Clinical outcomes in individuals at clinical high risk of psychosis who do not transition to psychosis: a meta-analysis

Aims: The clinical outcomes of individuals at clinical high risk of psychosis (CHR-P) who do not transition to psychosis are heterogeneous and inconsistently reported. We aimed to comprehensively evaluate longitudinally a wide range of outcomes in CHR-P individuals not developing psychosis. Methods: "Preferred Reporting Items for Systematic reviews and Meta-Analyses" and "Meta-analysis Of Observational Studies in Epidemiology"-compliant meta-analysis (PROSPERO: CRD42021229212) searching original CHR-P longitudinal studies in PubMed and Web of Science databases up to 01/11/2021. As primary analysis, we evaluated the following outcomes within CHR-P non-transitioning individuals: (a) change in the severity of attenuated psychotic symptoms (Hedge's g); (b) change in the severity of negative psychotic symptoms (Hedge's g); (c) change in the severity of depressive symptoms (Hedge's g); (d) change in the level of functioning (Hedge's g); (e) frequency of remission (at follow-up). As a secondary analysis, we compared these outcomes in those CHR-P individuals who did not transition vs. those who did transition to psychosis at follow-up. We conducted random-effects model meta-analyses, sensitivity analyses, heterogeneity analyses, meta-regressions and publication bias assessment. The risk of bias was assessed using a modified version of the Newcastle-Ottawa Scale (NOS). Results: Twenty-eight studies were included (2756 CHR-P individuals, mean age = 20.4, 45.5% females). The mean duration of follow-up of the included studies was of 30.7 months. Primary analysis: attenuated psychotic symptoms [Hedges' g = 1.410, 95% confidence interval (CI) 1.002-1.818]; negative psychotic symptoms (Hedges' g = 0.683, 95% CI 0.371-0.995); depressive symptoms (Hedges' g = 0.844, 95% CI 0.371-1.317); and functioning (Hedges' g = 0.776, 95% CI 0.463-1.089) improved in CHR-P non-transitioning individuals; 48.7% remitted at follow-up (95% CI 39.3-58.2%). Secondary analysis: attenuated psychotic symptoms (Hedges' g = 0.706, 95% CI 0.091-1.322) and functioning (Hedges' g = 0.623, 95% CI 0.375-0.871) improved in CHR-P individuals not-transitioning compared to those transitioning to psychosis, but there were no differences in negative or depressive symptoms or frequency of remission (p > 0.05). Older age was associated with higher improvements of attenuated psychotic symptoms (β = 0.225, p = 0.012); publication years were associated with a higher improvement of functioning (β = -0.124, p = 0.0026); a lower proportion of Brief Limited Intermittent Psychotic Symptoms was associated with higher frequencies of remission (β = -0.054, p = 0.0085). There was no metaregression impact for study continent, the psychometric instrument used, the quality of the study or proportion of females. The NOS scores were 4.4 ± 0.9, ranging from 3 to 6, revealing the moderate quality of the included studies. Conclusions: Clinical outcomes improve in CHR-P individuals not transitioning to psychosis but only less than half remit over time. Sustained clinical attention should be provided in the longer term to monitor these outcomes

Probability of Transition to Psychosis in Individuals at Clinical High Risk: An Updated Meta-analysis

Estimating the current likelihood of transitioning from a clinical high risk for psychosis (CHR-P) to psychosis holds paramount importance for preventive care and applied research

Longitudinal outcome of attenuated positive symptoms, negative symptoms, functioning and remission in people at clinical high risk for psychosis:a meta-analysis

