Cost-effectiveness analysis of oral N-acetylcysteine as a preventive treatment in chronic bronchitis.

UNLABELLED: Chronic bronchitis has a prevalence of approximately 11% in the population aged over 35 years and its frequent acute exacerbations (AECBs) are an important cause of morbidity and costs in health-care resources. Oral N -acetylcysteine (NAC) is administered during the winter months as a way of reducing AECBs. This cost-effectiveness analysis was done from the payers' point of view in the Swiss health-care system, based on a retrospective analysis of published placebo-controlled studies. The pooled data show that continuous administration of 400 mg day(-1)per os of NAC leads to a significant reduction in the number of AECBs (NAC: 16.2 vs 25.2% AECBs per month); a significantly smaller percentage of days of sick leave (NAC: 3.6 vs 5.3%) and a lower rate of hospitalizations (NAC: 1.5 vs 3.5% over a period of 6 months). Taking into account the poor compliance of these patients, calculations assumed a compliance of 80%. Direct costs were those of an NAC treatment, the management of an AECB (biological tests in 59%, X-rays in 65% and pulmonary function tests in 45%; antibiotics 70%, bronchodilators in 89%, corticosteroids in 24% and 'others' in 25% of the patients), and of hospitalizations (estimated at 10 days per case). Based on these figures, the mean direct costs of an untreated patient were CHF 869 vs CHF 700 in the NAC-treated patient. Univariate sensitivity analysis indicated that cost neutrality is reached with 0.6 (<0.25-1. 94, 95% CI) AECBs per 6 months. Indirect costs (based on sick leave) were also significantly different; the mean in untreated patients was CHF 1324 vs CHF 779 in the NAC-treated patients. CONCLUSION: Treating chronic bronchitis patients with NAC during the winter months is cost-effective both from the payer's and a social point of view.

Efficacy of oral long-term N-acetylcysteine in chronic bronchopulmonary disease: a meta-analysis of published double-blind, placebo-controlled clinical trials.

OBJECTIVE: This meta-analysis was performed to assess the possible prophylactic benefit of prolonged treatment with oral N-acetylcysteine (NAC) in chronic bronchitis (CB) based on qualifying clinical trials. Treatment of acute exacerbations with NAC was not investigated. BACKGROUND: Prolonged treatment with oral NAC has been investigated in a number of studies of patients with CB. NAC prevented acute exacerbations and symptoms of CB in some but not all trials. METHODS: The trials included in this analysis were selected from a MEDLINE search of the period from January 1, 1980, through June 30, 1995; references in the articles retrieved in the initial search; and consultation with 2 experts. Selection was based on the following criteria: published, double-blind, placebo-controlled, chronic bronchopulmonary disease, duration of therapy > or =2 months, and data sufficient to calculate an outcome variable permitting direct comparison of studies (effect size) for both NAC and placebo groups. The primary end point was the incidence of acute exacerbations in 7 of 8 trials and clinical assessment in the other. In 7 studies, inclusion criteria were based on Medical Research Council criteria for CB, with an additional criterion in some trials. For the meta-analysis, the end points of individual trials were transformed into an effect size as a common outcome. RESULTS: Of 21 trials initially identified, 8 qualified for inclusion. References from the 8 papers and consultation with the experts produced 8 additional publications, 1 of which qualified for inclusion. NAC was administered orally at a daily dose of 400 mg (1 study), 600 mg (5 studies), or 1200 mg (1 study). One other trial used a dose of 600 mg 3 times per week. The duration of treatment was 3 months (1 study), > or =5 months (2 studies), or 6 months (7 studies). The results of this meta-analysis showed a statistically significant effect size for NAC compared with placebo. The overall value of effect size was -1.37 (95% CI, -1.5 to -1.25). Sensitivity analyses did not significantly alter these results. In a subset analysis of trials with the number of acute exacerbations as a clinical end point, a mean difference of -0.32 clinical event (95% CI, -0.50 to -0.18) was found (ie, a 23% decrease in the number of acute exacerbations compared with placebo). CONCLUSION: These findings suggest that a prolonged course of oral NAC prevents acute exacerbations of CB, thus possibly decreasing morbidity and health care costs.

[Thyroid metastases of Grawitz tumors: apropos of a case]. / Métastases thyroïdiennes des tumeurs de Grawitz: à propos d'un cas.

Secondary localisations of malignant tumors to the ENT areas are rare. One case of renal adenocarcinoma metastasis to the thyroid has been followed in our department. After a quick recall of the clinical story, we will try to point out the epidemiological and physiopathological specificities of this localisation and to emphasize its therapeutic difficulties.

