Cold-stored platelets for acute bleeding in cardiac surgical patients: a narrative review.

PURPOSE: Cold-stored platelets (CSP) are an increasingly active topic of international research. They are maintained at 1-6 °C, in contrast to standard room-temperature platelets (RTP) kept at 20-24 °C. Recent evidence suggests that CSP have superior hemostatic properties compared with RTP. This narrative review explores the application of CSP in adult cardiac surgery, summarizes the preclinical and clinical evidence for their use, and highlights recent research. SOURCE: A targeted search of MEDLINE and other databases up to 24 February 2022 was conducted. Search terms combined concepts such as cardiac surgery, blood, platelet, and cold-stored. Searches of trial registries ClinicalTrials.gov and WHO International Clinical Trials Registry Platform were included. Articles were included if they described adult surgical patients as their population of interest and an association between CSP and clinical outcomes. References of included articles were hand searched. PRINCIPAL FINDINGS: When platelets are stored at 1-6 °C, their metabolic rate is slowed, preserving hemostatic function for increased storage duration. Cold-stored platelets have superior adhesion characteristics under physiologic shear conditions, and similar or superior aggregation responses to physiologic agonists. Cold-stored platelets undergo structural, metabolic, and molecular changes which appear to "prime" them for hemostatic activity. While preliminary, clinical evidence supports the conduct of trials comparing CSP with RTP for patients with platelet-related bleeding, such as those undergoing cardiac surgery. CONCLUSION: Cold-stored platelets may have several advantages over RTP, including increased hemostatic capacity, extended shelf-life, and reduced risk of bacterial contamination. Large clinical trials are needed to establish their potential role in the treatment of acutely bleeding patients.

RéSUMé: OBJECTIF: Les plaquettes conservées au froid (PCF) sont un sujet de recherche internationale de plus en plus populaire. Ces plaquettes sont maintenues à une température de 1-6 °C, contrairement aux plaquettes standard conservées à température ambiante (PTA), maintenues à 20­24 °C. Des données probantes récentes suggèrent que les PCF ont des propriétés hémostatiques supérieures aux PTA. Ce compte rendu narratif explore l'application de PCF en chirurgie cardiaque chez l'adulte, résume les données probantes précliniques et cliniques de leur utilisation, et met en évidence les recherches récentes. SOURCES: Une recherche ciblée dans MEDLINE et d'autres bases de données jusqu'au 24 février 2022 a été effectuée. Les termes de recherche combinaient des concepts en anglais tels que cardiac surgery, blood, platelet et cold-stored (soit chirurgie cardiaque, plaquette, et entreposage frigorifique). Des recherches dans les registres d'études ClinicalTrials.gov et le système d'enregistrement international des essais cliniques (ICTRP) de l'OMS ont été incluses. Les articles ont été inclus s'ils décrivaient des patient·es adultes de chirurgie en tant que population d'intérêt et une association entre les PCF et les issues cliniques. Les références des articles inclus ont fait l'objet d'une recherche manuelle. CONSTATATIONS PRINCIPALES: Lorsque les plaquettes sont conservées entre 1 et 6 °C, leur taux métabolique est ralenti, préservant la fonction hémostatique pour une durée d'entreposage accrue. Les plaquettes conservées au froid ont des caractéristiques d'adhésion supérieures dans des conditions de cisaillement physiologique et des réponses d'agrégation similaires ou supérieures aux agonistes physiologiques. Les plaquettes conservées au froid subissent des changements structurels, métaboliques et moléculaires qui semblent les « amorcer ¼ pour une activité hémostatique. Bien que préliminaires, les données probantes cliniques appuient la réalisation d'études comparant les PCF aux PTA chez la patientèle présentant des saignements liés aux plaquettes, tels que les personnes bénéficiant d'une chirurgie cardiaque. CONCLUSION: Les plaquettes conservées au froid peuvent présenter plusieurs avantages par rapport aux PTA, notamment une capacité hémostatique accrue, une durée de conservation prolongée et un risque réduit de contamination bactérienne. De grands essais cliniques sont nécessaires pour établir leur rôle potentiel dans le traitement de la patientèle en hémorragie aiguë.

Development of a repeated-measures predictive model and clinical risk score for mortality in ventilated COVID-19 patients.

