The association between neighborhood-level social fragmentation and distressing psychotic-like experiences in early adolescence: the moderating role of close friends.

BACKGROUND: Early exposure to neighborhood social fragmentation has been shown to be associated with schizophrenia. The impact of social fragmentation and friendships on distressing psychotic-like experiences (PLE) remains unknown. We investigate the relationships between neighborhood social fragmentation, number of friends, and distressing PLE among early adolescents. METHODS: Data were collected from the Adolescent Brain Cognitive Development Study. Generalized linear mixed models tested associations between social fragmentation and distressing PLE, as well as the moderating role of the number of total and close friends. RESULTS: Participants included 11 133 adolescents aged 9 to 10, with 52.3% being males. Greater neighborhood social fragmentation was associated with higher levels of distressing PLE (adjusted ß = 0.05; 95% CI: 0.01-0.09). The number of close but not total friends significantly interacted with social fragmentation to predict distressing PLE (adjusted ß = -0.02; 95% CI: -0.04 to <-0.01). Among those with fewer close friends, the association between neighborhood social fragmentation and distressing PLE was significant (adjusted ß = 0.07; 95% CI: 0.03-0.11). However, among those with more close friends, the association was non-significant (adjusted ß = 0.03; 95% CI: -0.01 to 0.07). CONCLUSIONS: Greater neighborhood social fragmentation is associated with higher levels of distressing PLE, particularly among those with fewer close friends. Further research is needed to disentangle aspects of the interaction between neighborhood characteristics and the quality of social interactions that may contribute to psychosis, which would have implications for developing effective interventions at the individual and community levels.

Developmental perspectives on the origins of psychotic disorders: The need for a transdiagnostic approach.

Research on serious mental disorders, particularly psychosis, has revealed highly variable symptom profiles and developmental trajectories prior to illness-onset. As Dante Cicchetti pointed out decades before the term "transdiagnostic" was widely used, the pathways to psychopathology emerge in a system involving equifinality and multifinality. Like most other psychological disorders, psychosis is associated with multiple domains of risk factors, both genetic and environmental, and there are many transdiagnostic developmental pathways that can lead to psychotic syndromes. In this article, we discuss our current understanding of heterogeneity in the etiology of psychosis and its implications for approaches to conceptualizing etiology and research. We highlight the need for examining risk factors at multiple levels and to increase the emphasis on transdiagnostic developmental trajectories as a key variable associated with etiologic subtypes. This will be increasingly feasible now that large, longitudinal datasets are becoming available and researchers have access to more sophisticated analytic tools, such as machine learning, which can identify more homogenous subtypes with the ultimate goal of enhancing options for treatment and preventive intervention.

Social connections as determinants of cognitive health and as targets for social interventions in persons with or at risk of Alzheimer's disease and related disorders: a scoping review.

BACKGROUND: Social connections have a significant impact on health across age groups, including older adults. Loneliness and social isolation are known risk factors for Alzheimer's disease and related dementias (ADRD). Yet, we did not find a review focused on meta-analyses and systematic reviews of studies that had examined associations of social connections with cognitive decline and trials of technology-based and other social interventions to enhance social connections in people with ADRD. STUDY DESIGN: We conducted a scoping review of 11 meta-analyses and systematic reviews of social connections as possible determinants of cognitive decline in older adults with or at risk of developing ADRD. We also examined eight systematic reviews of technology-based and other social interventions in persons with ADRD. STUDY RESULTS: The strongest evidence for an association of social connections with lower risk of cognitive decline was related to social engagement and social activities. There was also evidence linking social network size to cognitive function or cognitive decline, but it was not consistently significant. A number of, though not all, studies reported a significant association of marital status with risk of ADRD. Surprisingly, evidence showing that social support reduces the risk of ADRD was weak. To varying degrees, technology-based and other social interventions designed to reduce loneliness in people with ADRD improved social connections and activities as well as quality of life but had no significant impact on cognition. We discuss strengths and limitations of the studies included. CONCLUSIONS: Social engagement and social activities seem to be the most consistent components of social connections for improving cognitive health among individuals with or at risk for ADRD. Socially focused technology-based and other social interventions aid in improving social activities and connections and deserve more research.

