[Cutaneous squamous cell carcinomas in EBDR: how can they be detected?] / Carcinomes épidermoïdes cutanés au cours de l'EBDR : comment les dépister ?

The occurrence of cutaneous squamous cell carcinoma is a frequent and potentially serious complication in people with recessive dystrophic epidermolysis bullosa and junctional epidermolysis bullosa with chronic leg sores. Early diagnosis of early-stage carcinomas enables limited surgical excision and rapid healing without sequelae. Screening during skin care of patients at risk is therefore of major interest, and any atypical lesion should be shown to a doctor specializing in the disease and biopsied at the slightest doubt, preferably in an expert center for the disease.

[Pulmonary phenotypes of inborn errors of metabolism]. / Manifestations pulmonaires des maladies héréditaires du métabolisme.

Inborn metabolic diseases or inborn errors of metabolism comprise a large number of rare and heterogeneous genetic diseases categorized in several subgroups depending on their pathophysiologic mechanisms. In this review, we focus on different metabolic diseases with respiratory symptoms in adults: lysosomal glycosphingolipidoses such as acid sphingomyelinase deficiency (Niemann-Pick types A and B disease), Gaucher, Fabry, Pompe diseases and mucopolysaccharidoses in general. We also address classical homocystinuria, which is a monogenic vascular disease, Hermansky-Pudlak syndrome, which is associated with disorders in the lysosomal-related-organelles, and lysinuric protein intolerance, which is due to an amino-acid transporter defect. Presentation and prognosis of these diseases are highly heterogeneous, and respiratory impairment may be central and prognostic. Many are primarily pediatric, and diagnoses are often delivered during childhood. Improved pediatric management has enabled better prognosis and new phenotype of the diseases in the adulthood. Some others can be diagnosed during adulthood. While some diseases call for specific, specialized treatment, all necessitate systematic multidisciplinary management. It is of paramount importance that a pneumologist be familiar with these phenotypes, most of which can benefit from early diagnosis and early therapeutic management with dedicated innovative treatments.

[Impact of an early diagnosis program for childhood cancer in Abidjan?] / Impact d'un programme de diagnostic précoce des cancers de l'enfant à Abidjan ?

INTRODUCTION: To promote the early diagnosis of pediatric cancers in Ivory Coast, we have initiated a program to train local physicians in the warning signs and to raise public awareness. The aim of this work was to compare the times, stages and survival of patients before and three years after the initiation of the program. METHODS: This retrospective study involved children 0-17 years of age admitted from January to December 2014 and from May 2018 to April 2019. The Mann-Whitney non-parametric test and the Fisher's exact test were used to compare time limits, stages and survival. RESULTS: One hundred and fifty-nine doctors were trained and 1020 people were sensitized. The median age of the 216 children included was 7 years, sex ratio 1.4. For both periods, the median consultation times were 75 and 30 days (P=0.003) and the median diagnostic times were 120 and 105 days (P=0.033). High-risk lymphomas accounted for 60.5% and 58.5% (P=0.99) respectively and nephroblastoma 46.1% and 56.2% (P=0.51). The overall survival was 31% and 30.2% (P=0.92). DISCUSSION: The early diagnosis program had no impact. The diagnosis times and the proportion of cancer classified as high risk are comparable to the data reported in sub-Saharan Africa, which vary respectively from 7 to 15.8 weeks and from 60 to 71%. This program must be intensified, extended to all health workers and include improving access to care.

The potential for quality assurance systems to save costs and lives: the case of early infant diagnosis of HIV.

