Use of crushed tranexamic acid tablets in water for paediatric patients with bleeding disorders.

BACKGROUND: Ε-Aminocaproic acid oral solution (EACA OS) is the only commercially available antifibrinolytic for patients who cannot swallow tablets. Insurance denials and high costs remain barriers to its use. OBJECTIVES: To determine the safety and efficacy of crushed tranexamic acid tablets in water (cTXAw) for children with bleeding disorders. METHODS: We retrospectively reviewed records of children (<10 years) with bleeding disorders who received cTXAw or EACA OS from 1 December 2018, through 31 July 2022, at Mayo Clinic (Rochester, Minnesota). Bleeding outcomes were defined according to ISTH criteria. RESULTS: Thirty-two patients were included (median age, 3 years; male, n = 23). Diagnoses were VWD (n = 17), haemophilia (n = 5), FVII deficiency (n = 3), inherited platelet disorder (n = 4), ITP (n = 2), and combined FV and FVII deficiencies (n = 1). Thirty-two courses of cTXAw (monotherapy 24/32; mean duration 6 days) and fifteen courses of EACA (monotherapy 12/15; mean duration 5 days) were administered. No surgical procedures (n = 28) were complicated by bleeding. Of the 19 bleeding events, 16 had effective haemostasis, two had no reported outcome, and one had no response. cTXAw and EACA were equally effective in preventing and treating bleeding (p value > .1). No patients had adverse effects. Eight of 19 patients (42%) who were initially prescribed EACA OS did not receive it because of cost or insurance denial. The estimated average wholesale price of one treatment was $94 for cTXAw and $905 for EACA OS. CONCLUSIONS: CTXAw appears to be an effective, safe, and low-cost alternative option to EACA OS for young children with bleeding disorders.

A randomised controlled feasibility trial of Group Cognitive Behavioural Therapy for people with severe asthma.

OBJECTIVES: Evidence for the efficacy of Cognitive Behavioural Therapy (CBT) in asthma is developing but it is not known if this translates to benefits in severe asthma or if a group approach is acceptable to this patient group. This study aimed to assess the feasibility and acceptability of Group-CBT in severe asthma. METHOD: This was a two-centre, randomised controlled parallel group feasibility study. Eligible participants (patients with severe asthma and a clinically significant diagnosis of anxiety and/or depression - Hospital Anxiety and Depression Scale (HAD) score greater than 8 for the anxiety or depression sub-scale) received Group-CBT in weekly sessions for eight consecutive weeks and usual care or usual care only. Follow-up was for 16 weeks and end points were: Asthma Quality of Life Questionnaire, Asthma Control Questionnaire, HAD, Dyspnoea-12, EuroQual-5D and EuroQuol-VAS. RESULTS: 51 patients were randomised: 36% (51 out of 140) consent rate and attrition at week 16 was 12. Screening logs indicated that study take-up was influenced by patients living long distances from the treatment centre and inability to commit to the weekly demands of the programme. Drop-out was higher in Group-CBT compared due to inability to commit to the weekly programme because of poor health. Participants who contributed to focus group discussions reported that Group-CBT contributed to a better understanding of their illness and related approaches to anxiety management and acceptance of their asthma condition. Although weekly face-to-face sessions were challenging, this was the preferred method of delivery for these participants. CONCLUSIONS: This feasibility study shows that Group-CBT warrants further investigation as a potentially promising treatment option for patients with severe asthma. It has been possible but not easy to recruit and retain the sample. Options for a less demanding intervention schedule, such as less frequent face-to-face visits and the use of web-based interventions, require careful consideration.

Toxicity of lunar dust assessed in inhalation-exposed rats.

