Minority quasispecies of drug-resistant HIV-1 that lead to early therapy failure in treatment-naive and -adherent patients.

BACKGROUND: Early virological failure of antiretroviral therapy associated with the selection of drug-resistant human immunodeficiency virus type 1 in treatment-naive patients is very critical, because virological failure significantly increases the risk of subsequent failures. Therefore, we evaluated the possible role of minority quasispecies of drug-resistant human immunodeficiency virus type 1, which are undetectable at baseline by population sequencing, with regard to early virological failure. METHODS: We studied 4 patients who experienced early virological failure of a first-line regimen of lamivudine, tenofovir, and either efavirenz or nevirapine and 18 control patients undergoing similar treatment without virological failure. The key mutations K65R, K103N, Y181C, M184V, and M184I in the reverse transcriptase were quantified by allele-specific real-time polymerase chain reaction performed on plasma samples before and during early virological treatment failure. RESULTS: Before treatment, none of the viruses showed any evidence of drug resistance in the standard genotype analysis. Minority quasispecies with either the M184V mutation or the M184I mutation were detected in 3 of 18 control patients. In contrast, all 4 patients whose treatment was failing had harbored drug-resistant viruses at low frequencies before treatment, with a frequency range of 0.07%-2.0%. A range of 1-4 mutations was detected in viruses from each patient. Most of the minority quasispecies were rapidly selected and represented the major virus population within weeks after the patients started antiretroviral therapy. All 4 patients showed good adherence to treatment. Nonnucleoside reverse-transcriptase inhibitor plasma concentrations were in normal ranges for all 4 patients at 2 separate assessment times. CONCLUSIONS: Minority quasispecies of drug-resistant viruses, detected at baseline, can rapidly outgrow and become the major virus population and subsequently lead to early therapy failure in treatment-naive patients who receive antiretroviral therapy regimens with a low genetic resistance barrier.

Methadone maintenance treatment (MMT) in general practice or in specialized centers: profile of patients in the Swiss Canton of Vaud.

We studied profile of patients (n=1782) treated in specialized centers and general practice (GP) enrolled in methadone maintenance treatment (MMT) programs during 2001 in the Swiss Canton of Vaud. We found that GPs treated the majority of patients (76%). Specialized centers treated a higher proportion of patients with uncontrolled intravenous use of cocaine and heroin, and prescribed neuroleptics as concomitant medication three times more frequently than GPs. Patients treated in specialized centers were more likely to undergo screening for HIV, HBV, HCV, and receive complete HBV immunization. In conclusion, specialized centers are more likely to treat severely addicted patients and patients with a poor global assessment (physical, psychiatric, and social).

Hypertonie oculaire dans l'orbitopathie dysthyroidienne: considerations physiopathologiques, diagnostiques et therapeutiques. A propos de trois cas significatifs. [Intraocular high pressure in thyroid-associated orbitopathy: physiopathological mechanisms, diagnosis, and management. Three case reports]

PURPOSE: To determine the mechanisms and treatment of ocular hypertension in patients with thyroid-associated orbitopathy and to differenciate it from glaucomatous damage. DESIGN: Three case reports. METHODS: Retrospective review of clinical findings, course, and treatment of the three patients. RESULTS: Elevated intraocular pressure in thyroid-associated orbitopathy observed in the three cases may involve different physiopathological abnormalities such as disturbances of venous circulation, compression by infiltrative muscles, and long corticosteroid use. In the first two cases, defects demonstrated in the perimetry are in consistent with glaucomatous damage. In the third case, visual field abnormalities may be compatible with a glaucomatous disease, but all defects resolved after therapy. Treatement was of the greatest difficulty for the three cases, associating antiglaucomatous medication, steroids, orbital radiotherapy, orbital decompression and extraocular muscle surgery. Intraocular pressure was controlled in all cases. CONCLUSIONS: Elevated intraocular pressure in thyroid-associated orbitopathy is distinguished from glaucomatous disease by its physiopathological mechanisms, clinical course, visual field defects, and treatment. The management of this hypertension is closely related to the treatment of dysthyroid orbitopathy.

