STATIN trial: predictive performance of competing-risks model in screening for pre-eclampsia at 35-37 weeks' gestation.

OBJECTIVE: To examine the predictive performance of a previously reported competing-risks model of screening for pre-eclampsia (PE) at 35-37 weeks' gestation by combinations of maternal risk factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1) in a validation dataset derived from the screened population of the STATIN study. METHODS: This was a prospective third-trimester multicenter study of screening for PE in singleton pregnancies by means of a previously reported algorithm that combines maternal risk factors and biomarkers. Women in the high-risk group were invited to participate in a trial of pravastatin vs placebo, but the trial showed no evidence of an effect of pravastatin in the prevention of PE. Patient-specific risks of delivery with PE were calculated using the competing-risks model, and the performance of screening for PE by maternal risk factors alone and by various combinations of risk factors with MAP, UtA-PI, PlGF and sFlt-1 was assessed. The predictive performance of the model was examined by, first, the ability of the model to discriminate between the PE and no-PE groups using the area under the receiver-operating-characteristics curve (AUC) and the detection rate at a fixed false-positive rate of 10%, and, second, calibration by measurements of calibration slope and calibration-in-the-large. RESULTS: The study population of 29 677 pregnancies contained 653 that developed PE. In screening for PE by a combination of maternal risk factors, MAP, PlGF and sFlt-1 (triple test), the detection rate at a 10% false-positive rate was 79% (95% CI, 76-82%) and the results were consistent with the data used for developing the algorithm. Addition of UtA-PI did not improve the prediction provided by the triple test. The AUC for the triple test was 0.923 (95% CI, 0.913-0.932), demonstrating very high discrimination between affected and unaffected pregnancies. Similarly, the calibration slope was 0.875 (95% CI, 0.831-0.919), demonstrating good agreement between the predicted risk and observed incidence of PE. CONCLUSION: The competing-risks model provides an effective and reproducible method for third-trimester prediction of term PE. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Decreased gene expression of calretinin and ryanodine receptor type 1 in tottering mice.

Tottering mice are a spontaneously occurring animal model of human absence epilepsy. They carry a mutation in the P/Q-type calcium channel alpha1A subunit gene which is highly expressed by cerebellar Purkinje cells. In this study, we investigated the role of calretinin and ryanodine receptor type 1 (RyR1) gene expression in the cerebellum of tottering mice. Cerebellar tissue specimens from four experimental groups were processed for in situ hybridization histochemistry (ISHH): (1) wild-type (+/+); (2) heterozygous (tg/+) and two homozygous groups; either (3) without occurrence of an episode of paroxysmal dyskinesia (tg/tg-N); or (4) after an episode of paroxysmal dyskinesia (tg/tg-P) that lasted about 45 min on average. Quantitative analysis showed a statistically significant decrease (p = 0.0001, ANOVA) of calretinin gene expression at the level of the simple lobule of the cerebellum in both homozygous groups compared to the wild-type and heterozygous groups. RyR1 was decreased in the flocculus of the cerebellum in both the tg/tg-N and tg/tg-P groups compared to wild type (p = 0.0174, ANOVA). These results suggest that calretinin gene expression, as well as other genes involved in regulation of calcium homeostasis, such as RyR1, may play a role in the biochemical functional alterations present in tottering mice.

Diurnal variation in spontaneous eye-blink rate.

The daily pattern of spontaneous eye-blink rate (BR), a non-invasive peripheral measure of central dopamine activity, was investigated in 24 healthy subjects. The spontaneous eye-blink rate showed a stable pattern in morning, midday and afternoon hours. A significant increase was found at the evening time point (20.30 h). The finding is suggestive of a late evening increase of central dopamine activity. An increased level of subjective sleepiness was also found at the same evening point, at a time corresponding to the 'evening wake maintenance zone' or the 'forbidden zone for sleep'. A possible hypothesis is that the 'forbidden zone for sleep' may reflect a dopamine-mediated activation that counteracts a rising sleep drive. The role of diurnal variation of dopamine function should be considered both in the choice of the drug treatment regimen, and in the evaluation of biological and neuropsychological parameters.

Extrapyramidal syndromes in neuroleptic-treated patients: prevalence, risk factors, and association with tardive dyskinesia.

Prevalence and risk factors for extrapyramidal syndromes (EPS) were investigated in a sample of 1,559 patients. The overall prevalence of EPS was 29.4% (N = 458). Among the EPS-diagnosed patients, parkinsonism as assessed by the presence of core parkinsonian symptoms (rigidity, tremor, bradykinesia) was present in 65.9% of patients (N = 302), akathisia in 31.8% (N = 145), and acute dystonia in 2.1% (N = 10). Old age and long-term neuroleptic drug (NL) treatment were significantly associated with EPS in both the univariate and the multivariate analyses, whereas no relationship was observed with average NL daily doses and current NL treatment. EPS was diagnosed in 50.2% of 285 patients with persistent tardive dyskinesia (TD). Distribution of EPS in patients with TD showed that tremor and akathisia were more frequent in peripheral TD cases than in orofacial TD cases. Furthermore, there was a stronger association of NL-induced parkinsonism with peripheral TD than with orofacial TD. This study suggests that the association between EPS and TD may be limited to specific subtypes of TD. Peripheral TD showed a higher association with parkinsonism and with akathisia, suggesting that these symptoms may share a common pathophysiology.

