Evaluation of computer-aided design software methods for assessment of the three-dimensional geometry of the canine radius.

OBJECTIVE: To describe methods to measure the 3-D orientation of the proximal, diaphyseal, and distal segments of the canine radius by use of computer-aided design software (CADS) and to compare the repeatability and reliability of measurements derived by those methods. SAMPLE: 31 canine radii with biapical deformities and 24 clinically normal (control) canine radii. PROCEDURES: Select CT scans of radii were imported into a CADS program. Cartesian coordinate systems for the humerus and proximal, diaphyseal, and distal radial segments were developed. The orientation of each radial segment in the frontal, sagittal, and transverse planes was measured in triplicate by 3 methods. The repeatability and reliability of those measurements were calculated and compared among the 3 measurement methods. RESULTS: The mean ± SD within-subject repeatability of radial angular measurements for all 3 methods was 1.40 ± 0.67° in the frontal plane, 3.17 ± 2.21° in the sagittal plane, and 3.01 ± 1.11° in the transverse plane for control radii and 2.56 ± 1.95° in the frontal plane, 3.59 ± 2.39° in the sagittal plane, and 3.47 ± 1.19° in the transverse plane for abnormal radii. Mean ± SD bias between radial measurement methods was 1.88 ± 2.07° in the frontal plane, 6.44 ± 6.80° in the sagittal plane, and 2.27 ± 2.81° in the transverse plane. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that use of CADS to assess the 3-D orientation of the proximal, diaphyseal, and distal segments of normal and abnormal canine radii yielded highly repeatable and reliable measurements.

Pharmacist-Driven Step-Down of Long-Term Proton-Pump Inhibitor Therapy.

OBJECTIVE: To evaluate the appropriateness of proton-pump inhibitor (PPI) prescribing and reduce the number of outpatients on long-term PPI therapy, defined as greater than or equal to one year.
DESIGN: Phase I was retrospective and evaluated the appropriateness of PPI prescribing. Phase II was prospective and involved implementation of a pharmacist-driven PPI step-down protocol.
SETTING: This study was conducted in an outpatient setting at Veterans Affairs Hudson Valley Health Care System.
PATIENTS, PARTICIPANTS: Patients were limited to a single primary care provider and were required to fill an outpatient PPI prescription between August 15, 2015, and August 15, 2016.
INTERVENTIONS: After patients were identified in Phase I as having an inappropriate indication for long-term PPI therapy, they were contacted by a pharmacist to complete the step-down protocol. The patients then received a call two weeks after completing each step.
MAIN OUTCOME MEASURE(S): To determine the number of patients without an indication for long-term PPI therapy that could successfully complete the PPI step-down protocol.
RESULTS: Phase I identified that long-term PPI therapy was not indicated in 68.4% of patients. Phase II implementation demonstrated that 71.4% of patients were able to successfully step-down from PPI therapy in an average of 13 weeks with the use of alternative acid-suppression therapy.
CONCLUSION: This study concluded that a majority of PPI prescriptions were not indicated for a duration of greater than or equal to 1 year. With the implementation of a pharmacist-driven PPI step-down protocol, a majority of patients were able to tolerate the PPI step-down with the use of alternative acidsuppression therapy.

Lung lobe torsion in dogs: 52 cases (2005-2017).

OBJECTIVE: To report outcomes and risk factors for mortality in dogs that underwent surgical management of lung lobe torsion. STUDY DESIGN: Retrospective case series from 5 veterinary teaching hospitals (2005-2017). ANIMALS: Fifty dogs with 52 instances of lung lobe torsion. METHODS: Data collected from medical records included signalment, clinical findings, results of clinicopathologic testing and diagnostic imaging, surgical treatment, lung lobe affected, intraoperative and postoperative complications, histopathologic and microbiologic findings, and outcome. Follow-up was obtained from medical records and telephone contact with primary care veterinarians. RESULTS: Fifty-two instances of lung lobe torsion were identified in 50 dogs, with a median follow-up of 453 days (range, 0-3075). Forty-six (92%) dogs survived to discharge. Dogs with concurrent torsion of the right cranial and middle lung lobes were less likely to survive (2/4) than those with torsion of the left cranial lung lobe (22/22). No other risk factors for mortality prior to hospital discharge were identified. Overall median survival time after hospital discharge was 1369 days. Four dogs had >1 episode of lung lobe torsion. CONCLUSION: The percentage of dogs surviving to discharge after surgical treatment of lung lobe torsion was higher than previously reported. The short- and long-term prognosis was excellent with surgical treatment of lung lobe torsion. CLINICAL SIGNIFICANCE: Surgery should be recommended when lung lobe torsion is suspected because of the high survival to discharge rate and excellent long-term prognosis.

