Mentalizing in and out of awareness: A meta-analytic review of implicit and explicit mentalizing.

BACKGROUND: Mentalizing, making sense of mental states, is hypothesized to have a central role in self-organization and social learning. Findings support this notion, but the extent of the association between mentalizing and various correlates has not been meta-analyzed. Furthermore, mentalizing presumably occurs with (explicit) and without (implicit) awareness but few studies have attempted to disentangle these aspects. We conducted a meta-analysis of implicit and explicit mentalizing in relation to the domains of attachment security, personality, affect, psychopathology, and functioning. METHODS: We searched for studies of adult mentalizing in PsycINFO and in related reviews. Overall, 511 studies (N = 78,733) met criteria and were analyzed using multi-level meta-analysis. RESULTS: Implicit (r = 0.19-0.29) and explicit (r = 0.26-0.40) mentalizing were moderately correlated with psychopathology, functioning, personality, affect, and attachment security. The correlations of implicit mentalizing were stronger with more objectively measured correlates (b = 0.02, p < .001) while the correlations of explicit mentalizing were not (b = -0.07, p = .21). CONCLUSIONS: Mentalizing is associated with better intra- and interpersonal functioning. Implicit mentalizing is more strongly associated with objectively measured correlates. These findings underscore the importance of an integrative approach considering both implicit and explicit mentalizing.

Examining the referral of patients with elevated blood pressure to health resources in an under-resourced community in South Africa.

BACKGROUND: Low-and-middle income countries face a disproportionate burden of non-communicable diseases (NCDs) that threaten to overwhelm under-resourced health systems. Community health workers (CHWs) can promote NCD prevention, reach patients, and connect them to local community health resources; however, little has been done to examine how referrals to these resources are utilized by community members. The purpose of this study is to examine the use of referrals to community-based health resources and investigate the factors influencing patient utilization of referrals connecting them to appropriate health resources for elevated blood pressure (BP). METHODS: CHWs conducted home visits, which included BP screening and brief counseling, with community members in Soweto, South Africa. Participants with elevated (systolic BP: 121-139/ diastolic BP: 81-89 mmHg) or high (≥ 140/90 mmHg) BP were referred to either a local, community-based physical activity (PA) program managed by a non-governmental organization or local health clinics. The number of participants that received and utilized their referrals was tracked. Follow-up interviews were conducted with individuals given a referral who: (1) went to the PA program, (2) did not go to the PA program, (3) went to a clinic, and (4) did not go to a clinic. Interviews were transcribed and analyzed to identify common themes and differences between groups regarding their decisions to utilize the referrals. RESULTS: CHWs visited 1056 homes, with 1001 community members consenting to the screening; 29.2% (n = 292) of adults were classified as having optimal BP (≤120/80 mmHg), 35.8% (n = 359) had elevated BP, and 35.0% (n = 350) had high BP. One hundred and seventy-three participants accepted a referral to the PA program with 46 (26.6%) enrolling. Five themes emerged from the interviews: (1) prior knowledge and thoughts on BP, (2) psychosocial factors associated with BP control, (3) perception about receiving the referral, (4) contextual factors influencing referral utilization, and (5) perceived benefits of utilizing the referral. CONCLUSION: CHWs can successfully increase community members' access to health resources by providing appropriate referrals. However, greater attention needs to address community members' barriers and hesitancy to utilize health resources.

Acceptability and feasibility of home-based hypertension and physical activity screening by community health workers in an under-resourced community in South Africa.

Background: Low-middle-income countries (LMICs) face increasing burdens from non-communicable disease (NCDs) requiring primary care task shifting to community health workers (CHWs). This study explored community members' perceptions of NCD-focused, CHW-led home visits in a historically disadvantaged township of South Africa. Methods: Trained CHWs visited community member homes, performing blood pressure and physical activity (PA) screenings, followed by brief counselling and a satisfaction survey. Semi-structured interviews were conducted within 3 days of the visit to learn about their experiences. Results: CHWs visited 173 households, with 153 adult community members consenting to participate (88.4%). Participants reported that it was easy to understand CHW-delivered information (97%), their questions were answered well (100%), and they would request home service again (93%). Twenty-eight follow-up interviews revealed four main themes: 1) acceptance of CHW visits, 2) openness to counselling, 3) satisfaction with screening and a basic understanding of the results, and 4) receptiveness to the PA advice. Conclusion: Community members viewed CHW-led home visits as an acceptable and feasible method for providing NCD-focused healthcare services in an under-resourced community. Expanding primary care reach through CHWs offers more accessible and individualized care, reducing barriers for individuals in under-resourced communities to access support for NCD risk reduction.

Predictable Changes in Eelgrass Microbiomes with Increasing Wasting Disease Prevalence across 23° Latitude in the Northeastern Pacific.

