Joseph Nicholson

Overdiagnosis and Overtreatment of Prostate Cancer

CONTEXT Although prostate cancer (PCa) screening reduces the incidence of advanced disease and mortality, trade-offs include overdiagnosis and resultant overtreatment. OBJECTIVE To review primary data on PCa overdiagnosis and overtreatment. EVIDENCE ACQUISITION Electronic searches were conducted in Cochrane Central Register of Controlled Trials, PubMed, and Embase from inception to July 2013 for original articles on PCa overdiagnosis and overtreatment. Supplemental articles were identified through hand searches. EVIDENCE SYNTHESIS The lead-time and excess-incidence approaches are the main ways used to estimate overdiagnosis in epidemiological studies, with estimates varying widely. The estimated number of PCa cases needed to be diagnosed to save a life has ranged from 48 down to 5 with increasing follow-up. In clinical studies, generally lower rates of overdiagnosis have been reported based on the frequency of low-grade minimal tumors at radical prostatectomy (1.7-46.8%). Autopsy studies have reported PCa in 18.5-38.5%, although not all are low grade or low volume. Factors influencing overdiagnosis include the study population, screening protocol, and background incidence, limiting generalizability between settings. Reported rates of overtreatment vary widely in the literature, although contemporary international studies suggest increasing use of conservative management. CONCLUSIONS Epidemiological, clinical, and autopsy studies have been used to examine PCa overdiagnosis, with estimates ranging widely from 1.7% to 67%. Correspondingly, estimates of overtreatment vary widely based on patient features and may be declining internationally. Careful patient selection for screening and reducing overtreatment are important to preserve the benefits and reduce the downstream harms of prostate-specific antigen testing. Because all of these estimates are extremely population and context specific, this must be considered when using these data to inform policy. PATIENT SUMMARY Screening reduces spread and death from prostate cancer (PCa) but overdiagnoses some low-risk tumors that may not have caused harm. Because treatment has potential side effects, it is critical that not all patients with PCa receive aggressive treatment.

Active surveillance for prostate cancer: A systematic review of clinicopathologic variables and biomarkers for risk stratification

CONTEXT Active surveillance (AS) is an important strategy to reduce prostate cancer overtreatment. However, the optimal criteria for eligibility and predictors of progression while on AS are debated. OBJECTIVE To review primary data on markers, genetic factors, and risk stratification for patient selection and predictors of progression during AS. EVIDENCE ACQUISITION Electronic searches were conducted in PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to April 2014 for original articles on biomarkers and risk stratification for AS. EVIDENCE SYNTHESIS Patient factors associated with AS outcomes in some studies include age, race, and family history. Multiple studies provide consistent evidence that a lower percentage of free prostate-specific antigen (PSA), a higher Prostate Health Index (PHI), a higher PSA density (PSAD), and greater biopsy core involvement at baseline predict a greater risk of progression. During follow-up, serial measurements of PHI and PSAD, as well as repeat biopsy results, predict later biopsy progression. While some studies have suggested a univariate relationship between urinary prostate cancer antigen 3 (PCA3) and transmembrane protease, serine 2-v-ets avian erythroblastosis virus E26 oncogene homolog gene fusion (TMPRSS2:ERG) with adverse biopsy features, these markers have not been consistently shown to independently predict AS outcomes. No conclusive data support the use of genetic tests in AS. Limitations of these studies include heterogeneous definitions of progression and limited follow-up. CONCLUSIONS There is a growing body of literature on patient characteristics, biopsy features, and biomarkers with potential utility in AS. More data are needed on practical applications such as combining these tests into multivariable clinical algorithms and long-term outcomes to further improve AS in the future. PATIENT SUMMARY Several PSA-based tests (free PSA, PHI, PSAD) and the extent of cancer on biopsy can help to stratify the risk of progression during active surveillance. Investigation of several other markers is under way.

Chemoradiation therapy versus chemotherapy alone for gastric cancer after R0 surgical resection: a meta-analysis of randomized trials.

