Pulmonary tuberculosis in intensive care setting, with a focus on the use of severity scores, a multinational collaborative systematic review.

BACKGROUND AND AIM: Tuberculosis (TB) is associated with a high mortality in the intensive care unit (ICU), especially in subjects with Acute Respiratory Distress Syndrome (ARDS) requiring mechanical ventilation. Despite its global burden on morbidity and mortality, TB is an uncommon cause of ICU admission, however mortality is disproportionate to the advances in diagnosis and treatment made. Herein we report a systematic review of published studies. METHODS: Our Literature search was conducted to identify studies on outcomes of individuals with TB admitted to ICU. We report and review in-hospital mortality, predictors of poorer outcomes, usefulness of severity scoring systems and potential benefits of intravenous antibiotics. Searches from Pubmed, Embase, Cochrane and Medline were conducted from inception to March 2020. Only literature in English was included. RESULTS: Out of 529 potentially relevant articles, 17 were included. Mortality across all studies ranged from 29-95% with an average of 52.9%. All severity scores underestimated average mortality. The most common indication for ICU admission was acute respiratory failure (36.3%). Negative predictors of outcome included hospital acquired infections, need of mechanical ventilation and vasopressors, delay in initiation of anti-TB treatment, more than one organ failure and a higher severity score. Low income, high incidence countries showed a 23.4% higher mortality rate compared to high income, low TB incidence countries. CONCLUSION: Mortality in individuals with TB admitted to ICU is high. Earlier detection and treatment initiation is needed.

Determinants of non-adherence to anti-TB treatment in high income, low TB incidence settings: a scoping review.

BACKGROUND: Improving adherence to anti-TB treatment is a public health priority in high-income, low incidence (HILI) regions. We conducted a scoping review to identify reported determinants of non-adherence in HILI settings.METHODS: Key terms related to TB, treatment and adherence were used to search MEDLINE, EMBASE, Web of Science, PsycINFO and CINAHL in June 2019. Quantitative studies examining determinants (demographic, clinical, health systems or psychosocial) of non-adherence to anti-TB treatment in HILI settings were included.RESULTS: From 10,801 results, we identified 24 relevant studies from 10 countries. Definitions and methods of assessing adherence were highly variable, as were documented levels of non-adherence (0.9-89%). Demographic factors were assessed in all studies and clinical factors were frequently assessed (23/24). Determinants commonly associated with non-adherence were homelessness, incarceration, and alcohol or drug misuse. Health system (8/24) and psychosocial factors (6/24) were less commonly evaluated.CONCLUSION: Our review identified some key factors associated with non-adherence to anti-TB treatment in HILI settings. Modifiable determinants such as psychosocial factors are under-evidenced and should be further explored, as these may be better targeted by adherence support. There is an urgent need to standardise definitions and measurement of adherence to more accurately identify the strongest determinants.

The Barts Health NHS Trust COVID-19 cohort: characteristics, outcomes and risk scoring of patients in East London.

BACKGROUND: Barts Health National Health Service Trust (BHNHST) serves a diverse population of 2.5 million people in London, UK. We undertook a health services assessment of factors used to evaluate the risk of severe acute respiratory coronavirus 2 (SARS-CoV-2) infection.METHODS: Patients with confirmed polymerase chain reaction (PCR) test results admitted between 1 March and 1 August 2020 were included, alongwith clinician-diagnosed suspected cases. Prognostic factors from the 4C Mortality score and 4C Deterioration scores were extracted from electronic health records and logistic regression was used to quantify the strength of association with 28-day mortality and clinical deterioration using national death registry linkage.RESULTS: Of 2783 patients, 1621 had a confirmed diagnosis, of whom 61% were male and 54% were from Black and Minority Ethnic groups; 26% died within 28 days of admission. Mortality was strongly associated with older age. The 4C mortality score had good stratification of risk with a calibration slope of 1.14 (95% CI 1.01-1.27). It may have under-estimated mortality risk in those with a high respiratory rate or requiring oxygen.CONCLUSION: Patients in this diverse patient cohort had similar mortality associated with prognostic factors to the 4C score derivation sample, but survival might be poorer in those with respiratory failure.

