Enabling older adults with intellectual disability to become physical activity leaders in their community: Pilot study.

People with intellectual disabilities (ID) have high levels of sedentary behaviour and co-morbid health conditions. There is also increased longevity for this group which is an incredible success story but one which also poses challenges to the health system. For the first time, the mainstream health system needs to plan for and address age related health needs of people with ID. It also demands consideration of age-appropriate health-promotion efforts to support this ageing population with life-long disability. A physical activity programme, People with Intellectual Disability as Physical Activity Leaders (PPALs), was co-designed and co-developed with older adults (40+ years) with intellectual disability (ID). The process, content and outcomes of the pilot are presented in this paper. Expertise from three sectors: non-statutory academic and people with intellectual disabilities and their supporters worked collaboratively for successful completion of the project.

Irish social policy to family carers of adults with an intellectual disability: A critical analysis.

This paper explores contemporary Irish social policy for family caregivers with specific focus on the dynamic between the individual, the family and the state in terms of the social contract for care provision for people with intellectual disability. Drawing from Bacchi's analytical framework (Bacchi, 2009), the Irish National Carers' Strategy is interrogated specifically with regards to how it frames and assumes the social contract for family care provision for adults with an intellectual disability. We suggest that Irish social policy constructs family caregiving as the assumed natural and neutral point of departure for providing care within society, and this constructed identify is subsequently reinforced through the provisions contained with the policies themselves that seek to support such caregivers. A fundamental reconsideration of the social contract for such care provision and support with society would appear warranted.

COVID-19 IDD: Findings from a global survey exploring family members' and paid staff's perceptions of the impact of COVID-19 on individuals with intellectual and developmental disabilities (IDD) and their caregivers.

Background: A growing body of evidence attests to the disproportionate impact of COVID-19 on persons with intellectual and developmental disabilities (IDD) during the pandemic. This study asked caregivers about their perceptions of how COVID-19 impacted them and the people they support. Method: An online survey was conducted in 12 countries during August-September 2020 and sought information on demographics, support practices, information and training, experiences of COVID-19, social distancing, and wellbeing, as measured by the DASS12. This study reports on 3,754 family members, direct support professionals, and managers who participated in the survey. Results: Caregivers observed increases in depression/anxiety, stereotyped behaviours, aggression towards others and weight gain in the person(s) they supported. They also reported difficulties supporting the person(s) to access healthcare.  Families reported reducing or ceasing employment and absorbed additional costs when supporting their family member. Direct support professionals experienced changes in staff shifts, staff absences, increased workload and hiring of casual staff. Caregivers' wellbeing revealed high levels of stress, depression, and less so anxiety. The strongest predictor of wellbeing among families was observation of changes in mood in the person(s) they supported, while for direct support professionals, the strongest predictors of wellbeing were reorganisation of staff shifts and increases in new direct support staff.  Discussion: Findings support the contention of this population experiencing a disproportionate burden during the COVID-19 pandemic, reflecting historical inequities in access to healthcare and other human rights violations which are now protected under the United Nations Convention on the Rights of Persons with Disabilities.

Predictors of Productivity and Leisure for People Aging with Intellectual Disability.

Background. Adults aging with intellectual disability (ID) face barriers to engagement in occupation. Greater understanding of factors that affect engagement in work and leisure occupations is required to support occupational engagement in this population. Purpose. Identify predictors of engagement in work and leisure occupations for adults aging with an ID, and consider implications for occupational therapy practice. Method. Data from wave 2 of the Intellectual Disability Supplement to the Irish Longitudinal Study on Aging (IDS-TILDA) was analyzed using regression analysis to identify predictors of engagement in work and leisure occupations for adults aging with an ID. Findings. Adults who had difficulty getting around their home environment, poor physical health, or older age were less likely to engage in work and leisure activities. Implications. Occupational therapists can support adults aging with ID to age in place. Occupation-focused health promotion could enhance well-being through engagement in occupation.

The Future of Disability Research in Australia: Protocol for a Multiphase Research Agenda-Setting Study.

