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BACKGROUND Relapse is common in people who experience psychosis and is associated with many negative consequences, both societal and personal. People who relapse often exhibit changes (early warning signs [EWS]) in the period before relapse. Successful identification of EWS offers an opportunity for relapse prevention. However, several known barriers impede the use of EWS monitoring approaches. Early signs Monitoring to Prevent relapse in psychosis and prOmote Well-being, Engagement, and Recovery (EMPOWER) is a complex digital intervention that uses a mobile app to enhance the detection and management of self-reported changes in well-being. This is currently being tested in a pilot cluster randomized controlled trial. As digital interventions have not been widely used in relapse prevention, little is known about their implementation. Process evaluation studies run in parallel to clinical trials can provide valuable data on intervention feasibility. OBJECTIVE This study aims to transparently describe the protocol for the process evaluation element of the EMPOWER trial. We will focus on the development of a process evaluation framework sensitive to the worldview of service users, mental health staff, and carers; the aims of the process evaluation itself; the proposed studies to address these aims; and a plan for integration of results from separate process evaluation studies into one overall report. METHODS The overall process evaluation will utilize mixed methods across 6 substudies. Among them, 4 will use qualitative methodologies, 1 will use a mixed methods approach, and 1 will use quantitative methodologies. RESULTS The results of all studies will be triangulated into an overall analysis and interpretation of key implementation lessons. EMPOWER was funded in 2016, recruitment finished in January 2018. Data analysis is currently under way and the first results are expected to be submitted for publication in December 2019. CONCLUSIONS The findings from this study will help identify implementation facilitators and barriers to EMPOWER. These insights will inform both upscaling decisions and optimization of a definitive trial. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/15634

Sleep problems are highly prevalent in bipolar disorder (BD) and constitute an important therapeutic focus in this population: They are highly impairing and distressing, are an area of subjective importance to consumers, and likely play a role in predicting/triggering mood episodes. The aim of this review is to orient psychologists and psychotherapists to current research relevant to their clinical practice with people with BD, including (a) the prevalence and presentation of sleep problems, (b) the impacts and correlates of impaired sleep, and (c) the relationship between sleep problems and mood symptoms (including the predictive/triggering role of sleep in BD mood relapses). Detailed recommendations for assessment and cognitive-behavioural intervention strategies for use in BD are described. It will be concluded that although some sleep problems and comorbidities require interdisciplinary collaboration, a range of evidence-informed strategies can be effectively and appropriately applied by clinical psychologists and psychotherapists.

BACKGROUND Relapse in schizophrenia is a major cause of distress and disability and is predicted by changes in symptoms such as anxiety, depression, and suspiciousness (early warning signs [EWSs]). These can be used as the basis for timely interventions to prevent relapse. However, there is considerable uncertainty regarding the implementation of EWS interventions. OBJECTIVE This study was designed to establish the feasibility of conducting a definitive cluster randomized controlled trial comparing Early signs Monitoring to Prevent relapse in psychosis and prOmote Well-being, Engagement, and Recovery (EMPOWER) against treatment as usual (TAU). Our primary outcomes are establishing parameters of feasibility, acceptability, usability, safety, and outcome signals of a digital health intervention as an adjunct to usual care that is deliverable in the UK National Health Service and Australian community mental health service (CMHS) settings. We will assess the feasibility of candidate primary outcomes, candidate secondary outcomes, and candidate mechanisms for a definitive trial. METHODS We will randomize CMHSs to EMPOWER or TAU. We aim to recruit up to 120 service user participants from 8 CMHSs and follow them for 12 months. Eligible service users will (1) be aged 16 years and above, (2) be in contact with local CMHSs, (3) have either been admitted to a psychiatric inpatient service or received crisis intervention at least once in the previous 2 years for a relapse, and (4) have an International Classification of Diseases-10 diagnosis of a schizophrenia-related disorder. Service users will also be invited to nominate a carer to participate. We will identify the feasibility of the main trial in terms of recruitment and retention to the study and the acceptability, usability, safety, and outcome signals of the EMPOWER intervention. EMPOWER is a mobile phone app that enables the monitoring of well-being and possible EWSs of relapse on a daily basis. An algorithm calculates changes in well-being based on participants’ own baseline to enable tailoring of well-being messaging and clinical triage of possible EWSs. Use of the app is blended with ongoing peer support. RESULTS Recruitment to the trial began September 2018, and follow-up of participants was completed in July 2019. Data collection is continuing. The database was locked in July 2019, followed by analysis and disclosing of group allocation. CONCLUSIONS The knowledge gained from the study will inform the design of a definitive trial including finalizing the delivery of our digital health intervention, sample size estimation, methods to ensure successful identification, consent, randomization, and follow-up of participants, and the primary and secondary outcomes. The trial will also inform the final health economic model to be applied in the main trial. CLINICALTRIAL International Standard Randomized Controlled Trial Number (ISRCTN): 99559262; http://isrctn.com/ISRCTN99559262

