Inequity in cardiometabolic hospital admissions and blood screening in New Zealand Indigenous Maori with psychosis.

BACKGROUND: People with psychosis experience worse cardiometabolic health than the same-aged general population. In New Zealand, Indigenous Maori experiencing psychosis have greater risk of cardiometabolic and other physical health problems. AIMS: To identify a cohort of adults accessing secondary mental health and addiction services in New Zealand, with a previous psychosis diagnosis as of 1 January 2018, and compare odds of hospital admission outcomes, mortality and receipt of cardiometabolic blood screening between Maori and non-Maori in the following 2 years. METHOD: Crude and adjusted logistic regression models compared odds of hospital admission outcomes, mortality and receipt of cardiometabolic blood screening (lipids and haemoglobin A1c) between Maori and non-Maori, occurring between 1 January 2018 and 31 December 2019. RESULTS: A cohort (N = 21 214) of Maori (n = 7274) and non-Maori (n = 13 940) was identified. Maori had higher adjusted risk of mortality (odds ratio 1.26, 95% CI 1.03-1.54), and hospital admission with diabetes (odds ratio 1.64, 95% CI 1.43-1.87), cardiovascular disease (odds ratio 1.54, 95% CI 1.25-1.88) and any physical health condition (odds ratio 1.07, 95% CI 1.00-1.15) than non-Maori. Around a third of people did not receive recommended cardiometabolic blood screening, with no difference between Maori and non-Maori after covariate adjustment. CONCLUSIONS: Maori experiencing psychosis are more likely to die and be admitted to hospital with cardiovascular disease or diabetes than non-Maori. Because of the higher cardiometabolic risk borne by Maori, it is suggested that cardiometabolic screening shortfalls will lead to worsening physical health inequities for Maori experiencing psychosis.

Blood cancer incidence, mortality and survival for Maori in New Zealand.

BACKGROUND: Haematological ('blood') cancers are a diverse group of non-solid cancers with varying incidence, mortality and survival. While there is some evidence that Maori experience disparities in blood cancer outcomes relative to New Zealand's majority European population, there is a need for a comprehensive overview of the current state of evidence in this context. METHODS: Blood cancer registrations were derived from the NZ Cancer Registry for the 2007-2019 period (combined blood cancers: 2653 Maori, 20,458 Europeans), and linked to Mortality records. We calculated age-sex-standardised incidence and mortality rates, and conducted cancer-specific survival analysis, for four main categories of blood cancers (leukaemia, Hodgkin lymphoma, non-Hodgkin lymphoma and myeloma) as well as for sub-types of leukaemia non-Hodgkin lymphoma. RESULTS: We found that Maori are more likely to be diagnosed with (incidence) and to die from (mortality) both leukaemia and myeloma, and similarly likely to be diagnosed or die from Hodgkin and non-Hodgkin lymphoma, compared to Europeans. Maori had demonstrably poorer cancer-specific survival outcomes across most blood cancer types (age-sex-adjusted hazard ratios [HRs], Maori vs European: leukaemia 1.77, 95 % CI 1.57-2.00; Hodgkin lymphoma 1.18, 95 % CI 0.65-2.16; non-Hodgkin lymphoma 1.71, 95 % CI 1.50-1.95; myeloma 1.40, 95 % CI 1.19-1.64). CONCLUSION: Blood cancers are a common cancer type for Maori, and we found evidence of disparities in incidence, mortality and survival compared to Europeans. Further research is required to further pinpoint exactly where interventions should be aimed to reduce blood cancer incidence and address survival disparities for Maori.

Metabolic Dysfunction in New-Onset Idiopathic Intracranial Hypertension: Identification of Novel Biomarkers.

