Correlation between unproven therapies and delayed return-to-work for COVID-19-infected healthcare workers.

The objective of this study is to investigate factors influencing the time to return to work (RTW) of HealthCare Workers (HCW) infected with COVID-19 during the initial wave of the pandemic in a southern French university hospital. Data collection of 170 HCW (between March 16 to June 1, 2020) included demographic and professional information, clinical profiles, comorbidities, medical management, therapies and RT-PCR results. The mean time to RTW was 15.6 days. Multivariate analyses revealed that the time to RTW was shorter among laboratory and emergency workers, while it was longer for HCW aged 40 to 49 years, at higher risk of severe illness, with a delayed negative SARS-CoV-2 PCR or those treated with azithromycin and/or hydroxychloroquine. This study highlights diverse factors affecting HCW RTW post-COVID-19 infection, underscoring the importance of exercising caution in administering unproven therapies to HCW during the early stages of a novel infectious pandemic.

Permanent unfitness for work and mental disorders: a multicentric cross-sectional study of 2,788 unfit employees.

In France, Mental Disorders (MD) are the second most common medical cause of unfitness-for-work notices. The main objective is to describe the MD causing permanent medically unfitness at the workstation. A cross-sectional multicenter survey was conducted among employees followed by 323 physicians from occupational health services of the South of France in 2017. The MD responsible for unfitness for the job were coded according to the ICD-10 nomenclature and their occupational origin was estimated by each physician. On 359,966 employees screened, 2,788 were unfitted. Among the 2,779 unfitness cases which were analysed, 985 were unfitted for MD. The incidence rate of unfitness for MD was 2.78 unfit per 1,000 employees followed. Representing 36.8% (985 cases) of all grounds for unfitness, MD were estimated to be work-related in 614 (63.6%) of cases. The main MD were 449 (45.6%) cases of major depressive episodes, 227 (23.0%) anxiety disorders and 131 (13.3%) recurrent depressive disorders. Their occupational origin was mentioned in 296 (67.3%), 168 (74.7%), 62 (49.6%) cases and the link with a Burnout (BO) in 166 (38.3%), 61 (27.9%) and 41 (34.2%) cases respectively among 364 all pathologies reported to a BO. Unfitness for MD was more common among women (ORa = 1.79 95% CI [1.50-2.13]), working in trade, transport, accommodation and catering (ORa = 1.47 95% CI [1.04-2.09]) and increase with age (ORa = 4.24 95% CI [2.73-6.60] for over 55). Major depressive episodes represent the MD most frequently responsible for unfitness and the most related to occupational origin.

Job retention for people with bipolar disorder: A qualitative analysis.

At least half of people with bipolar disorder, whose global prevalence is greater than 1% of the general population, do not have a stable occupation. The objective of this study is to identify the factors perceived by bipolar people as having an impact on retention in employment. Semi-directed individual interviews were offered to subjects with bipolar disorder, of working age, who had been seen by three different hospital departments in the south of France. These people had to be medically stable and have at least one occupational experience. Each interview was recorded and transcribed manually and then analyzed according to a thematic classification of verbatims. Nineteen people participated in the interviews. Three major themes identified were classified into intrinsic (working routine and working environment) and extrinsic (external aids) factors for the bipolar person. The majority believe that working regular hours is a balancing factor. For everyone, night work and stress factors can lead to relapses. All stressed the need to destigmatize the disease. Most believe that it is necessary to develop employment support organizations specific to mental illnesses. This research helps to inform people with bipolar disorder about the occupational factors that help balance their condition. Personalized multidisciplinary care pathways involving occupational medicine must be developed in order to promote the balance of the disease and job retention.

Meta-analysis of effort-reward imbalance prevalence among physicians.

