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Abstract Background Public health practitioners and researchers for many years have been attempting to understand more clearly the links between social conditions and the health of populations. Until recently, most public health professionals in English-speaking countries were unaware that their colleagues in Latin America had developed an entire field of inquiry and practice devoted to making these links more clearly understood. The Latin American Social Medicine (LASM) database finally bridges this previous gap. Description This public health informatics case study describes the key features of a unique information resource intended to improve access to LASM literature and to augment understanding about the social determinants of health. This case study includes both quantitative and qualitative evaluation data. Currently the LASM database at The University of New Mexico http://hsc.unm.edu/lasm brings important information, originally known mostly within professional networks located in Latin American countries to public health professionals worldwide via the Internet. The LASM database uses Spanish, Portuguese, and English language trilingual, structured abstracts to summarize classic and contemporary works. Conclusion This database provides helpful information for public health professionals on the social determinants of health and expands access to LASM.

Background: Vaccination is important to reduce disease-associated morbidity and mortality in an ageing global population. While older adults are more likely than younger adults to accept vaccines, some remain hesitant. We sought to understand how traumatic events, psychological distress and social support contribute to older adults' intention to receive a COVID-19 vaccine and whether these experiences change with age., Methods: We analysed survey data collected as part of the Sax Institute's 45 and Up Study in a population of Australian adults aged 60 years and over. Data were derived from the COVID Insights study; a series of supplementary surveys about how participants experienced the COVID-19 pandemic., Results: Higher intention to receive a COVID-19 vaccine was associated with greater social support (adjusted odds ratio (aOR):1.08; 95%CI:1.06-1.11; p <.001) while lower intention was associated with personally experiencing a serious illness, injury or assault in the last 12 months (aOR:0.79; 95% CI:0.64-0.98; p =.03). Social support and the experience of traumatic events increased significantly with age, while psychological distress decreased., Conclusions: There may be factors beyond disease-associated risks that play a role in vaccine acceptance with age. Older Australians on the younger end of the age spectrum may have specific needs to address their hesitancy that may be overlooked., (© 2024. The Author(s).)

Hendra virus disease (HeVD) is an emerging zoonosis in Australia, resulting from the transmission of Hendra virus (HeV) to horses from Pteropus bats. Vaccine uptake for horses is low despite the high case fatality rate of HeVD in both horses and people. We reviewed evidence-based communication interventions to promote and improve HeV vaccine uptake for horses by horse owners and conducted a preliminary evaluation of potential drivers for HeV vaccine uptake using the Behavioural and Social Drivers of Vaccination (BeSD) framework developed by the World Health Organization. Six records were eligible for review following a comprehensive search and review strategy of peer-reviewed literature, but evidence-based communication interventions to promote and improve HeV vaccine uptake for horses were lacking. An evaluation of potential drivers for HeV vaccine uptake using the BeSD framework indicated that horse owners' perceptions, beliefs, social processes, and practical issues are similar to those experienced by parents making decisions about childhood vaccines, although the overall motivation to vaccinate is lower amongst horse owners. Some aspects of HeV vaccine uptake are not accounted for in the BeSD framework (for example, alternative mitigation strategies such as covered feeding stations or the zoonotic risk of HeV). Overall, problems associated with HeV vaccine uptake appear well-documented. We, therefore, propose to move from a problems-focused to a solutions-focused approach to reduce the risk of HeV for humans and horses. Following our findings, we suggest that the BeSD framework could be modified and used to develop and evaluate communication interventions to promote and improve HeV vaccine uptake by horse owners, which could have a global application to promote vaccine uptake for other zoonotic diseases in animals, such as rabies.

Issue Addressed: High levels of testing are crucial for minimising the spread of COVID-19. The aim of this study is to investigate what prevents people from getting a COVID-19 test when they are experiencing respiratory symptoms., Methods: Semi-structured, qualitative interviews were conducted with 14 purposively sampled adults between 20 November 2020 and 3 March 2021 in two capital cities of Australia and analysed thematically. The analysis included people who reported having respiratory symptoms but who did not undergo a COVID-19 test., Results: Participants appraised risks of having COVID-19, of infecting others or being infected whilst attending a testing site. They often weighed these appraisals against practical considerations of knowing where and how to get tested, inconvenience or financial loss., Conclusions: Clear public health messages communicating the importance of testing, even when symptoms are minor, may improve testing rates. Increasing the accessibility of testing centres, such as having them at transport hubs is important, as is providing adequate information about testing locations and queue lengths. SO WHAT?: The findings of our study suggest that more needs to be done to encourage people to get tested for COVID-19, especially when symptoms are minor. Clear communication about the importance of testing, along with easily accessible testing clinics, and financial support for those concerned about financial impacts may improve testing rates., (© 2022 The Authors. Health Promotion Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of Australian Health Promotion Association.)

Objectives: We sought to identify associations between the experience of traumatic life events and vaccination intention to inform whether trauma-affected individuals require targeted interventions when addressing vaccine hesitancy., Study Design: We conducted an online cross-sectional survey to identify whether direct or indirect exposure to various traumatic life events and the presence of post-traumatic stress disorder (PTSD) symptoms are associated with willingness to receive a COVID-19 vaccine in an Australian sample., Methods: A national online questionnaire was administered to a representative sample of 1050 Australian adults in September 2021., Results: Lower willingness to receive a COVID-19 vaccine was associated with direct experience of a fire or explosion (adjusted odds ratio [aOR]: 0.42; 95% confidence interval [CI]: 0.23-0.78; P = 0.006), direct experience of severe human suffering (aOR:0.39; 95% CI: 0.21-0.71; P = 0.002) and screening positive for PTSD symptoms (aOR:0.52; 95% CI: 0.33-0.82; P = 0.005). Conversely, higher willingness to receive a COVID-19 vaccine was associated with indirect exposure to severe human suffering (aOR: 2.0; 95% CI: 1.21-3.22; P = 0.007)., Conclusions: Our findings suggest that the experience of traumatic events and the presence of PTSD symptoms can contribute to vaccination decisions. Our work adds to the growing recognition of the need to effectively mediate the influence of traumatic experiences on encounters within the medical setting and supports the importance of addressing the needs of trauma-affected individuals in their vaccination experiences., (Copyright © 2022 The Royal Society for Public Health. All rights reserved.)

