Targeting of 3D oral cancer spheroids by αVß6 integrin using near-infrared peptide-conjugated IRDye 680.

BACKGROUND: In the treatment of oral cavity cancer, margin status is one of the most critical prognostic factors. Positive margins are associated with higher local recurrence and lower survival rates. Therefore, the universal goal of oral surgical oncology is to achieve microscopically clear margins. Near-infrared fluorescence guided surgery (FGS) could improve surgical resection using fluorescent probes. αVß6 integrin has shown great potential for cancer targeting due to its overexpression in oral cancers. Red fluorescent contrast agent IRDye 680 coupled with anti-αVß6 peptide (IRDye-A20) represents an asset to improve FGS of oral cancer. This study investigates the potential of IRDye-A20 as a selective imaging agent in 3D three-dimensional tongue cancer cells. METHODS: αVß6 integrin expression was evaluated by RT-qPCR and Western Blotting in 2D HSC-3 human tongue cancer cells and MRC-5 human fibroblasts. Targeting ability of IRDye-A20 was studied in both cell lines by flow cytometry technique. 3D tumor spheroid models, homotypic (HSC-3) and stroma-enriched heterotypic (HSC-3/MRC-5) spheroids were produced by liquid overlay procedure and further characterized using (immuno)histological and fluorescence-based techniques. IRDye-A20 selectivity was evaluated in each type of spheroids and each cell population. RESULTS: αVß6 integrin was overexpressed in 2D HSC-3 cancer cells but not in MRC-5 fibroblasts and consistently, only HSC-3 were labelled with IRDye-A20. Round shaped spheroids with an average diameter of 400 µm were produced with a final ratio of 55%/45% between HSC-3 and MRC-5 cells, respectively. Immunofluorescence experiments demonstrated an uniform expression of αVß6 integrin in homotypic spheroid, while its expression was restricted to cancer cells only in heterotypic spheroid. In stroma-enriched 3D model, Cytokeratin 19 and E-cadherin were expressed only by cancer cells while vimentin and fibronectin were expressed by fibroblasts. Using flow cytometry, we demonstrated that IRDye-A20 labeled the whole homotypic spheroid, while in the heterotypic model all cancer cells were highly fluorescent, with a negligible fluorescence in fibroblasts. CONCLUSIONS: The present study demonstrated an efficient selective targeting of A20FMDV2-conjugated IRDye 680 in 3D tongue cancer cells stroma-enriched spheroids. Thus, IRDye-A20 could be a promising candidate for the future development of the fluorescence-guided surgery of oral cancers.

Remote assessment of ADHD in children and adolescents: recommendations from the European ADHD Guidelines Group following the clinical experience during the COVID-19 pandemic.

The COVID-19 pandemic led ADHD services to modify the clinical practice to reduce in-person contact as much as possible to minimise viral spread. This had far-reaching effects on day-to-day clinical practice as remote assessments were widely adopted. Despite the attenuation of the acute threat from COVID, many clinical services are retaining some remote practices. The lack of clear evidence-based guidance about the most appropriate way to conduct remote assessments meant that these changes were typically implemented in a localised, ad hoc, and un-coordinated way. Here, the European ADHD Guidelines Group (EAGG) discusses the strengths and weaknesses of remote assessment methods of children and adolescents with ADHD in a narrative review based on available data and expert opinions to highlight key recommendations for future studies and clinical practice. We conclude that going forward, despite remote working in clinical services functioning adequately during the pandemic, all required components of ADHD assessment should still be completed following national/international guidelines; however, the process may need adaptation. Social restrictions, including changes in education provision, can either mask or exacerbate features associated with ADHD and therefore assessment should carefully chart symptom profile and impairment prior to, as well as during an ongoing pandemic. While remote assessments are valuable in allowing clinical services to continue despite restrictions and may have benefits for routine care in the post-pandemic world, particular attention must be paid to those who may be at high risk but not be able to use/access remote technologies and prioritize these groups for conventional face-to-face assessments.