OBJECTIVE: Estimate the effort-reward imbalance prevalence (ERI) among physicians. METHODS: A systematic review was conducted from 2005 to 2019 using PRISMA guidelines on the PubMed and EBSCOhost search engines. Data were classified according to the ERI definition used by the authors. A meta-analysis was performed on effort and reward scores and on ERI prevalence rates. RESULTS: Out of 3787 results, we selected 41 studies. The physicians' ERI prevalence rate ranged from 3.50 to 96.9%. The standardized pooled effort mean score was 58.5 for effort and 48.9 for a reward out of 100, respectively. The overall combined ERI rate (when the ratio between effort and reward scores was above 1) was 40.2% among 21,939 practitioners (31.7% in the working European population). ERI rate was 70.2% using a four-point Likert scale and 21.1% using a five-point Likert scale. The highest rate (96.9%) was observed among German rural general practitioners and the lowest rate (3.50%) among Swiss hospital practitioners. The low percentage of variability (I2 = 27%) attributed to effort scores heterogeneity between studies suggested that this dimension is not discriminant in the physician ERI assessment. The high heterogeneity in reward scores (I2 = 83%) indicated that this dimension is sensible in ERI assessment among physicians. The number of items used did not appear as a significant source of heterogeneity. CONCLUSION: Physician job ERI appeared to be higher than in the working population. Studying each dimension and item indicators could help improve psychosocial risk prevention.

Screening of health workers exposed to SARS-CoV-2 in a university hospital in the south of France.

INTRODUCTION: SARS-CoV-2, which causes COVID-19, is a virus that has caused a global pandemic. Health workers (HWs) are major players in the fight against this infection and are occupationally exposed to the virus in the course of their work. In this context, this study presents surveillance data on 1714 workers in a hospital center in the south of France for the period from March 17 to April 20, 2020. MATERIALS AND METHODS: Symptomatic HWs, contact cases and those with high anxiety were tested. Diagnosis of COVID-19 was performed by RT-PCR after nasopharyngeal sampling. RESULTS: During this period, 30.4% of hospital staff received 3028 nasal swabs. Of these, 8.0% were infected with SARS-CoV-2. Among the SARS-CoV-2 positive HWs, 24.3% were asymptomatic. Among COVID unit and non COVID unit, the positive HWs for SARS-CoV-2 were, respectively, 5.8% and 8.2% (p = 0.2). HWs over 50 years of age were less likely to be positive for SARS-CoV-2 (3.8%) than other younger HWs (9.1%) (p < 0.001). No serious cases of COVID-19 were reported in our population during this period. DISCUSSION: Our study suggests that HWs who tested positive for COVID-19 are often asymptomatic. Therefore, PPE is pivotal to prevent HWs to patients and HWs to HWs transmission during workshifts. Contact tracing and screening is essential to limit the spread of the virus within the hospital. On the other hand, HWs working in COVID-19 units are not more often infected probably because they have a higher risk awareness than other HWs.

Trpm5 channels encode bistability of spinal motoneurons and ensure motor control of hindlimbs in mice.

Bistable motoneurons of the spinal cord exhibit warmth-activated plateau potential driven by Na+ and triggered by a brief excitation. The thermoregulating molecular mechanisms of bistability and their role in motor functions remain unknown. Here, we identify thermosensitive Na+-permeable Trpm5 channels as the main molecular players for bistability in mouse motoneurons. Pharmacological, genetic or computational inhibition of Trpm5 occlude bistable-related properties (slow afterdepolarization, windup, plateau potentials) and reduce spinal locomotor outputs while central pattern generators for locomotion operate normally. At cellular level, Trpm5 is activated by a ryanodine-mediated Ca2+ release and turned off by Ca2+ reuptake through the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pump. Mice in which Trpm5 is genetically silenced in most lumbar motoneurons develop hindlimb paresis and show difficulties in executing high-demanding locomotor tasks. Overall, by encoding bistability in motoneurons, Trpm5 appears indispensable for producing a postural tone in hindlimbs and amplifying the locomotor output.

Cleavage of Na(+) channels by calpain increases persistent Na(+) current and promotes spasticity after spinal cord injury.

Upregulation of the persistent sodium current (I(NaP)) in motoneurons contributes to the development of spasticity after spinal cord injury (SCI). We investigated the mechanisms that regulate I(NaP) and observed elevated expression of voltage-gated sodium (Nav) 1.6 channels in spinal lumbar motoneurons of adult rats with SCI. Furthermore, immunoblots revealed a proteolysis of Nav channels, and biochemical assays identified calpain as the main proteolytic factor. Calpain-dependent cleavage of Nav channels after neonatal SCI was associated with an upregulation of I(NaP) in motoneurons. Similarly, the calpain-dependent cleavage of Nav1.6 channels expressed in human embryonic kidney (HEK) 293 cells caused the upregulation of I(NaP). The pharmacological inhibition of calpain activity by MDL28170 reduced the cleavage of Nav channels, I(NaP) in motoneurons and spasticity in rats with SCI. Similarly, the blockade of I(NaP) by riluzole alleviated spasticity. This study demonstrates that Nav channel expression in lumbar motoneurons is altered after SCI, and it shows a tight relationship between the calpain-dependent proteolysis of Nav1.6 channels, the upregulation of I(NaP) and spasticity.