An adverse event following immunization (AEFI) can have consequences for an individual's future decision making and may contribute to vaccine hesitancy. AEFIs vary in severity and can be experienced directly (by an individual themselves) or indirectly (through witnessed or recounted events). We sought to measure the prevalence of specific AEFIs and understand which AEFIs have the greatest associations with reduced willingness to receive a vaccine and how injection anxiety may moderate the relationship. We conducted a cross-sectional online survey with both qualitative and quantitative elements in a sample of adults aged 18 years and over in Australia. Nineteen percent of the 1050 respondents reported experiencing an AEFI that they found stressful. Those who experienced an AEFI reported significantly higher levels of injection anxiety than those who did not. Within the group who reported experiencing an AEFI, respondents were significantly less likely to be willing to receive a COVID-19 vaccine if they reported: indirect exposure to an uncommon/rare AEFI compared with other AEFIs (aOR:0.39; 95% CI: 0.18-0.87); indirect exposure to a scientifically unsupported AEFI compared with other AEFIs (aOR:0.18; 95% CI: 0.05-0.57). Direct exposure to an AEFI was not associated with willingness to receive a COVID-19 vaccine. For those who reported experiencing an AEFI, the odds of willingness to receive a COVID-19 vaccine decreased significantly with an increase in injection anxiety (aOR:0.94; 95% CI: 0.9-0.98). Our results suggest that more is needed to mitigate the consequences of AEFIs on vaccine willingness. Empathically acknowledging at a community level, the experience of both real and perceived AEFIs and incorporating accounts of positive vaccination experiences in vaccine hesitancy interventions may be useful., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Despite the apparent relationship between past experiences and subsequent vaccination decisions, the role of traumatic events has been overlooked when understanding vaccination intention and behaviour. We conducted a systematic review to synthesize what is known about the relationship between traumatic events and subsequent vaccination decisions. MEDLINE, PsycINFO and CINHAL electronic databases were searched, and 1551 articles were screened for eligibility. Of the 52 articles included in full-text assessment, five met the eligibility criteria. Findings suggest that the experience of trauma is associated with individual vaccination decisions. Social and practical factors related to both trauma and vaccination may mediate this relationship. As this is a relatively new field of inquiry, future research may help to clarify the nuances of the relationship. This review finds that the experience of psychological trauma is associated with vaccination intention and behaviour and points to the potential importance of a trauma-informed approach to vaccination interventions during the current global effort to achieve high COVID-19 vaccine coverage.

Background: Children around the world remain under-vaccinated for many reasons. To develop effective vaccine delivery programmes and monitor intervention impact, vaccine programme implementers need to understand reasons for under-vaccination within their local context. The World Health Organization (WHO) Working Group on the Behavioural and Social Drivers of Vaccination (BeSD) is developing standardised tools for assessing childhood vaccine acceptance and uptake that can be used across regions and countries. The tools will include: (1) a validated survey; (2) qualitative interview guides; and (3) corresponding user guidance. We report a user-centred needs assessment of key end-users of the BeSD tools., Methods: Twenty qualitative interviews (Apr-Aug 2019) with purposively sampled vaccine programme managers, partners and stakeholders from UNICEF and WHO country and regional offices. The interviews assessed current systems, practices and challenges in data utilisation and reflections on how the BeSD tools might be optimised. Framework analysis was used to code the interviews., Results: Regarding current practices, participants described a variety of settings, data systems, and frequencies of vaccination attitude measurement. They reported that the majority of data used is quantitative, and there is appetite for increased use of qualitative data. Capacity for conducting studies on social/behavioural drivers of vaccination was high in some jurisdictions and needed in others. Issues include barriers to collecting such data and variability in sources. Reflecting on the tools, participants described the need to explore the attitudes and practices of healthcare workers in addition to parents and caregivers. Participants were supportive of the proposed mixed-methods structure of the tools and training in their usage, and highlighted the need for balance between tool standardisation and flexibility to adapt locally., Conclusions: A user-centred approach in developing the BeSD tools has given valuable direction to their design, bringing the use of behavioural and social data to the heart of programme planning., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [NS is the director of the London Safety and Training Solutions Ltd, which offers training in patient safety, implementation solutions and human factors to healthcare organisations and the pharmaceutical industry, including Sanofi-MSD and Merck. NS also holds an unrestricted educational research grant by Sanofi Pasteur for the project ‘Social and psychological determinants of vaccination uptake – Linking attitudinal and behavioural data to policy analysis and implementation’, 2021-24. Gillian SteelFisher’s husband is a minority owner of a firm that does consulting work for Eli Lilly. The other authors have no conflicts of interest to declare.]., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Vaccine refusal is highly polarizing in Australia, producing a challenging social landscape for non-vaccinating parents. We sought to understand the lived experience of non-vaccinating parents in contemporary Australia., Methods: We recruited a national sample of non-vaccinating parents of children <18 yrs, advertising on national radio, in playgrounds in low vaccination areas, and using snowballing. Grounded Theory methodology guided data collection (via semi-structured interviews). Inductive analysis identified stigmatization as a central concept; stigma theory was adopted as an analytical lens., Results: Twenty-one parents from regional and urban locations in five states were interviewed. Parent's described experiences point to systematic stigmatization which can be characterized using Link & Phelan's five-step process. Parents experienced (1) labelling and (2) stereotyping, with many not identifying with the "anti-vaxxers" portrayed in the media and describing frustration at being labelled as such, believing they were defending their child from harm. Participants described (3) social "othering", leading to relationship loss and social isolation, and (4) status loss and discrimination, feeling "brushed off" as incompetent parents and discriminated against by medical professionals and other parents. Finally, (5) legislative changes exerted power over their circumstances, rendering them unable to provide their children with the same financial and educational opportunities as vaccinated children, often increasing their steadfastness in refusing vaccination., Conclusion: Non-vaccinating Australian parents feel stigmatized for defending their child from perceived risk of harm, reporting a range of social and psychological effects, as well as financial effects from policies which disadvantaged their children through differential financial treatment, and diminished early childhood educational opportunities. While it might be argued that social stigma and exclusionary policies directed a small minority for the greater good are justified, other more nuanced approaches based on better understandings of vaccine rejection could achieve comparable public health outcomes without the detrimental effect on unvaccinated families., Competing Interests: The authors have no interests to declare., (© 2021 The Authors.)

