Prognostic accuracy and clinical utility of psychometric instruments for individuals at clinical high-risk of psychosis: a systematic review and meta-analysis.

Accurate prognostication of individuals at clinical high-risk for psychosis (CHR-P) is an essential initial step for effective primary indicated prevention. We aimed to summarise the prognostic accuracy and clinical utility of CHR-P assessments for primary indicated psychosis prevention. Web of Knowledge databases were searched until 1st January 2022 for longitudinal studies following-up individuals undergoing a psychometric or diagnostic CHR-P assessment, reporting transition to psychotic disorders in both those who meet CHR-P criteria (CHR-P + ) or not (CHR-P-). Prognostic accuracy meta-analysis was conducted following relevant guidelines. Primary outcome was prognostic accuracy, indexed by area-under-the-curve (AUC), sensitivity and specificity, estimated by the number of true positives, false positives, false negatives and true negatives at the longest available follow-up time. Clinical utility analyses included: likelihood ratios, Fagan's nomogram, and population-level preventive capacity (Population Attributable Fraction, PAF). A total of 22 studies (n = 4 966, 47.5% female, age range 12-40) were included. There were not enough meta-analysable studies on CHR-P diagnostic criteria (DSM-5 Attenuated Psychosis Syndrome) or non-clinical samples. Prognostic accuracy of CHR-P psychometric instruments in clinical samples (individuals referred to CHR-P services or diagnosed with 22q.11.2 deletion syndrome) was excellent: AUC = 0.85 (95% CI: 0.81-0.88) at a mean follow-up time of 34 months. This result was driven by outstanding sensitivity (0.93, 95% CI: 0.87-0.96) and poor specificity (0.58, 95% CI: 0.50-0.66). Being CHR-P + was associated with a small likelihood ratio LR + (2.17, 95% CI: 1.81-2.60) for developing psychosis. Being CHR-P- was associated with a large LR- (0.11, 95%CI: 0.06-0.21) for developing psychosis. Fagan's nomogram indicated a low positive (0.0017%) and negative (0.0001%) post-test risk in non-clinical general population samples. The PAF of the CHR-P state is 10.9% (95% CI: 4.1-25.5%). These findings consolidate the use of psychometric instruments for CHR-P in clinical samples for primary indicated prevention of psychosis. Future research should improve the ability to rule in psychosis risk.

Drug-Related Hypersensitivity Reactions Leading to Emergency Department: Original Data and Systematic Review.

The aim of the present study is to describe pharmacological characteristics of drug-related allergies and anaphylaxis leading to the emergency department (ED). An 8-year post hoc analysis on the MEREAFaPS Study database was performed (2012−2019). Subjects who experienced drug-related hypersensitivity leading to an ED visit were selected. Logistic regression analyses were used to estimate the reporting odds ratios (RORs) of drug-related allergies and anaphylaxis adjusting for sex, age classes, and ethnicity. In addition, a systematic review of observational studies evaluating drug-related hypersensitivity reactions leading to ED visits in outpatients was performed. Out of 94,073 ED visits, 14.4% cases were drug-related allergies and 0.6% were anaphylaxis. Females accounted for 56%. Multivariate logistic regression showed a higher risk of drug-related allergy among males and all age classes < 65 years, while a higher risk of anaphylaxis was observed for females (ROR 1.20 [1.01−1.42]) and adults (ROR 2.63 [2.21−3.14]). The systematic review included 37 studies. ED visits related to allergy and anaphylaxis ranged from 0.004% to 88%, and drug-related allergies and anaphylaxis ranged from 0.007% to 88%. Both in our analysis and in primary studies, antibacterials, analgesics, and radiocontrast agents were identified as the most common triggers of hypersensitivity.

Risk of Hospitalization for Adverse Drug Events in Women and Men: A Post Hoc Analysis of an Active Pharmacovigilance Study in Italian Emergency Departments.

