Impact of sleep disturbance on longitudinal cognitive performance in patients with transient ischemic attack or mild stroke.

INTRODUCTION: Sleep disturbances including obstructive sleep apnea (OSA) and poor sleep quality are common after stroke, while its association with cognitive changes following transient ischemic attack (TIA) or mild stroke remains unclear. We aim to determine whether sleep duration, OSA parameters, or nocturnal hypoxemia is associated with a greater cognitive decline after stroke. METHODS: We prospectively followed-up patients with acute TIA/mild stroke [National Institute Health Stroke Scale (NIHSS) < 7] who underwent baseline sleep questionnaire [Pittsburgh Sleep Quality Index (PSQI)], and serial cognitive assessments [Montreal Cognitive Assessment (MoCA) 5-min, Stroop Test] at baseline and one-year. We also evaluated apnea-hypopnea index (AHI) and nocturnal hypoxemia by Home Sleep Apnea Test (HSAT) at one-year. Primary outcome was one-year change in MoCA 5-min score. RESULTS: One hundred and five patients with TIA/mild stroke (mean age 63 years, 65 % male) were included. Baseline short sleep (< 6 hour/night) and AHI ≥ 20/hour at one-year were independently associated with a decline in the MoCA 5-min total score after covariates adjustment [short sleep: ß = -2.36 95 % confidence interval (CI) (-4.13, -0.59), p = 0.009; AHI ≥ 20/hour: ß = -1.79 (-3.26, -0.32), p = 0.017; remained significant after multiple comparisons correction]. A lower mean MinSpO2 was associated with a decline in executive function [Stroop interference index: ß = 0.29 (0.04, 0.53), p = 0.021], but not with MoCA 5-min score at one-year. Moderation analysis indicated AHI ≥ 20/hour was associated with a pronounced decline in executive function only in men. CONCLUSIONS: Short sleep after stroke onset, AHI ≥ 20/hour and nocturnal hypoxemia at one-year contributed to an impaired cognitive trajectory at one-year following stroke in patients with TIA/mild stroke.

The declining affordability of dental care in New Zealand from 1978 to 2023.

BACKGROUND: In the early 2020s, nearly half of New Zealand adults reported that cost of treatment had prevented them from accessing dental care, with higher rates among Maori, Pasifika and individuals living in the most deprived areas. Unaffordable dental care may be explained by a rise in dental service fees over time relative to personal income, as documented in New Zealand between 1978 and 1993. However, there have been no contemporary estimates in New Zealand of how the affordability of dental care has changed. The aims of this study were to analyse the change in dental treatment fees and the personal income of New Zealanders from 1978 to 2023 and to explore differences in affordability of dental care by ethnicity. METHODS: Average fees for dental treatments were sourced from surveys completed by practising New Zealand dentists. Earnings (from 1978) and personal income data (full population from 2000 and by ethnicity from 2008) were sourced from Statistics NZ and NZ Official Yearbooks. Inflation-adjusted changes in average fees, weekly personal earnings and income were calculated as a percentage change from 1978 levels for fees and earnings and from 2000 for personal income. RESULTS: For the five dental treatments with data available from 1978 to 2023, fees increased in the range of 75%-236%, while earnings increased by 46% over the same period. Fees for other treatments (with data available from 1981 to 2009) similarly increased and mostly surpassed changes in earnings. From 2008 to 2023 the overall increase in personal income (about 21% across all ethnic groups) kept pace with the rising cost of most treatments. However, due to persistent income inequalities, in 2023, Maori and Pasifika would need to spend a higher proportion of their weekly income (approximately 16% and 23% respectively) to receive the same dental treatments as NZ Europeans. CONCLUSIONS: Fees for dental treatments have risen markedly in recent decades, more sharply than the price of other goods and services.

Adjuvant Atezolizumab in Patients with Sarcomatoid Renal Cell Carcinoma: A Prespecified Subgroup Analysis of IMmotion010.

