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.

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.

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.

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.

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.

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.

Rising Ethnic Inequalities in Acute Rheumatic Fever and Rheumatic Heart Disease, New Zealand, 2000-2018.

We describe trends in acute rheumatic fever (ARF), rheumatic heart disease (RHD), and RHD deaths among population groups in New Zealand. We analyzed initial primary ARF and RHD hospitalizations during 2000-2018 and RHD mortality rates during 2000-2016. We found elevated rates of initial ARF hospitalizations for persons of Maori (adjusted rate ratio [aRR] 11.8, 95% CI 10.0-14.0) and Pacific Islander (aRR 23.6, 95% CI 19.9-27.9) ethnicity compared with persons of European/other ethnicity. We also noted higher rates of initial RHD hospitalization for Maori (aRR 3.2, 95% CI 2.9-3.5) and Pacific Islander (aRR 4.6, 95% CI 4.2-5.1) groups and RHD deaths among these groups (Maori aRR 12.3, 95% CI 10.3-14.6, and Pacific Islanders aRR 11.2, 95% CI 9.1-13.8). Rates also were higher in socioeconomically disadvantaged neighborhoods. To curb high rates of ARF and RHD, New Zealand must address increasing social and ethnic inequalities.

Impact of COVID-19 on seizure-related emergency attendances and hospital admissions - A territory-wide observational study.

This is a territory-wide study to investigate the impact of coronavirus disease 2019 (COVID-19) pandemic on Accident and Emergency Department (A&E) attendances and acute ward admissions for seizures. Adult patients who presented to the A&E with seizures from January 23, 2020 to March 24, 2020 (study period) were included and compared with parallel intervals from 2015 to 2019 (control periods). Preexisting time trend in control periods and potential changes during COVID-19 were analyzed by Poisson, negative and logistic regression models. Accident and Emergency Department attendances and ward admissions for seizures decreased significantly during the COVID-19 pandemic. A total of 319 and 230 recorded ward admissions and A&E attendances for seizures were identified during the study period in 2020, compared with 494 and 343 per annum, respectively in the control periods. The ratio of acute ward admission per A&E attendance for seizures did not change significantly. Intensive care utility and mortality rates remained stable. For some patients, delaying medical attention due to fear of nosocomial COVID-19 cross-infection may lead to severe or even life-threatening consequences. This change in medical help-seeking behavior calls for new medical care models to meet the service gap. Education to patients with epilepsy and their caregivers is of utmost importance during this pandemic.

Employment among people with epilepsy in Hong Kong.

BACKGROUND: People with epilepsy (PWE) face difficulties in employment. Hong Kong depends heavily on tertiary industry and enjoys a low unemployment rate. However, there have been rare reports on employment of PWE in Hong Kong. We aimed at (1) investigating the employment status among PWE; (2) correlating demographic and clinical factors with employment status of PWE; and (3) describing the self-perceived impact of epilepsy on employment and their correlations with employment status. METHOD: This was a single center cross-sectional study conducted in 2019. Adult with epilepsy but without intellectual disability of year age 16-65 were recruited. Homemakers and retired persons were excluded. A questionnaire with two parts was given to each patient. The first part focused on objective data about employment. The second part focused on self-perception on the impact of epilepsy on employment. Responders expressed their opinions in 5-point Likert scale. Clinical data were retrieved from the computerized medical record system for interpretation. RESULTS: A total of 138 PWE were recruited. Unemployment rate among the PWE was 33%, which was much higher than the general population. Low education levels, drug-resistant epilepsy, psychiatric comorbidities, and high Charlson Comorbidity Index were correlated to unemployment in PWE. Unemployed respondents significantly more tend to regard that lack of education, stigma of epilepsy, and seizure frequency were main hurdles in employment. CONCLUSIONS: Unemployment is a severe social problem among PWE in Hong Kong. Various objective clinical and demographic factors correlated with unemployment. Work beliefs of a patient may also correlate with the employment status.

Early diagnosis of acute rheumatic fever and rheumatic heart disease as part of a secondary prevention strategy: Narrative review.

