How to start an antimicrobial stewardship programme in a hospital.

BACKGROUND: Antimicrobial stewardship (AMS) describes a coherent set of actions that ensure optimal use of antimicrobials to improve patient outcomes, while limiting the risk of adverse events (including antimicrobial resistance (AMR)). Introduction of AMS programmes in hospitals is part of most national action plans to mitigate AMR, yet the optimal components and actions of such a programme remain undetermined. OBJECTIVES: To describe how health-care professionals can start an AMS programme in their hospital, the components of such a programme and the evidence base for its implementation. SOURCES: National and society-led guidelines on AMS, peer-reviewed publications and experience of AMS experts conducting AMS programmes. CONTENT: We provide a step-by-step pragmatic guide to setting up and implementing a hospital AMS programme in high-income or low-and-middle-income countries. IMPLICATIONS: Antimicrobial stewardship programmes in hospitals are a vital component of national action plans for AMR, and have been shown to significantly reduce AMR, particularly when coupled with infection prevention and control interventions. This step-by-step guide of 'how to' set up an AMS programme will help health-care professionals involved in AMS to optimally design and implement their actions.

Surgery, stomas, and anxiety and depression in inflammatory bowel disease: a retrospective cohort analysis of privately insured patients.

AIM: Patients with inflammatory bowel disease (IBD) are diagnosed with anxiety/depression at higher rates than the general population. We aimed to determine the frequency of anxiety/depression among IBD patients and the temporal association with abdominal surgery and stoma formation. METHOD: We conducted a retrospective cohort study in adult patients with IBD using difference-in-difference methodology and a large commercial claims database (2003-2016). Outcomes were anxiety/depression diagnoses before and after major abdominal surgery or stoma formation. RESULTS: We identified 10 481 IBD patients who underwent major abdominal surgery, 18.8% of whom underwent stoma formation, and 41 924 nonsurgical age- and sex-matched IBD controls who were assigned random index dates. Rates of anxiety and depression increased among all cohorts (P < 0.001). Surgical patients had higher odds of anxiety [one surgery, adjusted OR 6.90 (95% CI 6.11-7.79), P < 0.001; two or more surgeries, 7.53 (5.99-9.46), P < 0.001] and depression [one surgery, 6.15 (5.57-6.80), P < 0.001; two or more surgeries, 6.88 (5.66-8.36), P < 0.001] than nonsurgical controls. Undergoing multiple surgeries was associated with a significant increase in depression from 'pre' to 'post' time periods [1.43 (1.18-1.73), P < 0.001]. Amongst surgical patients, stoma formation was independently associated with anxiety [1.40 (1.17-1.68), P < 0.001] and depression [1.23 (1.05-1.45), P = 0.01]. New ostomates experienced a greater increase in postoperative anxiety [1.24 (1.05-1.47), P = 0.01] and depression [1.19 (1.03-1.45), P = 0.01] than other surgical patients. CONCLUSION: IBD patients who undergo surgery have higher rates of anxiety and depression than nonsurgical patients. Rates of anxiety and depression increase following surgery. Stoma formation represents an additional risk factor. These findings suggest the need for perioperative psychosocial support services.

Patient decision-making in severe inflammatory bowel disease: the need for improved communication of treatment options and preferences.

AIM: Patients with inflammatory bowel disease and their physicians must navigate ever-increasing options for treatment. The aim of this study was to elucidate the key drivers of treatment decision-making in inflammatory bowel disease. METHODS: We conducted qualitative semi-structured in-person interviews of 20 adult patients undergoing treatment for inflammatory bowel disease at an academic medical centre who either recently initiated biologic therapy or underwent an operation or surgical evaluation. Interviews were audio-recorded, transcribed verbatim, iteratively coded, and discussed to consensus by five researchers. We used thematic analysis to explore factors influencing decision-making. RESULTS: Four major themes emerged as key drivers of treatment decision-making: perceived clinical state and disease severity, the patient-physician relationship, knowledge, attitudes and beliefs about treatment options, and social isolation and stigma. Patients described experiencing a clinical turning point as the impetus for proceeding with a previously undesired treatment such as infusion medication or surgery. Patients reported delays in care or diagnosis, inadequate communication with their physicians, and lack of control over their disease management. Patients often stated that they considered surgery to be the treatment of last resort, which further compounded the complexity of making treatment decisions. CONCLUSION: Patients described multiple barriers to making informed and collaborative decisions about treatment, especially when considering surgical options. Our study reveals a need for more comprehensive communication between the patient and their physician about the range of medical and surgical treatment options. We recommend a patient-centred approach toward the decision-making process that accounts for patient decision-making preferences, causes of social stress, and clinical status.

