Report to the Minister for Health from the Health Insurance Authority (Redacted) on an evaluation and analysis of returns for 1 July 2012 to 30 June 2013 including advice on risk equalisation credits

Report to the Minister for Health from the Health Insurance Authority (Redacted) on an evaluation and analysis of returns for 1 July 2012 to 30 June 2013 including advice on risk equalisation credits Click here to download PDF 11MB

HIA Report to the Minister for Health on an evaluation and analysis of returns for 1 July 2011 to 30 June 2012 including advice

HIA Report to the Minister for Health The Department of health requested that the Health Insurance Authority provide a report to the Minister ‘in anticipation of the enactment of the health Insurance (Amendment) Bill 2012.” Click here to download PDF 8.87MB The Health Insurance (Amendment) Bill 2012 Link to the Minister’s Second Stage Speech to the Dáil on 14 November 2012          

The Road to Recovery: A New Approach to Tackling Scotland's Drug Problem

The Scottish National Drugs Strategy requires the 22 regional Drug Action Teams to prepare and submit to the Scottish Executive annual action plans for tackling drug misuse in their areas. These plans should address national and local priorities, including their contribution to the achievement of national targets. These comprise three parts: Part A provides an overview of the DAT structures and working; Part B provides detailed information on current local services and Part C reports plans for 2003/04.This resource was contributed by The National Documentation Centre on Drug Use.

S. aureus surveillance report quarter ending 1 April 2013 to 30 June 2013

S. aureus surveillance report quarter ending 1 April 2013 to 30 June 2013

C.difficle surveillance report 1 April 2013 to 30 June 2013

C.difficle surveillance report quarter ending 1 April 2013 to 30 June 2013

Interaction between ATM and PARP-1 in response to DNA damage and sensitization of ATM deficient cells through PARP inhibition

ATM and PARP-1 are two of the most important players in the cell's response to DNA damage. PARP-1 and ATM recognize and bound to both single and double strand DNA breaks in response to different triggers. Here we report that ATM and PARP-1 form a molecular complex in vivo in undamaged cells and this association increases after gamma-irradiation. ATM is also modified by PARP-1 during DNA damage. We have also evaluated the impact of PARP-1 absence or inhibition on ATM-kinase activity and have found that while PARP-1 deficient cells display a defective ATM-kinase activity and reduced gamma-H2AX foci formation in response to gamma-irradiation, PARP inhibition on itself is able to activate ATM-kinase. PARP inhibition induced gamma H2AX foci accumulation, in an ATM-dependent manner. Inhibition of PARP also induces DNA double strand breaks which were dependent on the presence of ATM. As consequence ATM deficient cells display an increased sensitivity to PARP inhibition. In summary our results show that while PARP-1 is needed in the response of ATM to gamma irradiation, the inhibition of PARP induces DNA double strand breaks (which are resolved in and ATM-dependent pathway) and activates ATM kinase.

The impact of the nelfinavir resistance-conferring mutation D30N on the susceptibility of HIV-1 subtype B to other protease inhibitors

The human immunodeficiency virus type 1 (HIV-1) protease mutation D30N is exclusively selected by the protease inhibitor (PI) nelfinavir and confers resistance to this drug. We demonstrate that D30N increases the susceptibility to saquinavir (SQV) and amprenavir in HIV-1 subtype B isolates and that the N88D mutation in a D30N background neutralizes this effect. D30N also suppresses indinavir (IDV) resistance caused by the M46I mutation. Interestingly, in patients with viruses originally containing the D30N mutation who were treated with IDV or SQV, the virus either reversed this mutation or acquired N88D, suggesting an antagonistic effect of D30N upon exposure to these PIs. These findings can improve direct salvage drug treatment in resource limited countries where subtype B is epidemiologically important and extend the value of first and second line PIs in these populations.

