Habituation of the cold shock response: A systematic review and meta-analysis.

Cold water immersion (CWI) evokes the life-threatening reflex cold shock response (CSR), inducing hyperventilation, increasing cardiac arrhythmias, and increasing drowning risk by impairing safety behaviour. Repeated CWI induces CSR habituation (i.e., diminishing response with same stimulus magnitude) after ∼4 immersions, with variation between studies. We quantified the magnitude and coefficient of variation (CoV) in the CSR in a systematic review and meta-analysis with search terms entered to Medline, SportDiscus, PsychINFO, Pubmed, and Cochrane Central Register. Random effects meta-analyses, including effect sizes (Cohen's d) from 17 eligible groups (k), were conducted for heart rate (HR, n = 145, k = 17), respiratory frequency (fR, n = 73, k = 12), minute ventilation (Ve, n = 106, k = 10) and tidal volume (Vt, n = 46, k=6). All CSR variables habituated (p < 0.001) with large or moderate pooled effect sizes: ΔHR -14 (10) bt. min-1 (d: -1.19); ΔfR -8 (7) br. min-1 (d: -0.78); ΔVe, -21.3 (9.8) L. min-1 (d: -1.64); ΔVt -0.4 (0.3) L -1. Variation was greatest in Ve (control vs comparator immersion: 32.5&24.7%) compared to Vt (11.8&12.1%). Repeated CWI induces CSR habituation potentially reducing drowning risk. We consider the neurophysiological and behavioural consequences.

Pharmacy-based management for depression in adults.

BACKGROUND: It is common for peoples not to take antidepressant medication as prescribed, with around 50% of people likely to prematurely discontinue taking their medication after six months. Community pharmacists may be well placed to have a role in antidepressant management because of their unique pharmacotherapeutic knowledge and ease of access for people. Pharmacists are in an ideal position to offer proactive interventions to people with depression or depressive symptoms. However, the effectiveness and acceptability of existing pharmacist-based interventions is not yet well understood. The degree to which a pharmacy-based management approach might be beneficial, acceptable to people, and effective as part of the overall management for those with depression is, to date, unclear. A systematic review of randomised controlled trials (RCTs) will help answer these questions and add important knowledge to the currently sparse evidence base. OBJECTIVES: To examine the effects of pharmacy-based management interventions compared with active control (e.g. patient information materials or any other active intervention delivered by someone other than the pharmacist or the pharmacy team), waiting list, or treatment as usual (e.g. standard pharmacist advice or antidepressant education, signposting to support available in primary care services, brief medication counselling, and/or (self-)monitoring of medication adherence offered by a healthcare professional outside the pharmacy team) at improving depression outcomes in adults. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMD-CTR) to June 2016; the Cochrane Library (Issue 11, 2018); and Ovid MEDLINE, Embase, and PsycINFO to December 2018. We searched theses and dissertation databases and international trial registers for unpublished/ongoing trials. We applied no restrictions on date, language, or publication status to the searches.  SELECTION CRITERIA: We included all RCTs and cluster-RCTs where a pharmacy-based intervention was compared with treatment as usual, waiting list, or an alternative intervention in the management of depression in adults over 16 years of age. Eligible studies had to report at least one of the following outcomes at any time point: depression symptom change, acceptability of the intervention, diagnosis of depression, non-adherence to medication, frequency of primary care appointments, quality of life, social functioning, or adverse events.  DATA COLLECTION AND ANALYSIS: Two authors independently, and in duplicate, conducted all stages of study selection, data extraction, and quality assessment (including GRADE). We discussed disagreements within the team until we reached consensus. Where data did not allow meta-analyses, we synthesised results narratively.  MAIN RESULTS: Twelve studies (2215 participants) met the inclusion criteria and compared pharmacy-based management with treatment as usual. Two studies (291 participants) also included an active control (both used patient information leaflets providing information about the prescribed antidepressant). Neither of these studies reported depression symptom change. A narrative synthesis of results on acceptability of the intervention was inconclusive, with one study reporting better acceptability of pharmacy-based management and the other better acceptability of the active control. One study reported that participants in the pharmacy-based management group had better medication adherence than the control participants. One study reported adverse events with no difference between groups. The studies reported no other outcomes. Meta-analyses comparing pharmacy-based management with treatment as usual showed no evidence of a difference in the effect of the intervention on depression symptom change (dichotomous data; improvement in symptoms yes/no: risk ratio (RR), 0.95, 95% confidence interval (CI) 0.86 to 1.05; 4 RCTs, 475 participants; moderate-quality evidence; continuous data: standard mean difference (SMD) -0.04, 95% CI -0.19 to 0.10; 5 RCTs, 718 participants; high-certainty evidence), or acceptability of the intervention (RR 1.09, 95% CI 0.81 to 1.45; 12 RCTs, 2072 participants; moderate-certainty evidence). The risk of non-adherence was reduced in participants receiving pharmacy-based management (RR 0.73, 95% CI 0.61 to 0.87; 6 RCTs, 911 participants; high-certainty evidence). We were unable to meta-analyse data on diagnosis of depression, frequency of primary care appointments, quality of life, or social functioning. AUTHORS' CONCLUSIONS: We found no evidence of a difference between pharmacy-based management for depression in adults compared with treatment as usual in facilitating depression symptom change. Based on numbers of participants leaving the trials early, there may be no difference in acceptability between pharmacy-based management and controls. However, there was uncertainty due to the low-certainty evidence.

