Tissue perfusion in DIEP flaps using Indocyanine Green Fluorescence Angiography, Hyperspectral imaging, and Thermal imaging.

Flap necrosis continues to occur in skin free flap autologous breast reconstruction. Therefore, we investigated the benefits of indocyanine green angiography (ICGA) using quantitative parameters for the objective, perioperative evaluation of flap perfusion. In addition, we investigated the feasibility of hyperspectral (HSI) and thermal imaging (TI) for postoperative flap monitoring. A single-center, prospective observational study was performed on 15 patients who underwent deep inferior epigastric perforator (DIEP) flap breast reconstruction (n=21). DIEP-flap perfusion was evaluated using ICGA, HSI, and TI using a standardized imaging protocol. The ICGA perfusion curves and derived parameters, HSI extracted oxyhemoglobin (oxyHb) and deoxyhemoglobin (deoxyHb) values, and flap temperatures from TI were analyzed and correlated to the clinical outcomes. Post-hoc quantitative analysis of intraoperatively collected data of ICGA application accurately distinguished between adequately and insufficiently perfused DIEP flaps. ICG perfusion curves identified the lack of arterial inflow (n=2) and occlusion of the venous outflow (n=1). In addition, a postoperatively detected partial flap epidermolysis could have been predicted based on intraoperative quantitative ICGA data. During postoperative monitoring, HSI was used to identify impaired perfusion areas within the DIEP flap based on deoxyHb levels. The results of this study showed a limited added value of TI. Quantitative, post-hoc analysis of ICGA data produced objective and reproducible parameters that enabled the intraoperative detection of arterial and venous congested DIEP flaps. HSI appeared to be a promising technique for postoperative flap perfusion assessment. A diagnostic accuracy study is needed to investigate ICGA and HSI parameters in real-time and demonstrate their clinical benefit.

Changes in the prevalence of mental health problems during the first year of the pandemic: a systematic review and dose-response meta-analysis.

AIM: To describe the pattern of the prevalence of mental health problems during the first year of the COVID-19 pandemic and examine the impact of containment measures on these trends. METHODS: We identified articles published until 30 August 2021 that reported the prevalence of mental health problems in the general population at two or more time points. A crowd of 114 reviewers extracted data on prevalence, study and participant characteristics. We collected information on the number of days since the first SARS-CoV-2 infection in the study country, the stringency of containment measures and the number of cases and deaths. We synthesised changes in prevalence during the pandemic using a random-effects model. We used dose-response meta-analysis to evaluate the trajectory of the changes in mental health problems. RESULTS: We included 41 studies for 7 mental health conditions. The average odds of symptoms increased during the pandemic (mean OR ranging from 1.23 to 2.08). Heterogeneity was very large and could not be explained by differences in participants or study characteristics. Average odds of psychological distress, depression and anxiety increased during the first 2 months of the pandemic, with increased stringency of the measures, reported infections and deaths. The confidence in the evidence was low to very low. CONCLUSIONS: We observed an initial increase in the average risk of psychological distress, depression-related and anxiety-related problems during the first 2 months of the pandemic. However, large heterogeneity suggests that different populations had different responses to the challenges imposed by the pandemic.

Brain region-specific alterations in gene expression trajectories in the offspring born from influenza A virus infected mice.

