Improved glycemic control with decreased hypoglycemia prevents long-term complications in type 2 diabetes patients: long-term simulation analysis using the "diabetes mellitus model".

OBJECTIVE: The purpose of this study was to compare the effect of insulin glargine (glargine) and NPH insulin (NPH) on long-term outcomes in type 2 diabetes patients using the Diabetes Mellitus Model (DMM). METHODS: The DMM predicts short- and long-term complications over ten years using data in studies published previously. The main effect on outcome is the influence of the treatment on the HbA1c level which is simulated over time. The simulation was based on a cohort size of 10,000 type 2 diabetes patients taking either glargine or NPH. The best scenario, baseline scenario and worst case scenario were simulated based on differences of 0.13%, 0.44% and 0.85%, respectively, in HbA1c values and corresponding to potentially attainable improvements with comparable or lower hypoglycemia rates in glargine-treated patients and NPH-treated patients. Assumptions for scenarios 1, 2 and 3 were based on a regression analysis of clinical trial data (pooled data clinical trials comparing glargine and NPH) in which the effect of glargine on the HbA1c/hypoglycemia incidence ratio was superior to that of NPH. RESULTS: The relative risks (RR, glargine/NPH) obtained for scenarios 1, 2 and 3 were 0.97, 0.89 and 0.81, respectively, for long-term microvascular complications and 0.99, 0.95 and 0.91, respectively, for long-term macrovascular complications. RR reductions ranged from 1% in the less optimistic scenario to > 20% in the "best case" scenario. Sensitivity analyses showed that variations in the mean baseline HbA1c values and duration of the diabetes were without effect on these outcomes. CONCLUSIONS: Although there is a need to corroborate the results of these simulations with real, long-term clinical data, they have demonstrated that, assuming comparable or lower rates of hypoglycemia, a better glycemic control (HbA1c reduction) can be expected with glargine when compared to NPH together with a reduction in long-term complications, mortality and associated costs.

X-linked spinomuscular atrophy: a kindred with associated abnormal androgen receptor binding.

We studied androgen receptor function in cultured scrotal skin fibroblasts from eight subjects with X-linked spinal and bulbar muscular atrophy (SBMA) (Kennedy's syndrome) from four families. The neuromuscular and endocrine features were similar in all patients. High-affinity dihydrotestosterone binding (Bmax) was decreased in three patients from one family (average, 11.1 fmol/mg) similar to values in subjects with androgen resistance syndromes. Bmax was normal in five SBMA patients from three other families (average, 26.0 fmol/mg). This finding provides direct evidence for abnormal androgen receptor function in some patients with SBMA. There was some correlation between severity of neuromuscular and endocrine dysfunction, providing further evidence that the two types of manifestations are related.

Are quantitative functional measures more sensitive to worsening MS than traditional measures?

The authors used data collected prospectively during a multicenter trial in 133 patients with secondary progressive MS to assess the relative sensitivity of quantitative functional tests and traditional measures, including the Expanded Disability Status Scale (EDSS) and Ambulation Index. Quantitative functional measures worsened in 69% of patients during an average of 6 months of observation, whereas the Clinical Global Impression of Change worsened in 33% and the EDSS worsened in 25% of patients. These changes should be interpreted in the context of the test-retest reliability for each measure.

Incidence and significance of neutralizing antibodies to interferon beta-1a in multiple sclerosis. Multiple Sclerosis Collaborative Research Group (MSCRG)