Objective: Vaccination misinformation is widespread on social media. Vaccine-promoting organisations are working to curb its influence, but face obstacles. We aimed to analyse their social media strategies and the challenges they encounter., Methods: In this qualitative study, we purposively sampled 21 participants responsible for social media from vaccine-promoting organisations. We used Framework Analysis to explore the data., Results: Vaccine-promoting organisations faced obstacles using social media, including fast-paced change, limited resources, and insufficient organisational buy-in. They experienced difficulties reaching audiences, exploiting social media listening, and measuring impact. Consequently, they may miss opportunities to counter misinformation, connect with groups low in vaccine confidence, and determine diverse audience responses. They lack strong evidence linking social media strategies with behaviour change, and have difficulty understanding silent audiences., Conclusions: Vaccine-promoting organisations have an opportunity to embrace the participatory nature of social media. They could share listening insights with like-minded groups, and conduct research exploring associations between social media strategies and community attitude/behaviour change. Social media platforms could assist by renewing vaccine-promoting organisations' organic reach, supporting the development of tailored listening and credibility tools, and strengthening collaborations to promote credible content., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Recent research illuminates the characteristics of non-vaccinating parents in well-defined geographic communities, however the process by which they came to reject vaccines is less clearly understood. Between September 11th, 2017 and February 20th, 2019, we recruited a nationally derived sample of Australian parents of children under 18 years who rejected some or all vaccines for semi-structured interviews. We used various strategies, including advertising on national radio, in community centres and playgrounds in low coverage areas, and snowballing. Grounded Theory methodology guided data collection and analysis. Twenty-one parents from regional and urban locations were interviewed. All spoke of wanting happy, healthy, robust children. All endorsed parenting values and approaches aligned with modern societal expectations of taking responsibility for their child's health. They varied, however, in their lifestyle and vaccination trajectories. Participants self-identified as situated along an 'alternative' to 'mainstream' lifestyle spectrum and had moved both away from and toward vaccination over time. Some had decided before birth that they never would vaccinate their children and had not changed. Others stopped vaccinating after perceived post-vaccine reactions in their children. Still others initially rejected vaccines, but eventually accepted them. The variation and dynamic nature of the vaccination trajectories described in this study suggests that vaccine refusal is not a static trait but rather the result of ever-changing experience and continual risk assessment; not all non-vaccinating parents fit the 'alternative lifestyle' stereotype. This suggests that nuanced personalised engagement with non-vaccinating parents is more appropriate than a one-size-fits-all approach., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Pretravel health advice can play a crucial role in improving both travelers' awareness about disease risk and compliance with preventive measures. General practitioners (GPs) and the internet have been reported internationally to be the main sources of health advice for travelers to non-mass gathering (MG) destinations. However, few studies have attempted to investigate the sources of health advice among travelers to MGs including the Hajj pilgrimage, and none of these studies further investigated the impact of pretravel advice on pilgrims' health behaviors., Objective: The objective of this study was to investigate the impact of the source of pretravel health advice (from GPs and specialized Hajj travel agents) on Hajj pilgrims' awareness of and compliance with health recommendations, and the incidence of Hajj-associated illnesses., Methods: A prospective cohort study (before and during Hajj) was conducted among Australian pilgrims aged ≥18 years in 2015., Results: A total of 421 pilgrims participated prior to Hajj, and 391 (93%) provided follow-up data during Hajj. All participants obtained pretravel health advice from one or more sources, with Hajj travel agents (46%) and general practitioners (GPs; 40%) the most commonly reported sources. In total, 288 (74%) participants reported Hajj-related symptoms, of which 86% (248/288) were respiratory symptoms. Participants who obtained pretravel health advice from travel agents were more likely to be aware of the official Saudi recommendations (adjusted odds ratio [aOR] 2.1, 95% CI 1.2-3.8; P=.01), receive recommended vaccines before travel (aOR 2.4, 95% CI 1.4-3.9; P=.01), use hand sanitizers including soap (aOR 2.5, 95% CI 1.1-6.1; P=.03), and wash their hands after touching an ill person during Hajj (aOR 2.9, 95% CI 1.1-7.1; P=.01), compared to those who sought advice from GPs. However, neither advice from travel agents nor GPs was associated with a lower incidence of Hajj-related illnesses., Conclusions: Advice from travel agents appeared to be accessed by more travelers than that from GPs, and was associated with an increased likelihood of positive travel health behaviors., (©Amani S Alqahtani, Saeed A Alsharif, Mohammad A Garnan, Mohamed Tashani, Nasser F BinDhim, Anita E Heywood, Robert Booy, Kerrie E Wiley, Harunor Rashid, Hajj Research Group. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 14.07.2020.)

This study assessed Australian Hajj pilgrims' knowledge, attitude and practices throughout their Hajj journey to understand their health behaviors, use of preventative measures and development of illness symptoms. A prospective cohort study with data collection at three phases (before, during and after Hajj) was conducted among Australian pilgrims between August and December 2015. Baseline data were collected from 421 pilgrims before Hajj, with 391 providing follow-up data during Hajj and 300 after their home return. Most participants (78% [329/421]) received one or more recommended vaccines; travel agents' advice was the main factor affecting vaccination uptake. Most participants (69% [270/391]) practiced hand hygiene with soap and sanitizers frequently, followed by disposable handkerchief use (36% [139/391]) and washing hands with water only (28% [111/391]). During Hajj 74% (288/391) of participants reported one or more illness symptoms, 86% (248/288) of these symptoms were respiratory. Cough was less often reported among pilgrims who received vaccinations, cleaned their hands with soap or alcoholic hand rubs, while a runny nose was less common among those who frequently washed their hands with plain water but was more common among those who used facemasks. This study reveals that most Australian Hajj pilgrims complied with key preventative measures, and that tour group operators' advice played an important role in compliance. Pilgrims who were vaccinated and practiced hand hygiene were less likely to report infection symptoms.

The role of hand hygiene in the prevention of respiratory tract infections in Hajj pilgrims has not been assessed through a focussed systematic review of the literature. Considering this, a systematic review was undertaken to synthesize the up-to-date literature on the compliance and effectiveness of hand hygiene among Hajj attendees. Major databases, including OVID Medline, were searched by using a combination of MeSH terms and text words for potentially relevant articles. Data from identified articles were abstracted, quality assessed and combined into a summary effect. Twelve observational studies containing data of 6,320 pilgrims were included. The compliance of hand washing with non-alcoholic surfactants was 77.7% (ranged from 31.5% to 90.3% in individual studies) and the compliance of hand cleaning with alcoholic products was 44.9% (ranged from 30.7% to 67.4%). Education was a key influencer of hand hygiene practice. Only three of the six studies that assessed the effectiveness of hand hygiene against clinical disease found the practice to be effective, and only one of the two studies that evaluated its effectiveness against a laboratory-confirmed infection found it to be effective. This systematic review suggests that hand hygiene using non-alcoholic products is generally acceptable among Hajj pilgrims but there is no conclusive evidence on its effectiveness., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Vaccination misinformation is associated with serious public health consequences, such as a decrease in vaccination rates and a risk of disease outbreaks. Although social media offers organisations promoting vaccination unparalleled opportunities to promote evidence and counterbalance misinformation, we know relatively little about their internal workings. The aim of this paper is to explore the strategies, perspectives and experiences of communicators working within such organisations as they promote vaccination and respond to misinformation on social media., Methods: Using qualitative methods, we purposively sampled 21 participants responsible for routine social media activity and strategy from Australian organisations actively promoting vaccination on social media, including government health departments, local health services, advocacy groups, professional associations and technical/scientific organisations. We conducted semi-structured, in-depth interviews to explore their perspectives and practices. Applying Risk Communication principles as a lens, we used Framework Analysis to explore the data both inductively and deductively., Results: Organisations promoting vaccination face multiple challenges on social media, including misinformation, anti-science sentiment, a complex vaccination narrative and anti-vaccine activists. They developed a range of sophisticated strategies in response, including communicating with openness in an evidence-informed way; creating safe spaces to encourage audience dialogue; fostering community partnerships; and countering misinformation with care., Conclusions: We recommend that communicators consider directly countering misinformation because of the potential influence on their silent audience, i.e. those observing but not openly commenting, liking or sharing posts. Refutations should be straightforward, succinct and avoid emphasizing misinformation. Communicators should consider pairing scientific evidence with stories that speak to audience beliefs and values. Finally, organisations could enhance vaccine promotion and their own credibility on social media by forming strong links with organisations sharing similar values and goals.

