Shock decision algorithm for use during load distributing band cardiopulmonary resuscitation.

AIM: Chest compressions delivered by a load distributing band (LDB) induce artefacts in the electrocardiogram. These artefacts alter shock decisions in defibrillators. The aim of this study was to demonstrate the first reliable shock decision algorithm during LDB compressions. METHODS: The study dataset comprised 5813 electrocardiogram segments from 896 cardiac arrest patients during LDB compressions. Electrocardiogram segments were annotated by consensus as shockable (1154, 303 patients) or nonshockable (4659, 841 patients). Segments during asystole were used to characterize the LDB artefact and to compare its characteristics to those of manual artefacts from other datasets. LDB artefacts were removed using adaptive filters. A machine learning algorithm was designed for the shock decision after filtering, and its performance was compared to that of a commercial defibrillator's algorithm. RESULTS: Median (90% confidence interval) compression frequencies were lower and more stable for the LDB than for the manual artefact, 80 min-1 (79.9-82.9) vs. 104.4 min-1 (48.5-114.0). The amplitude and waveform regularity (Pearson's correlation coefficient) were larger for the LDB artefact, with 5.5 mV (0.8-23.4) vs. 0.5 mV (0.1-2.2) (p < 0.001) and 0.99 (0.78-1.0) vs. 0.88 (0.55-0.98) (p < 0.001). The shock decision accuracy was significantly higher for the machine learning algorithm than for the defibrillator algorithm, with sensitivity/specificity pairs of 92.1/96.8% (machine learning) vs. 91.4/87.1% (defibrillator) (p < 0.001). CONCLUSION: Compared to other cardiopulmonary resuscitation artefacts, removing the LDB artefact was challenging due to larger amplitudes and lower compression frequencies. The machine learning algorithm achieved clinically reliable shock decisions during LDB compressions.

Chest compression duration influences outcome between integrated load-distributing band and manual CPR during cardiac arrest.

BACKGROUND: The Circulation Improving Resuscitation Care (CIRC) Trial found equivalent survival in adult out-of-hospital cardiac arrest (OHCA) patients who received integrated load-distributing band CPR (iA-CPR) compared to manual CPR (M-CPR). We hypothesized that as chest compression duration increased, iA-CPR provided a survival benefit when compared to M-CPR. METHODS: A pre-planned secondary analysis of OHCA of presumed cardiac etiology from the randomized CIRC trial. Chest compressions duration was defined as the total number of minutes spent on compressions during resuscitation and identified from transthoracic impedance and accelerometer data recorded by the EMS defibrillator. Logistic regression was used to model the interaction between treatment and duration of chest compressions and was covariate-adjusted for trial site, patient age, witnessed arrest, and initial shockable rhythm. Primary outcome was survival to hospital discharge. RESULTS: We enrolled 4231 subjects and of those, 2012 iA-CPR and 2002 M-CPR had complete outcome and duration of chest compressions data. While covariate-adjusted odds ratio for survival to hospital discharge was 1.86 in favor of iA-CPR (95% CI 1.16-3.0), there was an interaction between duration and study arm. When this was factored into the multivariate equation, the odds ratio for survival to hospital discharge showed a significant benefit for iA-CPR vs. M-CPR for chest compression duration greater than 16.5 min. CONCLUSION: After adjusting for compression duration and duration-treatment interaction, iA-CPR showed a significant benefit for survival to hospital discharge vs. M-CPR in patients with OHCA if chest compression duration was longer than 16.5 min.

Trastuzumab in adjuvant breast cancer therapy. A model based cost-effectiveness analysis.

