Publications by authors named "Jenny L Donovan"

229 Publications

'Overnight, things changed. Suddenly, we were in it': a qualitative study exploring how surgical teams mitigated risks of COVID-19.

BMJ Open 2021 06 16;11(6):e046662. Epub 2021 Jun 16.

Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.

Objectives: COVID-19 presents a risk of infection and transmission for operating theatre teams. Guidelines to protect patients and staff emerged and changed rapidly based on expert opinion and limited evidence. This paper presents the experiences and innovations developed by international surgical teams during the early stages of the pandemic to attempt to mitigate risk.

Design: In-depth, semistructured interviews were audio recorded, transcribed and analysed thematically using methods of constant comparison.

Participants: 43 participants, including surgeons from a range of specialties (primarily general surgery, otolaryngology, neurosurgery, cardiothoracic and ophthalmology), anaesthetists and those in nursing roles.

Setting: The UK, Italy, Spain, the USA, China and New Zealand between March and May 2020.

Results: Surgical teams sought to mitigate COVID-19 risks by modifying their current practice with an abundance of strategies and innovations. Communication and teamwork played an integral role in how teams adapted, although participants reflected on the challenges of having to improvise in real time. Uncertainties remained about optimal surgical practice and there were significant tensions where teams were forced to balance what was best for patients while contemplating their own safety.

Conclusions: The perceptions of risks during a pandemic such as COVID-19 can be complex and context dependent. Management of these risks in surgery must be driven by evidence-based practice resulting from a pragmatic and novel approach to collation of global evidence. The context of surgery has changed dramatically, and surgical teams have developed a plethora of innovations. There is an urgent need for high-quality evidence to inform surgical practice that optimises the safety of both patients and healthcare professionals as the COVID-19 pandemic unfolds.
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http://dx.doi.org/10.1136/bmjopen-2020-046662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210660PMC
June 2021

What empirical research has been undertaken on the ethics of clinical research in India? A systematic scoping review and narrative synthesis.

BMJ Glob Health 2021 05;6(5)

Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.

Introduction: The post-2005 rise in clinical trials and clinical research conducted in India was accompanied by frequent reports of unethical practices, leading to a series of regulatory changes. We conducted a systematic scoping review to obtain an overview of empirical research pertaining to the ethics of clinical trials/research in India.

Methods: Our search strategy combined terms related to ethics/bioethics, informed consent, clinical trials/research and India, across nine databases, up to November 2019. Peer-reviewed research exploring ethical aspects of clinical trials/research in India with any stakeholder groups was included. We developed an evidence map, undertook a narrative synthesis and identified research gaps. A consultation exercise with stakeholders in India helped contextualise the review and identify additional research priorities.

Results: Titles/Abstracts of 9699 articles were screened, full text of 282 obtained and 80 were included. Research on the ethics of clinical trials/research covered a wide range of topics, often conducted with little to no funding. Studies predominantly examined what lay (patients/public) and professional participants (eg, healthcare staff/students/faculty) know about topics such as research ethics or understand from the information given to obtain their consent for research participation. Easily accessible groups, namely ethics committee members and healthcare students were frequently researched. Research gaps included developing a better understanding of the recruitment-informed consent process, including the doctor-patient interaction, in multiple contexts and exploring issues of equity and justice in clinical trials/research.

Conclusion: The review demonstrates that while a wide range of topics have been studied in India, the focus is largely on assessing knowledge levels across different population groups. This is a useful starting point, but fundamental questions remain unanswered about informed consent processes and broader issues of inequity that pervade the clinical trials/research landscape. A priority-setting exercise and appropriate funding mechanisms to support researchers in India would help improve the clinical trials/research ecosystem.
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http://dx.doi.org/10.1136/bmjgh-2020-004729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137180PMC
May 2021

Commissioner, clinician, and patient experiences of a pre-surgical health optimisation programme - a qualitative study.

BMC Health Serv Res 2021 May 1;21(1):409. Epub 2021 May 1.

Population health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.

Background: Health optimisation programmes are an increasingly popular policy intervention that aim to support patients to lose weight or stop smoking ahead of surgery. There is little evidence about their impact and the experience of their use. The aim of this study was to investigate the experiences and perspectives of commissioners, clinicians and patients involved in a locality's health optimisation programme in the United Kingdom. The programme alters access to elective orthopaedic surgery for patients who smoke or are obese (body mass index ≥ 30 kg/m), diverting them to a 12-week programme of behavioural change interventions prior to assessment for surgical referral.

Methods: A thematic analysis of semi-structured interviews (n = 20) with National Health Service and Local Authority commissioners and planners, healthcare professionals, and patients using the pathway.

Results: Health optimisation was broadly acceptable to professionals and patients in our sample and offered a chance to trigger both short term pre-surgical weight loss/smoking cessation and longer-term sustained changes to lifestyle intentions post-surgery. Communicating the nature and purpose of the programme to patients was challenging and consequently the quality of the explanation received and understanding gained by patients was generally low. Insight into the successful implementation of health optimisation for the hip and knee pathway, but failure in roll-out to other surgical specialities, suggests placement of health optimisation interventions into the 'usual waiting time' for surgical referral may be of greatest acceptability to professionals and patients.

Conclusions: Patients and professionals supported the continuation of health optimisation in this context and recognised likely health and wellbeing benefits for a majority of patients. However, the clinicians' communication to patients about health optimisation needs to improve to prepare patients and optimise their engagement.
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http://dx.doi.org/10.1186/s12913-021-06434-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088197PMC
May 2021

'We tend to get pad happy': a qualitative study of health practitioners' perspectives on the quality of continence care for older people in hospital.

BMJ Open Qual 2021 04;10(2)

Nursing and Midwifery, University of the West of England Faculty of Health and Applied Sciences, Bristol, UK.

Background: Bladder and bowel control difficulties affect 20% and 10% of the UK population, respectively, touch all age groups and are particularly prevalent in the older (65+ years) population. However, the quality of continence care is often poor, compromising patient health and well-being, increasing the risk of infection, and is a predisposing factor to nursing and residential home placement.

Objective: To identify factors that help or hinder good continence care for patients aged 65 years and over in hospital medical ward settings. Medical care, not surgical, was our exclusive focus.

