Children with disabilities lack access to nutrition, health and WASH services: A secondary data analysis.

Malnutrition and disability are major global public health problems. Poor diets, inadequate access to nutrition/health services (NaHS), and poor water, sanitation and hygiene (WASH) all increase the risk of malnutrition and infection. This leads to poor health outcomes, including disability. To better understand the relationship between these factors, we explored access to NaHS and household WASH and dietary adequacy among households with and without children with disabilities in Uganda. We used cross-sectional secondary data from 2021. Adjusted logistic regression was used to explore associations between disabilities, access to NaHS, WASH and dietary adequacy. Of the 6924 households, 4019 (57.9%) reported having access to necessary NaHS, with deworming and vaccination reported as both the most important and most difficult to access services. Access to services was lower for households with children with disabilities compared to those without, after adjusting for likely confounding factors (Odds ratio = 0.70; 95% CI 0.55-0.89, p = 0.003). There is evidence of an interaction between disability and WASH adequacy, with improved WASH adequacy associated with improved access to services, including for children with disabilities (interaction odds ratio = 1.12, 95% CI: 1.02-1.22, p = 0.012). The proportion of malnourished children was higher among households with children with disabilities than households without it (6.3% vs. 2.4% p < 0.001). There are concerning gaps in access to NaHS services in Uganda, with households with children with disabilities reporting worse access, particularly for those with low WASH adequacy. Improved and inclusive access to NaHS and WASH needs to be urgently prioritized, especially for children with disabilities.

Mid-upper arm circumference (MUAC) measurement usage among children with disabilities: A systematic review.

Background: Anthropometric measurements, including mid-upper arm circumference (MUAC), are used for monitoring and evaluating children's nutritional status. Evidence is limited on optimal nutritional assessment for children with disabilities, who are at high risk for malnutrition. Aim: This study describes MUAC use among children with disabilities. Methods: Four databases (Embase, Global Health, Medline, and CINHAL) were searched from January 1990 through September 2021 using a predefined search strategy. Of the 305 publications screened, 32 papers were included. Data included children 6 months to 18 years old with disabilities. Data including general study characteristics, methods for MUAC measurement, terminology, and measurement references were extracted into Excel. Due to heterogeneity of the data, a narrative synthesis was used. Results: Studies from 24 countries indicate that MUAC is being used as part of nutritional assessment, but MUAC measurement methods, references, and cutoffs were inconsistent. Sixteen (50%) reported MUAC as a mean ± standard deviation (SD), 11 (34%) reported ranges or percentiles, 6 (19%) reported z-scores, and 4 (13%) used other methods. Fourteen (45%) studies included both MUAC and weight-for-height but nonstandard reporting limited comparability of the indicators for identifying those at risk of malnutrition. Conclusion: Although its speed, simplicity, and ease of use afford MUAC great potential for assessing children with disabilities, more research is needed to understand its appropriateness, and how it performs at identifying nutritionally high-risk children in comparison to other measures. Without validated inclusive measures to identify malnutrition and monitor growth and health, millions of children could have severe consequences for their development.

Impact of COVID-19 on the associated complications of high-risk conditions in a statewide pediatric emergency network.