Trastuzumab has shown activity in early breast cancer patients that overexpress HER2. Significant resources have to be allocated to finance this therapy, underlining the need for cost-effectiveness analysis. A model was set up, societal costs were calculated and the discount rate was 3%. Life expectancy data were based on the literature and prolonged according to qualified guess (10% and 20% absolute improvement in overall survival (OS)). The comparator was the FEC(100) regimen. The median additional health care cost per patient treated was 33,597 euros. The yielding cost per life year gained (LYG) was 15,341 euros with a 20% improved OS and 35,947 euros with 10% improved OS. The corresponding net health care cost per quality adjusted life year (QALY) was 19,176 euros and 44,934 euros. Including all resource use the figures were 8148 euros and 30,290 euros per LYG. Sensitivity analyses documented survival gain, price of trastuzumab, production gain and discount rate to be the major factors influencing cost-effectiveness ratio. Trastuzumab is indicated cost effective in Norway.

Cost-effectiveness of antenatal screening for neonatal alloimmune thrombocytopenia.

OBJECTIVES: To estimate the costs and health consequences of three different screening strategies for neonatal alloimmune thrombocytopenia (NAIT). DESIGN: Cost-utility analysis on the basis of a decision tree that incorporates the relevant strategies and outcomes. SETTING: Three health regions in Norway encompassing a 2.78 million population. POPULATION: Pregnant women (n = 100,448) screened for human platelet antigen (HPA) 1a and anti-HPA 1a antibodies, and their babies. METHOD: Decision tree analysis. In three branches of the decision tree, pregnant women entered a programme while in one no screening was performed. The three different screening strategies included all HPA 1a negative women, only HPA 1a negative, HLA DRB3*0101 positive women or only HPA 1a negative women with high level of anti-HPA 1a antibodies. Included women underwent ultrasound examination and elective caesarean section 2-4 weeks before term. Severely thrombocytopenic newborn were transfused immediately with compatible platelets. MAIN OUTCOME MEASUREMENTS: Quality-adjusted life years (QALYs) and costs. RESULTS: Compared with no screening, a programme of screening and subsequent treatment would generate between 210 and 230 additional QALYs among 100,000 pregnant women, and at the same time, reduce health care costs by approximately 1.7 million euros. The sensitivity analyses indicate that screening is cost effective or even cost saving within a wide range of probabilities and costs. CONCLUSION: Our calculations indicate that it is possible to establish an antenatal screening programme for NAIT that is cost effective.

A monoclonal antibody against HER-2 (trastuzumab) for metastatic breast cancer: a model-based cost-effectiveness analysis.

BACKGROUND: The aim of this study was to evaluate the cost-effectiveness of trastuzumab in patients with metastatic breast cancer (MBC) in a model-based cost-effectiveness analysis (CEA). Trastuzumab has shown considerable activity in patients with MBC that overexpress HER2. However, significant resources have been allocated to finance this new therapy. Due to ever increasing pressures on health care budgets, economic evaluations are requested in order to compare health effects with costs. METHODS: All available data on trastuzumab in MBC presented at the San Antonio breast cancer conference in late 2003 and all data on Medline in December 2003 were analysed for life years (LY) gained and quality of life (QoL) with regard to the use of this new monoclonal antibody. Randomised studies comparing standard chemotherapy, with or without trastuzumab, were focused. The costs were calculated according to Norwegian prices as of January 2003. RESULTS: The LY gained ranged between 0.3 and 0.7 years. The median cost per patient treated was 44 196 yielding costs per life year saved in the range 63 137-162 417 depending on survival gain and discount rate employed. A sensitivity analysis documented the price of trastuzumab and the survival benefit the two major factors influencing the cost-effectiveness ratio. CONCLUSION: The economic evaluation indicates that trastuzumab is not cost effective in metastatic breast cancer. Reduced drug costs and/or improved survival may alter the conclusion.

Synthesis of new 3- and 4-substituted analogues of acyl homoserine lactone quorum sensing autoinducers.

The quorum sensing mechanism in Gram-negative bacteria uses small intercellular signal molecules, N-acyl-homoserine lactones (AHLs), to control transcription of specific genes in relation to population density. In this communication, we describe the parallel synthesis of new AHL analogues, in which substituents have been introduced into the 3- and 4-positions of the lactone ring. These analogues have been screened for their ability to activate and inhibit a Vibrio fischeri LuxI/LuxR-derived quorum sensing reporter system.

