Use of 5-alpha reductase inhibitors and risk of gastrointestinal cancers in men with benign prostatic hyperplasia: A population-based cohort study.

Pre-clinical evidence suggests that 5-alpha reductase inhibitors (5ARi's), prescribed in the treatment of benign prostatic hyperplasia, reduce colorectal and gastro-oesophageal cancer incidence via action on the male hormonal pathway. However, few studies to date have investigated this association at the population level. Our study aimed to investigate the risk of colorectal and gastro-oesophageal cancers with the use of 5ARi's. We conducted a retrospective cohort study of new users of 5ARi's and alpha-blockers among patients with benign prostatic hyperplasia in the UK Clinical Practice Research Datalink. Patients were followed until a first ever diagnosis of colorectal or gastro-oesophageal cancer, death from any cause or end of registration with the general practice or 31st of December 2017. Cox proportional hazards models with inverse probability of treatment weights were used to calculate weighted hazard ratios (HR) and 95% confidence intervals (CIs) of incident colorectal cancer or gastro-oesophageal cancer associated with the use of 5ARi's compared to alpha-blockers. During a mean follow-up of 6.6 years, we found no association between the use of 5ARi's and colorectal (HR: 1.13, 95% CI 0.91-1.41) or gastro-oesophageal (HR 1.14, 95% CI 0.76-1.63) cancer risk compared to alpha-blockers. Sensitivity analysis showed largely consistent results when varying lag periods, using multiple imputations, and accounting for competing risk of death. Our study found no association between the use of 5ARi's and risk of colorectal or gastro-oesophageal cancer in men with benign prostatic hyperplasia.

Oral prednisolone and warfarin and risk of oesophageal cancer: A case-control study.

BACKGROUND: A recent epidemiological study systematically screened 250 prescription medications for associations with oesophageal cancer risk, using Scottish data, and identified an increased risk with use of prednisolone and warfarin. We investigated whether oral prednisolone or warfarin use was associated with increased oesophageal cancer risk. METHODS: A case-control study was conducted within the Clinical Practice Research Datalink. In the primary analysis oesophageal cancer cases were identified from linked cancer registry records. Up to 5 cancer-free controls were matched to each case (based upon sex, birth year, GP practice and year of GP registration). Prednisolone and warfarin medications were identified from prescribing records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression after adjusting for covariates including demographics, comorbidities and medication use. RESULTS: There were 4552 oesophageal cancer cases and 22,601 matched control participants. Overall, there was no evidence of an increased risk of oesophageal cancer with oral prednisolone use (unadjusted OR=1.16 95% CI 1.06, 1.27 and adjusted OR=0.99 95% CI 0.89, 1.11) or warfarin use (unadjusted OR=1.12 95% CI 0.99, 1.28 and adjusted OR=1.08 95% CI 0.92, 1.27). CONCLUSIONS: In this large population-based study, oral prednisolone and warfarin were not associated with oesophageal cancer risk.

Total Patient Delay: A Comparison of Patient and Clinician/Health System Delays in the Diagnosis of Progressive Supranuclear Palsy and Corticobasal Syndrome.

BACKGROUND: Early diagnosis in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) is important for clinical care and key to developing successful disease-modifying agents. The patient-dependent phases of decision-making made before contact with a healthcare professional have been inadequately studied. OBJECTIVES: To evaluate the patient-dependent phases of decision-making from symptom onset, comparing this to clinician and/or health system delays within the overall diagnostic pathway. METHODS: Using the Anderson General Model of Total Patient Delay and a mixed-methods approach in participants with PSP/CBS and their caregivers recruited to the Scottish PSP and CBS cohort, we quantified and evaluated the determinants of "appraisal", "illness," and "behavioral" delay, comparing this to the clinician and/or health system delays ("treatment" delay) within the overall time from symptom onset to diagnosis. RESULTS: The time from index symptom onset to diagnosis was 3.26 (interquartile range [IQR] = 2.42, 4.75) years in PSP and 2.58 (IQR = 1.69, 4.08) years in CBS. Patient appraisal delay was 24 (IQR = 6, 60) weeks in PSP and 8 (IQR = 5, 24) weeks in CBS, illness delay 0 (IQR = -14, 0) weeks in PSP and 0 (IQR = -4, 0) weeks in CBS, with little perceived behavioral delay. Determinants of delay included the non-specificity of symptoms, normalization of symptoms within the context of age or normal physiological variability, and the extent of insight into new somatic symptoms. CONCLUSIONS: Although patient appraisal delay contributes to overall diagnostic delay in PSP/CBS, the greater proportion of overall diagnostic delay arises after contact with a healthcare professional (treatment delay).

