Pharmacological, non-invasive brain stimulation and psychological interventions, and their combination, for treating depression after stroke.

BACKGROUND: Depression is an important morbidity associated with stroke that impacts on recovery, yet is often undetected or inadequately treated. OBJECTIVES: To evaluate the benefits and harms of pharmacological intervention, non-invasive brain stimulation, psychological therapy, or combinations of these to treat depression after stroke. SEARCH METHODS: This is a living systematic review. We search for new evidence every two months and update the review when we identify relevant new evidence. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review. We searched the Specialised Registers of Cochrane Stroke, and Cochrane Depression Anxiety and Neurosis, CENTRAL, MEDLINE, Embase, five other databases, two clinical trials registers, reference lists and conference proceedings (February 2022). We contacted study authors. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing: 1) pharmacological interventions with placebo; 2) non-invasive brain stimulation with sham stimulation or usual care; 3) psychological therapy with usual care or attention control; 4) pharmacological intervention and psychological therapy with pharmacological intervention and usual care or attention control; 5) pharmacological intervention and non-invasive brain stimulation with pharmacological intervention and sham stimulation or usual care; 6) non-invasive brain stimulation and psychological therapy versus sham brain stimulation or usual care and psychological therapy; 7) pharmacological intervention and psychological therapy with placebo and psychological therapy; 8) pharmacological intervention and non-invasive brain stimulation with placebo and non-invasive brain stimulation; and 9) non-invasive brain stimulation and psychological therapy versus non-invasive brain stimulation and usual care or attention control, with the intention of treating depression after stroke. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risk of bias, and extracted data from included studies. We calculated mean difference (MD) or standardised mean difference (SMD) for continuous data, and risk ratio (RR) for dichotomous data, with 95% confidence intervals (CIs). We assessed heterogeneity using the I² statistic and certainty of the evidence according to GRADE. MAIN RESULTS: We included 65 trials (72 comparisons) with 5831 participants. Data were available for: 1) 20 comparisons; 2) nine comparisons; 3) 25 comparisons; 4) three comparisons; 5) 14 comparisons; and 6) one comparison. We found no trials for comparisons 7 to 9. Comparison 1: Pharmacological interventions Very low-certainty evidence from eight trials suggests pharmacological interventions decreased the number of people meeting the study criteria for depression (RR 0.70, 95% CI 0.55 to 0.88; P = 0.002; 8 RCTs; 1025 participants) at end of treatment and very low-certainty evidence from six trials suggests that pharmacological interventions decreased the number of people with inadequate response to treatment (RR 0.47, 95% CI 0.32 to 0.70; P = 0.0002; 6 RCTs; 511 participants) compared to placebo. More adverse events related to the central nervous system (CNS) (RR 1.55, 95% CI 1.12 to 2.15; P = 0.008; 5 RCTs; 488 participants; very low-certainty evidence) and gastrointestinal system (RR 1.62, 95% CI 1.19 to 2.19; P = 0.002; 4 RCTs; 473 participants; very low-certainty evidence) were noted in the pharmacological intervention than in the placebo group. Comparison 2: Non-invasive brain stimulation Very low-certainty evidence from two trials show that non-invasive brain stimulation had little to no effect on the number of people meeting the study criteria for depression (RR 0.67, 95% CI 0.39 to 1.14; P = 0.14; 2 RCTs; 130 participants) and the number of people with inadequate response to treatment (RR 0.84, 95% CI 0.52, 1.37; P = 0.49; 2 RCTs; 130 participants) compared to sham stimulation. Non-invasive brain stimulation resulted in no deaths. Comparison 3: Psychological therapy Very low-certainty evidence from six trials suggests that psychological therapy decreased the number of people meeting the study criteria for depression at end of treatment (RR 0.77, 95% CI 0.62 to 0.95; P = 0.01; 521 participants) compared to usual care/attention control. No trials of psychological therapy reported on the outcome inadequate response to treatment. No differences in the number of deaths or adverse events were found in the psychological therapy group compared to the usual care/attention control group. Comparison 4: Pharmacological interventions with psychological therapy No trials of this combination reported on the primary outcomes. Combination therapy resulted in no deaths. Comparison 5: Pharmacological interventions with non-invasive brain stimulation Non-invasive brain stimulation with pharmacological intervention reduced the number of people meeting study criteria for depression at end of treatment (RR 0.77, 95% CI 0.64 to 0.91; P = 0.002; 3 RCTs; 392 participants; low-certainty evidence) but not the number of people with inadequate response to treatment (RR 0.95, 95% CI 0.69 to 1.30; P = 0.75; 3 RCTs; 392 participants; very low-certainty evidence) compared to pharmacological therapy alone. Very low-certainty evidence from five trials suggest no difference in deaths between this combination therapy (RR 1.06, 95% CI 0.27 to 4.16; P = 0.93; 487 participants) compared to pharmacological therapy intervention and sham stimulation or usual care. Comparison 6: Non-invasive brain stimulation with psychological therapy No trials of this combination reported on the primary outcomes. AUTHORS' CONCLUSIONS: Very low-certainty evidence suggests that pharmacological, psychological and combination therapies can reduce the prevalence of depression while non-invasive brain stimulation had little to no effect on the prevalence of depression. Pharmacological intervention was associated with adverse events related to the CNS and the gastrointestinal tract. More research is required before recommendations can be made about the routine use of such treatments.

