Psychological burden associated with incident persistent symptoms and their evolution during the COVID-19 pandemic: a prospective population-based study.

BACKGROUND: Identifying factors that predict the course of persistent symptoms that occurred during the COVID-19 pandemic is a public health issue. Modifiable factors could be targeted in therapeutic interventions. OBJECTIVE: This prospective study based on the population-based CONSTANCES cohort examined whether the psychological burden associated with incident persistent symptoms (ie, that first occurred from March 2020) would predict having ≥1 persistent symptom 6-10 months later. METHODS: A total of 8424 participants (mean age=54.6 years (SD=12.6), 57.2% women) having ≥1 incident persistent symptom at baseline (ie, between December 2020 and February 2021) were included. The psychological burden associated with these persistent symptoms was assessed with the Somatic Symptom Disorder-B Criteria Scale (SSD-12). The outcome was having ≥1 persistent symptom at follow-up. Adjusted binary logistic regression models examined the association between the SSD-12 score and the outcome. FINDINGS: At follow-up, 1124 participants (13.3%) still had ≥1 persistent symptom. The SSD-12 score at baseline was associated with persistent symptoms at follow-up in both participants with (OR (95% CI) for one IQR increase: 1.42 (1.09 to 1.84)) and without SARS-CoV-2 infection prior to baseline (1.39 (1.25 to 1.55)). Female gender, older age, poorer self-rated health and infection prior to baseline were also associated with persistent symptoms at follow-up. CONCLUSIONS: The psychological burden associated with persistent symptoms at baseline predicted the presence of ≥1 persistent symptom at follow-up regardless of infection prior to baseline. CLINICAL IMPLICATIONS: Intervention studies should test whether reducing the psychological burden associated with persistent symptoms could improve the course of these symptoms.

ATYPICAL FOVEAL AND PARAFOVEAL ABNORMALITIES IN SICKLE CELL DISEASE.

PURPOSE: The primary aim was to describe the patterns of paramacular involvement, not yet reported but that optical coherence tomography angiography can now detect in patients with sickle cell disease. The secondary aim was to search arguments concerning the physiopathogeny of paramacular involvement. METHODS: This institutional cohort retrospective study was conducted in a Referral Center for Ophthalmological Rare Diseases. Follow-up included an ophthalmologic examination with optical coherent tomography and optical coherent tomography angiography. RESULTS: One hundred and thirty-two patients with SCD were included. Typical sickle cell maculopathy was observed in temporal area in 84 eyes (40.0%) of SS patients and eight eyes (14.8%) of SC patients ( P < 0.001). Enlargement of the foveal avascular zone was observed in 10 eyes of eight SS patients. Two atypical parafoveal abnormalities were found in SS patients only. The first one consisted of macular thinning with normal vascularization in 15 eyes of 11 patients. The second atypical maculopathy was large areas of loss of vascularization without retinal thinning 10 eyes of six patients. Multivariate analysis did not show a statistically significant relation between the peripheral sickle retinopathy stage and the different type of sickle cell maculopathy ( P = 0.21). CONCLUSION: Those atypical sickle cell maculopathy may correspond to early forms preceding a typical sickle cell disease maculopathy (SCDM). This would point toward several physiopathogenic mechanisms. The first one included the existence of ischemia that can be related to anemia. Presence of retinal thinning without vascular involvement point out to a neurogenic mechanism.

Management perspectives from patients with fibromyalgia experiences with the healthcare pathway: a qualitative study.