BACKGROUND: Interferon beta is an effective treatment for relapsing multiple sclerosis (MS). As with other protein drugs, neutralizing antibodies (NAB) can develop that reduce the effectiveness of treatment. OBJECTIVES: To determine the incidence and biological significance of NAB to interferon beta-la (IFN-beta-1a; Avonex; Biogen, Cambridge, MA) in MS patients. METHODS: A two-step assay for NAB to IFN-beta-1a was developed and used to assay serum samples from participants in the phase III clinical trial of IFN-beta-1a, and from patients in an ongoing open-label study of IFN-beta-1a. The biological significance of NAB to IFN-beta-1a was determined by relating the NAB assay result to in vivo induction of the IFN-inducible molecules neopterin and beta-2 microglobulin, and the clinical significance was determined by comparing clinical and MRI measures of disease activity after 2 years of IFN-beta-1a therapy in patients who were NAB+ and NAB-. The incidence of NAB was compared in MS patients who had used only IFN-beta-1a with the incidence in MS patients who had used only IFN-beta-1b. RESULTS: In patients in the open-label study, development of NAB to IFN-beta-1a resulted in a titer-dependent reduction in neopterin induction after interferon injections. In patients in the phase III study, development of NAB was associated with a reduction in beta-2 microglobulin induction. In the phase III study, a trend toward reduced benefit of IFN-beta-1a on MRI activity in NAB+ versus NAB- patients was observed. The incidence of NAB to IFN-beta-1a in the open-label study was approximately 5% over 24 months of treatment of IFN-beta-1a therapy, but was four- to sixfold higher using the same assay for patients exposed only to IFN-beta-1b for a similar duration. There were no clinical, MRI, or CSF characteristics that were predictive of which patients would develop NAB. CONCLUSIONS: NAB directed against IFN-beta have in vivo biological consequences in patients with MS. The frequency with which MS patients develop NAB against IFN-beta is significantly greater with IFN-beta-1b therapy compared with IFN-beta-1a therapy. Treatment decisions in MS patients treated with IFN-beta should take into account development of NAB.

A longitudinal study of brain atrophy in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG).

OBJECTIVE: To determine if progressive brain atrophy could be detected over 1- and 2-year intervals in relapsing MS, based on annual MR studies from the Multiple Sclerosis Collaborative Research Group (MSCRG) trial of interferon beta-1a (Avonex). METHODS: All subjects had mild to moderate disability, with baseline expanded disability status scores ranging from 1.0 to 3.5, and at least two relapses in the 3 years before study entry. Atrophy measures included third and lateral ventricle width, brain width, and corpus callosum area. RESULTS: Significant increases were detected in third ventricle width at year 2 and lateral ventricle width at 1 and 2 years. Significant decreases in corpus callosum area and brain width were also observed at 1 and 2 years. Multiple regression analyses suggested that the number of gadolinium-enhancing lesions at baseline was the single significant contributor to change in third ventricle width. Atrophy over 1 and 2 years as indicated by enlargement of the third and lateral ventricle and shrinkage of the corpus callosum was greater for patients entering the trial with enhancing lesions. Greater disability increments over 1 and 2 years were associated with more severe third ventricle enlargement. CONCLUSION: In patients with relapsing MS and only mild to moderate disability, significant cerebral atrophy is already developing that can be measured over periods of only 1 to 2 years. The course of cerebral atrophy in MS appears to be influenced by prior inflammatory disease activity as indicated by the presence of enhancing lesions. Brain atrophy measures are important markers of MS disease progression because they likely reflect destructive and irreversible pathologic processes.

A longitudinal study of T1 hypointense lesions in relapsing MS: MSCRG trial of interferon beta-1a. Multiple Sclerosis Collaborative Research Group.

BACKGROUND: T1 hypointense lesions (T1 black holes) are focal areas of relatively severe CNS tissue damage detected by MRI in patients with MS. OBJECTIVE: To determine the natural history of T1 hypointense lesions in relapsing MS and the utility of T1 hypointense lesions as outcome measures in MS clinical trials. METHODS: MR studies were from the Multiple Sclerosis Collaborative Research Group trial. Longitudinal results are reported in 80 placebo- and 80 interferon beta-1a (IFNbeta-1a)-treated patients with mild to moderate disability relapsing-remitting MS. RESULTS: There was a small but significant correlation between T1 hypointense lesion volume and disability at baseline and on trial (r = 0.22, r = 0.28). In placebo patients there was a 29.2% increase in the mean volume of T1 hypointense lesions (median 124.5 mm3) over 2 years (p < 0.001 for change from baseline), as compared to an 11.8% increase (median 40 mm3) in the IFNbeta-1a-treated patients (change from baseline not significant). These treatment group comparisons did not quite reach significance. The most significant contributor to change in T1 hypointense lesions was the baseline number of enhancing lesions (model r2 = 0.554). Placebo patients with more active disease, defined by enhancing lesions at baseline, were the only group to show a significant increase in T1 hypointense lesion volume from baseline. CONCLUSION: The development of T1 hypointense lesions is strongly influenced by prior inflammatory disease activity, as indicated by enhancing lesions. These results suggest that treatment with once weekly IM IFNbeta-1a (30 mcg) slows the 2-year accumulation of these lesions in the brain.

Impact of interferon beta-1a on neurologic disability in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG).

