Preterm preeclampsia as an independent risk factor for thromboembolism in a large national cohort.

BACKGROUND: Preterm preeclampsia, a product of vascular dysfunction, is associated with prolonged hospital admission and proteinuria, significant risk factors for thromboembolism in pregnancy. The risk of thromboembolism in preterm preeclampsia warrants further investigation. OBJECTIVE: To determine the relationship between preterm preeclampsia and thromboembolic risk. We hypothesize that preterm preeclampsia is an independent risk factor for thromboembolism in pregnancy. STUDY DESIGN: This is a retrospective cohort study using the National Inpatient Sample database via Healthcare Cost and Utilization Project-Agency for Healthcare Cost and Utilization Project from 2017-2019. All subjects with an International Classification of Diseases, Tenth Revision code for pregnancy or peripartum encounter were included. Subjects were excluded if the gestational age at delivery was <20 weeks or if they had a history of thromboembolism, inherited thrombophilia, or antiphospholipid syndrome. Patients with preterm (delivered <37 weeks) preeclampsia and term (delivered ≥37 weeks) preeclampsia were compared with those without preeclampsia. The primary outcome was a composite of any thromboembolic event, including pulmonary embolism, deep vein thrombosis, cerebral thrombosis or transient ischemic attack, or other thromboses. The secondary outcomes were rates of each type of thromboembolic event. The groups were compared via variance analysis, chi-square, and logistic regression analyses. The logistic regression included those variables that differed between groups with P<.05. RESULTS: Of individuals in the database, >2.2 million met the inclusion criteria. A total of 56,446 (2.7%) had preterm preeclampsia, and 86,152 (6.7%) had term preeclampsia. Those with preterm preeclampsia were more likely to be older, identify as non-Hispanic black, have obesity, have chronic hypertension among other chronic diseases, and be in the lowest quartile of income (P<.001). Among patients with preterm preeclampsia, 0.32% experienced thromboembolism, whereas those with term preeclampsia and without preeclampsia experienced thromboembolism at 0.10% and 0.09%, respectively. After controlling for confounders that differed between groups with P<.05, preterm preeclampsia remained independently associated with any thromboembolic event (adjusted odds ratio, 2.21 [95% confidence interval, 1.84-2.65]), and each type of thromboembolism. Term preeclampsia was not associated with an increased risk of thromboembolism (adjusted odds ratio, 1.18 [95% confidence interval, 0.94-1.48]). CONCLUSION: Preterm preeclampsia is independently associated with an increased risk of thromboembolic events.

Chemokines form complex signals during inflammation and disease that can be decoded by extracellular matrix proteoglycans.

Chemokine-driven leukocyte recruitment is a key component of the immune response and of various diseases. Therapeutically targeting the chemokine system in inflammatory disease has been unsuccessful, which has been attributed to redundancy. We investigated why chemokines instead have specific, specialized functions, as demonstrated by multiple studies. We analyzed the expression of genes encoding chemokines and their receptors across species, tissues, and diseases. This analysis revealed complex expression patterns such that genes encoding multiple chemokines that mediated recruitment of the same leukocyte type were expressed in the same context, such as the genes encoding the CXCR3 ligands CXCL9, CXCL10, and CXCL11. Through biophysical approaches, we showed that these chemokines differentially interacted with extracellular matrix glycosaminoglycans (ECM GAGs), which was enhanced by sulfation of specific GAGs. Last, in vivo approaches demonstrated that GAG binding was critical for the CXCL9-dependent recruitment of specific T cell subsets but not of others, irrespective of CXCR3 expression. Our data demonstrate that interactions with ECM GAGs regulated whether chemokines were presented on cell surfaces or remained more soluble, thereby affecting chemokine availability and ensuring specificity of chemokine action. Our findings provide a mechanistic understanding of chemokine-mediated immune cell recruitment and identify strategies to target specific chemokines during inflammatory disease.

Perspectives of Australian family carers of people with dementia on the 'cottage' model of respite: Compared to traditional models of residential respite provided in aged care facilities.