Background: Fibromyalgia is a prevalent condition affecting 1-2% of the general population and can result in significant disability. Physicians and patients frequently encounter challenges in managing this condition. Aim: The aim of this study was to explore novel management approaches through a qualitative analysis of the doctor-patient relationship. Design and setting: Telephonic interviews were conducted with fibromyalgia patients to investigate their healthcare experiences. Methods: Qualitative analysis was performed on patients' narratives using interpretative phenomenological analysis, a methodology that delves into each individual's subjectivity. Results: A total of 19 adult patients with fibromyalgia, primarily middle-aged women (84% women, mean age 49.8 years), recruited from two university centers in Paris, were included in the study. The narratives of participants revealed substantial suffering and considerable functional impairment, which is paradoxical for a condition often considered benign. They reported an ongoing sense of loss of control, exacerbated by an imbalanced patient-doctor relationship. Patients constantly feared not being heard or believed, and they frequently sought attention from their caregivers. Most participants displayed significant ambivalence toward the nature of their condition and actively sought causal links. Patients' adaptive strategies sometimes worsened their symptoms, as in the case of muscular deconditioning. The healthcare system appeared deficient in managing these patients, characterized by a lack of health professional training, frequent inappropriate responses from healthcare providers, and stigmatization of psychological conditions. Conclusion: Despite its perceived benign nature, fibromyalgia should be regarded as a severe condition due to its substantial long-term consequences. Participants reported a challenging experience with the doctor-patient relationship, marked by a strong sense of dependence and a lack of recognition. The care pathway for these patients appeared unsuitable and disorderly, potentially resulting in iatrogenic consequences. The management of patients with fibromyalgia should be enhanced and directed toward a patient-centered approach. The study provides practical recommendations regarding communication methods and patient care.

Relationship between paramacular thinning, cerebral vasculopathy, and hematological risk factors in sickle cell disease.

Purpose: To identify risk factors for sickle cell maculopathy due to hematological parameters (especially anemia and hemolysis) or cerebral vasculopathy. Methods: This retrospective study was conducted at a Referral Center. The follow-up included optical coherent tomography/optical coherent tomography angiography, neuro-radiological imaging, and a hematological assessment (hemoglobin, hemoglobin S level, reticulocytes, mean corpuscular volume, bilirubin, and lactate dehydrogenase). Results: Hundred and thirty-two sickle cell patients were included. Maculopathy was observed in 127 eyes of SS patients and 10 eyes of SC patients (p < 0.001), unrelated to peripheral retinopathy. Cerebral vasculopathy was more frequent in SS patients (p < 0.001) and was also associated with the presence of maculopathy (p = 0.049), and it was related to peripheral retinopathy (p < 0.001). All biological parameters significantly differed according to the genotype (p < 0.001) but not according to the presence of cerebral vasculopathy or maculopathy. In the multivariate analysis, reticulocytes and bilirubin were associated with the presence of cerebral vasculopathy and maculopathy. Conclusion: The data obtained were consistent with the role of anemia or hemolysis markers in cerebral vasculopathy and macular involvement. As a trend of hemolysis appears to be a risk factor for these complications, this validates the use of preventive plasmapheresis in these patients.

Association of haemolysis markers, blood viscosity and microcirculation function with organ damage in sickle cell disease in sub-Saharan Africa (the BIOCADRE study).

Sickle cell anaemia (SCA) is a monogenic disease with a highly variable clinical course. We aimed to investigate associations between microvascular function, haemolysis markers, blood viscosity and various types of SCA-related organ damage in a multicentric sub-Saharan African cohort of patients with SCA. In a cross-sectional study, we selected seven groups of adult patients with SS phenotype in Dakar and Bamako based on the following complications: leg ulcer, priapism, osteonecrosis, retinopathy, high tricuspid regurgitant jet velocity (TRV), macro-albuminuria or none. Clinical assessment, echocardiography, peripheral arterial tonometry, laboratory tests and blood viscosity measurement were performed. We explored statistical associations between the biological parameters and the six studied complications. Among 235 patients, 58 had high TRV, 46 osteonecrosis, 43 priapism, 33 leg ulcers, 31 retinopathy and 22 macroalbuminuria, whereas 36 had none of these complications. Multiple correspondence analysis revealed no cluster of complications. Lactate dehydrogenase levels were associated with high TRV, and blood viscosity was associated with retinopathy and the absence of macroalbuminuria. Despite extensive phenotyping of patients, no specific pattern of SCA-related complications was identified. New biomarkers are needed to predict SCA clinical expression to adapt patient management, especially in Africa, where healthcare resources are scarce.

