Reporting and conducting patient journey mapping research in healthcare: A scoping review.

AIM: To identify how patient journey mapping is being undertaken and reported. DESIGN: A scoping review of the literature was undertaken using JBI guidance. DATA SOURCES: Databases were searched in July 2021 (16th-21st), including Ovid's Medline, Embase, Emcare and PsycINFO; Scopus; Web of Science Core Collection, the Directory of Open Access Journals; Informit and; ProQuest Dissertations and Theses Global. REVIEW METHODS: Eligible articles included peer-reviewed literature documenting journey mapping methodologies and studies conducted in healthcare services. Reviewers used Covidence to screen titles and abstracts of located sources, and to screen full-text articles. A table was used to extract data and synthesize results. RESULTS: Eighty-one articles were included. An acceleration of patient journey mapping research was observed, with 76.5% (n = 62) of articles published since 2015. Diverse mapping approaches were identified. Reporting of studies was inconsistent and largely non-adherent with relevant, established reporting guidelines. CONCLUSION: Patient journey mapping is a relatively novel approach for understanding patient experiences and is increasingly being adopted. There is variation in process details reported. Considerations for improving reporting standards are provided. IMPACT: Patient journey mapping is a rapidly growing approach for better understanding how people enter, experience and exit health services. This type of methodology has significant potential to inform new, patient centred models of care and facilitate clinicians, patients and health professionals to better understand gaps and strategies in health services. The synthesised results of this review alert researchers to options available for journey mapping research and provide preliminary guidance for elevating reporting quality.

Long-term survival after low-dose-rate brachytherapy for prostate cancer: the Royal Surrey experience.

OBJECTIVES: To assess the long-term treatment efficacy of low-dose-rate (LDR) brachytherapy for the treatment of localized prostate cancer. PATIENTS AND METHODS: Cause-of-death annotation in our prospective database was supplemented with death certificate information obtained via an internal audit of patients treated from 1999 to 2017 with LDR prostate brachytherapy as monotherapy or as combination with androgen deprivation therapy and/or external beam radiotherapy. Overall and disease-specific survival were the primary outcomes, estimated with Kaplan-Meier and competing risks multi-state models. Clinical variables influencing mortality were assessed with Cox proportional hazards regression in a sub-analysis of men to assess the predictive value of prostate-specific antigen (PSA) level at 48 months post implant. RESULTS: The audit process began in October 2017 and culminated in June 2020 with a curated series of 2936 patients. All-cause and prostate cancer-specific death prevalence were 11% and 2.9%, respectively. The median (range) follow-up time was 10 (3-21) years and the median (range) time to death from any cause was 9 (3-21) years. At 15 years post implant the overall and prostate cancer-specific survival probability were 81% and 95%, respectively. The 15-year cumulative incidence rates of death not due and due to prostate cancer were 14% and 5%, respectively. A greater risk of death due to prostate cancer was conferred by increasing age at therapy (hazard ratio [HR] 1.1, P < 0.001), advanced clinical stages relative to T1a-T2a (HR 1.9, P = 0.048 for T2b; HR 2.7, P = 0.023 for T2c-T3b) and a 48-month PSA level >1.0 ng/mL (HR 6.8, P < 0.001). CONCLUSION: This study constitutes the largest retrospective analyses of long-term mortality outcomes from prospectively collected prostate brachytherapy data and confirms the excellent treatment efficacy of LDR prostate brachytherapy for localized prostate cancer. T2 clinical stage subdivisions and 48-month PSA level >1.0 ng/mL appear to be strong indicators of prostate cancer-related survival.

Robot-assisted salvage seminal vesicle excision for isolated recurrence after low-dose-rate prostate brachytherapy.

OBJECTIVES: To report clinical and functional outcomes for patients who have undergone salvage robot-assisted seminal vesicle excision (RA-SVE) for the focal treatment of isolated seminal vesical (SV) recurrence after treatment for prostate cancer by low-dose-rate brachytherapy. PATIENTS AND METHODS: Patients with rising prostate-specific antigen (PSA) after low-dose-rate prostate brachytherapy (LDR-PB) underwent multi-parametric magnetic resonance imaging (mp-MRI) of the prostate and 11 C-Choline or 68 Ga-prostate-specific membrane antigen (68 Ga-PSMA) positron emission tomography/computed tomography (PET/CT) scan, followed by targeted transperineal biopsy of the prostate and SVs. Isolated SV recurrence were identified in 17 (0.38%) LDR-PB patients. These 17 patients were offered RA-SVE. RESULTS: The median total operative time was 90 min and blood loss 50 mL with no postoperative transfusions required. The median hospital stay was 1 day. No intra- or postoperative complications were documented. Continence status was unaffected, no patient required urinary pads. Postoperative pathology confirmed SV invasion in all specimens. Surgical margins were positive in seven (41%) patients. All patients had at least one positive imaging study, although three (18%) mp-MRI and five (29%) PET/CT assessments were negative. One (6%) pre-SVE biopsy was also negative but with positive imaging. Salvage SVE failure, defined as three consecutive PSA rises or the need for further treatment, occurred in six patients of whom three had a positive margin. Overall failure-free survival rates were 86%, 67%, and 53% at 1, 2, and 3 years after SVE, respectively. CONCLUSIONS: Salvage RA-SVE appears to be a safe focal treatment, with very low morbidity, for patients with localised SV recurrence after LDR-PB. It permits deferral of androgen deprivation therapy in selected patients. Bilateral SVE is mandatory. This surgical option should be considered in patients with isolated prostate cancer recurrence to the SV.