Expanding the clinical spectrum of idiopathic intracranial hypertension.

PURPOSE OF REVIEW: Idiopathic intracranial hypertension (IIH) is a disorder of raised intracranial pressure (ICP). Although the majority of patients with IIH present classically with headache and papilledema, some patients may have unusual presentations or manifestations. Recent advancements in neuroimaging have facilitated the identification of other presentations associated with IIH. This review provides an overview of the expanding clinical spectrum of IIH. RECENT FINDINGS: Presentations of IIH that are considered unusual include highly asymmetric or unilateral papilledema, IIH without papilledema, and IIH associated with cranial nerve involvement. These presentations likely reflect differences in the way cerebrospinal fluid (CSF) pressure is transmitted intracranially. Radiological signs of intracranial hypertension are increasingly recognized in patients with IIH and provide further insights into the effects of raised ICP on intracranial structures. Osseous changes in the skull base leading to formation of meningoceles and encephaloceles have been identified in patients with IIH, spontaneous skull base CSF leak, and drug-resistant temporal lobe epilepsy, suggesting a possible association. SUMMARY: Clinicians should be familiar with the expanding clinical spectrum of IIH and the implications for the management of these presentations.

Lexical Diversity and Other Linguistic Measures in Schizophrenia: Associations With Negative Symptoms and Neurocognitive Performance.

ABSTRACT: Straightforward linguistic measures may be indicators of reduced language production and lexical diversity among individuals with schizophrenia with negative symptoms and neurocognitive impairments. We compared 98 patients with schizophrenia to 101 unaffected controls on six language variables ( e.g. , number of relationships between objects, use of complex transitions in the narrative structure), number of words produced, and lexical diversity computed as the moving average type-token ratio from both speaking and writing tasks. Patients differed from controls on nearly all of the linguistic measures; number of words produced had the strongest effect, with an average Cohen's d of 0.68; values pertaining to lexical diversity were 0.50 and 0.32, respectively, for the speaking tasks and the writing tasks. Most measures were correlated with alogia and other domains of negative symptoms (including avolition-apathy and anhedonia-asociality), as well as with diverse neurocognitive domains, especially those pertaining to working memory, verbal learning, and verbal category fluency. Further work is needed to understand longitudinal changes in these linguistic variables, as well as their utility as measures of alogia.

Presumptive Idiopathic Intracranial Hypertension Based on Neuroimaging Findings: A Referral Pattern Study.

