BACKGROUND:Half of patients with sarcoidosis have significant organ involvement and require long-lasting immunosuppressive treatment. We aimed to evaluate safety and immunological efficacy of a trivalent inactivated influenza vaccine in patients with sarcoidosis compared with healthy controls. METHODS:The SARCOVAC trial was an open-label, multicenter, prospective clinical trial. Influenza vaccination was performed in 2012-2013 in patients with both sarcoidosis and an indication for influenza vaccination, and in healthy controls. Antibody titers against A/H1N1, A/H3N2, and B influenza virus antigens were measured immediately before and 21 and 180 days after vaccination. The primary outcome was the comparison of seroconversion rates for each viral strain at day 21 between patients and controls. FINDINGS:We recruited 191 participants among whom 182 (83 patients, 99 controls) were included in the analysis. At D21, seroconversion rates were higher in patients than in controls for A/H1N1 strain (62.2% versus 45.4%, p = 0.025), and A/H3N2 strain (58.5% versus 35.1%, p = 0.002) but did not differ for B strain (72% versus 60.8%, p = 0.118). Seroprotection rates ranged between 73.2% and 90.7% at D21 and 59.4% and 79.4% at day 180 in patients and controls, respectively, with no statistical difference. The vaccination did not significantly impact the course of sarcoidosis. No difference in reactogenicity was found between patients and healthy controls. INTERPRETATION:Influenza vaccination is immunogenic in patients with sarcoidosis, including those with severe disease and immunosuppressive therapy. These results support the recommendations for influenza vaccination in patients with sarcoidosis who are at high risk of severe infections.

BACKGROUND:Long COVID is associated with poor health-related quality of life (QoL), with substantial interindividual variations. This study aimed to investigate the association between QoL and a diagnosis of functional somatic disorder (FSD) among patients seeking care for long COVID. METHODS:Data were drawn from the CASPer-COVID program, a multidisciplinary tertiary care program for patients with persistent symptoms following COVID-19. QoL was evaluated with the 36-Item Short-Form health survey (SF-36), yielding a Physical Component Summary (PCS) and a Mental Component Summary (MCS). Multivariable linear regression analyses were performed to investigate the associations between PCS or MCS scores and a diagnosis of FSD, adjusting for age, gender, body mass index, comorbidities, hospitalization for acute COVID-19, core persistent symptoms, symptom duration, depressive and anxiety symptoms, and physical activity. RESULTS:The analyses included 773 patients (median age [interquartile range (IQR)]: 44 [36-55] years; 64% women). QoL was markedly impaired (median PCS [IQR]: 44 [31-60]; median MCS [IQR]: 39 [31-49]). A diagnosis of FSD (76.5% of patients) was not associated with MCS (β [95% CI]: 1.11 [-1.30, 3.53]) or PCS (β [95% CI]: -1.60 [-3.88, 0.67]) scores in adjusted analyses. Lower PCS and MCS scores were associated with higher depressive and anxiety symptoms, lower physical activity levels, and pain. In addition, lower PCS scores were associated with female gender, hospitalization for acute COVID-19 and longer symptom duration. CONCLUSION:In patients seeking care for long COVID in a tertiary care setting, QoL did not differ significantly between those diagnosed with FSD and other patients.

Sickle Cell Disease (SCD) is highly prevalent in sub-Saharan Africa. Epidemiological data remain sparse, but regional screening and research initiatives are expanding. Due to genetic, environmental, and socioeconomic factors, the disease course differs markedly from that in high-income countries. Although mortality is improving and can be further lowered with simple interventions, it remains high, especially among undiagnosed children. Genetic factors, poor healthcare infrastructure, and poverty contribute to disease severity. While recent collaborative programs like SickleInAfrica offer hope, national policies that foster the training of healthcare workers, newborn screening, and access to treatment are crucial to reducing the burden of SCD across the region.