ANTECEDENTES: La depresión tiene una morbilidad importante asociada con el accidente cerebrovascular que repercute en la recuperación, pero que a menudo no se detecta o se trata de manera inadecuada. OBJETIVOS: Evaluar los efectos beneficiosos y perjudiciales de las intervenciones farmacológicas, la estimulación cerebral no invasiva, la terapia psicológica o las combinaciones de éstas para tratar la depresión después del accidente cerebrovascular. MÉTODOS DE BÚSQUEDA: Esta es una revisión sistemática continua. Cada dos meses se busca nueva evidencia y la revisión se actualiza cuando se identifica evidencia nueva relevante. Consultar el estado actual de esta revisión en la Base de Datos Cochrane de Revisiones Sistemáticas (Cochrane Database of Systematic Reviews). Se realizaron búsquedas en los Registros especializados del Grupo Cochrane de Accidentes cerebrovasculares (Cochrane Stroke) y del Grupo Cochrane de Depresión, ansiedad y neurosis (Cochrane Depression, Anxiety and Neurosis), en CENTRAL, MEDLINE, Embase, otras cinco bases de datos, dos registros de ensayos clínicos, listas de referencias y resúmenes de congresos (febrero de 2022). Se estableció contacto con autores de estudios. CRITERIOS DE SELECCIÓN: Ensayos controlados aleatorizados (ECA) que compararan: 1) intervenciones farmacológicas con placebo; 2) estimulación cerebral no invasiva con estimulación simulada o atención habitual; 3) terapia psicológica con atención habitual o control de atención; 4) intervención farmacológica y terapia psicológica con intervención farmacológica y atención habitual o control de atención; 5) intervención farmacológica y estimulación cerebral no invasiva con intervención farmacológica y estimulación simulada o atención habitual; 6) estimulación cerebral no invasiva y terapia psicológica versus estimulación cerebral simulada o atención habitual y terapia psicológica; 7) intervención farmacológica y terapia psicológica con placebo y terapia psicológica; 8) intervención farmacológica y estimulación cerebral no invasiva con placebo y estimulación cerebral no invasiva; y 9) estimulación cerebral no invasiva y terapia psicológica versus estimulación cerebral no invasiva y atención habitual o control de atención, con la intención de tratar la depresión después del accidente cerebrovascular. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos autores de la revisión, de forma independiente, seleccionaron los estudios, evaluaron el riesgo de sesgo y extrajeron los datos de los estudios incluidos. Se calculó la diferencia de medias (DM) o la diferencia de medias estandarizada (DME) para los datos continuos, y la razón de riesgos (RR) para los datos dicotómicos, con intervalos de confianza (IC) del 95%. La heterogeneidad se evaluó mediante la estadística I² y la certeza de la evidencia según GRADE. RESULTADOS PRINCIPALES: Se incluyeron 65 ensayos (72 comparaciones) con 5831 participantes. Se dispuso de datos para: 1) 20 comparaciones; 2) nueve comparaciones; 3) 25 comparaciones; 4) tres comparaciones; 5) 14 comparaciones; y 6) una comparación. No se encontraron ensayos para las comparaciones 7 a 9. Comparación 1: Intervenciones farmacológicas Evidencia de certeza muy baja de ocho ensayos indica que las intervenciones farmacológicas disminuyeron el número de personas que cumplían los criterios del estudio para la depresión (RR 0,70; IC del 95%: 0,55 a 0,88; p = 0,002; ocho ECA; 1025 participantes) al final del tratamiento y evidencia de certeza muy baja de seis ensayos indica que las intervenciones farmacológicas disminuyeron el número de personas con respuesta inadecuada al tratamiento (RR 0,47; IC del 95%: 0,32 a 0,70; p = 0,0002; seis ECA; 511 participantes) en comparación con placebo. Se observaron más eventos adversos relacionados con el sistema nervioso central (SNC) (RR 1,55; IC del 95%: 1,12 a 2,15; p = 0,008; cinco ECA; 488 participantes; evidencia de certeza muy baja) y el sistema gastrointestinal (RR 1,62; IC del 95%: 1,19 a 2,19; p = 0,002; cuatro ECA; 473 participantes; evidencia de certeza muy baja) en el grupo de intervención farmacológica que en el grupo placebo. Comparación 2: Estimulación cerebral no invasiva Evidencia de certeza muy baja de dos ensayos muestra que la estimulación cerebral no invasiva tuvo poco o ningún efecto sobre el número de personas que cumplían los criterios del estudio para la depresión (RR 0,67; IC del 95%: 0,39 a 1,14; p = 0,14; dos ECA; 130 participantes) y el número de personas con respuesta inadecuada al tratamiento (RR 0,84; IC del 95%: 0,52 a 1,37; p = 0,49; dos ECA; 130 participantes) en comparación con la estimulación simulada. La estimulación cerebral no invasiva no provocó muertes. Comparación 3: Terapia psicológica Evidencia de certeza muy baja de seis ensayos indica que la terapia psicológica disminuyó el número de personas que cumplían los criterios del estudio para la depresión al final del tratamiento (RR 0,77; IC del 95%: 0,62 a 0,95; p = 0,01; 521 participantes) en comparación con atención habitual/control de atención. Ningún ensayo de terapia psicológica informó sobre el desenlace respuesta inadecuada al tratamiento. No se encontraron diferencias en el número de muertes o eventos adversos en el grupo de terapia psicológica en comparación con el grupo de control de atención/atención habitual. Comparación 4: Intervenciones farmacológicas con terapia psicológica Ningún ensayo de esta combinación informó sobre los desenlaces principales. El tratamiento combinado no provocó muertes. Comparación 5: Intervenciones farmacológicas con estimulación cerebral no invasiva La estimulación cerebral no invasiva con intervención farmacológica redujo el número de personas que cumplían los criterios del estudio para la depresión al final del tratamiento (RR 0,77; IC del 95%: 0,64 a 0,91; p = 0,002; tres ECA; 392 participantes; evidencia de certeza baja), pero no el número de personas con respuesta inadecuada al tratamiento (RR 0,95; IC del 95%: 0,69 a 1,30; p = 0,75; tres ECA; 392 participantes; evidencia de certeza muy baja) en comparación con el tratamiento farmacológico solo. Evidencia de certeza muy baja de cinco ensayos no indica diferencias en las muertes entre este tratamiento combinado (RR 1,06; IC del 95%: 0,27 a 4,16; p = 0,93; 487 participantes) en comparación con la intervención de tratamiento farmacológico y la estimulación simulada o la atención habitual. Comparación 6: Estimulación cerebral no invasiva con terapia psicológica Ningún ensayo de esta combinación informó sobre los desenlaces principales. CONCLUSIONES DE LOS AUTORES: Evidencia de certeza muy baja indica que los tratamientos farmacológicos, las terapias psicológicas y los tratamientos combinados pueden reducir la prevalencia de la depresión, mientras que la estimulación cerebral no invasiva tuvo poco o ningún efecto sobre la prevalencia de la depresión. Las intervenciones farmacológicas se asociaron con eventos adversos relacionados con el SNC y el sistema gastrointestinal. Se necesitan más estudios de investigación antes de poder hacer recomendaciones sobre el uso habitual de dichos tratamientos.

The association of changes of sleep architecture related to donepezil: A systematic review and meta-analysis.

BACKGROUND: Donepezil had been recognized to have impact on sleep quality in demented patients. However, there was insufficient evidences about the actual effect of donepezil in the sleep architectures. Our meta-analysis aimed to evaluate the changes of sleep architectures related to donepezil use. METHODS: Followed the PRISMA2020 and AMSTAR2 guidelines, electronic search had been performed on the databases of PubMed, Embase, ScienceDirect, ClinicalKey, Cochrane CENTRAL, ProQuest, Web of Science, and ClinicalTrials.gov. The outcome measurement was changes of sleep parameters detected by polysomnography. A random-effects meta-analysis was conducted. RESULTS: Total twelve studies had been involved. The percentage of REM sleep would significantly increase after donepezil treatment (Hedges' g = 0.694, p < 0.001). Compared to placebo/controls, subjects with donepezil would had significantly increased percentage of REM sleep stage (Hedges' g = 0.556, p = 0.018). Furthermore, donepezil was also associated with the decreased stage 2 sleep percentage, sleep efficiency, or total sleep time in different analysis conditions. CONCLUSION: Our meta-analysis provided detailed changes of sleep architectures related to donepezil treatment. Further larger sample size studies with stricter control of potential moderators are needed to clarify these issues.

Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) might theoretically reduce post-stroke disability by direct effects on the brain. This Cochrane Review was first published in 2012 and last updated in 2019. OBJECTIVES: To determine if SSRIs are more effective than placebo or usual care at improving outcomes in people less than 12 months post-stroke, and to determine whether treatment with SSRIs is associated with adverse effects. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (last searched 7 January 2021), Cochrane Controlled Trials Register (CENTRAL, Issue 7 of 12, 7 January 2021), MEDLINE (1946 to 7 January 2021), Embase (1974 to 7 January 2021), CINAHL (1982 to 7 January 2021), PsycINFO (1985 to 7 January 2021), and AMED (1985 to 7 January 2021). PsycBITE had previously been searched (16 July 2018). We searched clinical trials registers. SELECTION CRITERIA: We included randomised controlled trials (RCTs) recruiting stroke survivors within the first year. The intervention was any SSRI, at any dose, for any period, and for any indication. The comparator was usual care or placebo. Studies reporting at least one of our primary (disability score or independence) or secondary outcomes (impairments, depression, anxiety, quality of life, fatigue, cognition, healthcare cost, death, adverse events and leaving the study early) were included in the meta-analysis. The primary analysis included studies at low risk of bias. DATA COLLECTION AND ANALYSIS: We extracted data on demographics, stroke type and, our pre-specified outcomes, and bias sources. Two review authors independently extracted data. We used mean difference (MD) or standardised mean differences (SMDs) for continuous variables, and risk ratios (RRs) for dichotomous variables, with 95% confidence intervals (CIs). We assessed bias risks and applied GRADE criteria. MAIN RESULTS: We identified 76 eligible studies (13,029 participants); 75 provided data at end of treatment, and of these two provided data at follow-up. Thirty-eight required participants to have depression to enter. The duration, drug, and dose varied. Six studies were at low risk of bias across all domains; all six studies did not need participants to have depression to enter, and all used fluoxetine. Of these six studies, there was little to no difference in disability between groups SMD -0.0; 95% CI -0.05 to 0.05; 5 studies, 5436 participants, high-quality evidence) or in independence (RR 0.98; 95% CI 0.93 to 1.03; 5 studies, 5926 participants; high-quality evidence) at the end of treatment. In the studies at low risk of bias across all domains, SSRIs slightly reduced the average depression score (SMD 0.14 lower, 95% CI 0.19 lower to 0.08 lower; 4 studies; 5356 participants, high-quality evidence) and there was a slight reduction in the proportion with depression (RR 0.75, 95% CI 0.65 to 0.86; 3 studies, 5907 participants, high-quality evidence). Cognition was slightly better in the control group (MD -1.22, 95% CI -2.37 to -0.07; 4 studies, 5373 participants, moderate-quality evidence). Only one study (n = 30) reported neurological deficit score (SMD -0.39, 95% CI -1.12 to 0.33; low-quality evidence). SSRIs resulted in little to no difference in motor deficit (SMD 0.03, -0.02 to 0.08; 6 studies, 5518 participants, moderate-quality evidence). SSRIs slightly increased the proportion leaving the study early (RR 1.57, 95% CI 1.03 to 2.40; 6 studies, 6090 participants, high-quality evidence). SSRIs slightly increased the outcome of a seizure (RR 1.40, 95% CI 1.00 to 1.98; 6 studies, 6080 participants, moderate-quality evidence) and a bone fracture (RR 2.35, 95% CI 1.62 to 3.41; 6 studies, 6080 participants, high-quality evidence). One study at low risk of bias across all domains reported gastrointestinal side effects (RR 1.71, 95% CI 0.33, to 8.83; 1 study, 30 participants). There was no difference in the total number of deaths between SSRI and placebo (RR 1.01, 95% CI 0.82 to 1.24; 6 studies, 6090 participants, moderate quality evidence). SSRIs probably result in little to no difference in fatigue (MD -0.06; 95% CI -1.24 to 1.11; 4 studies, 5524 participants, moderate-quality of evidence), nor in quality of life (MD 0.00; 95% CI -0.02 to 0.02, 3 studies, 5482 participants, high-quality evidence). When all studies, irrespective of risk of bias, were included, SSRIs reduced disability scores but not the proportion independent. There was insufficient data to perform a meta-analysis of outcomes at end of follow-up. Several small ongoing studies are unlikely to alter conclusions. AUTHORS' CONCLUSIONS: There is high-quality evidence that SSRIs do not make a difference to disability or independence after stroke compared to placebo or usual care, reduced the risk of future depression, increased bone fractures and probably increased seizure risk.

Bisphenol a Induces Autophagy Defects and AIF-Dependent Apoptosis via HO-1 and AMPK to Degenerate N2a Neurons.

Bisphenol A (BPA) is an environmental contaminant widely suspected to be a neurological toxicant. Epidemiological studies have demonstrated close links between BPA exposure, pathogenetic brain degeneration, and altered neurobehaviors, considering BPA a risk factor for cognitive dysfunction. However, the mechanisms of BPA resulting in neurodegeneration remain unclear. Herein, cultured N2a neurons were subjected to BPA treatment, and neurotoxicity was assessed using neuronal viability and differentiation assays. Signaling cascades related to cellular self-degradation were also evaluated. BPA decreased cell viability and axon outgrowth (e.g., by down-regulating MAP2 and GAP43), thus confirming its role as a neurotoxicant. BPA induced neurotoxicity by down-regulating Bcl-2 and initiating apoptosis and autophagy flux inhibition (featured by nuclear translocation of apoptosis-inducing factor (AIF), light chain 3B (LC3B) aggregation, and p62 accumulation). Both heme oxygenase (HO)-1 and AMP-activated protein kinase (AMPK) up-regulated/activated by BPA mediated the molecular signalings involved in apoptosis and autophagy. HO-1 inhibition or AIF silencing effectively reduced BPA-induced neuronal death. Although BPA elicited intracellular oxygen free radical production, ROS scavenger NAC exerted no effect against BPA insults. These results suggest that BPA induces N2a neurotoxicity characterized by AIF-dependent apoptosis and p62-related autophagy defects via HO-1 up-regulation and AMPK activation, thereby resulting in neuronal degeneration.

Pharmacological, psychological and non-invasive brain stimulation interventions for preventing depression after stroke.

