Is it feasible to learn research skills in addition to audit skills through clinical audit? A mixed methods study in general practice.

BACKGROUND: Involving medical students in research in their undergraduate careers may increase the likelihood that they will be research active after graduation. To date, there has been a paucity of published research of students doing research in general practice. AIM: The study aims to evaluate the impact of general practice clinical audits on early-stage graduate entry students' audit and research self-efficacy and explore feasibility issues from the student and GP perspective. METHODS: Two student questionnaires (pre- and post-intervention), a qualitative GP survey of the 25 participating GPs and semi-structured interviews of a purposeful sample of GPs were conducted. RESULTS: Participating students who completed the follow-up survey found that it had a positive educational impact (55%), increased their understanding of the audit cycle (72%) and real-world prescribing (77%). Research confidence wise, there was a statistically significant difference in the student group who completed the audit project compared to those students who did not in knowledge of the audit cycle and the difference between research and audit (p = 0.001) but not in other research skills. Ninety-six percent of responding GPs would be happy for students to do future audits in their practice but some feasibility issues similar to other research initiatives in general practice were identified. CONCLUSION: We found this audit initiative feasible and useful in helping students learn about audit skills, patient safety and real-world prescribing. GPs and students would benefit more if it were linked to a substantial clinical placement, focussed on a topic of interest and given protected time. Separate research projects may be needed to develop research skills confidence.

Curriculum initiatives to enhance research skills acquisition by medical students: a scoping review.

BACKGROUND: Although it is accepted that providing medical students with opportunities to engage in research activity is beneficial, little data has been collated on how medical degree curricula may address this issue. This review aims to address this knowledge gap by conducting a scoping review examining curriculum initiatives that seek to enhance research experience for medical students. METHODS: This review looks to specifically look at 'doing research' as defined by the MEDINE 2 consensus rather than 'using research' for the bachelor component of the Bologna Cycle. The framework developed by Arksey & O'Malley was utilised and a consultation with stakeholders was incorporated to clarify and enhance the framework. RESULTS: A total of 120 articles were included in this scoping review; 26 related to intercalated degree options and 94 to non-intercalated degree options. Research initiatives from the United States were most common (53/120 articles). For non-intercalated research options, mandatory and elective research projects predominated. The included studies were heterogeneous in their methodology. The main outcomes reported were student research output, description of curriculum initiative(s) and self-reported research skills acquisition. For intercalated degree options, the three main findings were descriptions of more 'novel' intercalated degree options than the traditional BSc, student perspectives on intercalating and the effect of intercalating on medical student performance and careers. CONCLUSIONS: There are several options available to faculty involved in planning medical degree programmes but further research is needed to determine whether research activity should be optional or mandatory. For now, flexibility is probably appropriate depending on a medical school's resources, curriculum, educational culture and population needs.

Ireland's Assisted Decision Making Capacity Act-the potential for unintended effects in critical emergencies: a cross-sectional study of Advanced Paramedic decision making.

OBJECTIVE: Irish legislation on Advance Healthcare Directives (Assisted Decision Making Capacity Act 2015, ADMC) proposes to change the basis of decision making from acting in the patient's best interests to following the expressed will and intentions of the patient. Refusal of life-saving care can occur, without sound reasons. The implications for care in life-threatening emergencies have not been explored among clinicians. DESIGN: An anonymous questionnaire survey of Advanced Paramedics (AP) covering awareness of the legislation, attitudes to and experience of refusal of care and potential actions in emergency scenarios now and if the legislation were in force. The scenarios covered end-of-life and deliberate self-harm situations potentially requiring resuscitation. SETTING: All 482 graduates of the Advanced Paramedic Training Programme were invited to take part. RESULTS: Overall, 85/389 (21.9%) valid contacts responded, with demographic characteristics similar to the overall population. Attitudes ranged from highly positive to highly negative in relation to the potential impact of the legislation on professional and operational responsibilities. Respondents described marked changes in whether they would offer resuscitation if the ADMC were in place. CONCLUSION: Irish legislation which changes the traditional basis of medical practice away from the best interests of the patient may affect the resuscitation practices of Advanced Paramedics in life-threatening situations. It has significant implications for medical education, professional practice and clinician-patient interactions. This legislation and similar planned legislation may have implications for other EU jurisdictions.

