Challenges and priorities for suicide prevention in Southeast Asia: Insights from the Partnerships for Life regional workshop on suicide prevention.

Compared to the West, suicide prevention in the Southeast Asian (SEA) region is challenging due to resource constraints, a relatively greater contribution of social compared to psychological factors, and low levels of general awareness coupled with high stigma around suicide and mental illness. Collaboration and knowledge sharing are essential to circumvent these challenges. The Partnerships for Life (PfL) initiative of the International Association of Suicide Prevention aims to enhance knowledge sharing, foster collaboration between nations, and support the development and implementation of evidence-informed approaches to suicide prevention. In February 2024, the SEA region of the PfL conducted the first regional workshop on suicide prevention, in which representatives from 10 out of 12 SEA nations participated. In this paper, we outline the key priorities, challenges, strengths, and opportunities for suicide prevention in the region with a view to inform resource-effective suicide prevention strategies that have optimal utility and uptake.

How, when and where to intervene in self-harm in youth in low- and middle-income countries: Thinking beyond healthcare systems.

BACKGROUND: Low- and middle-income countries (LMICs) account for 78% of global suicides. Self-harm is the clearest antecedent of suicide. The health and social systems have struggled to provide adequate evidence based help to young people with self-harm. In addition, the negative attitudes towards those who self-harm in these settings interfere with help-seeking behaviour. AIMS AND METHOD: In our submission of a comment, we discuss the reasons for thinking beyond healthcare systems in LMICs to address self-harm in youth and the possible ways to achieve it. RESULTS AND CONCLUSION: We truly believe that harnessing the potential of social systems such as schools is important for addressing self-harm in LMICs. We present our arguments in favour of feasible measures that can be implemented to achieve this.

Molecular classification and outcome of children with rare CNS embryonal tumors: results from St. Jude Children's Research Hospital including the multi-center SJYC07 and SJMB03 clinical trials.

Methylation profiling has radically transformed our understanding of tumors previously called central nervous system primitive neuro-ectodermal tumors (CNS-PNET). While this marks a momentous step toward defining key differences, reclassification has thrown treatment into disarray. To shed light on response to therapy and guide clinical decision-making, we report outcomes and molecular features of children with CNS-PNETs from two multi-center risk-adapted studies (SJMB03 for patients ≥ 3 years; SJYC07 for patients < 3 years) complemented by a non-protocol institutional cohort. Seventy patients who had a histological diagnosis of CNS-PNET or CNS embryonal tumor from one of the new categories that has supplanted CNS-PNET were included. This cohort was molecularly characterized by DNA methylation profiling (n = 70), whole-exome sequencing (n = 53), RNA sequencing (n = 20), and germline sequencing (n = 28). Clinical characteristics were detailed, and treatment was divided into craniospinal irradiation (CSI)-containing (SJMB03 and SJMB03-like) and CSI-sparing therapy (SJYC07 and SJYC07-like). When the cohort was analyzed in its entirety, no differences were observed in the 5-year survival rates even when CSI-containing therapy was compared to CSI-sparing therapy. However, when analyzed by DNA methylation molecular grouping, significant survival differences were observed, and treatment particulars provided suggestions of therapeutic response. Patients with CNS neuroblastoma with FOXR2 activation (CNS-NB-FOXR2) had a 5-year event-free survival (EFS)/overall survival (OS) of 66.7% ± 19.2%/83.3% ± 15.2%, and CIC rearranged sarcoma (CNS-SARC-CIC) had a 5-year EFS/OS both of 57.1% ± 18.7% with most receiving regimens that contained radiation (focal or CSI) and multidrug chemotherapy. Patients with high-grade neuroepithelial tumor with BCOR alteration (HGNET-BCOR) had abysmal responses to upfront chemotherapy-only regimens (5-year EFS = 0%), but survival extended with salvage radiation after progression [5-year OS = 53.6% ± 20.1%]. Patients with embryonal tumor with multilayered rosettes (ETMR) or high-grade glioma/glioblastoma multiforme (HGG/GBM) did not respond favorably to any modality (5-year EFS/OS = 10.7 ± 5.8%/17.9 ± 7.2%, and 10% ± 9.0%/10% ± 9.0%, respectively). As an accompaniment, we have assembled this data onto an interactive website to allow users to probe and query the cases. By reporting on a carefully matched clinical and molecular cohort, we provide the needed insight for future clinical management.

