BackgroundNon-tuberculous mycobacteria have long been identified as capable of causing human disease and the number at risk, due to immune-suppression, is rising. Several reports have suggested incidence to be increasing, yet routine surveillance-based evidence is lacking. We investigated recent trends in, and the epidemiology of, non-tuberculous mycobacterial infections in England, Wales and Northern Ireland, 1995-2006.MethodsHospital laboratories voluntarily report non-tuberculous mycobacterial infections to the Health Protection Agency Centre for Infections. Details reported include age and sex of the patient, species, specimen type and source laboratory. All reports were analysed.ResultsThe rate of non-tuberculous mycobacteria reports rose from 0.9 per 100,000 population in 1995 to 2.9 per 100,000 in 2006 (1608 reports). Increases were mainly in pulmonary specimens and people aged 60+ years. The most commonly reported species was Mycobacterium avium-intracellulare (43%); M. malmoense and M. kansasii were also commonly reported. M. gordonae showed the biggest increase over the study period rising from one report in 1995 to 153 in 2006. Clinical information was rarely reported.ConclusionsThe number and rate of reports increased considerably between 1995 and 2006, primarily in older age groups and pulmonary specimens. Increases in some species are likely to be artefacts but real changes in more pathogenic species, some of which will require clinical care, should not be excluded. Enhanced surveillance is needed to understand the true epidemiology of these infections and their impact on human health.

Longer-term maintenance drug or psychological treatment strategies are required to make significant inroads into the large disease burden associated with major depression in the Australian population.

The measurement of lifetime prevalence of depression in cross-sectional surveys is biased by recall problems. We estimated it indirectly for two countries using modelling, and quantified the underestimation in the empirical estimate for one. A microsimulation model was used to generate population-based epidemiological measures of depression. We fitted the model to 1-and 12-month prevalence data from The Netherlands Mental Health Survey and Incidence Study (NEMESIS) and the Australian Adult Mental Health and Wellbeing Survey. The lowest proportion of cases ever having an episode in their life is 30% of men and 40% of women, for both countries. This corresponds to a lifetime prevalence of 20 and 30%, respectively, in a cross-sectional setting (aged 15-65). The NEMESIS data were 38% lower than these estimates. We conclude that modelling enabled us to estimate lifetime prevalence of depression indirectly. This method is useful in the absence of direct measurement, but also showed that direct estimates are underestimated by recall bias and by the cross-sectional setting.

Background: Extrapulmonary tuberculosis appears to be increasing in England and Wales. The trends in extrapulmonary tuberculosis and factors associated with these trends were examined. Methods: National tuberculosis surveillance data from 1999-2006 for England and Wales were used, including demographic, clinical and laboratory information. Trends in the proportion of tuberculosis cases with extrapulmonary disease were investigated using the x 2 trend test and associated factors using logistic regression. Results: Among all the cases of tuberculosis, the proportion with extrapulmonary disease increased from 48% in 1999 (2717 cases) to 53% in 2006 (4205 cases, p,0.001). Regression analysis showed that the rise in extrapulmonary disease was associated with an increase in the proportion of non-UK born cases (odds ratio 2.7, 95% CI 2.6 to 2.8). A more than threefold increase was observed in the proportion of all tuberculosis cases with miliary tuberculosis from 0.7% of all cases (38 cases) to 2.2% (180 cases, p,0.001). This rise was not associated with changes in place of birth or in any of the other risk factors identified. Conclusions: The proportion of cases with extrapulmonary disease has increased over the study period. To a large extent this is due to an increasing proportion of non-UK born cases. Reasons for the rise in miliary tuberculosis require further investigation. Clinicians should have a higher index of clinical suspicion of extrapulmonary tuberculosis in non-UK born cases.

This study provides Class IV evidence that for patients with Pompe disease, long-term ERT positively affects muscle strength, pulmonary function, and daily life activities.

BackgroundEnzyme replacement therapy (ERT) in adults with Pompe disease, a progressive neuromuscular disorder, is of promising but variable efficacy. We investigated whether it alters the course of disease, and also identified potential prognostic factors.MethodsPatients in this open-label single-center study were treated biweekly with 20 mg/kg alglucosidase alfa. Muscle strength, muscle function, and pulmonary function were assessed every 3–6 months and analyzed using repeated-measures ANOVA.ResultsSixty-nine patients (median age 52.1 years) were followed for a median of 23 months. Muscle strength increased after start of ERT (manual muscle testing 1.4 percentage points per year (pp/y); hand-held dynamometry 4.0 pp/y; both p < 0.001). Forced vital capacity (FVC) remained stable when measured in upright, but declined in supine position (−1.1 pp/y; p = 0.03). Muscle function did not improve in all patients (quick motor function test 0.7 pp/y; p = 0.14), but increased significantly in wheelchair-independent patients and those with mild and moderate muscle weakness.Relative to the pre-treatment period (49 patients with 14 months pre-ERT and 22 months ERT median follow-up), ERT affected muscle strength positively (manual muscle testing +3.3 pp/y, p < 0.001 and hand-held dynamometry +7.9 pp/y, p < 0.001). Its effect on upright FVC was +1.8 pp/y (p = 0.08) and on supine FVC +0.8 (p = 0.38). Favorable prognostic factors were female gender for muscle strength, and younger age and better clinical status for supine FVC.ConclusionsWe conclude that ERT positively alters the natural course of Pompe disease in adult patients; muscle strength increased and upright FVC stabilized. Functional outcome is probably best when ERT intervention is timely.

This is the first European consensus recommendation for starting and stopping ERT in adult patients with Pompe disease, based on the extensive experience of experts from different countries.

ObjectiveTo determine the effects of 10 years of enzyme replacement therapy (ERT) in adult patients with Pompe disease, focusing on individual variability in treatment response. MethodsIn this prospective, multicenter cohort study, we studied 30 patients from the Netherlands and France who had started ERT during the only randomized placebo-controlled clinical trial with ERT in late-onset Pompe disease (NCT00158600) or its extension (NCT00455195) in 2005 to 2008. Main outcomes were walking ability (6-minute walk test [6MWT]), muscle strength (manual muscle testing using Medical Research Council [MRC] grading), and pulmonary function (forced vital capacity [FVC] in the upright and supine positions), assessed at 3-to 6-month intervals before and after the start of ERT. Data were analyzed with linear mixedeffects models for repeated measurements. ResultsMedian follow-up duration on ERT was 9.8 years (interquartile range [IQR] 8.3-10.2 years). At the group level, baseline 6MWT was 49% of predicted (IQR 41%-60%) and had deteriorated by 22.2 percentage points (pp) at the 10-year treatment point (p < 0.001). Baseline FVC upright was 54% of predicted (IQR 47%-68%) and decreased by 11 pp over 10 years (p < 0.001). Effects of ERT on MRC sum score and FVC supine were similar. At the individual level, 93% of patients had initial benefit of ERT. Depending on the outcome measured, 35% to 63% of patients had a secondary decline after ≈3 to 5 years. Still, at 10 years of ERT, 52% had equal or better 6MWT and/or FVC upright compared to baseline. ConclusionsThe majority of patients with Pompe disease benefit from long-term ERT, but many patients experience some secondary decline after ≈3 to 5 years. Individual variation, however, is considerable.Glossary ERT = enzyme replacement therapy; FVC = forced vital capacity; IQR = interquartile range; LOTS = Late-Onset Treatment Study; MEP = maximal expiratory pressure; MIP = maximal inspiratory pressure; MRC = Medical Research Council; M6P = mannose-6-phosphate; pp = percentage points; QMT = quantitative muscle testing; 6MWT = 6-minute walk test.