OBJECTIVES: Scaling up of point-of-care testing (POCT) for early infant diagnosis of HIV (EID) could reduce the large gap in infant testing. However, suboptimal POCT EID could have limited impact and potentially high avoidable costs. This study models the cost-effectiveness of a quality assurance system to address testing performance and screening interruptions, due to, for example, supply stockouts, in Kenya, Senegal, South Africa, Uganda and Zimbabwe, with varying HIV epidemics and different health systems. METHODS: We modelled a quality assurance system-raised EID quality from suboptimal levels: that is, from misdiagnosis rates of 5%, 10% and 20% and EID testing interruptions in months, to uninterrupted optimal performance (98.5% sensitivity, 99.9% specificity). For each country, we estimated the 1-year impact and cost-effectiveness (US$/DALY averted) of improved scenarios in averting missed HIV infections and unneeded HIV treatment costs for false-positive diagnoses. RESULTS: The modelled 1-year costs of a national POCT quality assurance system range from US$ 69 359 in South Africa to US$ 334 341 in Zimbabwe. At the country level, quality assurance systems could potentially avert between 36 and 711 missed infections (i.e. false negatives) per year and unneeded treatment costs between US$ 5808 and US$ 739 030. CONCLUSIONS: The model estimates adding effective quality assurance systems are cost-saving in four of the five countries within the first year. Starting EQA requires an initial investment but will provide a positive return on investment within five years by averting the costs of misdiagnoses and would be even more efficient if implemented across multiple applications of POCT.

OBJECTIFS: L'intensification du dépistage au point des soins (DPS) pour le diagnostic précoce du VIH chez le nourrisson (DPVN) pourrait réduire le grand écart dans le dépistage des nourrissons. Cependant, un DPVN DPS sous-optimal pourrait avoir un impact limité et des coûts évitables potentiellement élevés. Cette étude modélise la rentabilité d'un système d'assurance qualité pour traiter les performances des tests et les interruptions de dépistage, dues par exemple à des ruptures de stock, au Kenya, au Sénégal, en Afrique du Sud, en Ouganda et au Zimbabwe, avec des épidémies variables du VIH et des systèmes de santé différents. MÉTHODES: Nous avons modélisé une qualité de DPVN soulevée par le système d'assurance qualité à partir de niveaux sous-optimaux: c'est-à-dire des taux d'erreurs de diagnostic de 5%, 10% et 20% et des interruptions des tests de DPVN en mois, à des performances optimales ininterrompues (sensibilité de 98,5%, spécificité de 99,9%). Pour chaque pays, nous avons estimé l'impact sur un an et la rentabilité (en USD/DALY évitée) de scénarios améliorés pour éviter les infections à VIH manquées et les coûts inutiles de traitement du VIH pour les diagnostics faux positifs. RÉSULTATS: Les coûts modélisés sur un an d'un système national d'assurance qualité DPS vont de 69.359 USD en Afrique du Sud à 334.341 USD au Zimbabwe. Au niveau des pays, les systèmes d'assurance de la qualité pourraient potentiellement éviter entre 36 et 711 infections manquées (c'est-à-dire des faux négatifs) par an et des coûts de traitement inutiles entre 5.808 et 739.030 USD. CONCLUSIONS: Le modèle estime que l'ajout de systèmes d'assurance qualité efficaces permet de réaliser des économies dans quatre des cinq pays au cours de la première année. Le lancement de l'assurance qualité nécessite un investissement initial, mais fournira un retour sur investissement positif dans les cinq ans en évitant les coûts des diagnostics erronés et serait encore plus efficace s'il était mis en œuvre dans plusieurs applications de DPS.

[Pack-years threshold and HAS self-questionnaire for COPD early diagnosis]. / Seuil de paquets-années et auto-questionnaire HAS pour la recherche de bronchopneumopathie chronique obstructive.

INTRODUCTION: The Haute Autorité de santé (HAS) in France offers a patient self-questionnaire to optimize targeted chronic obstructive pulmonary disease (COPD) screening among at-risk patients in primary care. It includes smoking but does not have a threshold for pack-years (PY) smoked. The objective of this study was to compare the positive predictive values (PPV) of the HAS self-questionnaire alone and with the addition of a PY threshold. METHODS: This was a prospective pilot study conducted in a multi-professional health centre. Identification among smoking or former smoking patients without a COPD diagnosis of subjects with a positive HAS self-questionnaire, a positive PY threshold, or both. We performed spirometry after bronchodilatation. RESULTS: Thirty-five people were included in the study. All 35 had a positive PY threshold. The HAS questionnaire was positive for 22 of them (62.9%). Spirometry diagnosed 18 participants with COPD (51%). The PPV for the HAS questionnaire was 0.41 and the PPV for the HAS+PY questionnaire was 0.51. There was no statistically significant difference between these two PPVs (P=0.3692). CONCLUSIONS: The addition of a PY threshold to the HAS self-questionnaire may allow better targeting of the population at risk of developing COPD.