Cancer Informatics for Cancer Centers: Scientific Drivers for Informatics, Data Science, and Care in Pediatric, Adolescent, and Young Adult Cancer.

Cancer Informatics for Cancer Centers (CI4CC) is a grassroots, nonprofit 501c3 organization intended to provide a focused national forum for engagement of senior cancer informatics leaders, primarily aimed at academic cancer centers anywhere in the world but with a special emphasis on the 70 National Cancer Institute-funded cancer centers. This consortium has regularly held topic-focused biannual face-to-face symposiums. These meetings are a place to review cancer informatics and data science priorities and initiatives, providing a forum for discussion of the strategic and pragmatic issues that we faced at our respective institutions and cancer centers. Here, we provide meeting highlights from the latest CI4CC Symposium, which was delayed from its original April 2020 schedule because of the COVID-19 pandemic and held virtually over three days (September 24, October 1, and October 8) in the fall of 2020. In addition to the content presented, we found that holding this event virtually once a week for 6 hours was a great way to keep the kind of deep engagement that a face-to-face meeting engenders. This is the second such publication of CI4CC Symposium highlights, the first covering the meeting that took place in Napa, California, from October 14-16, 2019. We conclude with some thoughts about using data science to learn from every child with cancer, focusing on emerging activities of the National Cancer Institute's Childhood Cancer Data Initiative.

Effects of the Mental Health First Aid for the suicidal person course on beliefs about suicide, stigmatising attitudes, confidence to help, and intended and actual helping actions: an evaluation.

BACKGROUND: Suicide is a significant concern in Australia and globally. There is a strong argument for training community gatekeepers in how to recognise and support suicidal people in their social network. One such training course is the Mental Health First Aid for the Suicidal Person course. This course was developed using suicide prevention best practice guidelines based on expert opinion (determined using the Delphi Method). METHODS: We evaluated the impact of attending the Mental Health First Aid for the Suicidal Person course on suicide literacy and stigma, confidence in and quality of intended and actual helping behaviours towards a person who is suicidal, and course satisfaction. Surveys were administered before and immediately after the course, and at 6-month follow-up. Data were analysed to yield descriptive statistics (percentages, means, standard deviations), with linear mixed models and generalized linear mixed models being used to test the statistical significance of changes over occasions of measurement. RESULTS: We recruited 284 participants from workplaces and general community networks. The mean age was 41 years and 74% were female. 85% of people undertook the course as part of professional development, and almost half (44%) did the course because they had contact with a suicidal person. The majority (59%) of participants had previous mental health and suicide prevention training. The majority of participants held knowledge (suicide literacy) before undertaking the course. The major effect of training was to strengthen this knowledge. There was a significant improvement from pre-course (M = 1.79, SD 0.56) to post-course (M = 1.48, SD 0.82, p < 0.0001), which was maintained at follow-up (M = 1.51, SD 0.49, p < 0.0001). Confidence in gatekeeper skills significantly improved after the course and at follow-up (M = 3.15, SD 0.95 before the course to M = 4.02, SD 0.68 afterward and 3.87, SD 0.77 at follow-up, p < 0.0001 and p < 0.0001, respectively). The quality of intended helping behaviours significantly improved from pre-course (intended actions M = 4.28, SD 0.58) and to post-course (M = 4.70, SD 0.50, p < 0.0001) and were maintained at follow-up (M = 4.64, SD 0.41, p < 0.0001). There was significant improvement in some of the actions taken by participants to help a suicidal person from pre-course to post-course (e.g. asking about suicidal thoughts and plan, contacting emergency services). The course was highly acceptable to participants. CONCLUSION: These results indicate that this course is an acceptable intervention that delivers a broad spectrum of beneficial outcomes to community and workplace gatekeepers.

Retention and outcomes for clients attending a methadone clinic in a resource-constrained setting: a mixed methods prospective cohort study in Imphal, Northeast India.