BACKGROUND AND OBJECTIVE: A phase III double-blind, placebo-controlled clinical trial demonstrated that interferon beta-1a (IFN beta-1a) (Avonex, Biogen) significantly delayed progression of disability in relapsing MS patients. The primary clinical outcome was time from study entry until disability progression, defined as > or = 1.0 point worsening from baseline Kurtzke Expanded Disability Status Scale (EDSS) score persisting for at least two consecutive scheduled visits separated by 6 months. The objective of this study was to examine the magnitude of benefit on EDSS and its clinical significance. METHODS: Post hoc analyses related to disability outcomes using data collected during the double-blind, placebo-controlled phase III clinical trial. RESULTS: (1) Clinical efficacy related to disability did not depend on the definition of disability progression. A significant benefit in favor of IFN beta-1a was observed when > or = 2.0 point worsening from baseline EDSS was required or when worsening was required to persist for > or = 1.0 year. (2) Placebo recipients who reached the primary clinical outcome worsened by a larger amount from baseline EDSS than did IFN beta-1a recipients who reached the primary study outcome. (3) Significantly fewer IFN beta-1a recipients progressed to EDSS milestones of 4.0 (relatively severe impairment) or 6.0 (unilateral assistance needed to walk). (4) Cox proportional hazards models demonstrated that the only baseline characteristic strongly correlated with longer time to disability progression was IFN beta-1a treatment. CONCLUSIONS: The primary clinical outcome for the IFN beta-1a clinical trial underestimated clinical benefits of treatment. Results in this report demonstrate that IFN beta-1a treatment is associated with robust, clinically important beneficial effects on disability progression in relapsing MS patients.

Cerebrospinal fluid abnormalities in a phase III trial of Avonex (IFNbeta-1a) for relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group.

BACKGROUND AND OBJECTIVE: This report provides results of CSF analyses done in a subset of relapsing remitting MS patients participating in a placebo-controlled, double-blind, phase III clinical trial of IFNbeta-Studies supported by the National Multiple Sclerosis Society (grants RG2019, RG2827),a (Avonex , Biogen). The clinical trial demonstrated that IFNbeta-1a treatment resulted in significantly reduced disability progression, annual relapse rate, and new brain lesions visualized by cranial magnetic resonance imaging. The objectives of the current study were to determine: (a) whether CSF abnormalities in MS patients correlated with disease or MRI characteristics, and (b) effects of IFNbeta-1a therapy on these CSF abnormalities. METHODS: CSF was analyzed from 262 (87%) of the 301 study subjects at entry into the clinical trial, and a second CSF sample was analyzed from 137 of these 262 subjects after 2 years of therapy. CSF cell counts, oligoclonal bands (OCB), IgG index, and free kappa light chains were measured using standard assays. Baseline CSF results were compared with demographic, disease, and MRI parameters. Differences in on-study relapse rate, gadolinium enhancement, and EDSS change according to baseline CSF status was used to determine the predictive value of CSF for subsequent clinical and MRI disease activity. Change in CSF parameters after 104 weeks were used to determine the effects of treatment. RESULTS: (1) At study baseline, 37% of the subjects had abnormal CSF WBC counts, 61% had abnormal levels of CSF free kappa light chains, 84% had abnormal IgG index values, and 90% were positive for OCB. (2) Baseline IgG index, kappa light chains, and OCB showed weakly positive, statistically significant correlations with Gd-enhanced lesion volume and T2 lesion volume. WBC showed a statistically significant correlation with Gd-enhancing lesion volume but was uncorrelated with T2 lesion volume. (3) There was an associated between baseline CSF WBC counts and on-study clinical and MRI disease activity in placebo recipients. (4) IFNbeta-1a treatment resulted in significantly reduced CSF WBC counts, but there was no treatment-related change in CSF IgG index, kappa light chains, or OCB, which remained relatively stable over time in both patient groups. CONCLUSIONS: The current study documents significant reductions in CSF WBC counts in patients treated with IFNbeta-1a for 104 weeks. This finding is considered relevant to the therapeutic response, since CSF WBC counts were found to be positively correlated with subsequent clinical and MRI disease activity in placebo-treated relapsing MS patients.

What is new in the treatment of multiple sclerosis?