Predicting outcomes of marine disease outbreaks presents a challenge in the face of both global and local stressors. Host-associated microbiomes may play important roles in disease dynamics but remain understudied in marine ecosystems. Host-pathogen-microbiome interactions can vary across host ranges, gradients of disease, and temperature; studying these relationships may aid our ability to forecast disease dynamics. Eelgrass, Zostera marina, is impacted by outbreaks of wasting disease caused by the opportunistic pathogen Labyrinthula zosterae. We investigated how Z. marina phyllosphere microbial communities vary with rising wasting disease lesion prevalence and severity relative to plant and meadow characteristics like shoot density, longest leaf length, and temperature across 23° latitude in the Northeastern Pacific. We detected effects of geography (11%) and smaller, but distinct, effects of temperature (30-day max sea surface temperature, 4%) and disease (lesion prevalence, 3%) on microbiome composition. Declines in alpha diversity on asymptomatic tissue occurred with rising wasting disease prevalence within meadows. However, no change in microbiome variability (dispersion) was detected between asymptomatic and symptomatic tissues. Further, we identified members of Cellvibrionaceae, Colwelliaceae, and Granulosicoccaceae on asymptomatic tissue that are predictive of wasting disease prevalence across the geographic range (3,100 kilometers). Functional roles of Colwelliaceae and Granulosicoccaceae are not known. Cellvibrionaceae, degraders of plant cellulose, were also enriched in lesions and adjacent green tissue relative to nonlesioned leaves. Cellvibrionaceae may play important roles in disease progression by degrading host tissues or overwhelming plant immune responses. Thus, inclusion of microbiomes in wasting disease studies may improve our ability to understand variable rates of infection, disease progression, and plant survival. IMPORTANCE The roles of marine microbiomes in disease remain poorly understood due, in part, to the challenging nature of sampling at appropriate spatiotemporal scales and across natural gradients of disease throughout host ranges. This is especially true for marine vascular plants like eelgrass (Zostera marina) that are vital for ecosystem function and biodiversity but are susceptible to rapid decline and die-off from pathogens like eukaryotic slime-mold Labyrinthula zosterae (wasting disease). We link bacterial members of phyllosphere tissues to the prevalence of wasting disease across the broadest geographic range to date for a marine plant microbiome-disease study (3,100 km). We identify Cellvibrionaceae, plant cell wall degraders, enriched (up to 61% relative abundance) within lesion tissue, which suggests this group may be playing important roles in disease progression. These findings suggest inclusion of microbiomes in marine disease studies will improve our ability to predict ecological outcomes of infection across variable landscapes spanning thousands of kilometers.

Trading Patients: Applying the Alternative Model for Personality Disorders to Two Cases of DSM-5 Borderline Personality Disorder Over Time and Across Therapists.

The DSM-5 Alternative Model for Personality Disorders (AMPD) dimensionally defines personality pathology using severity of dysfunction and maladaptive style. As the empirical literature on the clinical utility of the AMPD grows, there is a need to examine changes in diagnostic profiles and personality expression in treatment over time. Assessing these changes in individuals diagnosed with borderline personality disorder (BPD) is complicated by the tendency for patients to cycle through multiple therapists over the course of treatment leaving the potential for muddled diagnostic clarity and disjointed case conceptualizations. Following patient trajectories across therapists offers a unique opportunity to examine the AMPD's sensitivity to and utility for capturing personality stability and change over time for patients with BPD. This article demonstrates the utility of the AMPD for two clinical cases in three distinct ways: (i) highlighting heterogeneity in BPD between patients, (ii) comparing improvements in personality severity and style over time, and (iii) elucidating profile change across therapist ratings. We present two patients diagnosed with DSM-5 Section II BPD, crossing between two therapists over the course of 3 years of psychodynamic psychotherapy. Treating clinicians rated patients for their respective treatment phases using the Level of Personality Functioning Scale (LPFS), capturing severity, and the Personality Inventory for the DSM-5 (PID-5), capturing style. AMPD diagnostic profiles differentiated patients with BPD in both severity and style, and captured within-patient change beyond within-therapist response bias. Results indicated greater improvements in personality severity while personality style remained more stable. Implications for the patients' treatment progress and associated challenges are discussed, as are considerations for the utility of the AMPD in therapy.

Impact of communication modality on caregiver ratings for deaf and hard of hearing children.

PURPOSE: Literature on children who are deaf or hard of hearing (DHH) suggests overall increased rates of difficulties in emotional/behavioral and adaptive functioning. However, limitations of this literature include the failure to integrate issues unique to the experience of children who are DHH, such as home and school communication modalities and the consistency of modalities across settings. METHOD: This study examined de-identified data from a clinical database. Data included caregiver ratings of emotional/behavioral and adaptive functioning in a diverse sample of clinically referred children who are DHH (N = 177). Caregivers also reported home and school communication modalities (e.g., match, partial match, different modalities). We examined mean score differences between our sample and normative samples and compared functioning across subgroups of children with various home-school communication modality combinations. RESULTS: Consistent with the literature, we found overall increased rates of emotional/behavioral and adaptive functioning concerns on parent rating scales. Emotional/behavioral concerns did not differ among children with spoken language match, sign language match, or partial match communication modalities combinations. Within adaptive functioning, communication and functional academics were significantly lower among children with partial match home-school communication modalities. Adaptive functioning did not differ between spoken language match and sign language match groups. CONCLUSIONS: Our findings suggest possible benefits to adaptive functioning among children who are DHH when home and school communication modalities match, regardless of which modality is used.