This post hoc analysis of an Italian active pharmacovigilance study describes pharmacological differences of ADEs leading to emergency department (ED) visits and hospitalization in women and men. During the study period (January 2007-December 2018), 61,855 reports of ADEs leading to ED visits were collected. Overall, 30.6% of ADEs resulted in hospitalization (30% in women and 31% in men). Multivariate logistic regression showed that, among women, drug classes significantly associated with an increased risk of hospitalization were heparins (ROR 1.41, CI 1.13-176), antidepressants (ROR 1.12, CI 1.03-1.23) and antidiabetics (ROR 1.13, CI 1.02-1.24). Among men, only vitamin K antagonists (ROR 1.28, CI 1.09-1.50), opioids (ROR 1.30, CI 1.06-1.60) and digitalis glycosides (ROR 1.32, CI 1.09-1.59) were associated with a higher risk of hospitalization. Overall, older age, multiple suspected drugs and the presence of comorbidities were significantly associated with a higher risk of hospitalization. A significantly reduced risk of hospitalization was observed in both women and men experiencing an adverse event following immunization (ROR 0.36, CI 0.27-0.48 and 0.83, 0.42-0.74, respectively) compared to drugs. Results obtained from this real-world analysis highlight important aspects of drug safety between sexes.

Analysis of fatal adverse drug events recorded in several Italian emergency departments (the MEREAFaPS study).

Fatal Adverse Events (FADEs) are a major public health problem, and some FADEs could be preventable. The aim of the present study is to describe the frequency, the drugs involved and the preventability in the FADEs collected through the MEREAFaPS Study between 2012 and 2018. All cases including the outcome "death" have been examined. We excluded cases with vaccine-related ADEs, overdose or suicide, and ADEs occurred during the hospitalisation. Two trained assessors evaluated all cases fulfilling the inclusion criteria. ADEs' preventability was evaluated applying the Schumock and Thornton algorithm. During the study period, we observed 429 cases of death, 92 of which were excluded. The remaining 337 cases involved 187 women and 150 men, with a mean age of 79 and of 77 years, respectively. For each report, the suspected drugs and concomitant ones were 1.26 and 4.20, respectively. Anticoagulants and antiplatelet agents account for more than 40% of FADE cases and the most frequent reactions are haemorrhages (37.5%). The 25% of the FADEs were preventable. This study confirms that FADEs are still a relevant clinical occurrence, and are often caused by widely used old drugs associated with adverse events. The death of one in four patients was preventable. Further efforts should be done to improve the appropriateness of the therapy, especially in older patients who are treated with anticoagulants.

The case for improved transdiagnostic detection of first-episode psychosis: Electronic health record cohort study.

BACKGROUND: Improving outcomes of a First Episode of Psychosis (FEP) relies on the ability to detect most individuals with emerging psychosis and treat them in specialised Early Intervention (EI) services. Efficacy of current detection strategies is undetermined. METHODS: RECORD-compliant clinical, 6-year, retrospective, transdiagnostic, lifespan-inclusive, Electronic Health Record (EHR) cohort study, representing real-world secondary mental healthcare in South London and Maudsley (SLaM) NHS. All individuals accessing SLaM in the period 2007-2017 and receiving any ICD-10 diagnosis other than persistent psychosis were included. Descriptive statistics, Kaplan-Meier curves, logistic regression, epidemiological incidence of psychosis in the general population were used to address pathways to care and detection power of EI services for FEP. RESULTS: A total of 106,706 individuals underwent the 6-year follow-up: they were mostly single (72.57%) males (50.51%) of white ethnicity (60.01%), aged on average 32.96 years, with an average Health Of the Nation Outcome Scale score of 11.12 and mostly affected with F40-48 Neurotic/stress-related/somatoform disorders (27.46%). Their transdiagnostic risk of developing a FEP cumulated to 0.072 (95%CI 0.067-0.077) at 6 years. Those individuals who developed a FEP (n = 1841) entered healthcare mostly (79.02%) through inpatient mental health services (29.76%), community mental health services (29.54%) or accident and emergency departments (19.50%); at the time of FEP onset, most of them (46.43%) were under the acute care pathway. Individuals contacting accident and emergency departments had an increased risk of FEP (OR 2.301, 95%CI 2.095-2.534, P < 0.001). The proportion of SLaM FEP cases that were eligible and under the care of EI services was 0.456 at any time. The epidemiological proportion of FEP cases in the sociodemographically-matched general population that was detected by EI service was 0.373. CONCLUSIONS: More than half of individuals who develop a FEP remain undetected by current pathways to care and EI services. Improving detection strategies should become a mainstream area in the future generation of early psychosis research.