Vaginal Estrogen Therapy Use and Survival in Females With Breast Cancer.

Importance: Genitourinary syndrome of menopause can be treated with vaginal estrogen therapy. However, there are concerns about the safety of vaginal estrogen therapy in patients with breast cancer. Objective: To determine whether the risk of breast cancer-specific mortality was higher in females with breast cancer who used vaginal estrogen therapy vs females with breast cancer who did not use hormone replacement therapy (HRT). Design, Setting, and Participants: This cohort study analyzed 2 large cohorts, one each in Scotland and Wales, of females aged 40 to 79 years with newly diagnosed breast cancer. These population-based cohorts were identified from national cancer registry records from 2010 to 2017 in Scotland and from 2000 to 2016 in Wales and were followed up for breast cancer-specific mortality until 2020. Females were excluded if they had a previous cancer diagnosis (except nonmelanoma skin cancer). Data analysis was performed between August 2022 and August 2023. Exposure: Use of vaginal estrogen therapy, including vaginal tablets and creams, was ascertained from pharmacy dispensing records of the Prescribing Information System for the Scotland cohort and from general practice prescription records for the Wales cohort. Main Outcomes and Measures: The primary outcome was time to breast cancer-specific mortality, which was obtained from national mortality records. Time-dependent Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% CIs for breast cancer-specific mortality, comparing vaginal estrogen therapy users with HRT nonusers and adjusting for confounders, including cancer stage and grade. Results: The 2 cohorts comprised 49 237 females with breast cancer (between 40 and 79 years of age) and 5795 breast cancer-specific deaths. Five percent of patients with breast cancer used vaginal estrogen therapy after breast cancer diagnosis. In vaginal estrogen therapy users compared with HRT nonusers, there was no evidence of a higher risk of breast cancer-specific mortality in the pooled fully adjusted model (HR, 0.77; 95% CI, 0.63-0.94). Conclusions and Relevance: Results of this study showed no evidence of increased early breast cancer-specific mortality in patients who used vaginal estrogen therapy compared with patients who did not use HRT. This finding may provide some reassurance to prescribing clinicians and support the guidelines suggesting that vaginal estrogen therapy can be considered in patients with breast cancer and genitourinary symptoms.

Label-free Medical Image Quality Evaluation by Semantics-aware Contrastive Learning in IoMT.

With the rapid development of the Internet-of-Medical-Things (IoMT) in recent years, it has emerged as a promising solution to alleviate the workload of medical staff, particularly in the field of Medical Image Quality Assessment (MIQA). By deploying MIQA based on IoMT, it proves to be highly valuable in assisting the diagnosis and treatment of various types of medical images, such as fundus images, ultrasound images, and dermoscopic images. However, traditional MIQA models necessitate a substantial number of labeled medical images to be effective, which poses a challenge in acquiring a sufficient training dataset. To address this issue, we present a label-free MIQA model developed through a zero-shot learning approach. This paper introduces a Semantics-Aware Contrastive Learning (SCL) model that can effectively generalise quality assessment to diverse medical image types. The proposed method integrates features extracted from zero-shot learning, the spatial domain, and the frequency domain. Zero-shot learning is achieved through a tailored Contrastive Language-Image Pre-training (CLIP) model. Natural Scene Statistics (NSS) and patch-based features are extracted in the spatial domain, while frequency features are hierarchically extracted from both local and global levels. All of this information is utilised to derive a final quality score for a medical image. To ensure a comprehensive evaluation, we not only utilise two existing datasets, EyeQ and LiverQ, but also create a dataset specifically for skin image quality assessment. As a result, our SCL method undergoes extensive evaluation using all three medical image quality datasets, demonstrating its superiority over advanced models.

Effectiveness of conservative management versus laparoscopic cholecystectomy in the prevention of recurrent symptoms and complications in adults with uncomplicated symptomatic gallstone disease (C-GALL trial): pragmatic, multicentre randomised controlled trial.

