Real-world treatment patterns in patients with nontuberculous mycobacterial lung disease in the Netherlands based on medication dispensing data.

PURPOSE: Real-world data on antibiotic management of nontuberculous mycobacterial lung disease (NTM-LD) is limited for many countries. This study aimed to evaluate real-world treatment practices of NTM-LD in the Netherlands using medication dispensing data. METHODS: A retrospective longitudinal real-world study was conducted using IQVIA's Dutch pharmaceutical dispensing database. The data are collected monthly and include approximately 70% of all outpatient prescriptions in the Netherlands. Patients initiated on specific NTM-LD treatment regimens between October 2015 and September 2020 were included. The main areas of investigation were initial treatment regimens, persistence on treatment, treatment switching, treatment compliance in terms of medication possession rate (MPR) and restarts of treatment. RESULTS: The database included 465 unique patients initiated on triple- or dual-drug regimens for the treatment of NTM-LD. Treatment switches were common and occurred approximately 1.6 per quarter throughout the treatment period. The average MPR of patients initiated on triple-drug therapy was 90%. The median time on therapy for these patients was 119 days; after six months and one year, 47% and 20% of the patients, respectively, were still on antibiotic therapy. Of 187 patients initiated on triple-drug therapy, 33 (18%) patients restarted antibiotic therapy after the initial treatment had been stopped. CONCLUSION: When on therapy, patients were compliant with the NTM-LD treatment; however, many patients stopped their therapy prematurely, treatment switches often occurred, and part of patients had to restart their therapy after a longer treatment gap. NTM-LD management should be improved through greater guideline adherence and appropriate involvement of expert centers.

Outcome of treatment of MDR-TB or drug-resistant patients treated with bedaquiline and delamanid: Results from a large global cohort.

The World Health Organization (WHO) recommends countries introduce new anti-TB drugs in the treatment of multidrug-resistant tuberculosis. The aim of the study is to prospectively evaluate the effectiveness of bedaquiline (and/or delamanid)- containing regimens in a large cohort of consecutive TB patients treated globally. This observational, prospective study is based on data collected and provided by Global Tuberculosis Network (GTN) centres and analysed twice a year. All consecutive patients (including children/adolescents) treated with bedaquiline and/or delamanid were enrolled, and managed according to WHO and national guidelines. Overall, 52 centres from 29 countries/regions in all continents reported 883 patients as of January 31st 2021, 24/29 countries/regions providing data on 100% of their consecutive patients (10-80% in the remaining 5 countries). The drug-resistance pattern of the patients was severe (>30% with extensively drug-resistant -TB; median number of resistant drugs 5 (3-7) in the overall cohort and 6 (4-8) among patients with a final outcome). For the patients with a final outcome (477/883, 54.0%) the median (IQR) number of months of anti-TB treatment was 18 (13-23) (in days 553 (385-678)). The proportion of patients achieving sputum smear and culture conversion ranged from 93.4% and 92.8% respectively (whole cohort) to 89.3% and 88.8% respectively (patients with a final outcome), a median (IQR) time to sputum smear and culture conversion of 58 (30-90) days for the whole cohort and 60 (30-100) for patients with a final outcome and, respectively, of 55 (30-90) and 60 (30-90) days for culture conversion. Of 383 patients treated with bedaquiline but not delamanid, 284 (74.2%) achieved treatment success, while 25 (6.5%) died, 11 (2.9%) failed and 63 (16.5%) were lost to follow-up.

Cardiac function in relation to myocardial injury in hospitalised patients with COVID-19.

BACKGROUND: Previous studies have reported on myocardial injury in patients with coronavirus infectious disease 19 (COVID-19) defined as elevated cardiac biomarkers. Whether elevated biomarkers truly represent myocardial dysfunction is not known. The aim of this study was to explore the incidence of ventricular dysfunction and assess its relationship with biomarker analyses. METHODS: This cross-sectional study ran from April 1 to May 12, 2020, and consisted of all consecutively admitted patients to the Radboud university medical centre nursing ward for COVID-19. Laboratory assessment included high-sensitivity Troponin T and N­terminal pro-B-type natriuretic peptide (NT-proBNP). Echocardiographic evaluation focused on left and right ventricular systolic function and global longitudinal strain (GLS). RESULTS: In total, 51 patients were included, with a median age of 63 years (range 51-68 years) of whom 80% was male. Troponin T was elevated (>14 ng/l) in 47%, and a clinically relevant Troponin T elevation (10â€¯× URL) was found in three patients (6%). NT-proBNP was elevated (>300 pg/ml) in 24 patients (47%), and in four (8%) the NT-proBNP concentration was >1,000 pg/ml. Left ventricular dysfunction (ejection fraction <52% and/or GLS >-18%) was observed in 27%, while right ventricular dysfunction (TAPSE <17 mm and/or RV S' < 10 cm/s) was seen in 10%. There was no association between elevated Troponin T or NT-proBNP and left or right ventricular dysfunction. Patients with confirmed pulmonary embolism had normal right ventricular function. CONCLUSIONS: In hospitalised patients, it seems that COVID-19 predominantly affects the respiratory system, while cardiac dysfunction occurs less often. Based on a single echocardiographic evaluation, we found no relation between elevated Troponin T or NT-proBNP, and ventricular dysfunction. Echocardiography has limited value in screening for ventricular dysfunction.