BACKGROUND: For people with disabilities to live a good life, it is essential that funded research in health and social care addresses their interests, meets their needs, and fills gaps in our understanding of the impact that services, systems, and policies may have on them. Decisions about research funding should be based on an understanding of the research priorities of people with disabilities, their supporters and allies, disability researchers, service providers, and policy makers working in the field. OBJECTIVE: The aim of this protocol is to describe the research design and methods of a large-scale, disability research agenda-setting exercise conducted in 2021 in Australia. METHODS: The research agenda-setting exercise involves 3 integrated phases of work. In the first phase, a previous audit of disability research in Australia is updated to understand previous research and continuing gaps in the research. Building on this, the second phase involves consultation with stakeholders-people with disabilities and their supporters and family members, the disability workforce, and people working within services and connected sectors (eg, aging, employment, education, and housing), academia, and public policy. Data for the second phase will be gathered as follows: a national web-based survey; a consultation process undertaken through the government and nongovernment sector; and targeted consultation with Aboriginal and Torres Strait Islander people, children with disabilities and their families, people with cognitive disability, and people with complex communication needs. The third phase involves a web-based survey to develop a research agenda based on the outcomes of all phases. RESULTS: We have started working on 2 parts of the research prioritization exercise. Through the research-mapping exercise we identified 1241 journal articles and book chapters (referred to as research papers) and 225 publicly available reports (referred to as research reports) produced over the 2018-2020 period. Data collection for the national survey has also been completed. We received 973 fully completed responses to the survey. Analysis of these data is currently underway. CONCLUSIONS: This multi-method research agenda-setting study will be the first to provide an indication of the areas of health and social research that people across the Australian disability community consider should be prioritized in disability research funding decisions. Project results from all phases will be made publicly available through reports, open-access journal publications, and Easy Read documents. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/31126.

COVID-19 IDD: A global survey exploring family members' and paid staff's perceptions of the impact of COVID-19 on individuals with intellectual and developmental disabilities and their caregivers.

Background: This protocol outlines research to explore the impact of coronavirus disease 2019 (COVID-19) on individuals who have intellectual and developmental disabilities and their caregivers. Evidence suggests that people with intellectual and developmental disabilities experience disparities in healthcare access and utilisation. This disparity was evident early in the pandemic when discussions arose regarding the potential exclusion of this population to critical care. Methods: An anonymous online survey will be conducted with caregivers, both family members and paid staff, to explore the impact of COVID-19 on this population in terms of demographics, living arrangements, access to services, the impact of social distancing, and also carer wellbeing. The survey will be developed by the research team, many of whom are experts in intellectual disability within their own jurisdictions. Using back-translation our team will translate the survey for distribution in 16 countries worldwide for international comparison. The survey team have extensive personal and professional networks in intellectual disability and will promote the survey widely on social media with the support of local disability and advocacy agencies. Statistical descriptive and comparative analyses will be conducted. Ethical approval has been obtained for this study from University College Dublin's Human Research Ethics Committee (HS-20-28-Linehan). Dissemination: Study findings will be prepared in a number of formats in order to meet the needs of different audiences. Outputs will include academic papers, lessons learned paper, practice guidelines, reports, infographics and video content. These outputs will be directed to families, frontline and management delivering disability services, national-level policy makers, healthcare quality and delivery authorities, national pandemic organisations and international bodies.

Effect of deinstitutionalisation for adults with intellectual disabilities on costs: a systematic review.

OBJECTIVE: To review systematically the evidence on the costs and cost-effectiveness of deinstitutionalisation for adults with intellectual disabilities. DESIGN: Systematic review. POPULATION: Adults (aged 18 years and over) with intellectual disabilities. INTERVENTION: Deinstitutionalisation, that is, the move from institutional to community settings. PRIMARY AND SECONDARY OUTCOME MEASURES: Studies were eligible if evaluating within any cost-consequence framework (eg, cost-effectiveness analysis, cost-utility analysis) or resource use typically considered to fall within the societal viewpoint (eg, cost to payers, service-users, families and informal care costs). SEARCH: We searched MEDLINE, PsycINFO, CENTRAL, CINAHL, EconLit, Embase and Scopus to September 2017 and supplemented this with grey literature searches and handsearching of the references of the eligible studies. We assessed study quality using the Critical Appraisals Skills Programme suite of tools, excluding those judged to be of poor methodological quality. RESULTS: Two studies were included; both were cohort studies from the payer perspective of people leaving long-stay National Health Service hospitals in the UK between 1984 and 1992. One study found that deinstitutionalisation reduced costs, one study found an increase in costs. CONCLUSION: A wide-ranging literature review found limited evidence on costs associated with deinstitutionalisation for people with intellectual disabilities. From two studies included in the review, the results were conflicting. Significant gaps in the evidence base were observable, particularly with respect to priority populations in contemporary policy: older people with intellectual disabilities and serious medical illness, and younger people with very complex needs and challenging behaviours. PROSPERO REGISTRATION NUMBER: CRD42018077406.

