Adult Online Hate, Harassment and Abuse: A Rapid Evidence Assessment

The development of email and social media platforms has changed the way in which people interact with each other. The open sharing of personal data in public forums has resulted in online harassment in its many forms becoming increasingly problematic. The number of people having negative online experiences is increasing, with close to half of adult internet users reporting having seen hateful content online in the past year. This report presents findings from a collaborative study undertaken by the University of East London (UEL) and the London School of Economics and Political Science (LSE). It describes the findings from a Rapid Evidence Assessment (REA) of the evidence base in relation to adult online safety undertaken on behalf of the Department for Digital, Culture, Media & Sport (DCMS). The research was undertaken on behalf of the UK Council for Internet Safety Evidence Group. This REA focuses on exploring internet safety issues amongst adults, given the expansion of the remit of the UK Council for Child Internet Safety (UKCCIS) to include adults in the context of the new Internet Safety Strategy (2018) and Online Harms White Paper (2019)

In-vitro and in-vivo evidence for uncoupling of BCR internalization and signaling in chronic lymphocytic leukemia

B-cell receptor activation, occurring within lymph nodes, plays a key role in the pathogenesis of chronic lymphocytic leukemia and is linked to prognosis. As well as activation of downstream signaling, receptor ligation triggers internalization, transit to acidified endosomes and degradation of ligand-receptor complexes. In the present study we investigated the relationship between these two processes in normal and leukemic B-cells. We found that leukemic B-cells, particularly anergic cases lacking the capacity to initiate downstream signaling, internalize and accumulate ligand in acidified endosomes more efficiently than normal B-cells. Furthermore, ligation of either surface CD79B, a Bcell receptor component required for downstream signaling, or surface IgM by cognate agonistic antibody, showed that the two molecules internalize independently of each other in leukemic but not normal B-cells. Since association with surface CD79B is required for surface retention of IgM, this suggests that uncoupling of B-cell receptor internalization from signaling may be due to dissociation of these two molecules in leukemic cells. Comparison of lymph node with peripheral blood cells from chronic lymphocytic leukemia patients showed that, despite recent B-cell receptor activation, lymph node B-cells expressed higher levels of surface IgM. This surprising finding suggests that the B-cell receptors of lymph node and peripheral blood derived leukemic cells might be functionally distinct. Finally, long-term therapy with the Bruton’s tyrosine kinase inhibitors ibrutinib or acalabrutinib resulted in a switch to an anergic pattern of B-cell receptor function with reduced signaling capacity, surface IgM expression and more efficient internalization

Dynamic pituitary-adrenal interactions in the critically ill after cardiac surgery

Context: Patients with critical illness are thought to be at risk of adrenal insufficiency. There are no models of dynamic hypothalamic-pituitary-adrenal (HPA) axis function in this group of patients and thus current methods of diagnosis are based on aggregated, static models.Objective: To characterize the secretory dynamics of the HPA axis in the critically ill (CI) after cardiac surgery.Design: Mathematical modeling of cohorts.Setting: Cardiac critical care unit.Patients: 20 male patients CI at least 48 hours after cardiac surgery and 19 healthy (H) male volunteers. Interventions: None.Main Outcome Measures: Measures of hormone secretory dynamics were generated from serum adrenocorticotrophic hormone (ACTH) sampled every hour and total cortisol every 10 min for 24 h.Results: All CI patients had pulsatile ACTH and cortisol profiles. CI patients had similar ACTH secretion (1036.4 [737.6] pg/mL/24 h) compared to the H volunteers (1502.3 [1152.2] pg/mL/24 h; P=.20), but increased cortisol secretion (CI: 14 447.0 [5709.3] vs H: 5915.5 [1686.7)] nmol/L/24 h; P<.0001). This increase in cortisol was due to nonpulsatile (CI: 9253.4 [3348.8] vs H: 960 [589.0] nmol/L/24 h, P<.0001), rather than pulsatile cortisol secretion (CI: 5193.1 [3018.5] vs H: 4955.1 [1753.6] nmol/L/24 h; P=.43). Seven (35%) of the 20 CI patients had cortisol pulse nadirs below the current international guideline threshold for critical illness-related corticosteroid insufficiency, but an overall secretion that would not be considered deficient.Conclusions: This study supports the premise that current tests of HPA axis function are unhelpful in the diagnosis of adrenal insufficiency in the CI. The reduced ACTH and increase in nonpulsatile cortisol secretion imply that the secretion of cortisol is driven by factors outside the HPA axis in critical illness.Diabetes mellitus: pathophysiological changes and therap

Response to Letter to the Editor from Richard Dorin:Dynamic pituitary-adrenal interactions in the critically ill after cardiac surgery

Diabetes mellitus: pathophysiological changes and therap

Experiences of HIV-positive postpartum women and health workers involved with community-based antiretroviral therapy adherence clubs in Cape Town, South Africa

