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.     

Reliability and validity of the UTBAS-TR (The Unhelpful Thoughts and Beliefs Scale-the Turkish version) in the Turkish population

Abstract

Purpose: This paper decribes the development of the Turkish adaptation of UTBAS (UTBAS-TR) and reports the results concerning its applicability and psychometric structure.

Method: The sample consisted of 81 males and 19 females diagnosed with developmental stuttering in two centres. Test-retest reliability score was obtained by correlating results of repeated aplications of the scale within a one-week interval and a paired t-test was calculated to see the differences in the total and UTBAS I, II and III scores. The internal consistency was assessed using the Cronbach’s alpha. Construct validity was also assessed by examining inter-scale correlations and with the correlations of the UTBAS-TR with two other scales (State-Trait Anxiety Inventory (STAI) and Beck Anxiety Inventory (BAI)).

Result: The internal consistency of the UTBAS-TR and the test and retest reliability score was stati?stically significant. The correlation between UTBAS-TR total score and the UTBAS-TR I, II and III correlations were high. A significant correlation was observed between UTBAS-TR total score with State Anxiety Inventory. However, the correlations between UTBAS-TR-Total Score and Trait Anxiety Inventory and Beck Anxiety Inventory were low.

Conclusion: The UTBAS-TR proved to be suitable for use with the Turkish population.     

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.     

Association between periodontitis and medication-related osteonecrosis of the jaw: A systematic review and meta-analysis

Consensus has yet to be reached about the prevention and treatment of medication-related osteonecrosis of the jaw (MRONJ), which is a treatment sequela of several antiresorptive therapies and other pharmaceutical interventions. Several epidemiologic studies have identified periodontal disease (PD) as a risk factor for this outcome. Thus, the objective of this systematic review and meta-analysis was to investigate this association and its magnitude. A systematic search in MEDLINE via PubMed, Scopus and ISI Web of Science, and a meta-analysis were undertaken. Observational studies that gathered information regarding prefixed definitions for both outcomes were selected, and the relevant information was then extracted, and their risk of bias was evaluated using the Newcastle-Ottawa Scale. The protocol of the study was registered on PROSPERO (CRD42019125646). The initial search yielded 757 eligible records, of which 12 were deemed adequate for inclusion (5 cohort studies and 7 case-control studies). On a random-effects meta-analysis, the risk of PD in MRONJ-affected sites compared with at-risk non-affected patients was significantly greater, with a risk ratio of 2.75 (95% CI: 1.67-4.52). Nonetheless, from a pooled analysis of three standardized periodontal measures (ie plaque index, clinical attachment loss and probing depth) no significant results were obtained. MRONJ appears to be associated with an increase in prevalence of PD. The direction of this association, and the factors influencing it must be investigated using further prospective data, and likewise, the possibility for using periodontal therapy as a prevention strategy must be looked into. Periodontal screening needs to be made an indispensable requisite for clinicians in order to establish a correct multidisciplinary approach in MRONJ.     

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.     

The Effect of Sacrificing the Posterior Cruciate Ligament in Total Knee Arthroplasties That Use a Highly Congruent Polyethylene Component

Background

There is continued debate regarding retention versus sacrificing of the posterior cruciate ligament (PCL) in total knee arthroplasty (TKA). We sought to determine if there was a difference in range of motion (ROM) after TKA between patients with PCL sacrifice versus PCL retention when using a highly congruent polyethylene insert.