Humans will again set foot on the moon. The moon is covered by a layer of fine dust, which can pose a respiratory hazard. We investigated the pulmonary toxicity of lunar dust in rats exposed to 0, 2.1, 6.8, 20.8 and 60.6 mg/m(3) of respirable-size lunar dust for 4 weeks (6 h/day, 5 days/week); the aerosols in the nose-only exposure chambers were generated from a jet-mill ground preparation of a lunar soil collected during the Apollo 14 mission. After 4 weeks of exposure to air or lunar dust, groups of five rats were euthanized 1 day, 1 week, 4 weeks or 13 weeks after the last exposure for assessment of pulmonary toxicity. Biomarkers of toxicity assessed in bronchoalveolar fluids showed concentration-dependent changes; biomarkers that showed treatment effects were total cell and neutrophil counts, total protein concentrations and cellular enzymes (lactate dehydrogenase, glutamyl transferase and aspartate transaminase). No statistically significant differences in these biomarkers were detected between rats exposed to air and those exposed to the two low concentrations of lunar dust. Dose-dependent histopathology, including inflammation, septal thickening, fibrosis and granulomas, in the lung was observed at the two higher exposure concentrations. No lesions were detected in rats exposed to ≤6.8 mg/m(3). This 4-week exposure study in rats showed that 6.8 mg/m(3) was the highest no-observable-adverse-effect level (NOAEL). These results will be useful for assessing the health risk to humans of exposure to lunar dust, establishing human exposure limits and guiding the design of dust mitigation systems in lunar landers or habitats.

Social Reactions to Intimate Partner Violence Disclosure Among Low-Income, Ethnically Diverse Community Women.

Friends and family members' reactions to intimate partner violence (IPV) disclosure play an important role in social support because disclosure often precedes requests for support. Perceptions of social reactions to IPV disclosure are likely to vary by context. Yet, research is limited on the role of ethnicity and severity of physical violence in perceptions of social reactions. We examined perceptions of social reactions to IPV disclosure using data from Wave 6 interviews for Project HOW: Health Outcomes of Women. Participants ( N = 201) were asked proportionately how many friends and family reacted positively and negatively to IPV disclosure. MANOVAs revealed significant differences in perceptions of positive social reactions by ethnicity and severity.

The longitudinal association between alcohol use and intimate partner violence among ethnically diverse community women.

Research has consistently demonstrated a strong link between substance misuse and the perpetration of intimate partner violence (IPV). However, studies examining whether substance misuse is associated with IPV victimization have been mixed. Using data collected from 835 low-income ethnically diverse community women, this study extends previous research by utilizing a longitudinal design, considering men's and women's alcohol use, and examining multiple forms of abuse. Despite overall decreases in drinking and abuse, the frequency of male partners' drinking continued to be associated with their perpetration of threats, violence, and sexual aggression. Women's alcohol use frequency was associated with sustaining physical violence, but not threats of violence or sexual aggression.

Women's motives for violent and nonviolent behaviors in conflicts.

Drawing from past research on women's motives for intimate partner violence (IPV) perpetration, correlates of women's perpetration, and correlates of nonviolent conflict, we created a scale containing 125 possible motives, representing 14 broad domains (e.g., self-defense, retaliation). Participants were an ethnically diverse sample of women who had perpetrated no physical IPV against their current partner (n = 243), threats but not physical IPV (n = 70), nonsevere physical IPV (n = 193), and at least one act of severe (e.g., choke) physical IPV (n = 93). An exploratory factor analysis yielded a seven-factor solution, representing Partners' Negative Behaviors, Increase Intimacy, Personal Problems, Retaliation, Childhood Experiences, Situation/Mood, and Partners' Personal Problems. Differences by women's IPV perpetration and race and/or ethnicity were tested with means representing these seven factors and a computed variable representing self-defense. Although motives differed by perpetration type, main effects for Partners' Negative Behavior, Personal Problems, Retaliation, and Childhood Experiences were modified by interactions, suggesting ethnicity should be considered when developing interventions.

Differing effects of partner and nonpartner sexual assault on women's mental health.

