Improved renal function after early conversion from a calcineurin inhibitor to everolimus: a randomized trial in kidney transplantation.

In an open-label, multicenter trial, de novo kidney transplant recipients at low to medium immunological risk were randomized at week 7 posttransplant to remain on CsA (n = 100, controls) or convert to everolimus (n = 102), both with enteric-coated mycophenolate sodium and corticosteroids. The primary endpoint, change in measured GFR (mGFR) from week 7 to month 12, was significantly greater with everolimus than controls: 4.9 (11.8) mL/min versus 0.0 (12.9) mL/min (p = 0.012; analysis of covariance [ANCOVA]). Per protocol analysis demonstrated a more marked difference: an increase of 8.7 (11.2) mL/min with everolimus versus a decrease of 0.4 (12.0) mL/min in controls (p < 0.001; ANCOVA). There were no differences in graft or patient survival. The 12-month incidence of biopsy-proven acute rejection (BPAR) was 27.5% (n = 28) with everolimus and 11.0% (n = 11) in controls (p = 0.004). All but two episodes of BPAR in each group were mild. Adverse events occurred in 95.1% of everolimus patients and 90.0% controls (p = 0.19), with serious adverse events in 53.9% and 38.0%, respectively (p = 0.025). Discontinuation because of adverse events was more frequent with everolimus (25.5%) than controls (3.0%; p = 0.030). In conclusion, conversion from CsA to everolimus at week 7 after kidney transplantation was associated with a greater improvement in mGFR at month 12 versus CNI-treated controls but discontinuations and BPAR were more frequent.

Regional fat mass by DXA: high leg fat mass attenuates the relative risk of insulin resistance and dyslipidaemia in obese but not in overweight postmenopausal women.

OBJECTIVE: To investigate the influence of regional fat mass (FM) on insulin resistance and dyslipidaemia in obese postmenopausal women (BMI >30 kg/m(2)) compared to overweight women (BMI <30 kg/m(2)). Leg FM may attenuate the increased risk of cardiovascular disease and diabetes imposed by increased trunk FM in normal and overweight postmenopausal women. MATERIAL AND METHODS: Cross-sectional and consecutively referred patients comprising 63 obese and 36 overweight postmenopausal women. Body composition and regional FM by dual X-ray absorptiometry (DXA), fasting glucose, fasting insulin and C-peptide, insulin resistance by homeostasis model assessment (HOMA-IR), insulin sensitivity by quantitative insulin sensitivity check index (QUICKI) and metabolic clearance rate (MCRestOGTT), insulin secretion (HOMAsecr) and serum lipids were assessed. RESULTS: In obese subjects, leg FM was favourably associated with HOMA-IR (p<0.05), QUICKI (p<0.05), fasting glucose (p<0.05), fasting insulin (p<0.05), HOMAsecr (p<0.05) and total cholesterol/HDL ratio (p<0.05). Trunk FM was unfavourably associated with MCRestOGTT (p<0.01), QUICKI (p<0.05) and fasting insulin (p<0.05). Compared to leg FM, leg/trunk FM ratio was more strongly associated with fasting insulin (p<0.001), fasting C-peptide (p<0.001), HOMA-IR (p<0.001), MCRestOGTT (p<0.001), QUICKI (p<0.001), HOMAsecr (p<0.001), fasting glucose (p<0.01) and triglycerides (p<0.01). Stepwise multiple regression demonstrated that leg/trunk FM ratio was the most important variable with partial R (2) = 0.26 (p<0.001) for HOMA and R (2) = 0.37 (p<0.001) when QUICKI was used as the dependent variable. In overweight women, no associations between fat mass and parameters of insulin resistance or dyslipidaemia were found. CONCLUSIONS: A high leg/trunk FM ratio as measured by DXA may give relative protection against diabetes and cardiovascular disease in obese postmenopausal women, but not in overweight women.

