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Biomedical subjects

J La Forge

Publications and source records attributed to J La Forge.

At least 19 recordsLinked to original sources

Economic evaluation of ciprofloxacin compared with usual antibacterial care for the treatment of acute exacerbations of chronic bronchitis in patients followed for 1 year.

OBJECTIVE: To undertake a 1-year prospective economic evaluation of ciprofloxacin compared with usual antibacterial care (any antibacterial other than a quinolone) for the treatment of acute exacerbations of chronic bronchitis (AECB) in adults presenting with a type I or type II AECB. DESIGN: Patients entered the study with an initial AECB and were randomised to the ciprofloxacin group or the usual care group. The following measurements were taken at the end of each AECB and every 3 months: resource utilisation, St. George's Respiratory Questionnaire, Nottingham Health Profile and Health Utilities Index (HUI). The following additional measurements were taken after each AECB: AECB-symptom days and willingness to pay to avoid the AECB. Economic evaluations were performed from the societal viewpoint and the viewpoint of a major third-party payer. Cost-effectiveness analysis was based on cost per AECB-symptom day averted; cost-utility analysis (CUA) was based on cost per quality-adjusted life-year (QALY) gained using the HUI as the basis for calculating QALYs. Cost-benefit analysis was based on the willingness-to-pay (WTP) data. SETTING: This was a study of outpatients enrolled from 46 family physicians and 2 respirologists in Ontario (29 sites) and Québec (19 sites), Canada, between November 1993 and June 1994. PATIENTS AND PARTICIPANTS: 240 adult male and female patients aged > or = 18 years with chronic bronchitis. MAIN OUTCOME MEASURES AND RESULTS: WTP data did not pass scope tests for reasonableness. Ciprofloxacin was more costly and provided better outcomes compared with usual antibacterial care. The base-case results are as follows (1994/1995 values): the incremental annual cost was 578 Canadian dollars ($Can) from the societal viewpoint and $Can840 for the third-party payer; the cost-effectiveness ratio per AECB-symptom day averted was $Can209 from the societal viewpoint and $Can304 for the third-party payer; the cost-utility ratio per QALY gained was $Can18,600 from the societal viewpoint and $Can27,000 for the third-party payer. According to Laupacis criteria, these CUA results are strong evidence in favour of adoption from the societal viewpoint and moderate evidence in favour from the viewpoint of the third-party payer. A subgroup analysis suggests that ciprofloxacin may be particularly cost effective, even 'win-win', in patients with more severe disease. CONCLUSIONS: The sensitivity analyses indicate that the results are relatively robust. Nevertheless, the statistical uncertainty in the results is sufficient that the findings cannot be accepted unequivocally. A further study with a larger sample size would be useful to confirm (or deny) the findings of this study.

Adult↗

Required levels of nasal continuous positive airway pressure during treatment of obstructive sleep apnoea.

The improvement in the severity of obstructive sleep-related breathing disorders during nasal continuous positive airway pressure (NCPAP) therapy can account for the decrease in the required NCPAP level with time. The aim of this study was to prospectively quantify the changes in the required NCPAP level over time of use in sleep apnoea-hypopnoea syndrome (SAHS). Forty sleep apnoea-hypopnoea patients were evaluated before and during the time course of NCPAP therapy. The effective NCPAP level was defined as the positive pressure level that abolished apnoeic and hypopnoeic events and snoring in all sleep stages and sleep positions. This pressure level was determined within 2 weeks after baseline diagnostic sleep study. Sleep studies with NCPAP and NCPAP titration were performed after 2 (n = 40), 8 (n = 40), and 20 (n = 24) months of NCPAP therapy. The initial effective NCPAP level was 9.6 +/- 0.4 cmH2O. It progressively decreased to 8.8 +/- 0.4, 7.9 +/- 0.4 and 7.7 +/- 0.5 after 2, 8 and 20 months, respectively; the difference being significant between the first three NCPAP nights. There was a poor relationship between the changes in the effective NCPAP and changes in weight recorded at the different visits. There was a weak negative relationship between the changes in NCPAP and the previous NCPAP level. In 13 patients, the apnoea-hypopnoea index (AHI) remained > 10 n.h-1 at the first NCPAP trial because the effective NCPAP level was not tolerated. Despite a suboptimal NCPAP level, their sleep architecture improved, and they all reported a subjective improvement in diurnal hypersomnolence.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Utility of nocturnal home oximetry for case finding in patients with suspected sleep apnea hypopnea syndrome.

