Families' healthcare experiences for children with inherited metabolic diseases: protocol for a mixed methods cohort study.

INTRODUCTION: Children with inherited metabolic diseases (IMDs) often have complex and intensive healthcare needs and their families face challenges in receiving high-quality, family centred health services. Improvement in care requires complex interventions involving multiple components and stakeholders, customised to specific care contexts. This study aims to comprehensively understand the healthcare experiences of children with IMDs and their families across Canada. METHODS AND ANALYSIS: A two-stage explanatory sequential mixed methods design will be used. Stage 1: quantitative data on healthcare networks and encounter experiences will be collected from 100 parent/guardians through a care map, 2 baseline questionnaires and 17 weekly diaries over 5-7 months. Care networks will be analysed using social network analysis. Relationships between demographic or clinical variables and ratings of healthcare experiences across a range of family centred care dimensions will be analysed using generalised linear regression. Other quantitative data related to family experiences and healthcare experiences will be summarised descriptively. Ongoing analysis of quantitative data and purposive, maximum variation sampling will inform sample selection for stage 2: a subset of stage 1 participants will participate in one-on-one videoconference interviews to elaborate on the quantitative data regarding care networks and healthcare experiences. Interview data will be analysed thematically. Qualitative and quantitative data will be merged during analysis to arrive at an enhanced understanding of care experiences. Quantitative and qualitative data will be combined and presented narratively using a weaving approach (jointly on a theme-by-theme basis) and visually in a side-by-side joint display. ETHICS AND DISSEMINATION: The study protocol and procedures were approved by the Children's Hospital of Eastern Ontario's Research Ethics Board, the University of Ottawa Research Ethics Board and the research ethics boards of each participating study centre. Findings will be published in peer-reviewed journals and presented at scientific conferences.

Combining respondent-driven sampling with a community-based participatory action study of people who smoke drugs in two cities in British Columbia, Canada.

BACKGROUND: The smoking of illicit drugs presents a serious social and economic burden in Canada. People who smoke drugs (PWSD) are at increased risk of contracting multiple infections through risky drug practices. Peer-led harm reduction activities, and the resulting social networks that form around them, can potentially minimize the dangers associated with the smoking illicit drugs. GOAL: The goals of this study were to pilot test the combined approaches of respondent driven sampling with community based participatory action research in these settings and compare the attributes and social networks of PWSD in two British Columbia cities with different harm reduction programs. METHODS: Using community-based participatory action research (CBPAR) and respondent-driven sampling (RDS), individuals with lived drug experiences were employed from communities in Abbotsford and Vancouver as peer researchers to interview ten contacts from their social networks. Contacts completed a questionnaire about their harm reduction behaviours and interactions. RESULTS: We found that PWSD residing in Abbotsford were more likely to report engaging in harm-promoting behaviours, such as sharing, reusing, or borrowing crack pipes. However, PWSD in the Downtown East side Community of Vancouver were more likely to report engaging in harm-reducing activities, such as being trained in naloxone use and CPR. We found no differences in network sizes between the two communities, despite the population differences and harm reduction programs CONCLUSION: The high participation rates and interactions between researchers, and peer researchers enriched the study implementation and successfully informed our results. The fact that there were no differences in network size suggests that people have similar support in Vancouver as in Abbotsford, and that drug use practices differ mainly due to availability of harm reduction programming and resources.

Social network support and harm reduction activities in a peer researcher-led pilot study, British Columbia, Canada.

