Adding caplacizumab to standard of care in thrombotic thrombocytopenic purpura: a systematic review and meta-analysis.

Immune thrombotic thrombocytopenic purpura (iTTP) is an acquired, fatal microangiopathy if untreated. Randomized controlled trials (RCTs) demonstrated faster time to response with addition of caplacizumab to standard of care (SOC). However, concerns about RCT selection bias and the high cost of caplacizumab warrant examination of all evidence, including real-world observational studies. In this systematic review and meta-analysis, we searched for comparative studies evaluating SOC with or without caplacizumab for the treatment of iTTP. We assessed risk of bias using the Cochrane risk-of-bias-2 tool (RCTs) and the Newcastle-Ottawa Scale (observational studies). The primary efficacy and safety outcomes were all-cause mortality and treatment-emergent bleeding, respectively. Secondary outcomes included exacerbation and relapse, refractory iTTP, and time to response. We included 2 high-quality RCTs and 3 observational studies at high risk of bias comprising 632 total participants. Compared with SOC, caplacizumab was associated with a nonsignificant reduction in the relative risk [RR] of death in RCTs (RR, 0.21; 95% confidence interval [CI], 0.05-1.74) and observational studies (RR, 0.62; 95% CI, 0.07-4.41). Compared with SOC, caplacizumab was associated with an increased bleeding risk in RCTs (RR, 1.37; 95% CI, 1.06-1.77). In observational studies, bleeding risk was not significantly increased (RR, 7.10; 95% CI, 0.90-56.14). Addition of caplacizumab was associated with a significant reduction in refractory iTTP and exacerbation risks and shortened response time but increased relapse risk. Frontline addition of caplacizumab does not significantly reduce all-cause mortality compared with SOC alone, although it reduces refractory disease risk, shortens time to response, and improves exacerbation rates at the expense of increased relapse and bleeding risk.

Associations between hospitalist physician workload, length of stay, and return to the hospital.

BACKGROUND: Hospitalist physicians' workload-the total number of patients they care for daily-is rising in the U.S. Hospitalists report that increased workload negatively affects patients care. OBJECTIVE: Measure the associations between hospitalist physicians' workload and clinical outcomes. DESIGN, SETTINGS, AND PARTICIPANTS: Observational study, using electronic health record (EHR) data, of adults hospitalized on the hospitalist service at Yale-New Haven Hospital from 2015-2018. MAIN OUTCOME AND MEASURES: We defined hospitalists' workload as the number of patients they cared for on the first full hospital day of a given patient's encounter. We used multilevel Poisson and logistic regression to examine associations between workload and length of stay (LOS), return to the Emergency Department (ED), and readmission. We adjusted for sociodemographic factors, patient complexity and severity of illness, and weekend admission (for LOS) or discharge (for ED visits or readmission). RESULTS: We analyzed 38,141 hospitalizations. Median patient age was 64 years (IQR 51-78 years), 53% were female, and 34% were nonwhite. Mean workload was 15 patients (SD 3 patients; range 10-34 patients). LOS was prolonged by 0.05 days (95% CI 0.02, 0.08; p(0.001) when comparing the 75th workload percentile (16 patients) to the 25th workload percentile (13 patients). There were no associations between workload and ED visits or readmission within 7 and 30 days. CONCLUSIONS: There was a statistically significant but modest relationship between workload and LOS; workload was not associated with ED visits or readmissions.Given clinical reports of the deleterious effects of increased hospitalist workload, there is a need for prospective research assessing a range of outcomes, beyond those measurable in contemporary EHR data.

Translating and validating a Japanese version of the Patient Care Ownership Scale: a multicenter cross-sectional study.

