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This study aim to derive and validate a simple and well-performing risk calculator (RC) for predicting psychosis in individual patients at clinical high risk (CHR). From the ongoing ShangHai-At-Risk-for-Psychosis (SHARP) program, 417 CHR cases were identified based on the Structured Interview for Prodromal Symptoms (SIPS), of whom 349 had at least 1-year follow-up assessment. Of these 349 cases, 83 converted to psychosis. Logistic regression was used to build a multivariate model to predict conversion. The area under the receiver operating characteristic (ROC) curve (AUC) was used to test the effectiveness of the SIPS-RC. Second, an independent sample of 100 CHR subjects was recruited based on an identical baseline and follow-up procedures to validate the performance of the SIPS-RC. Four predictors (each based on a subset of SIPS-based items) were used to construct the SIPS-RC: (1) functional decline; (2) positive symptoms (unusual thoughts, suspiciousness); (3) negative symptoms (social anhedonia, expression of emotion, ideational richness); and (4) general symptoms (dysphoric mood). The SIPS-RC showed moderate discrimination of subsequent transition to psychosis with an AUC of 0.744 (p < 0.001). A risk estimate of 25% or higher had around 75% accuracy for predicting psychosis. The personalized risk generated by the SIPS-RC provided a solid estimate of conversion outcomes in the independent validation sample, with an AUC of 0.804 [95% confidence interval (CI) 0.662-0.951]. The SIPS-RC, which is simple and easy to use, can perform in the same manner as the NAPLS-2 RC in the Chinese clinical population. Such a tool may be used by clinicians to counsel appropriately their patients about clinical monitor v. potential treatment options.

In the 1990s criteria were developed to detect individuals at high and imminent risk of developing a psychotic disorder. These are known as the at risk mental state, ultra high risk or clinical high risk criteria. Individuals meeting these criteria are symptomatic and help-seeking. Services for such individuals are now found worldwide. Recently Psychological Medicine published two articles that criticise these services and suggest that they should be dismantled or restructured. One paper also provides recommendations on how ARMS services should be operate. In this paper we draw on the existing literature in the field and present the perspective of some ARMS clinicians and researchers. Many of the critics' arguments are refuted. Most of the recommendations included in the Moritz et al. paper are already occurring. ARMS services provide management of current problems, treatment to reduce risk of onset of psychotic disorder and monitoring of mental state, including attenuated psychotic symptoms. These symptoms are associated with a range of poor outcomes. It is important to assess them and track their trajectory over time. A new approach to detection of ARMS individuals can be considered that harnesses broad youth mental health services, such as headspace in Australia, Jigsaw in Ireland and ACCESS Open Minds in Canada. Attention should also be paid to the physical health of ARMS individuals. Far from needing to be dismantled we feel that the ARMS approach has much to offer to improve the health of young people.

Progesterone administration has been shown to reduce the risk of preterm birth and neonatal morbidity in women at high risk, but there is uncertainty about longer term effects on the child. We did a double-blind, randomised, placebo-controlled trial of vaginal progesterone, 200 mg daily taken from 22–24 to 34 weeks of gestation, on pregnancy and infant outcomes in women at risk of preterm birth (because of previous spontaneous birth at ≤34 weeks and 0 days of gestation, or a cervical length ≤25 mm, or because of a positive fetal fibronectin test combined with other clinical risk factors for preterm birth [any one of a history in a previous pregnancy of preterm birth, second trimester loss, preterm premature fetal membrane rupture, or a history of a cervical procedure to treat abnormal smears]). The objective of the study was to determine whether vaginal progesterone prophylaxis given to reduce the risk of preterm birth affects neonatal and childhood outcomes. We defined three primary outcomes: fetal death or birth before 34 weeks and 0 days gestation (obstetric), a composite of death, brain injury, or bronchopulmonary dysplasia (neonatal), and a standardised cognitive score at 2 years of age (childhood), imputing values for deaths. Randomisation was done through a web portal, with participants, investigators, and others involved in giving the intervention, assessing outcomes, or analysing data masked to treatment allocation until the end of the study. Analysis was by intention to treat. This trial is registered at ISRCTN.com, number ISRCTN14568373. Between Feb 2, 2009, and April 12, 2013, we randomly assigned 1228 women to the placebo group (n=610) and the progesterone group (n=618). In the placebo group, data from 597, 587, and 439 women or babies were available for analysis of obstetric, neonatal, and childhood outcomes, respectively; in the progesterone group the corresponding numbers were 600, 589, and 430. After correction for multiple outcomes, progesterone had no significant effect on the primary obstetric outcome (odds ratio adjusted for multiple comparisons [OR] 0·86, 95% CI 0·61–1·22) or neonatal outcome (OR 0·72, 0·44–1·17), nor on the childhood outcome (cognitive score, progesterone group vs placebo group, 97·3 [SD 17·9] vs 97·7 [17·5]; difference in means –0·48, 95% CI –2·77 to 1·81). Maternal or child serious adverse events were reported in 70 (11%) of 610 patients in the placebo group and 59 (10%) of 616 patients in the progesterone group (p=0·27). Vaginal progesterone was not associated with reduced risk of preterm birth or composite neonatal adverse outcomes, and had no long-term benefit or harm on outcomes in children at 2 years of age. Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership. The EME Programme is funded by the MRC and NIHR, with contributions from the Chief Scientist Office in Scotland and National Institute for Social Care and Research in Wales.

