Seizure clusters, treatment patterns, and healthcare resource utilization in patients with epilepsy: A Wisconsin-based claims analysis.

BACKGROUND: Seizure clusters are underresearched and associated with adverse outcomes in patients with epilepsy. This study was a noninterventional, retrospective claims-based analysis using the Wisconsin Health Information Organization (WHIO) All-Payer Claims Database to characterize the epilepsy population in Wisconsin, with a focus on prevalence, treatment patterns, and healthcare resource utilization (HCRU) in patients with seizure clusters prior to the introduction of nasal spray rescue medications. This timeframe allows characterization of a historical baseline for future comparisons with newer treatments. METHODS: Four cohorts were defined: (1) all-epilepsy (all patients with epilepsy); and subcohorts of: (2) patients receiving a monotherapy antiseizure medication (ASM); (3) patients receiving ASM polytherapy; and (4) patients treated for seizure clusters (ie, those taking rescue medications and ≥ 1 ASM). Primary outcomes were HCRU over a 12-month follow-up period, which were descriptively analyzed. RESULTS: Between 2017 and 2019, 16,384 patients were included in the all-epilepsy cohort; 11,688 (71.3 %) were on monotherapy, 3,849 (23.5 %) were on polytherapy, and 526 (3.2 %) were treated for seizure clusters. Twelve-month retentions to the ASM treatments were 46.7 % (7,895/16,904) in the all-epilepsy cohort, and 40.0 % (4,679/11,688) and 40.1 % (1,544/3,849) in the monotherapy and polytherapy subcohorts, respectively. Rescue medication prescriptions were obtained 1,029 times by the 526 patients in the treated seizure cluster subcohort, with infrequent refill rates (mean 1.6-1.9 times/year). A higher proportion of patients in the treated seizure cluster subcohort had epilepsy-related outpatient visits (89.7 %), other visits (71.3 %), and hospitalizations (25.3 %) than patients in the monotherapy (72.2 %, 50.2 %, 19.3 %, respectively) and polytherapy (83.3 %, 63.3 %, 22.8 %, respectively) subcohorts. Mean (standard deviation) all-cause ($114,717 [$231,667]) and epilepsy-related ($76,134 [$204,930]) costs over 12 months were higher in the treated seizure cluster subcohort than the monotherapy ($89,324 [$220,181] and $30,745 [$145,977], respectively) and polytherapy ($101,506 [$152,931] and $49,383 [$96,285], respectively) subcohorts. CONCLUSIONS: Patients treated for seizure clusters incurred higher all-cause and epilepsy-related costs and epilepsy-related HCRU than other subcohorts and had infrequent rescue medication refills. The findings of this analysis highlight the need for appropriate treatment for those patients with epilepsy experiencing seizure clusters. The effect of newer rescue medications to alter these findings will be explored in a follow-up study. Regardless, specialist providers with expertise in treating refractory epilepsy and seizure cluster patients may help to reduce the burden of seizure clusters.

Population-Level Disease Prevalence Rates Correlate With COVID-19 Mortality.

INTRODUCTION: Initial reports identified preexisting conditions associated with COVID-19 mortality risk. The Centers for Disease Control and Prevention (CDC) 500 Cities Project provides prevalence rate estimates at the census tract level for these conditions. The frequency of these individual condition prevalence rates may associate with the census tracts with greater risk of COVID-19 deaths. OBJECTIVE/RESEARCH QUESTION: Can the census tract-level outcome of Milwaukee County COVID-19 death rates correlate with the census tract-level COVID-19 individual mortality risk condition prevalence rates? METHODS: This study used the 296 Milwaukee County, Wisconsin census tracts' COVID-19 death rates per 100,000 lives to perform a linear regression with individual COVID-19 mortality risk condition prevalence rates, obtained from the CDC's 500 Cities Project, and a multiple regression with 7 condition prevalence rates. The Milwaukee County Medical Examiner provided census tract identified deaths from COVID-19 from March 2020 through May 2020. Crude death rates for these 3 months per 100,000 population were analyzed in a multiple linear regression versus prevalence rates for these conditions in each census tract. RESULTS: There were 295 assessable COVID-19-related deaths in Milwaukee County in early 2020. The model of crude death rates showed statistical significance with the condition prevalence rates in Milwaukee County. A regression analysis of each condition's prevalence rate showed no association with crude death rates. CONCLUSIONS: This study supports a correlation between high COVID-19 mortality rate census tracts and prevalence rate estimates of conditions associated with high individual COVID-19 mortality rates. The study is limited by the small COVID-19 death sample and the use of a single location. The ability to focus COVID-19 health promotion may save future lives if mitigation strategies are applied extensively in these neighborhoods.