This study contrasted the effects of intimate partner and nonpartner sexual assault on women's mental health among a sample (N=835) of low-income, ethnically diverse community women. Compared to sexual assault by a previous partner or by a non-intimate partner, sexual assault by a current partner was the strongest predictor of PTSD, stress, and dissociation. Non-intimate partner sexual assault was only a significant predictor of PTSD and only for African American women. These findings suggest that the victim-offender relationship is important when considering the impact of sexual assault. Specifically, sexual assault perpetrated by an intimate partner may be especially traumatic.

A Mixed-Methods Study Using a Nonclinical Sample to Measure Feasibility of Ostrich Community: A Web-Based Cognitive Behavioral Therapy Program for Individuals With Debt and Associated Stress.

BACKGROUND: There are increasing concerns about the health and well-being of individuals facing financial troubles. For instance, in the United Kingdom, the relationship between debt and mental health difficulties is becoming more evident due to the economic downturn and welfare reform. Access to debt counseling services is limited and individuals may be reluctant to access services due to stigma. In addition, most of these services may not be appropriately resourced to address the psychological impact of debt. This study describes outcomes from an Internet-based cognitive behavioral therapy (ICBT) program, Ostrich Community (OC), which was developed to provide support to those struggling with debt and associated psychological distress. OBJECTIVE: The aim of this feasibility study was to assess the suitability and acceptability of the OC program in a nonclinical sample and examine mental health and well-being outcomes from using the program. METHODS: A total of 15 participants (who were not suffering from severe financial difficulty) were assisted in working through the 8-week ICBT program. Participants rated usability and satisfaction with the program, and after completion 7 participants took part in a semistructured interview to provide further feedback. Before the first session and after the final session all participants completed questionnaires to measure well-being and levels of depression, stress, and anxiety and pre- and postscores were compared. RESULTS: Satisfaction was high and themes emerging from the interviews indicate that the program has the potential to promote effective financial behaviors and improve financial and global psychosocial well-being. When postcompletion scores were compared with those taken before the program, significant improvements were identified on psychometric measures of well-being, stress, and anxiety. CONCLUSIONS: The OC program is the first ICBT program that targets poor mental health associated with financial difficulty. This feasibility study indicates that OC may be an effective intervention for increasing financial resilience, supporting individuals to become financially independent, and promoting positive financial and global well-being. Further work with individuals suffering from debt and associated emotional difficulties will help to examine clinical effectiveness more closely.

A mixed methods evaluation of a Mindfulness-Based Stress Reduction course for people with Parkinson's disease.

OBJECTIVE: The aim of this study was to evaluate the effects of an 8-week Mindfulness-Based Stress Reduction course (MBSR) on people with Parkinson's disease who experienced depression, anxiety, stress or difficulty coping with Parkinson's. METHODS: Thirteen participants were recruited and six completed the full MBSR course. Data were analysed using repeated measures analysis of variance and thematic analysis. RESULTS: There were significant improvements in levels of depression, anxiety and stress at weeks eight and sixteen, as measured by the Depression Anxiety and Stress Scale, short version (DASS-21). Themes of 'mindfulness as challenging' and 'mindfulness as life-enhancing' were identified from follow-up questionnaire responses. All participants reported they would recommend MBSR to other people with Parkinson's. CONCLUSION: This study supports previous preliminary findings that mindfulness-based interventions could benefit people with Parkinson's experiencing non-motor symptoms. Further research using larger sample sizes, a control group, and a longer follow-up period is required.

Physical and mental health outcomes of women in nonviolent, unilaterally violent, and mutually violent relationships.

Despite equivocal findings on whether men or women are more violent, the negative impact of violence is greatest for women. To determine how gender asymmetry in perpetration affects women's health status, we conducted a study in two phases with 835 African American, Euro-American, and Mexican American low-income women in Project HOW: Health Outcomes of Women. In Phase 1, we used severity and frequency of women's and male partners' violence to create six groups: nonviolent (NV), uni-directional male (UM) perpetrator, uni-directional female (UF) perpetrator and, when both partners were violent, symmetrical (SYM), male primary perpetrator (MPP), and female primary perpetrator (FPP). The MPP group sustained the most threats, violence, sexual aggression, and psychological abuse. They also reported the most fear. Injury was highest in the MPP and FPP groups. In Phase 2, we examined group differences in women's health status over time for 535 participants, who completed five annual interviews. Surprisingly, women's health in the MPP and FPP violence groups was similar and generally worse than if violence was uni-directional.