Seasonality of mood in Italy: role of latitude and sociocultural factors.

A mail survey of degree of seasonal suffering was conducted in Italy using the SPAQ (Seasonal Pattern Assessment Questionnaire). Experiencing seasonal changes as a problem was reported by more than half of the 543 responders. Both mean GSS (Global Seasonality Score) and circannual profile of 'feeling worst' yielded results similar to those reported in the USA at comparable latitudes. Global prevalences of SAD, Reverse-SAD and Sub-SAD were 4.4, 2.1 and 4.8%, respectively. Female sex and young age were associated with a higher degree of seasonal sensitivity. No clear evidence was found of higher sensitivity at higher latitudes or of a significant influence of sociocultural factors.

Effects of lithium treatment on hypothalamic-pituitary-thyroid axis: a longitudinal study.

Lithium carbonate, widely used in the treatment of bipolar patients, is well known to induce thyroid alterations. In this longitudinal study the thyroid function was investigated during lithium treatment over a period of 12 months in 12 euthymic bipolar patients with a normal thyroid function and absence of thyroid antibodies. Nine of the 12 patients were further studied on the 15th month, 5 of these 9 on the 18th month and 4 of the last-mentioned 5 on the 24th month. The mean basal and TRH-stimulated TSH values during lithium therapy were significantly higher as compared to those at the beginning of the treatment. More particularly, during lithium therapy, a significant increase of basal TSH over the normal range was found in 10 out of the 12 patients. A rise of TRH-stimulated TSH was found in 11 out of the 12 patients. The impairment of the hypothalamic-pituitary-thyroid (HPT) axis was transitory in the majority of cases. Two patients developed a nodular goiter during the treatment. Plasma T3, T4, FT3 and FT4 levels did not change during the treatment. Thyroid antibodies remained undetectable. The conclusions of the study are twofold: 1) Subclinical hypothyroidism during lithium therapy is much more frequent than previous cross-sectional studies suggest; 2) Thyroxine replacement in lithium-treated patients is advisable in order to prevent subclinical hypothyroidism and the risk of a subsequent goiter.

Persistent tardive dyskinesia: demographic and pharmacological risk factors.

The demographic, clinical and pharmacological risk factors for persistent tardive dyskinesia (TD) were investigated in a sample of 1745 patients. When simultaneously adjusting for the effects of demographic and pharmacological factors using multivariate logistic regression, female sex and advanced age were positively and significantly associated with increased risk of TD. Interaction between these two variables, investigated by cross-stratification, was significant. Furthermore, high neuroleptic dose and concomitant use of neuroleptic and antiparkinsonian drugs were both significantly associated with increased risk of TD. The results support the view that both vulnerability factors and high neuroleptic doses contribute to the occurrence of TD and further stress the relevance of a conservative use of antipsychotic medication, particularly in older women.

Dopamine D1 and D2 receptors mediate opposite functions in seizures induced by lithium-pilocarpine.

The effect of selective dopamine receptor blockade on epileptic activity was tested in rats, using the lithium-pilocarpine seizure model. One day after lithium pretreatment, systemic administration of the dopamine D1 antagonist, SCH 23390, prevented the convulsive activity induced by either 10 or 15 mg/kg of pilocarpine in a dose-dependent manner as revealed by behavioral and electroencephalographic alterations. No anticonvulsant effect was observed when SCH 23390 was injected at the same time as lithium and 24 h prior to pilocarpine. Furthermore, the D2 antagonists, raclopride and haloperidol, potently reduced the threshold for convulsions induced by 10 mg/kg of pilocarpine, following lithium pretreatment. Neither dopamine D1 nor D2 antagonists altered the limbic stereotypies induced by pilocarpine, supporting the view that the dopamine system is primarily involved in the mechanisms of convulsion generation and seizure spreading. These results indicate that dopamine receptor subtypes exert opposite functions on the regulation of convulsive activity.

[Admission to private psychiatric institutions: reliability of official data for epidemiological purposes]. / Ricoveri in strutture psichiatriche private: affidabilità dei dati ufficiali ai fini epidemiologici.

The authors have collected clinical data regarding patients admitted to a private psychiatric institutions in the Naples hinterland. The aim was that of determining the reliability of official data collected from the central regional statistical office of patients admitted in 1988. The duration of stay and the "revolving door" phenomenon of the cases as well as the nosographic classification at dismissal of the patients is influenced by variables not strictly of clinical nature. The information that becomes official and public for administration purposes is not reliable from the point of view of epidemiological studies.

Pattern of neuroleptic drug use in Italian mental health services.

