Correction to: Multicenter randomized controlled trial on the comparison of multi-family therapy (MFT) and systemic single-family therapy (SFT) in young patients with anorexia nervosa: study protocol of the THERAFAMBEST study.

After publication of our article [1] the authors have notified us of missing to include one name to the authorship list.

Practitioners' opinions on traumatic brain injury care pathways in Finland and France: different organizations, common issues.

OBJECTIVE: In traumatic brain injury (TBI), differences in health-care contexts have profound effects on care pathways. Objectives were to compare TBI pathways of care and practitioners' views on quality of care issues in two large European areas: Varsinais-Suomi, Finland and Ile-de-France, France. METHODS: Thematic analysis of semi-structured interviews was conducted with TBI practitioners (n = 10) from all stages of TBI care. Interviews addressed organization and financing of care, decision-making on care transitions, and perceived issues. The structure-process-outcome model of Donabedian was used to classify findings related to quality of care issues. RESULTS: Main differences in organization of care pathways for people with TBI were related to financing modalities, number of pathway alternatives, inpatient versus outpatient rehabilitation, and indirect versus direct referrals to rehabilitation. Similar categories of issues were raised in the two settings. Issues in structures involved availability of services, financial access, and heterogeneity of expertise. Issues in processes involved diagnosis and follow-up, training regarding cognitive impairments, decision-making for referrals, transition delays, and care pathways of very severely affected patients. CONCLUSIONS: These findings provide clues to address care pathways in further comparative studies. Determinants of care pathway quality could be classified as direct or indirect, binding or adaptive organizational factors.

Impact of the Early Start Denver Model on the cognitive level of children with autism spectrum disorder: study protocol for a randomised controlled trial using a two-stage Zelen design.

INTRODUCTION: Early intervention for autism spectrum disorder (ASD) in the European French-speaking countries is heterogeneous and poorly evaluated to date. Early intervention units applying the Early Start Denver Model (ESDM) for toddlers and young children with ASD have been created in France and Belgium to improve this situation. It is essential to evaluate this intervention for the political decision-making process regarding ASD interventions in European French-speaking countries. We will evaluate the effectiveness of 12 hours per week ESDM intervention on the cognitive level of children with ASD, over a 2-year period. METHODS AND ANALYSIS: The study will be a multicentre, randomised controlled trial, using a two-stage Zelen design. Children aged 15-36 months, diagnosed with ASD and with a developmental quotient (DQ) of 30 or above on the Mullen Scale of Early Learning (MSEL) will be included. We will use a stratified minimisation randomisation at a ratio 1:2 in favour of the control group. The sample size required is 180 children (120 in the control and 60 in the intervention group). The experimental group will receive 12 hours per week ESDM by trained therapists 10 hours per week in the centre and 2 hours in the toddlers' natural environment (alternatively by the therapist and the parent). The control group will receive care available in the community. The primary outcome will be the change in cognitive level measured with the DQ of the MSEL scored at 2 years. Secondary outcomes will include change in autism symptoms, behavioural adaptation, communicative and productive language level, sensory profile and parents' quality of life. The primary analysis will use the intention-to-treat principle. An economic evaluation will be performed. DISSEMINATION: Findings from the study will be disseminated through peer reviewed publications and meetings. TRIAL REGISTRATION NUMBER: NCT02608333 (clinicaltrials.gov); Pre-results.

Human spinal ejaculation generator.