Excellent reliability and validity of the Addiction Medicine Training Need Assessment Scale across four countries.

BACKGROUND: Addiction is a context specific but common and devastating condition. Though several evidence-based treatments are available, many of them remain under-utilized, among others due to the lack of adequate training in addiction medicine (AM). AM Training needs may differ across countries because of difference in discipline and level of prior AM training or contextual factors like epidemiology and availability of treatment. For appropriate testing of training needs, reliability and validity are key issues. The aim of this study was to evaluate the psychometric properties of the AM-TNA Scale: an instrument specifically designed to develop the competence-based curriculum of the Indonesian AM course. METHODS: In a cross-sectional study in Indonesia, Ireland, Lithuania and the Netherlands the AM-TNA was distributed among a convenience sample of health professionals working in addiction care in The Netherlands, Lithuania, Indonesia and General Practitioners in-training in Ireland. 428 respondents completed the AM-TNA scale. To assess the factor structure, we used explorative factor analysis. Reliability was tested using Cronbach's Alpha, ANOVA determined the discriminative validity. RESULTS: Validity: factor analysis revealed a two-factor structure: One on providing direct patient treatment and care (Factor 1: clinical) and one factor on facilitating/supporting direct patient treatment and care (Factor 2: non-clinical) AM competencies and a cumulative 76% explained variance. Reliability: Factor 1 α = 0.983 and Factor 2: α = 0.956, while overall reliability was (α = 0.986). The AM-TNA was able to differentiate training needs across groups of AM professionals on all 30 addiction medicine competencies (P = .001). CONCLUSIONS: In our study the AM-TNA scale had a strong two-factor structure and proofed to be a reliable and valid instrument. The next step should be the testing external validity, strengthening discriminant validity and assessing the re-test effect and measuring changes over time.

Paediatric airway management and concerns: a survey of advanced paramedics in Ireland.

BACKGROUND: Paediatric airway management is of fundamental importance in the critically unwell child. Pre-hospital paediatric airway management especially endotracheal intubation is however controversial. AIM: To explore Irish Advanced Paramedics (APs) training, experience and clinical practice in paediatric airway management as well as to examine clinician attitudes toward this topic. METHODS: An anonymous online survey of all graduates of the University College Dublin AP training program (N = 453). RESULTS: With duplicates and failed email deliveries excluded a valid sample of 382 individuals was obtained from whom a response rate of 185/382 (48.4%) was achieved. Three quarters of responding APs worked in urban or mixed practice with the remaining minority operating primarily in rural areas. One quarter of responding APs reported formal training in paediatric intubation. Almost 70% of APs had encountered a child requiring significant airway management in the preceding year. However, this was a rare exposure in terms of overall workload. Basic airway adjuncts were used frequently in such circumstances, with endotracheal intubation having been attempted by only a small minority of APs. Lack of practice was identified by many responding APs as a key issue causing concern in terms of paediatric intubation. CONCLUSION: Paediatric airway management has key relevance for pre-hospital care in Ireland. The overall frequency of exposure to children who may benefit from definitive airway management is however likely to represent a significant barrier to the acquisition and maintenance of competency. The ongoing practice of pre-hospital paediatric intubation by APs may not justify its risks.

Psychosocial interventions to reduce alcohol consumption in concurrent problem alcohol and illicit drug users.