BACKGROUND: Radiologic findings of intracranial hypertension (RAD-IH) are common in idiopathic intracranial hypertension (IIH) patients. Paralleling the increasing rates of obesity, the burden of IIH is growing. Urgent neuro-ophthalmology consultations for possible IIH in patients with incidentally detected RAD-IH are increasing, with many patients receiving unnecessary lumbar punctures (LPs) and treatments. This retrospective observational study aimed to determine the prevalence of neuro-ophthalmology consultations for RAD-IH, rate of funduscopic examination by referring providers, prevalence of papilledema, outcomes after neuro-ophthalmic evaluation, and rates of misdiagnosis. METHODS: Records of 1,262 consecutive new patients seen in one neuro-ophthalmology clinic from January 2019 to January 2020 were reviewed. We identified patients who were: 1) referred with concern for IIH because of findings of RAD-IH; 2) referred for "papilledema"; 3) referred with a diagnosis of IIH; and 4) referred for spontaneous cranial cerebrospinal fluid (CSF) leaks. In addition to basic demographic profiles for all groups, detailed information was collected for patients referred solely for RAD-IH, including referral patterns, prior history of IIH, previous LPs, prior medical or surgical treatment(s), risk factors for increased intracranial pressure (ICP), presenting symptoms, radiologic features observed on neuroimaging, and final disposition. When available, the neuroimaging was reviewed by an expert neuroradiologist. RESULTS: Of 1,262 consecutive new patients, 66 (5%) were referred specifically for RAD-IH; most referrals came from neurologists (58%); 8/66 (12%) patients had papilledema; 16/66 (24%) patients had prior LP and 13/66 (20%) were already treated based on MRI findings; and 22/66 (33%) patients had ≤2 RAD-IH. Only 34/66 (52%) of patients referred for RAD-IH had prior funduscopic examinations. We confirmed papilledema in 26/82 (32%) patients referred for "papilledema." Only 29/83 (35%) patients referred with a diagnosis of IIH had active papilledema, and 3/16 (19%) patients with spontaneous CSF leaks had papilledema. In total, 247/1,262 (20%) new patients were referred to our clinic over 1 year with concern for IIH, among whom only 66 (27%) were confirmed to have active IIH with papilledema. CONCLUSIONS: One in 5 new patient referrals seen in our neuro-ophthalmology clinic were referred because of concern for increased ICP, but only 1/4 had active papilledema. Most patients referred for isolated RAD-IH do not have papilledema, many having undergone unnecessary LPs and treatments. The burden of these "rule-out IIH" consultations is overwhelming and will only continue to increase with the concurrent rise of obesity and IIH, straining the already limited neuro-ophthalmologic resources available in the US.

Prevalence of Food Insecurity and Living in a Food Desert among Individuals with Serious Mental Illnesses in Public Mental Health Clinics.

Very little is known about the prevalence of food insecurity-and living in a food desert-among persons with serious mental illnesses, such as schizophrenia and major mood disorders. This study evaluated those prevalences and assessed for associations with six other variables. Surveys were conducted with 300 patients with a psychotic or mood disorder receiving outpatient services at five community mental health agencies in Washington, D.C. The prevalences of low food security and very low food security were 68.9% and 46.8%, compared to national rates of 13.7% (13.2% in Washington, D.C.) and 5.4% (4.8% in Washington, D.C.). 50.0% of participants lived in food desert census tracts, which was associated with both severe and morbid obesity (p = .02 and p = .03, respectively). Additional research, evaluation of clinical implications, and potential policy approaches to these concerning social determinants of physical and mental health, in an already vulnerable patient population, are warranted.

Developments in the Treatment of Leber Hereditary Optic Neuropathy.

PURPOSEOF REVIEW: To outline the current landscape of treatments for Leber hereditary optic neuropathy (LHON) along the therapeutic delivery pipeline, exploring the mechanisms of action and evidence for these therapeutic approaches. RECENT FINDINGS: Treatments for LHON can be broadly classified as either mutation-specific or mutation-independent. Mutation-specific therapies aim to correct the underlying mutation through the use of a gene-editing platform or replace the faulty mitochondrial DNA-encoded protein by delivering the wild-type gene using a suitable vector. Recent gene therapy clinical trials assessing the efficacy of allotopically expressed MT-ND4 for the treatment of LHON due to the m.11778G > A mutation in MT-ND4 have shown positive results when treated within 12 months of symptom onset. Mutation-independent therapies can have various downstream targets that aim to improve mitochondrial respiration, reduce mitochondrial stress, inhibit or delay retinal ganglion cell apoptosis, and/or promote retinal ganglion cell survival. Idebenone, a synthetic hydrosoluble analogue of co-enzyme Q10 (ubiquinone), is the only approved treatment for LHON. Mutation-independent approaches to gene therapy under pre-clinical investigation for other neurodegenerative disorders may have the potential to benefit patients with LHON. Although approved treatments are presently limited, innovations in gene therapy and editing are driving the expansion of the therapeutic delivery pipeline for LHON.