Background: The COVID-19 pandemic affected the volume and epidemiology of pediatric emergency department (ED) visits. We aimed to determine the rate of associated complications for 16 high-risk conditions in a Michigan statewide network of academic and community EDs during the pandemic. Methods: We conducted a cross-sectional study of pediatric ED visits among a network of 5 Michigan health systems during the pre-pandemic (March 1, 2019-March 10, 2020) and pandemic (March 11, 2020-March 31, 2021) periods. Data were collected from the medical record and included patient demographics, ED visit characteristics, procedure codes, and final International Classification of Diseases, 10th Revision, Clinical Modification diagnosis codes. Selection of codes for 16 high-risk conditions and diagnostic complications were identified using previously described methods. Characteristics of ED visits were compared before versus during the pandemic using χ2 and Fisher's exact tests. We used multilevel logistic regression to analyze covariates and potential confounders for being diagnosed with a high-risk condition or a complication of a high-risk condition. Results: A total of 417,038 pediatric ED visits were analyzed. The proportion of patients presenting with 10 of 16 high-risk conditions (including appendicitis, sepsis, and stroke) was higher in the pandemic period compared with pre-pandemic (P < 0.01). Despite this, there was no significant increase in the frequency of complications for any of the 16 high-risk conditions during the pandemic. The adjusted odds of being diagnosed with appendicitis (pre-pandemic 0.23% vs pandemic 0.52%; odds ratio [OR], 1.19 [95% confidence interval, CI, 1.00-1.41]), diabetic ketoacidosis (pre-pandemic 0.16% vs pandemic 0.52%; OR, 2.40 [95% CI, 2.07-2.78]), intussusception (pre-pandemic 0.05% vs pandemic 0.07%; OR, 1.64 [95% CI, 1.22-2.21)], and testicular torsion (pre-pandemic 0.10% vs pandemic 0.14%; OR, 1.64 [95% CI, 1.18-2.28]) was higher during the pandemic. Conclusions: Despite a higher proportion of ED visits attributed to high-risk conditions, there was no increase in complications, suggesting minimal impact of the pandemic on outcomes of pediatric ED visits.

Decision regret, adverse outcomes, and treatment choice in men with localized prostate cancer: Results from a multi-site randomized trial.

INTRODUCTION: Men diagnosed with localized prostate cancer must navigate a highly preference-sensitive decision between treatment options with varying adverse outcome profiles. We evaluated whether use of a decision support tool previously shown to decrease decisional conflict also impacted the secondary outcome of post-treatment decision regret. METHODS: Participants were randomized to receive personalized decision support via the Personal Patient Profile-Prostate or usual care prior to a final treatment decision. Symptoms were measured just before randomization and 6 months later; decision regret was measured at 6 months along with records review to ascertain treatment choices. Regression modeling explored associations between baseline variables including race and D`Amico risk, study group, and 6-month variables regret, choice, and symptoms. RESULTS: At 6 months, 287 of 392 (73%) men returned questionnaires of which 257 (89%) had made a treatment choice. Of that group, 201 of 257 (78%) completely answered the regret scale. Regret was not significantly different between participants randomized to the P3P intervention compared to the control group (P = 0.360). In univariate analyses, we found that Black men, men with hormonal symptoms, and men with bowel symptoms reported significantly higher decision regret (all P < 0.01). Significant interactions were detected between race and study group (intervention vs. usual care) in the multivariable model; use of the Personal Patient Profile-Prostate was associated with significantly decreased decisional regret among Black men (P = 0.037). Interactions between regret, symptoms and treatment revealed that (1) men choosing definitive treatment and reporting no hormonal symptoms reported lower regret compared to all others; and (2) men choosing active surveillance and reporting bowel symptoms had higher regret compared to all others. CONCLUSION: The Personal Patient Profile-Prostate decision support tool may be most beneficial in minimizing decisional regret for Black men considering treatment options for newly-diagnosed prostate cancer. TRIAL REGISTRATION: NCT01844999.

Decision Support with the Personal Patient Profile-Prostate: A Multicenter Randomized Trial.

PURPOSE: We evaluated the efficacy of the web based P3P (Personal Patient Profile-Prostate) decision aid vs usual care with regard to decisional conflict in men with localized prostate cancer. MATERIALS AND METHODS: A randomized (1:1), controlled, parallel group, nonblinded trial was performed in 4 regions of the United States. Eligible men had clinically localized prostate cancer and an upcoming consultation, and they spoke and read English or Spanish. Participants answered questionnaires to report decision making stage, personal characteristics, concerns and preferences plus baseline symptoms and decisional conflict. A randomization algorithm allocated participants to receive tailored education and communication coaching, generic teaching sheets and external websites plus a 1-page summary to clinicians (intervention) or the links plus materials provided in clinic (usual care). Conflict outcomes and the number of consultations were measured at 1 month. Univariate and multivariable models were used to analyze outcomes. RESULTS: A total of 392 men were randomized, including 198 to intervention and 194 to usual care, of whom 152 and 153, respectively, returned 1-month outcomes. The mean ± SD 1-month decisional conflict scale (score range 0 to 100) was 10.9 ± 16.7 for intervention and 9.9 ± 18.0 for usual care. The multivariable model revealed significantly reduced conflict in the intervention group (-5.00, 95% CI -9.40--0.59). Other predictors of conflict included income, marital or partner status, decision status, number of consultations, clinical site and D'Amico risk classification. CONCLUSIONS: In this multicenter trial the decision aid significantly reduced decisional conflict. Other variables impacted conflict and modified the effect of the decision aid, notably risk classification, consultations and resources. P3P is an effective adjunct for shared decision making in men with localized prostate cancer.