Influenza A virus (IAV) infection during pregnancy can increase the risk for neurodevelopmental disorders in the offspring, however, the underlying neurobiological mechanisms are largely unknown. To recapitulate viral infection, preclinical studies have traditionally focused on using synthetic viral mimetics, rather than live IAV, to examine consequences of maternal immune activation (MIA)-dependent processes on offspring. In contrast, few studies have used live IAV to assess effects on global gene expression, and none to date have addressed whether moderate IAV, mimicking seasonal influenza disease, alters normal gene expression trajectories in different brain regions across different stages of development. Herein, we show that moderate IAV infection during pregnancy, which causes mild maternal disease and no overt foetal complications in utero, induces lasting effects on the offspring into adulthood. We observed behavioural changes in adult offspring, including disrupted prepulse inhibition, dopaminergic hyper-responsiveness, and spatial recognition memory deficits. Gene profiling in the offspring brain from neonate to adolescence revealed persistent alterations to normal gene expression trajectories in the prefronal cortex, hippocampus, hypothalamus and cerebellum. Alterations were found in genes involved in inflammation and neurogenesis, which were predominately dysregulated in neonatal and early adolescent offspring. Notably, late adolescent offspring born from IAV infected mice displayed altered microglial morphology in the hippocampus. In conclusion, we show that moderate IAV during pregnancy perturbs neurodevelopmental trajectories in the offspring, including alterations in the neuroinflammatory gene expression profile and microglial number and morphology in the hippocampus, resulting in behavioural changes in adult offspring. Such early perturbations may underlie the vulnerability in human offspring for the later development of neurodevelopmental disorders, including schizophrenia. Our work highlights the importance of using live IAV in developing novel preclinical models that better recapitulate the real-world impact of inflammatory insults during pregnancy on offspring neurodevelopmental trajectories and disease susceptibility later in life.

Tumour microenvironment characterisation to stratify patients for hyperthermic intraperitoneal chemotherapy in high-grade serous ovarian cancer (OVHIPEC-1).

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival in patients with Stage III ovarian cancer following interval cytoreductive surgery (CRS). Optimising patient selection is essential to maximise treatment efficacy and avoid overtreatment. This study aimed to identify biomarkers that predict HIPEC benefit by analysing gene signatures and cellular composition of tumours from participants in the OVHIPEC-1 trial. METHODS: Whole-transcriptome RNA sequencing data were retrieved from high-grade serous ovarian cancer (HGSOC) samples from 147 patients obtained during interval CRS. We performed differential gene expression analysis and applied deconvolution methods to estimate cell-type proportions in bulk mRNA data, validated by histological assessment. We tested the interaction between treatment and potential predictors on progression-free survival using Cox proportional hazards models. RESULTS: While differential gene expression analysis did not yield any predictive biomarkers, the cellular composition, as characterised by deconvolution, indicated that the absence of macrophages and the presence of B cells in the tumour microenvironment are potential predictors of HIPEC benefit. The histological assessment confirmed the predictive value of macrophage absence. CONCLUSION: Immune cell composition, in particular macrophages absence, may predict response to HIPEC in HGSOC and these hypothesis-generating findings warrant further investigation. CLINICAL TRIAL REGISTRATION: NCT00426257.

Individual Patient Data Meta-Analysis Estimates the Minimal Detectable Change of the Geriatric Depression Scale-15.

OBJECTIVE: To use individual participant data meta-analysis (IPDMA) to estimate the minimal detectable change (MDC) of the Geriatric Depression Scale-15 (GDS-15) and to examine whether MDC may differ based on participant characteristics and study-level variables. STUDY DESIGN AND SETTING: This was a secondary analysis of data from an IPDMA on the depression screening accuracy of the GDS. Datasets from studies published in any language were eligible for the present study if they included GDS-15 scores for participants aged 60 or older. MDC of the GDS-15 was estimated via random-effects meta-analysis using 2.77 (MDC95) and 1.41 (MDC67) standard errors of measurement (SEM). Subgroup analyses were used to evaluate differences in MDC by participant age and sex. Meta-regression was conducted to assess for differences based on study-level variables, including mean age, proportion male, proportion with major depression, and recruitment setting. RESULTS: 5,876 participants (mean age 76 years, 40% male, 11% with major depression) from 21 studies were included. The MDC95 was 3.81 points (95% confidence interval [CI] 3.59, 4.04), and MDC67 was 1.95 (95% CI 1.83, 2.03). The difference in MDC95 was 0.26 points (95% CI 0.04, 0.48) between ≥ 80-year-olds and < 80-year-olds; MDC95 was similar for females and males (0.05, 95% CI -0.12, 0.22). The MDC95 increased by 0.29 points (95% CI 0.17, 0.41) per 10% increase in proportion of participants with major depression; mean age had a small association (0.04 points, 95% CI 0.00 to 0.09) with MDC95, but sex and recruitment setting were not significantly associated. CONCLUSIONS: The MDC95 was 3.81 points and MDC67 was 1.95 points. MDC95 increased with the proportion of participants with major depression. Results can be used to evaluate individual changes in depression symptoms and as a threshold for assessing minimal clinical important difference estimates.

