Hepatitis C infection among pregnant women in British Columbia: reported prevalence and critical appraisal of current prenatal screening methods.

BACKGROUND: Despite the fact that hepatitis C virus (HCV) is a relatively common infection in Canada, particularly in British Columbia (BC), there is a paucity of information on actual HCV prevalence in pregnant women. At present, pregnant women are only screened if they fit risk criteria, which may result in under-identification of HCV in this population. The purpose of this study was to determine the overall prevalence rate, age and geographic distribution of reported HCV infection among pregnant women in BC, and compare results to a previously conducted anonymous seroprevalence survey. METHODS: Reported HCV prevalence was determined through a confidential database linkage of all prenatal screening results at the Canadian Blood Services (CBS) with all HCV test results at the Provincial Laboratory, from May 2000 to Oct 2002. Data were stratified by age group and geographic location, and subsequently compared to an anonymous prenatal seroprevalence survey conducted in 1994. RESULTS: The overall HCV prevalence rate was 50.3/10,000 (95% CI 46.3-54.6), or 0.5% of the cohort. Prevalence was highest in the northern BC region (66.2/10,000, 95% CI 51.4-85.3) and lowest in the populous suburban region southwest of Vancouver (38.0/10,000, 95% CI 32.3-44.8). Of note, the rate of reported HCV among pregnant women was significantly lower than the anonymous seroprevalence rate: 50.3/10,000 vs. 91.3/10,000 (p < 0.0001). CONCLUSION: Rates of reported HCV among pregnant women were approximately 50% lower than the rates determined by the anonymous seroprevalence survey. Further research is needed to determine the relative merits of the current selective screening policy versus universal prenatal HCV screening in pregnancy.

Results of a model analysis to estimate cost utility and value of information for intravenous immunoglobulin in Canadian adults with chronic immune thrombocytopenic purpura.

OBJECTIVE: The aim of this work was to estimate the cost-effectiveness of intravenous immunoglobulin (IVIg) compared with oral prednisone as a treatment for Canadian adults with persistent chronic immune thrombocytopenic purpura (ITP). METHODS: The lifetime costs and effectiveness of IVIg and prednisone were estimated from the perspective of a publicly funded health care system in Canada, using a Markov model that was developed based on a systematic clinical and economic review and recommendations of clinical experts in Canada. Transition probabilities (ie, point estimates and 95% CIs) were estimated from the studies identified in a systematic literature review using a random-effect meta-analysis; point estimates were weighted-mean values from the meta-analysis. No published studies directly estimate the utility weight for patients with relapsed or refractory ITP; therefore, a value of 0.76 was used, based on the mean of the utilities for thrombocytopenia without major bleeding or hemorrhagic stroke. Costs and incremental cost-effectiveness ratios were reported as year-2007 Can $. RESULTS: The incremental costs and quality-adjusted life-years (QALYs) of IVIg versus prednisone were Can $8080 and 0.0071, respectively, resulting in an incremental cost-effectiveness ratio of Can $1.13 million/ QALY in the base-case analysis. The probability of IVIg being cost-effective was 0 if the maximum willingness-to-pay (WTP) value for an additional QALY was below Can $40,000. The probability that IVIg would be cost-effective was only 20%, even if the WTP increased to Can $100,000. The expected value of perfect information (EVPI) and expected value of partial perfect information (EVPPI) were 0 if the WTP was less than Can $30,000. If WTP increased to Can $100,000, the EVPI was Can $1700, and the EVPPI was Can $1010 for utility weights of relapse/refractory states, Can $136 for initial response rates of the treatments, and Can $6 for first-year relapse rates for the treatments. CONCLUSION: Based on the current available clinical evidence, this model analysis of hypothetical patients suggests that IVIg may not be a cost-effective option for adults with persistent chronic ITP in Canada.

Guidelines on the use of intravenous immune globulin for neurologic conditions.