TB management in the European Union/European Economic Area: a multi-centre survey.

BACKGROUND: Essential TB care in the European Union/European Economic Area (EU/EEA) comprises 21 standards for the diagnosis, treatment and prevention of TB that constitute the European Union Standards for Tuberculosis Care (ESTC).METHODS: In 2017, we conducted an audit on TB management and infection control measures against the ESTC standards. TB reference centres in five EU/EEA countries were purposely selected to represent the heterogeneous European TB burden and examine geographic variability.RESULTS: Data from 122 patients, diagnosed between 2012 and 2015 with multidrug-resistant TB (n = 49), extensively drug-resistant TB (XDR-TB) (n = 11), pre-XDR-TB (n = 29) and drug-susceptible TB (n = 33), showed that TB diagnosis and treatment practices were in general in agreement with the ESTC.CONCLUSION: Overall, TB management and infection control practices were in agreement with the ESTC in the selected EU/EEA reference centres. Areas for improvement include strengthening of integrated care services and further implementation of patient-centred approaches.

Facial emotion detection in Vestibular Schwannoma patients with and without facial paresis.

This study investigates whether there exist differences in facial emotion detection accuracy in patients suffering from Vestibular Schwannoma (VS) due to their facial paresis. Forty-four VS patients, half of them with, and half of them without a facial paresis, had to classify pictures of facial expressions as being emotional or non-emotional. The visual information of images was systematically manipulated by adding different levels of visual noise. The study had a mixed design with emotional expression (happy vs. angry) and visual noise level (10% to 80%) as repeated measures and facial paresis (present vs. absent) and degree of facial dysfunction as between subjects' factors. Emotion detection accuracy declined when visual information declined, an effect that was stronger for anger than for happy expressions. Overall, emotion detection accuracy for happy and angry faces did not differ between VS patients with or without a facial paresis, although exploratory analyses suggest that the ability to recognize emotions in angry facial expressions was slightly more impaired in patients with facial paresis. The findings are discussed in the context of the effects of facial paresis on emotion detection, and the role of facial mimicry, in particular, as an important mechanism for facial emotion processing and understanding.

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.

An open label, randomised controlled trial of rifapentine versus rifampicin based short course regimens for the treatment of latent tuberculosis in England: the HALT LTBI pilot study.

BACKGROUND: Ending the global tuberculosis (TB) epidemic requires a focus on treating individuals with latent TB infection (LTBI) to prevent future cases. Promising trials of shorter regimens have shown them to be effective as preventative TB treatment, however there is a paucity of data on self-administered treatment completion rates. This pilot trial assessed treatment completion, adherence, safety and the feasibility of treating LTBI in the UK using a weekly rifapentine and isoniazid regimen versus daily rifampicin and isoniazid, both self-administered for 12 weeks. METHODS: An open label, randomised, multi-site pilot trial was conducted in London, UK, between March 2015 and January 2017. Adults between 16 and 65 years with LTBI at two TB clinics who were eligible for and agreed to preventative therapy were consented and randomised 1:1 to receive either a weekly combination of rifapentine/isoniazid ('intervention') or a daily combination of rifampicin/isoniazid ('standard'), with both regimens taken for twelve weeks; treatment was self-administered in both arms. The primary outcome, completion of treatment, was self-reported, defined as taking more than 90% of prescribed doses and corroborated by pill counts and urine testing. Adverse events were recorded. RESULTS: Fifty-two patients were successfully enrolled. In the intervention arm 21 of 27 patients completed treatment (77.8, 95% confidence interval [CI] 57.7-91.4), compared with 19 of 25 (76.0%, CI 54.9-90.6) in the standard of care arm. There was a similar adverse effect profile between the two arms. CONCLUSION: In this pilot trial, treatment completion was comparable between the weekly rifapentine/isoniazid and the daily rifampicin/isoniazid regimens. Additionally, the adverse event profile was similar between the two arms. We conclude that it is safe and feasible to undertake a fully powered trial to determine whether self-administered weekly treatment is superior/non-inferior compared to current treatment. TRIAL REGISTRATION: The trial was funded by the NIHR, UK and registered with ISRCTN ( 26/02/2013-No.04379941 ).