PURPOSE: The COVID-19 pandemic has caused intensive care units (ICUs) to reach capacities requiring triage. A tool to predict mortality risk in ventilated patients with COVID-19 could inform decision-making and resource allocation, and allow population-level comparisons across institutions. METHODS: This retrospective cohort study included all mechanically ventilated adults with COVID-19 admitted to three tertiary care ICUs in Toronto, Ontario, between 1 March 2020 and 15 December 2020. Generalized estimating equations were used to identify variables predictive of mortality. The primary outcome was the probability of death at three-day intervals from the time of ICU admission (day 0), with risk re-calculation every three days to day 15; the final risk calculation estimated the probability of death at day 15 and beyond. A numerical algorithm was developed from the final model coefficients. RESULTS: One hundred twenty-seven patients were eligible for inclusion. Median ICU length of stay was 26.9 (interquartile range, 15.4-52.0) days. Overall mortality was 42%. From day 0 to 15, the variables age, temperature, lactate level, ventilation tidal volume, and vasopressor use significantly predicted mortality. Our final clinical risk score had an area under the receiver-operating characteristics curve of 0.9 (95% confidence interval [CI], 0.8 to 0.9). For every ten-point increase in risk score, the relative increase in the odds of death was approximately 4, with an odds ratio of 4.1 (95% CI, 2.9 to 5.9). CONCLUSION: Our dynamic prediction tool for mortality in ventilated patients with COVID-19 has excellent diagnostic properties. Notwithstanding, external validation is required before widespread implementation.

RéSUMé: OBJECTIF: En raison de la pandémie de COVID-19, les unités de soins intensifs (USI) ont atteint des taux d'occupation nécessitant un triage. Un outil pour prédire le risque de mortalité chez les patients sous ventilation atteints de COVID-19 pourrait éclairer la prise de décision et l'attribution des ressources tout en permettant des comparaisons populationnelles entre les établissements. MéTHODE: Cette étude de cohorte rétrospective a inclus tous les adultes atteints de COVID-19 sous ventilation mécanique admis dans trois USI de centres de soins tertiaires à Toronto, en Ontario, entre le 1er mars 2020 et le 15 décembre 2020. Des équations d'estimation généralisées ont été utilisées pour identifier les variables prédictives de mortalité. Le critère d'évaluation principal était la probabilité de décès à des intervalles de trois jours à partir du moment de l'admission à l'USI (jour 0), avec un nouveau calcul du risque tous les trois jours jusqu'au jour 15; le calcul final du risque a estimé la probabilité de décès au jour 15 et au-delà. Un algorithme numérique a été mis au point à partir des coefficients du modèle final. RéSULTATS: Cent vingt-sept patients étaient éligibles à l'inclusion. La durée médiane de séjour à l'USI était de 26,9 jours (écart interquartile, 15,4 à 52,0). La mortalité globale était de 42 %. Du jour 0 au jour 15, les variables que sont l'âge, la température, les taux de lactate, le volume courant de ventilation et l'utilisation de vasopresseurs ont constitué des prédicteurs significatifs de mortalité. Notre score de risque clinique final avait une aire sous la courbe ROC de 0,9 (intervalle de confiance [IC] à 95 %, 0,8 à 0,9). Pour chaque augmentation de dix points du score de risque, l'augmentation relative des risques de décès était d'environ 4, avec un rapport de cotes de 4,1 (IC 95 %, 2,9 à 5,9). CONCLUSION: Notre outil de prédiction dynamique de la mortalité pour les patients ventilés atteints de COVID-19 possède d'excellentes propriétés diagnostiques. Néanmoins, une validation externe est nécessaire avant sa mise en œuvre généralisée.

Albumin use for fluid resuscitation in cardiac surgical patients: a survey of Canadian perioperative care providers.

PURPOSE: To evaluate the perceptions and practices of Canadian cardiovascular anesthesiologists and intensivists towards intravenous albumin as a resuscitation fluid in patients undergoing cardiac surgery. METHODS: We conducted a cross-sectional survey of cardiac anesthesiologists and intensivists involved in the care of cardiac surgical patients. The 22-item survey included seven open-ended questions and assessed practice patterns and attitudes towards albumin. Descriptive statistics were analyzed using counts and proportions. Qualitative data were analyzed to identify themes describing albumin use patterns in Canada. RESULTS: A total of 133 respondents from seven provinces participated, with 83 (62%) using albumin perioperatively. The majority of respondents (77%) felt a low fluid balance in cardiac surgical patients was important, and that supplementing crystalloids with albumin was helpful for this objective (67%). There was poor agreement among survey respondents regarding the role of albumin for faster vasopressor weaning or intensive care discharge, and ≥ 90% did not feel albumin reduced mortality, renal injury, or coagulopathy. Nevertheless, cardiac surgical patients were identified as a distinct population where albumin may help to minimize fluid balance. There was an acknowledged paucity of formal evidence supporting possible benefits. Fewer than 10% of respondents could identify institutional or national guidelines for albumin use. A lack of evidence supporting albumin use in cardiac surgical patients, especially those at highest risk of complications, was a frequently identified concern. CONCLUSIONS: The majority of Canadian anesthesiologists and intensivists (62%) use albumin in cardiac surgical patients. There is clinical equipoise regarding its utility, and an acknowledged need for higher quality evidence to guide practice.