OBJECTIVE: Idiopathic intracranial hypertension (IIH) is a neurometabolic disease with an increasing incidence. The pathophysiology is unknown, but improvement of diagnosis and management requires discovery of novel biomarkers. Our objective was to identify such candidate biomarkers in IIH, and secondarily, test for associations between identified metabolites and disease severity. METHODS: This is a prospective case-control study with collection of cerebrospinal fluid (CSF), serum, and clinical data from new-onset, treatment-naïve patients with IIH (n = 60). Patients were included consecutively from 2 tertiary headache centers in Denmark, and age, sex, and body mass index (BMI) -matched healthy controls (n = 35) were recruited. Clinical data were retrieved at ocular remission (n = 55). Samples were analyzed using non-targeted mass spectrometry. RESULTS: Serum sphingosine 1-phosphate (S1P), adenosine, and glutamate were 0.46-fold (q < 0.0001), 0.25-fold (q = 0.0048), and 0.44-fold (q < 0.0001) lower, respectively, in IIH. CSF stearoyl-lysophosphatidylcholine (LysoPC-18) and 2-palmitoyl-lysophosphatidylcholine (LysoPC-16) were 0.42 (q = 0.0025) and 0.37 (q < 0.001) -fold lower. LysoPC-18 was higher in patients with moderate-severe versus mild papilledema (p = 0.022). LysoPC-18 correlated positively with retinal nerve fiber layer thickness (p = 0.0012, r = 0.42) and inversely with mean deviation on automated perimetry (p = 0.01, r = -0.35). Higher baseline serum S1P (p = 0.018) and lower CSF LysoPC-16 (p = 0.003) were associated with optic nerve atrophy at ocular remission. Pathway analysis suggests dysregulated lipid metabolism and redox disturbances in new-onset IIH. INTERPRETATION: We identify perturbed metabolism in new-onset IIH. S1P and LysoPC-16 demonstrate potential prognostic value due to association with subsequent optic nerve atrophy. This association between specific, differential metabolites and outcome provides substantial evidence for novel biomarkers of clinical significance that should be the focus of further targeted studies. ANN NEUROL 2024;96:595-607.

The physical health and premature mortality of Indigenous Maori following first-episode psychosis diagnosis: A 15-year follow-up study.

BACKGROUND: People experiencing psychosis are at greater risk of physical health conditions and premature mortality. It is likely that Indigenous Maori youth, who experience additional systemic inequities caused by settler-colonisation, face even greater physical health and mortality risks following a diagnosis of first-episode psychosis. OBJECTIVE: Compare Maori and non-Maori for risk of hospitalisation and mortality for up to 15 years following first-episode psychosis diagnosis. METHODS: A cohort (N = 14,122) of young people (16-24 years) with first-episode psychosis diagnosis between 2001 and 2019 were identified. Using crude Kaplan-Meier and adjusted Cox proportional hazards models, Maori (n = 5211) and non-Maori (n = 8911) were compared on hospitalisation and mortality outcomes for up to 15 years. RESULTS: In the 15 years following first-episode psychosis diagnosis, Maori had higher adjusted risk of all-cause mortality (hazard ratio = 1.21, 95% confidence interval = [1.01, 1.45]), hospitalisation with diabetes (hazard ratio = 1.44, 95% confidence interval = [1.15, 1.79]), injury/poisoning (hazard ratio = 1.11, 95% confidence interval = [1.05, 1.16]), general physical health conditions (hazard ratio = 1.07, 95% confidence interval = [1.02, 1.13]) and also appeared to be at greater risk of cardiovascular hospitalisations (hazard ratio = 1.34, 95% confidence interval = [0.97, 1.86]). Kaplan-Meier plots show hospitalisation and mortality inequities emerging approximately 4-7 years following first-episode psychosis diagnosis. CONCLUSIONS: Maori are at greater risk for hospitalisation and premature mortality outcomes following first-episode psychosis. Early screening and intervention, facilitated by culturally safe health service delivery, is needed to target these inequities early.

Maori Medical Student and Physician Exposure to Racism, Discrimination, Harassment, and Bullying.