Association of time preference for health with age and disease severity.

This study assessed the relationship between time preference for health and age and disease severity. An implicit time preference for health was inferred in 59 patients with chronic obstructive pulmonary disease (COPD) using the time tradeoff method with 10-year and 30-year perspectives. The preference rate was calculated by solving the resulting nonlinear equation, solvable for 50 patients.Among the resulting rates, 4 were negative, 8 zero, and 38 positive. The time preference rate ranged from -10.8% to 75.0%, with a median of 6.6%, and a mean of 11.5%. In correlation analysis, the implicit time preference rate was associated with age;however, there was little association with markers of disease severity. In multivariate analysis, only age was a significant predictor of time preference rate after controlling for the other variables in the model.

Equity in health: the importance of different health streams.

This paper develops a conceptual framework in which preferences about the distribution of future health gains depend on differences in four 'health streams'. These are as follows: (1) the amount of health to be gained; (2) the no-treatment profiles; (3) the amount of health experienced thus far: and (4) the amount of health gained previously as a result of public health interventions. This classification puts the well-established concerns for severity (stream 2) and age weights (stream 3) into a more complete analytical framework. Stream 4 has not been discussed to date and the paper suggests some moral arguments about the distributive relevance of this stream of health.

Theory versus practice: a review of 'willingness-to-pay' in health and health care.

This paper is based upon an extensive review of 71 willingness-to-pay (WTP) surveys of health and health care published in English during the period 1985--1998. The aim of the paper is to outline the arguments advanced for the superiority of WTP over quality-adjusted-life-years (QALYs) as a measure of benefit of health care programmes, and to review how empirical WTP studies adhere to their implications. An important argument is that WTP enables a more comprehensive valuation of benefits than QALYs. Our main focus is therefore to provide a careful review of the scenario descriptions used in the surveys, according to which types of benefits are being valued, and how comprehensively the descriptions are presented. Furthermore, the 'cost-benefit argument', that WTP can assist in improving social efficiency, is discussed before we inquire into the extent to which the studies actually compare WTP with social costs.

A note on eliciting distributive preferences for health.

While in theory the strength of preferences for equity in health can be expressed in an 'inequality aversion parameter', in practice, analysts would have to obtain them from people's choices. We are faced with a number of methodological problems when turning to this type of empirical research. This note investigates which types of preference could explain the choices people make when responding to equity-efficiency questions of this kind. Respondents may be heavily influenced by concerns that are not related to their equity preferences, something which may lead them to choose distributions that are not consistent with models on the equity-efficiency trade-off. Specifically, a threshold effect is identified, which could explain why some people would rather prefer to concentrate than to diffuse health gains. The second aim of this note is to offer some lessons from a survey which was designed for eliciting people's distributive preferences for health gains.

[How much money are we willing to spend on health services?]. / Hvor mye penger vil vi bruke på helsevesenet?

BACKGROUND: Like most other countries, Norway spends increasing sums of money on health care. The purpose of this study is to elicit people's views on whether society should spend more, and if so, their willingness to contribute to the financing of an expanded health service. MATERIAL AND METHODS: A random sample of the Norwegian population (2,089) were approached regarding a questionnaire study. 716 returned completed questionnaires (34%). Different versions of a questionnaire were used on three sub-samples in order to analyze the extent to which the distribution of answers depends on the wording of the questions. Variation in answers are sought explained by sociodemographic variables and political preferences. RESULTS: 70-80% held that society should spend more on health care. Their willingness to pay more in terms of "earmarked health care taxes" varied between the sub-samples. The mean annual figures were between NOK 1,314 and NOK 1,972. The proportions not willing to pay more varied between 39% and 46%. INTERPRETATION: It appears to be wide support for the idea that society should spend more on health care, but limited support for the idea of having to finance the desired expansion. One should be very cautious to generalize from preference surveys of this kind, because answers depend on the wording of the questions.

Combinatorial solid-phase synthesis of hapalosin mimetics.