Long-term survival after head and neck cancer surgery with immediate free flap reconstruction.

BACKGROUND: Head and neck cancer is one of the most frequent cancers worldwide. A combination treatment including surgery is known to have a better survival rate than exclusive radiotherapy-chemotherapy. In extreme cases of non-metastatic patients who have voluminous tumor, or complex location, surgery with immediate reconstruction by free flap could be an option to improve long term survival. PURPOSE: To share experience of long-term survival of patients with head and neck cancer who underwent oncologic surgery with immediate free flap reconstruction, and to analyze influencing factors. METHODS: All consecutive patients treated with free flaps for reconstruction of extensive defects after resection of head and neck cancer in our center (Nancy, France) were retrieved from the hospital database. Data was recorded in a systematic way. Bivariate and multivariate Cox proportional hazards models were used for statistical analysis. RESULTS: Between 1997 and December 2007, 70 patients underwent surgical resection of head and neck tumor with free flap reconstruction. 11 patients were excluded because of missing data. Follow-up time was 7.4 years, IQR from 4.3 to 11.3. Overall survival was 53.8%, 95% CI [39.9%; 65.8%] at 5 years and 38.6% [24.8%; 52.3%] at 10 years. Age>60 years at the surgery HR 2,373 (1,143; 4,927) and TNM score 3-4 HR 2,524 (1,093; 5,828) were statistically associated to a lesser survival rate. CONCLUSION: The ability to successfully and safely perform free flaps increases treatment options for patients with advanced head and neck cancer in a selected population. it seems worthwhile to perform these microvascular reconstructions.

Children with developmental dyslexia showed greater sleep disturbances than controls, including problems initiating and maintaining sleep.

AIM: Although there have been frequent clinical reports about sleep disturbances in children with learning disabilities, no data are available about the prevalence of sleep disturbances in children with developmental dyslexia (DD). This study evaluated sleep disturbances in children with DD referred to a hospital clinic and compared their scores with healthy controls. METHODS: We consecutively enrolled 147 children (66% male) aged 10.26 ± 2.63 years who were referred by clinical paediatricians to the Clinic for Child and Adolescent Neuropsychiatry at the Second University of Naples with DD and 766 children without DD (60% male) aged 10.49 ± 2.39 years recruited from schools in the same urban area. Sleep disturbances were assessed with the Sleep Disturbances Scale for Children (SDSC), which was filled out by the children's main carers. RESULTS: Compared with the controls, the children with DD showed significantly higher rates of above threshold scores on the total SDSC score (p < 0.001) and on the subscales for disorders in initiating and maintaining sleep (p < 0.001), sleep breathing disorders (p < 0.001) and disorders of arousal (p < 0.001). CONCLUSION: Sleep disorders were significantly more frequent in children with DD than in healthy controls. A possible relationship between dyslexia and sleep disorders may have relevant clinical implications.

Detection of disseminated tumor cells in aspirative drains after neck dissection.

The dissemination of individual tumor cells is a common phenomenon in solid cancers. Detection of tumor cells in bone marrow disseminated tumor cells (DTC) and in peripheral blood circulating tumor cells (CTC) in nonmetastatic situation is of high prognostic significance. Compared to breast, colon and prostate cancers, the studies on CTC and DTC in head and neck cancers are sparse. The objective of our study was to detect DTC in drains after neck dissection. Fourteen patients undergoing surgery for stages III and IV head and neck cancers were enrolled in this study--twelve presenting with squamous cell carcinoma and two with adenocarcinoma. Redon drain analysis was performed by the Cellsearch method using immunomagnetic and fluorescence approaches. A positivity threshold value was set at 2DTC/7.5 ml of the sample. Tumor cells were detected in drains of 69 % of patients a few days after surgery. The range of quantification was 3-2,094 DTC/5 ml and we showed morphological differences between the two types of carcinoma cells. DTC were detected after neck dissection both in squamous cell carcinoma and in adenocarcinoma. Potential clinical significance of tumor cells needs to be further investigated as their presence could affect pre-surgical and post-operative treatments.