OBJECTIVE: To evaluate prospectively the validity of home oximetry for case finding in patients clinically suspected of having the sleep apnea hypopnea syndrome (SAHS). DESIGN: Blinded comparison of home oximetry and polysomnographic nocturnal recordings. SETTING: Sleep clinic of a tertiary referral center. PATIENTS: A total of 240 outpatients referred because of reported sleep disturbances or daytime hypersomnia compatible with the diagnosis of SAHS. MEASUREMENTS: All participants had nocturnal home oximetry followed by a conventional polysomnographic study. The two recordings were interpreted blindly. Home oximetry test results were classified as abnormal (suspicion of sleep-related breathing abnormalities) in the presence of repetitive, short-duration arterial oxyhemoglobin saturation. (SaO2) fluctuations without any absolute or relative decrease in the SaO2 threshold. The diagnosis of SAHS was confirmed when the apnea-plus-hypopnea index was greater than 10. RESULTS: Based on the results of the polysomnographic sleep study, 110 patients had SAHS (apnea-plus-hypopnea index, 38.1 +/- 2.5/h; mean +/- SE). Home oximetry test results were interpreted as abnormal in 176 patients (this included 108 patients with SAHS and 68 without SAHS) and were read as normal in 62 patients without SAHS and in 2 with SAHS. Home oximetry testing had a sensitivity of 108/110 or 98.2% (95% Cl, 93.6% to 99.8%); a specificity of 62/130 or 47.7% (Cl, 38.8% to 56.6%); a positive predictive value of 108/176 or 61.4%; and a negative predictive value of 62/64 or 96.9%. CONCLUSIONS: A negative home oximetry test result is helpful in ruling out the diagnosis of SAHS in patients clinically suspected of having this syndrome, because a negative test result reduced the probability from 54.1% to 3.1% in our patients. However, a positive oximetry test increased the probability from 46% to 61.4% in our group of patients.

Adult↗

Long-term effects of protriptyline in patients with chronic obstructive pulmonary disease.

Protriptyline has been shown to improve nocturnal and diurnal hypoxemia in patients with chronic obstructive pulmonary disease in short trials. We prospectively evaluated the long-term effects of protriptyline on pulmonary functions (lung volume and expiratory flow, arterial blood gases) and sleep characteristics (sleep architecture, nocturnal desaturations) in these patients. Sixteen patients previously studied before and after 10 wk of protriptyline treatment were reevaluated after a long-term follow-up (range, 18 to 63 months); the results of those still receiving protriptyline were compared with those who stopped using the drug. Nine patients were still receiving protriptyline at the follow-up visit (10 to 20 mg/day at bedtime), and seven had stopped using the drug because of side effects. These two groups of patients did not differ in their follow-up duration, age, weight, pulmonary functions, and sleep architecture, or in their protriptyline-induced changes in diurnal arterial blood gases and nocturnal desaturation. At the follow-up visit, arterial blood gas determinations had returned to baseline values in all patients no longer receiving protriptyline. In the other group there was no difference between the baseline and follow-up PaO2 values (57.4 +/- 3.4 and 57.0 +/- 1.2 mm Hg, mean +/- SEM). There was no difference in the results of arterial blood gas determinations and pulmonary function tests obtained at the different visits between the two groups. Sleep architecture differed between these two groups, REM sleep time being shorter and the slow-wave sleep time being longer in the patients still receiving the drug. In both groups the cumulative SaO2 curves were similar to those obtained at baseline.(ABSTRACT TRUNCATED AT 250 WORDS)

Circadian Rhythm↗

Lymphocytic alveolitis and airway responsiveness in recently diagnosed sarcoidosis.