Methods: We conducted 27 qualitative interviews with nursing, medical and allied health practitioners in three hospitals. We used a purposive sample and analysed data thematically, both manually and with the aid of NVivo software.

Results: Interviews revealed perspectives on practice promoting or inhibiting good quality continence care, as well as suggestions for improvements. Good continence care was said to be advanced through person-centred care, robust assessment and monitoring, and a proactive approach to encouraging patient independence. Barriers to quality care centred on lack of oversight, automatic use of incontinence products and staffing pressures. Suggested improvements centred on participatory care, open communication and care planning with a higher bladder and bowel health profile. In order to drive such improvements, hospital-based practitioners indicate a need and desire for regular continence care training.

Conclusions: Findings help explain the persistence of barriers to providing good quality care for patients aged 65 years and over with incontinence. Resolute continence promotion, in hospitals and throughout the National Health Service, would reduce reliance on products and the accompanying risks of patient dependency and catheter-associated gram-negative bacteraemia. Robust assessment and care planning, open communication and regular continence care training would assist such promotion and also help mitigate resource limitations by developing safer, time-efficient continence care.
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http://dx.doi.org/10.1136/bmjoq-2021-001380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043035PMC
April 2021

Polygenic hazard score is associated with prostate cancer in multi-ethnic populations.

Nat Commun 2021 02 23;12(1):1236. Epub 2021 Feb 23.

Division of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Radiotherapy Related Research, The Christie Hospital NHS Foundation Trust, Manchester, UK.

Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS (PHS, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p < 10). Comparing the 80/20 PHS percentiles, hazard ratios for prostate cancer, aggressive cancer, and prostate-cancer-specific death are 5.32, 5.88, and 5.68, respectively. Within European, Asian, and African ancestries, hazard ratios for prostate cancer are: 5.54, 4.49, and 2.54, respectively. PHS risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.
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http://dx.doi.org/10.1038/s41467-021-21287-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902617PMC
February 2021

Circulating adiponectin and leptin and risk of overall and aggressive prostate cancer: a systematic review and meta-analysis.

Sci Rep 2021 01 11;11(1):320. Epub 2021 Jan 11.

Bristol Medical School, Population Health Sciences, University of Bristol, Bristol, UK.

Obesity is associated with an increased risk of advanced, recurrent and fatal prostate cancer. Adipokines may mediate this relationship. We conducted a systematic review and meta-analysis of associations of leptin and adiponectin with overall and aggressive prostate cancer. Bibliographic databases were systematically searched up to 1st April 2017. Log Odds Ratios (ORs) per 2.5 unit increase in adiponectin or leptin levels were derived and pooled. All analyses were stratified by study type (cross-sectional/prospective). 746 papers were retrieved, 34 eligible studies identified, 31 of these could be included in the meta-analysis. Leptin was not consistently associated with overall prostate cancer (pooled OR 1.00, 95%CI 0.98-1.02, per 2.5 ng/ml increase, prospective study OR 0.97, 95%CI 0.95-0.99, cross-sectional study OR 1.19, 95%CI 1.13-1.26) and there was weak evidence of a positive association with aggressive disease (OR 1.03, 95%CI 1.00-1.06). There was also weak evidence of a small inverse association of adiponectin with overall prostate cancer (OR 0.96, 95%CI 0.93-0.99, per 2.5 µg/ml increase), but less evidence of an association with aggressive disease (OR 0.98, 95%CI 0.94-1.01). The magnitude of any effects are small, therefore levels of circulating adiponectin or leptin alone are unlikely to be useful biomarkers of risk or prognosis.
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http://dx.doi.org/10.1038/s41598-020-79345-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801499PMC
January 2021

Additional SNPs improve risk stratification of a polygenic hazard score for prostate cancer.

Prostate Cancer Prostatic Dis 2021 Jun 8;24(2):532-541. Epub 2021 Jan 8.

Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, 02115, USA.

Background: Polygenic hazard scores (PHS) can identify individuals with increased risk of prostate cancer. We estimated the benefit of additional SNPs on performance of a previously validated PHS (PHS46).

Materials And Method: 180 SNPs, shown to be previously associated with prostate cancer, were used to develop a PHS model in men with European ancestry. A machine-learning approach, LASSO-regularized Cox regression, was used to select SNPs and to estimate their coefficients in the training set (75,596 men). Performance of the resulting model was evaluated in the testing/validation set (6,411 men) with two metrics: (1) hazard ratios (HRs) and (2) positive predictive value (PPV) of prostate-specific antigen (PSA) testing. HRs were estimated between individuals with PHS in the top 5% to those in the middle 40% (HR95/50), top 20% to bottom 20% (HR80/20), and bottom 20% to middle 40% (HR20/50). PPV was calculated for the top 20% (PPV80) and top 5% (PPV95) of PHS as the fraction of individuals with elevated PSA that were diagnosed with clinically significant prostate cancer on biopsy.

Results: 166 SNPs had non-zero coefficients in the Cox model (PHS166). All HR metrics showed significant improvements for PHS166 compared to PHS46: HR95/50 increased from 3.72 to 5.09, HR80/20 increased from 6.12 to 9.45, and HR20/50 decreased from 0.41 to 0.34. By contrast, no significant differences were observed in PPV of PSA testing for clinically significant prostate cancer.

Conclusions: Incorporating 120 additional SNPs (PHS166 vs PHS46) significantly improved HRs for prostate cancer, while PPV of PSA testing remained the same.
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http://dx.doi.org/10.1038/s41391-020-00311-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157993PMC
June 2021

Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.

Nat Genet 2021 01 4;53(1):65-75. Epub 2021 Jan 4.

Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.
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http://dx.doi.org/10.1038/s41588-020-00748-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148035PMC
January 2021

Active monitoring, radical prostatectomy and radical radiotherapy in PSA-detected clinically localised prostate cancer: the ProtecT three-arm RCT.

Health Technol Assess 2020 08;24(37):1-176

Department of Urology, Leeds Teaching Hospitals NHS Trust, Leeds, UK.

