Clinical correlates of comorbid attention deficit hyperactivity disorder in adults suffering from bipolar disorder: A meta-analysis.

OBJECTIVE: Attention deficit hyperactivity disorder is a frequent comorbid condition in adults with bipolar disorder. We performed a meta-analysis aimed at assessing sociodemographic and clinical correlates of attention deficit hyperactivity disorder in bipolar disorder. METHOD: We searched main electronic databases up to June 2021. Random-effects meta-analyses, with relevant meta-regression and quality-based sensitivity analyses, were carried out to estimate the association between attention deficit hyperactivity disorder and putative correlates, grading the quality of evidence. RESULTS: We included 43 studies, based on 38 independent samples. Attention deficit hyperactivity disorder participants were more likely to be males (odds ratio = 1.46; p < 0.001) and unemployed (odds ratio = 1.45; p = 0.045), and less likely to be married (odds ratio = 0.62; p = 0.014). They had an earlier onset of bipolar disorder (standardized mean difference = -0.36; p < 0.001); more mood episodes (standardized mean difference = 0.35; p = 0.007), particularly depressive (standardized mean difference = 0.30; p = 0.011) and mixed (standardized mean difference = 0.30; p = 0.031) ones; higher odds of using antidepressants (odds ratio = 1.80; p = 0.024) and attempted suicides (odds ratio = 1.83; p < 0.001) and lower odds of psychotic features (odds ratio = 0.63; p = 0.010). Moreover, they were more likely to have generalized anxiety disorder (odds ratio = 1.50; p = 0.019), panic disorder (odds ratio = 1.89; p < 0.001), social phobia (odds ratio = 1.61; p = 0.017), eating disorders (odds ratio = 1.91; p = 0.007), antisocial personality disorder (odds ratio = 3.59; p = 0.004) and substance (odds ratio = 2.29; p < 0.001) or alcohol (odds ratio = 2.28; p < 0.001) use disorders. Quality of the evidence was generally low or very low for the majority of correlates, except for bipolar disorder onset and alcohol/substance use disorders (high), and suicide attempts (moderate). CONCLUSION: Comorbid bipolar disorder/attention deficit hyperactivity disorder may have some distinctive clinical features including an earlier onset of bipolar disorder and higher comorbid alcohol/substance use disorder rates. Further research is needed to identify additional clinical characteristics of this comorbidity.

The kynurenine pathway in bipolar disorder: a meta-analysis on the peripheral blood levels of tryptophan and related metabolites.

Growing evidence suggests that a dysregulation of the kynurenine pathway (KP) occurs in bipolar disorder (BD). This systematic review and meta-analysis aimed at assessing the possible differences in peripheral blood levels of KP metabolites between individuals with BD and healthy controls. We searched Medline, Embase, and PsycInfo electronic databases for articles indexed up to February 2020. We included any observational study comparing the peripheral blood levels of at least one KP metabolite between adults with BD and healthy controls. Random-effects meta-analyses were carried out generating pooled standardized mean differences (SMDs). Heterogeneity between studies was estimated using the I2 index. Meta-regression and sensitivity analyses were conducted. Sixteen studies met inclusion criteria and were included in our study. Meta-analyses showed that individuals with BD have lower peripheral blood levels of tryptophan (SMD = -0.29), kynurenine (SMD = -0.28), kynurenic acid (SMD = -0.30), and xanthurenic acid (SMD = -0.55), along with lower kynurenic acid to kynurenine (SMD = -0.60) and kynurenic acid to quinolinic acid (SMD = -0.37) ratios, than healthy controls. Individuals with a manic episode showed the greatest reductions in tryptophan levels (SMD = -0.51), whereas kynurenic acid levels were more reduced among subjects in a depressive phase (SMD = -0.70). Meta-regression and sensitivity analyses confirmed our results. The findings of the present meta-analysis support the hypothesis of an abnormality of the KP in BD. Considering the partial inconsistency of the findings and the small-to-medium magnitude of the estimated effect sizes, additional research assessing possible mediators or confounders is needed.

Innovations in community-based mental health care: an overview of meta-analyses.