Importance: Discrimination, bullying, and harassment in medicine have been reported internationally, but exposures for Indigenous medical students and physicians, and for racism specifically, remain less examined. Objective: To examine the prevalence of racism, discrimination, bullying, and harassment for Maori medical students and physicians in New Zealand and associations with demographic and clinical characteristics. Design, Setting, and Participants: This cross-sectional study used data from an anonymous national survey of Maori medical students and physicians in New Zealand in late 2021 and early 2022. Data were analyzed from March 2022 to April 2024. Exposures: Age, gender, marginalized status (ie, in addition to being Maori, belonging to other groups traditionally marginalized or underrepresented in medicine), year of medical school, year of graduation, and main work role. Main Outcomes and Measures: Direct and witnessed racism, discrimination, bullying, and harassment were measured as any experience in the last year and ever. Any exposure to negative comments about social groups and witnessing discriminatory treatment toward Maori patients or whanau (extended family). Considering leaving medicine, including because of mistreatment, was measured. Results: Overall, 205 Maori medical students (median [IQR] age, 23.1 [21.6-24.3] years; 137 [67.2%] women) and 200 physicians (median [IQR] age, 36.6 [30.1-45.3] years; 123 [62.8%] women) responded. Direct and witnessed exposure to racism (184 students [91.5%]; 176 physicians [90.7%]) and discrimination (176 students [85.9%]; 179 physicians [89.5%]) ever in medical education, training, or work environments was common. Ever exposure to witnessed and direct bullying (123 students [66.5%]; 150 physicians [89.3%]) and harassment (73 students [39.5%]; 112 physicians [66.7%]) was also common. Most respondents reported witnessing Maori patients or their whanau being treated badly in clinical settings, in direct interactions (67 students [57.8%]; 112 physicians [58.9%]) or behind their backs (87 students [75.0%]; 138 physicians [72.6%]). One-quarter of Maori medical students (45 students), and 37.0% of physicians (61 physicians) had considered leaving or taken a break from medicine because of these experiences. Additional marginalized statuses were significantly associated with any direct experience of mistreatment in the last year for students and physicians. Exposure to some forms of mistreatment were also significantly associated with higher likelihood of thinking about leaving or taking a break from medicine for physicians. Conclusions and Relevance: In this study, Maori medical students and physicians reported high exposure to multiple forms of racism, discrimination, bullying, and harassment in medical education, training, and work environments, requiring an urgent response from medical institutions.

Racism and Health Among Aotearoa New Zealand Young People Aged 15-24 years: Analysis of Multiple National Surveys.

PURPOSE: This Aotearoa New Zealand-based study addresses a gap in literature focusing on individual experiences of racism among adolescents and young adults and its links to health. METHODS: This cross-sectional study uses data from multiple instances of the New Zealand Health Survey (2002/03, 2006/07, 2011/12, 2016/17) and General Social Survey (2008-2016) restricted to participants aged 15-24 years. Prevalence of reported experiences of racism are estimated. Meta-analytic techniques to pool data and multiple regression analyses are used to examine associations between experiences of racism and outcomes measures (mental and physical health, general health and well-being, life satisfaction, inability to access health care, and identity). The study used an ethical co-design process between university researchers and a rangatahi Maori (Maori young people) partnership group. RESULTS: Racism was higher among Maori, Pacific, and Asian young people compared to European young people. Racism was associated with all negative health and well-being measures examined for young people, including negative mental and physical health measures (12-Item Short Form Survey, Kessler Psychological Distress Scale), lower self-rated health, negative life satisfaction, higher unmet need for primary care, and identity measures (feelings of not belonging in New Zealand, less able to express their identity). DISCUSSION: The results of this study are concerning. Non-European young people disproportionately bear the burden of racism in Aotearoa New Zealand with a potentially substantial impact on their health and well-being. This is a breach of Indigenous (for Maori) and other international human rights and should be motivation to act to eliminate racism in all its forms.

Almost one in five emergency department presentations are by mental health clients: a secondary data analysis.

AIM: Mental health-related emergency department (ED) presentations are steadily increasing, including presentations for both mental health and non-mental health concerns by existing clients of mental health services. The study aim was to examine and compare mental health clients and non-clients' ED presentations, identify data and clinical gaps and make recommendations for improvement. METHOD: De-identified 2017/2018 ED data were used to describe presentations for current and recent (within last 5 years) clients of specialist public mental health and addiction services, compared to presentations of non-mental health clients. RESULTS: Of 49,170 presentations, 18% were by clients of mental health services. Compared to other ED presenters, mental health clients were often younger, female and Maori, required more urgent care and waited longer. Mental health-related International Classification of Diseases (ICD) codes/referrals were most common for presentations by current mental health clients, whereas pain and trauma were often the reason for prior mental health clients' presentations. Discharge diagnoses rarely included self-harm behaviour, and admissions for these clients were more commonly by ED rather than mental health services. CONCLUSION: Mental health clients are common in ED. Enhanced mental health data capture and improved systems and processes are needed to ensure that ED staff can better meet their often-complex needs.