BACKGROUND: People who smoke drugs (PWSD) are at high risk of both infectious disease and overdose. Harm reduction activities organized by their peers in the community can reduce risk by providing education, safer smoking supplies, and facilitate access to other services. Peers also provide a network of people who provide social support to PWSD which may reinforce harm reducing behaviors. We evaluated the numbers of supportive network members and the relationships between received support and participants' harm-reducing activities. METHODS: Initial peer-researchers with past or current lived drug use experience were employed from communities in Abbotsford and Vancouver to interview ten friends from their social networks who use illegal drugs mainly through smoking. Contacts completed a questionnaire about people in their own harm reduction networks and their relationships with each other. We categorized social support into informational, emotional, and tangible aspects, and harm reduction into being trained in the use of, or carrying naloxone, assisting peers with overdoses, using brass screens to smoke, obtaining pipes from service organizations and being trained in CPR. RESULTS: Fifteen initial peer researchers interviewed 149 participants who provided information on up to 10 people who were friends or contacts and the relationships between them. People who smoked drugs in public were 1.46 (95% CI, 1.13-1.78) more likely to assist others with possible overdoses if they received tangible support; women who received tangible support were 1.24 (95% CI; 1.02-1.45) more likely to carry and be trained in the use of naloxone. There was no relationship between number of supportive network members and harm reduction behaviors. CONCLUSIONS: In this pilot study, PWSD who received tangible support were more likely to assist peers in possible overdoses and be trained in the use of and/or carry naloxone, than those who did not receive tangible support. Future work on the social relationships of PWSD may prove valuable in the search for credible and effective interventions.

Environmentally-induced parental or developmental conditioning influences coral offspring ecological performance.

The persistence of reef building corals is threatened by human-induced environmental change. Maintaining coral reefs into the future requires not only the survival of adults, but also the influx of recruits to promote genetic diversity and retain cover following adult mortality. Few studies examine the linkages among multiple life stages of corals, despite a growing knowledge of carryover effects in other systems. We provide a novel test of coral parental conditioning to ocean acidification (OA) and tracking of offspring for 6 months post-release to better understand parental or developmental priming impacts on the processes of offspring recruitment and growth. Coral planulation was tracked for 3 months following adult exposure to high pCO2 and offspring from the second month were reciprocally exposed to ambient and high pCO2 for an additional 6 months. Offspring of parents exposed to high pCO2 had greater settlement and survivorship immediately following release, retained survivorship benefits during 1 and 6 months of continued exposure, and further displayed growth benefits to at least 1 month post release. Enhanced performance of offspring from parents exposed to high conditions was maintained despite the survivorship in both treatments declining in continued exposure to OA. Conditioning of the adults while they brood their larvae, or developmental acclimation of the larvae inside the adult polyps, may provide a form of hormetic conditioning, or environmental priming that elicits stimulatory effects. Defining mechanisms of positive acclimatization, with potential implications for carry over effects, cross-generational plasticity, and multi-generational plasticity, is critical to better understanding ecological and evolutionary dynamics of corals under regimes of increasing environmental disturbance. Considering environmentally-induced parental or developmental legacies in ecological and evolutionary projections may better account for coral reef response to the chronic stress regimes characteristic of climate change.

The development of respondent-driven sampling (RDS) inference: A systematic review of the population mean and variance estimates.

BACKGROUND: Respondent-driven sampling (RDS) is a successful data collection method used in hard-to-reach populations, like those experiencing or at high risk of drug dependence. Since its introduction in 1997, identifying appropriate methods for estimating population means and sampling variances has been challenging and numerous approaches have been developed for making inferences about these quantities. To guide researchers and practitioners in deciding which approach to use, this article reviews the literature on these methodological developments. METHODS: A systematic review using four electronic databases was conducted in order to summarize the progress of RDS inference over the last 20 years and to provide insight to researchers on using the appropriate estimators in analyzing RDS data. Two independent reviewers selected the relevant abstracts and articles; thirty-two studies were included. The content of the studies was further categorized into developing and evaluating RDS mean and variance estimators. RESULTS: The population mean estimator RDSIEGO and the sampling variance estimators associated with tree boot strapping were identified as promising methods as the most robust population mean and variance estimate, respectively; as these estimators rely on a fewer assumptions. CONCLUSIONS: RDS holds substantial promise as a sampling method for understanding populations at high risk. The varied approaches to inference with RDS data each rely on different assumptions, but some require fewer assumptions than others and provide more robust and accurate inferences, when their corresponding assumptions are met.

Network analysis of cases with methicillin-resistant Staphylococcus aureus and controls in a large tertiary care facility.

