Diagnostic specificity and familiality of early versus late evoked potentials to auditory paired stimuli across the schizophrenia‐bipolar psychosis spectrum

Disrupted sensory processing is a core feature of psychotic disorders. Auditory paired stimuli (PS) evoke a complex neural response, but it is uncertain which aspects reflect shared and/or distinct liability for the most common severe psychoses, schizophrenia (SZ) and psychotic bipolar disorder (BDP). Evoked time‐voltage/time‐frequency domain responses quantified with EEG during a typical PS paradigm (S1‐S2) were compared among proband groups (SZ [n = 232], BDP [181]), their relatives (SZrel [259], BDPrel [220]), and healthy participants (H [228]). Early S1‐evoked responses were reduced in SZ and BDP, while later/S2 abnormalities showed SZ/SZrel and BDP/BDPrel specificity. Relatives' effects were absent/small despite significant familiality of the entire auditorineural response. This pattern suggests general and divergent biological pathways associated with psychosis, yet may reflect complications with conditioning solely on clinical phenomenology.     

Incidence of Extended-Spectrum-β-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae Isolates That Test Susceptible to Cephalosporins and Aztreonam by the Revised CLSI Breakpoints

The incidence of aztreonam and cephalosporin susceptibility, determined using the revised CLSI breakpoints, for extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae isolates was evaluated. Our analysis showed that results for aztreonam and/or ≥1 cephalosporin were reported as susceptible or intermediate for 89.2% of ESBL-producing E coli isolates (569/638 isolates) and 67.7% of ESBL-producing K. pneumoniae isolates (155/229 isolates).     

A systematic review of cancer GWAS and candidate gene meta-analyses reveals limited overlap but similar effect sizes

Candidate gene and genome-wide association studies (GWAS) represent two complementary approaches to uncovering genetic contributions to common diseases. We systematically reviewed the contributions of these approaches to our knowledge of genetic associations with cancer risk by analyzing the data in the Cancer Genome-wide Association and Meta Analyses database (Cancer GAMAdb). The database catalogs studies published since January 1, 2000, by study and cancer type. In all, we found that meta-analyses and pooled analyses of candidate genes reported 349 statistically significant associations and GWAS reported 269, for a total of 577 unique associations. Only 41 (7.1%) associations were reported in both candidate gene meta-analyses and GWAS, usually with similar effect sizes. When considering only noteworthy associations (defined as those with false-positive report probabilities ≤0.2) and accounting for indirect overlap, we found 202 associations, with 27 of those appearing in both meta-analyses and GWAS. Our findings suggest that meta-analyses of well-conducted candidate gene studies may continue to add to our understanding of the genetic associations in the post-GWAS era.     

Microcephaly with or without chorioretinopathy,lymphoedema, or mental retardation (MCLMR): review of phenotype associated with KIF11 mutations

Microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation (MCLMR) (MIM No.152950) is a rare autosomal dominant condition for which a causative gene has recently been identified. Mutations in the kinesin family member 11 (KIF11) gene have now been described in 16 families worldwide. This is a review of the condition based on the clinical features of 37 individuals from 22 families. This report includes nine previously unreported families and additional information for some of those reported previously. The condition arose de novo in 8/20 families (40%). The parental results were not available for two probands. The mutations were varied and include missense, nonsense, frameshift, and splice site and are distributed evenly throughout the KIF11 gene. In our cohort, 86% had microcephaly, 78% had an ocular abnormality consistent with the diagnosis, 46% had lymphoedema, 73% had mild-moderate learning difficulties, 8% had epilepsy, and 8% had a cardiac anomaly. We identified three individuals with KIF11 mutations but no clinical features of MCLMR demonstrating reduced penetrance. The variable expression of the phenotype and the presence of mildly affected individuals indicates that the prevalence may be higher than expected, and we would therefore recommend a low threshold for genetic testing.     

Autosomal dominant SCA5 and autosomal recessive infantile SCA are allelic conditions resulting from SPTBN2 mutations

Although many genes have been identified for the autosomal recessive cerebellar ataxias (ARCAs), several patients are unlinked to the respective loci, suggesting further genetic heterogeneity. We combined homozygosity mapping and exome sequencing in a consanguineous Egyptian family with congenital ARCA, mental retardation and pyramidal signs. A homozygous 5-bp deletion in SPTBN2, the gene whose in-frame mutations cause autosomal dominant spinocerebellar ataxia type 5, was shown to segregate with ataxia in the family. Our findings are compatible with the concept of truncating SPTBN2 mutations acting recessively, which is supported by disease expression in homozygous, but not heterozygous, knockout mice, ataxia in Beagle dogs with a homozygous frameshift mutation and, very recently, a homozygous SPTBN2 nonsense mutation underlying infantile ataxia and psychomotor delay in a human family. As there was no evidence for mutations in 23 additional consanguineous families, SPTBN2-related ARCA is probably rare.     