BACKGROUND: Patient care ownership (PCO) is an essential component in medical professionalism and is crucial for delivering high-quality care. The 15-item PCO Scale (PCOS) is a validated questionnaire for quantifying PCO in residents; however, no corresponding tool for assessing PCO in Japan exists. This study aimed to develop a Japanese version of the PCOS (J-PCOS) and validate it among Japanese medical trainees. METHODS: We performed a multicenter cross-sectional survey to test the validity and reliability of the J-PCOS. The study sample was trainees of postgraduate years 1-5 in Japan. The participants completed the J-PCOS questionnaire. Construct validity was assessed through exploratory and confirmatory factor analyses. Internal consistency reliability was examined by calculating Cronbach's alpha coefficients and inter-item correlations. RESULTS: During the survey period, 437 trainees at 48 hospitals completed the questionnaire. Exploratory factor analysis of the J-PCOS extracted four factors: assertiveness, sense of ownership, diligence, and being the "go-to" person. The second factor had not been identified in the original PCOS, which may be related to a unique cultural feature of Japan, namely, a historical code of personal conduct. Confirmatory factor analysis supported this four-factor model, revealing good model fit indices. The analysis results of Cronbach's alpha coefficients and inter-item correlations indicated adequate internal consistency reliability. CONCLUSIONS: We developed the J-PCOS and examined its validity and reliability. This tool can be used in studies on postgraduate medical education. Further studies should confirm its robustness and usefulness for improving PCO.

The Patient Care Ownership Scale: External Validation of an Instrument that Measures Patient Care Ownership Among Internal Medicine Trainees-a Multi-Institutional Study.

BACKGROUND: Patient care ownership improves accountability, clinical skills, and quality of patient care among resident physicians, but appears to be gradually eroding. Research is limited by the lack of a reliable, objective measure of ownership. OBJECTIVE: To validate the Patient Care Ownership Scale, an instrument that measures decision ownership among internal medicine residents. DESIGN: Multi-institutional, cross-sectional study using a 66-item, online survey that queried residents on ownership's key constructs (advocacy, responsibility, accountability, follow-through, knowledge, communication, initiative, continuity of care, autonomy, self-efficacy, and perceived ownership) as well as mood and burnout. PARTICIPANTS: Internal medicine residents in five geographically diverse residency programs completing an inpatient rotation. MAIN MEASURES: We performed exploratory and confirmatory factor analysis in two randomly split groups to evaluate for subscales and inform item reduction. We conducted reliability testing with Cronbach's α. We performed bivariate analyses to examine construct validity and identify correlates of ownership. KEY RESULTS: Of the 785 eligible residents, 625 completed the survey (80% response rate); we included responses from 563 in the analysis. We identified three factors corresponding to assertiveness, conscientiousness, and confidence or perceived competence. After iterative item reduction, the 13-item ownership scale demonstrated good reliability (Cronbach's α = 0.82). Convergent validity was supported by a significant association with perceived ownership (eliminated from the final scale) (r = 0.67, p < 0.001). There was a positive association between ownership and training level (p < 0.01) and prior experience in the intensive care unit (p < 0.001). There were significant, inverse relationships between ownership and self-defined burnout (r = - 0.24, p < 0.001), depression (r = - 0.22, p < 0.001), detachment (r = - 0.26, p < 0.001), and frustration (r = - 0.15, p = 0.02), and significant positive associations between ownership and feeling energetic (r = 0.29, p < 0.001), happy (r = 0.33, p < 0.001), and fulfilled (r = 0.34, p < 0.001). CONCLUSIONS: The Patient Care Ownership Scale is valid in diverse residency program settings. Medical educators and investigators can use our scale to assess interventions aimed at fostering ownership.

Changes in Functional Status and Health-Related Quality of Life in Older Adults After Surgical, Interventional, or Medical Management of Acute Myocardial Infarction.