OBJECTIVE: To assess the clinical and cost effectiveness of conservative management compared with laparoscopic cholecystectomy for the prevention of symptoms and complications in adults with uncomplicated symptomatic gallstone disease. DESIGN: Parallel group, pragmatic randomised, superiority trial. SETTING: 20 secondary care centres in the UK. PARTICIPANTS: 434 adults (>18 years) with uncomplicated symptomatic gallstone disease referred to secondary care, assessed for eligibility between August 2016 and November 2019, and randomly assigned (1:1) to receive conservative management or laparoscopic cholecystectomy. INTERVENTIONS: Conservative management or surgical removal of the gallbladder. MAIN OUTCOME MEASURES: The primary patient outcome was quality of life, measured by area under the curve, over 18 months using the short form 36 (SF-36) bodily pain domain, with higher scores (range 0-100) indicating better quality of life. Other outcomes included costs to the NHS, quality adjusted life years (QALYs), and incremental cost effectiveness ratio. RESULTS: Of 2667 patients assessed for eligibility, 434 were randomised: 217 to the conservative management group and 217 to the laparoscopic cholecystectomy group. By 18 months, 54 (25%) participants in the conservative management arm and 146 (67%) in the cholecystectomy arm had received surgery. The mean SF-36 norm based bodily pain score was 49.4 (standard deviation 11.7) in the conservative management arm and 50.4 (11.6) in the cholecystectomy arm. The SF-36 bodily pain area under the curve up to 18 months did not differ (mean difference 0.0, 95% confidence interval -1.7 to 1.7; P=1.00). Conservative management was less costly (mean difference -£1033, (-$1334; -€1205), 95% credible interval -£1413 to -£632) and QALYs did not differ (mean difference -0.019, 95% credible interval -0.06 to 0.02). CONCLUSIONS: In the short term (≤18 months), laparoscopic surgery is no more effective than conservative management for adults with uncomplicated symptomatic gallstone disease, and as such conservative management should be considered as an alternative to surgery. From an NHS perspective, conservative management may be cost effective for uncomplicated symptomatic gallstone disease. As costs, complications, and benefits will continue to be incurred in both groups beyond 18 months, future research should focus on longer term follow-up to establish effectiveness and lifetime cost effectiveness and to identify the cohort of patients who should be routinely offered surgery. TRIAL REGISTRATION: ISRCTN registry ISRCTN55215960.

Validated frailty measures using electronic primary care records: a review of diagnostic test accuracy.

INTRODUCTION: Identification of people who have or are at risk of frailty enables targeted interventions, and the use of tools that screen for frailty using electronic records (which we term as validated electronic frailty measures (VEFMs)) within primary care is incentivised by NHS England. We carried out a systematic review to establish the sensitivity and specificity of available primary care VEFMs when compared to a reference standard in-person assessment. METHODS: Medline, Pubmed, CENTRAL, CINHAL and Embase searches identified studies comparing a primary care VEFM with in-person assessment. Studies were quality assessed using Quality Assessment of Diagnostic Accuracy Studies revised tool. Sensitivity and specificity values were extracted or were calculated and pooled using StatsDirect. RESULTS: There were 2,245 titles screened, with 10 studies included. These described three different index tests: electronic frailty index (eFI), claims-based frailty index (cFI) and polypharmacy. Frailty Phenotype was the reference standard in each study. One study of 60 patients examined the eFI, reporting a sensitivity of 0.84 (95% CI = 0.55, 0.98) and a specificity of 0.78 (0.64, 0.89). Two studies of 7,679 patients examined cFI, with a pooled sensitivity of 0.48 (95% CI = 0.23, 0.74) and a specificity of 0.80 (0.53, 0.98). Seven studies of 34,328 patients examined a polypharmacy as a screening tool (defined as more than or equal to five medications) with a pooled sensitivity of 0.61 (95% CI = 0.50, 0.72) and a specificity of 0.66 (0.58, 0.73). CONCLUSIONS: eFI is the best-performing VEFM; however, based on our analysis of an average UK GP practice, it would return a high number of false-positive results. In conclusion, existing electronic frailty tools may not be appropriate for primary care-based population screening.

The impact of travel time to cancer treatment centre on post-diagnosis care and mortality among cancer patients in Scotland.

Limited data exist on the effect of travelling time on post-diagnosis cancer care and mortality. We analysed the impact of travel time to cancer treatment centre on secondary care contact time and one-year mortality using a data-linkage study in Scotland with 17369 patients. Patients with longer travelling time and island-dwellers had increased incidence rate of secondary care cancer contact time. For outpatient oncology appointments, the incidence rate was decreased for island-dwellers. Longer travelling time was not associated with increased secondary care contact time for emergency cancer admissions or time to first emergency cancer admission. Living on an island increased mortality at one-year. Adjusting for cancer-specific secondary care contact time increased the hazard of death, and adjusting for oncology outpatient time decreased the hazard of death for island-dwellers. Those with longer travelling times experience the cancer treatment pathway differently with poorer outcomes. Cancer services may need to be better configured to suit differing needs of dispersed populations.

