CPAP Treatment Adherence in Women with Obstructive Sleep Apnea.

Untreated obstructive sleep apnea (OSA) has numerous negative health-related consequences. Continuous positive airway pressure (CPAP) is generally considered the treatment of choice for OSA, but rates of nonadherence are high. It is believed that OSA is more prevalent among men; therefore understanding how OSA presents among women is limited and treatment adherence has received little research attention. For this study, 29 women were recruited from primary care offices. They completed a questionnaire battery and underwent a night of nocturnal polysomnography (PSG) followed by a visit with a sleep specialist. Women diagnosed with OSA were prescribed CPAP; 2 years later CPAP adherence was evaluated. Results show that approximately half the sample was adherent. There were no significant differences between adherent and nonadherent women on OSA severity; however CPAP adherent women had worse nocturnal and daytime functioning scores at the time of diagnosis. Moreover, when the seven nocturnal and daytime variables were used as predictors in a discriminant analysis, they could predict 87% of adherent and 93% of the nonadherent women. The single most important predictor was nonrefreshing sleep. We discuss the implications of the findings for identifying women in primary care with potential OSA and offer suggestions for enhancing treatment adherence.

Amiodarone pulmonary toxicity.

Amiodarone is an antiarrhythmic agent commonly used to treat supraventricular and ventricular arrhythmias. This drug is an iodinecontaining compound that tends to accumulate in several organs, including the lungs. It has been associated with a variety of adverse events. Of these events, the most serious is amiodarone pulmonary toxicity. Although the incidence of this complication has decreased with the use of lower doses of amiodarone, it can occur with any dose. Because amiodarone is widely used, all clinicians should be vigilant of this possibility. Pulmonary toxicity usually manifests as an acute or subacute pneumonitis, typically with diffuse infiltrates on chest x-ray and high-resolution computed tomography. Other, more localized, forms of pulmonary toxicity may occur, including pleural disease, migratory infiltrates, and single or multiple nodules. With early detection, the prognosis is good. Most patients diagnosed promptly respond well to the withdrawal of amiodarone and the administration of corticosteroids, which are usually given for four to 12 months. It is important that physicians be familiar with amiodarone treatment guidelines and follow published recommendations for the monitoring of pulmonary as well as extrapulmonary adverse effects.

Assessing the impact of pulmonary rehabilitation on functional status in COPD.

BACKGROUND: The optimal way of assessing the impact of pulmonary rehabilitation on functional status in chronic obstructive pulmonary disease (COPD) is currently unknown. The minimal clinically important difference for the constant work rate cycling exercise test also needs to be investigated to facilitate its interpretation. A study was undertaken to evaluate the changes in the 6-min walking test and in the constant work rate cycle endurance test immediately following and 1 year after pulmonary rehabilitation, together with the importance of these changes in terms of health status in patients with COPD. METHODS: Patients with COPD of mean (SD) age 65 (8) years and mean (SD) forced expiratory volume in 1 s (FEV1) 45 (15)% predicted were recruited from a multicentre prospective cohort study and evaluated at baseline, immediately after a pulmonary rehabilitation programme (n = 157) and at 1 year (n = 106). The 6-min walking test and the cycle endurance test were performed at each evaluation. Health status was evaluated with the St George Respiratory Questionnaire. RESULTS: Following pulmonary rehabilitation, cycle endurance time increased (198 (352) s, p<0.001) and stayed over baseline values at 1 year (p<0.001). The 6-min walking distance also showed improvements following rehabilitation (25 (52) m, p<0.001) but returned to baseline values at the 1-year follow-up. Changes in cycle endurance time were more closely associated with changes in health status than with the 6-min walking test. An improvement of 100-200 s in the cycle endurance time was associated with clinically meaningful changes in the St George Respiratory Questionnaire scores. CONCLUSIONS: The cycle endurance test was more responsive than the 6-min walking test in detecting improvement in exercise tolerance following pulmonary rehabilitation, and was also better correlated with improvements in health status. An improvement in the cycle endurance time of 100-200 s appeared to be clinically meaningful.