Objective: Current national guidelines include category 1 recommendations for perioperative chemotherapy or adjuvant chemoradiation with surgical resection for patients with stage IB-IIIB gastric cancer. We conducted a meta-analysis of randomized trials in which chemotherapy was prospectively tested against chemoradiation with surgical resection. Methods: We electronically searched PubMed and EMBASE for randomized, controlled clinical trials involving patients with gastric adenocarcinoma, status post-R0 resection. The interventions compared were adjuvant chemotherapy versus chemoradiation, with any chemotherapy regimen. The primary outcomes of interest were disease-free survival and overall survival. The Mantel-Haenszel random-effects model was used to calculate effect sizes. Results: Six trials that included 1,171 patients were evaluated; 599 were randomized to adjuvant chemoradiation and 572 to chemotherapy alone. Chemoradiation was associated with a significant increase in disease-free survival (odds ratio 1.48, 95% confidence interval 1.08-2.03) when compared to chemotherapy alone. However, there was no significant difference in overall survival (odds ratio 1.27, 95% confidence interval 0.95-1.71). Five trials found no statistically significant differences in toxicities between the two groups. Conclusion: In patients with gastric cancer status post-R0 resection, adjuvant chemoradiation was associated with higher disease-free survival when compared to chemotherapy alone. It remains appropriate to design trials testing new systemic agents with radiotherapy.

The Benefits and Risks of Being a Standardized Patient: A Narrative Review of the Literature

Standardized patients (SPs) are a widely used, valid, and reliable means of teaching and evaluating healthcare providers (HCPs) across all levels of training and across multiple domains of both clinical and communication skills. Most research on SP programs focuses on outcomes pertinent to the learners (i.e., HCPs) rather than how this experience affects the SPs themselves. This review seeks to summarize the current literature on the risks and benefits of being an SP. We reviewed the literature on the effects that simulation has on adults, children/adolescents, and medical professionals who serve as SPs, in addition to real patients (RPs) who are involved in teaching by sharing their medical histories and experiences. To collect the literature, we conducted two separate systematic searches: one for SPs and one for RPs. Following the searches, we applied standardized eligibility criteria to narrow the literature down to articles within the scope of this review. A total of 67 studies were included that focused on the outcomes of SPs or RPs. The benefits for those portraying SP roles include improved health knowledge and attitudes, relationships with their HCPs, and changed health behaviors. Negative effects of being an SP include anxiety, exhaustion/fatigue, and physical discomfort immediately following a simulation, but the literature to date appears to indicate that there are no long-lasting effects. These findings are consistent across age groups and the type of role being simulated. They are also supported by studies of RPs who are involved in medical education. Overall, the benefits of being an SP appear to outweigh the known risks. However, there are significant limitations in the current literature, and additional studies are needed to better characterize the SP experience.

Diagnosis of Superior Labrum Anterior-to-Posterior Tears by Using MR Imaging and MR Arthrography: A Systematic Review and Meta-Analysis

Purpose To evaluate the diagnostic accuracies of nonenhanced magnetic resonance (MR) imaging and MR arthrography for diagnosis of superior labrum anterior-to-posterior (SLAP) tears by using a systematic review and meta-analysis. Materials and Methods A comprehensive literature search was performed on the two main concepts of MR imaging (MR imaging, and direct and indirect MR arthrography) and SLAP tears. Inclusion criteria consisted of original studies that assessed the diagnostic accuracy of MR imaging, direct MR arthrography, and/or indirect MR arthrography for the detection of SLAP tears, by using surgical findings as the reference standard. The Quality Assessment of Diagnostic Accuracy Studies 2, or QUADAS-2 Quality Assessment of Diagnostic Accuracy Studies 2 Quality Assessment of Diagnostic Accuracy Studies 2 , tool was used to assess methodologic quality. Meta-analyses were performed that compared MR imaging studies to direct MR arthrography studies and indirect MR arthrography studies, 3-T studies to 1.5-T studies, and low-bias MR imaging studies to low-bias direct MR arthrography studies. Study variation was analyzed by using the Cochran Q test of heterogeneity and the I2 statistic. Results Thirty-two studies met inclusion and exclusion criteria, including 3524 imaging examinations: 1963 direct MR arthrography examinations (23 studies), 1402 MR examinations (14 studies), and 159 indirect MR arthrography examinations (three studies). Twelve studies had low risk for bias, two had questionable risk, and 18 had high risk. Mean sensitivities of direct MR arthrography, MR imaging, and indirect MR arthrography for SLAP tear diagnosis were 80.4%, 63.0%, and 74.2%, respectively. Mean specificities of direct MR arthrography, MR imaging, and indirect MR arthrography were 90.7%, 87.2%, and 66.5%, respectively. Summary receiver operator characteristic (ROC) curve demonstrated superior accuracy of direct MR arthrography compared with those of MR imaging and indirect MR arthrography. Similar findings were observed in the low-bias subanalysis. Summary ROC curve demonstrated overall superiority of 3-T imaging, with or without intra-articular contrast material compared with 1.5-T imaging, with or without intra-articular contrast material. Significant variance was observed for MR imaging and direct MR arthrography (P < .001) studies for both mean sensitivity and specificity. Conclusion Direct MR arthrography appears to be more accurate than nonenhanced MR imaging for diagnosis of SLAP tears, whereas 3-T MR imaging with or without intra-articular contrast material appears to improve diagnostic accuracy compared with 1.5-T MR imaging with or without intra-articular contrast material.