Neighborhood Condition Prevalence Rates Correlate With COVID-19 Mortality in Milwaukee County, Wisconsin.

Purpose: We sought to determine if census tract-level (ie, neighborhood) COVID-19 death rates in Milwaukee County correlated with the census tract-level condition prevalence rates (CPRs) for individual COVID-19 mortality risk. Methods: This study used Milwaukee County-reported COVID-19 death rates per 100,000 lives for the 296 census tracts within the county to perform a linear regression with individual COVID-19 mortality risk CPR, mean age, racial composition of census tract (by percentage of non-White residents), and poverty (by percentage within census tract), followed by multiple regression with all 7 CPRs as well as the 7 CPRs combined with the additional demographic variables. CPR estimates were accessed from the Centers for Disease Control and Prevention 500 Cities Project. Demographics were accessed from the U.S. Census. The Milwaukee County Medical Examiner's office identified 898 deaths from COVID-19 in Milwaukee County from March 2020 to June 2021. Results: Among the variables included, crude death rate demonstrated a statistically significant association with the 7 COVID-19 mortality risk CPRs (as analyzed collectively), census tract mean age, and several of the CPRs individually. The addition of census tract age, race, and poverty in multiple regression did not improve the association of the 7 CPRs with crude death rate. Conclusions: Results from this population-level study indicated that census tracts with high COVID-19 mortality correlated with high-risk condition prevalence estimates within those census tracts, illustrating how health data collection and analysis at a census tract level could be helpful when planning pandemic-mitigating public health efforts.

Caffeine consumption within British fencing athletes.

The ergogenic effects of caffeine are well documented, yet despite the potential benefits of supplementation, there is a lack of understanding of caffeine habits and supplementation within fencing. British fencers (n = 136) completed a Web-based questionnaire, exploring self-reported caffeine consumption, reasons for use and education. Fencers (94.1%) habitually consumed caffeine, primarily due to the taste of the products (93.8%). Respondents ingested 183.4 ± 137.5 mg of caffeine daily, with a significant difference between age groups (p < 0.05). Many respondents (30.1%) consumed caffeine 60 mins prior/during fencing training and/or competition with the main reason highlighted as cognitive performance enhancement. Respondents ingested 140.8 ± 104.6 mg of caffeine during training/competition, mainly as energy drinks, bars, and powders. Education on caffeine supplementation was low (25.7%), with significant associations between age groups (p < 0.05). Evidence implies caffeine toxicity has been experienced by 35% of fencers, highlighting the need for education on caffeine consumption. To conclude there is evidence of caffeine supplementation in fencing, primarily to magnify cognitive performance. However, there is a requirement for targeted education on caffeine supplementation to fencers, so that negative side effects and potential anti-doping infringements can be avoided.

Neoadjuvant immunoradiotherapy results in high rate of complete pathological response and clinical to pathological downstaging in locally advanced head and neck squamous cell carcinoma.

BACKGROUND: Checkpoint inhibitors targeting programmed death receptor-1 (PD-1) have been tested in the neoadjuvant setting for the treatment of locoregionally advanced head and neck squamous cell carcinoma (HNSCC); however, response rates are modest. We hypothesized that adding stereotactic body radiation therapy (SBRT) to anti-PD-1 would be safe prior to definitive surgical resection and would enhance pathological response compared with historical cohorts of patients with locoregionally advanced HNSCC treated with checkpoint inhibitor alone. METHODS: The Neoadjuvant Immuno-Radiotherapy Trial was an investigator-initiated single institution phase Ib clinical trial that enrolled patients with previously untreated locally advanced HPV-positive and HPV-negative HNSCC between 2018 and 2019. Eligible patients were treated with neoadjuvant SBRT at a total dose of either 40 Gy in 5 fractions or 24 Gy in 3 fractions, delivered in a 1-week timespan, with or without nivolumab, prior to definitive surgical resection. Patients were then planned for treatment with adjuvant nivolumab for 3 months. The primary safety endpoint was unplanned delay in surgery considered to be at least possibly related to neoadjuvant treatment. The primary efficacy endpoints included pathological complete response (pCR), major pathological response (mPR), and the rate of clinical to pathological downstaging after neoadjuvant treatment. RESULTS: Twenty-one patients underwent neoadjuvant treatment, which was well tolerated and did not delay surgery, thus meeting the primary endpoint. Tissue responses were characterized by robust inflammatory infiltrates in the regression bed, plasma cells and cholesterol clefts. Among the entire study group, the mPR and pCR rate was 86% and 67%, respectively. Clinical to pathological downstaging occurred in 90% of the patients treated. CONCLUSION: These data demonstrate that radiation delivered only to the gross tumor volume combined with immunotherapy was safe, resulted in a high rate of mPR and should be further evaluated as a locally focused neoadjuvant therapy for patients with head and neck cancer. TRIAL REGISTRATION NUMBER: This study is registered with clinicaltrials.gov (NCT03247712) and is active, but closed to patient accrual.