Patients with sarcomatoid renal cell carcinoma (sRCC) have a poor prognosis. In the randomised, double-blind phase 3 IMmotion010 trial (NCT03024996), adjuvant atezolizumab did not demonstrate a disease-free survival (DFS) benefit versus placebo in the overall population of patients with locoregional renal cell carcinoma with an increased risk of recurrence following surgery. This prespecified subgroup analysis of efficacy and safety was completed in 104 patients with sRCC. Baseline characteristics were similar between treatment arms. At a median follow-up of 45 mo, the median DFS was not evaluable (NE; 95% confidence interval [CI], 12 mo-NE) in the atezolizumab arm (n = 37) and 23 mo (95% CI, 11-NE) in the placebo arm (n = 66; hazard ratio 0.77 [95% CI, 0.44-1.4]). In the sRCC subgroup, grade 3/4 treatment-related adverse events (TRAEs) occurred in one patient (2.7%) in the atezolizumab arm and two patients (3.0%) in the placebo arm. By comparison, 54 of 353 patients (15%) and 16 of 317 patients (5.0%) with non-sarcomatoid histology reported grade 3/4 TRAEs in the respective arms. In conclusion, the difference in DFS was not statistically significant between adjuvant atezolizumab and placebo in patients with sRCC. The safety profile was similar between patients with sRCC and non-sRCC. PATIENT SUMMARY: Patients with a specific type of locoregional kidney cancer (tumours with sarcomatoid features) were treated with atezolizumab or placebo after surgery. Slightly more patients treated with atezolizumab lived longer without the disease getting worse than those treated with placebo, although this finding was not statistically significant. The side effects were similar to those seen in patients with other types of kidney cancer treated with atezolizumab in the same study (IMmotion010). In patients with sarcomatoid kidney cancer, atezolizumab was tolerable and may be more effective than placebo, but this requires further study.

Risk of Seizure Aggravation after COVID-19 Vaccinations in Patients with Epilepsy.

Although Coronavirus disease 2019 (COVID-19) vaccinations are generally recommended for persons with epilepsy (PwE), a significant vaccination gap remains due to patient concerns over the risk of post-vaccination seizure aggravation (PVSA). In this single-centre, retrospective cohort study, we aimed to determine the early (7-day) and delayed (30-day) risk of PVSA, and to identify clinical predictors of PVSA among PwE. Adult epilepsy patients aged ≥18 years without a history of COVID-19 infection were recruited from a specialty epilepsy clinic in early 2022. Demographic, epilepsy characteristics, and vaccination data were extracted from a centralized electronic patient record. Seizure frequency before and after vaccination, vaccination-related adverse effects, and reasons for or against vaccination were obtained by a structured questionnaire. A total of 786 PwEs were included, of which 27.0% were drug-resistant. At the time of recruitment, 74.6% had at least 1 dose of the COVID-19 vaccine. Subjects with higher seizure frequency (p < 0.0005), on more anti-seizure medications (p = 0.004), or had drug-resistant epilepsy (p = 0.001) were less likely to be vaccinated. No significant increase in seizure frequency was observed in the early (7 days) and delayed phases (30 days) after vaccination in our cohort. On the contrary, there was an overall significant reduction in seizure frequency 30 days after vaccination (1.31 vs. 1.89, t = 3.436; p = 0.001). This difference was seen in both types of vaccine (BNT162b2 and CoronaVac) and drug-resistant epilepsy, but just missed significance for the second dose (1.13 vs. 1.87, t = 1.921; p = 0.055). Only 5.3% had PVSA after either dose of vaccine. Higher pre-vaccination seizure frequency of ≥1 per week (OR 3.01, 95% CI 1.05-8.62; p = 0.04) and drug-resistant status (OR 3.32, 95% CI 1.45-249 7.61; p = 0.005) were predictive of PVSA. Meanwhile, seizure freedom for 3 months before vaccination was independently associated with a lower risk of PVSA (OR 0.11, 95% CI 0.04-0.28; p < 0.0005). This may guide epilepsy treatment strategies to achieve better seizure control for at least 3 months prior to vaccination. As COVID-19 shifts to an endemic phase, this study provides important data demonstrating the overall safety of COVID-19 vaccinations among PwE. Identification of high-risk patients with subsequent individualized approaches in treatment and monitoring strategies may alleviate vaccination hesitancy among PwE.

Impact of renal function variability on long-term prognosis in ischemic stroke patients with atrial fibrillation.

Background: Although renal dysfunction is associated with adverse clinical outcomes in patients with atrial fibrillation (AF) following stroke, the impact of renal function variability is unclear. Aim: This study aimed to assess the association between renal function variability and various adverse clinical outcomes in patients with transient ischemic attack (TIA)/ischemic stroke and atrial fibrillation (AF). Methods: We conducted a population-based study and retrospectively identified patients hospitalized with a diagnosis of TIA/ischemic stroke and AF during 2016-2020 using the Clinical Data Analysis and Reporting System of Hong Kong. Serial serum creatinine tested upon the onset of TIA/ischemic stroke and during their subsequent follow-up was collected. Renal function variability was calculated using the coefficient of variation of the estimated glomerular filtration rate (eGFR). Clinical endpoints that occurred during the study period were captured and included ischemic stroke/systemic embolism, intracerebral hemorrhage (ICH), total bleeding, major adverse cardiovascular events (MACE), cardiovascular, non-cardiovascular, and all-cause mortality. Competing risk regression and Cox proportional hazard regression models were used to assess the associations of renal function variability with the outcomes of interest. Results: A total of 3,809 patients (mean age 80 ± 10 years, 43% men) who satisfied the inclusion and exclusion criteria were followed up for a mean of 2.5 ± 1.5 years (9,523 patient-years). The mean eGFR was 66 ± 22 mL/min/1.73 m2 at baseline, and the median number of renal function tests per patient during the follow-up period was 20 (interquartile range 11-35). After accounting for potential confounders, a greater eGFR variability was associated with increased risks of recurrent ischemic stroke/systemic embolism [fully adjusted subdistribution hazard ratio 1.11, 95% confidence interval (CI) 1.03-1.20], ICH (1.17, 1.01-1.36), total bleeding (1.13, 1.06-1.21), MACE (1.22, 1.15-1.30), cardiovascular (1.49, 1.32-1.69), non-cardiovascular (1.43, 1.35-1.52), and all-cause mortality (fully adjusted hazard ratio 1.44, 1.39-1.50). Conclusion: Visit-to-visit renal function variability is independently associated with adverse clinical outcomes in TIA/ischemic stroke patients with AF. Further large-scale studies are needed to validate our results.

