Multi-disciplinary Psychiatric Case Management Model in Hong Kong: Service Coverage and Risk Stratification.

INTRODUCTION: Community mental health services in Hong Kong follow a multi-disciplinary case management model. We investigated whether at-risk patients received higher intensity care and whether risk stratification concorded between personalised care programmes and integrated community centres of mental wellness. METHODS: Records of all patients in North Lantau and Mongkok districts who received case management services (from personalised care programmes and/or integrated community centres of mental wellness) between 1 April 2014 and 30 June 2015 were reviewed. Patients' levels of risk, demographic data, and clinical characteristics were analysed. RESULTS: Identified at-risk patients received high-intensity care from personalised care programmes and integrated community centres of mental wellness. Case management was coordinated between the Hospital Authority and non-government organisations. However, risk stratification did not correlate with assessment rating scores of psychopathology or psychosocial functioning. Assessment rating scales appear unsuitable to provide any optimal cut-off scores for risk stratification. CONCLUSIONS: Risk stratification should be a structured clinical judgement based on comprehensive and accurate information of protective and risk factors, rather than relying on cut-off scores of assessment rating scales.

Improving medication safety and diabetes management in Hong Kong: a multidisciplinary approach.

INTRODUCTION: Patients with diabetes often require complex medication regimens. The positive impact of pharmacists on improving diabetes management or its co-morbidities has been recognised worldwide. This study aimed to characterise drug-related problems among diabetic patients in Hong Kong and their clinical significance, and to explore the role of pharmacists in the multidisciplinary diabetes management team by evaluating the outcome of their clinical interventions. METHODS: An observational study was conducted at the Diabetes Clinic of a public hospital in Hong Kong from October 2012 to March 2014. Following weekly screening, and prior to the doctor's consultation, selected high-risk patients were interviewed by a pharmacist for medication reconciliation and review. Drug-related problems were identified and documented by the pharmacist who presented clinical recommendations to doctors to optimise a patient's drug regimen and resolve or prevent potential drug-related problems. RESULTS: A total of 522 patients were analysed and 417 drug-related problems were identified. The incidence of patients with drug-related problems was 62.8% with a mean of 0.9 (standard deviation, 0.6) drug-related problems per patient. The most common categories of drug-related problems were associated with dosing (43.9%), drug choice (17.3%), and non-allergic adverse reactions (15.6%). Drugs most frequently involved targeted the endocrine or cardiovascular system. The majority (71.9%) of drug-related problems were of moderate clinical significance and 28.1% were considered minor problems. Drug-related problems were totally solved (50.1%) and partially solved (11.0%) by doctors' acceptance of pharmacist recommendations, or received acknowledgement from doctors (5.5%). CONCLUSIONS: Pharmacists, in collaboration with the multidisciplinary team, demonstrated a positive impact by identifying, resolving, and preventing drug-related problems in patients with diabetes. Further plans for sustaining pharmacy service in the Diabetes Clinic would enable further studies to explore the long-term impact of pharmacists in improving patients' clinical outcomes in diabetes management.

An epidemiological survey of echinococcosis in intermediate and definitive hosts in Qinghai Province, China.

In order to understand the epidemiological status of alveolar and cystic echinococcosis in intermediate and definitive hosts in Qinghai Province, China, during the period 2007-2011, we investigated the infection in humans and animals, including yaks, Tibetan sheep, Tibetan dogs, and wild foxes distributed in different counties around the province. Sera from local residents were examined using a rapid serodiagnostic kit to detect specific antibodies against Echinococcus. Seropositive samples were confirmed with B-scan ultrasonography and X-ray examinations. Yaks and Tibetan sheep were checked at slaughterhouses, and cysts and suspicious lesions were collected for analysis. A rapid diagnostic strip was used to detect Echinococcus adults in Tibetan dogs. Positive dogs were dewormed and the parasites collected. Wild foxes were trapped and necropsies performed with particular attention to the intestine. Forty-eight of 735 (6.4%) humans tested were positive and 475 of 854 (55.6%) Tibetan sheep and 85 of 352 (24.15%) yaks were infected with Echinococcus. Across different counties, 214 of 948 (22.57%) Tibetan dogs were positive, and five of 36 (13.9%) wild foxes were infected with Echinococcus. Molecular studies showed that all the infections detected in humans, domestic yaks, and Tibetan sheep were the G1 genotype (E. granulosus), whereas the parasites from Tibetan foxes and Tibetan dogs were E. shiquicus and E. multilocularis, respectively. In conclusion, Echinococcosis is hyperendemic in Qinghai Province in both its intermediate and definitive hosts and the G1 genotype of cystic Echinococcus is the dominant strain.