Real-world implementation of precision psychiatry: Transdiagnostic risk calculator for the automatic detection of individuals at-risk of psychosis.

BACKGROUND: Risk estimation models integrated into Electronic Health Records (EHRs) can deliver innovative approaches in psychiatry, but clinicians' endorsement and their real-world usability are unknown. This study aimed to investigate the real-world feasibility of implementing an individualised, transdiagnostic risk calculator to automatically screen EHRs and detect individuals at-risk for psychosis. METHODS: Feasibility implementation study encompassing an in-vitro phase (March 2018 to May 2018) and in-vivo phase (May 2018 to April 2019). The in-vitro phase addressed implementation barriers and embedded the risk calculator (predictors: age, gender, ethnicity, index cluster diagnosis, age*gender) into the local EHR. The in-vivo phase investigated the real-world feasibility of screening individuals accessing secondary mental healthcare at the South London and Maudsley NHS Trust. The primary outcome was adherence of clinicians to automatic EHR screening, defined by the proportion of clinicians who responded to alerts from the risk calculator, over those contacted. RESULTS: In-vitro phase: implementation barriers were identified/overcome with clinician and service user engagement, and the calculator was successfully integrated into the local EHR through the CogStack platform. In-vivo phase: 3722 individuals were automatically screened and 115 were detected. Clinician adherence was 74% without outreach and 85% with outreach. One-third of clinicians responded to the first email (37.1%) or phone calls (33.7%). Among those detected, cumulative risk of developing psychosis was 12% at six-month follow-up. CONCLUSION: This is the first implementation study suggesting that combining precision psychiatry and EHR methods to improve detection of individuals with emerging psychosis is feasible. Future psychiatric implementation research is urgently needed.

Implementation of a Real-Time Psychosis Risk Detection and Alerting System Based on Electronic Health Records using CogStack.

Recent studies have shown that an automated, lifespan-inclusive, transdiagnostic, and clinically based, individualized risk calculator provides a powerful system for supporting the early detection of individuals at-risk of psychosis at a large scale, by leveraging electronic health records (EHRs). This risk calculator has been externally validated twice and is undergoing feasibility testing for clinical implementation. Integration of this risk calculator in clinical routine should be facilitated by prospective feasibility studies, which are required to address pragmatic challenges, such as missing data, and the usability of this risk calculator in a real-world and routine clinical setting. Here, we present an approach for a prospective implementation of a real-time psychosis risk detection and alerting service in a real-world EHR system. This method leverages the CogStack platform, which is an open-source, lightweight, and distributed information retrieval and text extraction system. The CogStack platform incorporates a set of services that allow for full-text search of clinical data, lifespan-inclusive, real-time calculation of psychosis risk, early risk-alerting to clinicians, and the visual monitoring of patients over time. Our method includes: 1) ingestion and synchronization of data from multiple sources into the CogStack platform, 2) implementation of a risk calculator, whose algorithm was previously developed and validated, for timely computation of a patient's risk of psychosis, 3) creation of interactive visualizations and dashboards to monitor patients' health status over time, and 4) building automated alerting systems to ensure that clinicians are notified of patients at-risk, so that appropriate actions can be pursued. This is the first ever study that has developed and implemented a similar detection and alerting system in clinical routine for early detection of psychosis.