Body composition analysis by dual X-ray absorptiometry: in vivo and in vitro comparison of three different fan-beam instruments.

BACKGROUND: Dual X-ray absorptiometry (DXA) is the preferred method for measuring body composition in clinical practice, but interchange between devices may pose problems with the interpretation of results. OBJECTIVE: To establish conversion equations for body composition variables between three fan-beam DXA systems. METHODS: Body composition was assessed in 21 subjects using Lunar Expert (Expert), Lunar Prodigy (Prodigy) and Hologic Delphi W (Delphi). Weekly measurements of Hologic whole body phantom 164 were performed. RESULTS: There were no significant differences between DXA-measured means of body weight, fat mass and lean body mass. Bland-Altman analysis revealed that Lunar Expert increasingly overestimated fat mass with increasing total mass (p<0.001) relative to Delphi and Prodigy, while Delphi produced a constant underestimation of fat mass. Correlations between scale weights and DXA-measured body weights, and between DXA-measured body weights and the sum of fat masses, lean body masses and bone mineral contents (BMC) between the three instruments, were excellent (Rsqr 0.998-0.910; p<0.001). Conversion factors to Prodigy for Expert and Delphi were respectively 1.003 and 1.011 for total body mass, 0.954 and 1.079 for fat mass, 1.018 and 0.967 for lean body mass and 1.049 and 1.136 for BMC (Rsqr 0.999-0.991; p<0.001). Standard error of estimate (SEE) for the slopes ranged from 0.20% to 2.10%. Phantom studies revealed stable instrument function with CV% commonly<2%, except for lean mass for Delphi (5.5%). CONCLUSIONS: Despite the significant differences in measurement of body composition between DXA fan-beam instruments, clinically relevant conversion factors can be established.

Long-term management of patients with symptoms of gastro-oesophageal reflux disease -- a Norwegian randomised prospective study comparing the effects of esomeprazole and ranitidine treatment strategies on health-related quality of life in a general practitioners setting.

This article reports quality of life (QoL) aspects of a study that investigated the efficacy of three treatment regimens in gastro-oesophageal reflux disease patients. Following a 4-week symptom-control phase (esomeprazole 40 mg once daily), patients were randomised to 6 months' esomeprazole 20 mg once daily continuously (n = 658), on-demand (n = 634) or ranitidine 150 mg twice daily continuously (n = 610). Esomeprazole 40 mg once daily improved QoL during the symptom-control phase. At 6 months, both esomeprazole regimens were more effective than ranitidine in all dimensions of the Quality of Life in Reflux and Dyspepsia questionnaire (p < 0.0001). Esomeprazole continuous and on-demand led to a significant improvement in symptoms (Overall Treatment Evaluation questionnaire) compared with ranitidine (continuous: 80.2%, on-demand: 77.8%, vs. ranitidine 47.0%; p < 0.001). Esomeprazole once daily continuously maintained QoL better than esomeprazole on-demand and was associated with greater patient satisfaction. In conclusion, esomeprazole 20 mg once daily continuously and on-demand were more effective than ranitidine continuously for maintaining QoL.

Six-month management of patients following treatment for gastroesophageal reflux disease symptoms -- a Norwegian randomized, prospective study comparing the costs and effectiveness of esomeprazole and ranitidine treatment strategies in a general medical practitioners setting.

This study assesses the difference in direct medical costs between on-demand treatment with esomeprazole 20 mg, continuous treatment with esomeprazole 20 mg once-daily and continuous treatment with ranitidine 150 mg twice-daily to prevent symptomatic relapse in patients with gastroesophageal reflux disease over 26 weeks. Two hundred eighty-one GP clinics in Norway enrolled 2156 patients to an open, randomized, parallel group, Norwegian society perspective study during 2000-2001. The total direct medical costs of each strategy were 171.9 Euros for on-demand esomeprazole (n = 634), 221.6 Euros for ranitidine (n = 610) and 248.8 Euros for continuous esomeprazole (n = 658). The total costs for on-demand and continuous esomeprazole treatment and ranitidine treatment were 221.5, 286.5 and 295.8 Euros, respectively. The highest proportion of costs was because of the study medication cost in each strategy. The on-demand and continuous treatment strategies with esomeprazole were found to be cost-effective, compared with ranitidine.