The solid-phase synthesis of a small library of mimetics of the cyclic depsipeptide hapalosin is described. 3-Amino-4-hydroxy-5-nitrobenzoic acid was anchored through the anilino moiety to a backbone amide linker (BAL) handle support. Using chemoselective reactions and without the need for protecting group manipulations, the benzoic acid group was first amidated, then the aniline nitrogen was acylated, and finally the nitro group was reduced to an amine and acylated or reductively alkylated, to generate a 12-member library.

Influence of cuff size on blood pressure among schoolchildren.

In 236 schoolchildren aged 7-15 years arm blood pressure was measured using a semiautomatic technique. Three different cuffs were chosen among four cuffs with bladder sizes of either 6 x 20 cm, 9 x 27 cm, 12 x 35 cm or 15 x 43 cm. Ideal cuff size in each pupil was defined as the one in which the width of the bladder was closest to 40% of arm circumference. In all subjects ideal cuffs were tested along with two cuffs bigger or smaller than the ideal one. The study showed that "normal blood pressure" in relation to age depended on the cuff used. Using the ideal one, systolic blood pressure increased from 105 mmHg at 7 years of age to 117-119 mmHg at age 11, with no further increase at higher ages, while diastolic blood pressure was almost unchanged in the different age groups. Normal blood pressure curves constructed using the same cuff in all children showed a steeper increase in both systolic and diastolic blood pressure in relation to age compared to the curve based on the ideal cuff in all children. It is strongly recommended that future studies should take the best-suited cuff problem into consideration when planning studies among children. Some of the differences between previous published studies may be explained by the differences introduced by different cuff sizes.

Production gains from health care: what should be included in cost-effectiveness analyses?

Recent literature has been concerned with the correct measurement of the 'indirect costs and benefits' of health care as well as the issue of including these items in economic evaluations. This article considers the question of which 'indirect benefits' to include in cost effectiveness analysis and cost utility analysis. Within the context of a collectively financed health scheme the relevant issues include not only the size of the net resource costs of providing health care but also which costs and benefits the society is prepared to consider in its assessment of health services. The strong preference for 'equal access for equal need' implies that some production gains may have to be disregarded in the social welfare function. We introduce the notion of socially relevant and socially irrelevant production gains. The analysis suggests that the magnitude of the socially relevant part of the production gains may vary between countries as it depends, first, upon differences in patients' potential contributions to the rest of society (tax rates), and second, the strength of preferences for equity.

Helicopters, hearts and hips: using willingness to pay to set priorities for public sector health care programmes.

The paper reports from a study that asked 150 interviewees their willingness to pay (WTP) in increased earmarked taxation for three different health care programmes: a helicopter ambulance service, more heart operations and more hip replacements. Reasons behind the stated WTP were asked for. Ordinary least squares regression analyses were used to analyse factors associated with WTP for each of the three programmes, and factors associated with the relative WTP for one programme compared with the total of the three. Comparisons were made of WTP for these programmes and the health outcome in terms of quality adjusted life years.

Theories of justice and their implications for priority setting in health care.

The paper aims to show how three theories of distributive justice; utilitarianism, egalitarianism and maximum, can provide a clearer understanding of the normative basis of different priority setting regimes in the health service. The paper starts with a brief presentation of the theories, followed by their prescriptions for distribution, as illustrated with their respective preferred points on a utility possibility frontier. After this general discussion, attention is shifted from utils to health. The paper discusses how the recent Norwegian guidelines for priority setting can be understood in the light of the theories.

Lumpectomy or mastectomy? Is breast conserving surgery too expensive?