The relationship between the prescribed daily dose of neuroleptic (NL) drugs and patient-, and drug-related characteristics was explored in a cross-sectional sample of 1141 patients treated in Italian mental health services. The results of a multiple linear regression showed that the prescribed daily dose was significantly lower in women, the elderly, and those with a shorter (one to six year) psychiatric history. In contrast, being an inpatient in psychiatric wards in general and public mental hospitals was significantly associated with a higher dose; marital status, education, and diagnosis were not. The number and potency (low to moderate vs. high) of the prescribed NLs were also significantly associated with the prescribed dose, and an interaction was found between the two. Implications of these findings for improvement in NL prescription patterns are discussed.

Plasma HVA, tardive dyskinesia and psychotic symptoms in long-term drug-free inpatients with schizophrenia.

Plasma homovanillic acid (pHVA) levels were measured in 16 chronically ill patients with schizophrenia who also suffered from tardive dyskinesia, and in a group of 14 chronically ill patients with schizophrenia who did not have tardive dyskinesia. All patients were studied following an extensive drug-free period (mean = 32.9 months). Patients with orofacial dyskinesia had significantly lower levels of pHVA than did controls. In patients without tardive dyskinesia, pHVA levels were significantly correlated with both positive and negative symptomatology. In contrast, pHVA levels from patients with tardive dyskinesia bore neither a significant nor a nearly significant relationship to symptomatology. The implications of these findings for dopaminergic models of tardive dyskinesia are discussed.

Revision of the Italian psychiatric reform: north/south differences and future strategies.

The Italian psychiatric reform of 1978 shifted the care of the mentally ill from the asylum to the community, by prohibiting new admissions to asylums and providing new community-oriented services. Ten years later, the Italian government is reviewing the effects of the psychiatric reform and is considering drastic revisions of the Law. However, few data are available to evaluate the impact of the new legislation on a national basis. The present cross-sectional study, conducted in North-Central and Southern Italy, showed that a more socially disadvantaged patient population was treated in Southern Italian mental health services. In both geographic regions, the probability of being currently treated in mental hospitals as compared to community services was increased by poor education, being unmarried, having a schizophrenia or organic diagnosis, a long psychiatric history, a long previous hospitalization, or a poor prognosis. However, a long psychiatric history was the main factor associated with current mental hospital treatment in Southern Italy but not in the North-Center, thus suggesting that the psychiatric reform has had different impacts on Northern and Southern mental hospitals. The inadequate provision of community-oriented services in Southern Italy regions, and the presence of private mental hospitals that are publicly reimbursed, contribute importantly to the unsatisfactory situation of mental health care delivery in Southern Italy. The reinstitutionalization of mental patients is currently proposed by some political parties in Italy. This article argues that new legislation must address the provision of effective community services in the South, better definition of the role of the private sector, and the creation of an effective information system to monitor the implementation of the proposed measures.

Pattern of therapeutic intervention and role of psychiatric settings: a survey in two regions of Italy.

A survey of therapeutic intervention was conducted on 1513 patients treated in different psychiatric settings-psychiatric hospitals (PH), private facilities (PF), community mental health centers (CMHC) and psychiatric wards in general hospitals (PWGH). Psychotropic drugs, mainly neuroleptics and benzodiazepines, were widely prescribed irrespective of diagnosis, and 39% of patients treated with neuroleptics received two or more drugs. Psychotherapeutic intervention and social measures were administered in 21% and 20% of cases respectively, and 17% of patients received no treatment. The observed distribution of treatments over settings was compared with the expected one under the hypothesis that the two factors were independent. Differences between settings in therapeutic strategies, after adjustment for possible confounders (sex, age, education, diagnosis) were: no specific treatment was more than expected in PH and largely below unity in PF and PWGH, where treatment with psychotropic drugs alone was overrepresented; CMHC showed the most balanced therapeutic approach.

Mental health care in Southern Italy: application of case-control methodology for the evaluation of the impact of the 1978 psychiatric reform.

A survey to analyse patients' characteristics and the care delivered to them was conducted in several psychiatric facilities, covering the whole range of care offered in the public sector in two regions of Southern Italy. A case-control method of analysis was chosen, and the relative risk estimates (RR), together with their 95% confidence intervals (CI), of being in custodial facilities were computed, comparing patients treated in custodial institutions ('cases') with those in community-based services ('controls') in respect of social and clinical variables. Factors more strongly associated with custodial treatment were: illiteracy (RR = 2.4), unmarried status (RR = 2.4), a history of prolonged illness (RR = 7.6), organic diagnosis (RR = 2.6), previous custodial treatment (RR = 3.9), and expected poor social functioning (RR = 2.4). The suitability and advantages of the case-control method of analysis in the field of psychiatric care evaluation are discussed.

Platelet 3H-imipramine binding in bipolar patients.

Platelet 3H-imipramine binding was investigated in 31 control subjects and 19 hospitalized bipolar patients, either in the hypomanic or the depressed phase of illness. The mean Bmax value in the bipolar depressed patients did not differ significantly from that in the control subjects or the hypomanic patients. Differences in timing of the assay after blood collection, membrane preparation, protein content used in the assay, or binding of radioactive ligand to the equipment do not appear to explain the discrepancy between these results and previous findings.