Predicting Clinical Outcome After Surgical Treatment in Patients With Carpal Tunnel Syndrome.

PURPOSE: Carpal tunnel release (CTR) is typically offered to symptomatic patients with electrophysiological abnormalities when night orthoses no longer prevent waking with numbness and preferably before there is any static numbness, weakness, or atrophy. The ability to predict the amount of symptom relief after CTR could be beneficial for managing patient expectations and, therefore, improve treatment satisfaction. Therefore, the aim of this study was to identify predictors for symptom relief after CTR and to determine their contribution to symptom relief at 6 months after surgery. METHODS: A total of 1,049 patients who underwent CTR between 2011 and 2015 at 1 of 11 Xpert Clinics in the Netherlands were asked to complete online questionnaires at intake and 3 and 6 months after surgery. Patient demographics, comorbidities, and baseline scores were considered potential predictors for the amount of symptom relief on the Boston Carpal Tunnel Questionnaire (BCTQ) score, which was the primary outcome measure. RESULTS: A low score on the BCTQ at intake, a codiagnosis of a trigger finger, ulnar nerve neuropathy, trapeziometacarpal joint arthrosis, and instability or arthrosis of the wrist were associated with a smaller improvement in the BCTQ domains after a CTR at 6 months after surgery and accounted for 35% to 42% of the variance on the BCTQ domains in our multivariable regression models. CONCLUSIONS: In this study, we showed that clinical severity of carpal tunnel syndrome at intake is the most important factor in estimating symptom relief after surgical treatment. Furthermore, this study contributes to a more precise understanding of the capabilities of CTR in relieving symptoms for different subgroups of patients. Results of our study can be used to manage patient expectation on symptom relief from CTR. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

The added value of quantitative multi-voxel MR spectroscopy in breast magnetic resonance imaging.

OBJECTIVE: To determine whether quantitative multivoxel MRS improves the accuracy of MRI in the assessment of breast lesions. METHODS: Twenty-five consecutive patients with 26 breast lesions ≥ 1 cm assessed as BI-RADS 3 or 4 with mammography underwent quantitative multivoxel MRS and contrast-enhanced MRI. The choline (Cho) concentration was calculated using the unsuppressed water signal as a concentration reference. ROC analysis established the diagnostic accuracy of MRI and MRS in the assessment of breast lesions. RESULTS: Respective Cho concentrations in 26 breast lesions re-classified by MRI as BI-RADS 2 (n = 5), 3 (n = 8), 4 (n = 5) and 5 (n = 8) were 1.16 ± 0.43 (mean ± SD), 1.43 ± 0.47, 2.98 ± 2.15 and 4.94 ± 3.10 mM. Two BI-RADS 3 lesions and all BI-RADS 4 and 5 lesions were malignant on histopathology and had Cho concentrations between 1.7 and 11.8 mM (4.03 ± 2.72 SD), which were significantly higher (P = 0.01) than that in the 11 benign lesions (0.4-1.5 mM; 1.19 ± 0.33 SD). Furthermore, Cho concentrations in the benign and malignant breast lesions in BI-RADS 3 category differed (P = 0.01). The accuracy of combined multivoxel MRS/breast MRI BI-RADS re-classification (AUC = 1.00) exceeded that of MRI alone (AUC = 0.96 ± 0.03). CONCLUSIONS: These preliminary data indicate that multivoxel MRS improves the accuracy of MRI when using a Cho concentration cut-off ≤ 1.5 mM for benign lesions. KEY POINTS: Quantitative multivoxel MR spectroscopy can improve the accuracy of contrast-enhanced breast MRI. Multivoxel-MRS can differentiate breast lesions by using the highest Cho-concentration. Multivoxel-MRS can exclude patients with benign breast lesions from further invasive diagnostic procedures.

[Radiofrequency ablation of colorectal metastases to the liver: results since the first application in the Netherlands]. / Radiofrequente ablatie van colorectale levermetastasen: resultaten vanaf de eerste toepassing in Nederland.

