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Background Pakistan’s explosive human immunodeficiency virus (HIV) epidemic among people who inject drugs (PWID) varies widely across cities. We evaluated possible drivers for these variations. Methods Multivariable regression analyses were undertaken using data from 5 national surveys among PWID (n = 18 467; 2005–2017) to determine risk factors associated with variations in city-level HIV prevalence. A dynamic HIV model was used to estimate the population-attributable fraction (PAF; proportion of HIV infections prevented over 10 years when that risk factor is removed) of these risk factors to HIV transmission and impact on HIV incidence of reducing their prevalence. Results Regression analyses suggested that city-level HIV prevalence is strongly associated with the prevalence of using professional injectors at last injection, heroin use in last month, and injecting ≥4 times per day. Through calibrating a model to these associations, we estimate that the 10-year PAFs of using professional injectors, heroin use, and frequent injecting are 45.3% (95% uncertainty interval [UI], 4.3%–79.7%), 45.9% (95% UI, 8.1%–78.4%), and 22.2% (95% UI, 2.0%–58.4%), respectively. Reducing to lowest city-level prevalences of using professional injectors (2.8%; median 89.9% reduction), heroin use (0.9%; median 91.2% reduction), and frequent injecting (0.1%; median 91.8% reduction) in 2020 reduces overall HIV incidence by 52.7% (95% UI, 6.1%–82.0%), 53.0% (95% UI, 11.3%–80.2%), and 28.1% (95% UI, 2.7%–66.6%), respectively, over 10 years. Conclusions Interventions should focus on these risk factors to control Pakistan’s explosive HIV epidemic among PWID, including a concomitant expansion of high-coverage needle/syringe provision, opioid substitution therapy, and antiretroviral therapy., Pakistan’s HIV epidemic among people who inject drugs varies widely across cities over time. We undertook statistical and mathematical modeling using national-level datasets to identify and evaluate key city-level drivers for these variations. Interventions should focus on these factors.

Introduction: Cancer is associated with significant health-care expenditure, but few studies have examined the cost of patients with cancer in the intensive care unit (ICU). We aimed to describe the costs and outcomes of patients admitted to the ICU with cancer. Methods: We conducted a retrospective cohort study of patients admitted between 2011 and 2016 to 2 tertiary-care ICUs. We included patients with a cancer-related most responsible diagnosis using International Classification of Disease, 10th Revision, Canada codes. We compared costs and outcomes of patients having cancer with noncancer controls matched for age, sex, and Elixhauser comorbidity score. We used logistic regression to determine predictors of mortality among patients with cancer. Results: There were 1022 patients with cancer during the study period. Mean age was 63.2 years and 577 (56.5%) were male. Inhospital mortality for all patients with cancer was 24.0%. Total cost per patient was higher for patients with cancer compared to noncancer patients (CAD$57 084 vs CAD$40 730; P < .001) but there were no differences in the cost per day (CAD$2868 vs CAD$2887; P = .76) or ICU cost (CAD$30 495 vs CAD$29 382; P = .42). Among patients with cancer, the cost per day was higher for nonsurvivors (CAD$3477 vs CAD$2677; P < .001). Liver disease (odds ratio [OR]: 2.96; 95% confidence interval [CI]: 1.22-7.81), mechanical ventilation (OR: 1.73; 95% CI: 1.25-2.39), hematologic malignancy (OR: 3.88; 95% CI: 2.31-6.54), and unknown primary site (OR: 2.13; 95% CI: 1.36-3.35) were independently associated with mortality in patients with cancer. Conclusion: Patients admitted to the ICU with cancer did not differ in cost per day, ICU cost, or mortality compared to matched noncancer controls. Among patients with cancer, nonsurvivors had significantly higher cost per day compared to survivors. Hematologic and unknown primaries, liver disease, and mechanical ventilation were independently associated with mortality in patients with cancer.

Purpose: Gender-diverse individuals in India face considerable discrimination, stigma, and violence. There is a dearth of published literature describing experiences of violence among this population and potential links to mental health. Methods: A questionnaire was administered to 282 study participants, 18 years of age and older, who self-identified as hijra, kothi, double decker, or bisexual and were actively enrolled in a local HIV prevention program in Bangalore, India in 2012. Responses were used to calculate a composite depression/anxiety score. Associations between sociodemographic characteristics and experiences of physical and sexual violence in the previous six months were tested and differences in depression/anxiety score based on experiences of violence were explored. Results: Recent physical violence was common among study participants and was reported among 46% of nirvan (emasculated) hijras (transgender), 42% of akwa (not emasculated) hijras, and 25% of kothis (feminine acting males). Rape in the previous year was particularly common among akwa hijras (39%). Factors associated with being raped included younger age, less education, and employment in basti (blessings), sex work, chela (disciple of hijra guru), or at a community-based organization. Kothis had the highest depression/anxiety score. No significant difference in depression/anxiety score based on recent history of physical violence or rape was found. Conclusions: Physical violence and poor mental health are common among gender-diverse individuals in Bangalore, Karnataka. There is a need for services that cater to the unique mental health needs of gender-diverse individuals in India, following rights-based approaches that address the underlying roots of oppression they encounter.

Objective To analyse the association between survival from critical illness and suicide or self-harm after hospital discharge. Design Population based cohort study using linked and validated provincial databases. Setting Ontario, Canada between January 2009 and December 2017 (inclusive). Participants Consecutive adult intensive care unit (ICU) survivors (≥18 years) were included. Linked administrative databases were used to compare ICU hospital survivors with hospital survivors who never required ICU admission (non-ICU hospital survivors). Patients were categorised based on their index hospital admission (ICU or non-ICU) during the study period. Main outcome measures The primary outcome was the composite of death by suicide (as noted in provincial death records) and deliberate self-harm events after discharge. Each outcome was also assessed independently. Incidence of suicide was evaluated while accounting for competing risk of death from other causes. Analyses were conducted by using overlap propensity score weighted, cause specific Cox proportional hazard models. Results 423 060 consecutive ICU survivors (mean age 61.7 years, 39% women) were identified. During the study period, the crude incidence (per 100 000 person years) of suicide, self-harm, and the composite of suicide or self-harm among ICU survivors was 41.4, 327.9, and 361.0, respectively, compared with 16.8, 177.3, and 191.6 in non-ICU hospital survivors. Analysis using weighted models showed that ICU survivors ( v non-ICU hospital survivors) had a higher risk of suicide (adjusted hazards ratio 1.22, 95% confidence interval 1.11 to 1.33) and self-harm (1.15, 1.12 to 1.19). Among ICU survivors, several factors were associated with suicide or self-harm: previous depression or anxiety (5.69, 5.38 to 6.02), previous post-traumatic stress disorder (1.87, 1.64 to 2.13), invasive mechanical ventilation (1.45, 1.38 to 1.54), and renal replacement therapy (1.35, 1.17 to 1.56). Conclusions Survivors of critical illness have increased risk of suicide and self-harm, and these outcomes were associated with pre-existing psychiatric illness and receipt of invasive life support. Knowledge of these prognostic factors might allow for earlier intervention to potentially reduce this important public health problem.

Purpose. Delirium frequently affects critically ill patients in the intensive care unit (ICU). The purpose of this study is to evaluate the impact of delirium on ICU and hospital length of stay (LOS) and perform a cost analysis. Materials and Methods. Prospective studies and randomized controlled trials of patients in the ICU with delirium published between January 1, 2015, and December 31, 2020, were evaluated. Outcome variables including ICU and hospital LOS were obtained, and ICU and hospital costs were derived from the respective LOS. Results. Forty-one studies met inclusion criteria. The mean difference of ICU LOS between patients with and without delirium was significant at 4.77 days ( p < 0.001 ); for hospital LOS, this was significant at 6.67 days ( p < 0.001 ). Cost data were extractable for 27 studies in which both ICU and hospital LOS were available. The mean difference of ICU costs between patients with and without delirium was significant at $3,921 ( p < 0.001 ); for hospital costs, the mean difference was $5,936 ( p < 0.001 ). Conclusion. ICU and hospital LOS and associated costs were significantly higher for patients with delirium, compared to those without delirium. Further research is necessary to elucidate other determinants of increased costs and cost-reducing strategies for critically ill patients with delirium. This can provide insight into the required resources for the prevention of delirium, which may contribute to decreasing healthcare expenditure while optimizing the quality of care.