In the last four decades, mental health services for people with Severe Mental Illness (SMI) have seen asylums replaced by a balanced model of Community Mental Healthcare (CMH). Innovative approaches and strategies in the field of CMH have been extensively researched. However, this research has been hampered by issues limiting their capacity to inform clinicians and policymakers. We conducted an overview of meta-analyses of the effectiveness of innovative CMH models focussing on clinical and psychosocial outcomes in comparisons with standard care in adults with SMI. Based on the 12 eligible studies, we appraised, synthesised and graded the resulting evidence. There was moderate quality evidence that case management, Early Intervention Services (EIS) and caregiver-directed interventions were superior to standard care in reducing hospital admission. In relation to psychosocial outcomes, EIS showed high quality evidence of a small effect on global functioning. There was moderate quality evidence for a similar effect of Intensive Case Management, and for a large effect of family intervention. For quality of life, both EIS and self-management education had a small effect, with moderate quality. The level of research about effective CMH models is therefore substantial. However, several gaps related to innovative CMH not yet covered in meta-analytic synthesis, need to be filled.

Office hysteroscopy in pre- and post-menopausal women: a predictive model.

OBJECTIVES: To assess the variables associated with success of office hysteroscopy (OH) in pre-menopausal and post-menopausal women and to develop a clinical model for predicting the outcome of OH. METHODS: This is a retrospective cohort study of consecutive patients (n = 3181) referred for an OH to a tertiary care university hospital between January 2018 and March 2020. Multivariate logistic regression analysis was used to investigate the variables for predicting the success of OH in all patients and in pre-menopausal and in post-menopausal patients separately. The logistic regression analysis of each variable was applied to develop a predictive model. RESULTS: The overall success rate of the procedure was 92.2%; 95.4% in pre-menopausal women and 87.6% in post-menopausal women. In the general population, independent predictors of procedure success were previous vaginally delivery and hysteroscopy, while previous cervical or uterine surgery were associated with incomplete OH. In the pre-menopausal group, the independent predictors of failure were treatment with GnRH, estroprogestins and infertility. In 89% of cases, our developed model was able to predict whether an OH would be successful in a particular patient. ROC analysis showed an area under the curve of 0.8746 (95% CI: 0.85354-0.89557). CONCLUSIONS: The present study demonstrates the development of a simple and reliable clinical model for the identification of both pre-menopausal and menopausal patients with a high chance of OH success.

Pre-Discharge Predictors of 1-Year Rehospitalization in Adolescents and Young Adults with Severe Mental Disorders: A Retrospective Cohort Study.

Background and objectives: Readmissions of youths hospitalized for a severe mental disorder are common events and bear a remarkable human, social, and economic burden. The current study aimed at evaluating predictors of 1-year rehospitalization in a sample of adolescents and young adults with severe mental disorders. Materials and Methods: Data for ≤25-year-old inpatients with a severe mental disorder and consecutively admitted between 1 January 2016 and 30 June 2019 were collected. Subjects were retrospectively assessed over a follow-up period of one year after the index discharge to track readmissions-i.e., the primary outcome variable. Standard descriptive statistics were used. The association between variables and 1-year rehospitalization was estimated using the univariate Cox proportional hazards regression model. We then carried out a multivariable Cox regression model, also estimating the covariate-adjusted survivor function. Hazard ratios (HRs) with related 95% confidence intervals (95% CIs) were provided. Results: The final sample included 125 individuals. The multivariable Cox regression model estimated that co-occurring substance use disorders (HR = 2.14; 95% CI: 1.08 to 4.26; p = 0.029) and being admitted for a suicide attempt (HR = 2.49; 95% CI: 1.13 to 5.49; p = 0.024) were both significant predictors of 1-year rehospitalization. Conclusions: Our study showed that comorbid substance use disorders and being admitted for a suicide attempt were predictors of early readmission in youths with severe mental disorders. Although their generalizability is limited, our findings could contribute to improve the quality of young patients' mental health care by identifying vulnerable subjects who may benefit from tailored interventions to prevent rehospitalizations.

Hypermethylation of HOXA10 gene in mid-luteal endometrium from women with ovarian endometriomas.

A decrease in HOXA10 gene expression in eutopic mid-secretory endometrium has been found in women with endometriosis-associated infertility. Promoter hypermethylation of HOXA10 is thought to be the leading mechanism for epigenetic gene regulation in patients with endometriosis. In our series we documented significantly higher HOXA10 promoter methylation levels in women with ovarian endometriomas than in healthy controls during the mid-luteal phase. Development of epigenetic-based strategies for non-surgical treatment of infertility related to ovarian endometriomas could be an attractive field of research in the coming years.