Sensitization of neonatal rat lumbar motoneuron by the inflammatory pain mediator bradykinin.

Bradykinin (Bk) is a potent inflammatory mediator that causes hyperalgesia. The action of Bk on the sensory system is well documented but its effects on motoneurons, the final pathway of the motor system, are unknown. By a combination of patch-clamp recordings and two-photon calcium imaging, we found that Bk strongly sensitizes spinal motoneurons. Sensitization was characterized by an increased ability to generate self-sustained spiking in response to excitatory inputs. Our pharmacological study described a dual ionic mechanism to sensitize motoneurons, including inhibition of a barium-sensitive resting K(+) conductance and activation of a nonselective cationic conductance primarily mediated by Na(+). Examination of the upstream signaling pathways provided evidence for postsynaptic activation of B2 receptors, G protein activation of phospholipase C, InsP3 synthesis, and calmodulin activation. This study questions the influence of motoneurons in the assessment of hyperalgesia since the withdrawal motor reflex is commonly used as a surrogate pain model.

Sodium-mediated plateau potentials in lumbar motoneurons of neonatal rats.

The development and the ionic nature of bistable behavior in lumbar motoneurons were investigated in rats. One week after birth, almost all (∼80%) ankle extensor motoneurons recorded in whole-cell configuration displayed self-sustained spiking in response to a brief depolarization that emerged when the temperature was raised >30°C. The effect of L-type Ca(2+) channel blockers on self-sustained spiking was variable, whereas blockade of the persistent sodium current (I(NaP)) abolished them. When hyperpolarized, bistable motoneurons displayed a characteristic slow afterdepolarization (sADP). The sADPs generated by repeated depolarizing pulses summed to promote a plateau potential. The sADP was tightly associated with the emergence of Ca(2+) spikes. Substitution of extracellular Na(+) or chelation of intracellular Ca(2+) abolished both sADP and the plateau potential without affecting Ca(2+) spikes. These data suggest a key role of a Ca(2+)-activated nonselective cation conductance ((CaN)) in generating the plateau potential. In line with this, the blockade of (CaN) by flufenamate abolished both sADP and plateau potentials. Furthermore, 2-aminoethoxydiphenyl borate (2-APB), a common activator of thermo-sensitive vanilloid transient receptor potential (TRPV) cation channels, promoted the sADP. Among TRPV channels, only the selective activation of TRPV2 channels by probenecid promoted the sADP to generate a plateau potential. To conclude, bistable behaviors are, to a large extent, determined by the interplay between three currents: L-type I(Ca), I(NaP), and a Na(+)-mediated I(CaN) flowing through putative TRPV2 channels.

Activity-dependent changes in extracellular Ca2+ and K+ reveal pacemakers in the spinal locomotor-related network.

Changes in the extracellular ionic concentrations occur as a natural consequence of firing activity in large populations of neurons. The extent to which these changes alter the properties of individual neurons and the operation of neuronal networks remains unknown. Here, we show that the locomotor-like activity in the isolated neonatal rodent spinal cord reduces the extracellular calcium ([Ca(2+)]o) to 0.9 mM and increases the extracellular potassium ([K(+)]o) to 6 mM. Such changes in [Ca(2+)]o and [K(+)]o trigger pacemaker activities in interneurons considered to be part of the locomotor network. Experimental data and a modeling study show that the emergence of pacemaker properties critically involves a [Ca(2+)]o-dependent activation of the persistent sodium current (INaP). These results support a concept for locomotor rhythm generation in which INaP-dependent pacemaker properties in spinal interneurons are switched on and tuned by activity-dependent changes in [Ca(2+)]o and [K(+)]o.