Hospital Cost Savings for Sequential COPD Patients Receiving Domiciliary Nasal High Flow Therapy.

Purpose: To estimate the 5-year budget impact to Aotearoa New Zealand (NZ) hospitals of domiciliary nasal high flow (NHF) therapy to patients with chronic obstructive pulmonary disease (COPD) who require long term oxygen therapy. Methods: Hospital admission counts along with length of stay were obtained from hospital records of 200 COPD patients enrolled in a 12-month randomized clinical trial of NHF in Denmark, both over a 12-month baseline and then in the study period while on randomized treatment (control or NHF). NZ costings from similar COPD patients were estimated using data from Middlemore Hospital, Auckland and were applied to the Danish trial. The budget impact of NHF was estimated over the predicted 5-year lifetime of the device when used by patients sequentially. Results: Fifty-five of 100 patients in the NHF group and 44 of 100 patients in the control group were admitted to hospital with a respiratory diagnosis during the baseline year. They had 108 admissions in the treatment group vs 89 in the control group, with 632 vs 438 days in hospital, and modeled annual costs of $9443 vs $6512 per patient, respectively. During the study period there were 38 vs 44 patients with 67 vs 80 admissions and 302 vs 526 days in hospital, at a modeled annual cost of $6961 vs $9565 per patient respectively. Taking into account capital expenditure and running costs, this resulted in cost savings of $5535 per patient-year (95% CI, -$36 to -$11,034). With 90% usage over the estimated five-year lifetime of the NHF device, amortized capital costs of $594 per year and annual running costs of $662, we estimate a 5-year undiscounted cost saving per NHF device of $18,626 ($16,934 when discounted to net present value at 5% per annum). There would still be annual cost savings over a wide range of assumptions. Conclusion: Domiciliary NHF therapy for patients with severe COPD has the potential to provide substantial hospital cost savings over the five-year lifetime of the NHF device.

Impact of age, sex, ethnicity, socio-economic deprivation and novel pharmaceuticals on the overall survival of patients with multiple myeloma in New Zealand.

The impact of age, ethnicity and socio-economic deprivation in the era of novel anti-myeloma agents is unclear. Using linked national data from New Zealand, we evaluated the incidence, prevalence and overall survival (OS) of individuals who were diagnosed with myeloma between 2004 and 2016. The crude incidence rate increased from 5·42 to 8·47/100 000 and the age-standardised rate increased from 4·01 to 5·28/100 000. The estimated prevalence in December 2016 was 37·8/100 000. Median OS increased from 34·8 (95% CI 31·4, 39·3) months in 2004-2007 to 50·7 (48·5, 57·3) months in 2012-2016. Following the public funding of bortezomib in 2011, the median OS for individuals >70 years increased from 19·4 (16·3, 23·1) to 28·6 (24·5, 32·8) months. For those ≤70 years of age who did not have autologous stem cell transplantation (ASCT), median OS increased from 49·1 (37·1, 57·5) to 62·7 (51·7, 79·2) months; but for those who had ASCT, there was no difference in median OS. Socio-economic deprivation was an independent adverse prognostic factor. Maori/Pasifika and those in the most deprived quintile experienced no improvement in survival after bortezomib was funded. Our study confirms the increasing incidence and improving survival of myeloma patients, and the negative impact of Maori/Pasifika ethnicity and socio-economic deprivation on survival.

Primary prevention of rheumatic fever in the 21st century: evaluation of a national programme.

Background: Acute rheumatic fever (ARF) has largely disappeared from high-income countries. However, in New Zealand (NZ) rates remain high in indigenous (Maori) and Pacific populations. In 2011, NZ launched an intensive and unparalleled primary Rheumatic Fever Prevention Programme (RFPP). We evaluated the impact of the school-based sore throat service component of the RFPP. Methods: The evaluation used national trends of all-age first episode ARF hospitalisation rates before (2009-11) and after (2012-16) implementation of the RFPP. A retrospective cohort study compared first-episode ARF incidence during time-not-exposed (23 093 207 person-days) and time-exposed (68 465 350 person-days) with a school-based sore throat service among children aged 5-12 years from 2012 to 2016. Results: Following implementation of the RFPP, the national ARF incidence rate declined by 28% from 4.0 per 100 000 [95% confidence interval (CI) 3.5-4.6] at baseline (2009-11) to 2.9 per 100 000 by 2016 (95% CI 2.4-3.4, P <0.01). The school-based sore throat service effectiveness overall was 23% [95% CI -6%-44%; rate ratio (RR) 0.77, 95% CI 0.56-1.06]. Effectiveness was greater in one high-risk region with high coverage (46%, 95% CI 16%-66%; RR 0.54, 95% CI 0.34-0.84). Conclusions: Population-based primary prevention of ARF through sore throat management may be effective in well-resourced settings like NZ where high-risk populations are geographically concentrated. Where high-risk populations are dispersed, a school-based primary prevention approach appears ineffective and is expensive.

