Localization of the Median Nerve and Flexor Pollicis Longus at the Carpal Tunnel Inlet in Patients With and Without Carpal Tunnel Syndrome Using Ultrasound.

BACKGROUND: Current illustrations of the carpal tunnel vary greatly. The relative positions of the components such as the median nerve and flexor pollicis longus (FPL) tendon seem often arbitrarily chosen. The purpose of this study was to determine the locations of the median nerve and FPL in the carpal tunnel using ultrasound (US) and to determine whether the position of the median nerve changes in carpal tunnel syndrome (CTS). METHOD: Patients with and without CTS underwent US examination of the wrist. A 4 × 10 grid was fitted to each saved cross-sectional image. The center points of the median nerve and FPL were identified, and their horizontal and vertical coordinates were recorded. RESULTS: The median nerve was identified in 115 wrists (average x = 0.70, y = 0.82), and FPL was identified in 90 wrists (average x = 0.86, y = 0.59). A scatter plot was created by stacking all US images to demonstrate the average positions of the median nerve and FPL. There were 97 wrists without CTS (No CTS) and 17 wrists with CTS. There was a significant difference in the vertical position of the median nerve between No CTS and CTS wrists (P = .0006). CONCLUSIONS: The locations of the median nerve and FPL within the carpal tunnel were determined using US of 115 wrists, and a heat map was created to illustrate these locations. The median nerve was found to be more superficial in the setting of CTS.

Exploration of novel ligands to target C-C Motif Chemokine Receptor 2 (CCR2) as a promising pharmacological treatment against traumatic brain injury.

It is widely reported that the overexpression of the C-C Motif Chemokine Receptor 2 (CCR2) has negative implications in neuroinflammatory diseases such as traumatic brain injury (TBI), although promising drugs to tackle this have been less forthcoming. As of 2016, only 2 drugs specifically targeting this receptor have made their way to market, with unsuccessful outcome unfortunately, suggesting that the search for more specific and precise ligands is utterly necessary. In this paper we hypothesized that by targeting Glu291, Met295, Trp98, Leu45 and Val189 amino acids, essential in the binding of CCR2 with C-C Motif Chemokine Ligand 2 (CCL2), the endogenous substrate, mitigates its activity in TBI. We used a pharmacophore model to screen for suitable ligands that may bind to CCR2, which returned 871 ligands. Docking and molecular dynamics results uncovered that two ligands (A102) and (A435) contained several of those important residues and showed a stability and compactness when in complex with CCR2, with these results confirmed by MMGBSA calculations with A102 recording a better interaction compared to A435. Finally, a PPI network was built to explore downstream signaling being regulated by both ligands in TBI, showing amyloid precursor protein (APP) as a key target and neuroactive-ligand receptor interaction (1.80E-27) the top functional annotated category. In conclusion, for the first time we report novel ligands A102 and A435 targeting CCR2 as a potential new pharmacological approach to target inflammation post-TBI.

Medication discrepancies despite pharmacist led medication reconciliation: the challenges of maintaining an accurate medication list in primary care.

OBJECTIVE: Describe the types of medication discrepancies that persist despite pharmacist-led medication reconciliation using the primary care electronic medical record (EMR). METHODS: Observational case series study of established patients from an urban, indigent care clinic. Medication reconciliation was conducted immediately prior to the physician visit at baseline and return visit. Main outcome measures included: frequency, types, and reasons for discrepancies, patient knowledge, and adherence. RESULTS: There was a 14.5% reduction in the number of patients with a discrepancy and the frequency of discrepancies was reduced by 7.3%. The rate of medication discrepancies in the chart was reduced by 31.3%. The most common type of discrepancy that persisted at follow up were medications listed on the chart that the patient stopped taking. Discrepancies were more likely to persist in Caucasian subjects when compared to African Americans. CONCLUSIONS: While pharmacist led medication reconciliation appears effective at reducing the likelihood of a medication discrepancy in the EMR, challenges persist in maintaining this accuracy specifically as it relates to patient driven changes to the medication regimen.

Medication discrepancies despite pharmacist led medication reconciliation: the challenges of maintaining an accurate medication list in primary care / Discrepancias de la medicación a pesar de la reconciliación de la medicación por farmacéutico: el reto de mantener una lista de medicación precisa en atención primaria

Objective: Describe the types of medication discrepancies that persist despite pharmacist-led medication reconciliation using the primary care electronic medical record (EMR). Methods: Observational case series study of established patients from an urban, indigent care clinic. Medication reconciliation was conducted immediately prior to the physician visit at baseline and return visit. Main outcome measures included: frequency, types, and reasons for discrepancies, patient knowledge, and adherence. Results: There was a 14.5% reduction in the number of patients with a discrepancy and the frequency of discrepancies was reduced by 7.3%. The rate of medication discrepancies in the chart was reduced by 31.3%. The most common type of discrepancy that persisted at follow up were medications listed on the chart that the patient stopped taking. Discrepancies were more likely to persist in Caucasian subjects when compared to African Americans. Conclusion: While pharmacist led medication reconciliation appears effective at reducing the likelihood of a medication discrepancy in the EMR, challenges persist in maintaining this accuracy specifically as it relates to patient driven changes to the medication regimen (AU)