Postpartum Depression: A Clinical Review of Impact and Current Treatment Solutions.

Depression during the first year postpartum (postpartum depression) impacts millions of women and their families worldwide. In this narrative review, we provide a summary of postpartum depression, examining the etiology and consequences, pharmacological and psychological treatments, and potential mechanisms of change and current barriers to care. Psychological treatments are effective and preferred by many perinatal patients over medications, but they often remain inaccessible. Key potential mechanisms underlying their effectiveness include treatment variables (e.g., dosage and therapeutic alliance) and patient behaviors (e.g., activation and avoidance and emotional regulation). Among pharmacological treatments, the selective serotonin reuptake inhibitor (SSRI) sertraline is generally the first-line antidepressant medication recommended to women in the postpartum period due to its minimal passage into breastmilk and the corresponding decades of safety data. Importantly, most antidepressant drugs are considered compatible with breastfeeding. Neurosteroids are emerging as an effective treatment for postpartum depression, although currently this treatment is not widely available. Barriers to widespread access to treatment include those that are systematic (e.g., lack of specialist providers), provider-driven (e.g., lack of flexibility in treatment delivery), and patient-driven (e.g., stigma and lack of time for treatment engagement). We propose virtual care, task-sharing to non-specialist treatment providers, and collaborative care models as potential solutions to enhance the reach and scalability of effective treatments to address the growing burden of postpartum depression worldwide and its negative impact on families and society.

Mental health sequelae in survivors of cardiogenic shock complicating myocardial infarction. A population-based cohort study.

PURPOSE: Cardiogenic shock secondary to acute myocardial infarction (AMI-CS) is associated with substantial short- and long-term morbidity and mortality. However, there are limited data on mental health sequelae that survivors experience following discharge. METHODS: We conducted a retrospective, population-based cohort study in Ontario, Canada of critically ill adult (≥ 18 years) survivors of AMI-CS, admitted to hospital between April 1, 2009 and March 31, 2019. We compared these patients to AMI survivors without shock. We captured outcome data using linked health administrative databases. The primary outcome was a new mental health diagnosis (a composite of mood, anxiety, or related disorders; schizophrenia/psychotic disorders; and other mental health disorders) following hospital discharge. We secondarily evaluated incidence of deliberate self-harm and death by suicide. We compared patients using overlap propensity score-weighted, cause-specific proportional hazard models. RESULTS: We included 7812 consecutive survivors of AMI-CS, from 135 centers. Mean age was 68.4 (standard deviation (SD) 12.2) years, and 70.3% were male. Median follow-up time was 767 days (interquartile range (IQR) 225-1682). Incidence of new mental health diagnosis among AMI-CS survivors was 109.6 per 1,000 person-years (95% confidence interval (CI) 105.4-113.9), compared with 103.8 per 1000 person-years (95% CI 102.5-105.2) among AMI survivors without shock. After propensity score adjustment, there was no difference in the risk of new mental health diagnoses following discharge [hazard ratio (HR) 0.99 (95% CI 0.94-1.03)]. Factors associated with new mental health diagnoses following AMI-CS included female sex, pre-existing mental health diagnoses, and discharge to a long-term hospital or rehabilitation institute. CONCLUSION: Survivors of AMI-CS experience substantial mental health morbidity following discharge. Risk of new mental health diagnoses was comparable between survivors of AMI with and without shock. Future research on interventions to mitigate psychiatric sequelae after AMI-CS is warranted.

The Role of Social Support in Perinatal Mental Health and Psychosocial Stimulation.