Acute rheumatic fever (ARF) and its sequela rheumatic heart disease (RHD) remain significant causes of morbidity and mortality. In New Zealand, ARF almost exclusively affects Indigenous Maori and Pacific children. This narrative review aims to present secondary interventions to improve early and accurate diagnosis of ARF and RHD, in order to minimise disease progression in New Zealand. Medline, EMBASE and Scopus databases were searched as well as other electronic publications. Included were 56 publications from 1980 onwards. Diagnosing ARF and RHD as early as possible is central to reducing disease progression. Recent identification of specific ARF biomarkers offer the opportunity to aid initial diagnosis and portable echocardiography has the potential to detect undiagnosed RHD in high-risk areas. However, further research into the benefits and risks to children with subclinical RHD is necessary, as well as an economic evaluation.

Structured review of primary interventions to reduce group A streptococcal infections, acute rheumatic fever and rheumatic heart disease.

Rheumatic heart disease (RHD) is a large, preventable, global public health burden. In New Zealand (NZ), acute rheumatic fever (ARF) and RHD rates are highest for Maori and Pacific children. This structured review explores the evidence for primary prevention interventions to diagnose and effectively treat group A Streptococcus (GAS) pharyngitis and skin infections to reduce rates of ARF and RHD. Medline, EMBASE and Scopus databases were searched as well as other electronic publications. Included were 50 publications from 1980 onwards. This review has identified that there is little available evidence for effective primary prevention strategies to reduce ARF rates in NZ. However, two primary intervention strategies that should be considered by communities at high-risk of ARF are: the use of school-based clinics to identify and treat GAS pharyngitis and GAS skin infections; and intramuscular benzathine penicillin G with lignocaine analgesia in children who present with a GAS positive throat.

Changes in pediatric seizure-related emergency department attendances during COVID-19 - A territory-wide observational study.

A territory-wide retrospective observational study was conducted in Hong Kong between January 23 to April 22, 2020 to demonstrate changes in pediatric seizure-related accident and emergency department (A&E) visits during the COVID-19 pandemic. Parallel periods from 2015 to 2019 were used as control. All-cause A&E attendances in all paediatric age groups decreased significantly during the study period. Seizure-related attendances decreased across all pediatric age-groups in 2020 (RR 0.379, 95% CI 0.245-0.588), with a disproportionately large decrease in the 0-6 years age group (RR 0.303, 95% CI 0.174-0.526) compared with the 7-18 years age group (RR 0.534, 95% CI 0.393-0.719). Decrease in RTI-related A&E attendances was also more drastic in the 0-6 age group. The two time trends are congruent in the 0-6 years but not the 7-18 years age group. Such a trend is suggestive of the usefulness of infection control measures in seizure prevention, especially amongst young children.

Delays in Stroke Onset to Hospital Arrival Time During COVID-19.

BACKGROUND AND PURPOSE: The current coronavirus disease 2019 (COVID-19) pandemic represents a global public health crisis, disrupting emergency healthcare services. We determined whether COVID-19 has resulted in delays in stroke presentation and affected the delivery of acute stroke services in a comprehensive stroke center in Hong Kong. METHODS: We retrospectively reviewed all patients with transient ischemic attack and stroke admitted via the acute stroke pathway of Queen Mary Hospital, Hong Kong, during the first 60 days since the first diagnosed COVID-19 case in Hong Kong (COVID-19: January 23, 2020-March 24, 2020). We compared the stroke onset to hospital arrival (onset-to-door) time and timings of inpatient stroke pathways with patients admitted during the same period in 2019 (pre-COVID-19: January 23, 2019-March 24, 2019). RESULTS: Seventy-three patients in COVID-19 were compared with 89 patients in pre-COVID-19. There were no significant differences in age, sex, vascular risk factors, nor stroke severity between the 2 groups (P>0.05). The median stroke onset-to-door time was ≈1-hour longer in COVID-19 compared with pre-COVID-19 (154 versus 95 minutes, P=0.12), and the proportion of individuals with onset-to-door time within 4.5 hours was significantly lower (55% versus 72%, P=0.024). Significantly fewer cases of transient ischemic attack presented to the hospital during COVID-19 (4% versus 16%, P=0.016), despite no increase in referrals to the transient ischemic attack clinic. Inpatient stroke pathways and treatment time metrics nevertheless did not differ between the 2 groups (P>0.05 for all comparisons). CONCLUSIONS: During the early containment phase of COVID-19, we noted a prolongation in stroke onset to hospital arrival time and a significant reduction in individuals arriving at the hospital within 4.5 hours and presenting with transient ischemic attack. Public education about stroke should continue to be reinforced during the COVID-19 pandemic.

