Robert Lindeboom

Surgical Excision versus Antibiotic Treatment for Nontuberculous Mycobacterial Cervicofacial Lymphadenitis in Children: A Multicenter, Randomized, Controlled Trial

BACKGROUND The optimal treatment of nontuberculosis mycobacterial cervical lymphadenitis in children has not been established. Until recently, surgical excision was the standard treatment, but the number of reports of successful antibiotic treatment is increasing, which questions whether surgery is the preferred treatment. In this randomized, multicenter trial, we compared surgical excision with antibiotic treatment. METHODS One hundred children with microbiologically proven nontuberculous mycobacterial cervicofacial lymphadenitis were randomly assigned to undergo surgical excision of the involved lymph nodes or to receive antibiotic therapy with clarithromycin and rifabutin for at least 12 weeks. The primary end point was cure, defined as regression of the lymph node enlargement by at least 75%, with cure of the fistula and total skin closure without local recurrence or de novo lesions after 6 months, as assessed by clinical and ultrasound evaluation. Secondary end points included complications of surgery and adverse effects of antibiotic therapy. RESULTS Intention-to-treat analysis revealed that surgical excision was more effective than antibiotic therapy (cure rates, 96% and 66%, respectively; 95% confidence interval for the difference, 16%-44%). Treatment failures were explained neither by noncompliance nor by baseline or acquired in vitro resistance to clarithromycin or rifabutin. Surgical complications were seen in 14 (28%) of 50 patients; staphylococcal wound infection occurred in 6 patients, and a permanent grade 2 facial marginal branch dysfunction occurred in 1 patient. The vast majority of patients who were allocated to antibiotic therapy reported adverse effects (39 [78%] of 50 patients), including 4 patients who had to discontinue treatment. CONCLUSIONS Surgical excision is more effective than antibiotic treatment for children with nontuberculous mycobacterial cervicofacial lymphadenitis.

Cervicofacial Lymphadenitis in Children Caused by Mycobacterium haemophilum

BACKGROUND Nontuberculous mycobacterial (NTM) lymphadenitis in children is most often caused by Mycobacterium avium. In a prospective, multicenter trial of the optimal treatment, 23.7% of the NTM cervicofacial lymphadenitis cases in children were caused by Mycobacterium haemophilum. In this article, we describe the epidemiological and clinical features of M. haemophilum cervicofacial lymphadenitis. METHODS The diagnosis of Mycobacterium avium or M. haemophilum infection was established by culture or polymerase chain reaction. Demographic characteristics and data regarding clinical presentation and possible environmental exposure were compared for patients infected with M. avium and those infected with M. haemophilum. RESULTS Ninety-four (69.9%) of 135 infections were caused by M. avium, 32 (23.7%) by M. haemophilum, and 9 (6.4%) by other NTM species. The median age of the M. haemophilum-infected children was 72 months, compared with 41 months for the M. avium-infected children (P < .001), with an equal distribution for both sexes. Involvement of multiple lymph nodes was frequently observed among the M. haemophilum-infected patients (56% of patients). Extranodal localizations were only observed in M. haemophilum-infected patients. Children with M. haemophilum infection were more likely to have a non-Dutch background (P = .001), and in most cases, they had a history of contact with swimming water (P = .03), whereas M. avium-infected patients were more likely to have a history of playing in sandpits (P = .01). In a multivariate analysis, only older age and a non-Dutch background were predisposing risk factors for M. haemophilum infection, compared with M. avium infection. CONCLUSION Higher age, non-Dutch background, and involvement of multiple cervicofacial lymph nodes with extranodal localizations distinguished M. haemophilum infection from M. avium infection.

Long-term effect of botulinum toxin on impairment and functional health in cervical dystonia

We investigated the long-term effect of botulinum toxin type A (BTA) on impairment as well as functional health in terms of disability, handicap, and quality of life in 64 patients with cervical dystonia. These patients, who first participated in a double-blind trial, were followed for another 12 months. Fifty-four patients continued treatment after 12 months of follow-up and showed improvement on all scales. Furthermore, this effectiveness appeared to increase during follow-up, which suggests a cumulative clinical effect of BTA.