Capturing the experiences of patients with inherited optic neuropathies: a systematic review of patient-reported outcome measures (PROMs) and qualitative studies.

PURPOSE: To identify and comprehensively evaluate studies capturing the experience of individuals affected by an inherited optic neuropathy (ION), focusing on patient-reported outcome measures (PROMs) and qualitative studies where the health status and quality of life (QoL) of these individuals have been explored. METHODS: Systematic review of five databases using a search strategy combining four concepts: (1) ION; (2) QoL and health status; (3) PROMs; and (4) qualitative research. Studies assessing the impact of ION on any QoL domain using a PROM or qualitative methodology were included and appraised, using criteria based on the COSMIN checklist (for PROM studies) and the CASP checklist (for qualitative studies). RESULTS: Of 1326 unique articles identified, six studies were included. Five PROMs were identified: Visual Function Index (VF-14); Hospital Anxiety and Depression Scale (HADS); a novel graphical online assessment tool (NGOAT) for reporting emotional response to vision loss; a new PROM informed by the DSM-V Criteria for Major Depressive Disorder; and an interpersonal and career 'impact rating' PROM. The psychometric performance of included PROMs were poorly described. Qualitative studies found that vision loss resulted in psychosocial losses including loss of social and communication skills and loss of independence and freedom. Factors that modified the response to vision loss were also identified. CONCLUSION: The current PROMs used by individuals with ION have poor content coverage, primarily measuring activity limitation and emotional well-being, and insufficient reporting of psychometric performance. There is a need to develop a PROM for individuals ION to report their experiences of living with their condition.

The Impact of Leber Hereditary Optic Neuropathy on the Quality of Life of Patients and Their Relatives: A Qualitative Study.

BACKGROUND: Leber hereditary optic neuropathy (LHON) is an inherited mitochondrial disease characterized by severe bilateral vision loss and chronic visual impairment. The objective of this study was to comprehensively explore the impact of LHON on the lives of patients and their relatives at the time of diagnosis and now. METHODS: Qualitative study design with 8 focus group interviews conducted in France, Germany, the United Kingdom, and the United States, involving 17 individuals with m.11778G>A mutation and their relatives. Separate focus groups for patients and their relatives were facilitated by a moderator in French, German, or English. Qualitative analysis of interviews using a pre-defined analytical framework. RESULTS: Participants reported feeling devastated by the diagnosis of LHON after a lengthy and worrisome diagnostic journey. Patients were frustrated by the loss of autonomy, which also affected their relatives. Participants described challenges across several domains: physical capabilities, emotional well-being, interpersonal relationships, work and studies, finances, and recreational activities. Access to disability allowances, vision aids, and funded or subsided idebenone varied by country, resulting in unequal financial impact. Patients are hopeful for therapy that would restore autonomy and improve their ability to enjoy a fulfilling life, while alleviating the demands placed on their relatives. CONCLUSIONS: The impact of LHON extends beyond vision-related activity limitations. Addressing the psychosocial impact of LHON and helping patients and their relatives adapt and cope with vision loss are vital. As part of this, an accurate and timely diagnosis is important to enable early intervention. Further investigation of specific unmet needs is required.

Impact of Payer Status on Hospitalization Outcomes in Pediatric Diabetic Ketoacidosis.