BACKGROUND: Depression is an important consequence of stroke that influences recovery yet often is not detected, or is inadequately treated. This is an update and expansion of a Cochrane Review first published in 2004 and previously updated in 2008. OBJECTIVES: The primary objective is to test the hypothesis that pharmacological, psychological therapy, non-invasive brain stimulation, or combinations of these interventions reduce the incidence of diagnosable depression after stroke. Secondary objectives are to test the hypothesis that pharmacological, psychological therapy, non-invasive brain stimulation or combinations of these interventions reduce levels of depressive symptoms and dependency, and improve physical functioning after stroke. We also aim to determine the safety of, and adherence to, the interventions. SEARCH METHODS: We searched the Specialised Register of Cochrane Stroke and the Cochrane Depression Anxiety and Neurosis (last searched August 2018). In addition, we searched the following databases; Cochrane Central Register of Controlled Trials, CENTRAL (the Cochrane Library, 2018, Issue 8), MEDLINE (1966 to August 2018), Embase (1980 to August 2018), PsycINFO (1967 to August 2018), CINAHL (1982 to August 2018) and three Web of Science indexes (2002 to August 2018). We also searched reference lists, clinical trial registers (World Health Organization International Clinical Trials Registry Platform (WHO ICTRP); to August 2018 and ClinicalTrials.gov; to August 2018), conference proceedings; we also contacted study authors. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing: 1) pharmacological interventions with placebo; 2) one of various forms of psychological therapy with usual care and/or attention control; 3) one of various forms of non-invasive brain stimulation with sham stimulation or usual care; 4) a pharmacological intervention and one of various forms of psychological therapy with a pharmacological intervention and usual care and/or attention control; 5) non-invasive brain stimulation and pharmacological intervention with a pharmacological intervention and sham stimulation or usual care; 6) pharmacological intervention and one of various forms of psychological therapy with placebo and psychological therapy; 7) pharmacological intervention and non-invasive brain stimulation with placebo plus non-invasive brain stimulation; 8) non-invasive brain stimulation and one of various forms of psychological therapy versus non-invasive brain stimulation plus usual care and/or attention control; and 9) non-invasive brain stimulation and one of various forms of psychological therapy versus sham brain stimulation or usual care plus psychological therapy, with the intention of preventing depression after stroke. DATA COLLECTION AND ANALYSIS: Review authors independently selected studies, assessed risk of bias, and extracted data from all included studies. We calculated mean difference (MD) or standardised mean difference (SMD) for continuous data and risk ratio (RR) for dichotomous data with 95% confidence intervals (CIs). We assessed heterogeneity using the I2 statistic and assessed the certainty of evidence using GRADE. MAIN RESULTS: We included 19 RCTs (21 interventions), with 1771 participants in the review. Data were available for 12 pharmacological trials (14 interventions) and seven psychological trials. There were no trials of non-invasive brain stimulation compared with sham stimulation or usual care, a combination of pharmacological intervention and one of various forms of psychological therapy with placebo and psychological therapy, or a combination of non-invasive brain stimulation and a pharmacological intervention with a pharmacological intervention and sham stimulation or usual care to prevent depression after stroke. Treatment effects were observed on the primary outcome of meeting the study criteria for depression at the end of treatment: there is very low-certainty evidence from eight trials (nine interventions) that pharmacological interventions decrease the number of people meeting the study criteria for depression (RR 0.50, 95% CI 0.37 to 0.68; 734 participants) compared to placebo. There is very low-certainty evidence from two trials that psychological interventions reduce the proportion of people meeting the study criteria for depression (RR 0.68, 95% CI 0.49 to 0.94, 607 participants) compared to usual care and/or attention control. Eight trials (nine interventions) found no difference in death and other adverse events between pharmacological intervention and placebo groups (RR 1.25, 95% CI 0.32 to 4.91; 496 participants) based on very low-certainty evidence. Five trials found no difference in psychological intervention and usual care and/or attention control groups for death and other adverse events (RR 1.18, 95% CI 0.73 to 1.91; 975 participants) based on very low-certainty evidence. AUTHORS' CONCLUSIONS: The available evidence suggests that pharmacological interventions and psychological therapy may prevent depression and improve mood after stroke. However, there is very low certainty in these conclusions because of the very low-certainty evidence. More trials are required before reliable recommendations can be made about the routine use of such treatments after stroke.

Pharmacological, psychological, and non-invasive brain stimulation interventions for treating depression after stroke.

BACKGROUND: Depression is an important morbidity associated with stroke that impacts on recovery yet often undetected or inadequately treated. This is an update and expansion of a Cochrane Review first published in 2004 and updated in 2008. OBJECTIVES: Primary objective • To determine whether pharmacological therapy, non-invasive brain stimulation, psychological therapy, or combinations of these interventions reduce the prevalence of diagnosable depression after stroke Secondary objectives • To determine whether pharmacological therapy, non-invasive brain stimulation, psychological therapy, or combinations of these interventions reduce levels of depressive symptoms, improve physical and neurological function and health-related quality of life, and reduce dependency after stroke • To assess the safety of and adherence to such treatments SEARCH METHODS: We searched the Specialised Registers of Cochrane Stroke and Cochrane Depression Anxiety and Neurosis (last searched August 2018), the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 1), in the Cochrane Library, MEDLINE (1966 to August 2018), Embase (1980 to August 2018), the Cumulative Index to Nursing and Alllied Health Literature (CINAHL) (1982 to August 2018), PsycINFO (1967 to August 2018), and Web of Science (2002 to August 2018). We also searched reference lists, clinical trial registers (World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) to August 2018; ClinicalTrials.gov to August 2018), and conference proceedings, and we contacted study authors. SELECTION CRITERIA: Randomised controlled trials comparing (1) pharmacological interventions with placebo; (2) one of various forms of non-invasive brain stimulation with sham stimulation or usual care; (3) one of various forms of psychological therapy with usual care and/or attention control; (4) pharmacological intervention and various forms of psychological therapy with pharmacological intervention and usual care and/or attention control; (5) non-invasive brain stimulation and pharmacological intervention with pharmacological intervention and sham stimulation or usual care; (6) pharmacological intervention and one of various forms of psychological therapy with placebo and psychological therapy; (7) pharmacological intervention and non-invasive brain stimulation with placebo plus non-invasive brain stimulation; (8) non-invasive brain stimulation and one of various forms of psychological therapy versus non-invasive brain stimulation plus usual care and/or attention control; and (9) non-invasive brain stimulation and one of various forms of psychological therapy versus sham brain stimulation or usual care plus psychological therapy, with the intention of treating depression after stroke. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risk of bias, and extracted data from all included studies. We calculated mean difference (MD) or standardised mean difference (SMD) for continuous data, and risk ratio (RR) for dichotomous data, with 95% confidence intervals (CIs). We assessed heterogeneity using the I² statistic and certainty of the evidence according to GRADE. MAIN RESULTS: We included 49 trials (56 comparisons) with 3342 participants. Data were available for: (1) pharmacological interventions with placebo (with 20 pharmacological comparisons); (2) one of various forms of non-invasive brain stimulation with sham stimulation or usual care (with eight non-invasive brain stimulation comparisons); (3) one of various forms of psychological therapy with usual care and/or attention control (with 16 psychological therapy comparisons); (4) pharmacological intervention and various forms of psychological therapy with pharmacological intervention and usual care and/or attention control (with two comparisons); and (5) non-invasive brain stimulation and pharmacological intervention with pharmacological intervention and sham stimulation or usual care (with 10 comparisons). We found no trials for the following comparisons: (6) pharmacological intervention and various forms of psychological therapy interventions versus placebo and psychological therapy; (7) pharmacological intervention and non-invasive brain stimulation versus placebo plus non-invasive brain stimulation; (8) non-invasive brain stimulation and one of various forms of psychological therapy versus non-invasive brain stimulation plus usual care and/or attention control; and (9) non-invasive brain stimulation and one of various forms of psychological therapy versus sham brain stimulation or usual care plus psychological therapy. Treatment effects observed: very low-certainty evidence from eight trials suggests that pharmacological interventions decreased the number of people meeting study criteria for depression (RR 0.70, 95% CI 0.55 to 0.88; 1025 participants) at end of treatment, and very low-certainty evidence from six trials suggests that pharmacological interventions decreased the number of people with less than 50% reduction in depression scale scores at end of treatment (RR 0.47, 95% CI 0.32 to 0.69; 511 participants) compared to placebo. No trials of non-invasive brain stimulation reported on meeting study criteria for depression at end of treatment. Only one trial of non-invasive brain stimulation reported on the outcome <50% reduction in depression scale scores; thus, we were unable to perform a meta-analysis for this outcome. Very low-certainty evidence from six trials suggests that psychological therapy decreased the number of people meeting the study criteria for depression at end of treatment (RR 0.77, 95% CI 0.62 to 0.95; 521 participants) compared to usual care/attention control. No trials of combination therapies reported on the number of people meeting the study criteria for depression at end of treatment. Only one trial of combination (non-invasive brain stimulation and pharmacological intervention) therapy reported <50% reduction in depression scale scores at end of treatment. Thus, we were unable to perform a meta-analysis for this outcome. Five trials reported adverse events related to the central nervous system (CNS) and noted significant harm in the pharmacological interventions group (RR 1.55, 95% CI 1.12 to 2.15; 488 participants; very low-certainty evidence). Four trials found significant gastrointestinal adverse events in the pharmacological interventions group (RR 1.62, 95% CI 1.19 to 2.19; 473 participants; very low-certainty evidence) compared to the placebo group. No significant deaths or adverse events were found in the psychological therapy group compared to the usual care/attention control group. Non-invasive brain stimulation interventions and combination therapies resulted in no deaths. AUTHORS' CONCLUSIONS: Very low-certainty evidence suggests that pharmacological or psychological therapies can reduce the prevalence of depression. This very low-certainty evidence suggests that pharmacological therapy, psychological therapy, non-invasive brain stimulation, and combined interventions can reduce depressive symptoms. Pharmacological intervention was associated with adverse events related to the CNS and the gastrointestinal tract. More research is required before recommendations can be made about the routine use of such treatments.

