Proactive integrated consultation-liaison psychiatry and time spent in hospital by older medical inpatients in England (The HOME Study): a multicentre, parallel-group, randomised controlled trial

Background: Older people admitted to hospital in an emergency often have prolonged inpatient stays that worsen their outcomes, increase health-care costs, and reduce bed availability. Growing evidence suggests that the biopsychosocial complexity of their problems, which include cognitive impairment, depression, anxiety, multiple medical illnesses, and care needs resulting from functional dependency, prolongs hospital stays by making medical treatment less efficient and the planning of post-discharge care more difficult. We aimed to assess the effects of enhancing older inpatients’ care with Proactive Integrated Consultation-Liaison Psychiatry (PICLP) in The HOME Study. We have previously described the benefits of PICLP reported by patients and clinicians. In this Article, we report the effectiveness and cost-effectiveness of PICLP-enhanced care, compared with usual care alone, in reducing time in hospital. Methods: We did a parallel-group, multicentre, randomised controlled trial in 24 medical wards of three English acute general hospitals. Patients were eligible to take part if they were 65 years or older, had been admitted in an emergency, and were expected to remain in hospital for at least 2 days from the time of enrolment. Participants were randomly allocated to PICLP or usual care in a 1:1 ratio by a database software algorithm that used stratification by hospital, sex, and age, and randomly selected block sizes to ensure allocation concealment. PICLP clinicians (consultation-liaison psychiatrists supported by assisting clinicians) made proactive biopsychosocial assessments of patients’ problems, then delivered discharge-focused care as integrated members of ward teams. The primary outcome was time spent as an inpatient (during the index admission and any emergency readmissions) in the 30 days post-randomisation. Secondary outcomes were the rate of discharge from hospital for the total length of the index admission; discharge destination; the length of the index admission after random allocation truncated at 30 days; the number of emergency readmissions to hospital, the number of days spent as an inpatient in an acute general hospital, and the rate of death in the year after random allocation; the patient's experience of the hospital stay; their view on the length of the hospital stay; anxiety (Generalized Anxiety Disorder-2); depression (Patient Health Questionnaire-2); cognitive function (Montreal Cognitive Assessment-Telephone version); independent functioning (Barthel Index of Activities of Daily Living); health-related quality of life (five-level EuroQol five-dimension questionnaire); and overall quality of life. Statisticians and data collectors were masked to treatment allocation; participants and ward staff could not be. Analyses were intention-to-treat. The trial had a patient and public involvement panel and was registered with ISRTCN (ISRCTN86120296). Findings: 2744 participants (1399 [51·0%] male and 1345 [49·0%] female) were enrolled between May 2, 2018, and March 5, 2020; 1373 were allocated to PICLP and 1371 to usual care. Participants’ mean age was 82·3 years (SD 8·2) and 2565 (93·5%) participants were White. The mean time spent in hospital in the 30 days post-randomisation (analysed for 2710 [98·8%] participants) was 11·37 days (SD 8·74) with PICLP and 11·85 days (SD 9·00) with usual care; adjusted mean difference –0·45 (95% CI –1·11 to 0·21; p=0·18). The only statistically and clinically significant difference in secondary outcomes was the rate of discharge, which was 8.5% higher (rate ratio 1·09 [95% CI 1·00 to 1·17]; p=0·042) with PICLP—a difference most apparent in patients who stayed for more than 2 weeks. Compared with usual care, PICLP was estimated to be modestly cost-saving and cost-effective over 1 and 3, but not 12, months. No intervention-related serious adverse events occurred. Interpretation: This is the first randomised controlled trial of PICLP. PICLP is experienced by older medical inpatients and ward staff as enhancing medical care. It is also likely to be cost-saving in the short-term. Although the trial does not provide strong evidence that PICLP reduces time in hospital, it does support and inform its future development and evaluation. Funding: UK National Institute for Health and Care Research

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Proactive integrated consultation-liaison psychiatry and time spent in hospital by older medical inpatients in England (The HOME Study): a multicentre, parallel-group, randomised controlled trial

