Clinical standards for drug-susceptible TB in children and adolescents.

BACKGROUND: These clinical standards aim to provide guidance for diagnosis, treatment, and management of drug-susceptible TB in children and adolescents.METHODS: Fifty-two global experts in paediatric TB participated in a Delphi consensus process. After eight rounds of revisions, 51/52 (98%) participants endorsed the final document.RESULTS: Eight standards were identified: Standard 1, Age and developmental stage are critical considerations in the assessment and management of TB; Standard 2, Children and adolescents with symptoms and signs of TB disease should undergo prompt evaluation, and diagnosis and treatment initiation should not depend on microbiological confirmation; Standard 3, Treatment initiation is particularly urgent in children and adolescents with presumptive TB meningitis and disseminated (miliary) TB; Standard 4, Children and adolescents should be treated with an appropriate weight-based regimen; Standard 5, Treating TB infection (TBI) is important to prevent disease; Standard 6, Children and adolescents should receive home-based/community-based treatment support whenever possible; Standard 7, Children, adolescents, and their families should be provided age-appropriate support to optimise engagement in care and clinical outcomes; and Standard 8, Case reporting and contact tracing should be conducted for each child and adolescent.CONCLUSION: These consensus-based clinical standards, which should be adapted to local contexts, will improve the care of children and adolescents affected by TB.

Fungal diversity in the gut microbiome of young South African children.

BACKGROUND: The fungal microbiome, or mycobiome, is a poorly described component of the gut ecosystem and little is known about its structure and development in children. In South Africa, there have been no culture-independent evaluations of the child gut mycobiota. This study aimed to characterise the gut mycobiota and explore the relationships between fungi and bacteria in the gut microbiome of children from Cape Town communities. METHODS: Stool samples were collected from children enrolled in the TB-CHAMP clinical trial. Internal transcribed spacer 1 (ITS1) gene sequencing was performed on a total of 115 stool samples using the Illumina MiSeq platform. Differences in fungal diversity and composition in relation to demographic, clinical, and environmental factors were investigated, and correlations between fungi and previously described bacterial populations in the same samples were described. RESULTS: Taxa from the genera Candida and Saccharomyces were detected in all participants. Differential abundance analysis showed that Candida spp. were significantly more abundant in children younger than 2 years compared to older children. The gut mycobiota was less diverse than the bacterial microbiota of the same participants, consistent with the findings of other human microbiome studies. The variation in richness and evenness of fungi was substantial, even between individuals of the same age. There was significant association between vitamin A supplementation and higher fungal alpha diversity (p = 0.047), and girls were shown to have lower fungal alpha diversity (p = 0.003). Co-occurrence between several bacterial taxa and Candida albicans was observed. CONCLUSIONS: The dominant fungal taxa in our study population were similar to those reported in other paediatric studies; however, it remains difficult to identify the true core gut mycobiota due to the challenges set by the low abundance of gut fungi and the lack of true gut colonising species. The connection between the microbiota, vitamin A supplementation, and growth and immunity warrants exploration, especially in populations at risk for micronutrient deficiencies. While we were able to provide insight into the gut mycobiota of young South African children, further functional studies are necessary to explain the role of the mycobiota and the correlations between bacteria and fungi in human health.

[Work, family, resources and unequal levels of psychological distress between working men and working women : vulnerability or gendered expression of stress?] / Inégalité de détresse psychologique entre les hommes et les femmes en emploi : vulnérabilité ou expression genrée du stress?

INTRODUCTION: This study aims to compare the vulnerability hypothesis and the expression hypothesis to explain a greater level of psychological distress among working women than among working men. METHOD: The two hypotheses were contrasted by integrating work stressors, family stressors, work-family conflicts and psychosocial resources. The conceptual models were tested by using multilevel path analyses on 2026 employees in Quebec (Canada) based in 63 work establishments. RESULTS: Results partially supported both hypotheses. According to the vulnerability hypothesis, single parenting, child-related problems and self-esteem were indirectly involved in the variation of psychological distress among women through family-to-work, otherwise known as work-family conflict. According to the expression hypothesis, although family-to-work conflict was closely associated with more psychological distress among women, this stressor was also closely associated with higher at-risk alcohol consumption among men. Couple-related problems and a sense of control likewise played a role in the expression mechanism through family-to-work conflict. CONCLUSION: These results underline the importance of considering that gender contributes to mental health inequalities through multiple mechanisms. They also call for a distinction between the two directions of work-family conflict as gendered mediators.