Graft Copolymers with Complex Polyether Structures: Poly(ethylene oxide)‐graft‐Poly(isobutyl vinyl ether) by Combination of Living Anionic and Photoinduced Cationic Graft Polymerization

A novel polymerization mechanism transformation strategy, involving anionic ring‐opening polymerization and photoinduced cationic polymerization, is successfully applied for the synthesis of poly(ethylene oxide)‐graft‐poly(isobutyl vinyl ether) (PEO‐g‐PIBVE). First, poly(ethylene oxide‐co‐ethoxyl vinyl glycidyl ether) [P(EO‐co‐EVGE)] is synthesized by living anionic polymerization. The vinyl moieties of the functional PEO‐based polymer are converted to the hydrogen iodide adduct by photolysis of diphenyliodonium iodide, monitored using NMR spectroscopy. A modified mode of Lewis acid‐catalyzed living cationic polymerization is performed as a “grafting from” method to generate PIBVE segments grafted onto the PEO main chain. Both the intermediates and the final graft copolymers are characterized by gel‐permeation chromato­graphy (GPC) and ¹H NMR analysis.

     

Classification of Lower Extremity Movement Patterns Based on Visual Assessment: Reliability and Correlation With 2-Dimensional Video Analysis

Context:

Abnormal movement patterns have been implicated in lower extremity injury. Reliable, valid, and easily implemented assessment methods are needed to examine existing musculoskeletal disorders and investigate predictive factors for lower extremity injury.

Objective:

To determine the reliability of experienced and novice testers in making visual assessments of lower extremity movement patterns and to characterize the construct validity of the visual assessments.

Design:

Cross-sectional study.

Setting:

University athletic department and research laboratory.

Patients or Other Participants:

Convenience sample of 30 undergraduate and graduate students who regularly participate in athletics (age = 19.3 ± 4.5 years). Testers were 2 experienced physical therapists and 1 novice postdoctoral fellow (nonclinician).

Main Outcome Measure(s):

We took videos of 30 athletes performing the single-legged squat. Three testers observed the videos on 2 occasions and classified the lower extremity movement as dynamic valgus, no change, or dynamic varus. The classification was based on the estimated change in frontal-plane projection angle (FPPA) of the knee from single-legged stance to maximum single-legged squat depth. The actual FPPA change was measured quantitatively. We used percentage agreement and weighted κ to examine tester reliability and to determine construct validity of the visual assessment.

Results:

The κ values for intratester and intertester reliability ranged from 0.75 to 0.90, indicating substantial to excellent reliability. Percentage agreement between the visual assessment and the quantitative FPPA change category was 90%, with a κ value of 0.85.

Conclusions:

Visual assessments were made reliably by experienced and novice testers. Additionally, movement-pattern categories based on visual assessments were in excellent agreement with objective methods to measure FPPA change. Therefore, visual assessments can be used in the clinic to assess movement patterns associated with musculoskeletal disorders and in large epidemiologic studies to assess the association between lower extremity movement patterns and musculoskeletal injury.Key Words: movement analysis, screening, athletic injuries, knee valgus

Key Points

• With training and the use of standardized techniques, both experienced and novice testers reliably classified lower extremity movement patterns based on visual assessment.
• Movement-pattern category-based visual assessments were in excellent agreement with objective methods to measure changes in frontal-plane projection angle.
• Visual assessment based on the methods described in this study may be used in the clinical setting, as well as in large epidemiologic studies and screening assessments for sport participation, to identify distinct categories of lower extremity movement patterns.