BACKGROUND: Despite increased awareness of infection control precautions, methicillin-resistant Staphylococcus aureus (MRSA) still spreads through patients and contaminated objects, causing a substantial burden of illness and cost. Our objective was to define risk factors for contracting MRSA in a tertiary health care facility using a historic case-control study and to validate health care network changes during pre-outbreak and outbreak periods. METHODS: We conducted a case-control study using secondary data on hospitalizations where infected or colonized cases were compared with matched controls who tested negative by age, sex, and campus over 1 year. Social networks of all cases and controls were built from links joining patients to rooms, roommates, and health care providers over time. RESULTS: Matched controls were similar to cases in comorbidity, lengths of stay, mortality, and number of roommates, rooms, and health care providers. As expected, the number of rooms and roommates increased in the outbreak by more than 50%. A timed animation of the network at one campus identified potential source patients linked to 2 rooms and many roommates, after which cases connected to those same rooms proliferated. CONCLUSIONS: Only the network animation over time revealed possible transmission of MRSA through the network, rather than attributes measured in the traditional case control study.

Factors associated with human West Nile virus infection in Ontario: a generalized linear mixed modelling approach.

BACKGROUND: West Nile Virus (WNV) is a mosquito-borne pathogen that has become established in North America. Risk for human infection varies geographically in accordance with climate and population factors. Though often asymptomatic, human WNV infection can cause febrile illness or, rarely, neurologic disease. WNV has become a public health concern in Canada since its introduction in 2001. METHODS: To identify predictors of human WNV incidence at the public health unit (PHU) level in Ontario, Canada, we combined data on environmental and population characteristics of PHUs with historical mosquito and human surveillance records from 2002 to 2013. We examined the associations between annual WNV incidence and monthly climate indices (e.g. minimum and maximum temperature, average precipitation), land cover (e.g. deciduous forest, water), population structure (e.g. age and sex composition) and the annual percentage of WNV-positive mosquito pools from 2002 to 2013. We then developed a generalized linear mixed model with a Poisson distribution adjusting for spatial autocorrelation and repeat measures. Further to this, to examine potential 'early season' predictors of WNV incidence in a given year, we developed a model based on winter and spring monthly climate indices. RESULTS: Several climate indices, including mean minimum temperature (o C) in February (RR = 1.58, CI: [1.42, 1.75]), and the annual percentage of WNV-positive mosquito pools (RR = 1.07, CI: [1.04, 1.11]) were significantly associated with human WNV incidence at the PHU level. Higher winter minimum temperatures were also strongly associated with annual WNV incidence in the 'early season' model (e.g. February minimum temperature (RR = 1.91, CI: [1.73, 2.12]). CONCLUSIONS: Our study demonstrates that early season temperature and precipitation indices, in addition to the percentage of WNV-positive mosquito pools in a given area, may assist in predicting the likelihood of a more severe human WNV season in southern regions of Ontario, where WNV epidemics occur sporadically.

Can Social Network Analysis Help Address the High Rates of Bacterial Sexually Transmitted Infections in Saskatchewan?

BACKGROUND: Saskatchewan has one of the highest rates of gonorrhea among the Canadian provinces-more than double the national rate. In light of these high rates, and the growing threat of untreatable infections, improved understanding of gonorrhea transmission dynamics in the province and evaluation of the current system and tools for disease control are important. METHODS: We extracted data from a cross-sectional sample of laboratory-confirmed gonorrhea cases between 2003 and 2012 from the notifiable disease files of the Regina Qu'Appelle Health Region. The database was stratified by calendar year, and social network analysis combined with statistical modeling was used to identify associations between measures of connection within the network and the odds of repeat gonorrhea and risk of coinfection with chlamydia at the time of diagnosis. RESULTS: Networks were highly fragmented. Younger age and component size were positively associated with being coinfected with chlamydia. Being coinfected, reporting sex trade involvement, and component size were all positively associated with repeat infection. CONCLUSIONS: This is the first study to apply social network analysis to gonorrhea transmission in Saskatchewan and contributes important information about the relationship of network connections to gonorrhea/chlamydia coinfection and repeat gonorrhea. This study also suggests several areas for change of systems-related factors that could greatly increase understanding of social networks and enhance the potential for bacterial sexually transmitted infection control in Saskatchewan.

The Sociospatial Network: Risk and the Role of Place in the Transmission of Infectious Diseases.