Depression and anxiety before and at the beginning of the COVID-19 pandemic and incident persistent symptoms: a prospective population-based cohort study.

Many patients affected by COVID-19 suffer from debilitating persistent symptoms whose risk factors remained poorly understood. This prospective study examined the association of depression and anxiety symptoms measured before and at the beginning of the COVID-19 pandemic with the incidence of persistent symptoms. Among 25,114 participants [mean (SD) age, 48.72 years (12.82); 51.1% women] from the SAPRIS and SAPRIS-Sérologie surveys nested in the French CONSTANCES population-based cohort, depression and anxiety symptoms were measured with the Center for Epidemiologic Studies-Depression scale and the 12-item General Health Questionnaire before the pandemic, and with the 9-item Patient Health Questionnaire and the 7-Item Generalized Anxiety Disorder scale at the beginning of the pandemic (i.e., between April 6, 2020 and May 4, 2020). Incident persistent symptoms were self-reported between December 2020 and January 2021. The following variables were also considered: gender, age, educational level, household income, smoking status, BMI, hypertension, diabetes, self-rated health, and SARS-CoV-2 infection according to serology/PCR test results. After a follow-up of seven to ten months, 2329 participants (9.3%) had been infected with SARS-CoV-2 and 4262 (17.0%) reported at least one incident persistent symptom that emerged from March 2020, regardless of SARS-CoV-2 infection. In multi-adjusted logistic regression models, participants in the highest (versus the lowest) quartile of depressive or anxiety symptom levels before or at the beginning of the pandemic were more likely to have at least one incident persistent symptom (versus none) at follow-up [OR (95%CI) ranging from 2.10 (1.89-2.32) to 3.01 (2.68-3.37)], with dose-response relationships (p for linear trend <0.001). Overall, these associations were significantly stronger in non-infected versus infected participants, except for depressive symptoms at the beginning of the pandemic. Depressive symptoms at the beginning of the pandemic were the strongest predictor of incident persistent symptoms in both infected and non-infected participants [OR (95%CI): 2.88 (2.01-4.14) and 3.03 (2.69-3.42), respectively]. In exploratory analyses, similar associations were found for each symptom taken separately in different models. Depression and anxiety symptoms should be tested as a potential target for preventive interventions against persistent symptoms after an infection with SARS-CoV-2.

[Role of psychological factors in post-COVID-19 condition]. / Rôle des facteurs psychologiques dans l'affection post-COVID-19.

Even after a mild episode of coronavirus disease 2019 (COVID-19), many patients suffer from persistent symptoms that can impair their quality of life for months. The potential role of psychological mechanisms in this post-COVID-19 condition, often referred to as long COVID, has been discussed early in the pandemic. Evidence supporting this hypothesis is now accumulating. First, a history of anxiety or depression is now an established risk factor for post-COVID-19 condition with a dose-response relationship and effect size similar to those of other known risk factors. This association extends to other forms of psychological distress, including perceived stress and loneliness. Second, specific beliefs about COVID-19 have been associated with the risk of subsequent similar symptoms, occurring weeks to several months later. Other studies, which have yet to be replicated, suggest an influence of the context of the initial infection (first versus second wave of the pandemic, before the emergence of significant variants and vaccination) and the trust in various sources of information about COVID-19 on the risk of subsequent symptoms. Bayesian models of perception can account for these results particularly well within a theoretical framework similar to that advanced for functional somatic disorders, integrating increased symptom expectations with decreased perception of the body internal state (interoception) and intolerance of uncertainty in the context of symptoms initially triggered by an infectious episode. These psychological mechanisms should obviously not be considered as exclusive. However, since they are modifiable, they could be targeted in clinical trials, within an integrative and multidisciplinary approach.

Trust in sources of information on COVID-19 at the beginning of the pandemic's first wave and incident persistent symptoms in the population-based CONSTANCES cohort: A prospective study.