Real-world digital implementation of the Psychosis Polyrisk Score (PPS): A pilot feasibility study.

BACKGROUND: The Psychosis Polyrisk Score (PPS) is a potential biomarker integrating non-purely genetic risk/protective factors for psychosis that may improve identification of individuals at risk and prediction of their outcomes at the individual subject level. Biomarkers that are easy to administer are direly needed in early psychosis to facilitate clinical implementation. This study digitally implements the PPS and pilots its feasibility of use in the real world. METHODS: The PPS was implemented digitally and prospectively piloted across individuals referred for a CHR-P assessment (n = 16) and healthy controls (n = 66). Distribution of PPS scores was further simulated in the general population. RESULTS: 98.8% of individuals referred for a CHR-P assessment and healthy controls completed the PPS assessment with only one drop-out. 96.3% of participants completed the assessment in under 15 min. Individuals referred for a CHR-P assessment had high PPS scores (mean = 6.2, SD = 7.23) than healthy controls (mean = -1.79, SD = 6.78, p < 0.001). In simulated general population data, scores were normally distributed ranging from -15 (lowest risk, RR = 0.03) to 39.5 (highest risk, RR = 8912.51). DISCUSSION: The PPS is a promising biomarker which has been implemented digitally. The PPS can be easily administered to both healthy controls and individuals at potential risk for psychosis on a range of devices. It is feasible to use the PPS in real world settings to assess individuals with emerging mental disorders. The next phase of research should be to include the PPS in large-scale international cohort studies to evaluate its ability to refine the prognostication of outcomes.

Prenatal and perinatal risk and protective factors for psychosis: a systematic review and meta-analysis.

BACKGROUND: Prenatal and perinatal insults are implicated in the aetiopathogenesis of psychotic disorders but the consistency and magnitude of their associations with psychosis have not been updated for nearly two decades. The aim of this systematic review and meta-analysis was to provide a comprehensive and up-to-date synthesis of the evidence on the association between prenatal or perinatal risk and protective factors and psychotic disorders. METHODS: In this systematic review and meta-analysis, we searched the Web of Science database for articles published up to July 20, 2019. We identified cohort and case-control studies examining the association (odds ratio [OR]) between prenatal and perinatal factors and any International Classification of Diseases (ICD) or Diagnostic and Statistical Manual of Mental Disorders (DSM) non-organic psychotic disorder with a healthy comparison group. Other inclusion criteria were enough data available to do the analyses, and non-overlapping datasets. We excluded reviews, meta-analyses, abstracts or conference proceedings, and articles with overlapping datasets. Data were extracted according to EQUATOR and PRISMA guidelines. Extracted variables included first author, publication year, study type, sample size, type of psychotic diagnosis (non-affective psychoses or schizophrenia-spectrum disorders, affective psychoses) and diagnostic instrument (DSM or ICD and version), the risk or protective factor, and measure of association (primary outcome). We did random-effects pairwise meta-analyses, Q statistics, I2 index, sensitivity analyses, meta-regressions, and assessed study quality and publication bias. The study protocol was registered at PROSPERO, CRD42017079261. FINDINGS: 152 studies relating to 98 risk or protective factors were eligible for analysis. Significant risk factors were: maternal age younger than 20 years (OR 1·17) and 30-34 years (OR 1·05); paternal age younger than 20 years (OR 1·31) and older than 35 years (OR 1·28); any maternal (OR 4·60) or paternal (OR 2·73) psychopathology; maternal psychosis (OR 7·61) and affective disorder (OR 2·26); three or more pregnancies (OR 1·30); herpes simplex 2 (OR 1·35); maternal infections not otherwise specified (NOS; OR 1·27); suboptimal number of antenatal visits (OR 1·83); winter (OR 1·05) and winter to spring (OR 1·05) season of birth in the northern hemisphere; maternal stress NOS (OR 2·40); famine (OR 1·61); any famine or nutritional deficits in pregnancy (OR 1·40); maternal hypertension (OR 1·40); hypoxia (OR 1·63); ruptured (OR 1·86) and premature rupture (OR 2·29) of membranes; polyhydramnios (OR 3·05); definite obstetric complications NOS (OR 1·83); birthweights of less than 2000 g (OR 1·84), less than 2500 g (OR 1·53), or 2500-2999 g (OR 1·23); birth length less than 49 cm (OR 1·17); small for gestational age (OR 1·40); premature birth (OR 1·35), and congenital malformations (OR 2·35). Significant protective factors were maternal ages 20-24 years (OR 0·93) and 25-29 years (OR 0·92), nulliparity (OR 0·91), and birthweights 3500-3999 g (OR 0·90) or more than 4000 g (OR 0·86). The results were corrected for publication biases; sensitivity and meta-regression analyses confirmed the robustness of these findings for most factors. INTERPRETATION: Several prenatal and perinatal factors are associated with the later onset of psychosis. The updated knowledge emerging from this study could refine understanding of psychosis pathogenesis, enhance multivariable risk prediction, and inform preventive strategies. FUNDING: None.