Sleep and circadian rhythms have been implicated in the onset, course, and treatment of bipolar disorder. The aim of the present review is to provide an update on emerging understandings of the role of sleep in BD. Recent research in this population has provided further clarity around the prevalence of sleep problems and comorbidities, their relationship to mood symptoms and other clinical features, and their assessment and treatment. A number of important trends are highlighted: the need for more granularity in the characterisation of sleep problems, the potentially disruptive role of commercial sleep monitoring technologies in assessment and treatment, and the urgent need for further research into pharmacological and psychosocial strategies to treat sleep problems in bipolar disorder.

Background Few studies have examined sex-specific associations of maternal gestational glycemia with cord blood hormones, which might predict later health. Methods In 976 women without pre-existing diabetes in the Project Viva cohort, we used linear regression to examine associations of maternal gestational glycemia with cord hormone concentrations, adjusted for maternal characteristics and stratified by infant sex. Results A total of 6.1% of women had gestational diabetes mellitus (GDM), 8.8% isolated hyperglycemia, 3.2% gestational impaired glucose tolerance, and 81.9% were normoglycemic. In boys, compared with infants of normoglycemic mothers, infants of GDM mothers had higher cord levels of IGF-2 (β 35.55 ng/mL; 95% CI: 2.60, 68.50), IGFBP-3 (111.2 ng/mL; 5.53, 216.8), insulin (4.66 uU/mL; 2.38, 6.95), C-peptide (0.46 ng/mL; 0.25, 0.67), and leptin (3.51 ng/mL; 1.37, 5.64), but lower IGF-1 (−6.71 ng/mL; −12.7, − 0.76, adjusted for IGFBP-3). In girls, GDM offspring had higher cord blood levels of IGF-1 adjusted for IGFBP-3 (12.45 ng/mL; 4.85, 20.04). Boys, but not girls, of mothers with abnormal glucose tolerance but not GDM also had higher levels of some hormones. Conclusion GDM was associated with growth factors and adipokines in cord blood from boys, but only IGF-1 in girls. These findings suggest sex differences in responses to fetal overnutrition.

OBJECTIVE To investigate the association among public health insurance, preconception care, and pregnancy outcomes in pregnant women with pregestational diabetes. METHODS This is a retrospective cohort of pregnant women with pregestational type 1 or type 2 diabetes from 2006 to 2011 in Massachusetts-a state with universal insurance coverage since 2006. Women delivering after 24 weeks of gestation and receiving endocrinology and obstetric care in a multidisciplinary clinic were included. Rates of preconception consultation, our primary outcome of interest, were then compared between publicly and privately insured women. We used univariate analysis followed by logistic regression to compare receipt of preconception consultation and other secondary diabetes care measures and pregnancy outcomes according to insurance status. RESULTS Fifty-four percent (n=106) of 197 women had public insurance. Publicly insured women were younger (median age 30.4 compared with 35.3 years, P

Background Self-management (SM) is increasingly emphasised as a key aspect of bipolar disorder (BD) treatment. However, little is known about the subjective experience of SM, which might have both positive and negative impacts. The present study aimed to advance this literature through qualitative investigation of the experiences of people with BD who participated in an SM intervention targeting quality of life (QoL). Methods Forty-three individuals with BD engaged with an SM intervention and were later questioned about personal experiences of engagement with the intervention, including attempts to enact self-management strategies. Thematic analysis was used to identify important aspects of the experience of SM in BD. Results Four themes describing people's experiences of SM were identified: 1) SM for BD is empowering, 2) individual responsibility to self-manage BD, 3) SM strategies lack power to control BD, and 4) the relationship of SM to the healthcare system. Limitations Potential limitations to generalisability may occur from self-selection bias in favour of SM and the QoL-focused nature of the present intervention. Conclusions The findings of this research generate novel insights into ways in which individuals with BD engage with SM interventions. For most people with BD, SM invokes a sense of empowerment and responsibility, although some feel symptoms remain beyond their control. A sense of partnership between consumers and clinicians may emerge from attention to SM, but traditional medical approaches were perceived as neglecting this aspect of care. Considerations from consumer perspectives are presented to assist clinicians and researchers utilising SM interventions in BD.

