Tobacco endgame intervention impacts on health gains and Maori:non-Maori health inequity: a simulation study of the Aotearoa/New Zealand Tobacco Action Plan.

BACKGROUND: The Aotearoa/New Zealand Government is aiming to end the tobacco epidemic and markedly reduce Maori:non-Maori health inequalities by legislating: (1) denicotinisation of retail tobacco, (2) 95% reduction in retail outlets and (c) a tobacco free-generation whereby people born after 2005 are unable to legally purchase tobacco. This paper estimates future smoking prevalence, mortality inequality and health-adjusted life year (HALY) impacts of these strategies. METHODS: We used a Markov model to estimate future yearly smoking and vaping prevalence, linked to a proportional multistate life table model to estimate future mortality and HALYs. RESULTS: The combined package of strategies (plus media promotion) reduced adult smoking prevalence from 31.8% in 2022 to 7.3% in 2025 for Maori, and 11.8% to 2.7% for non-Maori. The 5% smoking prevalence target was forecast to be achieved in 2026 and 2027 for Maori males and females, respectively.The HALY gains for the combined package over the population's remaining lifespan were estimated to be 594 000 (95% uncertainty interval (UI): 443 000 to 738 000; 3% discount rate). Denicotinisation alone achieved 97% of these HALYs, the retail strategy 19% and tobacco-free generation 12%.By 2040, the combined package was forcat to reduce the gap in Maori:non-Maori all-cause mortality rates for people 45+ years old by 22.9% (95% UI: 19.9% to 26.2%) for females and 9.6% (8.4% to 11.0%) for males. CONCLUSION: A tobacco endgame strategy, especially denicotinisation, could deliver large health benefits and dramatically reduce health inequities between Maori and non-Maori in Aotearoa/New Zealand.

Modelling the impacts of tobacco denicotinisation on achieving the Smokefree 2025 goal in Aotearoa New Zealand.

AIM: To provide preliminary high-level modelling estimates of the impact of denicotinisation of tobacco on changes in smoking prevalence in Aotearoa New Zealand relative to the New Zealand Government's Smokefree 2025 goal. METHODS: An Excel spreadsheet was populated with smoking and vaping prevalence data from the New Zealand Health Survey and we projected business-as-usual trends. Using various parameters from the literature (New Zealand trial data, New Zealand EASE-ITC Study results), we modelled the potential impact of denicotinisation of tobacco (with no other tobacco permitted for sale) out to 2025. In addition to the base case (considered most likely), Scenario 1 used estimates from a published expert knowledge elicitation process, and Scenario 2 considered the addition of extra mass-media campaign and Quitline support to the base case. RESULTS: With the denicotinisation intervention, adult daily smoking prevalences were estimated to decline to under 5% by 2025 for the European/Other ethnic grouping (in the base case and both scenarios) and in one scenario (Scenario 1) for Maori (2.5%). However, prevalence did not fall below 5% in the base case for Maori (7.7%) or in Scenario 2 (5.2%). In the base case, vaping was estimated to increase to 7.9% in the adult population by 2025, and up to 10.7% in one scenario (Scenario 1). CONCLUSIONS: This preliminary high-level modelling suggests that mandated denicotinisation has a plausible chance of achieving the New Zealand Government's Smokefree 2025 goal. The probability of success would increase if supplemented with interventions such as mass-media campaigns offering Quitline support (especially if predominantly designed for a Maori audience). Nevertheless, there is much uncertainty with these results and more sophisticated modelling is forthcoming.

Updated Health and Cost Impacts of Electronic Nicotine Delivery Systems, Using Recent Estimates of Relative Harm for Vaping Compared to Smoking.