Effect of deinstitutionalisation on quality of life for adults with intellectual disabilities: a systematic review.

OBJECTIVE: To review systematically the evidence on how deinstitutionalisation affects quality of life (QoL) for adults with intellectual disabilities. DESIGN: Systematic review. POPULATION: Adults (aged 18 years and over) with intellectual disabilities. INTERVENTIONS: A move from residential to community setting. PRIMARY AND SECONDARY OUTCOME MEASURES: Studies were eligible if evaluating effect on QoL or life quality, as defined by study authors. SEARCH: We searched MEDLINE, PsycINFO, CENTRAL, CINAHL, EconLit, Embase and Scopus to September 2017 and supplemented this with grey literature searches. We assessed study quality using the Critical Appraisal Skills Programme suite of tools, excluding those judged to be of poor methodological quality. RESULTS: Thirteen studies were included; eight quantitative studies, two qualitative, two mixed methods studies and one case study. There was substantial agreement across quantitative and qualitative studies that a move to community living was associated with improved QoL. QoL for people with any level of intellectual disabilities who move from any type of institutional setting to any type of community setting was increased at up to 1 year postmove (standardised mean difference [SMD] 2.03; 95% CI [1.21 to 2.85], five studies, 246 participants) and beyond 1 year postmove (SMD 2.34. 95% CI [0.49 to 4.20], three studies, 160 participants), with total QoL change scores higher at 24 months comparative to 12 months, regardless of QoL measure used. CONCLUSION: Our systematic review demonstrated a consistent pattern that moving to the community was associated with improved QoL compared with the institution. It is recommended that gaps in the evidence base, for example, with regard to growing populations of older people with intellectual disability and complex needs are addressed. PROSPERO REGISTRATION NUMBER: CRD42018077406.

A narrative synthesis scoping review of life course domains within health service utilisation frameworks.

Background: Current thinking in health recognises the influence of early life experiences (health and otherwise) on later life outcomes. The life course approach has been embedded in the work of the World Health Organisation since the Ageing and Health programme was established in 1995. Yet there has been limited debate on the relevancy of a life course lens to understanding health service utilisation. Aim: The aim of the review was twofold. Firstly, identify existing healthcare utilisation frameworks other than the dominant Andersen's behavioural model currently in use. Secondly, to identify if current frameworks incorporate the advocated life course perspective in understanding health service utilisation.     Methods: A scoping review of PubMed, Cinahl Plus, Emerald, PsycINFO, Web of Knowledge and Scopus was conducted. Data extraction used a framework approach with meta-synthesis guided by the four domains of the life course proposed by Elder (1979): human agency, location, temporality and relationships, and interdependencies. Results: A total of 551 papers were identified, with 70 unique frameworks (other than Andersen's Behavioural Model) meeting the inclusion criteria and included in the review. Conclusion: To date there has been limited explicit discussion of health service utilisation from a life course perspective. The current review highlights a range of frameworks that draw on aspects of the life course, but have been used with this perspective in mind. The life course approach highlights important gaps in understanding and assessing health service utilisation (HSU), such as utilisation over time. HSU is a complex phenomenon and applying a structured framework from a life course perspective would be of benefit to researchers, practitioners and policy makers.

Are frequent dental x-ray examinations associated with increased risk of vestibular schwannoma?

OBJECT: The authors evaluated the potential role of environmental risk factors, including exposure to diagnostic or therapeutic radiation and to wireless phones that emit nonionizing radiation, in the etiology of vestibular schwannoma (VS). METHODS: A total of 343 patients with VSs who underwent Gamma Knife surgery performed between 1997 and 2007 were age and sex matched to 343 control patients from the outpatient degenerative spinal disorders service at the University of Pittsburgh Medical Center. The authors obtained information on previous exposure to medical radiation, use of wireless phone technologies, and other environmental factors thought to be associated with the development of a VS. Conditional multivariate logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: After adjusting for race, education, cigarette smoking, alcohol consumption, occupational exposure to noise, use of cell phones, and family history of cancer, the authors identified only a single factor that was associated with a higher risk of VS: individuals exposed to dental x-rays once a year (aOR = 2.27, 95% CI = 1.01-5.09) or once every 2-5 years (aOR = 2.65, 95% CI = 1.20-5.85), compared with those exposed less than once every 5 years. Of interest, a history of exposure to radiation related to head or head-and-neck computed tomography was associated with a reduced risk of VS (aOR = 0.52, 95% CI = 0.30-0.90). No relationship was found between the use of cell phones or cordless phones and VS. CONCLUSIONS: Patients with acoustic neuromas reported significantly more exposure to dental x-rays than a matched cohort control group. Reducing the frequency of dental x-ray examinations may decrease the potential risk of VS.