Value of the preservation of an osseous mandibular rim with a fibula free flap reconstruction.

BACKGROUND: Reconstruction of the mandible with microvascularized fibula transplants is actually a well-established procedure, yet the major component is the limited diameter of the diaphysis that can induce oral rehabilitation's failure, especially in dentate patients. In this paper, we report our surgical procedure allowing preservation of the mandibular height. The primary objective was to assess aesthetic and functional improvements of preservation of an osseous mandibular rim with a fibula free flap reconstruction. PATIENTS AND METHODS: Five patients (all males, mean age of 60 years) were treated with this method. Aetiologies were tumour in 3 cases, and osteoradionecrosis in the two others cases. We described all step of our surgical procedure and the functional, aesthetic and carcinologic results were evaluated. The follow up varies from 6 to 30 months. RESULTS: One patient died at 12 days from unrelated affection. For the other patients, both the aesthetics and functional outcomes were better than in case of mandibular interruption surgery. In fact, the mandibular contour of the mandibule was preserved and the height of mandible was restored. One patient is in progress of dental rehabilitation with osseous implants. Carcinologically, no local recurrence was observed. CONCLUSION: This technique is reliable and enables to optimize oral rehabilitation with endosteal implants. Nevertheless, we consider that the 3D scanner is essential before the intervention to evaluate the osseous reach. Moreover, if necessarily the procedure can be modified intraoperatively.

Effects of mindfulness-based interventions on symptoms and interoception in trauma-related disorders and exposure to traumatic events: Systematic review and meta-analysis.

Interoception is defined as the sense of the internal state of the body. Dysfunctions in interoception are found in several mental disorders, including trauma-related conditions. Mindfulness-Based Interventions (MBIs) have been shown to influence interoceptive processes. Randomised controlled trials (RCTs) have investigated whether MBIs impact symptoms and interoception in patients with trauma-related disorders. We undertook a systematic review and meta-analysis to synthesize these data. We included RCTs with an MBI arm which enrolled adult patients with trauma related-disorders or exposure to a traumatic experience, and addressed changes in interoception and trauma-related symptoms. A random-effects multivariate meta-analytic model was performed to quantify group differences in score change from baseline to follow-up. Twelve studies were included in the systematic review, and eleven in the meta-analysis. Overall, MBIs showed small to moderate positive effects on both interoception and symptoms. Despite a high heterogeneity in results, sensitivity analyses confirmed the robustness of the findings. We conclude that the efficacy of MBIs on trauma-related symptoms and interoception is supported by randomised evidence. However, further research is needed to understand whether changes in interoception might underpin the effectiveness of MBIs in trauma-related disorders.

The lifetime impact of attention deficit hyperactivity disorder: results from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC).

BACKGROUND: The aim of the study was to present nationally representative data on the lifetime independent association between attention deficit hyperactivity disorder (ADHD) and psychiatric co-morbidity, correlates, quality of life and treatment seeking in the USA. METHOD: Data were derived from a large national sample of the US population. Face-to-face surveys of more than 34 000 adults aged 18 years and older residing in households were conducted during the 2004-2005 period. Diagnoses of ADHD, Axis I and II disorders were based on the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV version. RESULTS: ADHD was associated independently of the effects of other psychiatric co-morbidity with increased risk of bipolar disorder, generalized anxiety disorder, post-traumatic stress disorder, specific phobia, and narcissistic, histrionic, borderline, antisocial and schizotypal personality disorders. A lifetime history of ADHD was also associated with increased risk of engaging in behaviors reflecting lack of planning and deficient inhibitory control, with high rates of adverse events, lower perceived health, social support and higher perceived stress. Fewer than half of individuals with ADHD had ever sought treatment, and about one-quarter had ever received medication. The average age of first treatment contact was 18.40 years. CONCLUSIONS: ADHD is common and associated with a broad range of psychiatric disorders, impulsive behaviors, greater number of traumas, lower quality of life, perceived social support and social functioning, even after adjusting for additional co-morbidity. When treatment is sought, it is often in late adolescence or early adulthood, suggesting the need to improve diagnosis and treatment of ADHD.