Background: Q fever is a vaccine-preventable zoonotic infection with potentially severe health outcomes and high economic costs that affects agricultural workers, including beef and cattle industry workers, however this population historically have sub-optimal vaccine uptake., Objective: To gather quantitative and qualitative pilot data from Australian beef industry workers on their knowledge, attitudes and practices around Q fever and Q fever vaccination., Methods: A mixed methods approach was used to ascertain the Q fever disease risk perception and vaccination behavior of a purposive convenience sample of beef industry workers attending an industry expo in Rockhampton, Queensland, Australia between May 7th and 9th, 2018., Results: The quantitative survey response rate was 83% (n = 86). More than 70% of respondents reported exposure to known Q fever risk factors. Eighty six percent were aware of Q fever, the self-reported uptake of Q fever vaccine was 27% and 9% reported undertaking testing which showed evidence of previous infection. Five main themes emerged from the qualitative data: "Finding the time" among other life priorities to attend a doctor for a vaccine; "Employer responsibility" to provide the vaccine; "My doctor knows me" and could suggest Q fever vaccination; "Assigning Risk" across a range of attitudes, including thinking it would not happen to them, 'fatalism', and knowing the danger but taking the risk anyway; and "The Need for Outreach" vaccine delivery services in their communities., Significance: These data suggest that a coordinated public health approach to testing and vaccine provision, coupled with an awareness campaign among regional doctors to prompt them to routinely ask patients about their Q fever risk and vaccination history, should form part of a broad approach to Q fever control and prevention., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Pregnant women and their unborn children are at high risk from both pandemic and seasonal influenza., Aim: To explore views about influenza vaccination during pregnancy, in a pandemic and immediate post-pandemic context, among mothers and other carers of young children., Methods: In a mixed methods study, caregivers from 16 childcare centres in Sydney, Australia, were surveyed in November and December 2009, and interviews were conducted with caregivers from six childcare centres between June 2009 and May 2011., Findings: Emerging themes from 41 interviews conducted with mothers included: 'pregnancy as a protected state', 'risk negotiation' and 'centrality of healthcare worker interaction'. Of 972 surveys distributed, 431 were completed (a response rate of 44%). Respondents perceived pandemic influenza risks to be greater for pregnant women than for their unborn children. Only 2% (9/383) of women reported being vaccinated against swine flu during pregnancy and 45% (168/383) indicated intent to receive swine flu vaccination in a future pregnancy., Discussion: The low rates of maternal influenza vaccination revealed in this study contrast to recent gains in vaccine uptake. Vaccination decision-making in pregnancy can be complex and contextually driven for some women. Healthcare workers, including midwives, have a key role in addressing women's concerns about maternal influenza vaccination in both pandemic and interpandemic periods., Conclusions: Policy makers need to be cognisant of women's concerns and develop resources for both pregnant women and healthcare workers as part of both future pandemic planning and seasonal vaccination efforts., (Copyright © 2018 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Background: Travel agents are known to be one of the main sources of health information for pilgrims, and their advice is associated with positive health behaviors., Objective: This study aimed to investigate travel agents' health knowledge, what health advice they provide to the pilgrims, and their sources of health information., Methods: In-depth interviews were conducted among specialist Hajj travel agents in Sydney, Australia. Thematic analysis was undertaken., Results: Of the 13 accredited Hajj travel agents, 9 (69%) were interviewed. A high level of awareness regarding gastrointestinal infections, standard hygiene methods, and the risk of injury was noted among the participants and was included in advice provided to pilgrims. However, very limited knowledge and provision of advice about the risk of respiratory infections was identified. Knowledge of the compulsory meningococcal vaccine was high, and all participated travel agents reported influenza vaccine (a recommended vaccine) as a second "compulsory" vaccine for Hajj visas. Conversely, participants reported very limited knowledge about other recommended vaccines for Hajj. The Ministry of Hajj website and personal Hajj experience were the main sources of information., Conclusions: This study identifies a potential path for novel health promotion strategies to improve health knowledge among Hajj travel agents and subsequently among Hajj pilgrims., (©Amani S Alqahtani, Mohamed Tashani, Anita E Heywood, Robert Booy, Harunor Rashid, Kerrie E Wiley. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 23.05.2019.)

Background: Few genes have germline mutations which predispose men to more aggressive prostate cancer (PCa). This study evaluated the contribution of germline loss of function (LOF) variants in PPFIBP2 to risk of lethal PCa., Methods: A case-case study of 1414 PCa patients with lethal PCa and low-risk localized PCa was performed. Germline DNA samples from these patients were sequenced for PPFIBP2. Mutation carrier rates and association with lethal PCa were analyzed using the Fisher exact test, logistic regression, and Kaplan-Meier survival analysis., Results: In the entire study population, eight patients, all of European ancestry, were identified as carrying PPFIBP2 pathogenic or likely pathogenic mutations. Seven (1.52%) of 462 lethal PCa patients were carriers compared with only one (0.12%) carrier in 810 low-risk PCa patients, P = 0.0029. The estimated Odds Ratio (OR) of carrying PPFIBP2 mutation for lethal PCa was 13.8 in European American population. The PPFIBP2 loss-of-function mutation carrier rate in lethal PCa cases was also higher than in 33 370 non-Finnish European individuals from the Exome Aggregation Consortium (ExAC) (carrier rate of 0.17%, P = 1.92 × 10 -5 ) and in 498 men with localized PCa from The Cancer Genome Atlas cohort (TCGA) cohort (carrier rate of 0%, P = 0.0058). Survival analysis in European American lethal cases revealed PPFIBP2 mutation status as an independent predictor of shorter survival after adjusting for age at diagnosis, PSA at diagnosis, and genetic background (hazard ratio = 2.62, P = 0.034)., Conclusions: While larger studies are needed, germline mutations in a novel gene, PPFIBP2, differentiated risk for lethal PCa from low-risk cases and were associated with shorter survival times after diagnosis., (© 2018 Wiley Periodicals, Inc.)