Exposure to topiramate and acetazolamide causes endocrine disrupting effects in female rats during estrus.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a disease characterized by elevated intracranial pressure (ICP) and is a disease of young females. The first line pharmacological treatments include acetazolamide and topiramate and given the nature of IIH patients and the dosing regimen of these drugs, their effect on the endocrine system is important to evaluate. We aimed to assess the effects of acetazolamide and topiramate on steroid profiles in relevant endocrine tissues. METHODS: Female Sprague Dawley rats received chronic clinically equivalent doses of acetazolamide or topiramate by oral gavage and were sacrificed in estrus. Tissue specific steroid profiles of lateral ventricle CP, 4th ventricle CP, CSF, serum, uterine horn and fundus, ovaries, adrenal glands and pituitary glands were assessed by quantitative targeted LC-MS/MS. We determined luteinizing hormone (LH) and follicle stimulating hormones (FSH) levels in paired serum by ELISA. RESULTS: Topiramate increased the concentration of estradiol and decreased the concentration of DHEA in lateral choroid plexus. Moreover, it decreased the concentration of androstenediol in the pituitary gland. Topiramate increased serum LH. Acetazolamide decreased progesterone levels in serum and uterine fundus and increased corticosteroid levels in the adrenal glands. CONCLUSION: These results demonstrate that both acetazolamide and topiramate have endocrine disrupting effects in rats. Topiramate primarily targeted the choroid plexus and the pituitary gland while acetazolamide had broader systemic effects. Furthermore, topiramate predominantly targeted sex hormones, whereas acetazolamide widely affected all classes of hormones. A similar effect in humans has not yet been documented but these concerning findings warrants further investigations.

Tailored Prompting to Improve Adherence to Image-Based Dietary Assessment: Mixed Methods Study.

Background: Accurately assessing an individual's diet is vital in the management of personal nutrition and in the study of the effect of diet on health. Despite its importance, the tools available for dietary assessment remain either too imprecise, expensive, or burdensome for clinical or research use. Image-based methods offer a potential new tool to improve the reliability and accessibility of dietary assessment. Though promising, image-based methods are sensitive to adherence, as images cannot be captured from meals that have already been consumed. Adherence to image-based methods may be improved with appropriately timed prompting via text message. Objective: This study aimed to quantitatively examine the effect of prompt timing on adherence to an image-based dietary record and qualitatively explore the participant experience of dietary assessment in order to inform the design of a novel image-based dietary assessment tool. Methods: This study used a randomized crossover design to examine the intraindividual effect of 3 prompt settings on the number of images captured in an image-based dietary record. The prompt settings were control, where no prompts were sent; standard, where prompts were sent at 7:15 AM, 11:15 AM, and 5:15 PM for every participant; and tailored, where prompt timing was tailored to habitual meal times for each participant. Participants completed a text-based dietary record at baseline to determine the timing of tailored prompts. Participants were randomized to 1 of 6 study sequences, each with a unique order of the 3 prompt settings, with each 3-day image-based dietary record separated by a washout period of at least 7 days. The qualitative component comprised semistructured interviews and questionnaires exploring the experience of dietary assessment. Results: A total of 37 people were recruited, and 30 participants (11 male, 19 female; mean age 30, SD 10.8 years), completed all image-based dietary records. The image rate increased by 0.83 images per day in the standard setting compared to control (P=.23) and increased by 1.78 images per day in the tailored setting compared to control (P≤.001). We found that 13/21 (62%) of participants preferred to use the image-based dietary record versus the text-based dietary record but reported method-specific challenges with each method, particularly the inability to record via an image after a meal had been consumed. Conclusions: Tailored prompting improves adherence to image-based dietary assessment. Future image-based dietary assessment tools should use tailored prompting and offer both image-based and written input options to improve record completeness.

Cancer diagnosis after emergency presentations in people with mental health and substance use conditions: a national cohort study.

BACKGROUND: Cancer survival and mortality outcomes for people with mental health and substance use conditions (MHSUC) are worse than for people without MHSUC, which may be partly explained by poorer access to timely and appropriate healthcare, from screening and diagnosis through to treatment and follow-up. Access and quality of healthcare can be evaluated by comparing the proportion of people who receive a cancer diagnosis following an acute or emergency hospital admission (emergency presentation) across different population groups: those diagnosed with cancer following an emergency presentation have lower survival. METHODS: National mental health service use datasets (2002-2018) were linked to national cancer registry and hospitalisation data (2006-2018), to create a study population of people aged 15 years and older with one of four cancer diagnoses: lung, prostate, breast and colorectal. The exposure group included people with a history of mental health/addiction service contact within the five years before cancer diagnosis, with a subgroup of people with a diagnosis of bipolar disorder, schizophrenia or psychotic disorders. Marginal standardised rates were used to compare emergency presentations (hospital admission within 30 days of cancer diagnosis) in the exposure and comparison groups, adjusted for age, gender (for lung and colorectal cancers), ethnicity, area deprivation and stage at diagnosis. RESULTS: For all four cancers, the rates of emergency presentation in the fully adjusted models were significantly higher in people with a history of mental health/addiction service use than people without (lung cancer, RR 1.19, 95% CI 1.13, 1.24; prostate cancer RR 1.69, 95% CI 1.44, 1.93; breast cancer RR 1.42, 95% CI 1.14, 1.69; colorectal cancer 1.31, 95% CI 1.22, 1.39). Rates were substantially higher in those with a diagnosis of schizophrenia, bipolar disorder or psychotic disorders. CONCLUSIONS: Implementing pathways for earlier detection and diagnosis of cancers in people with MHSUC could reduce the rates of emergency presentation, with improved cancer survival outcomes. All health services, including cancer screening programmes, primary and secondary care, have a responsibility to ensure equitable access to healthcare for people with MHSUC.