Social support refers to the help someone receives emotionally or instrumentally from their social network. Poor social support in the perinatal period has been associated with increased risk for symptoms of common mental disorders, including depression and posttraumatic stress symptoms (PTS), which may impact parenting behavior. Whether social support impacts parenting behaviors, independent of mental health symptomatology, remains unclear. Among N=309 participants of the Scaling Up Maternal Mental healthcare by Increasing access to Treatment (SUMMIT Trial), a large perinatal depression and anxiety treatment trial, we explored the relations between perceived social support, perinatal depressive and PTS symptoms, and psychosocial stimulation provided by the parent in their home environment. Social support was measured at baseline using the Multidimensional Scale of Perceived Social Support (MSPSS). Perinatal depressive symptoms were measured by the Edinburgh Postnatal Depression Scale (EPDS) and PTS symptoms were measured by the Abbreviated PTSD Checklist (PCL-6) at baseline, 3-, and 6-months post-randomization. Psychosocial stimulation was assessed by the Home Observation Measurement of the Environment (HOME) when the infant was between 6 to 24 months. Using stepwise hierarchical regressions, we found: (1) perceived social support at baseline significantly predicted both depressive and PTS symptoms at 3-months post-randomization, even when controlling for baseline depressive and PTS symptoms; and (2) while neither depressive nor PTS symptoms were significantly associated with psychosocial stimulation, perceived social support at baseline was a significant predictor. Clinical implications regarding treatment of perinatal patients are discussed.

Mental Illness in the 2 Years Prior to Pregnancy in a Population With Traumatic Brain Injury: A Cross-Sectional Study: La maladie mentale dans les deux ans précédant une grossesse dans une population souffrant de lésion cérébrale traumatique : une étude transversale.

OBJECTIVE: Existing studies, in mostly male samples such as veterans and athletes, show a strong association between traumatic brain injury (TBI) and mental illness. Yet, while an understanding of mental health before pregnancy is critical for informing preconception and perinatal supports, there are no data on the prevalence of active mental illness before pregnancy in females with TBI. We examined the prevalence of active mental illness ≤2 years before pregnancy (1) in a population with TBI, and (2) in subgroups defined by sociodemographic, health, and injury-related characteristics, all compared to those without TBI. METHOD: This population-based cross-sectional study was completed in Ontario, Canada, from 2012 to 2020. Modified Poisson regression generated adjusted prevalence ratios (aPRs) of active mental illness ≤2 years before pregnancy in 15,585 females with TBI versus 846,686 without TBI. We then used latent class analysis to identify subgroups with TBI according to sociodemographic, health, and injury-related characteristics and subsequently compared them to females without TBI on their outcome prevalence. RESULTS: Females with TBI had a higher prevalence of active mental illness ≤2 years before pregnancy than those without TBI (44.1% vs. 25.9%; aPR 1.46, 95% confidence interval, 1.43 to 1.49). There were 3 TBI subgroups, with Class 1 (low-income, past assault, recent TBI described as intentional and due to being struck by/against) having the highest outcome prevalence. CONCLUSIONS: Females with TBI, and especially those with a recent intentional TBI, have a high prevalence of mental illness before pregnancy. They may benefit from mental health screening and support in the post-injury, preconception, and perinatal periods. PLAIN LANGUAGE TITLE: Mental illness in the 2 years before pregnancy in a population with traumatic brain injury. PLAIN LANGUAGE SUMMARY: Research has shown a strong association between traumatic brain injury (TBI) and mental illness. Most previous studies have been conducted in primarily male samples, like veterans and professional athletes. Understanding mental health before pregnancy is important for deciding what supports people need before and during pregnancy. However, there are no studies on the frequency of mental illness in females with TBI before a pregnancy. We examined the frequency of mental illness 2 years before pregnancy in a population with TBI, and in subgroups defined by different social, health, and injury-related characteristics, compared to those without TBI. We undertook a population-wide study of all females with and without TBI in Ontario, Canada, with a birth in 2012-2020. We used statistical models to compare these groups on the presence of mental illness in the 2 years before pregnancy, before and after accounting for social and health characteristics. We also identified subgroups with TBI according to their social (e.g., poverty), health (e.g., chronic conditions), and injury-related characteristics (e.g., cause of injury) and subsequently compared them to females without TBI on their frequency of mental illness in the 2 years before pregnancy. Forty-four percent of females with TBI had mental illness in the 2 years before pregnancy compared to 25% of those without TBI. There were 3 TBI subgroups. Females with low-income, past assault, and injuries that were described as being intentional had the highest frequency of mental illness in the 2 years before pregnancy. Females with TBI may benefit from mental health screening and support post-injury and around the time of pregnancy.