Multiple sclerosis (MS) is considered an autoimmune disease associated with immune activity directed against central nervous system antigens. Based on this concept, immunosuppression and immunomodualtion have been the mainstays of therapeutic strategies in MS. During the last decade new therapies have been shown to significantly improve MS disease course. The effective therapies have led to a better understanding of MS pathogenesis and further development of even more efficient therapeutic interventions. Recombinant interferon (IFN)beta represents the first breakthrough in MS therapy. Three large placebo-controlled, double-blind studies and several smaller studies have demonstrated the efficacy of different forms of IFNbeta administrated by either subcutaneous or intramuscular routes and at different doses in patients with active relapsing-remitting multiple sclerosis (RR-MS). The three IFNbeta drugs are IFNbeta-1b and two IFNbeta-1a preparations (Avonex and Rebif). Although each clinical trial had unique features and differences that make direct comparisons difficult, the aggregate results demonstrate a clear benefit of IFNbeta for decreasing relapses and probability of sustained clinical disability progression in patients with RR-MS. All forms of IFNbeta therapy had beneficial effects on the disease process measured by brain magnetic resonance imaging (MRI). IFNbeta-1a (Avonex) also showed benefit in slowing or preventing the development of MS related brain atrophy measured by MRI after 2 years of therapy. Glatiramer acetate, the acetate salt of a mixture synthetic polypeptides thought to mimic the myelin basic protein showed a significant positive results in reducing the relapse rate in patients with RR-MS. Follow up of these patients for approximately 3 years continued to show a beneficial effect on disease relapse rate. Recent MRI data supported the beneficial clinical results seen with glatiramer acetate in patients with RR-MS. Recent studies using intravenous immune globulin (IVIG) suggest that IVIG could be effective to some degree in patients with RR-MS. However, there is not enough evidence that IVIG is equivalent to IFNbeta or glatiramer acetate in the treatment of patients with RR-MS. There have also been recent therapeutical advances in secondary progressive MS (SP-MS). A recent large phase II, placebo-controlled study with IFNbeta-1b in patients with SP-MS convincingly documented that IFNbeta-1b slowed progression of the disease independent of the degree of the clinical disability at the time of treatment initiation and independent of presence of superimposed relapses. Mitoxantrone, an anthracenedione synthetic agent, was also shown to be effective as treatment for active SP-MS. It is well tolerated but the duration of treatment is limited by cumulative cardiotoxicity. There is a growing consensus that disease-modifying therapies should be initiated early in the course of the disease before irreversible clinical disability has developed. Different therapies should be considered and tailored based on patient condition. Combination therapies could be considered as a therapeutic option for patients that failed therapies with IFNbeta and/or glatiramer acetate. Currently, there are new ongoing studies testing safety and/or efficacy of different combination regimens (i.e. azathioprine with IFNbeta, IFNbeta with glatiramer acetate, or pulses of intravenous cyclophosphamide with IFNbeta). Determining the effect of different therapies on the course of the disease within large clinical studies appears easier than determining individual responsiveness. Therefore, standardised methods for evaluating individual patients receiving disease-modifying therapies and development of effective therapeutic algorithms are needed.

Onset of action during on-demand treatment with maalox suspension or low-dose ranitidine for heartburn.

AIM: To compare the onset of action of the local antacid Maalox and the systemic H2-antagonist ranitidine, during 'on demand' ambulant treatment of a single heartburn episode, using a randomized, parallel group, double-blind, double-dummy design. METHODS: Subjects with self-perceived heartburn without known gastrointestinal disease or interfering treatments were selected with questionnaires. The study was performed unsupervised, whenever heartburn required medication. An electronic patient diary gave instructions when to take study medication, and provided visual analogue scales and five-item relief ratings for heartburn, at frequent time intervals activated by an alarm-clock. RESULTS: After a study of the natural history of heartburn and the feasibility of the study procedures in 23 patients, 49 subjects took Maalox and 45 ranitidine. Half of these experienced meaningful heartburn relief within 19 min after Maalox, and within 70 min after ranitidine. One hour after intake, the average heartburn relief score was 3.43 in the Maalox group and 3.04 in the ranitidine group (3 means 'slight improvement' and 4 'strong improvement'). Heartburn was similar in both groups after 3 h. CONCLUSIONS: Maalox provides faster relief of heartburn than ranitidine. Heartburn can be assessed frequently and reliably under ambulant conditions using an electronic patient diary.

Urine screening strategy employing dipstick analysis and selective culture: an evaluation.

