Are we shortchanging frail older people when it comes to the pharmacological treatment of urgency urinary incontinence?

Overactive bladder and urgency incontinence are common and distressing conditions in older people, for which the first-line pharmacological treatment is a bladder antimuscarinic agent. Of these, oxybutynin is often recommended in guidelines, but is associated with a higher incidence of adverse drug effects, and in particular has been suggested to have deleterious cognitive effects. Despite this, guidelines often suggest oxybutynin as first-line treatment, and insurance based healthcare systems often require oxybutynin to be used as a first-line therapy and fail before reimbursement for the cost of newer anticholinergics is authorised. We reviewed the literature of bladder antimuscarinics in older adults, using the headings overactive bladder, urinary frequency, urgency, urge, oxybutynin, antimuscarinic, older, older people, and frail. In general, oxybutynin had a similar efficacy to other anticholinergic drugs, but a higher incidence of adverse drug events, in particular significant yet unnoticed cognitive impairment. We conclude that oxybutynin should not be used in frail older people.

Erectile dysfunction and lower urinary tract symptoms: a consensus on the importance of co-diagnosis.

Despite differences in design, many large epidemiological studies using well-powered multivariate analyses consistently provide overwhelming evidence of a link between erectile dysfunction (ED) and lower urinary tract symptoms (LUTS). Preclinical evidence suggests that several common pathophysiological mechanisms are involved in the development of both ED and LUTS. We recommend that patients seeking consultation for one condition should always be screened for the other condition. We propose that co-diagnosis would ensure that patient management accounts for all possible co-morbid and associated conditions. Medical, socio-demographic and lifestyle risk factors can help to inform diagnoses and should be taken into consideration during the initial consultation. Awareness of risk factors may alert physicians to patients at risk of ED or LUTS and so allow them to manage patients accordingly; early diagnosis of ED in patients with LUTS, for example, could help reduce the risk of subsequent cardiovascular disease. Prescribing physicians should be aware of the sexual adverse effects of many treatments currently recommended for LUTS; sexual function should be evaluated prior to commencement of treatment, and monitored throughout treatment to ensure that the choice of drug is appropriate.

A new model to evaluate the long-term cost effectiveness of orphan and highly specialised drugs following listing on the Australian Pharmaceutical Benefits Scheme: the Bosentan Patient Registry.

BACKGROUND: Pharmaceutical subsidy schemes are under increasing pressure to evaluate the cost effectiveness of new highly specialised and orphan drugs for universal subsidy. In the absence of longer-term outcome data, drug sponsors often present modelled data, which can carry a significant level of uncertainty over longer-term projections. Risk-sharing schemes between drug sponsor and government may provide an acceptable method of balancing the uncertainty of longer-term cost effectiveness with the public demand for equitable and timely access to new drugs. METHODS: The Bosentan Patient Registry (BPR) is an example of a unique risk-sharing model utilised in Australia aiming to provide clinical evidence to support the modelled predictions, with the registry survival outcomes linked to future price. Concomitant medication, health and vital status data was collected from clinicians, government health departments and death registries. RESULTS: The BPR has identified a number of issues surrounding registry governance, ethics and patient privacy, and the collection of timely and accurate data, which need to be addressed for the development of a generic registry model for systematic evaluation. CONCLUSION: The success of a generic drug registry model based on the BPR will be enhanced by addressing a number of operational issues identified during the implementation of this project.

Diverse genotypes of Kaposi's sarcoma associated herpesvirus (KSHV) identified in infant blood infections in African childhood-KS and HIV/AIDS endemic region.

Kaposi's sarcoma-associated herpesvirus (KSHV or HHV-8) has been associated with several neoplasias, including childhood endemic Kaposi's sarcoma (KS). It is possible that strain genotypes could contribute to the differences in regional presentation (mainly sub-Saharan Africa), childhood infection, lack of male sex bias, distinct disseminated forms and rapid fatality observed for childhood endemic KS. Early studies, at the advent of the HIV/AIDS epidemic, identified only the K1-A5 genotype in childhood KS biopsies as well as blood of a few HIV positive and negative febrile infants in Zambia, a highly endemic region. This current enlarged study analyses blood infections of 200 hospitalized infants (6-34 months age) with symptoms of fever as well as upper respiratory tract infection, diarrhoea, rash or rhinitis. KSHV and HIV viraemia and were prevalent in this group, 22% and 39%, respectively. Multiple markers at both variable ends of the genome (K1, K12, and K14.1/K15) were examined, showing diverse previously adult-linked genotypes (K1 A2, A5, B, C3, D, with K12 B1 and B2 plus K14.1/K15 P or M) detected in both HIV positive and negative infants, demonstrating little restriction on KSHV genotypes for infant/childhood transmission in a childhood endemic KS endemic region. This supports the interpretation that the acquisition of childhood KSHV infections and subsequent development of KS are due to additional co-factors.