BACKGROUND: Measuring population health and costs effects of liberalizing access to electronic nicotine delivery systems (ENDS) is an evolving field with high persisting uncertainty. A critical area of uncertainty for policy-makers are estimates of net harms from ENDS relative to cigarettes, therefore, we model these harms using updated estimates incorporating disease specificity. METHODS: We use updated estimates of relative harm of vaping vs smoking, based upon relevant biomarker studies to model the impact of liberalizing access to ENDS in New Zealand (NZ), relative to a ban (where ENDS are not legally available), in an existing proportional multi-state life-table model of 16 tobacco-related diseases. RESULTS: This modeling suggests that ENDS liberalization results in an expected gain of 195 000 quality-adjusted life-years (QALYs) over the remainder of the NZ population's lifespan. There was wide uncertainty in QALYs gained (95% uncertainty interval [UI] = -8000 to 406 000) with a 3.2% probability of net health loss (based upon the number of simulation runs returning positive QALY gains). The average per capita health gain was 0.044 QALYs (equivalent to an extra 16 days of healthy life). Health system cost-savings were expected to be NZ$2.8 billion (US$2.1 billion in 2020 US$; 95%UI: -0.3 to 6.2 billion [2011 NZ$]), with an estimated 3% chance of a net increase in per capita cost. CONCLUSIONS: This updated modeling around liberalizing ENDs in NZ, still suggests likely net health and cost-saving benefits-but of lesser magnitude than previous work and with a small possibility of net harm to population health. IMPLICATIONS: This study found evidence using updated biomarker studies that ENDS liberalization could result in QALY gains across the New Zealand population lifespan that are also cost-saving to the health system. Governments should include the information from these types of modeling studies in their decision-making around potentially improving access to ENDS for existing smokers, while at the same further reducing access to tobacco.

Improving on estimates of the potential relative harm to health from using modern ENDS (vaping) compared to tobacco smoking.

BACKGROUND: Although the harm to health from electronic nicotine delivery systems (ENDS) compared to smoked tobacco remains highly uncertain, society and governments still need to know the likely range of the relative harm to inform regulatory policies for ENDS and smoking. METHODS: We identified biomarkers with specificity of association with different disease groupings e.g., volatile organic compound (VOCs) for chronic obstructive pulmonary disease; and tobacco-specific N´-nitrosamines (TSNAs) and polycyclic aromatic hydrocarbons (PAHs) for all cancers. We conducted a review of recent studies (post January 2017) that compared these biomarkers between people exclusively using ENDS and those exclusively smoking tobacco. The percentage differences in these biomarkers, weighted by study size and adjusted for acrolein from other sources, were used as a proxy for the assumed percentage difference in disease harm between ENDS and smoking. These relative differences were applied to previously modelled estimates of smoking-related health loss (in health-adjusted life-years; HALYs). RESULTS: The respective relative biomarker levels (ENDS vs smoking) were: 28% for respiratory diseases (five results, three studies); 42% for cancers (five results, four studies); and 35% for cardiovascular (seven results, four studies). When integrated with the HALY impacts by disease, the overall harm to health from ENDS was estimated to be 33% that of smoking. CONCLUSIONS: This analysis, suggests that the use of modern ENDS devices (vaping) could be a third as harmful to health as smoking in a high-income country setting. But this estimate is based on a limited number of biomarker studies and is best be considered a likely upper level of ENDS risk given potential biases in our method (i.e., the biomarkers used being correlated with more unaccounted for toxicants in smoking compared to with using ENDS).

Should prioritising health interventions be informed by modelling studies? The case of cancer control in Aotearoa New Zealand.

In this viewpoint, we suggest that policymakers should prioritise health interventions by using evidence around health gain, impact on equity, health-system costs and cost-effectiveness. We take the example of the new cancer control agency in New Zealand, Te Aho o Te Kahu, and argue that its decision-making can now be informed by many methodologically compatible epidemiological and health economic analyses. These analyses span primary prevention of cancer (eg, tobacco control, dietary and physical activity interventions and HPV vaccination), cancer screening, cancer treatment and palliative care. The largest health gain and cost-savings from the available modelling work for New Zealand are seen in nutrition and tobacco control interventions in particular. Many of these interventions have potentially greater per capita health gain for Maori than non-Maori and are also found to be cost saving for the health sector. In summary, appropriate prioritisation of interventions can potentially both maximise health benefits as well as making best use of government funding of the health system.

Stereotactic ablative body radiotherapy in patients with oligometastatic cancers: a prospective, registry-based, single-arm, observational, evaluation study.

