Stochastic agent-based modeling of tuberculosis in Canadian Indigenous communities.

BACKGROUND: In Canada, active tuberculosis (TB) disease rates remain disproportionately higher among the Indigenous population, especially among the Inuit in the north. We used mathematical modeling to evaluate how interventions might enhance existing TB control efforts in a region of Nunavut. METHODS: We developed a stochastic, agent-based model of TB transmission that captured the unique household and community structure. Evaluated interventions included: (i) rapid treatment of active cases; (ii) rapid contact tracing; (iii) expanded screening programs for latent TB infection (LTBI); and (iv) reduced household density. The outcomes of interest were incident TB infections and total diagnosed active TB disease over a 10- year time period. RESULTS: Model-projected incidence in the absence of additional interventions was highly variable (range: 33-369 cases) over 10 years. Compared to the 'no additional intervention' scenario, reducing the time between onset of active TB disease and initiation of treatment reduced both the number of new TB infections (47% reduction, relative risk of TB = 0.53) and diagnoses of active TB disease (19% reduction, relative risk of TB = 0.81). Expanding general population screening was also projected to reduce the burden of TB, although these findings were sensitive to assumptions around the relative amount of transmission occurring outside of households. Other potential interventions examined in the model (school-based screening, rapid contact tracing, and reduced household density) were found to have limited effectiveness. CONCLUSIONS: In a region of northern Canada experiencing a significant TB burden, more rapid treatment initiation in active TB cases was the most impactful intervention evaluated. Mathematical modeling can provide guidance for allocation of limited resources in a way that minimizes disease transmission and protects population health.

Epidemiology, clinical features and outcomes of incident tuberculosis in children in Canada in 2013-2016: results of a national surveillance study.

PURPOSE: Childhood tuberculosis disease is difficult to diagnose and manage and is an under-recognised cause of morbidity and mortality. Reported data from Canada do not focus on childhood tuberculosis or capture key epidemiologic, clinical and microbiologic details. The purpose of this study was to assess demographics, presentation and clinical features of childhood tuberculosis in Canada. METHODS: We conducted prospective surveillance from 2013 to 2016 of over 2700 paediatricians plus vertical tuberculosis programmes for incident tuberculosis disease in children younger than 15 years in Canada using the Canadian Paediatric Surveillance Program (CPSP). RESULTS: In total, 200 cases are included in this study. Tuberculosis was intrathoracic in 183 patients of whom 86% had exclusively intrathoracic involvement. Central nervous system tuberculosis occurred in 16 cases (8%). Fifty-one per cent of cases were hospitalised and 11 (5.5%) admitted to an intensive care unit. Adverse drug reactions were reported in 9% of cases. The source case, most often a first-degree relative, was known in 73% of cases. Fifty-eight per cent of reported cases were Canadian-born Indigenous children. Estimated study rates of reported cases (per 100 000 children per year) were 1.2 overall, 8.6 for all Indigenous children and 54.3 for Inuit children. CONCLUSION: Childhood tuberculosis may cause significant morbidity and resource utilisation. Key geographies and groups have very high incidence rates. Elimination of childhood tuberculosis in Canada will require well-resourced community-based efforts that focus on these highest risk groups.

Mature results of the Ottawa phase II study of intermittent androgen-suppression therapy in prostate cancer: clinical predictors of outcome.

PURPOSE: To present the mature experience of a phase II trial of intermittent androgen suppression (IAS). METHODS AND MATERIALS: Intermittent androgen-suppression therapy was initiated in prostate-cancer patients to delay hormone resistance and minimize potential side effects of androgen-deprivation therapy (ADT). Patients received cyclical periods of ADT and observation (off-treatment interval [OTI]). Androgen-deprivation therapy was reinitiated when the level of prostate-specific antigen (PSA) rose above 10 ng/ml, or for disease progression. Associations between clinical factors and eligibility for OTI were measured. Kaplan-Meier and Cox regression analyses were used to determine factors predicting the duration of OTIs. RESULTS: Ninety-five patients completed 187 cycles of treatment. The median duration of OTIs was 8.5 months. Patients with higher PSA and metastatic disease were less likely to be eligible for the first OTI (p < 0.01). In multivariate analysis, patients with higher PSA and local relapse had significantly longer OTIs (p < 0.01) compared with metastatic patients. The median time to withdrawal from the study was 37 months. CONCLUSIONS: Intermittent androgen suppression appears to be a favorable treatment option for patients with biochemically (according to level of PSA) or locally recurrent prostate cancer with favorable long-term survival, a high probability of eligibility for OTIs, and durable OTIs.