We looked at the relationship between the intensity of the lymphocytic alveolitis and airway responsiveness to methacholine, in patients with recently diagnosed untreated pulmonary sarcoidosis. We studied 19 subjects, 13 M and 6 F, aged 19-58 (mean: 36.6) who had a diagnosis of pulmonary sarcoidosis within the last 6 months (radiologic stages: I, 10 subjects; II, 8; III, 1). One subject had a previous history of asthma but was currently asymptomatic. Five were smokers, 5 ex-smokers and 9 non-smokers. Initial assessment included a flexible bronchoscopy with bronchoalveolar lavage (BAL), measurement of expiratory flows, lung volumes, CO diffusion and a methacholine inhalation test. Pulmonary function tests were repeated six months later, and a second evaluation of airway responsiveness to methacholine was obtained in 13 patients. Mean % of lymphocytes, neutrophils and macrophages on BAL were respectively: 25.4, 2.3 and 72.4. Mean % of predicted values for FVC, FEV1, FEF25-75%, TLC, FRC and DLCO were respectively 91.3, 94.3, 88.8, 97.6, 102.1 and 91.2. In all subjects FEV1 was > or = 80% and PC20 was in the normal range (> 16 mg/ml in all subjects but one who had a PC20 of 12.0). There was no correlation between the % of BAL lymphocytes and the initial PC20. At 6 months, overall airway responsiveness was unchanged (geometric mean initial/6 month PC20 methacholine: 95.9/102.8) whether or not the subjects had a high intensity alveolitis (defined as > or = 30% lymphocytes on BAL).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Mechanisms of the effectiveness of continuous positive airway pressure in obstructive sleep apnea.

Nasal continuous positive airway pressure (NCPAP) is considered the most effective treatment of obstructive sleep apnea. Its beneficial effects are related to the normalization of breathing during sleep and to the prevention of nocturnal desaturations. NCPAP interacts with the pathophysiologic mechanisms of sleep apnea onset and with the consequences of these apneas. Upper airway patency is maintained with NCPAP by a pneumatic splinting effect while changes in lung volume and pre-apnea SaO2 level may be implicated in the improvement of apnea-related desaturations. An improvement in central chemosensitivity could account for the improvement in diurnal oxygenation observed with long term NCPAP therapy.

Airway Resistance↗

Validity of diurnal sleep recording in the diagnosis of sleep apnea syndrome.

Two polysomnographic studies were performed in 35 subjects who had a clinical suspicion of sleep apnea syndrome: one study was done at night (N) (from 10:00 p.m. to 8:00 a.m.) and the other during the day (D) starting after lunch (from noon to 5:00 p.m.). N and D sleep studies were performed in random order at a minimal interval of 36 h. No treatment (drug, CPAP) was initiated between the two studies. Both studies included the recording of sleep stages (EEG, EOG, EMG), nasal and mouth flows, thoracoabdominal movements, electrocardiogram, and SaO2 (ear oximetry). D sleep was present in all but one subject. As expected, the total sleep time (TST) was significantly shorter during the D than during the N study (2.6 +/- 0.2 and 6.2 +/- 0.2 h, respectively, mean +/- SEM, p less than 0.001, Wilcoxon's signed-rank test). Stages III-IV and REM were significantly less represented during the D (13.1 +/- 2.4 and 7.7 +/- 1.3%, respectively) than during the N study (18.5 +/- 1.7 and 15.3 +/- 0.8%, p less than or equal to 0.005). From the results of the N study, the diagnosis of sleep apnea syndrome (apnea index greater than 5 and/or apnea + hypopnea index greater than 10) was made in 25 patients, and it was confirmed by the same criteria in 22 by the D sleep recording. There was a significant correlation between the N and D values for these indices (r greater than or equal to 0.9, p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Circadian Rhythm↗

Prognostic value of bronchoalveolar lavage lymphocyte count in recently diagnosed pulmonary sarcoidosis.