Muddy, muddled, or muffled? Understanding the perception of audio quality in music by hearing aid users.

Introduction: Previous work on audio quality evaluation has demonstrated a developing convergence of the key perceptual attributes underlying judgments of quality, such as timbral, spatial and technical attributes. However, across existing research there remains a limited understanding of the crucial perceptual attributes that inform audio quality evaluation for people with hearing loss, and those who use hearing aids. This is especially the case with music, given the unique problems it presents in contrast to human speech. Method: This paper presents a sensory evaluation study utilising descriptive analysis methods, in which a panel of hearing aid users collaborated, through consensus, to identify the most important perceptual attributes of music audio quality and developed a series of rating scales for future listening tests. Participants (N = 12), with a hearing loss ranging from mild to severe, first completed an online elicitation task, providing single-word terms to describe the audio quality of original and processed music samples; this was completed twice by each participant, once with hearing aids, and once without. Participants were then guided in discussing these raw terms across three focus groups, in which they reduced the term space, identified important perceptual groupings of terms, and developed perceptual attributes from these groups (including rating scales and definitions for each). Results: Findings show that there were seven key perceptual dimensions underlying music audio quality (clarity, harshness, distortion, spaciousness, treble strength, middle strength, and bass strength), alongside a music audio quality attribute and possible alternative frequency balance attributes. Discussion: We outline how these perceptual attributes align with extant literature, how attribute rating instruments might be used in future work, and the importance of better understanding the music listening difficulties of people with varied profiles of hearing loss.

Non-fatal self-harm and suicide following postpartum psychiatric emergency department visits: A population-based retrospective cohort study.

In a population-based cohort of postpartum individuals in Ontario, Canada, this study aimed to determine the risk of non-fatal self-harm and suicide within one year of an initial postpartum psychiatric emergency department (ED) visit (2008-2020), and the key associated factors. Of 16,475 postpartum individuals with psychiatric ED visits, 714 (4.3 %) had non-fatal self-harm within one year, and 23 (0.15 %) died by suicide. Risk was substantially higher for those with self-harm at the initial presentation. Further efforts to connect individuals with postpartum psychiatric ED visits with needed inpatient care and outpatient follow-up are required to reduce non-fatal self-harm and suicide risk.

Nest positioning on motor development, sleep patterns, weight gain in preterm infants: systematic review.

The aim was to evaluate the effects of Nest Positioning (NP) on motor development, sleep patterns, and weight gain in preterm newborns (PTNB) hospitalized in a neonatal intensive care unit (NICU). This study was constructed based on PRISMA guideline criteria. Systematic research was carried out in electronic databases: MEDLINE via PubMed, Web of Science, Scopus, and VHL-BIREME following the PICOS strategy. Studies with PTNB populations who were hospitalized in the NICU and received therapeutic NP as an intervention strategy in this population were included in this study. We sought outcomes related to sleep patterns, weight gain, and motor development. After selection, 12 studies were included in this systematic review, of which 5 (41.7%) evaluated motor development as their primary outcome, 6 (50%) sleep-wake cycle patterns, and 1 (8.3%), weight gain and, subsequently, hospital discharge. Qualitative results indicate that prolonged exposure to decubitus variations may favor PTNB hospitalized in NICUs acquiring flexor postures, stimulate their midline, and increase their total sleep time. Studies reported no adverse effects regarding the use of NP. Evidence suggests that NP benefits motor development and sleep pattern in PTNB hospitalized in NICUs. IMPACT: Nest positioning improves sleep quality in preterm newborns hospitalized in neonatal intensive care unit. Nest positioning improves motor development in preterm newborns hospitalized in neonatal intensive care unit. No evidence of nest positioning on weight gain was observed. Half of the included clinical studies showed good methodological quality. Nesting positioning is a secure and cost-effective method.