BACKGROUND: Opioid substitution therapy (OST) with buprenorphine has been widely available in India since 2007, but the introduction of methadone occurred much later in 2012, and availability remains limited. Illicit injecting drug use is a long-standing public health problem in Manipur, a state in Northeast India characterised by major resource constraints and political unrest. We investigated retention and outcomes for clients attending a methadone-based OST program in Manipur with the aim of strengthening the evidence base for development of relevant policies and programs. METHODS: All clients enrolling in the methadone clinic over a 1 year period were invited to be part of a prospective cohort study, which followed up and surveyed both retained and defaulting clients for 12 months post-enrollment to assess retention as well as social, behavioural and mental health outcomes. Additionally, we conducted semi-structured qualitative interviews to supplement quantitative information and identify factors contributing to retention and drop-out. RESULTS: Of the 74 clients enrolled, 21 had dropped out and three had died (all defaulters) by 12 months post-enrollment, leaving 67.6% still in the program. Using an intention-to-treat analysis, meaningful and statistically significant gains were observed for all social, behavioural and mental health variables. Between baseline and 12 months there were reductions in needle sharing, drug use, property crime, anxiety, depression and suicidal thoughts; and improvements in physical health, mental health, quality of family relationships, employment and hopefulness. Factors contributing to retention and drop-out were identified, including the centrality of family, and general lack of awareness of and misunderstanding about methadone. CONCLUSION: Even in parts of India where resources are constrained, methadone is an effective treatment for opioid dependence. Scaling up the availability of methadone elsewhere in Manipur and in other areas of India experiencing problematic opioid dependence is indicated.

Service user and family participation in mental health policy making in Timor-Leste: a qualitative study with multiple stakeholders.

BACKGROUND: Participation in mental health system strengthening by people with mental health problems and their families is a cornerstone of people-centred mental health care, yet there is a dearth of research about participation from low- and middle-income countries (LMICs), particularly from the Asia Pacific region. Hence, this study aimed to assess the current situation, challenges, enabling factors and future actions for service user and family participation in mental health policy making in Timor-Leste. METHODS: In-depth interviews were conducted with 85 adults (≥18 years) who were: (1) mental health service users (n = 20) and their families (n = 10); (2) government decision makers (n = 10); (3) mental health and social service providers (n = 23); (4) civil society (n = 9); and (5) other groups (n = 13). Interview data was analysed using framework analysis. RESULTS: There was limited service user, family and community participation in mental health policy making in Timor-Leste. Perceptions that policy making is a technical exercise and that people with mental health problems lack cognitive capacity, and a lack of supportive mechanisms challenged participation. Enabling factors were a strong focus on human rights within the social sector, and existing mechanisms for advocacy and representation of people with disabilities in social policy making. Participants suggested bolstering civil society representation of people with mental health problems, and increasing mental health awareness and literacy, including government competencies to facilitate service user participation. CONCLUSION: The findings highlight the need for theoretical and practical focus on the role of family within mental health system development in LMICs. Global mental health research and practice should adopt a critical approach to mental health service user and family participation to ensure that the concept and strategies to achieve this are embedded in LMIC knowledge.

Intersectoral collaboration for people-centred mental health care in Timor-Leste: a mixed-methods study using qualitative and social network analysis.

BACKGROUND: Intersectoral collaboration is fundamental to the provision of people-centred mental health care, yet there is a dearth of research about how this strategy operates within mental health systems in low- and middle-income countries. This is problematic given the known attitudinal, structural and resource barriers to intersectoral collaboration in high-income country mental health systems. This study was conducted to investigate intersectoral collaboration for people-centred mental health care in Timor-Leste, a South-East Asian country in the process of strengthening its mental health system. METHODS: This study employed a mixed-methods convergent design. Qualitative data elicited from in-depth interviews with 85 key stakeholders and document review were complemented with quantitative social network analysis to assess understandings of, the strength and structure of intersectoral collaboration in the Timorese mental health system. RESULTS: There was consensus among stakeholder groups that intersectoral collaboration for mental health is important in Timor-Leste. Despite resource restrictions discussed by participants, interview data and social network analysis revealed evidence of information and resource sharing among organisations working within the health and social (disability and violence support) sectors in Timor-Leste (network density = 0.55 and 0.30 for information and resource sharing, respectively). Contrary to the assumption that mental health services and system strengthening are led by the Ministry of Health, the mixed-methods data sources identified a split in stewardship for mental health between subnetworks in the health and social sectors (network degree centralisation = 0.28 and 0.47 for information and resource sharing, respectively). CONCLUSIONS: Overall, the findings suggest that there may be opportunities for intersectoral collaborations in mental health systems in LMICs which do not exist in settings with more formalised mental health systems such as HICs. Holistic understandings of health and wellbeing, and a commitment to working together in the face of resource restrictions suggest that intersectoral collaboration can be employed to achieve people-centred mental health care in Timor-Leste.

