Antipsychotic medications are used by increasing numbers of women of reproductive age. The safety of these medications during pregnancy has not been well described. We undertook a systematic review ...and meta-analysis of the adverse obstetric and neonatal outcomes associated with exposure to antipsychotics during pregnancy.
PubMed, Reprotox, and ClinicalTrials.gov were searched to identify potential studies for inclusion.
Case-control or cohort studies estimating adverse birth outcomes associated with antipsychotic exposure during pregnancy were included. Pooled odds ratios (ORs) were used for dichotomous outcomes and weighted mean differences were used for neonatal birth weight and gestational age. Thirteen cohort studies, including 6,289 antipsychotic-exposed and 1,618,039 unexposed pregnancies, were included.
Antipsychotic exposure was associated with an increased risk of major malformations (absolute risk difference ARD 0.03, 95% confidence interval CI 0.00-0.05, P=.04, Z=2.06), heart defects (ARD 0.01, 95% CI 0.00-0.01, P<.001, Z=3.44), preterm delivery (ARD 0.05, 95% CI 0.03-0.08, P<.001, Z=4.10), small-for-gestational-age births (ARD 0.05, 95% CI 0.02-0.09, P=.006, Z=2.74), elective termination (ARD 0.09, 95% CI 0.05-0.13, P<.001, Z=4.69), and decreased birth weight (weighted mean difference -57.89 g, 95% CI -103.69 to -12.10 g, P=.01). There was no significant difference in the risk of major malformations (test for subgroup differences: χ²=0.07, degrees of freedom=1, P=.79) between typical (OR 1.55, 95% CI 1.21-1.99, P=.006) and atypical (OR 1.39, 95% CI 0.66-2.93, P=.38) antipsychotic medications. Antipsychotic exposure was not associated with risk of large-for-gestational-age births, stillbirth, and spontaneous abortion. Although antipsychotic exposure during pregnancy was associated with increased risk of adverse obstetric and neonatal outcomes, this association does not necessarily imply causation. This analysis was limited by the small number of included studies and limited adjustment in studies for possible confounders.
Women requiring antipsychotic treatment during pregnancy appear at higher risk of adverse birth outcomes, regardless of causation, and may benefit from close monitoring and minimization of other potential risk factors during pregnancy.
PIF1 is a 5' to 3' DNA helicase that can unwind double-stranded DNA and disrupt nucleic acid-protein complexes. In
, Pif1 plays important roles in mitochondrial and nuclear genome maintenance, ...telomere length regulation, unwinding of G-quadruplex structures, and DNA synthesis during break-induced replication. Some, but not all, of these functions are shared with other eukaryotes. To gain insight into the evolutionarily conserved functions of PIF1, we created
null mutants in
and assessed their phenotypes throughout development. We found that
mutant larvae exposed to high concentrations of hydroxyurea, but not other DNA damaging agents, experience reduced survival to adulthood. Embryos lacking PIF1 fail to segregate their chromosomes efficiently during early nuclear divisions, consistent with a defect in DNA replication. Furthermore, loss of the BRCA2 protein, which is required for stabilization of stalled replication forks in metazoans, causes synthetic lethality in third instar larvae lacking either PIF1 or the polymerase delta subunit POL32. Interestingly,
mutants have a reduced ability to synthesize DNA during repair of a double-stranded gap, but only in the absence of POL32. Together, these results support a model in which
PIF1 functions with POL32 during times of replication stress but acts independently of POL32 to promote synthesis during double-strand gap repair.
Clinical practice currently restricts the use of psychostimulant medications in children with tics or a family history of tics for fear that tics will develop or worsen as a side effect of treatment. ...Our goal was to conduct a meta-analysis to examine the risk of new onset or worsening of tics as an adverse event of psychostimulants in randomized, placebo-controlled trials.