Control of sexually transmitted infections and blood-borne pathogens is challenging due to their presence in groups exhibiting complex social interactions. In particular, sharing injection drug use equipment and selling sex (prostitution) puts people at high risk. Previous work examining the involvement of risk behaviours in social networks has suggested that social and geographic distance of persons within a group contributes to these pathogens' endemicity. In this study, we examine the role of place in the connectedness of street people, selected by respondent driven sampling, in the transmission of blood-borne and sexually transmitted pathogens. A sample of 600 injection drug users, men who have sex with men, street youth and homeless people were recruited in Winnipeg, Canada from January to December, 2009. The residences of participants and those of their social connections were linked to each other and to locations where they engaged in risk activity. Survey responses identified 101 unique sites where respondents participated in injection drug use or sex transactions. Risk sites and respondents' residences were geocoded, with residence representing the individuals. The sociospatial network and estimations of geographic areas most likely to be frequented were mapped with network graphs and spatially using a Geographic Information System (GIS). The network with the most nodes connected 7.7% of respondents; consideration of the sociospatial network increased this to 49.7%. The mean distance between any two locations in the network was within 3.5 kilometres. Kernel density estimation revealed key activity spaces where the five largest networks overlapped. Here, the combination of spatial and social entities in network analysis defines the overlap of vulnerable populations in risk space, over and above the person to person links. Implications of this work are far reaching, not just for understanding transmission dynamics of sexually transmitted infections by identifying activity "hotspots" and their intersection with each social network, but also for the spread of other diseases (e.g. tuberculosis) and targeting prevention services.

Behavioral and socioeconomic risk factors associated with probable resistance to ceftriaxone and resistance to penicillin and tetracycline in Neisseria gonorrhoeae in Shanghai.

Globally, incidence of Neisseria gonorrhoeae infection is once again the highest of the bacterial sexually transmitted infections. The bacterium can produce serious complications in those infected, and emerging resistance to third generation cephalosporins could usher in an era of potentially untreatable gonorrhea. This research aimed to identify risk factors for antibiotic resistant gonorrhea infection among clients at a Shanghai sexually transmitted infection clinic over two time periods, 2004-2005 and 2008-2011. Demographic and risk factor behavior data, and biological samples for antimicrobial resistance analysis, were collected. Statistical models were built to identify risk factors associated with probable resistance to ceftriaxone and resistance to penicillin and tetracycline. High levels of ciprofloxacin resistance (98%) in our sample precluded examining its risk factors; all isolates were susceptible to spectinomycin. Overall (P<0.001), chromosomal (P<0.001), and plasmid-mediated (P = 0.01) penicillin resistance decreased from the first to second period of the study. For tetracycline, chromosomal resistance decreased (P = 0.01) and plasmid-mediated resistance increased (P<0.001) between the first and second periods of study. In multi-level multivariable regression models, male gender (P = 0.03) and older age (P = 0.01) were associated with increased minimum inhibitory concentrations to ceftriaxone. Male gender (P = 0.03) and alcohol use (P = 0.02) were associated with increased odds of overall tetracycline resistance. Male gender was associated with increased odds of chromosomally-mediated tetracycline resistance (P = 0.04), and alcohol use was associated with increased odds of plasmid-mediated tetracycline resistance (P = 0.02). Additionally, individuals in middle-salary categories were found to have lower odds of plasmid-mediated resistance to tetracycline compared with those in the lowest salary category (P≤0.02). This study is one of the first to use multilevel analysis to consider the association between risk factors for gonorrhea infections and mechanisms of resistance to individual antibiotics. Such information is urgently needed to combat the growing threat of untreatable gonorrhea.

Outlier populations: individual and social network correlates of solvent-using injection drug users.