Functional status and health-related quality of life (HRQoL) are important outcomes, particularly among older patients. However, data on such patient-centered outcomes after cardiac surgery are limited. We evaluated the incidence and predictors of decline in functional status and HRQoL among older patients hospitalized for acute myocardial infarction (AMI). Participants were age 75 years or older hospitalized for AMI at 94 US sites. We examined decline in functional status (defined as decline in 1 or more activities of daily living, ADLs), as well as mental (MCS) and physical component scales (PCS) of the SF-12 to assess HRQoL (5-point decline or greater in each scale) between 1 month prior to the hospitalization and 6 months after. Multivariable model compared the risk of decline after coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI) and medical management. Among 3041 patients (1708 PCI, 362 CABG, and 971 medical management), 1525 (50.2%) experienced decline in 1 or more domain: 633 (20.8%) declined in ADLs, 786 (25.9%) declined in the MCS, and 1078 (35.5%) declined in the PCS. The unadjusted incidence of ADL decline was the lowest among patients who underwent CABG (n = 50, 13.8%) compared with PCI (n = 271, 15.9%) or medical management (n = 312, 32.1%). Patients who underwent CABG and PCI had lower adjusted risk of decline in functional and HRQoL compared with those who received medical therapy. The risks after CABG and PCI were not significantly different. Over half of older patients significantly declined in function or HRQoL after AMI. Compared with medical management, risk of decline was lower in those who underwent revascularization.

Which patients with unprovoked venous thromboembolism should receive extended anticoagulation with direct oral anticoagulants? A systematic review, network meta-analysis, and decision analysis.

INTRODUCTION: Direct oral anticoagulants (DOACs) effectively prevent recurrent venous thromboembolism (VTE). However, it is unknown which agents should be used to prevent recurrent VTE and which patients with unprovoked VTE should receive extended anticoagulation. We therefore sought to compare the efficacy and safety among DOACs for secondary prevention of VTE. We also determined a risk-adapted threshold for initiating extended anticoagulation based on the likelihood of VTE recurrence (without treatment) and bleeding (with treatment) in patients with unprovoked VTE. METHODS: Our systematic review of randomized controlled trials compares extended anticoagulation with DOACs to another DOAC, aspirin, or placebo for the prevention of recurrent VTE. We searched PubMed, EMBASE, and Cochrane Registry of Controlled Trials (CENTRAL) in October 2018. Our outcomes of interest were VTE recurrence, major bleeding, and all clinically relevant bleeding. We used network meta-analysis to make indirect comparisons among DOACs. We populated the threshold decision-analytic model with data from our meta-analysis to determine the risk of VTE recurrence above which the benefits of extended anticoagulation outweigh the harms compared with no treatment. RESULTS: We included four, high-quality, randomized trials comprising 8386 participants. Low-dose apixaban, full-dose apixaban, low-dose rivaroxaban, full-dose rivaroxaban, and dabigatran reduce VTE recurrence compared with placebo (RR = 0.19, 95% CI, 0.12-0.31; RR = 0.20, 95% CI, 0.12-0.32; RR = 0.08, 95% CI, 0.03-0.27; RR = 0.14, 95% CI, 0.06-0.35; RR = 0.19, 95% CI, 0.09-0.40, respectively). No DOACs increased major bleeding risk compared with placebo. A VTE recurrence risk above 0.3% to 0.4% at approximately 1 year is the threshold to treat a patient with unprovoked VTE with extended anticoagulation (with any DOAC). CONCLUSIONS: All DOACs exhibit comparable efficacy for the prevention of recurrent VTE. Given that the risk of VTE recurrence is much higher than the calculated threshold for treatment, extended thromboprophylaxis should be considered in all patients with unprovoked VTE who do not have increased bleeding risk.

The Patient Care Ownership Scale: Development of an Instrument to Measure Patient Care Ownership Among Internal Medicine Trainees.

