Psychotropic drug use in older people with mental illness with particular reference to antipsychotics: a systematic study of tolerability and use in different diagnostic groups

OBJECTIVE: The objective of the study was to provide observational clinical data on psychotropic drugs used in older people with mental illness. METHODS: This was an observational, single-centre, one-week prevalence study of psychiatric symptoms, disorders and psychotropic drug use in older with mental illness cared for by the South West people Yorkshire Mental Health NHS Trust (Wakefield Locality), UK. The clinical assessment included completion of the Psychosis Evaluation Tool for Common use by Caregivers. RESULTS: A total of 593/660 older patients with mental illness (mean +/- SD age, 76 +/- 8.1 years were assessed. 44.5% had dementia (excluding vascular dementia) and 33.7% had a mood disorder. Of the total, 20.4% did not receive CNS active medication. Of those receiving CNS active medication approximately half (51.3%) took antipsychotics and 46.2% antidepressants. Of 304 patients taking antipsychotics, 87% took only one medication. However, patients with schizophrenia and related disorders were significantly more likely to be prescribed two or more antipsychotics (p < 0.001). Risperidone was the most frequently prescribed antipsychotic (n = 136, 44.7%). Risperidone doses were significantly lower for patients with dementia and mood disorders than with schizophrenia (p < 0.002). Side-effects from antipsychotics were significantly greater in patients with schizophrenia, suggesting a dose-related effect. Risperidone appeared to be well tolerated in all patients with no evidence of cerebrovascular side-effects in patients taking it. CONCLUSIONS: Psychotropic drugs were commonly used by older people in contact with mental health services. The doses of antipsychotics used in dementia and affective disorders were significantly lower than in schizophrenia. Risperidone was the most commonly used drug in all diagnostic groups including dementia. Despite a relatively large numbers of patients receiving risperidone in this naturalistic study, no serious side-effects were reported or identified. In this paper we focus our findings on antipsychotics in the light of recent advice from the Committee on Safety of Medicines (UK).     

Global genetic diversity of human metapneumovirus fusion gene

We analyzed 64 human metapneumovirus strains from eight countries. Phylogenetic analysis identified two groups (A and B, amino acid identity 93%-96%) and four subgroups. Although group A strains predominated, accounting for 69% of all strains, as many B as A strains were found in persons >3 years of age.     

Distinct expression of phosphorylated N-methyl-D-aspartate receptor NR1 subunits by projection neurons and interneurons in the striatum of normal and amphetamine-treated rats

N-methyl-D-aspartate (NMDA) receptors are heteromeric assemblies of subunits (NR1 and NR2A-D), and are enriched in the striatum. Receptor phosphorylation has recently been demonstrated on the NR1 subunit at three serine residues, 897, 896, and 890, which appear to correspond to the level of receptor activity. In this study, expression of phospho-specific NR1 subunits at serine 897 (pNR1S897), serine 896 (pNR1S896), or serine 890 (pNR1S890) in neurochemically identified neurons of the adult rat striatum was detected by using double-immunofluorescent labeling or combined in situ hybridization and immunohistochemistry. In both the dorsal and ventral striatum, pNR1S897 was expressed at high levels in projection neurons containing >55% dynorphin (striatonigral) and >90% enkephalin (striatopallidal) and in interneurons that were 100% positive for choline, >90% positive for parvalbumin, and >45% positive for somatostatin (co-containing neuropeptide Y and neuronal nitric oxide synthase). Low levels of pNR1S896 were present in a small portion of projection neurons (<15% for both populations of projection neurons) and were almost lacking in the three types of interneurons. Interestingly, pNR1S890 was exclusively expressed in most parvalbumin-containing interneurons (70-80%). Acute administration of a psychostimulant, amphetamine, increased the number of dynorphin-containing projection neurons and parvalbumin interneurons showing detectable levels of pNR1S896 and pNR1S890, respectively. These results demonstrate the distinct expression of phospho-NR1 subunits in different populations of striatal projection neurons and interneurons at variable levels in normal rats; they also demonstrate that phosphorylation of NR1, at least on serine 896 and 890 sites, is sensitive to drug exposure.     