BACKGROUND:Persistent Physical Symptoms (PPS) are disabling bodily symptoms lasting several months, irrespective of their underlying cause. They share mechanisms with functional disorders, characterized by a mismatch between reported symptoms and objective findings. Functional dyspnea-self-reported shortness of breath in the absence of identifiable cardiopulmonary disease-may represent an early marker of vulnerability to PPS. We investigated whether functional dyspnea assessed before the COVID-19 pandemic was associated with the incidence of PPS during the pandemic. METHODS:In this population-based study, we included participants from the French CONSTANCES cohort with normal spirometry and no known condition causing dyspnea at inclusion (2012-2019). Functional dyspnea was assessed at inclusion and incident PPS lasting more than 8 weeks were reported during the COVID-19 pandemic, regardless of SARS-CoV-2 infection. Multivariable logistic regression models adjusted for age, sex, body mass index, and educational level were used to estimate the associations. RESULTS:Among 17,326 participants (mean age 47.8 years; 54.3% women), 2230 (12.9%) reported functional dyspnea at inclusion. During the pandemic, 6687 participants (39.0%) reported at least one PPS. Functional dyspnea at inclusion was associated with a higher risk of incident PPS (OR 1.79, 95% CI [1.64-1.97], p < 0.001). Results were consistent across sensitivity analyses, including those accounting for SARS-CoV-2 infection. Depressive symptoms and self-rated health explained only a small proportion of the association. CONCLUSION:In this population-based cohort study, functional dyspnea may be a marker of future PPS, supporting the hypothesis of mechanisms common to all PPS, regardless of their type or origin.

Les troubles fonctionnels affectent fréquemment l’appareil cardiorespiratoire. La douleur thoracique non cardiaque touche plus de 10 % de la population et est très souvent associée à des troubles anxiodépressifs, notamment au trouble panique. Le syndrome de tachycardie orthostatique posturale (POTS), plus rare, est caractérisé par une forte augmentation de la fréquence cardiaque en position debout, sans hypotension orthostatique. Ses mécanismes physiopathologiques incluent une neuropathie autonome « partielle », une hypovolémie et une activation noradrénergique, mais il est aussi associé aux troubles anxieux et au déconditionnement à l’effort. Les troubles respiratoires fonctionnels, notamment le syndrome d’hyperventilation, s’accompagne de manifestations variées allant des crises de « tétanie » aux symptômes gastro-intestinaux. Leur prévalence est élevée, surtout chez les femmes et les personnes anxieuses, et particulièrement en cas de maladie respiratoire associée. Le diagnostic du syndrome d’hyperventilation repose sur le questionnaire de Nijmegen. Sa physiopathologie n’implique pas nécessairement une hypocapnie mais relève de cercles vicieux incluant une anxiété anticipatoire activant le système nerveux autonome. Les troubles fonctionnels cardiorespiratoires sont souvent liés entre eux et à d’autres troubles somatiques fonctionnels et ont en commun une dysrégulation du système nerveux autonome. Les facteurs psychologiques, cognitifs et comportementaux jouent un rôle central dans leur persistance. Si chacun a ses spécificités, ils ont tous une causalité circulaire complexe. Leur prise en charge repose actuellement avant tout sur une rééducation physique et des traitements symptomatiques comme les bêtabloquants. La place des thérapies cognitives et comportementales mériterait d’être davantage explorée dans ces troubles.

Functional disorders affecting the cardiorespiratory system are common. Non-cardiac chest pain affects more than 10% of the population. It can result from gastro-oesophageal reflux or chest wall disorders but is also very often associated with anxiodepressive disorders, particularly panic disorder. Postural orthostatic tachycardia syndrome (POTS), a rarer entity, is characterized by a sharp increase in heart rate without orthostatic hypotension when standing. The pathophysiological mechanisms of POTS include 'partial' autonomic neuropathy, hypovolaemia and noradrenergic dysregulation, but it is also closely linked to anxiety disorders and deconditioning to exertion. Functional respiratory disorders, particularly hyperventilation syndrome, are accompanied by various manifestations ranging from tetany to gastrointestinal symptoms. They are highly prevalent, especially among women and people suffering from anxiety, and particularly in the case of associated respiratory disease such as asthma. The diagnosis of hyperventilation syndrome is based on the Nijmegen questionnaire. The pathophysiology does not necessarily involve hypocapnia but is related to cerebral conditioning phenomena and vicious circles linked to anticipatory anxiety. Cardiorespiratory functional disorders are often linked to each other and to other functional somatic disorders and have in common a dysregulation of the autonomic nervous system. Psychological, cognitive and behavioural factors play a central role in their persistence. While each has its specificities, all have a complex circular causality. Their management currently relies primarily on physical rehabilitation, often associated with symptomatic treatments such as beta-blockers. The place of cognitive and behavioral therapies would be well worth exploring in these disorders.