Environmental barriers, activity limitations and participation restrictions experienced by people with major limb amputation.

BACKGROUND: Limited research is available that explores major limb amputation and the World Health Organization's International Classification of Functioning, Disability and Health (ICF). OBJECTIVES: To investigate the barriers, participation restriction and functioning levels experienced by people with a major limb amputation. STUDY DESIGN: Secondary data analysis. METHOD: Relevant data for 148 people with major limb amputation were extracted from the National Physical and Sensory Disability Database in Ireland. RESULTS: The most common environmental barriers encountered were climate, physical environment and income. Participation restriction was most commonly experienced in sports/physical recreation, leisure/cultural activity and employment/job-seeking. For daily activities and functioning, the most common difficulties were with standing for long periods, walking long distances and the emotional effects of disability. Differences were found between people with an upper limb or lower limb prosthesis. CONCLUSION: This paper addresses the limited information available on environmental barriers, activity limitation and participation restriction of people with a major limb amputation. Greater understanding of the impact of amputation and prosthesis type on activity, participation and environmental barriers is important to facilitate improved management and planning at the individual, service and societal level. CLINICAL RELEVANCE: Improved understanding of environmental barriers and challenges, activity limitations and participation restrictions experienced by individuals with major limb amputation is a critical step in informing evidence-based service delivery, intervention and policy in order to improve outcomes for this group.

Time Trends and Racial Differences in Female Breast Cancer Incidence in Pennsylvania, 1985-2004.

Background: Differences in breast cancer incidence time trends can result from changes in ascertainment, new diagnostic codes, or possibly changes in underlying risk factors. Methods: Female breast cancer incidence data between 1985 and 2004 were obtained from the Pennsylvania Cancer Registry. Joinpoint regression was applied to characterize time trends of age-specific, race-specific, and histology-specific breast cancer incidence. Estimated annual percent change (APC) was calculated. Spatial analysis was applied to detect spatial clusters of county-specific incidence for breast cancer in Pennsylvania. Results: The age-adjusted incidence of invasive breast carcinoma and breast carcinoma in situ was higher in white women than in black women. Invasive breast carcinoma incidence began to decrease significantly in 2001 (APC -3.0%) among white women but has been stable among black women since 1987. Among white women, the age-adjusted incidence of ductal carcinoma in situ increased significantly from 1985 to 1999 but was stable for lobular carcinoma in situ. Among black women, the incidence for both ductal and lobular carcinoma in situ increased significantly over time. For women under the age of 40, breast carcinoma in situ incidence increased significantly over time (APC 4.5% and 10.0% in white women and black women, respectively, 1985-2004). Young black women had a higher incidence of both invasive breast carcinoma and breast carcinoma in situ compared to young white women. Conclusions: Although the increase in breast carcinoma in situ is partly explained by improved diagnosis and screening, other risk factors should be considered. In addition, factors responsible for higher breast cancer rates among younger black women and women living in urban areas should be carefully assessed.

Towards comparability of data: using the ICF to map the contrasting definitions of disability in Irish surveys and census, 2000-2006.

PURPOSE: To examine how disability was measured and understood within Irish data sources 2000-2006, using the International Classification of Functioning, Disability and Health (ICF) as a guiding framework for a more comprehensive and transformative definition of disability. METHOD: During the EU-funded Measuring Health and Disability in Europe (MHADIE) project (2003-2006), an audit of data sources which included a disability identifier question was conducted. Thirty Irish data sources were examined in total. An overview of these data sources was provided in 'Disability Data Sources in Ireland' (National Disability Authority, unpublished, 2007). Using guidelines developed by Cieza et al. (J Rehabil Med 2002;34:205-210, J Rehabil Med 2002;27:212-218) five data sources were selected for detailed examination and were mapped to the ICF. These were the census (2006), National Disability Survey (2006), National Physical and Sensory Disability Database (2006), Survey of Lifestyles, Attitudes and Nutrition (2002), Euro Student Survey (2003). Subsequent work conducted after the completion of the MHADIE project added to the findings. RESULTS AND CONCLUSIONS: The environmental dimension of disability dominated the data collection exercises which used the ICF as their framework-for the National Disability Survey (NDS) and the National Physical and Sensory Disability Database (NPSDD). Both also had strong focus on activity and participation. When mapped on to the ICF, the data sources which preceded the ICF or did not use it, are shown to focus more on activity and participation data than any other ICF component. Across the five selected data sources, limited information was collected on body function and body structure.