The majority of people living with dementia reside in the community and are often reliant on the support of informal carers to do so. Family carers face many challenges in supporting the person with dementia to remain at home, and short-term respite care is a valued service that offers a temporary break from the role. Respite cottages provide short-term care in a residential home-like setting with a limited number of clients and is a more flexible approach to accessing the service. Disproportionate use of cottage respite in Australia suggests this model is preferred over traditional respite within residential aged care facility (RACF) settings, yet limited research exists to compare these models. This study sought to understand the perceptions of carers who had used cottage respite in comparison to other models, and explore the contribution of cottage respite for supporting carers to continue in their role and maintain their care recipient (CR) living at home. Semi-structured interviews were conducted with 126 family carers who had used one of two New South Wales-based respite cottages within a 2-year period; 67 of whom had also used RACF respite. Thematic analysis revealed four main themes around the benefits of cottage respite: (a) an effective essential service, (b) flexibility, (c) familiarity and (d) appropriateness, especially for early stage or younger onset dementia. Carers indicated that the more homely, familiar and intimate cottage model of respite care was preferential to that of the larger, institutional-style RACF respite setting. Carers credited the cottage model of respite service with delaying their need for permanent residential placement by over 12 months. The cottage respite model provides an important avenue to supporting the individual needs of dementia dyads, with potential to delay permanent placement, and should be offered more broadly to provide people with more choice about their care.

Development of a cancer pain self-management resource to address patient, provider, and health system barriers to care.

OBJECTIVE: The majority of self-management interventions are designed with a narrow focus on patient skills and fail to consider their potential as "catalysts" for improving care delivery. A project was undertaken to develop a patient self-management resource to support evidence-based, person-centered care for cancer pain and overcome barriers at the levels of the patient, provider, and health system. METHOD: The project used a mixed-method design with concurrent triangulation, including the following: a national online survey of current practice; two systematic reviews of cancer pain needs and education; a desktop review of online patient pain diaries and other related resources; consultation with stakeholders; and interviews with patients regarding acceptability and usefulness of a draft resource. RESULT: Findings suggested that an optimal self-management resource should encourage pain reporting, build patients' sense of control, and support communication with providers and coordination between services. Each of these characteristics was identified as important in overcoming established barriers to cancer pain care. A pain self-management resource was developed to include: (1) a template for setting specific, measureable, achievable, relevant and time-bound goals of care, as well as identifying potential obstacles and ways to overcome these; and (2) a pain management plan detailing exacerbating and alleviating factors, current strategies for management, and contacts for support. SIGNIFICANCE OF RESULTS: Self-management resources have the potential for addressing barriers not only at the patient level, but also at provider and health system levels. A cluster randomized controlled trial is under way to test effectiveness of the resource designed in this project in combination with pain screening, audit and feedback, and provider education. More research of this kind is needed to understand how interventions at different levels can be optimally combined to overcome barriers and improve care.

Screening and Audit as Service-Level Strategies to Support Implementation of Australian Guidelines for Cancer Pain Management in Adults: A Feasibility Study.

BACKGROUND: Pain in people with cancer is common but often under-recognized and under-treated. Guidelines can improve the quality of pain care, but need targeted strategies to support implementation. AIM: To test the feasibility of two service-level strategies for supporting guideline implementation: a screening system and medical record audit. DESIGN: Multimethods. SETTING: One oncology outpatient service, and one palliative care outpatient and inpatient service. PARTICIPANTS: Patients with advanced cancer. METHODS: Patients were screened in the waiting room with a modified version of the Edmonton Symptom Assessment System-revised either electronically or in paper-based format. Feasibility indicated the percentage of patients successfully screened from the total number attending the services. An audit assessed adherence to key indicators of pain assessment and management. Feasibility thresholds were set at 75% incidence for screening and a median of 30 minutes per patient for audit. RESULTS: Of 452 patient visits, 95% (n = 429) were successfully screened, 34% (n = 155) electronically and 61% (n = 274) paper-based. Electronic pain screening was technically challenging and time-intensive for nurses. Thirty-one patients consented to have their records audited. The median audit time was 37.5 minutes (range 10-120 minutes). Variability arose from the number and type of record (outpatient or inpatient). Adherence to indicators varied from 63% (pain assessment at first presentation) to 94% (regular pain assessment and medication prescribed at regular intervals). CONCLUSIONS: This study confirmed the need to implement evidence-based guidelines for cancer pain and generated useful insights into the feasibility of pain screening and audit.