RéSUMé: OBJECTIF: Évaluer les perceptions et les pratiques des anesthésiologistes et intensivistes cardiovasculaires canadiens à l'égard de l'albumine intraveineuse comme liquide de réanimation pour les patients bénéficiant d'une chirurgie cardiaque. MéTHODE: Nous avons mené un sondage transversal auprès d'anesthésiologistes et d'intensivistes cardiaques impliqués dans les soins aux patients de chirurgie cardiaque. Le sondage en 22 éléments comprenait sept questions ouvertes et évaluait les habitudes de pratique et les attitudes des praticiens à l'égard de l'albumine. Les statistiques descriptives ont été analysées à l'aide de dénombrements et de proportions. Des données qualitatives ont été analysées pour identifier des thèmes décrivant les tendances d'utilisation de l'albumine au Canada. RéSULTATS: Au total, 133 répondants de sept provinces ont participé, et 83 (62 %) utilisent l'albumine en périopératoire. La majorité des répondants (77 %) estimaient qu'un bilan liquidien négatif était important chez les patients en chirurgie cardiaque et que la supplémentation en cristalloïdes par de l'albumine était utile pour atteindre cet objectif (67 %). Il y avait un faible accord parmi les répondants concernant le rôle de l'albumine pour accélérer le sevrage des vasopresseurs ou la sortie de soins intensifs, et ≥ 90 % ne pensaient pas que l'albumine réduisait la mortalité, les lésions rénales ou la coagulopathie. Néanmoins, les patients en chirurgie cardiaque ont été identifiés comme une population distincte pour laquelle l'albumine pourrait contribuer à minimiser le bilan liquidien. Il y avait un manque reconnu de données probantes formelles à l'appui des avantages possibles. Moins de 10 % des répondants ont pu trouver des lignes directrices institutionnelles ou nationales portant sur l'utilisation de l'albumine. Le manque de données probantes à l'appui de l'utilisation de l'albumine chez les patients en chirurgie cardiaque, en particulier chez ceux présentant le risque le plus élevé de complications, était une préoccupation fréquemment identifiée. CONCLUSION: La majorité des anesthésiologistes et intensivistes canadiens (62 %) utilisent l'albumine chez les patients en chirurgie cardiaque. Il existe un équilibre clinique quant à son utilité et un besoin reconnu de données probantes de meilleure qualité pour guider la pratique.

Pregnancy and Delivery Outcomes Following Benzodiazepine Exposure: A Systematic Review and Meta-analysis.

OBJECTIVE: Understanding the effects of benzodiazepines (BZDs) on maternal/fetal health remains incomplete despite their frequent use. This article quantifies the effects of antenatal BZD exposure on delivery outcomes. DATA SOURCES: Medline, PsycINFO, CINAHL, Embase, and the Cochrane Library were searched till June 30, 2018. STUDY SELECTION: English-language cohort studies comparing antenatal BZD exposure to an unexposed group on any delivery outcome were eligible. In all, 23,909 records were screened, 56 studies were assessed, and 14 studies were included. DATA EXTRACTION: Two reviewers independently assessed quality and extracted data. Estimates were pooled using random effects meta-analysis. Sub-analyses examined several potential moderators including timing of exposure. RESULTS: There were 9 outcomes with sufficient data for meta-analysis. Antenatal BZD exposure was significantly associated with increased risk of 6 outcomes initially: spontaneous abortion (pooled odds ratio = 1.86; 95% confidence interval [CI], 1.43 to 2.42), preterm birth (1.96; 95% CI, 1.25 to 3.08), low birth weight (2.24; 95% CI, 1.41 to 3.88), low Apgar score (2.19; 95% CI, 1.94 to 2.47), Neonatal Intensive Care Unit (NICU) admission (2.61; 95% CI, 1.64 to 4.14), and induced abortion (2.04; 95% CI, 1.23 to 3.40). There was significant heterogeneity between studies for most outcomes without consistent moderators. Birth weight (mean difference [MD]: -151.35 g; 95% CI, -329.73 to 27.03), gestational age (-0.49 weeks; 95% CI, -1.18 to 0.19), and small for gestational age (SGA; 1.42; 95% CI, 1.00 to 2.01) did not show significant associations although after adjusting for publication bias, gestational age, and SGA became significant, totaling 8 significant outcomes. CONCLUSIONS: Antenatal BZD exposure appears to be statistically associated with increased risk of several adverse perinatal outcomes. Although confounds cannot be ruled out, NICU admission does appear clinically relevant and consistent with the antidepressant literature.