A randomised prospective study comparing the effectiveness of esomeprazole treatment strategies in clinical practice for 6 months in the management of patients with symptoms of gastroesophageal reflux disease.

One option for patients with symptoms of gastroesophageal reflux disease (GERD) is treatment with proton pump inhibitors without prior endoscopy. Continuous or on-demand maintenance therapy are options for symptom-free patients. This study assessed the efficacy of three different treatment options in GERD patients in Norway. About 395 General Practitioners enrolled 2156 patients with symptoms of GERD in an open, randomised, parallel group trial. Following a 4-week symptom control phase [esomeprazole 40 mg once daily (od)], patients received either esomeprazole 20 mg od continuously or on-demand or ranitidine 150 mg twice-daily continuously for 6 months. The percentage of patients with no heartburn at the end of the study was maintained most effectively in the esomeprazole 20 mg continuous group (72.2%) and least effectively in the ranitidine group (32.5%). Significantly, more patients were completely/very satisfied with esomeprazole continuous (82.2%) and esomeprazole on-demand (75.4%) than with ranitidine continuous (33.5%) treatment (p < 0.0001). More patients were kept in remission, symptom free and were overall more satisfied with esomeprazole treatment than ranitidine.

Effect of metoprolol CR/XL on exercise tolerance in chronic heart failure - a substudy to the MERIT-HF trial.

BACKGROUND: Beta-blockade usually causes a slight reduction in exercise capacity among healthy subjects, while more variable results have been observed in chronic heart failure (CHF), probably related to patients studied, methods and agent used. The effect of metoprolol controlled release/extended release (CR/XL) on peak oxygen uptake (peak VO(2)) in this patient population has not previously been investigated. AIMS: We examined the effect of long-term treatment with the selective beta(1)-receptor blocker metoprolol CR/XL once daily on exercise capacity in patients with CHF. METHODS: Ninety-four patients (70 males and 24 females; mean age 63.6+/-10.6 years) with chronic symptomatic heart failure in New York Heart Association (NYHA) functional class II-IV, and with ejection fraction

Effectiveness of nystatin in polysymptomatic patients. A randomized, double-blind trial with nystatin versus placebo in general practice.

BACKGROUND: Antifungal therapy has been claimed to be effective in polysymptomatic patients with diffuse symptoms from multiple body systems and even well defined diseases, traditionally not related to fungi. Hypersensitivity to fungus proteins and mycotoxins has been proposed as the cause. METHODS: We conducted a 4-week randomized, double-blind, placebo-controlled study in 116 individuals selected by a 7-item questionnaire to determine whether the antifungal agent nystatin given orally was superior to placebo. At the onset of the study, the patients were free to select either their regular diet or a sugar- and yeast-free diet, which resulted in four different subgroups: nystatin + diet (ND); placebo + diet (PD); nystatin (N); and placebo (P). RESULTS: Nystatin was significantly better than placebo in reduction of the overall symptom score (P < 0.003). In six of the 45 individually recorded symptoms, the improvement was significant (P < 0.01). All three active treatment groups reduced their overall symptom scores significantly (P < 0.0001), while the placebo regimen had no effect (P = 0.83). The benefit of diet was significant within both the nystatin (ND > N) and the placebo groups (PD > P). CONCLUSIONS: Nystatin is superior to placebo in reducing localized and systemic symptoms in individuals with presumed fungus hypersensitivity as selected by a 7-item questionnaire. This superiority is probably enhanced even further by a sugar- and yeast-free diet.

Conjugated linoleic acid reduces body fat mass in overweight and obese humans.