Cerebral hemodynamic response in Chinese (first) and English (second) language processing revealed by event-related functional MRI.

Comparative functional neuroimaging studies using the block design paradigm have previously demonstrated that there are no significant differences in the location of areas of cerebral activation when native Chinese speakers independently process single words or sentences in both the Chinese (first) and English (second) languages. While it has also been documented that significant domains of brain response include the inferior to middle left frontal lobe, the latency, amplitude and duration of the associated hemodynamic changes during isolated neural processing of Chinese and English languages still remain unknown. The aim of this study, therefore, was to examine the characteristics of the hemodynamic alterations in the above-mentioned regions with event-related functional MRI (ER-fMRI) when native Chinese speakers performed verb generation tasks in both the Chinese (first) and English (second) languages. Our results demonstrate the presence of a similar neural activity-induced hemodynamic response in the inferior to middle left frontal lobe during both tasks. Further, there were also no statistically significant differences among the variables that described the hemodynamic response curves. These findings strongly imply that the underlying neural mechanism for Chinese (first) and English (second) language processing may be similar in native Chinese speakers.

The neural system underlying Chinese logograph reading.

Written Chinese as logographic script differs notably from alphabets such as English in visual form, orthography, phonology, and semantics. Thus, research on the Chinese language is important to advance our understanding of the universality and particularity of the organization of language systems in the brain. In this study, we examine the neural systems associated with logographic reading using functional magnetic resonance imaging. Two experimental tasks were devised, one based on semantic decision and the other on homophone decision. Compared to the fixation baseline, peak activations resulting from semantic as well as homophony decisions were localized in the left middle frontal gyrus (BA 9). Left inferior frontal cortex also mediated Chinese processing. In addition, more right hemisphere cortical regions (i.e., BAs 47/45, 7, 40/39, and the right visual system) were involved in reading Chinese relative to reading English. This is attributed to the square shape of the logograph which requires an elaborated analysis of the spatial information and locations of various strokes comprising the logographic character. We suggest that the left middle frontal area (BA 9) coordinates and integrates the intensive visuospatial analysis demanded by logographs' square configuration and the semantic (or phonological) analysis required by the present experimental tasks. Our study has implicated brain regions common to both logographic and alphabetic languages as well as brain regions specialized in processing logographs.

Brain activation in the processing of Chinese characters and words: a functional MRI study.

Functional magnetic resonance imaging was used to identify the neural correlates of Chinese character and word reading. The Chinese stimuli were presented visually, one at a time. Subjects covertly generated a word that was semantically related to each stimulus. Three sorts of Chinese items were used: single characters having precise meanings, single characters having vague meanings, and two-character Chinese words. The results indicated that reading Chinese is characterized by extensive activity of the neural systems, with strong left lateralization of frontal (BAs 9 and 47) and temporal (BA 37) cortices and right lateralization of visual systems (BAs 17-19), parietal lobe (BA 3), and cerebellum. The location of peak activation in the left frontal regions coincided nearly completely both for vague- and precise-meaning characters as well as for two-character words, without dissociation in laterality patterns. In addition, left frontal activations were modulated by the ease of semantic retrieval. The present results constitute a challenge to the deeply ingrained belief that activations in reading single characters are right lateralized, whereas activations in reading two-character words are left lateralized.

Reading Chinese characters for meaning: the role of phonological information.

Two experiments with the Stroop paradigm were conducted to investigate the role of phonological codes in access to the meaning of Chinese characters. Subjects named the ink color of viewed characters or color patches. Key items were color characters, their homophones with the same tone, homophones with different tones, and semantic associates. Apart from finding the usual Stroop interference effect, homophones produced significant interference in the incongruent condition, provided that they had the same tone as the color characters. The interference effect from homophones, however, was significantly smaller than that from color characters. Semantic associates generated an interference effect in the incongruent condition, an effect of the same magnitude as the effect from the same-tone homophones. Finally, in the congruent conditions, all the key items yielded facilitations compared to neutral controls, though the facilitation from color characters was larger than the facilitations from other types of characters. These findings suggest that phonological codes in Chinese are activated obligatorily and provide early sources of constraint in access to meaning.

Asymmetrical cross-language priming effects.