High burden of viral respiratory co-infections in a cohort of children with suspected pulmonary tuberculosis.

BACKGROUND: The presentation of pulmonary tuberculosis (PTB) in young children is often clinically indistinguishable from other common respiratory illnesses, which are frequently infections of viral aetiology. As little is known about the role of viruses in children with PTB, we investigated the prevalence of respiratory viruses in children with suspected PTB at presentation and follow-up. METHODS: In an observational cohort study, children < 13 years were routinely investigated for suspected PTB in Cape Town, South Africa between December 2015 and September 2017 and followed up for 24 weeks. Nasopharyngeal aspirates (NPAs) were tested for respiratory viruses using multiplex PCR at enrolment, week 4 and 8. RESULTS: Seventy-three children were enrolled [median age 22.0 months; (interquartile range 10.0-48.0); 56.2% male and 17.8% HIV-infected. Anti-tuberculosis treatment was initiated in 54.8%; of these 50.0% had bacteriologically confirmed TB. At enrolment, ≥1 virus were detected in 95.9% (70/73) children; most commonly human rhinovirus (HRV) (74.0%). HRV was more frequently detected in TB cases (85%) compared to ill controls (60.6%) (p = 0.02). Multiple viruses were detected in 71.2% of all children; 80% of TB cases and 60.6% of ill controls (p = 0.07). At follow-up, ≥1 respiratory virus was detected in 92.2% (47/51) at week 4, and 94.2% (49/52) at week 8. CONCLUSIONS: We found a high prevalence of viral respiratory co-infections in children investigated for PTB, irrespective of final PTB diagnosis, which remained high during follow up. Future work should include investigating the whole respiratory ecosystem in combination with pathogen- specific immune responses.

Droplets, dust and guinea pigs: an historical review of tuberculosis transmission research, 1878-1940.

The transmission of tuberculosis (TB) occurs mainly via inhalation of airborne droplet nuclei; however, the precise details of this process remain uncertain. We reviewed the literature from 1870 to 1940, when Mycobacterium tuberculosis was discovered and the concept of transmission emerged as a hallmark of the infectious disease. By 1940, laboratory experiments, animal studies and clinical observation had demonstrated that cough was central to TB transmission, and that guinea pigs close to patients with cough could be infected, mainly by patients coughing small droplets likely containing only 1-2 bacilli. A minority of pulmonary TB patients, usually during the early stages of the disease, with thin watery sputum, more successfully coughed small infectious droplets than patients with heavily smear-positive tenacious sputum who were often too ill and too weak to cough vigorously. There was ongoing debate regarding the possible importance of desiccated sputum particles found in surface dust. Investigation of TB transmission has a history of more than 130 years.

A2 to B Blood Type Incompatible Deceased Donor Kidney Transplantation in a Recipient Infected with the Human Immunodeficiency Virus: A Case Report.

BACKGROUND: With the introduction of the Kidney Allocation System in the United States in December 2014, transplant centers can list eligible B blood type recipients for A2 organ offers. There have been no prior reports of ABO incompatible A2 to B deceased donor kidney transplantation in human immunodeficiency virus-positive (HIV+) recipients to guide clinicians on enrolling or performing A2 to B transplantations in HIV+ candidates. We are the first to report a case of A2 to B deceased donor kidney transplantation in an HIV+ recipient with good intermediate-term results. METHODS AND RESULTS: We describe an HIV+ 39-year-old African American man with end-stage renal disease who underwent A2 to B blood type incompatible deceased donor kidney transplantation. Prior to transplantation, he had an undetectable HIV viral load. The patient was unsensitized, with his most recent anti-A titer data being 1:2 IgG and 1:32 IgG/IgM. Induction therapy of basiliximab and methylprednisolone was followed by a postoperative regimen of plasma exchange, intravenous immunoglobulin, and rituximab with maintenance on tacrolimus, mycophenolate mofetil, and prednisone. He had delayed graft function without rejection on allograft biopsy. Nadir serum creatinine was 2.0 mg/dL. He continued to have an undetectable viral load on the same antiretroviral therapy adjusted for renal function. CONCLUSIONS: To our knowledge, this is the first report of A2 to B deceased donor kidney transplantation in an HIV+ recipient with good intermediate-term results, suggesting that A2 donor kidneys may be considered for transplantation into HIV+ B-blood type wait list candidates.

Cancer incidence, mortality, and stage at diagnosis in First Nations living in Manitoba.

