National, regional, and global estimates of low birthweight in 2020, with trends from 2000: a systematic analysis.

BACKGROUND: Low birthweight (LBW; <2500 g) is an important predictor of health outcomes throughout the life course. We aimed to update country, regional, and global estimates of LBW prevalence for 2020, with trends from 2000, to assess progress towards global targets to reduce LBW by 30% by 2030. METHODS: For this systematic analysis, we searched population-based, nationally representative data on LBW from Jan 1, 2000, to Dec 31, 2020. Using 2042 administrative and survey datapoints from 158 countries and areas, we developed a Bayesian hierarchical regression model incorporating country-specific intercepts, time-varying covariates, non-linear time trends, and bias adjustments based on data quality. We also provided novel estimates by birthweight subgroups. FINDINGS: An estimated 19·8 million (95% credible interval 18·4-21·7 million) or 14·7% (13·7-16·1) of liveborn newborns were LBW worldwide in 2020, compared with 22·1 million (20·7-23·9 million) and 16·6% (15·5-17·9) in 2000-an absolute reduction of 1·9 percentage points between 2000 and 2020. Using 2012 as the baseline, as this is when the Global Nutrition Target began, the estimated average annual rate of reduction from 2012 to 2020 was 0·3% worldwide, 0·85% in southern Asia, and 0·59% in sub-Saharan Africa. Nearly three-quarters of LBW births in 2020 occurred in these two regions: of 19 833 900 estimated LBW births worldwide, 8 817 000 (44·5%) were in southern Asia and 5 381 300 (27·1%) were in sub-Saharan Africa. Of 945 300 estimated LBW births in northern America, Australia and New Zealand, central Asia, and Europe, approximately 35·0% (323 700) weighed less than 2000 g: 5·8% (95% CI 5·2-6·4; 54 800 [95% CI 49 400-60 800]) weighed less than 1000 g, 9·0% (8·7-9·4; 85 400 [82 000-88 900]) weighed between 1000 g and 1499 g, and 19·4% (19·0-19·8; 183 500 [180 000-187 000]) weighed between 1500 g and 1999 g. INTERPRETATION: Insufficient progress has occurred over the past two decades to meet the Global Nutrition Target of a 30% reduction in LBW between 2012 and 2030. Accelerating progress requires investments throughout the lifecycle focused on primary prevention, especially for adolescent girls and women living in the most affected countries. With increasing numbers of births in facilities and advancing electronic information systems, improvements in the quality and availability of administrative LBW data are also achievable. FUNDING: The Children's Investment Fund Foundation; the UNDP-UNFPA-UNICEF-WHO World Bank Special Programme of Research, Development and Research Training in Human Reproduction; and the Bill & Melinda Gates Foundation.

National, regional, and global estimates of preterm birth in 2020, with trends from 2010: a systematic analysis.

BACKGROUND: Preterm birth is the leading cause of neonatal mortality and is associated with long-term physical, neurodevelopmental, and socioeconomic effects. This study updated national preterm birth rates and trends, plus novel estimates by gestational age subgroups, to inform progress towards global health goals and targets, and aimed to update country, regional, and global estimates of preterm birth for 2020 in addition to trends between 2010 and 2020. METHODS: We systematically searched population-based, nationally representative data on preterm birth from Jan 1, 2010, to Dec 31, 2020 and study data (26 March-14 April, 2021) for countries and areas with no national-level data. The analysis included 679 data points (86% nationally representative administrative data [582 of 679 data points]) from 103 countries and areas (62% of countries and areas having nationally representative administrative data [64 of 103 data points]). A Bayesian hierarchical regression was used for estimating country-level preterm rates, which incoporated country-specific intercepts, low birthweight as a covariate, non-linear time trends, and bias adjustments based on a data quality categorisation, and other indicators such as method of gestational age estimation. FINDINGS: An estimated 13·4 million (95% credible interval [CrI] 12·3-15·2 million) newborn babies were born preterm (<37 weeks) in 2020 (9·9% of all births [95% CrI 9·1-11·2]) compared with 13·8 million (12·7-15·5 million) in 2010 (9·8% of all births [9·0-11·0]) worldwide. The global annual rate of reduction was estimated at -0·14% from 2010 to 2020. In total, 55·6% of total livebirths are in southern Asia (26·8% [36 099 000 of 134 767 000]) and sub-Saharan Africa (28·7% [38 819 300 of 134 767 000]), yet these two regions accounted for approximately 65% (8 692 000 of 13 376 200) of all preterm births globally in 2020. Of the 33 countries and areas in the highest data quality category, none were in southern Asia or sub-Saharan Africa compared with 94% (30 of 32 countries) in high-income countries and areas. Worldwide from 2010 to 2020, approximately 15% of all preterm births occurred at less than 32 weeks of gestation, requiring more neonatal care (<28 weeks: 4·2%, 95% CI 3·1-5·0, 567 800 [410 200-663 200 newborn babies]); 28-32 weeks: 10·4% [9·5-10·6], 1 392 500 [1 274 800-1 422 600 newborn babies]). INTERPRETATION: There has been no measurable change in preterm birth rates over the last decade at global level. Despite increasing facility birth rates and substantial focus on routine health data systems, there remain many missed opportunities to improve preterm birth data. Gaps in national routine data for preterm birth are most marked in regions of southern Asia and sub-Saharan Africa, which also have the highest estimated burden of preterm births. Countries need to prioritise programmatic investments to prevent preterm birth and to ensure evidence-based quality care when preterm birth occurs. Investments in improving data quality are crucial so that preterm birth data can be improved and used for action and accountability processes. FUNDING: The Children's Investment Fund Foundation and the UNDP, United Nations Population Fund-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction.