Adult report of childhood imaginary companions and adversity relates to concurrent prodromal psychosis symptoms.

Hallucination and dissociation have been found to be associated with imaginary friend play in childhood (CIC). Past studies have not investigated how this play relates to adult prodromal symptoms or how childhood adversity mediates the relationship. CIC play was examined in 278 participants, 18-24 years. CIC status predicted prodromal symptoms of hallucination only, whereas childhood adversity predicted all other symptoms. Mediation analysis found CIC's relation to hallucination symptoms was partially mediated by childhood adversity. Findings fit with views that CIC are a positive childhood experience which may convert to a negative developmental trajectory through the impact of childhood adversity.

Feasibility of training practice nurses to deliver a psychosocial intervention within a collaborative care framework for people with depression and long-term conditions.

BACKGROUND: Practice nurses (PNs) deliver much of the chronic disease management in primary care and have been highlighted as appropriately placed within the service to manage patients with long-term physical conditions (LTCs) and co-morbid depression. This nested qualitative evaluation within a service development pilot provided the opportunity to examine the acceptability of a Brief Behavioural Activation (BBA) intervention within a collaborative care framework. Barriers and facilitators to engaging with the intervention from the patient and clinician perspective will be used to guide future service development and research. METHODS: The study was conducted across 8 practices in one Primary Care Trust 1 in England. Through purposive sampling professionals (n = 10) taking part in the intervention (nurses, GPs and a mental health gateway worker) and patients (n = 4) receiving the intervention participated in semi-structured qualitative interviews. Analysis utilised the four Normalisation Process Theory (NPT) concepts of coherence, cognitive participation, collective action and reflexive monitoring to explore the how this intervention could be implemented in practice. RESULTS: Awareness of depression and the stigma associated with the label of depression meant that, from a patient perspective a PN being available to 'listen' was perceived as valuable. Competing practice priorities, perceived lack of time and resources, and lack of engagement by the whole practice team were considered the greatest barriers to the implementation of this intervention in routine primary care. CONCLUSION: Lack of understanding of, participation in, and support from the whole practice team in the collaborative care model exacerbated the pressures perceived by PNs. The need for formal supervision of PNs to enable them to undertake the role of case manager for patients with depression and long-term conditions is emphasised.

Behavioural activation therapy for adolescents 'at risk' for psychosis?

