Validation of diffuse correlation spectroscopy against 15O-water PET for regional cerebral blood flow measurement in neonatal piglets

Diffuse correlation spectroscopy (DCS) can non-invasively and continuously asses regional cerebral blood flow (rCBF) at the cot-side by measuring a blood flow index (BFI) in non-traditional units of cm²/s. We have validated DCS against positron emission tomography using ¹⁵O-labeled water (¹⁵O-water PET) in a piglet model allowing us to derive a conversion formula for BFI to rCBF in conventional units (ml/100g/min). Neonatal piglets were continuously monitored by the BabyLux device integrating DCS and time resolved near infrared spectroscopy (TRS) while acquiring ¹⁵O-water PET scans at baseline, after injection of acetazolamide and during induced hypoxic episodes. BFI by DCS was highly correlated with rCBF (R = 0.94, p < 0.001) by PET. A scaling factor of 0.89 (limits of agreement for individual measurement: 0.56, 1.39)×10⁹× (ml/100g/min)/(cm²/s) was used to derive baseline rCBF from baseline BFI measurements of another group of piglets and of healthy newborn infants showing an agreement with expected values. These results pave the way towards non-invasive, cot-side absolute CBF measurements by DCS on neonates.     

Routine diagnostics for neural antibodies,clinical correlates,treatment and functional outcome

Objective

To determine frequencies, interlaboratory reproducibility, clinical ratings, and prognostic implications of neural antibodies in a routine laboratory setting in patients with suspected neuropsychiatric autoimmune conditions.

Methods

Earliest available samples from 10,919 patients were tested for a broad panel of neural antibodies. Sera that reacted with leucine-rich glioma-inactivated protein 1 (LGI1), contactin-associated protein-2 (CASPR2), or the voltage-gated potassium channel (VGKC) complex were retested for LGI1 and CASPR2 antibodies by another laboratory. Physicians in charge of patients with positive antibody results retrospectively reported on clinical, treatment, and outcome parameters.

Results

Positive results were obtained for 576 patients (5.3%). Median disease duration was 6 months (interquartile range 0.6–46 months). In most patients, antibodies were detected both in CSF and serum. However, in 16 (28%) patients with N-methyl-d-aspartate receptor (NMDAR) antibodies, this diagnosis could be made only in cerebrospinal fluid (CSF). The two laboratories agreed largely on LGI1 and CASPR2 antibody diagnoses (κ = 0.95). The clinicians (413 responses, 71.7%) rated two-thirds of the antibody-positive patients as autoimmune. Antibodies against the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), NMDAR (CSF or high serum titer), γ-aminobutyric acid-B receptor (GABABR), and LGI1 had ≥ 90% positive ratings, whereas antibodies against the glycine receptor, VGKC complex, or otherwise unspecified neuropil had ≤ 40% positive ratings. Of the patients with surface antibodies, 64% improved after ≥ 3 months, mostly with ≥ 1 immunotherapy intervention.

Conclusions

This novel approach starting from routine diagnostics in a dedicated laboratory provides reliable and useful results with therapeutic implications. Counseling should consider clinical presentation, demographic features, and antibody titers of the individual patient.

     

Uveitis in Patients Treated with CTLA-4 and PD-1 Checkpoint Blockade Inhibition

ABSTRACT

Purpose: To investigate the link between treatment with CTLA-4 and PD-1 checkpoint blockade inhibitors and the development of noninfectious uveitis.

Methods: A survey was distributed to uveitis specialists to identify patients who developed uveitis while receiving either PD-1 inhibitors pembrolizumab and nivolumab; PD-L1 inhibitors atezolizumab, avelumab, and durvalumab; or the CTLA-4 inhibitor ipilimumab.

