Human immunodeficiency virus type 1: drug resistance in treated and untreated Brazilian children

Twenty-two vertically human immunodeficiency virus type 1 (HIV-1) infected Brazilian children were studied for antiretroviral drug resistance. They were separated into 2 groups according to the administration of antiretroviral therapy into those who presented disease symptoms or without symptoms and no therapy. Viral genome sequencing reactions were loaded on an automated DNA sampler (TruGene, Visible Genetics) and compared to a database of wild type HIV-1. In the former group 8 of 12 children presented isolates with mutations conferring resistance to protease inhibitors (PIs), 7 presented isolates resistant to nucleoside reverse transcriptase inhibitors (NRTIs) and 2 presented isolates resistant to non-nucleoside reverse transcriptase inhibitors (NNRTIs). Ten children were included in the antiretroviral naïve group. Eight were susceptible to NRTIs and all of them were susceptible to PIs; one presented the V108I mutation, which confers low-level resistance to NNRTIs. The data report HIV mutant isolates both in treated and untreated infants. However, the frequency and the level of drug resistance were more frequent in the group receiving antiretroviral therapy, corroborating the concept of selective pressure acting on the emergence of resistant viral strains. The children who presented alterations at polymorphism sites should be monitored for the development of additional mutations occurring at relevant resistance codons.

CD4+ T cell count recovery in HIV type 1-infected patients is independent of class of antiretroviral therapy.

BACKGROUND: In recent years, treatment options for human immunodeficiency virus type 1 (HIV-1) infection have changed from nonboosted protease inhibitors (PIs) to nonnucleoside reverse-transcriptase inhibitors (NNRTIs) and boosted PI-based antiretroviral drug regimens, but the impact on immunological recovery remains uncertain. METHODS: During January 1996 through December 2004 [corrected] all patients in the Swiss HIV Cohort were included if they received the first combination antiretroviral therapy (cART) and had known baseline CD4(+) T cell counts and HIV-1 RNA values (n = 3293). For follow-up, we used the Swiss HIV Cohort Study database update of May 2007 [corrected] The mean (+/-SD) duration of follow-up was 26.8 +/- 20.5 months. The follow-up time was limited to the duration of the first cART. CD4(+) T cell recovery was analyzed in 3 different treatment groups: nonboosted PI, NNRTI, or boosted PI. The end point was the absolute increase of CD4(+) T cell count in the 3 treatment groups after the initiation of cART. RESULTS: Two thousand five hundred ninety individuals (78.7%) initiated a nonboosted-PI regimen, 452 (13.7%) initiated an NNRTI regimen, and 251 (7.6%) initiated a boosted-PI regimen. Absolute CD4(+) T cell count increases at 48 months were as follows: in the nonboosted-PI group, from 210 to 520 cells/muL; in the NNRTI group, from 220 to 475 cells/muL; and in the boosted-PI group, from 168 to 511 cells/muL. In a multivariate analysis, the treatment group did not affect the response of CD4(+) T cells; however, increased age, pretreatment with nucleoside reverse-transcriptase inhibitors, serological tests positive for hepatitis C virus, Centers for Disease Control and Prevention stage C infection, lower baseline CD4(+) T cell count, and lower baseline HIV-1 RNA level were risk factors for smaller increases in CD4(+) T cell count. CONCLUSION: CD4(+) T cell recovery was similar in patients receiving nonboosted PI-, NNRTI-, and boosted PI-based cART.

TB: the disease, its treatment and prevention (English and 10 translations)

This booklet offers general advice on the control of tuberculosis (TB)