Hemi-ablative low-dose-rate prostate brachytherapy for unilateral localised prostate cancer.

OBJECTIVES: To report clinical outcomes of the Hemi-Ablative Prostate Brachytherapy (HAPpy) trial evaluating treatment-related toxicity and effectiveness of hemi-gland (HG) low-dose-rate (LDR) prostate brachytherapy as a focal approach to control unilateral localised prostate cancer. PATIENTS AND METHODS: Single institution phase IIS pilot study of patients treated with focal 4D Brachytherapy™ (BXTAccelyon, Burnham, Buckinghamshire, UK). The primary outcome was patient-reported toxicity 24 months after implant. The secondary outcome was assessment of disease control. Outcomes in HG patients were compared to whole-gland (WG) controls obtained from our prospective cohort registry by negative binomial and linear regression models. RESULTS: Pre-treatment demography was similar between the 30 HG patients and 362 WG controls. Post-implant dosimetry was similar for the prostate gland target volumes and significantly reduced for the urethra and bowel in HG patients relative to WG controls, but this did not translate into a difference in post-implant mean symptom scores between the two groups. Nevertheless, the change in score from baseline indicated that the impact on pre-treatment symptom status was less after HG implants. Only HG patients showed a return to baseline urinary scores as early as 12 months. Sexual potency was conserved in 73% and 67% of HG and WG patients, respectively (P = 0.84). Post-implant prostate-specific antigen (PSA) kinetics revealed that baseline PSA was reduced at 24 months by 78% and 88% in HG and WG patients, respectively (P < 0.05). Treatment relapse occurred in one (3%) HG patient 55 months after implant and in nine (3%) WG patients at 32-67 months after implant. CONCLUSION: This pilot study suggests that treatment-related toxicity and biochemical outcomes after HG implants are broadly similar to those observed with WG treatment despite the lower dose delivered by HG implants.

Long-term oncological outcomes and toxicity in 597 men aged ≤60 years at time of low-dose-rate brachytherapy for localised prostate cancer.

OBJECTIVES: To report oncological and functional outcomes of men treated with low-dose-rate (LDR) prostate brachytherapy aged ≤60 years at time of treatment. PATIENTS AND METHODS: Of 3262 patients treated with LDR brachytherapy at our centre up to June 2016, we retrospectively identified 597 patients aged ≤60 years at treatment with ≥3-years post-implantation follow-up and four prostate-specific antigen (PSA) measurements, of which one was at baseline. Overall survival (OS), prostate cancer-specific survival (PCSS) and relapse free survival (RFS) were analysed together with prospectively collected physician-reported adverse events and patient-reported symptom scores. RESULTS: The median (range) age was 57 (44-60) years, follow-up was 8.9 (1.5-17.2) years, and PSA follow-up 5.9 (0.8-15) years. Low-, intermediate- and high-risk disease represented 53%, 37% and 10% of the patients, respectively. At 10 years after implantation OS and PCSS were 98% and 99% for low-risk, 99% and 100% for intermediate-risk, and 93% and 95% for high-risk disease, respectively. At 10 years after implantation RFS, using the PSA level nadir plus 2 ng/mL definition, was 95%, 90% and 87% for low-, intermediate-, and high-risk disease, respectively. Urinary stricture was the most common genitourinary adverse event occurring in 19 patients (3.2%). At 5 years after implantation erectile function was preserved in 75% of the patients who were potent before treatment. CONCLUSION: LDR brachytherapy is an effective treatment with long-term control of prostate cancer in men aged ≤60 years at time of treatment. It was associated with low rates of treatment-related toxicity and can be considered a first-line treatment for prostate cancer in this patient group.

Low-dose-rate brachytherapy for the treatment of localised prostate cancer in men with a high risk of disease relapse.

OBJECTIVES: To report clinical outcomes of 125 I low-dose-rate prostate brachytherapy (LDR-PB) as monotherapy or combined with androgen-deprivation therapy (ADT) and/or external beam radiotherapy (EBRT) in high-risk localised prostate cancer. PATIENTS AND METHODS: Analysis of clinical outcomes from a prospective cohort of patients treated with LDR-PB alone or combined treatment in a single institution. Men with a high risk of disease relapse were identified by the National Institute for Health and Care Excellence (NICE) criteria or by the National Comprehensive Cancer Network (NCCN) criteria. Relapse-free survival (RFS), overall survival (OS), prostate cancer-specific survival (PCSS), and metastases-free survival (MFS), were analysed together with patient-reported symptom scores and physician-reported adverse events. RESULTS: The NICE and NCCN criteria identified 267 and 202 high-risk patients, respectively. NICE-defined patients had significantly lower pre-treatment PSA levels, Gleason scores <7, and a greater proportion of patients who received LDR-PB monotherapy. At 9 years after implantation RFS was 89% and 87% in the NICE and NCCN groups, respectively (log-rank P = 0.637), and OS 93% and 94%, respectively (log-rank P = 0.481). All of the survival estimates were similar between LDR-PB monotherapy and combined therapies. Cox proportional hazards regression confirmed RFS was similar between the treatment types. Treatment-related toxicity was also similar between the treatment methods. CONCLUSION: LDR-PB is effective at controlling localised prostate cancer in patients with a high risk of disease relapse. As the present study was not randomised, it is not possible to define those patients who need the addition of ADT and/or EBRT. However, the NICE criteria appear suitable to define treatment options where patients could benefit from LDR-PB as monotherapy or combined treatment. This choice should be discussed with the patient taking into account comorbidities and presence of multiple high-risk factors.