A case promoting use of ultrasound-guided sampling techniques to correctly diagnose MDR-TB in children.

A paediatric case of multidrug-resistant tuberculosis in which endo-oesophageal ultrasound-guided fine-needle aspiration using an endobronchial ultrasound-guided bronchoscope was used to collect a sample for microbial analyses is presented. In our experience, ultrasound-guided sampling techniques, both endo-oesophageal and endobronchial, can be safely used for the diagnosis of paediatric intrathoracic tuberculous lymphadenopathy in children aged 3 years. Interventional pulmonologists with experience in using these techniques should be part of the multidisciplinary team treating these patients.

Mycobacterium genavense in the Netherlands: an opportunistic pathogen in HIV and non-HIV immunocompromised patients. An observational study in 14 cases.

Mycobacterium genavense is an opportunistic non-tuberculous mycobacterium previously mostly associated with HIV-infected patients with CD4 counts below 100/µL. In this retrospective observational study of medical charts we studied all Dutch patients in whom M. genavense was detected between January 2002 and January 2010. Of the 14 patients identified, 13 (93%) showed clinically relevant M. genavense disease. All patients with M. genavense disease were severely immunocompromised, including HIV-infected patients, solid organ transplant recipients, those with chronic steroid use in combination with other immune modulating drugs, recipients of chemotherapy for non-Hodgkin lymphoma, and those with immunodeficiency syndromes. Two patients had non-disseminated pulmonary M. genavense disease. Of the 12 patients treated, eight (75%) showed a favourable outcome. Four patients died in this study, three despite treatment for M. genavense disease. We conclude that M. genavense is a clinically relevant pathogen in severely immunocompromised patients that causes predominantly disseminated disease with serious morbidity and mortality. M. genavense is increasingly seen among non-HIV immunocompromised patients.

Characterization of a novel variant of Mycobacterium chimaera.

In this study, nonchromogenic mycobacteria were isolated from pulmonary samples of three patients in the Netherlands. All isolates had identical, unique 16S rRNA gene and 16S-23S ITS sequences, which were closely related to those of Mycobacterium chimaera and Mycobacterium marseillense. The biochemical features of the isolates differed slightly from those of M. chimaera, suggesting that the isolates may represent a possible separate species within the Mycobacterium avium complex (MAC). However, the cell-wall mycolic acid pattern, analysed by HPLC, and the partial sequences of the hsp65 and rpoB genes were identical to those of M. chimaera. We concluded that the isolates represent a novel variant of M. chimaera. The results of this analysis have led us to question the currently used methods of species definition for members of the genus Mycobacterium, which are based largely on 16S rRNA or rpoB gene sequencing. Definitions based on a single genetic target are likely to be insufficient. Genetic divergence, especially in the MAC, yields strains that cannot be confidently assigned to a specific species based on the analysis of a single genetic target.

The changing pattern of clinical Mycobacterium avium isolation in the Netherlands.

SETTING: National Mycobacteria Reference Laboratory, The Netherlands. OBJECTIVE: To assess the role of factors other than laboratory improvements in the increasing frequency of isolation of non-tuberculous mycobacteria (NTM) in the Netherlands; laboratory improvements are often considered key factors in this increase. DESIGN: Laboratory database study. All clinically isolated NTM referred to the national reference laboratory between January 2000 and January 2007 were retrieved from the laboratory database and categorised by species, patient age group and sample origin. Data were compared with national demographic data. RESULTS: Clinical Mycobacterium avium isolates accounted for most of the increase in referred NTM. The number of respiratory M. avium samples in patients aged >40 years increased over time. This age group increased in size during the study. In this age group, the prevalence of chronic obstructive pulmonary disease (COPD) increased during the study period. M. avium isolation from lymph nodes in children remained stable, whereas extra-pulmonary M. avium isolation in the middle age group, including human immunodeficiency virus associated bloodstream isolates, decreased. CONCLUSIONS: The increasing NTM notification in the Netherlands is unlikely to have been a result of laboratory improvements alone: the ageing population with an increasing prevalence of COPD is likely as important. Environmental characteristics may specifically favour M.avium.

Renal infarction after cocaine abuse: a case report and review.

A 36-year-old male presented with sudden pain in the left lower abdomen caused by a left renal infarction. Cocaine metabolites were found in the urine and a cocaine-induced renal infarction was diagnosed. Cocaine-induced renal infarction is not frequently reported in the literature. Pathophysiologic mechanisms include direct cocaine-induced platelet activation in combination with vasoconstriction and endothelial damage. There is no proven therapy for this complication.

Clinical relevance of Mycobacterium malmoense isolation in The Netherlands.