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is increasingly being used to treat oligometastatic cancers, but high-level evidence to provide a basis for policy making is scarce. Additional evidence from a real-world setting is required. We present the results of a national study of patients with extracranial oligometastases undergoing SABR, representing the largest dataset, to our knowledge, on outcomes in this population so far. METHODS: In 2015, National Health Service (NHS) England launched a Commissioning through Evaluation scheme that funded a prospective, registry-based, single-arm, observational, evaluation study of patients with solid cancer and extracranial oligometastases treated with SABR. Prescribed doses ranged from 24-60 Gy administered in three to eight fractions. The study was done at 17 NHS radiotherapy centres in England. Patients were eligible for the scheme if aged 18 years or older with confirmed primary carcinoma (excluding haematological malignancies), one to three extracranial metastatic lesions, a disease-free interval from primary tumour development to metastases of longer than 6 months (with the exception of synchronous colorectal liver metastases), a WHO performance status of 2 or lower, and a life expectancy of at least 6 months. The primary outcome was overall survival at 1 year and 2 years from the start of SABR treatment. The study is now completed. FINDINGS: Between June 15, 2015, and Jan 30, 2019, 1422 patients were recruited from 17 hospitals in England. The median age of the patients was 69 years (IQR 62-76), and the most common primary tumour was prostate cancer (406 [28·6%] patients). Median follow-up was 13 months (IQR 6-23). Overall survival was 92·3% (95% CI 90·5-93·9) at 1 year and 79·2% (76·0-82·1) at 2 years. The most common grade 3 adverse event was fatigue (28 [2·0%] of 1422 patients) and the most common serious (grade 4) event was increased liver enzymes (nine [0·6%]). Notreatment-related deaths were reported. INTERPRETATION: In patients with extracranial oligometastatic cancer, use of SABR was associated with high overall survival and low toxicity. 'The study findings complement existing evidence from a randomised, phase 2 trial, and represent high-level, real-world evidence supporting the use of SABR in this patient cohort, with a phase 3 randomised, controlled trial to confirm these findings underway. Based on the selection criteria in this study, SABR was commissioned by NHS England in March, 2020, as a treatment option for patients with oligometastatic disease. FUNDING: NHS England Commissioning through Evaluation scheme.

Selective dorsal rhizotomy; evidence on cost-effectiveness from England.

OBJECTIVES: Selective dorsal rhizotomy (SDR) has gained interest as an intervention to reduce spasticity and pain, and improve quality of life and mobility in children with cerebral palsy mainly affecting the legs (diplegia). We evaluated the cost-effectiveness of SDR in England. METHODS: Cost-effectiveness was quantified with respect to Gross Motor Function Measure (GMFM-66) and the pain dimension of the Cerebral Palsy Quality of Life questionnaire for Children (CPQOL-Child). Data on outcomes following SDR over two years were drawn from a national evaluation in England which included 137 children, mean age 6.6 years at surgery. The incremental impact of SDR on GMFM-66 was determined through comparison with data from a historic Canadian cohort not undergoing SDR. Another single centre provided data on hospital care over ten years for 15 children undergoing SDR at a mean age of 7.0 years, and a comparable cohort managed without SDR. The incremental impact of SDR on pain was determined using a before and after comparison using data from the national evaluation. Missing data were imputed using multiple imputation. Incremental costs of SDR were determined as the difference in costs over 5 years for the patients undergoing SDR and those managed without SDR. Uncertainty was quantified using bootstrapping and reported as the cost-effectiveness acceptability curve. RESULTS: In the base case, the incremental cost-effectiveness ratios (ICERs) for SDR are £1,382 and £903 with respect to a unit improvement in GMFM-66 and the pain dimension of CPQOL-Child, respectively. Inclusion of data to 10 years indicates SDR is cheaper than management without SDR. Incremental costs and ICERs for SDR rose in sensitivity analysis applying an alternative regression model to cost data. CONCLUSIONS: Data on outcomes from a large observational study of SDR and long-term cost data on children who did and did not receive SDR indicates SDR is cost-effective.