The NHS visitor and migrant cost recovery programme - a threat to health?

BACKGROUND: In April 2014 the UK government launched the 'NHS Visitor and Migrant Cost Recovery Programme Implementation Plan' which set out a series of policy changes to recoup costs from 'chargeable' (largely non-UK born) patients. In England, approximately 75% of tuberculosis (TB) cases occur in people born abroad. Delays in TB treatment increase risk of morbidity, mortality and transmission in the community. We investigated whether diagnostic delay has increased since the Cost Recovery Programme (CRP) was introduced. METHODS: There were 3342 adult TB cases notified on the London TB Register across Barts Health NHS Trust between 1st January 2011 and 31st December 2016. Cases with missing relevant information were excluded. The median time between symptom onset and treatment initiation before and after the CRP was calculated according to birthplace and compared using the Mann Whitney test. Delayed diagnosis was considered greater or equal to median time to treatment for all patients (79 days). Univariable logistic regression was used to manually select exposure variables for inclusion in a multivariable model to test the association between diagnostic delay and the implementation of the CRP. RESULTS: We included 2237 TB cases. Among non-UK born patients, median time-to-treatment increased from 69 days to 89 days following introduction of CRP (p < 0.001). Median time-to-treatment also increased for the UK-born population from 75.5 days to 89.5 days (p = 0.307). The multivariable logistic regression model showed non-UK born patients were more likely to have a delay in diagnosis after the CRP (adjOR 1.37, 95% CI 1.13-1.66, p value 0.001). CONCLUSION: Since the introduction of the CRP there has been a significant delay for TB treatment among non-UK born patients. Further research exploring the effect of policies restricting access to healthcare for migrants is urgently needed if we wish to eliminate TB nationally.

Protocol for a cluster randomised control trial evaluating the efficacy and safety of treatment for latent tuberculosis infection in recent migrants within primary care: the CATAPuLT trial.

BACKGROUND: The identification and treatment of LTBI is a key component of the WHO's strategy to eliminate TB. Recent migrants from high TB-incidence countries are recognised to be at risk TB reactivation, and many high-income countries have focused on LTBI screening and treatment programmes for this group. However, migrants are the group least likely to complete the LTBI cascade-of-care. This pragmatic cluster-randomised, parallel group, superiority trial investigates whether a model of care based entirely within a community setting (primary care) will improve treatment completion compared with treatment in specialist TB services (secondary care). METHODS: The CATAPuLT trial (Completion and Acceptability of Treatment Across Primary Care and the community for Latent Tuberculosis) randomised 34 general practices in London, England, to evaluate the efficacy and safety of treatment for LBTI in recent migrants within primary care. GP practices were randomised to either provide management for LTBI entirely within primary care (GPs and community pharmacists) or to refer patients to secondary care. The target recruitment number for individuals is 576. The primary outcome is treatment completion (defined as taking at least 90% of antibiotic doses). The secondary outcomes assess adherence, acceptance of treatment, the incidence of adverse effects including drug-induced liver injury, the rates of active TB, patient satisfaction and cost-effectiveness of LTBI treatment. This protocol adheres to the SPIRIT Checklist. DISCUSSION: The CATAPuLT trial seeks to provide implementation research evidence for a patient-centred intervention to improve treatment completion for LTBI amongst recent migrants to the UK. TRIAL REGISTRATION: NCT03069807, March 2017, registered retrospectively.