Vaccine hesitancy in industrialised countries is an area of concern. Health professionals play a significant role in parental vaccination decisions, however, to date the role of midwives has not been widely explored. This review sought to describe the attitudes and communication practices of midwives in developed countries towards childhood vaccines. Medline, Cinahl, PsychInfo, Embase and the grey literature were searched. Inclusion criteria were qualitative and quantitative studies reporting midwives' beliefs, attitudes and communication practices toward childhood vaccination. The search returned 366 articles, of which 359 were excluded by abstract. Two additional articles were identified from the grey literature and references, resulting in nine studies from five countries included in the review. Across the studies, the majority of midwives supported vaccination, although a spectrum of beliefs and concerns emerged. A minority expressed reservations about the scientific justification for vaccination, which focussed on what is not yet known rather than mistrust of current evidence. Most midwives felt that vaccines were safe; a minority were unsure, or believed they were unsafe. The majority of midwives agreed that childhood vaccines are necessary. Among those who expressed doubt, a commonly held opinion was that vaccine preventable diseases such as measles are relatively benign and didn't warrant vaccination against them. Finally, the midwifery model of care was shown to focus on providing individualised care, with parental choice being placed at a premium. The midwifery model care appears to differ in approach from others, possibly due to a difference in the underpinning philosophies. Research is needed to understand how midwives see vaccination, and why there appears to be a spectrum of views on the subject. This information will inform the development of resources tailored to the midwifery model of care, supporting midwives in advocating for childhood vaccination., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Effective public health messaging is essential in both the planning phase and duration of a pandemic., Objectives: This study aimed to gain an understanding of parental information seeking, trusted sources and needs in relation to pandemic influenza A 2009 (pH1N1) to inform future policy planning and resource development., Patients/methods: We conducted a mixed methods study; parents from 16 childcare centres in Sydney, Australia, were surveyed between 16 November and 9 December 2009, and interviews were conducted with participants from six childcare centres between June 2009 and May 2011., Results: From 972 surveys distributed, 431 were completed; a response rate of 44%. Most parents (90%) reported that doctors were "trusted a lot" as a source of influenza information, followed by nurses (59%), government (56%) and childcare centres (52%). Less trusted sources included media (7% selected "trusted a lot"), antivaccination groups (6%) and celebrities (1%). Parents identified a range of key search terms for influenza infection and vaccine. From 42 in-depth interviews, key themes were as follows: "Action trigger," "In an emergency, think Emergency," "Fright to hype" and "Dr Google and beyond." Parents relied heavily on media messages, but cynicism emerged when the pandemic was milder than expected. Parents viewed a range of information sources as trustworthy, including doctors, authoritative hospital or government websites, and childcare centres and schools., Conclusions: A user-centred orientation is vital for pandemic communications including tailored information provision, via trusted sources based on what parents want to know and how they can find it., (© 2018 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Background: Germline mutations in BRCA1/2 and ATM have been associated with prostate cancer (PCa) risk., Objective: To directly assess whether germline mutations in these three genes distinguish lethal from indolent PCa and whether they confer any effect on age at death., Design, Setting, and Participants: A retrospective case-case study of 313 patients who died of PCa and 486 patients with low-risk localized PCa of European, African, and Chinese descent. Germline DNA of each of the 799 patients was sequenced for these three genes., Outcome Measurements and Statistical Analysis: Mutation carrier rates and their effect on lethal PCa were analyzed using the Fisher's exact test and Cox regression analysis, respectively., Results and Limitations: The combined BRCA1/2 and ATM mutation carrier rate was significantly higher in lethal PCa patients (6.07%) than localized PCa patients (1.44%), p=0.0007. The rate also differed significantly among lethal PCa patients as a function of age at death (10.00%, 9.08%, 8.33%, 4.94%, and 2.97% in patients who died ≤ 60 yr, 61-65 yr, 66-70 yr, 71-75 yr, and over 75 yr, respectively, p=0.046) and time to death after diagnosis (12.26%, 4.76%, and 0.98% in patients who died ≤ 5 yr, 6-10 yr, and>10 yr after a PCa diagnosis, respectively, p=0.0006). Survival analysis in the entire cohort revealed mutation carriers remained an independent predictor of lethal PCa after adjusting for race and age, prostate-specific antigen, and Gleason score at the time of diagnosis (hazard ratio=2.13, 95% confidence interval: 1.24-3.66, p=0.004). A limitation of this study is that other DNA repair genes were not analyzed., Conclusions: Mutation status of BRCA1/2 and ATM distinguishes risk for lethal and indolent PCa and is associated with earlier age at death and shorter survival time., Patient Summary: Prostate cancer patients with inherited mutations in BRCA1/2 and ATM are more likely to die of prostate cancer and do so at an earlier age., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: The Internet is increasingly a source of health information for parents, who use the Internet alongside health care providers for immunisation information. Concerns have been raised about the reliability of online immunisation information, however to date there has been no audit of the quality or quantity of what is available to Australian parents. The objective of this study was to address this gap by simulating a general online search for immunisation information, and assessing the quality and quantity of the web sites returned by the search., Methods: We used Google trends to identify the most common immunisation search terms used in Australia. The ten most common terms were entered into five search engines and the first ten non-commercial results from each search collated. A quality assessment tool was developed using the World Health Organization Global Advisory Committee on Vaccine Safety (GACVS) criteria for assessing the quality of vaccine safety web sites, and used to assess and score the quality of the sites., Results: Seven hundred web pages were identified, of which 514 were duplicates, leaving 186 pages from 115 web sites which were audited. Forty sites did not include human immunisation information, or presented personal opinion about individuals, and were not scored. Of the 75 sites quality scored, 65 (87%) were supportive of immunisation, while 10 (13%) were not supportive. The overall mean quality score was 57/100 (range 14/100 to 92/100). When stratified by pro and anti-vaccination stance, the average quality score for pro-vaccine sites was 61/100, while the average score for anti-vaccine sites was 30/100. Pro-vaccine information could be divided into three content groups: generalist overview with little detail; well-articulated and understandable detail; and lengthy and highly technical explanations. The main area found to be lacking in pro-vaccine sites was lack of transparent authorship., Conclusion: Our findings suggest a need for information which is easily found, transparently authored, well-referenced, and written in a way that is easily understood.

