when restricted to cancers of the same site, with greater discordance in people with psoriasis for some cancers of specific sites. The use of linked patient-level data is an important step in reducing misclassification of cancer outcomes in epidemiological studies using routinely collected electronic health records.
    • Effectiveness of collaborative care in reducing suicidal ideation: An individual participant data meta-analysis.

      Grigoroglou, Christos; email: christos.grigoroglou@manchester.ac.uk; van der Feltz-Cornelis, Christina; Hodkinson, Alexander; Coventry, Peter A; Zghebi, Salwa S; Kontopantelis, Evangelos; Bower, Peter; Lovell, Karina; Gilbody, Simon; Waheed, Waquas; et al. (2021-04-21)
      To assess whether CC is more effective at reducing suicidal ideation in people with depression compared with usual care, and whether study and patient factors moderate treatment effects. We searched Medline, Embase, PubMed, PsycINFO, CINAHL, CENTRAL from inception to March 2020 for Randomised Controlled Trials (RCTs) that compared the effectiveness of CC with usual care in depressed adults, and reported changes in suicidal ideation at 4 to 6 months post-randomisation. Mixed-effects models accounted for clustering of participants within trials and heterogeneity across trials. This study is registered with PROSPERO, CRD42020201747. We extracted data from 28 RCTs (11,165 patients) of 83 eligible studies. We observed a small significant clinical improvement of CC on suicidal ideation, compared with usual care (SMD, -0.11 [95%CI, -0.15 to -0.08]; I , 0·47% [95%CI 0.04% to 4.90%]). CC interventions with a recognised psychological treatment were associated with small reductions in suicidal ideation (SMD, -0.15 [95%CI -0.19 to -0.11]). CC was more effective for reducing suicidal ideation among patients aged over 65 years (SMD, - 0.18 [95%CI -0.25 to -0.11]). Primary care based CC with an embedded psychological intervention is the most effective CC framework for reducing suicidal ideation and older patients may benefit the most. [Abstract copyright: Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.]
    • Is health research undertaken where the burden of disease is greatest? Observational study of geographical inequalities in recruitment to research in England 2013–2018

      Bower, Peter; email: peter.bower@manchester.ac.uk; Grigoroglou, Christos; Anselmi, Laura; Kontopantelis, Evangelos; Sutton, Matthew; Ashworth, Mark; Evans, Philip; Lock, Stephen; Smye, Stephen; Abel, Kathryn (BioMed Central, 2020-05-18)
      Abstract: Background: Research is fundamental to high-quality care, but concerns have been raised about whether health research is conducted in the populations most affected by high disease prevalence. Geographical distribution of research activity is important for many reasons. Recruitment is a major barrier to research delivery, and undertaking recruitment in areas of high prevalence could be more efficient. Regional variability exists in risk factors and outcomes, so research done in healthier populations may not generalise. Much applied health research evaluates interventions, and their impact may vary by context (including geography). Finally, fairness dictates that publically funded research should be accessible to all, so that benefits of participating can be fairly distributed. We explored whether recruitment of patients to health research is aligned with disease prevalence in England. Methods: We measured disease prevalence using the Quality and Outcomes Framework in England (total long-term conditions, mental health and diabetes). We measured research activity using data from the NIHR Clinical Research Network. We presented descriptive data on geographical variation in recruitment rates. We explored associations between the recruitment rate and disease prevalence rate. We calculated the share of patient recruitment that would need to be redistributed to align recruitment with prevalence. We assessed whether associations between recruitment rate and disease prevalence varied between conditions, and over time. Results: There was significant geographical variation in recruitment rates. When areas were ranked by disease prevalence, recruitment was not aligned with prevalence, with disproportionately low recruitment in areas with higher prevalence of total long-term and mental health conditions. At the level of 15 local networks, analyses suggested that around 12% of current recruitment activity would need to be redistributed to align with disease prevalence. Overall, alignment showed little change over time, but there was variation in the trends over time in individual conditions. Conclusions: Geographical variations in recruitment do not reflect the suitability of the population for research. Indicators should be developed to assess the fit between research and need, and to allow assessment of interventions among funders, researchers and patients to encourage closer alignment between research activity and burden.
    • Mental health responses to the COVID-19 pandemic: a latent class trajectory analysis using longitudinal UK data.