Background. Critical Care Response Teams (CCRTs) represent an important interface between end-of-life care (EOLC) and critical care medicine (CCM). The aim of this study was to explore the roles and interactions of CCRTs in the provision of EOLC from the perspective of CCRT members. Methods. Twelve registered nurses (RNs) and four respiratory therapists (RTs) took part in focus groups, and one-on-one interviews were conducted with six critical care physicians. Thematic coding using a modified constructivist grounded theory approach was used to identify emerging themes through an iterative process involving a four-member coding team. Results. Three main perspectives were identified that spoke to CCRT interactions and perceptions of EOLC encounters. CCRT members felt that they provide a unique skill set of multidisciplinary expertise in treating critically ill patients and evaluating the utility of intensive care treatments. However, despite feeling that they possessed the skills and resources to deliver quality EOLC, CCRT members were ambivalent with respect to whether EOLC was a part of their mandate. Challenges were also identified that impacted the ability of CCRTs to deliver quality EOLC. Conclusions. This research aids in understanding for the first time CCRT roles in EOLC from the perspectives of individual CCRT members themselves. While CCRTs provide unique multidisciplinary expertise to evaluate the utility of intensive care treatments, opportunities exist to support CCRTs in EOLC, such as dedicated EOLC training, protocols for advance care planning, documentation, and transitions to palliative care.

ObjectiveThe novel coronavirus disease 2019 (Covid-19) has infected millions worldwide and impacted the lives of many folds more. Many clinicians share new Covid-19 related resources, research, and ideas within the online Free Open Access to Medical Education (FOAM) community of practice. This study provides a detailed content and contributor analysis of Covid-19 related tweets among the FOAM community.Design, Setting, ParticipantsTwitter was searched from November 1st, 2019 to March 21st, 2020 for English tweets discussing Covid-19 in the FOAM community. Tweets were classified into one of 13 pre-specified content categories: original research, editorials, FOAM resource, public health, podcast or video, learned experience, refuting false information, policy discussion, emotional impact, blatantly false information, other Covid-19, and non-Covid-19. Further analysis of linked original research and FOAM resources was performed. 1000 randomly selected contributor profiles and those deemed to have contributed false information were analyzed.ResultsThe search yielded 8541 original tweets from 4104 contributors. The number of tweets in each content category were: 1557 other Covid-19 (18·2%), 1190 emotional impact (13·9%), 1122 FOAM resources (13·1%), 1111 policy discussion (13·0%), 928 advice (10·9%), 873 learned experience (10·2%), 424 non-Covid-19 (5·0%), 410 podcast or video (4·8%), 304 editorials (3·6%), 275 original research (3·2%), 245 public health (2·9%), 83 refuting false information (1·0%), and 19 blatantly false (0·2%).ConclusionsEarly in the Covid-19 pandemic, the FOAM community used Twitter to share Covid-19 learned experiences, online resources, crowd-sourced advice, research, and to discuss the emotional impact of Covid-19. Twitter also provided a forum for post-publication peer review of new research. Sharing blatantly false information within this community was infrequent. This study highlights several potential benefits from engaging with the FOAM community on Twitter.

Background: Advanced care planning (ACP) provides an opportunity for individuals to explore and document their values concerning medical care decisions prior to an acute event. This manuscript explores the value of ACP and compares and contrasts 2 ACP models currently in practice. Methods: This hypothetical case describes an elderly, frail patient with end-stage chronic obstructive pulmonary disease who is also a high user of health care resources. A new palliative care-led outpatient ACP clinic model is described using this example. Results: Using the ACP clinic model in this case reveals how different a patient’s end of life experience may be when proper, proactive planning measures are in place. With proper education and discussion around this patient and family’s wishes pertaining to the end of his life, this man was able to change his plan of care from aggressive resuscitation treatment in hospital to a peaceful palliative experience at home. Conclusions: In this case description, the valuable role of ACP in preserving quality of life for patients, increasing satisfaction with care, and decreasing distress among family members during a medical event is demonstrated.

Purpose: Chronic obstructive pulmonary disease (COPD) is a common condition, accounting for a significant number of intensive care unit (ICU) admissions. However, little is known about outcomes and costs among ICU patients admitted with acute exacerbations of COPD (AECOPD). We studied predictors of inhospital mortality and costs of ICU admissions for AECOPD. Methods: Data were obtained from a prospectively maintained registry from 2 ICUs from 2011 to 2016, including adult patients (age ≥ 18) with an ICU discharge diagnosis of AECOPD. The primary outcome was hospital mortality. Secondary outcomes included ICU length of stay, resource utilization, total hospital costs, and cost per survivor. Results: We included 390 patients, of which 27.2% died in hospital. Independent predictors of inhospital mortality included age (odds ratio [OR]: 1.95, CI: 1.58-2.67) and the presence of clinical frailty (OR: 4.12, CI: 2.26-6.95). The mean total hospital costs were Can$35 059, with a cost per survivor of Can$48 191. Factors associated with increased cost included transfer from an inpatient setting, severity of illness, and previous ICU admission. Conclusions: Approximately a quarter of patients admitted to ICU with AECOPD died during hospitalization, and these patients accrued significant costs. This study identifies important factors associated with poor outcome in this at-risk population, which has value in risk stratification and patient or family discussions addressing goals of care.

Background: Frailty is characterized by vulnerability to stressors due to an accumulation of multiple functional deficits. Frailty is increasingly recognized as a risk factor for accelerated functional decline, increasing dependency, and risk of mortality. The objective of this study was to examine the association of frailty, at the time of critical care admission, with days alive at home and health care costs post-discharge. Methods: This retrospective cohort study used linked administrative data (2010-2016) in Ontario, Canada. We identified all patients admitted at the intensive care unit (ICU), aged 19 years and above, assessed using the Resident Assessment Instrument for Home Care (RAI-HC), within 6 months prior to index hospitalization including an ICU stay. Patients were stratified as robust, pre-frail, or frail based on a validated Frailty Index. The primary outcome was days alive at home in the year after admission. Secondary outcomes included mortality, health care–associated costs, ICU interventions, long-term care admissions, and hospital readmissions. Results: Frail patients spent significantly fewer days at home within 1 year of index hospitalization (mean 159 days vs 223 days in robust cohort, P < .001). Mortality was higher among frail patients at 1 year (59.6% in the frail cohort vs 45.9% in robust patients; odds ratio for death 1.59 [1.49-1.69]). Frail patients also had higher rates of long-term care admission within 1 year (30.1% vs 10.6% in robust patients). Total health care–associated costs per person alive were $30 450 higher the year after admission in the frail cohort. Conclusions: Frailty prior to ICU admission among patients who were eligible for RAI-HC assessment was associated with higher mortality and fewer days spent at home following admission. Frail patients had markedly higher rates of long-term care admission and increased costs per life saved following critical illness. These findings add to the discussion of risk–benefit trade-offs for ICU admission.