Opioid therapy for chronic non-cancer pain: guidelines for Hong Kong.

Opioids are increasingly used to control chronic non-cancer pain globally. International opioid guidelines have been issued in many different countries but a similar document is not generally available in Hong Kong. Chronic opioid therapy has a role in multidisciplinary management of chronic non-cancer pain despite insufficient evidence for its effectiveness and safety for long-term use. This document reviews the current literature to inform Hong Kong practitioners about the rational use of chronic opioid therapy in chronic non-cancer pain. It also aims to provide useful recommendations for the appropriate, effective, and safe use of such therapy in the management of chronic non-cancer pain in adults. Physicians should conduct a comprehensive biopsychosocial evaluation of patients prior to the commencement of opioid therapy. When opioid use is deemed appropriate, the patient should provide informed consent within an agreement that specifies treatment goals and expectations. A trial of opioid can be commenced and, provided there is progress towards treatment goals, then chronic therapy can be considered at a dose that minimises harm. Monitoring of effectiveness, safety, and drug misuse should be continued. Treatment should be stopped when opioids become ineffective, intolerable, or misused. The driving principles for opioid prescription in chronic pain management should be: start with a low dose, titrate slowly, and maintain within the shortest possible time.

The nature of anhedonia and avolition in patients with first-episode schizophrenia.

BACKGROUND: Patients with schizophrenia have intact ability to experience emotion, but empirical evidence suggests that they fail to translate emotional salience into effortful behaviour. Previous research in patients with chronic schizophrenia suggests that working memory is important in integrating emotion and behaviour. This study aimed to examine avolition and anhedonia in patients with first-episode schizophrenia and clarify the role of working memory in emotion-behaviour coupling. METHOD: We recruited 72 participants with first-episode schizophrenia and 61 healthy controls, and used a validated emotion-inducing behavioural paradigm to measure participants' affective experiences and how experienced emotion coupled with behaviour. Participants were given the opportunity to expend effort to increase or decrease their exposure to emotion-inducing photographs. Participants with schizophrenia having poor working memory were compared with those with intact working memory in their liking and emotion-behaviour coupling. RESULTS: Patients with first-episode schizophrenia experienced intact 'in-the-moment' emotion, but their emotion was less predictive of the effort expended, compared with controls. The emotion-behaviour coupling was significantly weaker in patients with schizophrenia with poor working memory than in those with intact working memory. However, compared with controls, patients with intact working also showed substantial emotion-behaviour decoupling. CONCLUSIONS: Our findings provide strong evidence for emotion-behaviour decoupling in first-episode schizophrenia. Although working memory deficits contribute to defective translation of liking into effortful behaviour, schizophrenia alone affects emotion-behaviour coupling.

Implementing a bar-code assisted medication administration system: effects on the dispensing process and user perceptions.

PURPOSE: We assessed the effects of a bar-code assisted medication administration system used without the support of computerised prescribing (stand-alone BCMA), on the dispensing process and its users. METHODS: The stand-alone BCMA system was implemented in one ward of a teaching hospital. The number of dispensing steps, dispensing time and potential dispensing errors (PDEs) were directly observed one month before and eight months after the intervention. Attitudes of pharmacy and nursing staff were assessed using a questionnaire (Likert scale) and interviews. RESULTS: Among 1291 and 471 drug items observed before and after the introduction of the technology respectively, the number of dispensing steps increased from five to eight and time (standard deviation) to dispense one drug item by one staff personnel increased from 0.8 (0.09) to 1.5 (0.12) min. Among 2828 and 471 drug items observed before and after the intervention respectively, the number of PDEs increased significantly (P<0.001). 'Procedural errors' and 'missing drug items' were the frequently observed PDEs in the after study. 'Perceived usefulness' and 'job relevance' of the technology decreased significantly (P=0.003 and P=0.004 respectively) among users who participated in the before (N=16) and after (N=16) questionnaires surveys. Among the interviewees, pharmacy staff felt that the system offered less benefit to the dispensing process (9/16). Nursing staff perceived the system as useful in improving the accuracy of drug administration (7/10). CONCLUSION: Implementing a stand-alone BCMA system may slow down and complicate the dispensing process. Nursing staff believe the stand-alone BCMA system could improve the drug administration process but pharmacy staff believes the technology would be more helpful if supported by computerised prescribing. However, periodical assessments are needed to identify weaknesses in the process after implementation, and all users should be educated on the benefits of using this technology.