BACKGROUND: Problem alcohol use is common among people who use illicit drugs (PWID) and is associated with adverse health outcomes. It is also an important factor contributing to a poor prognosis among drug users with hepatitis C virus (HCV) as it impacts on progression to hepatic cirrhosis or opioid overdose in PWID. OBJECTIVES: To assess the effectiveness of psychosocial interventions to reduce alcohol consumption in PWID (users of opioids and stimulants). SEARCH METHODS: We searched the Cochrane Drugs and Alcohol Group trials register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, and PsycINFO, from inception up to August 2017, and the reference lists of eligible articles. We also searched: 1) conference proceedings (online archives only) of the Society for the Study of Addiction, International Harm Reduction Association, International Conference on Alcohol Harm Reduction and American Association for the Treatment of Opioid Dependence; and 2) online registers of clinical trials: Current Controlled Trials, ClinicalTrials.gov, Center Watch and the World Health Organization International Clinical Trials Registry Platform. SELECTION CRITERIA: We included randomised controlled trials comparing psychosocial interventions with other psychosocial treatment, or treatment as usual, in adult PWIDs (aged at least 18 years) with concurrent problem alcohol use. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We included seven trials (825 participants). We judged the majority of the trials to have a high or unclear risk of bias.The psychosocial interventions considered in the studies were: cognitive-behavioural coping skills training (one study), twelve-step programme (one study), brief intervention (three studies), motivational interviewing (two studies), and brief motivational interviewing (one study). Two studies were considered in two comparisons. There were no data for the secondary outcome, alcohol-related harm. The results were as follows.Comparison 1: cognitive-behavioural coping skills training versus twelve-step programme (one study, 41 participants)There was no significant difference between groups for either of the primary outcomes (alcohol abstinence assessed with Substance Abuse Calendar and breathalyser at one year: risk ratio (RR) 2.38 (95% confidence interval [CI] 0.10 to 55.06); and retention in treatment, measured at end of treatment: RR 0.89 (95% CI 0.62 to 1.29), or for any of the secondary outcomes reported. The quality of evidence for the primary outcomes was very low.Comparison 2: brief intervention versus treatment as usual (three studies, 197 participants)There was no significant difference between groups for either of the primary outcomes (alcohol use, measured as scores on the Alcohol Use Disorders Identification Test (AUDIT) or Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) at three months: standardised mean difference (SMD) 0.07 (95% CI -0.24 to 0.37); and retention in treatment, measured at three months: RR 0.94 (95% CI 0.78 to 1.13), or for any of the secondary outcomes reported. The quality of evidence for the primary outcomes was low.Comparison 3: motivational interviewing versus treatment as usual or educational intervention only (three studies, 462 participants)There was no significant difference between groups for either of the primary outcomes (alcohol use, measured as scores on the AUDIT or ASSIST at three months: SMD 0.04 (95% CI -0.29 to 0.37); and retention in treatment, measured at three months: RR 0.93 (95% CI 0.60 to 1.43), or for any of the secondary outcomes reported. The quality of evidence for the primary outcomes was low.Comparison 4: brief motivational intervention (BMI) versus assessment only (one study, 187 participants)More people reduced alcohol use (by seven or more days in the past month, measured at six months) in the BMI group than in the control group (RR 1.67; 95% CI 1.08 to 2.60). There was no difference between groups for the other primary outcome, retention in treatment, measured at end of treatment: RR 0.98 (95% CI 0.94 to 1.02), or for any of the secondary outcomes reported. The quality of evidence for the primary outcomes was moderate.Comparison 5: motivational interviewing (intensive) versus motivational interviewing (one study, 163 participants)There was no significant difference between groups for either of the primary outcomes (alcohol use, measured using the Addiction Severity Index-alcohol score (ASI) at two months: MD 0.03 (95% CI 0.02 to 0.08); and retention in treatment, measured at end of treatment: RR 17.63 (95% CI 1.03 to 300.48), or for any of the secondary outcomes reported. The quality of evidence for the primary outcomes was low. AUTHORS' CONCLUSIONS: We found low to very low-quality evidence to suggest that there is no difference in effectiveness between different types of psychosocial interventions to reduce alcohol consumption among people who use illicit drugs, and that brief interventions are not superior to assessment-only or to treatment as usual. No firm conclusions can be made because of the paucity of the data and the low quality of the retrieved studies.

Ten years of cardiac arrest resuscitation in Irish general practice.

AIM: The aim of this study is to establish the role and outcome of general practitioner (GP) involvement in out of hospital cardiac arrest (OHCA) resuscitation in the Republic of Ireland. METHODS: A ten year prospective observational study involving a cohort of Irish general practices. SETTING: 521 general practice settings distributed throughout the Republic of Ireland, representing approximately one quarter of all practices and a third of Irish GPs. PARTICIPANTS: 534 patients suffering cardiac arrest in the community for whom resuscitation was attempted. INTERVENTIONS: Cardiac arrest with resuscitation attempted (CARA) in which a GP played a role. RESULTS: Over a ten year period almost half of participating practices reported one or more CARAs. A total of 534 CARAs were reported at a variety of locations; 161 (30%) had ROSC (return of spontaneous circulation) at some point, with outcome data available for 147/161; 90 patients survived to hospital discharge. Most survivors for whom follow up data are available were discharged home and were completely independent. The highest rate of survival was achieved when CARAs occurred at a GP practice premises (47.4%). CONCLUSIONS: Resuscitation following OHCA is a key task in general practice. Over time a significant number of GPs encounter OHCA, attempt resuscitation and achieve higher survival to hospital discharge rates than occur nationally among OHCAs in Ireland. We conclude that a defibrillator should be routinely available at all general practices and staff should have appropriate resuscitation skills.