A cost-effective urinalysis test strategy, employing screening dipstick analysis with sediment microscopy performed on urines positive for leukocyte esterase, nitrite, protein, or blood, is evaluated. Screening urine culture is done when greater than or equal to 5 WBC/HPF, greater than 10 bacteria/HPF, or yeasts are found on sediment microscopy. Predictive value, sensitivity, and specificity of the test strategy in predicting significant bacteriuria is compared with sediment microscopy, Gram staining of uncentrifuged urine and leukocyte chamber counting. Employment of the test protocol for routine urine specimens would decrease sediment microscopy by 49%, while effectively screening for significant bacteriuria with a sensitivity of 88.9% and predictive value of a negative result of 98.8%.

Pseudo-epileptic seizures: hypnosis as a diagnostic tool.

In this pilot study hypnosis was used in an attempt to provide evidence of a psychogenic component of pseudo-epileptic seizures. The criterion for psychogenesis was the reversal of the amnesia, which is often present in epileptic- and pseudo-epileptic seizures. The technique has been validated by a semi-blind referral of cases for analysis after the clinician had been able to make a firm diagnosis based on electro-encephalic corroboration of the nature of the seizure. In eight out of nine patients (of the original 13 patients, three patients dropped out and one patient was not evaluable), the experimental diagnosis corresponded with the clinical diagnosis. As pseudo-epileptic seizures can be characterized by their dissociative nature, a reasonable hypothesis is that patients with pseudo-epileptic seizures are more responsive to hypnosis than patients with epileptic seizures. Measurements of hypnotizability among seven patients with epileptic seizures and six patients with pseudo-epileptic seizures supported this supposition.

Ketoprofen, paracetamol and placebo in the treatment of episodic tension-type headache.

The aim of the study was to assess the efficacy and tolerability of a single oral dose of ketoprofen 25 mg in comparison with single doses of ketoprofen 2 x 25 mg, paracetamol 500 mg and 1,000 mg, and placebo in the treatment of episodic tension-type headache. The study was conducted as a single centre, double-blind, randomized, placebo-controlled, five-period, within-patient comparative trial in outpatients with episodic tension-type headache according to the International Headache Society's diagnostic criteria. Each patient had to treat five attacks of episodic tension-type headache with a single dose of each of the tested medications with a minimum interval of 72 h between two attacks. Details of the attack and response to treatment were recorded on a diary card. Altogether 30 patients treated 5 attacks and 2, 3, 1 and 4 patients treated 4, 3, 2 and 1 attack, respectively. The primary variable was decrease in headache pain intensity from baseline to 2 h after intake, evaluated by means of a 100 mm visual analogue scale. Ketoprofen 50 mg was significantly better than placebo and paracetamol for this main criterion. Neither of the paracetamol groups differed from the placebo group. Only a few adverse events were reported, usually of mild or moderate severity, with no difference between the treatments. Ketoprofen 50 mg may be considered an effective and well tolerated analgesic in the treatment of episodic tension-type headache of moderate or severe intensity.

An open, randomized study of ketoprofen in patients in surgery for Achilles or patellar tendinopathy.

OBJECTIVE: To assess the concentration of ketoprofen, after topical plaster application, in various tissues in relation to plasma levels in 60 patients undergoing surgery for Achilles or patellar tendinopathy; and to analyze whether tissues act as a reservoir of ketoprofen, by evaluating tissue concentrations in relation to plasma concentration at various time points after removal of the plaster. No attempt was made to study the clinical effect of treatment per se. METHODS: In random order to patients applied 30 mg plasters once daily for 5 consecutive days (n = 30), or took a single oral dose 50 mg (n = 30) before surgery. Tissue samples of skin, subcutaneous fat, tendon sheath, and tendon, and plasma were collected intraoperatively at 0, 6 and 14 hours after removal of the 5th plaster, and at 2, 6, and 14 hours after oral intake. Ketoprofen concentration was determined by a validated GC/MS method. The low limit of quantification was 0.5 ng/ml plasma and 0.5 ng/50 mg tissues. RESULTS: High concentrations of ketoprofen were observed in fat, tendon sheath, and tendon after topical applications, whereas plasma levels of ketoprofen were low. CONCLUSION: Ketoprofen attains high concentrations in subcutaneous tissues after multiple topical applications. Subcutaneous tissues appear to act as a reservoir of ketoprofen.

Intra-articular absorption and distribution of ketoprofen after topical plaster application and oral intake in 100 patients undergoing knee arthroscopy.

