A randomised controlled trial testing the efficacy of Fit after COVID, a cognitive behavioural therapy targeting severe post-infectious fatigue following COVID-19 (ReCOVer): study protocol.

BACKGROUND: Coronavirus disease 2019 (COVID-19) results in debilitating long-term symptoms, often referred to as Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), in a substantial subgroup of patients. One of the most prevalent symptoms following COVID-19 is severe fatigue. Prompt delivery of cognitive behavioural therapy (CBT), an evidence-based treatment that has shown benefit in reducing severe fatigue in other conditions, may reduce post-COVID-19 fatigue. Based on an existing CBT protocol, a blended intervention of 17 weeks, Fit after COVID, was developed to treat severe fatigue after the acute phase of infection with SARS-CoV-2. METHOD: The ReCOVer study is a multicentre 2-arm randomised controlled trial (RCT) to test the efficacy of Fit after COVID on severe post-infectious fatigue. Participants are eligible if they report severe fatigue 3 up to and including 12 months following COVID-19. One hundred and fourteen participants will be randomised to either Fit after COVID or care as usual (ratio 1:1). The primary outcome, the fatigue severity subscale of the Checklist Individual Strength (CIS-fatigue), is assessed in both groups before randomisation (T0), directly post CBT or following care as usual (T1), and at follow-up 6 months after the second assessment (T2). In addition, a long-term follow-up (T3), 12 months after the second assessment, is performed in the CBT group only. The primary objective is to investigate whether CBT will lead to a significantly lower mean fatigue severity score measured with the CIS-fatigue across the first two follow-up assessments (T1 and T2) as compared to care as usual. Secondary objectives are to determine the proportion of participants no longer being severely fatigued (operationalised in different ways) at T1 and T2 and to investigate changes in physical and social functioning, in the number and severity of somatic symptoms and in problems concentrating across T1 and T2. DISCUSSION: This is the first trial testing a cognitive behavioural intervention targeting severe fatigue after COVID-19. If Fit after COVID is effective in reducing fatigue severity following COVID-19, this intervention could contribute to alleviating the long-term health consequences of COVID-19 by relieving one of its most prevalent and distressing long-term symptoms. TRIAL REGISTRATION: Netherlands Trial Register NL8947 . Registered on 14 October 2020.

Shared Individual Formulation Therapy (SIFT): an open-label trial of a new therapy accommodating patient heterogeneity in functional neurological disorder.

BACKGROUND: Functional Neurological Disorder (FND) is a complex neuropsychiatric condition with a multifactorial aetiology. The heterogeneity of patients with FND is rarely considered in psychotherapy trials, which may contribute to variable outcomes. Shared Individual Formulation Therapy (SIFT) is a new, brief (four session) psychotherapy that aims to accommodate heterogeneity by providing a personalised, trans-theoretical formulation of the person's difficulties and accompanying management plan. METHODS: An open-label, prospective trial of outpatient SIFT for adults with FND was conducted, using health-related quality of life (SF-12) as the principal outcome measure, with secondary measures of mental health, dissociation, health care use and attitude to the FND diagnosis. Measures were collected at baseline, end of treatment and 6- and 12-month follow-ups. RESULTS: Twenty-nine participants with various FND symptoms enrolled. Twenty-four completed all four sessions and 25 completed follow-up measures at 12 months. SF-12 scores improved significantly at end of treatment and were sustained throughout follow-up with moderate effect sizes (0.39-0.47; all p < 0.001). Most secondary outcomes also improved significantly at all time points. The intervention was highly acceptable and tolerable to patients and perceived as beneficial. CONCLUSION: This trial provides preliminary evidence for initial and sustained benefit from SIFT for adults with FND. Further study is needed to validate these findings.

Provision of information on transplantation to cystic fibrosis patients and their relatives: Overview of French practices and recommendations.