Small babies, big risks: global estimates of prevalence and mortality for vulnerable newborns to accelerate change and improve counting.

Small newborns are vulnerable to mortality and lifelong loss of human capital. Measures of vulnerability previously focused on liveborn low-birthweight (LBW) babies, yet LBW reduction targets are off-track. There are two pathways to LBW, preterm birth and fetal growth restriction (FGR), with the FGR pathway resulting in the baby being small for gestational age (SGA). Data on LBW babies are available from 158 (81%) of 194 WHO member states and the occupied Palestinian territory, including east Jerusalem, with 113 (58%) having national administrative data, whereas data on preterm births are available from 103 (53%) of 195 countries and areas, with only 64 (33%) providing national administrative data. National administrative data on SGA are available for only eight countries. Global estimates for 2020 suggest 13·4 million livebirths were preterm, with rates over the past decade remaining static, and 23·4 million were SGA. In this Series paper, we estimated prevalence in 2020 for three mutually exclusive types of small vulnerable newborns (SVNs; preterm non-SGA, term SGA, and preterm SGA) using individual-level data (2010-20) from 23 national datasets (∼110 million livebirths) and 31 studies in 18 countries (∼0·4 million livebirths). We found 11·9 million (50% credible interval [Crl] 9·1-12·2 million; 8·8%, 50% Crl 6·8-9·0%) of global livebirths were preterm non-SGA, 21·9 million (50% Crl 20·1-25·5 million; 16·3%, 14·9-18·9%) were term SGA, and 1·5 million (50% Crl 1·2-4·2 million; 1·1%, 50% Crl 0·9-3·1%) were preterm SGA. Over half (55·3%) of the 2·4 million neonatal deaths worldwide in 2020 were attributed to one of the SVN types, of which 73·4% were preterm and the remainder were term SGA. Analyses from 12 of the 23 countries with national data (0·6 million stillbirths at ≥22 weeks gestation) showed around 74% of stillbirths were preterm, including 16·0% preterm SGA and approximately one-fifth of term stillbirths were SGA. There are an estimated 1·9 million stillbirths per year associated with similar vulnerability pathways; hence integrating stillbirths to burden assessments and relevant indicators is crucial. Data can be improved by counting, weighing, and assessing the gestational age of every newborn, whether liveborn or stillborn, and classifying small newborns by the three vulnerability types. The use of these more specific types could accelerate prevention and help target care for the most vulnerable babies.

Stillbirth risk by fetal size among 126.5 million births in 15 countries from 2000 to 2020: A fetuses-at-risk approach.

OBJECTIVE: To compare stillbirth rates and risks for small for gestational age (SGA), large for gestational age (LGA) and appropriate for gestational age (AGA) pregnancies at 24-44 completed weeks of gestation using a birth-based and fetuses-at-risk approachs. DESIGN: Population-based, multi-country study. SETTING: National data systems in 15 high- and middle-income countries. POPULATION: Live births and stillbirths. METHODS: A total of 151 country-years of data, including 126 543 070 births across 15 countries from 2000 to 2020, were compiled. Births were categorised into SGA, AGA and LGA using INTERGROWTH-21st standards. Gestation-specific stillbirth rates, with total births as the denominator, and gestation-specific stillbirth risks, with fetuses still in utero as the denominator, were calculated from 24 to 44 weeks of gestation. MAIN OUTCOME MEASURES: Gestation-specific stillbirth rates and risks according to size at birth. RESULTS: The overall stillbirth rate was 4.22 per 1000 total births (95% CI 4.22-4.23) across all gestations. Applying the birth-based approach, the stillbirth rates were highest at 24 weeks of gestation, with 621.6 per 1000 total births (95% CI 620.9-622.2) for SGA pregnancies, 298.4 per 1000 total births (95% CI 298.1-298.7) for AGA pregnancies and 338.5 per 1000 total births (95% CI 337.9-339.0) for LGA pregnancies. Applying the fetuses-at-risk approach, the gestation-specific stillbirth risk was highest for SGA pregnancies (1.3-1.4 per 1000 fetuses at risk) prior to 29 weeks of gestation. The risk remained stable between 30 and 34 weeks of gestation, and then increased gradually from 35 weeks of gestation to the highest rate of 8.4 per 1000 fetuses at risk (95% CI 8.3-8.4) at ≥42 weeks of gestation. The stillbirth risk ratio (RR) was consistently high for SGA compared with AGA pregnancies, with the highest RR observed at ≥42 weeks of gestation (RR 9.2, 95% CI 15.2-13.2), and with the lowest RR observed at 24 weeks of gestation (RR 3.1, 95% CI 1.9-4.3). The stillbirth RR was also consistently high for SGA compared with AGA pregnancies across all countries, with national variability ranging from RR 0.70 (95% CI 0.43-0.97) in Mexico to RR 8.6 (95% CI 8.1-9.1) in Uruguay. No increased risk for LGA pregnancies was observed. CONCLUSIONS: Small for gestational age (SGA) was strongly associated with stillbirth risk in this study based on high-quality data from high- and middle-income countries. The highest RRs were seen in preterm gestations, with two-thirds of the stillbirths born as preterm births. To advance our understanding of stillbirth, further analyses should be conducted using high-quality data sets from low-income settings, particularly those with relatively high rates of SGA.

