Antidepressant prescribing in Irish children: secular trends and international comparison in the context of a safety warning.

BACKGROUND: In 2003, the Irish Medicines Board (IMB) warned against the treatment of childhood depression with selective serotonin reuptake inhibitors (SSRIs) due to increased risk of suicide. This study examined the effect of this warning on the prevalence of anti-depressants in Irish children and compared age and gender trends and international comparisons of prescription rates. METHODS: A retrospective cohort study of the Irish Health Service Executive (HSE) pharmacy claims database for the General Medical Services (GMS) scheme for dispensed medication. Data were obtained for 2002-2011 for those aged ≤15 years. Prevalence of anti-depressants per 1000 eligible population, along with 95 % confidence intervals, were calculated. A negative binomial regression analysis was used to investigate trends and compare rates across years, sex and age groups (0-4, 5-11, 12-15 years). International prescribing data were retrieved from the literature. RESULTS: The prevalence of anti-depressants decreased from 4.74/1000 population (95 % CI: 4.47-5.01) in 2002 to 2.61/1000 population (95 % CI: 2.43-2.80) in 2008. SSRI rates decreased from 2002 to 2008. Prescription rates for contra-indicated SSRIs paroxetine, sertraline and citralopram decreased significantly from 2002 to 2005, and, apart from paroxetine, only small fluctuations were seen from 2005 onwards. Fluoxetine was the most frequently prescribed anti-depressant and rates increased between 2002 and 2011. Anti-depressant rates were higher for younger boys and older girls. The Irish prevalence was lower than the US, similar to the U.K. and higher than Germany and Denmark. CONCLUSIONS: The direction and timing of these trends suggest that medical practitioners followed the IMB advice

Photoactivated chemotherapy (PACT) : the potential of excited-state d-block metals in medicine

The fields of phototherapy and of inorganic chemotherapy both have long histories. Inorganic photoactivated chemotherapy (PACT) offers both temporal and spatial control over drug activation and has remarkable potential for the treatment of cancer. Following photoexcitation, a number of different decay pathways (both photophysical and photochemical) are available to a metal complex. These pathways can result in radiative energy release, loss of ligands or transfer of energy to another species, such as triplet oxygen. We discuss the features which need to be considered when developing a metal-based anticancer drug, and the common mechanisms by which the current complexes are believed to operate. We then provide a comprehensive overview of PACT developments for complexes of the different d-block metals for the treatment of cancer, detailing the more established areas concerning Ti, V, Cr, Mn, Re, Fe, Ru, Os, Co, Rh, Pt, and Cu and also highlighting areas where there is potential for greater exploration. Nanoparticles (Ag, Au) and quantum dots (Cd) are also discussed for their photothermal destructive potential. We also discuss the potential held in particular by mixed-metal systems and Ru complexes

Understanding Others' Regret: A fMRI Study

Previous studies showed that the understanding of others' basic emotional experiences is based on a “resonant” mechanism, i.e., on the reactivation, in the observer's brain, of the cerebral areas associated with those experiences. The present study aimed to investigate whether the same neural mechanism is activated both when experiencing and attending complex, cognitively-generated, emotions. A gambling task and functional-Magnetic-Resonance-Imaging (fMRI) were used to test this hypothesis using regret, the negative cognitively-based emotion resulting from an unfavorable counterfactual comparison between the outcomes of chosen and discarded options. Do the same brain structures that mediate the experience of regret become active in the observation of situations eliciting regret in another individual? Here we show that observing the regretful outcomes of someone else's choices activates the same regions that are activated during a first-person experience of regret, i.e. the ventromedial prefrontal cortex, anterior cingulate cortex and hippocampus. These results extend the possible role of a mirror-like mechanism beyond basic emotions

Prices and distribution margins of in-patent drugs in pharmacy: A comparison in seven European countries

