Management for severe Crohn's disease: a lifetime cost-utility analysis.

OBJECTIVES: Infliximab is a costly therapy for active Crohn's disease resistant to corticosteroids and immunosuppressive medication. The purpose of this study was to examine whether a treatment including infliximab (episodic re-infusions for relapse or maintenance therapy every 8 weeks) was relevant compared with conventional management (surgery and medical treatment without infliximab) for nonfistulizing resistant Crohn's disease. METHODS: We performed a life-time cost-utility analysis with an analytic Markov decision model from the perspective of the third-party payer system. Utility measurement using Standard Gamble was used to adjust the survival time for each health state of the disease. Direct costs were estimated from standard management based on expert opinion. A sensitivity analysis was conducted to gauge the effects of uncertainty in the values assigned to variables. RESULTS: The incremental effectiveness with infliximab therapy is .761 Quality-Adjusted Life Years (QALYs) for an added cost ranging from 48,478.79 euros to 596,990.35 euros, depending on treatment procedure. The incremental cost utility ratio expressed in euros per QALYs saved varied from 63,700.82 euros (episodic re-infusions) to over 762,245.09 euros (maintenance therapy). CONCLUSIONS: Infliximab therapy could be cost-effective in the case of relapse treatment only, whereas the marginal cost-utility ratio exceeds conventional benchmarks for maintenance therapy. This analysis will be supplemented by conducting further randomized controlled trials and prospective observational study, focused on the costs of illness (direct and indirect), patient preferences, the disease's clinical course, and infliximab safety.

[Chronic active ulcerative colitis. Efficacy of intravenous followed by oral cyclosporine combined with azathioprine]. / Rectocolite ulcéro-hémorragique chronique active. Efficacité de la ciclosporine intra-veineuse puis orale, associée à l'azathioprine.

OBJECTIVE: To know whether the therapeutic protocol applied in the case of severe acute ulcerative colitis (UC) associating ciclosporine and azathioprine was also effective in the case of moderate chronic active ulcerative colitis (UC). SUBJECTS AND METHODS: in this retrospective study 10 patients (31-65 years, 6 distal colitis, 1 left colitis, 3 pancolitis) moderately active and corticosteroid-resistant or dependent were included. Patients received ciclosporine intraveinously (4 mg/kg/d) and were evaluated 10 days later. If efficient, ciclosporine was given orally for 3 Months, azathioprine was introduced and steroids were progressively tapered. RESULTS: on inclusion the clinical score, based on the Mayo Clinic score, was of 5.7 +/- 0.5. On Day 10, the score decreased significantly (2.1 +/- 0.7, p<0.001) and the therapeutic effect was sustained at the third Month (1.8 +/- 0.7). With azathioprine, 4 patients were still in remission with a mean follow up of 23.3 +/- 15.5 Months. CONCLUSION: therapeutic scheme proposed in severe acute UC failing to respond to steroids may be helpful in some patients with a chronic active UC. Clinical improvement is rapid and long-term response is maintained in about 1 patient out of 2.

Is scintigraphic double-track appearance a sign of severe acute episodes of ulcerative colitis?

AIM: In comparison to endoscopy, clinical and biological criteria are less predictive of severity in attacks of ulcerative colitis (UC). Our aim was to assess the value of the double-track scintigraphic appearance in the assessment of the severity of acute UC by comparing it to endoscopic criteria. PATIENTS AND METHODS: We reviewed medical records of 52 patients hospitalized for an acute attack of UC, who had undergone within 48 hours of presentation both a technetium 99m hexamethyl propylene amine oxime (99mTc-HMPAO) granulocyte scintigraphy and endoscopic examination (colonoscopy: n=20; rectosigmoidoscopy: n=32). RESULTS: Taking into account the colonic segments examined together with both methods in the same patient or results obtained with colonoscopies, there was an excellent agreement between the double-track scintigraphic appearance and endoscopic criteria of severity. CONCLUSION: In patients with previously diagnosed UC, 99mTc-HMPAO granulocyte scintigraphy when available may replace endoscopic examination to assess the severity of attacks.

Exogenous oestrogen as an alternative to food allergy in the aetiology of angioneurotic oedema.