Opiate addiction and overdose: experiences, attitudes, and appetite for community naloxone provision.

BACKGROUND: More than 200 opiate overdose deaths occur annually in Ireland. Overdose prevention and management, including naloxone prescription, should be a priority for healthcare services. Naloxone is an effective overdose treatment and is now being considered for wider lay use. AIM: To establish GPs' views and experiences of opiate addiction, overdose care, and naloxone provision. DESIGN AND SETTING: An anonymous postal survey to GPs affiliated with the Department of Academic General Practice, University College Dublin, Ireland. METHOD: A total of 714 GPs were invited to complete an anonymous postal survey. Results were compared with a parallel GP trainee survey. RESULTS: A total of 448/714 (62.7%) GPs responded. Approximately one-third of GPs were based in urban, rural, and mixed areas. Over 75% of GPs who responded had patients who used illicit opiates, and 25% prescribed methadone. Two-thirds of GPs were in favour of increased naloxone availability in the community; almost one-third would take part in such a scheme. A higher proportion of GP trainees had used naloxone to treat opiate overdose than qualified GPs. In addition, a higher proportion of GP trainees were willing to be involved in naloxone distribution than qualified GPs. Intranasal naloxone was much preferred to single (P<0.001) or multiple dose (P<0.001) intramuscular naloxone. Few GPs objected to wider naloxone availability, with 66.1% (n = 292) being in favour. CONCLUSION: GPs report extensive contact with people who have opiate use disorders but provide limited opiate agonist treatment. They support wider availability of naloxone and would participate in its expansion. Development and evaluation of an implementation strategy to support GP-based distribution is urgently needed.

Development and process evaluation of an educational intervention for overdose prevention and naloxone distribution by general practice trainees.

BACKGROUND: Overdose is the most common cause of fatalities among opioid users. Naloxone is a life-saving medication for reversing opioid overdose. In Ireland, it is currently available to ambulance and emergency care services, but General Practitioners (GP) are in regular contact with opioid users and their families. This positions them to provide naloxone themselves or to instruct patients how to use it. The new Clinical Practice Guidelines of the Pre-hospital Emergency Care Council of Ireland allows trained bystanders to administer intranasal naloxone. We describe the development and process evaluation of an educational intervention, designed to help GP trainees identify and manage opioid overdose with intranasal naloxone. METHODS: Participants (N = 23) from one postgraduate training scheme in Ireland participated in a one-hour training session. The repeated-measures design, using the validated Opioid Overdose Knowledge (OOKS) and Attitudes (OOAS) Scales, examined changes immediately after training. Acceptability and satisfaction with training were measured with a self-administered questionnaire. RESULTS: Knowledge of the risks of overdose and appropriate actions to be taken increased significantly post-training [OOKS mean difference, 3.52 (standard deviation 4.45); P < 0.001]; attitudes improved too [OOAS mean difference, 11.13 (SD 6.38); P < 0.001]. The most and least useful delivery methods were simulation and video, respectively. CONCLUSION: Appropriate training is a key requirement for the distribution of naloxone through general practice. In future studies, the knowledge from this pilot will be used to inform a train-the-trainer model, whereby healthcare professionals and other front-line service providers will be trained to instruct opioid users and their families in overdose prevention and naloxone use.

Screening for atrial fibrillation in general practice: a national, cross-sectional study of an innovative technology.