National routine data for low birthweight and preterm births: Systematic data quality assessment for United Nations member states (2000-2020).

OBJECTIVE: Low birthweight (<2500 g) and preterm birth (<37 weeks) are markers of newborn vulnerability. To facilitate informed decisions about investments in prevention and care, it is imperative to enhance data quality and use. Hence, the objective of this study is to systematically assess the quality of data concerning low birthweight and preterm births within routine administrative data sources. DESIGN: Systematic data quality assessment by adopting the WHO Data Quality Framework. SETTING: National routine data system from UN member states. POPULATION: Livebirths. METHODS: National routine administrative data on low birthweight and preterm births for 195 countries from 2000 to 2020 were systematically collated, totalling >700 million live births. The WHO data quality framework was adapted to undertake standardised data quality assessments. MAIN OUTCOME MEASURES: Availability, reporting quality, internal and external consistency of low birthweight and preterm data. RESULTS: Most United States Member States (64%: 124/195) had national data on low birthweight and (40%: 82/195) had data on preterm birth. Routine data system reporting was highest in North America, Australasia and Europe, where more than 95% live births had data on low birthweight and over 75% had data preterm births. In contrast, data reporting was lowest in sub-Saharan Africa (13% for low birthweight, 8% for preterm births) and Southern Asia (16% for low birthweight, 5% for preterm births). Most countries collect individual-level data; but, aggregate data reporting from hospital-based systems remain common in sub-Saharan Africa and Southern Asia. While data quality was generally high in North America, Australasia and Europe, gaps remain in the availability of gestational age metadata. Consistency between low birthweight and preterm rates were poor in Southern Asia and sub-Saharan Africa regions across time. There was high external consistency between low birthweight rates obtained from routine administrative data compared with low birthweight rates obtained from survey data for countries with high data quality. CONCLUSIONS: Sub-Saharan Africa and South Asia countries have data gaps but also opportunities for rapid progress. Most births occure in facilities, electronic health information systems already include low birthweight, and adding accurate gestational age including with ultrasound assessment is becoming increasingly attainable. Moving toward the collection of individual level data would enable monitoring of quality of care and longer-term outcomes. This is crucial for every child and family and essential for measuring progress towards relevant sustainable development goals. The assessment will inform countries' actions for data quality improvement at national level and use of data for impact.

Stillbirths: Contribution of preterm birth and size-for-gestational age for 125.4 million total births from nationwide records in 13 countries, 2000-2020.

OBJECTIVE: To examine the contribution of preterm birth and size-for-gestational age in stillbirths using six 'newborn types'. DESIGN: Population-based multi-country analyses. SETTING: Births collected through routine data systems in 13 countries. SAMPLE: 125 419 255 total births from 22+0 to 44+6 weeks' gestation identified from 2000 to 2020. METHODS: We included 635 107 stillbirths from 22+0 weeks' gestation from 13 countries. We classified all births, including stillbirths, into six 'newborn types' based on gestational age information (preterm, PT, <37+0 weeks versus term, T, ≥37+0 weeks) and size-for-gestational age defined as small (SGA, <10th centile), appropriate (AGA, 10th-90th centiles) or large (LGA, >90th centile) for gestational age, according to the international newborn size for gestational age and sex INTERGROWTH-21st standards. MAIN OUTCOME MEASURES: Distribution of stillbirths, stillbirth rates and rate ratios according to six newborn types. RESULTS: 635 107 (0.5%) of the 125 419 255 total births resulted in stillbirth after 22+0 weeks. Most stillbirths (74.3%) were preterm. Around 21.2% were SGA types (PT + SGA [16.2%], PT + AGA [48.3%], T + SGA [5.0%]) and 14.1% were LGA types (PT + LGA [9.9%], T + LGA [4.2%]). The median rate ratio (RR) for stillbirth was highest in PT + SGA babies (RR 81.1, interquartile range [IQR], 68.8-118.8) followed by PT + AGA (RR 25.0, IQR, 20.0-34.3), PT + LGA (RR 25.9, IQR, 13.8-28.7) and T + SGA (RR 5.6, IQR, 5.1-6.0) compared with T + AGA. Stillbirth rate ratios were similar for T + LGA versus T + AGA (RR 0.7, IQR, 0.7-1.1). At the population level, 25% of stillbirths were attributable to small-for-gestational-age. CONCLUSIONS: In these high-quality data from high/middle income countries, almost three-quarters of stillbirths were born preterm and a fifth small-for-gestational age, with the highest stillbirth rates associated with the coexistence of preterm and SGA. Further analyses are needed to better understand patterns of gestation-specific risk in these populations, as well as patterns in lower-income contexts, especially those with higher rates of intrapartum stillbirth and SGA.