Association of LDL-cholesterol <1.8 mmol/L and statin use with the recurrence of intracerebral hemorrhage.

BACKGROUND: Recent intensive low-density lipoprotein cholesterol (LDL-C) lowering trials, including FOURIER, ODYSSEY OUTCOMES, and Treat Stroke to Target (TST) trials, have mostly refuted the concern surrounding statin use, LDL-C lowering, and intracerebral hemorrhage (ICH) risk. However, the results from these trials may not be fully applied to ICH survivors, as the populations studied were mainly patients without prior ICH, in whom the inherent ICH risk is more than 10 times lower than that of ICH survivors. Although available literature on statin use after ICH has demonstrated no excess risk of recurrent ICH, other potential factors that may modify ICH risk, especially hypertension control and ICH etiology, have not generally been considered. Notably, data on LDL-C levels following ICH are lacking. AIMS: We aim to investigate the association between LDL-C levels and statin use with ICH risk among ICH survivors, and to determine whether the risk differed with patients' characteristics, especially ICH etiology. METHODS: Follow-up data of consecutive spontaneous ICH survivors enrolled in the University of Hong Kong prospective stroke registry from 2011 to 2019 were retrospectively analyzed. ICH etiology was classified as cerebral amyloid angiopathy (CAA) using the modified Boston criteria or hypertensive arteriopathy, while the mean follow-up LDL-C value was categorized as <1.8 or ⩾1.8 mmol/L. The primary endpoint was recurrent ICH. The association of LDL-C level and statin use with recurrent ICH was determined using multivariable Cox regression. Pre-specified subgroup analyses were performed, including based on ICH etiology and statin prescription. Follow-up blood pressure was included in all the regression models. RESULTS: In 502 ICH survivors (mean age = 64.2 ± 13.5 years, mean follow-up LDL-C = 2.2 ± 0.6 mmol/L, 28% with LDL-C <1.8 mmol/L), 44 had ICH recurrence during a mean follow-up of 5.9 ± 2.8 years. Statin use after ICH was not associated with recurrent ICH (adjusted hazard ratio (AHR) = 1.07, 95% confidence interval (CI) = 0.57-2.00). The risk of ICH recurrence was increased for follow-up LDL-C <1.8 mmol/L (AHR = 1.99, 95% CI = 1.06-3.73). This association was predominantly observed in ICH attributable to CAA (AHR = 2.52, 95% CI = 1.06-5.99) and non-statin users (AHR = 2.91, 95% CI = 1.08-7.86). CONCLUSION: The association between post-ICH LDL-C <1.8 mmol/L and recurrent ICH was predominantly observed in CAA patients and those with intrinsically low LDL-C (non-statin users). While statins can be safely prescribed in ICH survivors, LDL-C targets should be individualized and caution must be exercised in CAA patients.

Prevalence and predictors of depressive symptoms among caregivers of patients with epilepsy in Hong Kong.

STUDY AIM: To estimate the prevalence of high caregiving burden and depressive symptoms among caregivers (CG) of patients with epilepsy (PWEs) in Hong Kong and identify risk and protective factors for both outcomes after the Model of Stress and Carer Burden (MSCB). METHODS: This cross-sectional study recruited participants from local epilepsy clinics to complete a 15-minute survey on a tablet. Caregiving burden (CB) was assessed using the 4-item Zarit Caregiver Burden Interview. Depressive symptoms were assessed using the 2-item Patient Health Questionnaire. Family functioning was assessed using the Short-Form Family Assessment Device General Functioning Subscale. Sociodemographic data of the caregivers and clinical data of the PWE they cared for were described. Hierarchical logistic regression models were used to analyze the factors associated with the outcomes. RESULTS: A hundred and fifty-one CGs of PWEs were recruited for this study. The prevalence of high caregiving burden (ZBI-4 > 7) for CGs of PWEs was 58.9% (n = 89), whereas the prevalence of high depressive symptoms (PHQ2 > 2) was 23.8% (n = 36). Hierarchical logistic regression analysis revealed that entering patient characteristics and care situations did not enhance the model's predictability. In the full model, a high perceived CB was a risk factor for elevated depressive symptoms. Good physical health protects against depressive symptoms. CONCLUSIONS: Among caregivers of PWE in Hong Kong, a high perceived caregiving burden was a risk factor for elevated depressive symptoms; however, the clinical characteristics of the PWEs were not. Self-reported physical health is a protective factor against increased depressive symptoms.