Psoas abscess due to Pasteurella multocida.

Psoas abscess is a pus collection within the muscle compartment. It is a very uncommon entity. It can be primary as a result of haematogenous spread or secondary as a consequence of a direct extension of an infectious focus. Diagnosis is usually delayed because nonspecific clinical presentation. Staphylococcus aureus is the most common organism cultured in this type of abscess. We describe a secondary psoas abscess in an elderly female patient. The patient presented with fever, right groin pain and malaise. Following laboratory, radiological and microbiological analyses the patient was diagnosed as having a psoas abscess due to Pasteurella multocida, which is a Gram negative bacteria, part of the normal oral flora of many animals and can causes human infections after animal scratches or bites. More rarely is to find this organism causing psoas abscesses. Because of insidious clinical presentation, the diagnosis of psoas abscess is a challenge and a high index of suspicion is required. We emphasize the importance of bacteriological confirmation of microorganism involved to choose the correct antibiotics. Percutaneous drainage is the treatment of choice. Open surgical drainage should be reserved if percutaneous drainage fails.

Combined transoral and suprahyoid approach for oropharyngeal cancers: an alternative to mandibulotomy.

UNLABELLED: Surgical treatment of oropharyngeal tumours usually requires mandibular osteotomy. Using this technique allows a better exposure and an easier excision, but this approach often generates complications. Since 1995, we used a less aggressive surgical technique, with a suprahyoid pharyngotomy when the oral approach was not sufficient, thus sparing the mandible. OBJECTIVE: The purpose of this study is to evaluate this technical evolution, ensuring that mandibular preservation doesn't affect quality of exeresis, local control and survival, while allowing a lower complication rate. MATERIAL AND METHODS: All patients who have had a surgical treatment for an oropharyngeal carcinoma between 1995 and 2001 in our center were included in this study. RESULTS: Mandibular sparing was used for 55 patients; 19 patients underwent mandibulotomy. The surgical procedure's quality was classified as clear, close, or insufficient margins. All adjuvant treatments were noted, functional and carcinologic results were evaluated. No significant differences are found for exeresis quality and local control. There are less complications (p = 0.045) and less surgical revisions (p = 0.023) in the preservation group. Survival and functional results are better in the preservation group, but without significant difference. For oropharyngeal tumours, survival is dependent on tumoural aggressivity, on general condition and co-morbidity and on the development of a second tumour. Results in local control rate (83.7% at 1 year) are satisfying compared to literature. CONCLUSION: Mandibular preservation is an efficient and safe procedure, even for T3/T4 tumours. Most of oropharyngeal tumours can be removed without mandibulotomy. The suprahyoid approach provides a good exposure when oral approach is insufficient, thus avoiding mandibulotomy and its complications.

Navigation in head and neck oncological surgery: an emerging concept.

Navigation surgery, initially applied in rhinology, neurosurgery and orthopaedic cases, has been developed over the last twenty years. Surgery based on computed tomography data has become increasingly important in the head and neck region. The technique for hardware fusion between RMI and computed tomography is also becoming more useful. We use such device since 2006 in head and neck carcinologic situation. Navigation allows control of the resection in order to avoid and protect the precise anatomical structures (vessels and nerves). It also guides biopsy and radiofrequency. Therefore, quality of life is much more increased and morbidity is decreased for these patients who undergo major and mutilating head and neck surgery. Here we report the results of 33 navigation procedures performed for 31 patients in our institution.

Evaluation of Plasma Disappearance Rate Indocyanine Green Clearance as a Predictor of Liver Graft Rejection in Donor Brain Death.

