Is cryptogenic stroke a tenable diagnosis? The Milpark Hospital patent foramen ovale closure experience

Patent foramen ovale (PFO) is increasingly being documented in patients presenting with “cryptogenic” neurological and peripheral ischemic events. Therapeutic options include the use of anti-platelet agents and in some cases non-surgical closure of the defect. In this article we present the Milpark Hospital experience of percutaneous closure of PFO to date. The importance of looking for this defect is highlighted, particularly in patients presenting with recurrent events despite antiplatelet therapy. Whilst routine closure of PFO is not advocated, it should be considered in certain select cases

Longitudinal associations of affective symptoms with midlife cognitive function: evidence from a British birth cohort

Background: Affective disorders are associated with poorer cognition in older adults; however, whether this association can already be observed in midlife remains unclear. Aims: This study investigated effects of affective symptoms over a period of 30 years on midlife cognitive function. First, we explored whether timing (sensitive period) or persistence (accumulation) of affective symptoms predicted cognitive function. Second, we tested how different longitudinal trajectories of affective symptoms were associated with cognitive function. Method: The study used data from the National Child Development Study. Memory, verbal fluency, information processing speed and accuracy were measured at age 50. Affective symptoms were measured at ages 23, 33, 42, and 50 and used to derive longitudinal trajectories. A structured modelling approach compared a set of nested models to test accumulation versus sensitive period hypotheses. Linear regressions and structural equation modelling were used to test for longitudinal associations of affective symptoms with cognitive function. Results: Accumulation of affective symptoms was found to be the best fit for the data, with persistent affective symptoms being associated with poorer immediate memory (B=-0.07, SE=0.03, P=.01), delayed memory (B=-0.13, SE=0.04, P<.001), and information processing accuracy (B=0.18, SE=0.08, P=.03), but not with information processing speed (B=3.15, SE=1.89, P=.10). Longitudinal trajectories of repeated affective symptoms were associated with poorer memory, verbal fluency, and information processing accuracy. Conclusions: Persistent affective symptoms can affect cognitive function in midlife. Effective management of affective disorders to prevent recurrence may reduce risk of poor cognitive outcomes and promote healthy cognitive ageing

Longitudinal associations of affective symptoms with mid-life cognitive function: evidence from a British birth cohort

Background Affective disorders are associated with poorer cognition in older adults; however, whether this association can already be observed in mid-life remains unclear. Aims To investigate the effects of affective symptoms over a period of 30 years on mid-life cognitive function. First, we explored whether timing (sensitive period) or persistence (accumulation) of affective symptoms predicted cognitive function. Second, we tested how different longitudinal trajectories of affective symptoms were associated with cognitive function. Method The study used data from the National Child Development Study. Memory, verbal fluency, information processing speed and accuracy were measured at age 50. Affective symptoms were measured at ages 23, 33, 42 and 50 and used to derive longitudinal trajectories. A structured modelling approach compared a set of nested models in order to test accumulation versus sensitive period hypotheses. Linear regressions and structural equation modelling were used to test for longitudinal associations of affective symptoms with cognitive function. Results Accumulation of affective symptoms was found to be the best fit for the data, with persistent affective symptoms being associated with poorer immediate memory (b = −0.07, s.e. = 0.03, P = 0.01), delayed memory (b = −0.13, s.e. = 0.04, P < 0.001) and information processing accuracy (b = 0.18, s.e. = 0.08, P = 0.03), but not with information processing speed (b = 3.15, s.e. = 1.89, P = 0.10). Longitudinal trajectories of repeated affective symptoms were associated with poorer memory, verbal fluency and information processing accuracy. Conclusions Persistent affective symptoms can affect cognitive function in mid-life. Effective management of affective disorders to prevent recurrence may reduce risk of poor cognitive outcomes and promote healthy cognitive ageing

Cash transfers and caregivers : working together to reduce vulnerability and HIV risk among adolescent girls in Johannesburg, South Africa

Abstract: In South Africa adolescent girls have the highest HIV incidence of any sex or age cohort. Scalable HIV-prevention interventions targeting this group are critical for epidemic control. Reaching 12.2 million children, the Child Support Grant mitigates the socio-structural drivers of HIV risk. This qualitative study of eight adolescents and their caregivers in Westbury, Johannesburg, explored how caregiving increases protective potential. ‘Caregiving’ enhanced the HIV risk-reduction benefits of ‘cash’ when characterised by substantial positive caregiver-adolescent involvement and adequate levels of control and consistency. Results underpin the value of social protection as an HIV-prevention modality and endorse investment in caregiver support programmes

Engaging under- and/or never-engaged populations in health services: A systematic review