[EN] Background: Little is known about clinical outcomes other than transition to psychosis in people at Clinical High-Risk for psychosis (CHR-P). Our aim was to comprehensively meta-analytically evaluate for the first time a wide range of clinical and functional outcomes beyond transition to psychosis in CHR-P individuals. Methods: PubMed and Web of Science were searched until November 2020 in this PRISMA compliant metaanalysis (PROSPERO:CRD42020206271). Individual longitudinal studies conducted in individuals at CHR-P providing data on at least one of our outcomes of interest were included. We carried out random-effects pairwise meta-analyses, meta-regressions, and assessed publication bias and study quality. Analyses were twotailed with a=0.05. Findings: 75 prospective studies were included (n=5,288, age=20.0 years, females=44.5%). Attenuated positive symptoms improved at 12 (Hedges’ g=0.753, 95%CI=0.495-1.012) and 24 (Hedges’ g=0.836, 95%CI=0.463- 1.209), but not 36 months (Hedges’ g=0.315. 95%CI=-0.176 0.806). Negative symptoms improved at 12 (Hedges’ g=0.496, 95%CI=0.315 0.678), but not 24 (Hedges’ g=0.499, 95%CI=-0.137 1.134) or 36 months (Hedges’ g=0.033, 95%CI=-0.439 0.505). Depressive symptoms improved at 12 (Hedges’ g=0.611, 95%CI=0.441 0.782) and 24 (Hedges’ g=0.583, 95%CI=0.364 0.803), but not 36 months (Hedges’ g=0.512 95%CI=-0.337 1.361). Functioning improved at 12 (Hedges’ g=0.711, 95%CI=0.488 0.934), 24 (Hedges’ g=0.930, 95%CI=0.553 1.306) and 36 months (Hedges’ g=0.392, 95%CI=0.117 0.667). Remission from CHRP status occurred in 33.4% (95%CI=22.6 44.1%) at 12 months, 41.4% (95%CI=32.3 50.5%) at 24 months and 42.4% (95%CI=23.4 61.3%) at 36 months. Heterogeneity across the included studies was significant and ranged from I2=53.6% to I2=96.9%. The quality of the included studies (mean§SD) was 4.6§1.1 (range=2-8). Interpretation: CHR-P individuals improve on symptomatic and functional outcomes over time, but these improvements are not maintained in the longer term, and less than half fully remit. Prolonged duration of care may be needed for this patient population to optimize outcomes.There was no funding source for this stud

Hypertension and migraine comorbidity: prevalence and risk of cerebrovascular events: evidence from a large, multicenter, cross-sectional survey in Italy (MIRACLES study)

OBJECTIVES: To estimate the prevalence of hypertension-migraine comorbidity; to determine their demographic and clinical characteristics versus patients with hypertension or migraine alone; and to see whether a history of cerebrovascular events was more common in the comorbidity group. METHODS: The MIRACLES, multicenter, cross-sectional, survey included 2973 patients with a known diagnosis of hypertension or migraine in a general practitioner setting in Italy. RESULTS: Five hundred and seventeen patients (17%) suffered from hypertension-migraine comorbidity, whereas 1271 (43%) suffered from hypertension only, and 1185 (40%) from migraine only. In the comorbidity group, the onset of comorbidity occurred at about 45 years of age, with migraine starting significantly later than in the migraine-only group, and hypertension significantly before than in the hypertension-only group; a familial history of both hypertension and migraine had a significantly higher frequency as compared with the hypertension and migraine group. Compared to hypertension (3.1%) and migraine (0.7%), the comorbidity group had a higher prevalence (4.4%) of history of cerebrovascular events, with an odds ratio of a predicted history of stroke/transient ischemic attack (TIA) of 1.76 [95% confidence interval (CI) 1.01-3.07] compared to the hypertension group. In patients without other recognized risk factors for stroke, stroke/TIA occurred more frequently in the comorbidity group, compared to the hypertension group. In the age range 40-49 years, prevalence of history of stroke/TIA was five-fold greater (4.8% in comorbidity vs. 0.9% in hypertension group). CONCLUSION: This cross-sectional study indicates that the prevalence of comorbidity hypertension-migraine is substantial and that patients with comorbidity have a higher probability of history of cerebrovascular events, compared to hypertensive patient