Background: Older people admitted to hospital in an emergency often have prolonged inpatient stays that worsen their outcomes, increase health-care costs, and reduce bed availability. Growing evidence suggests that the biopsychosocial complexity of their problems, which include cognitive impairment, depression, anxiety, multiple medical illnesses, and care needs resulting from functional dependency, prolongs hospital stays by making medical treatment less efficient and the planning of post-discharge care more difficult. We aimed to assess the effects of enhancing older inpatients’ care with Proactive Integrated Consultation-Liaison Psychiatry (PICLP) in The HOME Study. We have previously described the benefits of PICLP reported by patients and clinicians. In this Article, we report the effectiveness and cost-effectiveness of PICLP-enhanced care, compared with usual care alone, in reducing time in hospital. Methods:We did a parallel-group, multicentre, randomised controlled trial in 24 medical wards of three English acute general hospitals. Patients were eligible to take part if they were 65 years or older, had been admitted in an emergency, and were expected to remain in hospital for at least 2 days from the time of enrolment. Participants were randomly allocated to PICLP or usual care in a 1:1 ratio by a database software algorithm that used stratification by hospital, sex, and age, and randomly selected block sizes to ensure allocation concealment. PICLP clinicians (consultation-liaison psychiatrists supported by assisting clinicians) made proactive biopsychosocial assessments of patients’ problems, then delivered discharge-focused care as integrated members of ward teams. The primary outcome was time spent as an inpatient (during the index admission and any emergency readmissions) in the 30 days post-randomisation. Secondary outcomes were the rate of discharge from hospital for the total length of the index admission; discharge destination; the length of the index admission after random allocation truncated at 30 days; the number of emergency readmissions to hospital, the number of days spent as an inpatient in an acute general hospital, and the rate of death in the year after random allocation; the patient's experience of the hospital stay; their view on the length of the hospital stay; anxiety (Generalized Anxiety Disorder-2); depression (Patient Health Questionnaire-2); cognitive function (Montreal Cognitive Assessment-Telephone version); independent functioning (Barthel Index of Activities of Daily Living); health-related quality of life (five-level EuroQol five-dimension questionnaire); and overall quality of life. Statisticians and data collectors were masked to treatment allocation; participants and ward staff could not be. Analyses were intention-to-treat. The trial had a patient and public involvement panel and was registered with ISRTCN (ISRCTN86120296).Findings: 2744 participants (1399 [51·0%] male and 1345 [49·0%] female) were enrolled between May 2, 2018, and March 5, 2020; 1373 were allocated to PICLP and 1371 to usual care. Participants’ mean age was 82·3 years (SD 8·2) and 2565 (93·5%) participants were White. The mean time spent in hospital in the 30 days post-randomisation (analysed for 2710 [98·8%] participants) was 11·37 days (SD 8·74) with PICLP and 11·85 days (SD 9·00) with usual care; adjusted mean difference –0·45 (95% CI –1·11 to 0·21; p=0·18). The only statistically and clinically significant difference in secondary outcomes was the rate of discharge, which was 8.5% higher (rate ratio 1·09 [95% CI 1·00 to 1·17]; p=0·042) with PICLP—a difference most apparent in patients who stayed for more than 2 weeks. Compared with usual care, PICLP was estimated to be modestly cost-saving and cost-effective over 1 and 3, but not 12, months. No intervention-related serious adverse events occurred. Interpretation:This is the first randomised controlled trial of PICLP. PICLP is experienced by older medical inpatients and ward staff as enhancing medical care. It is also likely to be cost-saving in the short-term. Although the trial does not provide strong evidence that PICLP reduces time in hospital, it does support and inform its future development and evaluation