Canada's per capita use of intravenous immune globulin (IVIG) grew by approximately 115% between 1998 and 2006, making Canada one of the world's highest per capita users of IVIG. It is believed that most of this growth is attributable to off-label usage. To help ensure IVIG use is in keeping with an evidence-based approach to the practice of medicine, the National Advisory Committee on Blood and Blood Products (NAC) and Canadian Blood Services convened a panel of national experts to develop an evidence-based practice guideline on the use of IVIG for neurologic conditions. The mandate of the expert panel was to review evidence regarding use of IVIG for 22 neurologic conditions and formulate recommendations on IVIG use for each. A panel of 6 clinical experts, one expert in practice guideline development and 4 representatives from the NAC met to review the evidence and reach consensus on the recommendations for the use of IVIG. The primary sources used by the panel were 2 recent evidence-based reviews. Recommendations were based on interpretation of the available evidence and, where evidence was lacking, consensus of expert clinical opinion. A draft of the practice guideline was circulated to neurologists in Canada for feedback. The results of this process were reviewed by the expert panel, and modifications to the draft guideline were made where appropriate. This practice guideline will provide the NAC with a basis for making recommendations to provincial and territorial health ministries regarding IVIG use management. Recommendations for use of IVIG were made for 14 conditions, including acute disseminated encephalomyelitis, chronic inflammatory demyelinating polyneuropathy, dermatomyositis, diabetic neuropathy, Guillain-Barré syndrome, Lambert-Eaton myasthenic syndrome, multifocal motor neuropathy, multiple sclerosis, myasthenia gravis, opsoclonus-myoclonus, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, polymyositis, Rasmussen's encephalitis, and stiff person syndrome; IVIG was not recommended for 8 conditions including adrenoleukodystrophy, amyotropic lateral sclerosis, autism, critical illness polyneuropathy, inclusion body, myositis, intractable childhood epilepsy, paraproteinemic neuropathy (IgM variant), and POEMS syndrome. Development and dissemination of evidence-based clinical practice guidelines may help to facilitate appropriate use of IVIG.

Neuroendocrine differentiation in extrahepatic bile duct carcinomas and its prognostic significance.

Neuroendocrine differentiation is known to be one of the prognostic factors in many carcinomas. However, the characteristics of neuroendocrine differentiation are not well elucidated in extrahepatic bile duct (EBD) carcinomas. One hundred ninety-four cases of EBD carcinomas were analyzed using immunohistochemistry with synaptophysin and chromogranin. The tumors were graded as degree 0, 1, and 2 when the positive tumor cells were 5% or less, 6% to 25%, and 26% or more, respectively. Immunohistochemical results were compared with clinicopathologic variables and survival rate. Synaptophysin and chromogranin were positive in 54 (27.8%) and 74 (38.1%) cases, respectively. Thirty-four cases (17.5%) were positive for both synaptophysin and chromogranin, 20 (10.3%) and 40 cases (20.6%) were positive only for synaptophysin and for chromogranin, respectively, and 100 cases (51.6%) were negative for both markers. There was a significant survival difference between overall synaptophysin-positive (median, 27 months) and synaptophysin-negative (38 months) groups (P < .05). However, there was no survival difference between chromogranin-positive and chromogranin-negative groups. There was a significant survival difference between the dual-positive expression to synaptophysin and chromogranin group (median, 21 months) and the dual-negative expression group (median, 35 months; P < .05). In summary, synaptophysin expression was an important prognostic factor because synaptophysin-positive cases showed a worse prognosis than synaptophysin-negative cases. The more tumor cells expressed chromogranin, the poorer the survival. Therefore, immunohistochemical studies for neuroendocrine differentiation may be helpful in routine pathological examinations for evaluating the survival and the prognosis of patients with EBD carcinomas.

Health and socioeconomic status differences among antibody hepatitis C positive and negative transfusion recipients, 1986-1990.

OBJECTIVE: To characterize the socioeconomic and health status, disease symptoms of anti-HCV-positive and negative transfusion recipients. METHODS: A cross-sectional interviewer-administered survey of subjects identified through the British Columbia Blood Recipient Program. Study subjects were 18 years and over and had to have had a transfusion between August 1, 1986 and June 30, 1990 and completed an interview of satisfactory quality. Anti-HCV-positive subjects were those seeking monetary compensation from the provincial and Canadian governments and the comparison group was randomly selected from a pool of anti-HCV-negative subjects. The study was designed to detect an assumed difference of 20% in signs and symptoms between the two groups. Statistical comparisons were conducted using bivariate and multivariate logistic regression analyses. RESULTS: A total of 241 and 222 anti-HCV-positive and negative subjects were respectively interviewed and met the study's eligibility criteria. Results from the multivariate analysis indicated that anti-HCV-positive recipients were more likely to have two or more clinical symptoms (OR = 3.53; 95% CI: 1.44, 8.70), to be in worse health status as compared to ten years previous (OR = 1.60; 95% CI: 1.30, 1.96), to have a higher illness intrusiveness rating (OR = 1.35; 95% CI: 1.25, 1.46), and to be younger (OR = 0.97; 95% CI: 0.95, 0.98). CONCLUSION: Our results show that persons exposed to HCV were more likely to have had two or more clinical symptoms, be male, have worse health status as compared to ten years previous, have a higher illness intrusiveness rating, and be younger in age.

