Eligibility and enrollment of pregnant and breastfeeding women in psychiatry randomized controlled trials.

To describe the eligibility and enrollment of pregnant and breastfeeding women in psychiatry randomized controlled trials (RCTs). We screened citations published 2017-2019 in the three highest impact psychiatry and five highest impact general medicine journals. We excluded male, pediatric, geriatric, and postmenopausal-focused RCTs and publications reporting subgroup, pooled, or secondary analyses of RCTs. We reviewed appendices, protocols, and registries for additional data. In total 108 RCTs were included. Three (2.8%) permitted enrollment of pregnant women; 59/108 (55%) and 46/108 (43%) explicitly excluded pregnant women or did not report pregnancy inclusion criteria, respectively. All RCTs including pregnant women evaluated non-pharmacological interventions for depression during pregnancy or postpartum. Among RCTs excluding pregnant women, 5/59 (8.5%) provided a rationale for exclusion. Contraception and/or negative pregnancy testing were required for women with reproductive capacity in 31/59 (53%). Three (2.8%) RCTs permitted enrollment of breastfeeding women and 3/41 (7.3%) RCTs excluding breastfeeding women provided a rationale for exclusion. This study demonstrates a major gap in psychiatry research involving pregnant and breastfeeding women. A shift from exclusion by default to inclusion and integration of this population into the clinical research agenda is needed to ensure they receive evidence-based care for mental illness.

Impact of Ketamine on Analgosedative Consumption in Critically Ill Patients: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of this study was to synthesize evidence available on continuous infusion ketamine versus nonketamine regimens for analgosedation in critically ill patients. DATA SOURCES: A search of MEDLINE, EMBASE, CINAHL, CDSR, and ClinicalTrials.gov was performed from database establishment to November 2021 using the following search terms: critical care, ICU, ketamine, sedation, and anesthesia. All studies included the primary outcome of interest: daily opioid and/or sedative consumption. STUDY SELECTION AND DATA EXTRACTION: Relevant human studies were considered. Randomized controlled trials (RCT), quasi-experimental studies, and observational cohort studies were eligible. Two reviewers independently screened articles, extracted data, and appraised studies using the Cochrane RoB and ROBINS-I tools. DATA SYNTHESIS: A total of 13 RCTs, 5 retrospective, and 1 prospective cohort study were included (2255 participants). The primary analysis of six RCTs demonstrated reduced opioid consumption with ketamine regimens (n = 494 participants, -13.19 µg kg-1 h-1 morphine equivalents, 95% CI -22.10 to -4.28, P = 0.004). No significant difference was observed in sedative consumption, duration of mechanical ventilation (MV), ICU or hospital length of stay (LOS), intracranial pressure, and mortality. Small sample size of studies may have limited ability to detect true differences between groups. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This meta-analysis examining ketamine use in critically ill patients is the first restricting analysis to RCTs and includes up-to-date publication of trials. Findings may guide clinicians in consideration and dosing of ketamine for multimodal analgosedation. CONCLUSION: Results suggest ketamine as an adjunct analgosedative has the potential to reduce opioid exposure in postoperative and MV patients in the ICU. More RCTs are required before recommending routine use of ketamine in select populations.

Adapting obstetric and neonatal services during the COVID-19 pandemic: a scoping review.

BACKGROUND: The provision of care to pregnant persons and neonates must continue through pandemics. To maintain quality of care, while minimizing physical contact during the Severe Acute Respiratory Syndrome-related Coronavirus-2 (SARS-CoV2) pandemic, hospitals and international organizations issued recommendations on maternity and neonatal care delivery and restructuring of clinical and academic services. Early in the pandemic, recommendations relied on expert opinion, and offered a one-size-fits-all set of guidelines. Our aim was to examine these recommendations and provide the rationale and context to guide clinicians, administrators, educators, and researchers, on how to adapt maternity and neonatal services during the pandemic, regardless of jurisdiction. METHOD: Our initial database search used Medical subject headings and free-text search terms related to coronavirus infections, pregnancy and neonatology, and summarized relevant recommendations from international society guidelines. Subsequent targeted searches to December 30, 2020, included relevant publications in general medical and obstetric journals, and updated society recommendations. RESULTS: We identified 846 titles and abstracts, of which 105 English-language publications fulfilled eligibility criteria and were included in our study. A multidisciplinary team representing clinicians from various disciplines, academics, administrators and training program directors critically appraised the literature to collate recommendations by multiple jurisdictions, including a quaternary care Canadian hospital, to provide context and rationale for viable options. INTERPRETATION: There are different schools of thought regarding effective practices in obstetric and neonatal services. Our critical review presents the rationale to effectively modify services, based on the phase of the pandemic, the prevalence of infection in the population, and resource availability.