      Pierce, Matthias; email: matthias.pierce@manchester.ac.uk; McManus, Sally; Hope, Holly; Hotopf, Matthew; Ford, Tamsin; Hatch, Stephani L; John, Ann; Kontopantelis, Evangelos; Webb, Roger T; Wessely, Simon; et al. (2021-05-06)
      The mental health of the UK population declined at the onset of the COVID-19 pandemic. Convenience sample surveys indicate that recovery began soon after. Using a probability sample, we tracked mental health during the pandemic to characterise mental health trajectories and identify predictors of deterioration. This study was a secondary analysis of five waves of the UK Household Longitudinal Study (a large, national, probability-based survey that has been collecting data continuously since January, 2009) from late April to early October, 2020 and pre-pandemic data taken from 2018-19. Mental health was assessed using the 12-item General Health Questionnaire (GHQ-12). We used latent class mixed models to identify discrete mental health trajectories and fixed-effects regression to identify predictors of change in mental health. Mental health was assessed in 19 763 adults (≥16 years; 11 477 [58·1%] women and 8287 [41·9%] men; 3453 [17·5%] participants from minority ethnic groups). Mean population mental health deteriorated with the onset of the pandemic and did not begin improving until July, 2020. Latent class analysis identified five distinct mental health trajectories up to October 2020. Most individuals in the population had either consistently good (7437 [39·3%] participants) or consistently very good (7623 [37·5%] participants) mental health across the first 6 months of the pandemic. A recovering group (1727 [12·0%] participants) showed worsened mental health during the initial shock of the pandemic and then returned to around pre-pandemic levels of mental health by October, 2020. The two remaining groups were characterised by poor mental health throughout the observation period; for one group, (523 [4·1%] participants) there was an initial worsening in mental health that was sustained with highly elevated scores. The other group (1011 [7·0%] participants) had little initial acute deterioration in their mental health, but reported a steady and sustained decline in mental health over time. These last two groups were more likely to have pre-existing mental or physical ill-health, to live in deprived neighbourhoods, and be of Asian, Black or mixed ethnicity. Infection with SARS-CoV-2, local lockdown, and financial difficulties all predicted a subsequent deterioration in mental health. Between April and October 2020, the mental health of most UK adults remained resilient or returned to pre-pandemic levels. Around one in nine individuals had deteriorating or consistently poor mental health. People living in areas affected by lockdown, struggling financially, with pre-existing conditions, or infection with SARS-CoV-2 might benefit most from early intervention. None. [Abstract copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.]
    • The dynamic relationship between hearing loss, quality of life, socioeconomic position and depression and the impact of hearing aids: answers from the English Longitudinal Study of Ageing (ELSA).

      Tsimpida, Dialechti; orcid: 0000-0002-3709-5651; email: dialechti.tsimpida@manchester.ac.uk; Kontopantelis, Evangelos; Ashcroft, Darren M; Panagioti, Maria (2021-08-12)
      The adverse impact of hearing loss (HL) extends beyond auditory impairment and may affect the individuals' psychosocial wellbeing. We aimed to examine whether there exists a causal psychosocial pathway between HL and depression in later life, via socioeconomic factors and quality of life, and whether hearing aids usage alleviates depressive symptoms over time. We examined the longitudinal relationship between HL and depressive symptoms (CES-D) applying dynamic cross-lagged mediation path models. We used the full dataset of participants aged 50-89 years (74,908 person-years), from all eight Waves of the English Longitudinal Study of Ageing (ELSA). Their quality of life (CASP-19) and their wealth were examined as the mediator and moderator of this relationship, respectively. Subgroup analyses investigated differences among those with hearing aids within different models of subjectively and objectively identified HL. All models were adjusted for age, sex, retirement status and social engagement. Socioeconomic position (SEP) influenced the strength of the relationship between HL and depression, which was stronger in the lowest versus the highest wealth quintiles. The use of hearing aids was beneficial for alleviating depressive symptoms. Those in the lowest wealth quintiles experienced a lower risk for depression after the use of hearing aids compared to those in the highest wealth quintiles. HL poses a substantial risk for depressive symptoms in older adults, especially those who experience socioeconomic inequalities. The early detection of HL and provision of hearing aids may not only promote better-hearing health but could also enhance the psychosocial wellbeing of older adults, particularly those in a lower SEP. [Abstract copyright: © 2021. The Author(s).]