Cefazolin versus anti-staphylococcal penicillins for the treatment of patients with Staphylococcus aureus bacteraemia.

BACKGROUND: For patients with bacteraemia caused by methicillin-sensitive Staphylococcus aureus anti-staphylococcal penicillins (ASPs) or cefazolin are agents of choice. While ASPs are potentially nephrotoxic, cefazolin may be less effective in some S. aureus strains due to an inoculum effect. OBJECTIVES: To perform a systematic literature review and meta-analysis assessing current evidence comparing cefazolin with ASPs for patients with S. aureus bacteraemia (SAB). METHODS: We searched MEDLINE, ISI Web of Science (Science Citation Index Expanded) and the Cochrane Database as well as clinicaltrials.gov from inception to 26 June 2018. All studies investigating the effects of cefazolin versus ASP in patients with methicillin-sensitive SAB were eligible for inclusion regardless of study design, publication status or language. Additional information was requested by direct author contact. A meta-analysis to estimate relative risks (RRs) with the corresponding 95% confidence intervals (CIs) was performed. Statistical heterogeneity was estimated using I2. The primary endpoint was 90-day all-cause mortality. The Newcastle-Ottawa Scale (NOS) and Grading of Recommendations Assessment, Development and Evaluation (GRADE) were used for study and data quality assessment. RESULTS: Fourteen non-randomized studies were included. Seven reported the primary endpoint (RR 0.71 (0.50, 1.02), low quality of evidence). Cefazolin treatment may be associated with lower 30-day mortality rates (RR 0.70 (0.54, 0.91), low quality of evidence) and less nephrotoxicity (RR 0.36 (0.21, 0.59), (low quality of evidence)). We are uncertain whether cefazolin and ASP differ regarding treatment failure/relapse as the quality of the evidence has been assessed as very low (RR of 0.84 (0.59, 1.18)). For patients with endocarditis (RR 0.71 (0.12, 4.05)) or abscesses (RR 1.17 (0.30, 4.63)), cefazolin treatment may be associated with equal 30-day and 90-day mortality (low quality of evidence). CONCLUSIONS: Cefazolin seemed to be at least equally as effective as ASPs while being associated with less nephrotoxicity.

Prioritizing research areas for antibiotic stewardship programmes in hospitals: a behavioural perspective consensus paper.

SCOPE: Antibiotic stewardship programmes (ASPs) are necessary in hospitals to improve the judicious use of antibiotics. While ASPs require complex change of key behaviours on individual, team organization and policy levels, evidence from the behavioural sciences is underutilized in antibiotic stewardship studies across the world, including high-income countries (HICs). A consensus procedure was performed to propose research priority areas for optimizing effective implementation of ASPs in hospital settings using a behavioural perspective. METHODS: A workgroup for behavioural approaches to ASPs was convened in response to the fourth call for leading expert network proposals by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR). Eighteen clinical and academic specialists in antibiotic stewardship, implementation science and behaviour change from four HICs with publicly funded healthcare systems (e.g. Canada, Germany, Norway and the UK) met face-to-face to agree on broad research priority areas using a structured consensus method. Question addressed and recommendations: The consensus process assessing the ten identified research priority areas resulted in recommendations that need urgent scientific interest and funding to optimize effective implementation of ASPs for hospital inpatients in HICs with publicly funded healthcare systems. We suggest and detail behavioural science evidence-guided research efforts in the following areas: (a) comprehensively identifying barriers and facilitators to implementing ASPs and clinical recommendations intended to optimize antibiotic prescribing; (b) identifying actors ('who') and actions ('what needs to be done') of ASPs and clinical teams; (c) synthesizing available evidence to support future research and planning for ASPs; (d) specifying the activities in current ASPs with the purpose of defining a control group for comparison with new initiatives; (e) defining a balanced set of outcomes and measures to evaluate the effects of interventions focused on reducing unnecessary exposure to antibiotics; (f) conducting robust evaluations of ASPs with built-in process evaluations and fidelity assessments; (g) defining and designing ASPs; (h) establishing the evidence base for impact of ASPs on resistance; (i) investigating the role and impact of government and policy contexts on ASPs; and (j) understanding what matters to patients in ASPs in hospitals. CONCLUSIONS: Assessment, revisions and updates of our priority-setting exercise should be considered at intervals of 2 years. To propose research priority areas in low- and middle-income countries, the methodology reported here could be applied.