Targeted Wellness Initiatives Are Most Effective for Reducing Otolaryngology Resident Burnout.

OBJECTIVE: Investigate the effect of a targeted wellness program on burnout in Otolaryngology residents. METHODS: Residents and faculty collaboratively developed a program aimed at improving resident wellness. Program implementation began in July of 2018 and after 1 year, residents evaluated the program's effects on burnout. We used the Maslach Burnout Inventory (MBI) and a Likert scale to evaluate the effects of the program. RESULTS: After 1 year of the resident wellness program, the MBI results showed an increase in the number of residents in the "engaged" category and a decrease in those rated as "burnout." Residents rated favorably initiatives grouped into the following themes: time away from work, faculty engaging with residents outside of the hospital environment, efforts to enhance residents' self-efficacy, fostering a positive culture among residents, and providing easy access to physical activity. The majority of initiatives were targeted to the "culture of wellness" domain, as defined by the Stanford Well MD framework. Our program targeted to a lesser extent the other 2 domains, "efficiency of practice" and "personal resilience." CONCLUSION: After 1 year, the wellness program resulted in a trend toward improving burnout. Future efforts should be focused on targeting the multidimensional drivers of burnout as defined by established wellness frameworks. Realizing new stressors brought on by the COVID-19 pandemic will also be an area of active effort and research.

The Inflammatory Role of Pro-Resolving Mediators in Endometriosis: An Integrative Review.

The pathogenesis of endometriosis is still controversial, although it is known that the inflammatory immune response plays a critical role in this process. The resolution of inflammation is an active process where the activation of endogenous factors allows the host tissue to maintain homeostasis. The mechanisms by which pro-resolving mediators (PRM) act in endometriosis are still little explored. Thus, this integrative review aims to synthesize the available content regarding the role of PRM in endometriosis. Experimental and in vitro studies with Lipoxin A4 demonstrate a potential inhibitory effect on endometrial lesions' progression, attenuating pro-inflammatory and angiogenic signals, inhibiting proliferative and invasive action suppressing intracellular signaling induced by cytokines and estradiol, mainly through the FPR2/ALX. Investigations with Resolvin D1 demonstrated the inhibition of endometrial lesions and decreased pro-inflammatory factors. Annexin A1 is expressed in the endometrium and is specifically present in women with endometriosis, although the available studies are still inconsistent. Thus, we believe there is a gap in knowledge regarding the PRM pathways in patients with endometriosis. It is important to note that these substances' therapeutic potential is evident since the immune and abnormal inflammatory responses play an essential role in endometriosis development and progression.

Vitamin D supplementation for women during pregnancy.