Consumption of whole grains and cereal fiber in relation to cancer risk: a systematic review of longitudinal studies

CONTEXT Evidence from previous reviews is supportive of the hypothesis that whole grains may protect against various cancers. However, the reviews did not report risk estimates for both whole grains and cereal fiber and only case-control studies were evaluated. It is unclear whether longitudinal studies support this conclusion. OBJECTIVE To evaluate associations between whole grains and cereal fiber in relation to risk of lifestyle-related cancers data from longitudinal studies was evaluated. DATA SOURCES The following 3 databases were systematically searched: PubMed, EMBASE, and Cochrane CENTRAL. STUDY SELECTION A total of 43 longitudinal studies conducted in Europe and North America that reported multivariable-adjusted risk estimates for whole grains (n = 14), cereal fiber (n = 23), or both (n = 6) in relation to lifestyle-related cancers were included. DATA EXTRACTION Information on study location, cohort name, follow-up duration, sample characteristics, dietary assessment method, risk estimates, and confounders was extracted. DATA SYNTHESIS Of 20 studies examining whole grains and cancer, 6 studies reported a statistically significant 6%-47% reduction in risk, but 14 studies showed no association. Of 29 studies examining cereal fiber intake in relation to cancer, 8 showed a statistically significant 6%-49% reduction in risk, whereas 21 studies reported no association. CONCLUSIONS This systematic review concludes that most studies were suggestive of a null association. Whole grains and cereal fiber may protect against gastrointestinal cancers, but these findings require confirmation in additional studies.

Mobile phone messaging for illicit drug and alcohol dependence: A systematic review of the literature

ISSUES Mobile phone use has increased dramatically and concurrent with rapid developments in mobile phone-based health interventions. The integration of text messaging interventions promises to optimise the delivery of care for persons with substance dependence with minimal disruption to clinical workflows. We conducted a systematic review to assess the acceptability, feasibility and clinical impact of text messaging interventions for persons with illicit drug and alcohol dependence. APPROACH Studies were required to evaluate the use of text messaging as an intervention for persons who met Diagnostic and Statistical Manual of Mental Disorders, 4th edition criterion for a diagnosis of illicit drug and/or alcohol dependence. Authors searched for articles published to date in MEDLINE (pubmed.gov), the Cochrane Library, EMBASE, CINAHL, Google Scholar and PsychINFO. KEY FINDINGS Eleven articles met the search criteria for this review and support the acceptability and feasibility of text messaging interventions for addressing illicit drug and alcohol dependence. Most studies demonstrated improved clinical outcomes, medication adherence and engagement with peer support groups. Text messaging interventions also intervened on multiple therapeutic targets such as appointment attendance, motivation, self-efficacy, relapse prevention and social support. IMPLICATIONS Suggestions for future research are described, including intervention design features, clinician contact, privacy measures and integration of behaviour change theories. CONCLUSION Text messaging interventions offer a feasible platform to address a range of substances (i.e. alcohol, methamphetamine, heroin and alcohol), and there is increasing evidence supporting further larger-scale studies. [Tofighi B, Nicholson JM, McNeely J, Muench F, Lee JD. Mobile phone messaging for illicit drug and alcohol dependence: A systematic review of the literature. Drug Alcohol Rev 2017;36:477-491].