The Development of Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP).

New systemic therapies have prolonged the lives of men with metastatic castration-resistant prostate cancer (mCRPC). Use of these therapies in the adjuvant setting when the disease may be micrometastatic and potentially more sensitive to therapies may decrease mortality from prostate cancer. However, the conduct of adjuvant prostate cancer clinical trials is hampered by taking longer than a decade to reach the meaningful endpoint of overall survival (OS) and the fact that many men never die from prostate cancer, even if they relapse. A validated intermediate clinical endpoint (ICE) in prostate cancer that is a robust surrogate for OS has yet to be defined. This paper details the plans, process, and progress of the international Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) working group to pool individual patient data from all available clinical trials of radiation or prostatectomy for localized disease and conduct the requisite analyses to determine whether an ICE can be identified. This paper further details the challenges and the a priori statistical analytical plans and strategies to define an ICE for adjuvant prostate cancer clinical trials. In addition, a brief review of the health economic analyses to model the benefits to patients, society and manufacturers is detailed. If successful, the results from this work will provide a robust surrogate for OS that will expedite the design and conduct of future adjuvant therapy trials using new agents that have proven activity in mCRPC. Moreover, it will also define the health economic benefits to patients and societies.

Docetaxel, bevacizumab, and androgen deprivation therapy for biochemical disease recurrence after definitive local therapy for prostate cancer.

BACKGROUND: Patients with biochemical disease recurrence (BCR) after definitive treatment for prostate cancer comprise a heterogeneous population for whom standard therapy options are lacking. The purpose of the current trial was to evaluate the feasibility, toxicity, and efficacy of early multimodality systemic therapy in men with BCR. METHODS: Eligible patients had an increasing prostate-specific antigen (PSA) level, a PSA doubling time ≤10 months, and no evidence of metastases after radical prostatectomy (RP) and/or radiotherapy (RT) for localized disease. Treatment consisted of docetaxel at a dose of 75 mg/m(2) every 3 weeks for 4 cycles, bevacizumab at a dose of 15 mg/kg every 3 weeks for 8 cycles, and androgen deprivation therapy (ADT) for 18 months. The primary endpoint was the percentage of patients who were free from PSA progression 1 year after the completion of therapy. RESULTS: A total of 41 patients were included in the analysis. At 1 year after the completion of ADT, 45% of patients (13 of 29 patients) and 29% of patients (5 of 17 patients) with a testosterone level ≥100 ng/dL and ≥240 ng/dL, respectively, had a PSA <0.2 ng/mL. The median follow-up was 27.5 months (interquartile range, 21.8-38.1 months). Eight patients (20%) were free from PSA progression, 19 patients (46%) did not reinitiate ADT, and 34 patients (83%) were free from metastasis. Sixteen patients (39%) experienced grade 3 and 5 patients (12%) experienced grade 4 toxicities (toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events [version 3.0]). CONCLUSIONS: Multimodality systemic therapy with docetaxel, bevacizumab, and ADT is feasible and produces PSA responses in men with BCR. Long-term follow-up is needed to determine the percentage of patients with a durable PSA response who are able to avoid having to reinitiate prostate cancer therapy.

Screening for prostate cancer with the prostate-specific antigen test: a review of current evidence.