Increased urinary 8-hydroxy-2'-deoxyguanosine excretion in long-distance bus drivers in Taiwan.

Professional bus drivers are exposed to environments containing air pollution and reactive oxygen species (ROS) that can induce cellular oxidative stress and DNA damage. This study investigated environmental factors associated with oxidative DNA damage in a cohort of long-distance bus drivers. In a comparison study, urinary 8-hydroxydeoxyguanosine (8-OHdG), a biomarker of DNA oxidative damage, was examined in 120 male long-distance bus drivers and 58 male office workers in Taiwan. Multivariate logistic regression was used to analyze association between urinary 8-OHdG levels and environmental factors. Bus drivers had higher urinary 8-OHdG levels (adjusted odds ratio (aOR)=9.4, 95% confidence interval (CI)=3.5-28.2) compared with office workers. Increased urinary 8-OHdG level was significantly related to cigarette smoking (aOR=18.0, 95% CI=7.1-52.1), consumption of energy drinks (aOR=5.0, 95% CI=2.1-12.6), and regular exercise (aOR=3.8, 95% CI=1.5-10.2). A strong exposure-response relationship was found between urinary 8-OHdG and urinary cotinine (p<0.0001). Among nonsmokers, bus drivers (aOR=3.9, 95% CI=1.0-17.7) had higher urinary 8-OHdG than office workers. Among both bus drivers and office workers, those who drank energy drinks (aOR=3.7, 95% CI=1.2-12.2) had higher 8-OHdG levels than those who did not drink energy drinks. Adjusted for smoking, levels of 8-OHdG were increased in long-distance bus drivers exposed to traffic exhaust and ingested energy drinks. Future studies should explore what aspects of energy drinks may contribute to increased urinary 8-OHdG.

Barriers, activities and participation: incorporating ICF into service planning datasets.

PURPOSE: Guided by the World Health Organization's International Classification of Functioning, Disability and Health (ICF), a measure of activity and participation (MAP) was developed and incorporated into the National Physical and Sensory Disability Database in Ireland. The aims of this article are to investigate and explore the relationship between the barriers, participation restriction and functioning levels experienced by people with disabilities. METHOD: Seven thousand five hundred and sixty-two personal interviews with people meeting specific eligibility criteria for registering onto the database were conducted across four health service executive regions in Ireland. RESULTS: Overall, differences in barriers, participation restriction and activity limitations experienced by people with different types of disabilities were found to be significant. Furthermore, low functioning and experience of barriers were indicators of participation restriction. CONCLUSIONS: This article has shown that elements of the ICF have been successfully operationalised in a service planning tool through the development of the MAP. This provides a more holistic view of disability and will enable the impact of service interventions to be measured over time.

The need to develop centers for environmental oncology.

The scale and scope of the cancer problem in the United States today is much greater than four decades ago when the formal war against the disease was first announced. Patterns of the disease are not fully explained by known risk factors. Much progress has been made in understanding the molecular basis of carcinogenesis, particularly the near consensus (realization) that virtually all cancers arise from an accumulation of genetic mutations and the more recent recognition of the role of inflammation and the tissue microenvironment, in particular for hormone-dependent cancers. However, most genetic mutations that contribute to cancer are not inherited, and thus must be attributable to accumulation of somatic mutations and epigenetic changes, from as yet poorly understood environmental factors, that certainly cannot be explained entirely by tobacco, use and arise over the course of a lifetime. Much of the national effort to control cancer has focused on detecting and treating the disease--not on seeking approaches to prevent cases from arising. Given this reality, we present a cross-disciplinary framework for establishing comprehensive research and policy centers focused on environmental oncology to be based at selected academic cancer centers across the country. The principal goal of such centers is to improve the ability to prevent cancer, by developing effective interventions based on insights obtained from epidemiology, including molecular epidemiology and basic scientific research on genomic, metabolomic, and other biomarkers of exposure, susceptibility, and disease. As the needed scientific evidence for environmental factors contributing to cancer is revealed, these academic centers will develop specific interventions and/or policy recommendations regarding ways to lower the burden of cancer, based on existing information about cancer hazards in the personal, occupational, and general environment. Ultimately the centers will improve the ability to identify and control the underlying causes of the occurrence of cancer and its progression.