Pakistan is considered by the World Health Organization to currently have a "concentrated" HIV-1 epidemic due to a rapid rise in infections among people who inject drugs (PWID). Prevalence among the country's nearly 105,000 PWID is estimated to be 37.8% but has been shown to be higher in several large urban centers. A lack of public health resources, the common use of professional injectors and unsafe injection practices are believed to have fueled the outbreak. Here we evaluate the molecular characteristics of HIV-1 sequences (n = 290) from PWID in several Pakistani cities to examine transmission dynamics and the association between rates of HIV-1 transmission with regards to regional trends in opioid trafficking. Tip-to-tip (patristic) distance based phylogenetic cluster inferences and BEAST2 Bayesian phylodynamic analyses of time-stamped data were performed on HIV-1 pol sequences generated from dried blood spots collected from 1,453 PWID as part of a cross-sectional survey conducted in Pakistan during 2014/2015. Overall, subtype A1 strains were dominant (75.2%) followed by CRF02_AG (14.1%), recombinants/unassigned (7.2%), CRF35_AD (2.1%), G (1.0%) and C (0.3%). Nearly three quarters of the PWID HIV-1 sequences belonged to one of five distinct phylogenetic clusters. Just below half (44.4%) of individuals in the largest cluster (n = 118) did seek help injecting from professional injectors which was previously identified as a strong correlate of HIV-1 infection. Spikes in estimated HIV-1 effective population sizes coincided with increases in opium poppy cultivation in Afghanistan, Pakistan's western neighbor. Structured coalescent analysis was undertaken in order to investigate the spatial relationship of HIV-1 transmission among the various cities under study. In general terms, our analysis placed the city of Larkana at the center of the PWID HIV-1 epidemic in Pakistan which is consistent with previous epidemiological data.

Background Venues where people meet sexual partners are understood to be important locations where HIV transmission risk plays out and represent potential intervention points. Women involved in sex work and those seeking casual partners spend time in the same venues, forming sexual partnerships with some of the same people and experiencing the same risks. This study provides a characterization of key venues where women meet new sexual partners in Abuja, Nigeria, and describes the sexual behaviours, sexual networking patterns, and challenges experienced by women in these venues. Methods Key informant interviews were used to characterize 836 venues where people congregate for social activities in Abuja, Nigeria, in terms of number of patrons, busy times, and availability of harm reduction supplies. A questionnaire capturing demographics, behaviours, health, and experiences of violence was administered to 892 women who participate in sex work or casual sex at a random sample of 105 of the profiled venues. Descriptive analysis was conducted with stratification by type of venue. Results A diverse set of venues were identified, with bars/nightclubs identified as having the highest volume of patrons. Most of the women indicated meeting partners at bars/nightclubs as well as hotels/lodges. Half of the women had experienced a miscarriage or abortion and perceived themselves to be at great risk of HIV infection. Eighteen percent had experienced condom breakage in the previous week, 15% had ever been arrested, and 8% had been beaten in the past year. Conclusion A diverse set of women intermingle at different venues and have a diverse set of needs, including reproductive health, violence reduction, and infectious disease prevention. By re-orienting HIV programs towards venues where sexual partnerships form instead of towards specific key populations who are often blamed for transmission, the broader needs of a larger group of individuals who attend these venues may be addressed. Disclosure No significant relationships.

Background There are large numbers of people who inject drugs (PWID) in Pakistan, with a high and growing HIV prevalence in many cities. Cross-sectional bio-behavioural surveys conducted over fifteen years have shown heterogeneous HIV epidemic trajectories in different cities with inconsistent associations between aggregate and individual measures of behaviour and epidemic trajectories. This study triangulates behavioural, biological, and network data to gain new insights into drivers of local epidemics among PWID. Methods A questionnaire was administered to 1,439 PWID in five cities in Pakistan in 2014 and dried blood spots were collected for HIV testing and sequencing. The questionnaire collected locations where participants injected recently and these were used to construct place-based injection networks. Demographic, behavioral, geographic, and network structure data were tested for associations with HIV and HIV phylogenetic analysis was conducted to identify transmission clusters. Results HIV prevalence varied between the cities, from 8.6% to 45.3%. Although aggregate individual behaviours were not strongly associated with HIV, there were differences between cities in injecting practices and network configurations. Injection network configurations differed between cities, ranging from networks with dense sub-regions to widely dispersed networks. A city that experienced an explosive HIV outbreak showed particularly dense geospatial networks and a large phylogenetic cluster (n=52) suggesting a link between geospatial concentration and rapid HIV transmission. In a city where the use of professional injectors was associated with HIV at the individual level, there were dense network subregions and HIV+ individuals were more likely to be more centrally located in networks (p Conclusion Contextual factors shape the injection practices and network configurations among PWID in Pakistan. Factors that influence HIV transmission dynamics are more complex than individual behaviours, and include professional injectors and geographic and network clustering. Disclosure No significant relationships.

Background Pakistan‘s HIV epidemics among people who inject drugs (PWID) vary widely across different cities and has increased dramatically over time. To help guide future HIV programming, we used statistical and mathematical modelling to identify possible causes for these differing HIV epidemics. Methods Cross-sectional integrated biological and behavioural surveillance (IBBS) data describing high-risk behaviours and HIV status among PWID were collected by the Canada-Pakistan HIV/AIDS Surveillance Project (HASP) over five rounds from 2005–2017. We used regression analyses to identify city-level associations between the prevalence of HIV infection and different risk behaviours. We then developed a dynamic HIV transmission model to reflect these associations. The model was calibrated to the IBBS dataset to estimate relative risks of HIV transmission due to each risk factor, and their respective population-attributable fractions (PAFs) over 10-years. Lastly, we investigated the prevention benefit that could be achieved if these behaviours were reduced across different settings to the lowest observed values. Results Multivariable statistical analyses identified professional injecting use at last injection (‘ProfInj’) and heroin use within the past month (‘HeroinUse’) as key high-risk behaviours associated with city-level HIV infection, with HIV prevalence increasing by 4% and 2% for every 10% increase in the prevalence of each respective behaviour. Modelling projections estimated that ProfInj and HeroinUse increased the relative risk of HIV transmission by 7.9 (95%CrI 4.6–14.0) and 2.2 (1.1–3.7) times, respectively, with 10-year PAFs across all cities being 52% (37–61%) and 21% (3–34%), separately, and 61% (51–66%) combined. Lowering each behaviour’s prevalence across all cities to the lowest observed prevalence (11% ProfInj, 0% HeroinUse) reduced overall relative HIV incidence by 43.9% (36.9–47.7%) and 44.1% (11.0–60.5%) over 10-years, respectively. Conclusion Pakistan’s HIV epidemic is heterogeneous, with professional injecting and heroin use likely large contributors to the differing epidemics. Interventions focussed on these behaviours, especially professional injecting, could substantially reduce HIV incidence. Disclosure No significant relationships.

Objectives: The purpose of this study was to describe and explore potential driving factors of trends in reported chlamydia infections over time in Manitoba, Canada. Methods: Surveillance and laboratory testing data from Manitoba Health, Seniors and Active Living were analysed using SAS v9.4. Kaplan-Meier plots of time from the first to second chlamydia infection were constructed, and Cox proportional hazards regression was used to estimate the risk of second repeat chlamydia infections in males and females. Results: Overall, the number of reported infections found mirrored the number of tests conducted. From 2008 to 2014, the number of first infections found among females decreased as the number of first tests conducted among females also decreased. Between 2008 and 2012, the number of repeat tests among females increased and was accompanied by an increase in the number of repeat positive results from 2009 to 2013. From 2008 to 2016, the number of repeat tests and repeat positive results increased steadily among males. Conclusions: Chlamydia infection rates consistently included a subset composed of repeat infections. The number of cases identified appears to mirror testing volumes, drawing into question incidence calculations that do not include testing volumes. Summary Box: 1) What is the current understanding of this subject? Chlamydia incidence is high in Manitoba, particularly among young women and in northern Manitoba. 2) What does this report add to the literature? This report suggests that incidence calculated using case-based surveillance data alone does not provide an accurate estimate of chlamydia incidence in Manitoba and is heavily influenced by testing patterns. 3) What are the implications for public health practice? In general, improving testing rates in clinical practices as well as through the provision of rapid services in non-clinical venues could result in higher screening and treatment rates. In turn, this could lead to a better understanding of true disease occurrence.