Baculovirus entry into the central nervous system of Spodoptera exigua caterpillars is independent of the viral protein tyrosine phosphatase.

Neuroparasitism concerns the hostile take-over of a host's nervous system by a foreign invader, in order to alter the behaviour of the host in favour of the parasite. One of the most remarkable cases of parasite-induced host behavioural manipulation comprises the changes baculoviruses induce in their caterpillar hosts. Baculoviruses may manipulate caterpillar behaviour in two ways: hyperactivity (increased movement in the horizontal plane) and/or tree-top disease (movement to elevated levels in the vertical plane). Those behavioural changes are followed by liquefaction and death of the caterpillar. In Autographa californica multiple nucleopolyhedrovirus (AcMNPV)-infected Spodoptera exigua caterpillars, an enzymatic active form of the virally encoded protein tyrosine phosphatase (PTP) is needed for the expression of hyperactivity from 3 days post infection (dpi). Using eGFP-expressing recombinant AcMNPV strains, we show that infection of the caterpillar's central nervous system (CNS) can be observed primarily from 3 dpi onwards. In addition, we demonstrate that the structural and enzymatic function of PTP does not play a role in infection of the CNS. Instead we show that the virus entered the CNS via the trachea, progressing caudally to frontally through the CNS and that the infection progressed from the outermost cell layers towards the inner cell layers of the CNS, in a PTP independent manner. These findings help to further understand parasitic manipulation and the mechanisms by which neuroparasites infect the host nervous system to manipulate host behaviour.

Lessons learned from postmarketing withdrawals of expedited approvals for oncology drug indications.

In the past decade, there have been a record number of oncology therapy approvals by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Besides the EMA's conditional marketing authorisation programme and the FDA's Accelerated Approval Program, we observe a tendency towards fast approval for exploratory studies with non-randomised, uncontrolled designs and surrogate endpoints. This issue raises concerns about the robustness and effectiveness of accepted treatments, leaving patients and health-care professionals in a state of uncertainty. A substantial number of accelerated approvals have recently been withdrawn in the USA, with some still authorised in Europe, emphasising discrepancies in regulatory standards that affect both patients and society as a whole. We highlight examples of drugs, authorised on the basis of surrogate endpoints, that were later withdrawn due to an absence of overall survival benefit. Our findings address the challenges and consequences of accelerated approval pathways in oncology. In conclusion, this Policy Review calls for regulatory bodies to better align their procedures and insist on robust evidence, preferably through unbiased randomised controlled trials. Drug approval processes should prioritise patient benefit, overall survival, and quality of life to minimise risks and uncertainties for patients.

Maternal Deaths Using Coroner's Data: A Latent Class Analysis.

OBJECTIVE: Knowledge regarding the antecedent clinical and social factors associated with maternal death around the time of pregnancy is limited. This study identified distinct subgroups of maternal deaths using population-based coroner's data, and that may inform ongoing preventative initiatives. METHODS: A detailed review of coroner's death files was performed for all of Ontario, Canada, where there is a single reporting mechanism for maternal deaths. Deaths in pregnancy, or within 365 days thereafter, were identified within the Office of the Chief Coroner for Ontario database, 2004-2020. Variables related to the social and clinical circumstances surrounding the deaths were abstracted in a standardized manner from each death file, including demographics, forensic information, nature and cause of death, and antecedent health and health care factors. These variables were then entered into a latent class analysis (LCA) to identify distinct types of deaths. RESULTS: Among 273 deaths identified in the study period, LCA optimally identified three distinct subgroups, namely, (1) in-hospital deaths arising during birth or soon thereafter (52.7% of the sample); (2) accidents and unforeseen obstetric complications also resulting in infant demise (26.3%); and (3) out-of-hospital suicides occurring postpartum (21.0%). Physical injury (22.0%) was the leading cause of death, followed by hemorrhage (16.8%) and overdose (13.3%). CONCLUSION: Peri-pregnancy maternal deaths can be classified into three distinct sub-types, with somewhat differing causes. These findings may enhance clinical and policy development aimed at reducing pregnancy mortality.