Does diabetes affect breast cancer survival?

OBJECTIVES: The objective of this study is to investigate the influence of diabetes on breast cancer-specific survival among women with breast cancer in Aotearoa/New Zealand. METHODS: This study included women diagnosed with invasive breast cancer between 2005 and 2020, with their information documented in the Te Rehita Mate Utaetae-Breast Cancer Foundation National Register. Breast cancer survival curves for women with diabetes and those without diabetes were generated using the Kaplan-Meier method. The hazard ratio (HR) of breast cancer-specific mortality for women with diabetes compared to women without diabetes was estimated using the Cox proportional hazards model. RESULTS: For women with diabetes, the 5-year and 10-year of cancer-specific survival were 87% (95% CI: 85%-88%) and 79% (95% CI: 76%-81%) compared to 89% (95% CI: 89%-90%) and 84% (95% CI: 83%-85%) for women without diabetes. The HR of cancer-specific mortality for patients with diabetes compared to those without diabetes was 0.99 (95% CI: 0.89-1.11) after adjustment for patient demographics, tumor characteristics, and treatments. Age at cancer diagnosis and cancer stage had the biggest impact on the survival difference between the two groups. When stratified by cancer stage, the cancer-specific mortality between the two groups was similar. CONCLUSIONS: While differences in survival have been identified for women with diabetes when compared to women without diabetes, these are attributable to age and the finding that women with diabetes tend to present with more advanced disease at diagnosis. We did not find any difference in survival between the two groups due to differences in treatment.

Equity of travel to access surgery and radiation therapy for lung cancer in New Zealand.

PURPOSE: Centralisation of lung cancer treatment can improve outcomes, but may result in differential access to care for those who do not reside within treatment centres. METHODS: We used national-level cancer registration and health care access data and used Geographic Information Systems (GIS) methods to determine the distance and time to access first relevant surgery and first radiation therapy among all New Zealanders diagnosed with lung cancer (2007-2019; N = 27,869), and compared these outcomes between ethnic groups. We also explored the likelihood of being treated at a high-, medium-, or low-volume hospital. Analysis involved both descriptive and adjusted logistic regression modelling. RESULTS: We found that Maori tend to need to travel further (with longer travel times) to access both surgery (median travel distance: Maori 57 km, European 34 km) and radiation therapy (Maori 75 km, European 35 km) than Europeans. Maori have greater odds of living more than 200 km away from both surgery (adjusted odds ratio [aOR] 1.83, 95% CI 1.49-2.25) and radiation therapy (aOR 1.41, 95% CI 1.25-1.60). CONCLUSIONS: Centralisation of care may often improve treatment outcomes, but it also makes accessing treatment even more difficult for populations who are more likely to live rurally and in deprivation, such as Maori.

Access to and Timeliness of Lung Cancer Surgery, Radiation Therapy, and Systemic Therapy in New Zealand: A Universal Health Care Context.

PURPOSE: Lung cancer is the biggest cancer killer of indigenous peoples worldwide, including Maori people in New Zealand. There is some evidence of disparities in access to lung cancer treatment between Maori and non-Maori patients, but an examination of the depth and breadth of these disparities is needed. Here, we use national-level data to examine disparities in access to surgery, radiation therapy and systemic therapy between Maori and European patients, as well as timing of treatment relative to diagnosis. METHODS: We included all lung cancer registrations across New Zealand from 2007 to 2019 (N = 27,869) and compared access with treatment and the timing of treatment using national-level inpatient, outpatient, and pharmaceutical records. RESULTS: Maori patients with lung cancer appeared less likely to access surgery than European patients (Maori, 14%; European, 20%; adjusted odds ratio [adj OR], 0.82 [95% CI, 0.73 to 0.92]), including curative surgery (Maori, 10%; European, 16%; adj OR, 0.72 [95% CI, 0.62 to 0.84]). These differences were only partially explained by stage and comorbidity. There were no differences in access to radiation therapy or systemic therapy once adjusted for confounding by age. Although it appeared that there was a longer time from diagnosis to radiation therapy for Maori patients compared with European patients, this difference was small and requires further investigation. CONCLUSION: Our observation of differences in surgery rates between Maori and European patients with lung cancer who were not explained by stage of disease, tumor type, or comorbidity suggests that Maori patients who may be good candidates for surgery are missing out on this treatment to a greater extent than their European counterparts.