Enhancing clinical and immunological effects of anti-PD-1 with belapectin, a galectin-3 inhibitor.

BACKGROUND: PD-1/PD-L1 engagement and overexpression of galectin-3 (Gal-3) are critical mechanisms of tumor-induced immune suppression that contribute to immunotherapy resistance. We hypothesized that Gal-3 blockade with belapectin (GR-MD-02) plus anti-PD-1 (pembrolizumab) would enhance tumor response in patients with metastatic melanoma (MM) and head and neck squamous cell carcinoma (HNSCC). METHODS: We performed a phase I dose escalation study of belapectin+pembrolizumab in patients with advanced MM or HNSCC (NCT02575404). Belapectin was administered at 2, 4, or 8 mg/kg IV 60 min before pembrolizumab (200 mg IV every 3 weeks for five cycles). Responding patients continued pembrolizumab monotherapy for up to 17 cycles. Main eligibility requirements were a functional Eastern Cooperative Oncology Group status of 0-2, measurable or assessable disease, and no active autoimmune disease. Prior T-cell checkpoint antibody therapy was permitted. RESULTS: Objective response was observed in 50% of MM (7/14) and and 33% of HNSCC (2/6) patients. Belapectin+pembrolizumab was associated with fewer immune-mediated adverse events than anticipated with pembrolizumab monotherapy. There were no dose-limiting toxicities for belapectin within the dose range investigated. Significantly increased effector memory T-cell activation and reduced monocytic myeloid-derived suppressor cells (M-MDSCs) were observed in responders compared with non-responders. Increased baseline expression of Gal-3+ tumor cells and PD-1+CD8+ T cells in the periphery correlated with response as did higher serum trough levels of pembrolizumab. CONCLUSIONS: Belapectin+pembrolizumab therapy has activity in MM and HNSCC. Increased Gal-3 expression, expansion of effector memory T cells, and decreased M-MDSCs correlated with clinical response. Further investigation is planned.

The COVID-19 pandemic and global environmental change: Emerging research needs.

The outbreak of COVID-19 raised numerous questions on the interactions between the occurrence of new infections, the environment, climate and health. The European Union requested the H2020 HERA project which aims at setting priorities in research on environment, climate and health, to identify relevant research needs regarding Covid-19. The emergence and spread of SARS-CoV-2 appears to be related to urbanization, habitat destruction, live animal trade, intensive livestock farming and global travel. The contribution of climate and air pollution requires additional studies. Importantly, the severity of COVID-19 depends on the interactions between the viral infection, ageing and chronic diseases such as metabolic, respiratory and cardiovascular diseases and obesity which are themselves influenced by environmental stressors. The mechanisms of these interactions deserve additional scrutiny. Both the pandemic and the social response to the disease have elicited an array of behavioural and societal changes that may remain long after the pandemic and that may have long term health effects including on mental health. Recovery plans are currently being discussed or implemented and the environmental and health impacts of those plans are not clearly foreseen. Clearly, COVID-19 will have a long-lasting impact on the environmental health field and will open new research perspectives and policy needs.

Encouraging and Enabling Lifestyles and Behaviours to Simultaneously Promote Environmental Sustainability, Health and Equity: Key Policy Messages from INHERIT.