Low-dose inhaled and nasal corticosteroid use and the risk of cataracts.

Orally inhaled corticosteroid use has been convincingly linked to an increase in the risk of cataracts, although the risk at lower doses in common use remains uncertain. The potential risk of cataracts with the use of nasal corticosteroids is unknown. A matched nested case-control analysis was performed in a population-based cohort of elderly people who had been dispensed medications for airway disease, as identified through a universal drug benefit plan. Inhaled corticosteroid use was associated with a dose-related increase in both the risk of all cataracts and severe cataracts requiring extraction, and the increase in risk of severe cataracts was apparent even at daily doses of

Prevention of CAN graft loss in the medium term without HLA disparity reduction.

INTRODUCTION: This study compares the incidence of cadaveric graft failure from chronic allograft nephropathy in the medium term (1 to 5 years) using older and newer immunosuppressive regimens. The older regimen was established triple therapy and the newer regimen, almost universal replacement of azathioprine by mycophenolate. MATERIALS AND METHODS: In the older series, 76 (71 after death censoring) cadaveric renal grafts done from 1990 to mid-1996 in patients who survived for more than 1 year were analyzed. In the newer series, 49 (45 after death censoring) cadaveric grafts done 5 or more years ago in patients surviving 1 year were analyzed. In the older series, immunosuppression was combined steroids, cyclosporine, and azathioprine. In the newer series, mycophenolate replaced azathioprine in 85%, historically conventional immunosuppression was used in 7.5%, and miscellaneous in 7.5%. RESULTS: Cumulative deaths in years 1 to 5 with renal graft function were as follows: older series, 6.6% (5/76), newer 8.2% (4/49) (P = NS). In the older series, death-censored 1- to 5-year cumulative graft failure was 35.2% (24/71), newer series 4.4% (2/45) (chi-square 13.5, relative risk reduction 0.87 [0.51 to 0.97], P =.00021). ACE-inhibitor antihypertensive therapy was used in 25% (18/71) of the patients in the older series and in 53% (24/45) of patients in the newer series (chi-square 6.1, relative risk 1.8 [1.1 to 2.9], P =.01). CONCLUSION: Replacement of azathioprine with mainly myocophenolate in triple immunosuppression and enhanced use of ACE inhibitors are associated with near complete prevention (87%) of medium-term CAN graft failure, making death with graft function now the major cause of graft loss in this time.

Antihypertensives and myocardial infarction risk: the modifying effect of history of drug use.

PURPOSE: Confounding by indication is common in observational studies of outcomes that treatment is intended to affect. In light of the stepped-care approach to hypertension management, we reexamined the controversy around myocardial infarction (MI) risk in relation to antihypertensive agents by considering past drug history both as a confounder and as an effect modifier. METHODS: Case-control design nested within a cohort of 19,501 adults initiating therapy with angiotensin-converting enzyme inhibitors (ACEI), calcium channel blockers (CCB) or beta-blockers in Saskatchewan (1990-93) and followed up to 1997. MI cases were identified using death certificates and hospital discharge diagnoses (ICD-9,410). Four controls were matched to each case to account for duration and timing of follow-up. RESULTS: 812 MI cases were identified, of which 26% were fatal. At first, current use of CCB and ACEI (versus beta-blockers) appeared to be associated with an increased risk of MI (RR = 2.2; 95% CI = 1.8-2.7 and RR = 1.3; CI = 1.0-1.6 respectively). Adjustment for drug use history attenuated both associations (RR = 1.6; CI = 1.1-2.2 and RR = 1.0; CI = 0.7-1.4). Moreover, the risk for CCB use disappeared when restricted to patients who had already used these agents in the past (RR = 1.1; CI = 0.77-1.7) whereas a high risk of MI for ACEI was found in digoxin users (RR = 9.4; CI = 3.2-27.5). CONCLUSION: Past drug history can be both a confounder and an effect modifier in observational studies. We found adjustment for medication history to attenuate the associations between antihypertensive agents and MI risk. In addition, the estimates significantly varied across drug history profiles thus suggesting the presence of preferential prescribing of specific drug classes to high-risk patients.