The growing cancer burden: Age-period-cohort projections in Aotearoa New Zealand 2020-2044.

BACKGROUND: Cancer is a major cause of premature death and inequity, and global case numbers are rapidly expanding. This study projects future cancer numbers and incidence rates in Aotearoa New Zealand. METHODS: Age-period-cohort modelling was applied to 25-years of national data to project cancer cases and incidence trends from 2020 to 2044. Nationally mandated cancer registry data and official historical and projected population estimates were used, with sub-groups by age, sex, and ethnicity. RESULTS: Cancer diagnoses were projected to increase from 25,700 per year in 2015-2019 to 45,100 a year by 2040-44, a 76% increase (2.3% per annum). Across the same period, age-standardised cancer incidence increased by 9% (0.3% per annum) from 348 to 378 cancers per 100,000 person years, with greater increases for males (11%) than females (6%). Projected incidence trends varied substantially by cancer type, with several projected to change faster or in the opposite direction compared to projections from other countries. CONCLUSIONS: Increasing cancer numbers reinforces the critical need for both cancer prevention and treatment service planning activities. Investment in developing new ways of working and increasing the workforce are required for the health system to be able to afford and manage the future burden of cancer.

The impact of racism on subsequent healthcare use and experiences for adult New Zealanders: a prospective cohort study.

BACKGROUND: Racism is an important determinant of health and driver of racial/ethnic health inequities. Experience of racism has been linked to negative healthcare use and experiences although most studies have been cross-sectional. This study examines the relationship between reported experience of racism and subsequent use and experience of health services. METHODS: This is a prospective cohort study design. The 2016/2017 adult New Zealand Health Survey (NZHS) provided the sampling frame and baseline data on exposures, health status and confounders. This stand-alone study invited all exposed individuals to participate when sampled based on their reported experience of racism (ever), stratified by broad ethnic groupings (Maori, Pacific, Asian, European/Other). Equal numbers of unexposed participants were selected for invitation using propensity score matching (propensity to experience racism, based on key available predictive factors). Follow-up was one to two years after NZHS interview. Outcome variables (last 12 months) were: unmet healthcare need (overall, for mental health, for a general practitioner); satisfaction with usual medical centre; and experiences with general practitioners (explaining care, involvement in decision-making, treated with respect/dignity, confidence and trust). Logistic regression models examining the association between experience of racism (at baseline) and health service use and experience (at follow-up) used doubly-robust estimation to weight for propensity scores used in the sampling with additional adjustment for confounders. RESULTS: The study had 2010 participants. Experience of racism (ever) at baseline was associated with higher overall unmet need at follow-up (adjusted OR (aOR) = 1.71, 95% CI 1.31, 2.23), with similar patterns for other unmet need measures. Experience of racism was associated with higher dissatisfaction with a usual medical centre (aOR = 1.41, 95% CI 1.10, 1.81) and with higher reporting of negative patient experiences. CONCLUSION: In line with how racism structures oppression, exposure to racism is largely felt by non-European groups in Aotearoa New Zealand. Experiences of racism potentially lead to poorer healthcare and healthcare inequities through higher unmet need, lower satisfaction and more negative experiences of healthcare. The health system has a critical role to play in addressing racism within healthcare and supporting societal efforts to eliminate racism and ethnic inequities.

Addressing Intergenerational Inequity in Tobacco-Harm: What Helps Children of Smokers to Remain Nonsmokers?

