R. van Altena

QUALITY-OF-LIFE IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY-DISEASE IMPROVES AFTER REHABILITATION AT HOME

We have developed a rehabilitation programme at home and have investigated its effects on quality of life (QOL), lung function, and exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). We studied 43 patients with severe airflow obstruction: forced expiratory volume in one second (FEV1) 1.3 +/- 0.4 l (mean +/- SD), FEV1/inspiratory vital capacity (IVC) 37 +/- 7.9%. After stratification, 28 patients were randomly allocated in a home rehabilitation programme for 12 weeks. Fifteen patients in a control group received no rehabilitation. The rehabilitation group received physiotherapy by the local physiotherapist, and supervision by a nurse and a general practitioner. Quality of life was assessed by the four dimensions of the Chronic Respiratory Questionnaire (CRQ). We found a highly significant improvement in the rehabilitation group compared to the control group for the dimensions dyspnoea, emotion, and mastery. Lung function showed no changes in the rehabilitation group. The exercise tolerance improved significantly in the rehabilitation group compared to the control group. The improvement in quality of life was not correlated with the improvement in exercise tolerance. Rehabilitation of COPD patients at home may improve quality of life; this improvement is not correlated with an improvement in lung function and exercise tolerance.

Tuberculosis of the central nervous system: overview of neuroradiological findings

Abstract. This article presents the range of manifestations of tuberculosis (TB) of the craniospinal axis. Central nervous system (CNS) infection with Mycobacterium tuberculosis occurs either in a diffuse form as basal exudative leptomeningitis or in a localized form as tuberculoma, abscess, or cerebritis. In addition to an extensive review of computed tomography and magnetic resonance features, the pathogenesis and the relevant clinical setting are discussed. Modern imaging is a cornerstone in the early diagnosis of CNS tuberculosis and may prevent unnecessary morbidity and mortality. Contrast-enhanced MR imaging is generally considered as the modality of choice in the detection and assessment of CNS tuberculosis.

Relation of lung function, maximal inspiratory pressure, dyspnoea, and quality of life with exercise capacity in patients with chronic obstructive pulmonary disease.

BACKGROUND--Several studies have shown that both objective and subjective measurements are related to exercise capacity in patients with chronic obstructive pulmonary disease (COPD). In this study the relative contribution of lung function, maximal inspiratory pressure, dyspnoea, and quality of life to the performance in a walking distance test and a bicycle ergometer test was investigated. METHODS--Static lung volumes, forced expiratory volume in one second (FEV1), inspiratory slow vital capacity (IVC), transfer factor for carbon monoxide (TLCO) divided by the alveolar volume (TLCO/VA), static compliance (Cst), and maximal inspiratory peak pressure (PImaxPOES) were measured in 40 patients with COPD with severe airways obstruction (mean FEV1 44% predicted, mean FEV1/IVC 37% predicted). Quality of life was assessed by the Chronic Respiratory Questionnaire (CRQ) and dyspnoea by the Borg category scale. Exercise capacity was measured by both a six minute walking distance (test) and a maximal work load of the bicycle ergometer test (Wmax). RESULTS--Spirometric values and maximal inspiratory pressure were modestly correlated with both the six minute walking test and Wmax, r values ranging from 0.50 to 0.58. The TLCO was strongly correlated with the six minute walking test (r = 0.62) and with Wmax (r = 0.78). Quality of life showed no correlation with exercise capacity, while there was a correlation between dyspnoea and the six minute walking test (r = -0.41). Backward linear regression analysis selected TLCO and PImaxPOES as the most significant determinants for exercise performance. They explained 54% and 69% of the variance in the six minute walking test and Wmax, respectively. CONCLUSIONS--The results show that exercise capacity in patients with COPD with severe airways obstruction is more strongly related to inspiratory muscle strength and lung function than to dyspnoea and quality of life. The significant correlation between dyspnoea and the six minute walking test suggests that subjective variables are more strongly related to walking tests than to bicycle ergometer tests.

Long term benefits of rehabilitation at home on quality of life and exercise tolerance in patients with chronic obstructive pulmonary disease.

