Assessment of neurogenic bowel symptoms with the bowel dysfunction score in children with spina bifida: a prospective case-control study.

AIM: To compare the quality of life (QoL) in children with spina bifida with a control group of their peers using a validated questionnaire, the Neurogenic Bowel Dysfunction Score (NBDS). METHODS: The NBDS questionnaire was prospectively distributed to children attending a multi-disciplinary Spina Bifida clinic and healthy controls attending pediatric urology clinics. A score (out of 41) was assigned to each child based on their responses to the validated questionnaire. A lower score indicates better bowel function-related quality of life. SPSS software (v.25) was used for all statistical analysis. RESULTS: There were 98 respondents to the questionnaire, 48 children with spina bifida and 50 controls. The average age of respondents was 7.88 years (3-16 years). Of those with Spina Bifida, 33 (69%) were on retrograde rectal irrigations, [19 (58%) Peristeen® system, 11 (33%) tube rectal irrigations, and 3 (9%) Willis system], 6 (12%) were on laxatives, and 9 (19%) were on no treatment. The median NBDS for Spina Bifida patients was significantly higher 13.5 (2-32) compared to the control group 2 (0-26, p < 0.001). Amongst Spina Bifida patients, there was no difference in quality of life between the modalities of bowel management (p = 0.203). CONCLUSIONS: Despite active bowel management, children with spina bifida report a worse quality of life compared to the control group. In those with spina bifida, the lack of a difference between various bowel management strategies, including no treatment, indicates the need for a longitudinal study to evaluate the basis for this unexpected finding.

Economic Evaluation of Azacitidine in Elderly Patients with Acute Myeloid Leukemia with High Blast Counts.

BACKGROUND: Azacitidine is an hypomethylating agent widely adopted for the treatment of acute myeloid leukaemia (AML) in patients who are ineligible for curative-intent chemotherapy. Patients with low bone marrow blast counts (< 30%) experience improved survival with azacitidine, but the benefits are significantly lower in patients with > 30% blasts in the bone marrow. As such, there is uncertainty around the economic benefit of azacitidine in patients with higher blast counts. OBJECTIVE: We present a cost-utility analysis of azacitidine in patients with AML with > 30% blasts to determine the economic value of azacitidine in this patient population from the perspective of a third-party payer. METHODS: A Markov model was developed with a time horizon of 25 months divided into 22 cycles of 35 days each. The cost utility of azacitidine was compared with that of conventional care regimens (which include best supportive care, low-dose cytarabine and induction chemotherapy). A Canadian public healthcare system perspective was selected. RESULTS: In the base case, the incremental cost per quality-adjusted life-year gained (incremental cost-effectiveness ratio [ICER]) for azacitidine compared with conventional care regimens was $Can160,438, year 2018 values. The estimated ICER was insensitive to a longer time horizon but sensitive to the cost of azacitidine and to assumptions relating to survival in both treatment regimens, although the ICER always remained greater than Can$80,000 in all scenarios. CONCLUSION: Azacitidine is unlikely to be cost effective given that the estimated ICER exceeds the willingness to pay commonly used in the Canadian healthcare system.

Universal vs Risk Factor Screening for Methicillin-Resistant Staphylococcus aureus in a Large Multicenter Tertiary Care Facility in Canada.

OBJECTIVE To assess the clinical effectiveness of a universal screening program compared with a risk factor-based program in reducing the rates of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) among admitted patients at the Ottawa Hospital. DESIGN Quasi-experimental study. SETTING Ottawa Hospital, a multicenter tertiary care facility with 3 main campuses, approximately 47,000 admissions per year, and 1,200 beds. METHODS From January 1, 2006 through December 31, 2007 (24 months), admitted patients underwent risk factor-based MRSA screening. From January 1, 2008 through August 31, 2009 (20 months), all patients admitted underwent universal MRSA screening. To measure the effectiveness of this intervention, segmented regression modeling was used to examine monthly nosocomial MRSA incidence rates per 100,000 patient-days before and during the intervention period. To assess secular trends, nosocomial Clostridium difficile infection, mupirocin prescriptions, and regional MRSA rates were investigated as controls. RESULTS The nosocomial MRSA incidence rate was 46.79 cases per 100,000 patient-days, with no significant differences before and after intervention. The MRSA detection rate per 1,000 admissions increased from 9.8 during risk factor-based screening to 26.2 during universal screening. A total of 644 new nosocomial MRSA cases were observed in 1,448,488 patient-days, 323 during risk factor-based screening and 321 during universal screening. Secular trends in C. difficile infection rates and mupirocin prescriptions remained stable after the intervention whereas population-level MRSA rates decreased. CONCLUSION At Ottawa Hospital, the introduction of universal MRSA admission screening did not significantly affect the rates of nosocomial MRSA compared with risk factor-based screening. Infect. Control Hosp. Epidemiol. 2015;37(1):41-48.