OBJECTIVE: To provide an overview of the morbidity, mortality and survival following the introduction of radiofrequency ablation (RFA) of colorectal liver metastases in the Netherlands. DESIGN: Prospective, descriptive study. METHOD: Between June 1999 and December 2003 in eight hospitals in the Netherlands, 87 patients treated by RFA for colorectal liver metastases were included in the study. The outcome measures were morbidity, 30-day mortality and the percentage local recurrence. RESULTS: In 104 RFA procedures, 199 metastases were ablated; 31 procedures were performed percutaneously and 73 by laparotomy. In 29 procedures, RFA was combined with partial liver resection. The overall postoperative morbidity rate was 19% and the RFA-related morbidity was 14%. 1 patient died following right hemihepatectomy and RFA in the remaining parenchyma (mortality: 1%). Median survival following RFA was 25 months, with a median progression-free survival of 13 months. The overall local recurrence rate was 46%. Since January 2004, this percentage has decreased to approximately 6. Diameter and central location of the metastases were independent risk factors for the development of a local recurrence. CONCLUSION: RFA is an alternative treatment for patients who are not eligible for partial liver resection. The high local recurrence rate in this series reflects the limited experience with this technique during its introduction in the Netherlands. In specialised centres the percentage local recurrence is now 5. Treatment by RFA should always be weighed against the option of partial liver resection and possible (neoadjuvant) chemotherapy. RFA should therefore preferably be carried out in a centre with expertise in the field of liver surgery.

Assessment of systemic inflammatory response (SIR) in patients undergoing radiofrequency ablation or partial liver resection for liver tumors.

INTRODUCTION: Local therapies for liver tumors are considered to be safe. However, cryoablation (CA) has been associated with an exaggerated systemic inflammatory response (SIR). Aim of this study was to assess the degree of SIR after radiofrequency ablation (RFA) in comparison with major (MR) or minor (mR) liver resection. MATERIAL AND METHODS: Thirty-nine patients were treated with RFA (n = 11), MR (n = 10) or mR (n = 18). SIR parameters [white blood count (WBC) and C-reactive protein (CRP)], proinflammatory mediators [IL-6, TNF-alpha and sPLA2], liver damage parameters [AST/ALT] and platelet counts were determined at different time points. The volume of ablated liver was calculated on the first CT after RFA in order to correlate ablated liver volume with liver enzyme release and SIR. All data are expressed as median values with quartiles [25%, 75%]. RESULTS: RFA induced a moderate SIR, as demonstrated by a significant elevation of CRP (77 mg/L vs 3 mg/L), IL-6 (96 pg/ml vs 4 pg/ml) and sPLA2 (41 ng/ml vs 7 ng/ml, p < 0.05). Peak point values of SIR (WBC and CRP at 24 vs 48 h and 48 vs 72 h) and proinflammatory response parameters (24 vs 48 h) occurred earlier after RFA than after mR or MR. Time-to-time comparison revealed even increased levels of CRP (77 mg/L [59, 160]) 24h after RFA when compared to patients undergoing major or minor resection (50 mg/L [28, 66] and 59 mg/L [24, 91], respectively) and increased levels of IL-6 (67 pg/ml [42, 131]) 4 h after RFA when compared to patients undergoing minor resection (29 pg/ml [20, 55]). Postoperative levels of AST and LDH correlated significantly with the ablated liver volume 1h after RFA (RC = 0.860 and RC = 0.868, respectively, p < 0.05). CONCLUSION: RFA induced a moderate SIR of the same magnitude as in patients undergoing partial liver resection. None of the patients showed signs of an exaggerated SIR, as has been reported after cryoablation.

Adverse effects of radiofrequency ablation of liver tumours in the Netherlands.

BACKGROUND: Radiofrequency ablation (RFA) is a new treatment for liver tumours. Complications encountered after RFA in the Netherlands were evaluated in the present study. METHODS: Between June 1999 and November 2003 patients undergoing RFA of irresectable liver tumours in eight medical centres were registered prospectively. RESULTS: One hundred and forty-three RFA procedures were performed in 122 patients. RFA was combined with partial hepatectomy in 37 instances. Death occurred after two procedures (1.4 per cent), and was mainly due to concomitant partial hepatectomy. A total of 19 major complications occurred after ten procedures, including biliary tract damage (seven patients), liver failure (four), hepatic abscess (three), peritoneal infection (two), intrahepatic haematoma (one), hepatic artery aneurysm (one) and pulmonary embolism (one). Twenty-four minor complications were related to concomitant partial hepatectomy or laparotomy. The overall complication rate was 20.3 per cent and the rate of complications related directly to RFA was 9.8 per cent. CONCLUSION: The procedure-specific complication rate was almost 10 per cent and it is recommended that RFA should be performed only by an experienced team comprising a hepatobiliary surgeon, gastroenterologist, hepatologist and interventional radiologist. Biliary stricture, hepatic vascular damage and hepatic abscesses were the most common major complications.

