The effect of age on the pharmacokinetics of the opioid antagonist nalmefene

1 The disposition of nalmefene was evaluated in young and elderly normal healthy volunteers. Subjects received either a single 1  mg ( n =18 young; n =11 elderly) or 2  mg ( n =8 young; n =15 elderly) intravenous bolus dose of nalmefene.
2 Following the administration of nalmefene, the initial plasma concentrations were significantly higher in elderly vs young subjects. The higher concentrations were the result of the 30 to 40% smaller central compartment apparent volume of distribution that was observed in the elderly subjects as compared with the young volunteers (2.8±1.1 vs 3.9±1.1  l  kg⁻¹ for 1  mg dose). The elderly volunteers also had a significantly shorter distributional half-life ( t1/2λ1 ) than young volunteers (0.7±0.7 vs 1.3±0.8  h for 1  mg dose). No significant differences between groups were observed for the elimination half-life, clearance or steady-state apparent volume of distribution.
3 Although transiently higher nalmefene plasma concentrations were observed in the elderly immediately following drug administration, there was no association between this observation and adverse events. We conclude that no dosage alteration is warranted in elderly patients.     

A randomised controlled trial to test the feasibility of a collaborative care model for the management of depression in older people

BACKGROUND: Depression is the most common mental health disorder in people aged over 65 years. Late-life depression is associated with chronic illness and disability. AIM: To investigate the feasibility of a collaborative care model for depression in older people in a primary care setting. DESIGN OF STUDY: Randomised controlled trial with 16-weeks follow up. SETTING: A primary care trust in Manchester. METHOD: Participants were 105 people aged 60 years or older who scored 5 or more on the Geriatric Depression Scale; 53 were randomly allocated to an intervention group and 52 to a usual care group. The intervention group received care managed by a community psychiatric nurse who delivered an intervention comprising a facilitated self-help programme with close liaison with primary care professionals and old-age psychiatry according to a defined protocol. The usual care group received usual GP care. A nested qualitative study explored the views of the health professionals and patients regarding the acceptability and effectiveness of the intervention. RESULTS: The main outcome measure was recovery from depression. Patients in the intervention group were less likely to suffer from major depressive disorder at follow up compared with usual care (0.32, 95% confidence = interval = 0.11 to 0.93, P = 0.036). The qualitative component of the study demonstrated the acceptability of the intervention to patients. CONCLUSION: A model of collaborative care for older people with depression, used in a primary care setting with a facilitated self-help intervention is more effective than usual GP care. This study demonstrates that the implementation of a collaborative care model is feasible in UK primary care and that the intervention is effective and acceptable to patients.     

Acute optic neuritis: a virological study in relation to multiple sclerosis.

Previous ultrastructural examination of peripheral blood lymphocytes revealed the presence of intranuclear filamentous structures in multiple sclerosis (MS) and in some optic neuritis (ON) patients. The present investigation was undertaken in the attempt to correlate the presence of such structures with the etiology of ON and MS and possibly to demonstrate the viral origin of the filaments. Suitable virological and serological techniques were used to detect and isolate infectious agents from peripheral blood samples and body excretions of 12 monosymptomatic ON patients at their first acute attack. Nevertheless, any efforts to demonstrate the presence of a virus in these patients have been unsuccessful: no evidence of active viral infection was obtained by serological studies of serum and cerebrospinal fluid samples, nor could viral antigens or inclusions be observed by immunofluorescence and cytochemical analysis. Negative results were also obtained from studies performed in parallel on MS patients and various controls. The significance of the failure to isolate infectious agents from either ON and MS patients is discussed.     