The pattern of the discovery of medication errors in a tertiary hospital in Hong Kong.

BACKGROUND: The primary goal of reducing medication errors is to eliminate those that reach the patient. OBJECTIVE: We aimed to study the pattern of interceptions to tackle medication errors along the medication use processes. SETTING: Tertiary care hospital in Hong Kong. METHOD: The 'Swiss Cheese Model' was used to explain the interceptions targeting medication error reporting over 5 years (2006-2010). MAIN OUTCOME MEASURES: Proportions of prescribing, dispensing and drug administration errors intercepted by pharmacists and nurses; proportions of prescribing, dispensing and drug administration errors that reached the patient. RESULTS: Our analysis included 1,268 in-patient medication errors, of which 53.4% were related to prescribing, 29.0% to administration and 17.6% to dispensing. 34.1% of all medication errors (4.9% prescribing, 26.8% drug administration and 2.4% dispensing) were not intercepted. Pharmacy staff intercepted 85.4% of the prescribing errors. Nurses detected 83.0% of dispensing and 5.0% of prescribing errors. However, 92.4% of all drug administration errors reached the patient. CONCLUSIONS: Having a preventive measure at each stage of the medication use process helps to prevent most errors. Most drug administration errors reach the patient as there is no defense against these. Therefore, more interventions to prevent drug administration errors are warranted.

Patients with bipolar disorders share similar but attenuated prospective memory impairments with patients with schizophrenia.

BACKGROUND: Prospective memory (PM) refers to the ability to remember to carry out an intended action in the future. PM is consistently found to be impaired in individuals with schizophrenia. Bipolar disorder and schizophrenia may represent conditions along a continuum, and share similar neurocognitive and genetic architecture. This study aimed to compare the nature and extent of PM impairment in individuals with schizophrenia and bipolar disorder. METHOD: Participants were 38 out-patients with schizophrenia and 40 out-patients with bipolar disorder in an early psychosis intervention programme, and 37 healthy controls. Time-, event- and activity-based PMs were assessed using a dual-task laboratory paradigm. Self-reported PM performance was gauged using the Prospective and Retrospective Memory Questionnaire. Analysis of covariance (ANCOVA), with intelligence quotient (IQ) and education included as covariates, was used to examine group difference on various types of PM. Repeated measures of ANCOVA were used to examine the group × PM type interaction effect. Correspondence between laboratory and self-reported PM measures was examined using correlational analysis. RESULTS: The group × PM type interaction effect was not significant, but the main effect of group was significant. Patients with schizophrenia and patients with bipolar disorder both performed more poorly than healthy participants in PM. The two clinical groups did not significantly differ in PM. Laboratory and self-reported PM measures did not correlate significantly with each other. CONCLUSIONS: Patients with bipolar disorder shared a similar PM impairment with those with schizophrenia. Findings of this study extended the similarity in neurocognitive impairments between the two psychiatric disorders to PM.

Technology-related medication errors in a tertiary hospital: a 5-year analysis of reported medication incidents.

PURPOSE: Healthcare technology is meant to reduce medication errors. The objective of this study was to assess unintended errors related to technologies in the medication use process. METHODS: Medication incidents reported from 2006 to 2010 in a main tertiary care hospital were analysed by a pharmacist and technology-related errors were identified. Technology-related errors were further classified as socio-technical errors and device errors. This analysis was conducted using data from medication incident reports which may represent only a small proportion of medication errors that actually takes place in a hospital. Hence, interpretation of results must be tentative. RESULTS: 1538 medication incidents were reported. 17.1% of all incidents were technology-related, of which only 1.9% were device errors, whereas most were socio-technical errors (98.1%). Of these, 61.2% were linked to computerised prescription order entry, 23.2% to bar-coded patient identification labels, 7.2% to infusion pumps, 6.8% to computer-aided dispensing label generation and 1.5% to other technologies. The immediate causes for technology-related errors included, poor interface between user and computer (68.1%), improper procedures or rule violations (22.1%), poor interface between user and infusion pump (4.9%), technical defects (1.9%) and others (3.0%). In 11.4% of the technology-related incidents, the error was detected after the drug had been administered. CONCLUSIONS: A considerable proportion of all incidents were technology-related. Most errors were due to socio-technical issues. Unintended and unanticipated errors may happen when using technologies. Therefore, when using technologies, system improvement, awareness, training and monitoring are needed to minimise medication errors.

