The frequency of isolation of non-tuberculous mycobacteria (NTM) species from respiratory specimens is increasing, however the clinical relevance of such identifications vary by mycobacterial species and geographical location. A retrospective study of 853 NTM isolates from respiratory samples from 386 patients over seven years was performed. Clinical records and radiographic information were examined. Clinical significance was assessed by American Thoracic Society diagnostic criteria. 25% of all patients with respiratory isolates met criteria for non-tuberculous mycobacterial pulmonary disease (NTM-PD). Significant symptoms were weight loss, fever, night sweats, productive cough and haemoptysis. HIV co-infection was a significant risk factor for disease. Cavities, nodules and tree-in-bud were significant radiographic findings. Mycobacterium avium complex (MAC) were the dominant species isolated from this patient cohort. Mycobacterium abscessus (M. abscessus) was the species most likely to cause clinically significant disease and be sputum smear positive, thus warranting particular attention.
Human healthy (wild-type (WT)) and homozygous sickle (SS) red blood cells (RBCs) express a large number of surface receptors that mediate cell adhesion between RBCs, and between RBCs and white blood cells, platelets, and the endothelium. In sickle cell disease (SCD), abnormal adhesion of RBCs to endothelial cells is mediated by the intercellular adhesion molecule-4 (ICAM-4), which appears on the RBC membrane and binds to the endothelial αvβ3 integrin. This is a key factor in the initiation of vaso-occlusive episodes, the hallmark of SCD. A better understanding of the mechanisms that control RBC adhesion to endothelium may lead to novel approaches to both prevention and treatment of vaso-occlusive episodes in SCD. One important mechanism of ICAM-4 activation occurs via the cyclic adenosine monophosphate-protein kinase A (cAMP-PKA)-dependent signaling pathway. Here, we employed an in vitro technique called single-molecule force spectroscopy to study the effect of modulation of the cAMP-PKA-dependent pathway on ICAM-4 receptor activation. We quantified the frequency of active ICAM-4 receptors on WT-RBC and SS-RBC membranes, as well as the median unbinding force between ICAM-4 and αvβ3. We showed that the collective frequency of unbinding events in WT-RBCs is not significantly different from that of SS-RBCs. This result was confirmed by confocal microscopy experiments. In addition, we showed that incubation of normal RBCs and SS-RBCs with epinephrine, a catecholamine that binds to the β-adrenergic receptor and activates the cAMP-PKA-dependent pathway, caused a significant increase in the frequency of active ICAM-4 receptors in both normal RBCs and SS-RBCs. However, the unbinding force between ICAM-4 and the corresponding ligand αvβ3 remained the same. Furthermore, we demonstrated that forskolin, an adenylyl cyclase activator, significantly increased the frequency of ICAM-4 receptors in WT-RBCs and SS-RBCs, confirming that the activation of ICAM-4 is regulated by the cAMP-PKA pathway. Finally, we showed that A-kinase anchoring proteins play an essential role in ICAM-4 activation.
Findings suggest that embedding adult SCD centers within existing cancer centers can positively impact patterns of health care utilization and improve the quality of care.
This article describes the impact of the integration of a licensed clinical social worker (LCSW) with expertise in behavioral health on identification of risk factors for chronic pain in a cohort of adults with sickle cell disease. Authors conducted a retrospective chart review of all visits to the adult sickle cell center during the first six months of LCSW integration. Demographics, clinical history, and LCSW notes were reviewed. Overall, 71 patients were introduced to the LCSW; 55 percent of them had chronic pain. Patients with chronic pain were older, used opioids daily, took hydroxyurea, reported higher daily pain scores, and underwent more acute care visits and hospitalizations for pain with longer stays. Fifty-eight (81 percent) patients requested concrete social work services such as transportation and housing. Thirty-two patients (55 percent) expressed a desire for mental health counseling while receiving concrete services. Twenty-two (69 percent) of these patients self-disclosed at least one traumatic experience. In fact, a statistically significant relationship between chronic pain and a history of trauma was identified (p = 0.001). Results suggest that sickle cell patients should receive clinical social work services to assess for traumatic exposures that may influence chronic pain.
Background. A treatment algorithm for sickle cell disease (SCD) pain in adults presenting to a single emergency department (ED) was developed prioritizing initiation of patient controlled analgesia (PCA) for patients awaiting hospitalization. Objectives. Evaluate the proportion of ED visits in which PCA was started in the ED. Methods. A two-year retrospective chart review of consecutive SCD pain ED visits was undertaken. Data abstracted included PCA initiation, low versus high utilizer status, pain scores, bolus opioid number, treatment times, and length of hospitalization. Results. 258 visits resulted in hospitalization. PCA was initiated in 230 (89%) visits of which 157 (68%) were initiated in the ED. Time to PCA initiation was longer when PCA was begun after hospitalization versus in the ED (8.6 versus 4.5 hours, p < 0.001). ED PCA initiation was associated with fewer opioid boluses following decision to admit and less time without analgesic treatment (all p < 0.05). Mean pain intensity (MPI) reduction did not differ between groups. Among visits where PCA was begun in the ED, low utilizers demonstrated greater MPI reduction than high utilizers (2.8 versus 2.0, p = 0.04). Conclusions. ED PCA initiation for SCD-related pain is possible and associated with more timely analgesic delivery.
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