OBJECTIVE: We previously identified a high prevalence of Hepatitis C (HCV) amongst solvent-using injection drug users (S-IDU) relative to other injection drug users within the same locality. Here we incorporated social network variables to better characterize some of the behavioural characteristics that may be putting this specific subgroup of IDU at elevated disease risk. METHODS: A cross-sectional survey of at-risk populations was carried out in Winnipeg, Canada in 2009. Individuals reporting any history of injection drug and/or solvent use were included in the study. Associations between subgroup membership, infection with HCV and HIV and individual and social network variables were examined. RESULTS: In relation to other IDU, S-IDU were more likely to be infected with HCV, to report ever having shared a syringe, and to associate with other IDU. They were further differentiated in terms of their self-reported sexual orientation, ethnicity and in the injection drugs typically used. CONCLUSION: Solvent use stands as a proxy measure of numerous other characteristics that put this group of IDU at higher risk of infection. Provision of adequate services to ostracized subpopulations may result in wider population-level benefits.

Female partner notification is a promising prevention strategy for controlling sexually transmitted infections in Shanghai: demographic and behavioral data from a Shanghai clinic.

We identified predictors of partner presentation and condom use among male gonorrhea patients in Shanghai, China. Stable relationships, intercourse in the preceding week, and longer duration of symptoms were associated with partner presentation. Men were more likely to use condoms with their spouse and if they were 35 years or younger.

Understanding recruitment: outcomes associated with alternate methods for seed selection in respondent driven sampling.

BACKGROUND: Respondent driven sampling (RDS) was designed for sampling "hidden" populations and intended as a means of generating unbiased population estimates. Its widespread use has been accompanied by increasing scrutiny as researchers attempt to understand the extent to which the population estimates produced by RDS are, in fact, generalizable to the actual population of interest. In this study we compare two different methods of seed selection to determine whether this may influence recruitment and RDS measures. METHODS: Two seed groups were established. One group was selected as per a standard RDS approach of study staff purposefully selecting a small number of individuals to initiate recruitment chains. The second group consisted of individuals self-presenting to study staff during the time of data collection. Recruitment was allowed to unfold from each group and RDS estimates were compared between the groups. A comparison of variables associated with HIV was also completed. RESULTS: Three analytic groups were used for the majority of the analyses-RDS recruits originating from study staff-selected seeds (n = 196); self-presenting seeds (n = 118); and recruits of self-presenting seeds (n = 264). Multinomial logistic regression demonstrated significant differences between the three groups across six of ten sociodemographic and risk behaviours examined. Examination of homophily values also revealed differences in recruitment from the two seed groups (e.g. in one arm of the study sex workers and solvent users tended not to recruit others like themselves, while the opposite was true in the second arm of the study). RDS estimates of population proportions were also different between the two recruitment arms; in some cases corresponding confidence intervals between the two recruitment arms did not overlap. Further differences were revealed when comparisons of HIV prevalence were carried out. CONCLUSIONS: RDS is a cost-effective tool for data collection, however, seed selection has the potential to influence which subgroups within a population are accessed. Our findings indicate that using multiple methods for seed selection may improve access to hidden populations. Our results further highlight the need for a greater understanding of RDS to ensure appropriate, accurate and representative estimates of a population can be obtained from an RDS sample.

STI phase and the geography of sexual partnerships: prevalence of long-distance sexual contacts among chlamydia, gonorrhea, and coinfected STI cases in Manitoba, Canada.

We utilized public health data and a geographic information system (ArcGIS) to study long-distance sexual partnerships (opposite and same sex partnerships) among chlamydia, gonorrhea, and coinfected STI (sexually transmitted infection) cases. The top 10% of relationships among chlamydia and gonorrhea cases and their contacts equaled or exceeded 198 km and 237 km respectively; the top 15% of partnerships among coinfected cases equaled or exceeded 207 km. This research also detected proportionately more long-distance partnerships among gonorrhea cases than among chlamydia cases. Wasserheit and Aral's four-phase model for understanding the impact of control programs on STI incidence over time offers one framework for interpreting these results: as chlamydia was in an early decline phase during the period under study, while gonorrhea had reached a phase of low endemicity, our results could suggest that in later phases of an STI control program, the overall proportion of long-distance relationships among cases and contacts may increase.

Transmission patterns of HIV and hepatitis C virus among networks of people who inject drugs.