OBJECTIVE: A spinal ejaculation generator (SEG) has been identified in the rat with lumbar galaninergic interneurons playing a pivotal role (Science 2002;297:1566-1569). The aim was to evidence a SEG in humans. METHODS: Spatial distribution of galaninergic neurons was studied in postmortem spinal cord segments of 6 men and compared with that of 6 women for evidencing sexual dimorphism. Based on the identified segmental distribution of galaninergic neurons, the ability for penile vibratory stimulation (PVS) to elicit ejaculation when the concerned spinal segments were injured was studied in 384 patients with clinically complete spinal cord injury (SCI) and consequent anejaculation. Such patients represent a unique model to investigate the role of defined spinal segments in the control of ejaculation. RESULTS: Galaninergic neurons were mostly located between L2 and L5 segments in medial lamina VII, with a maximal density within L4. Three-dimensional 3D reconstruction showed that these neurons were grouped into single columns bilaterally to the central canal. In addition, galaninergic neuron density was found higher in L3 and L4 segments in men as compared to women supporting sexual dimorphism. In the patients' cohort, injury of L3-L5 segments was the sole independent predictor for failure of PVS to induce ejaculation. Although evidence from clinical observations was indirect, there is close correspondence to neuroanatomical data. INTERPRETATION: Organization and sexual dimorphism of human spinal galaninergic neurons were similar to the rat's SEG. Neurohistological data, together with clinical results, corroborate the existence of an SEG in humans in L3-L5 segments. Such a generator could be targeted to treat neurogenic and non-neurogenic ejaculatory disorders. ANN NEUROL 2017;81:35-45.

Factors influencing compliance with non-invasive ventilation at long-term in patients with myotonic dystrophy type 1: A prospective cohort.

This study evaluated compliance with non-invasive ventilation in patients with myotonic dystrophy type 1 and identified predictors of cessation at 5 years in a cohort of patients followed in a specialist center for Neuromuscular Diseases in France. Mechanical ventilation in these patients poses a very strong challenge to caregivers. Factors predicting relative compliance were identified using multivariate linear regressions. Cox proportional-hazards regression was used to estimate hazard ratios associated with risk of cessation. One hundred and twenty-eight patients were included. Compliance during the first year was higher when symptoms of respiratory failure were initially present (+25%, p < 0.003) and lower in the case of acute respiratory failure (-29%, p < 0.003). Long-term compliance was associated with symptoms of respiratory failure (+52%, p < 0.0001) and nocturnal arterial oxygen desaturation (+23%, p < 0.007). Cessation was more frequent in the cases of excessive leaks (HR = 7.81, IC [1.47-41.88], p < 0.01), ventilator dysfunction requiring emergency technical intervention (HR = 12.58, IC [1.22-129.69], p < 0.03) or high body mass index (p < 0.02). Cessation was less frequent for patients with a professional occupation or undergoing professional training (HR = 0.11, IC [0.02-0.77], p < 0.02). Compliance with non-invasive ventilation is poor in patients with no subjective symptoms of respiratory failure. It may be improved with appropriate education and follow-up.

Impact of invasive ventilation on survival when non-invasive ventilation is ineffective in patients with Duchenne muscular dystrophy: A prospective cohort.

BACKGROUND: Many patients with DMD undergo tracheostomy. Tracheostomy is associated with certain complications, however its effect on prognosis is not known. METHODS: The relationship between type of mechanical ventilation and survival at 12 years was evaluated in a prospective cohort of patients with Duchenne muscular dystrophy followed in a French reference center for Neuromuscular Diseases. Cox proportional-hazards regressions were used to estimate the hazard ratios associated with risk of switching from non-invasive to invasive ventilation, and with risk of death. RESULTS: One hundred and fifty patients were included. Initial use of invasive ventilation was associated with an episode of acute respiratory failure (p < 0.0001) and with a severe clinical status (p < 0.05). Risk of death was associated with swallowing disorders (2.51, IC [1.12-5.66], p < 0.03) and cardiac failure (p < 0.05) but not with type of mechanical ventilation. CONCLUSION: Switching to invasive ventilation is appropriate when non-invasive ventilation is ineffective.

Loss to Follow-Up and Social Background in an Inception Cohort of Patients With Severe Traumatic Brain Injury: Results From the PariS-TBI Study.