Accelerated versus standard epirubicin followed by cyclophosphamide, methotrexate, and fluorouracil or capecitabine as adjuvant therapy for breast cancer in the randomised UK TACT2 trial (CRUK/05/19): a multicentre, phase 3, open-label, randomised, controlled trial.

BACKGROUND: Adjuvant chemotherapy for early breast cancer has improved outcomes but causes toxicity. The UK TACT2 trial used a 2×2 factorial design to test two hypotheses: whether use of accelerated epirubicin would improve time to tumour recurrence (TTR); and whether use of oral capecitabine instead of cyclophosphamide would be non-inferior in terms of patients' outcomes and would improve toxicity, quality of life, or both. METHODS: In this multicentre, phase 3, randomised, controlled trial, we enrolled patients aged 18 years or older from 129 UK centres who had histologically confirmed node-positive or high-risk node-negative operable breast cancer, had undergone complete excision, and were due to receive adjuvant chemotherapy. Patients were randomly assigned to receive four cycles of 100 mg/m2 epirubicin either every 3 weeks (standard epirubicin) or every 2 weeks with 6 mg pegfilgrastim on day 2 of each cycle (accelerated epirubicin), followed by four 4-week cycles of either classic cyclophosphamide, methotrexate, and fluorouracil (CMF; 600 mg/m2 cyclophosphamide intravenously on days 1 and 8 or 100 mg/m2 orally on days 1-14; 40 mg/m2 methotrexate intravenously on days 1 and 8; and 600 mg/m2 fluorouracil intravenously on days 1 and 8 of each cycle) or four 3-week cycles of 2500 mg/m2 capecitabine (1250 mg/m2 given twice daily on days 1-14 of each cycle). The randomisation schedule was computer generated in random permuted blocks, stratified by centre, number of nodes involved (none vs one to three vs four or more), age (≤50 years vs >50 years), and planned endocrine treatment (yes vs no). The primary endpoint was TTR, defined as time from randomisation to first invasive relapse or breast cancer death, with intention-to-treat analysis of standard versus accelerated epirubicin and per-protocol analysis of CMF versus capecitabine. This trial is registered with ISRCTN, number 68068041, and with ClinicalTrials.gov, number NCT00301925. FINDINGS: From Dec 16, 2005, to Dec 5, 2008, 4391 patients (4371 women and 20 men) were recruited. At a median follow-up of 85·6 months (IQR 80·6-95·9) no significant difference was seen in the proportions of patients free from TTR events between the accelerated and standard epirubicin groups (overall hazard ratio [HR] 0·94, 95% CI 0·81-1·09; stratified p=0·42). At 5 years, 85·9% (95% CI 84·3-87·3) of patients receiving standard epirubicin and 87·1% (85·6-88·4) of those receiving accelerated epirubicin were free from TTR events. 4358 patients were included in the per-protocol analysis, and no difference was seen in the proportions of patients free from TTR events between the CMF and capecitabine groups (HR 0·98, 95% CI 0·85-1.14; stratified p=0·00092 for non-inferiority). Compared with baseline, significantly more patients taking CMF than those taking capecitabine had clinically relevant worsening of quality of life at end of treatment (255 [58%] of 441 vs 235 [50%] of 475; p=0·011) and at 12 months (114 [34%] of 334 vs 89 [22%] of 401; p<0·001 at 12 months) and had worse quality of life over time (p<0·0001). Detailed toxicity and quality-of-life data were collected from 2115 (48%) of treated patients. The most common grade 3 or higher adverse events in cycles 1-4 were neutropenia (175 [16%]) and fatigue (56 [5%]) of the 1070 patients treated with standard epirubicin, and fatigue (63 [6%]) and infection (34 [3%]) of the 1045 patients treated with accelerated epirubicin. In cycles 5-8, the most common grade 3 or higher adverse events were neutropenia (321 [31%]) and fatigue (109 [11%]) in the patients treated with CMF, and hand-foot syndrome (129 [12%]) and diarrhoea (67 [6%]) in the 1044 patients treated with capcitabine. INTERPRETATION: We found no benefit from increasing the dose density of the anthracycline component of chemotherapy. However, capecitabine could be used in place of CMF without significant loss of efficacy and with improved quality of life. FUNDING: Cancer Research UK, Amgen, Pfizer, and Roche.

Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial.

BACKGROUND: Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone. METHODS: Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m(2)) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544). FINDINGS: 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60-71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6%) men were previously treated with local therapy, and median prostate-specific antigen was 65 ng/mL (IQR 23-184). Median follow-up was 43 months (IQR 30-60). There were 415 deaths in the control group (347 [84%] prostate cancer). Median overall survival was 71 months (IQR 32 to not reached) for SOC-only, not reached (32 to not reached) for SOC + ZA (HR 0·94, 95% CI 0·79-1·11; p=0·450), 81 months (41 to not reached) for SOC + Doc (0·78, 0·66-0·93; p=0·006), and 76 months (39 to not reached) for SOC + ZA + Doc (0·82, 0·69-0·97; p=0·022). There was no evidence of heterogeneity in treatment effect (for any of the treatments) across prespecified subsets. Grade 3-5 adverse events were reported for 399 (32%) patients receiving SOC, 197 (32%) receiving SOC + ZA, 288 (52%) receiving SOC + Doc, and 269 (52%) receiving SOC + ZA + Doc. INTERPRETATION: Zoledronic acid showed no evidence of survival improvement and should not be part of standard of care for this population. Docetaxel chemotherapy, given at the time of long-term hormone therapy initiation, showed evidence of improved survival accompanied by an increase in adverse events. Docetaxel treatment should become part of standard of care for adequately fit men commencing long-term hormone therapy. FUNDING: Cancer Research UK, Medical Research Council, Novartis, Sanofi-Aventis, Pfizer, Janssen, Astellas, NIHR Clinical Research Network, Swiss Group for Clinical Cancer Research.

Modified transurethral resection of the prostate (TURP) for men with moderate lower urinary tract symptoms (LUTS) before brachytherapy is safe and feasible.

OBJECTIVE: To report the urinary toxicity outcomes for patients at greater risk of voiding symptoms and retention who received a modified limited transurethral resection of the prostate (TURP) before low-dose rate (LDR) brachytherapy. PATIENTS AND METHOD: Data were analysed from patients receiving the above procedures between 2006 to present, taken from the prospective brachytherapy database of 2000 patients at the St. Luke's Cancer Centre. The limited TURP (TURP(BXT) ) was performed at a median (range) of 64 (25-205) days before seed implantation with a median resection weight of 1.15 g. Selection criteria were based on patients with moderate lower urinary tract symptoms, poor flow or post-void residual urine volume (PVR), or a prominent middle lobe or high bladder neck on transrectal ultrasonography. Baseline prostate cancer characteristics, uroflowmetry, International Prostate Symptom Score (IPSS) and quality-of-life QoL scores were collected and compared with follow-up IPSS and QoL scores. RESULTS: Data for 112 patients was gathered from the database. The TURP(BXT) resulted in statistically significant improvements before LDR brachytherapy in maximum urinary flow rate (Qmax ) and PVR, IPSS and QoL scores (the mean Qmax before vs after the TURP(BXT) was 11.3 vs 16.7 mL/s). The IPSS and QoL scores at 6 months after seed implantation were increased compared with baseline values before the TURP(BXT) (mean IPSS at 6 months 11.7 vs 9.2 before TURP(BXT) ), but no difference at 1 year (mean IPSS 9), and improved scores at 2, 3, 4 and 5 years follow-up (mean IPSS of 7.9, 5.6, 5.3 and 7.4, respectively). CONCLUSION: The present study suggests patients at increased risk of deteriorating voiding symptoms, including urinary retention, are no longer contraindicated against LDR brachytherapy if they receive a modified TURP before seed implantation. This procedure does not appear to carry the risk of urinary incontinence thought to be associated with a conventional TURP before LDR brachytherapy.

Effects of the addition of gemcitabine, and paclitaxel-first sequencing, in neoadjuvant sequential epirubicin, cyclophosphamide, and paclitaxel for women with high-risk early breast cancer (Neo-tAnGo): an open-label, 2×2 factorial randomised phase 3 trial.