Outcome of regional and local ablative therapies for hepatocellular carcinoma: a collective review.

BACKGROUND: Transcatheter arterial (chemo) embolization (TACE), cryoablation (CA) and percutaneous ethanol injection (PEI) were the first regional and local ablative techniques that came into use for irresectable HCC. Radiofrequency ablation (RFA) and interstitial laser coagulation (ILC) followed and have now evolved rapidly. It would not be ethical to compare resection with ablation in patients well enough to undergo major surgery. Therefore, hepatic resection and hepatic transplantation remain the only curative treatment options for HCC. METHODS: On the basis of a Medline literature search and the authors' experiences, the principles, current status and prospects of TACE and local ablative techniques in HCC are reviewed. RESULTS: Complete tumour necrosis can be achieved in 60-100% of patients treated with PEI (70-100%), cryoablation (60-85%), RFA (80-90%) or ILC (70-97%). After TACE significant tumour response is achieved in 17-61.9% but complete tumour response is rare (0-4.8%) as viable tumour cells remain after TACE. Five-year survival rates are available for TACE (1-8%), PEI (0-70%) and cryoablation (40%). Only PEI and RFA were compared in one RCT. RFA was associated with fewer treatment sessions and a higher complete necrosis rate. Furthermore, all techniques are associated with low morbidity and mortality, but cryoablation seems to be associated with a higher morbidity rate. CONCLUSION: TACE has shown to be a valuable therapy with survival benefits in strictly selected patients with unresectable HCC. RFA and PEI are now considered as the local ablative techniques of choice for the treatment of, preferably small, HCC. When tumours are located close to bile ducts or large vessels, PEI remains a valuable therapy. Completeness of ablation can be more easily monitored during cryoablation and another advantage of cryoablation is the possibility of edge freezing. The results of ILC are comparable to RFA with only few side effects and high tumour response rates.

Plasma carotenoid levels in Dutch men and women, and the relation with vegetable and fruit consumption.

OBJECTIVE: Fruit and vegetable intake is inversely associated with cancer risk in many epidemiological studies. Accurate assessment of consumption of these foods is difficult, and biomarkers of intake would overcome several drawbacks of currently used dietary assessment methods. Therefore, we investigated the relation between plasma carotenoids and usual vegetable and fruit intake. DESIGN: Plasma carotenoid concentrations were measured and vegetable, fruit and juice consumption was assessed by a food frequency questionnaire (FFQ) in a random sample of 591 Dutch men and women aged 20-59 y from the MORGEN-project, one of the contributions to the European Prospective Investigation into Cancer and Nutrition (EPIC)-study. RESULTS: In this sample of the general Dutch population, in both genders, relative to the other carotenoids, plasma beta-cryptoxanthin was the best indicator for fruit intake, and for the sum of vegetable, fruit and juice intake, while lutein concentrations best reflected intake of vegetables, although quartiles of intake were not consistently separated. Since levels of lycopene were not associated with any of the main food groups examined, associations with total carotenoids improved when excluding lycopene, and monotonously increasing plasma levels were seen for intakes of vegetables, of fruits, and of the sum of vegetables, fruits and juices. Several vegetable types and orange/grapefruit juice were associated with plasma levels of one of the carotenoids. CONCLUSION: Plasma carotenoids were only crude indicators of vegetable and fruit intake as assessed by a FFQ; beta-cryptoxanthin for fruit intake and lutein for vegetable intake. None of the plasma carotenoids could distinguish all four quartiles of vegetables, fruit and/or juice intake.

Is Candida albicans a trigger in the onset of coeliac disease?

Coeliac disease is a T-cell-mediated autoimmune disease of the small intestine that is induced by ingestion of gluten proteins from wheat, barley, or rye. We postulate that Candida albicans is a trigger in the onset of coeliac disease. The virulence factor of C albicans-hyphal wall protein 1 (HWP1)-contains aminoacid sequences that are identical or highly homologous to known coeliac disease-related alpha-gliadin and gamma-gliadin T-cell epitopes. HWP1 is a transglutaminase substrate, and is used by C albicans to adhere to the intestinal epithelium. Furthermore, tissue transglutaminase and endomysium components could become covalently linked to the yeast. Subsequently, C albicans might function as an adjuvant that stimulates antibody formation against HWP1 and gluten, and formation of autoreactive antibodies against tissue transglutaminase and endomysium.