Rationale and development of a business case for antimicrobial stewardship programs in acute care hospital settings.

Background: Antimicrobial stewardship programs (ASPs) have been shown to reduce inappropriate antimicrobial use and its consequences. However, these programs lack legislative requirements in many places and it can be difficult to determine what human resources are required for these programs and how to create a business case to present to hospital administrators for program funding. The objectives of the current paper were to review legislative requirements and outline human resource requirements for ASPs, and to create a base business case for ASPs. Methods: A working group of antimicrobial stewardship experts from across Canada met to discuss the necessary components for creation of a business case for antimicrobial stewardship. A narrative review of the literature of the regulatory requirements and human resource recommendations for ASPs was conducted. Informed by the review and using a consensus decision-making process, the expert working group developed human resource recommendations based on a 1000 bed acute care health care facility in Canada. A spreadsheet based business case model for ASPs was also created. Results: Legislative and /or regulatory requirements for ASPs were found in 2 countries and one state jurisdiction. The literature review and consensus development process recommended the following minimum human resources complement: 1 physician, 3 pharmacists, 0.5 program administrative and coordination support, and 0.4 data analyst support as full time equivalents (FTEs) per 1000 acute care beds. Necessary components for the business case model, including the human resource requirements, were determined to create a spreadsheet based model. Conclusions: There is evidence to support the negative outcomes of inappropriate antimicrobial use as well as the benefits of ASPs. Legislative and /or regulatory requirements for ASPs are not common. The available evidence for human resource recommendations for ASPs using a narrative review process was examined and a base business case modelling scenario was created. As regulatory requirements for ASPs increase, it will be necessary to create accurate business cases for ASPs in order to obtain the necessary funding to render these programs successful.

Effect of an antimicrobial stewardship programme on antimicrobial utilisation and costs in patients with leukaemia: a retrospective controlled study.

OBJECTIVES: To examine the effectiveness of an antimicrobial stewardship programme on utilization and cost of antimicrobials in leukaemia patients in Canada. METHODS: We conducted a multisite retrospective observational time series study from 2005 to 2013. We implemented academic detailing as the intervention of an antimicrobial stewardship programme in leukaemia units at a hospital, piloted February-July 2010, then fully implemented December 2010-March 2013, with no intervention in August-November 2010. Internal control was the same hospital's allogeneic haematopoietic stem-cell transplantation unit. External control was the combined leukaemia-haematopoietic stem-cell transplantation unit at another hospital. Primary outcome was antimicrobial utilization (antibiotics and antifungals) in defined daily dose per 100 patient-days (PD). Secondary outcomes were antimicrobial cost (Canadian dollars per PD); cost and utilization by drug class; length of stay; 30-day inpatient mortality; and nosocomial Clostridium difficile infection. We used autoregressive integrated moving average models to evaluate the impact of the intervention on outcomes. RESULTS: The intervention group included 1006 patients before implementation and 335 during full implementation. Correspondingly, internal control had 723 and 264 patients, external control 1395 and 864 patients. Antimicrobial utilization decreased significantly in the intervention group (p <0.01, 278 vs. 247 defined daily dose per 100 PD), increased in external control (p = 0.02, 237.4 vs. 268.9 defined daily dose per 100 PD) and remained stable in internal control (p = 0.66). Antimicrobial cost decreased in the intervention group (p = 0.03; $154.59 per PD vs. $128.93 per PD), increased in external control (p = 0.01; $109.4 per PD vs. $135.97 per PD) but was stable in internal control (p = 0.27). Mortality, length of stay and nosocomial C. difficile rate in intervention group remained stable. CONCLUSIONS: The antimicrobial stewardship programme reduced antimicrobial use in leukaemia patients without affecting inpatient mortality and length of stay.

Staphylococcus aureus bacteremia in immunosuppressed patients: a multicenter, retrospective cohort study.