Patients with sickle cell anemia (SCA) have long been discouraged from physical activity (PA). The aim of the present study was to assess the impact of increasing daily step counts on physical fitness, pain and vascular function in patients with SCA. Thirty-eight patients with SCA were recruited and equipped with a Fitbit wrist-worn accelerometer-based PA tracker for five weeks to objectively quantify their baseline daily step counts. Patients were then randomly assigned to one of three groups: 1) control group - no specific information regarding PA was given for eight weeks (N=12); 2) PA1 group - daily step counts increased by 25% of baseline for eight weeks (N=12); 3) PA2 group - daily step counts increased by 25% for four weeks, then by 50% for an additional four weeks (N=14). Pain intensity and frequency decreased after the intervention in the PA1 and PA2 groups. In addition, patients from these two groups increased the distance walked in six minutes. Arterial stiffness decreased in both PA1 and PA2 groups, without any change in the autonomic nervous system activity. Several inflammatory markers slightly decreased in the PA2 group. Incubation of cultured endothelial cells with patient plasma showed a decrease in the percentage of ICAM-1 positive cells in the PA2 group. This study is the first to show that adopting a simple approach to increase daily PA (i.e., increasing daily step count by 25-50%) for eight weeks is sufficient to decrease pain, and improve physical condition and vascular function of patients with SCA.

BACKGROUND:Many doctors have a complicated relationship with patients with fibromyalgia (FM), whereas they feel more comfortable with patients with well-defined clinico-biological illnesses. The aim of the study was to compare the care pathways as experienced by patients with FM or those facing well-defined rheumatic diseases. METHODS:Consecutive participants diagnosed with FM, spondyloarthritis (SpA), or rheumatoid arthritis (RA) were prospectively recruited from a tertiary outpatient center. Utilizing a semi-structured guide, participants were interviewed. A quantitative analysis compared medical pathway characteristics, and a qualitative analysis explored their experiences. RESULTS:Nineteen participants with FM and 18 with PR or SpA were included. Patients with FM exhibited increased consumption of medical care, a stronger impact on their daily lives, and a diagnostic delay that was seven times longer. All participants reported an overwhelming experience of pain and a perceived lack of credibility regarding this pain. An altered doctor-patient relationship was more prevalent among participants with FM, who expressed pessimism, feelings of rejection, and an increased need for attentive listening. CONCLUSION:Compared to usual rheumatic diseases, fibromyalgia is characterized by a prolonged diagnostic latency and faces a lack of acknowledgment, leading to a distortion in the doctor-patient relationship. However, whatever the underlying disease, patients report a lack of consideration of their pain, as long as it is unexplained.

Context Numerous labels are used to describe physical symptoms that remain for at least several months and cause significant distress (i.e., persistent physical symptoms, PPS). This study aims to assess attitudes associated with various labels among lay participants and healthcare professionals. Methods Participants recruited via mailing lists of volunteers completed an online questionnaire assessing their views on underlying physical and mental causations for ten diagnostic labels accounting for PPS. Lay participants rated their feelings of offence associated with each label, and healthcare professionals their willingness to take care of a patient diagnosed with each label. Mixed regression models investigated the factors associated with feelings of offence and willingness to care. Results 266 lay participants (mean age: 43; 70 % women) and 126 healthcare professionals (mean age: 42; 69 % women) were included. Labels rated high on perceived mental causation tended to be rated low on physical causation and vice versa in both populations, although this effect was stronger in lay participants. “Long COVID”, “persistent physical symptoms” and “functional symptoms” were rated with higher physical causation by lay participants compared to health professionals (p < 0.001), whereas “somatic symptom disorder” and “psychosomatic” were rated with higher mental causation. Regression models showed that perceived mental causation was associated with feelings of offence in lay participants, while perceived physical causation was associated with less offence. Perceived physical causation was associated with willingness to care among healthcare professionals. Discussion Some diagnostic labels provoke negative attitudes, both among lay participants and healthcare professionals, probably hindering clinician/patient relationships and treatment.