BACKGROUND: To test the use of three lead monitoring as a screening tool for atrial fibrillation (AF) in general practice. AF is responsible for up to a quarter of all strokes and is often asymptomatic until a stroke occurs. METHODS: 26 randomly selected general practices identified 80 randomly selected patients aged 70 or older from their database and excluded those known to have AF, those with clinical issues or who had not attended for three years. Up to 40 eligible patients/practice were invited to attend for screening. A 2min three-lead ECG was recorded and collected centrally for expert cardiology assessment. Risk factor data was gathered. OUTCOMES: (i) point prevalence of AF, (ii) proportion of ECG tracings which were adequate for interpretation, (iii) uptake rate by patients and (iv) acceptability of the screening process to patients and staff (reported separately). RESULTS: Of 1447 current patients, 1003 were eligible for inclusion, 639 (64%) agreed to take part in screening and 566 (56%) completed screening. The point prevalence rate for AF was 10.3%-2.1% new cases (12 of 566 who were screened) and 9.5% existing cases (137 of 1447 eligible patients). Only four of 570 (0.7%) screening visits did not record a usable ECG and 11 (2.6%) three lead ECGs required a clarifying 12 lead ECG. CONCLUSIONS: Three lead screening for AF is feasible, effective and offers an alternative to pulse taking or 12 lead ECGs. The availability of this technology may facilitate more effective screening, leading to reduced stroke incidence.

Psychosocial interventions to reduce alcohol consumption in concurrent problem alcohol and illicit drug users.

BACKGROUND: Problem alcohol use is common among illicit drug users and is associated with adverse health outcomes. It is also an important factor contributing to a poor prognosis among drug users with hepatitis C virus (HCV) as it impacts on progression to hepatic cirrhosis or opiate overdose in opioid users. OBJECTIVES: To assess the effects of psychosocial interventions for problem alcohol use in illicit drug users (principally problem drug users of opiates and stimulants). SEARCH METHODS: We searched the Cochrane Drugs and Alcohol Group trials register (June 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 11, June 2014), MEDLINE (1966 to June 2014); EMBASE (1974 to June 2014); CINAHL (1982 to June 2014); PsycINFO (1872 to June 2014) and the reference lists of eligible articles. We also searched: 1) conference proceedings (online archives only) of the Society for the Study of Addiction, International Harm Reduction Association, International Conference on Alcohol Harm Reduction and American Association for the Treatment of Opioid Dependence; 2) online registers of clinical trials: Current Controlled Trials, Clinical Trials.org, Center Watch and the World Health Organization International Clinical Trials Registry Platform. SELECTION CRITERIA: Randomised controlled trials comparing psychosocial interventions with another therapy (other psychosocial treatment, including non-pharmacological therapies, or placebo) in adult (over the age of 18 years) illicit drug users with concurrent problem alcohol use. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: Four studies, involving 594 participants, were included. Half of the trials were rated as having a high or unclear risk of bias. The studies considered six different psychosocial interventions grouped into four comparisons: (1) cognitive-behavioural coping skills training versus 12-step facilitation (one study; 41 participants), (2) brief intervention versus treatment as usual (one study; 110 participants), (3) group or individual motivational interviewing (MI) versus hepatitis health promotion (one study; 256 participants) and (4) brief motivational intervention (BMI) versus assessment-only (one study; 187 participants). Differences between studies precluded any data pooling. Findings are described for each trial individually.Comparison 1: low-quality evidence; no significant difference for any of the outcomes considered Alcohol abstinence as maximum number of weeks of consecutive alcohol abstinence during treatment: mean difference (MD) 0.40 (95% confidence interval (CI) -1.14 to 1.94); illicit drug abstinence as maximum number of weeks of consecutive abstinence from cocaine during treatment: MD 0.80 (95% CI -0.70 to 2.30); alcohol abstinence as number achieving three or more weeks of consecutive alcohol abstinence during treatment: risk ratio (RR) 1.96 (95% CI 0.43 to 8.94); illicit drug abstinence as number achieving three or more weeks of consecutive abstinence from cocaine during treatment: RR 1.10 (95% CI 0.42 to 2.88); alcohol abstinence during follow-up year: RR 2.38 (95% CI 0.10 to 55.06); illicit drug abstinence as abstinence from cocaine during follow-up year: RR 0.39 (95% CI 0.04 to 3.98), moderate-quality evidence.Comparison 2: low-quality evidence, no significant difference for all the outcomes considered Alcohol use as AUDIT scores at three months: MD 0.80 (95% -1.80 to 3.40); alcohol use as AUDIT scores at nine months: MD 2.30 (95% CI -0.58 to 5.18); alcohol use as number of drinks per week at three months: MD 0.70 (95% CI -3.85 to 5.25); alcohol use as number of drinks per week at nine months: MD -0.30 (95% CI -4.79 to 4.19); alcohol use as decreased alcohol use at three months: RR 1.13 (95% CI 0.67 to 1.93); alcohol use as decreased alcohol use at nine months: RR 1.34 (95% CI 0.69 to 2.58), moderate-quality evidence.Comparison 3 (group and individual MI), low-quality evidence: no significant difference for all outcomes Group MI: number of standard drinks consumed per day over the past month: MD -0.40 (95% CI -2.03 to 1.23); frequency of drug use: MD 0.00 (95% CI -0.03 to 0.03); composite drug score (frequency*severity for all drugs taken): MD 0.00 (95% CI -0.42 to 0.42); greater than 50% reduction in number of standard drinks consumed per day over the last 30 days: RR 1.10 (95% CI 0.82 to 1.48); abstinence from alcohol over the last 30 days: RR 0.88 (95% CI 0.49 to 1.58).Individual MI: number of standard drinks consumed per day over the past month: MD -0.10 (95% CI -1.89 to 1.69); frequency of drug use (as measured using the Addiction Severity Index (ASI drug): MD 0.00 (95% CI -0.03 to 0.03); composite drug score (frequency*severity for all drugs taken): MD -0.10 (95% CI -0.46 to 0.26); greater than 50% reduction in number of standard drinks consumed per day over the last 30 days: RR 0.92 (95% CI 0.68 to 1.26); abstinence from alcohol over the last 30 days: RR 0.97 (95% CI 0.56 to 1.67).Comparison 4: more people reduced alcohol use (by seven or more days in the past month at 6 months) in the BMI group than in the control group (RR 1.67; 95% CI 1.08 to 2.60), moderate-quality evidence. No significant difference was reported for all other outcomes: number of days in the past 30 days with alcohol use at one month: MD -0.30 (95% CI -3.38 to 2.78); number of days in the past month with alcohol use at six months: MD -1.50 (95% CI -4.56 to 1.56); 25% reduction of drinking days in the past month: RR 1.23 (95% CI 0.96 to 1.57); 50% reduction of drinking days in the past month: RR 1.27 (95% CI 0.96 to 1.68); 75% reduction of drinking days in the past month: RR 1.21 (95% CI 0.84 to 1.75); one or more drinking days' reduction in the past month: RR 1.12 (95% CI 0.91 to 1.38). AUTHORS' CONCLUSIONS: There is low-quality evidence to suggest that there is no difference in effectiveness between different types of interventions to reduce alcohol consumption in concurrent problem alcohol and illicit drug users and that brief interventions are not superior to assessment-only or to treatment as usual. No firm conclusions can be made because of the paucity of the data and the low quality of the retrieved studies.

