Individual- and family-level associations between child psychopathology and parenting.

Parenting can protect against the development of, or increase risk for, child psychopathology; however, it is unclear if parenting is related to psychopathology symptoms in a specific domain, or to broad liability for psychopathology. Parenting differs between and within families, and both overall family-level parenting and the child-specific parenting a child receives may be important in estimating transdiagnostic associations with psychopathology. Data come from a cross-sectional epidemiological sample (N = 10,605 children ages 4-17, 6434 households). Parents rated child internalizing and externalizing symptoms and their parenting toward each child. General and specific (internalizing, externalizing) psychopathology factors, derived with bifactor modeling, were regressed on parenting using multilevel modeling. Less warmth and more aversive/inconsistent parenting in the family, and toward an individual child relative to family average, were associated with higher general psychopathology and specific externalizing problems. Unexpectedly, more warmth in the family, and toward an individual child relative to family average, was associated with higher specific internalizing problems in 4-11 (not 12-17) year-olds. Less warmth and more aversive/inconsistent parenting are broad correlates of child psychopathology. Aversive/inconsistent parenting, is also related to specific externalizing problems. Parents may behave more warmly when their younger children have specific internalizing problems, net of overall psychopathology.

Monthly correlates of longitudinal child mental health during the COVID-19 pandemic according to children and caregivers.

Multiple reviews identify the broad, pervasive initial impact of the global COVID-19 pandemic on the mental health of children, who may be particularly vulnerable to long-term psychiatric sequelae of the ongoing pandemic. However, limited longitudinal research examines persistence of, or change in, children's distress or psychiatric symptomatology. From June 2020 through December 2021, we enrolled two cohorts of families of children aged 8-13 from Southwestern Ontario into a staggered baseline, longitudinal design that leveraged multi-informant report (N = 317 families). In each family, one child and one parent/guardian completed a baseline assessment, 6 monthly follow-up assessments, and one final follow-up assessment 9 months post-baseline. At each assessment, the child and parent/guardian completed the CoRonavIruS health Impact Survey and measures of child anxiety, depressive, irritability, and posttraumatic stress syndromes. Children's mental health, indexed by the severity of multiple syndromes, fluctuated over the study period. Elevated local monthly COVID-19 prevalence, hospitalization, and death rates were associated with monthly elevations in children's reported worry about contracting COVID-19 and stress related to stay-at-home orders. In turn, both elevated monthly worry about contracting COVID-19 and stress related to stay-at-home orders were associated with monthly elevations in child- and parent-/guardian-report of children's emotional distress and psychiatric syndromes. This study illustrates the importance of, and informs the potential design of, longitudinal research to track the mental health of children, who may be particularly vulnerable to broad psychosocial sequelae of health crises such as the COVID-19 pandemic.

Review: Impact of urgent youth outpatient mental health care on patient and health system outcomes - a scoping review.

BACKGROUND: Young people often face barriers to psychiatric care and are increasingly seeking crisis services for mental health issues through the emergency department (ED). Urgent psychiatric care models provide youth in crisis with rapid access to time-limited mental health care on an outpatient basis. This scoping review aims to evaluate the impact of such urgent psychiatric services for youth aged 13-25 on patient and health system outcomes. METHODS: We conducted a literature search on PubMed, EMBASE, MEDLINE, PsycINFO, and the Cochrane Database of Systematic Reviews for studies published from inception to November 20, 2020. We included studies that described outpatient psychiatric services designed for youth aged 13 to 25, took place in a clinical setting, and offered any combination of assessment, treatment, and referral. We excluded studies describing suicide intervention programmes. RESULTS: Our search yielded six studies, four of which were descriptive studies and two of which were randomized controlled trials. Most studies found that access to urgent psychiatric care for youth was associated with reduced ED volumes, fewer health system costs, and fewer hospitalizations. None of the studies presented evidence that urgent psychiatric services are associated with improved patient symptomatology or functioning. CONCLUSIONS: The results of this scoping review highlight the scarcity of robust evidence evaluating the effectiveness of urgent care for youth mental health. Further experimental studies and a set of standardized quality measures for evaluating these services are needed to bridge this critical gap in mental health care for youth in crisis.

