Predictability of drug expenditures: An application using morbidity data

The growth of pharmaceutical expenditure and its prediction is a major concern for policy makers and health care managers. This paper explores different predictive models to estimate future drug expenses, using demographic and morbidity individual information from an integrated healthcare delivery organization in Catalonia for years 2002 and 2003. The morbidity information consists of codified health encounters grouped through the Clinical Risk Groups (CRGs). We estimate pharmaceutical costs using several model specifications, and CRGs as risk adjusters, providing an alternative way of obtaining high predictive power comparable to other estimations of drug expenditures in the literature. These results have clear implications for the use of risk adjustment and CRGs in setting the premiums for pharmaceutical benefits.

O financiamento por capitação ajustada pelo risco em contexto de integração vertical de cuidados de saúde : a utilização dos consumos com medicamentos como proxy da carga de doença em ambulatório

RESUMO - Introdução - Com o presente projecto de investigação pretendeu-se estudar o financiamento por capitação ajustado pelo risco em contexto de integração vertical de cuidados de saúde, recorrendo particularmente a informação sobre o consumo de medicamentos em ambulatório como proxy da carga de doença. No nosso país, factores como a expansão de estruturas de oferta verticalmente integradas, inadequação histórica da sua forma de pagamento e a recente possibilidade de dispor de informação sobre o consumo de medicamentos de ambulatório em bases de dados informatizadas são três fortes motivos para o desenvolvimento de conhecimento associado a esta temática. Metodologia - Este trabalho compreende duas fases principais: i) a adaptação e aplicação de um modelo de consumo de medicamentos que permite estimar a carga de doença em ambulatório (designado de PRx). Nesta fase foi necessário realizar um trabalho de selecção, estruturação e classificação do modelo. A sua aplicação envolveu a utilização de bases de dados informatizadas de consumos com medicamentos nos anos de 2007 e 2008 para a região de Saúde do Alentejo; ii) na segunda fase foram simulados três modelos de financiamento alternativos que foram propostos para financiar as ULS em Portugal. Particularmente foram analisadas as dimensões e variáveis de ajustamento pelo risco (índices de mortalidade, morbilidade e custos per capita), sua ponderação relativa e consequente impacto financeiro. Resultados - Com o desenvolvimento do modelo PRx estima-se que 36% dos residentes na região Alentejo têm pelo menos uma doença crónica, sendo a capacidade de estimação do modelo no que respeita aos consumos de medicamentos na ordem dos 0,45 (R2). Este modelo revelou constituir uma alternativa a fontes de informação tradicionais como são os casos de outros estudos internacionais ou o Inquérito Nacional de Saúde. A consideração dos valores do PRx para efeitos de financiamento per capita introduz alterações face a outros modelos propostos neste âmbito. Após a análise dos montantes de financiamento entre os cenários alternativos, obtendo os modelos 1 e 2 níveis de concordância por percentil mais próximos entre si comparativamente ao modelo 3, seleccionou-se o modelo 1 como o mais adequado para a nossa realidade. Conclusão - A aplicação do modelo PRx numa região de saúde permitiu concluir em função dos resultados alcançados, que já existe a possibilidade de estruturação e operacionalização de um modelo que permite estimar a carga de doença em ambulatório a partir de informação relativa ao seu perfil de consumo de medicamentos dos utentes. A utilização desta informação para efeitos de financiamento de organizações de saúde verticalmente integradas provoca uma variação no seu actual nível de financiamento. Entendendo este estudo como um ponto de partida onde apenas uma parte da presente temática ficará definida, outras questões estruturantes do actual sistema de financiamento não deverão também ser olvidadas neste contexto. ------- ABSTRACT - Introduction - The main goal of this study was the development of a risk adjustment model for financing integrated delivery systems (IDS) in Portugal. The recent improvement of patient records, mainly at primary care level, the historical inadequacy of payment models and the increasing number of IDS were three important factors that drove us to develop new approaches for risk adjustment in our country. Methods - The work was divided in two steps: the development of a pharmacy-based model in Portugal and the proposal of a risk adjustment model for financing IDS. In the first step an expert panel was specially formed to classify more than 33.000 codes included in Portuguese pharmacy national codes into 33 chronic conditions. The study included population of Alentejo Region in Portugal (N=441.550 patients) during 2007 and 2008. Using pharmacy data extracted from three databases: prescription, private pharmacies and hospital ambulatory pharmacies we estimated a regression model including Potential Years of Life Lost, Complexity, Severity and PRx information as dependent variables to assess total cost as the independent variable. This healthcare financing model was compared with other two models proposed for IDS. Results - The more prevalent chronic conditions are cardiovascular (34%), psychiatric disorders (10%) and diabetes (10%). These results are also consistent with the National Health Survey. Apparently the model presents some limitations in identifying patients with rheumatic conditions, since it underestimates prevalence and future drug expenditure. We obtained a R2 value of 0,45, which constitutes a good value comparing with the state of the art. After testing three scenarios we propose a model for financing IDS in Portugal. Conclusion - Drug information is a good alternative to diagnosis in determining morbidity level in a population basis through ambulatory care data. This model offers potential benefits to estimate chronic conditions and future drug costs in the Portuguese healthcare system. This information could be important to resource allocation decision process, especially concerning risk adjustment and healthcare financing.