IMPORTANCE: Prostate cancer screening with the prostate-specific antigen (PSA) test remains controversial. OBJECTIVE: To review evidence from randomized trials and related modeling studies examining the effect of PSA screening vs no screening on prostate cancer-specific mortality and to suggest an approach balancing potential benefits and harms. EVIDENCE ACQUISITION: MEDLINE, EMBASE, and the Cochrane Register of Controlled Trials were searched from January 1, 2010, to April 3, 2013, for PSA screening trials to update a previous systematic review. Another search was performed in EMBASE and MEDLINE to identify modeling studies extending the results of the 2 large randomized trials identified. The American Heart Association Evidence-Based Scoring System was used to rate level of evidence. RESULTS: Two trials-the Prostate, Lung, Colorectal and Ovarian (PLCO) screening trial and the European Randomized Study of Screening for Prostate Cancer (ERSPC)-dominate the evidence regarding PSA screening. The former trial demonstrated an increase in cancer incidence in the screening group (relative risk [RR], 1.12; 95% CI, 1.07-1.17) but no cancer-specific mortality benefit to PSA screening after 13-year follow-up (RR, 1.09; 95% CI, 0.87-1.36). The ERSPC demonstrated an increase in cancer incidence with screening (RR, 1.63; 95% CI, 1.57-1.69) and an improvement in the risk of prostate cancer-specific death after 11 years (RR, 0.79; 95% CI, 0.68-0.91). The ERSPC documented that 37 additional men needed to receive a diagnosis through screening for every 1 fewer prostate cancer death after 11 years of follow-up among men aged 55 to 69 years (level B evidence for prostate cancer mortality reduction). Harms associated with screening include false-positive results and complications of biopsy and treatment. Modeling studies suggest that this high ratio of additional men receiving diagnoses to prostate cancer deaths prevented will decrease during a longer follow-up (level B evidence). CONCLUSIONS AND RELEVANCE: Available evidence favors clinician discussion of the pros and cons of PSA screening with average-risk men aged 55 to 69 years. Only men who express a definite preference for screening should have PSA testing. Other strategies to mitigate the potential harms of screening include considering biennial screening, a higher PSA threshold for biopsy, and conservative therapy for men receiving a new diagnosis of prostate cancer.

Observation versus initial treatment for men with localized, low-risk prostate cancer: a cost-effectiveness analysis.

BACKGROUND: Observation is underutilized among men with localized, low-risk prostate cancer. OBJECTIVE: To assess the costs and benefits of observation versus initial treatment. DESIGN: Decision analysis simulating treatment or observation. DATA SOURCES: Medicare schedules, published literature. TARGET POPULATION: Men aged 65 and 75 years who had newly diagnosed low-risk prostate cancer (prostate-specific antigen level <10 µg/L, stage ≤T2a, Gleason score ≤3 + 3). TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: Treatment (brachytherapy, intensity-modulated radiation therapy, or radical prostatectomy) or observation (active surveillance [AS] or watchful waiting [WW]). OUTCOME MEASURES: Quality-adjusted life expectancy and costs. RESULTS OF BASE-CASE ANALYSIS: Observation was more effective and less costly than initial treatment. Compared with AS, WW provided 2 additional months of quality-adjusted life expectancy (9.02 vs. 8.85 years) at a savings of $15,374 ($24,520 vs. $39,894) in men aged 65 years and 2 additional months (6.14 vs. 5.98 years) at a savings of $11,746 ($18,302 vs. $30,048) in men aged 75 years. Brachytherapy was the most effective and least expensive initial treatment. RESULTS OF SENSITIVITY ANALYSIS: Treatment became more effective than observation when it led to more dramatic reductions in prostate cancer death (hazard ratio, 0.47 vs. WW and 0.64 vs. AS). Active surveillance became as effective as WW in men aged 65 years when the probability of progressing to treatment on AS decreased below 63% or when the quality of life with AS versus WW was 4% higher in men aged 65 years or 1% higher in men aged 75 years. Watchful waiting remained least expensive in all analyses. LIMITATION: Results depend on outcomes reported in the published literature, which is limited. CONCLUSION: Among these men, observation is more effective and costs less than initial treatment, and WW is most effective and least expensive under a wide range of clinical scenarios. PRIMARY FUNDING SOURCE: National Cancer Institute, U.S. Department of Defense, Prostate Cancer Foundation, and Institute for Clinical and Economic Review.