Results: Fifteen patients from seven institutions were identified. The most common cancer diagnosis (13/15) was malignant melanoma. Fourteen patients had a new uveitis diagnosis following checkpoint blockade administration (six anterior uveitis, six panuveitis, one posterior uveitis, one anterior/intermediate combined); one patient developed optic neuritis. Uveitis was diagnosed within 6 months after drug initiation for 11/12 patients (median 63 days). Corticosteroid treatment was effective for most patients, although two patients had permanent loss of vision.

Conclusions: Patients on checkpoint inhibitor therapy should be educated to seek care if they develop ocular symptoms, and prompt referral to specialists should be incorporated into oncology protocols.     

Opioid overdose prevention education for medical students: Adopting harm reduction into mandatory clerkship curricula

Abstract

Background: Opioid overdose deaths constitute a public health crisis in the United States. Strategies for reducing opioid-related harm are underutilized due in part to clinicians’ low knowledge about harm reduction theory and limited preparedness to prescribe naloxone. Educational interventions are needed to improve knowledge and attitudes about, and preparedness to address, opioid overdoses among medical students. Methods: Informed by the Department of Veterans Affairs’ Overdose Education and Naloxone Distribution (OEND) program and narrative medicine, we developed and led a mandatory workshop on harm reduction for clerkship medical students. Using validated scales, we assessed students’ knowledge and attitudes about, and preparedness to address, opioid overdoses before the workshop and 6 weeks after. Results: Of 75 participating students from February through December 2017, 55 (73%) completed pre-workshop and 38 (51%) completed both pre- and post-workshop surveys. At baseline, 40 (73%) encountered patients with perceived at-risk opioid use in the previous 6 weeks, but only 11 (20%) recalled their teams prescribing naloxone for overdose prevention. Among those completing both surveys, knowledge about and preparedness to prevent overdose showed large improvement (Cohen’s d?=?0.85, P?<?.001; Cohen’s d?=?1.24, P?<?.001, respectively) and attitudes showed moderate improvement (Cohen’s d?=?0.32, P = .04). Discussion: Educational interventions grounded in harm reduction theory can increase students’ knowledge and attitudes about, and preparedness to address, opioid overdoses.     

Differences between medical school and PGY1 learning outcomes: An explanation for new graduates not being “work ready”?

Abstract

Background: Widespread concerns about new medical graduates’ ‘work readiness’ may reflect, in part, differences in mandatory learning outcomes for medical students and new medical graduates.

Purpose: To examine differences between required medical student and PGY1 (first year resident) training program outcomes, and the nature and magnitude of these differences.

Method: Comparison, systematic identification and thematic analysis of differences between the graduate outcomes in the Australian Medical Council Standards for the Assessment and Accreditation of Primary Medical Programs and those in the New Zealand Curriculum Framework for Prevocational Training.

Results: The relationship between these outcome statements were categorized as: essentially similar; continuity; partial discontinuity; and complete discontinuity of learning trajectory. Areas requiring substantial new learning may reflect medical schools’ focus on individual student performance, and on learning and assessments based on single episodes of often uncomplicated illness. This contrasted with a post-graduate focus on integrated health care delivery by teams and management of complex illnesses over the whole patient care journey.

Conclusions: Characterizing these marked differences between pre-graduate and postgraduate standards, within a trajectory of learning, explains some of the difficulties in students’ preparation for work readiness. These could inform learning interventions to support new graduates’ professional development to ensure patient safety. Development and revision of accreditation standards should include formal review against the expectations of the preceding and succeeding phases of learning.     