Hospital admissions for chronic obstructive pulmonary disease in New Zealand.

AIM: To determine the number, distribution and cost of hospital admissions for chronic obstructive pulmonary disease (COPD) in New Zealand. METHODS: National patient-level routine data on admissions with a principal diagnosis of COPD (mostly ICD-10- AN J440 and J441) were obtained for the period July 1st 2008 to June 30th 2013. Admissions with length of stay (LOS) = 90 days were excluded. RESULTS: There were 61,516 admissions in 5 years. Admission rates and budget impact (in 2012/13 dollar values) were stable but the average length of stay (ALOS) declined from 5.09 to 4.37 days. In FY2012/13 the admission rate was 2.82 per 1000 population, with age standardised rate (ASR) 4.4- and 3.6-fold higher for Maori and Pacific peoples respectively than for European/others. For age = 15 years the ASR was 2.55 per 1000. Admission rates were higher for men than women and increased steeply with age and socioeconomic deprivation (NZDep06). The mean age at discharge was lower for Maori and Pacific peoples than for European/Others (63.4, 67.1 and 72.3 years). The mean 30-day readmission rate was 6.7%. The average LOS increased with age and was shorter for Maori (3.6 days) and Pacific peoples (3.5 days) than for European/Others (4.7 days). Admission rates varied widely across District Health Boards, and were higher in rural than urban regions. The estimated cost of admissions in FY2012/13 was $NZ59.6m. CONCLUSIONS: Hospital admissions for COPD are costly and are over-represented in high risk groups including rural, elderly, socioeconomically deprived and Maori and Pacific peoples. Effective interventions that are targeted to high risk groups are required to improve equity and reduce the burden of COPD.

Long-term air humidification therapy is cost-effective for patients with moderate or severe chronic obstructive pulmonary disease or bronchiectasis.

OBJECTIVE: To establish the cost-effectiveness of long-term humidification therapy (LTHT) added to usual care for patients with moderate or severe chronic obstructive pulmonary disease or bronchiectasis. METHODS: Resource usage in a 12-month clinical trial of LTHT was estimated from hospital records, patient diaries, and the equipment supplier. Health state utility values were derived from the St. Georges Respiratory Questionnaire (SGRQ) total score. All patients who remained in the trial for 12 months and who had at least 90 days of diary records were included (87 of 108). RESULTS: Clinical costs were NZ $3973 (95% confidence interval [CI] $1614-$6332) for the control group and NZ $3331 (95% CI $948-$6920) for the intervention group. The mean health benefit per patient was -6.9 SGRQ units (95% CI -13.0 to -7.2; P < 0.05) or +0.0678 quality-adjusted life-years (95% CI 0.001-0.135). With the intervention costing NZ $2059 annually, the mean cost per quality-adjusted life-year was NZ $20,902 (US $18,907) and the bootstrap median was NZ $19,749 (2.5th percentile -$40,923, 97.5th percentile $221,275). At a willingness-to-pay (WTP) threshold of NZ $30,000, the probability of cost-effectiveness was 61%, ranging from 49% to 72% as the cost of LTHT was varied by ±30%. At a WTP of NZ $20,000, the probability was 49% (range 34%-61%). CONCLUSIONS: LTHT is moderately cost-effective for patients with moderate to severe chronic obstructive pulmonary disease or bronchiectasis at a WTP threshold that is acceptable for public funding of medicines in New Zealand. These findings must be interpreted with caution because of the modest size of the clinical study, necessary lack of blinding in the clinical trial, and uncertainty in estimating health state utility from the SQRQ.