ASIST suicide prevention training - all-island evaluation report

The findings of a Public Health Agency evaluation report on a suicide prevention training programme were today presented at the North South Ministerial Council Health Sector meeting.ASIST, The Applied Suicide Intervention Skills Training programme, has to date been delivered to more than 20,000 people in the Republic of Ireland and more than 11,000 people in Northern Ireland. This two day course, delivered by a wide range of organisations including those from the voluntary/community sector, for professionals and the public helps individuals provide emergency help to people at risk of suicidal behaviour. It also develops a cooperative network among participants, since often many people have to work together to prevent suicide.Talking about the findings of this work, Dr Eddie Rooney, Chief Executive, PHA, said: "Both the PHA and the National Office for Suicide Prevention (NOSP), based in the Republic of Ireland, are concerned for any loss of life through suicide and we send our condolences to all families who have been bereaved. We know ASIST training brings a positive element to suicide prevention. Those who have been trained said that the two biggest advantages are that they know when, how and have the confidence to help people who are under pressure and that it helps to build positive links between community and voluntary organisations and the health service. I am pleased that this has been borne out in the evaluation and we hope ASIST will continue to be of enormous benefit and will contribute to a reduction in suicidal behaviour and the tragedy that this brings to our community".This evaluation found that within organisations where staff had participated in ASIST training, there were improvements in service development; staff attitudes, confidence and skills in relation to suicide and suicide intervention and in policies and procedures. At a community level, ASIST was found to have contributed to a sense of empowerment through an increased confidence in being able to deal with suicide and suicidal behaviour.The report also shows that the ASIST model offers a common language, helping communication between the community or voluntary organisations and those from a health background. In fact this training helped to cancel out any differences between those with mental health qualifications and those without, in terms of knowledge, skills, attitude and willingness to intervene. The study also confirmed that ASIST training was most relevant to those who were likely to be in contact with a person 'at risk'.In welcoming the publication of the report Geoff Day, Director of the NOSP, said: "This report is an independent evaluation of the ASIST programme, it has allowed us to demonstrate the effectiveness of the programme in increasing community participants confidence and ability to respond to individuals in suicidal crisis.He added: "The fact the evaluation was completed on an all-island basis allows the NOSP and the PHA to avoid duplication of resources, improve coordination of suicide prevention training programmes across both jurisdictions and allows us to learn from different approaches used in suicide prevention across the island of Ireland."He reiterated the Health Service Executive commitment to the continued implementation of quality assured training programmes as part of Reach out: the National Strategy for Action on Suicide Prevention.ASIST training is being rolled out in Northern Ireland as part of the implementation of the 'Protect Life' suicide prevention strategy, which was published by the Department of Health, Social Services and Public Safety in 2006.A copy of the evaluation report can be found below and in the publications section of this website, by clicking here

Consultation launched on Community Development Strategy - your views matter

Issued jointly by the Health and Social Care Board and Public Health AgencyThe Health and Social Care Board and the Public Health Agency have today launched, for public consultation, a new Community Development Strategy.The consultation period will run for 12 weeks from Friday 10 June until Friday 2 September 2011.The Board and Agency want to see strong, resilient communities where everyone has good health and wellbeing, places where people look out for each other and have community pride in where they live.Residents from deprived areas in Northern Ireland experience;lower life expectancy;higher rates of emergency admission to hospital;higher rates of lung cancer;higher rates of suicide; andhigher rates of smoking and alcohol related deaths.The kinds of health and social care issues which can be improved by community development approaches include depression; isolation; falls amongst elderly people; child protection; teenage pregnancy; childhood asthma; postnatal depression; drug and alcohol abuse; and ultimately also long term conditions such as obesity, diabetes and cancer.The Board and Agency seek a number of benefits from implementing this strategy such as; a reduction in health and wellbeing inequalities, which also means addressing the social factors that affect health; strengthening partnership working with service users, the community and voluntary sectors and other organisations; strengthening families and communities; supporting volunteering and making best use of our resources.John Compton, Chief Executive of the Health and Social Care Board said: "Community development is an important way to improving health and wellbeing - driving a message that 'prevention is better than cure' between different groups and communities, and helping to ensure the most effective use of the health and social care budget."Now more than ever we need to work in partnership with families and communities to achieve better health and wellbeing for those living in Northern Ireland.No one organisation can meet this challenge on its own and strong partnerships are needed. "Chief Executive of the Public Health Agency, Eddie Rooney added: "Every health and social care organisation should incorporate a community development approach into their programmes, and this strategy assists them to do so."The Board and Agency have jointly held pre-consultation workshops over the past few months across Northern Ireland on their Community Development Strategy and have engaged widely with the community and voluntary sectors. We are now keen to receive feedback from individuals, families and the wider community as your views are very important to us - they will help shape the future of community development across the province," he said.The draft Community Development Strategy, as well as information on how you can respond, can be found in the attachments below.