Consumption of Sugars, Sugary Foods, and Sugary Beverages in Relation to Cancer Risk: A Systematic Review of Longitudinal Studies

High sugar intake may increase cancer risk by promoting insulin-glucose dysregulation, oxidative stress, inflammation, and body adiposity, but epidemiologic evidence is unclear. Associations between dietary sugars and lifestyle-related cancer risk from longitudinal studies were evaluated. We systematically searched PubMed, Embase, and CINAHL and identified 37 prospective cohort studies (1990-2017) reporting multivariable adjusted risk estimates for dietary sugars in relation to cancer. Of 15 and 14 studies on total sugar and sucrose respectively, 11 reported a null association in relation to cancer. Of 14 studies on fructose, 8 reported null associations, and 2 reported protective and 4 reported detrimental associations. In two of five studies on added sugars, a 60-95% increased cancer risk was observed with higher intakes. In 8 of 15 studies on sugary foods and beverages, a 23-200% higher cancer risk was observed with higher sugary beverage consumption. In conclusion, most studies were indicative of a null association, but suggestive detrimental associations were reported for added sugars and sugary beverages.

Parental Management of Discharge Instructions: A Systematic Review

This is a systematic review of the literature related to parental management (knowledge and execution) of inpatient and ED discharge instructions. CONTEXT: Parents often manage complex instructions when their children are discharged from the inpatient setting or emergency department (ED); misunderstanding instructions can put children at risk for adverse outcomes. Parents’ ability to manage discharge instructions has not been examined before in a systematic review. OBJECTIVE: To perform a systematic review of the literature related to parental management (knowledge and execution) of inpatient and ED discharge instructions. DATA SOURCES: We consulted PubMed/Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, and Cochrane CENTRAL (from database inception to January 1, 2017). STUDY SELECTION: We selected experimental or observational studies in the inpatient or ED settings in which parental knowledge or execution of discharge instructions were evaluated. DATA EXTRACTION: Two authors independently screened potential studies for inclusion and extracted data from eligible articles by using a structured form. RESULTS: Sixty-four studies met inclusion criteria; most (n = 48) were ED studies. Medication dosing and adherence errors were common; knowledge of medication side effects was understudied (n = 1). Parents frequently missed follow-up appointments and misunderstood return precaution instructions. Few researchers conducted studies that assessed management of instructions related to diagnosis (n = 3), restrictions (n = 2), or equipment (n = 1). Complex discharge plans (eg, multiple medicines or appointments), limited English proficiency, and public or no insurance were associated with errors. Few researchers conducted studies that evaluated the role of parent health literacy (ED, n = 5; inpatient, n = 0). LIMITATIONS: The studies were primarily observational in nature. CONCLUSIONS: Parents frequently make errors related to knowledge and execution of inpatient and ED discharge instructions. Researchers in the future should assess parental management of instructions for domains that are less well studied and focus on the design of interventions to improve discharge plan management.

Self-assessment and goal-setting is associated with an improvement in interviewing skills

Purpose Describe the relationship between medical students’ self-assessment and goal-setting (SAGS) skills and development of interviewing skills during the first-year doctoring course. Method 157 first-year medical students completed three two-case standardized patient (SP) interviews. After each of the first two, students viewed videotapes of their interview, completed a SAGS worksheet, and reviewed a selected tape segment in a seminar. SAGS was categorized into good and poor quality and interviewing skills were rated by trained raters. Results SAGS improved over time (37% good week 1 vs. 61% good week 10). Baseline SAGS and interviewing skills were not associated. Initial SAGS quality was associated with change in interviewing skills – those with poor-quality SAGS demonstrated a decrease and those with good-quality SAGS demonstrated an increase in scores by 17 weeks (ANOVA F=4.16, p=0.024). For students whose SAGS skills were good at both week 1 and 10, interviewing skills declined in weeks 1–10 and then increased significantly at week 17. For those whose SAGS remained ‘poor’ in weeks 1–10, interviewing skills declined in weeks 10–17. Conclusions In general, the quality of students’ SAGS improved over time. Poor baseline SAGS skills and failure to improve were associated with a decrease in interviewing skills at 17 weeks. For students with better SAGS, interviewing skills increased at week 17. Improvement in SAGS skills was not associated with improved interviewing skills. Understanding structured self-assessment skills helps identify student characteristics that influence progressive mastery of communication skills and therefore may inform curriculum and remediation tailoring.