A systematic review and meta-analysis of the effects of antenatal anxiety on postpartum outcomes.

To systematically review and meta-analyze research investigating the association between maternal anxiety during pregnancy and outcomes for mother and baby following the immediate delivery period. MEDLINE, Medline In-Process & Other Non-Indexed Citations, PsycINFO, Embase, CINAHL, and the Cochrane library were searched. English-language, prospective studies providing data on outcomes following delivery in women with and without antenatal anxiety (defined by clinical diagnosis or score on validated scale) were included. Three-hundred-fifty-eight articles were retrieved and 13 were included. Titles and abstracts were screened; two reviewers independently reviewed full text articles, conducted quality assessments, extracted, and checked the data. Where available for > 2 studies, random effect meta-analysis was conducted and heterogeneity was quantified. Subanalyses explored moderators, regardless of heterogeneity, including type of anxiety assessment and timing, among others. There were two outcomes that were amenable to meta-analysis. Antenatal anxiety was significantly associated with postpartum depression (PPD) measured within 6 months postpartum (pooled odds ratio [OR] = 2.64, 95% CI 2.02-3.46; 8 studies), regardless of restricting analyses to those studies controlling for prenatal depression (2.45, 1.77-3.39; 6 studies). Associations were also significant when PPD was measured at 1-3 months (2.57, 1.94-3.40; 7 studies) and 6-10 months (4.42, 1.45-13.49; 3 studies). Maternal anxiety was also associated with reduced odds of breastfeeding (0.63, 0.53-0.74; 5 studies). Antenatal anxiety is associated with PPD up to the first 10 months, independent of prenatal depression, and with lower odds of breastfeeding.

Delayed cold-stored vs. room temperature stored platelet transfusions in bleeding adult cardiac surgery patients-a randomized multicentre pilot study (PLTS-1).

BACKGROUND: Platelets stored at 1-6 °C are hypothesized to be more hemostatically active than standard room temperature platelets (RTP) stored at 20-24 °C. Recent studies suggest converting RTP to cold-stored platelets (Delayed Cold-Stored Platelets, DCSP) may be an important way of extending platelet lifespan and increasing platelet supply while also activating and priming platelets for the treatment of acute bleeding. However, there is little clinical trial data supporting the efficacy and safety of DCSP compared to standard RTP. METHODS: This protocol details the design of a multicentre, two-arm, parallel-group, randomized, active-control, blinded, internal pilot trial to be conducted at two cardiac surgery centers in Canada. The study will randomize 50 adult (≥ 18 years old) patients undergoing at least moderately complex cardiac surgery with cardiopulmonary bypass and requiring platelet transfusion to receive either RTP as per standard of care (control group) or DCSP (intervention group). Patients randomized to the intervention group will receive ABO-identical, buffy-coat, pathogen-reduced, platelets in platelet additive solution maintained at 22 °C for up to 4 days then placed at 4 °C for a minimum of 24 h, with expiration at 14 days after collection. The duration of the intervention is from the termination of cardiopulmonary bypass to 24 h after, with a maximum of two doses of DCSP. Thereafter, all patients will receive RTP. The aim of this pilot is to assess the feasibility of a future RCT comparing the hemostatic effectiveness of DCSP to RTP (defined as the total number of allogeneic blood products transfused within 24 h after CPB) as well as safety. Specifically, the feasibility objectives of this pilot study are to determine (1) recruitment of ≥ 15% eligible patients per center per month); (2) appropriate platelet product available for ≥ 90% of patients randomized to the cold-stored platelet group; (3) Adherence to randomization assignment (> 90% of patients administered assigned product). DISCUSSION: DCSP represents a promising logistical solution to address platelet supply shortages and a potentially more efficacious option for the management of active bleeding. No prospective clinical studies on this topic have been conducted. This proposed internal pilot study will assess the feasibility of a larger definitive study. TRIAL REGISTRATION: NCT06147531 (clinicaltrials.gov).