Purpose: Men and transgender women who have sex with men (MTWSM) continue to be an at-risk population for human immunodeficiency virus (HIV) infection in India. Identification of risk factors and determinants of HIV infection is urgently needed to inform prevention and intervention programming. Methods: Data were collected from cross-sectional biological and behavioral surveys from four districts in Karnataka, India. Multivariable logistic regression models were constructed to examine factors related to HIV infection. Sociodemographic, sexual history, sex work history, condom practices, and substance use covariates were included in regression models. Results: A total of 456 participants were included; HIV prevalence was 12.4%, with the highest prevalence (26%) among MTWSM from Bellary District. In bivariate analyses, district (P = 0.002), lack of a current regular female partner (P = 0.022), and reported consumption of an alcoholic drink in the last month (P = 0.004) were associated with HIV infection. In multivariable models, only alcohol use remained statistically significant (adjusted odds ratios: 2.6, 95% confidence intervals: 1.2–5.8; P = 0.02). Conclusion: The prevalence of HIV continues to be high among MTWSM, with the highest prevalence found in Bellary district.

Critical care is a costly and finite resource that provides the ability to manage patients with life-threatening illnesses in the most advanced forms available. However, not every condition benefits from critical care. There are unrecoverable health states in which it should not be used to perpetuate. Such situations are considered futile. The determination of medical futility remains controversial. In this study we describe the length of stay (LOS), cost, and long-term outcomes of 12 cases considered futile and that have been or were considered for adjudication by Ontario’s Consent and Capacity Board (CBB). A chart review was undertaken to identify patients admitted to the Intensive Care Unit (ICU), whose care was deemed futile and cases were considered for, or brought before the CCB. Costs for each of these admissions were determined using the case-costing system of The Ottawa Hospital Data Warehouse. All 12 patients identified had a LOS of greater than 4 months (range: 122-704 days) and a median age 83.5 years. Seven patients died in hospital, while 5 were transferred to long term or acute care facilities. All patients ultimately died without returning to independent living situations. The total cost of care for these 12 patients was $7 897 557.85 (mean: $658 129.82). There is a significant economic cost of providing resource-intensive critical care to patients in which these treatments are considered futile. Clinicians should carefully consider the allocation of finite critical care resources in order to utilize them in a way that most benefits patients.

Background Program Science is an iterative, multi-phase research and program framework where programs drive the scientific inquiry, and both program and science are aligned towards a collective goal of improving population health. Discussion To achieve this, Program Science involves the systematic application of theoretical and empirical knowledge to optimize the scale, quality and impact of public health programs. Program Science tools and approaches developed for strategic planning, program implementation, and program management and evaluation have been incorporated into HIV and sexually transmitted infection prevention programs in Kenya, Nigeria, India, and the United States. Conclusion In this paper, we highlight key scientific contributions that emerged from the growing application of Program Science in the field of HIV and STI prevention, and conclude by proposing future directions for Program Science.

This study aimed to: (1) examine the relationship between interpersonal as well as social-demographic, cultural and structural factors, and condom non-use by sex workers' main intimate or other non-paying male sex partners (NPPs), as reported by a sample of sex workers (SWs); and (2) understand HIV/sexually transmitted infections (STIs) risk (e.g., numbers of sexual partners; condom use with different partners) among couples comprised of a sub-set of SWs and their NPPs. Bivariate and multivariable logistic regression was used to identify factors associated with condom non-use at last sex by the main NPP, as reported by SWs. Adjusted odds ratios and 95% confidence intervals are reported (AOR[95%CIs]). Data were drawn from cross-sectional surveys in Bagalkot District, Karnataka State, South India. Responses by SWs whose main NPPs agreed to enrol in the study and the main NPP enroled were linked; these responses by couples (pairs of SWs and NPPs) were examined to assess sexual risk for HIV/STIs. Overall, this study included 257 SWs and 76 NPPs. The data from 67 couples (88.2%) could be linked. In over a quarter of partnerships, at least one (SW or NPP) partner reported having another type of partner besides each other (and clients of SWs). In multivariable analysis, significantly increased odds of condom non-use at last sex with the main NPP were found for the following key factors: planning to have a child with their main NPP (AOR = 3.71[1.44-9.58]); and having decisions about condom use made by their main NPP (AOR = 9.87[4.03-24.16]) or both equally (AOR = 3.18[1.39-7.80]) (versus by the SWs herself). Our study highlights the potential risk for HIV/STI acquisition and transmission between NPPs and SWs, and between NPPs and their non-SWs wives and other sex partners. Study results underscore the need for HIV/STI prevention approaches that incorporate informed decision-making about childbearing and parenting, and empowerment strategies for SWs in the context of their relationships with NPPs.

SUMMARYWe evaluated syndromic indicators of influenza disease activity developed using emergency department (ED) data – total ED visits attributed to influenza-like illness (ILI) (‘ED ILI volume’) and percentage of visits attributed to ILI (‘ED ILI percent’) – and Google flu trends (GFT) data (ILI cases/100 000 physician visits). Congruity and correlation among these indicators and between these indicators and weekly count of laboratory-confirmed influenza in Manitoba was assessed graphically using linear regression models. Both ED and GFT data performed well as syndromic indicators of influenza activity, and were highly correlated with each other in real time. The strongest correlations between virological data and ED ILI volume and ED ILI percent, respectively, were 0·77 and 0·71. The strongest correlation of GFT was 0·74. Seasonal influenza activity may be effectively monitored using ED and GFT data.

The Bill and Melinda Gates Foundation has poured a tremendous amount of resources into epidemic prevention in India's high HIV prevalence zones, through their Avahan initiative. These community-centred programmes operate under the assumption that fostering community-based organisational development and empowering the community to take charge of HIV prevention and education will help to transform the wider social inequalities that inhibit access to health services. Focusing on the South Indian state of Karnataka, this paper explores a troubling set of local narratives that, we contend, hold broader implications for future programme planning and implementation. Although confronting stigma and discrimination has become a hallmark in community mobilisation discourse, communities of self-identified kothis (feminine men) who were involved in Avahan programme activities continued to articulate highly negative attitudes about their own sexualities in relation to various spheres of social life. Rather than framing an understanding of these narratives in psychological terms of 'internalized stigma', we draw upon medical anthropological approaches to the study of stigma that emphasise how social, cultural and moral processes create stigmatising conditions in the everyday lives of people. The way stigma continues to manifest itself in the self-perceptions of participants points to an area that warrants critical public health attention.

Background With competing interests, limited funding and a socially conservative context, there are many barriers to implementing evidence-informed HIV prevention programmes for sex workers and injection drug users in Pakistan. Meanwhile, the HIV prevalence is increasing among these populations across Pakistan. We sought to propose and describe an approach to resource allocation which would maximise the impact and allocative efficiency of HIV prevention programmes. Methods Programme performance reports were used to assess current resource allocation. Population size estimates derived from mapping conducted in 2011 among injection drug users and hijra , male and female sex workers and programme costs per person documented from programmes in the province of Sindh and also in India were used to estimate the cost to deliver services to 80% of these key population members across Pakistan. Cities were prioritised according to key population size. Results To achieve 80% population coverage, HIV prevention programmes should be implemented in 10 major cities across Pakistan for a total annual operating cost of approximately US$3.5 million, which is much less than current annual expenditures. The total cost varies according to the local needs and the purchasing power of the local currency. Conclusions By prioritising key populations at greatest risk of HIV in cities with the largest populations and limited resources, may be most effectively harnessed to quell the spread of HIV in Pakistan.