We prospectively looked at the prognostic value of bronchoalveolar lavage (BAL) lymphocyte count in 98 patients with recently diagnosed (less than 4 months) untreated sarcoidosis. These 50 men and 48 women (mean age, 37.4) were followed up for a period of 6 to 60 months (mean, 25.6), and were clinically evaluated every three to six months with repeated chest roentgenograms and pulmonary function tests. Twenty-four patients required steroid treatment during the study period. The proportion of treated patients was not significantly higher in the group presenting a BAL lymphocyte count less than or equal to 30 percent at diagnosis than in the group with fewer lymphocytes (31.9 and 17.7 percent of total group respectively, p = 0.10). No significant change in TLC, FRC, FVC, FEV1 or DLCO was found at follow-up between the groups with or without an initial high lymphocyte count. In the treated group, BAL lymphocyte percent weakly correlated with the improvement of FEV1 and FVC while on steroid treatment (mean duration: 3.5 months): r = 0.41, p = 0.031 and r = 0.36, p = 0.05 respectively; no correlation was found with lung volumes and DCO. We conclude that BAL lymphocyte count at the time of diagnosis is not a helpful predictor of lung function deterioration in recently diagnosed sarcoidosis and is not very useful in predicting response to treatment.

Adult↗

Influence of apnea type and sleep stage on nocturnal postapneic desaturation.

We examined the influence of apnea type and sleep stage on the severity of apnea-induced desaturations in 32 patients with a sleep apnea syndrome. The individual postapneic desaturations were evaluated by a desaturation curve; this curve was built by plotting the fall in SaO2 after an apnea against this apnea's length for each apneic event during the whole night recording. We considered only apneas where the preapneic SaO2 was greater than 90% and the lowest SaO2 value after the apnea was equal to or greater than 60% (limit of linearity of our oximeter). From the desaturation curve, we determined a desaturation surface defined as the area under the curve between 10s and a variable apnea duration. The upper bound used for the determination of the desaturation curve and the desaturation surface was the maximal length of apnea type with the shortest apnea duration between non-REM obstructive apnea and the other apnea types (i.e., obstructive and central apnea, obstructive and mixed apnea, etc.). The desaturation surface was determined separately for non-REM sleep apneas (obstructive apneas, mixed apneas, central apneas, and obstructive apneas with persistent expiratory flow) and REM sleep apnea (all obstructive in type). Non-REM obstructive apneas served as reference to evaluate the severity of apnea-induced desaturations of the other apneas. We found that the desaturation surface of obstructive apnea (OA) with expiratory flow and of REM sleep OA were significantly greater than for OA in non-REM sleep (p less than or equal to 0.005). The OA-related desaturation was significantly greater than those of central apneas (p = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

Influence of lung volume in sleep apnoea.

The influence of a constant increase in functional residual capacity on apnoea characteristics was studied in patients with the sleep apnoea syndrome. Pulmonary inflation was achieved by applying a continuous negative extrathoracic pressure into a Poncho type respirator. Nine patients slept in the Poncho for two consecutive nights, negative extrathoracic pressure being applied during the second night. There was no difference in the total sleep time, its composition within the different sleep stages, the apnoea and apnoea-hypopnoea indices, or the sleep time spent in apnoea between the two nights. The mean (SD) apnoea duration increased with negative extrathoracic pressure from 25.3 (2) to 30.5 (3) seconds (p = 0.003) and time spent in obstructive apnoea (percentage of apnoea time) from 56 (13) to 75 (8) (p = 0.02). The mixed apnoea time (%) decreased from 37 (7) to 21 (7) (p = 0.02). Despite the increase in apnoea duration, less time was spent below each oxygen saturation value during negative extrathoracic pressure. The results were similar for apnoeic episodes during non-REM (non-rapid eye movement) sleep, whereas no significant modifications were seen during REM sleep. It is concluded that the composition of apnoea time and resulting oxygen desaturation are influenced by lung volume.

Humans↗

Changes in day and night time oxygenation with protriptyline in patients with chronic obstructive lung disease.