Urban overdose hotspots: a 12-month prospective study in Dublin ambulance services.

BACKGROUND: Opioid overdose (OD) is the primary cause of death among drug users globally. Personal and social determinants of overdose have been studied before, but the environmental factors lacked research attention. Area deprivation or presence of addiction clinics may contribute to overdose. OBJECTIVES: The objective of the study is to examine the baseline incidence of all new ODs in an ambulance service and their relationship with urban deprivation and presence of addiction services. METHODS: A prospective chart review of prehospital advanced life support patients was performed on confirmed OD calls. Demographic, geographic, and clinical information, that is, presentation, treatment, and outcomes, was collected for each call. The census data were used to calculate deprivation. Geographical information software mapped the urban deprivation and addiction services against the overdose locations. RESULTS: There were 469 overdoses, 13 of which were fatal; most were male (80%), of a young age (32 years), with a high rate of repeated overdoses (26%) and common polydrug use (9.6%). Most occurred in daytime (275) and on the streets (212). Overdoses were more likely in more affluent areas (r = .15; P < .05) and in a 1000-m radius of addiction services. Residential overdoses were in more deprived areas than street overdoses (mean difference, 7.8; t170 = 3.99; P < .001). Street overdoses were more common in the city center than suburbs (χ(2)(1) = 33.04; P < .001). CONCLUSIONS: The identified clusters of increased incidence-urban overdose hotspots-suggest a link between environment characteristics and overdoses. This highlights a need to establish overdose education and naloxone distribution in the overdose hotspots.