Transient Elastography and Controlled Attenuation Parameter for Diagnosing Liver Fibrosis and Steatosis in Ontario: An Economic Analysis.

BACKGROUND: Liver fibrosis is characterized by a buildup of connective tissue due to chronic liver damage. Steatosis is the collection of excessive amounts of fat inside liver cells. Liver biopsy remains the gold standard for the diagnosis of liver fibrosis and steatosis, but its use as a diagnostic tool is limited by its invasive nature and high cost. OBJECTIVES: To evaluate the cost-effectiveness and budget impact of transient elastography (TE) with and without controlled attenuation parameter (CAP) for the diagnosis of liver fibrosis or steatosis in patients with hepatitis B, hepatitis C, alcoholic liver disease, and nonalcoholic fatty liver disease. DATA SOURCES: An economic literature search was performed using computerized databases. For primary economic and budget impact analyses, we obtained data from various sources, such as the Health Quality Ontario evidence-based analysis, published literature, and the Institute for Clinical Evaluative Sciences. REVIEW METHODS: A systematic review of existing TE cost-effectiveness studies was conducted, and a primary economic evaluation was undertaken from the perspective of the Ontario Ministry of Health and Long-Term Care. Decision analytic models were used to compare short-term costs and outcomes of TE compared to liver biopsy. Outcomes were expressed as incremental cost per correctly diagnosed cases gained. A budget impact analysis was also conducted. RESULTS: We included 10 relevant studies that evaluated the cost-effectiveness of TE compared to other noninvasive tests and to liver biopsy; no cost-effectiveness studies of TE with CAP were identified. All studies showed that TE was less expensive but associated with a decrease in the number of correctly diagnosed cases. TE also improved quality-adjusted life-years in patients with hepatitis B and hepatitis C. Our primary economic analysis suggested that TE led to cost savings but was less effective than liver biopsy in the diagnosis of liver fibrosis. TE became more economically attractive with a higher degree of liver fibrosis. TE with CAP was also less expensive and less accurate than liver biopsy. LIMITATIONS: The model did not take into account long-term costs and consequences associated with TE and liver biopsy and did not include costs to patients and their families, or patient preferences related to diagnostic information. CONCLUSIONS: TE showed potential cost savings compared to liver biopsy. Further investigation is needed to determine the long-term impacts of TE on morbidity and mortality in Canada and the optimal diagnostic modality for liver fibrosis and steatosis.

Pattern of Change in Renal Function Following Radical Nephrectomy for Renal Cell Carcinoma.

Radical nephrectomy (RN) is an independent risk factor for the development of chronic kidney disease (CKD) in those with renal cell carcinoma (RCC). We aimed to examine the pattern of change in post-operative renal function in patients who underwent RN for RCC over a 3 year period at our institution. We performed a retrospective review of histological and biochemical findings in patients undergoing RN for RCC over a 38 month period. Estimated glomerular filtration rate (eGFR) was recorded pre- and post-operatively and at follow-up. We analysed data on 131 patients (median follow-up 24 months). The proportion of patients with advanced CKD increased significantly at follow-up with 48 (85.7%) patients, classified as having stage 2 CKD pre-operatively, being re-classified as stage 3-5. Mean eGFR was significantly lower pre-operatively (76.6 mL/min/1.73 m2) compared to hospital discharge (61 mL/min/1.73 m2, p < 0.001) and follow-up (55.5 mL/min/1.73 m2, p < 0.001). Those with pT1 tumours sustained a significantly greater decline in eGFR compared to other stages. In conclusion, patients with pT1 a and pT1 b tumours sustain a disproportionate decline in renal function and may benefit the most from NSS.

