Showing papers by "Timothy J Wilt published in 2014"

Prevention and early detection of prostate cancer

Abstract: Prostate cancer is a common malignancy in men and the worldwide burden of this disease is rising. Lifestyle modifications such as smoking cessation, exercise, and weight control offer opportunities to reduce the risk of developing prostate cancer. Early detection of prostate cancer by prostate-specific antigen (PSA) screening is controversial, but changes in the PSA threshold, frequency of screening, and the use of other biomarkers have the potential to minimise the overdiagnosis associated with PSA screening. Several new biomarkers for individuals with raised PSA concentrations or those diagnosed with prostate cancer are likely to identify individuals who can be spared aggressive treatment. Several pharmacological agents such as 5α-reductase inhibitors and aspirin could prevent development of prostate cancer. In this Review, we discuss the present evidence and research questions regarding prevention, early detection of prostate cancer, and management of men either at high risk of prostate cancer or diagnosed with low-grade prostate cancer.

Antimicrobial stewardship programs in inpatient hospital settings: a systematic review.

Abstract: Objective Evaluate the evidence for effects of inpatient antimicrobial stewardship programs (ASPs) on patient, prescribing, and microbial outcomes Design Systematic review Methods Search of MEDLINE (2000 through November 2013), Cochrane Library, and reference lists of relevant studies We included English language studies with patient populations relevant to the United States (ie, infectious conditions and prescriptions required for antimicrobials) that evaluated ASP interventions and reported outcomes of interest Study characteristics and outcomes data were extracted and reviewed by investigators and trained research personnel Results Few intervention types (eg, audit and feedback, guideline implementation, and decision support) substantially impacted patient outcomes, including mortality, length of stay, readmission, or incidence of Clostridium difficile infection However, most interventions were not powered adequately to demonstrate impacts on patient outcomes Most interventions were associated with improved prescribing patterns as measured by decreased antimicrobial use or increased appropriate use Where reported, ASPs were generally associated with improvements in microbial outcomes, including institutional resistance patterns or resistance in the study population Few data were provided on harms, sustainability, or key intervention components Studies were typically of short duration, low in methodological quality, and varied in study design, populations enrolled, hospital setting, ASP intent, intervention composition and implementation, comparison group, and outcomes assessed Conclusions Numerous studies suggest that ASPs can improve prescribing and microbial outcomes Strength of evidence was low, and most studies were not designed adequately to detect improvements in mortality or other patient outcomes, but obvious adverse effects on patient outcomes were not reported

Can we deliver randomized trials of focal therapy in prostate cancer

Abstract: Tissue-preserving focal therapies, such as brachytherapy, cryotherapy, high-intensity focused ultrasound and photodynamic therapy, aim to target individual cancer lesions rather than the whole prostate. These treatments have emerged as potential interventions for localized prostate cancer to reduce treatment-related adverse-effects associated with whole-gland treatments, such as radical prostatectomy and radiotherapy. In this article, the Prostate Cancer RCT Consensus Group propose that a novel cohort-embedded randomized controlled trial (RCT) would provide a means to study men with clinically significant localized disease, which we defined on the basis of PSA level (≤ 15 ng/ml or ≤ 20 ng/ml), Gleason grade (Gleason pattern ≤ 4 + 4 or ≤ 4 + 3) and stage (≤ cT2cN0M0). This RCT should recruit men who stand to benefit from treatment, with the control arm being whole-gland surgery or radiotherapy. Composite outcomes measuring rates of local and systemic salvage therapies at 3-5 years might best constitute the basis of the primary outcome on which to change practice.

Lower urinary tract symptoms in men

Abstract: Benign prostatic hyperplasia (BPH) is a highly prevalent and costly condition that affects older men worldwide. Many affected men develop lower urinary tract symptoms, which can have a negative impact on their quality of life. In the past, transurethral resection of the prostate (TURP) was the mainstay of treatment. However, several efficacious drug treatments have been developed, which have transformed BPH from an acute surgical entity to a chronic medical condition. Specifically, multiple clinical trials have shown that α adrenoceptor antagonists can significantly ameliorate lower urinary tract symptoms. Moreover, 5α reductase inhibitors, alone or combined with an α adrenoceptor antagonist, can reverse the natural course of BPH, reducing the risk of urinary retention and the need for surgical intervention. Newer medical regimens including the use of antimuscarinic agents or phosphodiesterase type 5 inhibitors, have shown promise in men with predominantly storage symptoms and concomitant erectile dysfunction, respectively. For men who do not adequately respond to conservative measures or pharmacotherapy, minimally invasive surgical techniques (such as transurethral needle ablation, microwave thermotherapy, and prostatic urethral lift) may be of benefit, although they lack the durability of TURP. A variety of laser procedures have also been introduced, whose improved hemostatic properties abrogate many of the complications associated with traditional surgery.