The following hypothesis explores the possibility of using behavioural activation therapy for adolescents with an at-risk mental state for psychosis. Support is drawn from psychosis-related survey and pilot data as well as a robust evidence base for adult depression. However, we acknowledge that extensive feasibility work is required before exploring this hypothesis further.

Getting it right! Enhancing youth involvement in mental health research.

BACKGROUND: Few studies relating to youth mental health have actively involved young people in the design and conduct of research. AIMS: This qualitative study explores the perceptions of young people about involving them in mental health research. METHOD: An opportunistic sample of eight young people (aged 14-24 years) from non-statutory mental health organizations was interviewed. Interviews were transcribed verbatim, and inductive thematic analysis was conducted. RESULTS: Six key themes emerged reflecting a desire for young people to have the opportunity to actively contribute to every stage of the research process. Meaningful research involvement was perceived as offering opportunities to develop personal skills, contribute to making a difference and ensuring research projects were more relevant. CONCLUSIONS: Young people with an active interest in mental health promotion demonstrate a desire to be involved in research with training in research methods likely to facilitate this process. Researchers need training on how best to actively and meaningfully involve young people in mental health research.

Behavioural activation for depression; an update of meta-analysis of effectiveness and sub group analysis.

BACKGROUND: Depression is a common, disabling condition for which psychological treatments are recommended. Behavioural activation has attracted increased interest in recent years. It has been over 5 years since our meta-analyses summarised the evidence supporting and this systematic review updates those findings and examines moderators of treatment effect. METHOD: Randomised trials of behavioural activation for depression versus controls or anti-depressant medication were identified using electronic database searches, previous reviews and reference lists. Data on symptom level and study level moderators were extracted and analysed using meta-analysis, sub-group analysis and meta-regression respectively. RESULTS: Twenty six randomised controlled trials including 1524 subjects were included in this meta-analysis. A random effects meta-analysis of symptom level post treatment showed behavioural activation to be superior to controls (SMD -0.74 CI -0.91 to -0.56, k = 25, N = 1088) and medication (SMD -0.42 CI -0.83 to-0.00, k = 4, N = 283). Study quality was low in the majority of studies and follow- up time periods short. There was no indication of publication bias and subgroup analysis showed limited association between moderators and effect size. CONCLUSIONS: The results in this meta-analysis support and strengthen the evidence base indicating Behavioural Activation is an effective treatment for depression. Further high quality research with longer term follow-up is needed to strengthen the evidence base.

Comparison of the sensitivity of the UKCAT and A Levels to sociodemographic characteristics: a national study.

BACKGROUND: The UK Clinical Aptitude Test (UKCAT) was introduced to facilitate widening participation in medical and dental education in the UK by providing universities with a continuous variable to aid selection; one that might be less sensitive to the sociodemographic background of candidates compared to traditional measures of educational attainment. Initial research suggested that males, candidates from more advantaged socioeconomic backgrounds and those who attended independent or grammar schools performed better on the test. The introduction of the A* grade at A level permits more detailed analysis of the relationship between UKCAT scores, secondary educational attainment and sociodemographic variables. Thus, our aim was to further assess whether the UKCAT is likely to add incremental value over A level (predicted or actual) attainment in the selection process. METHODS: Data relating to UKCAT and A level performance from 8,180 candidates applying to medicine in 2009 who had complete information relating to six key sociodemographic variables were analysed. A series of regression analyses were conducted in order to evaluate the ability of sociodemographic status to predict performance on two outcome measures: A level 'best of three' tariff score; and the UKCAT scores. RESULTS: In this sample A level attainment was independently and positively predicted by four sociodemographic variables (independent/grammar schooling, White ethnicity, age and professional social class background). These variables also independently and positively predicted UKCAT scores. There was a suggestion that UKCAT scores were less sensitive to educational background compared to A level attainment. In contrast to A level attainment, UKCAT score was independently and positively predicted by having English as a first language and male sex. CONCLUSIONS: Our findings are consistent with a previous report; most of the sociodemographic factors that predict A level attainment also predict UKCAT performance. However, compared to A levels, males and those speaking English as a first language perform better on UKCAT. Our findings suggest that UKCAT scores may be more influenced by sex and less sensitive to school type compared to A levels. These factors must be considered by institutions utilising the UKCAT as a component of the medical and dental school selection process.