INTRODUCTION: Children of people who smoke are more likely to take up smoking themselves. In Aotearoa New Zealand (NZ), adolescent smoking declined dramatically between 2000 and 2016 despite limited change in parental smoking, demonstrating that the cycle can be broken. AIMS AND METHODS: This study aimed to identify modifiable factors associated with never smoking in Year 10 students (14-15 years) who had at least one caregiver who smoked. We used data from the Youth Insights Survey (2016 and 2018, pooled, N = 5,422) and identified students with at least one caregiver (mother, father, grandparent, other caregiver) who smoked (N = 2,205). To investigate modifiable factors potentially associated with nonsmoking we used logistic regression with marginally adjusted prevalence estimates. RESULTS: Overall, 41% of students had at least one caregiver who smoked. In this group, the majority (65%) had never smoked themselves. After adjustment, never-smoking was more prevalent among students attending low-deprivation (more affluent) schools (73% had never smoked) compared to high-deprivation schools (44%); students not exposed to others' smoking inside the home (72%) or in cars (70%) in the past week compared to those exposed (59% and 51%, respectively); and students whose parents would be upset if they were caught smoking (68% vs 49% for those whose parents would not be upset), or who had high self-esteem (69% vs 55% for those with low self-esteem). CONCLUSIONS: Modifiable factors independently associated with non-smoking in adolescents with caregiver(s) who smoked were: nonexposure to smoking inside the home and in cars, parental expectations of nonsmoking, and high self-esteem. IMPLICATIONS: Even in countries like NZ with relatively low adult smoking rates, children's exposure to caregiver smoking may be prevalent, particularly in structurally disadvantaged populations. This study suggests that action to promote smokefree homes and cars, build high self-esteem in young people, and communicate expectations of non-smoking are likely to help children of people who smoke to remain nonsmokers. A comprehensive approach that also addresses "upstream" factors (eg, socioeconomic deprivation) and underlying causes of structural inequity (eg, institutional racism) is needed. Such policy and community action may help to break intergenerational cycles of tobacco use and health inequity.

Acetazolamide and topiramate lower intracranial pressure through differential mechanisms: The effect of acute and chronic administration.

BACKGROUND AND PURPOSE: Diseases of raised intracranial pressure (ICP) cause severe morbidity and mortality. Multiple drugs are utilised to lower ICP including acetazolamide and topiramate. However, the evidence for their use is unclear. We aimed to assess the ICP modulatory effects and molecular effects at the choroid plexus (CP) of acetazolamide and topiramate. EXPERIMENTAL APPROACH: Female rats were implanted with telemetric ICP probes for physiological, freely moving 24/7 ICP recordings. Randomised cross-over studies were performed, where rats received acute (24 h) high doses of acetazolamide and topiramate, and chronic (10 days) clinically equivalent doses of acetazolamide and topiramate, all via oral gavage. Cerebrospinal fluid (CSF) secretion assays, and RT-qPCR and western blots on in vitro and in vivo CP, were used to investigate drug actions. KEY RESULTS: We demonstrate that acetazolamide and topiramate achieved maximal ICP reduction within 120 min of administration, and in combination doubled the ICP reduction over a 24-h period. Chronic administration of acetazolamide or topiramate lowered ICP by 25%. Topiramate decreased CSF secretion by 40%. Chronic topiramate increased the gene expression of Slc12a2 and Slc4a10 and protein expression of the sodium-dependent chloride/bicarbonate exchanger (NCBE), whereas chronic acetazolamide did not affect the expression of assessed genes. CONCLUSIONS AND IMPLICATIONS: Acetazolamide and topiramate are effective at lowering ICP at therapeutic levels. We provide the first evidence that topiramate lowers CSF secretion and that acetazolamide and topiramate may lower ICP via distinct molecular mechanisms. Thus, the combination of acetazolamide and topiramate may have utility for treating raised ICP.

Cycle-dependent sex differences in expression of membrane proteins involved in cerebrospinal fluid secretion at rat choroid plexus.

