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Abstract We investigate how European policy initiatives influenced market assessments of sovereign default risk and banking sector fragility during the sovereign debt crisis in four adversely affected countries — Portugal, Ireland, Spain and Italy. We focus on three broad groups of policies: (a) ECB policy actions (monetary and financial support), (b) EU programs (financial and fiscal rules as well as financial support in crisis countries), and (c) domestic austerity programs. We measure immediate market impact effects: what policies changed risk perceptions, using CDS spreads on sovereign bonds and banks in this assessment. We employ dynamic panel and event study methodologies in the empirical work. We find that a number of programs initially stabilized sovereign and bank bond markets (e.g. Outright Monetary Transactions program), although announcement and implementation impacts on markets differed in some cases (e.g. second Covered Market Bond Program). Actions designed to shore up sovereign markets often lowered risk assessments in bank bond markets and policies designed to ensure safety and soundness of the European banking system in some cases significantly impacted sovereign debt markets. Finally, a number of policies designed to stabilize markets had surprisingly little immediate impact on either sovereign or bank bond market risk assessments. [ABSTRACT FROM AUTHOR]

New indices of fiscal rule strength are constructed and, using a dynamic panel econometric model for 27 EU countries over the period 1990–2012, we assess whether national fiscal rules alone help to promote sustainable public finances in the EU or whether they must be supported by good governance in order to be effective. We find that fiscal rules are effective in reducing structural primary deficits at all levels of government efficiency. However, the effect is smaller as government efficiency increases, indicating that fiscal rules and government efficiency are institutional substitutes in terms of promoting fiscal sustainability. We also find that balanced budget rules are the most effective form of fiscal rules. Multiple fiscal rules are found to enhance fiscal solvency. Other institutional features that enhance the effectiveness of fiscal rules are transparency of policies and commitment to implementation of fiscal programs. Supranational rules, however, do not affect the effectiveness of national fiscal rules in reducing the deficit bias. Our results are robust to alternative estimation methods and endogeneity assumptions. [ABSTRACT FROM AUTHOR]

The paper presents a general method for estimating a country's level of fundamental house prices and its interaction with actual house prices. We set up a unified empirical model which can be used to analyze the time-series behavior of the fundamental house price and to test various hypotheses regarding its relation to the actual house price. Conditional forecasts from the model allow us to simulate policy experiments. To illustrate how the methods work, we apply it to data for Sweden. We find a tendency for actual house prices to converge on fundamental prices, albeit rather slowly. To achieve a significant fall in actual house prices it is necessary to increase the user cost substantially. • Estimation of fundamental house prices in Sweden. • Sources of fluctuations in actual and fundamental house prices. • Simulating policy-induced shocks to the housing market. [ABSTRACT FROM AUTHOR]

BACKGROUND: Adverse drug reactions (ADRs) are common in elderly patients. There are various reasons for this, including age- and disease-related alterations in pharmacokinetics and pharmacodynamics as well as the common practice of polypharmacy. The decline in renal function in elderly patients may also predispose them to pharmacological ADRs (type A, augmented). Patients receiving home healthcare may be at even higher risk. OBJECTIVES: To study ADRs as a cause of acute hospital admissions in a defined cohort of elderly patients (aged >or=65 years) registered to receive home healthcare services, with special reference to impaired renal function as a possible risk factor. METHODS: This was a retrospective study of 154 elderly patients aged >or=65 years admitted to the emergency department of a university hospital in Stockholm, Sweden, in October-November 2002. Estimated creatinine clearance (eCL(CR)) was calculated from the Cockcroft-Gault formula, and estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease (MDRD) equation. ADRs were defined according to WHO criteria. All medications administered to patients at admission and at discharge were collated. These and other data were collected from computerized hospital records. RESULTS: ADRs were judged to contribute to or be the primary cause of hospitalization in 22 patients, i.e. 14% of 154 patients registered to receive home healthcare. Eleven of the 22 patients were women. All but one ADR were type A. Excessive doses or drugs unsuitable in renal insufficiency were present in seven patients in the ADR group compared with only four patients in the group without ADRs (p = 0.0001). Patients with ADRs did not differ significantly from those without ADRs in relation to age, plasma creatinine, eCL(CR), weight or number of drugs prescribed at admission. However, women with ADRs were significantly older than women without ADRs (mean +/- SD age 88.8 +/- 5.7 years vs 82.5 +/- 8.0 years, respectively; p = 0.014) and had significantly lower mean +/- SD eCL(CR) values (25.5 +/- 10.8 and 37.1 +/- 17.1 mL/min, respectively; p = 0.035). Median MDRD eGFR was significantly higher than median eCL(CR) (59 [range 6-172] mL/min/1.73 m2 vs 38 [range 5-117] mL/min, respectively; p = 0.0001). CONCLUSIONS: In elderly patients registered to receive home healthcare, 14% of hospital admissions were primarily caused by ADRs. One-third of these ADRs were related to impaired renal function, generally in very old women. These ADRs may be avoided by close monitoring of renal function and adjustments to pharmacotherapy (drug selection and dose), particularly in very elderly women. [ABSTRACT FROM AUTHOR]