In vivo enzymatic activity of acetylCoA synthetase in skeletal muscle revealed by 13C turnover from hyperpolarized [1-13C]acetate to [1-13C]acetylcarnitine

BACKGROUND: Acetate metabolism in skeletal muscle is regulated by acetylCoA synthetase (ACS). The main function of ACS is to provide cells with acetylCoA, a key molecule for numerous metabolic pathways including fatty acid and cholesterol synthesis and the Krebs cycle. METHODS: Hyperpolarized [1-(13)C]acetate prepared via dissolution dynamic nuclear polarization was injected intravenously at different concentrations into rats. The (13)C magnetic resonance signals of [1-(13)C]acetate and [1-(13)C]acetylcarnitine were recorded in vivo for 1min. The kinetic rate constants related to the transformation of acetate into acetylcarnitine were deduced from the 3s time resolution measurements using two approaches, either mathematical modeling or relative metabolite ratios. RESULTS: Although separated by two biochemical transformations, a kinetic analysis of the (13)C label flow from [1-(13)C]acetate to [1-(13)C]acetylcarnitine led to a unique determination of the activity of ACS. The in vivo Michaelis constants for ACS were KM=0.35±0.13mM and Vmax=0.199±0.031μmol/g/min. CONCLUSIONS: The conversion rates from hyperpolarized acetate into acetylcarnitine were quantified in vivo and, although separated by two enzymatic reactions, these rates uniquely defined the activity of ACS. The conversion rates associated with ACS were obtained using two analytical approaches, both methods yielding similar results. GENERAL SIGNIFICANCE: This study demonstrates the feasibility of directly measuring ACS activity in vivo and, since the activity of ACS can be affected by various pathological states such as cancer or diabetes, the proposed method could be used to non-invasively probe metabolic signatures of ACS in diseased tissue.

Aptitude au volant: quelle conduite [Aptitude to drive: what road to take?].

Tout médecin de premier recours devrait pouvoir se prononcer sur l'aptitude à la conduite automobile de son patient. La problématique du conducteur âgé, dépendant soit de l'alcool ou de drogues, sous traitement de médicaments psychotropes, ou encore diabétique, est abordée à la lumière des dispositions légales et des récentes recommandations. Cet article aborde également les aspects relatifs aux problèmes neurologiques, cardiologiques et orthopédiques. Any primary care doctor should be able to decide on the fitness to drive of a given patient. The issue of an older driver, patients addicted to alcohol or drugs, under current psychotropic drug treatment, or diabetic, is discussed in the light of legal provisions and current recommendations. This article also discusses aspects associated with neurological, cardiac and orthopedic issues.

Multibacillary leprosy patients with high and persistent serum antibodies to leprosy IDRI diagnostic-1/LID-1: higher susceptibility to develop type 2 reactions

Leprosy inflammatory episodes [type 1 (T1R) and type 2 (T2R) reactions] represent the major cause of irreversible nerve damage. Leprosy serology is known to be influenced by the patient’s bacterial index (BI) with higher positivity in multibacillary patients (MB) and specific multidrug therapy (MDT) reduces antibody production. This study evaluated by ELISA antibody responses to leprosy Infectious Disease Research Institute diagnostic-1 (LID-1) fusion protein and phenolic glycolipid I (PGL-I) in 100 paired serum samples of 50 MB patients collected in the presence/absence of reactions and in nonreactional patients before/after MDT. Patients who presented T2R had a median BI of 3+, while MB patients with T1R and nonreactional patients had median BI of 2.5+ (p > 0.05). Anti-LID-1 and anti-PGL-I antibodies declined in patients diagnosed during T1R (p < 0.05). Anti-LID-1 levels waned in MB with T2R at diagnosis and nonreactional MB patients (p < 0.05). Higher anti-LID-1 levels were seen in patients with T2R at diagnosis (vs. patients with T1R at diagnosis, p = 0.008; vs. nonreactional patients, p = 0.020) and in patients with T2R during MDT (vs. nonreactional MB, p = 0.020). In MB patients, high and persistent anti-LID-1 antibody levels might be a useful tool for clinicians to predict which patients are more susceptible to develop leprosy T2R.

On ignoring scientific evidence: The bumpy road to enlightenment

It is well accepted that people resist evidence that contradicts their beliefs.Moreover, despite their training, many scientists reject results that are inconsistent withtheir theories. This phenomenon is discussed in relation to the field of judgment anddecision making by describing four case studies. These concern findings that clinical judgment is less predictive than actuarial models; simple methods have proven superiorto more theoretically correct methods in times series forecasting; equal weighting ofvariables is often more accurate than using differential weights; and decisions cansometimes be improved by discarding relevant information. All findings relate to theapparently difficult-to-accept idea that simple models can predict complex phenomenabetter than complex ones. It is true that there is a scientific market place for ideas.However, like its economic counterpart, it is subject to inefficiencies (e.g., thinness,asymmetric information, and speculative bubbles). Unfortunately, the market is only correct in the long-run. The road to enlightenment is bumpy.