Screening Pelvic Examinations in Asymptomatic, Average-Risk Adult Women: An Evidence Report for a Clinical Practice Guideline From the American College of Physicians

Abstract: Pelvic examination (excluding cervical cancer screening) has been a regular part of preventive care in women for decades. This systematic review for the American College of Physicians (ACP) evaluat...

Effectiveness of family and caregiver interventions on patient outcomes in adults with cancer: a systematic review.

Abstract: BACKGROUND Family and caregiver interventions typically aim to develop family members’ coping and caregiving skills and to reduce caregiver burden We conducted a systematic review of published randomized controlled trials (RCTs) evaluating whether family-involved interventions improve patient outcomes among adults with cancer

Prostate-Specific Antigen Screening in Prostate Cancer: Perspectives on the Evidence

Abstract: Ethan BaschDespite multiple prospective clinical trials, observational stud-ies, retrospective analyses, and simulation models, intense con-troversy persists regarding the value of screening for prostate cancer with the prostate-specific antigen (PSA) test. Similar data have been used to draw conflicting conclusions, and clinical practice guidelines appear discordant on the merits of screening (1–4).Where are the areas of guideline agreement? There is general consensus that there is limited or no benefit of PSA screening among older men (ie, those aged ≥70 or 75 years) or those with limited life expectancy (ie, <10–15 years). There is agreement that there are real harms associated with downstream clinical actions taken in response to PSA screening. And there is agreement that there is overtreatment of low-grade tumors once discovered, with growing encouragement to pursue programs of active surveillance in such men, with nascent but expanding evidence in this area (5). For men considering PSA screening, an informed discussion with their provider is universally advised.Although guidelines have recently come into greater agree-ment with each other, differences do remain. In 2012, the US Preventive Services Task Force (USPSTF) recommended against PSA screening in all men (1). The American Society of Clinical Oncology followed by agreeing with this approach only for older men but advising informed decision-making in younger men (2). Subsequently, the American Urological Association substantially revised its prior recommendations by advising against screening in men aged 70 years or older as well as in those aged less than 55 years unless at high risk of disease, with informed decision-mak-ing suggested for those between the ages of 55 and 69 years (3). These recommendations are similar to those from the American College of Physicians (4,6).Why has the scientific evidence been so challenging to inter-pret? The main culprit is the history of how PSA screening evolved, without rigorous prospective evaluation of its impact on outcomes that matter to people—such as survival and quality of life. The test became widely practiced starting in the 1980s in the absence of such evidence. It has been challenging to evaluate benefits and harms on a widely practiced test. For example, the rates of PSA screening “contamination” in the no-screening control arm of the Prostate, Lung, Colorectal and Ovarian trial was estimated at approximately 70% (7 ) and in the European Randomized Study of Screening for Prostate Cancer (ERSPC) was estimated at greater than 20% (8) (although in both cases it was likely higher).Unfortunately, the current regulatory context in which molecu-lar diagnostic tests are developed still does not require the gen-eration of clinically meaningful outcomes data (also referred to as clinical utility data). As a result, there is a substantial risk that future screening tests will emerge with similar evidence challenges. Most commercially available screening tests today are developed and marketed as laboratory diagnostic tests, which have low barriers to market entry and are not required to demonstrate evidence of clinical benefit (9). Many physicians likely assume incorrectly that these tests have proven effectiveness and safety.Recent efforts have been made to strengthen methodologi-cal standards for evaluation of diagnostic tests. For example, the Patient-Centered Outcomes Research Institute (PCORI), estab-lished in 2010 by the US Patient Protection and Affordable Care Act, has established a standard that recommends to “focus studies of diagnostic tests on patient-centered outcomes, using rigorous study designs with preference for randomized controlled trials” (10). In 2013, the Center for Medical Technology Policy (CMTP) issued an Effectiveness Guidance Document similarly recommend-ing that clinical utility be assessed prospectively for new diagnostic tests (11).However, the current US regulatory framework does not have any mechanism for requiring this level of evidence for diagnostic or screen-ing tests. This is an area of urgently needed attention as countless new tests are developed and marketed to our colleagues and patients.Two perspectives on the evidence for PSA screening are pro-vided in this issue of the Journal from opposing camps on this issue, first from Dr Timothy Wilt on the hazards of PSA screen-ing and then from Dr Peter Scardino on the merits of tailored PSA screening and treatment strategies. These perspectives, and the above comments, build on an educational session at the 2013 American Society of Clinical Oncology annual meeting on this topic (12).