Recurrent dedifferentiated paratesticular liposarcoma with synchronous renal cell carcinoma and prostate cancer.

Paratesticular liposarcoma is a very rare cause of scrotal mass. It is thought that they arise from spermatic cord lipomas most commonly. While well differentiated tumors tend to share many histological similarities with dedifferentiated tumors, the latter has a much more aggressive phenotype. We present an unusual case of a 69-year-old male with synchronous prostate adenocarcinoma and unilateral renal cell carcinoma who was found to have a dedifferentiated paratesticular liposarcoma. Treatment was with radical resection, preserving the testis, followed by radiotherapy. Unusually recurrence did not occur until 4 years following initial treatment. This case demonstrates the high propensity of dedifferentiated liposarcoma to recur locally and examines the most frequently employed management strategies.

Successful introduction of ring-fenced inpatient surgical beds in a general hospital setting.

This study aimed to assess the impact of ring-fenced inpatient general surgical beds on day of surgery (DOS) admission, duration of elective inpatient stay (DEIS), and cancellation rates over a 6 month period. In June 2010 17 of 60 surgical inpatient beds were decommissioned. The remainder (43) were ring-fenced for general surgery patients only. Comparative analysis examining admission rates, cancellation rates, and theatre activity was performed between a reference period (January-June 2010) and the study period (July-December 2010). Complexity of all operations was graded according to an index schedule of procedures. There was no difference between the reference and study periods in volumes of elective admissions (472 [53.03%] vs. 418 [4797%]) and emergency admissions (928 [50.03%] vs. 927 [49.97%]). DOS admissions increased 5-fold during the study period (38 [8.1%] vs. 190 [45.5%], P < 0.001). Average duration of elective inpatient stay reduced from 4.3 days to 3.06 days in the study period (P < 0.001). No difference was observed in volume of operations performed at all levels of complexity. There were 78 (58.2%) cancellations during the reference period and 56 (41.8%) during the study period with patient non-attendance the most common cause for cancellation in both periods. Ring-fenced surgical beds facilitated higher DOS admission rates and shorter duration of elective inpatient stay, leading to more efficient use of hospital resources.

Apheresis and transplant of hematopoietic progenitor cells (HPC) from allogeneic donors of age above 60 years.

Over the immediate past 4 years, our program has collected hematopoietic progenitor cells by apheresis from 48 individuals aged 61 and over (range 61-71 years of age). We have retrospectively analyzed the collection and transplant results associated with employing these donors, and have compared them with 175 donors aged 60 or less who were collected during the same time period. We have found no significant difference in venous access (P = 0.208), rate of post-transplant engraftment of neutrophils (P = 0.117) and platelets (P = 0.692), or in rate and grade of acute GVHD (P = 0.806). However, we have found that these older donors have a significantly lower mobilization of CD34 + cells as reflected in lower absolute counts of circulating CD34 + cells pre-apheresis (P = 0.016). This, in turn, results in lower CD34 + cell yields in apheresis products (P < 0.001), trending towards requiring more apheresis procedures (22.9 vs 13.7%, P = 0.095) to collect sufficient CD34 + cells for transplantation. We conclude that it is practical when necessary to employ donors aged 60 and above, as well as safe for both donor and intended recipient. However, concern over reduced CD34 + cell mobilization may be sufficient grounds to seek younger donors when possible.

Cancer antigen 125 in ovarian cancer surveillance: a decision analysis model.

We used decision analysis techniques with Markov cohort modeling to examine the role of cancer antigen 125 (CA-125) in follow-up surveillance strategies among patients with advanced ovarian cancer. Utilities were derived from a societal perspective.Using quality-adjusted life years (QALYS) as the outcome variable, the value of CA-125 monitoring for asymptomatic women with ovarian cancer was found to be reduced as compared with a strategy that includes CA-125 testing. Decisions to include CA-125 in surveillance strategies for ovarian cancer patients should be made after discussion with full disclosure of the preference-sensitive nature of CA-125. The model demonstrates that preferences and perspective can influence decisions in cancer care.