Risk of Repeat Psychiatric Emergency Department Visits in the Postpartum Period: A Population-Based Retrospective Cohort Study.

STUDY OBJECTIVE: Approximately 1 in 100 postpartum individuals visit an emergency department (ED) for a psychiatric reason. Repeat visits can signify problems with the quality of care received during or after the initial visit; this study aimed to understand risk for repeat postpartum psychiatric ED visits. METHODS: This population-based cohort study used Ontario, Canada health administrative data available through ICES (formerly the Institute for Clinical Evaluative Sciences) to identify all individuals discharged from postpartum psychiatric ED visits (2008 to 2021) and measured the proportion with one or more repeat psychiatric ED visit within 30 days. Using modified Poisson regression, we calculated the association between one or more repeat visits and sociodemographic, medical, obstetric, infant, continuity of care, past service use, and index ED visit characteristics both overall and stratified by psychiatric diagnosis. RESULTS: Of 14,100 individuals, 11.7% had one or more repeat psychiatric ED visits within 30 days. Repeat visit risk was highest for those with schizophrenia-spectrum disorders (28.2%, adjusted risk ratio 2.41; 95% confidence interval 1.88 to 3.08, versus 9.5% anxiety referent). Low (versus no) psychiatric care continuity, prior psychiatric ED visits and admissions, and initial visits within 90 days postpartum were also associated with increased risk, whereas intentional self-injury was associated with reduced risk. In diagnosis-stratified analyses, the factors most consistently associated with repeat ED visits were past psychiatric ED visits and admissions, and initial visits within 90 days postpartum. CONCLUSIONS: Over 1 in 10 postpartum psychiatric ED visits are followed by a repeat visit within 30 days. Targeted approaches are needed across clinical populations to reduce repeat ED visits in this population with young infants.

Differences in time to patient access to innovative cancer medicines in six European countries.

Patients across Europe face inequity regarding access to anticancer medicines. While access is typically evaluated through reimbursement status or sales data, patients can receive first access through early access programs (EAPs) or off-label use. This study aims to assess the time to patient access at the hospital level, considering different indications and countries. (Pre-)registered access to six innovative medicines (Olaparib, Niraparib, Ipilimumab, Osimeritinib, Nivolumab and Ibritunib) was measured using a cross-sectional survey. First patient access to medicines and indications were collected using the hospital databases. Nineteen hospitals from Hungary, Italy, the Netherlands, Belgium, Switzerland and France participated. Analysis showed that some hospitals achieved patient access before national reimbursement, primarily through EAPs. The average time from EMA-approval to patient access for these medicines was 2.1 years (Range: -0.9-7.1 years). Hospitals in Italy and France had faster access compared to Hungary and Belgium. Variation was also found within countries, with specialized hospitals (x̄: -0.9 years; SD: 2.0) more likely to provide patient access prior to national reimbursement than general hospitals (x̄: 0.4 years; SD: 2.9). Contextual differences were observed, with EAPs or off-label use being more prevalent in Switzerland than Hungary. Recent EMA-approved indications and drug combinations reached patients at a later stage. Substantial variation in patient access time was observed between and within countries. Improving pricing and reimbursement timelines, fostering collaboration between national health authorities and market authorization holders, and implementing nationally harmonized, data-generating EAPs can enhance timely and equitable patient access to innovative cancer treatments in Europe.