Summary: Purpose: Because frequent seizures constitute a major risk factor for sudden unexpected death in epilepsy (SUDEP), the treatment with antiepileptic drugs (AEDs) may play a role for the occurrence of SUDEP. We used data from routine therapeutic drug monitoring (TDM) to study the association between various aspects of AED treatment and the risk of SUDEP. Methods: A nested case–control study was based on a cohort consisting of 6,880 patients registered in the Stockholm County In Ward Care Register with a diagnosis of epilepsy. Fifty-seven SUDEP cases, and 171 controls, living epilepsy patients, were selected from the cohort. Clinical data including data on TDM were collected through medical record review. Results: The relative risk (RR) of SUDEP was 3.7 (95% CI, 1.0–13.1) for outpatients who had no TDM compared with those who had one to three TDMs during the 2 years of observation. RR was 9.5 (1.4–66.0) if carbamazepine (CBZ) plasma levels at the last TDM were above and not within the common target range (20–40 μM). High CBZ levels were associated with a higher risk in patients receiving polytherapy and in those with frequent dose changes. Although the subgroup of patients with high CBZ levels was small (six cases of 33 with CBZ therapy), and the result should be interpreted with caution, no similar associations were demonstrated for phenytoin plasma levels and risk of SUDEP. No association was found between SUDEP risk and within-patient variation in AED levels over time. Conclusions: Polytherapy, frequent dose changes, and high CBZ levels as identified risk factors for SUDEP all point to the risks associated with an unstable severe epilepsy. It is unclear whether high CBZ levels per se represent a risk factor or just reflect other unidentified aspects of a severe epilepsy. Our results, however, prompt further detailed analyses of the possible role of AEDs in SUDEP in larger cohorts and suggest that reasonable monitoring of the drug therapy may be useful to reduce risks. [ABSTRACT FROM AUTHOR]

Purpose: Our aim was to investigate outpatient antibiotic use and assess the impacts of intervention in five Chinese children's hospitals from 2002 to 2006. Methods: The Anatomical Therapeutical Chemical Classification/Defined Daily Doses and Drug Utilization 90% methodologies were used. We also analyzed the relationship between antibiotic consumption and resistant rate in one of the hospitals. Results: The overall antibiotic consumption decreased during the intervention period in some hospitals, and the variation in use between hospitals was also reduced. A decrease in penicillins and first-generation cephalosporins, and an increase in third-generation cephalosporins as well as in the combinations of penicillins and [beta]-lactamase inhibitors were observed. In addition, an increasing resistance to antibiotics was a concern due to antibiotic overconsumption. Conclusions: The intervention had effects on the overall antibiotic use in outpatients. However, over the span of 5 years, there was a decrease in the use of narrow-spectrum antibiotics and an increase in broad-spectrum antibiotics. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the influence of paroxetine on metoprolol concentrations and its effect in patients treated for acute myocardial infarction (AMI) who are routinely given paroxetine as a co-treatment of depression. METHODS: We recruited 17 depressed AMI patients who received metoprolol as a routine part of their therapy (mean dose 75 +/- 39 mg/day). Patients were genotyped for CYP2D6 *3, *4 and gene duplication. Metoprolol and alpha-hydroxy-metoprolol were analyzed in plasma 0, 2, 6 and 12 h post-dose. Heart rates (HR) at rest were registered after each sampling. Paroxetine 20 mg daily was then administered, and all measurements were repeated on day 8. RESULTS: All patients were genotypically extensive metabolizers (EMs) (nine with *1/*1 and eight with *1/*3 or *4). Following the administration of paroxetine, mean metoprolol areas under the concentration-time curve (AUC) increased (1064 +/- 1213 to 4476 +/- 2821 nM x h/mg per kg, P = 0.0001), while metabolite AUCs decreased (1492 +/- 872 to 348 +/- 279 n M x h/mg per kg, P < 0.0001), with an increase of metabolic ratios (MR) (0.9 +/- 1.3 to 26 +/- 29; P < 0.0001). Mean HRs were significantly lower after the study week at each time point. Mean area under the HR versus time curve (AUEC) decreased (835 +/- 88 to 728 +/- 84 beats x h/min; P = 0.0007). Metoprolol AUCs correlated with patients' AUECs at the baseline (Spearman r = -0.64, P < 0.01), but not on the eighth day of the study. A reduction of metoprolol dose was required in two patients due to excessive bradycardia and severe orthostatic hypotension. No other adverse effects of the drugs were identified. CONCLUSION: A pronounced inhibition of metoprolol metabolism by paroxetine was observed in AMI patients, but without serious adverse effects. We suggest, however, that the metoprolol dose is controlled upon initiation and withdrawal of paroxetine. [ABSTRACT FROM AUTHOR]