Historical literature reports risk of fetal demise after diabetic ketoacidosis (DKA) in pregnancy as high as 25–60% (1,2). However, estimates have generally been based on small sample sizes, with limited investigation of other fetal outcomes or risk factors associated with poor fetal outcomes. We aimed to provide an updated assessment of the incidence and risk factors for fetal demise and other adverse outcomes in women with DKA during pregnancy. This retrospective cohort study included pregnancies between 1996 and 2015 with at least one DKA event in women with type 1 diabetes at one of three teaching hospitals in Boston. Data were collected through medical record review. Pregnancies were excluded if information on birth status (live or demise) and gestational age at birth or demise were unknown. Among the 77 DKA events in 64 pregnancies in 62 women included in the study, fetal demise, preterm …

An extensive literature shows that greater left, relative to right, frontal cortical activity (LFA) is involved in approach-motivated affective states and reflects stable individual differences in approach motivation. However, relatively few studies have linked LFA to behavioral indices of approach motivation. In this study, we examine the relation between LFA and effort expenditure for reward, a behavioral index of approach motivation. LFA was calculated for 51 right-handed participants (55% female) using power spectral analysis of electroencephalogram recorded at rest. Participants also completed the effort expenditure for rewards task (EEfRT), which presents a series of trials requiring a choice between a low-reward low-effort task and a high-reward high-effort task. We found that individuals with greater resting LFA were more willing to expend greater effort in the pursuit of larger rewards, particularly when reward delivery was less likely. Our findings offer a more nuanced understanding of the motivational significance of LFA, in terms of processes that mitigate the effort- and uncertainty-related costs of pursuing rewarding goals.

Background Quality of life (QoL) is increasingly investigated in bipolar disorders (BD) research, yet little attention has been paid to its optimal definition and measurement. This is a significant limitation, as the broader QoL literature recognises a number of divergent meanings and measurement tensions. The aim here was to advance understanding of QoL in BD by clarifying use of the construct in the existing literature and considering measurement implications. Methods Thematic analysis techniques were used to interrogate articles identified via systematic search for (a) explicit discussion of QoL definitional/measurement issues, and (b) usage of the term QoL. Results A total of 275 articles were included in the analysis. A range of definitional and methodological issues confounding the study of QoL in BD were identified. While explicit definition of QoL proved rare, thematic analysis of usage of the construct revealed the concepts of functioning, health, subjective experience and wellbeing were thought to be relevant to QoL in BD. Limitations The review does not engage in top-down theory development. Our analysis was grounded in the empirical literature to support future theoretical work relevant to existing usage of QoL in BD. Conclusions There was no evidence of a consensus definition of QoL in BD. A plurality of QoL definitions is not necessarily a flaw in the literature, but points to empirical and conceptual issues demanding attention. Awareness of the diversity of constructs associated with QoL will enable clinicians to better select treatments on the basis of specific QoL outcomes. A research agenda and provisional considerations for empirical research are outlined based on the present analyses.

Objectives We sought to review the effect of immediate provision of postpartum contraception on postpartum follow-up and screening for type 2 diabetes in women with gestational diabetes mellitus (GDM). Study design We performed multivariate logistic regression to identify the association between immediate provision of postpartum contraception and attendance at the 6-week postpartum visit and performance of a 6- to 12-week oral glucose tolerance test, controlling for age, type of insurance, parity and race. Results Women who received contraception prior to hospital discharge were less likely to attend their postpartum visit [adjusted odds ratio (aOR) 0.59, 95% confidence interval (CI) 0.39–0.88], but just as likely to participate in postpartum diabetes screening (adjusted odds ratio (aOR) 1.27, 95% confidence interval (CI) 0.78–2.06). Attendance at the postpartum visit was associated with private insurance (OR 1.93, 95% CI 1.31–2.99). Conclusion Receiving contraception while admitted postpartum did not affect follow-up for diabetes screening for women with GDM.