This study examines the feasibility of using a smartphone application (app) to conduct surveys among travellers during the Hajj pilgrimage, where the use of apps has not been evaluated for infectious disease surveillance. A longitudinal study was conducted among pilgrims at the Hajj 2014 using an iPhone app with separate questionnaires for three study phases covering before, during, and after Hajj. Forty-eight pilgrims from 13 countries downloaded the app. Respondents were aged between 21 and 61 (median 36) years and 58.5% (24/41) were male. Of these, 85% (41/48) completed the first phase, 52% (25/41) completed both the second and third phases, and 25 of these reported meningococcal vaccination, with 36% (9/25) receiving other vaccines. All (25) reported hand hygiene use and 64% (16/25) wore a facemask at some point during the pilgrimage. Four (6%) reported close contact with camels. Respiratory symptoms commenced from the 4th day of Hajj, with sore throat (20%) and cough (12%) being the most common. Three participants (12%) reported respiratory symptoms after returning home. Conducting a prospective survey using a smartphone app to collect data on travel-associated infections and traveller compliance to prevention is feasible at mass gatherings and can provide useful data associated with health-related behaviour., (Copyright © 2015 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.)

Previous genome-wide association studies (GWAS) of prostate cancer risk focused on cases unselected for family history and have reported over 100 significant associations. The International Consortium for Prostate Cancer Genetics (ICPCG) has now performed a GWAS of 2511 (unrelated) familial prostate cancer cases and 1382 unaffected controls from 12 member sites. All samples were genotyped on the Illumina 5M+exome single nucleotide polymorphism (SNP) platform. The GWAS identified a significant evidence for association for SNPs in six regions previously associated with prostate cancer in population-based cohorts, including 3q26.2, 6q25.3, 8q24.21, 10q11.23, 11q13.3, and 17q12. Of note, SNP rs138042437 (p = 1.7e(-8)) at 8q24.21 achieved a large estimated effect size in this cohort (odds ratio = 13.3). 116 previously sampled affected relatives of 62 risk-allele carriers from the GWAS cohort were genotyped for this SNP, identifying 78 additional affected carriers in 62 pedigrees. A test for an excess number of affected carriers among relatives exhibited strong evidence for co-segregation of the variant with disease (p = 8.5e(-11)). The majority (92 %) of risk-allele carriers at rs138042437 had a consistent estimated haplotype spanning approximately 100 kb of 8q24.21 that contained the minor alleles of three rare SNPs (dosage minor allele frequencies <1.7 %), rs183373024 (PRNCR1), previously associated SNP rs188140481, and rs138042437 (CASC19). Strong evidence for co-segregation of a SNP on the haplotype further characterizes the haplotype as a prostate cancer predisposition locus.

Through a prospective cohort study the relationship between travellers' awareness of MERS-CoV, and compliance with preventive measures and exposure to camels was evaluated among Australian Hajj pilgrims who attended Hajj in 2015. Only 28% of Australian Hajj pilgrims were aware of MERS-CoV in Saudi Arabia. Those who were aware of MERS-CoV were more likely to receive recommended vaccines [odds ratio (OR) 3.1, 95% confidence interval (CI): 1.5-5.9, P < 0.01], but there was no significant difference in avoiding camels or their raw products during Hajj between those who were aware of MERS-CoV and those who were not (OR 1.2, 95% CI: 0.3-5.2, P = 0.7). Hajj pilgrims' awareness is reflected in some of their practices but not in all., (© International Society of Travel Medicine, 2016. All rights reserved. Published by Oxford University Press. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: For reasons that have yet to be elucidated, the uptake of preventive measures against infectious diseases by Hajj pilgrims is variable. The aim of this study was to identify the preventive advice and interventions received by Australian pilgrims before Hajj, and the barriers to and facilitators of their use during Hajj., Methods: Two cross-sectional surveys of Australians pilgrims aged ≥18 years were undertaken, one before and one after the Hajj 2014., Results: Of 356 pilgrims who completed the survey (response rate 94%), 80% had the influenza vaccine, 30% the pneumococcal vaccine, and 30% the pertussis vaccine. Concern about contracting disease at Hajj was the most cited reason for vaccination (73.4%), and not being aware of vaccine availability was the main reason for non-receipt (56%). Those who obtained pre-travel advice were twice as likely to be vaccinated as those who did not seek advice. Of 150 pilgrims surveyed upon return, 94% reported practicing hand hygiene during Hajj, citing ease of use (67%) and belief in its effectiveness (62.4%) as the main reasons for compliance; university education was a significant predictor of hand hygiene adherence. Fifty-three percent used facemasks, with breathing discomfort (76%) and a feeling of suffocation (40%) being the main obstacles to compliance., Conclusion: This study indicates that there are significant opportunities to improve awareness among Australian Hajj pilgrims about the importance of using preventive health measures., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Upon return from Hajj 2014, 150 Australian pilgrims were interviewed about their understanding of the Ebola epidemic. Most (89%, 134/150) knew of the epidemic before travelling and 60% (80/134) of those knew Ebola transmits through body fluids. Pilgrims who received pre-travel health advice were more conscious of Ebola (69% vs 31%, p = 0.01) and adhered better to hand hygiene after touching an ill person (68% vs 31%, p < 0.01). Mass media was the main information source (78%).

Internationally, pregnant and postpartum women have been the focus of influenza and pertussis immunization campaigns, with differing levels of vaccine acceptance. We used semistructured interviews to explore pregnant women's perspectives on influenza vaccination during pregnancy and postpartum pertussis vaccination. Many women saw pregnancy as a busy time filled with advice on what they "should" and "should not" do to ensure the health of their fetus, and vaccinating themselves was regarded as just one of these tasks needing consideration. Women were more concerned about potential risks to their infants' health before their own. They saw influenza as a disease affecting the mother, whereas they viewed pertussis as a threat to the baby and therefore comparatively more risky. They were thus more likely to intend to vaccinate against pertussis to protect their infant. Framing of vaccination information toward protection of the baby might help increase vaccine uptake among pregnant women., (© The Author(s) 2014.)

