Irritable bowel syndrome and health-related quality of life: a population-based study in Calgary, Alberta.

BACKGROUND: Little is known about the health-related quality of life (HRQOL) of nonclinical samples of people with irritable bowel syndrome (IBS) in Canada. In a pilot survey, the impact of IBS on HRQOL using a population-based, urban sample was examined. METHODS: A random sample of Calgary residents (18 years of age or older), selected by random digit dialing (n=1521), completed a structured questionnaire including ROME II Criteria and Medical Outcomes Study Short-Form 12-Item Health Survey, version 2 (SF-12v2). The mean scale and summary scores of SF-12v2 for those who did and did not meet ROME II criteria and for those who met ROME II criteria with and without visiting a physician in past three months were determined and compared using multiple regression analyses. RESULTS: Of the 951 households successfully contacted, 590 (62%) were willing to participate, of which 437 (74%) individuals were recruited. One hundred ten IBS cases (81 of which were women) and 327 non-IBS controls (180 of which were women) were identified. All of the eight mean scale scores and the two mean summary scores were significantly lower in people with IBS than in those without, whether or not adjusting for demographics. Forty-four of the 110 IBS cases (40%) sought medical help. Significantly lower mean physical component score and three scale scores (general health, social functioning and role physical) were found in those who sought medical help than in those who did not. CONCLUSIONS: People with IBS experience significant impairment in HRQOL, including both physical and mental well-being. People with IBS who seek medical help report worse physical health than those who do not, but their mental health is no different.     

Serum monitoring of antipsychotic drug levels during concomitant administration of sertraline and antipsychotic medication.

OBJECTIVE: To assess whether pharmacokinetic drug interactions occur when sertraline is added to antipsychotic medications. METHOD: Forty-eight patients with remitted DSM-IV schizophrenia and comorbid major depression were randomized to placebo for 6 weeks or sertraline 50 mg for 4 weeks followed by sertraline 50 mg to 100 mg for 2 weeks for nonresponders. Treatment with the patients' usual antipsychotic continued. Weekly clinical outcome assessments occurred for 6 weeks, and serum samples for drug monitoring were collected at Weeks 1, 5, and 6. Serum concentrations of sertraline and antipsychotics were measured with standard assays. RESULTS: In both placebo- and sertraline-treated groups, most patients displayed minor fluctuations in antipsychotic serum levels over 6 weeks. There was no clinical evidence of drug interactions in the sertraline-treated group. CONCLUSIONS: Clinically significant adverse effects did not occur despite variable antipsychotic serum levels with or without sertraline. Concern about pharmacokinetic interactions should not deter the use of sertraline for depression in individuals with schizophrenia.     

Performance measures for evaluating services for people with a first episode of psychosis

Aim: The purpose of this project was to operationalize and apply a previously identified set of performance measures designed to evaluate services for those experiencing a first episode of a schizophrenia spectrum disorder. Methods: Operational definitions were developed for previously identified measures through an iterative process of discussions between clinical experts and health‐care evaluators. Data were collected from existing sources including corporate databases, clinical databases and chart review. Results: Definitions were developed for 44 measures covering seven of eight domains recommended for service level evaluation by the Canadian Institute for Health Information domains. Forty measures could be calculated. Conclusions: The measures represent a comprehensive set of performance measures suitable for the evaluation of services for people with a first‐episode psychosis. The measures could be used by other services in order to establish standards and norms for routine clinical practice.     

Production and characterization of monoclonal antibodies to ARVCF

We have generated the first monoclonal antibodies (MAbs) to Armadillo repeat gene deleted in velo-cardiofacial syndrome (ARVCF), a recently identified Armadillo repeat-containing protein closely related to the catenin p120ctn. Six ARVCF-specific MAbs were characterized for isotype, species cross-reactivity, and utility in assays including immunofluorescence, immunoprecipitation, and Western blotting. All six antibodies were isotyped as IgG1 and several cross-reacted with ARVCF from a variety of species including human, rat, dog, and monkey, but not mouse. Importantly, none of the ARVCF MAbs cross-reacted with p120ctn, despite the high homology between these proteins. MAbs 3B2 and 4B1 were consistently the best in all applications and will provide valuable tools for further study of the role of ARVCF in cells.     