BACKGROUND: Vitamin D supplementation during pregnancy may be needed to protect against adverse pregnancy outcomes. This is an update of a review that was first published in 2012 and then in 2016. OBJECTIVES: To examine whether vitamin D supplementation alone or in combination with calcium or other vitamins and minerals given to women during pregnancy can safely improve maternal and neonatal outcomes. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register (12 July 2018), contacted relevant organisations (15 May 2018), reference lists of retrieved trials and registries at clinicaltrials.gov and WHO International Clinical Trials Registry Platform (12 July 2018). Abstracts were included if they had enough information to extract the data. SELECTION CRITERIA: Randomised and quasi-randomised trials evaluating the effect of supplementation with vitamin D alone or in combination with other micronutrients for women during pregnancy in comparison to placebo or no intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently i) assessed the eligibility of trials against the inclusion criteria, ii) extracted data from included trials, and iii) assessed the risk of bias of the included trials. The certainty of the evidence was assessed using the GRADE approach. MAIN RESULTS: We included 30 trials (7033 women), excluded 60 trials, identified six as ongoing/unpublished trials and two trials are awaiting assessments.Supplementation with vitamin D alone versus placebo/no interventionA total of 22 trials involving 3725 pregnant women were included in this comparison; 19 trials were assessed as having low-to-moderate risk of bias for most domains and three trials were assessed as having high risk of bias for most domains. Supplementation with vitamin D alone during pregnancy probably reduces the risk of pre-eclampsia (risk ratio (RR) 0.48, 95% confidence interval (CI) 0.30 to 0.79; 4 trials, 499 women, moderate-certainty evidence) and gestational diabetes (RR 0.51, 95% CI 0.27 to 0.97; 4 trials, 446 women, moderate-certainty evidence); and probably reduces the risk of having a baby with low birthweight (less than 2500 g) (RR 0.55, 95% CI 0.35 to 0.87; 5 trials, 697 women, moderate-certainty evidence) compared to women who received placebo or no intervention. Vitamin D supplementation may make little or no difference in the risk of having a preterm birth < 37 weeks compared to no intervention or placebo (RR 0.66, 95% CI 0.34 to 1.30; 7 trials, 1640 women, low-certainty evidence). In terms of maternal adverse events, vitamin D supplementation may reduce the risk of severe postpartum haemorrhage (RR 0.68, 95% CI 0.51 to 0.91; 1 trial, 1134 women, low-certainty evidence). There were no cases of hypercalcaemia (1 trial, 1134 women, low-certainty evidence), and we are very uncertain as to whether vitamin D increases or decreases the risk of nephritic syndrome (RR 0.17, 95% CI 0.01 to 4.06; 1 trial, 135 women, very low-certainty evidence). However, given the scarcity of data in general for maternal adverse events, no firm conclusions can be drawn.Supplementation with vitamin D and calcium versus placebo/no interventionNine trials involving 1916 pregnant women were included in this comparison; three trials were assessed as having low risk of bias for allocation and blinding, four trials were assessed as having high risk of bias and two had some components having a low risk, high risk, or unclear risk. Supplementation with vitamin D and calcium during pregnancy probably reduces the risk of pre-eclampsia (RR 0.50, 95% CI 0.32 to 0.78; 4 trials, 1174 women, moderate-certainty evidence). The effect of the intervention is uncertain on gestational diabetes (RR 0.33,% CI 0.01 to 7.84; 1 trial, 54 women, very low-certainty evidence); and low birthweight (less than 2500 g) (RR 0.68, 95% CI 0.10 to 4.55; 2 trials, 110 women, very low-certainty evidence) compared to women who received placebo or no intervention. Supplementation with vitamin D and calcium during pregnancy may increase the risk of preterm birth < 37 weeks in comparison to women who received placebo or no intervention (RR 1.52, 95% CI 1.01 to 2.28; 5 trials, 942 women, low-certainty evidence). No trial in this comparison reported on maternal adverse events.Supplementation with vitamin D + calcium + other vitamins and minerals versus calcium + other vitamins and minerals (but no vitamin D)One trial in 1300 participants was included in this comparison; it was assessed as having low risk of bias. Pre-eclampsia was not assessed. Supplementation with vitamin D + other nutrients may make little or no difference in the risk of preterm birth < 37 weeks (RR 1.04, 95% CI 0.68 to 1.59; 1 trial, 1298 women, low-certainty evidence); or low birthweight (less than 2500 g) (RR 1.12, 95% CI 0.82 to 1.51; 1 trial, 1298 women, low-certainty evidence). It is unclear whether it makes any difference to the risk of gestational diabetes (RR 0.42, 95% CI 0.10 to 1.73) or maternal adverse events (hypercalcaemia no events; hypercalciuria RR 0.25, 95% CI 0.02 to 3.97; 1 trial, 1298 women,) because the certainty of the evidence for both outcomes was found to be very low. AUTHORS' CONCLUSIONS: We included 30 trials (7033 women) across three separate comparisons. Our GRADE assessments ranged from moderate to very low, with downgrading decisions based on limitations in study design, imprecision and indirectness.Supplementing pregnant women with vitamin D alone probably reduces the risk of pre-eclampsia, gestational diabetes, low birthweight and may reduce the risk of severe postpartum haemorrhage. It may make little or no difference in the risk of having a preterm birth < 37 weeks' gestation. Supplementing pregnant women with vitamin D and calcium probably reduces the risk of pre-eclampsia but may increase the risk of preterm births < 37 weeks (these findings warrant further research). Supplementing pregnant women with vitamin D and other nutrients may make little or no difference in the risk of preterm birth < 37 weeks' gestation or low birthweight (less than 2500 g). Additional rigorous high quality and larger randomised trials are required to evaluate the effects of vitamin D supplementation in pregnancy, particularly in relation to the risk of maternal adverse events.

Single-Nucleotide-Polymorphism-Panel Population-Genetics Approach Based on the 1000 Genomes Database and Elite Soccer Players.

Purpose: Soccer is one of the most popular sports worldwide, a physical activity of great physiological demand and complexity. Currently, numerous trials involving physiological responses such as hypertrophy, energy expenditure, vasodilation, cardiac output, VO2max, and recovery have supported the possibility of genomic predictors' affecting performance. In a complementary way to association studies with single nucleotide polymorphisms (SNPs), the objective was to evaluate if the use of population genetics data from human-genomics databases can provide information for a better understanding of the relationship between heritability and sport performance. Methods: The study included 25 healthy male professional soccer players (25.5 [4.3] y, 177.4 [6.4] cm, 76.4 [6.4] kg, body fat 10.5% [4.3%]) from the Brazilian first-division soccer club. Anthropometric measurements and field and isokinetic tests were performed to evaluate performance and physiologic parameters of subjects. Moreover, 10 genetic polymorphisms previously related to performance were genotyped. The genotypes of the same polymorphisms were obtained for 2504 individuals from the populations deposited in the 1000 Genomes database. A principal-component analysis and matrix genetic-distances approach (Fst) were evaluated. Results: As expected, the admixture Brazilian population has numerous genetic similarities with the European and American populations from genomic databases. Although the African component is absolutely recognized in genomes from the Brazilian population, using the specific performance-related SNPs, surprisingly the African population was one of the most genetically distant of the players (P < .00001). Conclusions: The early results suggest a selective pressure on genes of elite soccer players, possibly related simultaneously to physical-performance, environmental, cognitive, and sociocultural aspects.