The Effects of Shared Decision Making on Cancer Screening – A Systematic Review

Abstract: s from the MEDLINE search (n=1640) were reviewed in duplicate, independently by investigators and co-investigators Abstracts from the CINAHL (n=460) and PsycINFO (n=268) searches were reviewed by a co-investigator Each article identified for full-text review was independently reviewed by 2 investigators or co-investigators We included RCTs comparing a SDM intervention to usual care (UC), alternative SDM interventions, or a combination We included studies that evaluated SDM interventions for cancer screening as part of the study, excluding studies in which participants made hypothetical cancer screening choices We included studies involving adults in a clinic setting, either at or shortly before an appointment, as a component to encourage SDM with the clinician To ensure that we did not include interventions that encouraged screening, we excluded studies that measured only Decision Action (not Decision Quality or Decision Impact) and studies evaluating interventions with the stated goal of promoting screening Excluded articles are presented in Appendix B Shared Decision Making for Cancer Screening Evidence-based Synthesis Program 17 9CONTENTS 34 DATA ABSTRACTION Study characteristics (population; sample age, gender, and race; study setting; length of followup), SDM intervention characteristics (format, delivery mode, delivery timing/location, inclusion of values clarification exercise, risk communication method, consideration of vulnerable populations, resources required), and outcomes (Decision Quality, Decision Impact, and Decision Action) were extracted onto evidence tables by one investigator or co-investigator and verified by a second

Cognitive Outcomes After Cardiovascular Procedures in Older Adults: A Systematic Review

Abstract: Objective To summarize current evidence on intermediate- and long-term cognitive outcomes after coronary and carotid revascularization, cardiac valve procedures, and ablation for atrial fibrillation in older adults, and their association with procedure-related stroke, transient ischemic attack (TIA), and other procedure and patient characteristics. Data Sources MEDLINE®, Cochrane Database of Systematic Reviews, Scopus, and ClinicalTrials.gov electronic databases from 1990 through July 2014; hand searches of references from relevant reviews and eligible studies. Review Methods We screened abstracts and full-text articles of identified references for randomized controlled trials (RCTs) and prospective cohort studies in adults aged ≥65 years that reported intermediate (3 to 12 months) and/or long-term (>12 months) cognitive outcomes after one or more of the above selected cardiovascular procedures. Cognitive outcomes of interest were clinical diagnoses (e.g., mild cognitive impairment), neuropsychological test results, and incident cognitive impairment derived from a composite of neuropsychological test results. We extracted data, rated individual study risk of bias, and graded strength of evidence (SOE). Results Seventeen RCTs and 4 prospective cohort studies were included. Eighty percent of participants were male and mean age was 68 years. Five studies excluded participants for some measure of abnormal baseline cognition. Nevertheless, more than half of studies reported mean baseline scores in the impaired range for at least one neuropsychological test, most frequently with slowing in timed tests. There was no significant difference in post-procedure cognitive function between on- versus off-pump coronary artery bypass grafting (CABG) (n=6) (low SOE), hypothermic versus normothermic CABG (n=3) (moderate to low SOE), or CABG versus medical management (n=1) (insufficient SOE). One trial reported lower risk of incident cognitive impairment at 3 months with minimal versus conventional extracorporeal bypass CABG (RR=0.34 [95%CI=0.16–0.73]). Two trials found no difference between surgical and endovascular carotid revascularization (low to insufficient SOE). One cohort study reported increased cognitive decline after transcatheter versus surgical aortic valve replacement at 3 months (28% versus 6 %, p=0.04), but results may have been limited by large selection and outcome measurement biases (insufficient SOE). Because study participants had few strokes and transient ischemic attacks, we could not determine whether these events affected post-procedure cognitive outcomes. We found no evidence from eligible studies about whether patient characteristics such as age and baseline cognitive function modify the association between these cardiovascular procedures and intermediate- or long-term post-procedure cognitive outcomes. This review was limited by the small number of eligible studies for each treatment comparison, including no eligible studies that assessed cognitive outcomes after ablation for atrial fibrillation; heterogeneity of cognitive outcomes; and limited individual study quality. Results may have limited generalizability to the elderly, women, or individuals with substantial baseline cognitive impairment. Conclusions Persistent cognitive impairment attributable to studied cardiovascular procedures in older adults appeared uncommon and may reflect pre-existing cognitive impairment. Specifically, CABG may have little intermediate to long-term cognitive effect in older adults, including numerous comparisons of different versions of CABG versus each other. Intermediate-term cognitive effects may be similar between those who undergo surgical versus endovascular carotid revascularization. Results suggesting better cognition after minimal versus conventional extracorporeal bypass CABG are promising but need confirmation. Confidence in review findings should be tempered by substantial limitations in primary data quantity and quality. Results may not be generalizable to old-old patients, to women, or to patients with substantial baseline cognitive impairment.