Background Pakistan is known to have large populations of female sex workers (FSWs) with considerable geographic heterogeneity in their characteristics. In this paper, we describe the social organisation and structural patterns of female sex work in different geographic regions of Pakistan. Methods We report geographic and network mapping data collected among FSWs in 15 cities across Pakistan in 2011 as part of the Canada-Pakistan HIV/AIDS Surveillance Project. Results A total number of 89 178 FSWs were estimated in the target cities for an average of 7.2 FSWs per 1000 adult males. 55% of the estimated number of FSWs concentrated in Karachi and Lahore. Based on the operations of female sex work, two major typologies of FSWs were identified: establishment-based and non-establishment-based. FSWs were further subtyped into those operating through brothels, homes, kothikhanas, streets and by cell phone. Cities varied considerably in terms of predominance of different FSW typologies. Conclusions There is considerable heterogeneity among FSWs in Pakistan, geographically and in terms of operational typology. Understanding the social organisation of sex work and the influence of social-cultural and legal factors in Pakistan is essential for the design of HIV prevention programmes and other services for FSWs.

Community-based participatory research (CBPR) has gained considerable popularity in recent decades given its ability to address social inequities, improve health outcomes and enhance community participation and ownership with respect to various health-related interventions. This paper describes the engagements of a community of self-identified men who have sex with men, most of whom also identified as male sex workers, in a long-term iterative and systematic process of knowledge production, reflection, and action. The project took place in 2006 in Mysore, South India, under the larger umbrella of an HIV intervention formed by the University of Manitoba and the sex workers collective known as Ashodaya Samithi, funded by the Bill & Melinda Gates Foundation (Avahan). CBPR is revealed as uniquely suited for tackling stigma and discrimination as subjects of scientific inquiry and as key methodological obstacles. As the community cultivated their own analysis around stigma, the concept became a key rallying poi...

Background Considerable HIV transmission occurs among injection drug users (IDUs) in Pakistan and recently the HIV prevalence has been increasing among male (MSW), hijra (transgender; HSW) and female (FSW) sex workers. We describe past and estimate future patterns of HIV emergence among these populations in several cities in Pakistan. Methods The density of these key populations per 1000 adult men was calculated using 2011 mapping data from Karachi, Lahore, Faisalabad, Larkana, Peshawar and Quetta, and surveillance data were used to assess bridging between these key populations. We used the UNAIDS Estimation and Projection Package model to estimate and project HIV epidemics among these key populations in Karachi, Lahore, Faisalabad and Larkana. Results The density and bridging of key populations varied across cities. Lahore had the largest FSW population (11.5/1000 adult men) and the smallest IDU population (1.7/1000 adult men). Quetta had the most sexual and drug injection bridging between sex workers and IDUs (6.7%, 7.0% and 3.8% of FSW, MSW and HSW, respectively, reported injecting drugs). Model evidence suggests that by 2015 HIV prevalence is likely to reach 17–22% among MSWs/HSWs in Karachi, 44–49% among IDUs in Lahore and 46–66% among IDUs in Karachi. Projection suggests the prevalence may reach as high as 65–75% among IDUs in Faisalabad by 2025. HIV prevalence is also estimated to increase among FSWs, particularly in Karachi and Larkana. Conclusions There is a need to closely monitor regional and subpopulation epidemic patterns and implement prevention programmes customised to local epidemics.

Background We sought to describe the characteristics and operational dynamics of male sex workers (MSW) and hijra sex workers (HSWs) in 11 cities across Pakistan in 2011. Methods We report descriptive statistics of self-reported sexual behaviour data from cross-sectional mapping and biological and behavioural surveys conducted among 1431 MSWs and 1415 HSWs in four cities across Pakistan in 2011. Results While Karachi had the largest numbers of MSWs and HSWs, Quetta had the largest relative population sizes, with 3.6 MSWs per 1000 male adults and 3.3 HSWs per 1000 male adults. There was considerable variability in the proportion of HSWs who operate through deras , ranging from 2.2% in Peshawar to 62.7% in Karachi. The number of HSWs per guru varies by city, from 1.5 in Quetta to 16.5 HSWs per guru in Karachi. Among HSWs, the use of mobile phones for solicitation ranged from 37.6% in Quetta to 83% in Peshawar and among MSWs the use of mobile phones ranged from 27% in Karachi to 52% in Quetta. In Quetta, a large proportion of HSWs (41%) find clients through gurus . Client volume tended to be higher among HSWs and among both MSWs and HSWs in Quetta and Peshawar. Condom use with clients was most consistent in Quetta, with 31% of MSWs and 41% of HSWs reporting always using condoms with clients. Peshawar had the greatest proportion reporting never using condoms. Conclusions There is considerable geographic heterogeneity in the characteristics and operational dynamics of MSWs and HSWs across Pakistan.

Background We sought to describe differences in individual and structural vulnerabilities faced by female sex workers (FSWs) in Pakistan between 2006 and 2011, and to characterise risk factors for inconsistent condom use and HIV prevalence in this population. Methods To describe differences in vulnerabilities, we analysed behavioural data from serial cross-sectional surveys conducted across nine cities in 2006 and 2011. Using data from 12 cities in 2011, we used logistic regression to characterise risk factors for (a) inconsistent condom use in the past month (N=6987), and (b) HIV (N=4301). Results Compared to FSWs in 2006, FSWs in 2011 were significantly more likely to solicit clients via cell phones, and to report a larger client volume and anal sex with clients, but also consistent condom use with clients (30.0% vs 23.6% in 2006). In 2011, independent risk factors for inconsistent condom use with clients included: recent sexual violence, recent sex with a person who injects drugs, and absence of programme exposure. HIV prevalence was 0.63% (95% CI 0.43% to 0.92%) in 2011, and was associated with a recent history of injection drug use and absence of programme exposure. Conclusions While condom use with clients was higher in 2011, protective behaviours remained low and vulnerabilities related to sex work may have risen. HIV is emerging in this population and an adaptive HIV prevention programme that addresses different vulnerabilities and the intersection of sexual networks with injection drug use is needed.

Objectives We describe the characteristics of injecting drug users (IDU) in Pakistan in 2006 and 2011, and assess the heterogeneity of IDU characteristics across different cities and years as well as factors associated with HIV infection. Methods Cross-sectional, integrated behavioural-biological surveys of IDU were conducted in 10 cities across Pakistan in 2006 and 2011. Univariate and multivariable analyses were used to describe the differences in HIV prevalence and risk behaviours between cities and over time. Results Large increases in HIV prevalence among injection drug users in Pakistan were observed, with overall HIV prevalence increasing from 16.2% in 2006 to 31.0% in 2011; an increase in HIV prevalence was also seen in all geographic areas except one. There was an increase in risk behaviours between 2006 and 2011, anecdotally related to a reduction in the availability of services for IDU. In 2011, larger proportions of IDU reported injecting several times a day and using professional injectors, and fewer reported always using clean syringes. An increase in the proportion living on the street was also observed and this was associated with HIV infection. Cities differ in terms of HIV prevalence, risk profiles, and healthcare seeking behaviours. Conclusions There is a high prevalence of HIV among injection drug users in Pakistan and considerable potential for further transmission through risk behaviours. HIV prevention programs may be improved through geographic targeting of services within a city and for involving groups that interact with IDU (such as pharmacy staff and professional injectors) in harm reduction initiatives.

Background From 2004 to 2011, a collaborative project was undertaken to enhance the capacity of the Government of Pakistan to implement an effective second-generation surveillance system for HIV/AIDS, known as the HIV/AIDS Surveillance Project (HASP). In four separate rounds, behavioural questionnaires were administered among injection drug users, and female, male and hijra (transgender) sex workers. Dried blood spots were collected for HIV testing. Methods Through interviews with project staff in Pakistan and Canada, we have undertaken a critical review of the role of HASP in generating, using and translating knowledge, with an emphasis on capacity building within both the donor and recipient countries. We also documented ongoing and future opportunities for the translation of knowledge produced through HASP. Results Knowledge translation activities have included educational workshops and consultations held in places as diverse as Colombia and Cairo, and the implementation of HASP methodologies in Asia, the Middle East and sub-Saharan Africa. HASP methodologies have been incorporated in multiple WHO reports. Importantly, the donor country, Canada, has benefited in significant ways from this partnership. Operational and logistical lessons from HASP have, in turn, improved how surveillance is performed in Canada. Through this project, significant capacity was built among the staff of HASP, non-governmental organisations which were engaged as implementation partners, data coordination units which were established in each province, and in the laboratory. As is to be expected, different organisations have different agendas and priorities, requiring negotiation, at times, to ensure the success of collaborative activities. Overall, there has been considerable interest in and opportunities made for learning about the methodologies and approaches employed by HASP. Conclusions Generally, the recognition of the strengths of the approaches and methodologies used by HASP has ensured an appetite for opportunities of mutual learning.