Background The rollout of universal, lifelong treatment for all HIV-positive pregnant and breastfeeding women (“Option B+”) has rapidly increased the number of women initiating antiretroviral treatment (ART) and requiring ART care postpartum. In a pilot project in South Africa, eligible postpartum women were offered the choice of referral to the standard of care, a local primary health care clinic, or a community-based model of differentiated ART services, the adherence club (AC). ACs have typically enrolled only non-pregnant and non-postpartum adults; postpartum women had not previously been referred directly from antenatal care. There is little evidence regarding postpartum women’s preferences for and experiences of differentiated models of care, or the capacity of this particular model to cater to their specific needs. This qualitative paper reports on feedback from both postpartum women and health workers who care for them on their respective experiences of the AC. Methods One-on-one in-depth qualitative interviews were conducted with 19 (23%) of the 84 postpartum women who selected the AC and were retained at approximately 12 months postpartum, and 9 health workers who staff the AC. Data were transcribed and thematically analysed using NVivo 11. Results Postpartum women’s inclusion in the AC was acceptable for both participants and health workers. Health workers were welcoming of postpartum women but expressed concerns about prospects for longer term adherence and retention, and raised logistical issues they felt might compromise trust with AC members in general. Conclusions Enrolling postpartum women in mixed groups with the general adult population is feasible and acceptable. Preliminary recommendations are offered and may assist in supporting the specific needs of postpartum women transitioning from antenatal ART care. Trial registration Number NCT02417675 clinicaltrials.gov/ct2/show/record/NCT02417675 (retrospective reg.

Integrating care: Learning from first generation integrated primary health care centres

Recent Australian health care policies have focused on strategies to increase efficiency, reduce inequalities and improve health outcomes by building a stronger primary health care system.1 At the time this research was commissioned, the establishment of GP Super Clinics was a significant strategic element of primary health care system reform, although this has now transitioned under subsequent governments to a focus on Health Care Homes.2 The research described in this report was funded by the Australian Primary Health Care Research Institute (APHCRI) in 2013 as part of a research program investigating the features of GP Super Clinics that contribute to achieving the objectives of integration. Specifically, this program of research explored co-location as a strategy for promoting service integration within multidisciplinary primary healthcare clinics, to identify developmental and operational characteristics that promote successful integration.3 Key elements of all 'extended general practice models' 4 are a focus on improving integration to drive quality of care, chronic disease management and prevention; coordination between and across services; increased access, and possibly the promotion of workforce development. While such services have been differentiated from broader primary health care centre models' such as Aboriginal Community Controlled Health Services (ACCHSs), both GP Super Clinics and ACCHSs share an integrated, co-located model of service. While we acknowledge there are significant differences (including the Non-Government Organisation (NGO) focus, not-for-profit status and specific Aboriginal employment contexts) for ACCHSs compared to Super Clinics, many of the challenges of establishing and sustaining integrated primary health care are common across both service types.4 Any initiative seeking to understand characteristics of integrated primary healthcare centres (IPHCs) is likely to derive useful lessons from ACCHSs, which predate the GP Super Clinic model by nearly 40 years. The ACCHS sector has established strategies to ensure collaboration across disciplines, to be properly responsive to changing community needs, and to build effective links within and across services. In many cases, these models have benefited from the fine tuning and maturity that accompanies several decades of implementation. Many of the quality innovations in primary health care which are now moving into broader general practice settings, from quality indicators to the Health Care Home, were pioneered in the ACCHS sector.5 Newer models of co-located integrated primary health care are also offered by some community-based refugee health services which provide co-located, integrated psychology, medical, nursing and social care services. These broad-based primary care services for specific populations offer more social service support than the IPHCs which focus on primary medical care for general populations, but both models share the primary care mandate to provide patient-centred, whole person care. This research report describes two case studies exploring characteristics of two different colocated, integrated services: a mature integrated ACCHS, Winnunga Nimmityjah Aboriginal Health Service (Winnunga Nimmityjah AHS); and a rapidly expanding IPHC, Companion House, supporting refugees and asylum seekers. These services are both award-winning organisations that provide primary general practice (GP) medical care as well as more generalised health services to members of their local community. They function as exemplar case models, each highlighting different challenges that IPHCs may have. Both organisations are important community hubs and have had to frequently adapt to shifting needs and priorities of both their communities and of government policies that impact them directly.The research reported in this paper is a project of the Australian Primary Health Care Research Institute which is supported by a grant from the Australian Government Department of Health and Ageing under the Primary Health Care Research Evaluation and Development Strategy

Integration of postpartum healthcare services for HIV-infected women and their infants in South Africa: A randomised controlled trial