Effect of fixed dose combination treatment on adherence and risk factor control among patients at high risk of cardiovascular disease: randomised controlled trial in primary care.

OBJECTIVE: To evaluate whether provision of fixed dose combination treatment improves adherence and risk factor control compared with usual care of patients at high risk of cardiovascular disease in primary care. DESIGN: Open label randomised control trial: IMPACT (IMProving Adherence using Combination Therapy). SETTING: 54 general practices in the Auckland and Waikato regions of New Zealand, July 2010 to August 2013. PARTICIPANTS: 513 adults (including 257 indigenous Maori) at high risk of cardiovascular disease (established cardiovascular disease or five year risk ≥ 15%) who were recommended for treatment with antiplatelet, statin, and two or more blood pressure lowering drugs. 497 (97%) completed 12 months' follow-up. INTERVENTIONS: Participants were randomised to continued usual care or to fixed dose combination treatment (with two versions available: aspirin 75 mg, simvastatin 40 mg, and lisinopril 10 mg with either atenolol 50 mg or hydrochlorothiazide 12.5 mg). All drugs in both treatment arms were prescribed by their usual general practitioners and dispensed by local community pharmacists. MAIN OUTCOME MEASURES: Primary outcomes were self reported adherence to recommended drugs (antiplatelet, statin, and two or more blood pressure lowering agents) and mean change in blood pressure and low density lipoprotein cholesterol at 12 months. RESULTS: Adherence to all four recommended drugs was greater among fixed dose combination than usual care participants at 12 months (81% v 46%; relative risk 1.75, 95% confidence interval 1.52 to 2.03, P<0.001; number needed to treat 2.9, 95% confidence interval 2.3 to 3.7). Adherence for each drug type at 12 months was high in both groups but especially in the fixed dose combination group: for antiplatelet treatment it was 93% fixed dose combination v 83% usual care (P<0.001), for statin 94% v 89% (P=0.06), for combination blood pressure lowering 89% v 59% (P<0.001), and for any blood pressure lowering 96% v 91% (P=0.02). Self reported adherence was highly concordant with dispensing data (dispensing of all four recommended drugs 79% fixed dose combination v 47% usual care, relative risk 1.67, 95% confidence interval 1.44 to 1.93, P<0.001). There was no statistically significant improvement in risk factor control between the fixed dose combination and usual care groups over 12 months: the difference in systolic blood pressure was -2.2 mm Hg (-4.5 v -2.3, 95% confidence interval -5.6 to 1.2, P=0.21), in diastolic blood pressure -1.2 mm Hg (-2.1 v -0.9, -3.2 to 0.8, P=0.22) and in low density lipoprotein cholesterol -0.05 mmol/L (-0.20 v -0.15, -0.17 to 0.08, P=0.46). The number of participants with cardiovascular events or serious adverse events was similar in both treatment groups (fixed dose combination 16 v usual care 18 (P=0.73), 99 v 93 (P=0.56), respectively). Fixed dose combination treatment was discontinued in 94 participants (37%). The most commonly reported reason for discontinuation was a side effect (54/75, 72%). Overall, 89% (227/256) of fixed dose combination participants' general practitioners completed a post-trial survey, and the fixed dose combination strategy was rated as satisfactory or very satisfactory for starting treatment (206/227, 91%), blood pressure control (180/220, 82%), cholesterol control (170/218, 78%), tolerability (181/223, 81%), and prescribing according to local guidelines (185/219, 84%). When participants were asked at 12 months how easy they found taking their prescribed drugs, most responded very easy or easy (224/246, 91% fixed dose combination v 212/246, 86% usual care, P=0.09). At 12 months the change in other lipid fractions, difference in EuroQol-5D, and difference in barriers to adherence did not differ significantly between the treatment groups. CONCLUSIONS: Among this well treated primary care population, fixed dose combination treatment improved adherence to the combination of all recommended drugs but improvements in clinical risk factors were small and did not reach statistical significance. Acceptability was high for both general practitioners and patients, although the discontinuation rate was high. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry ACTRN12606000067572.

Mortality and hospitalisation costs of rheumatic fever and rheumatic heart disease in New Zealand.