Health-related welfare prioritisation of canine disorders using electronic health records in primary care practice in the UK.

BACKGROUND: Evidence-based comparison of the disorder-specific welfare burdens of major canine conditions could better inform targeting of stakeholder resources, to maximise improvement of health-related welfare in UK dogs. Population-level disease related welfare impact offers a quantitative, welfare-centred framework for objective disorder prioritisation, but practical applications have been limited to date due to sparse reliable evidence on disorder-specific prevalence, severity and duration across the canine disease spectrum. The VetCompass™ Programme collects de-identified electronic health record data from dogs attending primary-care clinics UK-wide, and is well placed to fill these information gaps. RESULTS: The eight common, breed-related conditions assessed were anal sac disorder, conjunctivitis, dental disease, dermatitis, overweight/obese, lipoma, osteoarthritis and otitis externa. Annual period prevalence estimates (based on confirming 250 cases from total potential cases identified from denominator population of 455, 557 dogs) were highest for dental disorder (9.6%), overweight/obese (5.7%) and anal sac disorder (4.5%). Dental disorder (76% of study year), osteoarthritis (82%), and overweight/obese (70%) had highest annual duration scores. Osteoarthritis (scoring 13/21), otitis externa (11/21) and dermatitis demonstrated (10/21) highest overall severity scores. Dental disorder (2.47/3.00 summative score), osteoarthritis (2.24/3.00) and overweight/obese (1.67/3.00) had highest VetCompass Welfare Impact scores overall. DISCUSSION: Of the eight common, breed-related disorders assessed, dental disorder, osteoarthritis and overweight/obese demonstrated particular welfare impact, based on combinations of high prevalence, duration and severity. Future work could extend this methodology to cover a wider range of disorders. CONCLUSIONS: Dental disorders, osteoarthritis and overweight/obese have emerged as priority areas for health-related welfare improvement in the UK dog population. This study demonstrated applicability of a standardised methodology to assess the relative health-related welfare impact across a range of canine disorders using VetCompass clinical data.

Selective dorsal rhizotomy in ambulant children with cerebral palsy: an observational cohort study.

BACKGROUND: Selective dorsal rhizotomy (SDR) is an irreversible surgical procedure involving the division of selected sensory nerve roots, followed by intensive physiotherapy. The aim is to improve function and quality of life in children with cerebral palsy and a Gross Motor Function Classification System (GMFCS) level of II or III (walks with or without assistive devices, respectively). We assessed gross motor function before and after SDR and postoperative quality of life in a study commissioned by NHS England. METHODS: We did a prospective observational study in five hospitals in England who were commissioned to perform SDR on children aged 3-9 years with spastic diplegic cerebral palsy. The primary outcome was score changes in the 66-item Gross Motor Function Measure (GMFM-66) and seven domains of the Cerebral Palsy Quality of Life Questionnaire ([CP-QoL] social wellbeing and acceptance, feelings about functioning, participation and physical health, emotional wellbeing and self-esteem, access to services, family health, and pain and impact of disability) from before to 24 months after SDR. FINDINGS: From Sept 4, 2014, to March 21, 2016, 137 children underwent SDR. The mean age was 6·0 years (SD 1·8). The mean GMFM-66 score increased after SDR with an annual change of 3·2 units (95% CI 2·9 to 3·5, n=137). Of the seven CP-QoL domains, five showed significant improvements over time: feelings about functioning mean annual change 3·0 units (95% CI 2·0 to 4·0, n=133), participation and physical health 3·9 units (2·5 to 5·3, n=133), emotional wellbeing and self-esteem 1·3 units (0·2 to 2·3, n=133), family health 2·0 units (0·7 to 3·3, n=132), and pain and impact of disability -2·5 units (-3·9 to -1·2, n=133). 17 adverse events were reported in 15 children, of which none were severe and 15 (88%) resolved. INTERPRETATION: SDR improved function and quality of life in the 24 months after surgery in children with cerebral palsy classified as GMFCS levels II and III. On the basis of these findings, an interim national policy decision was made that SDR would be funded for eligible children in England from 2018. FUNDING: National Institute for Health and Care Excellence, National Institute for Health Research Biomedical Research Centre, NHS England.