Clinical predictors of survival in men with castration-resistant prostate cancer: evidence that Gleason score 6 cancer can evolve to lethal disease.

BACKGROUND: This study sought to characterize Modern patients with castration-resistant prostate cancer (CRPC) and identify pretreatment clinical predictors of survival. METHODS: A cohort of men with CRPC with and without metastases (M) treated with secondary hormonal therapy (2eHT) and/or chemotherapy (CT) was identified from the authors' institutional database. Associations of patient and disease characteristics at diagnosis, at androgen-deprivation therapy (ADT) initiation, at CRPC index date, and survival were evaluated. CRPC index date was defined as the start date of either 2eHT or CT, whichever came first. RESULTS: In the cohort of 622 men, 434 men (70%) had M-positive disease; 552 men (89%) received 2eHT and 70 men (11%) received CT as their initial CRPC treatment. There were 410 deaths (66%) at the time of analysis. Median overall survival (OS) was 35 months (quartile 1, quartile 3: 21 months, 61 months). In multivariate analyses, higher biopsy Gleason score, the presence of M at ADT initiation, shorter time from ADT start to CRPC, higher prostate-specific antigen and poorer Eastern Cooperative Oncology Group performance status at CRPC and M at CRPC were predictive of shorter OS. Interestingly, whereas some men with biopsy Gleason scores of 6 died of their disease (N = 42), they had a longer OS after CRPC compared with those with a Gleason score ≥ 7. CONCLUSIONS: This large retrospective study of patients with CRPC in a tertiary cancer center shows that biopsy Gleason score of 6 is associated with a less aggressive CRPC course, and the impact that M at ADT initiation and CRPC have on outcome is quantified.

Mapping patient goals to the International Classification of Functioning, Disability and Health (ICF): examining the content validity of the low back pain core sets.

OBJECTIVE: To determine whether the International Classification of Functioning, Disability and Health (ICF) Low Back Pain Core Sets are sufficient to cover the activity and participation goals that patients prioritize when commencing multidisciplinary rehabilitation. DESIGN: Prospective multi-site cross-sectional questionnaire study. SUBJECTS: Patients with chronic low back pain attending multidisciplinary outpatient clinics at two metropolitan hospitals in Australia. METHODS: Participants used the Patient Specific Functional Scale to record goals when commencing rehabilitation. Two raters employed a standardized procedure to extract and link goal concepts to the ICF. A description exploration was undertaken with reference to the low back pain Core Sets. Sample size was determined via saturation. RESULTS: Saturation was achieved with 33 participants. Ninety five goals were identified, from which 109 concepts were extracted. All of the concepts could be linked to the ICF, spanning 23 2nd-level categories. The comprehensive and brief core sets encompassed 95% and 65% of the concepts respectively. Maintaining body position (d415), doing housework (d640), changing basic body position (d410) and walking (d450) accounted for the majority (50.5%) of goals. CONCLUSION: This study confirms the content validity of the low back pain Core Sets from the patients' perspective. The Core Sets are likely to have good clinical utility, however, additional research is required to substantiate whether ratings of ICF based goals can be used to measure goal achievement.

Phase II trial of RAD001 and bicalutamide for castration-resistant prostate cancer.