[At-risk drinking screening by general practitioners: A survey of patients in primary care]. / Repérage de la consommation d'alcool à risque par les médecins généralistes : enquête auprès de patients en soins premiers.

BACKGROUND: The screening of patients who are at-risk drinkers, which means exceeding the thresholds defined by health authorities or associated with a specific situation (taking psychotropic drugs, having an organic pathology, driving a vehicle, drinking during pregnancy), represents a major issue in primary care. Few studies have offered perspective from the patients' standpoint. The main purpose of this study was to describe general practitioners at-risk drinking screening from their patients point of view. The secondary objective was to identify the factors associated with perception of satisfactory general practitioner knowledge about alcohol consumption. METHODS: A quantitative cross-sectional study was launched in 9 general practitioner offices over 6 months. Patients older than 18 were recruited to answer a questionnaire blinded from their general practitioner, indicating the level of their alcohol consumption and their perception regarding their general practitioner's screening methods. Descriptive, univariate and multivariate logistic regression analyses were performed. RESULTS: All in all, 445 patients were analyzed. Sixty-two at-risk drinkers were screened (13.9 %). Most of the patients declared they had not been interviewed about their alcohol consumption by their general practitioner either during initial consultations (86.1 %) or over time (83.3 %). Only 4.2 % of patients had previously initiated discussion about their consumption. Patients were not ashamed to talk about alcohol (99.2 %) and found their general practitioner to be competent on this topic (100 %). In multivariate analysis, independent factors associated with a good general practitioner knowledge about their patients' current consumption were the questions put forward by their general practitioner about alcohol consumption during their first visit (P<0.001) and during subsequent visits (P<0.001). CONCLUSION: This study showed a low general practitioner screening rate of their patients' at-risk drinking. Only a minority of patients, including at-risk drinkers, declared that their general practitioner was aware of their level of alcohol consumption. Screening could be improved by being systematized during initial consultations and regularly scheduled during subsequent visits, especially in at-risk situations.

[Assessment of mental states at risk of psychotic transition in a sample of young male prisoners in Tunisia]. / Évaluation des états mentaux à risque de transition psychotique dans un échantillon de jeunes détenus de sexe masculin en Tunisie.

BACKGROUND: Prevalence of psychotic disorders in a prison population is higher than in the general population. Recent research has shown that early intervention is feasible in prison settings, and that approximately 5% of screened prisoners have met ultra-high-risk (UHR) for psychosis criteria. We aimed to identify the prevalence of the UHR states for developing psychosis in a group of newly incarcerated men in the Jendouba Civil Prison and to analyze the association between UHR states and socio-demographic data and substance use. METHOD: We carried-out a cross-sectional study among 120 prisoners. Every prisoner was interviewed using the Comprehensive Assessment of At-Risk Mental States (CAARMS). The Social and Occupational Functioning Assessment Scale (SOFAS) was used to assess the participant's level of functioning. RESULTS: We found a prevalence of subjects meeting the UHR criteria of 21.3%. UHR subjects had significantly more psychiatric family history (P=0.035), personal history of suicide attempt(s) (0.035) and self-injury (P=0.013) compared to non-UHR subjects. Clinical self-evaluation found significantly more depression and anxiety in the UHR group (P=0.020 and P=0.035, respectively). In addition, social and occupational functioning was significantly more impaired in the UHR group (P=0.007). UHR subjects used significantly more cannabis in lifetime (P=0.015) as well as in the past year (P=0.022) and had a significantly higher frequency of cannabis use (P=0.01) compared to non-UHRs. CONCLUSION: Prison mental health teams face the challenge of identifying prisoners who need mental health services and providing early care to this vulnerable group; this challenge may offer a unique opportunity for intervention among a population that might not otherwise have had access to it.

Prospective study comparing the conventional and same-day strategies to diagnose pulmonary tuberculosis.