Peripherally inserted central catheter cushioning: a pilot study comparing gauze with silicone foam.

A pilot study was conducted to compare gauze with silicone foam that may be left in place for as long as seven days. Adult patients who were receiving treatment via peripherally inserted central catheters were recruited and alternately assigned to either the gauze or silicone foam group. Patient-reported itch and discomfort, nurse-reported ease of removal, and skin status were recorded for four weeks at each weekly dressing change.

Childhood and adolescent sexual abuse of community women: mediated effects on psychological distress and social relationships.

Possible mediators of sexual abuse severity were tested on the basis of D. Finkelhor and A. Browne's (1985) traumagenic dynamics model with 178 low-income African American, European American, and Mexican American community women interviewed for Project HOW: Health Outcomes of Women. This subsample reported contact sexual abuse before the age of 18 years. Severity was level of force, number of perpetrators, relationship to perpetrator, and age at first assault. As expected, structural equation modeling showed powerlessness, and stigmatization largely mediated the effects of sexual abuse severity on women's psychological distress in adulthood. Powerlessness also mediated the effects of severity on maladaptive social relationships. The expected path from betrayal to relationships was nonsignificant. Overall, the results support extension of D. Finkelhor and A. Browne's model. Possible interventions are addressed.

Extension of the behavioral model of healthcare utilization with ethnically diverse, low-income women.

OBJECTIVE: Psychosocial vulnerabilities were added to a model of healthcare utilization. This extension was tested among low-income women with ethnicity addressed as a moderator. DESIGN: Structured interviews were conducted at 2 points in time, approximately 1 year apart. The constructs of psychosocial vulnerability, demographic predisposing, barriers, and illness were measured by multiple indicators to allow use of Structural Equation Modeling to analyze results. The models were tested separately for each ethnic group. SETTING: Community office. PARTICIPANTS: African-American (N = 266), Euro-American (N = 200), and Mexican-American (N = 210) women were recruited from the Dallas Metropolitan area to participate in Project HOW: Health Outcomes of Women, a multi-year, multi-wave study. Face-to-face interviews were conducted with this sample. Participants had been in heterosexual relationships for at least 1 year, were between 20 and 49 years of age, and had incomes less than 200% of the national poverty level. MAIN OUTCOME MEASURES: Healthcare utilization, defined as physician visits and general healthcare visits. RESULTS: Illness mediated the effect of psychosocial vulnerability on healthcare utilization for African Americans and Euro-Americans. The model for Mexican Americans was the most complex. Psychosocial vulnerability on illness was partially mediated by barriers, which also directly affected utilization. CONCLUSIONS: Psychosocial vulnerabilities were significant utilization predictors for healthcare use for all low-income women in this study. The final models for the 2 minority groups, African Americans and Mexican Americans, were quite different. Hence, women of color should not be considered a homogeneous group in comparison to Euro-Americans.

Cross-validation by downweighting influential cases in structural equation modelling.

In the social and behavioural sciences, structural equation modelling has been widely used to test a substantive theory or causal relationship among latent constructs. Cross-validation (CV) is a valuable tool for selecting the best model among competing structural models. Influential cases or outliers are often present in practical data. Therefore, even the correct model for the majority of the data may not cross-validate well. This paper discusses various drawbacks of CV based on sample covariance matrices, and develops a procedure for using robust covariance matrices in the model calibration and validation stages. Examples illustrate that the CV index based on sample covariance matrices is very sensitive to influential cases, and even a single outlier can cause the CV index to support a wrong model. The CV index based on robust covariance matrices is much less sensitive to influential cases and thus leads to a more valid conclusion about the practical value of a model structure.