BACKGROUND: In the present study, we examined breast (bca) and colorectal cancer (crc) incidence and mortality and stage at diagnosis for First Nations (fn) individuals and all other Manitobans (aoms). METHODS: Several population-based databases were linked to determine ethnicity and to calculate age-standardized incidence and mortality rates. Logistic regression was used to compare bca and crc stage at diagnosis. RESULTS: From 1984-1988 to 2004-2008, the incidence of bca increased for fn and aom women. Breast cancer mortality increased for fn women and decreased for aom women. First Nations women were significantly more likely than aom women to be diagnosed at stages iii-iv than at stage i [odds ratio (or) for women ≤50 years of age: 3.11; 95% confidence limits (cl): 1.20, 8.06; or for women 50-69 years of age: 1.72; 95% cl: 1.03, 2.88). The incidence and mortality of crc increased for fn individuals, but decreased for aoms. First Nations status was not significantly associated with crc stage at diagnosis (or for stages i-ii compared with stages iii-iv: 0.98; 95% cl: 0.68, 1.41; or for stages i-iii compared with stage iv: 0.91; 95% cl: 0.59, 1.40). CONCLUSIONS: Our results underscore the need for improved cancer screening participation and targeted initiatives that emphasis collaboration with fn communities to reduce barriers to screening and to promote healthy lifestyles.

The risk of colorectal cancer is not increased after a diagnosis of urothelial cancer: a population-based study.

BACKGROUND: The data about whether patients with a prior urothelial cancer (uca) are at increased risk of colorectal cancer (crc) are conflicting. We used a competing risks analysis to determine the risk of crc after uca. METHODS: Historical cohorts were assembled by record linkage of Manitoba Cancer Registry and Manitoba Health databases. The incidence of crc for individuals with uca as their first cancer between 1987 and 2009 was compared with the incidence for randomly selected age-and sex-matched individuals without a cancer diagnosis at the index date (uca diagnosis date). Three competing outcomes (crc, another primary cancer, and death) were evaluated by competing risks proportional hazards models with adjustment for relevant confounders. RESULTS: The cohorts of 4591 patients with uca and 22,312 without uca were followed for a total of 179,287 person-years (py). After uca, the rate of subsequent colon cancer in uca patients was 4.5 per 1000 py compared with 3.6 per 1000 py in the non-cancer cohort. In the multivariable analysis, no overall increase in crc risk was observed for patients first diagnosed with uca (hazard ratio: 0.88; 95% confidence interval: 0.70 to 1.1; p = 0.26). CONCLUSIONS: Because of similar crc risk, a similar crc screening strategy should be applied for individuals with and without uca.

Type-specific human papillomavirus infections and Pap test findings in Inuit and non-Inuit women in Nunavut, Canada.

OBJECTIVE: To determine the prevalence and distribution of type-specific human papillomavirus (HPV) infections and their association with cytological outcomes in women living in the Canadian territory of Nunavut. METHODS: Surveillance of type-specific HPV infection was conducted. Cervical specimens of all Inuit, First Nations and non-Aboriginal women in Nunavut who presented for a Pap test in any clinical setting between January 2008 and March 2009 were tested for HPV infection. The association between high-grade cervical lesions and HPV type was also examined. RESULTS: HPV results were available for 4,043 individual women (13 to 77 years). Of those with known ethnicity (N=4,033), 89.2% were Inuit, 0.4% were First Nations and 10.4% were non-Aboriginal. First Nations women were included in all analyses except those making comparisons by ethnicity, due to the small number of individuals in this group. Overall, 29.9% of women were found to be infected with HPV (any type) and 19.9% with any high-risk HPV (type 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 or 59). Most often, women were infected with HPV 16 (6.4%) followed by HPV 31 (3.1%). There were no statistically significant differences between Inuit and non-Aboriginal (reference group) women 20 years of age and older regarding the prevalence of any HPV (odds ratios (OR): 1.19, 95% confidence intervals (CI): 0.92-1.54), high-risk HPV (OR: 1.06, 95% CI: 0.78-1.44) or HPV 16 and 18 (OR: 0.81, 95% CI: 0.51-1.27). HPV 31 was the only type that was significantly more frequent among Inuit than non-Aboriginal women (OR: 3.95, 95% CI: 1.24-12.54). There was no difference in the overall occurrence of cervical abnormalities between non-Aboriginal and Inuit women (p-value = 0.17). HPV 16 was strongly associated with cervical dysplasia, being present in 50.9% of specimens with a high-grade lesion. CONCLUSION: HPV is a significant public health issue in the territory of Nunavut. The findings presented in this article are similar to those in other studies among Inuit women, with prevalence of HPV being higher than in studies conducted among non-Inuit women in other regions of Canada. These results provide a baseline of HPV prevalence that precedes the introduction of the Nunavut HPV Immunization Program in 2010 and will allow for future evaluation. The high prevalence of HPV infection among women living in Nunavut can be reduced through immunization and associated high-grade cervical abnormalities mitigated by regular cervical screening.