Novel intranasal treatment for anxiety disorders using amiloride, an acid-sensing ion channel antagonist: Pharmacokinetic modeling and simulation.

OBJECTIVE: To develop a physiologically based pharmacokinetic (PBPK) model for amiloride, an acid-sensing ion channel (ASIC) antagonist, and to simulate its pharmacokinetics in plasma and the central nervous system following intranasal administration in a virtual human population. MATERIALS AND METHODS: We first developed a PBPK model of amiloride after oral administration and optimized the model using data from five clinical studies. Next, we added a nasal compartment to the amiloride oral PBPK model and parameterized using data from previous clinical studies. We simulated amiloride's pharmacokinetics in plasma, brain, and cerebrospinal fluid (CSF) after intranasal administration of amiloride at various doses in a virtual human population. RESULTS: The target amiloride concentration in the central nervous system required for maximal ASIC inhibition was achieved with a 75-mg intranasal amiloride dose. However, this finding is based on simulations performed using a mathematical model and needs to be further validated with appropriate clinical data. CONCLUSION: The nasal PBPK model of amiloride could be used to design future clinical studies and allow for successful clinical translation of intranasal amiloride formulation.

Mouse model of panic disorder: Vulnerability to early environmental instability is strain-dependent.

Early life experiences and genetic background shape phenotypic variation. Several mouse models based on early treatments have evaluated short- and long-term phenotypic alterations and explored their molecular mechanisms. The instability of maternal cues was used to model human separation anxiety in outbred mice, one of the etiopathogenetic factors that predict panic disorder (PD). Application of the repeated cross-fostering (RCF) protocol to inbred strains (C57 and DBA) allowed us to measure differential responses to the same experimental manipulation. Ultrasounds emitted during isolation indicated that after RCF, pups from both strains lose their ability to be comforted by nest cues, but the frequency modulation of separation calls increased in RCF-C57 and decreased in RCF-DBA mice. No strain-specific difference in olfactory ability explained these responses in RCF-exposed mice. Rather, disruption of the infant-mother bond may differentially affect separation calls in the two strains. Moreover, the RCF-associated increased respiratory response to hypercapnia-an endophenotype of human PD documented among mice outbred strains-was replicated in the C57 strain only. We suggest that RCF-induced instability of the early environment affects emotionality and respiratory physiology differentially, depending on pups' genetic background. These strain-specific responses provide a lead to understand differential vulnerability to emotional disorders.

The role of genetic and environmental factors in covariation between anxiety and anger in childhood.

Higher levels of anger expression, as well as lower levels of anger control, have been reported for adults with anxiety disorders compared to individuals without anxiety disorders. Different to the research on adults, very few studies examined the relationship between anxiety and anger in childhood. In our study, we investigated 398 Italian twin pairs (74 MZ male, 70 MZ female, 134 same-sex dizygotic-53 male, 81 female-, and 120 unlike-sex dizygotic twin pairs), aged 8-17 (mean 13.06 ± 2.59): (i) the heritability of a childhood anger phenotype; (ii) the association between five anxiety domains and anger; (iii) the role of possible common etiological factors in explaining the observed comorbidity and overlap in the risk between anxiety phenotypes and anger. The study demonstrated that anger, assessed by CBCL items, is heritable in children at a similar rate to prior studies (40%). Our research found low to moderate rate of correlation between anger and anxiety (from 0.10 to 0.19). Finally, the present study found that the majority of etiological influences on anxiety and anger are independent of each other. Data showed that shared environmental influences have some small effects on the phenotypic covariation between the anxiety phenotypes and anger (12%); whereas unique environmental influences have an almost negligible effect (1%). Our analyses did not reveal the effect of genetic effects in explaining the covariation between these phenotypes.