Human consumption and activity are damaging the global ecosystem and the resources on which we rely for health, well-being and survival. The COVID-19 crisis is yet another manifestation of the urgent need to transition to more sustainable societies, further exposing the weaknesses in health systems and the injustice in our societies. It also underlines that many of the factors leading to environmental degradation, ill health and social and health inequities are interlinked. The current situation provides an unprecedented opportunity to invest in initiatives that address these common factors and encourage people to live more healthily and sustainably. Such initiatives can generate the positive feedback loops needed to change the systems and structures that shape our lives. INHERIT (January 2016-December 2019), an ambitious, multisectoral and transnational research project that involved 18 organisations across Europe, funded by the European Commission, explored such solutions. It identified, defined and analysed promising inter-sectoral policies, practices and approaches to simultaneously promote environmental sustainability, protect and promote health and contribute to health equity (the INHERIT "triple-win") and that can encourage and enable people to live, move and consume more healthfully and sustainably. It also explored the facilitators and barriers to working across sectors and in public private cooperation. The insights were brought together in guidelines setting out how policy makers can help instigate and support local "triple-win" initiatives that influence behaviours as an approach to contributing to the change that is so urgently needed to stem environmental degradation and the interlinked threats to health and wellbeing. This article sets out this guidance, providing timely insights on how to "build back better" in the post pandemic era.

Retrospective Analysis of Route Selection for Hysterectomy for Benign Indications at Ochsner Baptist Hospital.

Background: Hysterectomy, the most common gynecologic procedure in the United States, can be performed in a number of ways. A shift in surgical practice toward cost-effective and minimally invasive approaches provides an impetus to maximize early training in vaginal surgery for resident physicians. Methods: A total of 62 abdominal, 303 robotic, and 41 vaginal hysterectomies performed between January 1, 2015 and December 31, 2017 at Ochsner Baptist Hospital in New Orleans, LA, that met inclusion criteria were retrospectively reviewed with a previously published route selection algorithm. We applied the algorithm using preoperative and postoperative data collected via medical record review to determine if our practices favor minimally invasive approaches. Results: Analysis using preoperative variables identified 152 robotic cases that were vaginal hysterectomy candidates (50.2%). Postoperative analysis of the same cases identified 127 (41.9%) vaginal hysterectomy candidates. Among abdominal cases, 37 (59.7%) called for a less invasive approach by preoperative findings: 7 (11.3%) vaginal and 30 (48.4%) laparoscopic. The algorithm sorted only 25 of the 62 abdominal cases (40.3%) to the abdominal approach. Conclusion: Use of a hysterectomy route selection algorithm preoperatively improves identification of candidates for minimally invasive hysterectomy.

Urban Green Space: Creating a Triple Win for Environmental Sustainability, Health, and Health Equity through Behavior Change.

Urbanization, costs of green space maintenance, and diminishing connection between people and nature all exert pressures on urban green space. This is regrettable as green space has the potential to create wins for environmental sustainability, health, and health equity. This paper explores this potential triple win and investigates how to increase the use of urban green space through behavior change. A narrative literature review was conducted and was supplemented with literature suggested by experts. Results show that creating well-designed green spaces and stimulating people to use them can indeed deliver this triple win. Providing accessible, attractive, well-maintained green space with room for socialization, and where people feel safe, may increase the opportunity and motivation of people to use it more often. Informing and educating people and organizing activities may increase capability (and motivation) to use green space. Since the use of green space depends on life stage, lifestyle factors and individual values, it is important to involve potential users in its design. We recommend a specific focus on those groups who may benefit most from the use of green space. More evaluation is needed to inform effective green space interventions and to assess related economic, social, and environmental benefits.

Ten Lessons for Good Practice for the INHERIT Triple Win: Health, Equity, and Environmental Sustainability.

The world's challenges of climate change, damage to ecosystems, and social and health inequalities require changes in human behaviours at every level of organisation, among governments, business, communities, and individuals. An important question is how behaviour change can be enabled and supported at the scale and speed required. The research reported in this paper describes important lessons for good practice in changing contexts to modify behaviours for a triple win for health, equity and environmental sustainability. Authors synthesised learning from qualitative, quantitative and cost benefit evaluations of 15 case studies conducted in 12 countries in Europe. The case studies address ways of living (green spaces and energy efficient housing), moving (active transport) and consuming (healthy and sustainable diets) that support the triple win. Ten lessons for good practice were identified. These include bringing a triple win mindset to policy and practice in planning interventions, with potential to improve environmental sustainability, health and equity at the same time. The lessons for good practice are intended to support governmental and non-governmental actors, practitioners and researchers planning to work across sectors to achieve mutual benefits for health and environmental sustainability and in particular to benefit poorer and more socio-economically disadvantaged groups.