Economies in Drug Usage in the Irish Healthcare Setting

Economies in Drug Usage in the Irish Healthcare Setting Click here to download PDF 237kb

Strategic Framework for Role Expansion of Nurses and Midwives: Promoting Quality Patient Care

This strategic document sets policy direction for the enhancement of nursing and midwifery roles. It builds on the achievements of the past ten years for nursing and midwifery and is set within the context of clinical and regulatory standards. The Programme for Government 2011 and policy initiatives such as legislative changes for the introduction of nurse and midwife medication prescribing create significant opportunities toexpand the role of nurses and midwives in a proactive manner.   Click here to download   PDF 1.12MB

Could moderate alcohol consumption help prevent the metabolic syndrome and diabetes mellitus ?

Aim and purpose: Moderate alcohol consumption has been associated with lower risk of diabetes mellitus, but few data exist on the metabolic syndrome and on the metabolic impact of heavy drinking. The aim of our study was to investigate the complex relationship between alcohol and the metabolic syndrome and diabetes mellitus in a population-based study in Switzerland with high mean alcohol consumption. Design and methods: In 6188 adults aged 35 to 75, alcohol consumption was categorized as 0, 1-6, 7-13, 14-20, 21-27, 28-34 and >= 35 drinks/week or as nondrinkers, moderate (1-13 drinks), high (14-34 drinks) and very high (>= 35 drinks) alcohol consumption. The metabolic syndrome was defined according to the ATP-III criteria and diabetes mellitus as fasting glycemia >= 7 mmol/l or self-reported medication.We used multivariate analysis adjusted for age, gender, smoking status, physical activity and education level to determine the prevalence of the conditions according to drinking categories. Results: 73% (n = 4502) of the participants consumed alcohol, 16% (n = 993) were high drinkers and 2% (n = 126) very high drinkers. In multivariate analysis, alcohol consumption had a U-shaped relationship with the metabolic syndrome and diabetes mellitus. The prevalence of the metabolic syndrome significantly differed between nondrinkers (24%), moderate (19%), high (20%) and very high drinkers (29%) (P<= 0.005). The prevalence of diabetes mellitus also significantly differed between nondrinkers (6.0%), moderate (3.6%), high (3.8%) and very high drinkers (6.7%) (P<= 0.05). These relationships did not differ according to beverage types. Conclusions: The prevalence of the metabolic syndrome and diabetes mellitus decrease with moderate alcohol consumption and increase with heavy drinking, without differences according to beverage types. Recommending to limit alcohol consumption to 1-2 drinks/day might help prevent these conditions in primary care Metabolic Syndrome and Diabetes Mellitus.

Cloona Oasis Centre - Davette Martin

The organisation helps those with mental ill health and those suffering addiction. This is their second community-pharmacy project. The first focussed on men and this project will move on to work with women. Women who have been referred to Cloona Oasis have been through hardship. The Pharmacist will work with them to develop their confidence, explain their medication and break down barriers so that they can access other services.

TB Factsheet

What is TB (tuberculosis)? TB is a serious but curable infectious disease. It usually affects the lungs but it can affect other parts of the body. What are the symptoms? Any of the following symptoms may occur: . Cough . Phlegm . High temperature . Sweating at night . Weight loss . Fatigue / general tiredness . Swollen glands If you are concerned that you might have TB, or develop any of these symptoms, please visit your family doctor for advice. How do you catch TB? It is usually spread through the air from someone with the infectious type of TB. The germ gets into the air when that person coughs, sneezes or spits. Who can get TB? Anyone can get TB but it is difficult to catch. It mainly depends on the amount of time that is spent in contact with someone with infectious TB. What if I have been in close contact with someone with infectious TB? If you are identified as a contact at risk from TB then you will be invited for screening. Initial screening consists of a skin test to determine if your immune system recognises TB. The skin test is called the Mantoux test, the result of which needs to be read 48 hours later. People who have a positive skin test and / or evidence of TB infection found on chest X-ray, or who are unwell will be investigated further by a specialist doctor and may be treated with a course of anti-TB medication. How is TB treated? TB is curable. Treatment consists of a long course of different types of specialist antibiotics. What happens next? If you have been identified as a close contact of the case, you will be invited for screening by the accompanying letter. Otherwise, you will have received a general information letter, and have not been identified as requiring screening at this time.