Trajectories of pain and anxiety in a longitudinal cohort of adolescent twins.

BACKGROUND: Adolescence is critical to intercept chronic/persistent pain and decipher its association with anxiety. We ascertained adolescent pain trajectories, their demographic and clinical correlates, the longitudinal association with opiate prescriptions at age 19, and the etiology of the covariation between adolescent pain problems and anxiety symptoms. METHODS: Longitudinal assessment of: 6 common pain problems at age 12, 13, 14, 15, and 17 years; 7 common anxiety symptoms at age 12, 13, and 14 years; opiates' prescriptions at age 19, in the Quebec Newborn Twin Study birth cohort of 667 twin pairs born between 1995-1998. RESULTS: Analyses yielded three trajectories of: "none-to-minimal" (34.3%), "sporadic" (56.7%), and "frequent" (9.0%) pain problems between age 12-17. Anxiety (odds ratios [OR] ORage12 : 2.38; confidence interval [CI]: 1.26-4.47; ORage13 : 3.96; CI: 1.73-9.05; ORage14 : 5.45; CI: 2.67-11.11), the female sex (OR: 3.69; CI: 2.20-6.21), and lower socioeconomic status (OR: 0.87; CI: 0.77-0.98) were associated with the "frequent" compared to the "none-to-minimal" pain trajectory. Only the "frequent" pain trajectory predicted opioid prescriptions at age 19 (OR: 4.14; CI: 1.16-14.55). A twin bivariate latent growth curve model and a cross-lagged model showed that genetic factors and non-shared environmental factors common to both phenotypes influence the longitudinal association between anxiety and adolescent pain problems. CONCLUSIONS: The relatively common, adolescent "frequent pain" trajectory predicts early opioid prescriptions, and anxiety and adolescent pain share multiple etiological components. These data can inform diagnostic reasoning, clinical practice, and help reducing opioid prescriptions and abuse.

Maternal depression symptoms and internalising problems in the offspring: the role of maternal and family factors.

Maternal depression symptoms (MDS) are a robust risk factor for internalising problems (IP) in the offspring. However, the relative importance of MDS and other factors associated with it (i.e. other types of maternal psychopathology, maternal parenting practices, family characteristics) is not well understood. To (a) identify a group of children with high levels of IP between 6 and 12 years using combined maternal and teacher assessments and (b) to quantify the associations between trajectories of MDS during early childhood and children's IP trajectories before and after controlling for family factors associated with MDS. MDS and family factors were assessed in a population-based sample in Canada (n = 1537) between 5 months and 5 years. The outcome variable was membership in trajectories of teacher- and mother-rated IP between ages 6 and 12 years. Family factors were included as covariates in a multinomial logistic regression model. There was a strong association between MDS and children's atypically high levels of IP in unadjusted analyses [OR 4.14 (95% CI 2.60; 6.61)]. The association was reduced, but remained strong [2.60 (1.55; 4.36)] when maternal psychopathology, maternal parenting, and family socioeconomic status were entered in the model. MDS, maternal anxiety, and low parental self-efficacy were associated with offspring's high IP trajectories. MDS is associated with high levels of children's IP independently of other maternal and family characteristics. Intervention targeting maternal psychopathology and parenting self-efficacy and testing the impact on children's IP would provide information on the putative causal pathways between maternal and offspring's symptomatology.

Early childhood trajectories of separation anxiety: Bearing on mental health, academic achievement, and physical health from mid-childhood to preadolescence.