Contexte La fibromyalgie (FM) est une pathologie difficile à appréhender pour les soignants, avec un parcours de soin plus complexe que celui de pathologies mieux définies sur le plan clinicobiologique. L’objectif de cette étude était de comparer les parcours de soins vécus par des patients atteints de FM ou de rhumatismes inflammatoires (RI) : polyarthrite rhumatoïde ou spondylarthrite ankylosante. Méthodes Des patients suivis à l’hôpital, diagnostiqués avec une FM ou un RI ont été recrutés de manière prospective et consécutive en consultation et interrogés via un entretien téléphonique. Une analyse quantitative comparait les caractéristiques des parcours de soins et une analyse qualitative explorait les expériences vécues des patients. Résultats Dix-neuf participants avec FM et 18 avec RI ont été inclus. Les patients atteints de FM avaient une consommation accrue de soins, un retentissement plus important, et un délai diagnostic médian sept fois plus long que ceux du groupe RI. Tous les participants ont rapporté un manque de reconnaissance de la douleur par les soignants. La relation médecin-patient était plus altérée parmi les participants atteints de FM, qui exprimaient une vision globale pessimiste, un sentiments de rejet, et une quête attentionnelle envers les soignants. Conclusion La FM se distingue des RI par une latence diagnostique prolongée et un plus grand manque de reconnaissance perçu par les patients avec un besoin de temps d’écoute accru. Toutefois, quelle que soit la maladie sous-jacente, la douleur semble toujours mal prise en considération par les médecins, tant qu’elle est inexpliquée.

The lack of specificity in its definition is a major obstacle to both explanatory and therapeutic research in long COVID. It brings together, on the one hand, patients with severe COVID-19 who suffer the classic complications of prolonged hospitalization and decompensation of comorbidities and, on the other hand, patients with non-severe acute COVID-19 who report multiple symptoms that cannot be fully explained by a biomechanical model. Indeed, despite numerous studies, it remains unclear how persistent viral infection, immunological or coagulation disturbances may contribute mechanistically to long COVID. Nevertheless, internal medicine should be in good place to manage these patients. Indeed, the diversity of symptoms may evoke a broad spectrum of differential diagnoses that are familiar to internists. Their experience in the exploration of unexplained symptoms is also valuable. It can reduce the need for multiple consultations with specialists and unnecessary laboratory or imaging tests. However, long COVID diagnosis cannot be limited to the exclusion of all other conditions one by one. An open and non-dualistic approach is required to identify other mechanisms that may explain the symptoms. Based on their clinical experience, most French internists who responded to an opinion survey consider that long COVID corresponds most closely to a functional somatic disorder (FSD) and seek the help of specialists in mental health care to assist in the management of the patients in a multi-disciplinary approach. However, as with other FSDs, patients with long COVID are usually reluctant to be managed by mental health care specialists, given the very physical nature of their presentation. Unfortunately, most physicians are in turn reluctant to take care of them, due to poor knowledge about FSD, leading to management failure. Alternatively, a comprehensive multidisciplinary care orchestrated by an experienced internist is generally well-accepted. It includes providing rational cognitive explanations for the symptoms and support for behavioral changes tailored to the patient. While waiting for hypothetical randomized controlled trials assessing drugs with positive results, such a holistic approach has been successfully applied in many individuals with severe long COVID. However, its generalization would require a much broader training for FSD of all health care providers.