Patient engagement is a mechanism used to facilitate person-centred care, however, has not been realized in all patient populations. Often, many marginalized populations still remain under- and/or never-engaged. The purpose of this systematic review was to: 1) identify methods or interventions that have been used to engage under- and/or never-engaged populations in health services and 2) identify outcomes that are associated with engaging under- and/or never-engaged populations in health services. A comprehensive search using the Ovid MEDLINE, EMBASE and CINAHL databases was conducted to examine literature between January 2002 and January 2015. Twenty-nine studies met the inclusion criteria. Data was extracted from these studies and findings are synthesized based on discrete themes that map to the research objectives. The majority of studies were quantitative, repeated-measures designs and concentrated in the United States. Hispanic and Latino/a populations were most frequently included in these studies. The main methods of recruitment included: 1) referral from a healthcare provider, 2) patient self-referral after seeing advertisements on mass media or targeted media, 3) directly approached by researcher in-person or telephone, and 4) administrative databases. Interventions occurred primarily at the individual-level, however some system-level interventions were identified. Five main outcomes resulted from the interventions, including: 1) behavioural change, 2) physiological, 3) psychosocial, 4) system and 5) process. Finally, culture-specific components were embedded in the interventions, both as surface and deep structures. This study provides future direction for patient engagement related projects, as it relates to under-and never-engaged population in healthcare. Experience Framework This article is associated with the Patient, Family & Community Engagement lens of The Beryl Institute Experience Framework. (http://bit.ly/ExperienceFramework) Access other PXJ articles related to this lens. Access other resources related to this lens

Structure and function of membrane proteins encapsulated in a polymer-bound lipid bilayer

New technologies for the purification of stable membrane proteins have emerged in recent years, in particular methods that allow the preparation of membrane proteins with their native lipid environment. Here, we look at the progress achieved with the use of styrene-maleic acid copolymers (SMA) which are able to insert into biological membranes forming nanoparticles containing membrane proteins and lipids. This technology can be applied to membrane proteins from any host source, and, uniquely, allows purification without the protein ever being removed from a lipid bilayer. Not only do these SMA lipid particles (SMALPs) stabilise membrane proteins, allowing structural and functional studies, but they also offer opportunities to understand the local lipid environment of the host membrane. With any new or different method, questions inevitably arise about the integrity of the protein purified: does it retain its activity; its native structure; and ability to perform its function? How do membrane proteins within SMALPS perform in existing assays and lend themselves to analysis by established methods? We outline here recent work on the structure and function of membrane proteins that have been encapsulated like this in a polymer-bound lipid bilayer, and the potential for the future with this approach

Socioeconomic predictors and consequences of depression among primary care attenders with non-communicable diseases in the Western Cape, South Africa:Cohort study within a randomised trial

Background: Socioeconomic predictors and consequences of depression and its treatment were investigated in 4393 adults with specified non-communicable diseases attending 38 public sector primary care clinics in the Eden and Overberg districts of the Western Cape, South Africa.   Methods: Participants were interviewed at baseline in 2011 and 14 months later, as part of a randomised controlled trial of a guideline-based intervention to improve diagnosis and management of chronic diseases. The 10-item Center for Epidemiologic Studies Depression Scale (CESD-10) was used to assess depression symptoms, with higher scores representing more depressed mood. Results: Higher CESD-10 scores at baseline were independently associated with being less educated (p=0.004) and having lower income (p=0.003). CESD-10 scores at follow-up were higher in participants with less education (p=0.010) or receiving welfare grants (p=0.007) independent of their baseline scores. Participants with CESD-10 scores of 10 or more at baseline (56% of all participants) had 25% higher odds of being unemployed at follow-up (p=0.016), independently of baseline CESD-10 score and treatment status. Among participants with baseline CESD-10 scores of 10 or more, antidepressant medication at baseline was independently more likely in participants who had more education (p=0.002), higher income (p<0.001), or were unemployed (p=0.001). Antidepressant medication at follow up was independently more likely in participants with higher income (p=0.023), and in clinics with better access to pharmacists (p=0.053) and off-site drug delivery (p=0.013).  Conclusions: Socioeconomic disadvantage appears to be both a cause and consequence of depression, and may also be a barrier to treatment. There are opportunities for improving the prevention, diagnosis and treatment of depression in primary care in inequitable middle income countries like South Africa.  Trial registration: The trial is registered with Current Controlled Trials (ISRCTN20283604) and the Office for Human Research Protections Database (IRB00001938, FWA00001637)