BACKGROUND: Separation anxiety disorder is the most prevalent childhood anxiety condition, but no study assessed children for separation anxiety at preschool age and followed them longitudinally and directly until mid-childhood/early adolescence. METHODS: Multi-informant (children, teachers, family), multipoint (at age 8, 10, 12, 13) assessments of 1,290 children of the Quebec Longitudinal Study of Child Development, who had been categorized between age 1.5 and 6 into four specific separation anxiety trajectories (1, low-persistent; 2, low-increasing; 3, high-decreasing, and the less common: 4, high-increasing) by growth mixture modeling. Participants in the high-increasing trajectory were compared to participants in the other three trajectories for: (a) child's internalizing and externalizing problem behavior; (b) physical health; (c) academic achievement; (d) maternal anxiety. RESULTS: Multivariate analyses of variance/covariance at separate time points showed the high-increasing trajectory mostly associated with: (a) higher internalizing, but not externalizing, behavior; (b) worse academic achievement (most consistently by comparisons to the normative low-persistent trajectory; (c) higher rates of maternal panic/agoraphobic anxiety; (d) worse physical health (most consistently by comparisons to the low-persistent trajectory). The high-increasing trajectory had twofold to threefold higher incidences of physical illnesses than the normative low-persistent group; this was specific for headaches at age 12 years, chronic asthma at age 10 and 13, and having received asthma-related medication during the past 12 months. CONCLUSIONS: High-increasing separation anxiety in preschool maintains longitudinal relationships to independent health and academic outcomes, at least until preadolescence. This knowledge can inform the deployment of clinical resources at the earlier signs of the more impairing manifestations.

Shared genetic influences among childhood shyness, social competences, and cortical responses to emotions.

Visual event-related potentials (ERPs) evoked by facial expressions are useful to map socioemotional responses among shy children and to predict transition into social phobia. We investigated the sources of covariation among childhood shyness, social competences, and ERPs to other children's happy, neutral, and angry expressions. Electrophysiological and twin analyses examined the phenotypic and etiological association among an index of childhood shyness, an index of social competences, and ERP responses to facial expressions in 200 twins (mean age=9.23years). Multivariate twin analyses showed that the covariation among shyness, social competences, and a composite of a frontal late negative component occurring around 200-400ms in response to happy, neutral, and angry expressions could be entirely explained by shared genetic factors. A coherent causal structure links childhood shyness, social competences, and the cortical responses to facial emotions. A common genetic substrate can explain the interrelatedness of individual differences for childhood shyness, social competences, and some associated electrophysiological responses to socioemotional signals.

Distinct trajectories of separation anxiety in the preschool years: persistence at school entry and early-life associated factors.

BACKGROUND: Little is known about how children differ in the onset and evolution of separation anxiety (SA) symptoms during the preschool years, and how SA develops into separation anxiety disorder. In a large, representative population-based sample, we investigated the developmental trajectories of SA symptoms from infancy to school entry, their early associated risk factors, and their associations with teachers' ratings of SA in kindergarten. METHODS: Longitudinal assessment of SA trajectories and risk factors in a cohort of 1,933 families between the ages of 1.5 and 6 years. RESULTS: Analyses revealed a best-fitting, 4-trajectory solution, including a prevailing, unaffected Low-Persistent group (60.2%), and three smaller groups of distinct developmental course: a High-Increasing (6.9%), a High-Decreasing (10.8%), and a Low-Increasing group (22.1%). The High-Increasing group remained high throughout the preschool years and was the only trajectory to predict teacher-assessed SA at age 6 years. Except for the High-Increasing, all trajectories showed substantial reduction in symptoms by age 6 years. The High-Increasing and High-Decreasing groups shared several early risk factors, but the former was uniquely associated with higher maternal depression, maternal smoking during pregnancy, and parental unemployment. CONCLUSIONS: Most children with high SA profile at age 1.5 years are expected to progressively recover by age 4-5. High SA at age 1.5 that persists over time deserves special attention, and may predict separation anxiety disorder. A host of child perinatal, parental and family-contextual risk factors were associated with the onset and developmental course of SA across the preschool years.

GRIN2B predicts attention problems among disadvantaged children.