BACKGROUND: Anthracyclines and taxanes have been the standard neoadjuvant chemotherapies for breast cancer in the past decade. We aimed to assess safety and efficacy of the addition of gemcitabine to accelerated paclitaxel with epirubicin and cyclophosphamide, and also the effect of sequencing the blocks of epirubicin and cyclophosphamide and paclitaxel (with or without gemcitabine). METHODS: In our randomised, open-label, 2×2 factorial phase 3 trial (Neo-tAnGo), we enrolled women (aged >18 years) with newly diagnosed breast cancer (tumour size >20 mm) at 57 centres in the UK. Patients were randomly assigned via a central randomisation procedure to epirubicin and cyclophosphamide then paclitaxel (with or without gemcitabine) or paclitaxel (with or without gemcitabine) then epirubicin and cyclophosphamide. Four cycles of each component were given. The primary endpoint was pathological complete response (pCR), defined as absence of invasive cancer in the breast and axillary lymph nodes. This study is registered with EudraCT (2004-002356-34), ISRCTN (78234870), and ClinicalTrials.gov (NCT00070278). FINDINGS: Between Jan 18, 2005, and Sept 28, 2007, we randomly allocated 831 participants; 207 received epirubicin and cyclophosphamide then paclitaxel; 208 were given paclitaxel then epirubicin and cyclophosphamide; 208 had epirubicin and cyclophosphamide followed by paclitaxel and gemcitabine; and 208 received paclitaxel and gemcitabine then epirubicin and cyclophosphamide. 828 patients were eligible for analysis. Median follow-up was 47 months (IQR 37-51). 207 (25%) patients had inflammatory or locally advanced disease, 169 (20%) patients had tumours larger than 50 mm, 413 (50%) patients had clinical involvement of axillary nodes, 276 (33%) patients had oestrogen receptor (ER)-negative disease, and 191 (27%) patients had HER2-positive disease. Addition of gemcitabine did not increase pCR: 70 (17%, 95% CI 14-21) of 404 patients in the epirubicin and cyclophosphamide then paclitaxel group achieved pCR compared with 71 (17%, 14-21) of 408 patients who received additional gemcitabine (p=0·98). Receipt of a taxane before anthracycline was associated with improved pCR: 82 (20%, 95% CI 16-24) of 406 patients who received paclitaxel with or without gemcitabine followed by epirubicin and cyclophosphamide achieved pCR compared with 59 (15%, 11-18) of 406 patients who received epirubicin and cyclophosphamide first (p=0·03). Grade 3 toxicities were reported at expected levels: 173 (21%) of 812 patients who received treatment and had full treatment details had grade 3 neutropenia, 66 (8%) had infection, 41 (5%) had fatigue, 41 (5%) had muscle and joint pains, 37 (5%) had nausea, 36 (4%) had vomiting, 34 (4%) had neuropathy, 23 (3%) had transaminitis, 16 (2%) had acute hypersensitivity, and 20 (2%) had a rash. 86 (11%) patients had grade 4 neutropenia and 3 (<1%) had grade 4 infection. INTERPRETATION: Although addition of gemcitabine to paclitaxel and epirubicin and cyclophosphamide chemotherapy does not improve pCR, sequencing chemotherapy so that taxanes are received before anthracyclines could improve pCR in standard neoadjuvant chemotherapy for breast cancer. FUNDING: Cancer Research UK, Eli Lilly, Bristol-Myers Squibb.

Does prostate HistoScanning™ play a role in detecting prostate cancer in routine clinical practice? Results from three independent studies.

OBJECTIVES: To evaluate the ability of prostate HistoScanning™ (PHS; Advanced Medical Diagnostics, Waterloo, Belgium) to detect, characterize and locally stage prostate cancer, by comparing it with transrectal ultrasonography (TRUS)-guided prostate biopsies, transperineal template prostate biopsies (TTBs) and whole-mount radical prostatectomy specimens. SUBJECTS AND METHODS: Study 1. We recruited 24 patients awaiting standard 12-core TRUS-guided biopsies of the prostate to undergo PHS immediately beforehand. We compared PHS with the TRUS-guided biopsy results in terms of their ability to detect cancer within the whole prostate and to localize it to the correct side and to the correct region of the prostate. Lesions that were suspicious on PHS were biopsied separately. Study 2. We recruited 57 patients awaiting TTB to have PHS beforehand. We compared PHS with the TTB pathology results in terms of their ability to detect prostate cancer within the whole gland and to localize it to the correct side and to the correct sextant of the prostate. Study 3. We recruited 24 patients awaiting radical prostatectomy for localized prostate cancer to undergo preoperative PHS. We compared PHS with standardized pathological analysis of the whole-mount prostatectomy specimens in terms of their measurement of total tumour volume within the prostate, tumour volume within prostate sextants and volume of index lesions identified by PHS. RESULTS: The PHS-targeted biopsies had an overall cancer detection rate of 38.1%, compared with 62.5% with standard TRUS-guided biopsies. The sensitivity and specificity of PHS for localizing tumour to the correct prostate sextant, compared with standard TRUS-guided biopsies, were 100 and 5.9%, respectively. The PHS-targeted biopsies had an overall cancer detection rate of 13.4% compared with 54.4% for standard TTB. PHS had a sensitivity and specificity for cancer detection in the posterior gland of 100 and 13%, respectively, and for the anterior gland, 6 and 82%, respectively. We found no correlation between total tumour volume estimates from PHS and radical prostatectomy pathology (Pearson correlation coefficient -0.096). Sensitivity and specificity of PHS for detecting tumour foci ≥0.2 mL in volume were 63 and 53%. CONCLUSIONS: These three independent studies in 105 patients suggest that PHS does not reliably identify and characterize prostate cancer in the routine clinical setting.

4D Brachytherapy, a novel real-time prostate brachytherapy technique using stranded and loose seeds.