Improving care transitions: optimizing medication reconciliation.

OBJECTIVE: To improve understanding of the medication reconciliation process, its effect on patient care and outcomes, and how pharmacists can contribute to improving this process using a standardized framework of service delivery defined in the context of medication therapy management. SUMMARY: Medication reconciliation is an integral part of the care transitions process in which health care professionals collaborate to improve medication safety as the patient transitions between patient care settings or levels of care. In 2005, medication reconciliation came to the forefront of health care when the Joint Commission on Accreditation designated it as a National Patient Safety Goal. Although individual health professionals have different roles in the process, the overall focus of the medication reconciliation process is on global patient safety and improved patient outcomes. CONCLUSION: Medication reconciliation research has been increasing, but more studies are needed on the implementation and adoption of effective medication reconciliation processes, with emphasis on the identification of current best practices for medication reconciliation. The application of the foundational concepts in this publication and future work on the enhancement of the medication reconciliation process will help to improve patient safety and patient care outcomes during care transitions.

The episodic nature of episodic-like memories.

Studying episodic memory in nonhuman animals has proved difficult because definitions in humans require conscious recollection. Here, we assessed humans' experience of episodic-like recognition memory tasks that have been used with animals. It was found that tasks using contextual information to discriminate events could only be accurately performed using recollection, not familiarity. However, tasks using temporal information to discriminate events could be accurately performed using either recollection or familiarity. The results strengthen the position that some episodic-like recognition memory tasks are a valid model of episodic memory. However, tasks that rely on temporal information may be susceptible to nonepisodic strategies.

Health information technology: A new world for pharmacy.

OBJECTIVES: To provide a health information technology (HIT) primer for pharmacists, including the current state of HIT, future expectations, basic information and vocabulary, HIT vendors, communication standards, barriers to implementation, and strategies for pharmacists to ensure success. DATA SOURCES: By the authors. SUMMARY: HIT is expected to provide integrated electronic health care with interactive exchange among patients, providers, government agencies, and insurers, resulting in an increase in the overall quality, safety, and efficiency of health care delivery with fewer medical errors, increased administrative efficiency, decreased health care costs, and expanded patient access to affordable health care. Government incentives are in place in an effort to expedite the nationwide implementation of HIT. CONCLUSION: With the government and IT industry applying pressure, HIT is a reality; the only remaining questions are how quickly and how thoroughly HIT will affect the health care system.

Binocular coordination during reading and non-reading tasks.

The goal of this review is to evaluate the literature on binocular coordination during reading and non-reading tasks in adult, child, and dyslexic populations. The review begins with a description of the basic characteristics of eye movements during reading. Then, reading and non-reading studies investigating binocular coordination are evaluated. Areas of future research in the field are identified and discussed. Finally, some general conclusions are made regarding binocular coordination. The review demonstrates that findings from traditionally independent areas of research are largely consistent and complementary. Throughout the review, theoretical and methodological commonalities are identified and clarified in order to advance current understanding of this fundamental aspect of human visual processing.

Early placental insulin-like protein (INSL4 or EPIL) in placental and fetal membrane growth.