INTRODUCTION: There currently exist no quantitative methods to assess graft viability before the donor procurement procedure. In Europe, around 20% of liver grafts evaluated "in situ" by an experienced surgeon are discarded. The aim of this study is to evaluate the use of the plasma disappearance rate indocyanine green (PDR-ICG) clearance in predicting liver graft rejection to avoid this 20% of futile surgeries. OBJECTIVES: To evaluate PDR-ICG as a predictor of liver graft rejection in death brain donors compared with the gold standard evaluation by an experienced surgeon. MATERIAL AND METHODS: Prospective observational single center study. From March 2017 to July 2019, 29 donors were included in the study, 17 were men and 12 women with a median age of 68 years ± 16.9 years. Donors had an intensive care unit stay of 2 days ± 4 days. PDR-ICG was measured with PICCO2 monitor. Indocyanine green clearance dose was 0.25 mg/kg injected intravenously in the operating room just before donor procurement procedure is initiated. The surgeon was unaware of the PDR-ICG measure until the decision of graft acceptance was taken. Data regarding the donors and biopsy results were included in a prospective database. RESULTS: PDR-ICG measure could be obtained in 10 minutes in all of the cases included. The median PDR-ICG obtained was 18%/min (range, 2.4-31%/min). Graft rejection took place in 15 out of the 29 donors. PDR-ICG value was less than 10%/min in 6 of these rejected grafts and less than 15%/min in 10 donors. All donor grafts with PDR-ICG <15% were discarded. The graft had been discarded in 5 donors with a PDR-ICG >15%. CONCLUSIONS: In our study a plasma disappearance rate <10 would have identified the grafts that would be rejected, thus avoiding the displacement work and expense of the surgical team. These results should be confirmed in a multicentric study.

Psychometric properties of a French version of the junior temperament and character inventory.

The junior temperament and character inventory (JTCI) has been developed for the assessment of temperament and character dimensions in childhood based on Cloninger's model of personality. We evaluated the psychometric proprieties of a French child and parent-rated version of the JTCI based on a previous German version, and assessed the correlations between the JTCI dimension scores and the scores on the child behavior checklist (CBCL) in a community sample of French children and adolescents aged 10-16 years. We used data from 452 child-rated and 233 -parent-rated JCTI. The psychometric properties (internal consistency and external validity in relation to the emotionality activity sociability (EAS) questionnaire) of the French JTCI were adequate in the parent-rated version. The parent-rated JTCI had overall better psychometric qualities than the child-rated version, but for both versions of the JTCI the confirmatory factor analysis showed low fit between the observed data and the original model. Dimensions of the EAS model were significantly correlated with the temperament scales of the JTCI. Further studies are required to improve the psychometric properties of the child-rated JTCI, and to provide insight about lacking fit of our data with the theoretical model.

[Microsurgical reconstruction and full management of patients with head and neck cancer: importance of a quality approach and a patient care team]. / Reconstruction microchirurgicale et prise en charge globale des patients porteurs de cancer ORL: l'importance d'une approche qualité et d'un circuit protocolisé.

UNLABELLED: MAIN OF STUDY: Management and surgical reconstruction of head and neck cancers remain a challenge. From the first consultation to surgery and radiotherapy it is necessary to gain time to ensure optimum treatment and better survival rates. OBJECTIVE: To establish a kind of quality approach to the management of patients with head and neck cancers. 54 patients who received microsurgical reconstruction after head and neck cancer were included in this study between 1997 and 2006. RESULTS: Multiple data were considered: body mass index (BMI), ASA stage, age, existence of a pre-or postoperative radiotherapy, the surgeon's experience and the number of drainage veins. The success rate is superior when more than one draining vein is sutured to the flap for patients with a BMI >20. Radiotherapy does not seem to affect the survival of the flap. CONCLUSION: According to current literature, the survival rate of these patients is better when the overall time care is less than 100 days. That period is possible with a perfect organization of the medical and paramedical team. Therefore, we propose to include these patients in a circuit protocolisation care, which saves time, to better inform patients and improve survival rates.

[Aneurysmal bone cyst of the ethmoid: paralateronasal or endoscopic surgery? Case report]. / Kyste anévrysmal osseux de l'ethmoïde: abord paralatéronasal ou endoscopique? A propos d'un cas.

