Spinal cord injury and Parkinson's disease: a population-based, propensity score-matched, longitudinal follow-up study.

OBJECTIVES: To investigate whether patients with spinal cord injury (SCI) are at an increased risk of developing Parkinson's disease (PD). STUDY DESIGN: A population-based, propensity score-matched, longitudinal follow-up cohort study. SETTING: The study was conducted using the National Health Insurance (NHI) Research Database. METHODS: A total of 10 125 patients with at least 2 ambulatory visits with a diagnosis of SCI in 2001 were enrolled in the SCI group. The non-SCI group comprised 10 125 propensity score-matched patients without SCI. The propensity scores were computed using a logistic regression model that included age, sex, comorbidities and socioeconomic status. The PD-free survival rates of the two groups were estimated using the Kaplan-Meier method. Stratified Cox proportional hazard regression was used to estimate the effect of SCI on subsequent occurrence of PD. RESULTS: During the 3-year follow-up period, 99 subjects in the SCI group and 59 in the non-SCI group developed PD. The hazard ratio of PD for the SCI group compared with the non-SCI group was 1.65 (95% confidence interval 1.16-2.33, P=0.0049). The PD-free survival rate for the SCI group was lower than that for the non-SCI group (P=0.0017). CONCLUSIONS: This study shows that SCI is associated with a subsequent increased risk of PD. Further studies are needed to elucidate the mechanism underlying this association.

Preferred and actual place of death in haematological malignancy.

OBJECTIVES: Home is considered the preferred place of death for many, but patients with haematological malignancies (leukaemias, lymphomas and myeloma) die in hospital more often than those with other cancers and the reasons for this are not wholly understood. We examined preferred and actual place of death among people with these diseases. METHODS: The study is embedded within an established population-based cohort of patients with haematological malignancies. All patients diagnosed at two of the largest hospitals in the study area between May 2005 and April 2008 with acute myeloid leukaemia, diffuse large B-cell lymphoma or myeloma, who died before May 2010 were included. Data were obtained from medical records and routine linkage to national death records. RESULTS: 323 deceased patients were included. A total of 142 (44%) had discussed their preferred place of death; 45.8% wanted to die at home, 28.2% in hospital, 16.9% in a hospice, 5.6% in a nursing home and 3.5% were undecided; 63.4% of these died in their preferred place. Compared to patients with evidence of a discussion, those without were twice as likely to have died within a month of diagnosis (14.8% vs 29.8%). Overall, 240 patients died in hospital; those without a discussion were significantly more likely to die in hospital than those who had (p≤0.0001). Of those dying in hospital, 90% and 75.8% received haematology clinical input in the 30 and 7 days before death, respectively, and 40.8% died in haematology areas. CONCLUSIONS: Many patients discussed their preferred place of death, but a substantial proportion did not and hospital deaths were common in this latter group. There is scope to improve practice, particularly among those dying soon after diagnosis. We found evidence that some people opted to die in hospital; the extent to which this compares with other cancers is of interest.

Variations in specialist palliative care referrals: findings from a population-based patient cohort of acute myeloid leukaemia, diffuse large B-cell lymphoma and myeloma.

OBJECTIVE: To develop and implement a methodology for capturing complete haematological malignancy pathway data and use it to identify variations in specialist palliative care (SPC) referrals. METHODS: In our established UK population-based patient cohort, 323 patients were diagnosed with acute myeloid leukaemia, diffuse large B-cell lymphoma or myeloma between May 2005 and April 2008, and died before April 2010. A day-by-day calendar approach was devised to collect pathway data, including SPC referrals, to supplement routinely collected information on clinical presentation, diagnosis, treatment, response, and date and place of death. RESULTS: 155 (47.9%) of the 323 patients had at least one SPC referral. The likelihood of referral increased with survival (OR 6.58, 95% CIs 3.32 to 13.03 for patients surviving ≥1 year compared to ≤1 month from diagnosis), and varied with diagnosis (OR 1.96, CIs 1.15 to 3.35 for myeloma compared to acute myeloid leukaemia). Compared to patients dying in hospital, those who died at home or in a hospice were also more likely to have had an SPC referral (OR 3.07, CIs 1.59 to 5.93 and 4.74, CIs 1.51 to 14.81, respectively). No associations were found for age and sex. CONCLUSIONS: Our novel approach efficiently captured pathway data and SPC referrals, revealing evidence of greater integration between haematology and SPC services than previously reported. The likelihood of referral was much higher among those dying outside hospital, and variations in practice were observed by diagnosis, emphasising the importance of examining diseases individually.

Hippocampal CRF, NE, and NMDA system interactions in memory processing in the rat.

In the present study, we investigated the neural mechanisms of corticotropin-releasing factor (CRF) and the interactions among CRF, norepinephrine (NE), and N-methyl-D-aspartate (NMDA) systems in the dentate gyrus (DG) of hippocampus in modulating the memory process of rats. One-way passive avoidance task was adopted. Results indicated that CRF (80 ng), when directly injected into the DG, consistently and significantly enhanced memory retention in rats. The noradrenergic neurotoxin DSP-4, at a high dose (4 micrograms), impaired memory. DSP-4 at a moderate dose (2 micrograms), which did not affect retention alone, antagonized the memory-enhancing effect of CRF. Similarly, the beta-adrenergic antagonist propranolol, at a high dose (8 micrograms), reduced retention. At a low dose (80 ng), which did not markedly affect retention by itself, propranolol also prevented the memory-improving effect of CRF. Moreover, direct NE infusions to the DG significantly improved retention performance in a dose-sensitive manner. Coadministration of CRF and NE did not further enhance retention. These results together suggest that CRF and NE facilitated memory probably through the same instead of independent mechanisms. In contrast, the selective NMDA receptor antagonists 2-amino-5-phosphonopentanoate (AP5) and MK801, at high doses markedly impaired memory retention (0.8 and 3.2 micrograms for AP5, 2 and 10 micrograms for MK801). At a dose of MK801 that did not significantly alter retention alone (80 ng), it completely blocked the memory-facilitating effect of CRF. These results indicate that CRF enhanced memory indirectly through NMDA receptor mediation also. Finally, MK801 at 80 ng also successfully antagonized the memory-facilitating effect of NE in the DG. We have demonstrated that MK801, at the dose chosen for interaction studies, did not markedly alter locomotor activity. These results together suggest that CRF, through a presynaptic facilitation mechanism, possibly facilitates NE release in the DG; increased NE release and stimulation of beta-adrenergic receptors in the DG result in NMDA receptor activations in the same area. This sequence of events enhance the memory consolidation process in the hippocampus and explained the neural mechanism of CRF in facilitating retention performance in rats. The same neuropeptide/neurotransmitter interactions may have other physiological and neuropathological implications.