BACKGROUND: Patient care ownership is essential to delivering high-quality medical care but appears to be eroding among trainees. The lack of an objective measure has limited the study of ownership in physicians. OBJECTIVE: To develop an instrument to measure psychological ownership of patient care. DESIGN: Cross-sectional study. PARTICIPANTS: Internal medicine trainees in a large, academic hospital completing an inpatient rotation. MAIN MEASURES: Our scale prototype adapted an existing ownership scale (developed in the non-medical setting) based on themes identified in qualitative studies of patient care ownership. We conducted cognitive interviews to determine face validity of the scale items. Our finalized scale measures ownership's key constructs: advocacy, responsibility, accountability, follow-through, knowledge, communication, initiative, continuity of care, autonomy, and perceived ownership. We distributed an online, anonymous, 46-question survey to 219 residents; 192 residents completed the survey; and 166 responses were included in the analysis. We calculated Cronbach's α to determine the scale's internal consistency. Exploratory factor analysis was used to explore possible subscales. We examined construct validity using bivariate and correlational analysis. KEY RESULTS: The 15-item ownership scale demonstrated good internal consistency (Cronbach's α = 0.89). We identified three possible subscales corresponding to assertiveness, being the "go-to" person, and diligence. Training level and prior intensive care unit experience significantly predicted ownership (p < 0.01). There was no significant relationship between ownership and age, gender, inpatient service type, call schedule, patient turnover, or supervisory experience of the attending physician. We found a significant negative correlation between ownership and perceived degree of burnout (r = - 0.33), depression (r = - 0.24), detachment (r = - 0.35), and frustration (r = - 0.31) and a significant positive association between ownership and fulfillment (r = 0.37) and happiness (r = 0.36). CONCLUSION: We developed an instrument to quantify patient care ownership in residents. Our scale demonstrates good internal consistency and preliminary evidence of validity. With further validation, we expect this to be a valuable tool to evaluate interventions aimed at improving ownership.

Prostate cancer screening with prostate-specific antigen (PSA) test: a systematic review and meta-analysis.

OBJECTIVE: To investigate the efficacy and safety of prostate-specific antigen (PSA) testing to screen for prostate cancer. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Electronic search of Cochrane Central Register of Controlled Trials, Web of Science, Embase, Scopus, OpenGrey, LILACS, and Medline, and search of scientific meeting abstracts and trial registers to April 2018. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials comparing PSA screening with usual care in men without a diagnosis of prostate cancer. DATA EXTRACTION: At least two reviewers screened studies, extracted data, and assessed the quality of eligible studies. A parallel guideline committee (BMJ Rapid Recommendation) provided input on the design and interpretation of the systematic review, including selection of outcomes important to patients. We used a random effects model to obtain pooled incidence rate ratios (IRR) and, when feasible, conducted subgroup analyses (defined a priori) based on age, frequency of screening, family history, ethnicity, and socioeconomic level, as well as a sensitivity analysis based on the risk of bias. The quality of the evidence was assessed with the GRADE approach. RESULTS: Five randomised controlled trials, enrolling 721 718 men, were included. Studies varied with respect to screening frequency and intervals, PSA thresholds for biopsy, and risk of bias. When considering the whole body of evidence, screening probably has no effect on all-cause mortality (IRR 0.99, 95% CI 0.98 to 1.01; moderate certainty) and may have no effect on prostate-specific mortality (IRR 0.96, 0.85 to 1.08; low certainty). Sensitivity analysis of studies at lower risk of bias (n=1) also demonstrates that screening seems to have no effect on all-cause mortality (IRR 1.0, 0.98 to 1.02; moderate certainty) but may have a small effect on prostate-specific mortality (IRR 0.79, 0.69 to 0.91; moderate certainty). This corresponds to one less death from prostate cancer per 1000 men screened over 10 years. Direct comparative data on biopsy and treatment related complications from the included trials were limited. Using modelling, we estimated that for every 1000 men screened, approximately 1, 3, and 25 more men would be hospitalised for sepsis, require pads for urinary incontinence, and report erectile dysfunction, respectively. CONCLUSIONS: At best, screening for prostate cancer leads to a small reduction in disease-specific mortality over 10 years but has does not affect overall mortality. Clinicians and patients considering PSA based screening need to weigh these benefits against the potential short and long term harms of screening, including complications from biopsies and subsequent treatment, as well as the risk of overdiagnosis and overtreatment. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42016042347.