What's known on the subject? and What does the study add? There are a number of techniques used successfully to perform brachytherapy, including 2-stage procedures and realtime techniques using loose seeds. This study demonstrates a one-stage realtime brachytherapy technique using stranded seeds with improved time efficiency and clinical outcome: 4D Brachytherapy. This paper reviews the development of a new one-stage prostate brachytherapy technique (4D Brachytherapy) using a combination of stranded and loose seeds. This novel technique utilizes a nomogram constructed from over 1000 procedures to calculate the seed requirement in advance of the implant. This allows stranded seeds to be pre-ordered and loaded prior to the procedure rather than per-operatively, resulting in a more efficient use of operating room time. The use of both stranded and loose seeds may reduce the risk of migration from peripherally placed seeds via the venous plexus, whilst maintaining the flexibility to optimize the dose within the prostate and especially at the apex of the gland. Prospectively collected data show significantly improved dosimetry: median D(90) 143 and 153 Gy (P < 0.005) and median V(100) 88% and 93% (P < 0.005) for the Seattle technique and 4D Brachytherapy implant technique, respectively. Also there was a reduced short-term urinary morbidity as assessed by the change in International Prostate Symptom Score (IPSS) at 3 months and 1 year compared with the Seattle technique. Mean (sd) change in IPSS from baseline at 1 year was 2.73 (5.92) and 0.97 (5.10) for the Seattle and 4D Brachytherapy series, respectively (P < 0.049).

A prospective, randomized pilot study evaluating the effects of metformin and lifestyle intervention on patients with prostate cancer receiving androgen deprivation therapy.

UNLABELLED: Study Type - Therapy (RCT) Level of Evidence 1b What's known on the subject? and What does the study add? Men with prostate cancer have higher rates of non-cancer mortality and CV morbidity and some of that excess risk has been attributed to the treatment they receive. ADT is an established treatment option for men with locally-advanced and metastatic prostate cancer and, although it has been shown to confer a disease-free survival advantage, it has also been associated with an increased incidence of CV disease and the metabolic syndrome (characterized by a cluster of CV risk factors, including insulin resistance). The benefits of the insulin sensitizer metformin and lifestyle intervention for reducing the incidence of metabolic syndrome have been shown in patients with impaired glucose tolerance. At the time of writing, the present study is the first to use metformin and lifestyle intervention in men with prostate cancer with the aim of reducing the risk of developing ADT-related CV morbidity and the metabolic syndrome. The study shows that lifestyle changes and metformin may indeed reduce the complications of androgen suppression in these men. Although further investigations are needed to establish which of the two interventions may be most beneficial, the favourable effects of a combination of these interventions on patients' quality of life and the potential for improved overall survival are of clinical significance. OBJECTIVE: To investigate the effects of metformin and lifestyle changes on the development of androgen deprivation therapy (ADT)-related metabolic syndrome. PATIENTS AND METHODS: Men with prostate cancer due to receive ADT were recruited and randomized. Controls received ADT alone. Men in the intervention arm received ADT with 6 months of metformin, a low glycaemic index diet and an exercise programme. All patients were investigated pretreatment and at 6 months for the metabolic syndrome, as well as for related biochemical and physical parameters. RESULTS: In total, 40 men were recruited and randomized (20 to each arm). After 6 months, significant improvements in abdominal girth (P= 0.05), weight (P < 0.001), body mass index (P < 0.001) and systolic blood pressure (P= 0.01) were seen in the intervention arm compared to controls. Biochemical markers of insulin resistance did not differ significantly. CONCLUSIONS: The present study shows the potential benefits of metformin and lifestyle changes in ADT-treated men. Further studies will aim to determine which intervention is most important, and may show that overall survival can be improved.

Long-term toxicity and quality of life up to 10 years after low-dose rate brachytherapy for prostate cancer.

OBJECTIVE: To report on the long-term toxicity outcome for patients with prostate cancer treated by low-dose rate (LDR) brachytherapy (BXT). PATIENTS AND METHODS: The study population comprised a cohort of men treated in our centre between March 1999 and April 2004 with LDR BXT for prostate cancer who had at least 5 years of follow-up post-implant. Patients who had died or experienced biochemical failure were excluded. We contacted eligible patients and asked them to complete a questionnaire to assess current urinary, erectile and bowel function. Urinary and erectile function was compared pre- and post-treatment and outcomes were assessed by treatment modality. RESULTS: Of the 226 LDR BXT-treated patients with >5 years of follow-up, 174 (77.0%) responded to the questionnaire. The mean International Prostate Symptom Score (IPSS) increased from 6.70 pre-BXT to 7.91 at follow-up (P = 0.003). Of the patients with mild symptoms pre-BXT (IPSS, 0-7), 64.2% retained mild symptoms at follow-up, 31.2% developed moderate symptoms (IPSS, 8-9) and 4.6% reported severe symptoms (IPSS, 20-35). A good or acceptable quality of life (QoL) secondary to urinary symptoms (IPSS QoL, 0-4) was reported by 98.0% of respondents. Of those patients potent (International Index of Erectile Function-5 ≥11) pre-BXT, 62.9% remained potent at follow-up. There were no differences in the proportion of patients who were potent when analyzed by the number of years post-implant. At follow-up, 51.7% and 45.4% of patients, respectively, had normal or mild bowel symptoms as indicated by the European Organisation for the Research and Treatment of Cancer questionnaire (QLQ-C30/PR25 scores, 4-8). Moderate bowel symptoms (QLQ-C30/PR25 scores, 9-12) were reported by 2.9% of respondents; none reported severe symptoms. CONCLUSION: The present study shows low morbidity after LDR BXT over the long-term for a large cohort of patients.