Location-Specific Hematoma Volume Cutoff and Clinical Outcomes in Intracerebral Hemorrhage.

BACKGROUND: Major intracerebral hemorrhage (ICH) trials have largely been unable to demonstrate therapeutic benefit in improving functional outcomes. This may be partly due to the heterogeneity of ICH outcomes based on their location, where a small strategic ICH could be debilitating, thus confounding therapeutic effects. We aimed to determine the ideal hematoma volume cutoff for different ICH locations in predicting ICH outcomes. METHODS: We retrospectively analyzed consecutive ICH patients enrolled in the University of Hong Kong prospective stroke registry from January 2011 to December 2018. Patients with premorbid modified Rankin Scale score >2 or who underwent neurosurgical intervention were excluded. ICH volume cutoff, sensitivity, and specificity in predicting respective 6-month neurological outcomes (good [modified Rankin Scale score 0-2], poor [modified Rankin Scale score 4-6], and mortality) for specific ICH locations were determined using receiver operating characteristic curves. Separate multivariate logistic regression models were also conducted for each location-specific volume cutoff to determine whether these cutoffs were independently associated with respective outcomes. RESULTS: Among 533 ICHs, the volume cutoff for good outcome according to ICH location was 40.5 mL for lobar, 32.5 mL for putamen/external capsule, 5.5 mL for internal capsule/globus pallidus, 6.5 mL for thalamus, 17 mL for cerebellum, and 3 mL for brainstem. ICH smaller than the cutoff for all supratentorial sites had higher odds of good outcomes (all P<0.05). Volumes exceeding 48 mL for lobar, 41 mL for putamen/external capsule, 6 mL for internal capsule/globus pallidus, 9.5 mL for thalamus, 22 mL for cerebellum, and 7.5 mL for brainstem were at greater risk of poor outcomes (all P<0.05). Mortality risks were significantly higher for volumes that exceeded 89.5 mL for lobar, 42 mL for putamen/external capsule, and 21 mL for internal capsule/globus pallidus (all P<0.001). All receiver operating characteristic models for location-specific cutoffs had good discriminant values (area under the curve >0.8), except in predicting good outcome for cerebellum. CONCLUSIONS: ICH outcomes differed with location-specific hematoma size. Location-specific volume cutoff should be considered in patient selection for ICH trials.

Simulating contact networks for livestock disease epidemiology: a systematic review.

Contact structure among livestock populations influences the transmission of infectious agents among them. Models simulating realistic contact networks therefore have important applications for generating insights relevant to livestock diseases. This systematic review identifies and compares such models, their applications, data sources and how their validity was assessed. From 52 publications, 37 models were identified comprising seven model frameworks. These included mathematical models (n = 8; including generalized random graphs, scale-free, Watts-Strogatz and spatial models), agent-based models (n = 8), radiation models (n = 1) (collectively, considered 'mechanistic'), gravity models (n = 4), exponential random graph models (n = 9), other forms of statistical model (n = 6) (statistical) and random forests (n = 1) (machine learning). Overall, nearly half of the models were used as inputs for network-based epidemiological models. In all models, edges represented livestock movements, sometimes alongside other forms of contact. Statistical models were often applied to infer factors associated with network formation (n = 12). Mechanistic models were commonly applied to assess the interaction between network structure and disease dissemination (n = 6). Mechanistic, statistical and machine learning models were all applied to generate networks given limited data (n = 13). There was considerable variation in the approaches used for model validation. Finally, we discuss the relative strengths and weaknesses of model frameworks in different use cases.

Social contact patterns relevant for infectious disease transmission in Cambodia.