OBJECTIVE: The WHO recommends same-day sputum smear microscopy for the diagnosis of smear-positive tuberculosis (TB) in countries with high TB burden for earlier diagnosis and treatment, a cornerstone to prevent air-borne transmission. We aimed to compare the conventional strategy (sputum collection on three consecutive days) and the same-day strategy (hour h, h+1, h+2) in France, a country with low TB burden. PATIENTS AND METHODS: Over a six-month period, all adult individuals presenting with presumptive smear-positive TB were eligible for the study, registered in https://clinicaltrials.gov/ ID (NCT02961569). Sputum specimens were collected three times the first day, then once on the second day and once on the third day. The concordance between the two strategies regarding smears and cultures were assessed. RESULTS: Of the 131 eligible individuals, 34 were given a TB treatment. Smears from hour h, h+1, h+2, day two and three were negative in 19 of these 34 patients. Positive smears were obtained in 15, 14, 15, 14, and 14 patients at hour h, h+1, h+2, on day two and three, respectively. Concordance regarding smear or culture was good, with Kappa 0.69 and 0.64, respectively. CONCLUSION: The same-day strategy seems to be a good alternative to the conventional strategy.

[The role of electromagnetic navigation bronchoscopy in the diagnosis of peripheral pulmonary lesions]. / Place de la navigation électromagnétique endobronchique pour le diagnostic de lésions pulmonaires périphériques.

INTRODUCTION: Electromagnetic navigation bronchoscopy (ENB) is a recent, minimally invasive procedure utilized to guide endoscopic diagnostic tools to peripheral pulmonary nodules. The place of this technology among other diagnostic procedures remains uncertain. METHOD: We analyzed our 30 first months of ENB used in the diagnosis of 106 lesions in 101 patients, from June 2016 to December 2018. Follow-up and final diagnosis was completed for 95 lesions (90%). RESULTS: ENB was performed for 3.5% of all patients referred for abnormal findings on pulmonary imaging, and represented 19% of second line procedures for peripheral pulmonary lesions. Procedures were performed under general anesthesia, with a mean duration of 35min. The sensitivity of ENB was 64% (95%CI: 52-74%) for lesions with a mean diameter of 21mm, with an improvement over time (sensitivity 69% in the last 18 months). The presence of a bronchus within the lesion (bronchus sign) was associated with an increased sensitivity of 74%. Pneumothorax occurred in 5 patients (5%) of which 4 required drainage. There was no hemoptysis, and no death related to the procedure. CONCLUSION: ENB is a minimally invasive procedure reaching acceptable sensitivity in the most difficult patients. ENB can be recommended for the diagnosis of peripheral pulmonary nodules when no other procedure is successful or possible. Its use as a first choice procedure is, for the moment, limited by the cost, but must be weighed against that of non-diagnostic procedures, and the cost of complications of trans-thoracic lung biopsies.

Accuracy of peripapillary versus macular vessel density in diagnosis of early to advanced primary open angle glaucoma.

PURPOSE: To evaluate macular and peripapillary vessel density (mVD, pVD) using optical coherence tomography angiography (OCT-A) in healthy subjects, patients with ocular hypertension (OHT) and primary open-angle glaucoma (POAG) patients. METHODS: In this prospective observational study, OCT-A images were obtained from 60 eyes of 36 healthy, ocular hypertension (OHT), preperimetric glaucoma (PPG), early glaucoma (EG) and moderate and advanced POAG subjects. Superficial mVD was acquired over a 6×6-mm cube centered on the foveal avascular zone and pVD over a 4.5×4.5-mm cube centered on the optic disc. Peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell complex (GCC) thickness was calculated using spectral-domain OCT. Correlations between vascular, structural and Humphrey VF indices were evaluated (Spearman's rank correlation coefficient). RESULTS: Median pVD and mVD in the PPG eyes were lower than in healthy eyes (51.87% and 47.23% versus 55.70% and 53.61%, respectively; P<0.001 and P=0.003), but higher than in mild glaucoma eyes (46.21% and 41.98%, P<0.001 compared to normal eyes) and moderate to advanced glaucoma eyes (37.45% and 39.89%, P<0.0001 compared to normal eyes). The highest correlations were found between structural parameters and pVD (r=0.87 and 0.86 for pRNFL and GCC, P<0.0001), followed by mVD (r=0.69 for both pRNFL and GCC, P<0.0001). Correlations with mean VF sensitivity were similar for pVD and mVD (r=0.61 and 0.56) and for GCC and pRNFL (r=0.60 and 0.52, P<0.0001 for all). CONCLUSIONS: VD measured with OCT-A shows reduction in POAG. Detection of this damage differentiates PPG from normal and perimetric POAG eyes with a high correlation with structural parameters. Peripapillary VD accuracy is higher than mVD in detecting the disease. These results suggest that OCT-A could improve POAG diagnosis and understanding of the pathophysiologic mechanisms behind glaucoma.