Trends in missed presentations and late HIV diagnosis in a UK teaching hospital: a retrospective comparative cohort study.

BACKGROUND: Late diagnosis is an important cause of HIV-related morbidity, mortality and healthcare costs in the UK and undiagnosed infection limits efforts to reduce transmission. National guidelines provide recommendations to increase HIV testing in all healthcare settings. We evaluated progress towards these recommendations by comparing missed opportunities for HIV testing and late diagnosis in two six year cohorts from North East Scotland. METHODS: We reviewed diagnostic pathways of all patients newly diagnosed with HIV referred to infectious diseases and genito-urinary medicine services between 1995 and 2000 (n=48) and 2004 to 2009 (n=117). Missed presentations (failure to diagnose≤1 month of a clinical or non-clinical indicator for testing), late diagnosis (CD4<350 cells/mm3), and time to diagnosis (months from first presentation to diagnosis) were compared between cohorts using χ2 and log-rank tests. Determinants of missed presentation were explored by multivariate logistic regression. Breslow-Day tests assessed change in diagnostic performance by patient subgroup. RESULTS: There were significant decreases in missed presentations (33% to 17%; P=0.02) and time to diagnosis (mean 17 months to 4 months; P=0.005) but not in late diagnosis (56% vs. 60%; P=0.57) between earlier and later cohorts. In the later cohort patients were significantly more likely to have acquired HIV abroad and presented with early HIV disease, and testing was more likely to be indicated by transmission risk or contact with GUM services than by clinical presentation. Missed presentation remained significantly less likely in the later cohort (OR=0.28, 95% CI 0.11 to 0.72; P=0.008) after adjustment for age, transmission risks and number of clinical indicators. Reductions in missed presentation were greater in patients<40 years, of non-UK origin, living in least deprived neighbourhoods and with early disease at presentation (P<0.05). 27% of missed presentations occurred in primary care and 46% in general secondary care. CONCLUSIONS: While early diagnosis has improved in epidemiological risk groups, clinical indications for HIV testing continue to be missed, particularly in patients who are older, of UK origin and from more deprived communities. Increasing testing in non-specialist services is a priority.

Reporting of patient journey mapping in current literature: a scoping review protocol.

OBJECTIVE: This scoping review will assess the literature that documents or utilizes patient journey mapping methodologies in health care settings. It will also examine the reporting processes of studies that use this methodology. INTRODUCTION: Health care systems are complex and can be challenging for patients to navigate. Using patient journey mapping as a research method promotes a deeper understanding of patient experiences when navigating these systems. Patient journey mapping provides valuable insights into where systems are working well, where gaps in care exist, and how the system could respond to these gaps. INCLUSION CRITERIA: This review will consider peer-reviewed articles and publicly available academic literature documenting patient journey mapping methodologies. The review will also consider studies providing guidance and recommendations on how to report patient journey mapping studies in health care services and systems. METHODS: The proposed review will follow JBI guidance for scoping reviews. The following databases will be searched: MEDLINE, Embase, Emcare, PsycINFO, Scopus, Web of Science Core Collection, the Directory of Open Access Journals, Informit, and ProQuest Dissertations and Theses Global. The search will not be limited to year of publication but will be limited to studies reported in English. The PRISMA-ScR extension will be used to document the literature search. Two reviewers will screen titles, abstracts, and full-text articles. An extraction table will be used to extract relevant data from all included articles and to facilitate data analysis.

Imaging Modality and Frequency in Surveillance of Stage I Seminoma Testicular Cancer: Results From a Randomized, Phase III, Noninferiority Trial (TRISST).

PURPOSE: Survival in stage I seminoma is almost 100%. Computed tomography (CT) surveillance is an international standard of care, avoiding adjuvant therapy. In this young population, minimizing irradiation is vital. The Trial of Imaging and Surveillance in Seminoma Testis (TRISST) assessed whether magnetic resonance images (MRIs) or a reduced scan schedule could be used without an unacceptable increase in advanced relapses. METHODS: A phase III, noninferiority, factorial trial. Eligible participants had undergone orchiectomy for stage I seminoma with no adjuvant therapy planned. Random assignment was to seven CTs (6, 12, 18, 24, 36, 48, and 60 months); seven MRIs (same schedule); three CTs (6, 18, and 36 months); or three MRIs. The primary outcome was 6-year incidence of Royal Marsden Hospital stage ≥ IIC relapse (> 5 cm), aiming to exclude increases ≥ 5.7% (from 5.7% to 11.4%) with MRI (v CT) or three scans (v 7); target N = 660, all contributing to both comparisons. Secondary outcomes include relapse ≥ 3 cm, disease-free survival, and overall survival. Intention-to-treat and per-protocol analyses were performed. RESULTS: Six hundred sixty-nine patients enrolled (35 UK centers, 2008-2014); mean tumor size was 2.9 cm, and 358 (54%) were low risk (< 4 cm, no rete testis invasion). With a median follow-up of 72 months, 82 (12%) relapsed. Stage ≥ IIC relapse was rare (10 events). Although statistically noninferior, more events occurred with three scans (nine, 2.8%) versus seven scans (one, 0.3%): 2.5% absolute increase, 90% CI (1.0 to 4.1). Only 4/9 could have potentially been detected earlier with seven scans. Noninferiority of MRI versus CT was also shown; fewer events occurred with MRI (two [0.6%] v eight [2.6%]), 1.9% decrease (-3.5 to -0.3). Per-protocol analyses confirmed noninferiority. Five-year survival was 99%, with no tumor-related deaths. CONCLUSION: Surveillance is a safe management approach-advanced relapse is rare, salvage treatment successful, and outcomes excellent, regardless of imaging frequency or modality. MRI can be recommended to reduce irradiation; and no adverse impact on long-term outcomes was seen with a reduced schedule.