Hybrid risk adjustment for pharmaceutical benefits

This paper analyses the application of hybrid risk adjustment versus either prospective orconcurrent risk adjustment formulae in the context of funding pharmaceutical benefits for thepopulation of an integrated healthcare delivery organization in Catalonia during years 2002 and2003. We apply a mixed formula and find that a hybrid risk adjustment model increasesincentives for efficiency in the provision of low risk individuals at health organizations not only asa whole but also at each internal department compared to only prospective models by reducingwithin-group variation of drug expenditures.

Profile, cost and pattern of prescriptions for polymedicated patients in Catalonia (Spain).

OBJECTIVES: Polypharmacy is one of the main management issues in public health policies because of its financial impact and the increasing number of people involved. The polymedicated population according to their demographic and therapeutic profile and the cost for the public healthcare system were characterised. DESIGN: Cross-sectional study. SETTING: Primary healthcare in Barcelona Health Region, Catalonia, Spain (5 105 551 inhabitants registered). PARTICIPANTS: All insured polymedicated patients. Polymedicated patients were those with a consumption of ≥16 drugs/month. MAIN OUTCOMES MEASURES: The study variables were related to age, gender and medication intake obtained from the 2008 census and records of prescriptions dispensed in pharmacies and charged to the public health system. RESULTS: There were 36 880 polymedicated patients (women: 64.2%; average age: 74.5±10.9 years). The total number of prescriptions billed in 2008 was 2 266 830 (2 272 920 total package units). The most polymedicated group (up to 40% of the total prescriptions) was patients between 75 and 84 years old. The average number of prescriptions billed monthly per patient was 32±2, with an average cost of 452.7±27.5. The total cost of those prescriptions corresponded to 2% of the drug expenditure in Catalonia. The groups N, C, A, R and M represented 71.4% of the total number of drug package units dispensed to polymedicated patients. Great variability was found between the medication profiles of men and women, and between age groups; greater discrepancies were found in paediatric patients (5-14 years) and the elderly (≥65 years). CONCLUSIONS: This study provides essential information to take steps towards rational drug use and a structured approach in the polymedicated population in primary healthcare.

Profile, cost and pattern of prescriptions for polymedicated patients in Catalonia, Spain

OBJECTIVES: Polypharmacy is one of the main management issues in public health policies because of its financial impact and the increasing number of people involved. The polymedicated population according to their demographic and therapeutic profile and the cost for the public healthcare system were characterised. DESIGN: Cross-sectional study. SETTING: Primary healthcare in Barcelona Health Region, Catalonia, Spain (5 105 551 inhabitants registered). PARTICIPANTS: All insured polymedicated patients. Polymedicated patients were those with a consumption of ≥16 drugs/month. MAIN OUTCOMES MEASURES: The study variables were related to age, gender and medication intake obtained from the 2008 census and records of prescriptions dispensed in pharmacies and charged to the public health system. RESULTS: There were 36 880 polymedicated patients (women: 64.2%; average age: 74.5±10.9 years). The total number of prescriptions billed in 2008 was 2 266 830 (2 272 920 total package units). The most polymedicated group (up to 40% of the total prescriptions) was patients between 75 and 84 years old. The average number of prescriptions billed monthly per patient was 32±2, with an average cost of 452.7±27.5. The total cost of those prescriptions corresponded to 2% of the drug expenditure in Catalonia. The groups N, C, A, R and M represented 71.4% of the total number of drug package units dispensed to polymedicated patients. Great variability was found between the medication profiles of men and women, and between age groups; greater discrepancies were found in paediatric patients (5-14 years) and the elderly (≥65 years). CONCLUSIONS: This study provides essential information to take steps towards rational drug use and a structured approach in the polymedicated population in primary healthcare.