Lesion progression with time and the effect of vascular occlusion following radiofrequency ablation of the liver.

BACKGROUND: The effectiveness of radiofrequency ablation (RFA) under selective vascular occlusion and its effects on architecture and viability of normal liver parenchyma was studied in a porcine model. METHODS: RFA was applied in the liver under general anaesthesia in 18 pigs. Six animals were killed immediately after the procedure and 12 at 24 h. RFA was performed sequentially under four conditions: (1) without vascular occlusion, (2) during occlusion of the hepatic artery, (3) during occlusion of the portal vein and (4) during occlusion of the hepatic artery and portal vein. Liver biopsies from the treated area were stained for conventional histological examination, reduced nicotinamide adenine dinucleotide diaphorase and 5'-nucleotidase activity. RESULTS: Vascular occlusion significantly increased the size of the coagulation centre after RFA. Combined portal venous and arterial occlusion had no additional effect on lesion size compared with venous or arterial occlusion alone. After 24 h, deterioration of viability was observed in the parenchyma up to 3 cm from the coagulated area. CONCLUSION: The efficacy of RFA in liver increases with occlusion of the portal vein or hepatic artery. The extent of secondary heat-induced necrosis in liver parenchyma should be considered for determination of the final size of the ablated area.

Cohort analysis of fruit and vegetable consumption and lung cancer mortality in European men.

Our aim was to examine the relationship between fruit and vegetable consumption and lung cancer mortality in a cohort of European males. Around 1970, dietary intake of Finnish, Italian and Dutch middle-aged men was assessed using a cross-check dietary history. Complete baseline information was available for 3,108 men, of whom 1,578 were baseline smokers. We used Cox proportional hazard analyses to calculate risk estimates for the consumption in country-specific tertiles on lung cancer in smokers. During 25 years of follow-up, 149 lung cancer deaths occurred in the smokers. Fruit consumption was inversely associated with lung cancer mortality among smokers; compared with the lowest, adjusted RRs for the intermediate and highest tertiles were 0.56 (0.37-0.84) and 0.69 (0.46-1.02), p-trend 0.05. Only in the Dutch cohort was this association statistically significant [adjusted relative risks (RRs) 1.00, 0.33 (0.16-0.70) and 0.35 (0.16-0.74), p-trend 0.004]. In Finland lung cancer risk was lower with higher fruit intake but not significantly, whereas in Italy no association was observed. Stratifying on cigarette smoking intensity (non, light and heavy) revealed an inverse association in the heavy smokers only [adjusted RRs (95% confidence intervals [CI]) 1; 0.47 (0.26-0.84); 0.40 (0.20-0.78)). Vegetable consumption was not related to lung cancer risk in smokers. However, analyses stratified on cigarette smoking intensity gave some indication for a lower lung cancer risk with higher intake. In conclusion, in this prospective analysis among European smoking men, fruit intake was inversely related to lung cancer mortality. This association was confined to heavy cigarette smokers.

Role of smoking and diet in the cross-cultural variation in lung-cancer mortality: the Seven Countries Study. Seven Countries Study Research Group.

We examined the role of smoking and diet in the cross-cultural variation in lung-cancer mortality, using aggregated data of the Seven Countries Study, a follow-up study comprising 12,763 middle-aged men in 16 cohorts in Europe, the United States and Japan, which started around 1960. Smoking habits were assessed with a standardised questionnaire. Dietary intake was collected in random sub-samples of each cohort by the dietary record method. Cohort-specific 25-year lung-cancer mortality among all men and among categories of smoking behaviour was related to smoking prevalence and population average dietary intake, respectively, using Poisson regression. Smoking prevalence was positively associated with lung-cancer mortality [risk ratio 1.47, 95% confidence interval (CI) 1.05-2.07, for an increase of 10 percentage points]. Lung-cancer mortality among smokers, which varied significantly among cultures, was positively associated with average fat intake, especially saturated fat intake (rate ratio 1.10, 95% CI 1.04-1.17, for an increase of 4.6 g) but not with unsaturated fat intake. Average fruit and vegetable intake were not related to lung-cancer mortality. Among never-smokers, the power to detect associations was low. In conclusion, both smoking prevalence and average fat intake, especially saturated fat, may play a role in the cross-cultural variation in lung-cancer mortality, either independently or by effect modification.