Matrix metalloproteinase-1 gene promoter polymorphism and risk of ovarian cancer

OBJECTIVE: It has been suggested that the 2G allele of a guanine insertion-deletion promoter polymorphism in the promoter of the matrix metalloproteinase-1 (MMP1) gene may increase susceptibility to ovarian cancer. The 2G allele also has been associated with increased MMP1 expression. We investigated the relationship between the MMP1 polymorphism and ovarian cancer risk in a large population-based, case-control study. METHODS: The MMP1 promoter polymorphism was examined in white blood cell DNA from 311 cases and 387 age- and race-matched controls using a radiolabeled polymerase chain reaction assay. In addition, genotyping of the MMP1 polymorphism performed in 42 advanced-stage invasive serous ovarian cancers was compared to their mean relative MMP1 expression from Affymetrix microarrays. RESULTS: The 2G allele frequency did not differ significantly between cases (0.49) and controls (0.48), and the distribution of genotypes was in Hardy-Weinberg equilibrium. Using 1G homozygotes as the reference group, neither 2G homozygotes (odds ratio 1.1, 95% confidence interval 0.7-1.7) nor heterozygotes plus 2G homozygotes (odds ratio 0.9, 95% confidence interval 0.7-1.3) had an increased risk of ovarian cancer. There was also no relationship between MMP1 genotype and histologic grade, histologic type, stage, or tumor behavior (borderline versus invasive). The mean MMP1 expression was twice as high in 2G homozygotes relative to 1G homozygotes, but this difference was not statistically significant. CONCLUSION: The reported association between the MMP1 promoter polymorphism and ovarian cancer risk was not supported by our data. There was a suggestion that the 2G allele may be associated with higher MMP1 expression, and this finding is worthy of further investigation.     

Reduced effectiveness of Haemophilus influenzae type b conjugate vaccine in children with a high prevalence of human immunodeficiency virus type 1 infection

BACKGROUND: Haemophilus influenzae type b (Hib) conjugate vaccines have successfully reduced the burden of invasive Hib disease in developed countries; however, their effectiveness in countries with a high incidence of pediatric HIV-1 is unknown. METHODS: The effectiveness of Hib conjugate vaccine was prospectively evaluated in South African children. The burden of invasive Hib disease in children < 1 year old was compared in 2 cohorts. The first cohort included 22,000 African children born in 1997 [969 (4.45%) of whom were estimated to be HIV-1-infected] who were not vaccinated with Hib conjugate vaccine. This group was compared with 19,267 children [1162 (6.03%) of whom were estimated to be HIV-1 infected] vaccinated at 6, 10 and 14 weeks of age with an Hib conjugate vaccine [TETRAMUNE (polyribosylribitol phosphate-CRM(197)-diphtheria-tetanus toxoids-whole cell pertussis)] between March, 1998, and June, 1999. RESULTS: The estimated burden of invasive Hib disease in nonimmunized HIV-1-infected children < 1 year of age was 5.9-fold [95% confidence interval (95% CI), 2.7 to 12.6] higher than in HIV-1-uninfected children. The overall estimated effectiveness of Hib conjugate vaccine in fully vaccinated children <1 year of age was 83.2% (95% CI 60.3 to 92.9). Vaccine effectiveness was significantly reduced in HIV-1-infected [43.9% (95% CI -76.1 to 82.1)] compared with uninfected children [96.5% (95% CI 74.4 to 99.5); P < 10(-5)]. Among three of the fully vaccinated HIV-1-infected children who developed invasive Hib disease, the anti-Hib polyribosylribitol phosphate serum antibody concentrations were 0.23, 0.25 and 0.68 microg/ml. CONCLUSION: Although the Hib conjugate vaccine was less effective among HIV-1-infected than among uninfected children, it was 83% effective in preventing overall invasive Hib disease and therefore should be considered for inclusion in the routine vaccination schedule by other African countries.     

Defining the potential impact of conjugate bacterial polysaccharide-protein vaccines in reducing the burden of pneumonia in human immunodeficiency virus type 1-infected and -uninfected children