The association of kynurenine pathway metabolites with symptom severity and clinical features of bipolar disorder: An overview.

BACKGROUND: The balance between neurotoxic and neuroprotective effects of kynurenine pathway (KP) components has been recently proposed as a key element in the pathophysiology of bipolar disorder (BD) and related mood episodes. This comprehensive overview explored the link of KP with symptom severity and other clinical features of BD. METHODS: We searched Medline, Embase, and PsycInfo electronic databases for studies assessing the association of peripheral and/or central concentrations of KP metabolites with putative clinical features, including symptom severity and other clinical domains in BD. RESULTS: We included the findings of 13 observational studies investigating the possible variations of KP metabolites according to symptom severity, psychotic features, suicidal behaviors, and sleep disturbances in BD. Studies testing the relationship between KP metabolites and depression severity generated mixed and inconsistent findings. No statistically significant correlations with manic symptoms were found. Moreover, heterogeneous variations of the KP across different clinical domains were shown. Few available studies found (a) higher levels of cerebrospinal fluid kynurenic acid and lower of plasma quinolinic acid in BD with psychotic features, (b) lower central and peripheral picolinic acid levels in BD with suicide attempts, and (c) no significant correlations between KP metabolites and BD-related sleep disturbances. CONCLUSIONS: An imbalance of KP metabolism toward the neurotoxic branches is likely to occur in people with BD, though evidence on variations according to specific clinical features of BD is less clear. Additional research is needed to clarify the role of KP in the etiopathogenesis of BD and related clinical features.

Effect of long-acting injectable antipsychotics on emergency department visits and hospital admissions in people with bipolar disorder: A retrospective mirror-image analysis from the Northern Milan Area Cohort (NOMIAC) study.

BACKGROUND: Mood recurrences in bipolar disorder (BD) are often associated with poor treatment adherence. Despite long-acting injectable antipsychotics (LAIs) may favor treatment compliance, their use in BD is still poorly explored. METHODS: This mirror-image study investigated the effect of LAIs initiation on the number of emergency department (ED) visits and days of hospitalization, among individuals with BD from the mental health services of a large area of the Metropolitan City of Milan. The mirror periods were 365 days either side of the LAI initiation. Individual medical records were retrospectively reviewed. RESULTS: Sixty-eight individuals with BD initiating a LAI over the index period were included. We estimated that LAI initiation overall reduced both ED visits (p = 0.002) and days of hospitalization (p < 0.001). This remained true only for those participants who i) continued LAI for the entire 12-month period of observation and ii) were treated with a second-generation antipsychotic LAI. In addition, LAI initiation reduced number of hospitalization days during hypo/manic (p = 0.013), but not depressive (p = 0.641) episodes, as well as compulsory admission days (p = 0.002). LIMITATIONS: Due to the retrospective design, we could not collect systematic information on symptom severity and reasons of LAI discontinuation. Moreover, the limited sample size did not allow us to estimate effectiveness of single LAI agents. CONCLUSIONS: Our study provides additional insight on the effectiveness of LAIs in BD, supporting their clinical utility for pragmatic outcomes such as ED visits and hospitalizations. Further longitudinal research is needed to clarify the real-world effectiveness of LAIs for BD clinical management.

Professionals' Digital Training for Child Maltreatment Prevention in the COVID-19 Era: A Pan-European Model.

The responsiveness of professionals working with children and families is of key importance for child maltreatment early identification. However, this might be undermined when multifaceted circumstances, such as the COVID-19 pandemic, reduce interdisciplinary educational activities. Thanks to technological developments, digital platforms seem promising in dealing with new challenges for professionals' training. We examined a digital approach to child maltreatment training through the ERICA project experience (Stopping Child Maltreatment through Pan-European Multiprofessional Training Programme). ERICA has been piloted during the pandemic in seven European centers involving interconnected sectors of professionals working with children and families. The training consisted of interactive modules embedded in a digital learning framework. Different aspects (technology, interaction, and organization) were evaluated and trainers' feedback on digital features was sought. Technical issues were the main barrier, however, these did not significantly disrupt the training. The trainers perceived reduced interaction between participants, although distinct factors were uncovered as potential favorable mediators. Based on participants' subjective experiences and perspectives, digital learning frameworks for professionals working with children and families (such as the ERICA model nested in its indispensable adaptation to an e-learning mode) can represent a novel interactive approach to empower trainers and trainees to tackle child maltreatment during critical times such as a pandemic, and as an alternative to more traditional learning frameworks.