Background: Telomeres are repetitive nucleotide sequences that stabilize the ends of chromosomes. Critically short telomeres are thought to contribute to cancer development by increasing chromosomal instability. We hypothesized that shorter leukocyte telomere length, a surrogate for inherited prostate cell telomere length, would be associated with increased risk of prostate cancer in hereditary prostate cancer (HPC) families., Methods: One hundred twelve affected and 63 unaffected men from 28 families were drawn from the Johns Hopkins HPC family database. Relative mean telomere length was measured in isolated peripheral leukocyte DNA by quantitative PCR. Conditional logistic regression was used to estimate the association between quartile of age-adjusted telomere length and prostate cancer., Results: Men in the shortest quartile of telomere length did not have increased odds of prostate cancer compared to men in the other three quartiles (OR = 0.84, 95% CI: 0.32-2.20, P = 0.73). However, when the analysis was restricted to affected men with blood drawn before or within a year of diagnosis (N = 39) and all unaffected men, shorter telomere length was moderately associated with increased odds of prostate cancer (OR = 3.55, 95% CI: 0.82-15.43, P = 0.09)., Conclusions: Though we found no association overall, shorter leukocyte telomere length may be associated with increased odds of prostate cancer when measured in pre-diagnostic samples. Further prospective research is warranted exploring the utility of telomere length as a prostate cancer biomarker., (© 2013 Wiley Periodicals, Inc.)

Previous GWAS studies have reported significant associations between various common SNPs and prostate cancer risk using cases unselected for family history. How these variants influence risk in familial prostate cancer is not well studied. Here, we analyzed 25 previously reported SNPs across 14 loci from prior prostate cancer GWAS. The International Consortium for Prostate Cancer Genetics (ICPCG) previously validated some of these using a family-based association method (FBAT). However, this approach suffered reduced power due to the conditional statistics implemented in FBAT. Here, we use a case-control design with an empirical analysis strategy to analyze the ICPCG resource for association between these 25 SNPs and familial prostate cancer risk. Fourteen sites contributed 12,506 samples (9,560 prostate cancer cases, 3,368 with aggressive disease, and 2,946 controls from 2,283 pedigrees). We performed association analysis with Genie software which accounts for relationships. We analyzed all familial prostate cancer cases and the subset of aggressive cases. For the familial prostate cancer phenotype, 20 of the 25 SNPs were at least nominally associated with prostate cancer and 16 remained significant after multiple testing correction (p ≤ 1E (-3)) occurring on chromosomal bands 6q25, 7p15, 8q24, 10q11, 11q13, 17q12, 17q24, and Xp11. For aggressive disease, 16 of the SNPs had at least nominal evidence and 8 were statistically significant including 2p15. The results indicate that the majority of common, low-risk alleles identified in GWAS studies for all prostate cancer also contribute risk for familial prostate cancer, and that some may contribute risk to aggressive disease.

Introduction: Post-partum vaccination of new mothers is currently recommended in Australia to reduce pertussis infection in infants. Internationally, vaccination recommendations now include pregnant women in some countries. Understanding the awareness of pertussis vaccination recommendations among pregnant women, and their willingness to have the vaccine while pregnant is important for informing vaccine program implementation., Objective: To determine awareness and intentions toward current recommendations for post-partum pertussis vaccination among Australian pregnant women, and their willingness to accept pertussis vaccine during pregnancy, should it be recommended in Australia in the future., Design: Quantitative self-administered survey, using a non-random stratified sampling plan based on representative proportions by age, parity and region of residence., Participants and Setting: Pregnant women receiving antenatal care through three large, demographically diverse referral hospitals in metropolitan, urban and rural New South Wales, Australia., Results: The response rate was 815/939 (87%). Most women (80%) reported willingness to have the pertussis vaccine during pregnancy, should it be recommended. Thirty four per cent of women intended to receive a pertussis vaccine post-partum, 17% had received it previously, while 45% had never heard of pertussis vaccine, had not thought about it, or were undecided about having it. Compared with those who had not received a recommendation to have the vaccine post-partum, women who had received a recommendation were 7 times more likely (95% CI 4-14) to report intention to have the vaccine., Conclusions: Health care provider recommendation is paramount to raising awareness of pertussis vaccination recommendations among pregnant women. Women's willingness to have the vaccine while pregnant is encouraging, and indicates the potential for high pertussis vaccine coverage among pregnant women, should it be recommended in Australia., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objectives: To determine influenza vaccination coverage among pregnant women in New South Wales, and factors associated with vaccine uptake during pregnancy., Design, Setting and Participants: Quantitative self-administered survey of pregnant women, using a non-random, stratified sample from antenatal clinics at three demographically diverse hospitals in NSW during the influenza season of 2011., Main Outcome Measures: Self-reported influenza vaccine uptake while pregnant; and attitudes, barriers and facilitators to vaccine acceptance during pregnancy., Results: Of 939 women approached, 815 participated (87%). Influenza vaccine uptake in pregnant women was 27%. Women who had received a recommendation to have the vaccine were 20.0 times (95% CI, 10.9-36.9) more likely to have been vaccinated. Forty-two per cent recalled receiving a recommendation to be vaccinated. Other factors associated with vaccination were study site, perceived infection severity, overall feelings toward vaccination during pregnancy, vaccine accessibility, and willingness to take up the vaccine if recommended. Concern about the baby's safety was negatively associated with vaccination (odds ratio, 0.5; 95% CI, 0.2-0.9), but 68% (95% CI, 63%-71%) of women who expressed concern agreed they would have the vaccine if their health care professional recommended it., Conclusion: Recommendation from a health care provider is strongly associated with influenza vaccine uptake among pregnant women and can overcome their concerns about safety, but less than half the women surveyed reported receiving such a recommendation. Educational material targeting pregnant women and professional education and support for antenatal health care providers are needed to increase awareness and recommendation.