[Study of the feasibility of spirometry in general practice]. / Étude de faisabilité de la spirométrie en médecine générale.

COPD is common but is under-diagnosed by general practitioners (GP). GP have a major role in the early diagnosis of this disease. GP could have access to spirometry. The aim of this study was to evaluate the quality and interpretation of spirometry performed by primary care residents following a short education session. Three residents were trained in spirometry for half a day. They then performed spirometry on all smokers over the age of 35 visiting five general practices. The results were reviewed blindly by an independent specialist pulmonologist to assess their quality and interpretation. Among 184 eligible patients, 89% agreed to participate and 66% (n=107) came for the second appointment. The pulmonologist evaluated the quality of spirometry as good in 72% of cases, of suboptimal but acceptable quality in 20% and of poor quality in 8%. Interpretation was accurate in 91% of tests. The Kappa concordance coefficient between GPs and the expert was 0.93. Airflow obstruction was detected in 17.5% of the screened subjects. The average time for a consultation with spirometry was 19minutes. The consultation dedicated to spirometry was well accepted by patients. A short training has to be structured to allow GPs to perform and interpret spirometry properly. This work needs to be extended to better assess reproducibility in cases of abnormal spirometry.

Atrial fibrillation: Neurogenic or myogenic?

A 55-year-old hypertensive patient presents atrial fibrillation after vasovagal syncope. Non-invasive cardiac workup is normal. Without antiarrhythmic therapy, the patient has no recurrence for the next 3years, then presents with a stroke. Echocardiography eventually reveals left atrial dilation. This sequence of events illustrates the well-known links between age, arterial hypertension, atrial fibrillation, atrial neuromyopathy and stroke. A frequently neglected common denominator in this equation is impaired sympathovagal balance. Contrary to what is often stated, autonomic imbalance is not a simple modulation factor of atrial fibrillation; both the trigger and the substrate of atrial fibrillation can be influenced by abnormal cardiac innervation. Here, we review the neurogenic theory of atrial fibrillation, based on literature and original data. We also provide evidence that this concept may help to improve atrial fibrillation prediction, early diagnosis and therapy.

Uptake and performance of prevention of mother-to-child transmission and early infant diagnosis in pregnant HIV-infected women and their exposed infants at seven health centres in Addis Ababa, Ethiopia.

OBJECTIVE: To assess the uptake of WHO-recommended PMTCT procedures in Ethiopia's health services. METHODS: Prospective observational study of HIV-positive pregnant mothers and their newborns attending PMTCT services at seven health centres in Addis Ababa. Women were recruited during antenatal care and followed up with their newborns at delivery, Day 6 and Week 6 post-partum. Retention to PMCTC procedures, self-reported antiretroviral treatment (ART) adherence and HIV infant outcome were assessed. Turnaround times of HIV early infant diagnosis (EID) procedures were extracted from health registers. RESULTS: Of 494 women enrolled, 4.9% did not complete PMTCT procedures due to active denial or loss to follow-up. HIV was first diagnosed in 223 (45.1%) and ART initiated in 321 (65.0%) women during pregnancy. ART was initiated in a median of 1.3 weeks (IQR 0-4.3) after HIV diagnosis. Poor self-reported treatment adherence was higher post-partum than during pregnancy (12.5% vs. 7.0%, P = 0.002) and significantly associated with divorced/separated marital status (RR 2.2, 95% CI 1.3-3.8), low family income (RR 2.1, 95% CI 1.1-4.1), low CD4 count (RR 1.7, 95% CI 1.0-3.0) and ART initiation during delivery (RR 2.5, 95% CI 1.1-5.6). Of 435 infants born alive, 98.6% received nevirapine prophylaxis. The mother-to-child HIV transmission rate was 0.7% after a median of 6.7 weeks (IQR 6.4-10.4), but EID results were received for only 46.6% within 3 months of birth. CONCLUSION: High retention in PMTCT services, triple maternal ART and high infant nevirapine prophylaxis coverage were associated with low mother-to-child HIV transmission. Declining post-partum ART adherence and challenges of EID linkage require attention.