For your heart's sake stop smoking

On World Heart Day, 29 September 2011, the Public Health Agency is urging all smokers to stop smoking and reduce their risk of developing heart disease (cardiovascular disease - CVD) or suffering a stroke or a heart attack.Heart disease is one of the leading causes of death and illness in the UK. Research shows that smoking is one of the main contributors of the disease, causing around 25,000 deaths a year in the UK. Cigarette smokers are two times more likely than non-smokers to suffer a heart attack.The majority of people who suffer a heart attack before the age of 50 are smokers. Cigarette smoke causes heart disease by:· reducing oxygen to the heart;· increasing blood pressure and heart rate;· increasing blood clotting;· damaging cells that line coronary arteries and other blood vessels, causing narrowing of the arteries.From the moment smoke reaches your lungs, your heart is forced to work harder. Your pulse quickens, forcing your heart to beat an extra 10 to 25 times per minute, as many as 36,000 additional times per day. Because of the irritating effect of nicotine and other components of tobacco smoke, your heartbeat is more likely to be irregular. This can contribute to cardiac arrhythmia and many other serious coronary conditions, such as heart attack.For smokers who already suffer from heart problems, quitting will dramatically help. Many heart patients notice an almost immediate improvement when they stop smoking. Often, they need less medication and can cope better with physical exertion.Gerry Bleakney, Head of Health and Social Wellbeing Improvement, PHA, said: "Smoking is one of the major causes of cardiovascular disease and smokers are almost twice as likely to have a heart attackas someone who has never smoked. One in every two long-term smokers will die prematurely from smoking-related diseases, many suffer very poor health before they die. However one year after successfully quitting smoking, an individual will have reduced their risk of having a heart attack to half that of a person continuing to smoke."Across Northern Ireland, there are over 600 support services for people who wish to stop smoking, based in GP surgeries, community pharmacies, hospitals, community centres and workplaces. I would encourage everyone who is thinking about quitting to log on to our Want 2 Stop website: www.want2stop.info and order a 'Quit Kit' free of charge alternatively contact the Smokers' Helpline on 0808 812 8008."

Hypertension artérielle réfractaire au traitement due au syndrome d'apnées du sommeil et à la prise de médicaments [Obstructive sleep apnea and drugs as causes of treatment-resistant hypertension].

Treatment-resistant hypertension is still common despite the availability of several types of antihypertensive agents acting by different mechanisms. The existence of refractory hypertension should lead to rule out "white-coat hypertension", poor adherence to prescribed drugs as well as classical causes of secondary hypertension such as renal artery stenosis, primary aldosteronism, pheochromocytoma and renal disease. It is also important to consider the possible existence of obstructive sleep apnea or the regular intake of vasopressive drugs or substances.

Fish pedicures: Information for the Public

Although the risk of catching an infection as a result of a fish spa pedicure is likely to be very low, it cannot be completely excluded. However, there are certain things you can do to further reduce your risk of catching or spreading an infection when having one of these treatments.Choosing a salonUse your personal judgment: as with all beauty salons, if it looks unsanitary, do not go there for your treatment. If you are very concerned about the cleanliness of a salon you visit, you can report this to your local Environmental Health department, who will be able to perform an inspection of the premises.When having a treatment, a trained member of staff should perform an inspection of your feet both beforehand, to check for any broken skin / infections, and afterwards, to check for signs of bleeding. They should also ask you to wash your feet with soap and water before putting them in the tank, to make sure that any products you have used that could be harmful to the fish are washed away, and to reduce the risk of spreading any infection.Ask your therapist what other procedures the salon has in place to minimise the risk of infection. The Health Protection Agency, England has produced a set of guidelines for salons which, if followed, will ensure any potential risk of infection is kept to an absolute minimum.Before having the treatment The HPA has identified a number of health conditions or prior treatments which may mean that you should not have a fish pedicure. These are:Leg waxing or shaving in last 24 hoursAny open cuts/wounds/abrasions/broken skin on the feet or lower legsInfection on the feet (including athlete's foot, verruca)Psoriasis, eczema or dermatitis affecting the feet or lower legsDiabetes (increased risk of infection)Infection with a blood borne virus such as Hepatitis B or Hepatitis C or HIVAny immune deficiency due to illness or medicationBleeding disorders or on anticoagulant medication (e.g. heparin or warfarinMore information and advice on fish spa pedicures and the full set of guidance can be found on the Health Protection website www.hpa.org.uk

Perinatal arrhythmias.