Documenting a long-term development model in the slums of Delhi.

BACKGROUND: Achieving development outcomes requires the inclusion of marginalised populations that have the least opportunity to participate in and benefit from development. Slum dwellers often see little of the 'urban advantage', suffering more from infectious diseases, increasing food costs, poor access to education and health care, inadequate water and sanitation, and informal employment. A recent Cochrane Review of the impact of slum upgrading strategies found a dearth of unbiased studies, making it difficult to draw firm conclusions. The Review calls for greater use of process data, and qualitative alongside quantitative methods of evaluation. India is a lower middle income nation with large gender disparities and around 65 million slum inhabitants. The Asha Community Health and Development Society, a non-governmental organisation based in Delhi, has delivered a multi-sectoral program across 71 slums since 1988. This article reports on a mixed-method study to document measureable health and social impacts, along with Asha's ethos and processes. METHODS: Several observational visits were made to 12 Asha slums where informal discussions were had with staff and residents (n = 50). Asha data records were analysed for change over time (and differences with greater Delhi) in selected indicators (maternal-child health, education, child sex ratio) using descriptive statistics. 34 semi-structured individual/small group interviews and 14 focus group discussions were held with staff, residents, volunteers, elected officials, civil servants, bankers, diplomats, school principals, slumlords and loan recipients (n = 147). RESULTS: Key indicators of health and social equity improved over time and compared favourably with those for greater Delhi. The Asha model emphasises rights, responsibilities, equity and non-violence. It employs strategies characterised by long-term involvement, systematic protocols and monitoring, development of civil society (especially women's and children's groups) to advocate for rights under the law, and links with foreign volunteers and fund-raisers. Stakeholders agreed that changes in community norms and living conditions were at least partly attributable to the Asha model. CONCLUSIONS: While lacking a control group or complete baseline data, evidence suggested substantial improvements in slum conditions and social equity. The Asha model offers some lessons for slum (and broader) development.

Recurrent stroke in childhood cancer survivors.

OBJECTIVE: To estimate the rates and predictors of recurrent stroke among survivors of pediatric cancer who have had a first stroke. METHODS: The Childhood Cancer Survivor Study is a retrospective cohort study with longitudinal follow-up that enrolled 14,358 survivors (<21 years old at diagnosis; diagnosed 1970-1986; survived ≥5 years after cancer diagnosis) and followed them prospectively since 1994. We surveyed 443 survivors who reported a first stroke to identify recurrent stroke, and estimated recurrent stroke rates ≥5 years after cancer diagnosis. RESULTS: Among 329 respondents (74% response rate), 271 confirmed a first stroke at a median age of 19 years (range 0-53), and 70 reported a second stroke at a median age of 32 years (range 1-56). In a multivariable Cox proportional hazards model, independent predictors of recurrent stroke included cranial radiation therapy (CRT) dose of ≥50 Gy (vs none, hazard ratio [HR] 4.4; 95% confidence interval [CI] 1.4-13.7), hypertension (HR 1.9; 95% CI 1.0-3.5), and older age at first stroke (HR 6.4; 95% CI 1.8-23; for age ≥40 vs age 0-17 years). The 10-year cumulative incidence of late recurrent stroke was 21% (95% CI 16%-27%) overall, and 33% (95% CI 21%-44%) for those treated with ≥50 Gy of CRT. CONCLUSION: Survivors of childhood cancer, particularly those previously treated with high-dose cranial radiation, have a high risk of recurrent stroke for decades after a first stroke. Although these strokes are mostly occurring in young adulthood, hypertension, an established atherosclerotic risk factor, independently predicts recurrent stroke in this population.

Sexual behaviours of men who inject drugs in northeast India.