User Experiences in a Digital Intervention to Support Total Skin Self-examination by Melanoma Survivors: Nested Qualitative Evaluation Embedded in a Randomized Controlled Trial.

BACKGROUND: Melanoma is a relatively common cancer type with a high survival rate, but survivors risk recurrences or second primaries. Consequently, patients receive regular hospital follow-up, but this can be burdensome to attend and not optimally timed to detect arising problems. Total skin self-examination (TSSE) supports improved clinical outcomes from melanoma via earlier detection of recurrences and second primaries, and digital technology has the potential to support TSSE. Recent research with app-based interventions aimed at improving the well-being of older adults has found that they can use the technology and benefit from it, supporting the use of digital health care in diverse demographic groups. Thus, the Achieving Self-directed Integrated Cancer Aftercare (ASICA) digital health care intervention was developed. The intervention provided melanoma survivors with a monthly prompt to perform a TSSE as well as access to a dermatology nurse who provided them with feedback on photographs and descriptions of their skin. OBJECTIVE: We aimed to explore participants' attitudes, beliefs, and experiences regarding TSSE practices. Furthermore, we explored how participants experienced technology and how it influenced their practice of TSSE. Finally, we explored the practical and technical experiences of ASICA users. METHODS: This was a nested qualitative evaluation within a dual-center randomized controlled trial of the ASICA intervention. We conducted semistructured telephone interviews with the participants during a randomized controlled trial. The participants were purposively sampled to achieve a representative sample with representative proportions by age, sex, and residential geography. Interviews were transcribed verbatim and analyzed using a framework analysis approach applied within NVivo 12. RESULTS: A total of 22 interviews were conducted with participants from both groups. In total, 40% (9/22) of the interviewed participants were from rural areas, and 60% (13/22) were from urban areas; 60% (13/22) were from the intervention group, and 40% (9/22) were from the control group. Themes evolved around skin-checking behavior, other people's input into skin checking, contribution of health care professionals outside ASICA and its value, ideas around technology, practical experiences, and potential improvements. ASICA appeared to change participants' perceptions of skin checking. Users were more likely to report routinely performing TSSE thoroughly. There was some variation in beliefs about skin checking and using technology for health care. Overall, ASICA was experienced positively by participants. Several practical suggestions were made for the improvement of ASICA. CONCLUSIONS: The ASICA intervention appeared to have positively influenced the attitudes and TSSE practices of melanoma survivors. This study provides important qualitative information about how a digital health care intervention is an effective means of prompting, recording, and responding to structured TSSE by melanoma survivors. Technical improvements are required, but the app offers promise for technologically enhanced melanoma follow-up in future. TRIAL REGISTRATION: ClinicalTrials.gov NCT03328247; https://clinicaltrials.gov/ct2/show/NCT03328247?term=ASICA&rank=1. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-019-3453-x.

Barriers and facilitators of adherence to the use of ASICA, a digital app designed to support people previously treated for melanoma: concise report of a qualitative study.

We developed the Achieving Self-directed Integrated Cancer Aftercare (ASICA) in melanoma app to support monthly total-skin self-examinations (TSSE) by people previously treated for melanoma. A randomized 12-month trial demonstrated ASICA supported optimal monthly TSSE adherence in a third of participants (ClinicalTrials.gov NCT03328247). However, a further third of participants adhered well initially but subsequently dropped off, and a final third did not adhere at all. This follow-up qualitative study investigated trial participants' perceptions of barriers and facilitators to TSSE adherence using the app. Three former trial participants participated in a single focus group and 11 participated in new semistructured telephone interviews. These were analysed thematically alongside secondary analysis of 13 qualitative interviews conducted during the trial. All transcripts were recorded, transcribed and analysed thematically. Five themes encompassing barriers and facilitators to ASICA adherence emerged. These were: technology, role of others, tailoring, disease journey and competing priorities. These data will inform further development of ASICA to increase user adherence.

Rural and Urban patients' Requirements and Experiences of Out-of-hours medical care after cancer (RUREO): a questionnaire study.