Background: The relative contribution of different categories of contact in transmitting pertussis to very young infants, who experience the most severe morbidity, is the most important single factor determining the likely benefit of pertussis vaccination of their close contacts (the "cocooning" strategy)., Objective: To identify, evaluate the quality of and summarise existing data on potential sources of infant pertussis infection in high income countries, focussing on infants under 6 months old., Data Sources: Online databases MEDLINE and EMBASE. Additional studies were identified from the reference lists of relevant articles. Study selection and analysis: Study quality was evaluated by standardised criteria, based on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. Pooled estimates of the proportion of pertussis cases attributable to various contact sources were calculated using data from the highest quality studies., Results: Nine studies met the inclusion criteria; seven included data on contacts of hospitalised infants less than 6 months old. Case definitions and methods of contact ascertainment were variable. Most identified sources were from the household, of which 39% (95%CI 33-45%) were mothers, 16% (95%CI 12-21%) fathers, and 5% (95%CI 2-10%) grandparents. Estimates for siblings (16-43%) and non-household contacts (4-22%) were more heterogeneous. For 32-52% of infant cases, no source was identified. Asymptomatic pertussis infection was found in 8-13% of contacts evaluated., Conclusions: These data suggest that the greatest potential impact of pertussis vaccination of adults to prevent severe disease in young infants comes from vaccinating mothers, followed by fathers, with grandparents having a minor role. Siblings varied in importance and, given recent data regarding waning immunity in vaccinated children, need further study. Non-household sources are also well documented, highlighting the potential limitations of the cocoon strategy to prevent severe infant disease., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Prostate cancer has a strong familial component but uncovering the molecular basis for inherited susceptibility for this disease has been challenging. Recently, a rare, recurrent mutation (G84E) in HOXB13 was reported to be associated with prostate cancer risk. Confirmation and characterization of this finding is necessary to potentially translate this information to the clinic. To examine this finding in a large international sample of prostate cancer families, we genotyped this mutation and 14 other SNPs in or flanking HOXB13 in 2,443 prostate cancer families recruited by the International Consortium for Prostate Cancer Genetics (ICPCG). At least one mutation carrier was found in 112 prostate cancer families (4.6 %), all of European descent. Within carrier families, the G84E mutation was more common in men with a diagnosis of prostate cancer (194 of 382, 51 %) than those without (42 of 137, 30 %), P = 9.9 × 10(-8) [odds ratio 4.42 (95 % confidence interval 2.56-7.64)]. A family-based association test found G84E to be significantly over-transmitted from parents to affected offspring (P = 6.5 × 10(-6)). Analysis of markers flanking the G84E mutation indicates that it resides in the same haplotype in 95 % of carriers, consistent with a founder effect. Clinical characteristics of cancers in mutation carriers included features of high-risk disease. These findings demonstrate that the HOXB13 G84E mutation is present in ~5 % of prostate cancer families, predominantly of European descent, and confirm its association with prostate cancer risk. While future studies are needed to more fully define the clinical utility of this observation, this allele and others like it could form the basis for early, targeted screening of men at elevated risk for this common, clinically heterogeneous cancer.

Multiple prostate cancer (PCa) risk-related loci have been discovered by genome-wide association studies (GWAS) based on case-control designs. However, GWAS findings may be confounded by population stratification if cases and controls are inadvertently drawn from different genetic backgrounds. In addition, since these loci were identified in cases with predominantly sporadic disease, little is known about their relationships with hereditary prostate cancer (HPC). The association between seventeen reported PCa susceptibility loci was evaluated with a family-based association test using 1,979 hereditary PCa families of European descent collected by members of the International Consortium for Prostate Cancer Genetics, with a total of 5,730 affected men. The risk alleles for 8 of the 17 loci were significantly over-transmitted from parents to affected offspring, including SNPs residing in 8q24 (regions 1, 2 and 3), 10q11, 11q13, 17q12 (region 1), 17q24 and Xp11. In subgroup analyses, three loci, at 8q24 (regions 1 and 2) plus 17q12, were significantly over-transmitted in hereditary PCa families with five or more affected members, while loci at 3p12, 8q24 (region 2), 11q13, 17q12 (region 1), 17q24 and Xp11 were significantly over-transmitted in HPC families with an average age of diagnosis at 65 years or less. Our results indicate that at least a subset of PCa risk-related loci identified by case-control GWAS are also associated with disease risk in HPC families.

Background: Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive., Methods: Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed., Results: Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2-3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM). For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when families used in the original published report of linkage to Xq27-28 were excluded., Conclusions: Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2-3 affected individuals and with some evidence of male to male disease transmission showed stronger linkage signals. Our results suggest that the genetic basis for prostate cancer in our families is much more complex than a single susceptibility locus on the X chromosome, and that future explorations of the Xq27-28 region should focus on the subset of families identified here with the strongest evidence of linkage to this region.

Background: In spite of intensive efforts, understanding of the genetic aspects of familial prostate cancer (PC) remains largely incomplete. In a previous microsatellite-based linkage scan of 1,233 PC families, we identified suggestive evidence for linkage (i.e., LOD ≥ 1.86) at 5q12, 15q11, 17q21, 22q12, and two loci on 8p, with additional regions implicated in subsets of families defined by age at diagnosis, disease aggressiveness, or number of affected members., Methods: In an attempt to replicate these findings and increase linkage resolution, we used the Illumina 6000 SNP linkage panel to perform a genome-wide linkage scan of an independent set of 762 multiplex PC families, collected by 11 International Consortium for Prostate Cancer Genetics (ICPCG) groups., Results: Of the regions identified previously, modest evidence of replication was observed only on the short arm of chromosome 8, where HLOD scores of 1.63 and 3.60 were observed in the complete set of families and families with young average age at diagnosis, respectively. The most significant linkage signals found in the complete set of families were observed across a broad, 37 cM interval on 4q13-25, with LOD scores ranging from 2.02 to 2.62, increasing to 4.50 in families with older average age at diagnosis. In families with multiple cases presenting with more aggressive disease, LOD scores over 3.0 were observed at 8q24 in the vicinity of previously identified common PC risk variants, as well as MYC, an important gene in PC biology., Conclusions: These results will be useful in prioritizing future susceptibility gene discovery efforts in this common cancer., (Copyright © 2011 Wiley Periodicals, Inc.)

Background: Family history is a significant risk factor for prostate cancer, although the molecular basis for this association is poorly understood. Linkage studies have implicated chromosome 17q21-22 as a possible location of a prostate-cancer susceptibility gene., Methods: We screened more than 200 genes in the 17q21-22 region by sequencing germline DNA from 94 unrelated patients with prostate cancer from families selected for linkage to the candidate region. We tested family members, additional case subjects, and control subjects to characterize the frequency of the identified mutations., Results: Probands from four families were discovered to have a rare but recurrent mutation (G84E) in HOXB13 (rs138213197), a homeobox transcription factor gene that is important in prostate development. All 18 men with prostate cancer and available DNA in these four families carried the mutation. The carrier rate of the G84E mutation was increased by a factor of approximately 20 in 5083 unrelated subjects of European descent who had prostate cancer, with the mutation found in 72 subjects (1.4%), as compared with 1 in 1401 control subjects (0.1%) (P=8.5x10(-7)). The mutation was significantly more common in men with early-onset, familial prostate cancer (3.1%) than in those with late-onset, nonfamilial prostate cancer (0.6%) (P=2.0x10(-6))., Conclusions: The novel HOXB13 G84E variant is associated with a significantly increased risk of hereditary prostate cancer. Although the variant accounts for a small fraction of all prostate cancers, this finding has implications for prostate-cancer risk assessment and may provide new mechanistic insights into this common cancer. (Funded by the National Institutes of Health and others.).