Ethnic inequalities in time to diagnosis of cancer: a systematic review

This is the final version of the article. Available from the publisher via the DOI in this record.BACKGROUND: Minimising diagnostic delays in cancer may help improve survival. Ethnic minorities have worse outcomes in some cancer types when compared to the majority; this may relate in part to differences during the diagnostic phase. Only a few British studies have specifically explored this relationship, and no synthesis of these exists. The present study aimed to systematically review evidence on ethnic inequalities in cancer diagnosis, focussing on patient and primary care intervals of diagnosis. METHODS: Six electronic databases were searched. Included studies were those conducted in the UK or elsewhere (where access to healthcare is comparable to the NHS) and those that described a time element during diagnosis. Study quality was evaluated using the Critical Appraisal Skills Programme (CASP) checklist for cohort studies and synthesis method was narrative. RESULTS: Seven of 8,520 studies retrieved by our search met the review criteria; six conducted in the UK, and one in New Zealand. Five (including one covering several sites) focused on breast cancer, one on prostate, and one on oesophagogastric cancer. The studies employed different methods of ascertainment and definition of ethnic groups and defined diagnostic delay in a non-standardised way; therefore, narrative synthesis was performed. In breast cancer, three studies reported longer diagnostic intervals among ethnic minorities and two found no evidence of differences by ethnicity. There was some evidence of longer diagnostic and referral intervals among ethnic minorities in oesophagogastric and colorectal cancers, but no evidence of this in prostate, non-Hodgkin's lymphoma, lung, and ovarian cancers. None of the studies identified shorter patient or primary care intervals in ethnic minorities. CONCLUSIONS: Existing studies provide insufficient evidence to confirm or refute ethnic inequalities in diagnostic intervals of cancer. Further studies are necessary to examine common cancer types including those frequently found in ethnic minorities (in addition to those covered here) and using current definitions of intervals in cancer diagnosis.The Policy Research Unit (PRU) in Cancer Awareness, Screening and Early Diagnosis receives funding for a research programme from the Department of Health Policy Research Programme. It is collaboration between researchers from seven institutions (Queen Mary University of London, UCL, King’s College London, London School of Hygiene and Tropical Medicine, Hull York Medical School, Durham University and Peninsula Medical School). The views expressed are those of the authors and not necessarily those of the NHS, or the Department of Health

How useful is thrombocytosis in predicting an underlying cancer in primary care? Systematic review protocol

Early diagnosis of cancer is imperative to reduce the cancer burden in the UK and improve cancer survival. Identifying early markers of cancer can help general practitioners to direct patients at the greatest risk of cancer to appropriate investigative services. A raised platelet count, or thrombocytosis, has been linked to malignancy and identified as a marker of poor prognosis in secondary care, but there is little evidence around the importance of this marker in a primary care setting, within a diagnostic context. This review aims to identify and explore the body of evidence concerning the association between thrombocytosis and cancer in primary care. This protocol was produced using guidance from the PRISMA-P statement

N of 1 trials and the optimal individualisation of drug treatments: a systematic review protocol

This is the final version of the article. Available from BioMed Central via the DOI in this record.BACKGROUND: Guidelines and evidence-based drug treatment recommendations are usually based on the results of clinical trials, which have limited generalisability in routine clinical settings due to their restrictive eligibility criteria. These trials are also conducted in ideal and rigorously controlled settings. N of 1 trials, which are single patient multiple crossover studies, offer a means of increasing the evidence base and individualising care for individuals in clinical practice. This systematic review of the N of 1 drug treatment trial aims to investigate its usefulness for achieving optimal individualised patient care. METHODS: The following databases will be searched for relevant articles: MEDLINE, EMBASE, PsycINFO (all via Ovid), AMED, CINAHAL (via EBSCO), The Cochrane Library (including CENTRAL, NHS EED, and DARE), and Web of Science (Thomson Reuters). Supplementary searches will include ongoing trial databases and organisational websites. All N of 1 trials in which patients have been treated with a drug will be considered. Outcomes will include information on the clinical usefulness of N of 1 trials-i.e. achievement of optimal individualised care, health-care utilisation of patients, frequently used practices, experiences of clinical care or participation in N of 1 trials, adherence to treatment plan, and unwanted effects of the treatment. Screening of included papers will be undertaken independently by two reviewers, while data extraction and the quality of reporting will be conducted by one reviewer and checked by another. Both quantitative and qualitative summaries will be reported using appropriate methods. DISCUSSION: This review will provide new insights into the clinical utility of N of 1 drug trials in helping participants find the most acceptable treatment as defined by patients and clinicians based on the selected outcome measures and the perspectives of participants involved in such trials. Findings from this review will inform the development of a stakeholder workshop and guidance to help physicians find the optimum therapy for their patients and will help guide future research on N of 1 trials. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016032452.This research was funded by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care South West Peninsula