Uncertainty exists about the clinical relevance of Mycobacterium malmoense isolation, especially in pulmonary samples. We therefore determined clinical relevance, treatment and outcome of M. malmoense isolation in The Netherlands. A retrospective medical file study was conducted for all patients in The Netherlands from whom Mycobacterium malmoense had been isolated between January 2002 and January 2006. Diagnostic criteria for nontuberculous mycobacterial (NTM) disease published by the American Thoracic Society (ATS) were used to determine clinical relevance. Treatment was compared with guidelines published by the British Thoracic Society. In total, 51 patients were found from whom M. malmoense was isolated. Of these, 40 (78%) patients had pulmonary isolates and 32 (80%) of them met the ATS diagnostic criteria. Cavitary disease was most common (n = 28; 88%). Patients with pulmonary disease were mostly males, with an average age of 56 yrs and pre-existing chronic obstructive pulmonary disease. Cervical lymphadenitis was the most common extrapulmonary disease type. Adherence to treatment guidelines was poor. A good clinical response to treatment was observed in 70% and 73% of patients treated for pulmonary and extrapulmonary disease, respectively. In conclusion, M. malmoense is a clinically highly relevant NTM in The Netherlands causing serious pulmonary morbidity. Adherence to treatment guidelines is not satisfactory.

Clinical relevance of non-tuberculous mycobacteria isolated in the Nijmegen-Arnhem region, The Netherlands.

BACKGROUND: The frequency of clinical isolation of non-tuberculous mycobacteria (NTM) in the Netherlands is increasing, but its clinical relevance is often uncertain. OBJECTIVE: To assess the frequency and clinical relevance of isolation of NTM in four associated hospitals in a single region in the Netherlands. METHODS: Medical files of all patients from whom NTM were isolated between January 1999 and January 2005 were reviewed retrospectively. Diagnostic criteria for non-tuberculous mycobacterial disease published by the American Thoracic Society (ATS) were used to determine clinical relevance. RESULTS: 232 patients were found, from whom NTM were isolated from the respiratory tract in 91% of cases. Patients were mostly white men, with an average age of 60 years and pre-existing pulmonary disease. Fifty-three of 212 patients (25%) with pulmonary isolates met the ATS diagnostic criteria for pulmonary NTM disease; this percentage differed by species. Most patients were treated with rifampicin, ethambutol and clarithromycin. Treatment outcome for pulmonary NTM disease was suboptimal but differed by species: overall, improvement was seen in 67% of treated patients, but in only 50% of those with pulmonary M avium disease. Lymphadenitis was the most common extrapulmonary disease type. CONCLUSIONS: Twenty-five per cent of all patients with pulmonary NTM isolates met the ATS criteria. Clinical relevance differs by species. NTM isolation increases over time. Species distribution differs from that of neighbouring countries and the M avium complex isolates have traits different from those reported in the USA. Adherence to diagnostic and treatment guidelines can be improved.

The rising incidence and clinical relevance of Mycobacterium malmoense: a review of the literature.

The incidence of Mycobacterium malmoense infections compared to other non-tuberculous mycobacteria (NTM) has increased since 1980, especially in northern Europe. Based on various epidemiological and clinical reports outside northern Europe, there is a wide distribution of these infections. Infections with M. malmoense cause pulmonary disease comparable with tuberculosis (TB). The main extra-pulmonary disease type is paediatric cervical lymphadenitis. M. malmoense isolates are clinically significant in about 70-80% of patients. Like other NTM infections, M. malmoense is often found in patients with chronic obstructive pulmonary disease (COPD) and may cause serious morbidity and mortality when inadequately treated. The best treatment consists of a 2-year regimen with rifampicin and ethambutol. The literature on infections with M. malmoense is reviewed with respect to epidemiology, clinical presentation, treatment and outcome.

Systematic review of quantitative clinical gait analysis in patients with dementia.

INTRODUCTION: Diminished mobility often accompanies dementia and has a great impact on independence and quality of life. New treatment strategies for dementia are emerging, but the effects on gait remains to be studied objectively. In this review we address the general effects of dementia on gait as revealed by quantitative gait analysis. METHODS: A systematic literature search with the (MESH) terms: 'dementia' and 'gait disorders' in Medline, CC, Psychlit and CinaHL between 1980-2002. Main inclusion criteria: controlled studies; patients with dementia; quantitative gait data. RESULTS: Seven publications met the inclusion criteria. All compared gait in Alzheimer's Disease (AD) with healthy elderly controls; one also assessed gait in Vascular Dementia (VaD). The methodology used was inconsistent and often had many shortcomings. However, there were several consistent findings: walking velocity decreased in dementia compared to healthy controls and decreased further with progressing severity of dementia. VaD was associated with a significant decrease in walking velocity compared to AD subjects. Dementia was associated with a shortened step length, an increased double support time and step to step variability. DISCUSSION: Gait in dementia is hardly analyzed in a well-designed manner. Despite this, the literature suggests that quantitative gait analysis can be sufficiently reliable and responsive to measure decline in walking velocity between subjects with and without dementia. More research is required to assess, both on an individual and a group level, how the minimal clinically relevant changes in gait in elderly demented patients should be defined and what would be the most responsive method to measure these changes.