The effect of protriptyline, a tricyclic antidepressant, on sleep architecture, nocturnal arterial oxygen desaturation, pulmonary function, and diurnal arterial blood gases was investigated in an open study of 14 patients with stable chronic obstructive lung disease. Daytime and overnight measurements were made before and 2 and 10 weeks after they started protriptyline (20 mg daily at bedtime). Two patients had to be excluded before the second visit and one before the third visit because of changes in treatment for their chest disease. Protriptyline caused mouth dryness in all patients and dysuria in six men. With protriptyline there were no significant changes in total sleep time, sleep period time, or the percentages of total sleep time occupied by stage I-II and stage III-IV sleep. The mean (SEM) percentage of total sleep time spent in rapid eye movement (REM) sleep decreased from 11.1 (1.7) to 4.6 (0.7) at two weeks and to 4.2 (1.0) at 10 weeks. After protriptyline the time spent during sleep with an arterial oxygen saturation (SaO2) below each 5% increment above 65% was less than the baseline time; the lowest SaO2 (%) reached during sleep increased from 64.5 (1.7) to 72.7 (2.1) at 2 weeks and to 77.4 (2.1) at 10 weeks. Lung volumes and expiratory flows were unchanged during the study. Daytime arterial oxygen tension (PaO2) increased from 57 (1.4) mm Hg before treatment to 62 (1.9) mm Hg at 2 weeks and to 66 (1.9) mm Hg at 10 weeks (7.6 (0.2), 8.3 (0.3), 8.8 (0.3) kPa). Carbon dioxide tension fell from 52 (2.3) mm Hg to 49 (1.4) mm Hg at 2 weeks and to 48 (2.0) mm Hg at 10 weeks (6.9 (0.3), 6.5 (0.2), 6.4 (0.3) kPa), but these changes were not significant. These results suggest that protriptyline may benefit patients with chronic obstructive lung disease by reducing the sleep induced falls in SaO2 and improving diurnal PaO2; a controlled trial is now required.

Aged↗

Influence of respiratory drive on upper airway resistance in normal men.

The variations in nasal and pharyngeal resistance induced by changes in the central inspiratory drive were studied in 10 normal men. To calculate resistances we measured upper airway pressures with two low-bias flow catheters; one was placed at the tip of the epiglottis and the other in the posterior nasopharynx, and we measured flow with a Fleisch no. 3 pneumotachograph connected to a tightly fitting mask. Both resistances were obtained continuously during CO2 rebreathing (Read's method) and during the 2 min after a 1-min voluntary maximal hyperventilation. The inspiratory drive was estimated by measurements of inspiratory pressure generated at 0.1 s after the onset of inspiration (P0.1) and by the mean inspiratory flow (VT/TI). In each subject both resistances decreased during CO2 rebreathing; these decreases were correlated with the increase in P0.1. During the posthyperventilation period, ventilation fell below base line in seven subjects; this was accompanied by an increase in both nasal and pharyngeal resistances. These resistances increased exponentially as VT/TI decreased. Parallel changes in nasal and pharyngeal resistances were seen during CO2 stimulus and during the period after the hyperventilation. We conclude that 1) the indexes quantifying the inspiratory drive reflect the activation of nasopharyngeal dilator muscles (as assessed by the changes in upper airway resistance) and 2) both nasal and pharyngeal resistances are similarly influenced by changes in the respiratory drive.

Adult↗

Effects of respiratory drive on upper airways in sleep apnea patients and normal subjects.

We compared the changes in nasal and pharyngeal resistance induced by modifications in the central respiratory drive in 8 patients with sleep apnea syndrome (SAS) with the results of 10 normal men. Upper airway pressures were measured with two low-bias flow catheters; one was placed at the tip of the epiglottis and the other above the uvula. Nasal and pharyngeal resistances were calculated at isoflow. During CO2 rebreathing and during the 2 min after maximal voluntary hyperventilation, we continuously recorded upper airway pressures, airflow, end-tidal CO2, and the mean inspiratory flow (VT/TI); inspiratory pressure generated at 0.1 s after the onset of inspiration (P0.1) was measured every 15-20 s. In both groups upper airway resistance decreased as P0.1 increased during CO2 rebreathing. When P0.1 increased by 500%, pharyngeal resistance decreased to 17.8 +/- 3.1% of base-line values in SAS patients and to 34.9 +/- 3.4% in normal subjects (mean +/- SE). During the posthyperventilation period the VT/TI fell below the base-line level in seven SAS patients and in seven normal subjects. The decrease in VT/TI was accompanied by an increase in upper airway resistance. When the VT/TI decreased by 30% of its base-line level, pharyngeal resistance increased to 319.1 +/- 50.9% in SAS and 138.5 +/- 4.7% in normal subjects (P less than 0.05). We conclude that 1) in SAS patients, as in normal subjects, the activation of upper airway dilators is reflected by indexes that quantify the central inspiratory drive and 2) the pharyngeal patency is more sensitive to the decrease of the central respiratory drive in SAS patients than in normal subjects.