Staphylococcus aureus bacteremia (SAB) causes significant morbidity and mortality. We assessed the disease severity and clinical outcomes of SAB in patients with pre-existing immunosuppression, compared with immunocompetent patients. A retrospective cohort investigation studied consecutive patients with SAB hospitalized across six hospitals in Toronto, Canada from 2007 to 2010. Patients were divided into immunosuppressed (IS) and immunocompetent (IC) cohorts; the IS cohort was subdivided into presence of one and two or more immunosuppressive conditions. Clinical parameters were compared between cohorts and between IS subgroups. A competing risk model compared in-hospital mortality and time to discharge. A total of 907 patients were included, 716 (79%) were IC and 191 (21%) were IS. Within the IS cohort, 111 (58%) had one immunosuppressive condition and 80 (42%) had two or more conditions. The overall in-hospital mortality was 29%, with no differences between groups (IS 32%, IC 28%, p = 0.4211). There were no differences in in-hospital mortality (sub-distribution hazard ratio [sHR] 1.17, 95% confidence interval [CI] 0.88-1.56, p = 0.2827) or time to discharge (sHR 0.94, 95% CI 0.78-1.15, p = 0.5570). Independent mortality predictors for both cohorts included hypotension at 72 h (IS: p < 0.0001, IC: p < 0.0001) and early embolic stroke (IS: p < 0.0001, IC: p = 0.0272). Congestive heart failure was a mortality predictor in the IS cohort (p = 0.0089). Fever within 24 h (p = 0.0092) and early skin and soft tissue infections (p < 0.0001) were survival predictors in the IS cohort. SAB causes significant mortality regardless of pre-existing immune status, but immunosuppressed patients do not have an elevated risk of mortality relative to immunocompetent patients.

Approach to evaluation of fever in ambulatory cancer patients receiving chemotherapy: A systematic review.

PURPOSE: To define the optimal model of care for patients receiving outpatient chemotherapy who experience a fever. Fever is a common symptom in patients receiving chemotherapy, but the approach to evaluation of fever is not standardized. METHODS: We conducted a search for existing guidelines and a systematic review of the primary literature from database inception to November 2015. Full-text reports and conference abstracts were considered for inclusion. The search focused on the following topics: the relationship between temperature and poor outcome; predictors for the development of febrile neutropenia (FN); the timing, location, and personnel involved in fever assessment; and the provision of information to patients receiving chemotherapy. RESULTS: Eight guidelines and 38 studies were included. None of the guidelines were directly relevant to the target population because they dealt primarily with the management of FN after diagnosis. The primary studies tended to include fever as one of many symptoms assessed in the setting of chemotherapy. Temperature level was a weak predictor of poor outcomes. We did not find validated prediction models for identifying patients at risk of FN among patients receiving chemotherapy. Several studies presented approaches to symptom management that included fever among the symptoms, but results were not mature enough to merit widespread adoption. CONCLUSION: Despite the frequency and risks of fever in the setting of chemotherapy, there is limited evidence to define who needs urgent assessment, where the assessment should be performed, and how quickly. Future research in this area is greatly needed to inform new models of care.

Clinical prediction rules in Staphylococcus aureus bacteremia demonstrate the usefulness of reporting likelihood ratios in infectious diseases.

Infectious diseases specialists often use diagnostic tests to assess the probability of a disease based on knowledge of the diagnostic properties. It has become standard for published studies on diagnostic tests to report sensitivity, specificity and predictive values. Likelihood ratios are often omitted. We compared published clinical prediction rules in Staphylococcus aureus bacteremia to illustrate the importance of likelihood ratios. We performed a narrative review comparing published clinical prediction rules used for excluding endocarditis in S. aureus bacteremia. Of nine published clinical prediction rules, only three studies reported likelihood ratios. Many studies concluded that the clinical prediction rule could safely exclude endocarditis based on high sensitivity and high negative predictive value. Of the studies with similar high sensitivity and high negative predictive value, calculated negative likelihood ratios were able to differentiate and identify the best clinical prediction rule for excluding endocarditis. Compared to sensitivity, specificity and predictive values, likelihood ratios can be more directly used to interpret diagnostic test results to assist in ruling in or ruling out a disease. Therefore, a new standard should be set to include likelihood ratios in reporting of diagnostic tests in infectious diseases research.

Developing and expanding hospital antimicrobial stewardship: The Ontario experience.

