The efficacy of psychotherapy, pharmacotherapy and their combination on functioning and quality of life in depression: a meta-analysis.

BACKGROUND: There is growing recognition of the importance of both functioning and quality of life (QoL) outcomes in the treatment of depressive disorders, but the meta-analytic evidence is scarce. The objective of this meta-analysis of randomized controlled trials (RCTs) was to determine the absolute and relative effects of psychotherapy, pharmacotherapy and their combination on functioning and QoL in patients with depression. METHOD: One hundred and fifty-three outcome trials involving 29 879 participants with depressive disorders were identified through database searches in Pubmed, PsycINFO and the Cochrane Central Register of Controlled Trials. RESULTS: Compared to control conditions, psychotherapy and pharmacotherapy yielded small to moderate effect sizes for functioning and QoL, ranging from g = 0.31 to g = 0.43. When compared directly, initial analysis yielded no evidence that one of them was superior. After adjusting for publication bias, psychotherapy was more efficacious than pharmacotherapy (g = 0.21) for QoL. The combination of psychotherapy and medication performed significantly better for both outcomes compared to each treatment alone yielding small effect sizes (g = 0.32 to g = 0.39). Both interventions improved depression symptom severity more than functioning and QoL. CONCLUSION: Despite the small number of comparative trials for some of the analyses, this study reveals that combined treatment is superior, but psychotherapy and pharmacotherapy alone are also efficacious for improving functioning and QoL. The overall relatively modest effects suggest that future tailoring of therapies could be warranted to better meet the needs of individuals with functioning and QoL problems.

Presenilin-dependent regulated intramembrane proteolysis and gamma-secretase activity.

Inhibiting the production of amyloid-beta by antagonising gamma-secretase activity is currently being pursued as a therapeutic strategy for Alzheimer's disease (AD). However, early pre-clinical studies have demonstrated that disruption of presenilin-dependent gamma-secretase alters many presenilin-dependent processes, leading to early lethality in several AD model organisms. Subsequently, transgenic animal studies have highlighted several gross developmental side effects arising from presenilin deficiency. Partial knockdown or tissue-specific knockout of presenilins has identified the skin, vascular and immune systems as very sensitive to loss of presenilin functions. A more appreciative understanding of presenilin biology is therefore demanded if gamma-secretase is to be pursued as a therapeutic target. Herein we review the current understanding of gamma-secretase complexes; their regulation, abundance of interacting partners and diversity of substrates. We also discuss regulation of the gamma-secretase complexes, with an emphasis on the functional role of presenilins in cell biology.

Genetic variation in the interleukin-10 gene promoter and risk of coronary and cerebrovascular events: the PROSPER study.

Proinflammatory cytokines, like interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), are implicated in the development of atherosclerosis. The role of anti-inflammatory cytokines, like IL-10, is largely unknown. We investigated the association of four single nucleotide polymorphisms (SNPs) in the promoter region of the IL-10 gene (4259AG, -1082GA, -592CA, and -2849GA), with coronary and cerebrovascular disease in participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial. All associations were assessed with Cox proportional hazards models adjusted for sex, age, pravastatin use, and country. Haplotype analysis of the four SNPs showed a significant association between haplotype 4 (containing the -592A variant allele) and risk of coronary events (P = 0.019). Moreover, analysis of separate SNPs found a significant association between -2849AA carriers with incident stroke (HR (95%CI) 1.50 (1.04-2.17), P value = 0.02). Our study suggests that not only proinflammatory processes contribute to atherosclerosis, but that also anti-inflammatory cytokines may play an important role.

The pattern of plasma sodium abnormalities in an acute elderly care ward: a cross-sectional study.

INTRODUCTION: The combination of ageing, illness, and medications can lead to hyponatraemia or hypernatraemia. AIMS: To describe the distribution of plasma sodium levels in older patients admitted to hospital. METHODS: We carried out a hospital based cross-sectional study examining 1,511 serum sodium concentrations ([Na+]) among 336 elderly patients and attempted to elucidate the cause(s) of the abnormal serum [Na+]. RESULTS: The study population had a mean age of 81.4. Ninety-two (27.4%) patients had hyponatraemia and seven patients (2.1%) had hypernatraemia during their hospitalisation. The distribution of [Na+] results was towards the lower end of the normal range. The mortality rate of patients with hyponatraemia was 14.1% and that of patients with normal serum [Na+] was 8.9%. Six patients with hypernatraemia died in hospital. Lower respiratory tract infection and medication accounted for the majority of cases. CONCLUSIONS: Deranged [Na+] is common among elderly patients admitted to hospital.

The financial implications of falls in older people for an acute hospital.