The influence of integrated geriatric outpatient clinics on the health care utilization of older people.

BACKGROUND: The number of people aged greater than 65 years is growing in many countries. Taiwan will be a superaged society in 2026, and health care utilization will increase considerably. Our study aimed to evaluate the efficacy of the geriatric integrated outpatient clinic model for reducing health care utilization by older people. METHODS: This was a retrospective case-control study. Patients aged greater than 65 years seen at the geriatric outpatient clinic (Geri-OPD) and non-geriatric outpatient clinic (non-Geri-OPD) at a single medical centre were age and sex matched. Data on the number of outpatient clinic visits, emergency department visits, hospitalizations and medical expenditures were collected during the first and second years. A subgroup analysis by Charlson comorbidity index (CCI) and older age (age≧80 years) was performed, and the results were compared between the Geri-OPD and non-Geri-OPD groups. RESULTS: A total of 6723 patients were included (3796 women and 2927 men). The mean age was 80.42 ± 6.39 years. There were 1291 (19.2%) patients in the Geri-OPD group and 5432 (80.8%) patients in the non-Geri-OPD group. After one year of regular follow-up, the Geri-OPD patients showed a significant reduction in the types of drugs included in each prescription (5.62 ± 10.85) and the number of clinic visits per year (18.18 ± 48.85) (P < 0.01). After a two-year follow-up, the number of clinic visits, emergency department visits, and hospitalizations and the annual medical costs were still decreased in the Geri-OPD patients. The Geri-OPD patients had more comorbidities and a higher rate of health care utilization than the non-Geri-OPD patients. In the subgroup analysis, patients with more comorbidities (CCI≧2) and an older age (≧80 years) in the Geri-OPD group showed a significant reduction in health care utilization. The Geri-OPD patients also showed a significant decrease in medical utilization in the second year compared with the non-Geri-POD patients. CONCLUSION: The Geri-OPD reduced medical costs, the number of drugs prescribed, and the frequency of outpatient clinic visits, emergency department visits and hospitalizations in older patients with complicated conditions. The effect was even better in the second year.

Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery.

BACKGROUND: Stroke is a major cause of adult disability. Selective serotonin reuptake inhibitors (SSRIs) have been used for many years to manage depression and other mood disorders after stroke. The 2012 Cochrane Review of SSRIs for stroke recovery demonstrated positive effects on recovery, even in people who were not depressed at randomisation. A large trial of fluoxetine for stroke recovery (fluoxetine versus placebo under supervision) has recently been published, and it is now appropriate to update the evidence. OBJECTIVES: To determine if SSRIs are more effective than placebo or usual care at improving outcomes in people less than 12 months post-stroke, and to determine whether treatment with SSRIs is associated with adverse effects. SEARCH METHODS: For this update, we searched the Cochrane Stroke Group Trials Register (last searched 16 July 2018), the Cochrane Controlled Trials Register (CENTRAL, Issue 7 of 12, July 2018), MEDLINE (1946 to July 2018), Embase (1974 to July 2018), CINAHL (1982 July 2018), PsycINFO (1985 to July 2018), AMED (1985 to July 2018), and PsycBITE March 2012 to July 2018). We also searched grey literature and clinical trials registers. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that recruited ischaemic or haemorrhagic stroke survivors at any time within the first year. The intervention was any SSRI, given at any dose, for any period, and for any indication. We excluded drugs with mixed pharmacological effects. The comparator was usual care or placebo. To be included, trials had to collect data on at least one of our primary (disability score or independence) or secondary outcomes (impairments, depression, anxiety, quality of life, fatigue, healthcare cost, death, adverse events and leaving the trial early). DATA COLLECTION AND ANALYSIS: We extracted data on demographics, type of stroke, time since stroke, our primary and secondary outcomes, and sources of bias. Two review authors independently extracted data from each trial. We used standardised mean differences (SMDs) to estimate treatment effects for continuous variables, and risk ratios (RRs) for dichotomous effects, with their 95% confidence intervals (CIs). We assessed risks of bias and applied GRADE criteria. MAIN RESULTS: We identified a total of 63 eligible trials recruiting 9168 participants, most of which provided data only at end of treatment and not at follow-up. There was a wide age range. About half the trials required participants to have depression to enter the trial. The duration, drug, and dose varied between trials. Only three of the included trials were at low risk of bias across the key 'Risk of bias' domains. A meta-analysis of these three trials found little or no effect of SSRI on either disability score: SMD -0.01 (95% CI -0.09 to 0.06; P = 0.75; 2 studies, 2829 participants; moderate-quality evidence) or independence: RR 1.00 (95% CI 0.91 to 1.09; P = 0.99; 3 studies, 3249 participants; moderate-quality evidence). We downgraded both these outcomes for imprecision. SSRIs reduced the average depression score (SMD 0.11 lower, 0.19 lower to 0.04 lower; 2 trials, 2861 participants; moderate-quality evidence), but there was a higher observed number of gastrointestinal side effects among participants treated with SSRIs compared to placebo (RR 2.19, 95% CI 1.00 to 4.76; P = 0.05; 2 studies, 148 participants; moderate-quality evidence), with no evidence of heterogeneity (I2 = 0%). For seizures there was no evidence of a substantial difference. When we included all trials in a sensitivity analysis, irrespective of risk of bias, SSRIs appeared to reduce disability scores but not dependence. One large trial (FOCUS) dominated the results. We identified several ongoing trials, including two large trials that together will recruit more than 3000 participants. AUTHORS' CONCLUSIONS: We found no reliable evidence that SSRIs should be used routinely to promote recovery after stroke. Meta-analysis of the trials at low risk of bias indicate that SSRIs do not improve recovery from stroke. We identified potential improvements in disability only in the analyses which included trials at high risk of bias. A further meta-analysis of large ongoing trials will be required to determine the generalisability of these findings.