Despite a fair amount of progress on understanding human immunodeficiency virus (HIV) epidemiology globally, the Middle East and North Africa (MENA) region is the only region where knowledge of the epidemic continues to be very limited, and subject to much controversy. It has been more than 25 years since the discovery of HIV, but no scientific study has provided a comprehensive data-driven synthesis of HIV/AIDS (acquired immunodeficiency syndrome) infectious spread in this region. The current report provides the first comprehensive scientific assessment and data-driven epidemiological synthesis of HIV spread in MENA since the beginning of the epidemic. It is based on a literature review and analysis of thousands of widely unrecognized publications, reports, and data sources extracted from scientific literature or collected from sources at the local, national, and regional levels. The recommendations provided here focus on key strategies related to the scope of this report and its emphasis on understanding HIV epidemiology in MENA as a whole. The recommendations are based on identifying the status of the HIV epidemic in MENA, through this synthesis, as a low HIV prevalence setting with rising concentrated epidemics among priority populations. General directions for prevention interventions as warranted by the outcome of this synthesis are also discussed briefly, but are not delineated because they are beyond the scope of this report. This report was not intended to provide intervention recommendations for each MENA country.

Childhood adversities have been reported to be more common among individuals at ultra-high risk (UHR) for psychosis. This paper systematically reviewed and meta-analysed (i) the severity and prevalence of childhood adversities (childhood trauma exposure, bullying victimisation and parental separation or loss) among the UHR, and (ii) the association between adversities and transition to psychosis (TTP). PsycINFO, PubMed and Embase databases were searched for studies reporting childhood adversities among UHR individuals. Only published articles were included. Risk of bias was assessed using Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline (von Elm et al., 2007) and the tool developed by Hoy et al. (2012). Seventeen case–control, cross-sectional and longitudinal studies were included. UHR individuals experienced significantly more severe trauma than controls, regardless of trauma subtype. UHR were 5.5, 2.5 and 3.1 times as likely to report emotional abuse, physical abuse and bullying victimisation, respectively. There was no association with parental separation. However, childhood trauma was not significantly associated with TTP (follow-up periods: 6 months to 15 years), suggesting that trauma alone may not be a sufficient risk factor. Sexual abuse was associated with TTP but this may have been driven by a single large study. Potential confounders and low rates of TTP among UHR are limitations of this review. This is the first meta-analysis that quantitatively summarises the associations between childhood adversities and TTP among UHR, and between specific abuse subtypes and TTP. Specific recommendations have been made to increase the quality of future research. PROSPERO registration no. CRD42017054884.

The clinical significance of intraductal carcinoma of the prostate (IDC‐P) in men with nonmetastatic prostate cancer (PCa) treated with high‐dose external‐beam radiation therapy remains unclear. The aim of this study was to evaluate the impact of IDC‐P in men who received intensity‐modulated radiation therapy (IMRT) for nonmetastatic PCa. All patients with high‐risk (H‐R) and very high–risk (VH‐R) PCa who received IMRT between September 2000 and December 2013 at our institution were analyzed retrospectively. We re‐reviewed biopsy cores for the presence of IDC‐P. Treatment consisted of IMRT (median: 78 Gy at 2 Gy per fraction) plus 6‐month neoadjuvant hormonal therapy (HT). In total, 154 consecutive patients with H‐R and VH‐R PCa were analyzed. Intraductal carcinoma of the prostate was present in 27.9% (n = 43). The median follow‐up period was 8.4 years. The 10‐year PCa‐specific survival, biochemical failure (BF), clinical failure, and castration‐resistant PCa rates were 90.0%, 47.8%, 27.5%, and 24.5% in patients with IDC‐P, and 96.6%, 32.6%, 10.8%, and 7.0% in those without IDC‐P, respectively (p = 0.12, 0.04, 0.0031, and 0.012, respectively). In multivariable analysis, IDC‐P was not identified as an independent predictive factor for BF (p = 0.26). The presence of IDC‐P was correlated with a significantly higher incidence of disease progression in men with H‐R and VH‐R PCa who received IMRT, although it was not identified as an independent predictive factor for BF. Further investigations are needed to determine the significance of IDC‐P as an independent predictive factor for survival outcomes. The clinical significance of intraductal carcinoma of the prostate (IDC‐P) in men with nonmetastatic prostate cancer (PCa) treated with definitive external‐beam radiation therapy remains unclear. We evaluated the impact of IDC‐P in men who received intensity‐modulated radiation therapy for high‐risk and very high‐risk prostate cancer. The presence of IDC‐P was correlated with a significantly higher incidence of disease progression, and PCa‐specific mortality in men, although it was not identified as an independent predictive factor for biochemical failure.

