RESUMO
BACKGROUND: Long-term use of antipsychotics confers increased risk of cardiometabolic disease. Ongoing need should be reviewed regularly by psychiatrists. AIM: To explore trends in antipsychotic management in general practice, and proportions of patients prescribed antipsychotics receiving psychiatrist review. DESIGN AND SETTING: A serial cross-sectional study using linked general practice and hospital data in Wales (2011-2020). METHOD: Participants were adults (≥18 years) registered with general practices in Wales. Outcome measures were prevalence of patients receiving ≥6 antipsychotic prescriptions annually, proportion of patients prescribed antipsychotics receiving annual psychiatrist review, and proportion of patients prescribed antipsychotics registered on UK Serious Mental Illness, Depression and/or Dementia registers, or not on any of these registers. RESULTS: Prevalence of adults prescribed long-term antipsychotics increased from 1.06% (95%CI 1.04 to 1.07%) in 2011 to 1.45% (95%CI 1.43 to 1.46%) in 2020. The proportion receiving annual psychiatrist review decreased from 59.6% (95%CI 58.9 to 60.4%) in 2011 to 52.0% (95C%CI 51.4 to 52.7%) in 2020. The proportion of antipsychotics prescribed to patients not on the Serious Mental Illness register increased from 50% (95%CI 49 to 51%) in 2011 to 56% (95%CI 56 to 57%) by 2020. CONCLUSIONS: Prevalence of long-term antipsychotic use is increasing. More patients are managed by general practitioners without psychiatrist review and are not on monitored disease registers; they thus may be less likely to undergo cardiometabolic monitoring and miss opportunities to optimise or deprescribe antipsychotics. These trends pose risks for patients and need to be addressed urgently.
RESUMO
The processes by which a Schwann cell (SC) migrates towards, wraps around and, in some cases, myelinates an axon are incompletely understood. The complex morphological rearrangements involved in these events require fundamental changes in the actin cytoskeleton. Sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) are two modulators of the actin cytoskeleton, and receptors for these signalling lipids are expressed on SCs at the time of differentiation. Previous work has revealed a role for LPA in SC survival, morphology and differentiation, but the effects of S1P have received less attention. Here we show that S1P and LPA both cause major rearrangements to the actin cytoskeleton in primary rat SCs and the SCL4.1/F7 rat SC line. S1P and LPA caused formation of lamellipodia and a circular geodesic actin network. We also show that S1P and LPA increased cell migration. The small GTPases RhoA and Rac1 were both activated by S1P/LPA treatment, but the actin rearrangements were dependent on Rac1 and not RhoA. These effects of S1P/LPA could be mimicked by SCL4.1/F7 cell-conditioned medium, which was found to contain S1P. Reduction in cellular synthesis of S1P by adding the sphingosine kinase inhibitor dimethyl sphingosine during medium conditioning reduced the ability of conditioned medium to cause actin rearrangements. These results support a role for S1P as an autocrine signal regulating the actin cytoskeleton during Schwann cell development.