AIM: To report a typical case operated on under endonasal endoscopic surgery. CASE REPORT: A 20 year old girl came to the clinic with a left eye exophtalmus. Nasal endoscopy revealed a tumour developped into the left nasal fossa. Imaging allowed to suspect an ethmoidal aneurysmal cyst. CT showed a large tumour involving the left ethmoid, extending into the frontal and maxillary sinuses, with a fluid level in the middle of the tumour. MRI eliminated intracranial extension, showed a cystic component in the middle of the tumour and the presence of hemosiderin signals on T2. Complete resection of the tumour was performed under endoscopic endonasal surgery thanks to a cleavage plane between tumour periorbit and dura. Follow-up was simple with no recurrence at 2 years. CONCLUSION: Despite its rarity, this tumour needs to be known by ENT surgeons, and our surgical experience demonstrates that it can be resected endoscopically.

Pharmacogenetics of methylphenidate response in attention deficit/hyperactivity disorder: association with the dopamine transporter gene (SLC6A3).

Pharmacogenetic studies investigating the 40-bp VNTR polymorphism at SLC6A3 and methylphenidate response have shown conflicting results and large differences in study design and efficacy endpoints. Our objective was to investigate the relation between the 3'-VNTR at SLC6A3 and variability in methylphenidate response in a sample of 141 ADHD children and adolescents, assessed before and after methylphenidate treatment with both clinical and neuropsychological outcome measures. 10-R homozygotes were significantly overrepresented in the low response group, but no genotype effect was shown in cognitive variables improvement. A meta-analysis of pharmacogenetic studies with comparable data (responders vs. non-responders) on a total of 475 subjects showed a significant association between the 10-10 genotype and low rates of methylphenidate response (mean Odds Ratio = 0.46; 95% CI [0.28-0.76]). Heterogeneity between these studies did not reach a significant level but, as publications with different endpoints were excluded from this meta-analysis, our results do not rule out a possible influence of study design.

Lack of association of the dopamine transporter gene in a French ADHD sample.

Discrepancies in the role of the 40 bp VNTR polymorphism of the dopamine transporter gene (DAT1) in attention-deficit hyperactivity disorder (ADHD) could be due to various sources of genetic or phenotypical heterogeneity. We therefore analyzed a sample of 146 ADHD children and their parents, with a transmission disequilibrium test (TDT) design, assessing age, inattention, and hyperactivity dimensions and total score of the ADHD Rating Scale, the number of errors and the total score at Stroop Color-Word test, and the total score at the Trail Making Test. The TDT for 10-repeat (10-R) allele shows a perfect lack of transmission bias (Mc Nemar chi(2) = 0) and PBAT analyses showed no role of this polymorphism for any of the studied endophenotypes. Lack of statistical power is always a possibility, but with a sample size above the average of the majority of previous studies, and an odds ratio (number of transmitted versus untransmitted 10-R allele) of 1.00 exactly, this possibility may be considered as not very likely.

Are the effects of methylphenidate uncertain?

OBJECTIVES: A recent systematic review and meta-analysis of randomised controlled trials of methylphenidate (MPH) in children and adolescents by a Cochrane group, led by Storebø, raised concern around the level of evidence supporting the use of this medication for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. This led to several critical responses from a number of ADHD experts. METHODS: This paper reviews the conclusions reached from the Storebø meta-analysis by a critical analysis of methodologies used along with drawing on extant literature. RESULTS: The controversy raised by the Cochrane meta-analysis should lead to a balanced reflection on the research priorities and needs for the field. CONCLUSIONS: It is hoped the controversy will ultimately lead to improve the quality of the research on the efficacy, effectiveness and tolerability of MPH for ADHD.

[Treatments for children and adolescents with attention deficit hyperactivity disorder: what is the evidence base to date?] / Tratamientos para niños y adolescentes con trastorno por deficit de atencion/hiperactividad: cual es la base de la evidencia hasta ahora?