Risk of Hospitalization Associated with Cardiovascular Medications in the Elderly Italian Population: A Nationwide Multicenter Study in Emergency Departments.

Background: There is a significant gap in knowledge addressing cardiovascular (CV) medications safety in elderly. In this context, our purposes were to define clinical and pharmacological characteristics of outpatients' adverse drug events (ADEs) related to CV medications leading to emergency department (ED) visits in the elderly Italian patients according to different age groups, and to evaluate the risk of hospitalization associated to ADEs in this population. Methods: A multicentre, retrospective study was performed on reports of suspected ADEs collected between 2007-2018 in 94 EDs involved in the MEREAFaPS Study. Elderly patients who experienced one or more CV medications-related ADEs leading to ED visit were selected. Patients' characteristics, suspected (ATC classes B and C) and concomitant drugs, and ADE description were collected. Elderly patients were stratified into three age groups (65-74, 75-84, and ≥85 years) and compared to adults (18-64 years). Logistic regression analyses were used to estimate the reporting odds ratios (RORs) with 95% confidence intervals (CIs) of ADE-related hospitalization adjusting for sex, presence of two or more suspected drugs, concomitant drugs, and one or more comorbidities. Results: Among elderly, 16,926 reports of suspected ADE related to CV medications were collected, and 6,694 (39.5%) resulted in hospitalization. Patients were mostly female, Caucasians, and middle-old (75-84). 78.9% of patients were treated with only one suspected drug, and 71.9% and 47.1% reported concomitant medications and comorbidities, respectively. Compared to adults, risk of hospitalization was significantly higher for middle-old and oldest-old patients exposed to vitamin K antagonists (1.29 [1.09-1.52] and 1.56 [1.30-187]), direct thrombin inhibitors (3.41 [1.44-8.08] and 4.12 [1.67-10.17]), antiplatelets (1.51 [1.26-1.81] and 2.09 [1.71-2.57]), and beta-blockers (1.89 [1.38-2.59 and 2.31 [1.60-3.35]). Overall, a higher risk of hospitalization was observed for renin-angiotensin system inhibitors (1.32 [1.04-1.68], 1.65 [1.32-2.06], and 2.20 [1.70-2.85]), presence of two or more concomitant drugs, and concomitant conditions. Conclusion: Our real-world findings underline relevant safety aspects of CV medications in the elderly Italian population. ED clinicians must always consider the higher risk of hospitalization related to the use of CV drugs in elderly, particularly in oldest-old ones, for antiarrhythmics, beta-blocking agents, renin-angiotensin system inhibitors, antiplatelets, and anticoagulants.

Predictors of Outcomes in Adolescents With Clinical High Risk for Psychosis, Other Psychiatric Symptoms, and Psychosis: A Longitudinal Protocol Study.