Techniques of laparoscopic myomectomy.

Myomectomy is one of the commonest gynaecological operations. Laparoscopic myomectomy has emerged over the last two decades as a possible alternative to the traditional laparotomy. Most studies have revealed that the laparoscopic procedure is at least as safe as the open procedure as to the rate of complications and may retain relevant advantages in terms of shorter admission and recovery times. Currently laparoscopic myomectomy is still a challenging operation that requires a well-trained surgical team, adequate instrumentation and accurate patient selection; the increasing slant of gynaecologists towards laparoscopic techniques, along with the advances in surgical instrumentation and suturing materials, will hopefully contribute to keep laparoscopic myomectomy no longer confined to tertiary care centres.

Quantitative variation analysis of fetal DNA in maternal plasma samples collected before and after amniocentesis.

AIMS: The aim of this study was to evaluate possible procedure-related variations in the levels of cell-free fetal DNA (fDNA) in maternal plasma of women undergoing genetic amniocentesis. MATERIALS AND METHODS: Blood samples were collected at 16-18 weeks' gestation from 33 pregnant women attending the Fetal Medicine Unit for genetic amniocentesis. For each woman, two blood samples were obtained: the first immediately before amniocentesis and the second one 15 min after the procedure. A real-time quantitative polymerase chain reaction assay, using primers for SRY and beta-globin genes, was used to assess fDNA concentrations in maternal plasma. A Wilcoxon signed-rank test was used for statistical analysis. RESULTS: The karyotype on cultured amniocytes showed that 15 out of 33 women had a male fetus. Real-time quantitative polymerase chain reaction results, on maternal plasma sample pairs from known male pregnancies, showed no significant variations of fDNA correlated to amniocentesis (P=0.394). CONCLUSIONS: Our preliminary study suggests that amniocentesis, although invasive, could be associated with minimal, if any, disruption at the fetal-maternal interface, as revealed by the lack of substantial modifications of fDNA levels in maternal circulation.

Disentangling the Association between ADHD and Alcohol Use Disorder in Individuals Suffering from Bipolar Disorder: A Systematic Review and Meta-Analysis.

Attention Deficit-Hyperactivity disorder (ADHD) may influence rates of Alcohol Use Disorder (AUD) among individuals suffering from Bipolar Disorder (BD). The aim of this systematic review and meta-analysis was to estimate the strength and consistency of the potential association between ADHD and AUD in BD. We searched main electronic databases for studies indexed up to November 2020. We included observational studies investigating the association between ADHD and AUD among individuals with BD. The association between ADHD and AUD was estimated using odds ratios (ORs) with 95% Confidence Intervals (CIs). Eleven studies, involving 2734 individuals with BD (516 with ADHD), were included in the meta-analysis. Individuals with both BD and ADHD had higher rates of AUD as compared with subjects with BD only (34.0% vs. 18.3%). The estimated OR of AUD for ADHD was 2.50 (95% CI: 1.91 to 3.27; I2 = 13.0%). Study-level characteristics did not influence the effect size. No risk of publication bias was estimated. Despite some limitations, this meta-analysis estimated an association between ADHD and AUD among individuals suffering from BD. At least a portion of the high rates of AUD in BD may, thereby, be related to comorbid ADHD. Longitudinal studies are needed to clarify the nature of this relationship.

Some of us are most at risk: Systematic review and meta-analysis of correlates of depressive symptoms among healthcare workers during the SARS-CoV-2 outbreak.