We conducted a PubMed search to identify all double-blind, randomized, placebo-controlled trials examining the efficacy of psychostimulant medications in the treatment of children with attention-deficit/hyperactivity disorder (ADHD). We used a fixed effects meta-analysis with risk ratio of new onset or worsening tics in children treated with psychostimulants compared to placebo. We used stratified subgroup analysis and meta-regression to examine the effects of stimulant type, dose, duration of treatment, recorder of side effect data, trial design, and mean age of participants on the measured risk of tics.
We identified 22 studies involving 2,385 children with ADHD for inclusion in our meta-analysis. New onset tics or worsening of tic symptoms were commonly reported in the psychostimulant (event rate = 5.7%, 95% CI = 3.7%-8.6%) and placebo groups (event rate = 6.5%, 95% CI = 4.4%-9.5%). The risk of new onset or worsening of tics associated with psychostimulant treatment was similar to that observed with placebo (risk ratio = 0.99, 95% CI = 0.78-1.27, z = -0.05, p = .962). Type of psychostimulant, dose, duration of treatment, recorder, and participant age did not affect risk of new onset or worsening of tics. Crossover studies were associated with a significantly greater measured risk of tics with psychostimulant use compared to parallel group trials.
Meta-analysis of controlled trials does not support an association between new onset or worsening of tics and psychostimulant use. Clinicians may want to consider rechallenging children who report new onset or worsening of tics with psychostimulant use, as these symptoms are much more likely to be coincidental rather than caused by psychostimulants.
To examine the association of age-appropriate maternal educational attainment in teenage and young mothers on infant health outcomes across racial/ethnic groups.
In this retrospective, ...cross-sectional study using Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research Natality data (2016-2017), we included live births comparing 14- to 19- year-old mothers with 20- to 24-year-old mothers. To analyze the association of maternal age-appropriate education (≥8th grade for 15-18 years of age, 9th-12th grade/completed high school for 19-24 years of age), we conducted multivariable regression adjusting for mothers' demographics, reporting adjusted incidence rate ratios with 95% CI for infant mortality rate, and logistic regression for extreme prematurity and low birth weight, reporting aORs with 95% CI.
From 2016 to 2017, there were 1 976 334 live births among women 14-24 years of age; 407 576 (20.6%) were in 14- to 19-year-olds. In the multivariable model, increased term infant mortality rate was associated with age 14-19 years (adjusted incidence rate ratio 1.18, 95% 1.10, 1.27), age-inappropriate education (adjusted incidence rate ratio 1.38, 95% CI 1.28, 1.48), and non-Hispanic Black mothers (adjusted incidence rate ratio 1.21, 95% CI 1.12, 1.30). Extreme prematurity was associated with women age 14-19 years (aOR 1.35, 95% CI 1.30, 1.40), non-Hispanic Black (aOR 2.50, 95% CI 2.39, 2.61), and Hispanic mothers (aOR 1.09, 95% CI 1.04, 1.15). Term infant low birth weight was associated with age 14-19 years (aOR 1.14, 95% CI 1.12, 1.16), age-inappropriate education for non-Hispanic White (aOR 1.16, 95% CI 1.11, 1.21), and non-Hispanic Black (aOR 1.08, 1.04, 1.12) mothers.