BACKGROUND--Pulmonary rehabilitation has been shown to have short term subjective and objective benefits for patients with chronic obstructive pulmonary disease (COPD). However, appropriately controlled studies have not previously been performed, nor have the benefits of different types of continuation programme for rehabilitation been investigated. Both these problems have been addressed in a single study of the long term effects of once monthly physiotherapy versus once weekly physiotherapy at home after a comprehensive home rehabilitation programme on quality of life and exercise tolerance in patients with COPD. METHODS--Thirty six patients with severe airways obstruction (mean SD) forced expiratory volume in one second (FEV1) 1.3(0.4) 1, FEV1/inspiratory vital capacity (IVC) 37.2(7.9)%) were studied. Twenty three patients followed a rehabilitation programme at home for 18 months consisting of physiotherapy and supervision by a nurse and general practitioner. During the first three months all 23 patients visited the physiotherapist twice a week for a 0.5 hour session. Thereafter, 11 patients (group A) received a session of physiotherapy once weekly while 12 patients (group B) received a session of physiotherapy once a month. The control group C (13 patients) received no rehabilitation at all. Quality of life was assessed by the Chronic Respiratory Questionnaire, exercise tolerance by the six minute walking distance, and lung function by FEV1 and IVC. Outcome measures were assessed at baseline and at three, six, 12, and 18 months. RESULTS--Long term improvements in quality of life were found in patients in groups A and B, but not in those in group C compared with baseline, but these only reached significance in group B at all time points. Patients in group B had a higher quality of life than those in group C only at three and 12 months. There was a decrease in both six minute walking distance (at 12 and 18 months) and IVC (at three, 12, and 18 months) in patients in group C compared with the baseline measurement. Between groups analysis showed no differences for six minute walking distance, FEV1, and IVC. CONCLUSIONS--This study is the first to show that rehabilitation at home for three months followed by once monthly physiotherapy sessions improves quality of life over 18 months. The change in quality of life was not associated with a change in exercise tolerance.

Reliability and validity of the chronic respiratory questionnaire (CRQ).

BACKGROUND--The Chronic Respiratory Questionnaire (CRQ) is frequently applied to assess quality of life in patients with chronic obstructive pulmonary disease (COPD). However, the reliability and validity of this questionnaire have not yet been determined. This study investigates the reliability and validity of the four separate dimensions of the CRQ. METHODS--The CRQ was administered on two consecutive days to 40 patients with COPD (mean FEV1 44% predicted, FEV1/IVC 37% predicted). Internal consistency reliability of each dimension was investigated by Cronbachs alpha reliability coefficient, test retest reliability by the Spearman-Brown reliability coefficient (p), and content validity by Pearsons correlation coefficient between the CRQ and the symptom checklist (SCL-90). RESULTS--Items of the fatigue, emotion, and mastery dimensions showed a high internal consistency reliability (alpha = 0.71-0.88) as well as a high test retest reliability (p above 0.90). These three dimensions correlated with comparable dimensions of the SCL-90. Items of the dyspnoea dimension showed a low internal consistency reliability (alpha = 0.53) and a test retest reliability of p = 0.73. CONCLUSIONS--Items of the dimensions fatigue, emotion, and mastery of the CRQ are reliable and valid and can be used to assess quality of life in patients with severe airways obstruction. Items of the dyspnoea dimension are less reliable and should not be included in the overall score of the CRQ in comparative research. However, by scoring the items of dyspnoea separately they may be useful for the evaluation of the effects of intervention in a specific patient.

Drug resistance beyond extensively drug-resistant tuberculosis: individual patient data meta-analysis