Reduction in symptomatic malaria prevalence through proactive community treatment in rural Senegal.

OBJECTIVES: We piloted a community-based proactive malaria case detection model in rural Senegal to evaluate whether this model can increase testing and treatment and reduce prevalence of symptomatic malaria in target communities. METHODS: Home care providers conducted weekly sweeps of every household in their village throughout the transmission season to identify patients with symptoms of malaria, perform rapid diagnostic tests (RDT) on symptomatic patients and provide treatment for positive cases. The model was implemented in 15 villages from July to November 2013, the high transmission season. Fifteen comparison villages were chosen from those implementing Senegal's original, passive model of community case management of malaria. Three sweeps were conducted in the comparison villages to compare prevalence of symptomatic malaria using difference in differences analysis. RESULTS: At baseline, prevalence of symptomatic malaria confirmed by RDT for all symptomatic individuals found during sweeps was similar in both sets of villages (P = 0.79). At end line, prevalence was 16 times higher in the comparison villages than in the intervention villages (P = 0.003). Adjusting for potential confounders, the intervention was associated with a 30-fold reduction in odds of symptomatic malaria in the intervention villages (AOR = 0.033; 95% CI: 0.017, 0.065). Treatment seeking also increased in the intervention villages, with 57% of consultations by home care providers conducted between sweeps through routine community case management. CONCLUSIONS: This pilot study suggests that community-based proactive case detection reduces symptomatic malaria prevalence, likely through more timely case management and improved care seeking behaviour. A randomised controlled trial is needed to further evaluate the impact of this model.

[Assessment of mental states at risk of psychotic transition: validation of the French version of the CAARMS]. / Évaluation des états mentaux à risque de transition psychotique: validation de la version française de la CAARMS.

This article aims to present the validation study of the French version of the Comprehensive Assessment of at risk mental states (CAARMS), an interview that seeks to determine whether young adults criteria for at-risk (AR) mental states, or psychosis. We assessed 40 young subjects, 15 were considered as "prodromal" (Prd) and 10 as experiencing a first episode of psychosis (PEP) by our expert clinician at the center - centre d'évaluation des jeunes adultes et adolescents, University Hospital Centre, Paris - and 15 were healthy controls matched for age and sex. When assessed with the CAARMS, 73 % (n=11) of the prodromal subjects reached the criteria for AR mental state, four subjects did not reach the criteria for AR, nor psychosis (P) and 100 % of the PEP reached the criteria for P. The three groups were significantly different on CAARMS total score (P<0.001) and subscores ; Prd subjects had intermediate scores between PEP (P<0.001) and controls (P<0.001) scores, PEP showing the highest scores. Post-hoc analysis showed that Prd significantly differed from Controls on each subscale (P<0.001) and that Prd differed from PEP on the "positive symptoms" subscale (P<0.001), as well as on "behavioural change" (P=0.021), owing to difference on the item "impaired role function". We used the brief psychiatric rating scale 24 items with anchor (BPRS24-EA) in addition to with the CAARMS, the AR group showed intermediate scores between controls and P subjects. Total scores of both scales were correlated (r=0.408 ; P=0.043) and the BPRS24-EA "positive symptoms" score was correlated with CAARMS' scores on the "Positive symptoms" subscale (r=0.456, P=0.022), "emotional disturbance" (r=0.506, P=0.01), and "behavioural change" (r=0.666 P=0.001). We found no correlation between BPRS negative and depression subscales and any of the CAARMS' subscales. When looking at its reliability, reliability coefficients (Cronbach's alpha) showed excellent reliability for "positive symptoms", "emotional disturbance", "behavioural change" and "general psychopathology" (respectively r=0.82, 0.75, 0.78, 0.84, 0.83) and moderate reliability for "cognitive change", "negative symptoms" and "motor/physical change" (respectively r=0.39, 0.59, 0.43). Overall, analysis of the results of construct validity, concurrent validity and reliability of the CAARMS indicates that the French version is valid and reliable. It is now available to develop and implement early detection programs in French speaking countries.