Social mixing patterns are key determinants of infectious disease transmission. Mathematical models parameterised with empirical data from contact pattern surveys have played an important role in understanding epidemic dynamics and informing control strategies, including for SARS-CoV-2. However, there is a paucity of data on social mixing patterns in many settings. We conducted a community-based survey in Cambodia in 2012 to characterise mixing patterns and generate setting-specific contact matrices according to age and urban/rural populations. Data were collected using a diary-based approach from 2016 participants, selected by stratified random sampling. Contact patterns were highly age-assortative, with clear intergenerational mixing between household members. Both home and school were high-intensity contact settings, with 27.7% of contacts occurring at home with non-household members. Social mixing patterns differed between rural and urban residents; rural participants tended to have more intergenerational mixing, and a higher number of contacts outside of home, work or school. Participants had low spatial mobility, with 88% of contacts occurring within 1 km of the participants' homes. These data broaden the evidence-base on social mixing patterns in low and middle-income countries and Southeast Asia, and highlight within-country heterogeneities which may be important to consider when modelling the dynamics of pathogens transmitted via close contact.

Is Xenopus laevis introduction linked with Ranavirus incursion, persistence and spread in Chile?

Ranaviruses have been associated with amphibian, fish and reptile mortality events worldwide and with amphibian population declines in parts of Europe. Xenopus laevis is a widespread invasive amphibian species in Chile. Recently, Frog virus 3 (FV3), the type species of the Ranavirus genus, was detected in two wild populations of this frog near Santiago in Chile, however, the extent of ranavirus infection in this country remains unknown. To obtain more information about the origin of ranavirus in Chile, its distribution, species affected, and the role of invasive amphibians and freshwater fish in the epidemiology of ranavirus, a surveillance study comprising wild and farmed amphibians and wild fish over a large latitudinal gradient (2,500 km) was carried out in 2015-2017. In total, 1,752 amphibians and 496 fish were tested using a ranavirus-specific qPCR assay, and positive samples were analyzed for virus characterization through whole genome sequencing of viral DNA obtained from infected tissue. Ranavirus was detected at low viral loads in nine of 1,011 X. laevis from four populations in central Chile. No other amphibian or fish species tested were positive for ranavirus, suggesting ranavirus is not threatening native Chilean species yet. Phylogenetic analysis of partial ranavirus sequences showed 100% similarity with FV3. Our results show a restricted range of ranavirus infection in central Chile, coinciding with X. laevis presence, and suggest that FV3 may have entered the country through infected X. laevis, which appears to act as a competent reservoir host, and may contribute to the spread the virus locally as it invades new areas, and globally through the pet trade.

Blood Pressure Control Targets and Risk of Cardiovascular and Cerebrovascular Events After Intracerebral Hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) survivors are at high risk for recurrent stroke and cardiovascular events. Blood pressure (BP) control represents the most potent intervention to lower these risks, but optimal treatment targets in this patient population remain unknown. We sought to determine whether survivors of ICH achieving more intensive BP control than current guideline recommendations (systolic BP <130 mmHg and diastolic BP <80 mmHg) were at lower risk of major adverse cardiovascular and cerebrovascular events and mortality. METHODS: We analyzed data for 1828 survivors of spontaneous ICH from 2 cohort studies. Follow-up BP measurements were recorded 3 and 6 months after ICH, and every 6 months thereafter. Outcomes of interest were major adverse cardiovascular and cerebrovascular events (recurrent ICH, incident ischemic stroke, myocardial infarction), vascular mortality (defined as mortality attributed to recurrent ICH, ischemic stroke, or myocardial infarction), and all-cause mortality. RESULTS: During a median follow-up of 46.2 months, we observed 166 recurrent ICH, 68 ischemic strokes, 69 myocardial infarction, and 429 deaths. Compared with survivors of ICH with systolic BP 120 to 129 mmHg, participants who achieved systolic BP <120 mmHg displayed reduced risk of recurrent ICH (adjusted hazard ratio [AHR], 0.74 [95% CI, 0.59-0.94]) and major adverse cardiovascular and cerebrovascular events (AHR, 0.69 [95% CI, 0.53-0.92]). All-cause mortality (AHR, 0.76 [95% CI, 0.57-1.03]) and vascular mortality (AHR, 0.68 [95% CI, 0.45-1.01]) did not differ significantly. Among participants aged >75 years or with modified Rankin Scale score 4 to 5, systolic BP <120 mmHg was associated with increased all-cause mortality (AHR, 1.38 [95% CI, 1.02-1.85] and AHR, 1.36 [95% CI, 1.03-1.78], respectively), but not vascular mortality. We found no differences in outcome rates between survivors of ICH with diastolic BP <70 versus 70 to 79 mmHg. CONCLUSIONS: Targeting systolic BP <120 mmHg in select groups of survivors of ICH could result in decreased major adverse cardiovascular and cerebrovascular events risk without increasing mortality. Our findings warrant investigation in dedicated randomized controlled trials.

Adjuvant atezolizumab versus placebo for patients with renal cell carcinoma at increased risk of recurrence following resection (IMmotion010): a multicentre, randomised, double-blind, phase 3 trial.