BACKGROUND: Female sex is a known risk factor of brain disorders with raised intracranial pressure (ICP) and sex hormones have been suggested to alter cerebrospinal fluid (CSF) dynamics, thus impairing ICP regulation in CSF disorders such as idiopathic intracranial hypertension (IIH). The choroid plexus (CP) is the tissue producing CSF and it has been hypothesized that altered hormonal composition could affect the activity of transporters involved in CSF secretion, thus affecting ICP. Therefore, we aimed to investigate if expression of various transporters involved in CSF secretion at CP were different between males and females and between females in different estrous cycle states. Steroid levels in serum was also investigated. METHODS: Female and male rats were used to determine sex-differences in the genes encoding for the transporters Aqp1 and 4, NKCC1, NBCe2, NCBE; carbonic anhydrase enzymes II and III (CA), subunits of the Na+/K+-ATPase including Atp1a1, Atp1b1 and Fxyd1 at CP. The estrous cycle stage metestrus (MET) and estrous (ES) were determined before euthanasia. Serum and CP were collected and subjected to RT-qPCR analysis and western blots. Serum was used to measure steroid levels using liquid chromatography tandem mass spectrometry (LC-MS/MS). RESULTS: Significant differences in gene expression and steroid levels between males and ES females were found, while no differences were found between male and MET females. During ES, expression of Aqp1 was lower (p < 0.01) and NKCC1 was higher in females compared to males. CAII was lower while CAIII was higher in ES females (p < 0.0001). Gene expression of Atp1a1 was lower in ES compared to male (p = 0.0008). Several of these choroidal genes were also significantly different in MET compared to females in ES. Differences in gene expression during the estrus cycle were correlated to serum level of steroid hormones. Protein expression of AQP1 (p = 0.008) and CAII (p = 0.035) was reduced in ES females compared to males. CONCLUSIONS: This study demonstrates for the first time that expression at CP is sex-dependent and markedly affected by the estrous cycle in female rats. Further, expression was related to hormone levels in serum. This opens a completely new avenue for steroid regulation of the expression of CSF transporters and the close link to the understanding of CSF disorders such as IIH.

Effects of caffeine on intracranial pressure and pain perception in freely moving rats.

OBJECTIVE: Caffeine, a non-selective adenosine receptor (AR) antagonist, is the most consumed psychostimulant in the world. Caffeine has been suggested to regulate cerebrospinal fluid secretion and is known both to alleviate and to trigger headache; however, its effect on the regulation of intracranial pressure (ICP) is not known. Therefore, we aimed to investigate the effects of caffeine on ICP and nociceptive responses. METHODS: Female Sprague-Dawley rats were implanted with a novel telemetric device for continuous ICP recordings, which allowed for continuous recordings in freely moving rats. A single dose of caffeine (30 or 120 mg/kg intraperitoneally) was given. In a second group (non-implanted), the acute effects of 30 mg/kg caffeine on periorbital threshold using Von Frey testing and spontaneous behavior were utilized using an automated behavioral registration platform (Laboratory, Animal, Behavior, Observation, Registration and Analysis System) in a randomized cross-over study. Quantitative polymerase chain reaction and immunofluorescence were used to localize ARs in the choroid plexus. RESULTS: A single dose of 30 mg/kg caffeine lowered the ICP by 35% at 165 min after administration (saline: 0.16 ± 0.9 vs caffeine: -1.18 ± 0.9 ΔmmHg, p = 0.0098) and lasted up to 12 h. Administration of 120 mg/kg caffeine showed a faster onset of decrease in ICP within 15 min by 50% (p = 0.0018) and lasted up to 12 h. The periorbital pain thresholds were higher after 1 h (saline: 224.6 ± 15.1 vs caffeine: 289.5 ± 8.7 g, p = 0.005) and lasted up to 5 h. Caffeine-treated rats had increased locomotor activity, speed, and changed grooming behavior. Expression of AR1 was found in the choroid plexus. CONCLUSIONS: This study demonstrates that caffeine has a lowering effect on ICP as an acute treatment. Interestingly, caffeine acutely caused an increased response in cephalic thresholds supporting hypoalgesic effects. Future studies investigating the beneficial effects of caffeine for elevated ICP are warranted.

Support for and potential impacts of key Smokefree 2025 strategies among Maori who smoke.

AIM: The recently passed Smokefree Environments and Regulated Products (Smoked Tobacco) Amendment Act has the potential to profoundly reduce smoking prevalence and related health inequities experienced among Maori. This study examined support for, and potential impacts of, key measures included within the legislation. METHOD: Data came from Wave 1 (2017-2019) of the Te Ara Auahi Kore longitudinal study, which was conducted in partnership with five primary health organisations serving Maori communities. Participants were 701 Maori who smoked. Analysis included both descriptive analysis and logistic regression. RESULTS: More Maori participants supported than did not support the Smokefree 2025 (SF2025) goal of reducing smoking prevalence to below 5%, and the key associated measures. Support was greatest for mandating very low nicotine cigarettes (VLNCs). Participants also believed VLNCs would prompt high rates of quitting. Participants who had made more quit attempts or reported less control over their life were more likely to support VLNCs. CONCLUSION: There was support for the SF2025 goal and for key measures that could achieve it. In particular, VLNCs may have significant potential to reduce smoking prevalence among Maori. As part of developing and implementing these measures it will be important to engage with Maori who smoke and their communities.