BACKGROUND: The evaluation of bacterial conjugate vaccines in preventing pneumonia requires the definition of suitable outcome measures against which their use can be evaluated. One such possible outcome measure is alveolar consolidation confirmed by chest radiograph (CXR). OBJECTIVE: To define the CXR presentation in relation to identified bacterial and respiratory viral pathogens among HIV-1-infected and -uninfected children. METHODS: The CXRs of 1186 of 1434 children hospitalized with severe lower respiratory tract infection were evaluated for the presence of alveolar consolidation (homogenous airspace infiltrate), bronchopneumonia (patchy airspace consolidation) or other CXR findings. Children were also investigated for bacterial infection by blood culture in 1364 of 1434 episodes and for respiratory viruses in 990 of 1434 episodes by immunofluorescein monoclonal antibody assays. RESULTS: The prevalence of HIV-1 infection among children who had CXRs in the study was 527 (46.2%) of 1142. Alveolar consolidation was more common in HIV-1-infected (63.7%) than in HIV-uninfected children (42.4%, P < 10(-5)) whereas bronchopneumonic changes (29.0% vs. 38.0%, P = 0.001) or a normal CXR occurred in 7.0 vs. 18.2% (P < 10(-5)) of HIV-1-infected and -uninfected children, respectively. Alveolar consolidation was the main CXR presentation in HIV-1-infected (78.6%) and HIV-uninfected children (64.9%, P = 0.14) with all-cause bacteremic pneumonia as well as those with bacteremic Streptococcus pneumoniae pneumonia (76.9% vs. 83.3%, respectively; P = 0.99). Respiratory virus-associated lower respiratory tract infection, however, was more likely to present with alveolar consolidation in HIV-1-infected (55.8%) than in HIV-uninfected (36.1%, P = 0.02) children. CONCLUSION: Although alveolar consolidation may be a useful tool in defining both the efficacy and burden of bacterial pneumonia in HIV-1-uninfected children, this may not be so for HIV-1-infected children. The higher occurrence of respiratory virus-associated alveolar consolidation, possibly coupled with Pneumocystis carinii pneumonia, may be significant confounders in the interpretation of CXR in HIV-1-infected children, limiting the use of alveolar consolidation as an outcome measure when evaluating the efficacy of bacterial conjugate vaccines in HIV-1-infected children.     

Popliteal artery injuries: the Kashmir experience

BACKGROUND: Popliteal artery injuries pose a serious threat to limb survival. Blunt trauma appears to be associated with a higher amputation rate than penetrating trauma, probably because of the more extensive nature of the injuries. METHODS: Two hundred seventy-two cases of popliteal artery injury were studied retrospectively from 1989 to 2001, a warlike period in Kashmir. Preoperative angiography was not performed. Thirty-two percent of patients had associated venous injury and 24.6% of patients had associated bone fracture. RESULTS: Overall morbidity was 55%, with the most common complication being infection (24%). Secondary amputation had to be performed in 16 patients (5.5%). The amputation rate was not influenced by cause of injury and type of repair or the presence of venous injury, but associated bone fracture significantly increased the risk of amputation (p < 0.05). The patients who underwent repair more than 12 hours after sustaining injury had a significantly greater amputation rate (p < 0.05). CONCLUSION: Prompt resuscitation, vascularization, and proper technique appear to be the only correctable factors that improve limb salvage.     

Pneumococcal conjugate vaccine--a health priority

Pneumonia is a major cause of childhood mortality and morbidity. Streptococcus pneumoniae is the most important bacterial pathogen causing pneumonia in children. The HIV epidemic has increased the burden and severity of childhood pneumococcal pneumonia and invasive disease fortyfold. Pneumococcal conjugate vaccine (PCV) is a highly effective intervention to reduce invasive pneumococcal disease and pneumonia. Studies evaluating a 9-valent PCV in South Africa and The Gambia reported a 72 - 77% reduction in vaccine-serotype-specific invasive disease in vaccinated children. As many of the pneumococcal serotypes associated with antibiotic resistance are included in PCV, vaccination has also been associated with a reduction in antimicrobial-resistant invasive disease. PCV may also reduce childhood mortality, especially in places with limited access to health care, as shown in Gambian study in which PCV reduced childhood mortality by 16%. In addition to the direct effects of PCV, there is a substantial reduction in disease burden through indirect protection of non-vaccinated populations. PCV is immunogenic in HIV-infected children and provides protection against invasive disease or pneumonia in a substantial number of children. Although the efficacy of PCV for prevention of invasive disease or pneumonia is lower in HIV-infected compared to -uninfected children, the overall burden of disease prevented is much greater in HIV-infected children because of the higher burden of pneumococcal disease in these children. Consequently, vaccine-preventable invasive disease is almost 60 times higher in HIV-infected compared to -uninfected children, while the reduction in pneumonia in HIV-infected children is 15 times greater. However, the long-term efficacy of PCV wanes in HIV-infected children who are not taking antiretroviral therapy, and booster doses are probably indicated. Although there is concern about the potential for replacement disease due to non-vaccine serotypes, a substantial and sustained reduction in invasive disease has occurred overall in populations with widespread childhood immunisation. Routine childhood immunisation is now the standard of care in most developed countries. However, PCV is much less accessible to children in developing countries due to cost and availability. Cost-effectiveness analysis indicates that use of PCV is potentially highly cost-effective, at tiered pricing, even in very low-income countries. Widespread availability and vaccination with PCV is urgently needed for all children under 2 years of age in South Africa. In addition, the use of PCV for all HIV-infected children under 9 years should be prioritised.