BACKGROUND: Promoting safer sex behaviours among people who inject drugs is important as drug-using populations with high HIV prevalence can contribute to transition from a concentrated to a generalised epidemic. This study describes the sexual behaviours of men who inject drugs in two Northeast Indian states (Manipur and Nagaland) where HIV prevalence is high, with a focus on the HIV risks for their regular female sexual partners. METHODS: Data were obtained from two cross-sectional surveys combined (N = 3,362)-both conducted in 2009 using respondent-driven sampling to recruit men who injected drugs. Both surveys asked about demographics, drug use, sexual and injecting risk behaviours, and interventions. One survey tested participants for HIV and syphilis. Statistical analyses included logistic regression modelling to predict inconsistent condom use with regular sexual partners. RESULTS: Two thirds of participants (68.2%) had a regular female sexual partner. Of these, 78.4% had sex with their regular partner in the last month, on average five times. Only 10.7% reported consistent condom use with regular partners. Unsafe injecting was common among men with regular partners, and 40.2% had more than one sexual partner in the last year. Half of those with regular partners (51.0%) had never had an HIV test, and 14.3% of those tested were HIV positive. After controlling for confounding, inconsistent condom use with regular partners was associated with being illiterate, married, sharing needle and syringe with others, never having had an HIV test and not receiving condoms from an NGO. CONCLUSION: The findings from this study among men who inject drugs in Manipur and Nagaland highlight the risk of HIV infection for their regular female sexual partners. Promoting better uptake of HIV testing among men who inject drugs will potentially benefit both them and their regular partners. While effectively reaching regular partners is challenging, a number of strategies for improving their situation in relation to HIV prevention are available.

Alcohol and condom use among HIV-positive and HIV-negative female sex workers in Nagaland, India.

This study examines the relationship between alcohol use, HIV status, and condom use among female sex workers in Nagaland, India. We analyzed data from a cross-sectional survey undertaken in 2009, using descriptive and multivariate statistics. Out of 417 female sex workers, one-fifth used alcohol daily and one-tenth were HIV-positive. HIV-positive female sex workers were more likely than HIV-negative female sex workers to consume alcohol daily (30.2% vs. 18.0%). HIV-positive daily alcohol users reported lower condom use at last sex with regular clients compared to HIV-positive non-daily alcohol users (46.2% vs. 79.3%), a relationship not evident among HIV-negative female sex workers. There is a need to promote awareness of synergies between alcohol use and HIV, and to screen for problematic alcohol use among female sex workers in order to reduce the spread of HIV.

Employer-sponsored health insurance coverage limitations: results from the Childhood Cancer Survivor Study.

PURPOSE: The Affordable Care Act (ACA) will expand health insurance options for cancer survivors in the USA. It is unclear how this legislation will affect their access to employer-sponsored health insurance (ESI). We describe the health insurance experiences for survivors of childhood cancer with and without ESI. METHODS: We conducted a series of qualitative interviews with 32 adult survivors from the Childhood Cancer Survivor Study to assess their employment-related concerns and decisions regarding health insurance coverage. Interviews were performed from August to December 2009 and were recorded, transcribed, and content analyzed using NVivo 8. RESULTS: Uninsured survivors described ongoing employment limitations, such as being employed at part-time capacity, which affected their access to ESI coverage. These survivors acknowledged they could not afford insurance without employer support. Survivors on ESI had previously been denied health insurance due to their preexisting health conditions until they obtained coverage through an employer. Survivors feared losing their ESI coverage, which created a disincentive to making career transitions. Others reported worries about insurance rescission if their cancer history was discovered. Survivors on ESI reported financial barriers in their ability to pay for health care. CONCLUSIONS: Childhood cancer survivors face barriers to obtaining ESI. While ACA provisions may mitigate insurance barriers for cancer survivors, many will still face cost barriers to affording health care without employer support.

Secondary gastrointestinal cancer in childhood cancer survivors: a cohort study.