Neoplasms involving the central nervous system in the older old

Geriatric cancer patients present special challenges for clinicians. Few large series have been published in the last 20 years on the types of neoplasms that involve the central nervous system (CNS) in older individuals. To review types of neoplasms involving the central CNS that are currently being encountered by pathologists and neurosurgeons, we identified from our databases for the years 1992-2002, inclusive, patients 75 years or older who had symptomatic lesions requiring neurosurgical interventions. Retrospective characterization of tumors by immunohistochemistry, in situ hybridization, and fluorescence in situ hybridization was performed whenever possible and relevant to tumor type. Neurosurgical procedures (n=125) on 119 patients were identified; 90 patients were diagnosed as having neoplasms, with clot evacuation or infections being the most frequent non-neoplastic conditions necessitating surgery. Tumor types included glioblastomas (36 patients), meningiomas (16), pituitary adenomas (12), lymphomas or other hematological malignancies (8), anaplastic gliomas (5), metastases (6), head and neck malignancies with direct intracranial extension (3), and other miscellaneous tumor types (4). Compared with older literature series, we encountered a larger number of elderly patients with CNS lymphomas and fewer who came to surgery for CNS metastatic disease. In the "older old", glioblastomas are the most frequent symptomatic tumors necessitating surgical intervention. Glioblastomas in this aged cohort display the signature features of the small cell phenotype (62%), high cell cycle labeling indices (mean MIB-1-labeling index=25.1%), and either amplification of epidermal growth factor receptor or gain of chromosome 7 by fluorescence in situ hybridization (93% of assessable cases).     

Intravenous and intramuscular pharmacokinetics of recombinant leukocyte a interferon

Summary Interferon is currently being evaluated for the treatment of disseminated cancer and viral diseases. Alpha interferons have shown to be effective in the treatment of a number of malignancies. Recombinant leukocyte A interferon (rIFN-A) is an alpha interferon produced by recombinant DNA techniques. A kinetic evaluation of rIFN-A following intravenous and intramuscular administration has not been adequately defined. The present study was designed to evaluate the kinetics of rIFN-A following intravenous and intramuscular administration of 3, 9 or 18×10⁶ units to patients with disseminated cancer.A preliminary report of this study was presented at the meeting of the American Society for Clinical Pharmacology and Therapeutics in San Diego, March 1983 (1).     

Plasticity of the central nervous system—a neurosurgeon's experience of cerebral compensation and decompensation

Summary Cerebral plasticity constitutes one of the most decisive factors in recovery and readaptation after cerebral lesions. In contrast to the considerable progress in current studies on normal neuronal plasticity including the idea of l'homme neuronal, the concept of plasticity postulated by Albrecht Bethe in 1929 received little attention. The author, as a neurosurgeon, has tried to describe cranial morphological plasticity, morphological and functional plasticity in infantile encephalopathies and especially in hemiatrophic lesions. It is supposed that a true morphological substrate exists due to compensatory hyperplasia of the uninvolved hemisphere.Modern neurosurgical techniques have demonstrated that the functional plastic capacity is much larger than has been supposed, even in the elderly. Some aspects of the mechanisms of compensation and decompensation of cortical and subcortical structures as well as of the central regulation systems are discussed. The full extent of the amazing recovery and functional reorganization is reached by plastic capacity, personal motivation, adequate training and sufficient time.The contribution ends with an exposition of a personal philosophy concerning psycho-somatic dualism, the body-mind problem, the future of the human brain and the ethical outlook, based on the progressive biological evolution of the basal neocortex and the immanent functional development (H. Spatz).In grateful memory of my paternal friends, the great German brain researchers Julius Hallervorden (1882–1965) and Hugo Spatz (1888–1969).     

Prediction and profile of the long-stay population. A nation-wide cohort of first time admitted patients

A nation-wide cohort of 12,737 first admitted patients aged 15 years or more to Danish psychiatric institutions was followed in the Danish Case Register for a 10-year period. Long stay patients were delineated as: 1) patients whose first admission lasted for more than 1 year (new long-stay); or 2) patients who later had an admission lasting for more than 1 year (late long-stay). Together they comprised 420 males and 527 females with an incidence rate of 0.22 males and 0.27 females per 1,000. Up to age 65 males dominated, after 65 females dominated. Thirty-three percent of demential disordered and 24 of schizophrenics became long-stay patients. A multiple contingency analysis showed that the variables "age group", "main diagnosis", "size of municipality of residence" and "marital status" were independently associated with the outcome "long-stay". The two long-stay groups differed. New long-stay patients tended to be females, older, suffering from demential disorders and with a total hospital stay shorter than that of the long-stay population. In a multiple contingency analysis the variables "age group" and "main diagnosis" were independently associated with the outcome "new long-stay" and the variables "age groups", "main diagnosis" and "size of municipality of residence" with the outcome "late long-stay".     