Association between immediate oxygenation response and survival in preterm infants receiving rescue inhaled nitric oxide therapy for hypoxemia from pulmonary hypertension: A systematic review and meta-analysis.

PURPOSE: To investigate whether immediate response to inhaled nitric oxide (iNO) therapy is associated with reduced mortality in preterm infants with hypoxemic respiratory failure (HRF) and pulmonary hypertension (PH). METHODS: A systematic review and meta-analysis of observational studies was conducted to examine the association between immediate response (improved oxygenation ≤6 h) compared to non-response, and all-cause mortality among preterm infants <34 weeks gestational age without congenital anomalies or genetic disorders who received iNO treatment. Adjusted and unadjusted odds ratio, were pooled using a random effects meta-analysis Hartung-Knapp-Sidik-Jonkman approach. Subgroup analyses were planned for infants with preterm premature rupture of membranes (PPROM) and those treated within 72 h after birth. RESULTS: The primary analysis included 5 eligible studies, a total of 400 infants (196 responders; 204 non-responders). The studies were rated as low to moderate risk of bias based on the Quality in Prognostic Studies tool. Immediate iNO responsiveness was associated with reduced odds of mortality [odds ratio (OR) 0.22, 95 % confidence interval (95 % CI) (0.10-0.49)]. Although there was insufficient data for a subgroup analysis of infants with PPROM, infants treated with iNO within 72 h demonstrated consistent findings of reduced mortality [OR 0.21 95 % CI (0.13-0.36)]. Based on the GRADE approach, considering the risk of bias of included studies, the overall strength of evidence was rated as moderate. CONCLUSION: There is evidence to suggest that immediate improvement in oxygenation following iNO therapy is associated with reduced odds of mortality before discharge in preterm infants with HRF and clinically suspected or confirmed PH.

Impact of surgeon and hospital factors on length of stay after colorectal surgery systematic review.

BACKGROUND: Although length of stay (LOS) after colorectal surgery (CRS) is associated with worse patient and system level outcomes, the impact of surgeon and hospital-level factors on LOS after CRS has not been well investigated. The aim of this study was to synthesize the evidence for the impact of surgeon and hospital-level factors on LOS after CRS. METHODS: A comprehensive database search was conducted using terms related to LOS and CRS. Studies were included if they reported the effect of surgeon or hospital factors on LOS after elective CRS. The evidence for the effect of each surgeon and hospital factor on LOS was synthesized using vote counting by direction of effect, taking risk of bias into consideration. RESULTS: A total of 13 946 unique titles and abstracts were screened, and 69 studies met the inclusion criteria. All studies were retrospective and assessed a total of eight factors. Surgeon factors such as increasing surgeon volume, colorectal surgical specialty, and progression along a learning curve were significantly associated with decreased LOS (effect seen in 87.5 per cent, 100 per cent, and 93.3 per cent of studies respectively). In contrast, hospital factors such as hospital volume and teaching hospital status were not significantly associated with LOS. CONCLUSION: Provider-related factors were found to be significantly associated with LOS after elective CRS. In particular, surgeon-related factors related to experience specifically impacted LOS, whereas hospital-related factors did not. Understanding the mechanisms underlying these relationships may allow for tailoring of interventions to reduce LOS.

Characterizing the inclusion of pregnant and breastfeeding people in infectious diseases randomized controlled trials: a targeted literature review.