BACKGROUND: How health-care professionals inform cystic fibrosis patients and their relatives about transplantation is not well known. Such information may not be provided in a timely or satisfactory manner. We conducted a survey about patient information practices among professionals from all French cystic fibrosis centers and transplant centers, to determine how they might be improved. METHODS: This was a national, retrospective, multicenter, descriptive assessment of practices involving health-care professionals, transplant recipients and their relatives, and peer patients who are themselves transplant recipients. Questionnaires were developed by the French working group on cystic fibrosis patient education (GETHEM: Groupe éducation thérapeutique et mucoviscidose). At the end of the questionnaires, respondents were invited to suggest ways to improve the current process. RESULTS: In all, 216 professionals, 55 patients, 30 relatives of these patients, and 17 peer patients responded to the questionnaires, which addressed topics in chronological order, from neonatal screening or later diagnosis of the illness to the time of the transplant, if one was performed. CONCLUSIONS: Study findings have allowed us to draft nine recommendations for professionals to improve patient information practices. A booklet now being prepared aims to facilitate the process for professionals, and e-learning modules are also forthcoming.

Freud's hysteria and its legacy.

Though Freud was himself interested in neurologic disorders, the model of hysteria he developed - of the repression of painful experiences, and their conversion into physical symptoms - made the disorder psychiatric, as the increasingly complex explanations came to rely on the "meaning" of events, which could not easily be understood neurologically. This evolved to become a prototype for psychiatric illness more broadly, a model which, though challenged by the First World War, enjoyed great success, notably in the USA, dominating psychiatric thinking for most of the 20th century. Concerns about the empiric basis for his ideas latterly led to a rapid decline in their importance, however, exemplified by 1980's "etiologically neutral" DSM-III. Hysteria, now renamed conversion disorder, retained its Freudian explanation for another 30 years, but as psychiatry lost its faith in Freud, so psychiatrists stopped seeing the disorder he had made theirs, and returned it once more to neurology.

Life events and escape in conversion disorder.

BACKGROUND: Psychological models of conversion disorder (CD) traditionally assume that psychosocial stressors are identifiable around symptom onset. In the face of limited supportive evidence such models are being challenged. METHOD: Forty-three motor CD patients, 28 depression patients and 28 healthy controls were assessed using the Life Events and Difficulties Schedule in the year before symptom onset. A novel 'escape' rating for events was developed to test the Freudian theory that physical symptoms of CD could provide escape from stressors, a form of 'secondary gain'. RESULTS: CD patients had significantly more severe life events and 'escape' events than controls. In the month before symptom onset at least one severe event was identified in 56% of CD patients - significantly more than 21% of depression patients [odds ratio (OR) 4.63, 95% confidence interval (CI) 1.56-13.70] and healthy controls (OR 5.81, 95% CI 1.86-18.2). In the same time period 53% of CD patients had at least one 'high escape' event - again significantly higher than 14% in depression patients (OR 6.90, 95% CI 2.05-23.6) and 0% in healthy controls. Previous sexual abuse was more commonly reported in CD than controls, and in one third of female patients was contextually relevant to life events at symptom onset. The majority (88%) of life events of potential aetiological relevance were not identified by routine clinical assessments. Nine per cent of CD patients had no identifiable severe life events. CONCLUSIONS: Evidence was found supporting the psychological model of CD, the Freudian notion of escape and the potential aetiological relevance of childhood traumas in some patients. Uncovering stressors of potential aetiological relevance requires thorough psychosocial evaluation.

A structural MRI study of motor conversion disorder: evidence of reduction in thalamic volume.

OBJECTIVE: To investigate potential abnormalities in subcortical brain structures in conversion disorder (CD) compared with controls using a region of interest (ROI) approach. METHODS: Fourteen patients with motor CD were compared with 31 healthy controls using high-resolution MRI scans with an ROI approach focusing on the basal ganglia, thalamus and amygdala. Brain volumes were measured using Freesurfer, a validated segmentation algorithm. RESULTS: Significantly smaller left thalamic volumes were found in patients compared with controls when corrected for intracranial volume. These reductions did not vary with handedness, laterality, duration or severity of symptoms. CONCLUSIONS: These differences may reflect a primary disease process in this area or be secondary effects of the disorder, for example, resulting from limb disuse. Larger, longitudinal structural imaging studies will be required to confirm the findings and explore whether they are primary or secondary to CD.