Community and Clinical Epidemiology of Borderline Personality Disorder.

Several studies of the prevalence of borderline personality disorder in community and clinical settings have been carried out to date. Although results vary according to sampling method and assessment method, median point prevalence is roughly 1%, with higher or lower rates in certain community subpopulations. In clinical settings, the prevalence is around 10% to 12% in outpatient psychiatric clinics and 20% to 22% among inpatient clinics. Further research is needed to identify the prevalence and correlates of borderline personality disorder in other clinical settings (eg, primary care) and to investigate the impact of demographic variables on borderline personality disorder prevalence.

The role of emotion regulation difficulties in the connection between childhood emotional abuse and borderline personality features.

In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services project, we examined the role of emotion dysregulation as a mediator between childhood abuse and borderline personality disorder (BPD) feature severity among a sample of 964 adults presenting for treatment at an outpatient clinic. A structural equation model suggested that emotional abuse relates to BPD features both directly and through difficulties with emotion regulation, whereas physical abuse showed only a weak indirect relation with BPD features. There was no link between sexual abuse and BPD feature severity in the model. Results add specificity to etiological theories of BPD and suggest that future research in treatment should focus on developing and strengthening emotion regulation strategies in clinical populations with a history of emotional abuse. Clinicians should be sure to assess the presence of childhood emotional abuse in addition to sexual and physical abuse. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Inclusion/exclusion criteria in late life depression antidepressant efficacy trials.

OBJECTIVE: The generalizability of antidepressant efficacy trials (AETs) has been questioned. No studies have examined the inclusion/exclusion criteria used in placebo-controlled studies of late life depression and compared them to the criteria used in non-late life AETs. METHOD: We conducted a comprehensive literature review of placebo-controlled AETs published from January, 1995 through December, 2014. We compared the inclusion/exclusion criteria used in the 18 studies of late life depression to those used in non-late life depression. RESULTS: There were nine inclusion/exclusion criteria that were used in more than half of the late life depression AETs: minimum severity on a symptom severity scale (100.0%), significant suicidal ideation (77.8%), psychotic features during the current episode of depression or history of a psychotic disorder (94.4%), history of bipolar disorder (77.8%), diagnosis of alcohol or drug abuse or dependence (83.3%), presence of a comorbid nondepressive, nonsubstance use Axis I disorder (55.6%), episode duration too short (66.7%), and an insufficient score on a cognitive screen (88.3%) or the presence of a cognitive disorder (55.6%). There were some differences between the late life and non-late life depression studies-use of a screening measure of cognitive functioning, presence of a cognitive disorder such as dementia, and the minimum depression severity cutoff score required at baseline. CONCLUSIONS: The inclusion/exclusion criteria in AETs of late life depression were generally similar to the criteria used in non-late life depression AETs. Copyright © 2016 John Wiley & Sons, Ltd.

The Psychiatric Inclusion and Exclusion Criteria in Placebo-Controlled Monotherapy Trials of Bipolar Depression: An Analysis of Studies of the Past 20 Years.

BACKGROUND: Concerns about the generalizability of pharmacotherapy efficacy trials to "real-world" patients have been raised for more than 40 years. Almost all of this literature has focused on treatment studies of major depressive disorder (MDD). OBJECTIVE: The aim of the study was to review the psychiatric inclusion and exclusion criteria used in placebo-controlled trials that assessed the efficacy of medications for bipolar depression (bipolar disorder efficacy trials [BDETs]) and compare the criteria used in BDETs with those used in efficacy trials of antidepressants to treat MDD (antidepressant efficacy trials [AETs]). METHODS: We searched the MEDLINE, Embase, and PsycINFO databases for articles published from January 1995 through December 2014. We identified 170 placebo-controlled AETs and 22 BDETs published during these 20 years. Two of the authors independently reviewed each article and completed a pre-specified information extraction form listing the psychiatric inclusion and exclusion criteria used in the study. RESULTS: Six inclusion/exclusion criteria were used in at least half of the BDETs: minimum severity on a depression symptom severity scale, significant suicidal ideation, diagnosis of alcohol or drug use disorder, presence of a comorbid nondepressive, nonsubstance use Axis I disorder, current episode of depression being too long, and absence of current manic symptoms. BDETs were significantly less likely than AETs to exclude patients with a history of psychotic features/disorders, borderline personality disorder, and post-traumatic stress disorder and more likely to exclude individuals who scored too low on the first item of the Hamilton Depression Rating Scale. Nearly two-thirds of the BDETs placed an upper limit on the duration of the current depressive episode, three times higher than the rate in the AETs. There was no difference on other variables between the AETs and BDETs. CONCLUSIONS: Similar to treatment studies of nonbipolar MDD, the treatment studies of bipolar depression frequently excluded patients with comorbid psychiatric and substance use disorders and insufficient severity of depressive symptoms as rated on standardized scales. These findings indicate that concerns about the generalizability of data from trials of recently approved medications for the treatment of bipolar depression are as relevant as the concerns that have been raised about studies of antidepressants for nonbipolar depression.