BACKGROUND: Falls are a common occurrence in older people and frequently lead to hospital admission. There is a current lack of cohesive fall prevention strategies in the Republic of Ireland. AIM: To demonstrate the cost of fall-related admissions to an acute hospital. METHODS: A review of Hospital Inpatient Enquiry (HIPE) data and medical case notes was performed for all fall-related admissions over a one-year period. The cost of fall-related admissions was calculated. In addition a detailed cost analysis was performed to determine the true cost of a hip fracture admission. RESULTS: There were 810 fall-related admissions, resulting in 8,300 acute bed days, and 6,220 rehabilitation bed days, costing euros 10.3 million. Fall-related readmissions resulted in 650 bed-days, bringing the total cost to euros 10.8 million. A typical hip fracture incident admission episode costs euros 14,300. CONCLUSION: Fall-related admissions of olderpeople are a significant financial burden to the health service.

A comparative study of the thermal inactivation of cytosolic and mitochondrial aspartate aminotransferases.

Rates of irreversible thermal inactivation of cytosolic and mitochondrial aspartate aminotransferases were measured over a large temperature range. Inactivation occurred by different kinetic pathways at high and low temperature with a transition point at about 60 degrees C. This suggests that the isoenzymes exist in different conformations above and below that temperature. Discontinuities in plots of ln(Vmax) against 1/T provided confirmatory evidence for this hypothesis. Activation parameters (deltaH and deltaS) for the thermal inactivation process were calculated in the high and low temperature ranges. At high temperature the greater rate of inactivation of the mitochondrial isoenzyme is determined largely by a high value of deltaS. This more than compensates for the fact that the deltaH is also greater for the mitochondrial isoenzyme indicative of greater intramolecular stabilising interactions compared with the cytosolic form. Thus the relative rates of inactivation are determined by the nature of the transition states rather than by intramolecular interactions in the folded proteins. At lower temperatures the kinetic stabilities of the isoenzymes reverse with the mitochondrial isoenzyme inactivating more slowly. This is largely because of a considerably smaller deltaS at low temperature which no longer compensates for the greater deltaH compared with the cytosolic isoenzyme.

The design of a prospective study of Pravastatin in the Elderly at Risk (PROSPER). PROSPER Study Group. PROspective Study of Pravastatin in the Elderly at Risk.

The PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) is a randomized, double-blind, placebo-controlled trial designed to test the hypothesis that treatment with pravastatin will diminish risk of subsequent major vascular events in a cohort of men and women (70 to 82 years old) with preexisting vascular disease or significant risk of developing this condition. Five thousand eight hundred four men and women in addition to receiving advice on diet and smoking, have been randomized equally to treatment with 40 mg pravastatin/day or matching placebo in 3 centers (Cork, Ireland, Glasgow, Scotland, and Leiden, The Netherlands). Following an average 3.5-year intervention period, a primary assessment will be made of the influence of this therapy on major vascular events (a combination of coronary heart disease, death, nonfatal myocardial infarction, and fatal and nonfatal stroke). A number of additional analyses will also be conducted on the individual components of the primary end point, on men, on women, and on subjects with and without previous evidence of vascular disease. Finally, an assessment will be made of the effects of treatment on cognitive function, disability, hospitalization or institutionalization, vascular mortality, and all-cause mortality.

Ovine corticotropin releasing hormone stimulation test: normal value study.

We determined the pituitary-adrenal response to 1 microgram/kg of ovine corticotropin releasing hormone (oCRH) administered as an intravenous bolus injection in 50 normal subjects. Brief facial flushing was noted in 44% of the subjects; no other side effects were reported. Plasma corticotropin levels increased from a median of 30.2 pg/ml at baseline to a median peak level of 77.8 pg/ml after administration of oCRH; the peak response occurred at the 30- to 45-minute or the 45- to 60-minute time point. Plasma cortisol levels increased from a median of 10.8 micrograms/dl at baseline to a median peak level of 22.0 micrograms/dl after administration of oCRH; the peak response occurred at the 45- to 60-minute time point. Plasma beta-endorphin levels increased from a median of 9.5 pg/ml at baseline to a median peak level of 23.0 pg/ml after administration of oCRH; the peak response occurred at the 15- to 30-minute or the 30- to 45-minute time point. The responsiveness to oCRH was unaffected by age, sex, or body mass index of the subjects.

Heart transplantation in patients with heparin-induced thrombocytopenia on the Novacor left ventricular assist system.

We report on two patients with development of heparin-induced thrombocytopenia with thrombosis while on the Novacor left ventricular assist system. Heart transplantation was successfully performed in both patients with heparin used for cardiopulmonary bypass after careful monitoring of heparin-associated antibodies. The approach to the patients' management and potential alternatives for anticoagulation are discussed.