BACKGROUND: Childhood cancer survivors develop gastrointestinal cancer more frequently and at a younger age than the general population, but the risk factors have not been well-characterized. OBJECTIVE: To determine the risk and associated risk factors for gastrointestinal subsequent malignant neoplasms (SMNs) in childhood cancer survivors. DESIGN: Retrospective cohort study. SETTING: The Childhood Cancer Survivor Study, a multicenter study of childhood cancer survivors diagnosed between 1970 and 1986. PATIENTS: 14 358 survivors of cancer diagnosed when they were younger than 21 years of age who survived for 5 or more years after the initial diagnosis. MEASUREMENTS: Standardized incidence ratios (SIRs) for gastrointestinal SMNs were calculated by using age-specific population data. Multivariate Cox regression models identified associations between risk factors and gastrointestinal SMN development. RESULTS: At median follow-up of 22.8 years (range, 5.5 to 30.2 years), 45 cases of gastrointestinal cancer were identified. The risk for gastrointestinal SMNs was 4.6-fold higher in childhood cancer survivors than in the general population (95% CI, 3.4 to 6.1). The SIR for colorectal cancer was 4.2 (CI, 2.8 to 6.3). The highest risk for gastrointestinal SMNs was associated with abdominal radiation (SIR, 11.2 [CI, 7.6 to 16.4]). However, survivors not exposed to radiation had a significantly increased risk (SIR, 2.4 [CI, 1.4 to 3.9]). In addition to abdominal radiation, high-dose procarbazine (relative risk, 3.2 [CI, 1.1 to 9.4]) and platinum drugs (relative risk, 7.6 [CI, 2.3 to 25.5]) independently increased the risk for gastrointestinal SMNs. LIMITATION: This cohort has not yet attained an age at which risk for gastrointestinal cancer is greatest. CONCLUSION: Childhood cancer survivors, particularly those exposed to abdominal radiation, are at increased risk for gastrointestinal SMNs. These findings suggest that surveillance of at-risk childhood cancer survivors should begin at a younger age than that recommended for the general population. PRIMARY FUNDING SOURCE: National Cancer Institute.

Preparing health services for climate change in Australia.

Although the implications of climate change for public health continue to be elucidated, we still require much work to guide the development of a comprehensive strategy to underpin the adaptation of the health system. Adaptation will be an evolving process as impacts emerge. The authors aim is to focus on the responses of the Australian health system to health risks from climate change, and in particular how best to prepare health services for predicted health risks from heat waves, bushfires, infectious diseases, diminished air quality, and the mental health impacts of climate change. In addition, the authors aim to provide some general principles for health system adaptation to climate change that may be applicable beyond the Australian setting. They present some guiding principles for preparing health systems and also overview some specific preparatory activities in relation to personnel, infrastructure, and coordination. Increases in extreme weather-related events superimposed on health effects arising from a gradually changing climate will place additional burdens on the health system and challenge existing capacity. Key characteristics of a climate change-prepared health system are that it should be flexible, strategically allocated, and robust. Long-term planning will also require close collaboration with the nonhealth sectors as part of a nationwide adaptive response.

Twenty-five year follow-up of childhood Wilms tumor: a report from the Childhood Cancer Survivor Study.

BACKGROUND: Treatment cures over 90% of children with Wilms tumor (WT) who subsequently risk late morbidity and mortality. This study describes the 25-year outcomes of 5-year WT survivors in the Childhood Cancer Survivor Study (CCSS). PROCEDURE: The CCSS, a multi-institutional retrospective cohort study, assessed WT survivors (N = 1,256), diagnosed 1970-1986, for chronic health conditions, health status, health care utilization, socioeconomic status, subsequent malignant neoplasms (SMNs), and mortality compared to the US population and a sibling cohort (N = 4,023). RESULTS: The cumulative incidence of all and severe chronic health conditions was 65.4% and 24.2% at 25 years. Hazard ratios (HR) were 2.0, 95% confidence interval (CI) 1.8-2.3 for grades 1-4 and 4.7, 95%CI 3.6-6.1 for grades 3 and 4, compared to sibling group. WT survivors reported more adverse general health status than the sibling group (prevalence ratio [PR] 1.7; 95%CI 1.2-2.4), but mental health status, socioeconomic outcome, and health care utilization were similar. The cumulative incidence of SMN was 3.0% (95%CI 1.9-4.0%) and of mortality was 6.1% (95%CI 4.7-7.4%). Radiation exposure increased the likelihood of congestive heart failure (CHF) (no doxorubicin-HR 6.6; 95%CI 1.6-28.3; doxorubicin ≤ 250 mg/m(2) -HR 13.0; 95%CI 1.9-89.7; doxorubicin >250 mg/m(2) -HR 18.3; 95%CI 3.8-88.2), SMN (standardized incidence ratio [SIR] 9.0; 95%CI 3.9-17.7 with and 4.9; 95%CI 1.8-10.6 without doxorubicin) and death. CONCLUSION: Long-term survivors of WT treated from 1970 to 1986 are at increased risk of treatment related morbidity and mortality 25 years from diagnosis.

The impact of indirect benefits of vaccination on postlicensure vaccine effectiveness estimates: A scenario analysis.