[Consider the diagnosis 'Bell's palsy' carefully]. / Overweeg de diagnose 'Bellse parese' zorgvuldig.

Patients with facial palsy present with both cosmetic and functional symptoms. When a facial palsy develops quickly (within 72 hours) with no other symptoms, and no cause can be identified, it is probably an idiopathic facial palsy or 'Bell's palsy'. The diagnosis Bell's palsy is, thus, to a certain extent a diagnosis 'per exclusionem'. We present three cases with an incorrectly diagnosed Bell's palsy or inadequate diagnostics or treatment: a 5-year-old male with recurrent facial palsy caused by acute otitis media; a 46-year-old male with facial palsy caused by a malignant parotid tumour; and a 75-year-old female with facial palsy caused by a facial nerve schwannoma in the mastoid segment of the facial nerve. We, therefore, emphasize the importance of thorough history-taking and adequate diagnostics and imaging when patients present with facial palsy.

Daily cough frequency in tuberculosis and association with household infection.

SETTING: Although cough in tuberculosis (TB) is presumed to be important for transmission, there is little objective supporting evidence. OBJECTIVE: To describe 24-h cough frequency in a group with TB, and investigate associations with household rates of infection. DESIGN: Patients with a new diagnosis of pulmonary TB underwent 24-h cough frequency measurement at or just before initiation of anti-tuberculosis treatment. A group with latent Mycobacterium tuberculosis infection (LTBI) acted as controls. Rates of infection among household contacts of sputum smear-positive TB were measured using the interferon-gamma release assay and the tuberculin skin test, and compared with variables relating to the contacts themselves, and to the index case, including cough frequency. RESULTS: Daily cough frequency in TB patients (n = 44) was variable (geometric mean [GM] 174, interquartile range [IQR] 68-475 coughs/24 h), higher than in LTBI (n = 17; GM 19 coughs/24 h, IQR 8-53; P < 0.001), and higher during the day than overnight (GM 8.9 coughs/h, IQR 4.1-19.0 vs. GM 2.9 coughs/h, IQR 0.7-13.4; P < 0.0001). Also, 24-h cough frequency in TB was associated with sputum smear status (P = 0.040), but not smoking (P = 0.475). Multivariable logistic regression confirmed that infection in contacts was independently associated with index case sputum smear grade (P = 0.014) and cough frequency (P = 0.022). CONCLUSION: Measurement of 24-h cough frequency in pulmonary TB helps predict infectiousness and transmission patterns.

Nationwide study of patients with head and neck paragangliomas carrying SDHB germline mutations.

BACKGROUND: Germline mutations in the succinate dehydrogenase B (SDHB) gene predispose to hereditary paraganglioma (PGL) syndrome type 4. The aim of this study was to evaluate the clinical characteristics and outcome of treatment strategies for patients with head and neck paraganglioma (HNPGL) carrying SDHB germline mutations. METHODS: This was a retrospective evaluation of patients with HNPGL carrying SDHB germline mutations in the Netherlands. RESULTS: In a Dutch nationwide cohort study of SDHB germline mutation carriers, 54 patients with a total of 62 HNPGLs were identified. Forty-one of 54 patients (76 per cent) visited the outpatient clinic because of associated complaints. Eight patients (15 per cent) had multiple PGLs. One patient (2 per cent) developed a phaeochromocytoma and three (6 per cent) developed a malignant PGL. Twenty-seven patients (50 per cent) had an operation for their HNPGL and 15 (28 per cent) received radiotherapy. Three patients with HNPGL (6 per cent) were diagnosed with additional non-paraganglionic tumours. CONCLUSION: If an SDHB germline mutation is identified in a patient with HNPGL, the clinician should be aware of the variable manifestations of the SDHB-linked tumour syndrome, the risk of catecholamine excess, concurrent phaeochromocytoma, and association with non-paraganglionic tumours.