[Eosinophilic pleural effusion related to taking valproic acid]. / Une pleurésie à éosinophiles liée à la prise d'acide valproïque.

Eosinophilic pleural effusions have multiple aetiologies. We report on the case of a 40-year-old man who experienced an eosinophilic pleural effusion with blood hypereosinophilia that occurred nine weeks after a treatment with valproic acid was introduced. Usual aetiologies of eosinophilic pleural effusion were excluded. Once valproic acid was discontinued, both pleural effusion and blood eosinophilia decreased rapidly. The persistence of a residual pleural effusion required the introduction of oral corticosteroids, which resulted in the effusion disappearing completely and rapidly. Valproic acid is a rare cause of eosinophilic pleural effusion. The effusion usually regresses when treatment is discontinued but short-term oral corticotherapy may be necessary in order to heal the patient.

[Management of acute and severe complications in adults with cystic fibrosis]. / Prise en charge des complications aiguës sévères chez l'adulte mucoviscidosique.

The natural history of cystic fibrosis (CF) may be associated both with acute respiratory complications (respiratory exacerbations, haemoptysis, pneumothorax) and with non-respiratory complications (distal intestinal obstruction syndrome, dehydration) that may result in hospitalizations. The aim of this article is to describe the main therapeutic approaches that are adopted in the management of acute complications occurring in CF adults, and to discuss indications for admission of these patients to intensive care units. Adult CF patients admitted to intensive care unit often benefit from antibiotic courses adapted to their chronic bronchial infection, especially when the hospitalization is related to respiratory disease (including haemoptysis and pneumothorax). Nutritional support, including hypercaloric diet, control of hyperglycemia and pancreatic enzyme supplementation is warranted. The recommended therapy for major haemoptysis is bronchial artery embolization. Patient with significant pneumothorax should have a chest tube inserted, while the treatment of distal intestinal obstruction syndrome will most often be medical. In case of respiratory failure, non-invasive ventilation is the preferred mode of ventilatory support because invasive ventilation is associated with poor outcomes. Therapeutic options should always have been discussed between the patient, family members and the CF medical team to allow for informed decision making.

[Indications and contraindications to lung transplant: patient selection]. / Indications et contre-indications à la greffe pulmonaire : sélection du receveur.

Lung transplant (LT) is a valid treatment for patients with end-stage lung disease such as cystic fibrosis, emphysema, pulmonary fibrosis and pulmonary arterial hypertension (85% of indications) and for selected candidates. The "good recipient" was introduced early to a specialised center, has had complete pre-LT assessment and complete information. At the end of this assessment, the absolute contraindications were eliminated (cardiovascular pathologies, recent neoplasia, active viral diseases, severe psychiatric disorders), advanced age risks were discussed, co-morbidities to treat were listed and an individualised therapeutic pre-LT program has been decided (based on exercise and muscle rehabilitation, nutritional support, anti-infectious treatments, active management of co-morbidities such as diabetes, hypertension, gastro-esophageal reflux…) with a psychological follow-up if necessary. Timely inscription on waiting list must be decided, early enough to avoid extreme handicap or risk pre-LT death, but not too early to have a survival benefit linked to LT. Death without LT prognosis criteria are still studied, and even if they do not fully define the risk of death of an individualised patient, they are taken into account by the recommendations of the societies; since 2006, LT indications are based on severity criteria of the selected patient, defined for each recipient diagnosis. LT aims to improve survival and quality of life of the patient, and this is especially true when the patient is referred, prepared and monitored early enough by the transplant team; the aim is to limit the risk of death before LT (before listing and on waiting list) and early post-LT morbimortality.

Altered connections on the road to psychopathy.