Cardiac arrhythmias are very frequent in fetuses and newborns. The prognosis depends on the nature of the arrhythmias but is most often either spontaneously benign or following short-term medication administration. A correct diagnosis is essential for both management and prognosis. It is based on echocardiography during the fetal period and mainly on history, physical exam, and electrocardiogram after birth, but other modalities are available to record transient arrhythmic events. Irregular rhythms are mostly benign and rarely require therapy. In most fetuses and infants, tachyarrhythmias resolve spontaneously or require short-term administration of antiarrhythmics. Approximately one third of these may recur later on, especially during adolescence. Persistent bradyarrhythmias might require pacemaker implantation when associated with failure to thrive or with risk of sudden death. CONCLUSION: Arrhythmias in fetuses and infants are very common and mostly benign. History, physical exam, and recording of the arrhythmia are essential to make a correct diagnosis and establish an appropriate management for the rare potentially harmful arrhythmias.

The expression of GABA receptors in the human auditory cortex

Abstract : GABA, the primary inhibitory neurotransmitter, and its receptors play an important role in modulating neuronal activity in the central nervous system and are implicated in many neurological disorders. In this study, GABAA and GABAB receptor subunit expression was visualized by immunohistochemistry in human auditory areas TC (= primary auditory area), TB, and TA. Both hemispheres from nine neurologically normal subjects and from four patients with subacute or chronic stroke were included. In normal brains, GABAA receptor subunit (α1, α2, & β2/3) labeling produced neuropil staining throughout all cortical layers as well as labeling fibers and neurons in layer VI for all auditory areas. Densitometry profiles displayed differences in GABAA subunit expression between primary and non-primary areas. In contrast to the neuropil labeling of GABAA subunits, GABAB1 and GABAB2 subunit immunoreactivity was revealed on neuronal somata and proximal dendritic shafts of pyramidal and non-pyramidal neurons in layers II-III, more strongly on supra- than in infragranular layers. No differences were observed between auditory areas. In stroke cases, we observed a downregulation of the GABAA receptor α2 subunit in granular and infragranular layers, while the other GABAA and the two GABAB receptor subunits remained unchanged. Our results demonstrate a strong presence of GABAA and GABAB receptors in the human auditory cortex, suggesting a crucial role of GABA in shaping auditory responses in the primary and non-primary auditory areas. The differential laminar and area expression of GABAA subunits that we have found in the auditory areas and which is partially different from that in other cortical areas speaks in favor of a fine turning of GABA-ergic transmission in these different compartments. In contrast, GABAB expression displayed laminar, but not areal differences; its basic pattern was also very similar to that of other cortical areas, suggesting a more uniform role within the cerebral cortex. In subacute and chronic stroke, the selective GABAA α2 subunit downregulation is likely to influence postlesional plasticity and susceptibility to medication. The absence of changes in the GABAB receptors suggests different regulation than in other pathological conditions, such as epilepsy, schizophrenia or bipolar disorder, in which a downregulation has been reported. Résumé : GABA, le principal neurotransmetteur inhibiteur, et ses récepteurs jouent un rôle important en tant que modulateur de l'activité neuronale dans le système nerveux central et sont impliqués dans de nombreux désordres neurologiques. Dans cette étude, l'expression des sous-unités des récepteur GABAA et GABAB a été visualisée par immunohistochimie dans les aires auditives du cortex humains: le TC (= aire auditif primaire), le TB, et le TA. Les deux hémisphères de neuf sujets considérés normaux du point de vue neurologique et de quatre patients ayant subis un accident cérébro-vasculaire et se trouvant dans la phase subaiguë ou chronique étaient inclues. Dans les cerveaux normaux, les immunohistochimies contre les sous-unités α1, α2, & β2/3 du récepteur GABAA ont marqué le neuropil dans toutes les couches corticales ainsi que les fibres et les neurones de la couche VI dans toutes les aires auditives. Le profile densitométrique montre des différences dans l'expression des sous-unités du récepteur GABAA entre les aires primaires et non-primaires. Contrairement au marquage de neuropil par les sous-unités du recepteur GABAA, 1'immunoréactivité des sous-unités GABAB1 et GABAB2 a été révélée sur les corps cellulaires neuronaux et les dendrites proximaux des neurones pyramidaux et non-pyramidaux dans les couches II-III et est plus dense dans les couches supragranulaires que dans les couches infragranulaires. Aucune différence n'a été observée entre les aires auditives. Dans des cas lésionnels, nous avons observé une diminution de la sous-unité α2 du récepteur GABAA dans les couches granulaires et infragranulaires, alors que le marquage des autres sous-unités du récepteur GABAA et des deux sous-unités de récepteur GABAB reste inchangé. Nos résultats démontrent une présence forte des récepteurs GABAA et GABAB dans le cortex auditif humain, suggérant un rôle crucial du neurotransmetteur GABA dans la formation de la réponse auditive dans les aires auditives primaires et non-primaires. L'expression différentielle des sous-unités de GABAA entre les couches corticales et entre les aires auditives et qui est partiellement différente de celle observée dans d'autres aires corticales préconise une modulation fine de la transmission GABA-ergic en ces différents compartiments. En revanche, l'expression de GABAB a montré des différences laminaires, mais non régionales ; son motif d'expression de base est également très semblable à celui d'autres aires corticales, suggérant un rôle plus uniforme dans le cortex cérébral. Dans les phases subaiguë et chronique des accidents cérébro-vasculaires, la diminution sélective de la sous-unité α2 du recepteur GABAA est susceptible d'influencer la plasticité et la susceptibilité postlésionnelle au médicament. L'absence de changement pour les récepteurs GABAB suggère que le récepteur est régulé différemment après un accident cerebro-vasculaire par rapport à d'autres conditions pathologiques, telles que l'épilepsie, la schizophrénie ou le désordre bipolaire, dans lesquels une diminution de ces sous-unités a été rapportée.