Neonatal mortality risk of large-for-gestational-age and macrosomic live births in 15 countries, including 115.6 million nationwide linked records, 2000-2020.

OBJECTIVE: We aimed to compare the prevalence and neonatal mortality associated with large for gestational age (LGA) and macrosomia among 115.6 million live births in 15 countries, between 2000 and 2020. DESIGN: Population-based, multi-country study. SETTING: National healthcare systems. POPULATION: Liveborn infants. METHODS: We used individual-level data identified for the Vulnerable Newborn Measurement Collaboration. We calculated the prevalence and relative risk (RR) of neonatal mortality among live births born at term + LGA (>90th centile, and also >95th and >97th centiles when the data were available) versus term + appropriate for gestational age (AGA, 10th-90th centiles) and macrosomic (≥4000, ≥4500 and ≥5000 g, regardless of gestational age) versus 2500-3999 g. INTERGROWTH 21st served as the reference population. MAIN OUTCOME MEASURES: Prevalence and neonatal mortality risks. RESULTS: Large for gestational age was common (median prevalence 18.2%; interquartile range, IQR, 13.5%-22.0%), and overall was associated with a lower neonatal mortality risk compared with AGA (RR 0.83, 95% CI 0.77-0.89). Around one in ten babies were ≥4000 g (median prevalence 9.6% (IQR 6.4%-13.3%), with 1.2% (IQR 0.7%-2.0%) ≥4500 g and with 0.2% (IQR 0.1%-0.2%) ≥5000 g). Overall, macrosomia of ≥4000 g was not associated with increased neonatal mortality risk (RR 0.80, 95% CI 0.69-0.94); however, a higher risk was observed for birthweights of ≥4500 g (RR 1.52, 95% CI 1.10-2.11) and ≥5000 g (RR 4.54, 95% CI 2.58-7.99), compared with birthweights of 2500-3999 g, with the highest risk observed in the first 7 days of life. CONCLUSIONS: In this population, birthweight of ≥4500 g was the most useful marker for early mortality risk in big babies and could be used to guide clinical management decisions.

Neonatal mortality risk for vulnerable newborn types in 15 countries using 125.5 million nationwide birth outcome records, 2000-2020.

OBJECTIVE: To compare neonatal mortality associated with six novel vulnerable newborn types in 125.5 million live births across 15 countries, 2000-2020. DESIGN: Population-based, multi-country study. SETTING: National data systems in 15 middle- and high-income countries. METHODS: We used individual-level data sets identified for the Vulnerable Newborn Measurement Collaboration. We examined the contribution to neonatal mortality of six newborn types combining gestational age (preterm [PT] versus term [T]) and size-for-gestational age (small [SGA], <10th centile, appropriate [AGA], 10th-90th centile or large [LGA], >90th centile) according to INTERGROWTH-21st newborn standards. Newborn babies with PT or SGA were defined as small and T + LGA was considered as large. We calculated risk ratios (RRs) and population attributable risks (PAR%) for the six newborn types. MAIN OUTCOME MEASURES: Mortality of six newborn types. RESULTS: Of 125.5 million live births analysed, risk ratios were highest among PT + SGA (median 67.2, interquartile range [IQR] 45.6-73.9), PT + AGA (median 34.3, IQR 23.9-37.5) and PT + LGA (median 28.3, IQR 18.4-32.3). At the population level, PT + AGA was the greatest contributor to newborn mortality (median PAR% 53.7, IQR 44.5-54.9). Mortality risk was highest among newborns born before 28 weeks (median RR 279.5, IQR 234.2-388.5) compared with babies born between 37 and 42 completed weeks or with a birthweight less than 1000 g (median RR 282.8, IQR 194.7-342.8) compared with those between 2500 g and 4000 g as a reference group. CONCLUSION: Preterm newborn types were the most vulnerable, and associated with the highest mortality, particularly with co-existence of preterm and SGA. As PT + AGA is more prevalent, it is responsible for the greatest burden of neonatal deaths at population level.