Further audiovestibular characterization of DFNB77, caused by deleterious variants in LOXHD1, and investigation into the involvement of Fuchs corneal dystrophy.

This study focuses on further characterization of the audiovestibular phenotype and on genotype-phenotype correlations of DFNB77, an autosomal recessive type of hearing impairment (HI). DFNB77 is associated with disease-causing variants in LOXHD1, and is genetically and phenotypically highly heterogeneous. Heterozygous deleterious missense variants in LOXHD1 have been associated with late-onset Fuchs corneal dystrophy (FCD). However, up to now screening for FCD of heterozygous carriers in DFNB77 families has not been reported. This study describes the genotype and audiovestibular phenotype of 9 families with DFNB77. In addition, carriers within the families were screened for FCD. Fifteen pathogenic missense and truncating variants were identified, of which 12 were novel. The hearing phenotype showed high inter- and intrafamilial variation in severity and progression. There was no evidence for involvement of the vestibular system. None of the carriers showed (pre-clinical) symptoms of FCD. Our findings expand the genotypic and phenotypic spectrum of DFNB77, but a clear correlation between the type or location of the variant and the severity or progression of HI could not be established. We hypothesize that environmental factors or genetic modifiers are responsible for phenotypic differences. No association was found between heterozygous LOXHD1 variants and the occurrence of FCD in carriers.

A meta-analysis on the surgical management of paraganglioma of the carotid body per Shamblin class.

OBJECTIVE: The aim of this study was to evaluate the risk associated with different types of surgery for carotid body paraganglioma of different Shamblin class. A meta-analysis was conducted to evaluate per tumour class, the local control, cranial nerve damage and complication rates of different techniques using internal carotid artery (ICA) and external carotid artery (ECA) ligation, clamping or bypassing, as well as the craniocaudal vs caudocranial techniques. DESIGN: A meta-analysis is conducted after a systematic search in PubMed and the Cochrane library, in accordance with the PRISMA guidelines. MAIN OUTCOME MEASURES: Local control, cranial nerve damage, complications, function recovery. RESULTS: Out of 3565 articles, 27 were selected. The overall quality of evidence of studies was low. Cranial nerve damage (3%, 17% and 39%) and complication rates (0%, 1% and 10%) were significantly related to Shamblin class (class 1, 2 and 3, respectively, P < .01). For class 3 tumours, an increased risk of complications was found associated with routine ICA manipulation/reconstruction (RR 3.12 with a 95% CI of 1.29-7.59), as well as a trend towards enhanced risk of routine ECA ligation (RR 3.48 with a 95% CI of 0.88-13.81). CONCLUSIONS: For class 1 and 2 tumours, surgery seems a viable treatment option. For class 3 tumours, morbidity in terms of cranial nerve deficit and complications is considerable; particularly, the use of ICA manipulation/reconstruction and potentially ECA ligation seem to be accompanied by high stroke incidence.

Psychological impact of a genetic diagnosis on hearing impairment-An exploratory study.

OBJECTIVE: Genetic testing for hereditary hearing impairment has become more routinely available as a diagnostic tool in the outpatient clinic. However, little is known about the psychological impact of a genetic diagnosis. To evaluate this impact, an exploratory study was conducted. DESIGN: Prospectively, 48 individuals who underwent genetic testing for hereditary hearing impairment were included in this study. Study participants were asked to fill out the following questionnaires: Hospital Anxiety Depression Scale, Impact of Event Scale, Self-Efficacy 24, Illness Cognition Questionnaire and the Inventory for Social Reliance. Questionnaires were filled out on three occasions: before genetic testing, directly after counselling on either positive or negative test results, and six weeks thereafter. RESULTS: No significant differences were found between the group that received a genetic diagnosis for their hearing impairment and the group that did not. CONCLUSION: This study did not demonstrate differences between receiving a genetic diagnosis or not; however, special attention to psychological well-being should be offered to hearing-impaired patients who seek a genetic diagnosis for their hearing impairment. Additionally, the psychological impact of sensorineural hearing impairment might be greater than the impact of a genetic diagnosis itself. Based on the current exploratory study, there are no psychological reasons in favour of or against genetic testing for hereditary hearing impairment.

