Specialised early intervention teams (extended time) for recent-onset psychosis.

BACKGROUND: Psychosis is an illness characterised by the presence of hallucinations and delusions that can cause distress or a marked change in an individual's behaviour (e.g. social withdrawal, flat or blunted effect). A first episode of psychosis (FEP) is the first time someone experiences these symptoms that can occur at any age, but the condition is most common in late adolescence and early adulthood. This review is concerned with FEP and the early stages of a psychosis, referred to throughout this review as 'recent-onset psychosis.' Specialised early intervention (SEI) teams are community mental health teams that specifically treat people who are experiencing, or have experienced, a recent-onset psychosis. SEI teams provide a range of treatments including medication, psychotherapy, psychoeducation, educational and employment support, augmented by assertive contact with the service user and small caseloads. Treatment is time limited, usually offered for two to three years, after which service users are either discharged to primary care or transferred to a standard adult community mental health team. Evidence suggests that once SEI treatment ends, improvements may not be sustained, bringing uncertainty about the optimal duration of SEI to ensure the best long-term outcomes. Extending SEI has been proposed as a way of providing continued intensive treatment and continuity of care, of usually up to five years, in order to a) sustain the positive initial outcomes of SEI; and b) improve the long-term trajectory of the illness. OBJECTIVES: To compare extended SEI teams with treatment as usual (TAU) for people with recent-onset psychosis. To compare extended SEI teams with standard SEI teams followed by TAU (standard SEI + TAU) for people with recent-onset psychosis. SEARCH METHODS: On 3 October 2018 and 22 October 2019, we searched Cochrane Schizophrenia's study-based register of trials, including registries of clinical trials. SELECTION CRITERIA: We selected all randomised controlled trials (RCTs) comparing extended SEI with TAU for people with recent-onset psychosis and all RCTs comparing extended SEI with standard SEI + TAU for people with recent-onset psychosis. We entered trials meeting these criteria and reporting usable data as included studies. DATA COLLECTION AND ANALYSIS: We independently inspected citations, selected studies, extracted data and appraised study quality. For binary outcomes we calculated the risk ratios (RRs) and their 95% confidence intervals (CIs). For continuous outcomes we calculated the mean difference (MD) and their 95% CIs, or if assessment measures differed for the same construct, we calculated the standardised mean difference (SMD) with 95% CIs. We assessed risk of bias for included studies and created a 'Summary of findings' table using the GRADE approach. MAIN RESULTS: We included three RCTs, with a total 780 participants, aged 16 to 35 years. All participants met the criteria for schizophrenia spectrum disorders or affective psychoses. No trials compared extended SEI with TAU. All three trials randomly allocated people approximately two years into standard SEI to either extended SEI or standard SEI + TAU. The certainty of evidence for outcomes varied from low to very low. Our primary outcomes were recovery and disengagement from mental health services. No trials reported on recovery, and we used remission as a proxy. Three trials reported on remission, with the point estimate suggesting a 13% increase in remission in favour of extended SEI, but this included wide confidence intervals (CIs) and a very uncertain estimate of no benefit (RR 1.13, 95% CI 0.97 to 1.31; 3 trials, 780 participants; very low-certainty evidence). Two trials provided data on disengagement from services with evidence that extended SEI care may result in fewer disengagements from mental health treatment (15%) in comparison to standard SEI + TAU (34%) (RR 0.45, 95% CI 0.27 to 0.75; 2 trials, 380 participants; low-certainty evidence). There may be no evidence of a difference in rates of psychiatric hospital admission (RR 1.55, 95% CI 0.68 to 3.52; 1 trial, 160 participants; low-certainty evidence), or the number of days spent in a psychiatric hospital (MD -2.70, 95% CI -8.30 to 2.90; 1 trial, 400 participants; low-certainty evidence). One trial found uncertain evidence regarding lower global psychotic symptoms in extended SEI in comparison to standard SEI + TAU (MD -1.90, 95% CI -3.28 to -0.52; 1 trial, 156 participants; very low-certainty evidence). It was uncertain whether the use of extended SEI over standard SEI + TAU resulted in fewer deaths due to all-cause mortality, as so few deaths were recorded in trials (RR 0.38, 95% CI 0.09 to 1.64; 3 trials, 780 participants; low-certainty evidence). Very uncertain evidence suggests that using extended SEI instead of standard SEI + TAU may not improve global functioning (SMD 0.23, 95% CI -0.29 to 0.76; 2 trials, 560 participants; very low-certainty evidence). There was low risk of bias in all three trials for random sequence generation, allocation concealment and other biases. All three trials had high risk of bias for blinding of participants and personnel due to the nature of the intervention. For the risk of bias for blinding of outcome assessments and incomplete outcome data there was at least one trial with high or unclear risk of bias. AUTHORS' CONCLUSIONS: There may be preliminary evidence of benefit from extending SEI team care for treating people experiencing psychosis, with fewer people disengaging from mental health services. Evidence regarding other outcomes was uncertain. The certainty of evidence for the measured outcomes was low or very low. Further, suitably powered studies that use a consistent approach to outcome selection are needed, but with only one further ongoing trial, there is unlikely to be any definitive conclusion for the effectiveness of extended SEI for at least the next few years.