Laser angioplasty in the lower extremities: an early surgical experience

From July 1988 through December 1988 laser "hot tip" angioplasties coupled with balloon dilations were performed on 95 patients at the Union Memorial and University of Maryland hospitals. The patients ranged in age from 42 to 84 years (mean, 66.4 years), and there were 61 men and 34 women in the study. Indications for the procedure included claudication in 70 (74%) and severe ischemia in 25 (26%). Noninvasive studies were performed on all patients before and after the procedure. One hundred seventeen segments were treated in 28 iliac arteries and 89 superficial femoral/popliteal arteries. No tibial arteries were treated. Fifty-two stenoses and 65 occlusions occurred. The procedures were performed percutaneously in 52 patients (55%), and open surgical technique was used in 43 patients (45%). Nine immediate failures (9.5%) and 86 successes (90.5%) were noted within 24 hours of the procedure. Follow-up ranged from 1 to 6 months with a mean of 3.2 months. Late failures within this time period occurred in 21 patients (22%). The total failure rate was 30/95 or 31.5%. Only one of the patients was made worse by a failed laser-assisted balloon angioplasty. Immediate complications consisted of formation of subcutaneous hematoma in 20 of the 52 patients having percutaneous procedures (38%) and healing difficulty in 3 of the 43 patients having open surgical procedures (7%). Hospital stay was usually 1 day longer in the latter group. No patient required surgical intervention for bleeding as a result of a vessel perforation. However, this phenomenon was noted during the course of three superficial femoral artery laser-assisted balloon angioplasties.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anti-SARS-CoV-2 activity of targeted kinase inhibitors: Repurposing clinically available drugs for COVID-19 therapy

Coronavirus disease 2019 (COVID-19) remains a major public health concern, and vaccine unavailability, hesitancy, or failure underscore the need for discovery of efficacious antiviral drug therapies. Numerous approved drugs target protein kinases associated with viral life cycle and symptoms of infection. Repurposing of kinase inhibitors is appealing as they have been vetted for safety and are more accessible for COVID-19 treatment. However, an understanding of drug mechanism is needed to improve our understanding of the factors involved in pathogenesis. We tested the in vitro activity of three kinase inhibitors against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including inhibitors of AXL kinase, a host cell factor that contributes to successful SARS-CoV-2 infection. Using multiple cell-based assays and approaches, gilteritinib, nintedanib, and imatinib were thoroughly evaluated for activity against SARS-CoV-2 variants. Each drug exhibited antiviral activity, but with stark differences in potency, suggesting differences in host dependency for kinase targets. Importantly, for gilteritinib, the amount of compound needed to achieve 90% infection inhibition, at least in part involving blockade of spike protein-mediated viral entry and at concentrations not inducing phospholipidosis (PLD), approached a clinically achievable concentration. Knockout of AXL, a target of gilteritinib and nintedanib, impaired SARS-CoV-2 variant infectivity, supporting a role for AXL in SARS-CoV-2 infection and supporting further investigation of drug-mediated AXL inhibition as a COVID-19 treatment. This study supports further evaluation of AXL-targeting kinase inhibitors as potential antiviral agents and treatments for COVID-19. Additional mechanistic studies are needed to determine underlying differences in virus response.     

A clinical evaluation of the Neurobehavioral Cognitive Status Examination in a general psychiatric inpatient population.

The Neurobehavioral Cognitive Status Examination (NCSE) is a structured test of cognitive functioning. The NCSE assesses a broader range of cognitive functioning than the Mini-Mental State Examination (MMSE), but remains brief enough to be administered at the bedside in clinical settings. The purpose of this study was to assess the sensitivity, specificity, predictive value and reliability of the NCSE as a clinical case-finding instrument for DSM-III-R defined organic mental disorders in psychiatric inpatients. Validity was assessed by comparing the results of the test (interpreted as "pass" or "fail") to a blind clinical assessment by an experienced psychiatrist. The NCSE was found to have superior sensitivity to the MMSE (83% versus 43%), but inferior specificity (47% versus 97%). The low specificity resulted in a positive predictive value of only 24%. The NCSE had good test-retest reliability (Kappa = .69), but the inter-rater reliability was not as good (Kappa = 0.57). The NCSE was too non-specific to be used as a case-finding instrument for organic mental disorders. In conclusion, although clinicians may find the NCSE to be a valuable instrument for the assessment of cognitive function, it cannot be used as a screening or case-finding instrument for organic disorders among psychiatric inpatients.