N of 1 trials and the optimal individualisation of drug treatments: a systematic review protocol

This is the final version of the article. Available from BioMed Central via the DOI in this record.BACKGROUND: Guidelines and evidence-based drug treatment recommendations are usually based on the results of clinical trials, which have limited generalisability in routine clinical settings due to their restrictive eligibility criteria. These trials are also conducted in ideal and rigorously controlled settings. N of 1 trials, which are single patient multiple crossover studies, offer a means of increasing the evidence base and individualising care for individuals in clinical practice. This systematic review of the N of 1 drug treatment trial aims to investigate its usefulness for achieving optimal individualised patient care. METHODS: The following databases will be searched for relevant articles: MEDLINE, EMBASE, PsycINFO (all via Ovid), AMED, CINAHAL (via EBSCO), The Cochrane Library (including CENTRAL, NHS EED, and DARE), and Web of Science (Thomson Reuters). Supplementary searches will include ongoing trial databases and organisational websites. All N of 1 trials in which patients have been treated with a drug will be considered. Outcomes will include information on the clinical usefulness of N of 1 trials-i.e. achievement of optimal individualised care, health-care utilisation of patients, frequently used practices, experiences of clinical care or participation in N of 1 trials, adherence to treatment plan, and unwanted effects of the treatment. Screening of included papers will be undertaken independently by two reviewers, while data extraction and the quality of reporting will be conducted by one reviewer and checked by another. Both quantitative and qualitative summaries will be reported using appropriate methods. DISCUSSION: This review will provide new insights into the clinical utility of N of 1 drug trials in helping participants find the most acceptable treatment as defined by patients and clinicians based on the selected outcome measures and the perspectives of participants involved in such trials. Findings from this review will inform the development of a stakeholder workshop and guidance to help physicians find the optimum therapy for their patients and will help guide future research on N of 1 trials. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016032452.This research was funded by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care South West Peninsula

Cancer incidence in patients with a high normal platelet count: a cohort study using primary care data.

This is the author accepted manuscript. The final version is available from Oxford University Press via the DOI in this record.Background A platelet count >400×109/l (i.e. thrombocytosis) is a recently discovered risk marker of cancer. The risk of undiagnosed cancer in patients with thrombocytosis is 11.6% for men and 6.2% for women; well above the 3% risk threshold set by NICE for cancer investigation. Patients with a platelet count at the upper end of the normal range (325-400x109/l) could be at increased risk of undiagnosed malignancy. Objective To quantify the risk of an undiagnosed cancer in patients with a platelet count at the upper end of the normal range. Methods A primary care-based cohort study using Clinical Practice Research Datalink (CPRD) data from 2000 - 2013. The study sample comprised 2704 individuals stratified by platelet count: 325-349 x 109/l; 350-374 x 109/l; 375-399 x 109/l. Incident cancer diagnoses in the year following that platelet count were obtained from patient records. Results Cancer incidence rose with increasing platelet count: 2.6% (95% CI 1.9 to 3.6) in subjects with a count of 325-349x109/l; 3.7% (95% CI 2.5 to 5.3) in subjects with a count of 350-374x109/l; and 5.1% (95% CI 3.4 to 7.5) in those with a count of 375-399x109/l. Colorectal cancer was the most commonly diagnosed type in all three groups. Cancer incidence was consistently higher in males than in females. Conclusion These results suggest that clinicians should consider cancer in patients with a platelet count >375x109/l, and review the reasons for blood testing and any additional reported symptoms. Until these results are replicated on a larger scale, recommendations for clinical action cannot be made.The Policy Research Unit in Cancer Awareness, Screening and Early Diagnosis receives funding for a research programme from the Department of Health Policy Research Programme. It is a collaboration between researchers from seven institutions (Queen Mary University of London, UCL, King’s College London, London School of Hygiene and Tropical Medicine, Hull York Medical School, Durham University, and the University of Exeter). Obioha Ukoumunne is supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care South West Peninsula. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health

The association between child and adolescent emotional disorder and poor attendance at school: a systematic review protocol.