Vulnerable newborn types: Analysis of population-based registries for 165 million births in 23 countries, 2000-2021.

OBJECTIVE: To examine the prevalence of novel newborn types among 165 million live births in 23 countries from 2000 to 2021. DESIGN: Population-based, multi-country analysis. SETTING: National data systems in 23 middle- and high-income countries. POPULATION: Liveborn infants. METHODS: Country teams with high-quality data were invited to be part of the Vulnerable Newborn Measurement Collaboration. We classified live births by six newborn types based on gestational age information (preterm <37 weeks versus term ≥37 weeks) and size for gestational age defined as small (SGA, <10th centile), appropriate (10th-90th centiles), or large (LGA, >90th centile) for gestational age, according to INTERGROWTH-21st standards. We considered small newborn types of any combination of preterm or SGA, and term + LGA was considered large. Time trends were analysed using 3-year moving averages for small and large types. MAIN OUTCOME MEASURES: Prevalence of six newborn types. RESULTS: We analysed 165 017 419 live births and the median prevalence of small types was 11.7% - highest in Malaysia (26%) and Qatar (15.7%). Overall, 18.1% of newborns were large (term + LGA) and was highest in Estonia 28.8% and Denmark 25.9%. Time trends of small and large infants were relatively stable in most countries. CONCLUSIONS: The distribution of newborn types varies across the 23 middle- and high-income countries. Small newborn types were highest in west Asian countries and large types were highest in Europe. To better understand the global patterns of these novel newborn types, more information is needed, especially from low- and middle-income countries.

Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial.

Importance: Psilocybin shows promise as a treatment for major depressive disorder (MDD). Objective: To evaluate the magnitude, timing, and durability of antidepressant effects and safety of a single dose of psilocybin in patients with MDD. Design, Setting, and Participants: In this phase 2 trial conducted between December 2019 and June 2022 at 11 research sites in the US, participants were randomized in a 1:1 ratio to receive a single dose of psilocybin vs niacin placebo administered with psychological support. Participants were adults aged 21 to 65 years with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of MDD of at least 60 days' duration and moderate or greater symptom severity. Exclusion criteria included history of psychosis or mania, active substance use disorder, and active suicidal ideation with intent. Participants taking psychotropic agents who otherwise met inclusion/exclusion criteria were eligible following medication taper. Primary and secondary outcomes and adverse events (AEs) were assessed at baseline (conducted within 7 days before dosing) and at 2, 8, 15, 29, and 43 days after dosing. Interventions: Interventions were a 25-mg dose of synthetic psilocybin or a 100-mg dose of niacin in identical-appearing capsules, each administered with psychological support. Main Outcomes and Measures: The primary outcome was change in central rater-assessed Montgomery-Asberg Depression Rating Scale (MADRS) score (range, 0-60; higher scores indicate more severe depression) from baseline to day 43. The key secondary outcome measure was change in MADRS score from baseline to day 8. Other secondary outcomes were change in Sheehan Disability Scale score from baseline to day 43 and MADRS-defined sustained response and remission. Participants, study site personnel, study sponsor, outcome assessors (raters), and statisticians were blinded to treatment assignment. Results: A total of 104 participants (mean [SD] age, 41.1 [11.3] years; 52 [50%] women) were randomized (51 to the psilocybin group and 53 to the niacin group). Psilocybin treatment was associated with significantly reduced MADRS scores compared with niacin from baseline to day 43 (mean difference,-12.3 [95% CI, -17.5 to -7.2]; P <.001) and from baseline to day 8 (mean difference, -12.0 [95% CI, -16.6 to -7.4]; P < .001). Psilocybin treatment was also associated with significantly reduced Sheehan Disability Scale scores compared with niacin (mean difference, -2.31 [95% CI, 3.50-1.11]; P < .001) from baseline to day 43. More participants receiving psilocybin had sustained response (but not remission) than those receiving niacin. There were no serious treatment-emergent AEs; however, psilocybin treatment was associated with a higher rate of overall AEs and a higher rate of severe AEs. Conclusions and Relevance: Psilocybin treatment was associated with a clinically significant sustained reduction in depressive symptoms and functional disability, without serious adverse events. These findings add to increasing evidence that psilocybin-when administered with psychological support-may hold promise as a novel intervention for MDD. Trial Registration: ClinicalTrials.gov Identifier: NCT03866174.

Preliminary evidence that oxytocin does not improve mentalizing in women with schizophrenia.