In children and adolescents, schizophrenia is one of the ten main causes of disability-adjusted life years. The identification of people at Clinical High Risk of developing Psychosis (CHR-P) is one of the most promising strategies to improve outcomes. However, in children and adolescents research on the CHR-P state is still in its infancy and the clinical validity of at-risk criteria appears understudied in this population. Furthermore, only few studies have evaluated the psychopathological, neuropsychological, neuroimaging characteristics and, especially, long-term outcomes of adolescents at high risk. We present here the protocol of an innovative longitudinal cohort study of adolescents aged 12-17. The sample will consist of patients admitted to a third level neuropsychiatric unit, belonging to one of the following three subgroups: 1) adolescents with established Diagnostic and Statistical Manual of Mental Disorder-Fifth Edition psychosis, 2) adolescents with CHR-P, and 3) adolescents with psychiatric symptoms other than established psychosis or CHR-P. The primary aim of our study is to evaluate the 2-year prognosis across the three groups. We will measure transition to psychosis (or the stability of the diagnosis of psychosis in the psychotic group), the risk of development of other psychiatric disorders, as well as socio-occupational functioning at outcome. The secondary aim will be to explore the effect of specific predictors (clinical, neuropsychological and neuroimaging factors) on the prognosis. At baseline, 1-year and 2-year follow-up participants will be assessed using standardized semi-structured interviews and instruments. Psychopathological and functioning variables, as well as neuropsychological domains will be compared across the three subgroups. Moreover, at baseline and 2-year follow-up all recruited patients will undergo a 3-Tesla magnetic resonance imaging examination and diffusion tensor imaging parameters will be analyzed. We believe that this study will advance our ability to predict outcomes in underage CHR-P samples. In particular, our data will enable a better understanding of the clinical significance of CHR-P in adolescents, and shed new light on prognostic factors that can be used to refine the prediction of clinical outcomes and the implementation of preventive interventions.

Real World Implementation of a Transdiagnostic Risk Calculator for the Automatic Detection of Individuals at Risk of Psychosis in Clinical Routine: Study Protocol.

Background: Primary indicated prevention in individuals at-risk for psychosis has the potential to improve the outcomes of this disorder. The ability to detect the majority of at-risk individuals is the main barrier toward extending benefits for the lives of many adolescents and young adults. Current detection strategies are highly inefficient. Only 5% (standalone specialized early detection services) to 12% (youth mental health services) of individuals who will develop a first psychotic disorder can be detected at the time of their at-risk stage. To overcome these challenges a pragmatic, clinically-based, individualized, transdiagnostic risk calculator has been developed to detect individuals at-risk of psychosis in secondary mental health care at scale. This calculator has been externally validated and has demonstrated good prognostic performance. However, it is not known whether it can be used in the real world clinical routine. For example, clinicians may not be willing to adhere to the recommendations made by the transdiagnostic risk calculator. Implementation studies are needed to address pragmatic challenges relating to the real world use of the transdiagnostic risk calculator. The aim of the current study is to provide in-vitro and in-vivo feasibility data to support the implementation of the transdiagnostic risk calculator in clinical routine. Method: This is a study which comprises of two subsequent phases: an in-vitro phase of 1 month and an in-vivo phase of 11 months. The in-vitro phase aims at developing and integrating the transdiagnostic risk calculator in the local electronic health register (primary outcome). The in-vivo phase aims at addressing the clinicians' adherence to the recommendations made by the transdiagnostic risk calculator (primary outcome) and other secondary feasibility parameters that are necessary to estimate the resources needed for its implementation. Discussion: This is the first implementation study for risk prediction models in individuals at-risk for psychosis. Ultimately, successful implementation is the true measure of a prediction model's utility. Therefore, the overall translational deliverable of the current study would be to extend the benefits of primary indicated prevention and improve outcomes of first episode psychosis. This may produce significant social benefits for many adolescents and young adults and their families.