Drug susceptibility testing of Mycobacterium tuberculosis by the broth microdilution method with 7H9 broth

In this study, we have evaluated the broth microdilution method (BMM) for susceptibility testing of Mycobacterium tuberculosis. A total of 43 clinical isolates of M. tuberculosis and H37Rv as a control strain were studied. All isolates were tested by the proportion method and the BMM for isoniazid (INH), rifampicin (RIF), streptomycin (STR), and ethambutol (ETM). The proportion method was carried out according to the National Committee for Clinical Laboratory Standards (NCCLS) on Löwenstein-Jensen (LJ) medium. The BMM was carried out using 7H9 broth with 96 well-plates. All strains were tested at 3.2-0.05 µg/ml, 16-0.25 µg/ml, 32-0.5 µg/ml, and 32-0.5 µg/ml concentrations for INH, RIF, STR, and ETM, respectively. When the BMM was compared with the proportion method, sensitivity was 100, 100, 96.9, and 90.2%, while specificity was 100, 85.7, 90.9, and 100% for INH, RIF, STR, and ETM, respectively. The plates were examined 7, 10, 14, and 21 days after incubation. The majority of the result were obtained at 14th days after incubation, while the proportion method result were ended in 21-28 days. According to our results, it may be suggested that the BMM is suitable for early determining of multidrug-resistance-M. tuberculosis strains in developed or developing countries.

Quality Standards for Services Promoting Mental and Emotional Wellbeing and Suicide Prevention

These standards will apply to all organisations providing mental & emotional wellbeing and suicide prevention services which are funded by the PHA.

Therapeutic Drug Monitoring of the new targeted anticancer agents imatinib, nilotinib, dasatinib, sunitinib, sorafenib and lapatinib by LC tandem mass spectrometry.

The treatment of some cancer patients has shifted from traditional, non-specific cytotoxic chemotherapy to chronic treatment with molecular targeted therapies. Imatinib mesylate, a selective inhibitor of tyrosine kinases (TKIs) is the most prominent example of this new era and has opened the way to the development of several additional TKIs, including sunitinib, nilotinib, dasatinib, sorafenib and lapatinib, in the treatment of various hematological malignancies and solid tumors. All these agents are characterized by an important inter-individual pharmacokinetic variability, are at risk for drug interactions, and are not devoid of toxicity. Additionally, they are administered for prolonged periods, anticipating the careful monitoring of their plasma exposure via Therapeutic Drug Monitoring (TDM) to be an important component of patients' follow-up. We have developed a liquid chromatography-tandem mass spectrometry method (LC-MS/MS) requiring 100 microL of plasma for the simultaneous determination of the six major TKIs currently in use. Plasma is purified by protein precipitation and the supernatant is diluted in ammonium formate 20 mM (pH 4.0) 1:2. Reverse-phase chromatographic separation of TKIs is obtained using a gradient elution of 20 mM ammonium formate pH 2.2 and acetonitrile containing 1% formic acid, followed by rinsing and re-equilibration to the initial solvent composition up to 20 min. Analyte quantification, using matrix-matched calibration samples, is performed by electro-spray ionization-triple quadrupole mass spectrometry by selected reaction monitoring detection using the positive mode. The method was validated according to FDA recommendations, including assessment of extraction yield, matrix effects variability (<9.6%), overall process efficiency (87.1-104.2%), as well as TKIs short- and long-term stability in plasma. The method is precise (inter-day CV%: 1.3-9.4%), accurate (-9.2 to +9.9%) and sensitive (lower limits of quantification comprised between 1 and 10 ng/mL). This is the first broad-range LC-MS/MS assay covering the major currently in-use TKIs. It is an improvement over previous methods in terms of convenience (a single extraction procedure for six major TKIs, reducing significantly the analytical time), sensitivity, selectivity and throughput. It may contribute to filling the current knowledge gaps in the pharmacokinetics/pharmacodynamics relationships of the latest TKIs developed after imatinib and better define their therapeutic ranges in different patient populations in order to evaluate whether a systematic TDM-guided dose adjustment of these anticancer drugs could contribute to minimize the risk of major adverse reactions and to increase the probability of efficient, long lasting, therapeutic response.

Trends in drug consumption and risk of transmission of HIV and hepatitis C virus among injecting drug users in Switzerland, 1993-2006

As a part of the HIV behavioural surveillance system in Switzerland, repeated cross-sectional surveys were conducted in 1993, 1994, 1996, 2000 and 2006 among attenders of all low threshold facilities (LTFs) with needle exchange programmes and/or supervised drug consumption rooms for injection or inhalation in Switzerland. Data were collected in each LTF over five consecutive days, using a questionnaire that was partly completed by an interviewer and partly self administered. The questionnaire was structured around three topics: socio-demographic characteristics, drug consumption, health and risk/preventive behaviour. Analysis was restricted to attenders who had injected drugs during their lifetime (IDUs). Between 1993 and 2006, the median age of IDUs rose by 10 years. IDUs are severely marginalised and their social situation has improved little. The borrowing of used injection equipment (syringe or needle already used by other person) in the last six months decreased (16.5% in 1993, 8.9% in 2006) but stayed stable at around 10% over the past three surveys. Other risk behaviour, such as sharing spoons, cotton or water, was reported more frequently, although also showed a decreasing trend. The reported prevalence of HIV remained fairly stable at around 10% between 1993 and 2006; reported levels of hepatitis C virus (HCV) prevalence were high (56.4% in 2006). In conclusion, the overall decrease in the practice of injection has reduced the potential for transmission of infections. However as HCV prevalence is high this is of particular concern, as the current behaviour of IDUs indicates a potential for further spreading of the infection. Another noteworthy trend is the significant decrease in condom use in the case of paid sex.