OBJECTIVES: To assess determinants of loss to follow-up (FU) at 2 time points of an inception traumatic brain injury (TBI) cohort. DESIGN AND PARTICIPANTS: The PariS-TBI study consecutively included 504 adults with severe TBI on the accident scene (76% male, mean age 42 years, mean Glasgow Coma Scale 5). No exclusion criteria were used. MAIN MEASURE: Loss to FU at 1 and 4 years was defined among survivors as having no outcome data other than survival status. RESULTS: Among 257 1-year survivors, 118 (47%) were lost to FU at 1 year and 98 (40%) at 4 years. Main reasons for loss to FU were impossibility to achieve contact (109 at 1 year, 52 at 4 years) and refusal to participate (respectively 5 and 24). At 1 year, individuals not working preinjury or with nonaccidental traumas were more often lost to FU in univariate and multivariable analyses. At 4 years, loss to FU was significantly associated with preinjury alcohol abuse and unemployment. Relationship with injury severity was not significant. CONCLUSIONS: Socially disadvantaged persons are underrepresented in TBI outcome research. It could result in overestimation of outcome and biased estimates of sociodemographic characteristics' effects. These persons, particularly unemployed individuals, require special attention in clinical practice.

The spinal control of ejaculation revisited: a systematic review and meta-analysis of anejaculation in spinal cord injured patients.

BACKGROUND After spinal cord injury (SCI), most men cannot ejaculate without medical assistance. A major advance in the knowledge of the spinal control of ejaculation has been achieved with the discovery of a spinal generator of ejaculation (SGE) in the rat. The aim of this report was to review studies about ejaculation after SCI in order to revisit the spinal control of ejaculation and especially to assess the existence of an SGE in man. METHODS Studies were identified from Embase, PubMed, EBSCOhost and Cochrane Library. Studies were eligible when they specify the occurrence of antegrade ejaculation as a function of the neurological characterization of SCI. Studies were excluded when ejaculation was elicited by rectal electrical stimulation or when ejaculation could not be discriminated from climax. Meta-analyses were performed to assess the reference ejaculation rates for each procedure used to elicit ejaculation, i.e. masturbation or coïtus, penile vibratory stimulation (PVS) or acetylcholine esterase (AchE) inhibitors prior to masturbation. Subgroup analyses were performed according to the procedure used to elicit ejaculation on (i) the completeness of the SCI and (ii) the upper and lower limits of the SCI. To assess the existence of an SGE, the effect of concurrent lesions of different spinal segments was assessed by means of a stratified bivariate analysis. RESULTS From 523 studies, 45 were selected (n = 3851). Ejaculation occurred in response to masturbation or coïtus, PVS or AchE inhibitors followed by masturbation in, respectively, 11.8% (n = 1161), 47.4% (n = 597) and 54.7% (n = 309) of patients with complete SCI and in, respectively, 33.2% (n = 343), 52.8% (n = 305) and 78.1% (n = 32) of patients with incomplete SCI. Ejaculation, in the case of complete lesion of the sympathetic centres (T12 to L2), of the parasympathetic and somatic centres (S2-S4) or of all spinal ejaculation centres (T12 to S5) occurred in response to PVS in none of the patients (respectively, n = 5, n = 4 and n = 21) and in response to AchE inhibitors followed by masturbation in 4.9% (n = 61), 30.8% (n = 26) and 0% (n = 16) of the patients, respectively. Ejaculation in response to PVS or AchE inhibitors prior to masturbation was rhythmic forceful in 97.9% (n = 48) of the patients with complete lesion strictly above Onuf's nucleus (segments S2-S4). Complete lesion of the S2-S4 segments precluded the occurrence of rhythmic forceful ejaculation (n = 5). Controlling for the number of the injured segments between T12 and L2, the ejaculation rate sharply decreased when the lesion extended to the L3 segment and below. CONCLUSIONS The results reinforce the crucial roles of the spinal sympathetic and parasympathetic centres for emission and the somatic centre for expulsion. The spinal segments between L2 and S2 is more than a pathway to connect the ejaculation centres and likely harbours an SGE in man located in the L3, L4 and L5 segments.

Cost-effectiveness of osteoporosis treatments in postmenopausal women using FRAX™ thresholds for decision.