Objectives To compare prices of in-patent active ingredients (AIs) in Europe at three levels (ex-factory prices, net distribution margins and third party payers' prices).Methods We compared the prices in seven EU countries (Belgium, France, Germany, Italy, the Netherlands, Spain and the UK) of the 20 in-patent AIs most sold on the Italian retail market in 2004, based on "sell in" sales data. We calculated the average ex-factory price per unit of each compound in each of the seven countries, weighted by the volumes of all reimbursable package sizes and strengths. We estimated net distribution margins according to the 2004 domestic regulations by deducting any type of mandatory discount. Finally, we added VAT to calculate "third party payer's prices". All prices were expressed in index numbers (Italy = 100).Results Italy had the lowest average ex-factory prices, the Netherlands and particularly the UK had by far the lowest distribution margins, while Germany had by far the highest third party payers' prices. The Netherlands and particularly UK showed a steep decrease from ex-factory to third party payers' prices, while Belgium, Italy and Spain gave the opposite pattern.Conclusions Our study suggests that public authorities can deal with drug prices both by strictly controlling ex-factory prices and by establishing appropriate distribution margins. The latter might be facilitated by liberalizing the distribution sector.

Cemented versus uncemented fixation in total hip replacement: a systematic review and meta-analysis of randomized controlled trials

The optimal method of fixation for primary total hip replacements (THR), particularly fixation with or without the use of cement is still controversial. In a systematic review and metaanalysis of all randomized controlled trials comparing cemented versus uncemented THRS available in the published literature, we found that there is no significant difference between cemented and uncemented THRs in terms of implant survival as measured by the revision rate. Better short-term clinical outcome, particularly an improved pain score can be obtained with cemented fixation. However, the results are unclear for the long-term clinical and functional outcome between the two groups. No difference was evident in the mortality and the post operative complication rate. On the other hand, the radiographic findings were variable and do not seem to correlate with clinical findings as differences in the surgical technique and prosthesis design might be associated with the incidence of osteolysis. We concluded in our review that cemented THR is similar if not superior to uncemented THR, and provides better short term clinical outcomes. Further research, improved methodology and longer follow up are necessary to better define specific subgroups of patients in whom the relative benefits of cemented and uncemented implant fixation can be clearly demonstrated

Effectiveness of medicines review with web-based pharmaceutical treatment algorithms in reducing potentially inappropriate prescribing in older people in primary care: a cluster randomized trial (OPTI-SCRIPT study protocol)

BACKGROUND: Potentially inappropriate prescribing in older people is common in primary care and can result in increased morbidity, adverse drug events, hospitalizations and mortality. In Ireland, 36% of those aged 70 years or over received at least one potentially inappropriate medication, with an associated expenditure of over €45 million. The main objective of this study is to determine the effectiveness and acceptability of a complex, multifaceted intervention in reducing the level of potentially inappropriate prescribing in primary care. METHODS/DESIGN: This study is a pragmatic cluster randomized controlled trial, conducted in primary care (OPTI-SCRIPT trial), involving 22 practices (clusters) and 220 patients. Practices will be allocated to intervention or control arms using minimization, with intervention participants receiving a complex multifaceted intervention incorporating academic detailing, medicines review with web-based pharmaceutical treatment algorithms that provide recommended alternative treatment options, and tailored patient information leaflets. Control practices will deliver usual care and receive simple patient-level feedback on potentially inappropriate prescribing. Routinely collected national prescribing data will also be analyzed for nonparticipating practices, acting as a contemporary national control. The primary outcomes are the proportion of participant patients with potentially inappropriate prescribing and the mean number of potentially inappropriate prescriptions per patient. In addition, economic and qualitative evaluations will be conducted. DISCUSSION: This study will establish the effectiveness of a multifaceted intervention in reducing potentially inappropriate prescribing in older people in Irish primary care that is generalizable to countries with similar prescribing challenges. TRIAL REGISTRATION: Current controlled trials ISRCTN4169400

Risk of drug-related mortality during periods of transition in methadone maintenance treatment: A cohort study