OBJECTIVE: To investigate how individuals diagnosed with cancer use out-of-hours (OOH) medical services, describe the behavioural determinants of OOH service use and explore whether there are differences between urban and rural dwellers. DESIGN AND SETTING: A cross-sectional questionnaire study conducted in Northeast Scotland. PARTICIPANTS: The questionnaire was sent to 2549 individuals diagnosed with cancer in the preceding 12 months identified through the National Health Service Grampian Cancer Care Pathway database. 490 individuals returned the questionnaire (19.2% response rate), 61.8% were urban and 34.9% were rural. OUTCOMES: Outcomes were differences in frequency of medical service use and attitudes towards OOH services between urban and rural participants. Patient experience (qualitative data) was compared. RESULTS: Daytime services were used much more frequently than OOH services-83.3% of participants had never contacted an OOH primary care service in the preceding 12 months but 44.2% had used their daytime general practitioner at least four times. There were no significant differences between urban and rural dwellers in the patterns of OOH or daytime service use, the behavioural determinants of service use or the experiences of OOH services. Rural dwellers were significantly less likely to agree that OOH services were close by and more likely to agree that where they lived made it difficult to access these services. Rural dwellers were no more likely to agree or disagree that distance would affect their decision to contact OOH services. Qualitative results highlighted barriers to accessing OOH services exist for all patients but that long travel distances can be offset by service configuration, travel infrastructure and access to a car. CONCLUSIONS: Urban and rural dwellers have similar beliefs, attitudes towards and patterns of OOH service use. In Northeast Scotland, place of residence is unlikely to be the most important factor in influencing decisions about whether to access OOH medical care.

The impact of rurality on patient experience and diagnostic pathway intervals in Scotland's cancer patients: Further results from a national cancer diagnosis audit.

BACKGROUND: In Scotland 17 % of the population reside rurally and previous research has demonstrated worse cancer outcomes in this group. The underlying reason for this is unclear. This study aims to determine whether patient presenting factors, GP consultation factors or the diagnostic pathways differ between urban and rural patients within Scotland. METHODS: This study combined two Scottish National Cancer Diagnosis Audits. Participating GPs collected data on the diagnostic pathway from primary to secondary care for cancer patients diagnosed during the audit period. Using the Scottish Government Urban Rural Classification, patients were designated as rural or urban dwellers and compared in descriptive analyses. Key cancer intervals (primary, diagnostic, secondary and treatment interval) were compared between urban and rural dwellers with an additional adjusted analysis for the main cancer sites. RESULTS: A total of 4309 cancer diagnoses were included in the study; 22 % were in patients from rural locations. Rural patients had significantly more consultations and investigations prior to referral than their urban counterparts. There was no difference in prolonged cancer pathways between the two groups except in lung cancer patients where rural patients had a significantly increased odds of a diagnostic interval of >90 days. CONCLUSION: Our findings suggest differences in the interaction between patients and GPs prior to referral in urban and rural settings. However, this does not appear to lead to prolonged patient pathways, except in lung cancer. Further research is needed to determine whether this delay is clinically significant and contributing to poorer outcomes in Scottish rural dwellers with lung cancer.

Exploring why European primary care physicians sometimes do not think of, or act on, a possible cancer diagnosis. A qualitative study.

BACKGROUND: While primary care physicians (PCPs) play a key role in cancer detection, they can find cancer diagnosis challenging, and some patients have considerable delays between presentation and onward referral. AIM: To explore European PCPs' experiences and views on cases where they considered that they had been slow to think of, or act on, a possible cancer diagnosis. DESIGN & SETTING: A multicentre European qualitative study, based on an online survey with open-ended questions, asking PCPs for their narratives about cases when they had missed a diagnosis of cancer. METHOD: Using maximum variation sampling, PCPs in 23 European countries were asked to describe what happened in a case where they were slow to think of a cancer diagnosis, and for their views on why it happened. Thematic analysis was used to analyse the data. RESULTS: A total of 158 PCPs completed the questionnaire. The main themes were as follows: patients' descriptions did not suggest cancer; distracting factors reduced PCPs' cancer suspicions; patients' hesitancy delayed the diagnosis; system factors not facilitating timely diagnosis; PCPs felt that they had acted wrongly; and problems with communicating adequately. CONCLUSION: The study identified six overarching themes that need to be addressed. Doing so should reduce morbidity and mortality in the small proportion of patients who have a significant, avoidable delay in their cancer diagnosis. The 'Swiss cheese' model of accident causation showed how the themes related to each other.

What influences GPs' use of pelvic examination? A qualitative investigation in primary care.