PURPOSE: FRAX™ is a fracture prediction algorithm to determine a patient's absolute fracture risk. There is a growing consensus that osteoporosis treatment should be based on individual 10-year fracture probability, as calculated in the FRAX™ algorithm, rather than on T-scores alone. OBJECTIVE: Our objective was to evaluate the cost-effectiveness of five years of branded alendronate therapy in postmenopausal French women with a known FRAX™ score. METHOD: A Markov cohort state transition model using FRAX™ values and whenever possible population-specific data and probabilities. We estimated the incremental cost-effectiveness ratio (ICER) of alendronate versus no treatment in postmenopausal women with FRAX™ ranging from 10 to 3%. OUTCOMES: Number of women to treat (NNT) for preventing hip fracture, costs, quality-adjusted life-years, incremental cost-effectiveness ratios. RESULTS: The incremental cost-effectiveness ratios (ICER) compared to no treatment at age 70 ranged from €104,183 to €413,473 per QALY when FRAX™ decreased from 10 to 3%. The NNTs for preventing one hip fracture ranged from 97 to 388 according to age (50-80 years) and FRAX™. Sensitivity analyses showed that the main determinants of cost-effectiveness were adherence to therapy and cost of treatment. CONCLUSION: Using French costs of branded drug and current estimates of treatment efficacy, alendronate therapy for 70-year-old women with 10-year probability of hip fracture of 10% just meets the accepted cost-effectiveness threshold. Improving treatment adherence and/or decreasing treatment cost lowers the ICER. The model however underestimates the potential benefit by excluding other fractures.

Long-term hepatitis B surface antigen (HBsAg) kinetics during nucleoside/nucleotide analogue therapy: finite treatment duration unlikely.

BACKGROUND & AIMS: Information regarding long-term HBsAg kinetics during treatment with nucleoside/nucleotide analogues is limited. The aim of the present study was to assess whether finite nucleoside/nucleotide analogue treatment duration could be envisaged during the patient's lifetime. METHODS: Patients with chronic hepatitis B receiving different schedules of nucleoside/nucleotide analogues were followed for a median duration of 102 months, i.e., 8.5 years (interquartile range: 88-119 months). Long-term HBV DNA and HBsAg level kinetics were modeled in order to estimate time to clear HBsAg during therapy in patients with undetectable HBV DNA. RESULTS: Antiviral therapy was associated with a slow but consistent reduction in the level of HBsAg in most of the patients. Three patterns of HBsAg level declines were identified: decline during both the detectable and undetectable HBV DNA phases; decline during the HBV DNA detectable period only; decline during the HBV DNA undetectable period only. The mean HBsAg titer at the time when HBV DNA became undetectable was 3.29 ± 0.49 Log10 international units (IU)/ml, and the mean slope was -0.007 ± 0.007 Log10 IU/month, i.e., an average decline of 0.084 Log10 IU/year. The corresponding calculated median number of years needed to clear HBsAg was 52.2 years (interquartile range: 30.8-142.7). CONCLUSIONS: This study, based on the very long-term follow-up of patients with chronic hepatitis B treated with potent nucleoside/nucleotide analogues, shows that HBsAg clearance is unlikely to occur during the patient's lifetime, even if HBV replication is well controlled. Thus, lifetime therapy is required in the vast majority of HBV-infected patients.

Hepatocellular adenomas: accuracy of magnetic resonance imaging and liver biopsy in subtype classification.

UNLABELLED: Hepatocellular adenomas (HCAs) are divided into genotype/phenotype subgroups associated with different evolutive profiles. Therefore, recognition of subtype is of clinical importance in patient management. Magnetic resonance imaging (MRI) is considered the most informative imaging modality and liver biopsy a key diagnostic tool whose role in HCA subtyping has never been extensively studied. The purpose of our study was to evaluate the diagnostic performance of MRI and liver biopsy with and without immunohistochemistry and to assess the interobserver agreement for MR classification in a consecutive series of resected HCAs. Forty-seven HCAs with preoperative MRI and biopsy were retrospectively included. MRI data were reviewed independently by two abdominal radiologists blind to the pathological results and classification. Subtyping of HCAs on liver biopsy was made blindly to clinical, biological, and imaging data and to final classification. Routine histological analysis was based on morphological criteria and immunohistochemistry was systematically performed when enough tissue was available. Final subtyping of HCA was based on the examination of the surgical specimen. Radiologists correctly classified HCAs in 85%. The interobserver kappa correlation coefficient was 0.86. Routine histological analysis led to 76.6% of correct classification and 81.6% when immunophenotypical characteristics were available. The additional value of immunophenotypical markers is best in HCAs containing steatosis. Agreement between MRI findings and routine histological analysis was observed in 74.5%, leading to a likelihood ratio of subtype diagnosis higher than 20. CONCLUSION: MRI and biopsy analysis are two efficient methods in subtyping HCAs and their association increases the diagnosis confidence. Interobserver variability in MRI criteria is very low.