Background: Prostate cancer is the most common cancer among men in the UK. Prostate-specific antigen testing followed by biopsy leads to overdetection, overtreatment as well as undertreatment of the disease. Evidence of treatment effectiveness has lacked because of the paucity of randomised controlled trials comparing conventional treatments.

Objectives: To evaluate the effectiveness of conventional treatments for localised prostate cancer (active monitoring, radical prostatectomy and radical radiotherapy) in men aged 50-69 years.

Design: A prospective, multicentre prostate-specific antigen testing programme followed by a randomised trial of treatment, with a comprehensive cohort follow-up.

Setting: Prostate-specific antigen testing in primary care and treatment in nine urology departments in the UK.

Participants: Between 2001 and 2009, 228,966 men aged 50-69 years received an invitation to attend an appointment for information about the Prostate testing for cancer and Treatment (ProtecT) study and a prostate-specific antigen test; 82,429 men were tested, 2664 were diagnosed with localised prostate cancer, 1643 agreed to randomisation to active monitoring ( = 545), radical prostatectomy ( = 553) or radical radiotherapy ( = 545) and 997 chose a treatment.

Interventions: The interventions were active monitoring, radical prostatectomy and radical radiotherapy.

Trial Primary Outcome Measure: Definite or probable disease-specific mortality at the 10-year median follow-up in randomised participants.

Secondary Outcome Measures: Overall mortality, metastases, disease progression, treatment complications, resource utilisation and patient-reported outcomes.

Results: There were no statistically significant differences between the groups for 17 prostate cancer-specific ( = 0.48) and 169 all-cause ( = 0.87) deaths. Eight men died of prostate cancer in the active monitoring group (1.5 per 1000 person-years, 95% confidence interval 0.7 to 3.0); five died of prostate cancer in the radical prostatectomy group (0.9 per 1000 person-years, 95% confidence interval 0.4 to 2.2 per 1000 person years) and four died of prostate cancer in the radical radiotherapy group (0.7 per 1000 person-years, 95% confidence interval 0.3 to 2.0 per 1000 person years). More men developed metastases in the active monitoring group than in the radical prostatectomy and radical radiotherapy groups: active monitoring,  = 33 (6.3 per 1000 person-years, 95% confidence interval 4.5 to 8.8); radical prostatectomy,  = 13 (2.4 per 1000 person-years, 95% confidence interval 1.4 to 4.2 per 1000 person years); and radical radiotherapy,  = 16 (3.0 per 1000 person-years, 95% confidence interval 1.9 to 4.9 per 1000 person-years;  = 0.004). There were higher rates of disease progression in the active monitoring group than in the radical prostatectomy and radical radiotherapy groups: active monitoring ( = 112; 22.9 per 1000 person-years, 95% confidence interval 19.0 to 27.5 per 1000 person years); radical prostatectomy ( = 46; 8.9 per 1000 person-years, 95% confidence interval 6.7 to 11.9 per 1000 person-years); and radical radiotherapy ( = 46; 9.0 per 1000 person-years, 95% confidence interval 6.7 to 12.0 per 1000 person years;  < 0.001). Radical prostatectomy had the greatest impact on sexual function/urinary continence and remained worse than radical radiotherapy and active monitoring. Radical radiotherapy's impact on sexual function was greatest at 6 months, but recovered somewhat in the majority of participants. Sexual and urinary function gradually declined in the active monitoring group. Bowel function was worse with radical radiotherapy at 6 months, but it recovered with the exception of bloody stools. Urinary voiding and nocturia worsened in the radical radiotherapy group at 6 months but recovered. Condition-specific quality-of-life effects mirrored functional changes. No differences in anxiety/depression or generic or cancer-related quality of life were found. At the National Institute for Health and Care Excellence threshold of £20,000 per quality-adjusted life-year, the probabilities that each arm was the most cost-effective option were 58% (radical radiotherapy), 32% (active monitoring) and 10% (radical prostatectomy).

Limitations: A single prostate-specific antigen test and transrectal ultrasound biopsies were used. There were very few non-white men in the trial. The majority of men had low- and intermediate-risk disease. Longer follow-up is needed.

Conclusions: At a median follow-up point of 10 years, prostate cancer-specific mortality was low, irrespective of the assigned treatment. Radical prostatectomy and radical radiotherapy reduced disease progression and metastases, but with side effects. Further work is needed to follow up participants at a median of 15 years.

Trial Registration: Current Controlled Trials ISRCTN20141297.

Funding: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in ; Vol. 24, No. 37. See the National Institute for Health Research Journals Library website for further project information.
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http://dx.doi.org/10.3310/hta24370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443739PMC
August 2020

The ProtecT randomised trial cost-effectiveness analysis comparing active monitoring, surgery, or radiotherapy for prostate cancer.

Br J Cancer 2020 09 16;123(7):1063-1070. Epub 2020 Jul 16.

Bristol Medical School, University of Bristol, Bristol, UK.

Background: There is limited evidence relating to the cost-effectiveness of treatments for localised prostate cancer.

Methods: The cost-effectiveness of active monitoring, surgery, and radiotherapy was evaluated within the Prostate Testing for Cancer and Treatment (ProtecT) randomised controlled trial from a UK NHS perspective at 10 years' median follow-up. Prostate cancer resource-use collected from hospital records and trial participants was valued using UK reference-costs. QALYs (quality-adjusted-life-years) were calculated from patient-reported EQ-5D-3L measurements. Adjusted mean costs, QALYs, and incremental cost-effectiveness ratios were calculated; cost-effectiveness acceptability curves and sensitivity analyses addressed uncertainty; subgroup analyses considered age and disease-risk.

Results: Adjusted mean QALYs were similar between groups: 6.89 (active monitoring), 7.09 (radiotherapy), and 6.91 (surgery). Active monitoring had lower adjusted mean costs (£5913) than radiotherapy (£7361) and surgery (£7519). Radiotherapy was the most likely (58% probability) cost-effective option at the UK NICE willingness-to-pay threshold (£20,000 per QALY). Subgroup analyses confirmed radiotherapy was cost-effective for older men and intermediate/high-risk disease groups; active monitoring was more likely to be the cost-effective option for younger men and low-risk groups.

Conclusions: Longer follow-up and modelling are required to determine the most cost-effective treatment for localised prostate cancer over a man's lifetime.