Etanercept for the treatment of rheumatoid arthritis.

BACKGROUND: Etanercept is a soluble tumour necrosis factor alpha-receptor DMARD for the treatment of rheumatoid arthritis (RA). OBJECTIVES: To assess the efficacy and safety of etanercept for the treatment of RA. SEARCH STRATEGY: Five electronic databases were searched from 1966 to February 2003 with no language restriction. SELECTION CRITERIA: All randomized controlled trials (minimum 6 month duration) comparing three possible combinations 1) etanercept (10 mg or 25 mg twice weekly) with methotrexate (MTX) to MTX alone 2) etanercept to MTX, or 3) etanercept to placebo were eligible. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data and assessed the methodological quality of the trails. The American College of Rheumatology (ACR) core set of disease activity measures for RA clinical trials, radiographic, withdrawals and toxicity outcomes were analyzed. MAIN RESULTS: Three trials were included in this review. Two trials compared an experimental group who were started on etanercept compared to a control group; both groups had the same ongoing background therapy of nonsteroidals in both trials plus in one trial one group was on stable methotrexate. In these two trials the ACR 20, ACR 50 and ACR 70 response rates at 6 months were statistically significantly and clinically important with etanercept 25 mg subcutaneous injections (SC) twice weekly. Sixty-four percent of people receiving etanercept ache vied an ACR 20 response compared to 15% of controls and the number needed to treat (NNT) with etanercept is 2 people. Thirty-nine percent of those receiving etanercept achieved an ACR 50 response compared to 4% of taking control treatment and the NNT is three. Fifteen percent of people taking etanercept achieved an ACR 70 compared to 1% of controls with a NNT of 7 people. In the third trial of starting etanercept compared to starting methotrexate the number of participants who achieved an ACR 20, 50 or response at 6 and 12 months were not statistically significant for either etanercept dose. Etanercept treatment showed a statistically significantly and clinically important affect on joint damage as measured by the Sharp erosion score. Among participants who received etanercept 72% had no increase in their erosion score compared to 60% of participants in the methotrexate group. Withdrawal and toxicity results were acceptable. REVIEWER'S CONCLUSIONS: Etanercept 25 mg SC twice weekly was more efficacious than control treatment for ACR 20, 50 and 70 at 6 months, and over 12 months it slowed joint damage.

Antibiotic-impregnated catheters associated with significant decrease in nosocomial and multidrug-resistant bacteremias in critically ill patients.

OBJECTIVE: To evaluate the impact of using central venous catheters (CVCs) impregnated with the combination of minocycline and rifampin on nosocomial bloodstream infections (BSIs), morbidity, and mortality in cancer patients in the ICU. DESIGN: Prospective surveillance study consisting of the following two time periods: September 1997 through August 1998 (ie, fiscal year [FY] 1998); and from September 1998 through August 1999 (ie, FY 1999). SETTING: ICUs of a tertiary care hospital in Houston, TX. PATIENTS: Cancer patients in the medical ICU (MICU) and surgical ICU (SICU). INTERVENTIONS: ICUs started using CVCs impregnated with the minocycline-rifampin combination at the beginning of FY 1999. MEASUREMENTS AND MAIN RESULTS: The rates of nosocomial BSIs and other patients' characteristics were compared for the two study periods to determine the impact of using the impregnated catheters in the ICU. Patients' characteristics, including antibiotic use, were comparable for the two study periods in both the MICU and the SICU. The rate of nosocomial BSIs in the MICU unit decreased from 8.3 to 3.5 per 1,000 patient-days (p < 0.01), and decreased in the SICU from 4.8 to 1.3 per 1,000 patient-days (p < 0.01) in FY 1999. Nosocomial vancomycin-resistant enterococcus (VRE) bacteremia also decreased significantly (p = 0.004). Length of stay in the MICU and SICU significantly decreased in FY 1999 (p < 0.01 and p = 0.03, respectively). The duration of hospitalization decreased for MICU and SICU patients (p = 0.06 and p < 0.01, respectively). The rate of catheter-related infections decreased from 3.1 to 0.7 per 1,000 patient-days in FY 1999 (p = 0.02). The decrease in infections resulted in net savings of at least $1,450,000 for FY 1999. CONCLUSIONS: The use of antibiotic-impregnated CVCs in the MICU and SICU was associated with a significant decrease in nosocomial BSIs, including VRE bacteremia, catheter-related infections, and lengths of hospital and ICU stays.