AIMS: To estimate the annual mortality and the cost of hospital admissions for acute rheumatic fever (ARF) and rheumatic heart disease (RHD) for New Zealand residents. METHODS: Hospital admissions in 2000-2009 with a principal diagnosis of ARF or RHD (ICD9_AM 390-398; ICD10-AM I00-I099) and deaths in 2000-2007 with RHD as the underlying cause were obtained from routine statistics. The cost of each admission was estimated by multiplying its diagnosis-related group (DRG) cost weight by the national price for financial year 2009/2010. RESULTS: There were on average 159 RHD deaths each year with a mean annual mortality rate of 4.4 per 100, 000 (95% confidence limit 4.2, 4.7). Age-adjusted mortality was five- to 10-fold higher for Maori and Pacific peoples than for non-Maori/Pacific. The mean age at RHD death (male/female) was 56.4/58.4 for Maori, 50.9/59.8 for Pacific and 78.2/80.6 for non-Maori, non-Pacific men and women. The average annual DRG-based cost of hospital admissions in 2000-2009 for ARF and RHD across all age groups was $12.0 million (95% confidence limit $11.1 million, $12.8 million). Heart valve surgery accounted for 28% of admissions and 71% of the cost. For children 5-14 years of age, valve surgery accounted for 7% of admissions and 27% of the cost. Two-thirds of the cost occurs after the age of 30. CONCLUSIONS: ARF and RHD comprise a burden of mortality and hospital cost concentrated largely in middle age. Maori and Pacific RHD mortality rates are substantially higher than those of non-Maori/Pacific.

Incidence of acute rheumatic fever in New Zealand children and youth.

AIM: To estimate acute rheumatic fever (ARF) incidence rates for New Zealand children and youth by ethnicity, socioeconomic deprivation and region. METHODS: National hospital admissions with a principal diagnosis of ARF (ICD9_AM 390-392; ICD10-AM I00-I02) were obtained from routine statistics and stratified by age, ethnicity, socioeconomic deprivation index (NZDep2006) and District Health Board (DHB). RESULTS: The mean incidence rate for ARF in 2000-2009 peaked at 9 to 12 years of age. Incidence rates for children 5 to 14 years of age for Maori were 40.2 (95% confidence interval 36.8, 43.8), Pacific 81.2 (73.4, 89.6), non-Maori/Pacific 2.1 (1.6, 2.6) and all children 17.2 (16.1, 18.3) per 100 000. Maori and Pacific incidence rates increased by 79% and 73% in 1993-2009, while non-Maori/Pacific rates declined by 71%. Overall rates increased by 59%. In 2000-2009, Maori and Pacific children comprised 30% of children 5-14 years of age but accounted for 95% of new cases. Almost 90% of index cases of ARF were in the highest five deciles of socioeconomic deprivation and 70% were in the most deprived quintile. A child living in the most deprived decile has about one in 150 risk of being admitted to the hospital for ARF by 15 years of age. Ten DHBs containing 76% of the population 5 to 14 years of age accounted for 94% of index cases of ARF. CONCLUSIONS: ARF with its attendant rheumatic heart disease is an increasing public health issue for disadvantaged North Island communities with high concentrations of Maori and/or Pacific families.

Burden and cost of hospital admissions for vaccine-preventable paediatric pneumococcal disease and non-typable Haemophilus influenzae otitis media in New Zealand.