Vitamin D supplementation for women during pregnancy.

BACKGROUND: Vitamin D deficiency or insufficiency is thought to be common among pregnant women. Vitamin D supplementation during pregnancy has been suggested as an intervention to protect against adverse pregnancy outcomes. OBJECTIVES: To examine whether oral supplements with vitamin D alone or in combination with calcium or other vitamins and minerals given to women during pregnancy can safely improve maternal and neonatal outcomes. MAIN RESULTS: In this updated review we included 15 trials assessing a total of 2833 women, excluded 27 trials, and 23 trials are still ongoing or unpublished. Nine trials compared the effects of vitamin D alone versus no supplementation or a placebo and six trials compared the effects of vitamin D and calcium with no supplementation. Risk of bias in the majority of trials was unclear and many studies were at high risk of bias for blinding and attrition rates.Vitamin D alone versus no supplementation or a placeboData from seven trials involving 868 women consistently show that women who received vitamin D supplements alone, particularly on a daily basis, had higher 25-hydroxyvitamin D than those receiving no intervention or placebo, but this response was highly heterogeneous. Also, data from two trials involving 219 women suggest that women who received vitamin D supplements may have a lower risk of pre-eclampsia than those receiving no intervention or placebo (8.9% versus 15.5%; risk ratio (RR) 0.52; 95% CI 0.25 to 1.05, low quality). Data from two trials involving 219 women suggest a similar risk of gestational diabetes among those taking vitamin D supplements or no intervention/placebo (RR 0.43; 95% CI 0.05, 3.45, very low quality). There were no clear differences in adverse effects, with only one reported case of nephritic syndrome in the control group in one study (RR 0.17; 95% CI 0.01 to 4.06; one trial, 135 women, low quality). Given the scarcity of data for this outcome, no firm conclusions can be drawn. No other adverse effects were reported in any of the other studies.With respect to infant outcomes, data from three trials involving 477 women suggest that vitamin D supplementation during pregnancy reduces the risk preterm birth compared to no intervention or placebo (8.9% versus 15.5%; RR 0.36; 95% CI 0.14 to 0.93, moderate quality). Data from three trials involving 493 women also suggest that women who receive vitamin D supplements during pregnancy less frequently had a baby with a birthweight below 2500 g than those receiving no intervention or placebo (RR 0.40; 95% CI 0.24 to 0.67, moderate quality).In terms of other outcomes, there were no clear differences in caesarean section (RR 0.95; 95% CI 0.69 to 1.31; two trials; 312 women); stillbirths (RR 0.35 95% CI 0.06, 1.99; three trials, 540 women); or neonatal deaths (RR 0.27; 95% CI 0.04, 1.67; two trials, 282 women). There was some indication that vitamin D supplementation increases infant length (mean difference (MD) 0.70, 95% CI -0.02 to 1.43; four trials, 638 infants) and head circumference at birth (MD 0.43, 95% CI 0.03 to 0.83; four trials, 638 women).Vitamin D and calcium versus no supplementation or a placeboWomen who received vitamin D with calcium had a lower risk of pre-eclampsia than those not receiving any intervention (RR 0.51; 95% CI 0.32 to 0.80; three trials; 1114 women, moderate quality), but also an increased risk of preterm birth (RR 1.57; 95% CI 1.02 to 2.43, three studies, 798 women, moderate quality). Maternal vitamin D concentration at term, gestational diabetes, adverse effects and low birthweight were not reported in any trial or reported only by one study. AUTHORS CONCLUSIONS: New studies have provided more evidence on the effects of supplementing pregnant women with vitamin D alone or with calcium on pregnancy outcomes. Supplementing pregnant women with vitamin D in a single or continued dose increases serum 25-hydroxyvitamin D at term and may reduce the risk of pre-eclampsia, low birthweight and preterm birth. However, when vitamin D and calcium are combined, the risk of preterm birth is increased. The clinical significance of the increased serum 25-hydroxyvitamin D concentrations is still unclear. In light of this, these results need to be interpreted with caution. Data on adverse effects were lacking in all studies.The evidence on whether vitamin D supplementation should be given as a part of routine antenatal care to all women to improve maternal and infant outcomes remains unclear. While there is some indication that vitamin D supplementation could reduce the risk of pre-eclampsia and increase length and head circumference at birth, further rigorous randomized trials are required to confirm these effects.