Objetivo: Describir los tipos de discrepancias que persisten a pesar de una reconciliación de la medicación hecha por farmacéutico usando la historia clínica electrónica (EMR) de atención primaria. Métodos: Estudio observacional de serie de casos en una clínica urbana de atención a indigentes. Se realizó reconciliación de la medicación inmediatamente antes de la consulta médica al inicio y en la visita de continuación. Los principales resultados medidos incluían: frecuencia, tipos y motivos de las discrepancias, conocimiento del paciente y cumplimiento. Resultados: Hubo una reducción del 14,5% en el número de pacientes con discrepancias y la frecuencia de discrepancias se redujo en un 7,3%. La tasa de discrepancias de medicación en la historia se redujo en un 31,3%. Los tipos más frecuentes de discrepancias que persistían en el seguimiento fueron medicaciones listadas en el historial que el paciente había dejado de tomar. Las discrepancias eran más frecuentes en individuos caucásicos que en afro-americanos. Concusión: Aunque la reconciliación de la medicación hecha por farmacéuticos parece ser efectiva reduciendo la probabilidad de discrepancias en la medicación de la EMR, existen retos para mantener la precisión, especialmente en lo que se refiere a los cambios del régimen de medicación realizados por el paciente (AU)

Identifying discrepancies in electronic medical records through pharmacist medication reconciliation.

OBJECTIVES: To describe the types and causes of medication discrepancies in the electronic medical record identified by pharmacist medication reconciliation during outpatient medical visits and to identify patient characteristics associated with the presence of discrepancies. DESIGN: Observational case series study. SETTING: Indigent primary care clinic in Pittsburgh, PA, from April 2009 to May 2010. PATIENTS: 219 adults presenting for follow-up medical visits and self-reporting medication use. INTERVENTION: Medication reconciliation as part of patient interview and concurrent chart review. MAIN OUTCOME MEASURES: Frequency, types, and reasons for medication discrepancies and demographic variables, patient knowledge, and adherence. RESULTS: Of 219 patients interviewed, 162 (74%) had at least one discrepancy. The most common type of discrepancy was an incorrect medication documented on the chart. The most common reasons included over-the-counter (OTC) use of medications and patients not reporting use of medications. The presence of one or more medication discrepancies was associated with the use of three or more medications. Patient factors such as gender, age, and race were not associated with discrepancies. Patients able to recall the strength for more than 75% of their medications had fewer discrepancies, while knowledge of the medication name, indication, or regimen had no association with discrepancies. CONCLUSION: Pharmacists play a critical role in identifying discrepancies between charted medication lists and self-reported medication use, independent of adherence. Inaccuracies in charted medications are frequent and often are related to use of OTC therapies and lack of communication and documentation during physician office visits. Knowledge of patient-related variables and other reasons for discrepancies may be useful in identifying patients at greatest risk for discrepancies and interventions to prevent and resolve them.

Retrospective analysis of hyperlipidemia management in a transplant population.

STUDY OBJECTIVES: To determine the prevalence of hyperlipidemia and the effectiveness of hyperlipidemia management in a large population of transplant recipients. A secondary objective was to assess the effect of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III guidelines on hyperlipidemia management compared with the effect from earlier guidelines. DESIGN: Retrospective review of computerized records. SETTING: University-affiliated transplantation center. PATIENTS: Three thousand four hundred fourteen patients with liver, kidney, or pancreas transplants. MEASUREMENTS AND MAIN RESULTS: To determine a diagnosis of hyperlipidemia and the effectiveness of treatment, we assessed the patients's lipid levels. Hyperlipidemia was defined as a total cholesterol level above 200 mg/dl and/or the use of antihyperlipidemic drugs. Of the 3414 patients in the study, 1638 (48%) had hyperlipidemia. Of these, 711 (43%) were receiving antihyperlipidemic drugs; 227 (32%) of the 711 patients had achieved the total cholesterol goal of 200 mg/dl or below. Low-density lipoprotein cholesterol (LDL) levels were available for 1953 (57%) patients. Of these, 537 patients were receiving cholesterol-lowering drugs, and 384 (72%) of the 537 patients achieved the LDL goal of less than 130 mg/dl. CONCLUSION: Although NCEP guidelines recommend monitoring LDL, only slightly more than half of these transplant recipients were monitored. In addition, the patients identified as having hyperlipidemia were not effectively treated to lower their cholesterol levels. Clinicians must be aggressive in diagnosing, monitoring, and treating hyperlipidemia to decrease the rate of cardiovascular disease and to prolong patient survival after transplantation.