INTRODUCTION: Streptococcus pneumoniae (Sp.) is a leading cause of paediatric bacterial meningitis, pneumonia and acute otitis media, as is non-typable Haemophilus influenzae (NTHi) for acute otitis media. In 2008, a 7-valent conjugated pneumococcal vaccine (PCV7) was included in the New Zealand (NZ) childhood immunization schedule. OBJECTIVE: To estimate the potentially vaccine-preventable annual hospital admissions and cost to the NZ Government of paediatric admissions for pneumococcal disease and NTHi otitis media prior to the immunization programme. METHODS: Admissions (2000-7) and deaths (2000-5) in children aged<20 years with pneumococcal meningitis or bacteraemia, pneumonia or otitis media were identified in national datasets and linked by unique patient identifiers. New episodes of illness were defined as admissions occurring >30 days after discharge from a previous admission. Informed by the literature, pneumococcal pneumonia episodes were estimated at 33% of all-cause pneumonia admissions; Sp. and NTHi otitis media episodes were estimated jointly at 72% of otitis media admissions. Each episode was assigned a single diagnosis according to the following hierarchy: meningitis>bacteraemia>pneumonia>otitis media. Incidence rates for episodes were determined for 2000-7 (meningitis, bacteraemia and pneumonia) and 2006-7 (otitis media). Annual DRG-based costs for pneumococcal meningitis, bacteraemia, pneumonia and otitis media were estimated as (episode rate)x(DRG cost weight per episode)x(2007 population)x(national price per cost weight). RESULTS: Episode rates for pneumococcal meningitis, bacteraemia and pneumonia were stable in 2000-7, highest in the second 6 months of life and declined steeply over the first 5 years of life. Mean rates per 100000 in 2000-7 were 18.4, 27.6 and 464 for pneumococcal meningitis, bacteraemia and pneumonia, respectively, for children aged<2 years; 8.4, 14.9 and 295 for children aged<5 years (including those aged<2 years); and 2.2, 4.4 and 97 for children aged<20 years (including those aged<5 years). Mean rates per 100000 in 2006-7 for Sp. and NTHi otitis media combined were 631 (surgical) and 197 (medical) for children aged<2 years; 691 and 116 for children aged<5 years; and 281 and 35 for children aged<20 years. Pacific Island and indigenous Maori children generally had higher rates than European/other children. Rates increased with socioeconomic disadvantage, across all diagnoses. The annual cost to Government of pneumococcal disease and NTHi otitis media admissions for children aged<20 years was estimated at New Zealand dollars ($NZ)9.95 million (range 7.7-12.2 million) [about $US7.1 million]. Most of this cost was shared between pneumococcal pneumonia (48%) and otitis media (45%), and 78% was incurred in the first 2 years of life. Estimated annual paediatric mortality rates per 100 000 for children aged<5 years were 0.48, 0.30 and 0.54 for pneumococcal meningitis, bacteraemia and pneumonia, respectively. The analysis predicted four or five pneumococcal deaths per year (range 1-8) for children aged<5 years. CONCLUSIONS: Prior to the introduction of a national Sp. immunization programme, hospital admissions for Sp. disease and NTHi otitis media in NZ cost about $NZ10 million annually, mostly for children aged<2 years and particularly for those living in relative socioeconomic deprivation and for Pacific Island and Maori children. There were about five pneumococcal deaths annually. With adjustment for local serotypes, vaccine serotype coverage and uptake, immunization with any of the three available pneumococcal vaccines would reduce this burden substantially.

Rotavirus infections and vaccines: burden of illness and potential impact of vaccination.

Rotaviruses are the most common cause of severe gastroenteritis in children. By 5 years of age virtually every child worldwide will have experienced at least one rotavirus infection. This leads to an enormous disease burden, where every minute a child dies because of rotavirus infection and another four are hospitalized, at an annual societal cost in 2007 of $US2 billion. Most of the annual 527 000 deaths are in malnourished infants living in rural regions of low and middle income countries. In contrast, most measurable costs arise from medical expenses and lost parental wages in high income countries. Vaccines are the only public health prevention strategy likely to control rotavirus disease. They were developed to mimic the immunity following natural rotavirus infection that confers protection against severe gastroenteritis and consequently reduces the risk of primary healthcare utilization, hospitalization and death. The two currently licensed vaccines--one a single human strain rotavirus vaccine, the other a multiple strain human-bovine pentavalent reassortant rotavirus vaccine--are administered to infants in a two- or three-dose course, respectively, with the first dose given at 6-14 weeks of age. In various settings they are safe, immunogenic and efficacious against many different rotavirus genotypes. In high and middle income countries, rotavirus vaccines confer 85-100% protection against severe disease, while in low income regions of Africa and Asia, protection is less, at 46-77%. Despite this reduced efficacy in low income countries, the high burden of diarrheal disease in these regions means that proportionately more severe cases are prevented by vaccination than elsewhere. Post-licensure effectiveness studies show that rotavirus vaccines not only reduce rotavirus activity in infancy but they also decrease rates of rotavirus diarrhea in older and unimmunized children. A successful rotavirus vaccination program will rely upon sustained vaccine efficacy against diverse and evolving rotavirus strains and efficient vaccine delivery systems. The potential introduction of rotavirus vaccines into the world's poorest countries with the greatest rates of rotavirus-related mortality is expected to be very cost effective, while rotavirus vaccines should also be cost effective by international standards when incorporated into developed countries immunization schedules. Nonetheless, cost effectiveness in each country still depends largely on the local rotavirus mortality rate and the price of the vaccine in relation to the per capita gross domestic product.