Heart-type fatty acid-binding protein: an overlooked cardiac biomarker

Abstract

Cardiac troponins (cTn) are currently the standard of care for the diagnosis of acute coronary syndromes (ACS) in patients presenting to the emergency department (ED) with chest pain (CP). However, their plasma kinetics necessitate a prolonged ED stay or overnight hospital admission, especially in those presenting early after CP onset. Moreover, ruling out ACS in low-risk patients requires prolonged ED observation or overnight hospital admission to allow serial measurements of c-Tn, adding cost. Heart-type fatty acid-binding protein (H-FABP) is a novel marker of myocardial injury with putative advantages over cTn. Being present in abundance in the myocellular cytoplasm, it is released rapidly (<1?h) after the onset of myocardial injury and could potentially play an important role in both earlier diagnosis of high-risk patients presenting early after CP onset, as well as in risk-stratifying low-risk patients rapidly. Like cTn, H-FABP also has a potential role as a prognostic marker in other conditions where the myocardial injury occurs, such as acute congestive heart failure (CHF) and acute pulmonary embolism (PE). This review provides an overview of the evidence examining the role of H-FABP in early diagnosis and risk stratification of patients with CP and in non-ACS conditions associated with myocardial injury.

• Key messages

• Heart-type fatty acid-binding protein is a biomarker that is elevated early in myocardial injury

• The routine use in the emergency department complements the use of troponins in ruling out acute coronary syndromes in patients presenting early with chest pain

• It also is useful in risk stratifying patients with other conditions such as heart failure and acute pulmonary embolism.

     

Effects of boron-containing compounds on immune responses: review and patenting trends

Introduction: Boron-containing compounds induce effects on immune responses. Such effects are interesting to the biomedical field for the development of therapeutic tools to modulate the immune system.

Areas covered: The scope of BCC use to modify immune responses is expanding, mainly with regard to inflammatory diseases. The information was organized to demonstrate the breadth of reported effects. BCCs act as modulators of innate and adaptive immunity, with the former including regulation of cluster differentiation and cytokine production. In addition, BCCs exert effects on inflammation induced by infectious and noninfectious agents, and there are also reports regarding their effects on mechanisms involving hypersensitivity and transplants. Finally, the authors discuss the beneficial effects of BCCs on pathologies involving various targets and mechanisms.

Expert opinion: Some BCCs are currently used as drugs in humans. The mechanisms by which these BCCs modulate immune responses, as well as the required structure–activity relationship for each observed mechanism of action, should be clarified. The former will allow for the development of improved immunomodulatory drugs with extensive applications in medicine. Patenting trends involve claims concerning the synthesis and actions of identified molecules with a defined profile regarding cytokines, cell differentiation, proliferation, and antibody production.     

Are HCAHPS Scores Higher for Private vs Double-Occupancy Inpatient Rooms in Total Joint Arthroplasty Patients?

Background

Private hospital rooms have a number of potential advantages compared to shared rooms, including reduced noise and increased control over the hospital environment. However, the association of room type with patient experience metrics in total joint arthroplasty (TJA) patients is currently unclear.

The Psychotherapy Outcome Problem: The Development of the Outcome Stability Index

Objective: Psychotherapy research commonly utilizes clients’ last session score as an indicator of treatment outcome. We examined whether this last session score is consistent with what would be predicted based on clients’ general trajectory in psychological functioning across sessions. We focused on the unstandardized residual variance at the last session, as this represents the degree to which the session score is divergent (or not) from what is predicted from the previous sessions (i.e., Outcome Stability Index; OSI). Method: The sample included 27,958 clients who attended on average 9.41 sessions. Each session, clients completed the Behavioral Health Measure-20 as a measure of psychological functioning. We converted the unstandardized residual variance for clients’ last session score into a Cohen’s d coefficient to aid in interpretation. Results: The mean OSI was 0.07 (SD?=?0.58), suggesting excellent stability in their last session therapy outcome scores. However, approximately 33% of clients demonstrated poor or extremely problematic stability in their last session therapy outcome scores. Clients who demonstrated poor stability were classified as demonstrating reliable deterioration. Conclusions: Researchers may want to consider reporting OSI to assist readers’ understanding of the stability of therapy outcomes.

Clinical or methodological significance of this article: Therapy outcome scores can vary from session to session, which can influence how we understand therapy outcomes that rely on last session scores. Studies examining therapy outcomes could report the Outcome Stability Index to better contextualize the results.