BRIEF - SYNOPSIS OF THE CURRENT EVIDENCE ON THE RISK OF HIV TRANSMISSION.

BACKGROUND: Knowledge of the risk of HIV transmission has evolved over the past decade as evidence on the impact of biological and behavioural co-factors, such as viral load, has come to light. We undertook a comprehensive review of the evidence on the risk of HIV transmission. METHODS: A search was conducted for literature published between January 2001 and May 2012. The search focused on systematic, meta-analytic, and narrative reviews. For topics where no reviews existed, primary research studies were included. RESULTS: The risk estimates for the sexual transmission of HIV, per sex act, ranged from 0.5% to 3.38% (with mid-range estimates of 1.4% to 1.69%) for receptive anal intercourse; 0.06% to 0.16% for insertive anal intercourse; 0.08% to 0.19% for receptive vaginal intercourse; and approximately 0.05% to 0.1% for insertive vaginal intercourse. For people who inject drugs, the risk of transmission from a contaminated needle, per injection, was estimated to be between 0.7% and 0.8%. A number of factors impact the risk, including viral load, the presence of other sexually transmitted infections (STIs), and male circumcision. CONCLUSIONS: Within each route of transmission, estimates of the risk of transmission varied widely, likely due to the role of behavioural and biological co-factors. Viral load appears to be an important predictor of transmission, regardless of the route of transmission. However, the evidence indicates that viral load is not the only determinant and that certain co-factors play a role in increasing (e.g., STIs) or decreasing (e.g., male circumcision) the risk of transmission.

Distribution of human papillomavirus types, cervical cancer screening history, and risk factors for infection in Manitoba.

OBJECTIVES: We conducted a study to investigate the prevalence of human papillomavirus (HPV) infections in an opportunistic sample of women in Manitoba, Canada. We inquired about risk factors associated with HPV infections and linked the HPV typing results with the cervical cancer screening history of the participants. METHODS: The study population included 592 women attending Papanicolaou (Pap) test clinics. After signing a consent form, participants were given a self-administered questionnaire on risk factors and received a conventional Pap test. Residual cells from the Pap tests were collected and sent for HPV typing. RESULTS: The mean age of the population was 43 years. A total of 115 participants (19.4%) had an HPV infection, 89 of whom had a normal Pap test. Of those who were HPV-positive, 61 (10.3%) had high-risk (Group 1) HPV. HPV-16 was the most prevalent type (15/115: 13.0% of infections). The most consistent risk factors for HPV infection were young age, Aboriginal ethnicity, higher lifetime number of sexual partners and higher number of sexual partners in the previous year. CONCLUSION: The prevalence of HPV types in Manitoba is consistent with the distributions reported in other jurisdictions. These data provide baseline information on type-specific HPV prevalence in an unvaccinated population and can be useful in evaluating the effectiveness of the HPV immunization program. An added benefit is in the validation of a proof of concept which links a population-based Pap registry to laboratory test results and a risk behaviour survey to assess early and late outcomes of HPV infection. This methodology could be applied to other jurisdictions across Canada where such capacities exist.

Projection of future cancer incidence and new cancer cases in Manitoba, 2006-2025.

INTRODUCTION: Projecting the burden of cancer is important for evaluating prevention strategies and for administrative planning at cancer facilities. METHODS: We projected cancer incidence and counts for the population of Manitoba using population projections from the Manitoba Bureau of Statistics for the years 2006 to 2025 and cancer incidence data from the Manitoba Cancer Registry for the years 1976 to 2005. Data were analyzed using a version of the age-period-cohort model with recommended modifications that was developed and tested in the Nordic countries. RESULTS: The overall incidence of cancer in Manitoba is not projected to change substantially from 2006 to 2025. However, the age-standardized incidence for lung cancer is expected to decrease, particularly for males, highlighting the importance of tobacco prevention. The total number of new cancer cases per year is expected to increase 36% over the projection period, attributable primarily to demographic changes. CONCLUSION: As the population of Manitoba increases, resource and infrastructure planning will need to account for the expected increase in cancer cases.