The COVID-19 pandemic has had a severe psychosocial impact on healthcare workers (HCWs). This systematic review and meta-analysis aimed at evaluating the association between individual features and depressive symptoms reported by HCWs during the pandemic. We searched Medline, Embase, and PsycInfo up to 23 June 2020. We included cross-sectional studies testing the association between individual correlates and depressive symptoms in HCWs during the SARS-CoV-2 outbreak. Fourteen studies met inclusion criteria, involving 14,173 HCWs (3,070 with depressive symptoms). Women (OR = 1.50; 95 %CI: 1.28-1.76; I2 = 40.0 %), individuals with suspected/confirmed COVID-19 (OR = 2.10; 95 %CI: 1.64-2.69; I2 = 0 %), and those with an infected family member or friend (OR = 1.67; 95 %CI: 1.37-2.04; I2 = 0%) were more likely to report depressive features, which, instead, were less frequent among doctors (compared with nurses) (OR = 0.80; 95 %CI: 0.66-0.98; I2 = 48.2 %) and HCWs who felt adequately protected (OR = 0.48; 95 %CI: 0.32-0.72; I2 = 36.3 %). Our study provided timely evidence on the correlates of depressive symptoms among HCWs during the pandemic. Early screening is crucial to develop tailored health interventions, redesigning the response to COVID-19.

Fetal cells in a transcervical cell sample collected at 5 weeks of gestation.

Transcervical cell (TCC) sampling is being investigated as a promising method for obtaining fetal cells for prenatal genetic diagnosis. The present case report describes the identification of fetal cells by both fluorescent in situ hybridisation (FISH) and quantitative fluorescent polymerase chain reaction (QF-PCR) analyses in a TCC sample collected by intrauterine lavage at 5 + 0 weeks. This finding underscores the possible relevance of TCC sampling for extremely early prenatal genetic diagnosis.

The 75-gram glucose load in pregnancy: relation between glucose levels and anthropometric characteristics of infants born to women with normal glucose metabolism.

OBJECTIVE: To investigate, in pregnant women without gestational diabetes mellitus (GDM), the relation among obstetric/demographic characteristics; fasting, 1-h, and 2-h plasma glucose values resulting from a 75-g glucose load; and the risk of abnormal neonatal anthropometric features and then to verify the presence of a threshold glucose value for a 75-g glucose load above which there is an increased risk for abnormal neonatal anthropometric characteristics. RESEARCH DESIGN AND METHODS: The study group consisted of 829 Caucasian pregnant women with singleton pregnancy who had no history of pregestational diabetes or GDM, who were tested for GDM with a 75-g, 2-h glucose load, used as a glucose challenge test, in two periods of pregnancy (early, 16-20 weeks; late, 26-30 weeks), and who did not meet the criteria for a GDM diagnosis. In the newborns, the following abnormal anthropometric characteristics were considered as outcome measures: cranial/thoracic circumference (CC/TC) ratio /=90th percentile for GA, and macrosomia (birth weight >/=90th percentile for GA), on the basis of growth standard development for our population. For the first part of the objective, logistic regression models were used to identify 75-g glucose load values as well as obstetric and demographic variables as markers for abnormal neonatal anthropometric characteristics. For the second part, the receiver operating characteristic (ROC) curve was performed for the 75-g glucose load values to determine the plasma glucose threshold value that yielded the highest combined sensitivity and specificity for the prediction of abnormal neonatal anthropometric characteristics. RESULTS: In both early and late periods, maternal age >35 years was a predictor of neonatal CC/TC ratio 35 years being an independent predictor for macrosomia. The 2-h, 75-g glucose load values were significantly associated in both periods with neonatal CC/TC ratio /=90th percentile, whereas maternal age >35 years was an independent predictor of both neonatal CC/TC ratio

Sonographic evaluation of fetal growth and body composition in women with different degrees of normal glucose metabolism.