BACKGROUND: The standard of care for locoregional renal cell carcinoma is surgery, but many patients experience recurrence. The objective of the current study was to determine if adjuvant atezolizumab (vs placebo) delayed recurrence in patients with an increased risk of recurrence after resection. METHODS: IMmotion010 is a randomised, double-blind, multicentre, phase 3 trial conducted in 215 centres in 28 countries. Eligible patients were patients aged 18 years or older with renal cell carcinoma with a clear cell or sarcomatoid component and increased risk of recurrence. After nephrectomy with or without metastasectomy, patients were randomly assigned (1:1) to receive atezolizumab (1200 mg) or placebo (both intravenous) once every 3 weeks for 16 cycles or 1 year. Randomisation was done with an interactive voice-web response system. Stratification factors were disease stage (T2 or T3a vs T3b-c or T4 or N+ vs M1 no evidence of disease), geographical region (north America [excluding Mexico] vs rest of the world), and PD-L1 status on tumour-infiltrating immune cells (<1% vs ≥1% expression). The primary endpoint was investigator-assessed disease-free survival in the intention-to-treat population, defined as all patients who were randomised, regardless of whether study treatment was received. The safety-evaluable population included all patients randomly assigned to treatment who received any amount of study drug (ie, atezolizumab or placebo), regardless of whether a full or partial dose was received. This trial is registered with ClinicalTrials.gov, NCT03024996, and is closed to further accrual. FINDINGS: Between Jan 3, 2017, and Feb 15, 2019, 778 patients were enrolled; 390 (50%) were assigned to the atezolizumab group and 388 (50%) to the placebo group. At data cutoff (May 3, 2022), the median follow-up duration was 44·7 months (IQR 39·1-51·0). Median investigator-assessed disease-free survival was 57·2 months (95% CI 44·6 to not evaluable) with atezolizumab and 49·5 months (47·4 to not evaluable) with placebo (hazard ratio 0·93, 95% CI 0·75-1·15, p=0·50). The most common grade 3-4 adverse events were hypertension (seven [2%] patients who received atezolizumab vs 15 [4%] patients who received placebo), hyperglycaemia (ten [3%] vs six [2%]), and diarrhoea (two [1%] vs seven [2%]). 69 (18%) patients who received atezolizumab and 46 (12%) patients who received placebo had a serious adverse event. There were no treatment-related deaths. INTERPRETATION: Atezolizumab as adjuvant therapy after resection for patients with renal cell carcinoma with increased risk of recurrence showed no evidence of improved clinical outcomes versus placebo. These study results do not support adjuvant atezolizumab for treatment of renal cell carcinoma. FUNDING: F Hoffmann-La Roche and Genentech, a member of the Roche group.

Medical Treatment for Rheumatic Heart Disease: A Narrative Review.

BACKGROUND: Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) are rare in high-income countries; however, in Aotearoa New Zealand ARF and RHD disproportionately affect Indigenous Maori and Pacific Peoples. This narrative review explores the evidence regarding non-surgical management of patients with clinically significant valve disease or heart failure due to RHD. METHODS: Medline, EMBASE and Scopus databases were searched, and additional publications were identified through cross-referencing. Included were 28 publications from 1980 onwards. RESULTS: Of the available interventions, improved anticoagulation management and a national RHD register could improve RHD outcomes in New Zealand. Where community pharmacy anticoagulant management services (CPAMS) are available good anticoagulation control can be achieved with a time in the therapeutic range (TTR) of more than 70%, which is above the internationally recommended level of 60%. The use of pharmacists in anticoagulation control is cost-effective, acceptable to patients, pharmacists, and primary care practitioners. There is a lack of local data available to fully assess other interventions; including optimal therapy for heart failure, equitable access to specialist RHD care, prevention, and management of endocarditis. CONCLUSION: As RHD continues to disproportionately affect Indigenous and minority groups, pro-equity tertiary prevention interventions should be fully evaluated to ensure they are reducing disease burden and improving outcomes in patients with RHD.

Health promoting and demoting consumption: What accounts for budget share differentials by ethnicity in New Zealand.

Background: Health demoting consumption of alcohol and tobacco are some of the most important risk factors for health loss worldwide, however there is limited information on these consumption risk factors in New Zealand (NZ) and whether inequities in the risk factors are ethnically patterned. Methods: We used three nationally representative Household Economic Survey waves (2006/07, 2009/10, 2012/13) (n = 9030) in NZ to examine household expenditure for key health risk-related components of consumption by ethnicity, and its contributors to the differences using non-parametric, parametric and decomposition methods. Results: Maori households (NZ indigenous population) were significantly poorer (25% less) than non-Maori households in terms of household per capita expenditure. However, our various econometric estimations suggested that, in relative terms, Maori spent more on tobacco and alcohol, and less on healthcare. The gaps become larger at upper quantiles of the budget share distributions; the composition effect (the gap due to differences in individual and household characteristics between Maori and non-Maori) explains most of the tobacco and alcohol budget share gap between the two groups, and less for healthcare. The structure effect (the gap due to returns to/or effect of individual and household characteristics) contributes very little to the budget share gap for tobacco and drink, but increasingly and predominantly when moving along the distribution of healthcare budget share.The differences between Maori and non-Maori in household ownership, education, and income negatively affect budget share on these health demoting consumption (tobacco and alcohol). The household head's age, education, and employment contributed most to the structure effect. Conclusions: Our study suggested ethnic inequities in the health risk consumption behaviour are evidenced in NZ. Interventions targeting education and employment that significantly affect household budget shares on risk factors (i.e., harmful consumption) for health loss may help narrow the gaps.