OBJECTIVES: Severe complications of infectious diseases can occur during pregnancy. Evidence-based prevention and treatment strategies are critical to improve maternal and neonatal health outcomes. Despite this medical need, pregnant and breastfeeding people have been systematically excluded from biomedical research. The objective of this study was to characterize representation of pregnant and breastfeeding people in randomized controlled trials (RCTs) evaluating a broad range of interventions for infectious diseases. METHODS: Pregnancy and breastfeeding inclusion criteria were examined in infectious diseases RCTs published between 1 January 2017, and 31 December 2019, in the top five highest impact general medicine and the top three highest impact infectious diseases and HIV journals. RESULTS: Of 376 RCTs, 5.3% and 1.9% included pregnant and breastfeeding people, respectively. Justification for exclusion was documented in 36/271 (13.3%) studies that explicitly excluded pregnant people. Most studies excluding pregnant people (177/271, 65.3%) required at least one form of contraception, abstinence and/or negative pregnancy test(s) as part of participation. Only 11/271 (4.1%) studies excluding pregnant people allowed participants to continue the intervention if unintended pregnancy occurred during the study. When both pregnant and non-pregnant people were eligible, pregnant people made up <3% of participants. Only 2/48 (4.2%) vaccine studies included pregnant people; 13/234 (5.5%) drug studies included pregnant people. All studies of procedures, devices, behaviour/education and supplements/vitamins explicitly excluded or did not address pregnancy eligibility criteria. Only 2/20 (10.0%) RCTs including pregnant people collected pharmacokinetic data. DISCUSSION: This study demonstrates widespread exclusion of pregnant and breastfeeding people from infectious disease RCTs.

Inclusion of pregnant and breastfeeding women in nonobstetrical randomized controlled trials.

BACKGROUND: There is an urgent need to prioritize and expedite the inclusion of pregnant and breastfeeding women in research. Characterizing trials that have successfully included these populations could inform the design and execution of future studies. In addition, up-to-date data on their inclusion in clinical research could assist in setting benchmarks, establishing targets, and monitoring progress toward more equitable inclusion. OBJECTIVE: This study aimed to characterize the eligibility and enrollment of pregnant and breastfeeding women in randomized controlled trials evaluating interventions for nonobstetrical conditions experienced by, but not limited to, these populations. STUDY DESIGN: We developed a literature search in collaboration with an information specialist. We included randomized controlled trials published between 2017 and 2019 in the 5 highest-impact general medicine journals and the 3 highest-impact specialty journals in cardiovascular disease, critical care, general infectious diseases, HIV, and psychiatry. We included randomized controlled trials that evaluated screening, diagnosis, prevention, or treatment of nonobstetrical medical conditions. We excluded randomized controlled trials exclusively focused on males, pediatrics, geriatrics, oncology, or postmenopausal women, and publications reporting subgroup, pooled, or follow-up analyses of previously published randomized controlled trials. We screened titles and abstracts independently and in duplicate, with discrepancies resolved by a third reviewer. We entered data into a standardized electronic case report form. We reviewed study protocols, appendices, and trial registries for additional data. RESULTS: Of the 1333 randomized controlled trials, pregnant and breastfeeding women were eligible for 13 (1.0%) and 6 (0.5%), respectively. Pregnancy and breastfeeding eligibility criteria were not addressed in 383 of 1333 (28.7%) and 710 of 1333 (53.3%) randomized controlled trials, respectively. In total, 102 of 937 (10.9%) and 33 of 617 (5.3%) randomized controlled trials that explicitly excluded pregnant and breastfeeding women documented the rationale. Most studies excluding pregnant women (542/937; 57.8%) required at least 1 method of contraception and/or pregnancy testing as part of trial participation for women with reproductive capacity. Among the 13 randomized controlled trials that allowed inclusion of pregnant women, 3 restricted eligibility to specific trimesters. Two randomized controlled trials enrolled pregnant women after the first year of the study following interim review of safety results in nonpregnant participants. Four randomized controlled trials reported the number of pregnant women enrolled, which ranged from 0.7% to 3.4% of the study population. None of the studies reported on pregnancy or perinatal outcomes. Compared with randomized controlled trials that excluded pregnant women, those including them more commonly had an infectious disease focus (12/13 [92.3%] vs 270/937 [28.8%]; p<.0001), including HIV (5/13 [38.5%] vs 96/937 [10.2%]; p=.0079), enrolled participants in sub-Saharan Africa (5/13 [38.5%] vs 111/937 [11.8%]; p=.0143), and had exclusively nonindustry sponsorship (13/13 [100%] vs 559/937 [59.7%]; p=.0025); inclusion varied by study phase, randomization level, and intervention type. CONCLUSION: This study illustrates a major inequity in research involving pregnant and breastfeeding women. As new health challenges arise, including novel pandemics, and the research community mobilizes to develop therapies and innovate in patient care, it is crucial that pregnant and breastfeeding women not be left behind. Greater regulatory support, in the form of explicit requirements and incentives, will be needed to ensure these populations are integrated into the research agenda.