The State of Synthetic Cannabinoid Medications for the Treatment of Pain.

Synthetic cannabinoids are compounds made in the laboratory to structurally and functionally mimic phytocannabinoids from the Cannabis sativa L. plant, including delta-9-tetrahydrocannabinol (THC). Synthetic cannabinoids (SCs) can signal via the classical endogenous cannabinoid system (ECS) and the greater endocannabidiome network, highlighting their signalling complexity and far-reaching effects. Dronabinol and nabilone, which mimic THC signalling, have been approved by the Food and Drug Administration (FDA) for treating nausea associated with cancer chemotherapy and/or acquired immunodeficiency syndrome (AIDS). However, there is ongoing interest in these two drugs as potential analgesics for a variety of other clinical conditions, including neuropathic pain, spasticity-related pain, and nociplastic pain syndromes including fibromyalgia, osteoarthritis, and postoperative pain, among others. In this review, we highlight the signalling mechanisms of FDA-approved synthetic cannabinoids, discuss key clinical trials that investigate their analgesic potential, and illustrate challenges faced when bringing synthetic cannabinoids to the clinic.

A systematic review of the efficacy of ketamine for craniofacial pain.

Background: Craniofacial pain (CFP) poses a burden on patients and health care systems. It is hypothesized that ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, can reverse central sensitization associated with causation and propagation of CFP. This systematic review aims to assess the role of ketamine for CFP. Methods: Databases were searched for studies published up to September 26, 2022, investigating the efficacy of ketamine for adults with CFP. Primary outcome was the change in pain intensity at 60 min postintervention. Two reviewers screened and extracted data. Registration with PROSPERO was performed (CRD42020178649). Results: Twenty papers (six randomized controlled trials [RCTs], 14 observational studies) including 670 patients were identified. Substantial heterogeneity in terms of study design, population, dose, route of administration, treatment duration, and follow-up was noted. Bolus dose ranged from 0.2-0.3 mg/kg (intravenous) to 0.4 mg/kg (intramuscular) to 0.25-0.75 mg/kg (intranasal). Ketamine infusions (0.1-1 mg/kg/h) were given over various durations. Follow-up was short in RCTs (from 60 min to 72 h) but longer in observational studies (up to 18 months). Ketamine by bolus treatment failed to reduce migraine intensity but had an effect by reducing intensity of aura, cluster headache (CH), and trigeminal neuralgia. Prolonged ketamine infusions showed sustainable reduction of migraine intensity and frequency of CH attacks, but the quality of the evidence is low. Conclusion: Current evidence remains conflicting on the efficacy of ketamine for CFP owing to low quality and heterogeneity across studies. Ketamine infusions are suggested to provide sustained improvement, possibly because of prolonged duration and higher dosage of administration. RCTs should focus on the dose-response relationship of prolonged ketamine infusions on CFP.