Vitamin D supplementation for women during pregnancy

ABSTRACT BACKGROUND: Vitamin D deficiency or insufficiency is thought to be common among pregnant women. Vitamin D supplementation during pregnancy has been suggested as an intervention to protect against adverse pregnancy outcomes. OBJECTIVES: To examine whether oral supplements with vitamin D alone or in combination with calcium or other vitamins and minerals given to women during pregnancy can safely improve maternal and neonatal outcomes. METHODS: Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (23 February 2015), the International Clinical Trials Registry Platform (31 January 2015), the Networked Digital Library of Theses and Dissertations (28 January 2015) and also contacted relevant organisations (31 January 2015). Selection criteria: Randomized and quasi-randomized trials with randomization at either individual or cluster level, evaluating the effect of supplementation with vitamin D alone or in combination with other micronutrients for women during pregnancy. Data collection and analysis: Two review authors independently i) assessed the eligibility of studies against the inclusion criteria ii) extracted data from included studies, and iii) assessed the risk of bias of the included studies. Data were checked for accuracy. The quality of the evidence was assessed using the GRADE approach. MAIN RESULTS: In this updated review we included 15 trials assessing a total of 2833 women, excluded 27 trials, and 23 trials are still ongoing or unpublished. Nine trials compared the effects of vitamin D alone versus no supplementation or a placebo and six trials compared the effects of vitamin D and calcium with no supplementation. Risk of bias in the majority of trials was unclear and many studies were at high risk of bias for blinding and attrition rates. Vitamin D alone versus no supplementation or a placebo Data from seven trials involving 868 women consistently show that women who received vitamin D supplements alone, particularly on a daily basis, had higher 25-hydroxyvitamin D than those receiving no intervention or placebo, but this response was highly heterogeneous. Also, data from two trials involving 219 women suggest that women who received vitamin D supplements may have a lower risk of pre-eclampsia than those receiving no intervention or placebo (8.9% versus 15.5%; risk ratio (RR) 0.52; 95% CI 0.25 to 1.05, low quality). Data from two trials involving 219 women suggest a similar risk of gestational diabetes among those taking vitamin D supplements or no intervention/placebo (RR 0.43; 95% CI 0.05, 3.45, very low quality). There were no clear differences in adverse effects, with only one reported case of nephritic syndrome in the control group in one study (RR 0.17; 95% CI 0.01 to 4.06; one trial, 135 women, low quality). Given the scarcity of data for this outcome, no firm conclusions can be drawn. No other adverse effects were reported in any of the other studies. With respect to infant outcomes, data from three trials involving 477 women suggest that vitamin D supplementation during pregnancy reduces the risk preterm birth compared to no intervention or placebo (8.9% versus 15.5%; RR 0.36; 95% CI 0.14 to 0.93, moderate quality). Data from three trials involving 493 women also suggest that women who receive vitamin D supplements during pregnancy less frequently had a baby with a birthweight below 2500 g than those receiving no intervention or placebo (RR 0.40; 95% CI 0.24 to 0.67, moderate quality). In terms of other outcomes, there were no clear differences in caesarean section (RR 0.95; 95% CI 0.69 to 1.31; two trials; 312 women); stillbirths (RR 0.35 95% CI 0.06, 1.99; three trials, 540 women); or neonatal deaths (RR 0.27; 95% CI 0.04, 1.67; two trials, 282 women). There was some indication that vitamin D supplementation increases infant length (mean difference (MD) 0.70, 95% CI -0.02 to 1.43; four trials, 638 infants) and head circumference at birth (MD 0.43, 95% CI 0.03 to 0.83; four trials, 638 women). Vitamin D and calcium versus no supplementation or a placebo Women who received vitamin D with calcium had a lower risk of pre-eclampsia than those not receiving any intervention (RR 0.51; 95% CI 0.32 to 0.80; three trials; 1114 women, moderate quality), but also an increased risk of preterm birth (RR 1.57; 95% CI 1.02 to 2.43, three studies, 798 women, moderate quality). Maternal vitamin D concentration at term, gestational diabetes, adverse effects and low birthweight were not reported in any trial or reported only by one study. AUTHORS CONCLUSIONS: New studies have provided more evidence on the effects of supplementing pregnant women with vitamin D alone or with calcium on pregnancy outcomes. Supplementing pregnant women with vitamin D in a single or continued dose increases serum 25-hydroxyvitamin D at term and may reduce the risk of pre-eclampsia, low birthweight and preterm birth. However, when vitamin D and calcium are combined, the risk of preterm birth is increased. The clinical significance of the increased serum 25-hydroxyvitamin D concentrations is still unclear. In light of this, these results need to be interpreted with caution. Data on adverse effects were lacking in all studies. The evidence on whether vitamin D supplementation should be given as a part of routine antenatal care to all women to improve maternal and infant outcomes remains unclear. While there is some indication that vitamin D supplementation could reduce the risk of pre-eclampsia and increase length and head circumference at birth, further rigorous randomized trials are required to confirm these effects.

Variability in the substance use disorder exclusion criterion in antidepressant efficacy trials.