OBJECTIVE: The primary objective of this study was to assess the kinetics of ketoprofen in synovial fluid and intra-articular tissues in relation to plasma. The secondary objective was to study whether intra-articular tissues act as reservoirs. METHODS: The ketoprofen concentration was analysed in plasma, synovial fluid and intra-articular tissues after single application of a 30 mg plaster (n = 40), multiple applications for 5 days (n = 30) or oral intake of 50 mg (n = 30) in patients undergoing knee arthroscopy. RESULTS: Median CMax values after topical application were 12.8 ng/ml in synovial fluid, 56.7 ng/g in synovial tissue, 349.3 ng/g in meniscus and 568.9 ng/g in cartilage. CONCLUSION: Topical applications of ketoprofen allow the attainment of high intra-articular tissue concentrations.

Correlation of clinical, magnetic resonance imaging, and cerebrospinal fluid findings in optic neuritis.

We found 42 of 74 patients (57%) with isolated monosymptomatic optic neuritis to have 1 to 20 brain lesions, by magnetic resonance imaging (MRI). All of the brain lesions were clinically silent and had characteristics consistent with multiple sclerosis (MS). None of the patients had ever experienced neurologic symptoms prior to the episode of optic neuritis. During 5.6 years of follow-up, 21 patients (28%) developed definite MS on clinical grounds. Sixteen of the 21 converting patients (76%) had abnormal MRIs; the other 5 (24%) had MRIs that were normal initially (when they had optic neuritis only) and when repeated after they had developed clinical MS in 4 of the 5. Of the 53 patients who have not developed clinically definite MS, 26 (49%) have abnormal MRIs and 27 (51%) have normal MRIs. The finding of an abnormal MRI at the time of optic neuritis was significantly related to the subsequent development of MS on clinical grounds, but interpretation of the strength of that relationship must be tempered by the fact that some of the converting patients had normal MRIs and approximately half of the patients who did not develop clinical MS had abnormal MRIs. We found that abnormal IgG levels in the cerebrospinal fluid correlated more strongly than abnormal MRIs with the subsequent development of clinically definite MS.

Large scale safety study of ketoprofen 25 mg (Toprec) in febrile and painful conditions.

OBJECTIVE: To assess the safety, tolerability and efficacy of low-dose ketoprofen (75-150 mg daily for 5 to 15 days) in a general practice setting. DESIGN: Open label, non-controlled study of ketoprofen 25 mg tablets in the treatment of pain in ENT diseases, dysmenorrhoea, and musculoskeletal disorders. SETTING: General practice, 600 investigators SUBJECTS: Four thousand and sixty-eight patients, aged 13-93 years, mean 42.3 years, 1009 with ENT diseases (mean age 38.8 (13-83) years, 53% female), 978 with dysmenorrhoea (mean age 30.3 (13-60) years, 100% female), 2081 with musculoskeletal disorders (mean age 49.6 (16-93) years, 54% female). MAIN OUTCOME MEASURES: Occurrence of adverse events, on patient and physician evaluation; dose and duration of treatment prescribed/taken (diary); global evaluation of efficacy by patient and physician. RESULT: Twenty-two patients were lost to follow-up (<1%); dose effectively taken was lower than prescribed (3.3 versus 3.6 tablets/day); treatment was stopped prematurely in 3.3% of patients because of adverse events, in 17.1% because of early success of therapy. Gastrointestinal adverse events (AE) were the most frequent (76%) of AE), occurring in 10% of patients. They were more frequent in patients with musculoskeletal pain, who were older and had more associated diseases. Five patients were hospitalized, two for preplanned hospitalizations, the others for one asthma attack, one worsening of low back pain, and one angina attack, none attributed to treatment by the GP. None of the AE was life-threatening. Identified risk factors for AE were age and previous medical history, especially of gastrointestinal disorders. CONCLUSIONS: Good quality large scale studies with little or no loss to follow-up can be done in a general practice setting. At the dose used, ketoprofen was generally well tolerated, and used at a lower dose than prescribed, it was not associated with severe or new side-effects. The results of this study could justify its use in self-medication in these indications.

Emphysematous prostatic abscess: diagnosis and treatment.

We report an unusual case of an emphysematous prostatic abscess. Prostatic abscess is a difficult clinical diagnosis associated with lower urinary tract symptomatology and frequently diabetes mellitus. Computerized axial tomography and transrectal or transurethral ultrasonography can assist in making a specific diagnosis. Definitive treatment is complete surgical drainage, which is achieved by transurethral resection of the prostate. Wide spectrum, adjuvant antibiotic therapy should be given to assure coverage of anaerobic bacteria.