Conjugated linoleic acid (CLA) has been shown to reduce body fat mass (BFM) in animals. To investigate the dose-response relationships of conjugated linoleic acid with regard to BFM in humans, a randomized, double-blind study including 60 overweight or obese volunteers (body mass index 25-35 kg/m(2)) was performed. The subjects were divided into five groups receiving placebo (9 g olive oil), 1.7, 3.4, 5.1 or 6.8 g conjugated linoleic acid per day for 12 wk, respectively. Dual-energy X-ray absorptiometry was used to measure body composition [measurements at wk 0 (baseline), 6 and 12]. Of the 60 subjects, 47 completed the study. Eight subjects withdrew from the study due to adverse events; however, no differences among treatment groups were found regarding adverse events. Repeated-measures analysis showed that a significantly higher reduction in BFM was found in the conjugated linoleic acid groups compared with the placebo group (P: = 0.03). The reduction of body fat within the groups was significant for the 3.4 and 6.8 g CLA groups (P: = 0.05 and P: = 0.02, respectively). No significant differences among the groups were observed in lean body mass, body mass index, blood safety variables or blood lipids. The data suggest that conjugated linoleic acid may reduce BFM in humans and that no additional effect on BFM is achieved with doses > 3.4 g CLA/d.

Sequence optimization in mangafodipir trisodium-enhanced liver and pancreas MRI.

To find an optimal magnetic resonance (MR) sequence for mangafodipir trisodium-enhanced liver and pancreas imaging, six healthy volunteers were studied using a 1.5 T MR system with different T1-weighted abdominal imaging sequences. These were turbo field (gradient)-echo (TFE), fast field (gradient)-echo (FFE), and spin-echo sequences before and after mangafodipir trisodium administration. Various parameter combinations were investigated within each sequence type, and then the best combination was found and compared with those of the other sequences. Signal intensity (SI) measurements were made in regions of interest in the liver, pancreas, and a reference marker with a known T1 value. Contrast index (CI, SItissue/SImarker) and contrast-to-noise ratio (CNR, [SItissue/SImarker]/SDbackground) were calculated, and percentage CI increase and CNR in the postcontrast images were used for the best sequence evaluation. Regarding CI, the TFE sequence with a TR/TE/flip angle of 15 msec/4.6 msec/20 degrees and inversion time of 300 msec had the largest pre- to postcontrast percentage increase. The FFE sequence with a TR/TE/flip angle of 140 msec/4.6 msec/90 degrees had the highest postcontrast CNR and is considered to be the optimal sequence for mangafodipir trisodium-enhanced MR imaging of the liver and pancreas.

Prediction of common bile duct stones prior to cholecystectomy: a prospective validation of a discriminant analysis function.

BACKGROUND: Selection routines for preoperative endoscopic retrograde cholangiopancreatography (ERCP) in patients with symptomatic gallstone disease should give a low frequency of both false-negative ERCP results and residual common bile duct stones (CBDS). OBJECTIVE: To validate a discriminant function (DF) based on retrospectively collected data, for characterization of patients with symptomatic gallstone disease as regards presence of CBDS, and to compare clinical, ultrasonographic, and DF characterization. DESIGN: Prospective registration of CBDS criteria in consecutive patients with symptomatic gallstone disease. SETTING: A department of surgical gastroenterology in a Norwegian central hospital. PATIENTS: One hundred ninety-two patients with gallbladder stones. INTERVENTION: Laparoscopic cholecystectomy or ERCP with or without endoscopic sphincterotomy. MAIN OUTCOME MEASUREMENTS: Sensitivity and specificity of the clinical, ultrasonographic, and DF characterizations, and test of the validity of the DF. RESULTS: Thirty-two patients had CBDS. The clinical criteria of CBDS were present in 152 patients (79.2%): 21.1% of these patients had CBDS and there were no false-negative results (sensitivity, 100%; specificity, 25%). The risk of CBDS in patients with normal bile ducts at ultrasonographic examination was 8 of 124, and in patients with dilated ducts or suspected CBDS, 17 of 47 (sensitivity, 68%; specificity, 80%). The DF was positive in 50 patients (26%): 60% of these had CBDS, and there were 2 false-negative results (sensitivity, 94%; specificity, 88%). A discriminant analysis of the prospectively registered data selected the same set of CBDS criteria, and a new DF did not alter the characterization of any patient. CONCLUSIONS: Clinical characterization had a higher sensitivity for CBDS detection than ultrasonography alone, but a lower specificity. The DF analysis was both more sensitive and specific than ultrasonography, and seemed efficient in selecting symptomatic gallstone patients for ERCP. It was reproducible and simple to use.