BACKGROUND: Substance use disorders are the most commonly excluded psychiatric disorder in antidepressant efficacy trials (AETs). In a recent review of AETs we noticed variability in the definition of the substance use disorder exclusion criterion. In the present report we examined in greater detail the variability in defining the substance use disorder exclusion criterion, the potential impact of this variability on excluding patients from an AET, and whether the definition of the criterion has changed in the past 20 years. METHODS: We identified 170 AETs published during the past 20 years and compared the studies published during the past 5 years (n=56) to the studies published during the 15 prior years (n=114). RESULTS: Substance abuse was more frequently used as an exclusion criterion than substance dependence. Six time frames have been used as the basis of exclusion, the most frequent being the past 12 months. The time frame had a greater impact on the number of patients who would be excluded than the abuse/dependence distinction. The definition of the substance use exclusion criterion was no different in the studies of the past 5 years compared to the prior 15 years. LIMITATIONS: A limitation of the present analysis is that it was based on published placebo-controlled studies of antidepressants. CONCLUSION: Studies varied in whether abuse or dependence was the basis of exclusion, whether alcohol or illicit drugs or both were the basis of exclusion, and the time frame of the disorders' presence. We raise the question of whether the routine exclusion of patients with a substance use disorder should be reflected in a product's label.

Symptom Severity and the Generalizability of Antidepressant Efficacy Trials: Changes During the Past 20 Years.

The most commonly used inclusion/exclusion criterion in antidepressant efficacy trials (AETs) is a minimum score on a symptom severity scale. In the present study, we reviewed placebo-controlled AETs published during the past 20 years to determine whether there has been a change in the symptom severity inclusion criterion threshold subsequent to publications that highlighted the unrepresentativeness of the depressed patients studied in AETs. We identified 170 AETs published during the past 20 years and compared the studies published during the past 5 years (2010-2104, n = 56) with the studies published during the previous 15 years (n = 114). The symptom severity threshold for inclusion has increased in the more recent cohort of studies. On the 17-item Hamilton Depression Rating Scale, almost half of the studies of the past 5 years used a cutoff of 22 or greater to select patients versus less than one-fifth of the studies during the previous 15 years (44.0% vs 17.5%; χ(2) = 7.4; P < 0.01). Similarly, the cutoff on the Montgomery-Asberg Depression Rating Scale required for study inclusion has been higher in studies of the past 5 years with approximately three-quarters of the recent studies using a cutoff of at least 25, in contrast to one-quarter of the older studies (76.2% vs 25.0%; χ(2) = 8.2; P < 0.01). A significantly higher percentage of patients in our clinical practice would be excluded on the basis of the severity thresholds of the past 5 years (59.3 ± 13.5 vs 49.0 ± 15.1; t121 = 3.1; P < 0.005). These findings suggest that the results of AETs may not be applicable to less severely depressed patients who make up at least half of the patients treated in routine clinical practice. Questions are raised about the Food and Drug Administration labeling of antidepressants.

Vitamin D supplementation during pregnancy: Updated meta-analysis on maternal outcomes.

BACKGROUND: Vitamin D deficiency is highly prevalent during pregnancy. It has been suggested that vitamin D supplementation during pregnancy may reduce the risk of adverse gestational outcomes. OBJECTIVES: To update a previous meta-analysis on the effects of oral vitamin D supplementation (alone or in combination with other vitamins and minerals) during pregnancy on maternal 25(OH)D levels and risk of developing pre-eclampsia, gestational diabetes, preterm birth, impaired glucose tolerance, caesarean section, gestational hypertension and other adverse conditions. METHODS: We searched for randomized and quasi-randomized trials through the Cochrane Pregnancy and Childbirth Group's Trials Register, the International Clinical Trials Registry Platform, the Networked Digital Library of Theses and Dissertations, and direct communications with relevant organizations. Assessments of inclusion criteria, extraction of data from included studies, and risk of bias' assessments of the included studies were done independently by two review authors. RESULTS: We included 15 trials, excluded 27 trials and 23 trials are still ongoing/unpublished. Data from seven trials with 868 women suggest that pregnant women supplemented with vitamin D had significantly higher 25(OH)D levels compared to controls (mean difference: 54.7nmol/L; 95% CI 36.6, 72.9). Two trials found a lower risk of preeclampsia (8.9% versus 15.5%; average risk ratio 0.52; 95% CI 0.25, 1.05) and two other trials found no difference in the risk of gestational diabetes with vitamin D supplementation. Also, three trials found that supplementation with vitamin D plus calcium reduced the risk of pre-eclampsia (5% versus 9%; average risk ratio 0.51; 95% CI 0.32, 0.80). CONCLUSION: Supplementing pregnant women with vitamin D led to significantly higher levels of 25(OH)D at term compared to placebo/control but results were inconsistent. Vitamin D supplementation, with or without calcium, may be related to lower risk of preeclampsia but more studies are needed to confirm this.

Problems in the Descriptions of the Psychiatric Inclusion and Exclusion Criteria in Publications of Antidepressant Efficacy Trials: A Qualitative Review and Recommendations for Improved Clarity.

We recently conducted a comprehensive review of the psychiatric inclusion and exclusion criteria used in 170 placebo-controlled antidepressant efficacy trials (AETs) that were published between 1995 and 2014. In conducting this literature review, we identified a number of instances in which the descriptions of the inclusion/exclusion criteria were vague, redundant, or difficult to interpret. In the present article, we describe nine problems we encountered in our literature review. We recommend that future publications follow the examples found in a few studies in which the inclusion/exclusion criteria are clearly defined and listed in a table.