The Paucity of Evidence Supporting Screening for Stages 1–3 CKD in Asymptomatic Patients with or without Risk Factors

Abstract: The American College of Physicians recently published a guideline on screening for CKD that recommends against screening for CKD in asymptomatic adults without risk factors. The generally accepted criteria for population-based screening for disease state that screening should improve important clinical outcomes while limiting harms for those individuals screened. However, CKD screening does not meet these criteria. There is currently no evidence evaluating or demonstrating benefits for providing early treatment for patients identified via screening who do not have risk factors. On the other hand, harms are associated with the screening and include false-positive results, unnecessary testing and treatment, and disease labeling.

Chronic Urinary Retention: Comparative Effectiveness and Harms of Treatments

Abstract: The findings and conclusions in this document are those of the authors, who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ. Therefore, no statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services. The information in this report is intended to help health care decisionmakers—patients and clinicians, health system leaders, and policymakers, among others—make well informed decisions and thereby improve the quality of health care services. This report is not intended to be a substitute for the application of clinical judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information, i.e., in the context of available resources and circumstances presented by individual patients. This report may be used, in whole or in part, as the basis for development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied. This report may periodically be assessed for the urgency to update. If an assessment is done, the resulting surveillance report describing the methodology and findings will be found on the Effective Health Care Program Web site at www.effectivehealthcare.ahrq.gov. Search on the title of the report. This document is in the public domain and may be used and reprinted without special permission. Citation of the source is appreciated. Persons using assistive technology may not be able to fully access information in this report. For assistance contact EffectiveHealthCare@ahrq.hhs.gov. None of the investigators have any affiliations or financial involvement that conflicts with the material presented in this report. Preface The Agency for Healthcare Research and Quality (AHRQ), through its Evidence-based Practice Centers (EPCs), sponsors the development of systematic reviews to assist public-and private-sector organizations in their efforts to improve the quality of health care in the United States. These reviews provide comprehensive, science-based information on common, costly medical conditions and new health care technologies and strategies. Systematic reviews are the building blocks underlying evidence-based practice; they focus attention on the strength and limits of evidence from research studies about the effectiveness and safety of a clinical intervention. In the context of developing recommendations for …

PSA screening for prostate cancer

Abstract: Achieve more for patients and payers by doing less Few healthcare issues have generated as much controversy as prostate specific antigen (PSA) based screening for prostate cancer.1 2 Enthusiasm for such screening is high in part because a seemingly simple blood test can lead to early detection and treatment of a common and potentially lethal disease. Screening has resulted in a noticeable increase in incidence of prostate cancer and near universal active treatment for screen detected disease. However, recent science shows that screening for prostate cancer, as with all screening strategies, is a complex process and double-edged sword. This provides the background for the linked paper by Carlsson and colleagues (doi:10.1136/bmj.g2296).3 Though some men may benefit from screening, many more are harmed by testing and the cascade of diagnostic and treatment related events that follow. Further, men and society bear the financial costs of this screening cascade. Rising healthcare costs and evidence that a large portion of healthcare is ineffective, unnecessary, costly, and potentially harmful require a re-evaluation of how better healthcare can be provided at lower costs—that is, how value can be improved. Screening strategies that yield similar benefits with fewer harms or lower costs provide better value; strategies that produce no benefit or where benefits do not justify harms or costs provide poor value. The value of effective screening tests can be modified by “screening intensity”—that is, by adjusting the population screened, the frequency of screening, or the …

Commentaries Pancreatic Adenocarcinoma: Treating a Systemic Disease With Systemic Therapy,

Abstract: Pancreatic adenocarcinoma, even when resectable, remains highly lethal. Although surgical outcomes have improved considerably, median overall survival after surgery and adjuvant therapy such as single-agent gemcitabine remains less than 2 years. We discuss preclinical and clinical data supporting the contention that even early-stage pancreatic cancer is a systemic disease. Autopsy series reveal that 70% to 85% of patients die of systemic recurrence, rather than local disease, after pancreatic cancer resection. Preclinical studies using genomics and mouse models reveal evidence of metastatic spread even before histopathologic evidence of a pancreatic tumor. Analogous to breast cancer, we propose that the Halstedian approach of treating pancreatic cancer as a local, surgical problem should be replaced by Fisher's alternative hypothesis of cancer as a systemic disease. Newer multiagent chemotherapy regimens have shown meaningful response rates and improvement in overall survival in the metastatic setting and, for the first time, offer investigators an opportunity to use effective systemic therapy. We emphasize that a surgery-first approach is not resonant with our current understanding of pancreatic adenocarcinoma biology and that an upfront systemic approach for even resectable pancreatic cancer warrants testing in clinical trials.