OBJECTIVE: To investigate the maternal demographic and metabolic factors contributing to the growth of fetal lean and fat body mass in women whose degree of glucose intolerance is less than that defining gestational diabetes in comparison with women with normal glucose metabolism. RESEARCH DESIGN AND METHODS: Longitudinal sonographic examinations of 66 singleton fetuses without anomalies of nonobese mothers with abnormal oral glucose challenge test (GCT) results and without gestational diabetes (group 1) were compared with those of 123 singleton fetuses without anomalies of nonobese mothers with normal GCT values (group 2). Lean body mass measurements included head circumference, femur length, mid-upper arm, and mid-thigh central areas. Fat body mass measurements included the anterior abdominal wall thickness, the subscapular thickness, and the mid-upper arm and mid-thigh subcutaneous areas. All the women performed a 24-h glucose profile on the day preceding the ultrasound scan. Multivariate logistic regression analysis established best-fit equations for fetal sonographic measurements of fat and lean body mass. Independent variables included groups 1 and 2, maternal age, parity, prepregnancy BMI, gestational age, weight gain during pregnancy, fetal sex, and the following averaged 24-h profile maternal capillary blood glucose values: preprandial, 1-h postprandial, and 2-h postprandial. RESULTS: No difference was found between the two groups with respect to fetal lean body mass parameters; the factors that contributed significantly and most frequently were gestational age and fetal sex (male). With respect to fetal fat body mass, all the measurements were significantly higher in group 1 than in group 2. In all instances, the significantly contributing factors were gestational age and maternal 1-h postprandial glucose values, whereas another frequent contributor was prepregnancy BMI. CONCLUSIONS: Our study suggests the possibility of using sonographically determined fetal fat and lean mass measurements as indicators of body composition. The assessment of these parameters, achievable in a noninvasive and reproducible fashion in pregnancies complicated by glucose intolerance, might enable the real-time detection of fetal overgrowth and disproportion, thus opening the possibility of exploring interventions to limit fetal fat accretion, birth weight, and potential resulting morbidity.

Use of the quantitative fluorescent-PCR assay in the study of fetal DNA from micromanipulated transcervical samples.

AIM: The purpose of this study was to evaluate the validity of the combined use of micromanipulation and quantitative fluorescent (QF)-PCR assay for the identification of fetal elements in transcervical cell (TCC) samples collected in early pregnancy. METHODS: TCC samples were obtained by intrauterine lavage (IUL) in 113 pregnant women who were between 7 and 12 weeks pregnant before termination of pregnancy. All IUL samples were screened under an inverted microscope, at which time the isolation of fetal cells by micromanipulation was attempted. QF-PCR assay, using 9 small tandem repeat (STR) markers for chromosomes 13, 18, 21, X, and Y, was performed in all specimens to identify fetal cells in TCC samples and the corresponding placental tissue and blood specimens. TCC samples from male fetuses in which either the micromanipulation or QF-PCR analysis were unsuccessful, were studied with fluorescent in situ hybridization (FISH), using probes for X and Y chromosomes. RESULTS: Isolation of supposed fetal material from IUL samples was carried out by means of micromanipulation in 93 cases (82.3%), where discernible chorionic villous filaments or cell clumps of probable trophoblastic origin were present. The QF-PCR analysis was performed in all 93 IUL samples and paternal peaks could be documented in 88 cases (94.6%) thus confirming the presence of fetal cells. Thirteen cases negative to micromanipulation and derived from male fetuses and four male cases not informative with QF-PCR analysis, after micromanipulation, were then tested with FISH assay using probes for sexual chromosomes. In six samples, rare (2-3%) male fetal cells were detected. Considering the combined results obtained from QF-PCR and FISH assays, the overall fetal sexing was correct in 83.2% of cases (94 of 113). CONCLUSION: This study provides evidence that fetal cells are present in a high proportion of IUL samples. Micromanipulation appears to be an extremely efficient method for the isolation of trophoblastic elements. This study also confirms the potential of IUL as a possible alternative to the traditional prenatal diagnostic procedures for the recovery of fetal cells in precocious stage of gestation, and validates the combination of the isolation of such fetal elements by means of micromanipulation and analysis with the QF-PCR assay for the identification of the most frequent prenatal chromosomal aneuploidies.

Detection of fetal DNA in the peritoneal cavity during pregnancy.

There is increasing evidence that fetal cells are commonly shed toward the cervix and in maternal circulation during pregnancy. In this study, a sample of peritoneal fluid was retrieved from a primigravida at 12 weeks' gestation undergoing urgent intervention for the torsion of an adnexal mass; the sample was then analysed by a polymerase chain reaction (PCR) assay using primers for X- and Y-chromosome specific sequences, and Y-derived sequences were identified. The course of pregnancy was then uneventful until term, when the patient delivered a male fetus, thus, supporting the hypothesis of a fetal origin for the Y-derived sequences detected in the peritoneal fluid. Further studies are required in order to confirm these findings and precisely define the origin of these sequences; however, this report seems to provide further evidence of the spreading of fetal cells during gestation and addresses relevant issues as to the possibility of collecting these cells by culdocentesis and intraperitoneal lavage for prenatal diagnosis.