Introducing the Needs in Recovery Assessment (NiRA) into clinical practice: protocol for a pilot study investigating the formal and systematic assessment of clinical and social needs experienced by service users at a tertiary, metropolitan mental health service.

BACKGROUND: The Needs in Recovery Assessment (NiRA) is a newly developed needs assessment tool, designed to identify the needs of people recovering from mental illness. This tool has been evaluated outside of the clinical context for validity and reliability. The aim of this study is to introduce the NiRA into clinical practice and to evaluate the value of the NiRA as an adjunct to service delivery from the perspectives of stakeholders and to evaluate the barriers and facilitators of embedding the NiRA in a mental health service. METHODS: The establishment of the NiRA in a tertiary mental health unit over a 6-month period will be evaluated using a multi-methods approach. Quantitative data will be collected using the NiRA itself and the Recovery Self-Assessment (RSA). Face-to-face interviews with service users and clinicians will be conducted following the initial completion of the NiRA, with a follow-up interview for service users on discharge from the service. Regular informal follow-up with clinicians throughout the study will support the introduction of the NiRA. Descriptive statistics will be used to analyse quantitative data, and descriptive qualitative methods will be used to analyse data from interviews. DISCUSSION: Aligning mental health services with recovery-oriented frameworks of care is imperative. The NiRA is a tool that has been designed in accordance with recovery principles and may assist services to be more recovery-oriented. If the NiRA is able to achieve the aims and objectives of this project, a larger implementation study will be conducted. Trial registration Australian and New Zealand Clinical Trial Registry (ANZCTR), ACTRN12621000316808.

Responding to catastrophe: A case study of learning from perinatal death in midwifery practice.

PROBLEM/BACKGROUND: Perinatal death has far reaching emotional effects for all involved in this devastating event. The opportunity for learning as a result of this catastrophe, however, remains unexplored. AIM: To explore midwives' experiences of caring through, and learning from, perinatal death, to better inform the effective planning and delivery of education that optimises both midwifery and self-care. METHODS: A naturalistic interpretive multiple case study design. Seventeen midwives, located in Australia, participated in an online group activity hosted as a blog, followed by telephonic focus groups and in-depth email interviews. FINDINGS: Thematic data analysis revealed seven major themes: Grappling with the reality of perinatal death; Struggling with personal and professional heartache; Seeking the space to grieve as a professional; Being with the woman and her family; Finding a new purpose; Strengthened through support; and Developing the courage to care. DISCUSSION: The initial turmoil and impact of loss reflected the catastrophic nature of perinatal death. Midwives uncovered a journey to acceptance and learning, realising a determination to enhance expertise and discovering value in experiential knowledge. Insecurity regarding competence and confidence to manage perinatal death and bereavement care was highlighted. However, sharing their stories revealed professional fulfilment, personal strength, and solidarity amongst midwives who have endured similar experiences. CONCLUSION: A coordinated approach to support and the dissemination of experiential knowledge and learning could be developed within an online model of narrative sharing and discussion. Debriefing, support and sharing of expertise in this way may foster engagement within and beyond the workplace.

A randomized controlled trial investigating the effects of celecoxib in patients with localized prostate cancer.

UNLABELLED: Cyclooxygenase-2 (COX-2) is associated with tumour promotion, inhibition of apoptosis, angiogenesis and metastasis. Celecoxib, a selective COX-2 inhibitor was investigated, in patients with clinically localized prostate cancer using immunohistochemistry. PATIENTS AND METHODS: Patients with cT1-2 prostate cancer (n=45) were randomized to celecoxib 400mg b.d. or no treatment for four weeks prior to radical prostatectomy. Histological sections of preoperative biopsy and matched radical prostatectomy specimens were stained for markers of cell proliferation (MIB-1/Ki-67), microvessel density (CD-31 with Weidner scoring), COX-2, apoptosis (TUNEL analysis), angiogenic factors (VEGF and KDR) and HIF-1. RESULTS: Celecoxib decreased tumour cell proliferation, microvessel density, angiogenesis and HIF-1 whilst enhancing apoptosis. These effects approached statistical significance in a multivariate model and the cell proliferation index approached statistical significance on univariate analysis. CONCLUSION: In this pilot study a 4 week regimen of celecoxib resulted in measurable biological effects in prostate cancer tissue. These findings warrant further investigation.