BACKGROUND: Omission of pelvic examination (PE) has been associated with diagnostic delay in women diagnosed with gynaecological cancer. However, PEs are often not carried out by GPs. AIM: To determine the perceptions of GPs about the role of PEs, the barriers to and facilitators of PEs, and GPs' experience of PEs in practice. DESIGN AND SETTING: Qualitative semi-structured interview study conducted in one health board in Scotland (mixed urban and rural) with an approximate population of 500 000. METHOD: Interviews were conducted face-to-face or by telephone between March and June 2019. Framework analysis used the COM-B behaviour change model concepts of capability, opportunity, and motivation. RESULTS: Data was compatible with all three domains of the COM-B framework. Capability related to training in and maintenance of skills. These went beyond carrying out the examination to interpreting it reliably. Opportunity related to the clinical environment and the provision of chaperones for intimate examination. Interviewees described a range of motivations towards or against PEs that were unrelated to either capability or opportunity. These all related to providing high-quality care, but this was defined in different ways: 'doing what is best for the individual', 'doctors examine', and 'GPs as pragmatists'. CONCLUSION: GPs' reasons for carrying out, or not carrying out, PEs in women with symptoms potentially indicating cancer are complex. The COM-B framework provides a way of understanding this complexity. Interventions to increase the use of PEs, and critics of its non-use, need to consider these multiple factors.

Exposure to weak opioids and risk of gastrointestinal tract cancers: A series of nested case-control studies.

AIMS: There is evidence gastrointestinal (GI) motility may play a role in the development of GI cancers. Weak opioids (codeine and dihydrocodeine) decrease GI motility, but their effect on GI cancer risk has not been assessed. We aim to assess the association between weak opioids and cancers of the GI tract. METHODS: A series of nested case-control studies was conducted using Scottish general practice records from the Primary Care Clinical Informatics Unit Research database. Oesophageal (n = 2432), gastric (n = 1443) and colorectal cancer (n = 8750) cases, diagnosed between 1999 and 2011, were identified and matched with up to five controls. Weak opioid use was identified from prescribing records. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression, adjusting for relevant comorbidities and medication use. RESULTS: There was no association between weak opioids and colorectal cancer (adjusted OR = 0.96, CI 0.90, 1.02, P = 0.15). There was an increased risk of oesophageal (adjusted OR = 1.16, CI 1.04, 1.29, P = 0.01) and gastric cancer (adjusted OR = 1.26, CI 1.10, 1.45, P = 0.001). The associations for oesophageal cancer, but not gastric cancer, were attenuated when weak opioid users were compared with users of another analgesic (adjusted OR = 1.03 CI 0.86, 1.22, P = 0.76 and adjusted OR = 1.29 CI 1.02, 1.64, P = 0.04 respectively). CONCLUSIONS: In this large population-based study, there was no consistent evidence of an association between weak opioids and oesophageal or colorectal cancer risk, but a small increased risk of gastric cancer. Further investigation is required to determine whether this association is causal or reflects residual confounding or confounding by indication.

5α-Reductase Inhibitors and Risk of Kidney and Bladder Cancers in Men with Benign Prostatic Hyperplasia: A Population-Based Cohort Study.

BACKGROUND: Preclinical evidence suggests that 5α-reductase inhibitors (5ARi), commonly used to treat benign prostatic hyperplasia (BPH), are associated with reduced incidence of certain urologic cancers, yet epidemiologic studies are conflicting. This study aimed to determine whether 5ARi's are associated with a reduced risk of kidney and bladder cancers. METHODS: We conducted a new-user active-comparator cohort study in the United Kingdom Clinical Practice Research Datalink. From a base cohort of patients with incident BPH, new users of 5ARi's and α-blockers were identified. Patients were followed up until a first ever diagnosis of kidney or bladder cancer, death from any cause, end of registration, or December 31, 2017. Cox proportional hazards models were used to calculate HRs and 95% confidence intervals (CI) for incident kidney and bladder cancer. RESULTS: There were 5,414 and 37,681 new users of 5ARi's and α-blockers, respectively. During a mean follow-up of 6.3 years, we found no association between the use of 5ARi's and kidney (adjusted HR, 1.26; 95% CI, 0.74-2.12; n = 23) or bladder (adjusted HR, 0.89; 95% CI, 0.64-1.23; n = 57) cancer risk compared with α-blockers. Similar results were observed across sensitivity analyses. CONCLUSIONS: In this study, we found no association between the use of 5ARi's and kidney or bladder cancer incidence in men with BPH when compared with α-blocker use. IMPACT: The findings of this study indicate that 5ARi's are unlikely to reduce kidney or bladder cancer risk.

The Achieving Self-directed Integrated Cancer Aftercare Intervention for Detection of Recurrent and Second Primary Melanoma in Survivors of Melanoma: Pilot Randomized Controlled Trial.