Effective rehabilitation programs targeting transdiagnostic mechanisms of persistent physical symptoms are needed in long COVID. We present a transparency-focused description of the protocol of an open-label randomized controlled trial designed to evaluate the efficacy and tolerance of a multidisciplinary intensive rehabilitation program versus usual care. After a day-hospital multidisciplinary evaluation program including minimal psychoeducation and personalized recommendations, patients presenting with persistent symptoms after COVID-19 are proposed to participate to the study. The intervention consists of a 6-week rehabilitation program with groups of 3 to 5 patients attending three day-hospital sessions per week. The rehabilitation program combines adapted physical activity (three sessions per week with progressive exertion thresholds), cognitive remediation (two computer-based personalized sessions per week) and cognitive behavioral therapy (CBT, two sessions per week: one group session and one individual session). CBT sessions encompass psychoeducation, cognitive restructuring, behavioral activation and gradual exposure, and problem-solving skills. Our primary outcome is health-related quality of life (HRQoL) at 6 months, measured with the Physical Component Score (PCS) of the 12-item Short-Form Health Survey. The secondary outcomes are the Mental Component Score (MCS) at 6 months, PCS and MCS at 3 months, the main persistent symptoms (fatigue, dyspnea, cognitive complaints, pain) and associated psychological burden at 3 and 6 months, and patients’ satisfaction at 3 months. All included patients undergo an inclusion visit including a physical condition evaluation, a neuropsychological assessment, a first consultation with the CBT therapist, and the completion of several questionnaires for the secondary outcomes (Pichot scale, Borg scale, Cognitive Difficulties Scale, pain numeric scale, and Somatic Symptom disorder-B criteria scale). These evaluations are repeated at 3- and 6-month follow-up. All analyses will be performed in intention to treat following CONSORT Statement recommendations. Our goal is to demonstrate that a multidisciplinary intensive rehabilitation program combining adapted physical activity, cognitive remediation, and CBT leads to an improvement in HRQoL in the long term (i.e., six months after a multidisciplinary evaluation program including minimal psychoeducation and personalized recommendations) in patients with long COVID, while being feasible, acceptable, and safe. NCT number NCT05532904, registration date: 2022–09-07.

Introduction: General Practitioners (GPs) play a key role of gatekeeper, as they coordinate patients' care. However, most of them reported having difficulty to refer patients to hospital, especially in semi-urgent context. To facilitate the referral of semi-urgent patients, we implemented an e-referral platform, named SIPILINK, within 4 wards from a large public French hospital (internal medicine, diabetology, gynaecological surgery and oncology wards). Here, we aimed to evaluate the SIPILINK e-referral platform after 2 years of implementation. Methods: The evaluation included a multidimensional assessment based on the RE-AIM framework with the analysis of implementation, requests, health professionals' satisfaction, and estimated hospital payment. Results: Over 2 years of implementation, GPs sent 113 requests to hospital. Hospital respected the time of response requested by GPs in 93 % of cases and proposed a consultation or hospitalization in respectively 40.7 % and 10.6 % of cases. 100 % of GPs and 78 % of Hospital Practitioners (HPs) were satisfied with the quality of exchanges. 77 % of HPs and 100 % of Care Pathway Managers (CPMs) found that patient care pathways were improved. Nearly all practitioners would recommend this platform for patient referrals. Discussion: SIPILINK shows promise in streamlining the referral process, enhancing communication, and improving patient care pathways. Further studies including the impact on the quality of care, are needed to assess its effectiveness and sustainability in healthcare settings.

Post-COVID-19 condition affects up to 10

Acute physical exercise may trigger vaso-occlusive crises (VOC) in patients with sickle cell anaemia (SCA), creating uncertainty around physical activity (PA) recommendations. This cross-sectional study examined the relationships between PA, VOC and steady-state pain in 104 Senegalese male patients with SCA. PA was objectively measured over 5 weeks, recording daily steps and time spent in different PA intensities (expressed in metabolic equivalent of task, MET). VOC occurrence was tracked, and steady-state days excluded VOC days plus 2 days before and after. Pain frequency and intensity on steady-state days were recorded via diaries, and blood viscosity was measured. Ninety-eight patients (29 ± 8 years old) completed the study, averaging 9611 ± 4040 steps/day, with 293 ± 108, 64 ± 69 and 28 ± 32 min in ≥1.5, ≥3.0, and ≥6.0 MET PA respectively. Median daily step count and PA duration were not associated with VOC occurrence. However, higher step counts and more time in ≥1.5 and ≥6.0 MET PA correlated with lower pain frequency and intensity (on steady-state days) and lower blood viscosity. These findings suggest that PA may benefit patients with SCA, but further research is needed to establish guidelines.