Specialised early intervention teams for recent-onset psychosis.

BACKGROUND: Psychosis is an illness characterised by the presence of hallucinations and delusions that can cause distress or a marked change in an individual's behaviour (e.g. social withdrawal, flat or blunted effect). A first episode of psychosis (FEP) is the first time someone experiences these symptoms that can occur at any age, but the condition is most common in late adolescence and early adulthood. This review is concerned with first episode psychosis (FEP) and the early stages of a psychosis, referred to throughout this review as 'recent-onset psychosis.' Specialised early intervention (SEI) teams are community mental health teams that specifically treat people who are experiencing, or have experienced a recent-onset psychosis. The purpose of SEI teams is to intensively treat people with psychosis early in the course of the illness with the goal of increasing the likelihood of recovery and reducing the need for longer-term mental health treatment. SEI teams provide a range of treatments including medication, psychotherapy, psychoeducation, and occupational, educational and employment support, augmented by assertive contact with the service user and small caseloads. Treatment is time limited, usually offered for two to three years, after which service users are either discharged to primary care or transferred to a standard adult community mental health team. A previous Cochrane Review of SEI found preliminary evidence that SEI may be superior to standard community mental health care (described as 'treatment as usual (TAU)' in this review) but these recommendations were based on data from only one trial. This review updates the evidence for the use of SEI services. OBJECTIVES: To compare specialised early intervention (SEI) teams to treatment as usual (TAU) for people with recent-onset psychosis. SEARCH METHODS: On 3 October 2018 and 22 October 2019, we searched Cochrane Schizophrenia's study-based register of trials, including registries of clinical trials. SELECTION CRITERIA: We selected all randomised controlled trials (RCTs) comparing SEI with TAU for people with recent-onset psychosis. We entered trials meeting these criteria and reporting useable data as included studies. DATA COLLECTION AND ANALYSIS: We independently inspected citations, selected studies, extracted data and appraised study quality. For binary outcomes we calculated the risk ratios (RRs) and their 95% confidence intervals (CIs). For continuous outcomes we calculated the mean difference (MD) and their 95% CIs, or if assessment measures differed for the same construct, we calculated the standardised mean difference (SMD) with 95% CIs. We assessed risk of bias for included studies and created a 'Summary of findings' table using the GRADE approach. MAIN RESULTS: We included three RCTs and one cluster-RCT with a total of 1145 participants. The mean age in the trials was between 23.1 years (RAISE) and 26.6 years (OPUS). The included participants were 405 females (35.4%) and 740 males (64.6%). All trials took place in community mental healthcare settings. Two trials reported on recovery from psychosis at the end of treatment, with evidence that SEI team care may result in more participants in recovery than TAU at the end of treatment (73% versus 52%; RR 1.41, 95% CI 1.01 to 1.97; 2 studies, 194 participants; low-certainty evidence). Three trials provided data on disengagement from services at the end of treatment, with fewer participants probably being disengaged from mental health services in SEI (8%) in comparison to TAU (15%) (RR 0.50, 95% CI 0.31 to 0.79; 3 studies, 630 participants; moderate-certainty evidence). There was low-certainty evidence that SEI may result in fewer admissions to psychiatric hospital than TAU at the end of treatment (52% versus 57%; RR 0.91, 95% CI 0.82 to 1.00; 4 studies, 1145 participants) and low-certainty evidence that SEI may result in fewer psychiatric hospital days (MD -27.00 days, 95% CI -53.68 to -0.32; 1 study, 547 participants). Two trials reported on general psychotic symptoms at the end of treatment, with no evidence of a difference between SEI and TAU, although this evidence is very uncertain (SMD -0.41, 95% CI -4.58 to 3.75; 2 studies, 304 participants; very low-certainty evidence). A different pattern was observed in assessment of general functioning with an end of trial difference that may favour SEI (SMD 0.37, 95% CI 0.07 to 0.66; 2 studies, 467 participants; low-certainty evidence). It was uncertain whether the use of SEI resulted in fewer deaths due to all-cause mortality at end of treatment (RR 0.21, 95% CI 0.04 to 1.20; 3 studies, 741 participants; low-certainty evidence). There was low risk of bias for random sequence generation and allocation concealment in three of the four included trials; the remaining trial had unclear risk of bias. Due to the nature of the intervention, we considered all trials at high risk of bias for blinding of participants and personnel. Two trials had low risk of bias and two trials had high risk of bias for blinding of outcomes assessments. Three trials had low risk of bias for incomplete outcome data, while one trial had high risk of bias. Two trials had low risk of bias, one trial had high risk of bias, and one had unclear risk of bias for selective reporting. AUTHORS' CONCLUSIONS: There is evidence that SEI may provide benefits to service users during treatment compared to TAU. These benefits probably include fewer disengagements from mental health services (moderate-certainty evidence), and may include small reductions in psychiatric hospitalisation (low-certainty evidence), and a small increase in global functioning (low-certainty evidence) and increased service satisfaction (moderate-certainty evidence). The evidence regarding the effect of SEI over TAU after treatment has ended is uncertain. Further evidence investigating the longer-term outcomes of SEI is needed. Furthermore, all the eligible trials included in this review were conducted in high-income countries, and it is unclear whether these findings would translate to low- and middle-income countries, where both the intervention and the comparison conditions may be different.

