Context Racial and ethnic differences in end-of-life care may be attributable to both patient preferences and healthcare disparities. Identifying factors that differentiate preferences from disparities may enhance end-of-life care for critically ill patients and their families. Objectives To understand the association of minority race/ethnicity and education with family ratings of the quality of dying and death, taking into consideration possible markers of patient and family preferences for end-of-life care as mediators of this association. Methods Data were obtained from 15 ICUs participating in a cluster-randomized trial of a palliative care intervention. Family members of decedents completed self-report surveys evaluating quality of dying. We used regression analyses to identify associations between race/ethnicity, education and quality of dying ratings. We then used path analyses to investigate whether advance directives and life-sustaining treatment acted as mediators between patient characteristics and ratings of quality of dying. Results Family members returned 1290 surveys for 2850 decedents. Patient and family minority race/ethnicity were both associated with lower ratings of quality of dying. Presence of a living will and dying in the setting of full support mediated the relationship between patient race and family ratings; patient race exerted an indirect, rather than direct, effect on quality of dying. Family minority race had a direct effect on lower ratings of quality of dying. Neither patient nor family education was associated with quality of dying. Conclusion Minority race/ethnicity was associated with lower family ratings of quality of dying. This association was mediated by factors that may be markers of patient and family preferences (living will, death in the setting of full support); family member minority race/ethnicity was directly associated with lower ratings of quality of dying. Our findings generate hypothesized pathways that require future evaluation.
The relationship between tissue inflammation and clearance of the opportunistic pathogen Pneumocystis carinii is poorly understood. We asked whether the anti-inflammatory cytokine interleukin-10 (IL-10) is released during the host response to infection with P. carinii and whether local delivery of the IL-10 gene could suppress tissue inflammatory responses without compromising clearance of infection. Control and CD4-depleted mice were inoculated with P. carinii, and at serial intervals after inoculation, lung tissue was assayed for IL-10 by enzyme-linked immunosorbent assay. We found that IL-10 was released in lung tissue in control mice and was present in higher concentrations in CD4-depleted mice with progressive infection. Control and CD4-depleted mice were then pretreated with 10 9 PFU of intratracheally administered adenoviral vector containing the viral IL-10 gene or the luciferase gene followed by inoculation with P. carinii. Pretreatment with viral IL-10 did not alter clearance of infection in control mice or severity of infection in CD4-depleted mice but did decrease tissue inflammation. We then asked whether gene transfer of viral IL-10 could decrease tissue inflammation during immune reconstitution. In these experiments, immunodeficient scid mice were inoculated with P. carinii and were heavily infected after 4 weeks. When these mice are immunologically reconstituted by intravenous administration of spleen cells from normal mice, a hyperinflammatory reaction developed in lung tissue, associated with high mortality. In comparison to control mice, mice treated with viral IL-10 prior to reconstitution showed significantly decreased lung wet weight, bronchoalveolar lavage fluid (BALF) lactate dehydrogenase, and BALF neutrophils. In contrast, infection intensity, as measured by PCR for P. carinii rRNA, was unchanged between the IL-10 and luciferase groups. Survival was also improved in the IL-10-treated mice. We conclude that release of IL-10 is part of the host response to infection with P. carinii and that gene therapy with viral IL-10 can lessen excessive tissue inflammation without altering pathogen clearance. In the setting of immune reconstitution and P. carinii pneumonia, pretreatment with the viral IL-10 gene decreases excessive tissue inflammation and improves survival. These results are relevant to acute respiratory failure after initiation of antibiotic treatment for human P. carinii pneumonia and to immune reconstitution syndromes in human immunodeficiency virus-positive patients started on highly active antiretroviral therapy.
Obstructive sleep apnea (OSA) is a highly prevalent disorder that has profound implications on the outcomes of patients with chronic lung disease. The hallmark of OSA is a collapse of the oropharynx resulting in a transient reduction in airflow, large intrathoracic pressure swings, and intermittent hypoxia and hypercapnia. The subsequent cytokine-mediated inflammatory cascade, coupled with tractional lung injury, damages the lungs and may worsen several conditions, including chronic obstructive pulmonary disease, asthma, interstitial lung disease, and pulmonary hypertension. Further complicating this is the sleep fragmentation and deterioration of sleep quality that occurs because of OSA, which can compound the fatigue and physical exhaustion often experienced by patients due to their chronic lung disease. For patients with many pulmonary disorders, the available evidence suggests that the prompt recognition and treatment of sleep-disordered breathing improves their quality of life and may also alter the course of their illness. However, more robust studies are needed to truly understand this relationship and the impacts of confounding comorbidities such as obesity and gastroesophageal reflux disease. Clinicians taking care of patients with chronic pulmonary disease should screen and treat patients for OSA, given the complex bidirectional relationship OSA has with chronic lung disease.
To prospectively compare the effects of endoscopic stapling, division and suture ligation, and suture ligation with suspension of the dorsal venous complex (DVC) on continence during robot-assisted laparoscopic radical prostatectomy (RARP). Patients and methods In all, 300 consecutive patients undergoing RARP by a single surgeon were randomised to three groups: endoscopic stapling, cut and suture ligation, and suture ligation with suspension. The only difference between the groups was the technique to control the DVC. Pad-free continence (PFC) and overall continence (0 pads/day with or without security pad) were assessed with patient reported pad usage records and validated questionnaires (Expanded Prostate Cancer Index) at 3, 12, and 15 months. Secondary endpoints were erectile function (EF) recovery (defined as erections sufficient for sexual activity) and the rate of apical surgical margins. Univariate and multivariate analyses were conducted to determine predictors for recovery of both urinary continence and EF. Results The three groups were comparable in terms of age, body mass index, prostate size, American Urological Association symptom score, Sexual Health Inventory for Men, and clinical stage. There were no differences found in terms of operative times, estimated blood loss, pathological stage, and positive apical margin. There was no difference between the three groups with regard to overall continence or PFC at 3 months. However, overall continence at 15 months for ligation and suspension was 99% and was superior to stapler (88%) (P = 0.002) and cut and suture ligation (88%) (P = 0.002). Additionally, PFC at 15 months was superior for ligation and suspension (87%) as compared to stapler (73%) and cut and suture ligation (75%) (P = 0.045). The technique of DVC control did not impact EF. Men with nerve sparing had better continence compared to no nerve sparing at 3 months (62% vs 42%, P = 0.045), but not at 15 months. The median time to continence was 2 months for patients receiving nerve sparing compared to 4.5 months for non-nerve sparing (P = 0.02). Conclusion Suture suspension of the DVC during RARP contributes to higher overall continence rates compared to stapling and cut and suture. Nerve sparing contributes to earlier return of continence than non-nerve sparing.
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