Basal sympathetic predominance in periodic limb movements in sleep after continuous positive airway pressure.

PURPOSE: This study investigated the basal autonomic regulation in patients with obstructive sleep apnea (OSA) showing periodic limb movements in sleep (PLMS) emerging after therapy with continuous positive airway pressure (CPAP). METHODS: Data of patients with OSA undergoing a first polysomnography for diagnosis and a second polysomnography for therapy with CPAP were reviewed. Patients with OSA showing PLMS on the first polysomnography were excluded. By using heart rate variability analysis, epochs without any sleep events and continuous effects from the second polysomnography were retrospectively analyzed. RESULTS: Of 125 eligible patients, 30 with PLMS after therapy with CPAP (PLMS group) and 30 not showing PLMS on both polysomnography (non-PLMS group) were randomly selected for the analysis. No significant differences in the demographic characteristics and variables of polysomnographies were identified between the groups. Although one trend of low root mean square of successive differences (RMSSD) between intervals of adjacent normal heart beats (NN intervals) in the PLMS group was observed, patients in the PLMS group had significantly low normalized high-frequency (n-HF) and high-frequency (HF) values, but high normalized low frequency (n-LF) and high ratio of LF to HF (LF/HF ratio). After adjustment for confounding variables, PLMS on the second polysomnography was significantly associated with RMSSD (ß = - 6.7587, p = 0.0338), n-LF (ß = 0.0907, p = 0.0148), n-HF (ß = - 0.0895, p = 0.0163), log LF/HF ratio (ß = 0.4923, p = 0.0090), and log HF (ß = - 0.6134, p = 0.0199). CONCLUSIONS: Patients with OSA showing PLMS emerging after therapy with CPAP may have a basal sympathetic predominance with potential negative cardiovascular effects.

Traumatic Thoracic Burst Fracture Associated with Bronchial Rupture.

BACKGROUND: Rupture of, or injury to, the tracheobronchial tree is a rare occurrence in blunt chest trauma. CASE REPORT: We present a case of bronchial rupture caused by fragmented bone from a spinal burst fracture after blunt chest trauma. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although tracheobronchial injury is infrequent, clinicians should be aware of this possible complication after blunt chest trauma. Bronchoscopy can help in the diagnosis.

Basal sympathetic predominance in periodic limb movements in sleep with obstructive sleep apnea.

Because the impact of periodic limb movements in sleep (PLMS) is controversial, no consensus has been reached on the therapeutic strategy for PLMS in obstructive sleep apnea (OSA). To verify the hypothesis that PLMS is related to a negative impact on the cardiovascular system in OSA patients, this study investigated the basal autonomic regulation by heart rate variability (HRV) analysis. Sixty patients with mild-to-moderate OSA who underwent polysomnography (PSG) and completed sleep questionnaires were analysed retrospectively and divided into the PLMS group (n = 30) and the non-PLMS group (n = 30). Epochs without any sleep events or continuous effects were evaluated using HRV analysis. No significant difference was observed in the demographic data, PSG parameters or sleep questionnaires between the PLMS and non-PLMS groups, except for age. Patients in the PLMS group had significantly lower normalized high frequency (n-HF), high frequency (HF), square root of the mean of the sum of the squares of difference between adjacent NN intervals (RMSSD) and standard deviation of all normal to normal intervals index (SDNN-I), but had a higher normalized low frequency (n-LF) and LF/HF ratio. There was no significant difference in the Epworth Sleepiness Scale, the Pittsburgh Sleep Quality Index, the Short-Form 36 and the Hospital Anxiety and Depression Scale between the two groups. After adjustment for confounding variables, PLMS remained an independent predictor of n-LF (ß = 0.0901, P = 0.0081), LF/HF ratio (ß = 0.5351, P = 0.0361), RMSSD (ß = -20.1620, P = 0.0455) and n-HF (ß = -0.0886, P = 0.0134). In conclusion, PLMS is related independently to basal sympathetic predominance and has a potentially negative impact on the cardiovascular system of OSA patients.

More severe hypoxemia is associated with better subjective sleep quality in obstructive sleep apnea.

BACKGROUND: Perceived sleep quality may play an important role in diagnosis and therapy for obstructive sleep apnea (OSA). However, few studies have assessed factors that are associated with perceived sleep quality in OSA patients. Hypoxemia depresses the central nervous system and attenuates the perceived respiratory load in asthmatic patients. This study aimed to investigate the factors related to perceived sleep quality, focusing on the role of hypoxemia. METHODS: Polysomnography studies of 156 OSA patients were reviewed. Traditional polysomnographic parameters, including parameters of oxy-hemoglobin saturation (SpO2), were calculated, and the sleep questionnaire and scales were used. Considering the possible pitfalls of absolute values of SpO2 and individualized responses to hypoxemia, the amplitude of desaturation was further computed as "median SpO2 minus lowest 5 % SpO2 "and "highest 5 % SpO2 minus median 5 % SpO2". Correlations between these parameters and perceived sleep quality, represented as the Pittsburgh sleep quality index (PSQI), were performed. Multiple linear regression analysis was also conducted to investigate the factors associated with the PSQI. RESULTS: Although the PSQI was not correlated with the apnea-hypopnea index (r = -0.113, p = 0.162) and oxygen desaturation index (r = -0.085, p = 0.291), the PSQI was negatively correlated with "median SpO2 minus lowest 5 % SpO2" (r = -0.161, p = 0.045). After adjusting for age, total sleep time, the periodic limb movements index, tendency of depression, and the lowest 5 % SpO2, the "median SpO2 minus lowest SpO2" was still a significant predictor for a lower PSQI (ß = -0.357, p = 0.015). CONCLUSIONS: More severe hypoxemia is associated with better perceived sleep quality among OSA patients. This paradox may be associated with hypoxemia-related impairment of perception. The effect of hypoxemia did not appear to be significant in relatively mild hypoxemia but become significant in severe hypoxemia." Median SpO2 minus lowest 5 % SpO2" may also be a better predictor of perceived sleep quality than the apnea-hypopnea index because of the disproportionate effects of hypoxemia. Additionally, further studies are necessary to confirm the role of hypoxemia on perceived sleep quality and identify the possible threshold of hypoxemia in OSA patients.