From 2004 to 2011, the Canada-Pakistan HIV/AIDS Surveillance Project (HASP) worked with government and non-government partners in Pakistan to design and implement an HIV second generation surveillance (SGS) system. Insights into the development of scalable cost effective surveillance methodologies, implementation, use of data for HIV prevention and human rights were gained over the course of HASP. An ideal SGS system would be affordable, able to be implemented independently by local partners and produce data that could be readily applied in policy and programmes. Flexibility in design and implementation is important to ensure that any SGS system is responsive to information needs, political changes and changes in key population dynamics and HIV epidemics. HASP's mapping methodology is innovative and widely accepted as best practice, but sustainability of the SGS system it developed is a challenge.

Please cite this paper as: Mahmud et al. (2012) Outbreaks of influenza-like illness in long-term care facilities in Winnipeg, Canada. Influenza and Other Respiratory Viruses 10.1111/irv.12052 Background Outbreaks of influenza-like illness (ILI) are common in long-term care facilities (LTCFs) and result in significant morbidity and mortality among residents. Objectives We describe patterns of reported ILI outbreaks in LTCFs in Winnipeg, Canada, and examine LTCF and outbreak characteristics that influence the clinical outcomes of these outbreaks. Methods We analyzed the electronic records of all ILI outbreaks reported by LTCFs in Winnipeg from 2003 to 2011. Outbreak duration, ILI attack rates among staff and residents, and residents’ death rates were calculated by presumed viral etiology, staff vaccination rates, type of influenza chemoprophylaxis used, and time to notification to public health. Results Of a total of 154 reported outbreaks, most (N = 80) were attributed to influenza, and these outbreaks tended to have higher attack and death rates among LTCF residents compared with outbreaks caused by other respiratory viruses (12) or those of unknown etiology (62). About 92% of residents and 38% of staff of the average LTCFs were vaccinated. Chemoprophylaxis was used in 57·5% of influenza outbreaks. Regardless of presumed viral etiology, outbreaks reported within 3 days of onset ended sooner and had lower attack and mortality rates among residents. Conclusions Influenza-like illness outbreaks still occur among highly immunized LTCF residents, so in addition to vaccination of staff and residents, it is important to maintain competent infection control practices. Early identification and notification to public health authorities and possibly early initiation of control measures could improve clinical outcomes of ILI outbreaks.

In the present study, the social linkages of street-involved youth and correlates of infection with chlamydia and gonorrhea are explored. This is the first study to assess the social linkages of street- involved youth using RDS. Eleven street-involved youth aged 14 to 24 were selected as seeds to recruit their peers into the study using RDS (N=169). Study staff administered a questionnaire, obtained a urine specimen, and provided recruitment coupons to participants. A week later, participants were provided with test results and treatment if necessary. RDS Analysis Tool was used to assess the effectiveness of RDS and define the social linkages. A Fisher’s Exact test was used to identify any correlates of infection. Gender was the only variable that correlated with infection status (22 percent of females vs. 8 percent of males). A high proportion of male participants had never been tested before. Despite the fact that most female participants had been tested before, high infection rates indicate that more accessible and frequent testing is required. Street-involved youth are connected socially to those who share similar health related behaviors. There is a need for increased testing options and opportunities for street-involved youth.

Objective.TO apply interim surveillance definitions of Clostridium difficile infection (CDI) cases to 1 year of data from the provincewide surveillance system of Manitoba, Canada, to determine the epidemiology of CDI incident cases in a population.Methods.CDI cases were categorized with interim surveillance definitions developed by an ad hoc C. difficile surveillance working group. Incident cases recorded in the provincial CDI database between July 2005 and June 2006 were linked to the provincial hospitalization and nursing home databases and analyzed.Results.One thousand six incident cases were identified over 1 year. Five hundred fifteen (51%) cases were associated with and began in a healthcare facility (HCF), whereas 275 (27%) were associated with and began in the community. An additional 131 (13%) cases were HCF associated but began in the community, while 85 (8%) were of indeterminate origin. Cases of HCF-associated CDI occurred in patients who were older than did cases of community-associated CDI (P < .0001). The provincial rate of community-onset cases was 23.4 per 100,000 person-years, and rates varied among geographic areas. HCF-associated CDI rates among the 10 largest hospitals varied from 0.5 to 8.4 per 10,000 patient-days. The time to CDI onset after hospital admission indicated that 25% of nosocomial cases began by the 8th day, and 50% began by the 17th day.Conclusions.Although the majority of CDI cases were associated with exposure to a HCF, 40% of incident CDI began in the community. Populations with HCF- and community-associated CDI demonstrated significantly different age distributions. The wide variation of rates among HCFs requires explanation. The high percentage of incident cases in the community warrants increased study.

BACKGROUND: Relatively few enhanced surveillance studies have been undertaken to investigate the extent to which verotoxin-producing non-O157 serotypes ofEscherichia colioccur in stool samples received for the detection of verotoxin-producing organisms.OBJECTIVES: To describe the prevalence, molecular and epidemiological characteristics, and geographical patterns associated with non-O157 verotoxin-producingE coli(VTEC) in Manitoba.RESULTS: Thirty-two VTEC isolates consisting of 10 serogroups and 13 different serotypes were isolated over a 22-month period. Twenty-three isolates (71.8%) possessed verotoxin-encoding gene stx1 only, five isolates (15.6%) possessedstx2only, two isolates (6.3%) possessed bothstx1andstx2, and two isolates (6.3%) possessedstx2c. Only three instances of indistinguishable pulsed-field gel electrophoresis patterns were identified. The age of the individuals from whom non-O157 VTEC were isolated ranged from eight months to 87 years. Mean and median ages were 30 and 22 years of age, respectively. Some areas of the province appeared to experience a higher than expected number of non-O157E coliin comparison with the number of stools that were received from these areas.CONCLUSIONS: The present study demonstrated a large number of infections associated with non-O157 VTEC in Manitoba. Most non-O157 cases appear to result from sporadic infections, and these occur typically in rural areas. Continued enhanced surveillance is necessary to understand the temporal patterns of non-O157 VTEC and the underlying epidemiological factors driving these patterns.

There is limited literature on programmatic challenges in the implementation of a treatment-as-prevention (TasP) strategy among human immunodeficiency virus (HIV) and drug-resistant tuberculosis (DR-TB) co-infected individuals in sub-Saharan Africa (SSA). This paper highlights specific programmatic challenges surrounding the implementation of this strategy among HIV and DR-TB co-infected populations in SSA. In SSA, limitations in administrative, human and financial resources and poor health infrastructure, as well as increased duration and complexity of providing long-term treatment for HIV individuals co-infected with DR-TB, pose substantial challenges to the implementation of a TasP strategy and warrant further investigation. A comprehensive approach must be devised to implement TasP strategy, with special attention paid to the sizable HIV and DR-TB co-infected populations. We suggest that evidence-informed and human rights-based guidelines for participant protection and strategies for programme delivery must be developed and tailored to maximise the benefits to those most at risk of developing HIV and DR-TB co-infection. Assessing regional circumstances is crucial, and TasP programmes in the region should be complemented by combined prevention strategies to achieve the intended goals.