A questionnaire survey on attitudes and understanding towards mental disorders.

OBJECTIVES. To obtain information about basic knowledge towards mental disorders and to evaluate public attitudes towards mental disorders in the Hong Kong Chinese population. METHODS. Questionnaires which collected basic demographic information, opinions about potential stigmas and myths, and knowledge on case vignettes depicting fictional characters with symptoms of mental illness were delivered to subjects in a secondary school, 2 homes for the elderly, a private housing estate, and a public housing estate in Hong Kong. RESULTS. Completed questionnaires were collected from 1035 subjects. In general, the participants' acceptance of mental illness was good. Regular contacts with such patients were associated with better knowledge (t = -2.71, p < 0.01) and better acceptance (t = 2.77, p < 0.01) of mental illness. Younger participants aged 15 to 19 years had a lower level of knowledge about mental health problems compared with other age-groups (p < 0.001). CONCLUSIONS. Personal contact with people with mental illness may help to improve knowledge and acceptance. Younger people in secondary school should be the target and prioritised group for mental health education. Apart from the delivery of mental health knowledge, strategies to increase social contact of the public with people having mental illness could be considered in the design and implementation of anti-stigma programmes.

Clinically relevant drug interactions between anticancer drugs and psychotropic agents.

Drug interactions are commonly seen in the treatment of cancer patients. Psychotropics are often indicated for these patients since they may also suffer from pre-existing psychological disorders or experience insomnia and anxiety associated with cancer therapy. Thus, the risk of anticancer drug (ACD)-psychotropic drug-drug interactions (DDIs) is high. Drug interactions were compiled from the British National Formulary (53rd edn), Lexi-Comp's Drug Information Handbook (15th edn), Micromedex (v5.1), Hansten & Horn's Drug Interactions (2000) and Drug Interaction Facts (2008 edn). Product information of the individual drugs, as well as documented literature on ACD-psychotropic interactions from PubMed and other databases was also incorporated. This paper identifies clinically important ACD-psychotropic DDIs that are frequently observed. Pharmacokinetic DDIs were observed for tyrosine kinase inhibitors, corticosteroids and antimicrotubule agents due to their inhibitory or inductive effects on cytochrome P450 isoenzymes. Pharmacodynamic DDIs were identified for thalidomide with central nervous system depressants, procarbazine with antidepressants, myelosuppressive ACDs with clozapine and anthracyclines with QT-prolonging psychotropics. Clinicians should be vigilant when psychotropics are prescribed concurrently with ACDs. Close monitoring of plasma drug levels should be carried out to avoid toxicity in the patient, as well as to ensure adequate chemotherapeutic and psychotropic coverage.

6-Shogaol, an active constituent of ginger, inhibits breast cancer cell invasion by reducing matrix metalloproteinase-9 expression via blockade of nuclear factor-κB activation.

BACKGROUND AND PURPOSE: Shogaols are reported to possess anti-inflammatory and anticancer activities. However, the antimetastatic potential of shogaols remains unexplored. This study was performed to assess the effects of shogaols against breast cancer cell invasion and to investigate the underlying mechanisms. EXPERIMENTAL APPROACH: The anti-invasive effect of a series of shogaols was initially evaluated on MDA-MB-231 breast cancer cells using the matrigel invasion assay. The suppressive effects of 6-shogaol on phorbol 12-myristate 13-acetate (PMA)-induced matrix metalloproteinase-9 (MMP-9) gelatinolytic activity and nuclear factor-κB (NF-κB) activation were further determined. KEY RESULTS: Shogaols (6-, 8- and 10-shogaol) inhibited PMA-stimulated MDA-MB-231 cell invasion with an accompanying decrease in MMP-9 secretion. 6-Shogaol was identified to display the greatest anti-invasive effect in association with a dose-dependent reduction in MMP-9 gene activation, protein expression and secretion. The NF-κB transcriptional activity was decreased by 6-shogaol; an effect mediated by inhibition of IκB phosphorylation and degradation that subsequently led to suppression of NF-κB p65 phosphorylation and nuclear translocation. In addition, 6-shogaol was found to inhibit JNK activation with no resulting reduction in activator protein-1 transcriptional activity. By using specific inhibitors, it was demonstrated that ERK and NF-κB signalling, but not JNK and p38 signalling, were involved in PMA-stimulated MMP-9 activation. CONCLUSIONS AND IMPLICATIONS: 6-Shogaol is a potent inhibitor of MDA-MB-231 cell invasion, and the molecular mechanism involves at least in part the down-regulation of MMP-9 transcription by targeting the NF-κB activation cascade. This class of naturally occurring small molecules thus have potential for clinical use as antimetastatic treatments.