Reducing inpatient heritable thrombophilia testing using a clinical decision-making tool.

AIMS: To evaluate the impact of a clinical decision-making tool, designed to educate physicians regarding heritable thrombophilia (HT) testing, on the volume of testing in hospitalised patients in the tertiary care setting. METHODS: We performed a retrospective cohort study over a 6-year period (2007-2012) at a single tertiary care centre intervention site and two regional control sites. In January 2010, the intervention site instituted a policy change whereby physicians ordering HT testing on inpatients needed to complete a pre-preprinted order (PPO) form that outlined the limitations of HT testing in the hospitalised setting. Failure to complete the PPO within 24 h resulted in test cancellation. Our main outcome measure was the volume of HT testing performed at the three study sites. RESULTS: Introduction of the PPO resulted in a 79.4% (95% CI 71.2% to 87.6%) reduction in factor V Leiden (FVL) testing at the intervention site. This decrease was significantly greater compared with those in the two control teaching hospitals over the same time periods (33.7% and 43.6%; both p<0.001). Reductions in FVL testing postintervention were observed among all ordering specialists. Similar postintervention reductions in testing volumes were observed for antithrombin (57.4%), protein C (61.9%) and protein S (62.2%) activity assays. CONCLUSIONS: In a large tertiary care hospital, the introduction of a clinical decision-making tool significantly reduced HT testing in inpatients across clinical specialties. The impact on patient outcome should be assessed in further studies.

An evaluation of autoimmune antibody testing patterns in a Canadian health region and an evaluation of a laboratory algorithm aimed at reducing unnecessary testing.

Autoantibody tests are often ordered inappropriately. We aimed to evaluate the ordering patterns of these tests in our local health region and to develop a laboratory algorithm aimed at reducing unnecessary tests. Laboratory data including the number and sequence of tests, ordering physician specialties and results for antinuclear (ANA), extractable nuclear antigen (ENA) and anti-double stranded DNA (anti-dsDNA) antibody tests from 2007 to 2009 were evaluated. Based on this information and a clinical consensus meeting, an algorithm was developed and applied retrospectively to 1 year of inpatient laboratory data to simulate potential cost savings. We identified a large volume of these autoantibody tests performed, equating to testing costs of $862,706.72, where less than 17 % of each were positive. Repeated ANA tests were mostly ordered after a previously negative result, and 1 % of patients with negative results changed to ≥1:160 on repeat testing. Close to half of all ENA and anti-dsDNA tests that were ordered were done so simultaneously with ANA, suggesting their use as screening tests. This was done more frequently in the inpatient setting. An algorithm was developed where ENA and anti-dsDNA tests would be cancelled if ANA was negative in the same sample. ANA repeated within 1 year would be cancelled and the prior result provided. Application of the algorithm retrospectively simulated a 30 % cost savings. Repeat testing and simultaneous ordering of multiple tests contributed to the excessive ordering of autoantibody tests in our health region. Our proposed algorithm would reduce testing costs and should be accompanied by appropriate educational information for physicians.

Appropriateness of the use of intravenous immune globulin before and after the introduction of a utilization control program.