OBJECTIVE: To examine the association between trust in different sources of information on COVID-19 at the beginning of the pandemic and the burden of incident persistent symptoms. METHODS: This prospective study used data from the SAPRIS and SAPRIS-Sérologie surveys nested in the French CONSTANCES population-based cohort. Trust in different information sources was measured between April 6 and May 4, 2020. Persistent symptoms that emerged afterwards were self-reported between December 2020 and January 2021. The associated psychological burden was measured with the somatic symptom disorder B criteria scale (SSD-12). The analyses were adjusted for gender, age, education, income, self-rated health, SARS-CoV-2 serology tests, and self-reported COVID-19. RESULTS: Among 20,985 participants [mean age (SD), 49.0 years (12.7); 50.2% women], those with higher trust in government/journalists at baseline had fewer incident persistent symptoms at follow-up (estimate (SE) for one IQR increase: -0.21 (0.03), p < 0.001). Participants with higher trust in government/journalists and medical doctors/scientists were less likely to have ≥1 symptom (odds ratio (95% confidence interval) for one IQR increase: 0.87 (0.82-0.91) and 0.91 (0.85-0.98), respectively). Among 3372 participants (16.1%) who reported ≥1 symptom, higher trust in government/journalists and medical doctors/scientists predicted lower SSD-12 scores (-0.39 (0.17), p = 0.02 and - 0.85 (0.24), p < 0.001, respectively), whereas higher trust in social media predicted higher scores in those with lower trust in government/journalists (0.90 (0.34), p = 0.008). These associations did not depend upon surrogate markers of infection with SARS-CoV-2. CONCLUSIONS: Trust in information sources on COVID-19 may be associated with incident persistent symptoms and associated psychological burden, regardless of infection with SARS-CoV-2.

Acute chest syndrome in adult patients with sickle cell disease: The relationship with the time to onset after hospital admission.

Data on acute chest syndrome (ACS) in adult sickle cell disease patients are scarce. In this study, we describe 105 consecutive ACS episodes in 81 adult patients during a 32-month period and compare the characteristics as a function of the time to onset after hospital admission for a vaso-occlusive crisis (VOC), that is early-onset episodes (time to onset ≤24 h, 42%) versus secondary episodes (>24 h, 58%; median [interquartile range] time to onset: 2 [2-3] days). The median age was 27 [22-34] years, 89% of the patients had an S/S or S/ß0 -thalassaemia genotype; 81% of the patients had a history of ACS (median: 3 [2-5] per patient), only 61% were taking a disease-modifying treatment at the time of the ACS. Fever and chest pain were noted in respectively 54% and 73% of the episodes. Crackles (64%) and bronchial breathing (32%) were the main abnormal auscultatory findings. A positive microbiological test was found for 20% of episodes. Fifty percent of the episodes required a blood transfusion; ICU transfer and mortality rates were respectively 29% and 1%. Secondary and early-onset forms of ACS did not differ significantly. Disease-modifying treatments should be revaluated after each ACS episode because the recurrence rate is high.

Somatic symptom disorder in patients with post-COVID-19 neurological symptoms: a preliminary report from the somatic study (Somatic Symptom Disorder Triggered by COVID-19).

OBJECTIVES: To assess the diagnosis of somatic symptom disorder (SSD) in patients with unexplained neurological symptoms occurring after SARS-CoV-2 infection, also referred to as long COVID. DESIGN: Single-centre observational study. PARTICIPANTS: Adult patients experiencing unexplained long-lasting neurological symptoms after mild COVID. Of the 58 consecutive patients referred in our centre, 50 were included. INTERVENTION: Patients were contacted for a standardised psychometric evaluation by phone, followed by a self-survey. MAIN OUTCOME: Positive diagnosis of SSD according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5). RESULTS: Although the patients did not meet the DSM-5 criteria for a functional neurological symptom disorder specifically, SSD diagnosis based on DSM-5 criteria was positive in 32 (64%) patients. In the remaining 18 patients, SSD was considered possible given the high score on diagnostic scales. Physical examination were normal for all. Brain MRI showed unspecific minor white matter hyperintensities in 8/46 patients. Neuropsychological assessment showed exclusively mild impairment of attention in 14 out of 15 tested patients, in discrepancy with their major subjective complaint. Forty-five (90%) patients met criteria for Chronic Fatigue Syndrome. Seventeen (32%) patients were screened positive for mood-anxiety disorders, 19 (38%) had a history of prior SSD and 27 (54%) reported past trauma. Additional self-survey highlighted post-traumatic stress disorder in 12/43 (28%), high levels of alexithymia traits and perfectionism. Long-lasting symptoms had a major impact with a high rate of insomnia (29/43, 67%), psychiatric follow-up (28/50, 56%) and work or pay loss (25/50, 50%). CONCLUSION: A majority of patients with unexplained long-lasting neurological symptoms after mild COVID met diagnostic criteria for SSD and may require specific management. TRIAL REGISTRATION NUMBER: NCT04889313.