SARS-CoV-2 genome and antibodies in breastmilk: a systematic review and meta-analysis.

OBJECTIVE: To systematically review and meta-analyse the rate of SARS-CoV-2 genome identification and the presence of SARS-CoV-2 antibodies in breastmilk of mothers with COVID-19. DESIGN: A systematic review of studies published between January 2019 and October 2020 without study design or language restrictions. SETTING: Data sourced from Ovid Embase Classic+Embase, PubMed, Web of Science, Scopus, relevant bibliographies and the John Hopkins University COVID-19 database. PATIENTS: Mothers with confirmed COVID-19 and breastmilk tested for SARS-CoV-2 by RT-PCR or for anti-SARS-CoV-2 antibodies. MAIN OUTCOME MEASURES: Presence of SARS-CoV-2 genome and antibodies in breastmilk. RESULTS: We included 50 articles. Twelve out of 183 women from 48 studies were positive for SARS-CoV-2 genome in their breastmilk (pooled proportion 5% (95% CI 2% to 15%; I2=48%)). Six infants (50%) of these 12 mothers tested positive for SARS-CoV-2, with one requiring respiratory support. Sixty-one out of 89 women from 10 studies had anti-SARS-CoV-2 antibody in their breastmilk (pooled proportion 83% (95% CI 32% to 98%; I2=88%)). The predominant antibody detected was IgA. CONCLUSIONS: SARS-CoV-2 genome presence in breastmilk is uncommon and is associated with mild symptoms in infants. Anti-SARS-CoV-2 antibodies may be a more common finding. Considering the low proportion of SARS-CoV-2 genome detected in breastmilk and its lower virulence, mothers with COVID-19 should be supported to breastfeed.

The role of ultrasound in front-of-neck access for cricothyroid membrane identification: A systematic review.

PURPOSE: Conventional palpation techniques for cricothyroid membrane (CTM) identification are inaccurate and unreliable. Ultrasound plays a multi-faceted role in airway management, however there is limited literature around its use for CTM identification prior to cricothyrotomies. This review sought to compare ultrasound to palpation in the general population, identify its indications in subjects with ill-defined neck anatomy, and determine its role in defining neck anatomy. METHODS: Two reviewers independently assessed titles, abstracts and full-text English articles through the Ovid Medline and EMBASE databases. Studies related to ultrasound for CTM assessment and/or cricothyrotomy in subjects older than 12 years were included. RESULTS: Fourteen studies were selected. Compared to palpation, ultrasound has greater accuracy, but longer CTM identification times in those with normal airway anatomy. Interestingly, ultrasound offers comparable times to palpation in patients with difficult airways. Ultrasound also helps define anatomical parameters in the neutral and extended neck positions thereby underscoring the importance of neck positioning during cricothyrotomies and confirming consensus-based incision recommendations set by the Difficult Airway Society. CONCLUSION: Ultrasound appears to be superior to palpation for CTM localization especially in those with difficult airway anatomy and objectively defines neck anatomy. Its pre-emptive use should be incorporated during difficult airway management.