BACKGROUND: Intravenous immune globulin (IVIG) is an expensive and sometimes scarce blood product that carries some risk. It may often be used inappropriately. We evaluated the appropriateness of IVIG use before and after the introduction of an utilization control program to reduce inappropriate use. METHODS: We used the RAND/UCLA Appropriateness Method to measure the appropriateness of IVIG use in the province of British Columbia (BC) in 2001 and 2003, before and after the introduction of a utilization control program designed to reduce inappropriate use. For comparison, we measured the appropriateness of use during the same periods in the province of Alberta, which had no control program. RESULTS: Of 2256 instances of IVIG use, 54.1% were deemed to be appropriate, 17.4% were of uncertain benefit, and 28.5% were deemed inappropriate. The frequency of inappropriate use in BC after the introduction of the utilization control program did not differ significantly from the frequency before the program or the frequency in Alberta. INTERPRETATION: Almost half of IVIG use in BC and Alberta was judged to be inappropriate or of uncertain benefit, and the frequency of inappropriate use did not decrease after implementation of a utilization control program in BC. More effective utilization controls are necessary to prevent wasted resources and unnecessary risk to patients.

Application of linear discriminant analysis in performance evaluation of extractable nuclear antigen immunoassay systems in the screening and diagnosis of systemic autoimmune rheumatic diseases.

This study applied a linear discriminant analysis model to evaluate the performance of 2 types of commercially available extractable nuclear antigen (ENA) immunoassays for the screening and diagnosis of systemic autoimmune rheumatic diseases (SARDs) in a large tertiary hospital reference laboratory: (1) an enzyme-linked immunosorbent assay (ELISA) and (2) a multiplex bead-based immunoassay (MPBI). The results of the study showed both ENA immunoassays had comparable sensitivity for the detection of SARDs compared with the antinuclear antigen immunofluorescence (ANA-IF) method (ANA-IF: 85.6%, ENA-ELISA: 91.5%, ENA-MPBI: 83.1%, pairwise comparisons with ANA-IF: P > .05). However, both ENA immunoassays offered improved specificity compared with the ANA-IF (ANA-IF: 24.2%; ENA-ELISA: 39.8%; ENA-MPBI: 53.1%; pairwise comparison with ANA-IF: P < .001). The use of a more specific screening immunoassay with comparable sensitivity to ANA-IF is important in a tertiary hospital with high prevalence of non-SARD immune diseases. Diagnostic performance of the ENA/dsDNA components by the MPBI and ELISA methods did not differ significantly (area under the curve [AUC], 81.0% vs 83.0%, respectively, P > .05), but the key ENA/dsDNA variables contributing to the discriminating power of the assays for the diagnosis of specific SARDs were reagent/method dependent.

Body mass index, periprocedural bleeding, and outcome following percutaneous coronary intervention (from the British Columbia Cardiac Registry).

The incidence of obesity is increasing throughout the industrialized world and is a major public health concern. Some studies have shown a paradoxical protective effect of moderate obesity on outcome after percutaneous coronary intervention (PCI). The association between bleeding, body mass, and outcome is not well established and formed the basis for the present study, which examined major bleeding rates and mortality after PCI in British Columbia during a 6-year period. We identified 38,346 consecutive patients from the British Columbia Cardiac Registry who underwent PCI from 1999 to 2005. Data were cross-referenced to determine outcomes at 30 days and 1 year. Information about bleeding after PCI was obtained by cross-referencing the British Columbia Cardiac Registry with the Central Transfusion Registry. Baseline patient characteristics were compared among body mass index (BMI) categories. A clear bimodal (U-shaped) relation was seen between BMI and mortality. BMI was a potent independent predictor of mortality, particularly evident in the underweight (BMI <18.5 kg/m(2); odds ratio [OR] 1.98, 95% confidence interval [CI] 1.6 to 2.5, p <0.0001) and morbidly obese (> or =40 kg/m(2); OR 1.61, 95% CI 1.28 to 2.08, p <0.0001) groups. Periprocedural transfusion was also associated with adverse outcome (OR 2.86, 95% CI 2.52 to 3.25, p <0.0001). Transfusion adopted the same bimodal distribution across the entire cohort. Emergent PCI and femoral access were procedural factors associated with outcome. In conclusion, major bleeding conferred an adverse long-term prognosis after PCI. Identifying demographic and procedural factors that increase risk will facilitate more accurate risk scoring of patients undergoing PCI and allow targeted bleeding-avoidance strategies. Body mass and female gender identified subgroups at much higher risk of bleeding after PCI, an observation that merits further study.

Declining hepatitis C rates in first-time blood donors: insight from surveillance and case-control risk factor studies.