Risks and Benefits of Prophylactic Transfusion before Cholecystectomy in Sickle Cell Disease.

Preoperative transfusion (PT) reduces acute postoperative vaso-occlusive events (VOE) in sickle cell disease (SCD), but exposes patients to alloimmunization, encouraging a recent trend towards transfusion sparing. The aim of this study was to investigate the benefit-risk ratio of PT before cholecystectomy on the occurrence of postoperative VOE. Adult SCD patients who underwent cholecystectomy between 2008 and 2019 in our center were included. Patients' characteristics, collected retrospectively, were compared according to PT. A total of 79 patients were included, 66% of whom received PT. Gallbladder histopathology found chronic cholecystitis (97%) and gallstones (66%). Transfused patients underwent more urgent surgeries and had experienced more painful vaso-occlusive crises (VOC) in the month before surgery (p = 0.05). Four (8.5%) post-transfusion alloimmunizations occurred, and two of them caused a delayed hemolytic transfusion reaction (DHTR) (4.3%). The occurrence of postoperative VOE was similar between the groups (19.2% vs. 29.6%, p = 0.45). Though not statistically significant, a history of hospitalized VOC within 6 months prior to surgery seemed to be associated to postoperative VOE among non-transfused patients (75% vs. 31.6%, p = 0.10). PT before cholecystectomy exposes to risks of alloimmunization and DHTR that could be avoided in some patients. Recent VOCs appear to be associated with a higher risk of postoperative VOE and prompt the preemptive transfusion of these patients.

Estimating the risk of child mortality attributable to sickle cell anaemia in sub-Saharan Africa: a retrospective, multicentre, case-control study.