Impact of a computerized physician order entry system on compliance with prescription accuracy requirements.

OBJECTIVE: To assess the change in non-compliant items in prescription orders following the implementation of a computerized physician order entry (CPOE) system named PreDiMed. SETTING: The department of internal medicine (39 and 38 beds) in two regional hospitals in Canton Vaud, Switzerland. METHOD: The prescription lines in 100 pre- and 100 post-implementation patients' files were classified according to three modes of administration (medicines for oral or other non-parenteral uses; medicines administered parenterally or via nasogastric tube; pro re nata (PRN), as needed) and analyzed for a number of relevant variables constitutive of medical prescriptions. MAIN OUTCOME MEASURE: The monitored variables depended on the pharmaceutical category and included mainly name of medicine, pharmaceutical form, posology and route of administration, diluting solution, flow rate and identification of prescriber. RESULTS: In 2,099 prescription lines, the total number of non-compliant items was 2,265 before CPOE implementation, or 1.079 non-compliant items per line. Two-thirds of these were due to missing information, and the remaining third to incomplete information. In 2,074 prescription lines post-CPOE implementation, the number of non-compliant items had decreased to 221, or 0.107 non-compliant item per line, a dramatic 10-fold decrease (chi(2) = 4615; P < 10(-6)). Limitations of the computerized system were the risk for erroneous items in some non-prefilled fields and ambiguity due to a field with doses shown on commercial products. CONCLUSION: The deployment of PreDiMed in two departments of internal medicine has led to a major improvement in formal aspects of physicians' prescriptions. Some limitations of the first version of PreDiMed were unveiled and are being corrected.

Soilse annual review 2010.

Soilse, the HSE addiction rehabilitation programme in Dublin North Central, experienced another challenging year in 2010. However, despite budget constraints and logistical and building difficulties, we prioritised the needs of recovering drug abusers with considerable success. Throughout the year, we had enquiries, referrals, programme uptake and successful outcomes. In terms of addiction, the problems are as enduring as ever with complex needs and limited progression opportunities. The rehabilitation strategy published in 2007 has had no practical effect. Yet Soilse saw a clear and positive impact from our work in terms of: stabilising service users; achieving detox; encouraging participants to move from our prescribed medication to our drugfree service; and consolidating these outcomes. Our evidence base continually validates our approach with people who want to become independent of services being facilitated to do so. Soilse did well in 2010 in terms of educational and vocational outcomes, particularly through FETAC but also through comprehensive care planning. We faced protracted difficulties as a result of the staff moratorium and budget cuts, but continued to deliver a professional service, keeping morale and performance high. Our service is based on the following practice standards: holistic assessment care planning care management interagency work quality assurance, and customer service involvementThis resource was contributed by The National Documentation Centre on Drug Use.