Diagnostic efficacy of MnDPDP in MR imaging of the liver. A phase III multicentre study.

PURPOSE: To assess the diagnostic efficacy, safety and tolerability of mangafodipir trisodium (MnDPDP, Teslascan) in MR imaging of the liver. MATERIAL AND METHODS: Eighty-two patients from 4 centres underwent MR imaging with pre-contrast sequences including T1-weighted SE and GRE, and T2-weighted turbo SE sequences. MnDPDP at a dose of 5 mumol/kg b.w. was administered by slow i.v. infusion, and 20-60 min after infusion the T1-weighted SE and GRE sequences were repeated. Diagnostic efficacy was evaluated by counting the number of lesions and by evaluating whether more information for lesion characterisation was available in post-contrast images. Safety and tolerability were assessed by recording adverse events and infusion-related discomfort. RESULTS: Significantly more lesions were found in MnDPDP-enhanced T1-weighted SE and GRE images than in unenhanced images of the same sequences. More lesions were also found in these images compared with T2-weighted images at a level of marginal significance. More information was obtained from MnDPDP-enhanced images in 40 cases. Mild to moderate adverse events were experienced by 17% of the patients. CONCLUSION: MnDPDP-enhanced images can improve lesion detection in the liver and are helpful for lesion characterisation. To obtain optimal diagnostic information of liver lesions T2-weighted images are also valuable. MnDPDP is a safe contrast agent for MR imaging of liver lesions.

[Diclofenac in the short-term prevention of recurrent colic from ureteral calculi. A placebo controlled double-blind study]. / Korttidsprofylakse med diklofenak mot residiv av uretersteinskolikk. En placebokontrollert dobbeltblind undersøkelse.

We have conducted a double-blind randomised placebo controlled trial with oral diclofenac to study the prophylactic effect on recurrence of renal colic and rate of spontaneous stone expulsion. 41 patients were given 50 mg oral diclofenac three times a day for seven days after being discharged for a colic episode from Oslo Emergency Hospital and 39 patients were given matching placebo tablets. The number of new ureteral colic episodes per accumulated patient treatment days was 64/287 in the diclofenac group and 119/273 in the placebo group (p < 0.01). The difference was greatest during the first four days of treatment. A similar trend was found for pain intensity, with the greatest difference on day one. There was no difference in reported type or frequency of side effects in the two treatment groups. Stone expulsion rate was almost identical. The effect of the treatment was not affected by fluid intake. Re-admission rates to Oslo Emergency Hospital or other hospitals were 10 and 67% (p < 0.001).

Intramuscular diclofenac versus intravenous indomethacin in the treatment of acute renal colic.

