Impact of community based, specialist palliative care teams on hospitalisations and emergency department visits late in life and hospital deaths: a pooled analysis

Objective: To determine the pooled effect of exposure to one of 11 specialist palliative care teams providing services in patients’ homes.Design: Pooled analysis of a retrospective cohort study.Setting: Ontario, Canada.Participants: 3109 patients who received care from specialist palliative care teams in 2009-11 (exposed) matched by propensity score to 3109 patients who received usual care (unexposed).Intervention: The palliative care teams studied served different geographies and varied in team composition and size but had the same core team members and role: a core group of palliative care physicians, nurses, and family physicians who provide integrated palliative care to patients in their homes. The teams’ role was to manage symptoms, provide education and care, coordinate services, and be available without interruption regardless of time or day.Main outcome measures: Patients (a) being in hospital in the last two weeks of life; (b) having an emergency department visit in the last two weeks of life; or (c) dying in hospital.Results: In both exposed and unexposed groups, about 80% had cancer and 78% received end of life homecare services for the same average duration. Across all palliative care teams, 970 (31.2%) of the exposed group were in hospital and 896 (28.9%) had an emergency department visit in the last two weeks of life respectively, compared with 1219 (39.3%) and 1070 (34.5%) of the unexposed group (P<0.001). The pooled relative risks of being in hospital and having an emergency department visit in late life comparing exposed versus unexposed were 0.68 (95% confidence interval 0.61 to 0.76) and 0.77 (0.69 to 0.86) respectively. Fewer exposed than unexposed patients died in hospital (503 (16.2%) v 887 (28.6%), P<0.001), and the pooled relative risk of dying in hospital was 0.46 (0.40 to 0.52).Conclusions: Community based specialist palliative care teams, despite variation in team composition and geographies, were effective at reducing acute care use and hospital deaths at the end of life.

Deficiency of the ferrous iron transporter FeoAB is linked with metronidazole resistance in Bacteroides fragilis

Background Metronidazole is the most commonly used antimicrobial for Bacteroides fragilis infections and is recommended for prophylaxis of colorectal surgery. Metronidazole resistance is increasing and the mechanisms of resistance are not clear.

Methods A transposon mutant library was generated in B. fragilis 638R (BF638R) to identify the genetic loci associated with resistance to metronidazole.

Results Thirty-two independently isolated metronidazole-resistant mutants had a transposon insertion in BF638R_1421 that encodes the ferrous transport fusion protein (feoAB). Deletion of feoAB resulted in a 10-fold increased MIC of metronidazole for the strain. The metronidazole MIC for the feoAB mutant was similar to that for the parent strain when grown on media supplemented with excess iron, suggesting that the increase seen in the MIC of metronidazole was due to reduced cellular iron transport in the feoAB mutant. The furA gene repressed feoAB transcription in an iron-dependent manner and disruption of furA resulted in constitutive transcription of feoAB, regardless of whether or not iron was present. However, disruption of feoAB also diminished the capacity of BF638R to grow in a mouse intraperitoneal abscess model, suggesting that inorganic ferrous iron assimilation is essential for B. fragilis survival in vivo.

Conclusions Selection for feoAB mutations as a result of metronidazole treatment will disable the pathogenic potential of B. fragilis and could contribute to the clinical efficacy of metronidazole. While mutations in feoAB are probably not a direct cause of clinical resistance, this study provides a key insight into intracellular metronidazole activity and the link with intracellular iron homeostasis.

Predictors of place of death for those in receipt of home-based palliative care services in Ontario, Canada

Many cancer patients die in institutional settings despite their preference to die at home. A longitudinal, prospective cohort study was conducted to comprehensively assess the determinants of home death for patients receiving home-based palliative care. Data collected from biweekly telephone interviews with caregivers (n=302) and program databases were entered into a multivariate logistic model. Patients with high nursing costs (odds ratio [OR]: 4.3; confidence interval [CI]: 1.8-10.2) and patients with high personal support worker costs (OR: 2.3; CI: 1.1-4.5) were more likely to die at home than those with low costs. Patients who lived alone were less likely to die at home than those who cohabitated (OR: 0.4; CI: 0.2-0.8), and those with a high propensity for a home-death preference were more likely to die at home than those with a low propensity (OR: 5.8; CI: 1.1-31.3). An understanding of the predictors of place of death may contribute to the development of effective interventions that support home death.