This is the final version of the article. Available from BioMed Central via the DOI in this record.BACKGROUND: Anxiety and depression are common in young people and are associated with a range of adverse outcomes. Research has suggested a relationship between emotional disorder and poor school attendance, and thus poor attendance may serve as a red flag for children at risk of emotional disorder. This systematic review aims to investigate the association between child and adolescent emotional disorder and poor attendance at school. METHODS: We will search electronic databases from a variety of disciplines including medicine, psychology, education and social sciences, as well as sources of grey literature, to identify any quantitative studies that investigate the relationship between emotional disorder and school attendance. Emotional disorder may refer to diagnoses of mood or anxiety disorders using standardised diagnostic measures, or measures of depression, anxiety or "internalising symptoms" using a continuous scale. Definitions for school non-attendance vary, and we aim to include any relevant terminology, including attendance, non-attendance, school refusal, school phobia, absenteeism and truancy. Two independent reviewers will screen identified papers and extract data from included studies. We will assess the risk of bias of included studies using the Newcastle-Ottawa Scale. Random effects meta-analysis will be used to pool quantitative findings when studies use the same measure of association, otherwise a narrative synthesis approach will be used. DISCUSSION: This systematic review will provide a detailed synthesis of evidence regarding the relationship between childhood emotional disorder and poor attendance at school. Understanding this relationship has the potential to assist in the development of strategies to improve the identification of and intervention for this vulnerable group. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016052961.This research is being carried out as part of a PhD studentship funded by the University of Exeter Medical School

Prescribing of medication for attention deficit hyperactivity disorder among young people in the Clinical Practice Research Datalink 2005-2013: analysis of time to cessation

This is the author accepted manuscript. The final version is available from Springer Verlag via the DOI in this record.The aim of this study was to examine the time to cessation of ADHD medication amongst young people with ADHD aged 16 in the period 2005-2013. Previous studies of prescribing in primary care reported high rates of medication cessation amongst 16 and 17 year olds with ADHD. The examination of trends since the introduction of new NICE guidance in 2008 will support service planning and improvement of outcomes over the vulnerable transition period from child to adult services. We used primary care records from the Clinical Practice Research Datalink and identified cases prescribed ADHD medication at the time of their 16th birthday during the study period. The outcome was time to medication cessation from the age of 16. Cessation of medication was defined as occurring at the beginning of a gap of over 6 months in prescriptions. 1620 cases were included. The median time to cessation was 1.51 years (95% CI 1.42-1.67).The estimated probability of remaining on medication was 0.63 (95% CI 0.61-0.65) at age 17 (i.e., at 1 year) and 0.41 (95% CI 0.39-0.43) at age 18. Young people with ADHD remain at high risk of cessation of medication during the transition from child to adult services. Despite the restriction that only primary care prescribing data were available, the results suggest continuing disparity between expected levels of symptom persistence and continuation of medication.This research was funded as part of a Doctoral Research Fellowship from the National Institute for Health Research held by Tamsin Newlove-Delgado (Reference: DRF-2012-05-221). Tamsin Newlove-Delgado is currently funded by an NIHR Academic Clinical Lectureship. Ken Stein and Obioha C. Ukoumunne were funded by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsula at Royal Devon and Exeter NHS Foundation Trust. This report is independent research and the views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health