Contexte: La douleur crânio-faciale représente un fardeau pour les patients et les systèmes de soins de santé. L'hypothèse a été émise que la kétamine, un antagoniste du récepteur N-méthyl-D-aspartate (NMDA), peut inverser la sensibilisation centrale associée à la causalité et à la propagation de la douleur crânio-faciale. Cette revue systématique vise à évaluer le rôle de la kétamine dans la douleur crânio-faciale.Méthodes: Les bases de données ont été consultées pour y repérer les études publiées jusqu'au 26 septembre 2022 qui portaient sur l'efficacité de la kétamine chez les adultes atteints de douleur crânio-faciale. Le critère de jugement principal était le changement de l'intensité de la douleur 60 minutes après l'intervention. Deux évaluateurs ont examiné et extrait les données. L'inscription auprès de PROSPERO a été réalisée (CRD42020178649).Résultats: Vingt articles (six essais contrôlés randomisés, 14 études observationnelles) incluant 670 patients ont été répertoriées. Une hétérogénéité considérable en matière de devis d'étude, de population, de dose, de voie d'administration, de durée du traitement et de suivi a été notée. La dose bolus variait de 0,2 à 0,3 mg/kg (voie intraveineuse) à 0,4 mg/kg (voie intramusculaire) et à 0,25-0,75 mg/kg (voie intranasale). Les perfusions de kétamine (0,1-1 mg/kg/h) étaient administrées sur différentes durées. Le suivi était court dans les études contrôllées randomisées (de 60 min à 72 h) mais plus long dans les études observationnelles (jusqu'à 18 mois). La kétamine par traitement bolus n'a pas réussi à réduire l'intensité de la migraine mais a eu un effet en réduisant l'intensité de l'aura, la céphalée en grappe et la névralgie du trijumeau. Les perfusions de kétamine prolongées ont montré une réduction durable de l'intensité de la migraine et la fréquence des crises de CH, mais la qualité des données probantes est faible.Conclusions: Les données probantes actuelles demeurent contradictoires sur l'efficacité de la kétamine pour la douleur crânio-faciale en raison de la faible qualité et de l'hétérogénéité des études. Il est suggéré que les perfusions de kétamine procurent une amélioration soutenue, peut-être en raison de leur durée prolongée et de leur posologie d'administration plus élevée. Les essais contrôlés randomisés devraient se concentrer sur la relation dose-réponse des perfusions prolongées de kétamine sur la douleur crâno-faciale.

Rapid implementation of an outpatient arthroplasty care pathway: a COVID-19-driven quality improvement initiative.

BACKGROUND: Hip and knee total joint arthroplasty (TJA) procedures are two of the most common inpatient surgical procedures worldwide. Outpatient TJA has emerged as a feasible option. COVID-19 caused significant constraints on inpatient surgical resources and contributed to a growing surgical backlog. We present a quality improvement (QI) initiative aimed at adding an outpatient TJA pathway to our pre-existing inpatient TJA programme, with the target of performing 25% of our primary TJA as outpatients. METHODS: This was a QI study at a tertiary level arthroplasty centre. To achieve our aim, a patient-centred needs analysis revealed the need to develop patient selection criteria, perform a specific and tailored anaesthetic, provide patient education and conduct virtual care follow-up. Based on these findings, an outpatient TJA intervention bundle was developed and implemented. RESULTS: After implementing the outpatient pathway, 65 patients were scheduled for outpatient TJA. Fifty-five (84.6%) patients were successfully discharged home on the day of surgery. Successful outpatient TJA accounted for 33.3% of all primary TJAs performed at our intuition throughout the study period. There was excellent adherence to the intervention protocols, with the success hinging on multidisciplinary team and supported QI culture. Thirty-day emergency department visits for inpatient and outpatient TJAs were 8.93% and 6.15%, respectively. No outpatient TJA patients required hospital readmission within 30 days. CONCLUSION: Our study demonstrates that implementation of an outpatient TJA pathway in response to inpatient resource constraints during the COVID-19 pandemic is feasible. The findings of this report will be of interest to surgical centres facing surgical backlog and constraints on inpatient resources during and after the pandemic.

The Premenstrual Symptoms Screening Tool revised for adolescents (PSST-A): prevalence of severe PMS and premenstrual dysphoric disorder in adolescents.

The Premenstrual Symptoms Screening Tool was modified for use in adolescents and piloted in 578 girls at three international sites. Nearly one third (29.6%) reported experiencing severe PMS or PMDD, with irritability being the most commonly reported symptom. Rates of menstrual-related pain were high, particularly in those with severe PMS or PMDD. Severe PMS and PMDD present with similar rates and symptoms in adolescents as in adults, and the Premenstrual Symptoms Screening Tool modified for adolescents is a fast, reliable tool to screen for these syndromes in adolescents.

Benzodiazepine Use During Pregnancy Alone or in Combination With an Antidepressant and Congenital Malformations: Systematic Review and Meta-Analysis.