The broadest pattern of tuberculosis drug resistance for which a consensus definition exists is extensively drug-resistant tuberculosis (XDR-TB). It is not known if additional drug resistance portends worsened patient outcomes. This study compares treatment outcomes of XDR-TB patients with and without additional resistance to explore the need for a new definition. Individual patient data on XDR-TB outcomes were included in a meta-analysis comparing outcomes between XDR-alone and three non-mutually exclusive XDR-TB patient groups: XDR plus resistance to all the second-line injectables (sli) capreomycin and kanamycin/amikacin (XDR+2sli); XDR plus resistance to second-line injectables and to ≥1 Group 4 drug, i.e. : ethionamide/prothionamide, cycloserine/terizidone or PAS (XDR+sliG4); and XDR+sliG4 plus resistance to ethambutol and/or pyrazinamide (XDR+sliG4EZ). Of 405 XDR-TB cases, 301 were XDR-alone; 68 XDR+2sli; 48 XDR+sliG4; and 42 XDR+sliG4EZ. In multivariate analysis, the odds of cure were significantly lower in XDR+2sli (adjusted Odds Ratio (aOR): 0.4; 95% Confidence Interval: 0.2–0.8) compared to XDR-alone, while odds of failure+death were higher in all XDR patients with additional resistance (aOR range: 2.6–2.8). Patients with additional resistance beyond XDR-TB showed poorer outcomes. Limitations in availability, accuracy and reproducibility of current DST methods preclude the adoption of a useful definition beyond the one currently used for XDR-TB.The broadest pattern of tuberculosis (TB) drug resistance for which a consensus definition exists is extensively drug-resistant (XDR)-TB. It is not known if additional drug resistance portends worsened patient outcomes. This study compares treatment outcomes of XDR-TB patients with and without additional resistance in order to explore the need for a new definition. Individual patient data on XDR-TB outcomes were included in a meta-analysis comparing outcomes between XDR alone and three nonmutually exclusive XDR-TB patient groups: XDR plus resistance to all the second-line injectables (sli) and capreomycin and kanamycin/amikacin (XDR+2sli) XDR plus resistance to second-line injectables and to more than one group 4 drug, i.e. ethionamide/protionamide, cycloserine/terizidone or para-aminosalicylic acid (XDR+sliG4) and XDR+sliG4 plus resistance to ethambutol and/or pyrazinamide (XDR+sliG4EZ). Of 405 XDR-TB cases, 301 were XDR alone, 68 XDR+2sli, 48 XDR+sliG4 and 42 XDR+sliG4EZ. In multivariate analysis, the odds of cure were significantly lower in XDR+2sli (adjusted OR 0.4, 95% CI 0.2–0.8) compared to XDR alone, while odds of failure and death were higher in all XDR patients with additional resistance (adjusted OR 2.6–2.8). Patients with additional resistance beyond XDR-TB showed poorer outcomes. Limitations in availability, accuracy and reproducibility of current drug susceptibility testing methods preclude the adoption of a useful definition beyond the one currently used for XDR-TB.

Effects of home rehabilitation on physical performance in patients with chronic obstructive pulmonary disease (COPD)

We investigated whether 12 weeks of rehabilitation at home in patients with chronic obstructive pulmonary disease (COPD) had a beneficial effect on lactate production, metabolic gas exchange data, workload of the inspiratory muscles, and dyspnoea during a maximal bicycle ergometer test. A second aim was to assess whether a change in dyspnoea was related to a change of inspiratory muscle workload. Forty three COPD patients with severe airways obstruction were included in the study: mean forced expiratory volume in one second (FEV1) 1.3 +/- 0.4 L (44% predicted), mean FEV1/inspiratory vital capacity (IVC) 37 +/- 8%. Twenty eight patients started a rehabilitation programme, whilst 15 patients received no rehabilitation. Rehabilitation was carried out at home; patients were supervised by a general practitioner, a physiotherapist and a nurse. Exercise tolerance was measured by means of a 6 min walking distance test (6MWD) and maximal workload (Wmax) during an incremental symptom-limited cycle ergometer test. Inspiratory muscle workload at Wmax was assessed with the Tension Time Index (TTI), and dyspnoea at Wmax with the Borg scale. After 12 weeks, the rehabilitation group showed a significantly larger increase in 6MWD (from 438 to 447 m) and in Wmax (from 70 to 78 W) compared with the control group. A significant improvement in oxygen consumption (V1O2) (from 1.0 to 1.1 L), lactate level (from 3.7 to 3.1 mEq.L(-1)), dyspnoea (from 6.0 to 4.5) and TTI (from 0.10 to 0.08) at Wmax occurred in the rehabilitation group during the programme. The reduction in TTI was not significantly correlated with the fall in dyspnoea, as assessed by the Borg scale. We conclude that 12 weeks of rehabilitation at home in COPD patients increases symptom-limited V1O2 in combination with an increased Wmax. At this significantly higher Wmax, there was a reduction in dyspnoea, lactate level and inspiratory muscle workload. The reduction in dyspnoea was not related to a decreased inspiratory muscle workload. This study shows that rehabilitation at home can produce beneficial physiological improvements during exercise in patients with chronic obstructive pulmonary disease.