Therapeutic Alliance With a Fully Automated Mobile Phone and Web-Based Intervention: Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: Studies of Internet-delivered psychotherapies suggest that clients report development of a therapeutic alliance in the Internet environment. Because a majority of the interventions studied to date have been therapist-assisted to some degree, it remains unclear whether a therapeutic alliance can develop within the context of an Internet-delivered self-guided intervention with no therapist support, and whether this has consequences for program outcomes. OBJECTIVE: This study reports findings of a secondary analysis of data from 90 participants with mild-to-moderate depression, anxiety, and/or stress who used a fully automated mobile phone and Web-based cognitive behavior therapy (CBT) intervention called "myCompass" in a recent randomized controlled trial (RCT). METHODS: Symptoms, functioning, and positive well-being were assessed at baseline and post-intervention using the Depression, Anxiety and Stress Scale (DASS), the Work and Social Adjustment Scale (WSAS), and the Mental Health Continuum-Short Form (MHC-SF). Therapeutic alliance was measured at post-intervention using the Agnew Relationship Measure (ARM), and this was supplemented with qualitative data obtained from 16 participant interviews. Extent of participant engagement with the program was also assessed. RESULTS: Mean ratings on the ARM subscales were above the neutral midpoints, and the interviewees provided rich detail of a meaningful and collaborative therapeutic relationship with the myCompass program. Whereas scores on the ARM subscales did not correlate with treatment outcomes, participants' ratings of the quality of their emotional connection with the program correlated significantly and positively with program logins, frequency of self-monitoring, and number of treatment modules completed (r values between .32-.38, P≤.002). The alliance (ARM) subscales measuring perceived empowerment (r=.26, P=.02) and perceived freedom to self-disclose (r=.25, P=.04) also correlated significantly in a positive direction with self-monitoring frequency. CONCLUSIONS: Quantitative and qualitative findings from this analysis showed that a positive therapeutic alliance can develop in the Internet environment in the absence of therapist support, and that components of the alliance may have implications for program usage. Further investigation of alliance features in the Internet environment and the consequences of these for treatment outcomes and user engagement is warranted. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Number (ACTRN): 12610000625077; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=335772&isReview=true (Archived by WebCite at http://www.webcitation.org/6efAc5xj4).

Breaking Open the Black Box: Isolating the Most Potent Features of a Web and Mobile Phone-Based Intervention for Depression, Anxiety, and Stress.

BACKGROUND: Internet-delivered mental health (eMental Health) interventions produce treatment effects similar to those observed in face-to-face treatment. However, there is a large degree of variation in treatment effects observed from program to program, and eMental Health interventions remain somewhat of a black box in terms of the mechanisms by which they exert their therapeutic benefit. Trials of eMental Health interventions typically use large sample sizes and therefore provide an ideal context within which to systematically investigate the therapeutic benefit of specific program features. Furthermore, the growth and impact of mobile phone technology within eMental Health interventions provides an opportunity to examine associations between symptom improvement and the use of program features delivered across computer and mobile phone platforms. OBJECTIVE: The objective of this study was to identify the patterns of program usage associated with treatment outcome in a randomized controlled trial (RCT) of a fully automated, mobile phone- and Web-based self-help program, "myCompass", for individuals with mild-to-moderate symptoms of depression, anxiety, and/or stress. The core features of the program include interactive psychotherapy modules, a symptom tracking feature, short motivational messages, symptom tracking reminders, and a diary, with many of these features accessible via both computer and mobile phone. METHODS: Patterns of program usage were recorded for 231 participants with mild-to-moderate depression, anxiety, and/or stress, and who were randomly allocated to receive access to myCompass for seven weeks during the RCT. Depression, anxiety, stress, and functional impairment were examined at baseline and at eight weeks. RESULTS: Log data indicated that the most commonly used components were the short motivational messages (used by 68.4%, 158/231 of participants) and the symptom tracking feature (used by 61.5%, 142/231 of participants). Further, after controlling for baseline symptom severity, increased use of these alert features was associated with significant improvements in anxiety and functional impairment. Associations between use of symptom tracking reminders and improved treatment outcome remained significant after controlling for frequency of symptom tracking. Although correlations were not statistically significant, reminders received via SMS (ie, text message) were more strongly associated with symptom reduction than were reminders received via email. CONCLUSIONS: These findings indicate that alerts may be an especially potent component of eMental Health interventions, both via their association with enhanced program usage, as well as independently. Although there was evidence of a stronger association between symptom improvement and use of alerts via the mobile phone platform, the degree of overlap between use of email and SMS alerts may have precluded identification of alert delivery modalities that were most strongly associated with symptom reduction. Future research using random assignment to computer and mobile delivery is needed to fully determine the most ideal platform for delivery of this and other features of online interventions. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN): 12610000625077; http://www.anzctr.org.au/TrialSearch.aspx? (Archived by WebCite http://www.webcitation.org/6WPqHK0mQ).