OBJECTIVE: To summarize the effects of antenatal benzodiazepine exposure as monotherapy and in combination with antidepressants on the risk of congenital malformations. DATA SOURCES: MEDLINE, PsycINFO, CINAHL, Embase, and the Cochrane Library were searched from inception to June 30, 2018, using controlled vocabulary and keywords (eg, prenatal, benzodiazepines, malformation). STUDY SELECTION: English-language cohort studies with prospectively collected data on the risk of malformations in benzodiazepine-exposed and -unexposed offspring were evaluated. 23,909 records were screened, 56 studies were assessed for eligibility, and 8 studies were included. DATA EXTRACTION: Quality was assessed by 2 independent reviewers and data extracted. Random-effects models were used for outcomes (≥ 3 studies). Subanalyses examined effect of potential moderators including study quality and timing of exposure, among others. RESULTS: Prenatal benzodiazepine use was not associated with an increased risk of congenital malformations (odds ratio [OR] = 1.13; 95% CI, 0.99 to 1.30, 8 studies, n = 222/5,195 exposed and 64,335/2,082,467 unexposed), including with first trimester exposure specifically (OR = 1.08; 95% CI, 0.93 to 1.25, P = .33; 5 studies, n = 181/4,331 exposed and 64,308/2,081,463 unexposed). There was no significant association with cardiac malformation following exposure (OR = 1.27; 95% CI, 0.98 to 1.65, P = .07; 4 studies, n = 61/4,414 exposed and 19,260/2,033,402 unexposed). However, concurrent use of benzodiazepine and antidepressants during pregnancy was associated with a significantly increased risk of congenital malformations (OR = 1.40; 95% CI, 1.09 to 1.80, P = .008; 3 studies). CONCLUSIONS: Benzodiazepine exposure during pregnancy does not appear to be associated with congenital malformations or with cardiac malformations specifically. There may be an increased risk of congenital malformations when benzodiazepines are used in conjunction with antidepressants, suggesting that caution with this combination is warranted.

Maternal Anxiety During Pregnancy and the Association With Adverse Perinatal Outcomes: Systematic Review and Meta-Analysis.

OBJECTIVE: This systematic review and meta-analysis examined the association between maternal antenatal anxiety (AA) and a range of perinatal outcomes. DATA SOURCES: Ovid MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, PsycINFO, CINAHL, Embase, and the Cochrane Library were searched to May 31, 2016, using controlled vocabulary and keywords (eg, prenatal, anxiety, preterm). STUDY SELECTION: Perinatal outcomes of women with and without AA (diagnosed or self-reported using validated scale) derived from English language, prospectively collected data were included. 1,458 abstracts were reviewed, 306 articles were retrieved, and 29 articles were included. DATA EXTRACTION: Two independent reviewers extracted data and assessed quality. Random-effects models were utilized for outcomes (≥ 3 studies). Subanalyses examined potential effect moderators including study quality and diagnostic versus self-reported anxiety among others. RESULTS: Antenatal anxiety was associated with increased odds for preterm birth (pooled odds ratio [OR] = 1.54; 95% confidence interval [CI], 1.39 to 1.70, 16 studies) and spontaneous preterm birth (OR = 1.41; 95% CI, 1.13 to 1.75), lower mean birth weight (mean difference = -55.96 g; 95% CI, -93.62 to -18.31 g), increased odds for low birth weight (OR = 1.80; 95% CI, 1.48 to 2.18), earlier gestational age (mean difference = -0.13 wk; 95% CI, -0.22 to -0.04 wk), increased odds for being small for gestational age (OR = 1.48; 95% CI, 1.26 to 1.74), and smaller head circumference (mean difference = -0.25 cm; 95% CI, -0.45 to -0.06 cm). Heterogeneity between studies was not significant for most outcomes. Subanalyses for birth weight found women with diagnosed anxiety had infants with significantly lower birth weight (P < .03) compared to those identified with rating scales (although both subanalyses were significant [P < .01]). Associations between anxiety and preeclampsia, cesarean delivery, and Apgar scores were nonsignificant. CONCLUSIONS: Antenatal anxiety is associated with multiple adverse perinatal outcomes and is not benign. The impact of treating anxiety on these associations is unknown.

Antenatal depression in a multi-ethnic, community sample of Canadian immigrants: psychosocial correlates and hypothalamic-pituitary-adrenal axis function.

