This exploratory follow-up of the START provides the first randomized data to suggest that adding exercise to standard chemotherapy may improve breast cancer outcomes. A definitive phase III trial is warranted.

Objectives To examine the relationship between non-fatal overdose and risk of subsequent fatal overdose. Methods We assessed risk factors for overdose death among two prospective cohorts of persons who inject drugs (PWID) in Vancouver, Canada. Extended Cox regression was used to examine if reports of non-fatal overdose were associated with the time to fatal overdose while adjusting for other behavioral, social and structural confounders. Results Between May, 1996 and December, 2011, 2,317 individuals were followed for a median of 60.8 months. In total, 134 fatal overdose deaths were identified for an incidence density of 8.94 (95% confidence interval [CI]: 7.55 – 10.59) deaths per 1,000 person-years. During the study period there were 1795 reports of non-fatal overdose. In a multivariate model, recent non-fatal overdose was independently associated with the time to overdose mortality (adjusted hazard ratio [AHR] = 1.95; 95% CI: 1.17 - 3.27). As well, there was a dose response effect of increasing cumulative reports of non-fatal overdose on subsequent fatal overdose. Conclusion Reports of recent non-fatal overdose were independently associated with subsequent overdose mortality in a dose-response relationship. These findings suggest that individuals reporting recent non-fatal overdose should be engaged with intensive overdose prevention interventions.

Cumulative incidence has been widely used to estimate the cumulative probability of developing an event of interest by a given time, in the presence of competing risks. When it is of interest to measure the total burden of recurrent events in a population, however, the cumulative incidence method is not appropriate because it considers only the first occurrence of the event of interest for each individual in the analysis: Subsequent occurrences are not included. Here, we discuss a straightforward and intuitive method termed "mean cumulative count," which reflects a summarization of all events that occur in the population by a given time, not just the first event for each subject. We explore the mathematical relationship between mean cumulative count and cumulative incidence. Detailed calculation of mean cumulative count is described by using a simple hypothetical example, and the computation code with an illustrative example is provided. Using follow-up data from January 1975 to August 2009 collected in the Childhood Cancer Survivor Study, we show applications of mean cumulative count and cumulative incidence for the outcome of subsequent neoplasms to demonstrate different but complementary information obtained from the 2 approaches and the specific utility of the former.

In the present study, we sought to identify rates, causes, and predictors of death among male and female injection drug users (IDUs) in Vancouver, British Columbia, Canada, during a period of expanded public health interventions. Data from prospective cohorts of IDUs in Vancouver were linked to the provincial database of vital statistics to ascertain rates and causes of death between 1996 and 2011. Mortality rates were analyzed using Poisson regression and indirect standardization. Predictors of mortality were identified using multivariable Cox regression models stratified by sex. Among the 2,317 participants, 794 (34.3%) of whom were women, there were 483 deaths during follow-up, with a rate of 32.1 (95% confidence interval (CI): 29.3, 35.0) deaths per 1,000 person-years. Standardized mortality ratios were 7.28 (95% CI: 6.50, 8.14) for men and 15.56 (95% CI: 13.31, 18.07) for women. During the study period, mortality rates related to infection with human immunodeficiency virus (HIV) declined among men but remained stable among women. In multivariable analyses, HIV seropositivity was independently associated with mortality in both sexes (all P < 0.05). The excess mortality burden among IDUs in our cohorts was primarily attributable to HIV infection; compared with men, women remained at higher risk of HIV-related mortality, indicating a need for sex-specific interventions to reduce mortality among female IDUs in this setting.

BackgroundIllicit drug injecting is a well-established risk factor for morbidity and mortality. However, a limited number of prospective studies have examined the independent effect of unstable housing on mortality among persons who inject drugs (PWIDs). In this study we sought to identify if a relationship exists between unstable housing and all-cause mortality among PWIDs living in Vancouver, Canada.MethodsPWIDs participating in two prospective cohort studies in Vancouver, Canada were followed between May 1996 and December 2012. Cohort data were linked to the provincial vital statistics database to ascertain mortality rates and causes of death. We used multivariate Cox proportional hazards regression to determine factors associated with all-cause mortality and to investigate the independent relationship between unstable housing and time to all-cause mortality.ResultsDuring the study period, 2453 individuals were followed for a median of 69 months (Inter-quartile range [IQR]: 34 – 113). In total, there were 515 (21.0%) deaths for an incidence density of 3.1 (95% Confidence Interval [CI]: 2.8 – 3.4) deaths per 100 person years. In multivariate analyses, after adjusting for potential confounders including HIV infection and drug use patterns, unstable housing remained independently associated with all-cause mortality (adjusted hazard ratio [AHR] = 1.30, 95% CI: 1.08 – 1.56).ConclusionsThese findings demonstrate that unstable housing is an important risk factor for mortality independent of known risk factors including HIV infection and patterns of drug use. This study highlights the urgent need to provide supportive housing interventions to address elevated levels of preventable mortality among this population.