Virtual Touch™ Quantification to Diagnose and Monitor Liver Fibrosis in Hepatitis B and Hepatitis C: A NICE Medical Technology Guidance.

Virtual Touch™ Quantification (VTq) is a software application used with Siemens Acuson ultrasound scanners to assess the stiffness of liver tissue. The National Institute for Health and Care Excellence (NICE) Medical Technologies Advisory Committee (MTAC) selected VTq for evaluation and invited the company to submit clinical and economic evidence. King's Technology Evaluation Centre, an External Assessment Centre (EAC) commissioned by NICE, independently assessed the evidence submitted. The EAC conducted its own systematic review, meta-analysis and economic analysis to supplement the company's submitted evidence. The meta-analyses comparing VTq and transient elastography (TE) with liver biopsy (LB) provided pooled estimates of liver stiffness and stage of fibrosis for the study populations (hepatitis B, hepatitis C or combined populations). When comparing significant fibrosis (Metavir score F ≥ 2) for both hepatitis B and C, VTq had slightly higher values for both sensitivity and specificity (77 and 81 %) than TE (76 and 71 %). The overall prevalence of cirrhosis (F4, combined populations) was similar with VTq and TE (23 vs. 23 %), and significant fibrosis (F ≥ 2) was lower for VTq than for TE (55 vs. 62 %). The EAC revised the company's de novo cost model, which resulted in a cost saving of £53 (against TE) and £434 (against LB). Following public consultation, taking into account submitted comments, NICE Medical Technology Guidance MTG27 was published in September 2015. This recommended the adoption of the VTq software to diagnose and monitor liver fibrosis in patients with hepatitis B or hepatitis C.

A Multicenter Prospective Study to Investigate the Diagnostic Accuracy of the SeHCAT Test in Measuring Bile Acid Malabsorption: Research Protocol.

BACKGROUND: Bile acid malabsorption (BAM) is one possible explanation for chronic diarrhea. BAM may be idiopathic, or result from ileal resection or inflammation including Crohn's disease, or may be secondary to other conditions, including cholecystectomy, peptic ulcer surgery, and chronic pancreatitis. No "gold standard" exists for clinical diagnosis of BAM, but response to treatment with a bile acid sequestrant (BAS) is often accepted as confirmation. The SeHCAT (tauroselcholic [selenium-75] acid) test uses a radiolabeled synthetic bile acid and provides a diagnostic test for BAM, but its performance against "trial of treatment" is unknown. Fibroblast growth factor 19 (FGF-19) and 7-alpha-hydroxy-4-cholesten-3-one (C4) also offer potential new biomarkers of BAM. OBJECTIVE: This protocol describes a multicenter prospective study to evaluate the diagnostic accuracy of SeHCAT and 2 biomarkers in predicting BAM as assessed by trial of treatment. METHODS: Participating gastroenterology centers should have a minimum workload of 30 SeHCAT patients per annum. Patients should not be pregnant, on medication that could confound follow-up, or have any severe comorbidity. All eligible patients attending a gastrointestinal appointment will be invited to participate. On attending the SeHCAT test, blood and fecal samples will be collected for analysis of FGF-19 by enzyme-linked immunosorbent assay and for C4 and fractionated bile acids by liquid chromatography-mass spectrometry. A capsule containing radiolabeled SeHCAT will be administered orally and a scan performed to measure SeHCAT activity. Patients will return on day 7 to undergo a second scan to measure percentage SeHCAT retention. The test result will be concealed from clinicians and patients. BAS will be dispensed to all patients, with a follow-up gastroenterologist appointment at 2 weeks for clinical assessment of treatment response and adherence. Patients responding positively will continue treatment for a further 2 weeks and all patients will have a final follow-up at 8 weeks. The diagnostic accuracy of the SeHCAT test and biomarkers will be analyzed at different thresholds using sensitivity, specificity, positive and negative predictive value, likelihood ratios, and area under the curve in a sample of 600 patients. Multivariable logistic regression models will be used to assess the association between presence of BAM and continuous SeHCAT retention levels after adjustment for confounders. RESULTS: Funding is being sought to conduct this research. CONCLUSIONS: The SeHCAT test for diagnosis of BAM has been in common use in the United Kingdom for more than 30 years and an evidence-based assessment of its accuracy is overdue. The proposed study has some challenges. Some forms of BAS treatment are unpleasant due to the texture and taste of the resin powder, which may negatively affect recruitment and treatment adherence. Trial of treatment is not as "golden" a standard as would be ideal, and itself warrants further study.