OBJECTIVES: Immigrant women living in Canada present with higher rates of prenatal depressive symptomatology than Canadian-born women; however, the associated psychosocial correlates remain understudied. Antenatal depression and stress negatively affect maternal health and infant development, in part through changes in maternal hypothalamic-pituitary-adrenal (HPA) axis activity. We aimed to examine the factors associated with prenatal depressive symptoms, including altered HPA axis function, in an ethnically diverse community sample of Canadian immigrant women. METHODS: Seventy-eight pregnant immigrant women were recruited from the community at 19 weeks' gestation and provided information on health, mood, stressful life events (SLEs), and social support. Fifty-seven of these women also provided saliva samples for measurement of the cortisol awakening response and nighttime cortisol levels. RESULTS: Seventeen per cent of the sample had a high level of prenatal depressive symptoms, and these women reported more perceived stress, more somatic symptoms, lower social support, and were less often working or attending school during pregnancy. Controlling for wake time, parity, and region of origin, high levels of prenatal depressive symptoms were associated with elevated nighttime cortisol levels, whereas SLEs were not associated with any measures of HPA axis activity. CONCLUSIONS: High levels of prenatal depressive symptoms are common in immigrant women living in Canada, and are associated with identifiable factors. Preliminary evidence suggests a similar pattern of HPA axis activity characterizing depressive symptomatology in this subpopulation as previously seen in clinically depressed patients.

Objectifs : Les femmes immigrantes habitant le Canada présentent des taux plus élevés de symptomatologie dépressive prénatale que les femmes canadiennes de naissance; cependant, les corrélats psychosociaux associés demeurent sous-étudiés. La dépression prénatale et le stress influent négativement sur la santé maternelle et le développement du bébé, en partie à cause de changements d'activité de l'axe hypothalamo-hypophyso-surrénalien (HHS) maternel. Nous cherchions à examiner les facteurs associés aux symptômes dépressifs prénataux, notamment la fonction altérée de l'axe HHS, dans un échantillon communautaire ethniquement diversifié de femmes immigrantes canadiennes. Méthodes : Soixante-dix-huit immigrantes enceintes ont été recrutées dans la communauté à 19 semaines de gestation et ont reçu de l'information sur la santé, l'humeur, les événements stressants de la vie (ESV), et le soutien social. Cinquante-sept d'entre elles ont aussi fourni des échantillons de salive afin de mesurer la réponse du cortisol à l'éveil et les niveaux de cortisol le soir. Résultats : Dix-sept pour cent de l'échantillon avait un taux élevé de symptômes dépressifs prénataux, et ces femmes déclaraient avoir plus de stress perçu, plus de symptômes somatiques, un soutien social plus faible, et elles travaillaient ou allaient à l'école moins souvent durant la grossesse. Après contrôle pour la durée de l'éveil, pour la parité, et la région d'origine, les niveaux élevés de symptômes dépressifs prénataux étaient associés aux taux élevés de cortisol le soir, alors que les ESV n'étaient associés à aucune mesure de l'activité de l'axe HHS. Conclusions : Les niveaux élevés de symptômes dépressifs prénataux sont communs chez les femmes immigrantes habitant le Canada, et ils sont associés à des facteurs identifiables. Les données probantes préliminaires suggèrent un modèle semblable d'activité de l'axe HHS caractérisant la symptomatologie dépressive dans cette sous-population comme il a été vu précédemment chez des patients cliniquement déprimés.

The premenstrual tension syndrome rating scales: an updated version.

BACKGROUND: The Premenstrual Tension Syndrome (PMTS) Rating Scales have been widely used as inclusion criteria and/or outcome measures in clinical trials of treatment of Premenstrual Syndromes (PMS). However, both the PMTS Observer Rating Scale (PMTS-O) and the PMTS Self Rating Scale (PMTS-SR) are outdated. We propose to bring them in line with the DSM-IV criteria for Premenstrual Dysphoric Disorder (PMDD) by updating the PMTS-O and replacing the PMTS-SR with a Multiple Visual Analogue Scale (PMTS-VAS). METHODS: A convenience sample of 23 Caucasian, English-speaking women in their reproductive years with regular menstrual cycles was recruited. Participants were administered the revised PMTS-O (PMTS-OR) by a trained clinician and then instructed to complete the PMTS-SR and the new PMTS-VAS, both of which were timed. The participants were also asked which of the instruments they preferred. RESULTS: The PMTS-OR and the new PMTS-VAS were sensitive to the variation in severity of premenstrual symptoms among the study participants. All 3 questionnaires showed very high inter-correlations. The PMTS-VAS took less time to complete, and most women preferred the PMTS-VAS to the original PMTS-SR, especially those with PMDD and severe PMS. CONCLUSIONS: By making minor modifications to the PMTS-O we have ensured that all criteria for the DSM-IV definition of PMDD are now represented in the PMTS-OR. The new PMTS-VAS mirrors the PMTS-OR but now also captures the severity of self rated symptoms. These scales are simple to complete for both clinicians and clients, and are reliable, valid and sensitive to change.