Incidental focal solid liver lesions: diagnostic performance of contrast-enhanced ultrasound and MR imaging.

OBJECTIVE: To prospectively assess the diagnostic performance of contrast-enhanced ultrasound (CEUS) and MR imaging in incidental solid focal liver lesions not characterised on ultrasound. MATERIALS AND METHODS: Forty-seven patients with 50 lesions underwent MR imaging and CEUS: 24 focal nodular hyperplasias (FNH), 11 adenomas, 10 haemangiomas, 1 focal fatty change and 4 malignant lesions were identified. Two experienced radiologists randomly reviewed contrast-enhanced MR imaging and CEUS data, and provided the most likely diagnosis. Sensitivity (Se), specificity (Sp), likelihood ratios (LR) and kappa value were calculated. RESULTS: A histotype diagnosis was obtained in 66-52% with MR imaging and 52-53% with CEUS, respectively, for both readers. Se, Sp and LR for haemangioma were 100-100, 100-100 and 78-78 with MR imaging and 89-89, 100-100 and 68-70 with CEUS; for FNH with MR imaging they were 88-63, 96-100 and 23-34 and 74-67, 88-96 and 6-17 with CEUS. If the diagnosis of haemangioma was uncertain with CEUS, MR imaging always confirmed the diagnosis. If the diagnosis of FNH was uncertain with either CEUS or MR imaging, the other imaging technique confirmed the diagnosis in approximately half the cases. CONCLUSION: Both CEUS and MR imaging have a high diagnostic performance in incidental focal liver lesions and are complementary when diagnosis is uncertain.

France: Health system review.

The Health Systems in Transition (HiT) profiles are country-based reports that provide a detailed description of a health system and of policy initiatives in progress or under development. HiTs examine different approaches to the organization, financing and delivery of health services and the role of the main actors in health systems; describe the institutional framework, process, content and implementation of health and health care policies; and highlight challenges and areas that require more in-depth analysis. The French health care system is a mix of public and private providers and insurers. Public insurance, financed by both employees and employer contributions and earmarked taxes, is compulsory and covers almost the whole population, while private insurance is of a complementary type and voluntary. Providers of outpatient care are largely private. Hospital beds are predominantly public or private non-profit-making. The French population enjoys good health and a high level of choice of providers. It is relatively satisfied with the health care system. However, as in many other countries, the rising cost of health care is of concern with regards to the objectives of the health care system. Many measures were or are being implemented in order to contain costs and increase efficiency. These include, for example, developing pay-for-performance for both hospitals and self-employed providers and increasing quality of professional practice; refining patient pathways; raising additional revenue for statutory health insurance (SHI); and increasing the role of voluntary health insurance (VHI). Meanwhile, socioeconomic disparities and geographic inequality in the density of health care professionals remain considerable challenges to providing a good level of equity in access to health care. Organizational changes at the regional level are important in attempting to tackle both equity and efficiency-related challenges. While the organizational structure of the system remained very stable until the mid 1990s, in the following decade many changes occurred and several new institutions were created. Concurrently, the respective power and involvement of the parliament, government, local authorities and SHI in the policy-making process have evolved. However, the Ministry of Health has retained substantial control over the health system, although ongoing reforms at both the regional and the national levels may challenge its traditional role. This edition of the French HiT was written concurrently with the vote and implementation of the 2009 Hospital, Patients, Health and Territories Act, which dramatically changed again the organizational structure and management of the health care system at the regional and local level. In order to ensure a comprehensive description and understanding of the system, the HiT, therefore, describes both the previous organization and the reorganization following the Act. However, the implementation process of the Act and its formal application was still a work in progress at the time of completing the French HiT.