BACKGROUND: Melanoma is common with increasing incidence. Guidelines recommend monthly total skin self-examinations (TSSEs) by survivors to detect recurrent and new primary melanomas. TSSE is underperformed despite evidence of benefit. OBJECTIVE: This study compares the effect on psychological well-being and TSSE practice of a self-directed digital intervention with treatment as usual in patients treated for a first stage 0 to IIC primary cutaneous melanoma within the preceding 60 months. METHODS: This randomized clinical trial was conducted at 2 UK National Health Service hospitals (Aberdeen Royal Infirmary, Grampian, and Addenbrooke's, Cambridge). Adults (≥18 years) diagnosed with a first 0 to IIC primary cutaneous melanoma were randomized to receive Achieving Self-directed Integrated Cancer Aftercare (ASICA), a tablet-based intervention prompting and supporting TSSE in survivors of melanoma, or to usual care. The hypothesis was that ASICA would increase TSSE practice in users affected by melanoma and compared with controls without affecting psychological well-being. The main primary outcomes were melanoma worry (Melanoma Worry Scale), anxiety and depression (Hospital Anxiety and Depression Scale), and quality of life (EQ-5D-5L) as well as secondary outcomes collected using postal questionnaires 3, 6, and 12 months following randomization. RESULTS: A total of 240 recruits were randomized (1:1) into the ASICA (n=121, 50.4%) or control (n=119, 49.6%) groups. There were no significant differences between groups for melanoma worry at 12 months (mean difference: 0.12, 95% CI -0.6 to 0.84; P=.74), 3 months (0.23, 95% CI -0.31 to 0.78; P=.40), or 6 months (-0.1, 95% CI -0.7 to 0.51; P=.76). The ASICA group had lower anxiety scores at 12 months (-0.54, 95% CI -1.31 to 0.230; P=.17), 3 months (-0.13, 95% CI -0.79 to 0.54; P=.71), and significantly at 6 months (-1.00, 95% CI -1.74 to -0.26; P=.009). Depression scores were similar, being lower at 12 months (-0.44, 95% CI -1.11 to 0.23; P=.20) and 3 months (-0.24, 95% CI -0.84 to 0.35; P=.42) but only significantly lower at 6 months (-0.77, 95% CI -1.41 to -0.12; P=.02). The ASICA group had significantly higher quality of life scores at 12 months (0.044, 95% CI 0.003-0.085; P=.04) and 6 months (0.070, 95% CI 0.032-0.107; P<.001) and nonsignificantly at 3 months (0.024, 95% CI -0.006 to 0.054; P=.11). ASICA users reported significantly more regular (>5) TSSEs during the study year and significantly higher levels of self-efficacy in conducting TSSE. They also reported significantly higher levels of planning and intention to perform TSSE in the future. CONCLUSIONS: Using ASICA for 12 months does not increase melanoma worry, can reduce anxiety and depression, and may improve quality of life. ASICA has the potential to improve the well-being and vigilance of survivors of melanoma and enable the benefits of regular TSSE. TRIAL REGISTRATION: ClinicalTrials.gov NCT03328247; https://clinicaltrials.gov/ct2/show/NCT03328247. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-019-3453-x.

Using a discrete choice experiment to develop a decision aid tool to inform the management of persistent pain in pharmacy: a protocol for a randomised feasibility study.

INTRODUCTION: In an era of personalised healthcare, it has become increasingly important to elicit individual-level preferences. While discrete choice experiments (DCEs) are widely used to measure patient preferences in the delivery of healthcare, the focus has been sample-level analysis. Using the DCE methodology, this project has designed a digital decision aid tool (DAT) with the potential to estimate individual preferences in real time to inform clinical consultation decisions in persistent pain management. METHODS: Using a feasibility randomised control trial, this study aims to assess the feasibility of using this Understanding Persistent Pain (UPP) DAT in a pharmacy-based clinical setting and to test processes for a future definite randomised trial. Community and practice-based pharmacists (up to 10) will be recruited in The National Health Service (NHS) Grampian and trained in the use of the digital UPP DAT. Pharmacists will recruit up to 60 patients who are living with persistent pain. Patients will be randomised to one of two groups: using the UPP DAT or usual care. Pharmacists will follow-up patients as needed according to clinical need and following standard practice. DCE response data collected by the UPP DAT will be analysed using the penalised logit model, allowing estimation of individual preferences in real time. We will follow-up pharmacists and patients who use the UPP DAT to gather feedback on their experiences. ETHICS AND DISSEMINATION: This study received ethical approval from the North of Scotland Research Ethics Committee (21/NS/0059) and received Research & Development Management Permission to proceed from NHS Grampian (2021UA003E). The study has been registered in the ClinicalTrials.gov database. Findings will be disseminated in peer-reviewed publications, presentations and newsletters and made available in the University of Aberdeen and Pharmacy Research UK websites. Participants gave informed consent to participate in the study before taking part. TRIAL REGISTRATION NUMBER: NCT05102578; clinicaltrials.gov.