Prospective community programme versus parent-driven care to prevent respiratory morbidity in children following hospitalisation with severe bronchiolitis or pneumonia.

BACKGROUND: Hospitalisation with severe lower respiratory tract infection (LRTI) in early childhood is associated with ongoing respiratory symptoms and possible later development of bronchiectasis. We aimed to reduce this intermediate respiratory morbidity with a community intervention programme at time of discharge. METHODS: This randomised, controlled, single-blind trial enrolled children aged <2 years hospitalised for severe LRTI to 'intervention' or 'control'. Intervention was three monthly community clinics treating wet cough with prolonged antibiotics referring non-responders. All other health issues were addressed, and health resilience behaviours were encouraged, with referrals for housing or smoking concerns. Controls followed the usual pathway of parent-initiated healthcare access. After 24 months, all children were assessed by a paediatrician blinded to randomisation for primary outcomes of wet cough, abnormal examination (crackles or clubbing) or chest X-ray Brasfield score ≤22. FINDINGS: 400 children (203 intervention, 197 control) were enrolled in 2011-2012; mean age 6.9 months, 230 boys, 87% Maori/Pasifika ethnicity and 83% from the most deprived quintile. Final assessment of 321/400 (80.3%) showed no differences in presence of wet cough (33.9% intervention, 36.5% controls, relative risk (RR) 0.93, 95% CI 0.69 to 1.25), abnormal examination (21.7% intervention, 23.9% controls, RR 0.92, 95% CI 0.61 to 1.38) or Brasfield score ≤22 (32.4% intervention, 37.9% control, RR 0.85, 95% CI 0.63 to 1.17). Twelve (all intervention) were diagnosed with bronchiectasis within this timeframe. INTERPRETATION: We have identified children at high risk of ongoing respiratory disease following hospital admission with severe LRTI in whom this intervention programme did not change outcomes over 2 years. TRIAL REGISTRATION NUMBER: ACTRN12610001095055.

Effects of historic and projected climate change on the range and impacts of an emerging wildlife disease.

The global trend of increasing environmental temperatures is often predicted to result in more severe disease epidemics. However, unambiguous evidence that temperature is a driver of epidemics is largely lacking, because it is demanding to demonstrate its role among the complex interactions between hosts, pathogens, and their shared environment. Here, we apply a three-pronged approach to understand the effects of temperature on ranavirus epidemics in UK common frogs, combining in vitro, in vivo, and field studies. Each approach suggests that higher temperatures drive increasing severity of epidemics. In wild populations, ranavirosis incidents were more frequent and more severe at higher temperatures, and their frequency increased through a period of historic warming in the 1990s. Laboratory experiments using cell culture and whole animal models showed that higher temperature increased ranavirus propagation, disease incidence, and mortality rate. These results, combined with climate projections, predict severe ranavirosis outbreaks will occur over wider areas and an extended season, possibly affecting larval recruitment. Since ranaviruses affect a variety of ectothermic hosts (amphibians, reptiles, and fish), wider ecological damage could occur. Our three complementary lines of evidence present a clear case for direct environmental modulation of these epidemics and suggest management options to protect species from disease.

Mass media promotion of a smartphone smoking cessation app: modelled health and cost-saving impacts.