Intracranial injuries on computed tomography head scans in infants investigated for suspected physical abuse: a retrospective review.

BACKGROUND: UK national guidelines recommend that investigation of infants (aged <12 months) with suspected physical abuse should always include CT head scans. Such imaging carries small but recognised risks from radiation exposure. Studies report a range of yields for occult intracranial injuries in suspected physical abuse. AIMS: To report the yield of intracranial injuries on CT head scans carried out for suspected physical abuse in infants, compare yields for those presenting with or without signs of head injury and to describe selected clinical and radiological features. METHODS: A retrospective cross-sectional review of case records of infants undergoing skeletal survey for suspected physical abuse in Wessex, England. The main outcome measure was yield of intracranial injuries on CT head scan. RESULTS: In total, n=363 CT head scans were included (n=275 aged <6 months). The overall yield of intracranial injury was 37 (10%). Among 68 infants presenting with neurological signs or skull fractures, yield was 36 (53%) compared with just 1 (0.34%) of 295 without neurological signs or skull fractures. This one intracranial injury was found to be consistent with an accidental fall. Scalp injury was the only additional clinical feature associated with intracranial injury. CONCLUSION: In suspected physical abuse, CT head scans should be carried out in infants who present with neurological signs, skull fractures or scalp injuries. However, in balancing potential risks and benefits, we question the value of performing a CT head scan in every infant investigated for suspected physical abuse.

Modular and Versatile Spatial Functionalization of Tissue Engineering Scaffolds through Fiber-Initiated Controlled Radical Polymerization.

Native tissues are typically heterogeneous and hierarchically organized, and generating scaffolds that can mimic these properties is critical for tissue engineering applications. By uniquely combining controlled radical polymerization (CRP), end-functionalization of polymers, and advanced electrospinning techniques, a modular and versatile approach is introduced to generate scaffolds with spatially organized functionality. Poly-ε-caprolactone is end functionalized with either a polymerization-initiating group or a cell-binding peptide motif cyclic Arg-Gly-Asp-Ser (cRGDS), and are each sequentially electrospun to produce zonally discrete bilayers within a continuous fiber scaffold. The polymerization-initiating group is then used to graft an antifouling polymer bottlebrush based on poly(ethylene glycol) from the fiber surface using CRP exclusively within one bilayer of the scaffold. The ability to include additional multifunctionality during CRP is showcased by integrating a biotinylated monomer unit into the polymerization step allowing postmodification of the scaffold with streptavidin-coupled moieties. These combined processing techniques result in an effective bilayered and dual-functionality scaffold with a cell-adhesive surface and an opposing antifouling non-cell-adhesive surface in zonally specific regions across the thickness of the scaffold, demonstrated through fluorescent labelling and cell adhesion studies. This modular and versatile approach combines strategies to produce scaffolds with tailorable properties for many applications in tissue engineering and regenerative medicine.

Leukocyte infiltration and activation of the NLRP3 inflammasome in white adipose tissue following thermal injury.