Budget impact and cost-effectiveness of including a pentavalent rotavirus vaccine in the New Zealand childhood immunization schedule.

OBJECTIVES: To estimate: 1) rotavirus disease burden in New Zealand children aged under 5 years, and 2) health benefits, budget impact, and cost-effectiveness of incorporating a pentavalent rotavirus vaccine (PRV) into the national immunization schedule. METHODS: A static equilibrium model was developed to evaluate health benefits and budget impact of vaccinating five successive birth cohorts with PRV at $50 per dose and 85% coverage (three doses). Cost-effectiveness was estimated from the societal perspective in year 5 of the program, with future health benefits discounted at 3.5% per annum. RESULTS: By the age of 5 years, one in five children will have sought medical advice for rotavirus gastroenteritis and one in 43 will have been hospitalized. In 2009, we estimate 1506 hospitalizations (476 per 100,000; 95% confidence interval 451, 502), 3086 Emergency Department (ED) presentations not requiring hospitalization, plus 10,120 cases of rotavirus gastroenteritis managed solely in primary care. The annual societal cost is $7.07 million, including 41% from hospitalization and 25% from caregiver income loss. Health benefits will increase and the cost of illness will decline by 78% in year 5 as successive birth cohorts are immunized. In the fifth year, 1191 hospitalizations, 2442 ED treated cases, 9762 primary care consultations, and 0.8 deaths will be averted. It requires six vaccinated children to avoid one primary care consultation, 49 to avert one hospitalization, and 73,357 to prevent one death. The incremental cost is $2.99 million and the break-even price per vaccine dose is $32.39 at 2006 prices. The cost is $2509 to avert one hospitalization and $305 to prevent one case seeking health-care assistance. The cost per life-year gained in year 5 is $143,097 and the cost per quality-adjusted life-year (QALY) gained is $46,092 (US$26,774). The cost per QALY is sensitive to incidence rates, vaccine price and efficacy, loss of quality of life by the child, case fatality, and caregiver income loss. CONCLUSIONS: From a societal perspective, addition of PRV to the New Zealand childhood immunization schedule would confer important clinical gains at a modest cost per QALY gained.

Quantifying the effect of age on short-term and long-term case fatality in 14,000 patients with incident cases of cardiovascular disease.

BACKGROUND: Age is a major determinant of case fatality following acute cardiovascular disease (CVD) events. Its impact, however, varies by time after the event, sex and diagnostic category. We were able to quantify these effects with good precision in a large cohort of patients. DESIGN: A national cohort of 14,227 CVD patients representing all the recorded first-CVD events in people aged 35-84 years in New Zealand in 1995 were examined, using electronic linkage of routine health data. METHODS: Case fatality by age was assessed in three phases: prehospital deaths, fatality after hospitalization up to 28 days and from 28 days up to 5 years after the event. It was assessed in these phases by sex and by the diagnostic categories: acute myocardial infarction (AMI), stroke and other coronary heart diseases. RESULTS: Case fatality in the prehospital phase showed substantial age differences. In particular, a strong positive monotonic age gradient was observed for AMI, but a U-shaped age-case-fatality gradient for stroke. From admission to 28 days, AMI case fatality demonstrated the strongest age gradient. In contrast, there was minimal age effect on 28-day stroke mortality, and case fatality for other coronary heart diseases was low. From 28 days to 5 years, there was a substantial positive monotonic age by case-fatality gradient for all diagnoses. CONCLUSION: Age has a large impact on case fatality following cardiovascular events, although the effect varies significantly by time elapsed after the event, diagnostic category and sex. As the lifetime benefits of many cardiovascular interventions depend on preintervention risk and case fatality, the role of age needs careful attention while making treatment decisions.

Quality-of-life valuations of advanced breast cancer by New Zealand women.