[Correlations between anatomy and x-ray computed tomography in cancers of the pharyngo-larynx. Apropos of a prospective study of 35 patients]. / Corrélations anatomo-scanographiques des cancers du pharyngo-larynx. A propos d'une étude prospective portant sur 35 patients.

A prospective study has been conducted in 35 cases of pharyngolaryngeal's carcinoma, between december 1990 and june 1992 in the department of Head and Neck Surgery of Strasbourg. The authors compared, in a statistic analysis, Computed Tomography and histopathologic's correlations. The operative specimen were sectioned in the horizontal plane to correspond with the CT sections. 11 structures were studied more particularly. Results revealed an excellent sensibility for the study of the pre-epiglottic spaces (100%). Inversely, the study of the para glottic space is less good (69% of sensibility). We found that the CT Scan was of no value for the study of the thyroid cartilage, particularly for detection of subclinical lesions. Overall, this study allowed to confirm the value of the CT Scan in the investigation of pharyngolaryngeal tumors but its limits also.

[Neuroendocrine giant-cell epithelioma. Description of a clinical case and review of the literature]. / Les épithéliomas neuroendocrines à grandes cellules. Description d'un cas clinique et revue de la littérature.

Neuroendocrine tumors are rare neoplasms of the larynx and hypopharynx. This tumors are divided in paragangliomas (usually benign, although malignant case have been reported), large cell neuroendocrine carcinoma, described in this case as a primary pharyngo-laryngeal locate, and small cell neuroendocrine carcinoma (characterized by early and diffuse metastatic disease, and best treated by radiotherapy and chemotherapy). Through the international literature, the authors reviewed the characteristics of the large cell neuroendocrine tumors and their management.

[Laryngeal sarcoidosis: apropos of a case]. / Sarcoïdose laryngée: mise au point a propos d'un cas.

The authors report an unusual case of laryngeal sarcoidosis. After having explained it, they describe the elements of diagnosis about this rarely isolated pathology, its complications and treatment as well.

[Sudden deafness. Analysis of a series of 117 cases]. / Surdités brusques. Analyse d'une série de 117 cas.

A retrospective study have been conducted in 117 cases of sudden sensori-neural hearing loss, between 1988 and 1991, int he department of Head and Neck Surgery (Strasbourg). After a brief review of actually treatments, they show, in a statistic and comparative analysis, that efficacy of therapeutics are never significant. This results are compared with international bibliography, and show that treatments of sudden loss remains doubtful.

In-vitro versus in-vivo activities of new 5-lipoxygenase inhibitors with antiinflammatory activity.

The possible relationship between in-vitro inhibition of lipoxygenase (LO)/cyclooxygenase (CO) and in-vivo antiinflammatory effects of compounds such as isoflavanes (Zy 16369, Zy 16372, Zy 16681) was investigated. The latter were all shown to be potent 5-LO inhibitors when tested in vitro on human peritoneal macrophages (IC50 = 1-7 mumol/l). Zy 16372 and Zy 16681 also inhibited the 12- and 15-LO and, to a minor extent, the CO. In order to evaluate the antiinflammatory and antiproliferative effects of these compounds in vivo they were applied topically to mice. No definite correlation could be made between the inhibition of the ear oedema induced by arachidonic acid (AA), the inhibition of the epidermal ornithine-decarboxylase (ODC) activity induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), and the in-vitro activities of the compounds. Zy 16372 appeared to inhibit the oedema dose-dependently (ED50 = 5 mumol/ear) and seemed to be the most potent among the 3 compounds tested and slightly more potent than the reference compound nordihydroguaiaretic acid. As inhibitors of TPA-induced ODC, all 3 compounds exhibited comparable activity. These results suggest that the in-vivo effects of the compounds might be mediated by components other than AA metabolites, and/or be related to their specific kinetic patterns.

A pneumotoxin, O,O,S-trimethyl phosphorothioate, induces hemorheological alteration in rats.

O,O,S-trimethyl phosphorothioate (OOS-TMP), an impurity present in widely used organophosphorus insecticides, has been shown to induce lung injury after oral administration. To date, very little is known about the hemorheological changes which may occur during the inflammation of lung caused by OOS-TMP. The present study has demonstrated that oral administration of OOS-TMP (10 mg/kg, 20 mg/kg) to rats produced an increase in whole blood apparent viscosity at 24, 48 and 72 h following the treatment in rats. Concomitantly, the plasma fibrinogen level and red blood cell (RBC) aggregation were increased at 24 and 48 h. There was no change in RBC filterability. Thus, OOS-TMP, a pneumotoxin, was capable of causing a systemic hemorheological alteration, probably via increase in fibrinogen content, an acute-phase protein, in rats.