Long Term Mental Health Effects of Partner Violence Patterns and Relationship Termination on Low-Income and Ethnically Diverse Community Women.

Intimate partner violence (IPV) is associated with psychological distress; however, differences in the impact of unidirectional IPV, typically male-dominated, and bidirectional IPV have not been examined. To address this gap in the literature, we compared the effects of various IPV patterns on women's reports of dissociation, post-traumatic stress disorder, and stress in 6 interviews over eight years. We also examined whether differences by IPV pattern existed in women's mental health upon leaving a violent relationship. The 489 low-income women completing all interviews were African American (40%), Euro-American (30%), and Mexican American (30%), over half of whom (58%) were no longer with Wave 1 partners by Wave 6. In general, worse mental health was associated with relationship termination and bidirectional violence.

Lethal hypoglycemic ketosis and glyceroluria in mice lacking both the mitochondrial and the cytosolic glycerol phosphate dehydrogenases.

The activities of either the mitochondrial or cytosolic glycerol phosphate dehydrogenase (mGPD, cGPD) plus that of glycerol kinase are required for the use of glycerol in aerobic metabolism and gluconeogenesis. A knockout mouse lacking mGPD has reduced body weight and fertility but shows remarkably normal liver and muscle metabolite levels. The BALB/cHeA mouse strain, which lacks cGPD, breeds well and is phenotypically normal, although it demonstrates metabolite abnormalities in certain tissues. Crosses were made between these two strains, and mice were generated that lacked both dehydrogenases. These mice, although active and nursing well for several days, failed to grow, and usually died within the first week. Liver glycerol phosphate levels were elevated 30-fold, whereas liver ATP, ADP, and AMP levels were reduced by 30-40%. Plasma glycerol was elevated 30- to 50-fold to 30-50 mm, and urine glycerol exceeded 0.45 m (4% w/v). GPD-deficient mice were hypoglycemic, had a 50% increase in plasma free fatty acids, and developed ketonuria within the first day of life. Uncoupling protein-1 mRNA in brown adipose tissue was reduced 60%. These mice share some features of both glycerol kinase deficiency and hereditary fructose intolerance, suggesting the phenotype may be due to the combined effects of the loss of a gluconeogenic substrate, the osmotic effects of glycerol, and the metabolic effects of the accumulation of a phosphorylated metabolite.

Normal thyroid thermogenesis but reduced viability and adiposity in mice lacking the mitochondrial glycerol phosphate dehydrogenase.

The mitochondrial glycerol phosphate dehydrogenase (mGPD) is important for metabolism of glycerol phosphate for gluconeogenesis or energy production and has been implicated in thermogenesis induced by cold and thyroid hormone treatment. mGPD in combination with the cytosolic glycerol phosphate dehydrogenase (cGPD) is proposed to form the glycerol phosphate shuttle, catalyzing the interconversion of dihydroxyacetone phosphate and glycerol phosphate with net oxidation of cytosolic NADH. We made a targeted deletion in Gdm1 and produced mice lacking mGPD. On a C57BL/6J background these mice showed a 50% reduction in viability compared with wild-type littermates. Uncoupling protein-1 mRNA levels in brown adipose tissue did not differ between mGPD knockout and control pups, suggesting normal thermogenesis. Pups lacking mGPD had decreased liver ATP and slightly increased liver glycerol phosphate. In contrast, liver and muscle metabolites were normal in adult animals. Adult mGPD knockout animals had a normal cold tolerance, normal circadian rhythm in body temperature, and demonstrated a normal temperature increase in response to thyroid hormone. However, they were found to have a lower body mass index, a 40% reduction in the weight of white adipose tissue, and a slightly lower fasting blood glucose than controls. The phenotype may be secondary to consequences of the obligatory production of cytosolic NADH from glycerol metabolism in the mGPD knockout animal. We conclude that, although mGPD is not essential for thyroid thermogenesis, variations in its function affect viability and adiposity in mice.