Long-Term Blood Pressure Variability and Major Adverse Cardiovascular and Cerebrovascular Events After Intracerebral Hemorrhage.

Background Survivors of intracranial hemorrhage (ICH) are at increased risk for major adverse cardiovascular and cerebrovascular events (MACCE), in the form of recurrent stroke and myocardial Infarction. We investigated whether long-term blood pressure (BP) variability represents a risk factor for MACCE after ICH, independent of average BP. Methods and Results We analyzed data from prospective ICH cohort studies at Massachusetts General Hospital and the University of Hong Kong. We captured long-term (ie, visit-to-visit) BP variability, quantified as individual participants' variation coefficient. We explored determinants of systolic and diastolic BP variability and generated survival analyses models to explore their association with MACCE. Among 1828 survivors of ICH followed for a median of 46.2 months we identified 166 with recurrent ICH, 68 with ischemic strokes, and 69 with myocardial infarction. Black (coefficient +3.8, SE 1.3) and Asian (coefficient +2.2, SE 0.4) participants displayed higher BP variability. Long-term systolic BP variability was independently associated with recurrent ICH (subhazard ratio [SHR], 1.82; 95% CI, 1.19-2.79), ischemic stroke (SHR, 1.62; 95% CI, 1.06-2.47), and myocardial infarction (SHR, 1.54; 95% CI, 1.05-2.24). Average BP during follow-up did not modify the association between long-term systolic BP variability and MACCE. Conclusions Long-term BP variability is a potent risk factor for recurrent hemorrhage, ischemic stroke, and myocardial infarction after ICH, even among survivors with well-controlled hypertension. Our findings support the hypothesis that combined control of average BP and its variability after ICH is required to minimize incidence of MACCE.

Estimated Healthcare Costs of Melanoma and Keratinocyte Skin Cancers in Australia and Aotearoa New Zealand in 2021.

Australia and Aotearoa New Zealand have the highest incidence of melanoma and KC in the world. We undertook a cost-of-illness analysis using Markov decision-analytic models separately for melanoma and keratinocyte skin cancer (KC) for each country. Using clinical pathways, the probabilities and unit costs of each health service and medicine for skin cancer management were applied. We estimated mean costs and 95% uncertainty intervals (95% UI) using Monte Carlo simulation. In Australia, the mean first-year costs of melanoma per patient ranged from AU$644 (95%UI: $642, $647) for melanoma in situ to AU$100,725 (95%UI: $84,288, $119,070) for unresectable stage III/IV disease. Australian-wide direct costs to the Government for newly diagnosed patients with melanoma were AU$397.9 m and AU$426.2 m for KCs, a total of AU$824.0 m. The mean costs per patient for melanoma ranged from NZ$1450 (95%UI: $1445, $1456) for melanoma in situ to NZ$77,828 (95%UI $62,525, $94,718) for unresectable stage III/IV disease. The estimated total cost to New Zealand in 2021 for new patients with melanoma was NZ$51.2 m, and for KCs, was NZ$129.4 m, with a total combined cost of NZ$180.5 m. These up-to-date national healthcare costs of melanoma and KC in Australia and New Zealand accentuate the savings potential of successful prevention strategies for skin cancer.

Antiepileptic drugs for the primary and secondary prevention of seizures after stroke.