Personal care products that contain estrogens or xenoestrogens may increase breast cancer risk.

Established models of breast cancer risk, such as the Gail model, do not account for patterns of the disease in women under the age of 35, especially in African Americans. With the possible exceptions of ionizing radiation or inheriting a known genetic mutation, most of the known risk factors for breast cancer are related to cumulative lifetime exposure to estrogens. Increased risk of breast cancer has been associated with earlier onset of menses or later age at menopause, nulliparity or late first parity, use of hormonal contraceptives or hormone replacement therapy, shorter lactation history, exposure to light at night, obesity, and regular ingestion of alcohol, all of which increase circulating levels of unbound estradiol. Among African Americans at all ages, use of hormone-containing personal care products (PCPs) is more common than among whites, as is premature appearance of secondary sexual characteristics among infants and toddlers. We hypothesize that the use of estrogen and other hormone-containing PCPs in young African American women accounts, in part, for their increased risk of breast cancer prior to menopause, by subjecting breast buds to elevated estrogen exposure during critical windows of vulnerability in utero and in early life. These early life and continuing exposures to estrogenic and xenoestrogenic agents may also contribute to the increased lethality of breast cancer in young women in general and in African American women of all ages. Public disclosure by manufacturers of proprietary hormonally active ingredients is required for this research to move forward.

Metastatic lung disease to the central nervous system: in vitro response to chemotherapeutic agents.

BACKGROUND: Metastatic lung disease to the central nervous system (CNS) comprises a significant percentage of cranial metastases. For those cases where chemotherapy may be of palliative or therapeutic benefit, in vitro chemoresponse testing may identify the agent(s) most likely to be effective clinically. METHODS: Tumor-derived cell cultures were established from 14 surgically excised lung lesions metastatic to the CNS. In vitro chemoresponse testing was performed with a variety of anticancer agents on the tumor cells that grew out of the cultured tissue specimens. Drug concentrations and exposure times were adjusted to bracket approximate average peak plasma levels that are observed typically in vivo. For each tumor-derived cell culture, a complete dose-response curve was established for each chemotherapeutic agent tested. RESULTS: Approximately 80% of the 14 tumor cell cultures had a definitive response to one or more chemotherapeutic agents in vitro, with approximately one-third of these cultures displaying a response to at least three of the drugs tested. There was considerable heterogeneity in the response of individual tumor cell cultures to the chemotherapeutic drugs. The agents that showed the highest cytotoxic response rate against the individual tumor cell cultures included lomustine, carboplatin, cisplatin and etoposide. CONCLUSIONS: The tumor cells isolated from individuals with lung lesions metastatic to the brain demonstrated differential chemoresponses to the agents tested. No single agent was effective against every tumor cell culture. These data suggest that in vitro chemoresponse testing of cultured tumor cells may be useful to identify biologically effective chemotherapeutic agents for individual patients, thereby addressing at least one factor in this complex therapeutic challenge.

Diversity oriented synthesis and branching reaction pathway to generate natural product-like compounds.

Combinatorial chemistry can be used to synthesize diversified molecules on a large scale. As with all large-scale experiments, this process requires a major investment in equipment, consumables and time. Therefore, careful design is critical. As the complexity of the libraries to be generated increases, additional considerations become important. What are the issues that should be considered when planning combinatorial chemistry projects? Which features in the design strategy are critical to consider ensuring that all of the potential products will be synthesized? How are the reactants selected to optimize product synthesis and yield? Over the last several years, through an experimental process, we have successfully developed and optimized our synthetic strategy. Our approach incorporates a number of critical components into a tightly controlled process that generates molecules with maximal structural complexity. This complexity emanates from carbon-carbon bond formation, which is extremely stable and it is reminiscent of complex natural product molecules. Our studies have illustrated that transition metal catalysts are powerful reagents that can be used to drive the synthesis of diverse small molecules from less complex starting materials. In this review, we will describe some of our recent efforts to synthesize natural product-like molecules and their derivative structures to successfully create libraries of complex molecules for drug discovery applications. Our diversity-oriented synthesis methods incorporate transition metal catalysts, as a versatile tool for creating carbon-carbon bonds and structural complexity, and the branched reaction pathway, as a method for incorporating diversity into the molecular scaffolds. We will review our combinatorial chemistry program, focusing on the decisions that we made for (1) the scaffold selection; (2) the design of a diversity oriented approach for library synthesis; (3) the incorporation of the branched reaction pathway to generate natural product-like molecules from the same starting material; and (4) the process steps that we selected for chemistry development and library generation.