2', 3'-O-(2,4,6,trinitrophenyl)-ATP and A-317491 are competitive antagonists at a slowly desensitizing chimeric human P2X3 receptor.

(1) Rapid desensitization of ligand-gated ion channel receptors can alter the apparent activity of receptor modulators, as well as make detection of fast-channel activation difficult. Investigation of the antagonist pharmacology of ATP-sensitive homomeric P2X3 receptors is limited by agonist-evoked fast-desensitization kinetics. (2) In the present studies, chimeric receptors were created using the coding sequence for the N-terminus and the first transmembrane domain of either the nondesensitizing human P2X2a or fast-desensitizing P2X3 receptor joined to the sequence encoding the extracellular loop, second transmembrane domain, and C-terminus of the other receptor (designated P2X2-3 and P2X3-2, respectively). These clones were stably transfected into 1321N1 astrocytoma cells for biophysical and pharmacological experiments using both electrophysiological and calcium-imaging methods. (3) Chimeric P2X2-3 and P2X3-2 receptors were inwardly rectifying and agonist responses showed desensitization properties similar to the wild-type human P2X2a and P2X3 receptors, respectively. (4) The P2X2-3 chimera displayed an agonist pharmacological profile similar to the P2X3 wild-type receptor being activated by low concentrations of both ATP and alpha,beta-meATP. In contrast, the P2X3-2 chimera had markedly reduced sensitivity to both agonists. (5) The P2X3 receptor antagonists TNP-ATP and A-317491 were shown to be potent, competitive antagonists of the P2X2-3 chimera (Ki=2.2 and 52.1 nm, respectively), supporting the hypothesis that rapid receptor desensitization can mask the competitive antagonism of wild-type homomeric P2X3 receptors.

Alteration of dorsal root ganglion P2X3 receptor expression and function following spinal nerve ligation in the rat.

One subtype of ATP-gated ion channel, the P2X(3) receptor, is expressed primarily on peripheral sensory neurons. While it is known that P2X(3) receptors can participate in certain forms of nociceptive signaling, their involvement in neuropathic pain transmission is not known. We have examined the expression and function of P2X(3) receptors in a rat spinal nerve ligation model of neuropathic pain. Fourteen days following L5/L6 spinal nerve ligation, the corresponding dorsal root ganglia (DRG) were removed from animals exhibiting mechanical allodynia, and these were studied using immunohistochemical and electrophysiological techniques. Using a polyclonal antibody to label the P2X(3) receptor, a significant reduction in neuronal P2X(3) immunoreactivity was observed in the ipsilateral (injured) L5 and L6 DRG following nerve ligation. In vitro electrophysiological analysis of acutely isolated DRG neurons revealed a similar decrease in functional P2X(3)-containing receptors. In small diameter (22-25 micro m) neurons, a significant reduction in the number of cells exhibiting a response to alpha,beta-meATP was observed. However, a subset of small diameter neurons retained P2X(3) responses of equal amplitude to those recorded from naive and sham control DRG neurons. Interestingly, P2X(3) immunoreactivity and P2X(3)-like responses were also detected in a subset of larger diameter (50 micro m) neurons and the number and amplitude of these responses were unchanged after spinal nerve ligation. These results suggest that, while there appears to be a decrease in fast desensitizing P2X(3) receptors following L5/L6 nerve ligation injury, certain subsets of small and large DRG neurons maintain normal P2X(3) receptor expression and function. These remaining receptors may provide a P2X(3) receptor-mediated component to neuropathic pain.

Potent desensitization of human P2X3 receptors by diadenosine polyphosphates.

In this study, the receptor desensitizing effects of diadenosine polyphosphates at recombinant human P2X3 (hP2X3) receptors were examined. Administration of Ap3A, Ap4A, Ap5A or Ap6A inhibited the hP2X3 receptor-mediated response to a subsequent application of 3 muM alphabeta-methyleneATP (alphabeta-meATP), in a concentration-dependent manner, with IC50 values 2707, 42, 59 and 46 nM, respectively. These agonists did not desensitize alphabeta-meATP responses mediated by the slowly desensitizing heteromeric human P2X2/3 receptor. hP2X3 receptor desensitization was reversible and was not observed following the increase in intracellular Ca2+ levels produced by carbachol. A similar pattern of desensitization evoked by Ap5A was also observed using electrophysiological recordings of Xenopus oocytes expressing hP2X3 receptors. These data demonstrate that diadenosine polyphosphates, found endogenously in the central nervous system, can readily desensitize hP2X3 receptors at nanomolar concentrations that are 10-fold lower than are required to produce agonist-induced receptor activation. Thus, P2X3 receptor desensitization by diadenosine polyphosphates may provide an important modulatory mechanism of P2X3 receptor activation in vivo.