Background As the number of HIV-infected women initiating lifelong antiretroviral therapy (ART) during pregnancy increases globally, concerns have emerged regarding low levels of retention in HIV services and suboptimal adherence to ART during the postpartum period. We examined the impact of integrating postpartum ART for HIV+ mothers alongside infant follow-up within maternal and child health (MCH) services in Cape Town, South Africa. Methods and findings We conducted a randomised trial among HIV+ postpartum women aged ≥18 years who initiated ART during pregnancy in the local antenatal care clinic and were breastfeeding when screened before 6 weeks postpartum. We compared an integrated postnatal service among mothers and their infants (the MCH-ART intervention) to the local standard of care (control)—immediate postnatal referral of HIV+ women on ART to general adult ART services and their infants to separate routine infant follow-up. Evaluation data were collected through medical records and trial measurement visits scheduled and located separately from healthcare services involved in either arm. The primary trial outcome was a composite endpoint of women’s retention in ART care and viral suppression (VS) (viral load < 50 copies/ml) at 12 months postpartum; secondary outcomes included duration of any and exclusive breastfeeding, mother-to-child HIV transmission, and infant mortality. Between 5 June 2013 and 10 December 2014, a total of 471 mother–infant pairs were enrolled and randomised (mean age, 28.6 years; 18% nulliparous; 57% newly diagnosed with HIV in pregnancy; median duration of ART use at randomisation, 18 weeks). Among 411 women (87%) with primary endpoint data available, 77% of women (n = 155) randomised to the MCH-ART intervention achieved the primary composite outcome of retention in ART services with VS at 12 months postpartum, compared to 56% of women (n = 117) randomised to the control arm (absolute risk difference, 0.21; 95% CI: 0.12–0.30; p < 0.001). The findings for improved retention in care and VS among women in the MCH-ART intervention arm were consistent across subgroups of participants according to demographic and clinical characteristics. The median durations of any breastfeeding and exclusive breastfeeding were longer in women randomised to the intervention versus control arm (6.9 versus 3.0 months, p = 0.006, and 3.0 versus 1.4 months, p < 0.001, respectively). For the infants, overall HIV-free survival through 12 months of age was 97%: mother-to-child HIV transmission was 1.2% overall (n = 4 and n = 1 transmissions in the intervention and control arms, respectively), and infant mortality was 1.9% (n = 6 and n = 3 deaths in the intervention and control arms, respectively), and these outcomes were similar by trial arm. Interpretation of these findings should be qualified by the location of this study in a single urban area as well as the self-reported nature of breastfeeding outcomes. Conclusions In this study, we found that integrating ART services into the MCH platform during the postnatal period was a simple and effective intervention, and this should be considered for improving maternal and child outcomes in the context of HIV

Modelling the dynamic interaction of systemic inflammation and the hypothalamic-pituitary-adrenal (HPA) axis during and after cardiac surgery

Major surgery and critical illness produce a potentially life-threatening systemic inflammatory response. The hypothalamic–pituitary–adrenal (HPA) axis is one of the key physiological systems that counterbalances this systemic inflammation through changes in adrenocorticotrophic hormone (ACTH) and cortisol. These hormones normally exhibit highly correlated ultradian pulsatility with an amplitude modulated by circadian processes. However, these dynamics are disrupted by major surgery and critical illness. In this work, we characterize the inflammatory, ACTH and cortisol responses of patients undergoing cardiac surgery and show that the HPA axis response can be classified into one of three phenotypes: single-pulse, two-pulse and multiple-pulse dynamics. We develop a mathematical model of cortisol secretion and metabolism that predicts the physiological mechanisms responsible for these different phenotypes. We show that the effects of inflammatory mediators are important only in the single-pulse pattern in which normal pulsatility is lost—suggesting that this phenotype could be indicative of the greatest inflammatory response. Investigating whether and how these phenotypes are correlated with clinical outcomes will be critical to patient prognosis and designing interventions to improve recovery

Current evidence shows no influence of women's menstrual cycle phase on acute strength performance or adaptations to resistance exercise training

Introduction: The bias towards excluding women from exercise science research is often due to the assumption that cyclical fluctuations in reproductive hormones influence resistance exercise performance and exercise-induced adaptations. Methods: Hence, the purpose of this umbrella review was to examine and critically evaluate the evidence from meta-analyses and systematic reviews on the influence of menstrual cycle phase on acute performance and chronic adaptations to resistance exercise training (RET). Results: We observed highly variable findings among the published reviews on the ostensible effects of female sex hormones on relevant RET-induced outcomes, including strength, exercise performance, and hypertrophy. Discussion: We highlight the importance of comprehensive menstrual cycle verification methods, as we noted a pattern of poor and inconsistent methodological practices in the literature. In our opinion, it is premature to conclude that short-term fluctuations in reproductive hormones appreciably influence acute exercise performance or longer-term strength or hypertrophic adaptations to RET

Re-recruiting postpartum women living with HIV into a follow-up study in Cape Town, South Africa

Objective Recruitment and retention present major challenges to longitudinal research in maternal and child health, yet there are few insights into optimal strategies that can be employed in low-resource settings. Following prior participation in a longitudinal study following women living with HIV through pregnancy and breastfeeding in Cape Town, women were re-contacted at least 18 months after the last study contact and were invited to attend an additional follow-up visit. We describe lessons learnt and offer recommendations for a multiphase recruitment approach. Results Using telephone calls, home visits, clinic tracing and Facebook/WhatsApp messages, we located 387 of the 463 eligible women and successfully enrolled 353 (91% of those contacted). Phone calls were the most successful strategy, yielding 67% of enrolments. Over half of the women had changed their contact information since participation in the previous study. We recommend that researchers collect multiple contact details and use several recruitment strategies in parallel from the start of a study. Participants in longitudinal studies may require frequent contact to update contact information, particularly in settings where mobility is common