The evidence base from empirical studies is one of the elements, along with patients' preference and consideration of particular clinical state and circumstances, that should be taken into account in the process of clinical decision making. This paper provides an overview of the current evidence base for the treatment of attention-deficit-hyperactivity disorder (ADHD), drawing on the results of the most recent meta-analyses of randomized controlled trials assessing the pharmacological and non-pharmacological treatment of ADHD. Overall, available recent meta-analyses show that psychostimulants, and, although to a less extent, non psychostimulants, are efficacious in terms of control of core ADHD symptoms, at least in the short term; and although the efficacy of non-pharmacological treatments (behavioral interventions, diet, cognitive training and neurofeedback) for ADHD core symptoms remains uncertain, some non-pharmacological approach are efficacious for ADHD-related problems, such as behavioral interventions for oppositional problems and parenting skills, and cognitive training for working memory deficits. However, most of the available randomized controlled trials are short-term efficacy trials recruiting selected populations of patients and, as such, they are not fully informative for the daily clinical practice. Head-to-head trials, pragmatic trials, placebo-withdrawal trials, network meta-analyses and individual patient data meta-analyses are encouraged in the field to bridge the gap between theoretical evidence and daily clinical practice.

TITLE: Tratamientos para niños y adolescentes con trastorno por deficit de atencion/hiperactividad: cual es la base de la evidencia hasta ahora?La evidencia obtenida a partir de estudios empiricos constituye un elemento clave que, junto con la preferencia del paciente y la consideracion de su estado clinico y circunstancias particulares, deberia tenerse en cuenta en el proceso de toma de decisiones clinicas. Este articulo proporciona una vision global de la evidencia actual en relacion con el tratamiento del trastorno por deficit de atencion/hiperactividad (TDAH), y expone los resultados de los mas recientes metaanalisis de ensayos controlados aleatorizados que evaluan los tratamientos farmacologicos y no farmacologicos. En general, los recientes metaanalisis disponibles muestran que los psicoestimulantes, y en menor medida los no psicoestimulantes, son eficaces en terminos de control de los sintomas nucleares del TDAH, al menos a corto plazo, y que la eficacia para tratar los sintomas nucleares del TDAH de los tratamientos no farmacologicos (programas comportamentales, dietas, entrenamientos cognitivos y neurofeedback) continua siendo dudosa, aunque algunas intervenciones terapeuticas no farmacologicas son eficaces para resolver problemas asociados al trastorno, como las intervenciones conductuales para las conductas oposicionistas y las habilidades parentales, y el entrenamiento cognitivo para los deficits en la memoria de trabajo. No obstante, la mayoria de los ensayos controlados aleatorizados son ensayos de eficacia a corto plazo con muestras de pacientes reclutadas en poblaciones seleccionadas y, como tal, no son completamente ilustrativos para la practica clinica diaria. Con el fin de establecer una conexion entre la evidencia teorica y la practica clinica diaria, tenemos ensayos clinicos comparativos, ensayos pragmaticos, ensayos retirada-placebo, metaanalisis en red y metaanalisis con datos del paciente individual.

Guidance on conducting systematic reviews/meta-analyses of pharmacoepidemiological studies of safety outcomes: the gap is now filled.

Until recently, no comprehensive guidance specifically on the conduction of systematic reviews and meta-analyses of pharmacoepidemiological studies of safety outcomes was available. In December 2015, the European Network of Centres for Pharmacoepidemiology and Pharamacovigilance (ENCePP), a network coordinated by the European Medicines Agency, published their 'Guidance on conducting systematic reviews and meta-analyses of completed comparative pharmacoepidemiological studies of safety outcomes', filling an important gap in the field. This paper highlights the ENCePP recommendations in terms of study identification, data extraction, study quality appraisal and analytical plan. Although the ENCePP document should not be considered as definitive, since it will likely be refined following researchers' feedback, it is expected that it will be highly influential and useful for the field, with the ultimate goal to improve and standardise the conduction and reporting of systematic reviews/meta-analyses of pharmacoepidemiological studies of safety outcomes.