Aquaporin-4 water channel expression by thymoma of patients with and without myasthenia gravis.

BACKGROUND: Neuromyelitis optica (NMO) is a serious idiopathic inflammatory demyelinating disorder characterized by acute transverse myelitis and optic neuritis. A significant proportion of NMO patients are seropositive for NMO-IgG, an autoantibody targeting aquaporin-4 (AQP4) water channel. Paraneoplastic NMO associated various tumors were recently reported. AIM: We studied the expression of AQP4 by thymoma from patients with and without myasthenia gravis (MG). METHODS: Thymoma obtained from thymomectomy in patients with and without MG were studied by immunohistochemistry and western blot. RESULTS: Ten thymoma patients (9 with MG) and two control patients without thymoma or MG were studied. Immunohistochemistry revealed AQP4 immunoreactivity in cell membrane of thymoma cells from all ten thymoma specimens whereas thymic tissues from patients without thymoma or MG were negative for AQP4 immunoreactivity. Western blot revealed that lysates of nine of the ten thymoma specimens reacted with anti-human AQP4 antibody with a band of ~30 kDa compatible with the molecular weight of AQP4. Interestingly, immunofluorescence revealed that IgG isolated from 2 NMO patients seropositive for NMO-IgG bound to cell membrane of thymoma cells from all ten thymoma specimens while IgG from healthy control subject did not. CONCLUSION: Thymoma cells of patients with and without MG express AQP4. AQP4 autoantibodies from serum of NMO patients bound to AQP4 expressed on thymoma cell membrane.

Tropism and innate host responses of the 2009 pandemic H1N1 influenza virus in ex vivo and in vitro cultures of human conjunctiva and respiratory tract.

The novel pandemic influenza H1N1 (H1N1pdm) virus of swine origin causes mild disease but occasionally leads to acute respiratory distress syndrome and death. It is important to understand the pathogenesis of this new disease in humans. We compared the virus tropism and host-responses elicited by pandemic H1N1pdm and seasonal H1N1 influenza viruses in ex vivo cultures of human conjunctiva, nasopharynx, bronchus, and lung, as well as in vitro cultures of human nasopharyngeal, bronchial, and alveolar epithelial cells. We found comparable replication and host-responses in seasonal and pandemic H1N1 viruses. However, pandemic H1N1pdm virus differs from seasonal H1N1 influenza virus in its ability to replicate in human conjunctiva, suggesting subtle differences in its receptor-binding profile and highlighting the potential role of the conjunctiva as an additional route of infection with H1N1pdm. A greater viral replication competence in bronchial epithelium at 33 degrees C may also contribute to the slight increase in virulence of the pandemic influenza virus. In contrast with highly pathogenic influenza H5N1 virus, pandemic H1N1pdm does not differ from seasonal influenza virus in its intrinsic capacity for cytokine dysregulation. Collectively, these results suggest that pandemic H1N1pdm virus differs in modest but subtle ways from seasonal H1N1 virus in its intrinsic virulence for humans, which is in accord with the epidemiology of the pandemic to date. These findings are therefore relevant for understanding transmission and therapy.

Influenza H5N1 virus infection of polarized human alveolar epithelial cells and lung microvascular endothelial cells.