BACKGROUND: Many children with sickle cell disease living in sub-Saharan Africa die before reaching age 5 years. We estimate the child mortality associated with sickle cell anaemia using an indirect approach to overcome the absence of systematic screening at birth. METHODS: We did a retrospective, multicentre, case-control study in five countries in sub-Saharan Africa (Burkina Faso, Democratic Republic of the Congo, Côte d'Ivoire, Mali, and Senegal). Women with at least one child with a confirmed SS haemoglobin phenotype (sickle cell anaemia) and who had at least three (alive or deceased) children from the same father born more than 5 years ago were recruited at an outpatient consultation in a sickle cell disease care centre. Women who had children without sickle cell disease (control group) were recruited from the same area, with inclusion criteria of being a neighbour or relative of one of the mothers included in the study who had a child with sickle cell anaemia, having no child or other first-degree relative with major sickle cell syndrome, having at least three children (alive or deceased) born more than 5 years ago, and having a confirmed haemoglobin AA phenotype. During the mothers' interview, we collected data concerning the mortality of siblings from the same father of a child with sickle cell anaemia and characteristics of the family, such as age at the time of the survey and the level of education of both parents. Mortality rates were calculated for children younger than 1, 5, and 10 years using the Kaplan-Meier method after excluding the index children. We assumed, as per Mendel law, that in families who have a child with sickle cell anaemia and healthy heterozygous parents, 25% of children born on average have sickle cell anaemia. A multivariate Cox model was used to describe socioeconomic and geographical factors associated with mortality. FINDINGS: Between Sept 1, 2017, and Nov 30, 2020, 1563 women who had at least one child with sickle cell anaemia and 4972 women from the same neighbourhood who had children without sickle cell disease were assessed for eligibility. Of 1563 women, 248 were excluded because the genotype of the index child was SC or S ß-thalassaemia. 1315 families with cases of sickle cell anaemia and 1243 control families were included in the study. The median age of children (alive) was 14 years (IQR 8-20) in control families and 13 years (8-19) in families with cases of sickle cell anaemia. 5532 [50·6%] of 10 924 children were male. Mortality rates were 15·3% (95% CI 13·3-17·3) for children with sickle cell anaemia younger than 1 year, 36·4% (33·4-39·4) for those younger than 5 years, and 43·3% (39·3-47·3) for those younger than 10 years. Multivariate Cox survival analysis showed that belonging to a family with sickle cell anaemia (hazard ratio [HR] 2·23, 95% CI 1·96-2·54), living in the Democratic Republic of the Congo (HR 1·64, 1·34-2·01), having an older parent (father or mother age had similar effect; HR 1·12, 1·05-1·19 per 10 years of age), or a significantly higher global Multidimensional Poverty Index (HR 1·09, 1·03-1·14), independently increased the risk of mortality. Whereas, living in Senegal (HR 0·70, 95% CI 0·57-0·86) or having a mother with higher education (high school HR 0·66, 0·55-0·80 or advanced HR 0·41, 0·28-0·61) independently decreased the risk of mortality. INTERPRETATION: Although higher than in high-income countries and affected by non-specific socioeconomic factors, the estimated mortality in children with sickle cell anaemia living in sub-Saharan African cities was substantially lower than previous estimates, suggesting an improvement of sickle cell anaemia care in this setting. FUNDING: Fondation Pierre Fabre. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Neurological complications of varicella zoster virus reactivation: Prognosis, diagnosis, and treatment of 72 patients with positive PCR in the cerebrospinal fluid.

BACKGROUND: VZV infection can involve every level of the neurologic system: from the central nervous system (CNS) to the peripheral nervous system (PNS), including aseptic meningitis. Prognosis seems to differ between these neurological involvements. Prognostic factors remain unknown. METHODS: This is a retrospective multicenter study including all patients with a positive VZV polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF) from eight centers in Paris (France) between 2011 and 2018. Unfavorable outcome was defined as mortality linked to VZV or incomplete recovery. Modified Rankin Scale (mRS) evaluated disability before and after the infection, with the difference designated as Rankin Delta. RESULTS: Seventy-two patients were included (53% male, median age 51 years, median mRS 0). Immunosuppression was reported in 42%. The clinical spectrum included 26 cases of meningitis, 27 instances of CNS involvement, 16 of PNS involvement, and 3 isolated replications (positive PCR but no criteria for neurological complications from VZV). Antiviral treatment was administered to 69 patients (96%). Sixty-two patients completed follow-up. Death linked to VZV occurred in eight cases. Unfavorable outcome (UO) occurred in 60% and was significantly associated with a higher prior mRS (Odd-ratio (OR) 3.1 [1.4-8.8] p = .012) and the presence of PNS or CNS manifestations (OR 22 [4-181] p = .001, OR 6.2 [1.3-33] p = .03, respectively, compared to meningitis). In the CSF, higher protein level (p < .0001) was also significantly associated with a higher Rankin Delta. CONCLUSIONS: Neurological complications of VZV with evidence of CSF viral replication are heterogeneous: aseptic meningitis has a good prognosis, whereas presence of CNS and PNS involvement is associated with a higher risk of mortality and of sequelae, respectively.

Ketoacidosis in a non-diabetic lactating woman: A case report and literature review.

We report the case of a 36-year-old woman who developed non-diabetic ketoacidosis following a low carbohydrate diet in order to lose weight while actively breast feeding her newborn. She was admitted in intensive care unit because of severe metabolic acidosis. She rapidly recovered after refeeding process. Lactation ketoacidosis, a special condition that occurs in non-diabetic breastfeeding women, is rare and life-threatening. This report highlights the importance of nutritional education of lactating women in the post-partum period.