Patterns of multiple chronic conditions in pregnancy: Population-based study using latent class analysis.

BACKGROUND: Adults with multiple chronic conditions (MCC) are a heterogeneous population with elevated risk of future adverse health outcomes. Yet, despite the increasing prevalence of MCC globally, data about MCC in pregnancy are scarce. OBJECTIVES: To estimate the population prevalence of MCC in pregnancy and determine whether certain types of chronic conditions cluster together among pregnant women with MCC. METHODS: We conducted a population-based cohort study in Ontario, Canada, of all 15-55-year-old women with a recognised pregnancy, from 2007 to 2020. MCC was assessed from a list of 22 conditions, identified using validated algorithms. We estimated the prevalence of MCC. Next, we used latent class analysis to identify classes of co-occurring chronic conditions in women with MCC, with model selection based on parsimony, clinical interpretability and statistical fit. RESULTS: Among 2,014,508 pregnancies, 324,735 had MCC (161.2 per 1000, 95% confidence interval [CI] 160.6, 161.8). Latent class analysis resulted in a five-class solution. In four classes, mood and anxiety disorders were prominent and clustered with one additional condition, as follows: Class 1 (22.4% of women with MCC), osteoarthritis; Class 2 (23.7%), obesity; Class 3 (15.8%), substance use disorders; and Class 4 (22.1%), asthma. In Class 5 (16.1%), four physical conditions clustered together: obesity, asthma, chronic hypertension and diabetes mellitus. CONCLUSIONS: MCC is common in pregnancy, with sub-types dominated by co-occurring mental and physical health conditions. These data show the importance of preconception and perinatal interventions, particularly integrated care strategies, to optimise treatment and stabilisation of chronic conditions in women with MCC.

Traditional postpartum rituals among immigrant and non-immigrant Chinese women.

Due to cultural and systemic factors, Chinese-Canadians tend to use mental health services less or when mental health problems are more severe. Services need to be more culturally responsive in their treatment of mental illness. Around important life events, when there may be heightened vulnerability to mental illness, this is especially important. In this study, postpartum cultural practices were examined among recent immigrant, longer-term immigrant, and Canadian-born Chinese women. We conducted a longitudinal cohort study of 493 women in Toronto, Ontario, with livebirths in 2011-2014. Participants completed a demographic survey and Postpartum Rituals Questionnaire. Most women (82.2%) practiced at least one postpartum ritual. Younger age (OR 0.93; 95% CI 0.87-0.99) and greater participation in the heritage culture (OR 1.28; 95% CI 1.02-1.61) were associated with ritual practice. From among five types of postpartum rituals identified (i.e., avoidance of homeostatic disturbances, dietary practices, wind avoidance, organized support, and cold avoidance), dietary practices were most commonly undertaken and cold avoidance was least commonly undertaken. There were differences in postpartum ritual patterns by immigration status, with immigrant women being more likely to undertake a greater number of rituals, to attribute these rituals to Chinese culture, and to ascribe health benefits to these rituals and being less likely to feel forced into performing these rituals. Our findings underscore the importance of clinicians becoming more aware of Chinese postpartum rituals to provide women with culturally competent and patient-centered care.

Ginsenosides enhance P2X7-dependent cytokine secretion from LPS-primed rodent macrophages.

The activation of P2X7 is a well-known stimulus for the NLRP3-caspase 1 inflammasome and subsequent rapid IL-1ß secretion from monocytes and macrophages. Here we show that positive allosteric modulators of P2X7, ginsenosides, can enhance the release of three important cytokines, IL-1ß, IL-6 and TNF-α from LPS-primed rodent macrophages using the J774 mouse macrophage cell line and primary rat peritoneal macrophages. We compared the immediate P2X7 responses in un-primed and LPS-primed macrophages and found no difference in calcium response amplitude or kinetics. These results suggest that under inflammatory conditions positive allosteric modulators are capable of increasing cytokine secretion at lower concentrations of ATP, thus boosting the initial pro-inflammatory signal. This may be important in the control of intracellular infections.