BACKGROUND: Diabetic ketoacidosis (DKA) is a life-threatening complication seen in patients suffering from type I diabetes (T1D) with a cost burden of over $5 billion in the U.S. annually. Often, children are first diagnosed with T1D when they present with DKA. Our study examines the impact of payer type on pediatric DKA. We hypothesize that Medicaid payer type negatively impacts costs and care outcomes in pediatric patients with DKA as compared to private payers. METHODS: We utilized the Agency for Healthcare Research and Quality (AHRQ) 2012 Kids' Inpatient Database (KID) for analysis. Our inclusion criterion included All Patient Refined Diagnosis Related Groups (APR-DRG) coding for T1D DKA admissions with a uniform severity and an identifiable payer of Medicaid or private insurance. RESULTS: 27,241 weighted and severity-adjusted discharges met criterion (51.6 percent Medicaid payers, 48.4 percent private). Comparing Medicaid vs. private payer status, we found: length of stay (2.24 days vs. 2.09), number of procedures received (0.13 vs. 0.12), and total charges ($16,449 vs. $16,107). Limiting analysis to a crude measure of bottom quartile income showed: length of stay (2.26 days vs. 2.14), number of procedures received (0.12 vs. 0.12), and total charges ($15,393 vs. $14,063). CONCLUSIONS: Children admitted in DKA and covered by Medicaid had longer hospitalizations, more procedures performed, and higher total costs of care. Even after controlling for socioeconomic status, similar effects persisted. Further evaluations are warranted to reveal the causative factors behind these correlative findings which suggest DKA patients receive different care depending on their payer status.

Infant With Acute Bilateral Pneumothorax During Air Transport.

In rural settings, medically complicated patients may require air transport to facilities that are capable of providing higher levels of care. Extra consideration must be given to pulmonary pathologies when considering this mode of transport. Altitude changes impact both air pressure and volume as described by Boyle's law. These changes can complicate the care of these patients in several ways. We present a case of patient with respiratory failure secondary to viral infection who developed acute bilateral pneumothorax (PTX) while mechanically ventilated during a transport on a fixed-wing aircraft. In this article we outline the unique risks of air travel on the development and progression of PTX as well as the unique challenges with diagnosis and treatment during air transport.

Prediction of Postoperative Risk of Raised Intracranial Pressure After Spontaneous Skull Base Cerebrospinal Fluid Leak Repair.

BACKGROUND: A relationship between idiopathic intracranial hypertension and spontaneous skull base cerebrospinal fluid (CSF) leaks has been proposed, by which CSF leak decreases intracranial pressure (ICP) and masks the symptoms and signs of elevated ICP. These patients are at risk of developing papilledema, symptoms of elevated ICP, or a recurrent CSF leak after CSF leak repair. The objective of this study was to assess whether radiographic signs of raised ICP on preoperative magnetic resonance or computed venography (MRI or CTV) are predictors of postoperative papilledema, recurrence of CSF leak, or need for CSF shunt surgery. METHODS: We performed a retrospective review of systematically collected demographics, fundus examination, and presurgical brain MRI and magnetic resonance venography/computed tomography venography (MRV/CTV) in patients seen at 1 institution between 2013 and 2019 with spontaneous skull base CSF leak repair. Patients were divided into 2 groups depending on whether they developed papilledema, recurrent CSF leak, or required CSF shunting (Group 1) or not (Group 2). RESULTS: Fifty-seven patients were included, among whom 19 were in Group 1. There was no difference in demographic characteristics or clinical features between patients in Group 1 and Group 2. Controlling for other imaging features, bilateral transverse venous sinus stenosis (TVSS) on preoperative imaging increased the odds of being in Group 1 by 4.2 times (95% confidence interval [CI], 1.04-21.2, P = 0.04), optic nerve tortuosity decreased the odds of being in Group 1 by 8.3 times (95% CI: 1.4-74.6, P = 0.02). CONCLUSION: Imaging of the intracranial venous system with MRV or CTV is warranted before repair of spontaneous CSF leak, as bilateral TVSS is an independent risk factor for postoperative papilledema, CSF leak recurrence, or need for a CSF shunting procedure.

Optic Nerve Angle in Idiopathic Intracranial Hypertension.