Knowle Hill

In the heat of endless summer, a grassy hill can become a boundless world. Halcyon days merge as grass tickled feet sprint to the top. Beads of sweat dry on salty skin.The pressures of adulthood are far from sight, so far that the horizon lifts and falls before adolescence, and summer days end long before dark. Childhood embodies a constant unveiling, boundaries blur between the newly imagined and the just discovered. We assume the roles of explorers, venturing into uncharted territories both external and internal, unearthing treasures and perils alike. Local haunts take on preternatural significance, as the grassy knoll becomes an ancient tomb and the crooked tree morphs into a bandits lair.View these works through lenses of renewal, rekindle moments long past, from a time of primordial personhood. Forage in the undergrowth of nostalgia, under a dense thicket of culture and conditioning, until we may delight in the archaeology of our innocence and the artefacts we unearth

Knowle Hill

In the heat of endless summer, a grassy hill can become a boundless world. Halcyon days merge as grass tickled feet sprint to the top. Beads of sweat dry on salty skin.The pressures of adulthood are far from sight, so far that the horizon lifts and falls before adolescence, and summer days end long before dark. Childhood embodies a constant unveiling, boundaries blur between the newly imagined and the just discovered. We assume the roles of explorers, venturing into uncharted territories both external and internal, unearthing treasures and perils alike. Local haunts take on preternatural significance, as the grassy knoll becomes an ancient tomb and the crooked tree morphs into a bandits lair.View these works through lenses of renewal, rekindle moments long past, from a time of primordial personhood. Forage in the undergrowth of nostalgia, under a dense thicket of culture and conditioning, until we may delight in the archaeology of our innocence and the artefacts we unearth

Defining the distinct, intrinsic properties of the novel type I interferon, IFNϵ

The type I interferons (IFNs) are a family of cytokines with diverse biological activities, including antiviral, antiproliferative, and immunoregulatory functions. The discovery of the hormonally regulated, constitutively expressed IFNϵ has suggested a function for IFNs in reproductive tract homeostasis and protection from infections, but its intrinsic activities are untested. We report here the expression, purification, and functional characterization of murine IFNϵ (mIFNϵ). Recombinant mIFNϵ (rmIFNϵ) exhibited an α-helical fold characteristic of type I IFNs and bound to IFNα/β receptor 1 (IFNAR1) and IFNAR2, but, unusually, it had a preference for IFNAR1. Nevertheless, rmIFNϵ induced typical type I IFN signaling activity, including STAT1 phosphorylation and activation of canonical type I IFN signaling reporters, demonstrating that it uses the JAK–STAT signaling pathway. We also found that rmIFNϵ induces the activation of T, B, and NK cells and exhibits antiviral, antiproliferative, and antibacterial activities typical of type I IFNs, albeit with 100–1000-fold reduced potency compared with rmIFNα1 and rmIFNβ. Surprisingly, although the type I IFNs generally do not display cross-species activities, rmIFNϵ exhibited high antiviral activity on human cells, suppressing HIV replication and inducing the expression of known HIV restriction factors in human lymphocytes. Our findings define the intrinsic properties of murine IFNϵ, indicating that it distinctly interacts with IFNAR and elicits pathogen-suppressing activity with a potency enabling host defense but with limited toxicity, appropriate for a protein expressed constitutively in a sensitive mucosal site, such as the reproductive tract.Full Tex

Interferon-epsilon is a novel regulator of NK cell responses in the uterus

Abstract The uterus is a unique mucosal site where immune responses are balanced to be permissive of a fetus, yet protective against infections. Regulation of natural killer (NK) cell responses in the uterus during infection is critical, yet no studies have identified uterine-specific factors that control NK cell responses in this immune-privileged site. We show that the constitutive expression of IFNε in the uterus plays a crucial role in promoting the accumulation, activation, and IFNγ production of NK cells in uterine tissue during Chlamydia infection. Uterine epithelial IFNε primes NK cell responses indirectly by increasing IL-15 production by local immune cells and directly by promoting the accumulation of a pre-pro-like NK cell progenitor population and activation of NK cells in the uterus. These findings demonstrate the unique features of this uterine-specific type I IFN and the mechanisms that underpin its major role in orchestrating innate immune cell protection against uterine infection