Early presentation of primary glioblastoma.

BACKGROUND: Clinical and neuroimaging findings of glioblastomas (GBM) at an early stage have rarely been described and those tumors are most probably under-diagnosed. Furthermore, their genetic alterations, to our knowledge, have never been previously reported. METHODS: We report the clinical as well as neuroimaging findings of four early cases of patients with GBM. RESULTS: In our series, early stage GBM occurred at a mean age of 57 years. All patients had seizures as their first symptom. In all early stages, MRI showed a hyperintense signal on T2-weighted sequences and an enhancement on GdE-T1WI sequences. A hyperintense signal on diffusion sequences with a low ADC value was also found. These early observed occurrences of GBM developed rapidly and presented the MRI characteristics of classic GBM within a few weeks. The GBM size was multiplied by 32 in one month. Immunohistochemical analysis indicated the de novo nature of these tumors, i.e. absence of mutant IDH1 R132H protein expression, which is a diagnostic marker of low-grade diffuse glioma and secondary GBM. CONCLUSIONS: A better knowledge of early GBM presentation would allow a more suitable management of the patients and may improve their prognosis.

CD4 count outperforms World Health Organization clinical algorithm for point-of-care HIV diagnosis among hospitalised HIV-exposed Malawian infants.

OBJECTIVE: To determine, for the WHO algorithm for point-of-care diagnosis of HIV infection, the agreement levels between paediatricians and non-physician clinicians, and to compare sensitivity and specificity profiles of the WHO algorithm and different CD4 thresholds against HIV PCR testing in hospitalised Malawian infants. METHODS: In 2011, hospitalised HIV-exposed infants <12 months in Lilongwe, Malawi, were evaluated independently with the WHO algorithm by both a paediatrician and clinical officer. Blood was collected for CD4 and molecular HIV testing (DNA or RNA PCR). Using molecular testing as the reference, sensitivity, specificity and positive predictive value (PPV) were determined for the WHO algorithm and CD4 count thresholds of 1500 and 2000 cells/mm(3) by paediatricians and clinical officers. RESULTS: We enrolled 166 infants (50% female, 34% <2 months, 37% HIV infected). Sensitivity was higher using CD4 thresholds (<1500, 80%; <2000, 95%) than with the algorithm (physicians, 57%; clinical officers, 71%). Specificity was comparable for CD4 thresholds (<1500, 68%, <2000, 50%) and the algorithm (paediatricians, 55%, clinical officers, 50%). The positive predictive values were slightly better using CD4 thresholds (<1500, 59%, <2000, 52%) than the algorithm (paediatricians, 43%, clinical officers 45%) at this prevalence. CONCLUSION: Performance by the WHO algorithm and CD4 thresholds resulted in many misclassifications. Point-of-care CD4 thresholds of <1500 cells/mm(3) or <2000 cells/mm(3) could identify more HIV-infected infants with fewer false positives than the algorithm. However, a point-of-care option with better performance characteristics is needed for accurate, timely HIV diagnosis.

Towards an earlier diagnosis of Alzheimer's disease presenting with visuospatial disorders (posterior cortical atrophy).

Progressive visual complaints related to visuospatial disorders, and less often to visuoperceptual disorders, may be the presenting and isolated manifestation of a focal degeneration in the posterior cortical areas, called posterior cortical atrophy (PCA). PCA is a clinical syndrome corresponding to a focal variant of Alzheimer's disease in 80% of cases. The predominant dysfunction in the occipitoparietal pathways results in predominant visuospatial disorders, manifesting primarily as dorsal simultanagnosia, alone or associated with other symptoms of Balint's syndrome. PCA is rare and affects young patients who are fully aware of their deficits. Diagnosis of PCA is often delayed, due to insidious onset and development of symptoms, and to poor awareness of the condition in the medical community. An earlier diagnosis requires both better knowledge of PCA among ophthalmologists and neurologists and better recognition of visual complaints, leading to simple bedside tasks that can tackle the syndrome.