Objectives: Early psychopathology in children diagnosed with Bipolar Disorder (BD) remains
poorly characterized. Parental retrospective reports provide helpful details on the earliest manifestations
...and their evolution over time. These symptoms occur early in the course of BD, often before a formal
diagnosis is made and/or treatment is implemented, and are of great importance to early recognition and
prevention.
Methods: Parents of pre-pubertal children and adolescents with DSM-IV diagnoses of BD attending an
outpatient mood disorders clinic provided retrospective ratings of 37 symptoms of child psychopathology.
Stability and comorbidity of diagnoses were evaluated, and severity of symptoms for each subject was
assessed by identifying the earliest occurrence of the reported symptoms causing impairment.
Results: Severe mood instability, temper tantrums, anxiety symptoms, sleep disturbances and aggression
were among the most common signs of psychopathology reported in children diagnosed with BD before
puberty. Symptoms were already apparent in the first three years in 28%, and formal diagnoses were
made before the age of 8 y in the majority of cases.
Conclusions: Retrospective parental reports of early symptoms of psychopathology in pre-pubertal
children with BD revealed a very early occurrence of affective precursors (irritability and mood
dysregulation) and clinical risk factors like impulsive aggression and anxiety that can precede the
syndromal onset of mania by several years. These findings support previous reports suggesting a
progression of symptoms from abnormal, non-specific presentations to sub-threshold and finally
syndromal BD. The importance of early identification and intervention is discussed.
Abstract Objectives Intravenous ketamine, a glutamate N -methyl- d -aspartate (NMDA) receptor antagonist, has been shown to exert a rapid antidepressant effect in adults with treatment resistant ...depression. Children with bipolar disorder (BD) often respond poorly to pharmacotherapy, including polypharmacy. A pediatric-onset Fear of Harm (FOH) phenotype has been described, and is characterized by severe clinical features and resistance to accepted treatments for BD. The potential efficacy and safety of intranasal ketamine in children with BD with FOH-phenotype were assessed by a systematic retrospective chart review of a case series from the private practice of one of the authors, including cases with clear refractoriness to mood stabilizers, antipsychotics and benzodiazepines. Methods A comparison was made between routinely collected symptom measures 1–2 weeks prior to and after the administration of ketamine, in 12 treatment-refractory youth, 10 males 2 females ages 6–19 years. Results Ketamine administration was associated with a substantial reduction in measures of mania, fear of harm and aggression. Significant improvement was observed in mood, anxiety and behavioral symptoms, attention/executive functions, insomnia, parasomnias and sleep inertia. Treatment was generally well-tolerated. Conclusions Intranasal ketamine administration in treatment-resistant youth with BD-FOH produced marked improvement in all symptomatic dimensions. A rapid, substantial therapeutic response, with only minimal side effects was observed. Formal clinical trials to assess safety and efficacy are warranted.
Abstract Background Mixed states have been a fundamental part of Kraepelin׳s conceptualization of the manic-depressive illness. However, after Kraepelin, the study of mixed states was not of great ...interest, until the publication of the RDC criteria (1978) and then the DSM-III edition (1980), where criteria for mixed manic states were operationalized. The most notable victims of DSM nosology were depressive mixed states, in particular depression with flight of ideas and excited (agitated) depression. Methods We briefly review the clinical work of Athanasios Koukopoulos on depressive mixed states (in particular agitated depression) pointing out the diagnostic and therapeutic contributions, especially in the lights of Koukopoulos׳ first description of depressive mixed syndrome in 1992. Results The mixed depressive syndrome is not a transitory state but a state of long duration, which may last weeks or several months. The clinical picture is characterized by dysphoric mood, emotional lability, psychic and/or motor agitation, talkativeness, crowded and/or racing thoughts, rumination, initial or middle insomnia. Impulsive suicidal attempts may be frequent. The family observes incessant complaints, irritability, occasional verbal outbursts, occasional physical aggression, and occasional hypersexuality. Treatment with antipsychotics and ECT is very effective; antidepressants can worsen the clinical picture. Limitations Selective but not systematic review of the literature on depressive mixed states. Relatively little research data is currently available for validation of the criteria proposed by Koukopoulos. Conclusions Koukopoulos׳ proposal of mixed depression, besides its diagnostic implications, clearly identifying it as manifestations of bipolar disorder, allows for better clinical characterization of cases and improves treatment decisions.
Aim
Preterm infants are at high risk of developing motor delay, learning difficulties and behavioural problems and the availability of valid neurodevelopmental assessments is a major clinical issue. ...This study evaluated the relationship between preterm infants' neurofunctional assessment at term equivalent age and neurodevelopment outcome at three years of chronological age.
Methods
Neurofunctional assessment was performed in 70 very low birth weight infants at term equivalent age and neurodevelopmental outcome was assessed at three years of chronological age with the Griffiths Mental Development Scale – Extended Revised.
Results
At term equivalent age, 81% of the children had normal neurofunctional scores and 82.5% of those showed normal neurodevelopmental outcome at three years. Of the 19% who had impaired development at term equivalent age, 38.5% had neurodevelopmental delay at three years. Impaired neurofunctional status was associated with an increased risk of developmental delay in the global quotient (odds ratio 12.1) and locomotor sub‐quotient (odds ratio 18.35) compared with normal neurofunctional status. Infants with sepsis or necrotising enterocolitis also faced a higher risk of neurodevelopmental delay.
Conclusion
Neurofunctional assessment performed at term equivalent age appeared to provide early identification of preterm infants at risk of neurodevelopmental delay at three years of chronological age.
