A case report and review of the locked metacarpophalangeal joint

A 59-year-old female with metacarpal joint locking is presented. The successful closed manipulation is described with a review of the literature.     

Development of a Method That Eliminates False-Positive Results due to Nerve Growth Factor Interference in the Assessment of Fulranumab Immunogenicity

Fulranumab, a human IgG2 monoclonal antibody that neutralizes nerve growth factor (NGF), is currently in development for the treatment of pain. Our initial immunogenicity test method was found to be prone to NGF interference, leading to a high apparent incidence of anti-drug antibody (ADA) in phase 1 studies. The ADA immunoassay comprised a homogeneous bridging electrochemiluminescence (ECL) format with biotin and ruthenium-labeled fulranumab bound together (“bridged”) by ADA in test samples for detection. In this assay, NGF produced a false-positive signal due to its ability to bridge fulranumab molecules. Thus, we developed a specificity assay to eliminate the NGF false-positive results. We encountered the challenge of eliminating drug interference as well as drug target interference, and discovered that the acid-dissociation-based pretreatment of samples used for mitigating drug interference dramatically increased drug target interference. Several strategies were investigated to eliminate the NGF interference; yet only one strategy specifically removed NGF and produced true fulranumab-specific ADA results by using competitive inhibition with fulranumab and utilizing an alternative NGF binding antibody to eliminate NGF interference. Using this new method, we confirmed that the high apparent anti-fulranumab antibody incidence (>60%) in clinical study samples was in fact due to fulranumab-bound NGF released during the acid-dissociation step of the ADA testing method. We conclude that our revised method accurately identifies anti-fulranumab antibodies by incorporating steps to eliminate fulranumab and NGF interference. We advise that acid-dissociation pretreatment must not be universally applied to improve ADA assays without investigating its bioanalytical risks versus benefits.     

General and Acute Care Surgical Procedures in Patients with Left Ventricular Assist Devices

Background

Left ventricular assist devices (LVADs) have become common as a bridge to heart transplant as well as destination therapy. Acute care surgical (ACS) problems in this population are prevalent but remain ill-defined. Therefore, we reviewed our experience with ACS interventions in LVAD patients.

Methods

A total of 173 patients who received HeartMate^® XVE or HeartMate^® II (HMII) LVADs between December 2001 and March 2010 were studied. Patient demographics, presentation of ACS problem, operative intervention, co-morbidities, transplantation, complications, and survival were analyzed.

Results

A total of 47 (27 %) patients underwent 67 ACS procedures at a median of 38 days after device implant (interquartile range 15–110), with a peri-operative mortality rate of 5 % (N = 3). Demographics, device type, and acuity were comparable between the ACS and non-ACS groups. A total of 21 ACS procedures were performed emergently, eight were urgent, and 38 were elective. Of 29 urgent and emergent procedures, 28 were for abdominal pathology. In eight patients, the cause of the ACS problem was related to LVADs or anticoagulation. Cumulative survival estimates revealed no survival differences if patients underwent ACS procedures (p = 0.17). Among HMII patients, transplantation rates were unaffected by an ACS intervention (p = 0.2).

Conclusions

ACS problems occur frequently in LVAD patients and are not associated with adverse outcomes in HMII patients. The acute care surgeon is an integral member of a comprehensive approach to effective LVAD management.     

A systematic review of the literature to support an evidence-based Precepting Program

Aim

To provide a systematic review of the literature regarding development of an evidence-based Precepting Program for nurses transitioning to burn specialty practice.

Background

Burned patients are admitted to specialty Burn Centers where highly complex nursing care is provided. Successful orientation and integration into such a specialized work environment is a fundamental component of a nurse's ability to provide safe and holistic patient care.

Design

A systematic review of the literature was performed for the period 1995–2011 using electronic databases within PUBMED and Ovid search engines.

Data sources

Databases included Medline, CINHAL, ProQuest for Dissertations and Thesis, and Cochran Collaboration using key search terms: preceptor, preceptee, preceptorship, precept*, nurs*, critical care, personality types, competency-based education, and learning styles.

Review methods

Nurses graded the level and quality of evidence of the included articles using a modified 7-level rating system and the Johns Hopkins Nursing Quality of Evidence Appraisal during journal-club meetings.