Background Methadone maintenance therapy (MMT) is among the most effective treatment modalities available for the management of opioid use disorder. However, the effect of MMT on mortality, and optimal strategies for delivering methadone are less clear. This study sought to estimate the effect of low-threshold MMT and its association with all-cause mortality among persons who inject drugs (PWID) in a setting where methadone is widely available through primary care physicians and community pharmacies at no cost through the setting’s universal medical insurance plan. Methods Between May, 1996 and December, 2011 data were collected as part of two prospective cohort studies of PWID in Vancouver, Canada, and were linked to the provincial vital statistics database to ascertain rates and causes of death. The association of MMT with all-cause mortality was estimated using multivariable extended Cox regression with timedependent variables. Results Of 2335 PWID providing 15027 person-years of observation, 511 deaths were observed for a mortality rate of 3.4 (95% Confidence Interval [CI]: 3.1 – 3.7) deaths per 100 person-years. After adjusting for potential confounders including age and HIV seropositivity, MMT enrolment was found to be associated with lower mortality (adjusted hazard ratio [AHR] = 0.73, 95% CI: 0.61 – 0.88). Conclusions While observed all-cause mortality rates among PWID in this setting were high, participation in low-threshold MMT was significantly associated with improved survival. These findings add to the known benefits of providing low-threshold MMT on reducing the harms associated with injection drug use.

Background and Aims For HIV-positive individuals who use illicit opioids, engagement in methadone maintenance therapy (MMT) can contribute to improved HIV treatment outcomes. However, to our knowledge, the role of methadone dosing in adherence to antiretroviral therapy (ART) has not yet been investigated. We sought to examine the relationship between methadone dose and ART adherence among a cohort of persons who use illicit opioids. Design and Setting We used data from the ACCESS study, an ongoing prospective observational cohort of HIV-positive persons who use illicit drugs in Vancouver, Canada, confidentially linked to comprehensive HIV treatment data in a setting of universal no-cost medical care including medications. We evaluated the longitudinal relationship between methadone dose and the likelihood of ≥ 95% adherence to ART among ART-exposed participants during periods of engagement in MMT. Participants 297 ART-exposed individuals on MMT were recruited between December 2005 and May 2013 and followed for a median of 42.1 months. Measurements We measured methadone dose at ≥ 100 vs < 100 mg/day and the likelihood of ≥ 95% adherence to ART. Findings In adjusted generalized estimating equation (GEE) analyses, MMT dose ≥ 100 mg/day was independently associated with optimal adherence to ART (adjusted odds ratio [AOR] = 1.38; 95% confidence interval [CI]: 1.08 – 1.77, p = 0.010). In a sub-analysis, we observed a dose-response relationship between increasing MMT dose and ART adherence (AOR = 1.06 per 20 mg/day increase, 95% CI: 1.00 – 1.12, p = 0.041). Conclusion Among HIV-positive individuals in methadone maintenance therapy, those receiving higher doses of methadone (≥ 100 mg/day) are more likely to achieve ≥ 95% adherence to antiretroviral therapy than those receiving lower doses.

Background North America is in the midst of an opioid overdose epidemic. Although take-home naloxone and other measures have been an effective strategy to reduce overdoses, many events are unwitnessed and mortality remains high amongst those using drugs alone. While wearable devices that can detect and alert others of an overdose are being developed, willingness of people who use drugs to wear such a device has not been described. Methods Drug using persons enrolled in a community-recruited cohort in Vancouver, Canada, were asked whether or not they would be willing to wear a device against their skin that would alert others in the event of an overdose. Logistic regression was used to identify factors independently associated with willingness to wear such a device. Results Among the 1061 participants surveyed between December 2017 and May 2018, 576 (54.3%) were willing to wear an overdose detection device. Factors independently associated with willingness included ever having overdosed (adjusted odds ratio [AOR] = 1.39, 95% confidence interval [CI] 1.06–1.83), current methadone treatment (AOR = 1.86, 95% CI 1.45–2.40), female gender AOR = 1.41, 95% CI 1.09–1.84) and a history of chronic pain (AOR = 1.53, 95% CI 1.19–1.96). Whereas homelessness (AOR = 0.67, 95% CI 0.50–0.91) was negatively associated with willingness. Conclusions A high level of willingness to wear an overdose detection device was observed in this setting and a range of factors associated with overdose were positively associated with willingness. Since some factors, such as homelessness may be a barrier, further research is needed to investigate explanations for unwillingness and to evaluate real world acceptability of a wearable overdose detection devices as this technology becomes available.