Homicide-suicide is a form of fatal violence in which an individual commits homicide and subsequently kills him- or herself. One hundred and sixteen homicide-suicide events involving 119 female homicide victims in North Carolina from 1988-1992 were identified through state medical examiner files. Case files were reviewed retrospectively to identify event characteristics, precursors, and typologies. In 86% of cases the perpetrator was the current or former partner of the victim. During the study period, 24% of men who killed their female partners in North Carolina subsequently committed suicide and another 3% attempted suicide but survived. Victim separation from the perpetrator was the most prevalent precursor (41%), followed by a history of domestic violence (29%). In nearly half of the cases with a history of domestic violence, the victim had previously sought protection from the perpetrator in the form of an arrest warrant, restraining order, or intervention by a law enforcement officer. Children of the victim (and/or perpetrator) witnessed the homicide-suicide, were in the immediate vicinity, found their parents’ bodies, or were killed, in 43% of cases. The prevalence of separation and domestic violence suggests several potential points of intervention, including stronger domestic violence legislation. Future research should place priority on assessing the impact of partner homicidesuicides on the families in which they occur. Such studies are essential for the informed development of preventive and therapeutic interventions for the families of both the victims and perpetrators of these fatal events. In addition, research focused on assisting men in coping with issues of control and separation is needed.

INTRODUCTION: Effective contraception allows women with gestational diabetes mellitus (GDM) time to optimize their health before future pregnancies. We therefore sought to evaluate use of long-acting reversible contraception (LARC) in women with GDM compared with women with preexisting DM. METHODS: We identified 404 pregnancies with GDM and 232 with preexisting DM cared for at Brigham and Womens Hospital between 2006 and 2011. We compared the likelihood of receiving LARC in women with GDM compared with women with preexisting DM with bivariate analyses using Fishers exact test or t tests as appropriate. We performed multivariate logistic regression to identify factors associated with LARC uptake. RESULTS: Women with GDM were less likely to have had a planned pregnancy than women with preexisting DM (P=.04). Of 404 pregnancies with GDM 21.5% with A1GDM and 21.6% with A2GDM received LARC. Of 232 pregnancies with preexisting DM 24.4% with type 1 DM and 18.5% with type 2 DM received LARC. There was no significant difference among the groups (P=.79). Women who had received contraception during their postpartum hospitalization were less likely to attend their postpartum visit (odds ratio 0.58 95% confidence interval 0.39-0.86). CONCLUSION: Although women with GDM were as likely as women with preexisting DM to receive LARC postpartum they were more likely to have an unplanned pregnancy highlighting the need for effective contraception in this population. Our findings suggest that further study is needed to understand how best to provide contraception while still engaging women in postpartum care.