Fruits and vegetables in the prevention of cancer and cardiovascular disease.

OBJECTIVE: We quantified the public health benefit of fruits and vegetables on the prevention of cancer and cardiovascular disease (CVD), using currently available human data. DESIGN: We reviewed over 250 observational studies on cancer and CVD. Relative risks (RRs) for high versus low intake of fruits and vegetables were obtained. The preventable proportion of chronic diseases, i.e. the per cent of cases attributable to low consumption of fruits and vegetables, was estimated using three scenarios: best guess, optimistic (using stronger RRs) and conservative (using weaker RRs and eliminating the contribution of smoking and/or drinking). The preventable proportion was calculated for increasing average intake from the current 250 g day(-1) to the recommended 400 g day(-1) among the general Dutch population. RESULTS: It is estimated that in the Netherlands cancer incidence could be reduced by 19% (12,000 cases annually, best guess), ranging from 6% (conservative) to 28% (optimistic). Cardiovascular deaths could be reduced by 16% (8000 deaths annually, best guess), ranging from 6% to 22%. Evidence is most abundant for gastrointestinal cancers, followed by hormone-related cancers, but limited for other sites and CVD. CONCLUSIONS: Increasing consumption of fruits and vegetables carries a large public health potential. Population trials and biological mechanisms should eventually provide scientific proof of their efficacy. The available evidence is sufficient to justify public health education and promotion aimed at a substantial increase in the consumption of fruits and vegetables.

Consumption of plant foods and stomach cancer mortality in the seven countries study. Is grain consumption a risk factor? Seven Countries Study Research Group.

Plant foods are generally considered to be beneficial for health. A higher consumption of fruits, and to a lesser extent vegetables, is consistently associated with a lower risk of stomach cancer. Results on the association between stomach cancer and grain consumption are less clear. We associated plant food consumption with 25-year stomach cancer mortality at population level in the Seven Countries Study. Around 1960, > 12,000 men aged 40-59 years from 7 countries and 16 cohorts were enrolled. In each cohort, dietary information was collected in small random samples. Crude and adjusted associations were calculated for a change of 10% of mean intake. Results differed for the plant foods studied: an inverse association was observed for fruits (adjusted rate ratio = 0.96, 95% confidence interval = 0.91-0.99), a positive relation for refined grains (adjusted rate ratio = 1.07, 95% confidence interval = 1.03-1.12), and no association for total plant foods, vegetables, whole grains, and potatoes. A high intake of refined grains was correlated with a low consumption of fruits. In conclusion, high intake of refined grains may increase stomach cancer risk. However, because adjustment could only be limited in this study, high intake of refined grains may just reflect the deleterious effect of a diet low in fruits or other characteristics associated with low fruit consumption.

Dietary fiber and plant foods in relation to colorectal cancer mortality: the Seven Countries Study.

Many observational studies have found that higher consumption of vegetables, and to a lesser extent of fruits, was associated with lower risk of colorectal cancer. In particular, fiber or foods high in fiber have received attention in the potential prevention of colorectal cancer. We performed an ecological analysis with data of the Seven Countries Study, to investigate whether intake of fiber and plant foods contributes to cross-cultural differences in 25-year colorectal-cancer mortality in men. In the Seven Countries Study, around 1960 12,763 men aged 40 to 59 were enrolled in 16 cohorts in 7 countries. Baseline dietary information was gathered in small random samples per cohort, and nutrient intakes were based on chemical analyses of the average diets per cohort. Crude and energy-adjusted mortality-rate ratios were calculated for a change of 10% of the mean intake of fiber and plant foods, i.e., total plant foods, fruits, vegetables, potatoes, grains, and related sub-groups. Fiber intake was inversely associated with colorectal-cancer mortality with an energy-adjusted rate ratio of 0.89 (95% confidence interval 0.80-0.97). An increase of 10 gram of daily intake of fiber was associated with a 33% lower 25-year colorectal-cancer mortality risk. Intakes of vitamin B6 [0.84 (0.71-0.99)] and alpha-tocopherol [0.94 (0.89-0.99)] were also inversely associated with risk. Consumption of plant foods and related sub-groups was not related to colorectal cancer. It appears that fiber intake best indicates the part of plant food consumption, including whole grains, that is relevant for lowering colorectal cancer risk.

