Communication between nurse care managers and patients who take opioids for chronic pain: Strategies for exploring aberrant behavior.

OBJECTIVE: One approach to potential misuse of prescription opioids by patients with chronic pain is team-based collaborative primary care, with primary care visits complemented by frequent visits with nurse care managers (NCMs) specializing in addiction care. However, little is known about the communication strategies NCMs employ in these visits. This study aimed to describe strategies NCMs used with patients when discussing aberrancies encountered during opioid monitoring. DESIGN: Observational study of NCM-patient interactions. Patients' primary care providers had been randomized to the treatment arm of a study evaluating an intervention, of which NCM visits were part, to change opioid prescribing patterns. The overall intervention was found to be successful. SETTING: Four primary care settings. PARTICIPANTS: Two NCMs and 41 patients. MAIN OUTCOME MEASURE: Forty one interactions between two NCMs and 41 unique patients were directly observed, and the detailed field notes coded for strategies using conventional content analysis. RESULTS: Five themes describing strategies that NCMs use to navigate aberrant patient behavior emerged: (1) NCM develops therapeutic relationship with patient; (2) NCM encourages adherence to monitoring strategies by contextualizing intensive opioid management for patient; (3) NCM inquires into discrepancies between patient's narrative and objective data to further understand aberrancy; (4) NCM assesses patient's medication use and pain to obtain more information about aberrancy and determine risk for opioid misuse; and (5) NCM educates patient and makes recommendations to guide appropriate medication use. CONCLUSIONS: These findings provide a potential model for the replication of intensive care management strategies utilizing NCMs in primary care.

The provision of cell phones as a recruitment and retention strategy for people who inject drugs enrolling in a randomized trial.

BACKGROUND: Studies of drug-using populations often restrict enrollment by limiting participation to those with a working telephone. It is unknown whether supplying phones could broaden recruitment and sustain retention among an urban population of people who inject drugs (PWID). We compare the feasibility of offering pay-by-month phones to gift card compensation as part of an ongoing randomized controlled trial of hospitalized PWID. METHODS: Participants were recruited from inpatient services at an urban hospital in Boston, MA to participate in an ongoing randomized trial testing a motivational interviewing (MI) intervention. Participants who did not have their own phone at the time of enrollment were offered a pay-by-month phones as compensation for study participation. RESULTS: Eighty-one participants met study criteria, were enrolled, and completed the study at the time of analysis. We used a generalized estimating equation to compare the overall likelihood of attending interviews during the 12-month follow-up period. Participants receiving phones tended to have lower mean educational attainment (11.4 years vs. 12.1 years), were significantly (Fisher's exact p < 0.001) more likely to report homelessness during the past 90 days (86.7% vs. 37.3%), and were significantly less likely (Fisher's exact p = .044) to be employed (3.3% vs. 20.4%) compared to those receiving gift cards. Participants in each group were equally likely to attend follow-up interviews during the study (83.3% vs. 88.3%, p = 0.53). CONCLUSION: Offering phones as a compensation method allows recruitment of a more disenfranchised population without impacting study retention and therefore may improve generalizability of study results.

Gliotoxin Suppresses Macrophage Immune Function by Subverting Phosphatidylinositol 3,4,5-Trisphosphate Homeostasis.

UNLABELLED: Aspergillus fumigatus, an opportunistic fungal pathogen, spreads in the environment by releasing numerous conidia that are capable of reaching the small alveolar airways of mammalian hosts. In otherwise healthy individuals, macrophages are responsible for rapidly phagocytosing and eliminating these conidia, effectively curbing their germination and consequent invasion of pulmonary tissue. However, under some circumstances, the fungus evades phagocyte-mediated immunity and persists in the respiratory tree. Here, we report thatA. fumigatusescapes macrophage recognition by strategically targeting phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] metabolism through gliotoxin, a potent immunosuppressive mycotoxin. Time-lapse microscopy revealed that, in response to the toxin, macrophages cease to ruffle, undergo abrupt membrane retraction, and fail to phagocytose large targets effectively. Gliotoxin was found to prevent integrin activation and interfere with actin dynamics, both of which are instrumental for phagocytosis; similar effects were noted in immortalized and primary phagocytes. Detailed studies of the underlying molecular mechanisms of toxicity revealed that inhibition of phagocytosis is attributable to impaired accumulation of PtdIns(3,4,5)P3and the associated dysregulation of downstream effectors, including Rac and/or Cdc42. Strikingly, in response to the diacylglycerol mimetic phorbol 12-myristate 13-acetate, gliotoxin-treated macrophages reactivate beta integrins, reestablish actin dynamics, and regain phagocytic capacity, despite the overt absence of plasmalemmal PtdIns(3,4,5)P3 Together, our findings identify phosphoinositide metabolism as a critical upstream target of gliotoxin and also indicate that increased diacylglycerol levels can bypass the requirement for PtdIns(3,4,5)P3signaling during membrane ruffling and phagocytosis. IMPORTANCE: Aspergillus fumigatusis the most frequent cause of human infections in theAspergillusgenus. In immunocompromised populations, invasive aspergillosis (IA) is associated with a mortality rate of up to 90%, and current antifungal therapies have failed to prevent or reverse the infection. Therefore, a deeper understanding of the interactions betweenA. fumigatusand its host is required. In healthy humans, alveolar macrophages can ingest and eliminate fungal spores, thus limiting their germination into mycotoxin-producing hyphae. Our studies reveal that gliotoxin-the most abundantAspergillusmycotoxin-undermines the ability of phagocytes to carry out their protective functions. By targeting PtdIns(3,4,5)P3signaling and downregulating phagocytic immune defenses, the toxin could also exacerbate polymicrobial infections. Notably, we were able to reverse gliotoxin toxicity by addition of diacylglycerol analogues, which may provide the basis for therapeutic interventions.

Incidence and prevalence of hepatitis C in prisons and other closed settings: results of a systematic review and meta-analysis.

UNLABELLED: People detained in prisons and other closed settings are at elevated risk of infection with hepatitis C virus (HCV). We undertook a systematic review and meta-analysis with the aim of determining the rate of incident HCV infection and the prevalence of anti-HCV among detainees in closed settings. We systematically searched databases of peer-reviewed literature and widely distributed a call for unpublished data. We calculated summary estimates of incidence and prevalence among general population detainees and detainees with a history of injection drug use (IDU), and explored heterogeneity through stratification and meta-regression. The summary prevalence estimates were used to estimate the number of anti-HCV positive prisoners globally. HCV incidence among general detainees was 1.4 per 100 person-years (py; 95% confidence interval [CI]: 0.1, 2.7; k = 4), and 16.4 per 100 py (95% CI: 0.8, 32.1; k = 3) among detainees with a history of IDU. The summary prevalence estimate of anti-HCV in general detainees was 26% (95% CI: 23%, 29%; k = 93), and in detainees with a history of IDU, 64% (95% CI: 58%, 70%; k = 51). The regions of highest prevalence were Central Asia (38%; 95% CI 32%, 43%; k = 1) and Australasia (35%; 95% CI: 28%, 43%; k = 9). We estimate that 2.2 million (range: 1.4-2.9 million) detainees globally are anti-HCV positive, with the largest populations in North America (668,500; range: 553,500-784,000) and East and Southeast Asia (638,000; range: 332,000-970,000). CONCLUSION: HCV is a significant concern in detained populations, with one in four detainees anti-HCV-positive. Epidemiological data on the extent of HCV infection in detained populations is lacking in many countries. Greater attention towards prevention, diagnosis, and treatment of HCV infection among detained populations is urgently required.