OBJECTIVES: To obtain health-related quality-of-life (HR-QOL) valuations (or 'utilities') from New Zealand women for four health states representative of advanced (metastatic) breast cancer, suitable for use in cost-utility analysis, and to compare four valuation methodologies. METHODS: Written case descriptions of four health states representative of advanced breast cancer (hormonal therapy, chemotherapy, radiotherapy and hypercalcaemia) were developed in consultation with nine oncology professionals. Time trade-off (TTO) and visual analogue scale (VAS) valuations were obtained via interviews from a sample of 50 women, aged 25-69 years, randomly selected from the New Zealand general public and through informal networks. Representations of the four health states on the EQ-5D health state classification system were also obtained from the respondents and later valued using New Zealand and UK EQ-5D social tariffs. RESULTS: The four valuation methods ranked the four states' mean valuations identically: hormonal therapy > chemotherapy > or = radiotherapy > hypercalcaemia. All methods except the TTO distinguished between chemotherapy and radiotherapy. In order of the VAS and TTO methods and the EQ-5D with NZ and UK tariffs, respectively, the valuations [mean (95% CI)] were: hormonal therapy 0.54 (0.48, 0.59); 0.65 (0.57, 0.73); 0.54 (0.51, 0.58); 0.60 (0.54, 0.65); chemotherapy 0.46 (0.41, 0.51); 0.49 (0.40, 0.57); 0.48 (0.43, 0.53); 0.51 (0.43, 0.59); radiotherapy for severe bone pain 0.35 (0.30, 0.40); 0.45 (0.37, 0.54); 0.31 (0.27, 0.35); 0.25 (0.18, 0.33); and moderate to severe hypercalcaemia 0.13 (0.09, 0.17); -0.17 (-0.29, -0.05); -0.05 (-0.07, -0.03); -0.52 (-0.56, -0.48). The four valuation methods gave similar results for chemotherapy, but for the three other states the TTO valuations differed from those obtained from the VAS method and the NZ and UK EQ-5D tariffs. There were significant pairwise correlations between the four methods across all four health states, although the valuation for hypercalcaemia obtained from the UK EQ-5D tariff was very low compared with the three other methods, and the VAS valuation was positive rather than negative. CONCLUSION: Our study suggests that women in the New Zealand general public are able to consistently evaluate and value case descriptions of advanced breast cancer using either direct methods (VAS or TTO) or the EQ-5D health state classification system. Some of the valuations elicited using the four methods differ quantitatively, especially for hypercalcaemia. As our sample size was modest (50) and it turned out to be unrepresentative of the New Zealand female population, this study serves as a pilot study.

Treatment with drugs to lower blood pressure and blood cholesterol based on an individual's absolute cardiovascular risk.

In this review, we outline the rationale for targeting blood pressure and blood cholesterol lowering drug treatments to patients at high absolute cardiovascular risk, irrespective of their blood pressure or blood cholesterol levels. Because the specific levels of blood pressure and cholesterol are of little clinical relevance when considered in isolation from other risk factors, terms such as hypertension or hypercholesterolaemia have limited value. Separate management guidelines for raised blood pressure and blood cholesterol need to be replaced by integrated cardiovascular risk management guidelines, and absolute cardiovascular risk prediction scores should be used routinely. Since cardiovascular risk factors interact with each other, moderate reductions in several risk factors can be more effective than major reductions in one. An affordable daily pill combining low doses of various drugs could be useful for the many individuals with slightly abnormal cardiovascular risk factors.

Habituation to sham testing procedures modifies tail-flick latencies: effects on nociception rather than vasomotor tone.

Habituation of rats to the testing environment and procedures reduces flexor withdrawal latencies to those of spinalised animals. We have now recorded surface temperatures at 3 sites on the tail and tail-flick latencies simultaneously in experimentally naive (novice) rats and in habituated rats. At usual ambient temperatures (20 +/- 1 degree C), tail temperatures fluctuated in accordance with the predictions of an on-off controller. There was an inverse correlation between the tail-flick latency and the temperature at the site of noxious stimulation. A similar correlation was found when the pre-stimulus temperature of the tip of the tail was held at temperatures ranging from 21 degrees C to 35 degrees C. Habituated animals exhibited a similar linear regression slope factor but lower latencies than novice animals at each temperature. We conclude (1) that tail-flick latency is determined partly by the pre-stimulus temperature at the site of noxious thermal stimulation, and (2) that the effects of habituation on tail-flick latency are more likely to be explained by differences in nociception than in regional vasomotor tone.