Cancer physicians' attitudes toward colorectal cancer follow-up.

BACKGROUND: The optimal follow-up strategy for colorectal cancer is unknown. MATERIALS AND METHODS: We surveyed all Canadian radiation oncologists, medical oncologists and surgeons specializing in colorectal cancer to assess their recommendations for follow-up after potentially curative treatment, the beliefs and attitudes underlying these practices, and the cost implications of different follow-up strategies. RESULTS: One hundred and sixty practitioners (58%) returned completed surveys. Most recommended clinical assessments every 3-4 months in the first 2 years including carcino-embryonic antigen testing, gradually decreasing in frequency over 5 years. Ninety per cent recommend a surveillance colonoscopy in the first year. The majority felt that specialist involvement in follow-up was important because of the increased opportunities for patients to contribute to research (76%) and teaching (73%). About half felt that specialists were more efficient at providing follow-up than primary care physicians, but these same physicians recommended significantly longer and more expensive follow-up routines on average than others. Primary care physicians were felt to be important allies, especially in managing the psychosocial concerns of patients. CONCLUSIONS: Surveillance practices are generally in keeping with published recommendations. Most specialists feel that they should remain involved in follow-up, but this may result in increased resource utilization.

The assessment of the economic return from controlled clinical trials. A framework applied to clinical trials of colorectal cancer follow-up.

Clinical trials can be considered health interventions as their primary aim is to impact on the health of a population. Given that resources are scarce for both health care and health related research, trials could be designed such that they can be demonstrated to be cost-effective, i.e., the costs of conducting the trial are justified given the forecasted long-term benefits. We demonstrate how a model can be used to predict the cost-effectiveness of undertaking a clinical trial comparing alternative regimens of colorectal cancer follow-up. The model forecasts costs and survival under two scenarios, with and without conducting a clinical trial, with the outcome assessed in terms of years to payback for the clinical trial. The methodology shown can be used both to provide information on appropriate trial design and/or in prioritizing between potential trials.

Surveillance mammography after treatment of primary breast cancer: a systematic review.

As the prevalence of diagnosed breast cancer increases, it is important to define how best to provide long-term follow-up. Whereas many aspects of follow-up remain controversial, guidelines recommend surveillance mammograms as the only investigation to be performed routinely. We conducted a systematic review of the literature to elucidate the effect of routine surveillance mammograms on detecting ipsilateral recurrence (IR) and contralateral breast cancers (CBC). The systematic review yielded 15 articles. All were observational studies and ranked as level II-2 or III evidence. There were no randomized controlled trials identified. Most of the ten studies on detection of IR did not report on outcomes after detection. When reported, most studies found that the method of detection of IR did not influence overall survival or disease-free survival. Two of the nine studies on detection of CBC found that the CBC was detected at an earlier stage than the initial breast cancer, but did not report on long-term outcomes. This systematic review highlights the need for further research to help better define the optimum surveillance mammography regimen.

The impact of risk on preference values: implications for evaluations of postmenopausal osteoporosis therapy.