This study aims to identify periods of elevated risk of drug-related mortality during methadone maintenance treatment (MMT) in primary care using a cohort of 3,162 Scottish drug users between January 1993 and February 2004. Deaths occurring during treatment or within 3 days after last methadone prescription expired were considered as cases “on treatment.” Fatalities occurring 4 days or more after leaving treatment were cases “off treatment.” Sixty-four drug-related deaths were identified. The greatest risk of drug-related death was in the first 2 weeks of treatment (adjusted hazard ratio 2.60, 95% confidence interval 1.03–6.56). Risk of drug-related death was lower after the first 30 days following treatment cessation, relative to the first 30 days off treatment. History of psychiatric admission was associated with increased risk of drug-related death in treatment. Increasing numbers of treatment episodes and urine testing were protective. History of psychiatric admission, increasing numbers of urine tests, and coprescriptions of benzodiazepines increased the risk of mortality out of treatment. The risk of drug-related mortality in MMT is elevated during periods of treatment transition, specifically treatment initiation and the first 30 days following treatment dropout or discharg

Depressive vulnerabilities predict depression status and trajectories of depression over one year in persons with acute coronary syndrome

Depression is prevalent in patients with coronary heart disease, with the prevalence estimated at approximately 20% in patients with myocardial infarction [1]. This is significantly higher than that seen in general population samples [2]. The importance of depression is highlighted not only in its prevalence, and its impact on quality of life, but also on the ability of depression to predict cardiovascular prognosis [3-5]. However, while a large literature concerns the prediction of prognosis in depressed cardiac patients, relatively little research is concerned with what happens to depression after the acute hospitalisation phase. Depression is a chronic, episodic condition, and therefore research on what happens to depressive symptoms in the post-acute phase potentially provides vital information for intervention design. While the prevalence of depression is comparatively steady over time, this masks the different trajectories symptoms of depression take [6-8]. Indeed, sophisticated studies have shown different patterns of resolving and persistent depression in patients with heart disease [7, 8]. For example, Martens et al. [7] surveyed 287 patients post-hospitalisation for myocardial infarction at 2 and 12 months. They categorised four groups of patients in relation to depressive symptom status: non-depressed, mildly depressed, moderately depressed and severely depressed. Similarly, Kaptein et al. [8] followed 475 patients with myocardial infarction every 3 months over one year, and their results showed that five distinct groups regarding depression:no depressive symptoms, mild depressive symptoms, moderate and increasing depressive symptoms, significant but decreasing depressive symptoms and significant and increasing depressive symptoms. Thus, the evolution of depression is complex, and in order to design optimal interventions, more knowledge on the predictors of depressive symptoms and such depressive trajectories is needed [9]. While some research has established predictors of depression in patients with coronary heart disease from easily available variables recorded as part of standard hospital care, the results are often contradictory [7, 8, 10-12]. For example, age, sex, medications and left ventricular function have been shown to predict depression in cardiac patients in some of these findings, but not in others. Furthermore, such findings are atheoretical, and thus provide little clue as to how to intervene in such populations [9, 13]. A paucity of evidence exists assessing the relative importance of theoretical vulnerabilities, and their associated interventions, regarding risk of depression and trajectories of depression after acute coronary syndrome (ACS) [14]. While a small number of studies have assessed theoretical vulnerabilities to depression – for example, stressful life events, personality and cognitions have all been associated with depression in cardiac patients [7, 15, 16] – such studies have not measured these vulnerabilities simultaneously, or have not assessed their association with trajectories of depression post-ACS. These vulnerabilities are especially important, given recent findings which suggest that, in patients with ACS, such vulnerabilities predict depression better than do demographic or disease variables [13, 17]. However, both these studies were limited, as they were cross-sectional, and did not allow for the direction of causality to be determined [13, 17]. Also, it was possible that recall bias in depressed patients contributed to a higher self-reported level of such vulnerabilities – thus to inflated correlations between the variables. We therefore report on longitudinal data from our cohort. We aimed to determine a) whether depressive vulnerabilities predicted depression over time, when controlling for baseline depression, and b) whether these vulnerabilities better predicted different types of depression (e.g. persistent depression).</p