BACKGROUND: The risk-related behaviours and practices associated with injection drug use remain a driver of HIV and hepatitis C virus (HCV) transmission throughout the world. Here we evaluated HIV and HCV transmission patterns in the context of social networks of injection drug users (IDU) recruited from a higher incidence region in order to better understand factors that contribute to ongoing transmission among IDU. METHODS: IDU recruited through a chain-referral method provided biological specimens for analysis. HIV and HCV positive specimens were sequenced and analyzed using phylogenetic methods (Neighbour-joining and bayesian) and transmission patterns of HIV and HCV evaluated in the context of the recruitment networks. RESULTS: Among the 407 recruited IDU, HCV and HIV prevalence were 60.6% and 10.1%, respectively; 98% of HIV positive individuals were co-infected with HCV. Thirty-six percent of HCV sequences were associated with clusters, compared to 67% of HIV sequences. Four (16.7%) of the 24 HCV clusters contained membership separated by 2 or fewer recruitment cycles, compared to 10 (41.6%) derived from more than one recruitment component. Two (28.6%) of the 7 HIV clusters contained membership separated by 2 or fewer recruitment cycles while 6 (85.7%) were composed of inter component membership. CONCLUSIONS: Few HIV and HCV transmissions coincided with the recruitment networks, suggesting that they occurred in a different social context or a context not captured by the recruitment network. However, among the complete cohort, a higher degree of HIV clustering indicates many are recent infections originating from within current social networks, whereas a larger proportion of HCV infections may have occurred earlier in injecting history and in the context of a different social environment.

A network view of the transmission of sexually transmitted infections in Manitoba, Canada.

Diez Roux has used the concept of complex systems to describe approaches for the incorporation of social factors into health research. These systems consist of heterogeneous interdependent units that also exhibit emergent properties. The latter embodies the concept that the interdependent units interact with and affect each other such that the resulting properties are not simple aggregates of the individual-level properties. This paper reviews research from Manitoba with a view towards conceptualising and phrasing the observed patterns within a complex system framework. A review of the temporal and spatial patterns seen within two large sexual network databases from Manitoba was undertaken and framed against the overlying patterns of sexually transmitted infection (STI) transmission within Manitoba. The review includes a summation of STI epidemiological patterns in Manitoba over a 5-year time frame, a comparison of temporal sexual network patterns, and an analysis of network patterns in relation to disparity in STI rates. Hypotheses are generated that focus on how individual-level behaviours and interactions create the observed complex system (network) patterns.

Increased risk for hepatitis C associated with solvent use among Canadian Aboriginal injection drug users.

BACKGROUND: Solvent abuse is a particularly serious issue affecting Aboriginal people. Here we examine the association between solvent use and socio-demographic variables, drug-related risk factors, and pathogen prevalence in Aboriginal injection drug users (IDU) in Manitoba, Canada. METHODS: Data originated from a cross-sectional survey of IDU from December 2003 to September 2004. Associations between solvent use and variables of interest were assessed by multiple logistic regression. RESULTS: A total of 266 Aboriginal IDU were included in the analysis of which 44 self-reported recent solvent use. Hepatitis C infection was 81% in solvent-users, compared to 55% in those reporting no solvent use. In multivariable models, solvent-users were younger and more likely to be infected with hepatitis C (AOR: 3.5; 95%CI: 1.3,14.7), to have shared needles in the last six months (AOR: 2.6; 95%CI:1.0,6.8), and to have injected talwin & Ritalin (AOR: 10.0; 95%CI: 3.8,26.3). INTERPRETATION: High hepatitis C prevalence, even after controlling for risky injection practices, suggests that solvent users may form closed networks of higher risk even amongst an already high-risk IDU population. Understanding the social-epidemiological context of initiation and maintenance of solvent use is necessary to address the inherent inequalities encountered by this subpopulation of substance users, and may inform prevention strategies for other marginalized populations.

A global look at national Immunization Technical Advisory Groups.

This paper presents the results of a global survey that aimed to collect information on country's immunization policy development processes, particularly on the presence and function of national Immunization Technical Advisory Groups (ITAGs). Characteristics of national ITAGs are described as well as attributes of these groups that appear to be imperative for an effective ITAG. ITAGs provide a valued service to over 89 countries that reported their establishment, some of which have been in existence for over 40 years. This paper provides basic information on the functioning of these groups and encourages future efforts to address gaps in knowledge and research in this area.