Results

A total of 43 articles related to competency (n = 8), knowledge acquisition and personality characteristics (n = 8), learning style (n = 5), preceptor development (n = 7), and Precepting Programs (n = 14).

Conclusions

A significant clinical gap existed between the scientific evidence and actual precepting practice of experienced nurses at the Burn Center. Based on this extensive review of the literature, it was determined that a sufficient evidence base existed for development of an evidence-based Precepting Program.     

Extracting data from electronic medical records: validation of a natural language processing program to assess prostate biopsy results

Objective

The extraction of specific data from electronic medical records (EMR) remains tedious and is often performed manually. Natural language processing (NLP) programs have been developed to identify and extract information within clinical narrative text. We performed a study to assess the validity of an NLP program to accurately identify patients with prostate cancer and to retrieve pertinent pathologic information from their EMR.

Materials and methods

A retrospective review was performed of a prospectively collected database including patients from the Southern California Kaiser Permanente Medical Region that underwent prostate biopsies during a 2-week period. A NLP program was used to identify patients with prostate biopsies that were positive for prostatic adenocarcinoma from all pathology reports within this period. The application then processed 100 consecutive patients with prostate adenocarcinoma to extract 10 variables from their pathology reports. The extraction and retrieval of information by NLP was then compared to a blinded manual review.

Results

A consecutive series of 18,453 pathology reports were evaluated. NLP correctly detected 117 out of 118 patients (99.1 %) with prostatic adenocarcinoma after TRUS-guided prostate biopsy. NLP had a positive predictive value of 99.1 % with a 99.1 % sensitivity and a 99.9 % specificity to correctly identify patients with prostatic adenocarcinoma after biopsy. The overall ability of the NLP application to accurately extract variables from the pathology reports was 97.6 %.

Conclusions

Natural language processing is a reliable and accurate method to identify select patients and to extract relevant data from an existing EMR in order to establish a prospective clinical database.     

Not small adults: the emerging role of pediatric pain services

Purpose

This review article explores the need for specialized pain care for children and adolescents and provides some historical context for our current knowledge base and clinical practice.

Principal findings

Pediatric patients have specialized needs with respect to assessment and management of pain. Acute pain care is modified by developmental considerations in both these areas; chronic pain encompasses a wide range of complex developmental, social, and psychological factors requiring the skills of different health disciplines to provide the best care.

Conclusions

Awareness of children’s pain has increased dramatically over the past three decades, and Canadians have performed a leadership role in much of the research. Specific multidisciplinary teams are a more recent phenomenon, but they are shown to be more effective and probably more cost effective than traditional treatment models. Important gaps in availability of resources to manage these patients remain.     

Comparison of the Heritability of Schizophrenia and Endophenotypes in the COGS-1 Family Study

Background:

Twin and multiplex family studies have established significant heritability for schizophrenia (SZ), often summarized as 81%. The Consortium on the Genetics of Schizophrenia (COGS-1) family study was designed to deconstruct the genetic architecture of SZ using neurocognitive and neurophysiological endophenotypes, for which heritability estimates ranged from 18% to 50% (mean = 30%). This study assessed the heritability of SZ in these families to determine whether there is a “heritability gap” between the diagnosis and related endophenotypes.

Methods:

Nuclear families (N = 296) with a SZ proband, an unaffected sibling, and both parents (n = 1366 subjects; mean family size = 4.6) underwent comprehensive endophenotype and clinical characterization. The Family Interview for Genetic Studies was administered to all participants and used to obtain convergent psychiatric symptom information for additional first-degree relatives of interviewed subjects (N = 3304 subjects; mean family size = 11.2). Heritability estimates of psychotic disorders were computed for both nuclear and extended families.

Results:

The heritability of SZ was 31% and 44% for nuclear and extended families. The inclusion of bipolar disorder increased the heritability to 37% for the nuclear families. When major depression was added, heritability estimates dropped to 34% and 20% for nuclear and extended families, respectively.

Conclusions:

Endophenotypes and psychotic disorders exhibit comparable levels of heritability in the COGS-1 family sample. The ascertainment of families with discordant sibpairs to increase endophenotypic contrast may underestimate diagnostic heritability relative to other studies. However, population-based studies also report significantly lower heritability estimates for SZ. Collectively, these findings support the importance of endophenotype-based strategies and the dimensional view of psychosis.Key words: schizophrenia, psychosis, endophenotypes, cognition, biomarkers, heritability