Clinical Pharmacokinetics of a Lipid-Based Formulation of Risperidone, VAL401: Analysis of a Single Dose in an Open-Label Trial of Late-Stage Cancer Patients.

BACKGROUND AND OBJECTIVES: A clinical trial was conducted to measure and analyse the pharmacokinetic parameters of a lipid formulation of risperidone, VAL401. The VAL401 formulation is designed to repurpose risperidone from an antipsychotic to an adenocarcinoma treatment, with the lipid formulation altering the cellular uptake of risperidone, thus enabling anticancer biology to be exhibited in preclinical testing. METHODS: This first human trial of VAL401 measured the concentrations of risperidone and its primary metabolite, 9-hydroxyrisperidone, in the blood of patients after treatment with a single 2-mg dose of VAL401. RESULTS: The trial provided information on differences in the pharmacokinetic profile of risperidone in VAL401 that may be caused by the formulation and/or the nature of the cancer patient population. VAL401 provided the following key pharmacokinetic parameters for the risperidone plasma concentration after a single 2-mg dose of VAL401, with results normalised to a dosage of 1 mg for comparison with literature values: Tmax, 2 h; Cmax, 8 ng/ml; half-life, 3.5 h; area under the plasma concentration-time curve from time zero to infinity (AUC0-∞), 58.2 ng h2/mL. CONCLUSIONS: Further comparisons of the pharmacokinetic parameters of risperidone and 9-hydroxyrisperidone in plasma of patients administered VAL401 and the corresponding parameters obtained from published data for conventionally formulated risperidone provide evidence for altered biological processing of VAL401 as compared to risperidone. The absolute values obtained provide support for future studies of VAL401 as a cancer treatment, as the Cmax demonstrates sufficient exposure to reach the concentrations seen during preclinical anticancer testing, yet the overall exposure to the active moiety supports the use of the safety and tolerability data from conventional risperidone during future clinical trials.

How Good Is our Place-Implementation of the Place Standard Tool in North Macedonia.

This study describes the implementation, in North Macedonia, of a "tool", initially devised in Scotland, to generate community and stakeholder discussion about the places in which they live and notably a place's capacity to generate health wellbeing and greater equity among citizens. In this study, the "place standard tool" (PST) is viewed from the perspective of creating places which can deliver a triple win of health and wellbeing, equity, and environmental sustainability. Skopje, North Macedonia's capital, inevitably differs economically, culturally, and politically from Scotland, thus providing an opportunity to augment existing knowledge on adaptability of the tool in shaping agendas for policy and action. Тhe PST was tested through seminars with selected focus groups and an online questionnaire. Over 350 respondents were included. Information on priorities enabled the distillation of suggestions for improvement and was shared with the Mayor and municipal administration. Skopje citizens valued an approach which solicited their views in a meaningful way. Specific concerns were expressed relating to heavy traffic and related air and noise pollution, and care and maintenance of places and care services. Responses varied by geographic location. Application of the PST increased knowledge and confidence levels among citizens and enthusiasm for active involvement in decision making. Effective implementation relies heavily on: good governance and top-level support; excellent organization and good timing; careful training of interviewers and focus group moderators; and on prior knowledge of the participants/respondents.

Making the Case for "Whole System" Approaches: Integrating Public Health and Housing.

Housing conditions have been an enduring focus for public health activity throughout the modern public health era. However, the nature of the housing and health challenge has changed in response to an evolution in the understanding of the diverse factors influencing public health. Today, the traditional public health emphasis on the type and quality of housing merges with other wider determinants of health. These include the neighbourhood, community, and "place" where a house is located, but also the policies which make access to a healthy house possible and affordable for everyone. Encouragingly, these approaches to policy and action on housing have the potential to contribute to the "triple win" of health and well-being, equity, and environmental sustainability. However, more effective housing policies (and in public health in general) that adopt more systemic approaches to addressing the complex interactions between health, housing, and wider environment are needed. This paper illustrates some of the key components of the housing and health challenge in developed countries, and presents a conceptual model to co-ordinate activities that can deliver the "triple win." This is achieved by offering a perspective on how to navigate more effectively, inclusively and across sectors when identifying sustainable housing interventions.

The INHERIT Model: A Tool to Jointly Improve Health, Environmental Sustainability and Health Equity through Behavior and Lifestyle Change.