Trial Registration: Current Controlled Trials number, ISRCTN20141297: http://isrctn.org (14/10/2002); ClinicalTrials.gov number, NCT02044172: http://www.clinicaltrials.gov (23/01/2014).
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http://dx.doi.org/10.1038/s41416-020-0978-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524753PMC
September 2020

The implementation and utility of patient screening logs in a multicentre randomised controlled oncology trial.

Trials 2020 Jul 8;21(1):629. Epub 2020 Jul 8.

Clinical Trials and Statistics Unit at the Institute of Cancer Research (ICR-CTSU), London, SM2 5NG, UK.

Background: The utility of patient screening logs and their impact on improving trial recruitment rates are unclear. We conducted a retrospective exploratory analysis of screening data collected within a multicentre randomised controlled trial investigating chemotherapy for upper tract urothelial carcinoma.

Methods: Participating centres maintained a record of patients meeting basic screening criteria stipulated in the trial protocol, submitting logs regularly to the clinical trial coordinating centre (CTC). Sites recorded the number of patients ineligible, not approached, declined and randomised. The CTC monitored proportions of eligible patients, approach rate (proportion of eligible patients approached) and acceptance rate (proportion recruited of those approached). Data were retrospectively analysed to identify patterns of screening activity and correlation with recruitment.

Results: Data were collected between May 2012 and August 2016, during which time 71 sites were activated-a recruitment period of 2768 centre months. A total of 1138 patients were reported on screening logs, with 2300 requests for logs sent by the CTC and 47% of expected logs received. A total of 758 patients were reported as ineligible, 36 eligible patients were not approached and 207 declined trial participation. The approach rate was 91% (344/380), and the acceptance rate was 40% (137/344); these rates remained consistent throughout the data collection. The main reason patients provided for declining (99/207, 48%) was not wanting to receive chemotherapy. There was a moderately strong correlation (r = 0.47) between the number reported on screening logs and the number recruited per site. Considerable variation in data between centres was observed, and 54/191 trial participants (28%) enrolled during this period were not reported on logs.

Conclusions: Central collection of screening logs can identify reasons for patients declining trial participation and help monitor trial activity at sites; however, obtaining complete data can be challenging. There was a correlation between the number of patients reported on logs and recruitment; however, this was likely confounded by sites' available patient population. The use of screening logs may not be appropriate for all trials, and their use should be carefully considered in relation to the associated workload. No evidence was found that central collection of screening logs improved recruitment rates in this study, and their continued use warrants further investigation.

Trial Registration: ISRCTN98387754 . Registered on 31 January 2012.
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http://dx.doi.org/10.1186/s13063-020-04559-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346417PMC
July 2020

A Genetic Risk Score to Personalize Prostate Cancer Screening, Applied to Population Data.

Cancer Epidemiol Biomarkers Prev 2020 09 24;29(9):1731-1738. Epub 2020 Jun 24.

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.

Background: A polygenic hazard score (PHS), the weighted sum of 54 SNP genotypes, was previously validated for association with clinically significant prostate cancer and for improved prostate cancer screening accuracy. Here, we assess the potential impact of PHS-informed screening.

Methods: United Kingdom population incidence data (Cancer Research United Kingdom) and data from the Cluster Randomized Trial of PSA Testing for Prostate Cancer were combined to estimate age-specific clinically significant prostate cancer incidence (Gleason score ≥7, stage T3-T4, PSA ≥10, or nodal/distant metastases). Using HRs estimated from the ProtecT prostate cancer trial, age-specific incidence rates were calculated for various PHS risk percentiles. Risk-equivalent age, when someone with a given PHS percentile has prostate cancer risk equivalent to an average 50-year-old man (50-year-standard risk), was derived from PHS and incidence data. Positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was calculated using PHS-adjusted age groups.

Results: The expected age at diagnosis of clinically significant prostate cancer differs by 19 years between the 1st and 99th PHS percentiles: men with PHS in the 1st and 99th percentiles reach the 50-year-standard risk level at ages 60 and 41, respectively. PPV of PSA was higher for men with higher PHS-adjusted age.

Conclusions: PHS provides individualized estimates of risk-equivalent age for clinically significant prostate cancer. Screening initiation could be adjusted by a man's PHS.

Impact: Personalized genetic risk assessments could inform prostate cancer screening decisions.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-1527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483627PMC
September 2020

The effect of sample size on polygenic hazard models for prostate cancer.

Eur J Hum Genet 2020 10 8;28(10):1467-1475. Epub 2020 Jun 8.

Humangenetik Tuebingen, Paul-Ehrlich-Str 23, D-72076, Tuebingen, Germany.

We determined the effect of sample size on performance of polygenic hazard score (PHS) models in prostate cancer. Age and genotypes were obtained for 40,861 men from the PRACTICAL consortium. The dataset included 201,590 SNPs per subject, and was split into training and testing sets. Established-SNP models considered 65 SNPs that had been previously associated with prostate cancer. Discovery-SNP models used stepwise selection to identify new SNPs. The performance of each PHS model was calculated for random sizes of the training set. The performance of a representative Established-SNP model was estimated for random sizes of the testing set. Mean HR (hazard ratio of top 2% to average in test set) of the Established-SNP model increased from 1.73 [95% CI: 1.69-1.77] to 2.41 [2.40-2.43] when the number of training samples was increased from 1 thousand to 30 thousand. Corresponding HR of the Discovery-SNP model increased from 1.05 [0.93-1.18] to 2.19 [2.16-2.23]. HR of a representative Established-SNP model using testing set sample sizes of 0.6 thousand and 6 thousand observations were 1.78 [1.70-1.85] and 1.73 [1.71-1.76], respectively. We estimate that a study population of 20 thousand men is required to develop Discovery-SNP PHS models while 10 thousand men should be sufficient for Established-SNP models.
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http://dx.doi.org/10.1038/s41431-020-0664-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608255PMC
October 2020

Systematic review and meta-analysis of the associations between body mass index, prostate cancer, advanced prostate cancer, and prostate-specific antigen.

Cancer Causes Control 2020 May 11;31(5):431-449. Epub 2020 Mar 11.

Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, England.

Purpose: The relationship between body mass index (BMI) and prostate cancer remains unclear. However, there is an inverse association between BMI and prostate-specific antigen (PSA), used for prostate cancer screening. We conducted this review to estimate the associations between BMI and (1) prostate cancer, (2) advanced prostate cancer, and (3) PSA.

Methods: We searched PubMed and Embase for studies until 02 October 2017 and obtained individual participant data from four studies. In total, 78 studies were identified for the association between BMI and prostate cancer, 21 for BMI and advanced prostate cancer, and 35 for BMI and PSA. We performed random-effects meta-analysis of linear associations of log-PSA and prostate cancer with BMI and, to examine potential non-linearity, of associations between categories of BMI and each outcome.

Results: In the meta-analyses with continuous BMI, a 5 kg/m increase in BMI was associated with a percentage change in PSA of - 5.88% (95% CI - 6.87 to - 4.87). Using BMI categories, compared to normal weight men the PSA levels of overweight men were 3.43% lower (95% CI - 5.57 to - 1.23), and obese men were 12.9% lower (95% CI - 15.2 to - 10.7). Prostate cancer and advanced prostate cancer analyses showed little or no evidence associations.

Conclusion: There is little or no evidence of an association between BMI and risk of prostate cancer or advanced prostate cancer, and strong evidence of an inverse and non-linear association between BMI and PSA. The association between BMI and prostate cancer is likely biased if missed diagnoses are not considered.
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http://dx.doi.org/10.1007/s10552-020-01291-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105428PMC
May 2020

Systematic review and meta-analysis of the associations between body mass index, prostate cancer, advanced prostate cancer, and prostate-specific antigen.

Cancer Causes Control 2020 May 11;31(5):431-449. Epub 2020 Mar 11.

Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, England.

Purpose: The relationship between body mass index (BMI) and prostate cancer remains unclear. However, there is an inverse association between BMI and prostate-specific antigen (PSA), used for prostate cancer screening. We conducted this review to estimate the associations between BMI and (1) prostate cancer, (2) advanced prostate cancer, and (3) PSA.

Methods: We searched PubMed and Embase for studies until 02 October 2017 and obtained individual participant data from four studies. In total, 78 studies were identified for the association between BMI and prostate cancer, 21 for BMI and advanced prostate cancer, and 35 for BMI and PSA. We performed random-effects meta-analysis of linear associations of log-PSA and prostate cancer with BMI and, to examine potential non-linearity, of associations between categories of BMI and each outcome.

Results: In the meta-analyses with continuous BMI, a 5 kg/m increase in BMI was associated with a percentage change in PSA of - 5.88% (95% CI - 6.87 to - 4.87). Using BMI categories, compared to normal weight men the PSA levels of overweight men were 3.43% lower (95% CI - 5.57 to - 1.23), and obese men were 12.9% lower (95% CI - 15.2 to - 10.7). Prostate cancer and advanced prostate cancer analyses showed little or no evidence associations.

Conclusion: There is little or no evidence of an association between BMI and risk of prostate cancer or advanced prostate cancer, and strong evidence of an inverse and non-linear association between BMI and PSA. The association between BMI and prostate cancer is likely biased if missed diagnoses are not considered.
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http://dx.doi.org/10.1007/s10552-020-01291-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105428PMC
May 2020

Adjuvant chemotherapy in upper tract urothelial carcinoma (the POUT trial): a phase 3, open-label, randomised controlled trial.

Lancet 2020 04 5;395(10232):1268-1277. Epub 2020 Mar 5.

The Institute of Cancer Research, Clinical Trials and Statistics Unit, London, UK.

Background: Urothelial carcinomas of the upper urinary tract (UTUCs) are rare, with poorer stage-for-stage prognosis than urothelial carcinomas of the urinary bladder. No international consensus exists on the benefit of adjuvant chemotherapy for patients with UTUCs after nephroureterectomy with curative intent. The POUT (Peri-Operative chemotherapy versus sUrveillance in upper Tract urothelial cancer) trial aimed to assess the efficacy of systemic platinum-based chemotherapy in patients with UTUCs.

Methods: We did a phase 3, open-label, randomised controlled trial at 71 hospitals in the UK. We recruited patients with UTUC after nephroureterectomy staged as either pT2-T4 pN0-N3 M0 or pTany N1-3 M0. We randomly allocated participants centrally (1:1) to either surveillance or four 21-day cycles of chemotherapy, using a minimisation algorithm with a random element. Chemotherapy was either cisplatin (70 mg/m) or carboplatin (area under the curve [AUC]4·5/AUC5, for glomerular filtration rate <50 mL/min only) administered intravenously on day 1 and gemcitabine (1000 mg/m) administered intravenously on days 1 and 8; chemotherapy was initiated within 90 days of surgery. Follow-up included standard cystoscopic, radiological, and clinical assessments. The primary endpoint was disease-free survival analysed by intention to treat with a Peto-Haybittle stopping rule for (in)efficacy. The trial is registered with ClinicalTrials.gov, NCT01993979. A preplanned interim analysis met the efficacy criterion for early closure after recruitment of 261 participants.

Findings: Between June 19, 2012, and Nov 8, 2017, we enrolled 261 participants from 57 of 71 open study sites. 132 patients were assigned chemotherapy and 129 surveillance. One participant allocated chemotherapy withdrew consent for data use after randomisation and was excluded from analyses. Adjuvant chemotherapy significantly improved disease-free survival (hazard ratio 0·45, 95% CI 0·30-0·68; p=0·0001) at a median follow-up of 30·3 months (IQR 18·0-47·5). 3-year event-free estimates were 71% (95% CI 61-78) and 46% (36-56) for chemotherapy and surveillance, respectively. 55 (44%) of 126 participants who started chemotherapy had acute grade 3 or worse treatment-emergent adverse events, which accorded with frequently reported events for the chemotherapy regimen. Five (4%) of 129 patients managed by surveillance had acute grade 3 or worse emergent adverse events. No treatment-related deaths were reported.

Interpretation: Gemcitabine-platinum combination chemotherapy initiated within 90 days after nephroureterectomy significantly improved disease-free survival in patients with locally advanced UTUC. Adjuvant platinum-based chemotherapy should be considered a new standard of care after nephroureterectomy for this patient population.