BACKGROUND: The tortuosity of the optic nerve can be quantified radiologically by measuring the angle of optic nerve deformation (the "optic nerve angle" [ONA]). In patients with idiopathic intracranial hypertension (IIH), lowering the intracranial pressure (ICP) to a normal range by lumbar puncture leads to straightening of the optic nerve and an increase in the measured sagittal ONA on MRI. It is uncertain whether there is any correlation between ONA and cerebrospinal fluid (CSF) opening pressure or visual function. METHODS: Retrospective study of patients with and without IIH who had MRI of the brain followed by lumbar puncture with CSF opening pressure within 24 hours of MRI. Before LP and within 24 hours of MRI of the brain, all patients with IIH had neuro-ophthalmologic assessment including visual acuity, Humphrey Visual Field (HVF), and fundus photography. Sagittal ONA was measured on multiplanar T2-SPACE images on a DICOM viewer. Papilledema on the fundus photographs was graded using the Frisén scale. RESULTS: Fifty-four patients with IIH and 30 unmatched controls were included. The IIH group was 6.3 years younger (95% CI 2.4-10.3, P = 0.002), had 8.7 kg/m2 higher body mass index (4.9-12.5, P < 0.001), and 26.3% more women (P = 0.011) compared with controls. In both eyes, the ONA was significantly smaller in patients with IIH by 12° compared with controls (7°-17°, P < 0.00001). In the IIH group, no correlation between ONA and the CSF opening pressure was present in either eye (right eye r = 0.19, P = 0.15; left eye r = 0.18, P = 0.19) The ONA did not correlate with logarithm of the minimum angle of resolution visual acuity (right eye r = 0.26, P = 0.063; left eye r = 0.15, P = 0.27), HVF mean deviation (right eye r = 0.0059, P = 0.97; left eye r = -0.069, P = 0.63), or Frisén grade (Spearman's rho right eye 0.058, P = 0.67; left eye 0.14, P = 0.30). CONCLUSIONS: The ONA is significantly smaller in patients with IIH compared to controls, but does not correlate with CSF opening pressure, severity of papilledema, or visual function. The ONA may be useful in identifying patients with raised ICP, but not necessarily those with a poor visual prognosis.

[Nocebo, informed consent and doctor-patient communication]. / Nocebo, Aufklärung und Arzt-Patienten-Kommunikation.

Negative previous experiences (conditioning), observational learning and expectations can trigger nocebo effects. They are responsible for a substantial proportion of the side effects of medical treatment, and are induced primarily by risk information for informed consent. This has been demonstrated in studies on patient groups with or without modified medical information. Drug trials in the field of neurology and psychiatry have regularly revealed side effects and drop-out also in placebo groups. The underlying neurobiological mechanisms were experimentally investigated especially for nocebo-induced hyperalgesia, whereby the specifically involved regions of the brain could be identified by functional imaging as well as changes in the dopamine, endorphin and cholecystokinin systems. Nocebo effects are specific, i.e. they are closely related to patient information and can induce or aggravate exactly the symptoms addressed. Nevertheless, informed consent is an essential part of doctor-patient communication; however, information on risks can be markedly less damaging when unnecessary repetitions are avoided, misunderstandings are recognized or resolved and several different options are given. In addition, risks should always be named together with positive aspects, such as the advantages of the appropriate treatment, the prophylactic measures applied or the early detection and treatment of developing side effects. The best protection against harm caused by information on risks is a trustful doctor-patient relationship. Poor knowledge of nocebo effects or lack of countermeasures constitute a serious threat to patients and according to the current state of knowledge could be rated as medical malpractice.

The PARACELSUS score: a novel diagnostic tool for pyoderma gangrenosum.