Dietary Supplementation with Selenium and Coenzyme Q10 Prevents Increase in Plasma D-Dimer While Lowering Cardiovascular Mortality in an Elderly Swedish Population

A low intake of selenium is associated with increased cardiovascular mortality. This could be reduced by supplementation with selenium and coenzyme Q₁₀. D-dimer, a fragment of fibrin mirroring fibrinolysis, is a biomarker of thromboembolism, increased inflammation, endothelial dysfunction and is associated with cardiovascular mortality in ischemic heart disease. The objective was to examine the impact of selenium and coenzyme Q₁₀ on the level of D-dimer, and its relationship to cardiovascular mortality. D-dimer was measured in 213 individuals at the start and after 48 months of a randomised double-blind placebo-controlled trial with selenium yeast (200 µg/day) and coenzyme Q₁₀ (200 mg/day) (n = 106) or placebo (n = 107). The follow-up time was 4.9 years. All included individuals were low in selenium (mean 67 μg/L, SD 16.8). The differences in D-dimer concentration were evaluated by the use of T-tests, repeated measures of variance and ANCOVA analyses. At the end, a significantly lower D-dimer concentration was observed in the active treatment group in comparison with those on placebo (p = 0.006). Although D-dimer values at baseline were weakly associated with high-sensitive CRP, while being more strongly associated with soluble tumour necrosis factor receptor 1 and sP-selectin, controlling for these in the analysis there was an independent effect on D-dimer. In participants with a D-dimer level above median at baseline, the supplementation resulted in significantly lower cardiovascular mortality compared to those on placebo (p = 0.014). All results were validated with a persisting significant difference between the two groups. Therefore, supplementation with selenium and coenzyme Q₁₀ in a group of elderly low in selenium and coenzyme Q₁₀ prevented an increase in D-dimer and reduced the risk of cardiovascular mortality in comparison with the placebo group. The obtained results also illustrate important associations between inflammation, endothelial function and cardiovascular risk.     

Robot-Assisted vs Laparoscopic Right Hemicolectomy in Octogenarians

ObjectiveWith increasing age, there is greater need for right-sided colonic resections than its left-sided counterparts. Older age is associated with limited physical and functional status, which carries greater operative risk. Improvements in robotic surgery questions its role, especially in older adults, compared with laparoscopy. The objective is to investigate whether robotic right hemicolectomy (RRH) is as safe and effective as laparoscopic right hemicolectomy (LHR) in octogenarians (age >80 years).DesignRetrospective cross-sectional analysis.Settings and ParticipantsOctogenarians who underwent elective RRH and LRH by the Tweed Colorectal Group over 5 years.MethodsComplications within 30 days, age, gender, smoking status, immunocompromised status, presence of diabetes, American Society of Anesthesiologists (ASA) physical status score, preoperative Eastern Cooperative Oncology Group (ECOG) performance status, mFI-5 (modified frailty index), operative time, method of anastomosis, postoperative length of stay (LOS), need for rehabilitation, and short-term oncologic data using the TNM criteria were compared using univariate and multivariate analysis.ResultsSeventy-eight elective patients were included. LRH and RRH groups had similar median ages, gender distribution, and comorbidities. Across the entire cohort, 61.5% had no 30-day complications. RRH had nonsignificantly shorter operative time but significantly shorter LOS (5 vs 8 days) and fewer minor complications (24.5% vs 34.5%). Major complications and overall complications were not significantly different between the groups. Lower ASA and ECOG status were associated with lower complication rates across both groups. Oncologic resection outcomes were similar for both approaches.Conclusions and ImplicationsRRH does not confer an increased risk of complications compared to LRH in the octogenarians and may be a viable alternative in the field of minimally invasive surgery for older patients. Future research should focus on intracorporeal anastomoses, as it is a potential confounder leading to the shorter inpatient LOS shown in our robotic group.