Effects of mental health self-efficacy on outcomes of a mobile phone and web intervention for mild-to-moderate depression, anxiety and stress: secondary analysis of a randomised controlled trial.

BACKGROUND: Online psychotherapy is clinically effective yet why, how, and for whom the effects are greatest remain largely unknown. In the present study, we examined whether mental health self-efficacy (MHSE), a construct derived from Bandura's Social Learning Theory (SLT), influenced symptom and functional outcomes of a new mobile phone and web-based psychotherapy intervention for people with mild-to-moderate depression, anxiety and stress. METHODS: STUDY I: Data from 49 people with symptoms of depression, anxiety and/or stress in the mild-to-moderate range were used to examine the reliability and construct validity of a new measure of MHSE, the Mental Health Self-efficacy Scale (MHSES). STUDY II: We conducted a secondary analysis of data from a recently completed randomised controlled trial (N = 720) to evaluate whether MHSE effected post-intervention outcomes, as measured by the Depression, Anxiety and Stress Scales (DASS) and Work and Social Adjustment Scale (WSAS), for people with symptoms in the mild-to-moderate range. RESULTS: STUDY I: The data established that the MHSES comprised a unitary factor, with acceptable internal reliability (Cronbach's alpha = .89) and construct validity. STUDY II: The intervention group showed significantly greater improvement in MHSE at post-intervention relative to the control conditions (p's < = .000). MHSE mediated the effects of the intervention on anxiety and stress symptoms. Furthermore, people with low pre-treatment MHSE reported the greatest post-intervention gains in depression, anxiety and overall distress. No effects were found for MHSE on work and social functioning. CONCLUSION: Mental health self-efficacy influences symptom outcomes of a self-guided mobile phone and web-based psychotherapeutic intervention and may itself be a worthwhile target to increase the effectiveness and efficiency of online treatment programs. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12610000625077.

Impact of a mobile phone and web program on symptom and functional outcomes for people with mild-to-moderate depression, anxiety and stress: a randomised controlled trial.

BACKGROUND: Mobile phone-based psychological interventions enable real time self-monitoring and self-management, and large-scale dissemination. However, few studies have focussed on mild-to-moderate symptoms where public health need is greatest, and none have targeted work and social functioning. This study reports outcomes of a CONSORT-compliant randomised controlled trial (RCT) to evaluate the efficacy of myCompass, a self-guided psychological treatment delivered via mobile phone and computer, designed to reduce mild-to-moderate depression, anxiety and stress, and improve work and social functioning. METHOD: Community-based volunteers with mild-to-moderate depression, anxiety and/or stress (N = 720) were randomly assigned to the myCompass program, an attention control intervention, or to a waitlist condition for seven weeks. The interventions were fully automated, without any human input or guidance. Participants' symptoms and functioning were assessed at baseline, post-intervention and 3-month follow-up, using the Depression, Anxiety and Stress Scale and the Work and Social Adjustment Scale. RESULTS: Retention rates at post-intervention and follow-up for the study sample were 72.1% (n = 449) and 48.6% (n = 350) respectively. The myCompass group showed significantly greater improvement in symptoms of depression, anxiety and stress and in work and social functioning relative to both control conditions at the end of the 7-week intervention phase (between-group effect sizes ranged from d = .22 to d = .55 based on the observed means). Symptom scores remained at near normal levels at 3-month follow-up. Participants in the attention control condition showed gradual symptom improvement during the post-intervention phase and their scores did not differ from the myCompass group at 3-month follow-up. CONCLUSIONS: The myCompass program is an effective public health program, facilitating rapid improvements in symptoms and in work and social functioning for individuals with mild-to-moderate mental health problems. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN 12610000625077.

Smartphones for smarter delivery of mental health programs: a systematic review.