Three experiments were conducted to examine cross-language priming in bilinguals. The first was a cross-language primed lexical decision task experiment with Chinese-English bilinguals. Subjects made lexical decisions about primary associate targets in the two languages at the same rate, but priming occurred only when the prime was in their first language (L1), Chinese, and the target was in their second language (L2), English. Experiment 2 produced the same pattern of asymmetrical priming with two alphabetic languages, French and Dutch. In Experiment 3, the crucial stimuli were translation equivalents. In contrast to the results of Experiments 1 and 2, priming occurred across languages in both the L1-L2 and L2-L1 conditions. However, this priming was also asymmetrical, with more priming occurring in the L1-L2 condition. A tentative separate-interconnected model of bilingual memory is described. It suggests that the representations of words expressed in different languages are stored in separate memory systems, which may be interconnected via one-to-one links between some translation-equivalent representations as well as meaning-integration processes.

Satellite vibration measurements with an autodyne CO(2) laser radar.

Vibration signatures of the Low Power Atmospheric Compensation Experiment satellite were obtained with a ground-based CO(2) laser radar. The laser radar operated in a cw mode and used autodyne receivers to extract relative target velocity information between a germanium retroreflector located at the base of the satellite and a retroreflector array located at the tip of an extended forward boom. Time-frequency analysis algorithms were applied to the vibration data to investigate the correlation between excitations and modal structure. The resultant analysis suggests that vibration modes of an on-orbit spacecraft can be suppressed with simple open-loop techniques.

Coping strategies of schizophrenic patients and their relationship to outcome.

The experience and perception of effective sources of help of 101 schizophrenic patients were studied. A combination of professional help, social support, and self-coping efforts was listed as helpful. The more experiences patients had with the various sources of help, the better were their outcomes. Premorbid adjustment, exposure to the magnitude and nature of helpful sources, as well as the patients' own ability and motivation to make use of available helpful sources were thought to be important mediating variables for a better outcome. Apart from psychotropic medications, over half of the patients were not using any one of the sources of help mentioned. It remains an important research question whether or not schizophrenic patients may benefit from direct coaching in self-help skills in conjunction with making optimal use of professional and environmental supports.

Particulate air pollution and hospitalization for asthma.

Age-specific quarterly asthmatic hospital discharge rates in Hong Kong during 1983 to 1989 were examined in relation to mean levels of six pollutants: sulfur dioxide (SO2), ozone (O3), total suspended particles (TSP), respiratory suspended particles (RSP), nitrogen dioxide (NO2), and nitrogen oxides (NOX). Discharges from the hospital of children under 14 years of age represented 56% of 33,952 discharges recorded in all age groups. Trends of adult hospitalization rates over time remained stable during the study period. In children, however, there was an increase in these rates, particularly marked in the age group of 1 to 4 years. Univariate analysis revealed a strong correlation between quarterly mean TSP and hospital discharge rate for the 1 to 4-year-old children (r = .62, P less than .001). In the 5 to 14-year-old age group, there was an inverse relationship between hospital discharge rate and sulfur dioxide level (r = -.38, P less than .05). Stepwise multiple regression analysis, controlling for confounding variables (seasonal and annual trends of asthma hospitalizations) confirmed these relationships. A highly significant linear regression equation was derived between hospitalization rate for ages 1 to 4 years and total suspended particles (P less than .001). The highly significant correlation between pollution and asthmatic hospitalization rate for the 1 to 4-year-old group suggests that young children are vulnerable to the adverse environmental effects of pollution. Auditing these relationships offers a logical basis for approaching control.

Patterns of outcome in schizophrenia in Hong Kong.

A total of 153 schizophrenic subjects were included for outcome assessment in different aspects of their life functions. The same group of subjects was followed-up 1 year later to assess the consistency of their outcome pattern. A factor analysis on the outcome measures was conducted, and 5 independent factors were noted. Outcome on symptomatic control was most favourable but less consistent over time. Psychosocial deficits, on the other hand, were more enduring and noted in a significant proportion of the subjects.

Effect of the orienting response on sensory discriminability.

The effects of orienting responses to different types of stimuli on acquisition of information were studied. Subjects underwent a standard habituation series of 15 trials. On Trial 16, they received one of following three stimuli: (a) no-change stimulus--same stimulus as habituation stimulus, (b) innocuous-change stimulus, (c) significant-change stimulus--the subject's own name. These orienting stimuli were followed 500 msec. later by an imperative stimulus (100 msec.) which contained a number of Chinese characters. The subjects were then unexpectedly asked to recall and recognize these characters. Recall and recognition were consistently superior in conditions with significant and innocuous change relative to no change, which indicated that the orienting response to unexpected stimuli is related to a generalized perceptual enhancement. The data pose problems for the position that the orienting response reflects only the passive 'registration' of the eliciting stimulus information. While digital pulse-amplitude data showed no difference among the conditions for the change trial, these conditions were differentiated by electrodermal and cardiac changes.