Selective serotonin reuptake inhibitors for stroke recovery.

CLINICAL QUESTION: Are selective serotonin reuptake inhibitors (SSRIs) associated with better recovery after stroke? BOTTOM LINE: SSRIs may be associated with improved recovery after stroke, even in persons without depression. However, much of the evidence is of poor quality. Large, high-quality trials are needed to evaluate the validity of the current evidence and improve precision of estimates of any treatment benefits.

SGLT2 Inhibitor Canagliflozin Alleviates High Glucose-Induced Inflammatory Toxicity in BV-2 Microglia.

Patients with diabetes mellitus can experience hyperglycemia, which affects brain function and produces cognitive impairment or neurodegeneration. Neuroinflammation is an important cause of cognitive dysfunction. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are antihyperglycemic agents that reportedly possess anti-inflammatory properties and may produce beneficial cognitive effects. We hypothesized that SGLT2 inhibitors alleviate hyperglycemia-related inflammation in brain immune cells. Cultured BV-2 microglia were exposed to high glucose (HG) in the absence or presence of SGLT2 inhibitors including canagliflozin (Cana), dapagliflozin (Dapa), empagliflozin (Empa), and ertugliflozin (Ertu). Afterward, we evaluated the cytotoxic and inflammatory responses by specific biochemical assays. Treatments with non-toxic Cana or Dapa, but not Empa or Ertu, inhibited proliferation without cell death. Only Cana rescued BV-2 microglia from HG-induced cytotoxicity, including apoptosis or autophagic degradation. None of SGLT2 inhibitors affected the HG-stimulated induction of stress proteins HO-1 and HSP70. Also, compared to the other three SGLT2 inhibitors, Cana was better at inhibiting HG-induced oxidative/inflammatory stress, as evidenced by its ability to repress proinflammatory factors (e.g., oxygen free radicals, iNOS, NLRP3, IL-1ß, and TNF-α) other than COX-2. Cana's action to alleviate HG insults was mediated not by altering SGLT2 protein expression, but by reducing HG-stimulated signaling activities of NFκB, JNK, p38, and PI3K/Akt pathways. Particularly, Cana imitated the effects of NFκB inhibitor on HG-induced iNOS and COX-2. Of the four SGLT2 inhibitors, Cana provided BV-2 microglia with the best protection against HG-induced inflammatory toxicity. Thus, Cana may help to reduce innate neuroimmune damage caused by hyperglycemia.

Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery.

BACKGROUND: Stroke is the major cause of adult disability. Selective serotonin reuptake inhibitors (SSRIs) have been used for many years to manage depression. Recently, small trials have demonstrated that SSRIs might improve recovery after stroke, even in people who are not depressed. Systematic reviews and meta-analyses are the least biased way to bring together data from several trials. Given the promising effect of SSRIs on stroke recovery seen in small trials, a systematic review and meta-analysis is needed. OBJECTIVES: To determine whether SSRIs improve recovery after stroke, and whether treatment with SSRIs was associated with adverse effects. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (August 2011), Cochrane Depression Anxiety and Neurosis Group Trials Register (November 2011), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 8), MEDLINE (from 1948 to August 2011), EMBASE (from 1980 to August 2011), CINAHL (from 1982 to August 2011), AMED (Allied and Complementary Medicine) (from 1985 to August 2011), PsycINFO (from 1967 to August 2011) and PsycBITE (Pyschological Database for Brain Impairment Treatment Efficacy) (March 2012). To identify further published, unpublished and ongoing trials we searched trials registers, pharmaceutical websites, reference lists, contacted experts and performed citation tracking of included studies. SELECTION CRITERIA: We included randomised controlled trials that recruited stroke survivors (ischaemic or haemorrhagic) at any time within the first year. The intervention was any SSRI, given at any dose, for any period. We excluded drugs with mixed pharmacological effects. The comparator was usual care or placebo. In order to be included, trials had to collect data on at least one of our primary (dependence and disability) or secondary (impairments, depression, anxiety, quality of life, fatigue, healthcare cost, death, adverse events and leaving the trial early) outcomes. DATA COLLECTION AND ANALYSIS: We extracted data on demographics, type of stroke, time since stroke, our primary and secondary outcomes, and sources of bias. For trials in English, two review authors independently extracted data. For Chinese papers, one review author extracted data. We used standardised mean differences (SMD) to estimate treatment effects for continuous variables, and risk ratios (RR) for dichotomous effects, with their 95% confidence intervals (CIs). MAIN RESULTS: We identified 56 completed trials of SSRI versus control, of which 52 trials (4059 participants) provided data for meta-analysis. There were statistically significant benefits of SSRI on both of the primary outcomes: RR for reducing dependency at the end of treatment was 0.81 (95% CI 0.68 to 0.97) based on one trial, and for disability score, the SMD was 0.91 (95% CI 0.60 to 1.22) (22 trials involving 1343 participants) with high heterogeneity between trials (I(2) = 87%; P < 0.0001). For neurological deficit, depression and anxiety, there were statistically significant benefits of SSRIs. For neurological deficit score, the SMD was -1.00 (95% CI -1.26 to -0.75) (29 trials involving 2011 participants) with high heterogeneity between trials (I(2) = 86%; P < 0.00001). For dichotomous depression scores, the RR was 0.43 (95% CI 0.24 to 0.77) (eight trials involving 771 participants) with high heterogeneity between trials (I(2) = 77%; P < 0.0001). For continuous depression scores, the SMD was -1.91 (95% CI -2.34 to -1.48) (39 trials involving 2728 participants) with high heterogeneity between trials (I(2) = 95%; P < 0.00001). For anxiety, the SMD was -0.77 (95% CI -1.52 to -0.02) (eight trials involving 413 participants) with high heterogeneity between trials (I(2) = 92%; P < 0.00001). There was no statistically significant benefit of SSRI on cognition, death, motor deficits and leaving the trial early. For cognition, the SMD was 0.32 (95% CI -0.23 to 0.86), (seven trials involving 425 participants) with high heterogeneity between trials (I(2) = 86%; P < 0.00001). The RR for death was 0.76 (95% CI 0.34 to 1.70) (46 trials involving 3344 participants) with no heterogeneity between trials (I(2) = 0%; P = 0.85). For motor deficits, the SMD was -0.33 (95% CI -1.22 to 0.56) (two trials involving 145 participants). The RR for leaving the trial early was 1.02 (95% CI 0.86 to 1.21) in favour of control, with no heterogeneity between trials. There was a non-significant excess of seizures (RR 2.67; 95% CI 0.61 to 11.63) (seven trials involving 444 participants), a non-significant excess of gastrointestinal side effects (RR 1.90; 95% CI 0.94 to 3.85) (14 trials involving 902 participants) and a non-significant excess of bleeding (RR 1.63; 95% CI 0.20 to 13.05) (two trials involving 249 participants) in those allocated SSRIs. Data were not available on quality of life, fatigue or healthcare costs.There was no clear evidence from subgroup analyses that one SSRI was consistently superior to another, or that time since stroke or depression at baseline had a major influence on effect sizes. Sensitivity analyses suggested that effect sizes were smaller when we excluded trials at high or unclear risk of bias.Only eight trials provided data on outcomes after treatment had been completed; the effect sizes were generally in favour of SSRIs but CIs were wide. AUTHORS' CONCLUSIONS: SSRIs appeared to improve dependence, disability, neurological impairment, anxiety and depression after stroke, but there was heterogeneity between trials and methodological limitations in a substantial proportion of the trials. Large, well-designed trials are now needed to determine whether SSRIs should be given routinely to patients with stroke.