Potential savings in the diagnosis of vestibular schwannoma.

INTRODUCTION: Magnetic resonance imaging (MRI) is used to screen patients at risk for vestibular schwannoma (VS). These MRIs are costly and have an extremely low yield; only 3% of patients in the screening population has an actual VS. It might be worthwhile to develop a test to predict VS and refer only a subset of all patients for MRI. OBJECTIVE: To examine the potential savings of such a hypothetical diagnostic test before MRI. DESIGN: We built a decision analytical model of the diagnostic strategy of VS. Input was derived from literature and key opinion leaders. The current strategy was compared to hypothetical new strategies, assigning MRI to the following: (i) all patients with pathology, (ii) all patients with important pathology and (iii) only patients with VS. This resulted in potential cost savings for each strategy. We conducted a budget impact analysis to predict nationwide savings for the Netherlands and the United Kingdom (UK), and a probabilistic sensitivity analysis to address uncertainty. RESULTS: Mean savings ranged from €256 (95%CI €250 - €262) or approximately US$284 (95%CI US$277 - US$291) per patient for strategy 1 to €293 (95%CI €290 - €296) or approximately US$325 (95%CI US$322 - US$328) per patient for strategy 3. Future diagnostic strategies can cost up to these amounts per patient and still be cost saving. Annually, for the Netherlands, €2.8 to €3.2 million could be saved and €10.8 to €12.3 million for the UK. CONCLUSIONS: The model shows that substantial savings could be generated if it is possible to further optimise the diagnosis of VS.

Results of a systematic literature review of treatment modalities for jugulotympanic paraganglioma, stratified per Fisch class.

OBJECTIVE: Key for successful jugulotympanic paraganglioma management is a personalised approach aiming for the best practice for each individual patient. To this end, a systematic review is performed, evaluating the local control and complication rates for the different treatment modalities stratified by the broadly accepted Fisch classification. DESIGN: A systematic literature review according to the PRISMA statement was performed. A detailed overview of individual treatment outcomes per Fisch class is provided. MAIN OUTCOME MEASURES: Local control, cranial nerve damage, complications, function recovery. RESULTS: Eighteen studies were selected, resembling 83 patients treated with radiotherapy and 299 with surgery. Excellent local control was found post-surgery for class A and B tumours, and risk of cranial nerve damage was <1%. For class C1-4 tumours, local control was 80%-95% post-surgery (84% post-radiotherapy), and cranial nerve damage was found in 71%-76% (none post-radiotherapy; P < .05). There was no difference in treatment outcomes between tumours of different C class. For class C1-4De/Di tumours, local control was 38%-86% (98% post-radiotherapy; P < .05) and cranial nerve damage/complication rates were 67%-100% (3% post-radiotherapy; P < .05). C1-4DeDi tumours showed lesser local control and cranial nerve damage rates when compared to C1-4De tumours. CONCLUSIONS: An individual risk is constituted for surgery and radiotherapy, stratified per Fisch class. For class A and B tumours, surgery is a suitable treatment option. For class C and D tumours, radiotherapy results in lower complication rates and similar or better local control rates when compared to the surgical group.

Diagnostic accuracy of high-resolution T2-weighted MRI vs contrast-enhanced T1-weighted MRI to screen for cerebellopontine angle lesions in symptomatic patients.