UNLABELLED: Study Type--Therapy (cohort) Level of Evidence 2a. What's known on the subject? and What does the study add? Despite expanding treatment options for castration-resistant prostate cancer (CRPC), therapies with long response duration remain intangible due to prostate cancer cells' natural ability to develop iterative resistance. Androgen receptor (AR) signaling has been shown to play a critical role in CRPC and its expression is regulated by the PI3K-Akt pathway. Thus inhibition of AR signalling and PI3K-Akt-mTOR (a downstream mediator of the PI3K-Akt pathway) pathway is a logical combination in CRPC and we report a phase II trial of RAD001 and bicalutamide. Our study is the first clinical trial report of an AR inhibitor of PI3K-Akt-mTOR. The AR pathway and the PI3K-Akt-mTOR pathway are two of the most relevant growth pathway for CRPC. Despite low efficacy results from our trial there will be significant interest in the field for these data (dose, schedule, response, toxicity, trial design) as newer generations of both AR inhibitors and PI3K-Akt-mTOR inhibitors are in development and likely will be tested in combination in CRPC. OBJECTIVES: • To determine best overall response and duration of response of RAD001, a selective inhibitor of mammalian target of rapamycin, in combination with bicalutamide in castration-resistant prostate cancer (CRPC). • To characterize the toxicity profile of RAD001 in combination with bicalutamide in patients with CRPC. PATIENTS AND METHODS: • A phase II study was conducted to explore the efficacy and tolerability of RAD001 (10 mg daily) in combination with bicalutamide (50 mg daily) in men with progressive CRPC. • The primary endpoint was a composite of prostate-specific antigen (PSA) level and measurable disease response by standard criteria. • This single-stage trial with a sample size of 38 eligible patients provided 90% power to differentiate a response rate of ≥ 40% from a response rate of ≤ 20%, as expected for bicalutamide alone (α= 0.10, power = 0.90). RESULTS: • In total, 36 men were enrolled, with a median (range) age of 68 (60-72) years and median (range) baseline PSA level of 22.2 (8.4-121.3) ng/mL, and 89% had metastatic disease. • There were 31 (86%) patients had previously used bicalutamide for a median duration of 7.4 months. • There were two patients with a confirmed PSA level decline ≥ 50%. • The median (interquartile range) time to progression was 8.7 (7.9-15.9) weeks. • The most common toxicity was grade 1/2 mucositis, which was observed in 20 (56%) patients. CONCLUSION: • The combination of RAD001 and bicalutamide in men with CRPC was well tolerated but had low activity and failed to achieve the primary endpoint of improved response compared to the results previously achieved for bicalutamide alone in this population.

Phase 2 study of neoadjuvant docetaxel plus bevacizumab in patients with high-risk localized prostate cancer: a Prostate Cancer Clinical Trials Consortium trial.

BACKGROUND: Treatment of high-risk localized prostate cancer remains inadequate. The authors performed a phase 2 multicenter trial of neoadjuvant docetaxel plus bevacizumab before radical prostatectomy. METHODS: Eligibility included any of the following: prostate-specific antigen (PSA) >20 ng/mL or PSA velocity >2 ng/mL/y, cT3 disease, any biopsy Gleason score 8 to 10, and Gleason score 7 with T3 disease by endorectal magnetic resonance imaging (MRI) at 1.5 T. Also, those with ≥50% biopsy cores involved and either Gleason score 7, PSA >10, or cT2 disease were eligible. Patients were treated with docetaxel 70 mg/m(2) every 3 weeks for 6 cycles and bevacizumab 15 mg/m(2) every 3 weeks for 5 cycles. The primary endpoint was partial response by endorectal MRI. RESULTS: Forty-one patients were treated. Median age was 55 years (range, 40-66 years). Baseline characteristics included: median PSA, 10.1 ng/mL; cT2, 49%, cT3, 32%; and Gleason score 8 to 10, 73%. Thirty-eight of 41 (93%) patients completed all 6 cycles. Grade ≥3 adverse events were rare, although 3 of 41 (7%) experienced febrile neutropenia. Twelve patients (29%; 95% confidence interval [CI], 16%-45%) achieved a >50% reduction in tumor volume, and 9 patients (22%; 95% CI, 11%-38%) achieved a >50% post-treatment decline in PSA. Thirty-seven of the 41 patients underwent radical prostatectomy; there were no complete pathologic responses. CONCLUSIONS: Neoadjuvant docetaxel and bevacizumab is safe, and results in reductions in both tumor volume and serum PSA, in men with high-risk localized prostate cancer. The role of neoadjuvant chemotherapy in prostate cancer, and perioperative antiangiogenic therapy in general, requires further elucidation through ongoing and planned trials.