Preterm small for gestational age (SGA) infants may be at risk for increased adiposity, especially when experiencing rapid postnatal weight gain. Data on the dynamic features of body weight and fat ...mass (FM) gain that occurs early in life is scarce. We investigated the postnatal weight and FM gain during the first five months after term in a cohort of preterm infants.
Changes in growth parameters and FM were prospectively monitored in 195 infants with birth weight ≤1500 g. The infants were categorized as born adequate for gestational age (AGA) without growth retardation at term (GR-), born AGA with growth retardation at term (GR+), born SGA. Weight and FM were assessed by an air displacement plethysmography system. At five months, weight z-score was comparable between the AGA (GR+) and the AGA (GR-), whereas the SGA showed a significantly lower weight.The mean weight (g) differences (95% CI) between SGA and AGA (GR-) and between SGA and AGA (GR+) infants at 5 months were -613 (-1215; -12) and -573 (-1227; -79), respectively. At term, the AGA (GR+) and the SGA groups showed a significantly lower FM than the AGA (GR-) group. In the first three months, change in FM was comparable between the AGA (GR+) and the SGA groups and significantly higher than that of the AGA (GR-) group.The mean difference (95% CI) in FM change between SGA and AGA (GR-) and between AGA (GR+) and AGA (GR-) from term to 3 months were 38.6 (12; 65); and 37.7 (10; 65). At three months, the FM was similar in all groups.
Our data suggests that fetal growth pattern influences the potential to rapidly correct anthropometry whereas the restoration of fat stores takes place irrespective of birth weight. The metabolic consequences of these findings need to be elucidated.
Pertuzumab disrupts heterodimerization between human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR), HER3, and HER4. Thus, pertuzumab could result in adverse ...events similar to those observed with EGFR antagonists, such as diarrhea. We report the incidence and severity of diarrhea observed with pertuzumab in the CLEOPATRA, NeoSphere, and TRYPHAENA studies.
Patients (n = 1443) had metastatic CLEOPATRA (n = 804) or early-stage breast cancer NeoSphere (n = 416) and TRYPHAENA (n = 223). The incidence and severity of diarrhea were analyzed by treatment received. The incidence of febrile neutropenia concurrent with diarrhea and the effect of pre-existing gastrointestinal comorbidities were also evaluated. Subgroup analyses were carried out using CLEOPATRA data.
The incidence of all-grade diarrhea across studies was generally greater for pertuzumab-based treatment, ranging from 28% to 72% (grade 1, 21%–54%; grade 2, 8%–37%; grade 3, 0%–12%; grade 4, 0%). Incidence was highest during the first pertuzumab-containing cycle, decreasing with subsequent cycles. Dose delays or discontinuations due to diarrhea were infrequent, ranging from 0% to 8%. Among pertuzumab-treated patients with diarrhea, 47%–67% received pharmacological intervention, most commonly with loperamide. Overlap between diarrhea and febrile neutropenia was uncommon, ranging from 0% to 11%. No relationship was observed between pre-existing gastrointestinal comorbidities and diarrhea. In CLEOPATRA, patients ≥65 years treated with pertuzumab had a higher incidence of grade 3 diarrhea than patients <65 years (19% versus 8%). All-grade diarrhea occurred at greater frequency among pertuzumab-treated Asian versus white patients with metastatic breast cancer (74% versus 63%); the corresponding rates in the control arm were 53% and 45%, respectively.
In both the metastatic and early-stage breast cancer settings, diarrhea was common but manageable for all pertuzumab-containing regimens. Diarrheal episodes were mainly low grade and occurred most often during the first treatment cycle. Diarrheal-related drug delays or discontinuations were uncommon.
NCT00567190 (CLEOPATRA), NCT00545688 (NeoSphere), NCT00976989 (TRYPHAENA).
The purpose of this study is to test the hypothesis that higher consumption of human milk (HM) in preterm infants with birth weight (BW) <1000 g is associated with improved lung function in a ...dose-dependent manner over the first 2 years of corrected age (CA). This retrospective study at an academic medical center included infants with BW <1000g. They had lung function assessment by the tidal breathing flow-volume loop (TBFVL) follow-up visits at 0–3-, 3–6-, 6–12-, 12–18-, and 18–24-month CA. One hundred eighty infants were included in the study with a mean (SD) gestational age 26.5 (1.90) weeks and BW 772.4 (147.0) g, 50% were female, and 60% developed BPD. 62.8% of infants received HM during the NICU stay. According to a general linear model (including GA, being small for GA (SGA), sex, human milk percentage, sepsis, and BPD), on average, each week of GA resulted in a higher tPTEF/tE of 1.24 (
p
= 0.039) and being SGA in a lower tPTEF/tE of 5.75 (
p
= 0.013) at 0–3-month CA. A higher percentage of human milk out of the total enteral intake was associated with better tPTEF/tE
z
-scores at 0–3 months (
p
= 0.004) and 18–24 months of CA (
p
= 0.041). BPD diagnosis was associated with a relevantly worse tPTEF/tE
z
-score at 6–12 months of CA (
p
= 0.003).
Conclusion
: Preterm infants with higher consumption of HM had significantly less airway obstruction across the first 2 years, suggesting that human milk may contribute in a dose-dependent manner to improve lung function in early childhood in former preterm infants born ELBW.
What is Known:
• Human milk feeding reduces the risk of prematurity-related morbidities, including necrotizing enterocolitis, sepsis, lower respiratory tract infections, and BPD. Both exclusive and partial human milk feeding appear to be associated with a lower risk of BPD in preterm infants.
What is New:
• This cohort study of 180 preterm infants with birth weight < 1000 g found that exposure to human milk during hospitalization improves airway obstruction markers tPTEF/tE z-score over the first 2 years of corrected age in a dose-dependent manner.
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