Psychopathy is strongly associated with serious criminal behaviour (for example, rape and murder) and recidivism. However, the biological basis of psychopathy remains poorly understood. Earlier studies suggested that dysfunction of the amygdala and/or orbitofrontal cortex (OFC) may underpin psychopathy. Nobody, however, has ever studied the white matter connections (such as the uncinate fasciculus (UF)) linking these structures in psychopaths. Therefore, we used in vivo diffusion tensor magnetic resonance imaging (DT-MRI) tractography to analyse the microstructural integrity of the UF in psychopaths (defined by a Psychopathy Checklist Revised (PCL-R) score of > or = 25) with convictions that included attempted murder, manslaughter, multiple rape with strangulation and false imprisonment. We report significantly reduced fractional anisotropy (FA) (P<0.003), an indirect measure of microstructural integrity, in the UF of psychopaths compared with age- and IQ-matched controls. We also found, within psychopaths, a correlation between measures of antisocial behaviour and anatomical differences in the UF. To confirm that these findings were specific to the limbic amygdala-OFC network, we also studied two 'non-limbic' control tracts connecting the posterior visual and auditory areas to the amygdala and the OFC, and found no significant between-group differences. Lastly, to determine that our findings in UF could not be totally explained by non-specific confounds, we carried out a post hoc comparison with a psychiatric control group with a past history of drug abuse and institutionalization. Our findings remained significant. Taken together, these results suggest that abnormalities in a specific amygdala-OFC limbic network underpin the neurobiological basis of psychopathy.

[The diagnosis of cystic fibrosis in adults: lessons from a family story]. / Le diagnostic de mucoviscidose chez l'adulte: les enseignements d'une histoire de famille!

INTRODUCTION: Cystic fibrosis is usually diagnosed during the first years of life. Diagnosis may be achieved in adults with milder forms of the disease at any age. CASE REPORTS: We report the diagnosis of cystic fibrosis in three adults within the same family. A 39 yr old man, was diagnosed with congenital absence of the vas deferens; the diagnosis of cystic fibrosis was achieved based on a positive chloride sweat test and the identification of two mutations in the CFTR gene. His mother experienced repeated bronchial infections that began when she was 12 years old. The diagnosis of cystic fibrosis was considered at the age of 74 yr after her son was diagnosed with this disease. Sweat test showed normal chloride concentrations and cystic fibrosis was suspected based on elevated basal transepithelial nasal potential difference. Genetic testing for the 33 most frequent mutations in the CFTR gene showed only one mutation. A second rare mutation was identified by complete sequencing of the CFTR gene, confirming the diagnosis of cystic fibrosis. A third case of pauci-symptomatic cystic fibrosis was diagnosed in a brother of the index case. CONCLUSION: These observations illustrate the challenge of diagnosing milder forms of cystic fibrosis in adult subjects. The recognition of this diagnosis may lead to improvement in patient's care and to genetic counselling.

Malnutrition in adults with cystic fibrosis.

OBJECTIVE: To determine the prevalence and clinical features of malnutrition and its relationship with the CFTR genotype in a cystic fibrosis (CF) adult population. DESIGN: Cross-sectional study. SETTING: Department of Pulmonology, Cochin Hospital, Paris, France. SUBJECTS: 163 CF adults seen between 1997 and 1999. RESULTS: Mean age was 28.8 y. Mean body mass index (BMI) was 19.1 kg/m2. Malnutrition (BMI<18.5 kg/m2) was seen in 81 patients (49.7%). Its severity was associated with diagnosis of CF before the age of 18 y (P<0.01), FEV1 values below 30% (P<0.01), the yearly decline of FEV1 (P<0.01), pancreatic insufficiency (P<0.01) and gastro-oesophageal reflux (P<0.01). Malnutrition was observed in 58.7% of patients with a severe CFTR genotype but in 28.6% of patients with a mild genotype (P<0.001). CONCLUSION: Malnutrition remains frequent in adults with CF except in patients presenting with a mild CFTR genotype (leading to a mild phenotype and to later diagnosis).