BACKGROUND: Smartphones are increasingly available and some high quality apps are available for smoking cessation. However, the cost-effectiveness of promoting such apps has never been studied. We therefore aimed to estimate the health gain, inequality impacts and cost-utility from a five-year promotion campaign of a smoking cessation smartphone app compared to business-as-usual (no app use for quitting). METHODS: A well-established Markov macro-simulation model utilising a multi-state life-table was adapted to the intervention (lifetime horizon, 3% discount rate). The setting was the New Zealand (NZ) population (N = 4.4 million). The intervention effect size was from a multi-country randomised trial: relative risk for quitting at 6 months = 2.23 (95%CI: 1.08 to 4.77), albeit subsequently adjusted to consider long-term relapse. Intervention costs were based on NZ mass media promotion data and the NZ cost of attracting a smoker to smoking cessation services (NZ$64 per person). RESULTS: The five-year intervention was estimated to generate 6760 QALYs (95%UI: 5420 to 8420) over the remaining lifetime of the population. For Maori (Indigenous population) there was 2.8 times the per capita age-standardised QALY gain relative to non-Maori. The intervention was also estimated to be cost-saving to the health system (saving NZ$115 million [m], 95%UI: 72.5m to 171m; US$81.8m). The cost-saving aspect of the intervention was maintained in scenario and sensitivity analyses where the discount rate was doubled to 6%, the effect size halved, and the intervention run for just 1 year. CONCLUSIONS: This study provides modelling-level evidence that mass-media promotion of a smartphone app for smoking cessation could generate health gain, reduce ethnic inequalities in health and save health system costs. Nevertheless, there are other tobacco control measures which generate considerably larger health gains and cost-savings such as raising tobacco taxes.

Studying third-parties and environments: New Zealand sun-safety research.

Wearable cameras have been used to study health behaviours, but their utility in assessing third-party behaviours and the built environment is uncertain. This paper reports on the feasibility of using wearable cameras for this purpose in a study of sun-protective behaviours and shade availability during school lunch-breaks. The Kids'Cam study provided 168 children (aged 11-13 years), recruited from 16 randomly selected schools in the Wellington region of New Zealand, with wearable cameras. The devices automatically captured images every 7 s from the child's perspective. Images captured during school lunch-breaks by a random sample of 15 children who took part during terms 4 and 1 (October 2014-April 2015) were selected and assessed for usability. The feasibility of studying third-party sun-protective behaviours and school shade availability was assessed for a subset of 320 images. Of the 3492 eligible lunch-break images, 96.4% were useable; the remainders were excluded due to obstruction, blurriness or unsuitable camera position. Overall, 1278 children and 108 shade structures were observed in the sample images. The use of shade, hats, sleeves, collars and sunglasses could be determined for 97.0%, 77.2%, 74.4%, 47.6% and 54.9% of children, respectively. All shade structures could be classified according to type, and canopy composition could be assessed for 95.4% of structures. Wearable cameras are a feasible tool for assessing sun-safety, particularly shade availability, hat wearing and shade use. This methodology could be used to objectively study other third-party health-related behaviours, and other features of the built environment.

A national quitline service and its promotion in the mass media: modelling the health gain, health equity and cost-utility.

BACKGROUND: Mass media campaigns and quitlines are both important distinct components of tobacco control programmes around the world. But when used as an integrated package, the effectiveness and cost-effectiveness are not well described. We therefore aimed to estimate the health gain, health equity impacts and cost-utility of the package of a national quitline service and its promotion in the mass media. METHODS: We adapted an established Markov and multistate life-table macro-simulation model. The population was all New Zealand adults in 2011. Effect sizes and intervention costs were based on past New Zealand quitline data. Health system costs were from a national data set linking individual health events to costs. RESULTS: The 1-year operation of the existing intervention package of mass media promotion and quitline service was found to be net cost saving to the health sector for all age groups, sexes and ethnic groups (saving $NZ84 million; 95%uncertainty interval 60-115 million in the base-case model). It also produced greater per capita health gains for Maori (indigenous) than non-Maori (2.2 vs 0.73 quality-adjusted life-years (QALYs) per 1000 population, respectively). The net cost saving of the intervention was maintained in all sensitivity and scenario analyses for example at a discount rate of 6% and when the intervention effect size was quartered (given the possibility of residual confounding in our estimates of smoking cessation). Running the intervention for 20 years would generate an estimated 54 000 QALYs and $NZ1.10 billion (US$0.74 billion) in cost savings. CONCLUSIONS: The package of a quitline service and its promotion in the mass media appears to be an effective means to generate health gain, address health inequalities and save health system costs. Nevertheless, the role of this intervention needs to be compared with other tobacco control and health sector interventions, some of which may be even more cost saving.