BACKGROUND: Seizures after stroke are an important clinical problem and may result in poor outcomes. The indications of antiepileptic drugs (AEDs) for seizure prophylaxis after stroke remain unclear. This is an updated version of the Cochrane Review previously published in 2014. OBJECTIVES: To assess the effects of AEDs for the primary and secondary prevention of seizures after stroke. For primary prevention, we aimed to assess whether AEDs reduce the likelihood of seizures in people who have a stroke but do not have a seizure. For secondary prevention, we aimed to assess whether AEDs reduce the likelihood of further seizures in people who have a stroke and at least one post-stroke seizure. SEARCH METHODS: We searched the following databases on 9 March 2021: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to March 08, 2021). CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organisation International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialised Registers of Cochrane Review Groups including Epilepsy and Stroke. We also checked the reference lists of articles retrieved from these searches. SELECTION CRITERIA: We selected randomised and quasi-randomised controlled studies that recruited participants with a clinical diagnosis of stroke, either ischaemic or haemorrhagic. We excluded studies that only recruited participants with subarachnoid haemorrhage, subdural haemorrhage, extradural haemorrhage, or other non-stroke diagnoses such as tumour- or infection-related infarction or haemorrhage. We also excluded studies that recruited only participants who had undergone neurosurgery. We included participants of all ages suffering any seizure type who were assigned to AEDs or placebo groups. DATA COLLECTION AND ANALYSIS: In accordance with standard methodological procedures expected by The Cochrane Collaboration, two review authors independently assessed trials for inclusion before evaluating trial risk of bias and extracting relevant data. The primary outcome assessed was the proportion of participants who experienced seizures in the follow-up period. We presented results as summary risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences (MDs) with 95% CIs for continuous outcomes. Where we had sufficient data, we calculated random-effects (Mantel-Haenszel) meta-analyses for dichotomous outcomes; otherwise, we reported results narratively. We used the I2 statistic to analyse statistical heterogeneity. We planned to use funnel plots to assess publication bias in meta-analyses with at least 10 included studies. We used the GRADE approach to assess the certainty of the evidence. MAIN RESULTS: Two studies with a total of 856 subjects were included. AEDs were not shown to be effective in primary prophylaxis of post-stroke seizure (RR 0.65, 95% CI 0.34 to 1.26; 2 studies, 856 participants; moderate-certainty evidence). The first study was a randomised double-blind study comparing valproic acid with placebo for primary seizure prevention up to one year after stroke. The study included 72 adults with intracerebral haemorrhage. There was no difference in the risk of post-stroke seizures (RR 0.88, 95% CI 0.35 to 2.16) or of death (RR 1.20, 95% CI 0.40 to 3.58). The second study was a substudy on the use of diazepam in acute stroke. It was a randomised double-blind study, comparing a three-day diazepam treatment versus placebo for primary seizure prevention up to three months after stroke in 784 adults with acute stroke. There was no evidence of a difference in the risk of post-stroke seizures for all stroke or subgroups of haemorrhagic or ischaemic stroke (RR for all stroke 0.47, 95% CI 0.18 to 1.22). In a subgroup analysis of anterior circulation cortical infarcts, primary prophylaxis with diazepam was associated with a reduced risk of post-stroke seizures (RR 0.21, 95% CI 0.05 to 0.95). Risks of mortality did not differ between the diazepam and the placebo group at two weeks (RR 0.84, 95% CI 0.56 to 1.26) and three months follow-up (RR 0.95, 95% CI 0.72 to 1.26). We assessed both studies to be at a low overall risk of bias. Using the GRADE approach, we assessed the overall certainty of the evidence as low to moderate. AUTHORS' CONCLUSIONS: There is insufficient evidence to support the routine use of AEDs on the primary and secondary prevention of seizures after stroke. Further well-conducted studies are warranted for this important clinical problem.

Generating political priority for skin cancer primary prevention: A case study from Aotearoa New Zealand.

ISSUES ADDRESSED: Skin cancer is highly prevalent but preventable, yet little research has been done on the challenges in generating political priority for skin cancer prevention. This qualitative study aimed to identify the political challenges to, facilitators of, and strategies to strengthen skin cancer prevention. The focus was on the case of Aotearoa New Zealand (NZ): a country with high skin cancer rates, but limited investment in primary prevention. METHODS: Data sources included 18 national key informant interviews and documentary analysis. Data were analysed inductively for emerging themes and framed using a conceptual framework of political priority. RESULTS: Challenges to advocates for skin cancer primary prevention include limited resources and competing priorities. Political-level challenges include a lack of quick results compared with other initiatives vying for political attention, lack of negative externalities and, in NZ, misalignment with health system priorities. Challenges in the evidence base include the perceived conflict of sun protection with Vitamin D and physical activity, the lack of data on the financial burden of skin cancer and relatively low temperatures in NZ. Facilitators include strong policy community cohesion and issue framing, and weak opposition. Promising strategies to strengthen skin cancer prevention in NZ could include network building, using framing that resonates with policy makers and addressing key knowledge gaps in NZ, such as the financial burden of skin cancer. CONCLUSION: Advocacy for skin cancer prevention faces challenges due to advocates' limited resources, political challenges such as lack of quick results and gaps in evidence. Nonetheless, the initiative encounters little opposition and can be framed in ways that resonate with policy makers. SO WHAT?: Skin cancer is highly preventable, but advocates for prevention initiatives have struggled to gain political traction. This study identifies several strategies that could help raise the political profile for skin cancer prevention.