France: health system review

The Health Systems in Transition (HiT) country profiles provide an analytical description of each health system and of policy initiatives in progress or under development. They aim to provide relevant comparative information to support policy-makers and analysts in the development of health systems and reforms in the countries of the WHO European Region and beyond. The HiT profiles are building blocks that can be used: to learn in detail about different approaches to the financing, organization and delivery of health services; to describe accurately the process, content and implementation of health reform programmes; to highlight common challenges and areas that require more in-depth analysis; and to provide a tool for the dissemination of information on health systems and the exchange of experiences of reform strategies between policy-makers and analysts in countries of the WHO European Region. This series is an ongoing initiative and material is updated at regular intervals.

Pancreatic endocrine tumors: tumor blood flow assessed with perfusion CT reflects angiogenesis and correlates with prognostic factors.

PURPOSE: To prospectively correlate multidetector computed tomographic (CT) perfusion measurement of pancreatic endocrine tumors with tumor microvascular density (MVD) assessed by using histologic techniques and to determine whether perfusion CT parameters differ between tumor grades. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Thirty-six patients (15 men, 21 women; mean age, 53 years; range, 18-78 years) with resectable pancreatic endocrine tumors underwent presurgical dynamic perfusion CT. Twenty-eight (78%) of 36 patients were included in the study group; eight were excluded because of artifacts that were not compatible with perfusion postprocessing. Multidetector CT perfusion data were analyzed to calculate tumor and normal pancreatic blood flow, blood volume, mean transit time, and permeability-surface area product. Multidetector CT perfusion parameters were compared with intratumoral MVD by using the Spearman correlation coefficient and with World Health Organization (WHO) classification, tumor size, tumor proliferation index, hormonal profile, and presence of metastases by using Mann-Whitney tests. RESULTS: High correlation (r = 0.620, P < .001) was observed between tumor blood flow and intratumoral MVD. Blood flow was significantly higher (P = .02) in the group of benign tumors (WHO 1) than in the groups of tumors of indeterminate prognosis (WHO 2) or well-differentiated carcinomas (WHO 3). Blood flow was significantly higher in tumors with a proliferation index of 2% or less (P = .005) and in those without histologic signs of microscopic vascular involvement (P = .008). Mean transit time was longer in tumors with lymph node (P = .02) or liver (P = .05) metastasis. CONCLUSION: Perfusion CT is feasible in patients with pancreatic endocrine tumors and reflects MVD. Perfusion CT measurements are correlated with histoprognostic factors, such as proliferation index and WHO classification.

Magnetic resonance imaging of the cervix during pregnancy: effect of gestational age and prior vaginal birth.

OBJECTIVE: To investigate how gestational age and prior vaginal birth affect cervical anatomy on magnetic resonance imaging during pregnancy. STUDY DESIGN: Magnetic resonance images of the cervix were obtained in consecutive patients referred for a suspected fetal abnormality. We used an image processing protocol to measure cervical dimensions, orientation, and signal intensity. We determined how outcome variables were affected by gestational age and prior vaginal birth. RESULTS: Adequate images were obtained in 53 of 57 patients at 17 to 36 weeks. As gestational age increased by 12 weeks, the mean cross-sectional area of the cervical canal and cervical stroma increased 31% (95% confidence interval 0% to 73%) and 31% (95% confidence interval 11% to 55%), respectively. The normalized signal intensity of the stroma increased from 0.83 (95% confidence interval 0.81 to 0.85) at 20 weeks to 0.91 (95% confidence interval 0.88 to 0.94) at 32 weeks. None of the outcome variables were affected by prior vaginal birth. CONCLUSION: Magnetic resonance imaging revealed that cross-sectional area and signal intensity of the cervical stroma increase with increasing gestational age.