OBJECTIVE: We have conducted a clinical trial to compare the pain-relieving effect and safety of diclofenac administered intramuscularly to indomethacin given intravenously. METHODS: The study was designed as a randomized single-blind trial. It was carried out at Oslo Emergency Hospital (outpatient setting or stay < 24 h). 41 patients with a mean age of 41.6 years received 75 mg diclofenac and 42 patients with a mean age of 45.2 years were given 50 mg indomethacin. The two groups were similar in regard to baseline characteristics except gender distribution. RESULTS: Statistically significant reduction in pain intensity was achieved after 5 min in the diclofenac group (p < 0.01), and after 10 min in the indomethacin group (p < 0.01). The probability of having pain after 1 h was 52% in the indomethacin group and 37% in the diclofenac group (p = 0.11). Rescue medication with pethidine after 2 h was given in 9 and 5 patients, respectively. Four patients in the diclofenac group reported one occurrence of adverse effect each, while 9 patients on indomethacin experienced 14 occurrences, mainly dizziness and nausea. CONCLUSION: These findings together with a simpler mode of administration indicate that diclofenac may be preferred in the analgesic treatment of renal colic.

Selection criteria for endoscopic retrograde cholangiopancreaticography (ERCP) in patients with gallstone disease.

Endoscopic retrograde cholangiopancreatography (ERCP) has been used in patients referred to cholecystectomy when clinical information, biochemical values, or ultrasonography (clinical characterization) have indicated possible presence of common bile duct stones. A retrospective study of 599 patients treated for gallstone disease was used to develop a characterization procedure for predicting common bile duct stones by a discriminant analysis procedure. The variables selected by the analysis as the best combination for CBDS prediction were age (years), the values of bilirubin (micromol/l), ALAT (U/l) and gamma GT (U/l). The characterization was false positive in 22 cases (3.7%) and false negative in 11 cases (1.8%), compared to 198 false positive cases (33.1%) and three false negative cases (0.5%) by the clinical characterization. A leaving-one-out correction did not change the results. In a test set of 157 cholecystectomy patients, clinical characterization was false positive in 44.6% of the patients, compared to 4.5% false positive results when using the discriminant analysis procedure. The discriminant analysis procedure would have missed one patient with common bile duct stones. Selection by the discriminant analysis characterization procedure seems to reduce the frequency of preoperative ERCP significantly without an increase in undetected common bile duct stones.

Oral diclofenac in the prophylactic treatment of recurrent renal colic. A double-blind comparison with placebo.

We have conducted a double-blind, randomized, placebo-controlled trial with oral diclofenac to study the prophylactic effect on renal colic recurrence and spontaneous stone expulsion rate. Forty-one patients were given 50 mg oral diclofenac 3 times a day for 7 days after being discharged for a colic episode from Oslo Emergency Hospital (< 24 h stay) and 39 patients were given matching placebo tablets. The number of new renal colic episodes per accumulated patient treatment days was 64/287 in the diclofenac group and 119/273 in the placebo group (p < 0.01). This difference was greatest during the first 4 treatment days. A similar trend was found for pain intensity (0-10 cm VAS) with the greatest difference on day 1 (4.3 vs. 2.8, p = 0.05). Side effects, mainly gastrointestinal, were reported for 14% of the treatment days in both treatment groups. Stone expulsion rate was almost identical (28 vs. 29 days), regardless of stone size. Readmission rate to Oslo Emergency Hospital/other hospitals were 10 and 67% (p < 0.001). In conclusion, oral treatment with diclofenac was effective as short-term prophylaxis of new colic episodes, especially during the first 4 days, and reduces the number of hospital readmissions significantly. The stone passage rate appears not to be affected.

Therapeutic effect of loratadine on pruritus in patients with atopic dermatitis. A multi-crossover-designed study.

The aim of the study was to assess the therapeutic efficacy of loratadine on pruritus in patients with atopic dermatitis, considering the patients' sensation of itch. Sixteen patients, mean age 24.8 years, with moderate or severe atopic dermatitis were included in a double-blind and placebo-controlled study with a six-period, multi-crossover design. The patients were given 10 mg loratadine or placebo every day, alternating between loratadine and placebo every 2 weeks. The degree of pruritus during the day and during the night was recorded by the patients every morning and every evening, respectively, on a 10-cm visual analog scale. The study detected a significant effect of loratadine, as compared with placebo, on pruritus during the day, pruritus during the night, and severity of rash. At least nine of the 16 patients included were classified as responders and only one as a nonresponder to loratadine treatment. It is concluded that loratadine may be tried as an adjuvant therapy in the management of severe and moderate atopic dermatitis, in patients complaining of pruritus.