It is well established that adversities and GRIN2B (coding an N-methyl-D-aspartate receptor subunit) are independently associated with behavioral and cognitive impairments in childhood. However, a high proportion of children exposed to adversities have good, long-term outcomes. We hypothesized that among children exposed to adversities, GRIN2B variants would predict the worst cognitive and behavioral outcomes. 6 single nucleotide polymorphisms of GRIN2B were genotyped in 625 children aged 6-11 years from an Italian community-based sample. The interacting effect of GRIN2B variants with 4 measures of adversities [low socioeconomic status (SES), preterm delivery, maternal smoking during pregnancy, and absence of breastfeeding] was investigated upon blindly assessed cognitive abilities (vocabulary, block design, digit spans of Wechsler's Intelligence Scale, and Rey complex figure) and parents-rated behavioral problems (Child Behavior Checklist/6-18). Rs2268119 × SES interaction (Hotelling's Trace = 0.07; F(12,1154) = 3.53; p = 0.00004) influenced behavior, with more attention problems among children in the 'either A/T or T/T genotype and low SES' group, compared to all other groups. This interaction effect was not significant in an independent, replication sample of 475 subjects from an Italian community-based sample. GRIN2B variants predict children with the worst outcome in attention functioning among children exposed to low SES. Our findings, if replicated, could help in the identification of children with the highest risk and may prompt cost-effective preventive/treatment strategies.

Postnatal aversive experience impairs sensitivity to natural rewards and increases susceptibility to negative events in adult life.

Evidence shows that maternal care and postnatal traumatic events can exert powerful effects on brain circuitry development but little is known about the impact of early postnatal experiences on processing of rewarding and aversive stimuli related to the medial prefrontal cortex (mpFC) function in adult life. In this study, the unstable maternal environment induced by repeated cross-fostering (RCF) impaired palatable food conditioned place preference and disrupted the natural preference for sweetened fluids in the saccharin preference test. By contrast, RCF increased sensitivity to conditioned place aversion (CPA) and enhanced immobility in the forced swimming test. Intracerebral microdialysis data showed that the RCF prevents mpFC dopamine (DA) outflow regardless of exposure to rewarding or aversive stimuli, whereas it induces a strong and sustained prefrontal norepinephrine (NE) release in response to different aversive experiences. Moreover, the selective mpFC NE depletion abolished CPA, thus indicating that prefrontal NE is required for motivational salience attribution to aversion-related stimuli. These findings demonstrate that an unstable maternal environment impairs the natural propensity to seek pleasurable sources of reward, enhances sensitivity to negative events in adult life, blunts prefrontal DA outflow, and modulates NE release in the reverse manner depending on the exposure to rewarding or aversive stimuli.

Post-stroke spasticity: follow-up and functional implications of chronic long-term treatment with botulinum toxin.

BACKGROUND: Around 40% of stroke survivor develop spasticity. Plantar flexors (PF) muscles are often affected, with severe functional impairment. The treatment of choice is botulinum toxin type A (BoNT-A) combined with adjuvant treatments. The temporary pharmacological effect implies periodic reassessment and reinjection. These long-term chronic programs require monitoring the functional impact of each cycle and the clinical evolution in relation to aging and repeated interventions. AIM: Evaluating changes of functional level in patients with post-stroke spasticity treated with BoNT-A by assessing the long-term maintenance of the therapeutic efficacy. DESIGN: Retrospective longitudinal observational study. SETTING: Outpatients. POPULATION: Chronic stroke survivors undergoing BoNT-A treatment and subsequent intensive rehabilitation (10 sessions in a day-hospital regime). METHODS: Medical records of the enrolled patients were consulted. The primary endpoint was the change in PF spasticity by at least 1 point on the Modified Ashworth Scale (MAS) at each cycle. Secondary endpoints were the assessment of possible trends in gait parameters (Six Minute Walking Test [6MWT]; Timed Up and Go [TUG], and 10 Meters Walking Test [10mWT]) pre- and post-injection and at each cycle. RESULTS: Thirty-six patients were enrolled. A reduction of at least one MAS point for PF was recorded after each cycle in all subjects. A time-dependent reduction in the proportion of patients reporting an improvement higher than the minimal clinically important difference (MCID) in 6MWT and 10mWT was observed. In the case of TUG, this data kept stable at all cycles. A one-point increase in the basal functional ambulation classification (FAC) score resulted in a reduction in the probability of having a TUG improvement greater than the MCID. The opposite correlation was found for 6MWT and 10mWT. CONCLUSIONS: With the proposed treatment, the clinical significance TUG improvement remains constant throughout repeated cycles and the proportion of patients with improvement in 6MWT and 10mWT tends to decline over time. The predictive value of basal FAC on the functional variables expected improvement may provide a potential treatment targeting tool. CLINICAL REHABILITATION IMPACT: These results may deliver prognostic indication allowing an optimized integration of different post-BoNT-A rehabilitation approaches, agreeing with current evidence. Adequate monitoring and treatment protocols are crucial for the stability of functional level and may prevent excessive fluctuations.