BACKGROUND: Hepatitis C virus (HCV) rates have decreased steadily in first-time donors in Canada since testing was implemented but reasons are unclear. A description of factors that may have played a role in this decline is reported. STUDY DESIGN AND METHODS: Descriptive analysis of first-time blood donors by HCV positivity status and year (1993--2006), sex, and age was carried out. HCV-positive first-time donors and matched controls participated in a confidential scripted telephone interview about risk factors in 1993 through 1994 and in 2005 through 2006, and risk factors independently predicting HCV positivity were determined with multiple logistic regression. RESULTS: HCV-positive donations occurred most frequently in donors born between 1945 and 1964 and decreased in this birth cohort over time (p < 0.01). At present, most first-time donors (74%) are born after 1964. History of intravenous drug use, sex with an intravenous drug user, blood transfusion, and tattoo independently predicted (p < 0.01) HCV positivity in both periods (1993--1994 and 2005--2006). CONCLUSION: Most HCV-positive donors were born between 1945 and 1964, and the decline in HCV rates is associated primarily with this birth cohort. The key risk factors predicting HCV positivity did not change over the 13 years of the study. With approximately two-thirds of HCV-positive Canadians in the general population having been tested for HCV, potential donors may be aware of their HCV status and be likely to self-defer. This, and an increasing proportion of first-time donors born after 1964, may contribute to declining HCV rates in first-time donors.

Superficial vs deep pancreatic parenchymal invasion in the extrahepatic bile duct carcinomas: a significant prognostic factor.

Pancreatic invasion of the extrahepatic bile duct (EBD) carcinomas is known to have a poor outcome. We hypothesized that EBD carcinoma showing shallow invasion to the pancreas may have a better outcome than the usual deep pancreatic invasion. We divided 87 cases of the distal EBD carcinomas into superficial and deep pancreatic invasion groups according to degrees of the pancreatic invasion. The superficial pancreatic invasion group included cases with tumor abutting the pancreatic lobule or pancreatic parenchymal invasion equal to or less than 1 mm from the uppermost portion of the pancreatic lobule or tumors invading into the fibroadipose tissue between pancreatic lobules without parenchymal invasion. The deep invasion group consisted of tumors with more than 1 mm pancreatic parenchymal invasion. The cases with superficial pancreatic invasion showed significantly better survival rate than those with deep pancreatic invasion (P<0.001). Therefore, we recommend that a specific remark on the pathology report about the presence or absence of parenchymal invasion and the depth of invasion of the pancreas is required for managing patients and determining the prognosis. We also recommend that the current pT3 stage of distal EBD carcinomas be subdivided into superficial (pT3a) and deep pancreatic invasion (pT3b).

Analysis of extrahepatic bile duct carcinomas according to the New American Joint Committee on Cancer staging system focused on tumor classification problems in 222 patients.

BACKGROUND: Although the sixth edition of the American Joint Committee on Cancer (AJCC) staging system for extrahepatic bile duct carcinoma was updated, the system has a problem on T classification due to its ambiguous definition of T1 as "tumor confined to bile duct histologically" and T2 as "tumor invading beyond the bile duct." METHODS: The authors considered the outermost part of the muscle layer or fibrous tissue as within the extrahepatic bile duct and considered the area starting from large clusters of adipose tissue as beyond the extrahepatic bile duct. After designing a precise definition of the extrahepatic bile duct wall, they analyzed the new AJCC staging system in 222 patients with of extrahepatic bile duct carcinomas. Then, other clinicopathologic variables for prognosis were evaluated using univariate and multivariate analyses. RESULTS: The 5-year survival rates for patients with tumors that were classified as T1, T2, T3, and T4 were 53.1%, 29.7%, 24.9%, and 0%, respectively. There was a significant difference in survival between patients with T1 tumors and T2 tumors (P < 0.05), but not between patients with T2 tumors and T3 tumors. Significant prognostic factors included depth of invasion (P < 0.005), lymph node metastasis (P < 0.005), and patient age (P < 0.05). CONCLUSIONS: Based on a proposed histologic definition, depth of invasion was practical for evaluating the prognosis of patients with middle and upper extrahepatic bile duct carcinomas. Therefore, the authors recommended changing the current pT1 and pT2 classifications to more precise pathologic terminology.