Early placental insulin-like protein (INSL4 or EPIL) is a member of the insulin superfamily of hormones, which is highly expressed in the placenta. We have confirmed this at term and shown it to be expressed by the maternal decidua. Although an abundance of locally acting growth factors are produced within the uterus during pregnancy, we hypothesized that INSL4 plays an important role in fetal and placental growth. We have demonstrated with cell lines and primary cells that it has a growth-inhibitory effect by causing apoptosis and loss of cell viability. We used primary amniotic epithelial cells for flow cytometry to show that INSL4 caused apoptosis, which was dose-related and significant (P < 0.05) at 50 ng/ml. This was confirmed by measurement of the nuclear matrix protein in the media. In comparison, relaxin treatment (up to 200 ng/ml) had no effect on apoptosis. The addition of INSL4 (3-30 ng/ml) also caused a loss of cell viability, although it had no effect on the numbers of cells at different phases of the cell cycle. Placental apoptosis is an important process in both normal placental development and in fetal growth restriction. Therefore, an in vivo clinical correlate was sought in fraternal twins exhibiting discordant growth. Expression of the INSL4 gene was doubled in the placenta of the growth-restricted twin compared to the normally grown sibling, suggesting that it may be linked to a higher level of apoptosis and loss of cell viability and, therefore, that it may contribute to fetal growth restriction.

Human decidual relaxin and preterm birth.

Relaxin in human pregnancy is both a systemic hormone from the corpus luteum and an autocrine/paracrine hormone at the maternal-fetal interface formed by the decidua/placenta and fetal membranes. We have focused our studies on the autocrine/paracrine roles of relaxin, especially in the preterm premature rupture of the fetal membranes, which causes 30-40% of preterm births. By using different techniques and different tissue collections, our laboratory has shown that expression of the relaxin genes and proteins in the decidua and placenta is increased in patients with preterm premature rupture of the fetal membranes. Relaxin binding and the expression of LGR7 are primarily in the chorion and decidua and are downregulated after spontaneous labor and delivery both at term and preterm. However, expression of LGR7 in the fetal membranes is significantly greater in all clinical situations at preterm than term, suggesting an important role for relaxin in these tissues at that time. The roles of the relaxin system in three potential causes of preterm birth are discussed: in the growth and proliferation of the membranes important for fetal membrane accommodation to fetal and placental growth, in acute infection, and in the inflammatory response leading to the initiation of labor.

Relaxin causes proliferation of human amniotic epithelium by stimulation of insulin-like growth factor-II.

OBJECTIVE: The study was conducted to determine whether relaxin has a proliferative effect on amniotic epithelial cells and to show that this effect is caused by its stimulation of the insulin-like growth factor-II (IGF-II) gene. STUDY DESIGN: Immunolocalization and Northern analysis were used to confirm the expression of IGF-II by the fetal cells in the membranes. Human amniotic epithelial (WISH) cells were treated with doses of IGF-II or human relaxin and their proliferative effects measured. The mechanism of the effect of relaxin on cellular proliferation was studied with the use of an IGF-II-blocking antibody and Northern analysis for IGF-II gene expression after treatment with relaxin. An in vivo correlate was sought by quantitation of relaxin gene expression in 10 fetal membranes from women with normally grown and large for gestational age infants. RESULTS: The amniotic epithelial and cytotrophoblast cells of the fetal membranes expressed IGF-II, as did the amniotic epithelial-like (WISH) cell line. Treatment of WISH cells with IGF-II or relaxin caused a significant (P <.03) and dose-related increase in WISH cell proliferation over 5 days. The concurrent treatment with a blocking antibody to IGF-II significantly decreased the proliferative response to IGF-II (P <.002) and relaxin (P <.002). Treatment with relaxin caused a significant increase (P <.003) in the transcription of IGF-II in 24 hours. In fetal membranes, the levels of relaxin gene expression correlated with fetal membrane surface area (r = 0.76) and was significantly greater (P <.008) in the membranes from macrosomic infants (4020-4729 g) compared with those normally grown (2855-3830 g). CONCLUSION: IGF-II and relaxin both caused the proliferation of WISH cells. Concurrent treatment with an IGF-II-blocking antibody abrogated the proliferative effects of both hormones. Relaxin increased the transcription of IGF-II, and its expression levels in the fetal membranes correlated with the membrane surface area as well as neonatal birth weight. These data suggest that relaxin is a growth factor for the fetal membranes.