Health-Related Quality of Life Assessment in Dermatology: Interpretation of Skindex-29 Scores Using Patient-Based Anchors

In dermatology, the clinical use of health-related quality of life (HRQL) scores is impeded by lack of empirically and clinically based interpretation of these scores. We aimed to facilitate the interpretation of Skindex-29 domain and overall scores by identifying clinically meaningful cut-off scores, using patient-based anchors. Consecutively included dermatology outpatients completed the Skindex-29 and four sets of anchor-based questions, such as questions on the impact of skin disease on HRQL, on global disease severity, and on psychiatric morbidity. Pearsons correlations and receiver operating characteristic analysis were used to identify the optimal Skindex-29 cut-off scores corresponding to severely impaired HRQL. A total of 339/434 patients completed the questionnaires (response rate 78%), of which 322 could be used for data analysis. Cut-off scores associated with the patient-based anchors on the impact of skin disease on HRQL showed the highest accuracy (area under the curve ranged from 0.83 to 0.91). The corresponding Skindex-29 cut-off scores for severely impaired HRQL were as follows: > or =52 points on symptoms, > or =39 on emotions, > or =37 on functioning, and > or =44 on the overall score. The estimated cut-off scores can be used in clinical practice to identify patients with (very) severely impaired HRQL.

Tuberculin Skin Testing Is Useful in the Screening for Nontuberculous Mycobacterial Cervicofacial Lymphadenitis in Children

BACKGROUND We evaluated the diagnostic usefulness of tuberculin skin testing in the screening for nontuberculous mycobacterial (NTM) infection in children. METHODS We enrolled 180 children who had chronic cervicofacial lymphadenitis in our study. Skin testing was done using antigens of Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium kansasii, and Mycobacterium scrophulaceum. The reference standard for NTM infection was a positive culture result, identification by PCR, or both. Receiver operating characteristic analysis was used to identify the optimal cutoff point in skin induration for the detection of NTM infection. Accuracy of the mycobacterial skin tests was quantified using sensitivity and specificity rates and positive and negative predictive values at the optimal skin induration cutoff. RESULTS A total of 112 NTM infections were identified, of which 83 were caused by M. avium, 21 by Mycobacterium haemophilum, and 8 by other NTM species. At the optimal cutoff for a positive test (5 mm), tuberculin skin testing had a sensitivity and specificity of 70% and 98%, respectively, and a positive predictive value and a negative predictive value of 98% and 64%, respectively, compared with a sensitivity and a specificity of 93% and 97%, respectively; M. avium sensitin, the best-performing skin test, had positive and negative predictive values of 98% and 90%, respectively. CONCLUSION Tuberculin skin testing could be valuable as a first step in the diagnostic analysis of cervicofacial lymphadenitis in children without a history of TB exposure or bacille Calmette-Guérin vaccination.

Accuracy of the MacArthur competence assessment tool for clinical research (MacCAT-CR) for measuring children's competence to consent to clinical research

IMPORTANCE An objective assessment of childrens competence to consent to research participation is currently not possible. Age limits for asking childrens consent vary considerably between countries, and, to our knowledge, the correlation between competence and childrens age has never been systematically investigated. OBJECTIVES To test a standardized competence assessment instrument for children by modifying the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), to investigate its reliability and validity, and to examine the correlation of its assessment with age and estimate cutoff ages. DESIGN, SETTING, AND PARTICIPANTS This prospective study included children and adolescents aged 6 to 18 years in the inpatient and outpatient departments of allergology, gastroenterology, oncology, ophthalmology, and pulmonology from January 1, 2012, through January 1, 2014. Participants were eligible for clinical research studies, including observational studies and randomized clinical trials. EXPOSURES Competence judgments by experts aware of the 4 relevant criteria-understanding, appreciation, reasoning, and choice-were used to establish the reference standard. The index test was the MacCAT-CR, which used a semistructured interview format. MAIN OUTCOMES AND MEASURES Interrater reliability, validity, and dimensionality of the MacCAT-CR and estimated cutoff ages for competence. RESULTS Of 209 eligible patients, we included 161 (mean age, 10.6 years; 47.2% male). Good reproducibility of MacCAT-CR total and subscale scores was observed (intraclass correlation coefficient range, 0.68-0.92). We confirmed unidimensionality of the MacCAT-CR. By the reference standard, we judged 54 children (33.5%) to be incompetent; by the MacCAT-CR, 61 children (37.9%). Criterion-related validity of MacCAT-CR scores was supported by high overall accuracy in correctly classifying children as competent against the reference standard (area under the receiver operating characteristics curve, 0.78). Age was a good predictor of competence on the MacCAT-CR (area under the receiver operating characteristics curve, 0.90). In children younger than 9.6 years, competence was unlikely (sensitivity, 90%); in those older than 11.2 years, competence was probable (specificity, 90%). The optimal cutoff age was 10.4 years (sensitivity, 81%; specificity, 84%). CONCLUSIONS AND RELEVANCE The MacCAT-CR demonstrated strong psychometric properties. In children aged 9.6 to 11.2 years, consent may be justified when competence can be demonstrated in individual cases by the MacCAT-CR. The results contribute to a scientific underpinning of regulations for clinical research directed toward children.