Treatment of stage I seminoma: a 15-year review.

PURPOSE: To review the treatment and outcomes in patients with stage I seminoma after orchidectomy. METHODS: A retrospective chart review of all patients with stage I seminoma referred for initial treatment during the last 15 years was performed. Initial treatment approaches and outcomes were analyzed. Comparisons were made between patients treated with adjuvant radiotherapy and those receiving no adjuvant therapy (surveillance group). RESULTS: A total of 150 patients with stage I seminoma was seen between 1989 and 2003. Median age at diagnosis was 37.5 years (range 19-79), with a median follow-up of 54 months (range 1-162). Of the patients, 71% were treated with adjuvant radiotherapy, and 29% were placed on a surveillance protocol. The 5-year relapse-free survival and overall survival for the entire group were 95% and 100%, respectively. The 5-year relapse-free survival for the adjuvant radiotherapy group was 100% compared with 79% for the surveillance group (P < 0.001). Of the 6 patients who had a relapse, 5 were salvaged with radiation, but 1 required chemotherapy as well. One patient who had a relapse is currently refusing treatment for recurrence. CONCLUSIONS: Our results confirm the excellent prognosis for patients with stage I seminoma and indicate that surveillance does not compromise survival. This result adds to the evidence that surveillance is a good option for many patients and also supports our current approach, which favors surveillance for most patients with stage I seminoma after orchidectomy who are willing to go on our surveillance protocol.

A prospective clinical trial of green tea for hormone refractory prostate cancer: an evaluation of the complementary/alternative therapy approach.

PURPOSE: To evaluate the efficacy and toxicity of green tea, prescribed as an alternative complementary (CAM) formulation on hormone refractory prostate cancer (HRPC). METHODS: Patients with HRCP were prescribed green tea extract capsules at a dose level of 250 mg twice daily. Efficacy and toxicity were evaluated during monthly visits. The primary endpoint was prostate-specific antigen (PSA) or measurable disease progression after a minimum of 2 months of therapy. RESULTS: Nineteen patients were enrolled into the study. The treatment was generally well tolerated. Twelve patients reported at least one side effect; only two of these were of moderate or severe grade. Primary toxicity was related to gastrointestinal irritation or caffeine intake. Four patients did not complete the minimum 2 months of therapy because of: intolerance (two patients), physician stoppage (one patient), death from cerebrovascular accident (one patient). Fifteen patients completed at least 2 months of therapy. Nine of these patients had progressive disease within 2 months of starting therapy. Six patients developed progressive disease after additional 1 to 4 months of therapy. CONCLUSION: Green tea, as CAM therapy, was found to have minimal clinical activity against hormone refractory prostate cancer.

Multidrug and extensively drug-resistant tuberculosis in Canada 1997-2008: demographic and disease characteristics.

SETTING: Nationwide Canadian public health surveillance. OBJECTIVE: Description of demographic features and disease characteristics of drug-resistant tuberculosis (TB) in Canada over a 12 year period. DESIGN: Continuous surveillance of all cases of culture-confirmed TB in Canada. Demographic and microbiologic features were analyzed and comparisons between drug-susceptible, multidrug-resistant (MDR), and drug-resistant not-MDR were made. Cases of extensively drug resistant TB are described. RESULTS: 15,993 cases of culture-confirmed TB were reported during the study period. There were 5 cases of XDR-TB, 177 cases of MDR-TB, and 1,234 cases of first-line drug resistance not-MDR. The majority of drug-resistant cases were reported in foreign-born individuals, with drug-resistant cases diagnosed earlier post-arrival in Canada compared to drug-susceptible cases. In MDR-TB isolates, there was a high rate of drug-resistance to other first- and second-line drugs, making reliable empiric therapeutic recommendations for MDR-TB difficult. There was a statistically significant association between both MDR and drug-resistance not-MDR, and the risk of a negative treatment outcome (defined as treatment failure, absconded, or treatment ongoing >3 yrs). CONCLUSION: Drug-resistance complicates TB management even in developed nations with well-established TB control programs. The predominantly international origin of drug-resistant cases highlights the need for global strategies to combat TB.

Outcomes of second-line chemotherapy in patients with relapsed extensive small cell lung cancer.