Static postural stability and neuropsychological performance after awakening from REM and NREM sleep in patients with chronic insomnia: a randomized, crossover, overnight polysomnography study.

STUDY OBJECTIVES: Chronic insomnia disorder (CID) is a common sleep disorder, with a prevalence ranging from 6%-10% worldwide. Individuals with CID experience more fragmented sleep than healthy control patients do. They awaken frequently during the night and have a higher risk of injury from falling. Awakening from different sleep stages may have different effects on postural stability and waking performance. However, limited research has been conducted on this topic. METHODS: This prospective randomized crossover study was conducted between January 2015 and January 2017. We included 20 adults aged 20-65 years who fulfilled the diagnosis criteria for CID. Participants underwent 2 overnight polysomnography studies with an interval of at least 7 days. They were awakened during either rapid eye movement (REM) sleep or stage N1/N2 sleep alternatively. We compared measurements of static postural stability, vigilance scores, and neuropsychological tests between REM sleep and stage N1/N2 sleep awakening. RESULTS: Polysomnography parameters between the 2 nights were comparable. Participants who were awakened from REM sleep had worse static postural stability than those with stage N1/N2 sleep awakening. Compared with stage N1/N2 sleep awakening, larger mean sway areas of center of pressure (P = .0413) and longer center-of-pressure mean distances (P = .0139) were found in REM sleep awakening. There were no statistically significant differences in vigilance scores or neuropsychological tests between the 2 nights. CONCLUSIONS: REM sleep awakening was associated with worse static postural stability than was stage N1/N2 sleep awakening. No statistically significant differences were found in waking performance in alertness or in neuropsychological tests between stage N1/N2 and REM sleep awakening. CITATION: Yeh W-C, Chuang Y-C, Yen C-W, et al. Static postural stability and neuropsychological performance after awakening from REM and NREM sleep in patients with chronic insomnia: a randomized, crossover, overnight polysomnography study. J Clin Sleep Med. 2022;18(8):1983-1992.

Rapid eye movement sleep reduction in patients with epilepsy: A systematic review and meta-analysis.

BACKGROUND: Compared to healthy controls, adults with epilepsy have a disrupted sleep architecture. Changes in sleep macrostructure may be associated with the refractoriness of epilepsy. However, there is no consensus regarding the changes in sleep architecture in patients with epilepsy. This meta-analysis aimed to elucidate the differences in sleep architecture between patients with epilepsy and healthy controls. METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. The PubMed, Embase, and Cochrane Central databases were searched (until May 2021) for studies comparing polysomnographic sleep macrostructures between patients with epilepsy and healthy controls. A meta-analysis was performed using a random-effects model. The percentage of rapid eye movement (REM) sleep, slow-wave sleep (SWS), and sleep efficiency (SE) were compared between patients with epilepsy and healthy controls. RESULTS: Overall, 24 studies involving 789 patients with epilepsy and 599 healthy controls fulfilled the eligibility criteria. Compared to healthy controls, patients with focal epilepsy had decreased REM sleep and SE. Patients with generalised epilepsy had increased SWS and decreased SE. Subgroup analyses focussed on the potential effect of seizure control on sleep architecture. The results revealed that both antiseizure medication (ASM)-untreated and treated patients had decreased SE. ASM treatment may restore REM sleep in patients with generalised epilepsy but not in patients with focal epilepsy. CONCLUSIONS: This meta-analysis revealed statistically significant differences in the sleep macrostructure between patients with epilepsy and healthy controls. There were significant differences in the sleep macrostructure between ASM-untreated patients and healthy controls, which may be an intrinsic change attributable to epilepsy.

Non-rapid eye movement sleep instability in adults with epilepsy: a systematic review and meta-analysis of cyclic alternating pattern.

STUDY OBJECTIVES: Epilepsy is characterized by disrupted sleep architecture. Studies on sleep macro- and microstructure revealed that patients with epilepsy experience disturbed rapid eye movement (REM) sleep; however, no consensus has been reached on non-REM (NREM) sleep changes. Cyclic alternating pattern (CAP) is a marker of sleep instability that occurs only during NREM sleep. This meta-analysis investigated CAP differences between patients with epilepsy and healthy controls. METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines in searching PubMed, Embase, and Cochrane Central database for studies comparing polysomnographic sleep microstructures between patients with epilepsy and healthy controls. A meta-analysis using a random-effects model was performed. We compared CAP rates, percentages of phase A1, A2, A3 subtypes, and phase B durations between patients with epilepsy and healthy controls. RESULTS: A total of 11 studies, including 209 patients with epilepsy and 197 healthy controls, fulfilled the eligibility criteria. Compared with healthy controls, patients with epilepsy had significantly increased CAP rates and decreased A1 subtype percentages, and patients with sleep-related epilepsy had increased A3 subtype percentages. Subgroup analyses revealed that antiseizure medications (ASMs) decreased CAP rates and increased phase B durations but did not affect the microstates of phase A in patients with sleep-related epilepsy. CONCLUSIONS: This meta-analysis detected statistically significant differences in CAP parameters between patients with epilepsy and healthy controls. Our findings suggest patients with epilepsy experience NREM sleep instability. ASMs treatment may decrease NREM instability but did not alter the microstates of phase A.