OBJECTIVES: Severe thermal injury is associated with extreme and prolonged inflammatory and hypermetabolic responses, resulting in significant catabolism that delays recovery or even leads to multiple organ failure and death. Burned patients exhibit many symptoms of stress-induced diabetes, including hyperglycemia, hyperinsulinemia, and hyperlipidemia. Recently, the nucleotide-binding domain, leucine-rich family (NLR), pyrin-containing 3 (NLRP3) inflammasome has received much attention as the sensor of endogenous "danger signals" and mediator of "sterile inflammation" in type II diabetes. Therefore, we investigated whether the NLRP3 inflammasome is activated in the adipose tissue of burned patients, as we hypothesize that, similar to the scenario observed in chronic diabetes, the cytokines produced by the inflammasome mediate insulin resistance and metabolic dysfunction. DESIGN: Prospective cohort study. SETTING: Ross Tilley Burn Centre & Sunnybrook Research Institute. PATIENTS: We enrolled 76 patients with burn sizes ranging from 1% to 70% total body surface area. All severely burned patients exhibited burn-induced insulin resistance and hyperglycemia. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We examined the adipose tissue of control and burned patients and found, via flow cytometry and gene expression studies, increased infiltration of leukocytes-especially macrophages-and evidence of inflammasome priming and activation. Furthermore, we observed increased levels of interleukin-1ß in the plasma of burned patients when compared to controls. CONCLUSIONS: In summary, our study is the first to show activation of the inflammasome in burned humans, and our results provide impetus for further investigation of the role of the inflammasome in burn-induced hypermetabolism and, potentially, developing novel therapies targeting this protein complex for the treatment of stress-induced diabetes.

Tissue engineering and regenerative medicine: a year in review.

It is an exciting time to be involved in tissue engineering and regenerative medicine (TERM) research. Despite its relative youth, the field is expanding fast and breaking new ground in both the laboratory and clinically. In this "Year in Review," we highlight some of the high-impact advances in the field. Building upon last year's article, we have identified the recent "hot topics" and the key publications pertaining to these themes as well as ideas that have high potential to direct the field. Based on a modified methodology grounded on last year's approach, we have identified and summarized some of the most impactful publications in five main themes: (1) pluripotent stem cells: efforts and hurdles to translation, (2) tissue engineering: complex scaffolds and advanced materials, (3) directing the cell phenotype: growth factor and biomolecule presentation, (4) characterization: imaging and beyond, and (5) translation: preclinical to clinical. We have complemented our review of the research directions highlighted within these trend-setting studies with a discussion of additional articles along the same themes that have recently been published and have yet to surface in citation analyses. We conclude with a discussion of some really interesting studies that provide a glimpse of the high potential for innovation of TERM research.

Cutis verticis gyrata as a clinical manifestation of Touraine-Solente-Gole' syndrome (pachydermoperiostosis).

Cutis verticis gyrata is a descriptive term for a condition of the scalp consisting of deep grooves and convolutions that resemble the surface of the brain. We present a case of a 22-year-old man who presented with pain and swelling of both knees and hands. Enlarged wrists, ankles and feet were also noted, along with facial seborrhoea, thickening of the skin and deformity of the fingers. Physical examination of the scalp showed a cerebriform appearance with accentuating folds and deep furrows (cutis verticis gyrata), thickening in the face, frontal and parietal regions. Bone enlargement of the hands, knees, ankles and feet was also found. Secondary causes of pachydermoperiostosis were negative.

Face allotransplantation and burns: a review.

Burns may represent one of the main indications for face allotransplantation. Severely disfigured faces featuring a devastating appearance and great functional impairments are not only seen as burn sequelae but also occur as a result of other traumatic injuries, oncological surgical resections, benign tumors (eg, neurofibromatosis), and major congenital malformations. To date, 20 human face composite tissue allotransplants have been performed with success. Despite the initial scepticism about its applicability, due mainly to ethical and technical reasons, the previous worldwide cases and their associated positive outcomes, including acceptable immunosuppressive regimens, excellent aesthetic and functional results, and good psychological acceptance by the recipient, enable the conclusion that face composite tissue allotransplantation has become another therapeutic strategy in the reconstructive surgical armamentarium, which bears special consideration when dealing with severely disfigured burned patients. The aim of this review is to describe the basics of face composite tissue allotransplantation and give an overview of some of the cases performed until now, with special attention paid to debating the pros and cons of its applicability in burn patients.

Redox regulation of macrophage migration inhibitory factor expression in rat neurons.