Fatal vertebral giant cell arteritis.

Death due to giant cell arteritis (GCA) is rare, and is usually caused by coronary or vertebral arteritis in the acute phase of the disease. A case of fatal GCA is reported in a woman with a normal erythrocyte sedimentation rate, who had been treated for temporal arteritis for eight months. Post mortem examination showed a dissection and thrombosis of the intracranial portion of the left vertebral artery caused by giant cell arteritis. Focal coronary artery GCA was also found. As far as is known, this is the only case in which dissection of the vertebral artery attributable to GCA has been reported.

Antibiotic prescribing policy and Clostridium difficile diarrhoea.

BACKGROUND: Broad-spectrum antibiotics, particularly intravenous cephalosporins, are associated with Clostridium difficile diarrhoea. Diarrhoea due to C. difficile is a growing problem in hospitals, especially among elderly patients. AIM: To establish whether changing an antibiotic policy with the aim of reducing the use of injectable cephalosporins leads to a reduction in the incidence of C. difficile diarrhoea in elderly patients. DESIGN: Retrospective analysis. METHODS: A group of patients who were subject to the new antibiotic policy from the period following July 2000, were compared with patients who were admitted prior to July 2000 and were not subject to the new policy. Infections, antibiotic prescriptions and mortality rates were determined from case notes, and C. difficle diarrhoea rates from microbiological data. RESULTS: Intravenous cephalosporin use fell from 210 to 28 defined daily doses (p < 0.001) following the change in antibiotic policy, with a corresponding increase in piperacillin-tazobactam (p < 0.001) and moxifloxacin (p < 0.001) use. The new policy led to a significant reduction in C. difficile diarrhoea cases. The relative risk of developing C. difficile infection with the old policy compared to the new policy was 3.24 (95%CI 1.07-9.84, p = 0.03). DISCUSSION: The antibiotic policy was successfully introduced into an elderly care service. It reduced both intravenous cephalosporin use and C. difficile diarrhoea.

Relationship between metabolism and peripheral blood mononuclear cell mitochondrial complex I activity before and after a short-term refeeding in weight-losing cancer patients.

BACKGROUND AND AIMS: Previous investigations showed that mitochondrial complex I activity seems to be a specific marker of dietary malnutrition in human. Since cancer has a more complex etiology than simple calorie deficiency, the aim of this study was to investigate the relationship between mitochondrial complex I activity and cancer. METHODS: Nine cancer patients (CaPs) with weight loss and 14 age-matched healthy volunteers (HVs) were recruited. Body mass index (BMI), body composition as well as resting energy expenditure (REE) and RQ were measured. Mitochondrial complex I activity was measured as described previously in isolated peripheral blood mononuclear cells. Six patients were investigated again after 7 days of refeeding. RESULTS: Weight loss in CaPs was mainly due to a loss of fat mass (FM), while fat-free mass (FFM) was preserved. The RQ was significantly lower in CaPs compared to HVs (P<0.001) and peripheral blood mononuclear cell complex I activity was significantly correlated with the %FM and RQ in CaPs. Furthermore, complex I activity increased significantly after 1 week of refeeding. CONCLUSIONS: Our study showed that mitochondrial complex I activity was inversely correlated to parameters of increased fat oxidation and reduced FM, which are indices of dietary insufficiency rather than loss of lean body mass, which is an index of increased catabolism in cancer.

Cell-cell contact and membrane spreading in an ultrasound trap.

An ultrasonic standing wave trap [Langmuir 19 (2003) 3635] in which the morphologies of 2-D latex-microparticle aggregates, forming a pressure node plane, were characterised has been applied here to different cell suspensions with increasing order of specificity of cross-linking molecule, i.e. polylysine with chondrocytes; wheat germ agglutinin (WGA) with erythrocytes and surface receptors on neural cells. The outcome of initial cell-cell contact, i.e. whether the cells stuck at the point of contact (collision efficiency = 1) or rolled around each other (collision efficiency = 0), was monitored in situ by video-microscopy. The perimeter fractal dimensions (FD) of 2-D hexagonally symmetric, closely packed aggregates of control erythrocytes and chondrocytes were 1.16 and 1.18, respectively while those for the dendrititc aggregates formed initially by erythrocytes in 0.5microg/ml WGA and chondrocytes in 20 microg/ml polylysine were 1.49 and 1.66. The FDs for control and molecularly cross-linked cells were typical of reaction-limited aggregation (RLA) and transport diffusion-limited aggregation (DLA), respectively. The FDs of the aggregates of cross-linked cells decreased with time to give more closely packed aggregates without clear hexagonal symmetry. Suspensions of neural cells formed dendritic aggregates. Spreading of inter-cellular membrane contact area occurred over 15 min for both erythrocyte and neural cell dendritic aggregates. The potential of the technique to characterise and control the progression of cell adhesion in suspension away from solid substrata is discussed.