Costs and effects of inhaled corticosteroids and bronchodilators in asthma and chronic obstructive pulmonary disease.

The objective of this study was to determine the costs and effects of combined bronchodilator and anti-inflammatory therapy. In a 2.5-yr randomized controlled study, combined beta 2-agonist/corticosteroid therapy (BA + CS) and combined beta 2-agonist/anticholinergic therapy (BA + AC) were compared with beta 2-agonist/placebo therapy (BA + PL). Included in the study were 274 patients 18 to 60 yr of age with moderately severe obstructive airways disease. The main clinical endpoints were lung function, hyperresponsiveness, restricted activity days, and symptom-free days. The economic endpoints were the costs of health care utilization. Compared with BA + PL, BA + CS led to significant improvements in FEV1, PC20, and symptom-free days. BA + AC did not differ from BA + PL in this respect. The respective annual acquisition costs of BA + CS, BA + AC, and BA + PL were 532 US$, 277 US$, and 156 US$. Thus, BA + CS costs 376 US$ more than BA + PL. However, compared with BA + PL therapy, BA + CS led to statistically significant savings in other health care costs of about 175 US$ (95% CI from 46 to 303 US$). Thus, more than half of the additional costs of adding the inhaled corticosteroid are compensated for by a reduction in the costs of other health care services. Overall, inhaled corticosteroids lead to a small but net increase in health care costs of 201 US$ per patient per year.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of resistant starch on breath-hydrogen and methane excretion in healthy volunteers.

Colonic fermentation of dietary carbohydrates and fiber might produce a protective effect against the development of large bowel cancer. Resistant starch, ie, starch that escapes small bowel digestion, is a candidate fermentable substrate that has been hitherto little studied. We supplemented 19 healthy volunteers with 15 g native amylomaize (Hylon-VII) three times a day, containing 28 g type II resistant starch, or with dextrins as a placebo for 7 d in a crossover design. Pre-experimentally, 11 subjects regularly produced breath methane and 8 did not. Resistant starch increased 24-h integrated excretion of breath hydrogen. The mean rise relative to placebo was 35% (P = 0.03) for all subjects and 60% for eight subjects not producing methane (P = 0.02). The 11 methane producers showed a 93% increase in breath-methane excretion on resistant starch (P = 0.03). Continued consumption of 28 g type II resistant starch/d is well tolerated and increases colonic fermentation in healthy volunteers.

Cost effectiveness of inhaled corticosteroid plus bronchodilator therapy versus bronchodilator monotherapy in children with asthma.

In an incremental cost-effectiveness analysis, combined inhaled beta 2-receptor agonist plus inhaled corticosteroid therapy (BA + CS) was compared with inhaled beta 2-agonist plus placebo (BA + PL) in 116 asthmatic children aged 7 to 16 years. Clinical data have been reported previously. To account for the selective withdrawal rate due to pulmonary problems that occurred in the group receiving BA + PL, costs were calculated using 2 approaches: (1) the cumulative cost approach and (2) the patient-year approach. Besides improvements in forced expiratory volume in 1 second (FEV 1) and airway responsiveness expressed as the provocative dose of histamine required to give a 20% fall in FEV 1 (PD 20), the frequency of asthma symptoms and school absenteeism were significantly reduced in the BA + CS group. Annual drug acquisition costs for the group receiving BA + CS were NLG480 higher than for the BA + PL group ($US1 = NLG2.12, 1989 prices). Based on conservative calculations using the cumulative cost approach, annual savings due to reduced healthcare utilisation, excluding the cost of study drugs, by the group receiving BA + CS compared with BA + PL were estimated to be about NLG273 per patient. The incremental cost effectiveness of BA + CS was estimated to be about NLG175 per 10% increase in FEV 1, or somewhat less than NLG10 per symptom-free day gained. The patient-year approach estimated savings due to corticosteroids of about 43% of the costs of BA + PL (95% confidence intervals, 21 to 58%). Savings were larger when the indirect costs that a family incurred during school absenteeism were considered. Addition of an inhaled corticosteroid to an inhaled beta 2-receptor agonist is a cost-effective treatment option that could even result in net healthcare savings.