OBJECTIVE: The objective was to assess the impact of different levels of risk of disease on a woman's preferences for health states. Women were provided with health scenarios incorporating different levels of lifetime risks for breast cancer, hip fracture, and coronary heart disease (CHD). In this way, we were able to determine the incremental effect of changes in risks of each disease on preference values. METHODS AND DATA: Preference values and utility scores were obtained for six health scenarios by both the feeling thermometer (FT) and standard gamble (SG) methods. Scenarios presented the different lifetime risks of CHD, breast cancer, and hip fracture associated with and not associated with long-term use of hormone replacement therapy (HRT) and raloxifene. Risks of breast cancer were based on perceived risks and population risks. The sample population consisted of 40 healthy female volunteers aged between 45 and 65 years randomly selected from the Ottawa-Carleton district. RESULTS: Based on their perceived risk of breast cancer, the women had higher value scores for the raloxifene risk profile than for both HRT (p = .002) and no therapy (p = .003), with similar results for analyses based on population risks and from utility scores. Regression analysis showed that the risk of breast cancer (p < .001) was the only disease risk that was statistically significantly associated with women's preferences. CONCLUSIONS: Women had significant preferences over the different risk profiles, primarily due to the incremental effect on changes in values for the risk of breast cancer. Therefore, studies evaluating therapies for osteoporosis should consider patient preferences for living with different risk profiles.

A clinical and economic review of disease-modifying antirheumatic drugs.

Rheumatoid arthritis is one of the most common chronic systemic inflammatory diseases, affecting approximately 1% of the adult population. Disease-modifying antirheumatic drugs (DMARDs) have been the mainstay of treatment for rheumatoid arthritis when combined with physical therapy and aspirin (acetylsalicylic acid) or nonsteroidal anti-inflammatory drugs. Recently, a number of new biological therapies have been introduced for the treatment of this condition and will have a major impact on the future management of this disabling disease. In this review, we summarise data on the efficacy and tolerability of the currently available DMARDs, including gold compounds, antimalarials, penicillamine, cytotoxic drugs (azathioprine and cyclophosphamide), sulfasalazine, methotrexate, leflunomide, cyclosporin, anti-tumour necrosis factor agents, combination therapy and apheresis. A literature review and quality assessment of economic evaluations of DMARDs is presented, illustrating that there has been a paucity of economic evaluations on these agents and showing the variable quality of those studies that are available. The manuscript also addresses the pharmacoeconomic implications of the new agents for rheumatoid arthritis; the need for formal long term economic evaluations in order to determine the cost effectiveness of these costly, but highly effective, new treatments is emphasised.

Canadian CT head rule study for patients with minor head injury: methodology for phase II (validation and economic analysis).

Prospective validation on a new set of patients is an essential test of a new decision rule. However, many clinical decision rules are not prospectively assessed to determine their accuracy, reliability, clinical sensibility, or potential impact on practice. This validation process is important because many statistically derived rules or guidelines do not perform well when tested in a new population. The methodologic standards for a validation study are similar to those described in the article on phase I for derivation studies in the August 2001 issue of Annals of Emergency Medicine. The goal of phase II is to prospectively assess the accuracy, reliability, and acceptability of the decision rule in a new set of patients with minor head injury. This will determine the clinical utility of the rule and is essential if such a rule is to be widely adopted into clinical practice.

Analyzing differences in the costs of treatment across centers within economic evaluations.

OBJECTIVES: Assessments of health technologies increasingly include economic evaluations conducted alongside clinical trials. One particular concern with economic evaluations conducted alongside clinical trials is the generalizability of results from one setting to another. Much of the focus relating to this topic has been on the generalizability of results between countries. However, the characteristics of clinical trial design require further consideration of the generalizability of cost data between centers within a single country, which could be important in decisions about adoption of the new technology. METHODS: We used data from a multicenter clinical trial conducted in the United Kingdom to assess the degree of variation in costs between patients and between treatment centers and the determinants of the degree of such variation. RESULTS: The variation between patients was statistically significant for both the experimental and conventional treatments. However, the degree of variation between centers was only statistically significant for the experimental treatment. Such variation appeared to be a result of hospital practice, such as payment mechanisms for staff and provision of hostel accommodation, rather than variations in physical resource use or substantive differences in cost structure. CONCLUSIONS: Multicenter economic evaluations are necessary for determining the variations in hospital practice and characteristics that can in turn determine the generalizability of study results to other settings. Such analyses can identify issues that may be important in adopting a new health technology. Analysis is required of similar large multicenter trials to confirm these conclusions.