Accelerated Stability Assessment of Extemporaneously Compounded Amiloride Nasal Spray.

Amiloride is a U.S. Food and Drug Administration-approved diuretic agent used to treat hypertension and congestive heart failure. Recent human and animal studies have suggested that amiloride may also have a role in treating anxiety through its acid-sensing ion channel antagonism. Intranasal administration of amiloride nasal spray via an extemporaneously compounded preparation has the potential for rapid delivery to the site of action to achieve therapeutic outcomes in individual patients with anxiety disorders. However, these patient-specific preparations do not have the pre-formulation characterization, including chemical stability, that conventional manufactured dosage forms have. The objective of this study was to assess the estimated chemical stability of compounded amiloride nasal spray over 6 months and 12 months utilizing accelerated degradation with high heat and the Arrhenius equation. A stability-indicating highperformance liquid chromatography analytical method was employed at appropriate intervals over a 12-month period to reveal that amiloride remained chemically stable over the period tested and by extrapolation. Physical stability and compatibility with the preservative benzyl alcohol were also confirmed via visual inspection, pH monitoring, and measurement of turbidity.

Role of Diagnostic Nerve Blocks in the Goal-Oriented Treatment of Spasticity with Botulinum Toxin Type A: A Case-Control Study.

The goal-setting process is pivotal in managing patients with disabling spasticity. This case-control study assessed the role of diagnostic nerve blocks in guiding the goal-setting process within goal-targeted treatment of spasticity with botulinum neurotoxin-A. In this case-control study, patients with disabling spasticity underwent either a goal-setting process based on the patient's needs and clinical evaluation (control group) or additional diagnostic nerve block procedures (case group). All enrolled patients underwent a focal treatment with botulinum neurotoxin-A injection and a 1-month follow-up evaluation during which goal achievement was quantified using the goal attainment scaling-light score system. Data showed a higher goal achievement rate in the case group (70%) than in the control group (40%). In conclusion, diagnostic nerve blocks may help guide the goal-setting process within goal-targeted treatment of spasticity with botulinum neurotoxin-A towards more realistic and achievable goals, thereby improving the outcomes of botulinum neurotoxin-A injection. Future studies should better explore the role of diagnostic nerve blocks to further personalize botulinum neurotoxin-A according to individual patients' preferences and requirements.

The Toronto Adolescent and Youth Cohort Study: Study Design and Early Data Related to Psychosis Spectrum Symptoms, Functioning, and Suicidality.