Vaccine efficacy is measured in randomized, prelicensure clinical trials where vaccination typically affords only direct protection to the vaccinated individual. Vaccine effectiveness is measured in postlicensure observational studies where vaccination might provide indirect benefits to a population as a whole in addition to directly protecting the vaccinated individual. The potential discrepancy in effectiveness and efficacy estimates would depend on the postlicensure study design. We developed a mathematical model to assess the impact of indirect benefits on vaccine effectiveness as measured by the common cohort study design under scenarios of homogenous and heterogenous vaccine allocation. We found that under the cohort design, effectiveness estimates equaled efficacy if either the indirect effects were assumed to be negligible or vaccine allocation in the community was homogenous. However, in presence of indirect benefits, effectiveness estimates would be biased upward compared with vaccine efficacy if one of the two sub-populations in the same study had a higher rate of vaccination. Because of indirect effects of vaccination, even in studies where other biases can be eliminated, the presence of distinct sub-populations with varying rates of vaccination can lead to discrepancies between effectiveness and efficacy estimates.

Testicular cancer survivorship: research strategies and recommendations.

Testicular cancer represents the most curable solid tumor, with a 10-year survival rate of more than 95%. Given the young average age at diagnosis, it is estimated that effective treatment approaches, in particular, platinum-based chemotherapy, have resulted in an average gain of several decades of life. This success, however, is offset by the emergence of considerable long-term morbidity, including second malignant neoplasms, cardiovascular disease, neurotoxicity, nephrotoxicity, pulmonary toxicity, hypogonadism, decreased fertility, and psychosocial problems. Data on underlying genetic or molecular factors that might identify those patients at highest risk for late sequelae are sparse. Genome-wide association studies and other translational molecular approaches now provide opportunities to identify testicular cancer survivors at greatest risk for therapy-related complications to develop evidence-based long-term follow-up guidelines and interventional strategies. We review research priorities identified during an international workshop devoted to testicular cancer survivors. Recommendations include 1) institution of lifelong follow-up of testicular cancer survivors within a large cohort setting to ascertain risks of emerging toxicities and the evolution of known late sequelae, 2) development of comprehensive risk prediction models that include treatment factors and genetic modifiers of late sequelae, 3) elucidation of the effect(s) of decades-long exposure to low serum levels of platinum, 4) assessment of the overall burden of medical and psychosocial morbidity, and 5) the eventual formulation of evidence-based long-term follow-up guidelines and interventions. Just as testicular cancer once served as the paradigm of a curable malignancy, comprehensive follow-up studies of testicular cancer survivors can pioneer new methodologies in survivorship research for all adult-onset cancer.

Increased kidney transplantation utilizing expanded criteria deceased organ donors with results comparable to standard criteria donor transplant.

OBJECTIVE: To compare outcomes in recipients of expanded criteria donor (ECD) versus standard criteria donor (SCD) kidneys at a single center using a standardized approach with similar immunosuppression. SUMMARY BACKGROUND DATA: Expanded criteria deceased organ donors (ECD) are a source of kidneys that permit more patients to benefit from transplantation. ECD is defined as all deceased donors older than 60 years and donors older than 50 years with 2 of the following: hypertension, stroke as the cause of death, or pre-retrieval serum creatinine (SCr) greater than 1.5 mg/dl. METHODS: We retrospectively studied 90 recipients of adult deceased donor kidneys transplanted from October 1, 2001 to February 17, 2003, including 37 (41%) from ECDs and 53 (59%) from SCDs. ECD kidneys were used by matching estimated renal functional mass to recipient need, including the use of dual kidney transplants (n = 7). ECD kidney recipients were further selected on the basis of older age, HLA-matching, low allosensitization, and low body mass index. All patients received a similar immunosuppressive regimen. Minimum follow up was 9 months. RESULTS: There were significant differences in donor and recipient characteristics between ECD and SCD transplants. Patient (99%) and kidney graft survival (88%) rates and morbidity were similar between the 2 groups, with a mean follow-up of 16 months. Initial graft function and the mean 1-week and 1-, 3-, 6-, 12-, and 18-month SCr levels were similar among groups. CONCLUSIONS: The use of ECD kidneys at our center effectively doubled our transplant volume within 1 year. A systematic approach to ECD kidneys based on nephron mass matching and nephron sparing measures may provide optimal utilization with short-term outcomes and renal function comparable to SCD kidneys.