BACKGROUND: The lack of objective diagnostic criteria renders pyoderma gangrenosum (PG) a diagnosis of exclusion. The diagnostic approaches proposed to date have not been systematically evaluated. Thus, PG remains a challenging and frequently misdiagnosed disorder. OBJECTIVES: To develop and assess a comprehensive, yet clinically practicable, sensitive diagnostic scoring system for PG. METHODS: Clinical history and images of a total of 60 participants with previously confirmed PG located on the lower extremity and a control cohort of 50 patients with venous leg ulcers were retrospectively evaluated by expert teams at two tertiary dermatological centres specializing in wound care using a newly developed diagnostic scoring system composed of 10 criteria. RESULTS: The three major diagnostic criteria are rapidly progressing disease, assessment of relevant differential diagnoses and a reddish-violaceous wound border (prevalent in 98% of patients with PG). Minor criteria (evident in 61-95% of patients with PG) include amelioration by immunosuppressant drugs, characteristically irregular shape of ulceration, extreme pain > 4/10 on a visual analogue scale and localization of lesion at the site of the trauma. Three additional criteria (observed in up to 60% of patients with PG) encompass suppurative inflammation in histopathology, undermined wound borders and systemic disease associated. A total score value of 10 points or higher indicates a high likelihood of PG and differentiates PG from venous leg ulcers. The initial letters of the above-listed criteria form the acronym PARACELSUS. CONCLUSIONS: The PARACELSUS score represents a novel, easily implementable, effective and sensitive diagnostic tool for PG.

Criteria for Critical Care Infants and Children: PICU Admission, Discharge, and Triage Practice Statement and Levels of Care Guidance.

OBJECTIVES: To update the American Academy of Pediatrics and Society of Critical Care Medicine's 2004 Guidelines and levels of care for PICU. DESIGN: A task force was appointed by the American College of Critical Care Medicine to follow a standardized and systematic review of the literature using an evidence-based approach. The 2004 Admission, Discharge and Triage Guidelines served as the starting point, and searches in Medline (Ovid), Embase (Ovid), and PubMed resulted in 329 articles published from 2004 to 2016. Only 21 pediatric studies evaluating outcomes related to pediatric level of care, specialized PICU, patient volume, or personnel. Of these, 13 studies were large retrospective registry data analyses, six small single-center studies, and two multicenter survey analyses. Limited high-quality evidence was found, and therefore, a modified Delphi process was used. Liaisons from the American Academy of Pediatrics were included in the panel representing critical care, surgical, and hospital medicine expertise for the development of this practice guidance. The title was amended to "practice statement" and "guidance" because Grading of Recommendations, Assessment, Development, and Evaluation methodology was not possible in this administrative work and to align with requirements put forth by the American Academy of Pediatrics. METHODS: The panel consisted of two groups: a voting group and a writing group. The panel used an iterative collaborative approach to formulate statements on the basis of the literature review and common practice of the pediatric critical care bedside experts and administrators on the task force. Statements were then formulated and presented via an online anonymous voting tool to a voting group using a three-cycle interactive forecasting Delphi method. With each cycle of voting, statements were refined on the basis of votes received and on comments. Voting was conducted between the months of January 2017 and March 2017. The consensus was deemed achieved once 80% or higher scores from the voting group were recorded on any given statement or where there was consensus upon review of comments provided by voters. The Voting Panel was required to vote in all three forecasting events for the final evaluation of the data and inclusion in this work. The writing panel developed admission recommendations by level of care on the basis of voting results. RESULTS: The panel voted on 30 statements, five of which were multicomponent statements addressing characteristics specific to PICU level of care including team structure, technology, education and training, academic pursuits, and indications for transfer to tertiary or quaternary PICU. Of the remaining 25 statements, 17 reached consensus cutoff score. Following a review of the Delphi results and consensus, the recommendations were written. CONCLUSIONS: This practice statement and level of care guidance manuscript addresses important specifications for each PICU level of care, including the team structure and resources, technology and equipment, education and training, quality metrics, admission and discharge criteria, and indications for transfer to a higher level of care. The sparse high-quality evidence led the panel to use a modified Delphi process to seek expert opinion to develop consensus-based recommendations where gaps in the evidence exist. Despite this limitation, the members of the Task Force believe that these recommendations will provide guidance to practitioners in making informed decisions regarding pediatric admission or transfer to the appropriate level of care to achieve best outcomes.