Characterization of responders and nonresponders to tiaprofenic acid and naproxen in the treatment of patients with osteoarthritis.

OBJECTIVE: To characterize responders/nonresponders to 2 nonsteroidal antiinflammatory drugs by a combination of start variables in the treatment of patients with osteoarthritis (OA) of the hip(s)/knee(s). METHODS: Two hundred eight patients participated in a 3-week randomized double blind parallel group trial. RESULTS: The responder rate to tiaprofenic acid and naproxen was 52 and 59%, respectively. Correctly characterized by use of a combination of 6 baseline variables were 79% of the patients treated with tiaprofenic acid and 81% treated with naproxen. CONCLUSION: Both active drugs were found effective compared with placebo in patients with OA, but with different characteristics.

Loratadine and terfenadine in perennial allergic rhinitis. Treatment of nonresponders to the one drug with the other drug.

The efficacy of loratadine and terfenadine in perennial allergic rhinitis was evaluated in a double-blind, selected cross-over study consisting of two phases. During the first phase, 76 patients with perennial allergic rhinitis, 8-67 years old, were included in the study. Of these, 41 patients received loratadine 10 mg daily, and 35 patients received terfenadine 60 mg twice daily, for 2 weeks. According to symptoms and side-effects, 32 patients were classified as responders to loratadine, and 28 patients as responders to terfenadine. All observed symptoms were significantly reduced in both treatment groups, but with no significant differences between the two groups. Side-effects were few and mild. In patients with normal IgE, loratadine was significantly superior to terfenadine in relieving nasal secretion, whereas terfenadine was significantly superior to loratadine in relieving nasal congestion. In patients with increased IgE, patients treated with loratadine showed significantly greater reduction in sneezing than patients treated with terfenadine. A positive correlation between total IgE and reduction in overall symptoms was found for patients treated with loratadine, whereas a negative correlation was found for patients treated with terfenadine. During the second study phase, the nonresponders received the other drug for 2 weeks. All seven nonresponders to terfenadine responded to loratadine after crossing over, whereas four of nine nonresponders to loratadine responded to terfenadine. Nonresponders to one drug may respond to the other drug. Thus, more than one antihistamine drug should be tried in perennial allergic rhinitis if the first fails.

Ketoprofen controlled release (CR) in the treatment of osteoarthrosis; a double blind, randomized multicentre study of single morning versus evening dose. Norwegian Study Group of General Practitioners.

OBJECTIVE: To compare the morning and evening dose of 200 mg ketoprofen controlled release formulation with regard to both efficacy and GI tolerability. DESIGN: Double-blind, randomized multicentre prospective trial with cross-over design combined with a parallel design. PARTICIPANTS: One hundred and eight female and 55 male patients with osteoarthrosis in hip(s) or knee(s) necessitating treatment with nonsteroidal antiinflammatory drugs. MAIN OUTCOME MEASURE: The degrees of pain and stiffness and joint movement ability in joints with osteoarthrosis. RESULTS: Both the morning and the evening dose demonstrated a significant effect (p < 0.01) on all efficacy variables. The reduction in degree of pain in the afternoon and in the evening was significantly higher (p < 0.01) for the morning dose. The total frequency and degree of gastrointestinal discomfort increased significantly (p < 0.01) during both treatment periods. The increases were mainly caused by increased gastric pain and constipation. No significant differences were found between the two regimes regarding tolerability. CONCLUSION: Ketoprofen controlled release given once daily in the morning compared to the evening to patients with osteoarthrosis may increase the efficacy without reducing the tolerability of the drug.