INTRODUCTION: Mentalizing, the ability to infer other people's intentions and emotions, is commonly impaired in schizophrenia and may represent an endophenotype. The hypothalamic neuropeptide oxytocin has been shown to improve mentalizing in men with schizophrenia, but its effects in women remain unclear. Given sex differences in the clinical manifestations of schizophrenia and oxytocin system function, this is an important gap to address. METHODS: We tested the effects of a single-dose oxytocin challenge (40 IU) on mentalizing task performance among 26 women with schizophrenia and 38 healthy control women using a randomized, placebo-controlled, double-blind, crossover design. We aimed to replicate our prior study of oxytocin effects on mentalizing in men with schizophrenia, using the same oxytocin administration procedures and performance-based assessments. We used mixed-effects models and equivalence testing as well as Bayesian hierarchical models to examine oxytocin effects. RESULTS: In contrast to our previous finding in a male sample, oxytocin did not improve mentalizing in this sample of women with schizophrenia. Exploratory analyses showed that higher anti-dopaminergic medication dosage was associated with a decreased response to oxytocin, consistent with previous findings in men. CONCLUSION: These findings provide preliminary evidence that exogenous oxytocin administration may have sex-specific effects on mentalizing in schizophrenia. Inclusion of women in future clinical studies with larger samples is critical, as oxytocin effects observed in men may not extend to women with the disorder.

Self-managed, computerised word finding therapy as an add-on to usual care for chronic aphasia post-stroke: An economic evaluation.

OBJECTIVE: To examine the cost-effectiveness of self-managed computerised word finding therapy as an add-on to usual care for people with aphasia post-stroke. DESIGN: Cost-effectiveness modelling over a life-time period, taking a UK National Health Service (NHS) and personal social service perspective. SETTING: Based on the Big CACTUS randomised controlled trial, conducted in 21 UK NHS speech and language therapy departments. PARTICIPANTS: Big CACTUS included 278 people with long-standing aphasia post-stroke. INTERVENTIONS: Computerised word finding therapy plus usual care; usual care alone; usual care plus attention control. MAIN MEASURES: Incremental cost-effectiveness ratios (ICER) were calculated, comparing the cost per quality adjusted life year (QALY) gained for each intervention. Credible intervals (CrI) for costs and QALYs, and probabilities of cost-effectiveness, were obtained using probabilistic sensitivity analysis. Subgroup and scenario analyses investigated cost-effectiveness in different subsets of the population, and the sensitivity of results to key model inputs. RESULTS: Adding computerised word finding therapy to usual care had an ICER of £42,686 per QALY gained compared with usual care alone (incremental QALY gain: 0.02 per patient (95% CrI: -0.05 to 0.10); incremental costs: £732.73 per patient (95% CrI: £674.23 to £798.05)). ICERs for subgroups with mild or moderate word finding difficulties were £22,371 and £21,262 per QALY gained respectively. CONCLUSION: Computerised word finding therapy represents a low cost add-on to usual care, but QALY gains and estimates of cost-effectiveness are uncertain. Computerised therapy is more likely to be cost-effective for people with mild or moderate, as opposed to severe, word finding difficulties.

Victory is its own reward: oxytocin increases costly competitive behavior in schizophrenia.

BACKGROUND: Aberrant sensitivity to social reward may be an important contributor to abnormal social behavior that is a core feature of schizophrenia. The neuropeptide oxytocin impacts the salience of social information across species, but its effect on social reward in schizophrenia is unknown. METHODS: We used a competitive economic game and computational modeling to examine behavioral dynamics and oxytocin effects on sensitivity to social reward among 39 men with schizophrenia and 54 matched healthy controls. In a randomized, double-blind study, participants received one dose of oxytocin (40 IU) or placebo and completed a 35-trial Auction Game that quantifies preferences for monetary v. social reward. We analyzed bidding behavior using multilevel linear mixed models and reinforcement learning models. RESULTS: Bidding was motivated by preferences for both monetary and social reward in both groups, but bidding dynamics differed: patients initially overbid less compared to controls, and across trials, controls decreased their bids while patients did not. Oxytocin administration was associated with sustained overbidding across trials, particularly in patients. This drug effect was driven by a stronger preference for winning the auction, regardless of monetary consequences. Learning rate and response variability did not differ between groups or drug condition, suggesting that differences in bidding derive primarily from differences in the subjective value of social rewards. CONCLUSIONS: Our findings suggest that schizophrenia is associated with diminished motivation for social reward that may be increased by oxytocin administration.

Postpartum depression screening in the pediatric emergency department.