The Effects of Shared Decision Making on Cancer Screening – A Systematic Review [Internet]

Abstract: Decisions about cancer screening have become increasingly complex. Patients must decide whether to get screened, which screening modality to use, and how often to undergo and when to stop screening. Some cancer screening decisions are considered “preference-sensitive,” meaning that, due to closely-balanced benefits and harms, the “right” decision is in part dependent on an individual's values and preferences for particular outcomes. Most organizations publishing clinical practice guidelines for cancer screening now recommend that preference-sensitive cancer screening decisions be made individually, using a process that considers the available evidence on the benefits and harms of particular options, and incorporates patient values and preferences relevant to those options. This approach is sometimes referred to as shared decision making (SDM). The goal of SDM interventions is to facilitate this approach. Adjuncts for the usual counseling for specific decisions, SDM interventions may include: (1) tools to help patients comprehend information about the risks and benefits of options, clarify their personal values related to these options, and participate in decisions consistent with these values and preferences (sometimes referred to as “decision aids”) and (2) other interventions to prepare health care providers and/or systems to support this process. SDM interventions differ from many health-related interventions in that they primarily seek to elicit and support patient values and preferences in making health care-related decisions rather than to promote a particular health care strategy per se.In this review we examine the effects of SDM interventions for cancer screening in adults on constructs from the Ottawa Decision Support Framework, a commonly-used theoretical model of decision making. We examined the constructs of Decision Quality, Decision Impact, and, for studies reporting those outcomes, Decision Action. Decision Quality includes knowledge, values clarity (patients' clarity of their personal values regarding the risks and benefits of decision options), and the patients' participatory role in decision making. Decision Impact includes decisional conflict (personal uncertainty about which course of action to take), use of services (eg, consultation length), and satisfaction with the decision. Decision Action includes screening intention and behavior. The ideal SDM intervention would enhance Decision Quality (ie, increase knowledge and values clarity) and Impact (ie, increase satisfaction, reduce decision conflict, and have minimal impact on service utilization). The desired impact on Decision Action depends on the screening decision. For decisions about how to screen (such as colorectal cancer screening), the ideal SDM intervention would exert the desired effects on Decision Quality and Impact without reducing measures of Decision Action such as screening intention and behavior. For decisions about whether to screen (such as breast, cervical, and prostate cancer in some age groups and risk categories), the goal is to facilitate personalized decision making based on values and preferences. Hence, there are no desired effects on Decision Action per se in this context. We examine patient, provider, system, and multi-level SDM interventions, and therefore do not restrict this review to the most commonly employed SDM intervention of patient-directed decision aids.This topic was nominated by Linda Kinsinger, MD, MPH, VA Chief Consultant for Preventive Medicine at the VA National Center for Health Promotion and Disease Prevention (NCP). The evidence review is intended to examine the effects of SDM interventions for cancer screening practices and to inform what types of interventions NCP will disseminate with their cancer screening guidelines.

Comparative effectiveness research in clinical practice.

Abstract: The Agency for Healthcare Research and Quality (AHRQ) has funded systematic reviews of comparative effectiveness research in 17 areas over the last 10 years as part of a federal mandate. These reviews provide a reliable and unbiased source of comprehensive information about the effectiveness and risks of treatment alternatives for patients and clinicians. This article describes comparative effectiveness research, provides an overview of how physicians can use it in clinical practice, and references important contributions made by the Minnesota Evidence-based Practice Center.

Chronic Urinary Retention

Abstract: Important causes of bladder outlet obstruction Benign prostatic hyperplasia (BPH) is by far the most common cause and is a common sequelae of male ageing. Prostatic carcinoma can obstruct the urethra either by a direct mass effect (as in BPH) or by invasion of the wall. Drugs causing bladder sphincter dysfunction include: [2] Antispasmodics. Antihistamines. Anticholinergics. Botulinum toxin (used to treat overactive bladder). [3]