In January 2006 the US Food and Drug Administration approved the first inhalable insulin preparation for treatment of types 1 and 2 diabetes mellitus. This preparation, marketed by Pfizer, is a dry, powdered, human, regular insulin that is made into an aerosol mechanically by a handheld device at the time of inhalation. The powder is prepackaged in 1 mg foil packets that deliver 3 units of insulin and 3 mg packets that deliver 9 units. Because one unit of subcutaneous insulin corresponds to about 30 μg insulin, the activity of inhaled insulin is only about 10% of injected insulin on a weight basis. This “inefficiency” in comparison to subcutaneous insulin brings up the reproducibility of dosing. Firstly, in clinical trials the overall incidence of hypoglycaemia seems comparable with inhaled and subcutaneous insulin when comparable levels of glycaemic control are obtained. However, severe hypoglycaemia was more common and mild hypoglycaemia less common with the inhaled product in some trials. This will bear watching in longer term follow-up studies. Secondly, pulmonary factors (specifically smoking status and asthma) affect the absorption of inhaled insulin, with increased absorption in smokers and decreased absorption with asthma. Therefore, populations in whom the variability of absorption is greatest (current and recent smokers) are not considered appropriate candidates for inhaled insulin therapy. Inhaled insulin is rapid acting, with a peak plasma exposure between 30 and 90 minutes after dosage (similar to rapid acting insulin analogues). However, inhaled insulin taken before a meal has been observed to have a more marked effect on fasting glycaemia in humans than pre-meal subcutaneous insulin,1 suggesting a prolonged action. Also, in animal studies, inhaled insulin seems to have a lesser effect on hepatic glucose production, with a correspondingly greater effect on peripheral glucose disposal, than intravenously infused regular insulin.2 Whether this will apply to humans is not known. Considering efficacy, phase 3 trials are reasonably convincing that overall glycaemic control as assessed by haemoglobin A1c is similar with pre-meal subcutaneous regular insulin and the inhaled product in patients with type 1 diabetes or type 2 diabetes. In patients with type 1 diabetes, preprandial inhaled insulin has been studied in combination with insulin glargine, bedtime ultralente,3 and twice daily isophane insulin (NPH).4 Efficacy in patients with type 2 diabetes has been assessed in patients suboptimally controlled by diet and exercise randomised to maximal dose rosiglitazone versus pre-meal inhaled insulin5 as well as those receiving stable basal or bolus insulin treatment.6 The effect of pre-meal inhaled insulin when added to an existing oral regimen was studied in a phase 2 trial of patients in whom oral treatment with sulfonylurea or metformin had failed.7 For type 1 diabetes, inhaled insulin is likely to be accepted by both the public and the medical community. It is perhaps surprising how frequently individuals with longstanding type 1 diabetes, who seem to have adapted to multiple daily injections, are excited by the potential of needing only a single, long acting insulin injection daily, with inhaled insulin replacing pre-meal injections. The market for inhaled insulin in type 2 diabetes is more complex. Inhaled insulin has been under development for a number of years. Thus it will enter a very different therapeutic landscape for type 2 diabetes than was evident at the time of its initial study. In addition to the newer thiazolidenediones, the recent introduction of both exenatide (Byetta) and pramlintide (Symlin) and the likely imminent introduction of the dipeptidyl peptidase-4 (DPP-4) inhibitors allow additional therapeutic combinations with established oral hypoglycaemic agents. Why then consider insulin? One reason relates to potency. Insulin, regardless of route of administration, remains our most potent glucose lowering therapy. A second reason may be safety. Insulin has been used for 80 years and its side effects are well known; therefore, inhaled insulin has the potential to be beneficial in the long term too. The effect of treating hyperglycaemia for even four or five years with DPP-4 inhibitors or exenatide is unknown. But do we know all the risks of inhaled insulin, or does the route of insulin delivery affect the risk of adverse events? Approval was delayed substantially so that the clinical importance of increases of anti-insulin antibody production and small decreases in lung function seen during phase 3 trials could be evaluated.8,9 Current evidence indicates that these adverse findings are not clinically worrisome, although longer term monitoring is planned. Other potential barriers to acceptance of inhaled insulin include cost and patient satisfaction. The cost of inhaled insulin and the accompanying delivery device is not set, but it will certainly substantially exceed that of injectable insulin. Regarding patient satisfaction, perception of tolerability of the regimen and ease of use were significantly greater in patients randomised to inhaled insulin, and a large proportion of patients randomised to inhaled insulin chose to continue with that regimen. These findings held regardless of type of diabetes or whether inhaled insulin was added to subcutaneous insulin therapy or oral agents.10-12 Given the comparable glycaemic control and safety profile seen with the inhaled insulin preparation in comparison to subcutaneous administration, patient acceptance may prove to be the primary determinant of marketplace success. For some patients, doctors and budget holders, the issue of drug costs, cost effectiveness, and uncertainty regarding potential long term adverse effects related to pulmonary route of delivery will outweigh the perceived benefits of ease of administration. Both considerations contributed to the recent decision by NICE (the National Institute for Health and Clinical Excellence) to decline funding for inhaled insulin for the NHS. This opinion will be revisited after several months of public commentary.13 However, patients with type 1 diabetes or insulin dependent type 2 diabetes who are distressed by frequent injections may be able to improve their blood sugar control substantially and avoid complications from diabetes with this new product. For patients with type 2 diabetes with failing oral agents who are reluctant to start treatment with insulin, inhaled insulin offers the same efficacy as subcutaneous insulin, without multiple daily injections. When added to oral agents, it may obviate the need for subcutaneous insulin entirely.