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

Background The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. Objective To 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 and 997 who declined randomisation and chose treatment. Outcome measurements and statistical analysis Analysis was carried out to assess mortality, metastasis and progression and health-related quality of life impacts on urinary, bowel, and sexual function using patient-reported outcome measures. Analysis was based on comparisons between groups defined by treatment received for both randomised and treatment choice cohorts in turn, with pooled estimates of intervention effect obtained 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 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and changes in the protocol for AM 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 95 out of every 100 men with low or intermediate risk localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are better after active monitoring, but the risks of spreading of prostate cancer are more common

Functional and quality of life outcomes of localised prostate cancer treatments (prostate testing for cancer and treatment [ProtecT] study)

Objective To investigate the functional and quality of life (QoL) outcomes of treatments for localised prostate cancer and inform treatment decision-making. Patients and Methods Men aged 50–69 years diagnosed with localised prostate cancer by prostate-specific antigen testing and biopsies at nine UK centres in the Prostate Testing for Cancer and Treatment (ProtecT) trial were randomised to, or chose one of, three treatments. Of 2565 participants, 1135 men received active monitoring (AM), 750 a radical prostatectomy (RP), 603 external-beam radiotherapy (EBRT) with concurrent androgen-deprivation therapy (ADT) and 77 low-dose-rate brachytherapy (BT, not a randomised treatment). Patient-reported outcome measures (PROMs) completed annually for 6 years were analysed by initial treatment and censored for subsequent treatments. Mixed effects models were adjusted for baseline characteristics using propensity scores. Results Treatment-received analyses revealed different impacts of treatments over 6 years. Men remaining on AM experienced gradual declines in sexual and urinary function with age (e.g., increases in erectile dysfunction from 35% of men at baseline to 53% at 6 years and nocturia similarly from 20% to 38%). Radical treatment impacts were immediate and continued over 6 years. After RP, 95% of men reported erectile dysfunction persisting for 85% at 6 years, and after EBRT this was reported by 69% and 74%, respectively (P < 0.001 compared with AM). After RP, 36% of men reported urinary leakage requiring at least 1 pad/day, persisting for 20% at 6 years, compared with no change in men receiving EBRT or AM (P < 0.001). Worse bowel function and bother (e.g., bloody stools 6% at 6 years and faecal incontinence 10%) was experienced by men after EBRT than after RP or AM (P < 0.001) with lesser effects after BT. No treatment affected mental or physical QoL. Conclusion Treatment decision-making for localised prostate cancer can be informed by these 6-year functional and QoL outcomes

Spot-testing urine pH, a novel dietary biomarker? A randomised cross-over trial.

AimSpot-tests of urine pH are claimed to be an accessible biomarker of net acid excretion (NAE), and as such, they may be able to determine changes in an individual's intake of acid- or base-forming foods. To test this hypothesis, we aimed to determine if spot-tests of urine pH could index NAE and relay the consumption of a fruit and vegetable (F&amp;V) concentrate whilst determining this concentrate's capacity to modulate NAE.MethodsIn a double blind, placebo-controlled, cross-over trial, healthy adults (n = 13) were allocated by simple randomisation to receive a F&amp;V concentrate or placebo for three days each, with diet standardised throughout. Measurements of 24-hour NAE, 24-hour urine pH and spot-tests of urine pH were taken throughout the study.ResultsThe 24-hour urine pH predicted 24-hour NAE (P = &lt;0.0001). However, spot-tested urine pH displayed prediction intervals too wide to infer 24-hour NAE and inconsistent ability to reflect concentrate ingestion, despite 24-hour NAE and 24-hour urine pH decreasing (-25.8 mEq, 95% CI -44.3 to -7.4, P = 0.01, d = 0.94) and increasing (+0.51, 95% CI 0.25-0.79, P = 0.002, d = 1.3), respectively, following supplementation.ConclusionsSpot-tests of urine pH are not a valid dietary biomarker of daily NAE and were unable to reliably track changes, despite a F&amp;V concentrate clearly modulating the daily rate of NAE

Spot-testing urine pH, a novel dietary biomarker? A randomised cross-over trial.