PURPOSE: This study aimed to determine the prevalence of and risk factors for postpartum depression (PPD) in mothers of young infants presenting to the pediatric emergency department (PED). METHODS: This was a prospective, observational study to evaluate the prevalence of PPD in a sample of mothers of young infants presenting to the PED of an urban, tertiary care children's hospital. A convenience sample of mothers with infants younger than 4 months who presented to our urban, tertiary care PED was surveyed in English or Spanish using the Edinburgh Postpartum Depression Scale (EPDS). Demographic information was collected. Members of the study team evaluated and counseled those mothers who screened positive on the EPDS (score ≥ 10). During the PED visit, social work consultation and mental health resources were also offered. Resource use and additional mental health needs were assessed, with a follow-up telephone call 4 weeks after the initial ED presentation. Performance characteristics of a brief, 3-question anxiety subset were compared using a positive EPDS as the reference standard. All study participants were given information about community resources for new mothers. Data were analyzed using t test or Χ (with Yates correction as necessary). RESULTS: A convenience sample of 200 mothers was enrolled; 31 (16%) of these mothers had an EPDS score of 10 or greater. Mothers had a mean age of 27 years (range, 15-41); 45% were first-time mothers; 40% got pediatric care in a state-funded clinic; and 10% were Spanish speaking. There were no statistically significant differences in baseline demographic characteristics of mothers with and without PPD. Mothers who were depressed were more likely to report that they either strongly agreed or agreed with the statement "I feel that my child is always fussy" (P = 0.004). The anxiety subscale produced a sensitivity of 0.87 (95% confidence interval [CI], 0.69-0.96), a specificity of 0.70 (95% CI, 0.63-0.77), and a negative predictive value of 0.97 (95% CI, 0.91-0.99). The majority of participants (92%) reached at follow-up reported improvement in their mood. Fifty percent reported discussing their mood with someone else, although only 33% of these women did so with a medical provider. CONCLUSIONS: Postpartum depression affects a significant number of mothers of young infants who present to the PED for medical care. There are no clear demographic identifiers of these at-risk mothers, making universal screening an advisable approach. Capture of at-risk mothers during PED visits may accelerate connection with mental health resources. Anxiety seems to be a significant contributor. Mothers with PPD often characterize their infants to have a "fussy" temperament. The most appropriate referral for these women in this setting merits further investigation.

Psychedelic-assisted psychotherapy: where is the psychotherapy research?

RATIONALE: Psychedelic-assisted psychotherapy (PAP) has emerged as a potential treatment for a variety of mental health conditions, including substance use disorders and depression. Current models of PAP emphasize the importance of psychotherapeutic support before, during, and after ingestion of a psychedelic to maximize safety and clinical benefit. Despite this ubiquitous assumption, there has been surprisingly little empirical investigation of the "psychotherapy" in PAP, leaving critical questions about the necessary and sufficient components of PAP unanswered. OBJECTIVES: As clinical trials for psychedelic compounds continue the transition from safety- and feasibility-testing to evaluating efficacy, the role of the accompanying psychotherapy must be better understood to enhance scientific understanding of the mechanisms underlying therapeutic change, optimize clinical outcomes, and inform cost-effectiveness. RESULTS: The present paper first reviews the current status of psychotherapy in the PAP literature, starting with recent debates regarding "psychotherapy" versus "psychological support" and then overviewing published clinical trial psychotherapy models and putative models informed by theory. We then delineate lessons that PAP researchers can leverage from traditional psychotherapy research regarding standardizing treatments (e.g., publish treatment manuals, establish eligibility criteria for providers), identifying mechanisms of change (e.g., measure established mechanisms in psychotherapy), and optimizing clinical trial designs (e.g., consider dismantling studies, comparative efficacy trials, and cross-lagged panel designs). Throughout this review, the need for increased research into the psychotherapeutic components of treatment in PAP is underscored. CONCLUSIONS: PAP is a distinct, integrative, and transdisciplinary intervention. Future research designs should consider transdisciplinary research methodologies to identify best practices and inform federal guidelines for PAP administration.

Quantifying abnormal emotion processing: A novel computational assessment method and application in schizophrenia.

Abnormal emotion processing is a core feature of schizophrenia spectrum disorders (SSDs) that encompasses multiple operations. While deficits in some areas have been well-characterized, we understand less about abnormalities in the emotion processing that happens through language, which is highly relevant for social life. Here, we introduce a novel method using deep learning to estimate emotion processing rapidly from spoken language, testing this approach in male-identified patients with SSDs (n = 37) and healthy controls (n = 51). Using free responses to evocative stimuli, we derived a measure of appropriateness, or "emotional alignment" (EA). We examined psychometric characteristics of EA and its sensitivity to a single-dose challenge of oxytocin, a neuropeptide shown to enhance the salience of socioemotional information in SSDs. Patients showed impaired EA relative to controls, and impairment correlated with poorer social cognitive skill and more severe motivation and pleasure deficits. Adding EA to a logistic regression model with language-based measures of formal thought disorder (FTD) improved classification of patients versus controls. Lastly, oxytocin administration improved EA but not FTD among patients. While additional validation work is needed, these initial results suggest that an automated assay using spoken language may be a promising approach to assess emotion processing in SSDs.

Content analysis of Reddit posts about coadministration of selective serotonin reuptake inhibitors and psilocybin mushrooms.