An Update on the "Novel" and Direct Oral Anticoagulants, and Long-Term Anticoagulant Therapy.

The mainstay of treatment of venous thromboembolism (VTE) is anticoagulation. Direct oral anticoagulants (DOAC) have revolutionized anticoagulation management, although their efficacy and safety in specialized populations such as antiphospholipid syndrome, advanced renal disease, cancer thrombosis, and geriatric patients remain uncertain. Concerns about bleeding risks of DOACs persist despite reassuring data in the literature and the development of specific antidotes. In this article, the authors present an overview of the basic pharmacology of DOACs and discuss their use in acute VTE, secondary VTE prevention, and specialized VTE patient populations and discuss therapeutic monitoring and reversal in the event of major bleeding.

Thinking Styles and Regret in Physicians.

BACKGROUND: Decision-making relies on both analytical and emotional thinking. Cognitive reasoning styles (e.g. maximizing and satisficing tendencies) heavily influence analytical processes, while affective processes are often dependent on regret. The relationship between regret and cognitive reasoning styles has not been well studied in physicians, and is the focus of this paper. METHODS: A regret questionnaire and 6 scales measuring individual differences in cognitive styles (maximizing-satisficing tendencies; analytical vs. intuitive reasoning; need for cognition; intolerance toward ambiguity; objectivism; and cognitive reflection) were administered through a web-based survey to physicians of the University of South Florida. Bonferroni's adjustment was applied to the overall correlation analysis. The correlation analysis was also performed without Bonferroni's correction, given the strong theoretical rationale indicating the need for a separate hypothesis. We also conducted a multivariate regression analysis to identify the unique influence of predictors on regret. RESULTS: 165 trainees and 56 attending physicians (age range 25 to 69) participated in the survey. After bivariate analysis we found that maximizing tendency positively correlated with regret with respect to both decision difficulty (r=0.673; p<0.001) and alternate search strategy (r=0.239; p=0.002). When Bonferroni's correction was not applied, we also found a negative relationship between satisficing tendency and regret (r=-0.156; p=0.021). In trainees, but not faculty, regret negatively correlated with rational-analytical thinking (r=-0.422; p<0.001), need for cognition (r=-0.340; p<0.001), and objectivism (r=-0.309; p=0.003) and positively correlated with ambiguity intolerance (r=0.285; p=0.012). However, after conducting a multivariate regression analysis, we found that regret was positively associated with maximizing only with respect to decision difficulty (r=0.791; p<0.001), while it was negatively associated with satisficing (r=-0.257; p=0.020) and objectivism (r=-0.267; p=0.034). We found no statistically significant relationship between regret and overall accuracy on conditional inferential tasks. CONCLUSION: Regret in physicians is strongly associated with their tendency to maximize; i.e. the tendency to consider more choices among abundant options leads to more regret. However, physicians who exhibit satisficing tendency - the inclination to accept a "good enough" solution - feel less regret. Our observation that objectivism is a negative predictor of regret indicates that the tendency to seek and use empirical data in decision-making leads to less regret. Therefore, promotion of evidence-based reasoning may lead to lower regret.

Clinicopathologic predictors of sentinel lymph node metastasis in thin melanoma.