A Single-centre Early Phase Randomised Controlled Three-arm Trial of Open, Robotic, and Laparoscopic Radical Cystectomy (CORAL).

BACKGROUND: Laparoscopic radical cystectomy (LRC) and robot-assisted radical cystectomy (RARC) are increasingly popular, but high-level evidence for these techniques remains lacking. OBJECTIVE: To compare the outcomes of patients undergoing open radical cystectomy (ORC), RARC, and LRC. DESIGN, SETTING, AND PARTICIPANTS: From March 2009 to July 2012, 164 patients requiring radical cystectomy for muscle-invasive bladder cancer or high-risk non-muscle-invasive bladder cancer were invited to participate, with an aim of recruiting 47 patients into each arm. Overall, 93 were suitable for trial inclusion; 60 (65%) agreed and 33 (35%) declined. INTERVENTION: ORC, RARC, or LRC with extracorporeal urinary diversion. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary end points were 30- and 90-d complication rates. Secondary end points were perioperative clinical, pathologic, and oncologic outcomes, and quality of life (QoL). The Fisher exact test and analysis of variance were used for statistical analyses. RESULTS AND LIMITATIONS: The 30-d complication rates (classified by the Clavien-Dindo system) varied significantly between the three arms (ORC: 70%; RARC: 55%; LRC: 26%; p=0.024). ORC complication rates were significantly higher than LRC (p<0.01). The 90-d complication rates did not differ significantly between the three arms (ORC: 70%; RARC: 55%; LRC 32%; p=0.068). Mean operative time was significantly longer in RARC compared with ORC or LRC. ORC resulted in a slower return to oral solids than RARC or LRC. There were no significant differences in QoL measures. Major limitations are the small sample size and potential surgeon bias. CONCLUSIONS: The 30-d complication rates varied by type of surgery and were significantly higher in the ORC arm than the LRC arm. There was no significant difference in 90-d Clavien-graded complication rates between the three arms. PATIENT SUMMARY: We compared patients having open, robotic, or laparoscopic bladder removal surgery for bladder cancer and found no difference in Clavien-graded complication rates at 90 d.

Impact of appropriate empirical antimicrobial therapy on outcome of dogs with septic peritonitis.

OBJECTIVE: To determine whether appropriate empirical antimicrobial therapy influenced survival in dogs with septic peritonitis. DESIGN: Retrospective case series (2003-2011). SETTING: University teaching hospital. ANIMALS: Eighty-six dogs with cytological confirmation or positive bacterial culture of abdominal sepsis and subsequent surgical intervention. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Forty-nine of 86 dogs (57%) survived to hospital discharge. Thirty-seven of 86 dogs were classified as having ''abdominal infection,'' 31/86 as ''severe sepsis,'' and the remaining 18/86 as in ''septic shock.'' Mortality was greatest in the ''septic shock'' category (94%). Empirical antimicrobial treatments were appropriate in 41/78 dogs (52.6%). Appropriateness was not associated with treatment outcome overall or when compared between sepsis severity groups. Antimicrobials had been given in the 30 days before admission in 63/86 (73.3%) dogs. Prior therapy with antimicrobials showed no association with outcome (P = 0.512) but was associated with subsequent inappropriate empirical antimicrobial selection (P = 0.031). Recent abdominal surgery was associated with subsequent inappropriate empirical antimicrobial selection (P = 0.021). CONCLUSIONS: In this population, appropriateness of empirical antimicrobial choice was not associated with survival to discharge. Previous antimicrobial administration or abdominal surgery was associated with subsequent inappropriate empirical antimicrobial selection.