Abnormal movement patterns of the lower extremity have been implicated in noncontact anterior cruciate ligament (ACL) injuries¹ and other musculoskeletal problems, such as patellofemoral pain^2–4 and acetabular labral tears.⁵ In addition, correcting these abnormal movement patterns has been shown to prevent ACL injury⁶ and is proposed to reduce symptoms in people with preexisting pain conditions.^5,7,8 Thus, assessment of lower extremity movement patterns may be a way to guide treatment of existing musculoskeletal pain problems and to identify people at risk for future injury or musculoskeletal pain. To facilitate the examination of existing musculoskeletal disorders and the investigation of predictive factors of lower extremity injury, reliable, valid, and feasible methods to assess lower extremity movement patterns are needed.One method to assess lower extremity movement patterns is the Landing Error Scoring System (LESS).^9–11 The LESS uses a standard technique to make visual assessments of movement patterns during a drop vertical jump. The LESS is reliable and valid^9–11; however, the drop vertical jump is a relatively high-level activity and may not be the best way to assess movement patterns in patients with existing injury or in athletes whose sports do not involve landing from a jump. In addition, the drop vertical jump is a bilateral activity that may allow the participant to use 1 limb to compensate for the other. Visual assessment of the single-legged squat (SLSquat), a unilateral limb task, may provide an alternative to the LESS.We have developed standardized methods using a visual assessment of the frontal-plane projection angle (FPPA) to classify the lower extremity movement pattern during an SLSquat. The FPPA is a 2-dimensional (2-D) representation of the lower extremity position¹² and has been used to identify differences between men and women¹² and between women with patellofemoral pain and control participants^4,13 and to detect change in movement patterns after specific training.¹⁴ We established specific criteria to define the categories of lower extremity movement pattern based on the change in FPPA (FPPA change) during motion. The tester observes the angle formed between a line that bisects the thigh and a line that bisects the lower leg. During movement tests, the tester compares the FPPA at the start position with the FPPA at the end position. For example, to assess an SLSquat, the examiner compares the FPPA during the start position of single-legged stance with the end position of maximum squat depth. The difference observed in FPPA from the start to the end position can then be classified as dynamic valgus (change in the valgus direction), no change, or dynamic varus (change in the varus direction). We have used this assessment extensively in the clinical setting, but we have not assessed the rater reliability or the construct validity of our visual assessments.The purpose of this study was to assess the intratester and intertester reliability of 3 testers (2 experienced, 1 novice) categorizing the lower extremity movement pattern demonstrated during an SLSquat. A standardized protocol was used to assess videos of healthy participants performing the SLSquat. We hypothesized that the testers, both experienced and novice, would demonstrate good to excellent reliability using the standardized methods. In addition, we used the objective measure of quantifying FPPA as described by Willson and Davis¹² to determine the construct validity of our visual assessments. We hypothesized that we would see good to excellent agreement between our visual assessments and the quantitative FPPA change.     

Benefits of implementing a rapid access clinic in a high-volume inflammatory bowel disease center:Access,resource utilization and outcomes

BACKGROUND Emergency situations in inflammatory bowel diseases(IBD)put significant burden on both the patient and the healthcare system.AIM To prospectively measure Quality-of-Care indicators and resource utilization after the implementation of the new rapid access clinic service(RAC)at a tertiary IBD center.METHODS Patient access,resource utilization and outcome parameters were collected from consecutive patients contacting the RAC between July 2017 and March 2019 in this observational study.For comparing resource utilization and healthcare costs,emergency department(ED)visits of IBD patients with no access to RAC services were evaluated between January 2018 and January 2019.Time to appointment,diagnostic methods,change in medical therapy,unplanned ED visits,hospitalizations and surgical admissions were calculated and compared.RESULTS 488 patients(Crohn’s disease:68.4%/ulcerative colitis:31.6%)contacted the RAC with a valid medical reason.Median time to visit with an IBD specialist following the index contact was 2 d.Patients had objective clinical and laboratory assessment(C-reactive protein and fecal calprotectin in 91%and 73%).Fast-track colonoscopy/sigmoidoscopy was performed in 24.6%of the patients,while computed tomography/magnetic resonance imaging in only 8.1%.Medical therapy was changed in 54.4%.ED visits within 30 d following the RAC visit occurred in 8.8%(unplanned ED visit rate:5.9%).Diagnostic procedures and resource utilization at the ED(n=135 patients)were substantially different compared to RAC users:Abdominal computed tomography was more frequent(65.7%,P<0.001),coupled with multiple specialist consults,more frequent hospital admission(P<0.001),higher steroid initiation(P<0.001).Average medical cost estimates of diagnostic procedures and services per patient was$403 CAD vs$1885 CAD comparing all RAC and ED visits.CONCLUSION Implementation of a RAC improved patient care by facilitating easier access to IBD specific medical care,optimized resource utilization and helped avoiding ED visits and subsequent hospitalizations.