Although frequently reported as an aetiology for chronic angioneurotic oedema or urticaria, food allergy is often a diagnosis proposed in the absence of more convincing evidence, as illustrated by the disappointing results of eviction regimens. We report a series of women with an initial diagnosis of food allergy, but in whom the role of oral contraceptives was subsequently demonstrated. Detailed medical history was obtained from 26 young women presenting with chronic angioneurotic oedema or urticaria initially attributed to food allergy, but in whom C1-esterase inhibitor (C1 INH) deficiency was demonstrated. We investigated the effects of oral contraception on C1 INH levels, C1 INH activity and clinical symptoms of these patients. Discontinuation of oral contraception induced an increase in C1 INH levels and C1 INH activity, associated with recovery or marked improvement of the clinical symptoms formerly attributed to food allergy. The relatively high frequency of women taking cyproterone acetate in this population appeared to be a remarkable finding. Replacement of the initial contraception containing ethinylestradiol by a progestogen maintained or even accentuated these good therapeutic results. Exogenous oestrogens, such as those contained in most oral contraceptives, may play an iatrogenic role in the aetiology of chronic angioneurotic oedema or urticaria.

Butyrate strongly inhibits in vitro stimulated release of cytokines in blood.

We studied the in vitro effects of butyrate on the stimulated release of proinflammatory cytokines and cytokines involved in the Th-1/Th-2 balance using the whole-blood model in nine healthy humans. Cytokines were measured without (control) and after stimulation by bacterial lipopolysaccharides (LPS) and phytohemagglutinin (PHA) alone or with addition of butyrate at six different concentrations (0.0625, 0.125, 0.25, 0.5, 1, and 2 mM). We found that butyrate at the six tested concentrations induced a significant decrease (P < 0.001) in the stimulated release of TNF-alpha, IFN-gamma, and IL-12, whereas IL-6 release was not altered. At concentrations > or = 0.25 mM, butyrate significantly reduced the stimulated release of IL-5, IL-10, and IL-13; the stimulated release of IFN-gamma, IL-12, IL-5, and IL-13 was nearly abolished when compared to the unstimulated control sample. We concluded that butyrate has a wide spectrum of inhibitory activity on cytokine release stimulated by LPS + PHA in a whole-blood model. Confirmation of these results on colonic samples would show that butyrate is a factor by which the luminal contents may modulate the immune system in order to maintain the colonic mucosa in a noninflammatory state.

Lhermitte sign and urinary retention: atypical presentation of oxaliplatin neurotoxicity in four patients.

BACKGROUND: Regimens combining oxaliplatin with fluorouracil and folinic acid are standard therapeutic options for patients with metastatic colorectal carcinoma. Oxaliplatin has a good safety profile, although it is responsible for dose-limiting neurotoxicity typically consisting of two distinct clusters of symptoms. Cold-induced distal paresthesiae occur during or shortly after infusion in most patients and are usually transient and mild. A persistent sensory peripheral neuropathy may develop with prolonged treatment, eventually causing superficial and deep sensory loss, sensory ataxia and functional impairment. METHODS: The authors report four cases of atypical neurotoxicity induced by oxaliplatin in patients treated for metastatic colorectal carcinoma. Two patients were male and two were female, with an age range of 52-59 years. RESULTS: Three patients experienced Lhermitte sign and two experienced urinary retention. In all cases, the cumulative dose of oxaliplatin was higher than 1000 mg (range, 1248-2040 mg). Brain and spinal magnetic resonance imaging was performed in two patients and was normal. Somatosensory evoked potentials were recorded in two patients and suggested cervical dorsal column dysfunction. Symptoms resolved a few weeks after discontinuation of oxaliplatin. CONCLUSIONS: Lhermitte sign may be induced via a neurotoxic effect on the ascending axons of these T-shaped neurons. An atonic bladder may be the result of damage to the sensory portion of the sacral reflex arc, either in the dorsal roots, as for example in diabetic neuropathy, or in the posterior columns, as in tabes dorsalis. Alternatively, it may result from a paralysis of the parasympathetic fibers that control the bladder musculature. It is unclear at present whether the micturition difficulties observed in patients in the current series are due to sensory neuropathy or to autonomic neuropathy, event if the former hypothesis seems more likely, as autonomic neuropathy has not been previously observed with oxaliplatin, and its association with cisplatin is exceedingly rare and controversial.