Global literature on female sex workers suggests that being in an intimate relationship is associated with barriers to practising safe sex behaviours. Condom use within intimate relationships is often seen as a sign of infidelity and fosters mistrust which could affect longevity, trust and intimacy within partnerships. Using qualitative data from Devadasi sex workers and their intimate male partners in Bagalkot District, Karnataka, India, we examined both partners' perspectives to understand the quality and dynamics of these relationships and the factors that influence condom use in intimate relationships. Our thematic analysis of individual interviews conducted in May 2011 with 20 couples suggests that many Devadasi sex workers and their intimate partners define their relationships as 'like marriage' which reduced their motivation to use condoms. Evidence from this study suggests that active participation in sex workers' collectives (sanghas) can increase condom use, education and family planning services, among other things, and could be helpful for both Devadasis and their intimate partners to better understand and accept safer sexual practices. Our work has direct implications for designing couple-based health interventions for traditional Devadasi sex workers and their intimate partners in India.

BACKGROUND: The HIV epidemic in Nigeria is complex with diverse factors driving the epidemic. Accordingly, Nigeria's National Agency for the Control of AIDS is coordinating a large-scale initiative to conduct HIV epidemic appraisals across all states. These appraisals will help to better characterize the drivers of the epidemic and ensure that the HIV prevention programmes match the local epidemic context, with resources allocated to interventions that have the greatest impact locally. Currently, the mapping and size estimation of Female Sex Workers (FSWs)--a major component of the appraisal has been completed in seven states. These states are using the data generated to plan, prioritize and scale-up sub-national HIV prevention programmes. METHODOLOGY: It involved a two-level process of identifying and validating locations where FSWs solicit and/or meet clients ("hotspots"). In the first level, secondary key informants were interviewed to collect information about the geographic location and description of the hotspots. For the second level, FSWs were interviewed at each hotspot and information on population size estimates, typologies and operational dynamics of the FSWs were collected. RESULTS: Across the seven states, a total of 17,266 secondary key informants and 5,732 FSWs were interviewed. 10,233 hotspots were identified with an estimated 126,489 FSWs ranging from 5,920 in Anambra to 46,691 in Lagos. The most common hotspots were bars/nightclubs (30%), hotels/lodges (29.6%), streets (16.6%), and brothels (14.6%). Furthermore, the population density of FSWs (per thousand adult men) across the states ranged from 2 in Anambra to 17 in the Federal Capital Territory. CONCLUSION: FSW populations in Nigeria are large and diverse, with substantial differences between and within states. Improved understanding of the location, population size, density, organizational typologies and clients of sex work has informed and is central to Nigeria's planning process for scaling up focused HIV prevention programmes.

More than a decade ago UNAIDS and the WHO published a set of guidelines for the conduct of what was termed ‘second-generation HIV surveillance’, which encouraged the enhancement of HIV surveillance to provide better information about the patterns, status and trajectory of the HIV epidemic to better inform policies and programmes.1 As Rehle and colleagues have noted, key aspects of the second-generation approach include: combining information from different components of surveillance to achieve higher degrees of explanatory power, targeting segments of the population in which most new HIV infections are occurring; and integrating surveillance based on biological markers of infection (ie, HIV serosurveillance) with behavioural data.2 Since then, second-generation surveillance has become widely used in diverse global contexts, with substantial emphasis on two key components. The first component, sentinel HIV surveillance, has been conducted at convenient venues to track the amplitude and trends of HIV prevalence among populations based on presumed stratification of risk, such as women attending antenatal clinics, men and women attending public sexually transmitted disease clinics, and key populations at higher risk (such as female sex workers) receiving HIV prevention services. While this approach has provided important insights into the distribution and trends of HIV in different population segments, it has substantial constraints. Perhaps most importantly, it sacrifices representativeness for sampling efficiency, leading to uncertainty as to how well the results truly reflect the HIV prevalence in these populations. In addition, sentinel surveillance does not incorporate any assessment of behavioural trends, or the linkage between biological, socio-demographic, and behavioural variables with HIV status. As a result, it does not provide information about patterns and trends in the key behaviours that influence epidemics, nor does it permit a more in-depth understanding of relationships between socio-demographic characteristics and behaviours with HIV prevalence. To address this deficit, the …

Chromosome instability (CIN) is defined as an increase in the rate at which whole chromosomes or large chromosomal fragments are gained or lost. It is hallmark of cancer that occurs frequently in both solid and liquid tumors. In addition, CIN is associated with highly aggressive tumors, the acquisition of multi-drug resistance, tumor recurrence and poor patient prognosis. Despite this, the majority of human CIN genes have yet to be elucidated, highlighting the need for studies aimed at identifying the defective genes that underlie CIN. In this study we utilized two complementary, image-based approaches capable of detecting CIN-associated phenotypes following RNAi-based silencing of candidate CIN genes. The first assay involves quantifying nuclear areas following silencing, where changes in mean nuclear area relative to controls act as a surrogate marker of CIN. The second approach monitors micronucleus (MN) formation where increases in the number of micronuclei are indicative of DNA damage or the mitotic defects that underlie CIN. These assays were employed in a high-content screen of 164 human candidate CIN genes in two unrelated cell lines, HT1080 and hTERT. In HT1080, the nuclear area and MN enumeration assays identified 88 and 96 putative CIN genes, respectively. In hTERT, the nuclear area and MN assays identified 112 and 19 putative CIN genes, respectively. Promising putative CIN genes such as SKP1 were identified and prioritized for subsequent validation based on the number of assays that identified the gene, and the strength of the CIN phenotype. Preliminary data collected through Western blotting, mitotic chromosome spreads and flow cytometry, provides evidence to support the validation of SKP1 as a bona fide human CIN gene. Identification and characterization of human CIN genes will provide critical insights into CIN and tumorigenesis, as well as identify potential targets that could be exploited in novel, precision medicine approaches for superior cancer treatment. Citation Format: Laura Thompson, Allison Baergen, Zelda Lichtensztejn, Kirk McManus. Multiplexed nuclear area and micronucleus screening identifies SKP1 as a human chromosome instability gene. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3587.

Chromosome Instability (CIN) is defined as an increase in the rate at which whole chromosomes or large parts are gained or lost. CIN is not only associated with virtually all tumor types, but it is associated with aggressive tumors, the acquisition of multi-drug resistance and consequently poor patient prognosis. Despite these associations, the genes and molecular defects that contribute to CIN are only poorly understood. Recently, we performed a high content screen that identified KIF11, a microtubule associated motor protein, as a candidate CIN gene. Here, we couple RNAi-based gene silencing with biochemistry and cell biology to show that diminished KIF11 expression and/or function induce CIN. HCT116 cells were employed, as they are a karyotypically stable colorectal cancer cell line of epithelial origin that has been used for similar CIN studies. KIF11 was either silenced (both individual and pooled siRNA duplexes) or inhibited (Monostrol) and expression levels were determined by Western blots. To determine whether KIF11 silencing or inhibition affects DNA content, two phenotypes frequently associated with CIN, namely increases in nuclear area and micronucleus formation were evaluated. Fluorescence microscopy was employed on DAPI-counterstained samples and revealed statistically significant increases both nuclear area and micronucleus formation following KIF11 silencing and inhibition relative to controls. Next, flow cytometry was performed on propidium iodide labeled samples to assess whether increases in DNA content were associated with the changes in nuclear area. As predicted, increases in the proportion of cells with >G2/M DNA content occurred within the KIF11 silenced populations. Finally, mitotic chromosome spreads were generated and chromosomes were manually enumerated from 100 spreads per condition/control. Subsequent Kolmogorov-Smirnov tests identified statistically significant increases in the cumulative distribution frequencies of mitotic chromosome numbers within the spreads generated from the KIF11 silenced cells relative to controls. To extend our findings beyond the colorectal cancer cell context employed above, analogous studies were performed in hTERT cells (karyotypically stable fibroblast cell line) with very similar results. Collectively, these data indicate that KIF11 expression and function are normally required to maintain genome integrity. They further suggest that the loss of KIF11 expression and/or function may be a contributing factor in the etiology of tumorigenesis in colorectal cancer and perhaps other tumor types as well. Citation Format: Yasamin Asbaghi, Zelda Lichtensztejn, Laura Thompson, Kirk McManus. KIF11 silencing or inhibition induces chromosome instability. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3585.