RATIONALE: Treatments with the serotonergic psychedelic psilocybin are being investigated for multiple neuropsychiatric disorders. Because many patients with these disorders use selective serotonin reuptake inhibitors (SSRIs), understanding interactions between psilocybin and SSRIs is critical for evaluating the safety, efficacy, and scalability of psilocybin-based treatments. Current knowledge about these interactions is limited, as most clinical psilocybin research has prohibited concomittant SSRI use. OBJECTIVES: We aimed to explore potential interactions between psilocybin and SSRIs by characterizing peoples' real-world experiences using psilocybin mushrooms and SSRIs together. METHODS: We conducted a systematic search of Reddit for posts describing psilocybin mushroom and SSRI coadministration. We identified 443 eligible posts and applied qualitative content analysis to each. RESULTS: 8% of posts reported negative physical or psychological effects resulting from coadministration. These included 13 reports that may reflect serotonin toxicity, and 1 concerning for a psychotic/manic episode. 54% of posts described reduced intensity of the acute psilocybin experience, but 39% reported unchanged intensity with SSRI coadministration. CONCLUSIONS: Psilocybin's interactions with SSRIs are likely complex and may depend on multiple factors. Prospective studies are needed to evaluate whether psilocybin treatments are reliably safe and effective in the setting of SSRI use.

Benign inoperable tracheal stenosis in COVID versus non-COVID patients at the pandemic epicenter: a case series.

Background: The COVID-19 pandemic has exponentially expanded the number of patients requiring treatment for chronic respiratory failure. One consequence is an increase in the number of patients requiring intubation and mechanical ventilation. Benign inoperable tracheal stenosis presents a challenge, especially in COVID-19 patients. Methods: We describe a case series of 15 patients with Benign inoperable tracheal stenosis treated with interventional bronchoscopy over a 15-month period. These patients were divided into two groups, COVID and non-COVID. We used an electrocautery snare as an electrocautery knife to cut the stenotic segment followed by four injections of 1 mg submucosal Decadron via a Wang needle. Patients were subsequently followed by the pulmonary clinic. Institutional review board approval was not required as per our institutional policy for a retrospective case series. Results: There was a high degree of success with this intervention, with a low rate of recurrence. We also noticed the following differences between the two subgroups. COVID tracheal stenosis was longer in length, had a higher percentage of cartilage involvement, and was located more distal to cords than the non-COVID group. The median age was younger in the COVID group. Conclusions: COVID pandemic an enormous number of intubations and tracheotomies have been performed. As a result, there will be an increased prevalence of tracheal stenosis. Most of these cases can be effectively treated with surgery. Dealing with complex inoperable cases remains a dilemma. Our case series/research article is an attempt to provide an easy technique with a high cure rate.

Control of intestinal bacterial proliferation in regulation of lifespan in Caenorhabditis elegans.

BACKGROUND: A powerful approach to understanding complex processes such as aging is to use model organisms amenable to genetic manipulation, and to seek relevant phenotypes to measure. Caenorhabditis elegans is particularly suited to studies of aging, since numerous single-gene mutations have been identified that affect its lifespan; it possesses an innate immune system employing evolutionarily conserved signaling pathways affecting longevity. As worms age, bacteria accumulate in the intestinal tract. However, quantitative relationships between worm genotype, lifespan, and intestinal lumen bacterial load have not been examined. We hypothesized that gut immunity is less efficient in older animals, leading to enhanced bacterial accumulation, reducing longevity. To address this question, we evaluated the ability of worms to control bacterial accumulation as a functional marker of intestinal immunity. RESULTS: We show that as adult worms age, several C. elegans genotypes show diminished capacity to control intestinal bacterial accumulation. We provide evidence that intestinal bacterial load, regulated by gut immunity, is an important causative factor of lifespan determination; the effects are specified by bacterial strain, worm genotype, and biologic age, all acting in concert. CONCLUSIONS: In total, these studies focus attention on the worm intestine as a locus that influences longevity in the presence of an accumulating bacterial population. Further studies defining the interplay between bacterial species and host immunity in C. elegans may provide insights into the general mechanisms of aging and age-related diseases.

Psilocybin for Trauma-Related Disorders.

Posttraumatic stress disorder (PTSD) is a debilitating, chronic disorder and efficacy rates of current PTSD treatments are underwhelming. There is a critical need for innovative approaches. We provide an overview of trauma and PTSD and cite literature providing converging evidence of the therapeutic potential of psilocybin for PTSD. No study to date has investigated psilocybin or psilocybin-assisted psychotherapy (PAP) as treatments for PTSD. An open-label study in traumatized AIDS survivors found that PAP reduced PTSD symptoms, attachment anxiety, and demoralization. Several PAP trials show preliminary efficacy in facilitating confronting traumatic memories, decreasing emotional avoidance, depression, anxiety, pessimism, and disconnection from others, and increasing acceptance, self-compassion, and forgiveness of abusers, all of which are relevant to PTSD recovery. There is also early evidence that other classic psychedelics may produce large reductions in PTSD symptoms in combat veterans. However, this body of literature is small, mechanisms are not yet well understood, and the risks of using psychedelic compounds for trauma-related disorders need further study. In sum, evidence supports further investigation of PAP as a radically new approach for treating PTSD.