Funding: Cancer Research UK.
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http://dx.doi.org/10.1016/S0140-6736(20)30415-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181180PMC
April 2020

Patients' experiences of life after bariatric surgery and follow-up care: a qualitative study.

BMJ Open 2020 02 6;10(2):e035013. Epub 2020 Feb 6.

Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.

Objectives: Bariatric surgery is the most clinically effective treatment for people with severe and complex obesity, however, the psychosocial outcomes are less clear. Follow-up care after bariatric surgery is known to be important, but limited guidance exists on what this should entail, particularly related to psychological and social well-being. Patients' perspectives are valuable to inform the design of follow-up care. This study investigated patients' experiences of life after bariatric surgery including important aspects of follow-up care, in the long term.

Design: A qualitative study using semistructured individual interviews. A constant comparative approach was used to code data and identify themes and overarching concepts.

Setting: Bariatric surgery units of two publicly funded hospitals in the South of England.

Participants: Seventeen adults (10 women) who underwent a primary operation for obesity (mean time since surgery 3.11 years, range 4 months to 9 years), including Roux-en-Y gastric bypass, adjustable gastric band and sleeve gastrectomy, agreed to participate in the interviews.

Results: Experiences of adapting to life following surgery were characterised by the concepts of 'normality' and 'ambivalence', while experiences of 'abandonment' and 'isolation' dominated participants' experiences of follow-up care. Patients highlighted the need for more flexible, longer-term follow-up care that addresses social and psychological difficulties postsurgery and integrates peer support.

Conclusions: This research highlights unmet patient need for more accessible and holistic follow-up care that addresses the long-term multidimensional impact of bariatric surgery. Future research should investigate effective and acceptable follow-up care packages for patients undergoing bariatric surgery.
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http://dx.doi.org/10.1136/bmjopen-2019-035013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045271PMC
February 2020

Evidence of detrimental effects of prenatal alcohol exposure on offspring birthweight and neurodevelopment from a systematic review of quasi-experimental studies.

Int J Epidemiol 2021 01;49(6):1972-1995

MRC Integrative Epidemiology Unit, Department of Population Health Sciences, University of Bristol, Bristol, UK.

Background: Systematic reviews of prenatal alcohol exposure effects generally only include conventional observational studies. However, estimates from such studies are prone to confounding and other biases.

Objectives: To systematically review the evidence on the effects of prenatal alcohol exposure from randomized controlled trials (RCTs) and observational designs using alternative analytical approaches to improve causal inference.

Search Strategy: Medline, Embase, Web of Science, PsychINFO from inception to 21 June 2018. Manual searches of reference lists of retrieved papers.

Selection Criteria: RCTs of interventions to stop/reduce drinking in pregnancy and observational studies using alternative analytical methods (quasi-experimental studies e.g. Mendelian randomization and natural experiments, negative control comparisons) to determine the causal effects of prenatal alcohol exposure on pregnancy and longer-term offspring outcomes in human studies.

Data Collection And Analysis: One reviewer extracted data and another checked extracted data. Risk of bias was assessed using customized risk of bias tools. A narrative synthesis of findings was carried out and a meta-analysis for one outcome.

Main Results: Twenty-three studies were included, representing five types of study design, including 1 RCT, 9 Mendelian randomization and 7 natural experiment studies, and reporting on over 30 outcomes. One study design-outcome combination included enough independent results to meta-analyse. Based on evidence from several studies, we found a likely causal detrimental role of prenatal alcohol exposure on cognitive outcomes, and weaker evidence for a role in low birthweight.

Conclusion: None of the included studies was judged to be at low risk of bias in all domains, results should therefore be interpreted with caution.

Systematic Review Registration: This study is registered with PROSPERO, registration number CRD42015015941.
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http://dx.doi.org/10.1093/ije/dyz272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825937PMC
January 2021

The ProtecT trial: analysis of the patient cohort, baseline risk stratification and disease progression.

BJU Int 2020 04 12;125(4):506-514. Epub 2020 Feb 12.

Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.

Objective: To test the hypothesis that the baseline clinico-pathological features of the men with localized prostate cancer (PCa) included in the ProtecT (Prostate Testing for Cancer and Treatment) trial who progressed (n = 198) at a 10-year median follow-up were different from those of men with stable disease (n = 1409).

Patients And Methods: We stratified the study participants at baseline according to risk of progression using clinical disease stage, pathological grade and PSA level, using Cox proportional hazard models.

Results: The findings showed that 34% of participants (n = 505) had intermediate- or high-risk PCa, and 66% (n = 973) had low-risk PCa. Of 198 participants who progressed, 101 (51%) had baseline International Society of Urological Pathology Grade Group 1, 59 (30%) Grade Group 2, and 38 (19%) Grade Group 3 PCa, compared with 79%, 17% and 5%, respectively, for 1409 participants without progression (P < 0.001). In participants with progression, 38% and 62% had baseline low- and intermediate-/high-risk disease, compared with 69% and 31% of participants with stable disease (P < 0.001). Treatment received, age (65-69 vs 50-64 years), PSA level, Grade Group, clinical stage, risk group, number of positive cores, tumour length and perineural invasion were associated with time to progression (P ≤ 0.005). Men progressing after surgery (n = 19) were more likely to have a higher Grade Group and pathological stage at surgery, larger tumours, lymph node involvement and positive margins.

Conclusions: We demonstrate that one-third of the ProtecT cohort consists of people with intermediate-/high-risk disease, and the outcomes data at an average of 10 years' follow-up are generalizable beyond men with low-risk PCa.
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http://dx.doi.org/10.1111/bju.14987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187290PMC
April 2020

Ten-year Mortality, Disease Progression, and Treatment-related Side Effects in Men with Localised Prostate Cancer from the ProtecT Randomised Controlled Trial According to Treatment Received.

Eur Urol 2020 03 24;77(3):320-330. Epub 2019 Nov 24.

Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.

Background: The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer (PCa) randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy.

Objective: To determine report outcomes according to treatment received in men in randomised and treatment choice cohorts.

Design, Setting, And Participants: This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy.