Concerns remain regarding the heterogeneity in overlapping human immunodeficiency virus (HIV) risk behaviors among sex workers (SWs) in Pakistan; specifically, the degree to which SWs interact with people who inject drugs (PWID) through sex and/or needle sharing. Following an in-depth mapping performed in 2011 to determine the size and distribution of key populations at highest risk of HIV acquisition in Pakistan, a cross-sectional biological and behavioral survey was conducted among PWID, female (FSWs), male (MSWs), and hijra/transgender (HSWs) sex workers, and data from 8 major cities were used for analyses. Logistic regression was used to identify factors, including city of residence and mode of SW-client solicitation, contributing to the overlapping risks of drug injection and sexual interaction with PWID. The study comprised 8483 SWs (34.5% FSWs, 32.4% HSWs, and 33.1% MSWs). Among SWs who had sex with PWID, HSWs were 2.61 (95% confidence interval [CI], 1.19–5.74) and 1.99 (95% CI, 0.94–4.22) times more likely to inject drugs than MSWs and FSWs, respectively. There was up to a 3-fold difference in drug injecting probability, dependent on where and/or how the SW solicited clients. Compared with SWs in Larkana, the highest likelihood of drug injection use was among SWs in Multan (OR = 4.52; 95% CI: 3.27–6.26), followed by those in Lahore, Quetta, and Faisalabad. Heterogeneity exists in the overlapping patterns of HIV risk behaviors of SWs. The risk of drug injection among SWs also varies by city. Some means of sexual client solicitation may be along the pathway to overlapping HIV risk vulnerability due to increased likelihood of drug injection among SWs. There is a need to closely to monitor the mixing patterns between SWs and PWID and underlying structural factors, such as means of sexual client solicitation, that mediate HIV risk, and implement prevention programs customized to local subepidemics.

Background Since the completion of three clinical trials indicating that voluntary medical male circumcision (VMMC) is an effective method to reduce men’s chances of acquiring HIV, use of the procedure has been advocated in Kenya. Media messages shape popular understandings of the benefits and limitations of male circumcision. The objectives of this study were to (1) investigate promotion messages in a popular online newspaper to determine how the limitations of male circumcision are represented, and whether condom use is still being promoted; and (2) gain insight into popular understandings of the limitations of this new procedure through newspaper reader comments. Methods A content analysis was conducted on 34 online media articles published by the Daily Nation between January 1, 2008 and December 31, 2010. Information about condom promotion, partial immunity, limitations and complications of the procedure, as well as emergent themes, were analyzed. Results Results demonstrated an irregular and occasionally misleading presentation of these topics and a perceived lack of objective information about the risks and limitations of VMMC. Conclusions There is a need for governmental and non-governmental public health organizations to engage with the media to improve risk messaging.

BackgroundTo design HIV prevention programmes, it is critical to understand the temporal and geographic aspects of the local epidemic and to address the key behaviours that drive HIV transmission. Two methods have been developed to appraise HIV epidemics and guide prevention strategies. The numerical proxy method classifies epidemics based on current HIV prevalence thresholds. The Modes of Transmission (MOT) model estimates the distribution of incidence over one year among risk-groups. Both methods focus on the current state of an epidemic and provide short-term metrics which may not capture the epidemiologic drivers. Through a detailed analysis of country and sub-national data, we explore the limitations of the two traditional methods and propose an alternative approach.Methods and findingsWe compared outputs of the traditional methods in five countries for which results were published, and applied the numeric and MOT model to India and six districts within India. We discovered three limitations of the current methods for epidemic appraisal: (1) their results failed to identify the key behaviours that drive the epidemic; (2) they were difficult to apply to local epidemics with heterogeneity across district-level administrative units; and (3) the MOT model was highly sensitive to input parameters, many of which required extraction from non-regional sources. We developed an alternative decision-tree framework for HIV epidemic appraisals, based on a qualitative understanding of epidemiologic drivers, and demonstrated its applicability in India. The alternative framework offered a logical algorithm to characterize epidemics; it required minimal but key data.ConclusionsTraditional appraisals that utilize the distribution of prevalent and incident HIV infections in the short-term could misguide prevention priorities and potentially impede efforts to halt the trajectory of the HIV epidemic. An approach that characterizes local transmission dynamics provides a potentially more effective tool with which policy makers can design intervention programmes.

Background: Hospitalization and lab confirmed cases of H1N1 have been reported during the first wave of the 2009 pandemic but these are not accurate measures of influenza incidence in the population. We estimated the cumulative incidence of pandemic (H1N1) influenza among pregnant women in the province of Manitoba during the first wave of the 2009 pandemic. Methods: Two panels of stored frozen serum specimens collected for routine prenatal screening were randomly selected for testing before (March 2009, n = 252) and after (August 2009, n = 296) the first wave of the pandemic. A standard hemagglutination inhibition assay was used to detect the presence of IgG antibodies against the pandemic (H1N1) 2009 virus. The cumulative incidence of pandemic (H1N1) influenza was calculated as the difference between the point prevalence rates in the first and second panels. Results: Of the specimens collected in March, 7.1% were positive for the IgG antibodies (serum antibody titre ≥ 1:40). The corresponding prevalence was 15.7% among the specimens collected in August. The difference indicated a cumulative incidence of 8.6% (95% confidence interval [CI] 3.2%–13.7%). The rate differed geographically, the highest being in the northern regions (20.8%, 95% CI 7.9%–31.8%), as compared with 4.0% (95% CI 0.0%–11.9%) in Winnipeg and 8.9% (95% CI 0.0%–18.8%) in the rest of the province. Interpretation: We estimated that the cumulative incidence of pandemic (H1N1) influenza among pregnant women in Manitoba during the first wave of the 2009 pandemic was 8.6%. It was 20.8% in the northern regions of the province.

Canadian data regarding the characteristics of HIV-positive patients admitted to hospital as well as the causes and patterns of admissions remain limited. Chart reviews were performed to ascertain admission diagnosis, co-morbidities and CD4 counts among this sub-population, which had an over-representation of Aboriginal persons. Infectious diseases, particularly pneumonia, represent the most common admission diagnosis for HIV-positive persons in Winnipeg. Further, individuals presenting to hospital often have very low CD4 counts, representing significant immune suppression. Earlier HIV diagnosis and treatment in an effort to delay the onset of advanced disease and hospitalization is needed.

Background A high HIV prevalence (19–32%) has been reported among men who have sex with men (MSM) in South India. Indeed, sexual networks play a central role in the spread of HIV in these communities but have rarely been studied because of intense social stigma and methodological and ethical challenges. Although cell phones are commonly used among MSM to contact sexual partners in India, few studies have explored the formation of such sexual networks. This study sought to understand the structure, context and evolution of cell phone-based sexual networks of MSM in three South Indian cities. Methods Sampling frames in the three cities were established using MSM contacts stored in the cell phones of community-based researchers (CBRs). Study participant “seeds” were randomly selected from these social networks. Seeds were asked to recruit their sexual partners, who completed surveys about their sexual practices with regular partners and 7-day partners. Network diagrams were constructed using non-nominal codes linking study participants. Results Cell phone contacts represent a useful resource for constructing social networks. Preliminary results indicate the diversity of sexual networks and sexual practices within these networks. Conclusions New community-based methods of exploring sexual networks were assessed, and sexual practices, partner concurrency, and risk behaviours were explored. This information can be used to tailor more specific services for MSM in these communities. As this methodology sampled from social networks, more hidden “individuals who do not access health services were included in the study.”