Identifying children and adolescents at ultra high risk of psychosis in Italian neuropsychiatry services: a feasibility study.

The past 20 years have seen the evolution of the construct of a clinical high-risk (hereafter, HR) state for psychosis. This construct is designed to capture the pre-psychotic phase. Some aspects of this approach, such as its feasibility in children and adolescents, are still under investigation. In the present study, we address the feasibility of implementing prodrome clinics for HR individuals within the framework of Italy's national child and adolescent neuropsychiatry services and the clinical relevance of a HR diagnosis in this population. Using the Comprehensive Assessment of At-Risk Mental States (CAARMS) to identify help-seeking patients meeting at least one HR criterion at baseline (HR+), we recruited 50 subjects for a feasibility study. The results obtained show that the Italian version of the CAARMS is easily administrable, causing patients no substantial discomfort. The prevalence of HR+ in our cohort was 44 %, which increased by an additional 18 % when negative symptoms were considered as an experimental inclusion criterion (HRNeg). The HR+ subjects were significantly more impaired in their social and occupational functioning than their HR- peers (subjects not at HR). The cumulative 1-year transition risk of psychosis of the HR+ group was 26.7 %. When the HRNeg group was added, the 1-year transition risk was 17.3 %. We suggest that administration of the CAARMS to children and adolescents with putative prodromal psychosis is feasible and that this assessment can easily be integrated into existing Italian neuropsychiatry services although clinicians should interpret results with caution as results in this age group still have to be replicated.

Relaxed open mouth as a playful signal in wild ring-tailed lemurs.

Play signals are commonly used by animals to communicate their playful motivation and to limit the risk that rough acts are misunderstood by playmates. The relaxed open mouth is the most common facial expression performed during play in many mammals and represents the ritualized version of the movement anticipating a play bite. The signaling nature of this expression has been proven in many haplorrhine species but never demonstrated in strepsirrhines. Our purpose was assessing whether, also in strepsirrhines, the relaxed open mouth has an actual communicative function. We studied wild ring-tailed lemurs (Lemur catta), characterized by highly social habits including intense playful interactions. They largely use playful signals, mostly performed with the black and white tail. The signaling function of the tail (tail play) has been widely demonstrated. We analyzed both tail play and the relaxed open mouth to verify how their distribution is affected by different play variables (e.g., play session symmetry, number of play mates, previous use of the same pattern). Indeed, ring-tailed lemurs use the relaxed open mouth as a communicative signal during play. Relaxed open mouth was more frequent during unbalanced interactions showing the highest asymmetry in the patterns performed by the two players (offensive/neutral). Compared to tail play, relaxed open mouth was more frequent during dyadic than polyadic interactions and, as a highly directional signal, it was more frequently replicated by the play mate. Therefore, the relaxed open mouth needs to be performed face-to-face so that signal detection can be optimized. Similar to previous findings in monkeys and apes, the relaxed open mouth in lemurs seems to be a ritualized signal used to engage and, perhaps, sustain playful interaction.

A questionnaire on sleep behaviour in the first years of life: preliminary results from a normative sample.

The authors developed a questionnaire in Italian for investigating sleep problems in infants and toddlers. Applying the questionnaire, they conducted an exploratory investigation into the sleep behaviour of a sample of normal children during their first three years of life in order to gather preliminary data regarding the ease of use of the instrument. The questionnaire and the results of its first application (in an Italian sample of 50 healthy children aged 10-39 months) are presented. The results provide interesting information on the sleep behaviour of the young children in our sample and prompt reflections in relation to the instrument employed. The sleep behaviour questionnaire emerged, above all, as easy to use and readily comprehensible to those participating in this research study. Furthermore, it provided parents with an opportunity to reflect upon their child and his/her rhythms (in particular sleep-wake rhythms) and upon their own ability to manage these rhythms. This instrument seems, on the basis of these preliminary data, to allow the tracing of a well-defined and complete picture of the sleep behaviour of the healthy child in the first years of life.