The function of BK channels extracted and purified within SMALPs

Human BK channels are large voltage and Ca2+-activated K+ channels, involved in several important functions within the body. The core channel is a tetramer of α subunits, and its function is modulated by the presence of β and γ accessory subunits. BK channels composed of α subunits, as well as BK channels composed of α and β1 subunits, were successfully solubilised from HEK cells with styrene maleic acid (SMA) polymer and purified by nickel affinity chromatography. Native SMA-PAGE analysis of the purified proteins showed the α subunits were extracted as a tetramer. In the presence of β1 subunits, they were co-extracted with the α subunits as a heteromeric complex. Purified SMA lipid particles (SMALPs) containing BK channel could be inserted into planar lipid bilayers (PLB) and single channel currents recorded, showing a high conductance (≈ 260 pS), as expected. The open probability was increased in the presence of co-purified β1 subunits. However, voltage dependent gating of the channel was restricted. In conclusion, we have demonstrated that SMA can be used to effectively extract and purify large, complex, human ion channels, from low expressing sources. That these large channels can be incorporated into PLB from SMALPs and display voltage-dependent channel activity. However, the SMA appears to reduce the voltage dependent gating of the channels

Reproducible disease phenotyping at scale: Example of coronary artery disease in UK Biobank

IMPORTANCE: A lack of internationally agreed standards for combining available data sources at scale risks inconsistent disease phenotyping limiting research reproducibility. OBJECTIVE: To develop and then evaluate if a rules-based algorithm can identify coronary artery disease (CAD) sub-phenotypes using electronic health records (EHR) and questionnaire data from UK Biobank (UKB). DESIGN: Case-control and cohort study. SETTING: Prospective cohort study of 502K individuals aged 40-69 years recruited between 2006-2010 into the UK Biobank with linked hospitalization and mortality data and genotyping. PARTICIPANTS: We included all individuals for phenotyping into 6 predefined CAD phenotypes using hospital admission and procedure codes, mortality records and baseline survey data. Of these, 408,470 unrelated individuals of European descent had a polygenic risk score (PRS) for CAD estimated. EXPOSURE: CAD Phenotypes. MAIN OUTCOMES AND MEASURES: Association with baseline risk factors, mortality (n = 14,419 over 7.8 years median f/u), and a PRS for CAD. RESULTS: The algorithm classified individuals with CAD into prevalent MI (n = 4,900); incident MI (n = 4,621), prevalent CAD without MI (n = 10,910), incident CAD without MI (n = 8,668), prevalent self-reported MI (n = 2,754); prevalent self-reported CAD without MI (n = 5,623), yielding 37,476 individuals with any type of CAD. Risk factors were similar across the six CAD phenotypes, except for fewer men in the self-reported CAD without MI group (46.7% v 70.1% for the overall group). In age- and sex- adjusted survival analyses, mortality was highest following incident MI (HR 6.66, 95% CI 6.07-7.31) and lowest for prevalent self-reported CAD without MI at baseline (HR 1.31, 95% CI 1.15-1.50) compared to disease-free controls. There were similar graded associations across the six phenotypes per SD increase in PRS, with the strongest association for prevalent MI (OR 1.50, 95% CI 1.46-1.55) and the weakest for prevalent self-reported CAD without MI (OR 1.08, 95% CI 1.05-1.12). The algorithm is available in the open phenotype HDR UK phenotype library (https://portal.caliberresearch.org/). CONCLUSIONS: An algorithmic, EHR-based approach distinguished six phenotypes of CAD with distinct survival and PRS associations, supporting adoption of open approaches to help standardize CAD phenotyping and its wider potential value for reproducible research in other conditions

Recent Patterns in Population-Based HIV Prevalence in Swaziland

Background: The 2011 Swaziland HIV Incidence Measurement Survey (SHIMS) was conducted as part of a national study to evaluate the scale up of key HIV prevention programs. Methods: From a randomly selected sample of all Swazi households, all women and men aged 18-49 were considered eligible, and all consenting adults were enrolled and received HIV testing and counseling. In this analysis, population-based measures of HIV prevalence were produced and compared against similarly measured HIV prevalence estimates from the 2006-7 Swaziland Demographic and Health. Also, measures of HIV service utilization in both HIV infected and uninfected populations were documented and discussed. Results: HIV prevalence among adults aged 18-49 has remained unchanged between 2006-2011 at 31-32%, with substantial differences in current prevalence between women (39%) and men (24%). In both men and women, between since 2006-7 and 2011, prevalence has fallen in the young age groups and risen in the older age groups. Over a third (38%) of the HIV-infected population was unaware of their infection status, and this differed markedly between men (50%) and women (31%). Of those aware of their HIV-positive status, a higher percentage of men (63%) than women (49%) reported ART use. Conclusions: While overall HIV prevalence remains roughly constant, age-specific changes strongly suggest both improved survival of the HIV-infected and a reduction in new HIV infections. Awareness of HIV status and entry into ART services has improved in recent years but remains too low. This study identifies opportunities to improve both HIV preventive and care services in Swaziland