Gene discovery for Mendelian conditions via social networking: de novo variants in KDM1A cause developmental delay and distinctive facial features.

PURPOSE: The pace of Mendelian gene discovery is slowed by the "n-of-1 problem"-the difficulty of establishing the causality of a putatively pathogenic variant in a single person or family. Identification of an unrelated person with an overlapping phenotype and suspected pathogenic variant in the same gene can overcome this barrier, but it is often impeded by lack of a convenient or widely available way to share data on candidate variants/genes among families, clinicians, and researchers. METHODS: Social networking among families, clinicians, and researchers was used to identify three children with variants of unknown significance in KDM1A and similar phenotypes. RESULTS: De novo variants in KDM1A underlie a new syndrome characterized by developmental delay and distinctive facial features. CONCLUSION: Social networking is a potentially powerful strategy to discover genes for rare Mendelian conditions, particularly those with nonspecific phenotypic features. To facilitate the efforts of families to share phenotypic and genomic information with each other, clinicians, and researchers, we developed the Repository for Mendelian Genomics Family Portal (RMD-FP; http://uwcmg.org/#/family). Design and development of MyGene2 (http://www.mygene2.org), a Web-based tool that enables families, clinicians, and researchers to search for gene matches based on analysis of phenotype and exome data deposited into the RMD-FP, is under way.Genet Med 18 8, 788-795.

Assessor status influences pain recall.

UNLABELLED: Anecdotal clinical reports suggest that patients report differing levels of pain, depending on the status within the medical hierarchy of the individual gathering the pain rating. This observation has clinical relevance, given the practice of delegating the assessment of pain to lower status clinic staff members. In this study, both pain and mood were assessed in 70 patients diagnosed with low back pain at pretreatment, immediately after epidural lumbar injection, and again 2 weeks later by phone. At the 2-week follow-up, patients were also asked to recall the postprocedural rating that they had given immediately after the injection. This rating was obtained by either the treating physician or by a research assistant who was present at the time of injection, on a randomly determined basis. Current ratings of pain and mood did not differ for either group before the epidural injection, after the epidural injection, or at the 2-week follow-up. Two-week recall of postprocedural pain did, however, differ depending on assessor status. Those called by the physician provided recalled pain ratings that closely matched the ratings provided immediately after the procedure. Those called by the research assistant provided ratings that were 86% higher (that is, worse) than their original ratings. This status-driven bias in recalled postprocedural pain reporting is discussed in the context of social demands inherent in the physician-patient relationship, with implications for assessing treatment effectiveness in clinical practice and research. PERSPECTIVE: Accurate assessment of patients' pain is critical to effective pain management and treatment planning. This study found evidence of a status-based bias in which physicians elicited lower ratings of previously experienced pain associated with treatment procedures than did staff members of lower status.

Cerebrospinal fluid corticotropin-releasing factor concentration is associated with pain but not fatigue symptoms in patients with fibromyalgia.