Influence of food and antacid administration on fluoride bioavailability from enteric-coated sodium fluoride tablets.

The relative bioavailability of enteric-coated sodium fluoride (NaF) tablets (10 mg F-) has been assessed following administration with a standard calcium-rich breakfast or calcium-poor lunch, and 2 h before or simultaneously with antacid administration (2.4 g aluminum-magnesium hydroxide), versus intake on an empty stomach. Twelve volunteers were studied 3 times according to an open, three-way crossover design over a 24 h period at weekly intervals. Meals were found to decrease the peak serum concentration of NaF from 122 micrograms/L during fasting (after baseline subtraction) to 71 and 88 micrograms/L with breakfast and lunch respectively, and to slow its absorption rate with Tmax increasing from 3.3 to 7.3 and 11.2 hours, without altering its bioavailability. Antacid impaired the bioavailability of NaF by 80% when administered simultaneously, with AUC decreasing from 987 to 155 micrograms.h/L, but had no significant effect when taken 2 h before NaF. In conclusion, the enteric-coated NaF tablets used in this study can be administered with food or after a 2-hour delay following antacid administration, but should not be taken simultaneously with antacid.

Preferred VDT workstation settings, body posture and physical impairments.

In a field study an adjustable VDT workstation was given to each of the 68 operators for one week. The preferred settings, the body postures and subjective evaluations were assessed during normal working activities of the operators. The preferred ranges disclose the following figures: keyboard height (home row above floor) 71-87 cm, screen height (centre above floor) 92-116 cm, viewing angles (eye to screen centre) + 2 to -26 degrees, visual distance (eye to screen) 61-93 cm. There was practically no correlation between preferred settings and anthropometric data of body length or eye levels above floor. The study of body postures revealed that the great majority of operators tend to lean backwards with trunk inclinations between 97 degrees and 121 degrees (95% confidence interval). Some of the preferred settings strongly differ from those recommended in many brochures and standards. The physical complaints in the neck-shoulder and back area are diminished with the preferred settings.

Industrial noise in residential areas: effects on residents.

In the surroundings of five industrial plants, noise immissions (industrial noise and non-industrial noise) were measured and residents asked by a questionnaire about the effects (annoyance and reactions) caused by industrial noise. The questionnaires of a total of 1498 (58%) residents could be analyzed. The Leq for the industrial noise ranges from 37 to 68 dB(A) in the daytime and from 37 to 59 dB(A) in the nighttime. Ten to 20% of the residents are already strongly annoyed at industrial noise Leq levels of 50 dB(A). The sensitivity to noise is higher in the evening and at night. Residents are disturbed mainly during their rest and recreation and often react by closing the windows. Limits for noise immissions caused by industrial plants in residential areas are proposed (Switzerland).

Azathioprine-associated acute pancreatitis in the course of chronic active hepatitis.

We have described a 22-year-old man with an HBsAg-positive chronic active hepatitis who developed an attack of pancreatitis during the course of treatment with prednisone and azathioprine. Clinical and biochemical abnormalities subsided when azathioprine was stopped and reappeared after rechallenge with the drug. Azathioprine-associated acute pancreatitis is well recognized mostly during treatment of Crohn's disease and after renal transplantation. This adverse effect should, therefore, also be kept in mind during the treatment of chronic active hepatitis.

[Occupational medicine studies of train conductors and switchmen of the Federal Swiss Railway]. / Arbeitsmedizinische Untersuchungen bei Zugbegleitern und Stellwerkbeamten der SBB.

Railway controllers and points men of the Swiss Railways retire more often prematurely because of medical reasons than civil servants. A pilot study on 120 controllers and 60 points men revealed adverse effects of the irregular working hours as well as of mental loads. Furthermore, the controllers disclose symptoms and signs caused by physical and environmental loads.

[Studies on an adjustable video screen work station]. / Untersuchungen eines verstellbaren Bildschirmarbeitsplatzes.

An adjustable VDT workstation was studied under practical working conditions. The preferred settings of keyboard and screen were assessed in a vertical and horizontal plane. The great majority of operators preferred a backward leaning trunk posture which was associated with a lower incidence of physical complaints.