BACKGROUND: Highly pathogenic avian influenza (HPAI) H5N1 virus is entrenched in poultry in Asia and Africa and continues to infect humans zoonotically causing acute respiratory disease syndrome and death. There is evidence that the virus may sometimes spread beyond respiratory tract to cause disseminated infection. The primary target cell for HPAI H5N1 virus in human lung is the alveolar epithelial cell. Alveolar epithelium and its adjacent lung microvascular endothelium form host barriers to the initiation of infection and dissemination of influenza H5N1 infection in humans. These are polarized cells and the polarity of influenza virus entry and egress as well as the secretion of cytokines and chemokines from the virus infected cells are likely to be central to the pathogenesis of human H5N1 disease. AIM: To study influenza A (H5N1) virus replication and host innate immune responses in polarized primary human alveolar epithelial cells and lung microvascular endothelial cells and its relevance to the pathogenesis of human H5N1 disease. METHODS: We use an in vitro model of polarized primary human alveolar epithelial cells and lung microvascular endothelial cells grown in transwell culture inserts to compare infection with influenza A subtype H1N1 and H5N1 viruses via the apical or basolateral surfaces. RESULTS: We demonstrate that both influenza H1N1 and H5N1 viruses efficiently infect alveolar epithelial cells from both apical and basolateral surface of the epithelium but release of newly formed virus is mainly from the apical side of the epithelium. In contrast, influenza H5N1 virus, but not H1N1 virus, efficiently infected polarized microvascular endothelial cells from both apical and basolateral aspects. This provides a mechanistic explanation for how H5N1 virus may infect the lung from systemic circulation. Epidemiological evidence has implicated ingestion of virus-contaminated foods as the source of infection in some instances and our data suggests that viremia, secondary to, for example, gastro-intestinal infection, can potentially lead to infection of the lung. HPAI H5N1 virus was a more potent inducer of cytokines (e.g. IP-10, RANTES, IL-6) in comparison to H1N1 virus in alveolar epithelial cells, and these virus-induced chemokines were secreted onto both the apical and basolateral aspects of the polarized alveolar epithelium. CONCLUSION: The predilection of viruses for different routes of entry and egress from the infected cell is important in understanding the pathogenesis of influenza H5N1 infection and may help unravel the pathogenesis of human H5N1 disease.

DAS181 inhibits H5N1 influenza virus infection of human lung tissues.

DAS181 is a novel candidate therapeutic agent against influenza virus which functions via the mechanism of removing the virus receptor, sialic acid (Sia), from the adjacent glycan structures. DAS181 and its analogues have previously been shown to be potently active against multiple strains of seasonal and avian influenza virus strains in several experimental models, including cell lines, mice, and ferrets. Here we demonstrate that DAS181 treatment leads to desialylation of both alpha2-6-linked and alpha2-3-linked Sia in ex vivo human lung tissue culture and primary pneumocytes. DAS181 treatment also effectively protects human lung tissue and pneumocytes against the highly pathogenic avian influenza virus H5N1 (A/Vietnam/3046/2004). Two doses of DAS181 treatment given 12 h apart were sufficient to block H5N1 infection in the ex vivo lung tissue culture. These findings support the potential value of DAS181 as a broad-spectrum therapeutic agent against influenza viruses, especially H5N1.

A 3-year study of medication incidents in an acute general hospital.

BACKGROUND AND OBJECTIVE: Inappropriate medication use may harm patients. We analysed medication incident reports (MIRs) as part of the feedback loop for quality assurance. METHODS: From all MIRs in a university-affiliated acute general hospital in Hong Kong in the period January 2004-December 2006, we analysed the time, nature, source and severity of medication errors. RESULTS: There were 1278 MIRs with 36 (range 15-107) MIRs per month on average. The number of MIRs fell from 649 in 2004, to 353 in 2005, and to 276 in 2006. The most common type was wrong strength/dosage (36.5%), followed by wrong drug (16.7%), wrong frequency (7.7%), wrong formulation (7.0%), wrong patient (6.9%) and wrong instruction (3.1%). 60.9%, 53.7% and 84.0% of MIRs arose from handwritten prescription (HP) rather than the computerized medication order entry in 2004, 2005 and 2006 respectively. In 43.1% of MIRs, preregistration house officers were involved. Most errors (80.2%) were detected before any drug was wrongly administered. The medications were administered in 212 cases (19.7%), which resulted in an untoward effect in nine cases (0.8%). CONCLUSIONS: The most common errors were wrong dosage and wrong drug. Many incidents involved preregistration house officers and HPs. Our computerized systems appeared to reduce medication incidents.

Tropism of avian influenza A (H5N1) in the upper and lower respiratory tract.