A point-prevalence survey of five European university hospitals was performed to benchmark antimicrobial drug use in order to identify potential problem areas in prescribing practice and to aid in establishing appropriate and attainable goals. All inpatients at the university hospitals of Rijeka (Croatia), Tartu (Estonia), Riga (Latvia), Vilnius (Lithuania) and Karolinska-Huddinge (Sweden) were surveyed for antimicrobial drug use during a single day. The frequency of antimicrobial drug use was 24% in Rijeka, 30% in Tartu, 26% in Riga, 14% in Vilnius and 32% in Huddinge. Surgical patients were treated with antimicrobial agents more often than medical patients in Riga (53% vs. 31%), Tartu (39% vs. 26%) and Vilnius (54% vs. 25%). Two-thirds of patients in Rijeka, Tartu, Riga and Vilnius, and fewer than half of the patients in Huddinge, received antimicrobial agents intravenously. Broad-spectrum antimicrobial agents were used most commonly in Rijeka. The prevalence of nosocomial infections treated with antibiotics was 9% at Huddinge, and 3–5% at the other centres. Benchmarking antimicrobial drug use at five university hospitals identified differences and problem areas. The high rates of intravenous administration, poor compliance with guidelines, and prolonged surgical prophylaxis were general problems that deserved specific attention at all centres. A change in prescription practices may reduce unnecessary drug use and decrease antimicrobial resistance. [ABSTRACT FROM AUTHOR]

It is a major clinical and public health problem that there is no clear strategy as to how we best make use of information obtained when pregnant women take drugs. For this reason, some pregnant women are not treated as they should be and some are given drugs they should not use. We suggest a monitoring system that combines some of the available datasets in Europe. Using these sources as a starting point, one can develop a system that has sufficient power to detect even rare diseases like congenital malformations and sufficient diversity to detect several possible outcomes from spontaneous abortions to childhood disorders. We also suggest that case-crossover designs should be used in case-control monitoring systems that carry a high risk of recall bias. These considerations are based upon our results from a European Union-funded concerted action called EuroMaP (Medicine and Pregnancy). [ABSTRACT FROM AUTHOR]

A response by U. Bergman and colleagues to a letter to the editor regarding their study on severe acne, occurrence of suicide attempts, and treatment with isotretinoin in the 2010 issue is presented.

To assess the risk for suicide attempt before, during and after treatment with isotretinoin for severe acne. Retrospective cohort-study linking a named patient register of isotretinoin-users 1980–1989 to the hospital discharge- and cause of death registers 1980–2001. 5,756 patients prescribed isotretinoin for severe acne observed for 17,192 person-years before, 2,905 on and 87,120 after treatment. Main outcome measures Standardized Incidence Ratio (SIR): observed divided by expected number of suicide attempts standardized by sex, age and calendar-year, calculated up to three years before, during and up to 15 years after end of treatment. 128 patients were hospitalized for suicide attempt. During the year preceding treatment, the SIR for suicide attempt was elevated: 1.57 (95% CI 0.86 to 2.63) for all (including repeat) attempts, and 1.36 (95% CI 0.65 to 2.50) counting only first attempts. For all and first attempts, SIRs during and up to 6 months after treatment was 1.78 (1.04 to 2.85) and 1.93 (1.08 to 3.18) respectively. The observed number of attempts was close to the expected during the 15 years of follow-up. The number needed to harm was 2,300 new 6-months’ treatments per year, for one additional first suicide attempt to occur. An increased risk for suicide attempt was observed up to six months after treatment with isotretionoin, which motivates a close monitoring of patients regarding suicidal behaviour for up to a year after treatment has ended. The risk for suicide attempts were rising already before treatment, and therefore, an additional risk due to the isotretinoin treatment cannot be established. [ABSTRACT FROM AUTHOR]