PURPOSE: Indications for sentinel lymph node biopsy (SLNB) for thin melanoma are continually evolving. We present a large multi-institutional study to determine factors predictive of sentinel lymph node (SLN) metastasis in thin melanoma. PATIENTS AND METHODS: Retrospective review of the Sentinel Lymph Node Working Group database from 1994 to 2012 identified 1,250 patients who had an SLNB and thin melanomas (≤ 1 mm). Clinicopathologic characteristics were correlated with SLN status and outcome. RESULTS: SLN metastases were detected in 65 (5.2%) of 1,250 patients. On univariable analysis, rates of Breslow thickness ≥ 0.75 mm, Clark level ≥ IV, ulceration, and absence of regression differed significantly between positive and negative SLN groups (all P < .05). These four variables and mitotic rate were used in multivariable analysis, which demonstrated that Breslow thickness ≥ 0.75 mm (P = .03), Clark level ≥ IV (P = .05), and ulceration (P = .01) significantly predicted SLN metastasis with 6.3%, 7.0%, and 11.6% of the patients with these respective characteristics having SLN disease. Melanomas < 0.75 mm had positive SLN rates of < 5% regardless of Clark level and ulceration status. Median follow-up was 2.6 years. Melanoma-specific survival was significantly worse for patients with positive versus negative SLNs (P = .001). CONCLUSION: Breslow thickness ≥ 0.75 mm, Clark level ≥ IV, and ulceration significantly predict SLN disease in thin melanoma. Most SLN metastases (86.2%) occur in melanomas ≥ 0.75 mm, with 6.3% of these patients having SLN disease, whereas in melanomas < 0.75 mm, SLN metastasis rates are < 5%. By using a 5% metastasis risk threshold, SLNB is indicated for melanomas ≥ 0.75 mm, but further study is needed to define indications for SLNB in melanomas < 0.75 mm.

Screening for prostate cancer.

BACKGROUND: Any form of screening aims to reduce disease-specific and overall mortality, and to improve a person's future quality of life. Screening for prostate cancer has generated considerable debate within the medical and broader community, as demonstrated by the varying recommendations made by medical organizations and governed by national policies. To better inform individual patient decision-making and health policy decisions, we need to consider the entire body of data from randomised controlled trials (RCTs) on prostate cancer screening summarised in a systematic review. In 2006, our Cochrane review identified insufficient evidence to either support or refute the use of routine mass, selective, or opportunistic screening for prostate cancer. An update of the review in 2010 included three additional trials. Meta-analysis of the five studies included in the 2010 review concluded that screening did not significantly reduce prostate cancer-specific mortality. In the past two years, several updates to studies included in the 2010 review have been published thereby providing the rationale for this update of the 2010 systematic review. OBJECTIVES: To determine whether screening for prostate cancer reduces prostate cancer-specific mortality or all-cause mortality and to assess its impact on quality of life and adverse events. SEARCH METHODS: An updated search of electronic databases (PROSTATE register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CANCERLIT, and the NHS EED) was performed, in addition to handsearching of specific journals and bibliographies, in an effort to identify both published and unpublished trials. SELECTION CRITERIA: All RCTs of screening versus no screening for prostate cancer were eligible for inclusion in this review. DATA COLLECTION AND ANALYSIS: The original search (2006) identified 99 potentially relevant articles that were selected for full-text review. From these citations, two RCTs were identified as meeting the inclusion criteria. The search for the 2010 version of the review identified a further 106 potentially relevant articles, from which three new RCTs were included in the review. A total of 31 articles were retrieved for full-text examination based on the updated search in 2012. Updated data on three studies were included in this review. Data from the trials were independently extracted by two authors. MAIN RESULTS: Five RCTs with a total of 341,342 participants were included in this review. All involved prostate-specific antigen (PSA) testing, with or without digital rectal examination (DRE), though the interval and threshold for further evaluation varied across trials. The age of participants ranged from 45 to 80 years and duration of follow-up from 7 to 20 years. Our meta-analysis of the five included studies indicated no statistically significant difference in prostate cancer-specific mortality between men randomised to the screening and control groups (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.86 to 1.17). The methodological quality of three of the studies was assessed as posing a high risk of bias. The European Randomized Study of Screening for Prostate Cancer (ERSPC) and the US Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial were assessed as posing a low risk of bias, but provided contradicting results. The ERSPC study reported a significant reduction in prostate cancer-specific mortality (RR 0.84, 95% CI 0.73 to 0.95), whilst the PLCO study concluded no significant benefit (RR 1.15, 95% CI 0.86 to 1.54). The ERSPC was the only study of the five included in this review that reported a significant reduction in prostate cancer-specific mortality, in a pre-specified subgroup of men aged 55 to 69 years of age. Sensitivity analysis for overall risk of bias indicated no significant difference in prostate cancer-specific mortality when referring to the meta analysis of only the ERSPC and PLCO trial data (RR 0.96, 95% CI 0.70 to 1.30). Subgroup analyses indicated that prostate cancer-specific mortality was not affected by the age at which participants were screened. Meta-analysis of four studies investigating all-cause mortality did not determine any significant differences between men randomised to screening or control (RR 1.00, 95% CI 0.96 to 1.03). A diagnosis of prostate cancer was significantly greater in men randomised to screening compared to those randomised to control (RR 1.30, 95% CI 1.02 to 1.65). Localised prostate cancer was more commonly diagnosed in men randomised to screening (RR 1.79, 95% CI 1.19 to 2.70), whilst the proportion of men diagnosed with advanced prostate cancer was significantly lower in the screening group compared to the men serving as controls (RR 0.80, 95% CI 0.73 to 0.87). Screening resulted in a range of harms that can be considered minor to major in severity and duration. Common minor harms from screening include bleeding, bruising and short-term anxiety. Common major harms include overdiagnosis and overtreatment, including infection, blood loss requiring transfusion, pneumonia, erectile dysfunction, and incontinence. Harms of screening included false-positive results for the PSA test and overdiagnosis (up to 50% in the ERSPC study). Adverse events associated with transrectal ultrasound (TRUS)-guided biopsies included infection, bleeding and pain. No deaths were attributed to any biopsy procedure. None of the studies provided detailed assessment of the effect of screening on quality of life or provided a comprehensive assessment of resource utilization associated with screening (although preliminary analyses were reported). AUTHORS' CONCLUSIONS: Prostate cancer screening did not significantly decrease prostate cancer-specific mortality in a combined meta-analysis of five RCTs. Only one study (ERSPC) reported a 21% significant reduction of prostate cancer-specific mortality in a pre-specified subgroup of men aged 55 to 69 years. Pooled data currently demonstrates no significant reduction in prostate cancer-specific and overall mortality. Harms associated with PSA-based screening and subsequent diagnostic evaluations are frequent, and moderate in severity. Overdiagnosis and overtreatment are common and are associated with treatment-related harms. Men should be informed of this and the demonstrated adverse effects when they are deciding whether or not to undertake screening for prostate cancer. Any reduction in prostate cancer-specific mortality may take up to 10 years to accrue; therefore, men who have a life expectancy less than 10 to 15 years should be informed that screening for prostate cancer is unlikely to be beneficial. No studies examined the independent role of screening by DRE.