Previous studies have identified stress system dysregulation in fibromyalgia (FM) patients; such dysregulation may be involved in the generation and/or maintenance of pain and other symptoms. Corticotropin-releasing factor (CRF) is the principal known central nervous system mediator of the stress response; however, to date no studies have examined cerebrospinal fluid (CSF) CRF levels in patients with FM. The relationship between CSF CRF level, heart rate variability (HRV), and pain, fatigue, and depressive symptoms was examined in patients with FM. Among participants (n=26), CSF CRF levels were associated with sensory pain symptoms (r=0.574, p=0.003) and affective pain symptoms (r=0.497, p=0.011), but not fatigue symptoms. Increased HRV was also strongly associated with increased CSF CRF and FM pain. In multivariate analyses adjusting for age, sex, and depressive symptoms, the association between CSF CRF and sensory pain symptoms (t=2.54, p=0.027) persisted. Women with FM who reported a history of physical or sexual abuse had lower CSF CRF levels than women who did not report such a history. CSF CRF levels are associated with both pain symptoms and variation in autonomic function in FM. Differences in CSF CRF levels among women with and without a self-reported history of physical or sexual abuse suggest that subgroups of FM patients may exist with different neurobiological characteristics. Further studies are needed to better understand the nature of the association between CSF CRF and pain symptoms in FM.

What do tender points measure? Influence of distress on 4 measures of tenderness.

OBJECTIVE: To examine the relationship between current pain, distress, and ascending and random measures of tenderness. METHODS: Manual tender point counts and dolorimeter measures of the pressure pain threshold were determined in a sample of 47 women representative of the general population with respect to tenderness. In addition, discrete pressure stimuli of varying intensities to the left thumb were applied in random fashion. Distress was measured with the Brief Symptom Inventory and the Beck Depression Inventory, and pain was evaluated with the Short Form McGill Pain Questionnaire. RESULTS: Only the random measure of tenderness was relatively independent of an individual's current psychological state. The respective correlation coefficients between measures of tenderness and psychological state were generally greatest for the manual tender point count and also significant for the dolorimeter measures. In contrast, all measures were highly correlated with ratings of spontaneous pain, again with the manual tender point count showing the strongest, and the random method the weakest, correlations. Linear regression analysis replicated the results of the correlational analysis. CONCLUSION: As a measure of tenderness, the number of positive tender points is clearly influenced by an individual's distress. Other more sophisticated measures of tenderness that randomly present stimuli in an unpredictable fashion appear to be relatively immune to these biasing effects, although our results obtained in a research setting have yet to be replicated in clinical practice.

Effects of intravenous ketamine, alfentanil, or placebo on pain, pinprick hyperalgesia, and allodynia produced by intradermal capsaicin in human subjects.

The importance of N-methyl-D-aspartate (NMDA) receptor-mediated sensitization of central nervous system (CNS) neurons is well established in animal models of acute and chronic pain. A human model of central sensitization would be useful in screening new NMDA antagonists and establishing dose regimens for clinical trials in patients with pain related to sensitization of CNS neurons. We used this model to examine the effects of intravenous infusions of two centrally acting analgesics, the NMDA receptor antagonist ketamine and the morphine-like opioid agonist alfentanil. Twelve normal subjects completed a 3-session, randomized, double-blind, crossover study. From 25 to 60 min after capsaicin injection, subjects were given intravenous infusions of ketamine (mean dose: 32 mg), alfentanil (mean dose: 3075 micrograms), or saline placebo. Both drugs significantly reduced ongoing pain and pinprick-evoked hyperalgesia during the infusion. The reduction in allodynia evoked by light stroking was statistically significant only for alfentanil. Mean reduction +/- SEM relative to placebo were for ongoing pain: ketamine, 36 +/- 9%; alfentanil, 51 +/- 5%; area of pinprick hyperalgesia: ketamine, 34 +/- 7%; alfentanil, 35 +/- 7%; and area of mechanical allodynia: ketamine, 52 +/- 20%; alfentanil, 70 +/- 12%. Because the drugs were given systemically and produced side effects in all subjects, we cannot specify the site or sites of action nor conclusively rule out a non-specific 'active placebo' response as the cause for reduction of symptoms. Arguing against an 'active placebo' response, however, was the lack of analgesic effect of intravenous midazolam (mean dose; 3.4 mg, titrated to produce side effects of similar magnitude to ketamine and alfentanil) given at 145 min after capsaicin in 9 subjects who had received saline from 25 to 60 min. The results of this study suggest that neural systems sensitive to NMDA receptor antagonists and opioids participate in capsaicin-evoked pain phenomena, and support the feasibility of pharmacological studies using the intradermal capsaicin model.