Mount Sinai Hospital and University Health Network, two academic health science centres in Toronto, Ontario, jointly established a robust, well-resourced antimicrobial stewardship program (ASP). Over the course of four years, we spread our program to five intensive care units (ICUs), learned which change management practices worked and which did not, and leveraged our ICU successes to other areas of our hospitals. We identified the following two factors as critical to establishing ASPs in hospitals: strong leadership with clear accountability; and valid, reliable data to monitor progress. Subsequently we have led the spread of our program to 14 academic hospital ICUs, and more recently we leveraged to help community hospitals implement ASPs without in-house infectious diseases specialists. We introduced three new data fields into the provincial critical care information system: days of antibacterial therapy, days of antifungal therapy, and ICU-onset C. difficile, which will help standardize data collection moving forward. This model-starting with academic health sciences centres, and antimicrobial stewardship experts and leaders who are then supported to mentor and develop new experts and leaders-could be copied in other jurisdictions both within and outside of Canada.

External validation of bedside prediction score for diagnosis of late-onset neonatal sepsis.

OBJECTIVE: To prospectively validate performance of a prediction score for diagnosis of late-onset neonatal sepsis (LNS) in a new patient population. STUDY DESIGN: Data were prospectively collected from March 2003 to May 2004. Newborns were enrolled if they were in the neonatal intensive care unit (NICU) between 2 and 90 days, and during the first episode of clinical sepsis suspected. LNS was defined as a positive blood or cerebrospinal fluid (CSF) culture, which became the criterion standard. RESULTS: A total of 105 neonates were evaluated for sepsis. Demographic characteristics were as follows: (mean (s.d.)) were gestational age (GA) 29 (3) weeks; birth weight (BW) 1232 (620) g and postnatal age 17.5 day (12). Thirty-five (33%) neonates had LNS (35 positive blood cultures; 2 positive CSF). No significant differences in GA, BW, gender, age and central line utilization were found between LNS positive and LNS negative groups. Using a cut-off score of < or = 3, the score predicted positive culture with sensitivity of 0.97 (95% confidence interval 0.85, 0.99) and a negative likelihood ratio of 0.07. The discrimination and calibration ability of LNS score was acceptable. CONCLUSIONS: A simple clinical decision rule previously developed to predict LNS performs equally in an independent population and NICU.

Validation of screening measures for assessing mood in stroke patients.

PURPOSE: There are few validated measures to assess mood in stroke patients and even fewer suitable for all stroke patients, including those with communication problems. The aim of this study was to compare the Stroke Aphasic Depression Questionnaire Hospital version (SADQ-H), Signs of Depression Scale (SODS), Visual Analogue Mood Scale (VAMS) and Visual Analogue Self-esteem Scale (VASES) in screening for mood problems after stroke. METHODS: Fifty healthy older adults and 100 stroke patients in hospital completed the VAMS and VASES. A nurse completed the SADQ-H and SODS in relation to the stroke patients. A relative/carer completed the SADQ-H and SODS in relation to the healthy older adults. Those without communication problems also completed the Hospital Anxiety and Depression Scale (HADS). RESULTS: The internal consistency of the scales was low in healthy older adults. In stroke patients the internal consistency of the SADQ-H, VAMS, and VASES was high (alpha = .71-.84) but that of the SODS was low (alpha = .53). In healthy older adults, correlations between the HADS and the VAMS and VASES were high but low between the HADS and SADQ-H and SODS. In stroke patients, the HADS depression scale correlated significantly with all the scales (0.35-0.55) but only the SADQ-H 10, VAMS, and VASES were significantly correlated with the HADS anxiety scale (0.40-0.52). Appropriate cut-offs were found for the SADQ-H (17/18), SADQ-H 10 (5/6), SODS (1/2), and VAMS 'sad' item (22/23) in comparison to depression on the HADS. No appropriate cut-offs were identified in comparison to anxiety on the HADS. CONCLUSIONS: The SADQ-H, SADQ-H10 and SODS were all appropriate for screening for possible depression after stroke but not for screening for possible anxiety. The SADQ-H 10 had greater internal consistency and higher sensitivity and specificity than the SODS and is shorter than the SADQ-H. It was also significantly correlated with both the anxiety and depression scales of the HADS. The SADQ-H 10 was therefore recommended as the most appropriate for screening purposes. The VAMS and VASES provided no clear cut-offs for use in screening but scores were highly correlated with the HADS. They are therefore more suitable for assessing severity of low mood rather than for screening purposes. The cut-offs identified need further validation in an independent sample of stroke patients, including a higher proportion with low mood.