In the last decade, breast cancer patients have enjoyed an increase in breast conserving surgery (BCS). At present, modified radical mastectomy (MRM) and BCS offers equal expectations of survival. During the last few years, however, a drop in the frequency of BCS has been reported by several authors. Is this new trend due to economic concerns? To clarify the costs of breast cancer therapy (stage I and II), we review the literature and include a cost-utility and a cost-minimisation analysis comparing MRM and BCS. The treatment cost (per patient) of BCS and MRM in Norway was calculated at $9,564 and $5,596, respectively. Employing a quality of life gain in BCS of 0.03 (0-1 scale) and a 5% discount rate, the cost per QALY in BCS compared to MRM was $20,508. In cost-minimising analysis, BCS and mastectomy followed by reconstructive surgery had a cost of $10,748 and $8,538, respectively. This indicates that BCS remains within reasonable cost and should not be displaced by mastectomy on economic grounds.

Adjuvant chemotherapy (5-fluorouracil and levamisole) in Dukes' B and C colorectal carcinoma. A cost-effectiveness analysis.

BACKGROUND: Adjuvant chemotherapy (5-fluorouracil, levamisole) is now standard practice in the treatment of Dukes' B and C coloretal carcinoma (CRC), and this has increased the financial burden on health care systems world-wide. PATIENTS AND METHODS: Between 1993 and 1996, 95 patients in northern Norway were included in a national randomised CRC study, and assigned to surgery plus adjuvant chemotherapy or surgery alone. In April 1996, 94 of the patients were evaluable and 82 were still alive. The total treatment costs (hospital stay, surgery, chemotherapy, administrative and travelling costs) were calculated. A questionnaire was mailed to all survivors for assessment of the quality of their lives (QoL) (EuroQol questionnaire, a simple QoL-scale, global QoL-measure of the EORTC QLQ-C30), and 62 of them (76%) responded. RESULTS: Adjuvant chemotherapy in Dukes' B and C CRC raised the total treatment costs by 3,369 pounds. The median QoL was 0.83 (0-1 scale) in both arms. Employing a 5% discount rate and an improved survival of adjuvant therapy ranging from 5% to 15%, we calculated the cost of one gained quality-adjusted life-year (QALY) to be between 4,800 pounds and 16,800 pounds. CONCLUSION: Using a cut-off point level of 20,000 pounds per QALY, adjuvant chemotherapy in CRC appears to be cost-effective only when the improvement in 5-year survival is > or = 5%. Adjuvant chemotherapy does not affect short-term QoL.

Aiding priority setting in health care: is there a role for the contingent valuation method?

The paper discusses some methodological and measurement aspects with the contingent valuation (CV) method which appear to create problems when eliciting preferences for the relative social valuation of alternative health care programmes. After pointing to biases which tend to exaggerate the true valuations, emphasis is placed on framing issues when applied to health care. Thereafter the paper discusses the extent to which preferences elicited through one's willingness to pay can be used to infer how the respondent would prioritize between the health care programmes in question. New empirical evidence is presented which suggest discrepancies between a CV ranking and the ranking expressed when making a direct ordinal comparison.

A cost-effectiveness approach to the Norwegian follow-up programme in colorectal cancer.

BACKGROUND: Today, continued periodic follow-up of patients treated for colorectal cancer (CRC) seems often to be routine because of tradition, rather than its demonstrated value. Recently, the Norwegian Gastrointestinal Cancer Group (NGICG) has recommended a standard surveillance programme in this malignancy. In this protocol patients are suggested followed for four years with CEA monitoring, ultrasound of the liver, chest radiograph and colonoscopy at regular intervals. MATERIALS AND METHODS: In this study, the cost-effectiveness of this programme was addressed employing Norwegian cost data and data from the Cancer Registry of Norway. Clinical data from the existing English language literature was used in the analysis. RESULTS: The basic cost of the NGICG recommended programme was 1,232 Pounds per patient. Including extended investigation due to suspected relapse in 45% of cases, the figure raised to 1,943 Pounds per patient. The cost per life year saved was indicated to 9,525 Pounds-16,192 Pounds. The corresponding cost per quality adjusted life year (QALY) was indicated to 11,476 Pounds-19,508 Pounds. CONCLUSION: We conclude the NGICG recommended follow-up programme in CRC cost-effective. Excluding CEA monitoring may improve the cost-effectiveness.