Twenty-four-hour energy expenditure and thermogenesis: response to progressive carbohydrate overfeeding in man.

Short-term overfeeding with carbohydrate induced a marked stimulation of energy expenditure, amounting to 33 per cent of the excess energy intake on the 7th day of overfeeding. This value is larger than that previously reported in man. Stimulation of lipogenesis and increased activity of the sympathetic nervous system seem to be the two major mechanisms which account for the stimulation of energy expenditure during carbohydrate overfeeding.

The effects of catechin rich teas and caffeine on energy expenditure and fat oxidation: a meta-analysis.

Different outcomes of the effect of catechin-caffeine mixtures and caffeine-only supplementation on energy expenditure and fat oxidation have been reported in short-term studies. Therefore, a meta-analysis was conducted to elucidate whether catechin-caffeine mixtures and caffeine-only supplementation indeed increase thermogenesis and fat oxidation. First, English-language studies measuring daily energy expenditure and fat oxidation by means of respiration chambers after catechin-caffeine mixtures and caffeine-only supplementation were identified through PubMed. Six articles encompassing a total of 18 different conditions fitted the inclusion criteria. Second, results were aggregated using random/mixed-effects models and expressed in terms of the mean difference in 24 h energy expenditure and fat oxidation between the treatment and placebo conditions. Finally, the influence of moderators such as BMI and dosage on the results was examined as well. The catechin-caffeine mixtures and caffeine-only supplementation increased energy expenditure significantly over 24 h (428.0 kJ (4.7%); P < 0.001 and 429.1 kJ (4.8%); P < 0.001, respectively). However, 24 h fat oxidation was only increased by catechin-caffeine mixtures (12.2 g (16.0%); P < 0.02 and 9.5 g (12.4%); P = 0.11, respectively). A dose-response effect on 24 h energy expenditure and fat oxidation occurred with a mean increase of 0.53 kJ mg(-1) (P < 0.01) and 0.02 g mg(-1) (P < 0.05) for catechin-caffeine mixtures and 0.44 kJ mg(-1) (P < 0.001) and 0.01 g mg(-1) (P < 0.05) for caffeine-only. In conclusion, catechin-caffeine mixtures or a caffeine-only supplementation stimulates daily energy expenditure dose-dependently by 0.4-0.5 kJ mg(-1) administered. Compared with placebo, daily fat-oxidation was only significantly increased after catechin-caffeine mixtures ingestion.

Effect of a novel beta-adrenoceptor agonist (Ro 40-2148) on resting energy expenditure in obese women.

The aim of this single-blind, placebo-controlled study was to investigate the effects of the new beta-adrenergic compound Ro 40-2148 on resting energy expenditure (REE) at rest and after an oral glucose load in non-diabetic obese women before and after two weeks of treatment. After one week of placebo administration and after an overnight fast and one hour rest, REE and glucose and lipid oxidation rates were measured by indirect calorimetry (hood system) before and for 6 h after a single dose of placebo solution. A 75 g oral glucose tolerance test (OGTT) was performed during this period starting 90 min after the placebo administration. During the following two weeks, using a randomization design, six patients received Ro 40-2148 at a dose of 400 mg diluted in 100 ml water twice a day (i.e. 800 mg per day), while six others continued with the placebo administration. The same tests and measurements were repeated after two weeks, except for the treatment group which received the drug instead of the placebo. The 14-day period of drug administration did not increase REE measured in post-absorptive conditions. Similarly, there was no acute effect on REE of a 400 mg dose of Ro 40-2148. In contrast, glucose-induced thermogenesis was significantly increased after two weeks in the treatment group (means +/- s.e.m.: 3.7 +/- 1.3%, P = 0.047), while no change was observed in the placebo group (-0.8 +/- 0.7%, not significant). Since there was no significant change in the respiratory quotient, the increase in energy expenditure observed in the treatment group was due to stimulation of both lipid and glucose oxidation. The drug induced no variations in heart rate, blood pressure, axillary temperature or in plasma glucose, insulin and free fatty acid levels. In conclusion, this study shows that Ro 40-2148 activates glucose-induced thermogenesis in obese non-diabetic patients.

Effect of ethanol on energy expenditure.