Threefold increased risk of infertility: a meta-analysis of infertility after ileal pouch anal anastomosis in ulcerative colitis.

BACKGROUND: Increased infertility in women has been reported after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis but reported infertility rates vary substantially. AIMS: (1) To perform a systematic review and meta-analysis of the relative risk of infertility post-IPAA compared with medical management; (2) to estimate the rate of infertility post-IPAA; and (3) to identify modifiable risk factors which contribute to infertility. METHODS: Medline, EMBASE, Current Contents, meeting abstracts, and bibliographies were searched independently by two investigators. The titles and abstracts of 189 potentially relevant studies were reviewed; eight met the criteria and all data were extracted independently. Consensus was achieved on each data point, and fixed effects meta-analyses, a funnel plot, and sensitivity analyses were performed. RESULTS: The initial meta-analysis of eight studies had significant heterogeneity (p = 0.004) due to one study with very high preoperative infertility (38%). When this study was omitted, the relative risk of infertility after IPAA was 3.17 (2.41-4.18), with non-significant heterogeneity. The weighted average infertility rate in medically treated ulcerative colitis was 15% for all seven studies, and the weighted average infertility rate was 48% after IPAA (50% if all eight studies are included). We were unable to identify any procedural factors that consistently affected the risk of infertility. CONCLUSIONS: IPAA increases the risk of infertility in women with ulcerative colitis by approximately threefold. Infertility, defined as achieving pregnancy in 12 months of attempting conception, increased from 15% to 48% in women post-IPAA for ulcerative colitis. This provides a basis for counselling patients considering colectomy with IPAA. Further studies of modifiable risk factors are needed.

A proposed protocol for the development of a register of trials of weight management of childhood overweight and obesity.

INTRODUCTION: Currently, there is no international co-ordinated approach to research into childhood obesity. This is despite much research activity in this area and the universality of the condition. METHOD: This proposal involves the development of an international register of randomized controlled trials of weight management in overweight and obese children. The primary purpose of the register will be to generate and perform important, focussed prospective meta-analysis of data from trials using the conventional weight management strategies. Prospective meta-analysis is an emerging methodology and has some methodological advantages over retrospective meta-analysis. PROPOSAL: The fundamental initial tasks will be to create scientific interest in the proposal, to identify and co-ordinate Management and Advisory Committees with international membership, to determine and define inclusion and exclusion criteria for trial registration, to define the questions that need to be addressed by prospective meta-analysis and finally to engage investigators to register.

Adjuvant radiation for rectal cancer: do we measure up to the standard of care? An epidemiologic analysis of trends over 25 years in the United States.

PURPOSE: In the United States, adjuvant radiation therapy is currently recommended for most patients with rectal cancer. We conducted this population-based study to evaluate the rate of radiation therapy and the factors affecting its delivery. METHODS: We used the Surveillance Epidemiology and End Results database to assess treatment of patients with nonmetastatic rectal cancer diagnosed over a 25-year period (1976 through 2000). We evaluated the rate of radiation therapy use and its timing (preoperative vs. postoperative) and the influence of factors such as tumor stage and grade; patient gender and race; and geographic location. RESULTS: In this 25-year period, 45,627 patients met our selection criteria. The rate of radiation therapy use increased dramatically over time: from 17 percent of advanced-stage patients in 1976 to 65 percent in 2000 (P < 0.0001). Until 1996, the increase was due almost entirely to postoperative radiation therapy. Since 1996, the rate of preoperative radiation therapy use has increased (P < 0.0001) and the rate of postoperative radiation therapy use has begun to decline. We found, after controlling for the year of diagnosis, that female patients, African Americans, older patients, and patients with low-grade lesions were less likely to undergo radiation therapy (P < 0.0001). Geographic location was also an important predictor of radiation therapy use. CONCLUSIONS: The use of radiation therapy for patients with rectal cancer has dramatically increased over the 25-year period studied, with a recent shift to the use of preoperative radiation therapy; however, in 2000, over 30 percent of patients with advanced-stage nonmetastatic rectal cancer did not undergo radiation therapy. Given the variation in radiation therapy use that we found to be due to demographic factors, access to adjuvant radiation therapy can be improved.