Active surveillance compared with initial treatment for men with low-risk prostate cancer: a decision analysis.

CONTEXT: In the United States, 192,000 men were diagnosed as having prostate cancer in 2009, the majority with low-risk, clinically localized disease. Treatment of these cancers is associated with substantial morbidity. Active surveillance is an alternative to initial treatment, but long-term outcomes and effect on quality of life have not been well characterized. OBJECTIVE: To examine the quality-of-life benefits and risks of active surveillance compared with initial treatment for men with low-risk, clinically localized prostate cancer. DESIGN AND SETTING: Decision analysis using a simulation model was performed: men were treated at diagnosis with brachytherapy, intensity-modulated radiation therapy (IMRT), or radical prostatectomy or followed up by active surveillance (a strategy of close monitoring of newly diagnosed patients with serial prostate-specific antigen measurements, digital rectal examinations, and biopsies, with treatment at disease progression or patient choice). Probabilities and utilities were derived from previous studies and literature review. In the base case, the relative risk of prostate cancer-specific death for initial treatment vs active surveillance was assumed to be 0.83. Men incurred short- and long-term adverse effects of treatment. PATIENTS: Hypothetical cohorts of 65-year-old men newly diagnosed as having clinically localized, low-risk prostate cancer (prostate-specific antigen level <10 ng/mL, stage ≤T2a disease, and Gleason score ≤6). MAIN OUTCOME MEASURE: Quality-adjusted life expectancy (QALE). RESULTS: Active surveillance was associated with the greatest QALE (11.07 quality-adjusted life-years [QALYs]), followed by brachytherapy (10.57 QALYs), IMRT (10.51 QALYs), and radical prostatectomy (10.23 QALYs). Active surveillance remained associated with the highest QALE even if the relative risk of prostate cancer-specific death for initial treatment vs active surveillance was as low as 0.6. However, the QALE gains and the optimal strategy were highly dependent on individual preferences for living under active surveillance and for having been treated. CONCLUSIONS: Under a wide range of assumptions, for a 65-year-old man, active surveillance is a reasonable approach to low-risk prostate cancer based on QALE compared with initial treatment. However, individual preferences play a central role in the decision whether to treat or to pursue active surveillance.

Androgen-suppression therapy for prostate cancer and the risk of death in men with a history of myocardial infarction or stroke.

OBJECTIVE: To examine the effect of short-course androgen-suppression therapy (AST) before brachytherapy on all-cause mortality (ACM) rates, stratified by the presence or absence of a history of myocardial infarction (MI) or stroke. AST is used to reduce prostate size to enable men with favourable-risk prostate cancer to undergo brachytherapy, but no disease-specific benefit has been reported for this practice, and AST use has been associated with an increased risk of ACM in some men with pre-existing cardiovascular disease. PATIENTS AND METHODS: The study comprised 12792 men with favourable-risk disease, i.e. a prostate-specific antigen (PSA) level of <20 ng/mL, Gleason score ≤7 and clinical category ≤T2c, treated between 1991 and 2007 at community-based medical centres with brachytherapy ± neoadjuvant AST. Multivariable Cox regression analysis was used to assess whether there were significant associations between AST use in men with a history of MI or stroke and the risk of ACM, adjusting for age, treatment year, and known prognostic factors of prostate cancer. RESULTS: After a median (interquartile range) follow-up of 3.8 (2.0-5.9) years there were 1557 deaths. The risk of ACM was lower in men with no history of MI or stroke than in those with this history, whether AST was used (adjusted hazard ratio 0.79, 95% confidence interval 0.67-0.92; P= 0.003) or not (0.74, 0.65-0.85; P < 0.001). However, men with a history of MI or stroke treated with AST had a greater risk of ACM than those not treated with AST (1.2, 1.05-1.38; P= 0.008). CONCLUSION: The use of short-course AST in men with a history of MI or stroke is associated with a greater risk of ACM in men with favourable-risk prostate cancer.