The role of WNT singling activation and its blockage in the focal retinal lesion of Ccl2-/-/Cx3cr1-/- mice with and without rd8 background

Purpose: The canonical Wnt signaling is activated by retinal injury. Under disease conditions, the Wnt mediates inflammatory responses. Inflammation has been detected in age-related macular degeneration (AMD) retinas and Ccl2-/-/Cx3cr1-/- (DKO) mice with or without rd8 background, a model with progressive AMD-like lesions including focal photoreceptor/RPE degeneration and A2E accumulation. We evaluated the effects of Wnt-β-catenin activation and an antibody against LRP6, the co-receptor of Wnt on these two models.

Methods: anti-LRP6 antibody (2F1, 1 μl of 5 μg/μL) was intravitreally injected into the right eyes in 3 separate experiments (DKOrd8, N=35; DKO, N=10). The left eyes were injected with mouse IgG as controls. Fundoscopy was taken before injection and sequentially monthly after injection. Two months after injection, light-adapted ERG responses were recorded; then the eyes were harvested for histopathology, the determination of retinal A2E, and molecular analysis. The microarray of ocular mRNA of 92 Wnt genes was compared between the treated and the control eyes. The phosphorylated types of LRP6 and β-catenin and endogenous forms of the proteins were assayed by Western blotting.

Results: For DKOrd8 mice, the fundus showed a slower progression or alleviation of retinal lesions in the right eyes as compared to the left eyes. Among 35 pairs of eyes, 26 (74.3%) were improved, 7 (20%) stayed the same and 2 (5.7%) remained progressing. Histology confirmed the clinical observation. Light-adapted ERG of the treated eyes exhibited larger amplitudes compared to control eyes (n=6), with greater improvements under UV light stimulus. There was a significantly lower A2E in the treated eyes compared to controls. Microarray of 92 Wnt genes expression pattern was similar in both eyes. Western blotting indicated local administration of 2F1 antibody to suppress the activation of Wnt pathway in the retina. For DKO mice, the treatment improved ERG but less effect on RPE degeneration.

Conclusions: The canonical Wnt signaling plays a role in the focal retina lesion of both DKOrd8 and DKO mice; and intravitreal anti-LRP6 antibody might be neuroprotective via deactivation of canonical Wnt pathway.

Predictors of caregiver burden across the home-based palliative care trajectory in Ontario, Canada

Family caregivers of patients enrolled in home-based palliative care programmes provide unpaid care and assistance with daily activities to terminally ill family members. Caregivers often experience caregiver burden, which is an important predictor of anxiety and depression that can extend into bereavement. We conducted a longitudinal, prospective cohort study to comprehensively assess modifiable and non-modifiable patient and caregiver factors that account for caregiver burden over the palliative care trajectory. Caregivers (n = 327) of patients with malignant neoplasm were recruited from two dedicated home-based palliative care programmes in Southern Ontario, Canada from 1 July 2010 to 31 August 2012. Data were obtained from bi-weekly telephone interviews with caregivers from study admission until death, and from palliative care programme and home-care agency databases. Information collected comprised patient and caregiver demographics, utilisation of privately and publicly financed resources, patient clinical status and caregiver burden. The average age of the caregivers was 59.0 years (SD: 13.2), and almost 70% were female. Caregiver burden increased over time in a non-linear fashion from study admission to patient death. Increased monthly unpaid care-giving time costs, monthly public personal support worker costs, emergency department visits and low patient functional status were associated with higher caregiver burden. Greater use of hospice care was associated with lower burden. Female caregivers tended to report more burden compared to men as death approached, and burden was higher when patients were male. Low patient functional status was the strongest predictor of burden. Understanding the influence of modifiable and non-modifiable factors on the experience of burden over the palliative trajectory is essential for the development and targeting of programmes and policies to support family caregivers and reduce burden. Supporting caregivers can have benefits such as improved caregiver health outcomes, and enhancing their ability to meet care-giving demands, thereby potentially allowing for longer patient care in the home setting.