Stroke and dementia risk: A systematic review and meta-analysis

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordIntroduction: Stroke is an established risk factor for all-cause dementia, though meta-analyses are needed to quantify this risk. Methods: We searched Medline, PsycINFO, and Embase for studies assessing prevalent or incident stroke versus a no-stroke comparison group and the risk of all-cause dementia. Random effects meta-analysis was used to pool adjusted estimates across studies, and meta-regression was used to investigate potential effect modifiers. Results: We identified 36 studies of prevalent stroke (1.9 million participants) and 12 studies of incident stroke (1.3 million participants). For prevalent stroke, the pooled hazard ratio for all-cause dementia was 1.69 (95% confidence interval: 1.49–1.92; P <.00001; I2 = 87%). For incident stroke, the pooled risk ratio was 2.18 (95% confidence interval: 1.90–2.50; P <.00001; I2 = 88%). Study characteristics did not modify these associations, with the exception of sex which explained 50.2% of between-study heterogeneity for prevalent stroke. Discussion: Stroke is a strong, independent, and potentially modifiable risk factor for all-cause dementia.Mary Kinross Charitable TrustHalpin TrustNational Institute for Health Research (NIHR)National Institute on Aging (NIA)/National Institutes of Health (NIH)National Institute of Neurological Disorders and Stroke (NIH/NINDS

Visual Impairment, Eye Diseases, and Dementia Risk: A Systematic Review and Meta-Analysis

BACKGROUND: Visual impairment and eye diseases have been associated with dementia, though with mixed findings and often in cross-sectional studies. OBJECTIVE: To identify prospective studies investigating associations between visual impairment or common eye diseases and risk of all-cause dementia or key dementia subtypes. METHODS: We searched Medline, PsycINFO, and Embase from inception to January 2020. We also conducted backward and forward citation searches of included studies and set up alerts to identify studies published after the search date. Random-effects meta-analysis was used to combine adjusted estimates across studies. RESULTS: Thirty studies met our eligibility criteria. For visual impairment, pooled estimates indicated an increased risk of all-cause dementia (37,705 participants, 3,415 cases, risk ratio [RR] = 1.38, 95% confidence interval [CI]: 1.19-1.59, I2 = 28.6%). Pooled estimates also suggested an increased dementia risk associated with cataract (6,659 participants, 1,312 cases, hazard ratio [HR] = 1.17, 95% CI: 1.00-1.38, I2 = 0.0%) and diabetic retinopathy (43,658 participants, 7,060 cases, HR = 1.34, 95% CI: 1.11-1.61, I2 = 63.9%), respectively. There was no evidence of an association between glaucoma (175,357 participants, 44,144 cases, HR = 0.97, 95% CI: 0.90-1.04, I2 = 51.5%) or age-related macular degeneration (7,800,692 participants, > 2,559 cases, HR = 1.15, 95% CI: 0.88-1.50, I2 = 91.0%) and risk of dementia, respectively. CONCLUSION: As visual impairment, cataract, and diabetic retinopathy are associated with an increased likelihood of developing dementia, early diagnosis may help identify those at risk of dementia. Given most causes of visual impairment are treatable or preventable, the potential for dementia prevention warrants further investigation

A cross-sectional study on the prevalence of illness in coastal bathers compared to non-bathers in England and Wales: Findings from the Beach User Health Survey

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.The risks of illness associated with bathing in UK coastal waters have not been quantified since the early 1990s. Efforts have been made since then to improve the quality of bathing waters. The aim of this study was to quantify the prevalence of symptoms of illness associated with sea bathing in bathers in England and Wales. A cross-sectional study was conducted between June 2014 and April 2015. An online survey collected information from sea bathers and non-bathers on their visits to beaches in England and Wales along with the occurrence of symptoms of illness. 2631 people (1693 bathers, 938 non-bathers) responded to the survey. Compared to non-bathers, bathers were more likely to report skin ailments (adjusted prevalence odds ratio (AOR) = 2.64, 95% confidence interval (CI) 1.23 to 5.65, p = 0.01), ear ailments (AOR = 3.77, 95% CI 1.84 to 7.73, p < 0.001), and any symptoms of illness (AOR = 3.73, 95% CI 2.63 to 5.29, p < 0.001). There was weak evidence of an increase in the odds of gastrointestinal illness (AOR = 1.59, 95% CI 0.96 to 2.65, p = 0.07), respiratory ailments (AOR = 2.44, 95% CI 0.92 to 6.48, p = 0.07) and eye ailments (AOR = 2.12, 95% CI 0.83 to 5.39, p = 0.11). While the study design does not allow inference of causality, we do observe an association between sea bathing in England and Wales and reported symptoms of ill health. This suggests that despite higher rates of compliance with water quality criteria among bathing waters nowadays, the odds of illness for bathers relative to non-bathers is similar in magnitude to estimates made in the 1990s.Natural Environment Research Council (NERC)European Regional Development FundNational Institute for Health Researc