Osteosarcoma in New Zealand: an outcome study comparing survival rates between 1981-1987 and 1994-1999.

AIMS: To review the data and outcome of patients with osteosarcoma in New Zealand from 1994 to 1999 and to compare this to data retrieved from a similar study from 1981 to 1987. METHODS: Data from 1994-1999 was obtained from the New Zealand Cancer Registry; raw data was also retrieved from the 1981-1987 study. RESULTS: There were 96 cases in the 1981-1987 cohort and 84 cases in the 1994-1999 cohort. Overall, 5-year survival from osteosarcoma improved from 32.3% to 44.0% between the cohorts. When the cohorts were compared, there was a trend toward improved outcome in most subgroups CONCLUSIONS: The outcome in patients with osteosarcoma in New Zealand has improved over the study period and is similar to that seen in the overseas literature.

Ectopic expression of HLA-DO in mouse dendritic cells diminishes MHC class II antigen presentation.

The MHC class II-like molecule HLA-DM (DM) (H-2M in mice) catalyzes the exchange of CLIP for antigenic peptides in the endosomes of APCs. HLA-DO (DO) (H-2O in mice) is another class II-like molecule that is expressed in B cells, but not in other APCs. Studies have shown that DO impairs or modifies the peptide exchange activity of DM. To further evaluate the role of DO in Ag processing and presentation, we generated transgenic mice that expressed the human HLA-DOA and HLA-DOB genes under the control of a dendritic cell (DC)-specific promoter. Our analyses of DCs from these mice showed that as DO levels increased, cell surface levels of A(b)-CLIP also increased while class II-peptide levels decreased. The presentation of some, but not all, exogenous Ags to T cells or T hybridomas was significantly inhibited by DO. Surprisingly, H-2M accumulated in DO-expressing DCs and B cells, suggesting that H-2O/DO prolongs the half-life of H-2M. Overall, our studies showed that DO expression impaired H-2M function, resulting in Ag-specific down-modulation of class II Ag processing and presentation.

Comparison of the transcriptional regulation of classical and non-classical MHC class II genes.

The class II transactivator (CIITA) regulates expression of the classical and non-classical MHC class II genes, HLA-DR, -DP, -DQ and -DM, but not the B cell-specific HLA-DO (DO). Here we show that only HLA-DR expression is completely dependent on CIITA, since residual expression of HLA-DM, -DP and the beta chain of DQ was observed in CIITA-deficient RJ2.2.5 cells. Although DO shows a unique expression pattern compared to other MHC class II genes, prolonged IFN-gamma treatment of HeLa cells induced DOB expression. Similar to all MHC class II promoters, the DOB promoter contains the highly conserved W, X1, and Y boxes in addition to a putative OCT box. Mutational analysis of the DOB promoter demonstrated that the X1, Y and OCT boxes are necessary for maximum promoter activity.Furthermore, our results demonstrate that CREB-1, RFXANK and Oct-2 occupy the DOB promoter in vivo, However, CIITA and Bob-1 were only minimally recruited. Finally, fusion of Bjab, a DOB-negative B cell line, with.174 B cells that lack the complete MHC class II region (including the DO genes), lead to DO expression. These data indicate that the expression of DO is regulated by an unidentified factor in B cells.

Germinal center B cells regulate their capability to present antigen by modulation of HLA-DO.

Peptide acquisition by MHC class II molecules is catalyzed by HLA-DM (DM). In B cells, HLA-DO (DO) inhibits or modifies the peptide exchange activity of DM. We show here that DO protein levels are modulated during B cell differentiation. Remarkably, germinal center (GC) B cells, which have low levels of DO relative to naive and memory B cells, are shown to have enhanced antigen presentation capabilities. DM protein levels also were somewhat reduced in GC B cells; however, the ratio of DM to DO in GC B cells was substantially increased, resulting in more free DM in GC B cells. We conclude that modulation of DM and DO in distinct stages of B cell differentiation represents a mechanism by which B cells regulate their capacity to function as antigen-presenting cells. Efficient antigen presentation in GC B cells would promote GC B cell-T cell interactions that are essential for B cells to survive positive selection in the GC.