Evaluation of moxifloxacin for the treatment of tuberculosis : 3 years of experience

Moxifloxacin (MFX) is a powerful second-line anti-tuberculosis (TB) agent, but the optimal dose has not yet been established and long-term safety data are scarce. We retrospectively reviewed the medical charts of TB patients treated at the Tuberculosis Centre Beatrixoord, University Medical Centre Groningen (Haren, the Netherlands) receiving MFX 400 mg once daily as part of their TB treatment between January 1 2006 and January 1 2009. Safety data and drug–drug interactions were evaluated. Efficacy was predicted based on the area under the concentration–time curve up to 24 h post-dosage (AUC0–24h)/minimal inhibitory concentration (MIC) ratio. 89 patients were treated with a median dose of 6.9 mg·kg−1 MFX once daily for a median period of 74 days. Discontinuation of therapy occurred in only three patients due to gastrointestinal side-effects and hypersensitivity. Pharmacokinetic analysis showed an AUC0–24h/MIC ratio <100 in eight out of 16 patients. A large variation in protein binding affected the unbound AUC0–24h considerably. These data show that MFX treatment was well tolerated in 89 patients receiving a dose of 400 mg once daily for a prolonged period. Considering the variability in (un)bound AUC0–24h/MIC ratio, therapeutic drug monitoring is recommended in selected patients (i.e. rifampicin co-medication; MIC ≥0.25 mg·L−1) to assess optimal therapy.

Relation between beta-lactamase producing bacteria and patient characteristics in chronic obstructive pulmonary disease (COPD).

BACKGROUND--In addition to bronchodilator and anti-inflammatory therapy, exacerbations in patients with chronic obstructive pulmonary disease (COPD) are often treated with antibiotics. Haemophilus influenzae and Moraxella (Branhamella) catarrhalis, two important respiratory pathogens, may produce beta-lactamase which makes them resistant to ampicillin. Surveillance studies conducted in various countries have shown an increasing incidence of these beta-lactamase producing bacteria. Although this may simply be a consequence of the increasing use of antibiotics, it is possible that other factors are important. A study was undertaken to investigate whether clinical factors are related to the presence of beta-lactamase forming bacteria in the sputum of patients with COPD. METHODS--One hundred patients with COPD aged over 40 years were sequentially selected from an outpatient clinic on the basis of sputum culture results. Fifty had beta-lactamase positive (beta L+) and 50 had beta-lactamase negative (beta L-) bacteria in their sputum. Patients were included only if sputum culture results yielded one pathogen. The files of these patients were investigated for possible causative factors present during the two preceding years. RESULTS--Both groups were almost identical in terms of lung function, maintenance medication, and smoking history. The total number of antibiotic courses in the beta L+ group was higher, as were individual courses of cephalosporins, tetracyclines, and macrolides. The number of patients admitted to hospital was higher in the beta L+ group, but admissions were of equal duration in both groups. Patients admitted to hospital had poorer lung function. Risk factors for beta-lactamase producing bacteria were identified by logistic regression analysis which revealed an odds ratio for one course of antibiotics of 1.15 (95% CI 1.04 to 1.28). CONCLUSIONS--An increased number of antibiotic courses is related to a higher incidence of beta-lactamase producing bacteria and more patients had hospital admissions in the beta L+ group. beta-lactamase stable antibiotics were used more frequently in the beta L+ group, probably because prescribing was adapted to the presence of beta-lactamase producing bacteria. No other differences were found between the beta L+ and beta L- groups.

Population pharmacokinetics and limited sampling strategy for first-line tuberculosis drugs and moxifloxacin

Therapeutic drug monitoring (TDM) of tuberculosis (TB) drugs currently focuses on peak plasma concentrations, yet total exposure [area under the 24-h concentration-time curve (AUC₀₋₂₄)] is probably most relevant to the efficacy of these drugs. We therefore assessed population AUC₀₋₂₄ data for all four first-line TB drugs (rifampicin, isoniazid, pyrazinamide and ethambutol) as well as moxifloxacin and developed limited sampling strategies to estimate AUC₀₋₂₄ values conveniently. AUC₀₋₂₄ and other pharmacokinetic (PK) parameters were determined following intensive PK sampling in two Dutch TB referral centres. Best subset selection multiple linear regression was performed to derive limited sampling equations. Median percentage prediction error and median absolute percentage prediction error were calculated via jackknife analysis to evaluate bias and imprecision of the predictions. Geometric mean AUC₀₋₂₄ values for rifampicin, isoniazid, pyrazinamide, ethambutol and moxifloxacin were 41.1, 15.2, 380, 25.5 and 33.6 hmg/L, respectively. Limited sampling at various fixed sampling points enabled an accurate and precise prediction of AUC₀₋₂₄ values of all drugs separately and simultaneously. In the absence of clinically validated target values for AUC₀₋₂₄, average AUC₀₋₂₄ values can be used as reference values in TDM. Limited sampling of AUC₀₋₂₄ is feasible in many settings and allows for TDM to be performed at a larger scale.