Use of simulated sputum specimens to estimate the specificity of laboratory-diagnosed tuberculosis.

SETTING: Cross-contamination is not uncommon in mycobacteriology laboratories of high-income countries, as documented by bacterial genotyping. The extent of this problem in low-income countries is largely unknown, where this method is impractical. OBJECTIVE: To estimate the rate of cross-contamination in a high-volume tuberculosis (TB) laboratory in South Africa. DESIGN: Simulated sputum specimens labelled with false names were sent from a TB clinic, interspersed with patient samples, and processed for culture and microscopy. Results were interpreted in the context of the observed proportion of samples with positive microscopy and culture results. RESULTS: With microscopy, 6/190 (3.2%) simulated specimens were positive (estimated specificity = 96.8%). Considering the 881 positive microscopy results in 6093 clinical samples, we extrapolate that 19.3% (95%CI 7.0-42.8) of positive smears were false-positives. On culture, 2/190 (1.1%) of the simulated specimens were positive for Mycobacterium tuberculosis (estimated specificity = 98.9%). Considering the 1862 positive cultures from 6093 clinical samples, we estimate that 2.4% (95%CI 0.3-8.8) of positive cultures were false-positives. CONCLUSION: Simulated specimens offer a simple means of estimating the proportion of false-positive results, providing information on all sources of potential error from the clinic, through the laboratory and to reporting of results.

Does location matter? Rural vs urban outcomes after blood and marrow transplantation in a population-based Canadian cohort.

Specialized health services, such as blood and marrow transplantation (BMT), are usually based in large urban centers. Previous research has suggested that rural patients undergoing BMT have a higher risk of death. We performed a cohort study using data from both the Manitoba BMT Program and the provincial Cancer Registry to determine whether patients from the rural areas would have inferior survival after BMT and whether rural patients have reduced access to BMT. A total of 463 adult Manitobans, who underwent BMT between January 1990 and December 2006, were assessed. We analyzed area of residence (rural vs urban), disease and BMT characteristics, and calculated the OS. Patients undergoing autologous and allogeneic transplants were analyzed separately. When adjusted for gender, age at BMT and year of BMT, area of residence was not a significant predictor of mortality. A relative survival analysis was also conducted, and area of residence was again not a significant predictor of mortality. To measure access to BMT in urban vs rural patients, we evaluated all patients with newly diagnosed Hodgkin's Lymphoma (HL) during this same period. Of 432 Manitobans diagnosed with HL, 182 (42%) were rural and 250 (58%) were urban. In contrast, 69% of patients undergoing transplant for HL were urban. In conclusion, using population-based data from a Canadian province, we were unable to show a survival disadvantage for rural patients after controlling for other variables. BMT utilization in rural populations deserves further study.

High incidence of chronic lymphocytic leukemia (CLL) diagnosed by immunophenotyping: a population-based Canadian cohort.

Incidence and outcomes of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) are not well established at the population level, especially since the widespread use of immunophenotyping. We studied the epidemiology of CLL in Manitoba (Canada) by combining data from a centralized flow cytometry facility and the provincial cancer registry for the period 1998-2003. Of 616 cases identified, 27% of patients identified by flow cytometry were not on the cancer registry. The age-adjusted incidence of 7.99/100,000 is substantially higher than the reported incidence in registry reports. We also noted differences in relative survival based on age and gender.

Incidence of right-sided colorectal cancer after breast cancer: a population-based study.

OBJECTIVES: Estrogen levels, which are involved in the development of breast cancer, may also be responsible for a higher incidence of right-sided colorectal neoplasia in women. Our objective was to determine the incidence of right-sided colorectal cancer (CRC) after the diagnosis of breast cancer. METHODS: All cases of breast cancers diagnosed between 1956 and 2006 were identified from the Manitoba Cancer Registry (MCR) and followed up until the diagnosis of any invasive cancer, death, migration out of the province, or 31 December 2006. Standardized incidence ratios (SIRs) for all CRC and right-sided CRC (cecum, ascending colon, and hepatic flexure) were calculated to compare the observed CRC incidence with that expected in the general population. Stratified analysis was performed to determine the risk at different follow-up time intervals, age at breast cancer diagnosis, and for tamoxifen use. RESULTS: There were 23,377 cases of breast cancer diagnosed between 1956 and 2006 with a total follow-up of 221,364 patient-years. The SIR for all CRC was 0.96 (95% confidence interval (CI) 0.87-1.06) and for right-sided CRC it was 1.02 (95% CI 0.87-1.20). The SIRs remained close to unity at different time intervals, for different age groups, and in analysis restricted to more recent years (1985-2006). Tamoxifen use did not alter the risk of all CRC (SIR 1.22; 95% CI 0.92-1.62) or right-sided CRC (SIR 0.90; 95% CI 0.48-1.54). CONCLUSIONS: There is no increase in the overall risk for CRC or for right-sided CRC after the diagnosis of breast cancer. CRC screening strategy for breast cancer survivors should be similar to that for the general population.