Screening for prostate cancer: systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: To examine the evidence on the benefits and harms of screening for prostate cancer. DESIGN: Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: Electronic databases including Medline, Embase, CENTRAL, abstract proceedings, and reference lists up to July 2010. Review methods Included studies were randomised controlled trials comparing screening by prostate specific antigen with or without digital rectal examination versus no screening. Data abstraction and assessment of methodological quality with the GRADE approach was assessed by two independent reviewers and verified by the primary investigator. Mantel-Haenszel and inverse variance estimates were calculated and pooled under a random effects model expressing data as relative risks and 95% confidence intervals. RESULTS: Six randomised controlled trials with a total of 387 286 participants that met inclusion criteria were analysed. Screening was associated with an increased probability of receiving a diagnosis of prostate cancer (relative risk 1.46, 95% confidence interval 1.21 to 1.77; P<0.001) and stage I prostate cancer (1.95, 1.22 to 3.13; P=0.005). There was no significant effect of screening on death from prostate cancer (0.88, 0.71 to 1.09; P=0.25) or overall mortality (0.99, 0.97 to 1.01; P=0.44). All trials had one or more substantial methodological limitations. None provided data on the effects of screening on participants' quality of life. Little information was provided about potential harms associated with screening. CONCLUSIONS: The existing evidence from randomised controlled trials does not support the routine use of screening for prostate cancer with prostate specific antigen with or without digital rectal examination.