BACKGROUND: The rapid growth in the use of mobile phone applications (apps) provides the opportunity to increase access to evidence-based mental health care. OBJECTIVE: Our goal was to systematically review the research evidence supporting the efficacy of mental health apps for mobile devices (such as smartphones and tablets) for all ages. METHODS: A comprehensive literature search (2008-2013) in MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, PsycINFO, PsycTESTS, Compendex, and Inspec was conducted. We included trials that examined the effects of mental health apps (for depression, anxiety, substance use, sleep disturbances, suicidal behavior, self-harm, psychotic disorders, eating disorders, stress, and gambling) delivered on mobile devices with a pre- to posttest design or compared with a control group. The control group could consist of wait list, treatment-as-usual, or another recognized treatment. RESULTS: In total, 5464 abstracts were identified. Of those, 8 papers describing 5 apps targeting depression, anxiety, and substance abuse met the inclusion criteria. Four apps provided support from a mental health professional. Results showed significant reductions in depression, stress, and substance use. Within-group and between-group intention-to-treat effect sizes ranged from 0.29-2.28 and 0.01-0.48 at posttest and follow-up, respectively. CONCLUSIONS: Mental health apps have the potential to be effective and may significantly improve treatment accessibility. However, the majority of apps that are currently available lack scientific evidence about their efficacy. The public needs to be educated on how to identify the few evidence-based mental health apps available in the public domain to date. Further rigorous research is required to develop and test evidence-based programs. Given the small number of studies and participants included in this review, the high risk of bias, and unknown efficacy of long-term follow-up, current findings should be interpreted with caution, pending replication. Two of the 5 evidence-based mental health apps are currently commercially available in app stores.

Selected variants of the steroid-5-alpha-reductase isoforms SRD5A1 and SRD5A2 and the sex steroid hormone receptors ESR1, ESR2 and PGR: no association with female pattern hair loss identified.

Female pattern hair loss (FPHL) is a common disorder with a complex mode of inheritance. Although understanding of its etiopathogenesis is incomplete, an interaction between genetic and hormonal factors is assumed to be important. The involvement of an androgen-dependent pathway and sex steroid hormones is the most likely hypothesis. We therefore selected a total of 21 variants from the steroid-5-alpha-reductase isoforms SRD5A1 and SRD5A2, the sex steroid hormone receptors ESR1, ESR2 (oestrogen receptor) and PGR (progesterone receptor) and genotyped these in a case-control sample of 198 patients (145 UK; 53 German patients) and 329 controls (179 UK; 150 German). None of these variants showed any significant association, either in the overall UK and German samples or in the subgroup analyses. In summary, the present results, while based on a limited selection of gene variants, do not point to the involvement of SRD5A1, SRD5A2, ESR1, ESR2 or PGR in FPHL.

Host predisposition by endogenous Transforming Growth Factor-beta1 overexpression promotes pulmonary fibrosis following bleomycin injury.

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is a progressive diffuse disease involving the lung parenchyma. Despite recent advances, the molecular mechanisms of the initiation and progression of this disease remain elusive. Previous studies have demonstrated TGFbeta1 as a key effector cytokine in the development of lung fibrosis. METHODS: In this study we have used a transgenic mouse based strategy to identify the effect of overexpression of this key effector mediator on the development of pulmonary fibrosis in response to exogenous injury. We bred two lines (line 25 and 18) of transgenic mice (Tr+) that overexpressed active TGFbeta1. Three-month old transgenic and wild type mice were subsequently wounded with intraperitoneal bleomycin. Mice were sacrificed at 6 weeks post-bleomycin and their lungs analysed histologically and biochemically. RESULTS: The severity of lung fibrosis was significantly greater in the Tr+ mice compared to the wild type mice. Using an oligonucleotide microarray based strategy we identified discrete patterns of gene expression contributing to TGFbeta1 associated pulmonary fibrosis. CONCLUSION: This data emphasises the importance of a host predisposition in the form of endogenous TGFbeta1, in the development of pulmonary fibrosis in response to an exogenous injury.

Animal models for adult dermal wound healing.

Wound healing in adult mammals proceeds by a series of overlapping highly coordinated events. Dermal wound repair commences with the arrest of hemorrhage followed by an inflammatory response, re-epithelialization of the wound, and formation of granulation tissue within the wound space, culminating in the production of a scar. In order to study the processes involved in the repair of wounded tissue, we have developed a rodent model utilizing full thickness incisional and excisional dermal wounds, which allow for macroscopic observations and also provide tissue for the histological and immunocytochemical analysis of acute wounds and scarring.

Primary postpartum haemorrhage in an Australian tertiary hospital: a case-control study.

The present study aimed to determine the incidence of primary postpartum haemorrhage (PPH) after vaginal birth at an Australian tertiary hospital, and to investigate risk factors for primary PPH at this hospital. A case-control study of women delivering vaginally at a tertiary hospital from February to June 2003 was performed. Demographic, antenatal, intrapartum, treatment and outcome data were abstracted from patient records. The study population comprised 125 cases and 125 controls, with a primary PPH rate of 12.1 per 100 vaginal births. Risk factors on multivariate analysis were past history of PPH, second stage labour > 60 min, forceps delivery, and incomplete placenta/ragged membranes.