The thermogenic response induced by ethanol ingestion in humans has not been extensively studied. This study was designed to determine the thermic effect of ethanol added to a normal diet in healthy nonalcoholic subjects, using indirect calorimetry measurements over a 24-h period in a respiration chamber. The thermic effect of ethanol was also measured when ethanol was ingested in the fasting state, using a ventilated hood system during a 5-h period. Six subjects ingested 95.6 +/- 1.8 (SE) g ethanol in 1 day partitioned over three meals; there was a 5.5 +/- 1.2% increase in 24-h energy expenditure compared with a control day in which all conditions were identical except that no ethanol was consumed. The calculated ethanol-induced thermogenesis (EIT) was 22.5 +/- 4.7% of the ethanol energy ingested. Ingestion of 31.9 +/- 0.6 g ethanol in the fasting state led to a 7.4 +/- 0.6% increase in energy expenditure over baseline values, and the calculated EIT was 17.1 +/- 2.2%. It is concluded that in healthy nonalcoholic adults ethanol elicits a thermogenic response equal to approximately 20% of the ethanol energy. Thus the concept of the apparently inefficient utilization of ethanol energy is supported by these results which show that only approximately 80% of the ethanol energy is used as metabolizable energy for biochemical processes in healthy nonalcoholic moderate ethanol consumers.

Effect of dexfenfluramine on energy expenditure in man.

A short review has been made of the experimental studies performed in man, in which the effect of dexfenfluramine (D-F) on resting energy expenditure has been explored. It appears that the extent to which D-F possesses thermogenic properties (in addition to its anorectic effect) still remains controversial. Some investigators found either no significant increase in energy expenditure in response to the drug or a moderate effect in post-absorptive and/or postprandial state. It may be reasonable to assume that the supplementary weight loss observed with D-F as compared to a placebo can be primarily attributed to its anorectic effect rather than to its putative thermogenic effect.

Changes in protein turnover and resting energy expenditure after treatment of malaria in Gambian children.

To explore the changes in resting energy expenditure (REE) and whole body protein turnover induced by malaria, 23 children aged 6 to 14 y (23.9 +/- 1.0 kg, 1.3 +/- 0.02 m) were studied on three separate days after treatment (d 1, d 2, and 15 d later). REE was assessed by indirect calorimetry (hood), whereas whole body protein turnover was estimated using a single dose of [15N]glycine administered p.o. by measuring the isotopic enrichment of [15N]ammonia in urine over 12 h. Within the first 3.5 h after treatment, the body temperature dropped from 39.8 +/- 0.1 to 37.8 +/- 0.1 degrees C (p < 0.0001), and REE followed the same pattern, decreasing rapidly from 223 +/- 6 to 187 +/- 4 kJ/kg/d (p < 0.0001). Whole body protein synthesis and breakdown were significantly higher during the 1st day (5.65 +/- 0.38 and 6.21 +/- 0.43 g/kg/d, respectively) than at d 15 (2.95 +/- 0.17 and 2.77 +/- 0.2 g/kg/d). It is concluded that Gambian children suffering from an acute episode of malaria have an increased REE averaging 37% of the control value (d 15) and that this was associated with a substantial increase (by a factor of 2) in whole body protein turnover. A rapid normalization of the hypermetabolism and protein hypercatabolism states after treatment was observed.

Effect of elective antibiotic therapy on resting energy expenditure and inflammation in cystic fibrosis.

Cystic fibrosis (CF) patients often present with malnutrition which may partly be due to increased resting energy expenditure (REE) secondary to inflammation. Both REE and tumour necrosis factor-alpha (TNF-alpha), as other markers of inflammation, are elevated during respiratory exacerbations and decrease after antibiotic treatment. However, the effect of antibiotic therapy on REE and inflammation in patients without respiratory exacerbation is not known. The aim of our study was to determine the effect of such an elective antibiotic therapy on REE, TNF-alpha, and other serum markers of inflammation. Twelve CF patients 5F/7M, age 15.9 +/- 6.1 years, weight for height ratio 89 +/- 8% without clinically obvious exacerbation and treated by intravenous antibiotics were studied. Both before (D0) and after (D14) treatment, pulmonary function tests were performed. REE was measured by indirect calorimetry and blood taken to measure inflammation parameters. Body weight increased by 1.1 kg from D0 to D14 (P < 0.001), composed of 0.3 kg fat mass and 0.8 kg fat-free mass (FFM). The forced expiratory volume at 1 s increased from 43 +/- 15% of predicted at D0 to 51 +/- 15% of predicted at D14 (P < 0.01). Mean REE was 41.1 +/- 7.6 kcal/kg FFM per day at D0 and did not change significantly at D14 (40.6 +/- 8.5 kcal/kg FFM per day). Serum markers of inflammation decreased from D0 to D14: C-reactive protein 17 +/- 17 mg/l to 4 +/- 7 mg/l (P < 0.05), elastase 62 +/- 29 microg/l to 45 +/- 18 microg/l (P < 0.02), orosomucoid acid 1.25 +/- 0.11 g/l to 0.80 +/- 0.15 g/l (P < 0.001), and TNF-alpha 37 +/- 14 pg/ml to 29 +/- 6 pg/ml (P = 0.05). Individual values showed a correlation between changes in REE and in TNF-alpha (P < 0.02). The contribution of inflammation to energy expenditure is possible but appears to be minimal in cystic fibrosis patients treated by antibiotics on a regular basis in the absence of clinically obvious exacerbation.