OBJECTIVE: To evaluate diagnostic accuracy of high-resolution T2-weighted MRI (T2w) for detecting cerebellopontine angle (CPA) lesions compared to a combined protocol including gadolinium enhanced T1-weighted MRI (GdT1w). SETTING: Department of Radiology & Nuclear Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands. PARTICIPANTS: A random sample of MRIs from 350 patients (700 CPAs) with asymmetrical audiovestibular complaints was used, acquired between 2013 and 2016. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative predictive values of T2w results compared to GdT1w and, in patients with any suggestion of CPA pathology, to the complete examination (T1w, GdT1w and T2w). Inter-rater agreement between an experienced neuroradiologist and a less experienced observer was calculated. RESULTS: Results of 678 CPAs in 340 patients were analysed. On T2w, the neuroradiologist identified all 27 lesions >2 mm in size out of a total of 30 CPA lesions (sensitivity: 90% [95% CI: 73.5%-97.9%]). Negative predictive value reached 99.5% (95% CI: 98.7-99.9). One missed lesion of 2 mm would have been detected in clinical practice, as this was one of 14 patients for which additional GdT1w would have been ordered based on T2w alone, increasing sensitivity to 93% (95% CI: 77.9%-99.2%) and negative predictive value to 99.7% (95% CI: 98.9%-100%). Inter-rater agreement for T2w was 98% (95% CI: 96.4-98.8). CONCLUSION: T2w has a very high diagnostic accuracy for the presence of CPA lesions in patients with asymmetrical audiovestibular complaints. However, in a screening protocol with T2w only, smallest vestibular schwannomas as well as rare differential diagnoses that probably only would be detected on GdT1w may remain unnoticed.

The penetrance of paraganglioma and pheochromocytoma in SDHB germline mutation carriers.

Germline mutations in succinate dehydrogenase B (SDHB) predispose to hereditary paraganglioma (PGL) syndrome type 4. The risk of developing PGL or pheochromocytoma (PHEO) in SDHB mutation carriers is subject of recent debate. In the present nationwide cohort study of SDHB mutation carriers identified by the clinical genetics centers of the Netherlands, we have calculated the penetrance of SDHB associated tumors using a novel maximum likelihood estimator. This estimator addresses ascertainment bias and missing data on pedigree size and structure. A total of 195 SDHB mutation carriers were included, carrying 27 different SDHB mutations. The 2 most prevalent SDHB mutations were Dutch founder mutations: a deletion in exon 3 (31% of mutation carriers) and the c.423+1G>A mutation (24% of mutation carriers). One hundred and twelve carriers (57%) displayed no physical, radiological or biochemical evidence of PGL or PHEO. Fifty-four patients had a head and neck PGL (28%), 4 patients had a PHEO (2%), 26 patients an extra-adrenal PGL (13%). The overall penetrance of SDHB mutations is estimated to be 21% at age 50 and 42% at age 70 when adequately corrected for ascertainment. These estimates are lower than previously reported penetrance estimates of SDHB-linked cohorts. Similar disease risks are found for different SDHB germline mutations as well as for male and female SDHB mutation carriers.

Tuberculosis and latent tuberculous infection screening of migrants in Europe: comparative analysis of policies, surveillance systems and results.

Migration patterns into and within Europe have changed over the last decade. In 2015, European Union (EU) countries received over 1.2 million asylum requests, more than double the number registered in the previous year. This review compares the published literature on policies for tuberculosis (TB) and latent tuberculous infection (LTBI) screening in EU and European Free Trade Association (EFTA) countries with the existing TB/LTBI screening programmes for migrants in 11 EU/EFTA countries based on a survey of policy and surveillance systems. In addition, we provide a systematic review of the literature on the yield of screening migrants for active TB and LTBI in Europe. Published studies provide limited information about screening coverage and the yield of screening evaluations in EU/EFTA countries. Furthermore, countries use different screening strategies and settings, and different definitions for coverage and yield of screening for active TB and LTBI. We recommend harmonising case definitions, reporting standards and policies for TB/LTBI screening. To achieve TB elimination targets, a European platform for multi-country data collection and analysis, sharing of countries' policies and practices, and harmonisation of migrant screening strategies is needed.