Performance status, but not the hematopoietic cell transplantation comorbidity index (HCT-CI), predicts mortality at a Canadian transplant center.

The hematopoietic cell transplantation-specific comorbidity index (HCT-CI) was developed at a single center to predict outcomes for allogeneic transplant recipients who have comorbidities. The HCT-CI has not been widely validated in unselected transplant recipients. We evaluated whether the HCT-CI and other readily available pre-transplant variables predicted NRM and OS at a Canadian transplant center. Using a prospective cohort design, we analyzed consecutive adult allogeneic HCT recipients. Of 187 patients, HCT-CI risk was low in 22 (12%), intermediate in 50 (27%), high in 104 (55%) and undetermined in 11 (6%). Two-year OS was 45% (95% CI: 24-64%), 55% (95% CI: 40-68%) and 42% (95% CI: 32-51%) in the low, intermediate and high-risk HCT-CI groups, respectively. Two-year NRM was 36% (95% CI: 17-56%), 26% (95% CI: 15-39%) and 30% (95% CI: 22-39%) in the low, intermediate and high-risk HCT-CI groups, respectively. In multivariate analysis, the HCT-CI failed to predict OS or NRM. However, KPS of <90% at HCT was a strong predictor of NRM. In conclusion, the HCT-CI was not associated with NRM or OS. In contrast, KPS was an independent indicator of survival. International multi-center studies are required before the HCT-CI is used in clinical practice.

Survival and treatment trends of rectal cancer patients in a population with suboptimal local control.

AIM: To explore trends in rectal cancer survival in Manitoba, particularly in patients where local control was an issue. METHOD: Patients diagnosed with rectal or rectosigmoid adenocarcinoma from 1985 to 1999 were included. Demographic, treatment and mortality information were abstracted from the registry. Relative survival was examined for all patients for the periods 1985-1989, 1990-1994 and 1995-1999, and subsequently limited to those who underwent major surgery (Hartmann's, anterior, and abdominal perineal resection). RESULTS: Of the 2925 patients identified, 2163 (74%) had undergone a major surgery. Five-year relative survival was 46%, 54% and 53% for all patients for the three periods, respectively; major surgery results were 53%, 59% and 60%. Radiotherapy was used in 32% of cases in 1985-1989 and in 40% of cases in 1995-1999. Chemotherapy was used in 13% of cases in 1985-1989 and in 37% of cases in 1995-1999. CONCLUSION: Consistent with other studies, overall rectal cancer survival in Manitoba has improved since 1985. Better local control, as suggested in other studies, does not appear to be a major factor in that improvement. Future work should include review of the local control strategy in Manitoba and factors to explain the improved survival.

High rate of discordance between clinical and autopsy diagnoses in blood and marrow transplantation.

We analyzed autopsies performed in a Canadian blood and marrow transplantation (BMT) program. We aimed to assess variables that predict the performance of an autopsy, whether rates of autopsy are changing, and the rate of discordance between clinical and autopsy diagnoses. All deceased adult patients from January 1990 to December 2004 were reviewed. Autopsy rates were compared to a large teaching hospital. Of 476 myeloablative BMT patients, 225 died and 48 (27%) underwent autopsy. Autopsy was more likely in patients dying: <100 days post-BMT, in the intensive care unit, after allografting, and on weekends. Autopsy rates among BMT patients declined during the three time periods (1990-1994, 1995-1999, 2000-2004). The autopsy rate at the teaching hospital showed a similar downward temporal trend. Major and minor disagreements at autopsy were present in 16 (34%) and 14 (30%) of cases, respectively. There was no change in discordance rates over time. Thus, despite advances in diagnostic procedures, high levels of disagreement between clinical and autopsy diagnoses for BMT patients persist as autopsy rates decline. We recommend that the autopsy regains its role as a valuable investigation. This may become especially relevant in an era where patients with medical comorbidities are undergoing reduced-intensity BMT.