INTRODUCTION: Extensive-disease small cell lung cancer (ED SCLC) is characterized by initial chemosensitivity, followed inevitably by relapse. The optimal role of additional chemotherapy at the time of progression is controversial. We reviewed the experience of all patients over a 5-year period with ED SCLC to describe outcomes of second-line chemotherapy. METHODS: Records of all patients registered at The Ottawa Hospital Regional Cancer Centre with ED SCLC were reviewed, and baseline prognostic factors, chemotherapy delivered, and treatment outcomes were extracted. Multivariate analyses were performed to determine the effect of second-line chemotherapy on survival. RESULTS: Of 192 patients who completed first-line chemotherapy, only 62 (32%) received second-line therapy; these patients were younger and fitter, and lived longer from the time of relapse (5.2 vs. 1.5 months). Second-line therapy was an independent predictor of survival. Benefit was observed in patients with relapse either before or after 60 days from the completion of first-line therapy. CONCLUSIONS: Second-line chemotherapy given at the time of relapse of ED SCLC seems to be associated with prolongation of survival, even in patients traditionally felt to have chemoresistant disease. The majority of patients, however, do not receive second-line therapy because of poor clinical status at relapse.

Smoking is associated with worse outcomes in patients with prostate cancer treated by radical radiotherapy.

OBJECTIVE: To investigate the effect of smoking on the outcome in a cohort of men treated for localized prostate cancer at one institution with a uniform protocol of radical external beam radiotherapy (EBRT). PATIENTS AND METHODS: The study was a retrospective review of 434 patients with cT1-T4 N0m0 prostate cancer treated with curative intent with EBRT (66 Gy in 33 fractions) between 1990 and 1999. Univariate and multivariate Cox regression analyses were used to estimate the risk associated with smoking on biochemical failure (American Society for Therapeutic Radiology and Oncology definition), local failure, distant failure, overall and disease-specific survival. RESULTS: The median follow-up was 70.3 months. A smoking history was obtained in 96% of cases; 16.8% were current smokers, 54.4% previous smokers and 28.8% non-smokers. Current smokers presented at a younger median age, by 3.6 years (P = 0.06). There were no differences in clinical T stage, Gleason score or prostate-specific antigen level amongst the three patient groups. Smoking conferred a higher risk of developing metastatic disease in both current smokers (hazard ratio 5.24; 95% confidence interval 1.75-15.72) and previous smokers (2.90, 1.09-7.67). There were also increases in risk, although not quite significant, for biochemical failure (1.49, 0.88-2.40) and overall survival (1.72, 0.94-3.15). CONCLUSIONS: After curative treatment with EBRT, a history of smoking was associated with a greater risk of developing metastatic disease. Smoking status was not associated with worse disease on presentation.

Effective palliative radiotherapy for symptomatic recurrent or residual ovarian cancer.

OBJECTIVE: To evaluate the efficacy of radiotherapy (RT) for symptomatic recurrent or residual ovarian cancer. METHODS: A review was conducted on patients (pts) treated with palliative RT for symptomatic ovarian cancer at The Ottawa Hospital Regional Cancer Centre between 1990 and 2003. Patient demographics, tumor factors, treatment variables, and clinical outcome were entered into a database. Symptom response was defined as complete (CR), partial (PR), or none. RESULTS: 62 courses of RT were delivered to 53 pts. The symptoms treated were: bleeding (40%), pain (37%), and "others" (23%). The most common dose fractionation scheme was 30 Gy in 10 fractions (f) (range: 5 Gy/1 f to 52.5 Gy/20 f). The overall response rate was 100%, with 68% achieving a CR. The CR rates were 88, 65, and 36% for the symptoms of bleeding, pain, and "others", respectively (P = 0.003). The median duration of response was 4.8 months (range: 1-71 months). In multivariate analysis, the only factors that were found to be significant positive predictors of symptom control were: the symptom bleeding (P = 0.015) and stage III/IV disease at presentation (P = 0.01). The most commonly reported toxicities were grades 1 and 2 nausea/vomiting and diarrhea. There were no grade 3/4 toxicities reported. CONCLUSIONS: Radiotherapy is highly effective in palliating symptomatic ovarian cancer. Excellent results are achieved for patients presenting with bleeding or pain. Symptomatic patients should be strongly considered for palliative radiotherapy. Higher doses of radiotherapy should be considered for those with symptoms other than bleeding or pain and those with longer life expectancies.