Describing, predicting and explaining adherence to total skin self-examination (TSSE) in people with melanoma: a 12-month longitudinal study.

OBJECTIVES: To describe trajectories in melanoma survivors' adherence to monthly total skin self-examination (TSSE) over 12 months, and to investigate whether adherence trajectories can be predicted from demographic, cognitive or emotional factors at baseline. DESIGN: A longitudinal observational study nested within the intervention arm of the ASICA (Achieving Self-Directed Integrated Cancer Aftercare) randomised controlled trial. SETTING: Follow-up secondary care in Aberdeen and Cambridge UK. PARTICIPANTS: n=104 adults (48 men/56 women; mean age 58.83 years, SD 13.47, range 28-85 years; mean Scottish Index of Multiple Deprivation score 8.03, SD 1.73, range 2-10) who had been treated for stage 0-IIC primary cutaneous melanoma in the preceding 60 months and were actively participating in the intervention arm of the ASICA trial. INTERVENTIONS: All participants were using the ASICA intervention-a tablet-based intervention designed to support monthly TSSE. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was adherence to guideline recommended (monthly) TSSE over 12 months. This was determined from time-stamped TSSE data recorded by the ASICA intervention app. RESULTS: Latent growth mixture models identified three TSSE adherence trajectories (adherent -41%; drop-off -35%; non-adherent -24%). People who were non-adherent were less likely to intend to perform TSSE as recommended, intending to do it more frequently (OR=0.21, 95% CI 0.06 to 0.81, p=0.023) and were more depressed (OR=1.31, 95% CI 1.06 to 1.61, p=0.011) than people who were adherent. People whose adherence dropped off over time had less well-developed action plans (OR=0.78, 95% CI 0.63 to 0.96, p=0.016) and lower self-efficacy about TSSE (OR=0.92, 95% CI 0.86 to 0.99, p=0.028) than people who were adherent. CONCLUSIONS: Adherence to monthly TSSE in people treated for melanoma can be differentiated into adherent, drop-off and non-adherent trajectories. Collecting information about intentions to engage in TSSE, depression, self-efficacy and/or action planning at outset may help to identify those who would benefit from additional intervention. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT03328247).

Randomised controlled trial comparing the clinical and cost-effectiveness of various washout policies versus no washout policy in preventing catheter associated complications in adults living with long-term catheters: study protocol for the CATHETER II study.

BACKGROUND: Various washout policies are widely used in adults living with long-term catheters (LTC). There is currently insufficient evidence on the benefits and potential harms of prophylactic LTC washout policies in the prevention of blockages and other LTC-related adverse events, such as urinary tract infections. CATHETER II tests the hypothesis that weekly prophylactic LTC washouts (normal saline or citric acid) in addition to standard LTC care reduce the incidence of catheter blockage requiring intervention compared to standard LTC care only in adults living with LTC. METHODS: CATHETER II is a pragmatic three-arm open multi-centre superiority randomised controlled trial with an internal pilot, economic analysis, and embedded qualitative study. Eligible participants are adults aged ≥ 18 years, who have had a LTC in use for ≥ 28 days, have no plans to discontinue the use of the catheter, are able to undertake the catheter washouts, and complete trial documentation or have a carer able to help them. Participants are identified from general practitioner practices, secondary/tertiary care, community healthcare, care homes, and via public advertising strategies. Participants are randomised 1:1:1 to receive a weekly saline (0.9%) washout in addition to standard LTC care, a weekly citric acid (3.23%) washout in addition to standard LTC care or standard LTC care only. Participants and/or carers will receive training to administer the washouts. Patient-reported outcomes are collected at baseline and for 24 months post-randomisation. The primary clinical outcome is catheter blockage requiring intervention up to 24 months post-randomisation expressed per 1000 catheter days. Secondary outcomes include symptomatic catheter-associated urinary tract infection requiring antibiotics, catheter change, adverse events, NHS/ healthcare use, and impact on quality of life. DISCUSSION: This study will guide treatment decision-making and clinical practice guidelines regarding the effectiveness of various prophylactic catheter washout policies in men and women living with LTC. This research has received ethical approval from Wales Research Ethics Committee 6 (19/WA/0015). TRIAL REGISTRATION: ISRCTN ISRCTN17116445 . Registered prospectively on 06 November 2019.