The need for analysis and action across the interrelated domains of human behaviors and lifestyles, environmental sustainability, health and inequality is increasingly apparent. Currently, these areas are often not considered in conjunction when developing policies or interventions, introducing the potential for suboptimal or conflicting outcomes. The INHERIT model has been developed within the EU-funded project INHERIT as a tool to guide thinking and intersectoral action towards changing the behaviors and lifestyles that play such an important role in today’s multidisciplinary challenges. The model integrates ecological public health and behavioral change models, emphasizing inequalities and those parts of the causal process that are influenced by human behaviors and lifestyles. The model was developed through web-based and live discussions with experts and policy stakeholders. To test the model’s usability, the model was applied to aspects of food consumption. This paper shows that the INHERIT model can serve as a tool to identify opportunities for change in important −food-related behaviors and lifestyles and to examine how they impact on health, health inequalities, and the environment in Europe and beyond. The INHERIT model helps clarify these interrelated domains, creating new opportunities to improve environmental health and health inequality, while taking our planetary boundaries into consideration.

Facilitating Factors and Barriers to Weight Management in Women: Physician Perspectives.

PURPOSE: The complexity of addressing overweight and obesity in women has been an ongoing public health and health care challenge. While the mechanism for addressing overweight and obesity in women remains unclear, it has been speculated that disparities in overweight and obesity by race and gender contribute to the complexity. The purpose of the present study was to examine perceptions of primary care physicians when discussing weight management with their patients. METHODS: We conducted focus group discussions exploring facilitators and barriers to discussing weight management and weight loss among women patients. Participants included 18 family medicine and internal medicine physicians who were recruited using a snowball sampling technique from two large urban institutions. Focus group discussions were transcribed verbatim. Responses were then codified and analyzed in frequency of occurrence using specialized computer software. RESULTS: Nine themes emerged from group discussions. These recurring themes reflected three overarching critical points: 1) potential utility of the primary care setting to address weight management; 2) the importance of positive patient-provider communication in supporting weight loss efforts; and 3) acknowledgement of motivation as intrinsic or extrinsic, and its role in obesity treatment. CONCLUSIONS: Physician perceptions of their own lack of education or training and their inability to influence patient behaviors play crucial roles in discussing weight management with patients.

Patient Barriers for Weight Management Among African American Women.

PURPOSE: The primary aim of this study was to assess the perceptions of local African American women who are overweight or obese using semi-structured focus groups to identify barriers to weight management and factors that support strategy success. The secondary aim of this study was to determine recommendations for patient-centered weight management interventions established specifically for African American women in the Milwaukee-area community. METHODS: Three semi-structured focus groups to explore barriers to weight management were performed among women patients. Participants (N=41) were recruited via email, postal mail, and phone as available from an academic medical center in Milwaukee, Wisconsin. Focus group discussions were transcribed verbatim, reviewed by the study team, and coded based on recurring themes within and across interviews. Responses were analyzed by frequency of occurrence using qualitative computer software. RESULTS: Five primary barriers to weight management were identified from focus groups: food choices, lifestyle changes, social support, locus of control, and health education. Based on participant reports, improvements to present practice and health literacy for patients may be merited. There was expressed interest by patients for being involved in future research and development of patient-centered interventions. CONCLUSIONS: This study provides support for the use of a community-based participatory research approach in determining appropriate considerations for weight management interventions suitable for this patient population. Future research should include stakeholders not included in this study, such as community organization leaders, and primary care physicians to develop a refined intervention targeting the primary barriers to weight management.

Scoping the proximal and distal dimensions of climate change on health and wellbeing.

The impacts of climate on health and wellbeing occur in time and space and through a range of indirect, complicated mechanisms. This diversity of pathways has major implications for national public health planning and influence on interventions that might help to mitigate and adapt to rapidly changing environmental conditions, nationally and internationally. This paper draws upon evidence from public health and adverse impact studies across climate science, hydrology, agriculture, public health, and the social sciences. It presents a conceptual model to support decision-making by recognizing both the proximal and distal pathways from climate-induced environmental change to national health and wellbeing. The proximal and distal pathways associated with food security, migration and mobility illustrate the diverse climate change influences in different geographic locations over different timescales. We argue that greater realization and articulation of proximal and distal pathways should radically alter how climate change is addressed as a national and international public health challenge.