Low-dose inhaled corticosteroids and the prevention of death from asthma.

BACKGROUND: Although inhaled corticosteroids are effective for the treatment of asthma, it is uncertain whether their use can prevent death from asthma. METHODS: We used the Saskatchewan Health data bases to form a population-based cohort of all subjects from 5 through 44 years of age who were using antiasthma drugs during the period from 1975 through 1991. We followed subjects until the end of 1997, their 55th birthday, death, emigration, or termination of health insurance coverage; whichever came first. We conducted a nested case-control study in which subjects who died of asthma were matched with controls within the cohort according to the length of follow-up at the time of death of the case patient (the index date), the date of study entry, and the severity of asthma. We calculated rate ratios after adjustment for the subject's age and sex; the number of prescriptions of theophylline, nebulized and oral beta-adrenergic agonists, and oral corticosteroids in the year before the index date; the number of canisters of inhaled beta-adrenergic agonists used in the year before the index date; and the number of hospitalizations for asthma in the two years before the index date. RESULTS: The cohort consisted of 30,569 subjects. Of the 562 deaths, 77 were classified as due to asthma. We matched the 66 subjects who died of asthma for whom there were complete data with 2681 controls. Fifty-three percent of the case patients and 46 percent of the control patients had used inhaled corticosteroids in the previous year, most commonly low-dose beclomethasone. The mean number of canisters was 1.18 for the patients who died and 1.57 for the controls. On the basis of a continuous dose-response analysis, we calculated that the rate of death from asthma decreased by 21 percent with each additional canister of inhaled corticosteroids used in the previous year (adjusted rate ratio, 0.79; 95 percent confidence interval, 0.65 to 0.97). The rate of death from asthma during the first three months after discontinuation of inhaled corticosteroids was higher than the rate among patients who continued to use the drugs. CONCLUSIONS: The regular use of low-dose inhaled corticosteroids is associated with a decreased risk of death from asthma.

Heightened CD40 ligand gene expression in peripheral CD4+ T cells from patients with kidney allograft rejection.

BACKGROUND: CD40 ligand (CD40L) gene expression is increased in rejecting allograft biopsies. We, therefore, tested the possibility that CD40L gene expression is heightened in peripheral CD4+ T cells during renal allograft rejection. METHODS: CD40L gene expression in peripheral blood CD4+ T cells from two renal transplant groups was measured by quantitative reverse transcription-polymerase chain reaction (RT-PCR). Group 1: 20 patients with excellent renal transplant function; group 2: 25 patients with findings of acute and/or chronic allograft nephropathy (CAN); and group 3 of 12 normal controls. CD4+ cells were isolated by positive selection. The modifying effect of cyclosporine (CsA) and FK506 on CD40L gene expression was further tested in vitro in CD4+ T lymphocytes separated from pokeweed mitogen- (PWM) activated peripheral blood lymphocytes (PBL) preparations. RESULTS: Mean+/-SD expressions of CD40L gene, in aM, in groups 1-3 were as follows: 0.0052+/-0.0094; 0.022+/-0.023 (P=0.0038 vs. group 2); and 0.014+/-0.005. Levels of CD40L gene expression correlated significantly with acute rejection Banff 97 score (R2=0.44, P=0.0004) and severity of intertubular capillary changes (ITCC) (R2=0.33, P=0.011). After in vitro activation, CD40L gene expression increased by approximately 4-fold and the addition of CsA or FK506 diminished CD40L gene expression to a base level. CONCLUSION: Peripheral CD4+ T cell CD40L gene expression increases significantly in acute rejection and CAN and may serve as a non-invasive method to monitor allograft function and determine the biological response to CsA and FK506.

The generalization of the odds ratio, risk ratio and risk difference to r x k tables.