BACKGROUND: Psychosis spectrum symptoms (PSSs) occur in a sizable percentage of youth and are associated with poorer cognitive performance, poorer functioning, and suicidality (i.e., suicidal thoughts and behaviors). PSSs may occur more frequently in youths already experiencing another mental illness, but the antecedents are not well known. The Toronto Adolescent and Youth (TAY) Cohort Study aims to characterize developmental trajectories in youths with mental illness and understand associations with PSSs, functioning, and suicidality. METHODS: The TAY Cohort Study is a longitudinal cohort study that aims to assess 1500 youths (age 11-24 years) presenting to tertiary care. In this article, we describe the extensive diagnostic and clinical characterization of psychopathology, substance use, functioning, suicidality, and health service utilization in these youths, with follow-up every 6 months over 5 years, including early baseline data. RESULTS: A total of 417 participants were enrolled between May 4, 2021, and February 2, 2023. Participants met diagnostic criteria for an average of 3.5 psychiatric diagnoses, most frequently anxiety and depressive disorders. Forty-nine percent of participants met a pre-established threshold for PSSs and exhibited higher rates of functional impairment, internalizing and externalizing symptoms, and suicidality than participants without PSSs. CONCLUSIONS: Initial findings from the TAY Cohort Study demonstrate the feasibility of extensive clinical phenotyping in youths who are seeking help for mental health problems. PSS prevalence is much higher than in community-based studies. Our early data support the critical need to better understand longitudinal trajectories of clinical youth cohorts in relation to psychosis risk, functioning, and suicidality.

Evidence for distinct genetic effects associated with response to 35% CO2.

BACKGROUND: Carbon dioxide (CO2 ) hypersensitivity represents an individual difference response to breathing CO2 enriched air. People with a history of panic attacks or panic disorder are particularly prone to anxious response, suggesting that CO2 hypersensitivity is a robust risk marker of panic spectrum vulnerability. METHODS: Twin pairs (n = 346) from the general population-based Norwegian NIPH Mental Health Study completed a measure of anxiety before and after vital capacity inhalation of 35% CO2 air and before and after inhalation of regular air. Three hypotheses regarding genetic factors for CO2 hypersensitivity were examined: (1) a single set of genetic risk factors impacts anxiety before exposure to CO2 and these same genes constitute the only genetic influences on anxiety in response to CO2 , (2) the genetic effects on pre-CO2 anxiety are entirely different from the genetic effects on anxiety in response to exposure to CO2 (i.e., new genetic effects), and (3) pre-CO2 anxiety influences anxiety in response to CO2 as well as unique genetic factors that become activated by respiratory stimulation. RESULTS: Our results support the latter hypothesis for response to 35% CO2 , with additive genetic and unique environmental factors best fitting the data. Evidence of new genetic effects was observed, accounting for 20% unique variance in post 35% CO2 anxiety response. New genetic effects were not observed for anxiety ratings made post regular air where only preregular air anxiety ratings explained significant variance in this outcome. CONCLUSIONS: These data suggest that there are distinct genetic factors associated with responsivity to respiratory stimulation via 35% CO2 .

Tolerability, Safety and Efficacy of a Specific Rehabilitation Treatment Protocol for Axillary Web Syndrome: An Observational Retrospective Study.

Axillary web syndrome (AWS) is a highly prevalent surgical complication affecting BC survivors. It presents as a subcutaneous cording that limits the upper limb range of motion (ROM) and causes pain. Its etiology is still debated, and its treatment is not well defined. Therefore, we aimed to investigate the safety, tolerability and efficacy of our specific AWS rehabilitative treatment protocol. We conducted an observational retrospective study on a cohort of 92 AWS patients referred to the oncological outpatient service of a university hospital. We collected data from medical records before (T0) and after (T1) the treatment. The studied protocol was composed of 60-min sessions, carried out 3 times/week by specialized physiotherapists, until the clinical resolution of AWS. We found that a mean of 8.74 ± 2.12 rehabilitative sessions were needed, and only one patient stopped early. At T1, shoulder ROM was complete in both abduction and flexion in 98% of patients; AWS was no longer detectable in 64% of them, and pain significantly decreased compared to T0. In conclusion, our protocol proved to be safe, well-tolerated and seemed to be effective in treating AWS.