Clofibrate in insulin-dependent diabetes.

Forty-four diabetic patients maintained on insulin entered a doubleblind crossover trial. They were given clofibrate 2 g daily for 6 weeks, either before or after a period of 6 weeks on placebo.Clofibrate did not cause any material change in insulin requirements and there was no change in body weight. Drug tolerance was good.The mean blood glucose was significantly lowered while taking clofibrate. Plasma fibrinogen and pre-beta-lipoprotein concentrations were also significantly decreased following clofibrate therapy.

Anticonvulsant use in elderly patients in long-term care units.

BACKGROUND: Elderly patients in long-term care units are frailer than their community-dwelling peers and may be more at risk from toxic side-effects of anticonvulsant medication at standard doses. AIM: To examine the prescribing of anticonvulsants to patients in elderly care units. METHODS: Drug prescription sheets and case notes were reviewed. Serum anticonvulsant concentration, renal and liver profiles and albumin level were measured. RESULTS: Anticonvulsants were prescribed to twice as many male as female patients (32 vs 14%; p<0.03) and to 33% of those younger than 80 years of age versus 10% of those aged 80 years or older (p<0.0002). No patient had significant hypoalbuminaemia and routine measurement of serum anticonvulsant concentration did not indicate an alteration of dosage. CONCLUSIONS: Anticonvulsants appear to be well tolerated in these patients. The younger age of those receiving anticonvulsants is inadequately explained by the characteristics of the patient cohort and may reflect a shift towards a younger age in patients requiring anticonvulsants due to increased mortality in this group.

Brain abscess: an update.

Brain abscess has been a known complication of head trauma, dental and rhinogenic infections and congenital heart defects, but is rapidly becoming a new diagnosis in the ever-growing population of the immunocompromised patient. Organ transplantation has become commonplace. But, with the advent of more sophisticated agents to prevent organ rejection, comes the threat of brain abscess. In addition to the transplanted patient, the acquired immunodeficiency syndrome patient population is also at risk for development of brain abscess, making brain abscess an important diagnosis. A combination of surgical excision and antimicrobial therapy is usually indicated. Nursing care of these patients involves current knowledge of the antimicrobial agents used and their adverse effects, as well as availability of home health services and need for follow-up care.

The effects of hospital admission on drug prescribing in an elderly population.

307 consecutive patients admitted to our unit were studied. The reasons for altering patients' drug regimens were noted. The price difference between the patients' drugs on admission to those on discharge was calculated. While over 40% of drugs regimens on admission were unchanged on discharge some adjustments were made in the remainder. The most common reason for stopping a drug was that the hospital physician could find no indication for its use. A 30.3% reduction in price of discharge drugs compared with drugs on admission was achieved.

The significance of basal systolic murmurs in the elderly.

Aortic stenosis is common in the elderly. Basal systolic murmurs are also common. We studied 512 patients over the age of 65 years to ascertain the prevalence of basal systolic murmurs and by using echocardiography on those with basal murmurs to determine the prevalence of significant aortic stenosis. 29% (148) of patients had basal systolic murmurs. 81 (55%) patients of this group had echocardiography carried out and 21 (25.9%) had a gradient across the aortic valve of 30 mmHg or more.

Regular planned respite admissions to a geriatric unit.

A programme of regular planned respite admissions to the geriatric unit in Cork was established in 1984, for dependent elderly being cared for at home. Retrospective analysis of the respite programme sought to establish its bed utilisation, type of patients admitted, factors in their selection process, their outcome and any associated hospital morbidity. Twenty-four patients have used the scheme during the four years since its commencement, with an efficiency of bed utilisation in 1987 of 14 patients occupying a mean of 4.33 beds per month. The median number of medical problems per patients was five; their median age 77 years and the percentage over 80 years was 46%. Twenty-two patients were already receiving intensive rehabilitation before being placed on the programme, mobility problems dominated. Nine patients continue on the programme with a mean of 23.9 months of respites to date, eight were discharged and seven died. There was no significant difference between the number of respite stays in hospital and "at home" stays complicated by morbidity. The results suggest that even for a highly selected group of dependent elderly, a planned programme of respite admissions is an effective form of care, uses hospital beds efficiently without associated morbidity and may provide an alternative to long stay institutional care.