Familiar measures of association for 2 x 2 tables are the odds ratio, the risk ratio and the risk difference. Analagous measures of outcome-exposure association are desirable when there are several degrees of severity of both exposure and disease outcome. One such measure (alpha), which we label the general odds ratio (OR(G)), was proposed by Agresti. Convenient methods are given for calculation of both standard error and 95 per cent confidence intervals for OR(G). Other approaches to generalizing the odds ratio entail fitting statistical models which might not fit the data, and cannot handle some zero frequencies. We propose a generalization of the risk ratio (RR(G)) following the statistical approaches of Agresti, Goodman and Kruskal. A method of calculating the standard error and 95 per cent confidence interval for RR(G) is provided. A known statistic, Somers' d, fulfils the characteristics necessary for a generalized risk difference (RD(G)). These measures have straightforward interpretations, are easily computed, are at least as precise as other methods and do not require fitting statistical models to the data. We also examine the pooling of such measures as in, for example, meta-analysis.

Accuracy of oximetry with thermistor (OxiFlow) for diagnosis of obstructive sleep apnea and hypopnea.

OBJECTIVES: To evaluate the diagnostic accuracy for obstructive sleep apnea and hypopnea (OSAH) of the OxiFlow (OF) device which combines oximetry with recording of thermistor airflow. DESIGN & SETTING: Patients scheduled for overnight diagnostic polysomnography (PSG) were studied with OF either simultaneously during laboratory PSG (L-OF, n=86), at home on a separate night (H-OF, n=66), or both (n=55). PATIENTS: 97 patients with suspected OSAH, of whom 40 had OSAH defined as an apnea-hypopnea index (AHI) of more than 15 events per hour of sleep on PSG. INTERVENTIONS: NA. MEASUREMENTS & RESULTS: The automated respiratory disturbance index (RDI) generated by the OF software considerably underestimated the AHI by PSG for both L-OF and H-OF. Altering the parameters for hypopnea identification by the software did not improve this. Visual inspection of the computerized OF tracings added considerable diagnostic information, but a manual count of RDI during visual review overestimated AHI. For the identification of cases vs. non-cases of OSAH, receiver operating characteristic area-under-the-curve statistics ranged from 0.77-0.90 for L-OF and from 0.71-0.77 for H-OF. Combining automated analysis with subsequent visual inspection of OF tracings yielded an overall sensitivity of 86% and specificity of 74% for the diagnosis of OSAH during H-OF recordings. Analysis of potential technician time saved indicated a benefit from the use of OF. CONCLUSIONS: OF has diagnostic utility for the identification of OSAH. However, because of hardware and software limitations, it is unclear whether this device is superior to oximetry alone.

Randomized trial of prolonged chloroquine therapy in advanced pulmonary sarcoidosis.

Sarcoidosis may cause severe ventilatory impairment requiring corticosteroid treatment. Chloroquine (CQ) can be an effective treatment for lung sarcoidosis with few side effects, but has not been accepted as standard therapy. We investigated the benefits of prolonged CQ therapy in 23 symptomatic patients with biopsy-proven pulmonary sarcoidosis (duration, >/= 2 yr). Patients were initially treated for 6 mo with CQ, 750 mg/d, tapering every 2 mo to 250 mg/d. Eighteen patients were then randomized to either a Maintenance group (CQ, 250 mg/d) or to an Observation group (no CQ). After the initial treatment, significant improvement was observed in symptoms, pulmonary function, angiotensin-converting enzyme, and lung gallium scan. Patients randomized to the Maintenance group showed a slower decline in pulmonary function (FEV1, 51.4 +/- 28.2 ml/yr [Maintenance] versus 196.3 +/- 33.4 ml/yr [Observation], p < 0.02) and had fewer relapses: 2 of 10 patients in the Maintenance group at 29.5 +/- 4.9 mo versus 6 of 8 patients in the Observation group at 15.5 +/- 2.9 mo. Adverse effects were seen mainly during high-CQ dosage. We conclude that CQ should be an important consideration for the treatment and maintenance of chronic pulmonary sarcoidosis.