Macrophage migration inhibitory factor (MIF) expression is induced by angiotensin II (Ang II) in normal rat neurons and serves a negative regulatory role by blunting the chronotropic actions of this peptide. The aim here was to determine whether hydrogen peroxide (H(2)O(2)), a reactive oxygen species (ROS) that is a key intracellular mediator of the neuronal actions of Ang II, is a trigger for MIF production in neurons. Thus, we tested the effects of H(2)O(2) on MIF expression in primary neuronal cultures from newborn normotensive (Wistar Kyoto [WKY] or Sprague-Dawley [SD]) rat brain, cells that respond to Ang II by increasing MIF levels. Treatment of WKY or SD rat neuronal cultures with a non-cytotoxic concentration of H(2)O(2) elicited a significant, time-dependent increase in MIF mRNA and protein levels. Glucose oxidase, which produces H(2)O(2) via oxidation of glucose in the cell-culture medium, elicited a similar increase in neuronal MIF mRNA levels. The stimulatory action of H(2)O(2) was not apparent in neuronal cultures from spontaneously hypertensive rats (SHR), cells that fail to express increased MIF in response to Ang II. Finally, preincubation of SD rat cultures with either polyethylene glycol-catalase or actinomycin D abolished the H(2)O(2)-induced increase in MIF, suggesting that this ROS is acting intracellularly to increase transcription of the MIF gene. These results suggest the presence of a redox regulatory mechanism for induction of MIF in normotensive rat neurons.

Basal and angiotensin II-inhibited neuronal delayed-rectifier K+ current are regulated by thioredoxin.

In previous studies, we determined that macrophage migration inhibitory factor (MIF), acting intracellularly via its intrinsic thiol-protein oxidoreductase (TPOR) activity, stimulates basal neuronal delayed-rectifier K(+) current (I(Kv)) and inhibits basal and angiotensin (ANG) II-induced increases in neuronal activity. These findings are the basis for our hypothesis that MIF is a negative regulator of ANG II actions in neurons. MIF has recently been recategorized as a member of the thioredoxin (Trx) superfamily of small proteins. In the present study we have examined whether Trx influences basal and ANG II-modulated I(Kv) in an effort to determine whether the Trx superfamily can exert a general regulatory influence over neuronal activity and the actions of ANG II. Intracellular application of Trx (0.8-80 nM) into rat hypothalamic/brain stem neurons in culture increased neuronal I(Kv), as measured by voltage-clamp recordings. This effect of Trx was abolished in the presence of the TPOR inhibitor PMX 464 (800 nM). Furthermore, the mutant protein recombinant human C32S/C35S-Trx, which lacks TPOR activity, failed to alter neuronal I(Kv). Trx applied at a concentration (0.08 nM) that does not alter basal I(Kv) abolished the inhibition of neuronal I(Kv) produced by ANG II (100 nM). Given our observation that ANG II increases Trx levels in neuronal cultures, it is possible that Trx (like MIF) has a negative regulatory role over basal and ANG II-stimulated neuronal activity via modulation of I(Kv). Moreover, these data suggest that TPOR may be a general mechanism for negatively regulating neuronal activity.

Evaluation of a framework for case development and simulated patient training for complex procedures.

BACKGROUND: Simulation for training and assessing clinicians is increasing but often overlooks the patient's perspective. In this paper, actors are trained to portray patients undergoing operations under local anesthetic within a high-fidelity simulated operating theater (SOT). There are few published accounts of approaches to case development and simulated patient (SP) training. We assess the feasibility of SPs playing complex surgical roles and evaluate a three-phased framework for case development and SP training. METHODS: We developed two patient roles for carotid endarterectomy (CEA) under local anesthesia. In all cases, the conscious patient interacted with the surgical team throughout the procedure. SPs were trained to simulate routine and crisis situations, using our framework. After consulting with each SP, surgeons "performed" a CEA upon a model attached to the SP. Evaluation of the framework used interviews, observations, and written evaluations with SPs, surgeons, and the project team. Descriptive statistics summarize surgeons' ratings of realism and qualitative data are analyzed thematically. RESULTS: In all, 46 simulations were conducted with 23 surgeons and three SPs. Real patient interview transcripts provided SPs with authentic information. The SP framework was easy to use, SP training was successful and surgeons' rated SP realism very highly. SPs valued guidance from the SOT control room using an audiolink. CONCLUSIONS: Actors can be trained to portray patients undergoing complex procedures. Our framework for case development and SP training was effective in creating realistic roles. Future studies could evaluate this framework for additional procedures.