Adult↗

[Physiopathology of obstructive sleep apneas].

The syndrome of obstructive sleep apnoea is associated with an increased morbidity (the consequence of diurnal hypersomnolence and cardiovascular complications). The contraction of the dilator muscles of the upper airways (nose and pharynx) allows their patency at the time of inspiration. The obstruction of the airways resulted in a disequilibrium between the forces which tend to their collapse (negative inspiratory transpharyngeal pressure gradient) and those which contribute to their opening (muscle contraction). The mechanisms which underlie the triggering of obstructive apnoea are multiple including a reduction in the calibre of the superior airways, an increase in their compliance, and a reduction in the activity of the muscle dilators. This latter is intimately linked to the respiratory muscles and these muscles respond in a similar manner to a stimulation or a depression of the respiratory centre. The ventilatory fluctuations observed during sleep (alternately hyper and hypo ventilation of periodic respiration) thus favours an instability of the superior airways and the occurrence of oropharyngeal obstruction. The depth of post-apnoeic desaturation depends on the value of the arterial oxygen saturation at the beginning of apnoea, the duration of the period of apnoea and the pulmonary volume as the period of apnoea passes off. The cardiovascular consequences of apnoea include disorders of rhythm (bradycardia, auriculoventricular block, ventricular extrasystoles) and haemodynamic (pulmonary and systemic hypertension). This results in a stimulatory metabolic and mechanical effect on the autonomic nervous system. The electroencephalographic awakening which precedes the easing of obstruction of the upper airways is responsible for the fragmentation of sleep. The factors implicated in the cessation of the apnoea include hypoxia and hypercapnia but one also invokes a role for the negative pressure generated during the course of the apnoea.

Airway Resistance↗

Role of lung volumes in sleep apnoea-related oxygen desaturation.

We studied the influence of lung volumes on apnoea-induced desaturation in ten subjects with sleep apnoea syndrome. Lung volumes were measured by helium dilution in the sitting and supine position and closing volume with the single-breath nitrogen washout test. To characterize the severity of apnoea-induced desaturations, we determined a desaturation curve for each patient. This curve was obtained by plotting the fall in arterial oxygen saturation (SaO2) reached at the end of each apnoea against the apnoea duration. From this curve we selected two indices: 1) the SaO2 fall following 30 s of obstructive apnoea (delta SaO2 30); and 2) the desaturation surface between 10-30 s of obstructive apnoea (DS 10-30). Both the delta SaO2 30 and the DS 10-30 were significantly correlated with the expiratory reserve volume (ERV), measured in the sitting (r = 0.77 and 0.65, respectively; p less than 0.05) and the supine positions (r = 0.96 and 0.87; p less than 0.005). A strong correlation was also observed with the difference between the supine ERV and the seated closing volume CV) (r = 0.99 with delta SaO2 30 and 0.89 with DS 10-30; p less than 0.005). Obesity influenced sitting and supine ERV values. We conclude that, among lung volumes, supine ERV and supine ERV-seated CV are the best indicators of the severity of apnoea-induced desaturation.

Humans↗

Increasing the functional residual capacity may reverse obstructive sleep apnea.

We describe the reversal of obstructive sleep apnea with a 0.5 L increase in the functional residual capacity (FRC) in a patient with sleep apnea syndrome. The patient had been treated with medroxyprogesterone acetate for 8 months. The increase in FRC was obtained by applying a constant negative extrathoracic pressure (NEP) with a poncho-type respirator. With pulmonary inflation, there was a dramatic decrease in the apnea index and the percent apnea time, and an improvement in sleep architecture. At all sleep stages, the desaturation duration was shorter with NEP. The exact mechanisms by which pulmonary expansion improved sleep apnea in this patient remain unclear; lung volume dependence of upper airway patency and the improvements in apnea-induced desaturation may be contributing factors. Our observation illustrates that lung volumes may be an important factor in the pathophysiology of obstructive sleep apnea, especially in the apnea onset and in the apneic-induced desaturation.

Airway Obstruction↗