AimSpot-tests of urine pH are claimed to be an accessible biomarker of net acid excretion (NAE), and as such, they may be able to determine changes in an individual's intake of acid- or base-forming foods. To test this hypothesis, we aimed to determine if spot-tests of urine pH could index NAE and relay the consumption of a fruit and vegetable (F&amp;V) concentrate whilst determining this concentrate's capacity to modulate NAE.MethodsIn a double blind, placebo-controlled, cross-over trial, healthy adults (n = 13) were allocated by simple randomisation to receive a F&amp;V concentrate or placebo for three days each, with diet standardised throughout. Measurements of 24-hour NAE, 24-hour urine pH and spot-tests of urine pH were taken throughout the study.ResultsThe 24-hour urine pH predicted 24-hour NAE (P = &lt;0.0001). However, spot-tested urine pH displayed prediction intervals too wide to infer 24-hour NAE and inconsistent ability to reflect concentrate ingestion, despite 24-hour NAE and 24-hour urine pH decreasing (-25.8 mEq, 95% CI -44.3 to -7.4, P = 0.01, d = 0.94) and increasing (+0.51, 95% CI 0.25-0.79, P = 0.002, d = 1.3), respectively, following supplementation.ConclusionsSpot-tests of urine pH are not a valid dietary biomarker of daily NAE and were unable to reliably track changes, despite a F&amp;V concentrate clearly modulating the daily rate of NAE

Accuracy and precision of estimation equations to predict net endogenous acid excretion using the Australian food database.

AimThe gold standard of measurement for net endogenous acid production (NEAP) is net acid excretion (NAE), a test that is not readily available, and consequently, estimative equations by Remer and Manz and Frassetto et al. are often used. These equations rely on nutrient databases and it is recommended that their validity be assessed using a country's database before their application in research in that country. We sought to delineate the accuracy and precision of these estimation equations using the Australian food database.MethodsIn a double blind, randomised, cross-over fashion, healthy participants (n = 13) residing in regional Australia were exposed to varying net acid loads while they collected weighted food diaries and 24-hour urine samples for measurement of NAE.ResultsIn comparison to the Frassetto et al. equations (equation one bias = -57.1 mEq/day, equation two bias = -32.8 mEq/day), only the Remer and Manz equation was accurate (bias = -5.4 mEq/day); however, all equations were imprecise.ConclusionsUsing the Australian database, the performance of these equations to predict NEAP appears equal to other databases; however, caveats apply in their application. For future research, the equation by Remer and Manz is preferential for group estimates. None of the equations are recommended for individual estimates

Defining work-focused cognitive behavioural therapy (W-CBT) and whether it is effective at facilitating return to work for people experiencing mental health conditions: A systematic review and narrative synthesis

It is unclear what constitutes Work Focused Cognitive Behaviour Therapy (W-CBT). This review sought to define W-CBT and ascertain its effectiveness at facilitating return to work (RTW) for people experiencing mental health conditions. A systematic review and narrative synthesis were undertaken. Five databases were searched (Medline, ProQuest, PsychInfo, Scopus, and Web of Science). English publications with an intervention combining CBT with RTW were selected. Quality checklists from the Joanna Briggs Institute were applied. Searching yielded 16,863 results. 23 moderate-to-high quality studies from 25 articles were included (13 experimentally designed studies, 3 pilots/case studies and 7 reviews). Results indicated W-CBT is effective at facilitating RTW for mild-to-moderate mental health conditions. For a program to be labelled W-CBT it is recommended it is (1) a stand-alone intervention; (2) delivered with an understanding RTW is the goal; and, (3) the CBT components are always framed by matters, subjects and contexts related to work

Defining work-focused cognitive behavioural therapy (W-CBT) and whether it is effective at facilitating return to work for people experiencing mental health conditions: A systematic review and narrative synthesis

Supplemental Material for Defining work-focused cognitive behavioural therapy (W-CBT) and whether it is effective at facilitating return to work for mental health disorders: A systematic review and narrative synthesis by Dylan Slater, Anthony Venning, Lynda Matthews, Ross Iles, Paula Redpath in Health Psychology Open</p