Esthetic outcome of surgical excision versus antibiotic therapy for nontuberculous mycobacterial cervicofacial lymphadenitis in children.

One hundred children with microbiologically proven nontuberculous mycobacterial cervicofacial lymphadenitis were randomly assigned to excision of the involved lymph nodes, or antibiotic therapy consisting of clarithromycin and rifabutin. The esthetic outcome was rated using a revised and weighted Observer Scar Assessment Scale. The median weighted esthetic outcome in surgical patients was significantly better (30.6) than that for patients treated with antibiotics (42.2).

The AMC Linear Disability Score project in a population requiring residential care: psychometric properties

BackgroundCurrently there is a lot of interest in the flexible framework offered by item banks for measuring patient relevant outcomes, including functional status. However, there are few item banks, which have been developed to quantify functional status, as expressed by the ability to perform activities of daily life.MethodThis paper examines the psychometric properties of the AMC Linear Disability Score (ALDS) project item bank using an item response theory model and full information factor analysis. Data were collected from 555 respondents on a total of 160 items.ResultsFollowing the analysis, 79 items remained in the item bank. The remaining 81 items were excluded because of: difficulties in presentation (1 item); low levels of variation in response pattern (28 items); significant differences in measurement characteristics for males and females or for respondents under or over 85 years old (26 items); or lack of model fit to the data at item level (26 items).ConclusionsIt is conceivable that the item bank will have different measurement characteristics for other patient or demographic populations. However, these results indicate that the ALDS item bank has sound psychometric properties for respondents in residential care settings and could form a stable base for measuring functional status in a range of situations, including the implementation of computerised adaptive testing of functional status.

Assessing children’s competence to consent in research by a standardized tool: a validity study

BackgroundCurrently over 50% of drugs prescribed to children have not been evaluated properly for use in their age group. One key reason why children have been excluded from clinical trials is that they are not considered able to exercise meaningful autonomy over the decision to participate. Dutch law states that competence to consent can be presumed present at the age of 12 and above; however, in pediatric practice children’s competence is not that clearly presented and the transition from assent to active consent is gradual. A gold standard for competence assessment in children does not exist. In this article we describe a study protocol on the development of a standardized tool for assessing competence to consent in research in children and adolescents.Methods/designIn this study we modified the MacCAT-CR, the best evaluated competence assessment tool for adults, for use in children and adolescents. We will administer the tool prospectively to a cohort of pediatric patients from 6 to18 years during the selection stages of ongoing clinical trials. The outcomes of the MacCAT-CR interviews will be compared to a reference standard, established by the judgments of clinical investigators, and an expert panel consisting of child psychiatrists, child psychologists and medical ethicists. The reliability, criterion-related validity and reproducibility of the tool will be determined. As MacCAT-CR is a multi-item scale consisting of 13 items, power was justified at 130–190 subjects, providing a minimum of 10–15 observations per item. MacCAT-CR outcomes will be correlated with age, life experience, IQ, ethnicity, socio-economic status and competence judgment of the parent(s). It is anticipated that 160 participants will be recruited over 2 years to complete enrollment.DiscussionA validity study on an assessment tool of competence to consent is strongly needed in research practice, particularly in the child and adolescent population. In this study we will establish a reference standard of children’s competence to consent, combined with validation of an assessment instrument. Results can facilitate responsible involvement of children in clinical trials by further development of guidelines, health-care policies and legal policies.

Three sides of the same coin: measuring global cognitive impairment with the MMSE, ADAS-cog and CAMCOG

The total scores of the ADAS‐cog, MMSE and CAMCOG, comprising various cognitive tasks, are widely used to measure a dimension of global cognitive impairment. It is unknown, however, whether this dimension is common to these instruments. This hampers comparisons when either of these instruments is used. The extent to which these instruments share a common dimension of global cognitive impairment and how their scores relate was examined.