Poor human-to-human transmission of influenza A H5N1 virus has been attributed to the paucity of putative sialic acid alpha2-3 virus receptors in the epithelium of the human upper respiratory tract, and thus to the presumed inability of the virus to replicate efficiently at this site. We now demonstrate that ex vivo cultures of human nasopharyngeal, adenoid and tonsillar tissues can be infected with H5N1 viruses in spite of an apparent lack of these receptors.

Incidence of corneal pigmented arc and factors associated with its appearance in orthokeratology.

PURPOSE: To determine the incidence of the corneal pigmented arc in orthokeratology (ortho-k) lens wearers over 12 months of lens wear and the factors associated with its appearance. METHOD: Thirty-five ortho-k subjects were recruited; refractive and corneal changes after lens wear (single-lens protocol) were monitored over 12 months. The incidence of the pigmented arc after 3, 6 and 12 months of lens wear was determined. RESULTS: The incidence of corneal pigmented arc was 17% (27%), 49% (49%) and 90% (93%) after 3, 6 and 12 months lens wear respectively in the left and right eyes. For subjects with arcs observed in the left eye within the first 6 months of lens wear, the mean +/- S.D. period of lens wear before initial detection of the arc was 14 +/- 7.4 weeks, and no correlation was found between this factor and the baseline spherical and cylindrical refractive errors (i.e. refractive sphere and cylinder, respectively), spherical equivalent refractive error (SERE), the target myopia reduction, the amount of refractive sphere (or SERE) reduction and changes in central and peripheral corneal curvatures after 6 months of lens wear. Baseline refractive sphere, baseline SERE, target, amount of myopia reduction, and change in central corneal curvature were significantly larger (p < 0.05) in those subjects with pigmented arcs after about 6 months of lens wear. The intensity of the observed pigmented arcs after about 6 months of lens wear was significantly related to the time when it was first observed (p = 0.003). Significant correlation was also found between the intensity of the arcs and the following parameters: baseline refractive sphere and SERE, target, change in central corneal curvature, and amount of myopia reduction (p < 0.006). After about 12 months of lens wear, the intensity of observed arcs was significantly related to the baseline refractive sphere, SERE and the target (p < 0.006). CONCLUSION: The incidence of ortho-k-associated pigmented arc increases from 17% after 3 months of lens wear to over 90% after 12 months of lens wear. The intensity of the arc is related to the time when the arc first appeared. Both the incidence and the intensity of the arc are related to the period of lens wear, baseline refractive sphere, SERE and the target.

Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells.

BACKGROUND: Fatal human respiratory disease associated with influenza A subtype H5N1 has been documented in Hong Kong, and more recently in Vietnam, Thailand and Cambodia. We previously demonstrated that patients with H5N1 disease had unusually high serum levels of IP-10 (interferon-gamma-inducible protein-10). Furthermore, when compared with human influenza virus subtype H1N1, the H5N1 viruses in 1997 (A/Hong Kong/483/97) (H5N1/97) were more potent inducers of pro-inflammatory cytokines (e.g. tumor necrosis factor-a) and chemokines (e.g. IP-10) from primary human macrophages in vitro, which suggests that cytokines dysregulation may play a role in pathogenesis of H5N1 disease. Since respiratory epithelial cells are the primary target cell for replication of influenza viruses, it is pertinent to investigate the cytokine induction profile of H5N1 viruses in these cells. METHODS: We used quantitative RT-PCR and ELISA to compare the profile of cytokine and chemokine gene expression induced by H5N1 viruses A/HK/483/97 (H5N1/97), A/Vietnam/1194/04 and A/Vietnam/3046/04 (both H5N1/04) with that of human H1N1 virus in human primary alveolar and bronchial epithelial cells in vitro. RESULTS: We demonstrated that in comparison to human H1N1 viruses, H5N1/97 and H5N1/04 viruses were more potent inducers of IP-10, interferon beta, RANTES (regulated on activation, normal T cell expressed and secreted) and interleukin 6 (IL-6) in primary human alveolar and bronchial epithelial cells in vitro. Recent H5N1 viruses from Vietnam (H5N1/04) appeared to be even more potent at inducing IP-10 than H5N1/97 virus. CONCLUSION: The H5N1/97 and H5N1/04 subtype influenza A viruses are more potent inducers of proinflammatory cytokines and chemokines in primary human respiratory epithelial cells than subtype H1N1 virus. We suggest that this hyper-induction of cytokines may be relevant to the pathogenesis of human H5N1 disease.