Inadequate maternal educational attainment, which is influenced by modifiable social policies, is associated with increased adverse infant outcomes in mothers 14-24 years of age.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Human trafficking is a public health issue and humanitarian crisis. Most alarming is that children are especially at risk. Although many studies demonstrate that the majority of trafficked persons ...surveyed engage with the health‐care system during the time in which they are trafficked, health‐care practitioners lack the knowledge, tools and resources to assist these patients. The present efforts in training health‐care professionals have been fragmented and largely ineffective. While prior training has produced short‐term changes in knowledge or attitudes of health professionals, it has not produced sustained changes in knowledge and attitudes nor meaningful changes in screening or intervention. No training has demonstrated changes in patient outcomes. Trafficked persons, particularly children and survivors of labour trafficking, are inadequately served by our present training options for health‐care practitioners, and evidence‐based protocols are needed to care for this underserved, disenfranchised and traumatised population. To provide optimal care for trafficked youth, health‐care practitioners may benefit from: (i) evaluating training for health care providers (HCP) rigorously and meaningfully; (ii) advocating for high‐quality training for all HCPs; (iii) fostering partnerships with key stakeholders to inform training and practice; and (iv) designing HCP training that is comprehensive, spanning all forms of human trafficking and including all populations involved.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background Sex trafficking is a public health problem in the United States. Although most victims of sex trafficking do come into contact with a healthcare provider during the time in which they are ...trafficked, the majority of physicians are not trained to recognize victims of sex trafficking, intervene on their behalf, or refer victims to appropriate psychiatric, legal, and social services. While medical professionals agree that knowledge about sex trafficking is important to their clinical practice, they acknowledge a lack of knowledge and confidence regarding how to work with patients who are victims of sex trafficking. We sought to determine whether a 45-minute interactive workshop would improve medical students' knowledge and confidence when working with patients who are victims of sex trafficking. Methods We assessed medical students' baseline knowledge and confidence in identifying, interviewing, and assisting sex-trafficking victims via a 10-question online survey administered immediately before the workshop, as well as short-term and long-term retention of knowledge and confidence within one week and at five months after the workshop. We used repeated-measures ANOVA to test for statistically significant differences in scores on the survey questions before the workshop and at the two follow-up time points. Missing data was handled by listwise deletion. Results Compared to baseline levels before the workshop, students immediately (within one week) after the workshop demonstrated statistically-significant improvements in knowledge F(1,173)=63.13, p<0.001 and confidence F(1,173)=84.92, p<0.001. These improvements persisted to a significant albeit lesser degree at 5-month follow up for knowledge F(1,190)= 38.17, p<0.01 and confidence F(1,189)=18.89, p<0.01. Prior exposure to a sex trafficking educational lecture and participant gender did not confound the data. Conclusions A 45-minute workshop to equip medical students to better identify, interview, and assist patients who are victims of sex trafficking produced significant short- and long-term retention of knowledge and confidence. Further research is needed to demonstrate retention beyond pre-clinical years. Additional research on the effectiveness of this intervention on medical house staff may prove this to be an effective teaching tool for more advanced medical trainees as well.
This secondary analysis of the Child/Adolescent Anxiety Multimodal Study (CAMS) used baseline patient characteristics to identify prognostic subgroups of children based on likelihood of remission. We ...also investigated predictors and moderators of outcome. CAMS randomized 488 youths with generalized, social, and separation anxiety disorders to cognitive behavioral therapy (CBT), sertraline, both, or pill placebo. Outcomes were Week 12 child, parent, and independent evaluator (IE) ratings of child anxiety. We used receiver operating characteristics analysis and stepwise regression to identify predictors and moderators of outcome. Severe anxiety, lower socioeconomic status, and comorbid obsessive-compulsive disorder predicted higher IE-rated anxiety posttreatment; child-rated social anxiety predicted poorer outcomes reported by all informants. Regarding moderators, Hispanic ethnicity predicted higher IE-rated anxiety after CBT and higher parent-rated anxiety after sertraline. In youths with severe anxiety (Pediatric Anxiety Rating Scale ≥ 20, n = 220), combination treatment increased remission (relative risk RR = 2.85, p < .001), 95% confidence interval (CI) 1.51, 5.39, whereas CBT (RR = 1.55, p = .20), 95% CI 0.77, 3.10, and sertraline (RR = 1.27, p = .53), 95% CI 0.59, 2.73, did not significantly increase remission relative to placebo. These are the first findings demonstrating that a combination of CBT and a selective serotonin reuptake inhibitor, not monotherapy, is likely key for achieving remission in severe anxiety. CAMS was not powered to detect treatment efficacy after stratification by anxiety severity, so further research is needed regarding effective treatments in severe anxiety. Our main effect findings suggest youth with severe anxiety (especially social phobia), low socioeconomic status and obsessive-compulsive disorder benefit less from current first-line treatments relative to other anxious youth. ClinicalTrials.gov: NCT00052078.
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BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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