Intervention: Two cohorts included 1643 men who agreed to be randomised; 997 declined randomisation and chose treatment.

Outcome Measurements And Statistical Analysis: Health-related quality of life impacts on urinary, bowel, and sexual function were assessed using patient-reported outcome measures. Analysis was carried out based on treatment received for each cohort and on pooled estimates using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores.

Results And Limitations: According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p=0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p=0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6mo) and urinary incontinence (55% at 6mo) after surgery, and of sexual dysfunction (88% at 6mo) and bowel dysfunction (5% at 6mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and outdating of the interventions being evaluated during the lengthy follow-up required in trials of screen-detected PCa.

Conclusions: Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group.

Patient Summary: More than 90 out of every 100 men with localised prostate cancer do not die of prostate cancer within 10yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are much better after active monitoring, but the risks of spreading of prostate cancer are more common.
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http://dx.doi.org/10.1016/j.eururo.2019.10.030DOI Listing
March 2020

Dressing use issues in primary abdominal wounds: a qualitative study of health staff and patient views.

Br J Nurs 2019 Nov;28(20):S10-S18

Senior Lecturer in Qualitative and Mixed Methods Applied Research, Institute of Applied Health Research, University of Birmingham.

Primary surgical abdominal wounds are usually covered with a dressing. However, little is known about the practical issues and costs around these dressings. This study aimed to provide an in-depth description of patients' and health professionals' perspectives on the clinical and practical issues associated with standard and novel dressing (glue-as-a-dressing) use on primary surgical wounds, and to establish whether and how their experience compares with these perspectives. During semi-structured interviews, patients and health professionals discussed their positive experience of glue-as-a-dressing and no dressing around six themes: wound contamination and infection, wound healing, wound care, physical protection afforded by simple dressings, the potential psychological impact of an exposed wound, and ability to carry out everyday tasks. Current views on the practice of dressings for primary abdominal wounds are influenced by ingrained clinical practice. These views can be challenged when exposed to novel dressing strategies or as new evidence of the clinical effect of dressing strategies emerges.
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http://dx.doi.org/10.12968/bjon.2019.28.20.S10DOI Listing
November 2019

Catheter-based closure of the patent ductus arteriosus in preterm infants: considerations in the design of a randomized trial.

J Perinatol 2019 11 12;39(11):1437-1438. Epub 2019 Sep 12.

Center for Perinatal Research, Nationwide Children's Hospital, Columbus, OH, USA.

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http://dx.doi.org/10.1038/s41372-019-0484-9DOI Listing
November 2019

Three wound-dressing strategies to reduce surgical site infection after abdominal surgery: the Bluebelle feasibility study and pilot RCT.

Health Technol Assess 2019 08;23(39):1-166

Worcestershire Acute Hospitals NHS Trust, Worcester, UK.

Background: Surgical site infection (SSI) affects up to 20% of people with a primary closed wound after surgery. Wound dressings may reduce SSI.

Objective: To assess the feasibility of a multicentre randomised controlled trial (RCT) to evaluate the effectiveness and cost-effectiveness of dressing types or no dressing to reduce SSI in primary surgical wounds.

Design: Phase A - semistructured interviews, outcome measure development, practice survey, literature reviews and value-of-information analysis. Phase B - pilot RCT with qualitative research and questionnaire validation. Patients and the public were involved.

Setting: Usual NHS care.

Participants: Patients undergoing elective/non-elective abdominal surgery, including caesarean section.

Interventions: Phase A - none. Phase B - simple dressing, glue-as-a-dressing (tissue adhesive) or 'no dressing'.

Main Outcome Measures: Phase A - pilot RCT design; SSI, patient experience and wound management questionnaires; dressing practices; and value-of-information of a RCT. Phase B - participants screened, proportions consented/randomised; acceptability of interventions; adherence; retention; validity and reliability of SSI measure; and cost drivers.

Data Sources: Phase A - interviews with patients and health-care professionals (HCPs), narrative data from published RCTs and data about dressing practices. Phase B - participants and HCPs in five hospitals.

Results: Phase A - we interviewed 102 participants. HCPs interpreted 'dressing' variably and reported using available products. HCPs suggested practical/clinical reasons for dressing use, acknowledged the weak evidence base and felt that a RCT including a 'no dressing' group was acceptable. A survey showed that 68% of 1769 wounds (727 participants) had simple dressings and 27% had glue-as-a-dressing. Dressings were used similarly in elective and non-elective surgery. The SSI questionnaire was developed from a content analysis of existing SSI tools and interviews, yielding 19 domains and 16 items. A main RCT would be valuable to the NHS at a willingness to pay of £20,000 per quality-adjusted life-year. Phase B - from 4 March 2016 to 30 November 2016, we approached 862 patients for the pilot RCT; 81.1% were eligible, 59.4% consented and 394 were randomised (simple,  = 133; glue,  = 129; no dressing,  = 132); non-adherence was 3 out of 133, 8 out of 129 and 20 out of 132, respectively. SSI occurred in 51 out of 281 participants. We interviewed 55 participants. All dressing strategies were acceptable to stakeholders, with no indication that adherence was problematic. Adherence aids and patients' understanding of their allocated dressing appeared to be key. The SSI questionnaire response rate overall was 67.2%. Items in the SSI questionnaire fitted a single scale, which had good reliability (test-retest and Cronbach's alpha of > 0.7) and diagnostic accuracy (-statistic = 0.906). The key cost drivers were hospital appointments, dressings and redressings, use of new medicines and primary care appointments.

Limitations: Multiple activities, often in parallel, were challenging to co-ordinate. An amendment took 4 months, restricting recruitment to the pilot RCT. Only 67% of participants completed the SSI questionnaire. We could not implement photography in theatres.

Conclusions: A main RCT of dressing strategies is feasible and would be valuable to the NHS. The SSI questionnaire is sufficiently accurate to be used as the primary outcome. A main trial with three groups (as in the pilot) would be valuable to the NHS, using a primary outcome of SSI at discharge and patient-reported SSI symptoms at 4-8 weeks.

Trial Registration: Phase A - Current Controlled Trials ISRCTN06792113; Phase B - Current Controlled Trials ISRCTN49328913.

Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 23, No. 39. See the NIHR Journals Library website for further project information. Funding was also provided by the Medical Research Council ConDuCT-II Hub (reference number MR/K025643/1).
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http://dx.doi.org/10.3310/hta23390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698727PMC
August 2019

Comparison of Multiparametric Magnetic Resonance Imaging and Targeted Biopsy With Systematic Biopsy Alone for the Diagnosis of Prostate Cancer: A Systematic Review and Meta-analysis.

JAMA Netw Open 2019 08 2;2(8):e198427. Epub 2019 Aug 2.

National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care West, University Hospitals Bristol National Health Service Foundation Trust, Bristol, United Kingdom.

Importance: The current diagnostic pathway for patients with suspected prostate cancer (PCa) includes prostate biopsy. A large proportion of individuals who undergo biopsy have either no PCa or low-risk disease that does not require treatment. Unnecessary biopsies may potentially be avoided with prebiopsy imaging.

Objective: To compare the performance of systematic transrectal ultrasonography-guided prostate biopsy vs prebiopsy biparametric or multiparametric magnetic resonance imaging (MRI) followed by targeted biopsy with or without systematic biopsy.

Data Sources: MEDLINE, Embase, Cochrane, Web of Science, clinical trial registries, and reference lists of recent reviews were searched through December 2018 for randomized clinical trials using the terms "prostate cancer" and "MRI."

Study Selection: Randomized clinical trials comparing diagnostic pathways including prebiopsy MRI vs systematic transrectal ultrasonography-guided biopsy in biopsy-naive men with a clinical suspicion of PCa.

Data Extraction And Synthesis: Data were pooled using random-effects meta-analysis. Risk of bias was assessed using the revised Cochrane tool. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. All review stages were conducted by 2 reviewers.

Main Outcomes And Measures: Detection rate of clinically significant and insignificant PCa, number of biopsy procedures, number of biopsy cores taken, and complications.

Results: Seven high-quality trials (2582 patients) were included. Compared with systematic transrectal ultrasonography-guided biopsy alone, MRI with or without targeted biopsy was associated with a 57% (95% CI, 2%-141%) improvement in the detection of clinically significant PCa, a 33% (95% CI, 23%-45%) potential reduction in the number of biopsy procedures, and a 77% (95% CI, 60%-93%) reduction in the number of cores taken per procedure. One trial showed reduced pain and bleeding adverse effects. Systematic sampling of the prostate in addition to the acquisition of targeted cores did not significantly improve the detection of clinically significant PCa compared with systematic biopsy alone.

Conclusions And Relevance: In this meta-analysis, prebiopsy MRI combined with targeted biopsy vs systematic transrectal ultrasonography-guided biopsy alone was associated with improved detection of clinically significant PCa, despite substantial heterogeneity among trials. Prebiopsy MRI was associated with a reduced number of individual biopsy cores taken per procedure and with reduced adverse effects, and it potentially prevented unnecessary biopsies in some individuals. This evidence supports implementation of prebiopsy MRI into diagnostic pathways for suspected PCa.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.8427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6686781PMC
August 2019

"What's fair to an individual is not always fair to a population": A qualitative study of patients and their health professionals using the Cancer Drugs Fund.

Health Policy 2019 08 21;123(8):706-712. Epub 2019 Jun 21.

Bristol Medical School, Population Health Sciences, 39 Whatley Rd, Bristol, BS8 2PS, UK. Electronic address:

Objective: To understand the values attached to cancer treatment at the end of life (EoL) to inform policy decisions around the Cancer Drugs Fund (CDF) and the National Institute for Health and Care Excellence (NICE) EoL criterion.

Design: Semi-structured interviews with patients and health professionals. Purposive recruitment was performed iteratively alongside analysis of interview transcripts using constant comparison.

Participants: Patients with incurable prostate and colorectal cancer (n = 22) who received drugs funded through the CDF and oncologists and palliative care professionals (n = 16) treating patients on CDF drugs.

Results: While the majority of patient and oncologist participants expressed gratitude for access to the CDF, some patient participants reported experiencing a sense of guilt, and many oncologists admitted to concern about the justice of a ring-fenced fund solely for anti-cancer drugs. For patient and professional participants, cancer drugs were not necessarily seen as a funding priority over other calls on the NHS purse. Overall, patients and health professionals emphasised prioritising quality over quantity at the end of life, with only a minority describing improved quality of life at the end of life which added value.

Conclusion: While patients and oncologists appreciated the drugs available through the CDF, most expressed concern about its fairness. Competing participant views about the added value of the end of life is challenging for resource allocation.
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http://dx.doi.org/10.1016/j.healthpol.2019.05.022DOI Listing
August 2019

Factors associated with trial recruitment, preferences, and treatments received were elucidated in a comprehensive cohort study.

J Clin Epidemiol 2019 09 3;113:200-213. Epub 2019 Jun 3.

Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.

Objectives: Recruitment to pragmatic trials is often difficult, and little is known about factors associated with key participation and treatment decisions. These were explored in the Prostate cancer testing and Treatment (ProtecT) study.

Study Design And Setting: Baseline sociodemographic, patient-reported outcome, clinical history, and prostate cancer biopsy data were collected for all patients eligible to take part in the ProtecT trial, in a comprehensive cohort design. Men who rejected randomization specified a preferred option and were followed up identically to the randomized cohort. Factors associated with participation decisions, patient preferences, and reasons for changing treatment were explored.

Results: Of 2,664 men with clinically localized prostate cancer, 997 (37%) rejected randomization. Their treatment preferences and subsequent treatment choices/changes in both randomized and treatment choice cohorts were strongly associated with prostate cancer risk features: toward active monitoring for low-risk disease and toward radical options with higher risk prostate cancer. Among many factors measured, only a small number of weak associations were found for occupation groups and some patient symptoms. Similar percentages changed from the random allocation and initially stated preference.

Conclusion: The comprehensive cohort design provided new insights into trial recruitment and participation decisions. Opportunities to improve recruitment by supporting recruiters with equipoise and patient preferences were identified.
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http://dx.doi.org/10.1016/j.jclinepi.2019.05.036DOI Listing
September 2019