Inhibition of Na(+)-K(+)-ATPase by digoxin and its relation with energy expenditure and nutrient oxidation rate.

This study investigates the effects of digoxin, an inhibitor of the Na+ pump (Na(+)-K(+)-ATPase), on resting metabolic rate (RMR), respiratory quotient (RQ), and nutrient oxidation rate. Twelve healthy male subjects followed a double-blind protocol design and received either 1 mg/day digoxin or a placebo 2 days before indirect calorimetry measurements. Digoxin induced a 0.22 +/- 0.07 kJ/min or 3.8 +/- 1.5% (mean +/- SE, P = 0.01) decrease in RMR and a 0.40 +/- 0.13 kJ/min (P = 0.01) decrease in fat oxidation rate, whereas carbohydrate and protein oxidation rates did not change significantly. A dose-response relationship between serum digoxin and RQ was observed. These results suggest that digoxin reduces not only RMR but also fat oxidation rate by mechanisms that remain to be elucidated. Because a linkage and an association between genes coding the Na(+)-K(+)-ATPase and the RQ have been previously observed, the present demonstration of an effect of Na(+)-K(+)-ATPase inhibition on fat oxidation rate strengthens the concept that the activity of this enzyme may play a role in body weight regulation.

Changes in sleeping and basal energy expenditure and substrate oxidation induced by short term thyroxin administration in man.

The present study was designed to explore the thermogenic effect of thyroid hormone administration and the resulting changes in nitrogen homeostasis. Normal male volunteers (n = 7) received thyroxin during 6 weeks. The first 3-week period served to suppress endogenous thyroid secretion (180 micrograms T4/day). This dose was doubled for the next 3 weeks. Sleeping energy expenditure (respiratory chamber) and BMR (hood) were measured by indirect calorimetry, under standardized conditions. Sleeping heart rate was continuously recorded and urine was collected during this 12-hour period to assess nitrogen excretion. The changes in energy expenditure, heart rate and nitrogen balance were then related to the excess thyroxin administered. After 3 weeks of treatment, serum TSH level fell to 0.15 mU/L, indicating an almost complete inhibition of the pituitary-thyroid axis. During this phase of treatment there was an increase in sleeping EE and sleeping heart rate, which increased further by doubling the T4 dose (delta EE: +8.5 +/- 2.3%, delta heart rate +16.1 +/- 2.2%). The T4 dose, which is currently used as a substitutive dose, lead to a borderline hyperthyroid state, with an increase in EE and heart rate. Exogenous T4 administration provoked a significant increase in urinary nitrogen excretion averaging 40%. It is concluded that T4 provokes an important stimulation of EE, which is mostly mediated by an excess protein oxidation.

Effects of mental stress on insulin-mediated glucose metabolism and energy expenditure in lean and obese women.

The effects of the sympathetic activation elicited by a mental stress on insulin sensitivity and energy expenditure (VO(2)) were studied in 11 lean and 8 obese women during a hyperinsulinemic-euglycemic clamp. Six lean women were restudied under nonselective beta-adrenergic blockade with propranolol to determine the role of beta-adrenoceptors in the metabolic response to mental stress. In lean women, mental stress increased VO(2) by 20%, whole body glucose utilization ([6,6-(2)H(2)]glucose) by 34%, and cardiac index (thoracic bioimpedance) by 25%, whereas systemic vascular resistance decreased by 24%. In obese women, mental stress increased energy expenditure as in lean subjects, but it neither stimulated glucose uptake nor decreased systemic vascular resistance. In the six lean women who were restudied under propranolol, the rise in VO(2), glucose uptake, and cardiac output and the decrease in systemic vascular resistance during mental stress were all abolished. It is concluded that 1) in lean subjects, mental stress stimulates glucose uptake and energy expenditure and produces vasodilation; activation of beta-adrenoceptors is involved in these responses; and 2) in obese patients, the effects of mental stress on glucose uptake and systemic vascular resistance, but not on energy expenditure, are blunted.