Selective increase of cerebrospinal fluid IL-6 during experimental systemic inflammation in humans: association with depressive symptoms.

Systemic inflammation is accompanied by profound behavioral and mood changes that resemble symptoms of depression. Findings in animals suggest that pro-inflammatory cytokines released by activated immune cells in the periphery evoke these behavioral symptoms by driving inflammatory changes in the brain. However, experimental data in humans are lacking. Here we demonstrate in healthy male volunteers (10 endotoxin treated, 8 placebo treated) that intravenous administration of low-dose endotoxin (0.8 ng/kg body weight), a prototypical pathogen-associated molecular pattern that activates the innate immune system, not only induces a significant increase in peripheral blood cytokine concentrations (that is, tumor necrosis factor-α, interleukin (IL)-6, IL-10) but also results, with some latency, in a robust and selective increase of IL-6 in the cerebrospinal fluid (CSF). Moreover, we found a strong association between the endotoxin-induced increase of IL-6 in the CSF and the severity of mood impairment, with larger increases in CSF IL-6 concentration followed by a greater deterioration in mood. Taken together, these findings suggest that the appearance of depressive symptoms in inflammatory conditions might be primarily linked to an increase in central IL-6 concentration, identifying IL-6 as a potential therapeutic target in mood disorders.

Cyclical cardiorenal syndrome in late-stage kidney disease
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INTRODUCTION: In patients with late-stage chronic kidney disease (LS-CKD, estimated glomerular filtration rate (eGFR) < 30 mL/min) there is a high prevalence of congestive heart failure (CHF). We have observed a cyclical nature in the "cardiorenal syndrome" in LS-CKD, not previously described. The purpose of this article is to describe the syndrome and review its characteristics. MATERIALS AND METHODS: Patients enrolled in the Northwell Health Healthy Transitions in Late Stage Kidney Disease Program (HT) were followed, all with eGFR 0 - 30 mL/min. Patients were observed for a 1-year period for signs of destabilized cardiorenal syndrome. The primary outcome of interest was an episode of cyclical cardiorenal syndrome (CCRS), defined as CHF symptoms leading to increased diuretic dose or increased renin-angiotensin-aldosterone system inhibitors (RAASi) followed within 60 days by acute kidney failure (AKI), or, conversely, an episode of AKI with reduction in diuretic or RAASi, followed within 60 days by worsening of CHF. RESULTS: Of 302 HT patients, 63 (20.9%) patients had at least one episode of CCRS. Of the 63 patients, there were 89 CCRS episodes (ranging 1 - 3 per patient) and 32 (35.0%) associated hospitalizations for CHF. Of 89 CCRS episodes, 67 (75.3%) started with an episode of CHF, 22 (24.7%) started with AKI. Of 67 cases of CHF with subsequent AKI, the associated medication change was a diuretic dose increase in 61 cases (91.0%), increase in RAASi dose in 3 cases (4.5%), and increases in both in 3 cases (4.5%). Of 22 cases of AKI leading to subsequent CHF, the associated medication change was a diuretic dose decrease in 19 (86.4%) and a decrease in both diuretic and RAASi dose in 3 (13.6%). CONCLUSION: CCRS occurs in ~ 1/5 of late-stage CKD patients with CHF. Further study would help to elucidate the extent to which fragmented care between cardiologists and nephrologists contributes to the problem.
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Permanent peritoneal ports for the management of recurrent malignant ascites: a retrospective review of safety and efficacy.

Large volume paracentesis is effective in relieving the symptoms of malignant ascites, but frequent procedures are often required. Permanent peritoneal ports are an alternative to repeated procedures. We describe our experience with the use of peritoneal ports in patients at Middlemore Hospital (Auckland, New Zealand) who had a port inserted for the drainage of malignant ascites. Twenty-eight ports were inserted in 26 patients and accessed a total of 257 times with acceptably low rates of complications including cellulitis, peritonitis and wound dehiscence.