A Cannabis Reader: Global Issues and Local Experiences

The EMCDDA’s cannabis monograph addresses one basic question. How can I find quality information on cannabis, amid all the bias and opinion? The monograph is divided into two volumes. The first volume centres on political, legislative, commercial and social developments relating to cannabis. Its core audience thus comprises policymakers, sociologists, historians, journalists and those involved in enforcement. The second volume is targeted at drugs professionals working in the fields of treatment, prevention and healthcare.This resource was contributed by The National Documentation Centre on Drug Use.

Routes of administration of cannabis used for nonmedical purposes and associations with patterns of drug use.

PURPOSE: Little is known regarding cannabis administration routes for nonmedical use-that is, its delivery methods (e.g., joints, water pipe, food). Therefore, we examined the prevalence rates of different cannabis delivery methods and assessed the relationship of the distinct administration routes with problematic drug use. Subgroups of cannabis users were also investigated (i.e., "pure" cannabis users, previously described as employing a harmless route of administration, and water pipe users, previously described as using a harmful route of administration). METHODS: As part of the Cohort Study on Substance Use Risk Factors, 1,763 cannabis users answered questions concerning their drug use (i.e., routes of administration, problematic cannabis use, other illicit drug use). Descriptive statistics, latent class analysis, correlations and t-tests were assessed. RESULTS: The main administration route was "joints with tobacco"; other routes of administration had prevalence rates from 23.99% to 38.23%. In addition, increasing the number of administration routes was associated with more problematic cannabis use, as well as heavier illicit drug use. Water pipes without tobacco were especially linked to heavy drug use patterns, whereas "pure" cannabis use seemed less harmful. CONCLUSIONS: Our findings highlighted that diversification in routes of administration can be associated with heavier illicit drug use. This was especially true for water pipe users, whereas "pure" cannabis users, who did not mix cannabis with tobacco, were an exception. Indeed, these results may be useful for future preventive programs, which may need to focus on those who have diversified routes of administration for cannabis.

A Report from a Local Initiative Concerning Alcohol / Drug Use Among Teenagers 1998-1999

This study was carried out by participants in a North Tipperary Community Services drug/alcohol awareness course. Its objectives were to: assess the level of drug and alcohol awareness among second-level students under the age of 18 years; to find out the extent of under-age drinking;to find out the extent of the use of illegal substances as well as stimulants such as glue and solvents in this age group; and to use this information to develop educational programmes for parents and students. Date was obtained through a survey of 1500 secondary school students in the North Tippeary area. The survey found that, although ilict drug use was very low, abuse of alcohol was quite common.This resource was contributed by The National Documentation Centre on Drug Use.

A Study to Examine the Attitudes of General Practitioners Towards Drug Users in the North East Region of Ireland

The research examines general practitioners attitudes and how these effect the management of drug misusers within their practice. The methodology is quantitative in approach. The instrument used is a structured postal questionnaire. Participants include all general practitioners within the North East region of Ireland. Anonymity and confidentiality of all respondents are guaranteed. Data was collected over a six week period, under the following headings - attitudes and beliefs, factors influencing treatment, treatment options, training and demographics. Attitudes and beliefs towards drug users were measured using a five point Likert scale ranging from strongly agrees to strongly disagree. The data was analysed with the aid of a computer package, SPSS allowing descriptive statistics to be presented. Results indicate that the majority of respondents are male. There appears to be sympathy towards drug users and that treatment approaches should be holistic. However, there appears to be a major lack of confidence in treating and managing drug misusers. Patient, social and practice factors all influence the decision to the drug misuser. Treatment options are varied, ranging from methadone maintenance to referral for residential treatment. However, a number of respondents offer no treatment for drug misusers. General practitioners do not feel adequately trained in treating and/or managing this client group. Results indicate that improved communication, ongoing education and more research is needed in this area.This resource was contributed by The National Documentation Centre on Drug Use.