Emerging meta-analytical evidence indicates that baseline exposure to antipsychotics in individuals at clinical high-risk for psychosis (CHR-P) is associated with a higher risk of an imminent transition to psychosis. Despite their tolerability profile and potential beneficial effects, baseline exposure to antidepressants (AD) in CHR-P has surprisingly received far less attention as a potential risk modulator for transition to psychosis. The current systematic review and meta-analysis were performed to fix such a knowledge gap. Systematic scrutiny of Medline and Cochrane library, performed up to 1 August 2021, searching for English-language studies on CHR-P reporting numeric data about the sample, the transition outcome at a predefined follow-up time and raw data on AD baseline exposure in relation to such outcome. Of 1942 identified records, 16 studies were included in the systematic review and meta-analysis. 26% of the participants were already exposed to AD at baseline; at the end of the follow-up 13.5% (95% CI 10.2-17.1%) of them ( = 448) transitioned to psychosis against 21.0% (18.9 to 23.3%) of non-AD exposed CHR-P ( = 1371). CHR-P participants who were already under AD treatment at baseline had a lower risk of transition than non-AD exposed CHR-P. The RR was 0.71 (95% CI 0.56-0.90) in the fixed-effects model ( = -2.79; = 0.005), and 0.78 (0.58-1.05) in the random-effects model ( = -1.77; = 0.096; tau-squared = 0.059). There was no relevant heterogeneity (Cochran's = 18.45; df = 15; = 0.239; = 18.7%). Ongoing AD exposure at inception in CHR-P is associated to a reduced risk of transition to psychosis at follow up.

Suicide and self-harm are prevalent in individuals diagnosed with psychotic disorders. However, less is known about the level of self-injurious thinking and behaviour in those individuals deemed to be at ultra-high risk (UHR) of developing psychosis, despite growing clinical interest in this population. This review provides a synthesis of the extant literature concerning the prevalence of self-harm and suicidality in the UHR population, and the predictors and correlates associated with these events. A search of electronic databases was undertaken by two independent reviewers. A meta-analysis of prevalence was undertaken for self-harm, suicidal ideation and behaviour. A narrative review was also undertaken of analyses examining predictors and correlates of self-harm and suicidality. Twenty-one eligible studies were identified. The meta-analyses suggested a high prevalence of recent suicidal ideation (66%), lifetime self-harm (49%) and lifetime suicide attempts (18%). Co-morbid psychiatric problems, mood variability and a family history of psychiatric problems were among the factors associated with self-harm and suicide risk. Results suggest that self-harm and suicidality are highly prevalent in the UHR population, with rates similar to those observed in samples with diagnosed psychotic disorders. Appropriate monitoring and managing of suicide risk will be important for services working with the UHR population. Further research in this area is urgently needed considering the high rates identified.

This study evaluated whether the addition of a monoclonal antibody against the tumor-associated disialoganglioside GD2, in combination with GM-CSF and interleukin-2, to standard therapy consisting of isotretinoin alone improved outcomes in children with high-risk neuroblastoma. Neuroblastoma, a cancer of the sympathetic nervous system responsible for 12% of deaths associated with cancer in children under 15 years of age, 1 is a heterogeneous disease, with nearly 50% of patients having a high-risk phenotype characterized by widespread dissemination of the cancer and poor long-term survival, even if intensive multimodal treatments are used. 2 The initial results of the last randomized, controlled trial showing a significant improvement in outcomes were published over a decade ago 3 , 4 and established the standard therapy for high-risk neuroblastoma: myeloablative therapy with stem-cell rescue, followed by the treatment of minimal residual disease with isotretinoin. However, . . .

To improve early intervention and personalise treatment for individuals early on the psychosis continuum, a greater understanding of symptom dynamics is required. We address this by identifying and evaluating the movement between empirically derived attenuated psychotic symptomatic substates-clusters of symptoms that occur within individuals over time. Data came from a 90-day daily diary study evaluating attenuated psychotic and affective symptoms. The sample included 96 individuals aged 18-35 on the psychosis continuum, divided into four subgroups of increasing severity based on their psychometric risk of psychosis, with the fourth meeting ultra-high risk (UHR) criteria. A multilevel hidden Markov modelling (HMM) approach was used to characterise and determine the probability of switching between symptomatic substates. Individual substate trajectories and time spent in each substate were subsequently assessed. Four substates of increasing psychopathological severity were identified: (1) low-grade affective symptoms with negligible psychotic symptoms; (2) low levels of nonbizarre ideas with moderate affective symptoms; (3) low levels of nonbizarre ideas and unusual thought content, with moderate affective symptoms; and (4) moderate levels of nonbizarre ideas, unusual thought content, and affective symptoms. Perceptual disturbances predominantly occurred within the third and fourth substates. UHR individuals had a reduced probability of switching out of the two most severe substates. Findings suggest that individuals reporting unusual thought content, rather than nonbizarre ideas in isolation, may exhibit symptom dynamics with greater psychopathological severity. Individuals at a higher risk of psychosis exhibited persistently severe symptom dynamics, indicating a potential reduction in psychological flexibility.