Prevalence and determinants of unintended double medication of antihypertensive, lipid-lowering, and hypoglycemic drugs in Austria: a nationwide cohort study.

PURPOSE: Double medication is defined as the unintended overlapping prescription of two identical substances with the same route of administration by two different prescribers to the same patient. Consequences of double medication are reduced patient safety and excess healthcare costs. Based on nationwide prescription data from 2011 covering 97% of Austria's population, we estimated double medication prevalences for treatment of hypertension, hyperlipidemia, and diabetes mellitus. METHODS: We investigated prescriptions of 88 antihypertensive, 16 lipid-lowering and 29 hypoglycemic substances in 7,971,323 persons in 2011. Prevalence of double medication was calculated patientwise (prevalence by patients) and timewise (prevalence by patient-years). Risk factors for double medication were identified by logistic regression. RESULTS: For antihypertensive, lipid-lowering, and hypoglycemic subtances, overall 15.0% (men: 15.1%, women: 15.0%), 13.1% (13.7%, 12.5%), and 13.0% (13.0%, 13.4%) of patients were doubly medicated, respectively. Corresponding prevalences by patient-years were 1.6%, 2.0%, and 1.2%. Logistic regression confirmed lower age and copayment waiver as independent risk factors of double medication. Furthermore, double medication occurred more often with prescriptions from hospitals or internal medicine specialists compared with general practitioners, as well as in August compared with earlier or later in the calendar year. CONCLUSION: While appropriate care or comanagement of patients by internal medicine specialists and general practitioners may explain some of the double prescriptions, our data indicate that unintended double medication is frequent. In Austria, lack of financial incentives of patients to avoid filling duplicate prescriptions explains a considerable fraction of double medication occurrences.

Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation.

BACKGROUND: Good neurological outcome after cardiac arrest is difficult to achieve. Interventions during the resuscitation phase and treatment within the first hours after the event are critical. Experimental evidence suggests that therapeutic hypothermia is beneficial, and several clinical studies on this topic have been published. This review was originally published in 2009; updated versions were published in 2012 and 2016. OBJECTIVES: We aimed to perform a systematic review and meta-analysis to assess the influence of therapeutic hypothermia after cardiac arrest on neurological outcome, survival and adverse events. SEARCH METHODS: We searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 10); MEDLINE (1971 to May 2015); EMBASE (1987 to May 2015); the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1988 to May 2015); and BIOSIS (1989 to May 2015). We contacted experts in the field to ask for information on ongoing, unpublished or published trials on this topic.The original search was performed in January 2007. SELECTION CRITERIA: We included all randomized controlled trials (RCTs) conducted to assess the effectiveness of therapeutic hypothermia in participants after cardiac arrest, without language restrictions. We restricted studies to adult populations cooled by any cooling method, applied within six hours of cardiac arrest. DATA COLLECTION AND ANALYSIS: We entered validity measures, interventions, outcomes and additional baseline variables into a database. Meta-analysis was performed only for a subset of comparable studies with negligible heterogeneity. We assessed the quality of the evidence by using standard methodological procedures as expected by Cochrane and incorporated the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach. MAIN RESULTS: We found six RCTs (1412 participants overall) conducted to evaluate the effects of therapeutic hypothermia - five on neurological outcome and survival, one on only neurological outcome. The quality of the included studies was generally moderate, and risk of bias was low in three out of six studies. When we compared conventional cooling methods versus no cooling (four trials; 437 participants), we found that participants in the conventional cooling group were more likely to reach a favourable neurological outcome (risk ratio (RR) 1.94, 95% confidence interval (CI) 1.18 to 3.21). The quality of the evidence was moderate.Across all studies that used conventional cooling methods rather than no cooling (three studies; 383 participants), we found a 30% survival benefit (RR 1.32, 95% CI 1.10 to 1.65). The quality of the evidence was moderate.Across all studies, the incidence of pneumonia (RR 1.15, 95% CI 1.02 to 1.30; two trials; 1205 participants) and hypokalaemia (RR 1.38, 95% CI 1.03 to 1.84; two trials; 975 participants) was slightly increased among participants receiving therapeutic hypothermia, and we observed no significant differences in reported adverse events between hypothermia and control groups. Overall the quality of the evidence was moderate (pneumonia) to low (hypokalaemia). AUTHORS' CONCLUSIONS: Evidence of moderate quality suggests that conventional cooling methods provided to induce mild therapeutic hypothermia improve neurological outcome after cardiac arrest, specifically with better outcomes than occur with no temperature management. We obtained available evidence from studies in which the target temperature was 34°C or lower. This is consistent with current best medical practice as recommended by international resuscitation guidelines for hypothermia/targeted temperature management among survivors of cardiac arrest. We found insufficient evidence to show the effects of therapeutic hypothermia on participants with in-hospital cardiac arrest, asystole or non-cardiac causes of arrest.

Vasopressors for hypotensive shock.

BACKGROUND: Initial goal-directed resuscitation for hypotensive shock usually includes administration of intravenous fluids, followed by initiation of vasopressors. Despite obvious immediate effects of vasopressors on haemodynamics, their effect on patient-relevant outcomes remains controversial. This review was published originally in 2004 and was updated in 2011 and again in 2016. OBJECTIVES: Our objective was to compare the effect of one vasopressor regimen (vasopressor alone, or in combination) versus another vasopressor regimen on mortality in critically ill participants with shock. We further aimed to investigate effects on other patient-relevant outcomes and to assess the influence of bias on the robustness of our effect estimates. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015 Issue 6), MEDLINE, EMBASE, PASCAL BioMed, CINAHL, BIOSIS and PsycINFO (from inception to June 2015). We performed the original search in November 2003. We also asked experts in the field and searched meta-registries to identify ongoing trials. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing various vasopressor regimens for hypotensive shock. DATA COLLECTION AND ANALYSIS: Two review authors abstracted data independently. They discussed disagreements between them and resolved differences by consulting with a third review author. We used a random-effects model to combine quantitative data. MAIN RESULTS: We identified 28 RCTs (3497 participants) with 1773 mortality outcomes. Six different vasopressors, given alone or in combination, were studied in 12 different comparisons.All 28 studies reported mortality outcomes; 12 studies reported length of stay. Investigators reported other morbidity outcomes in a variable and heterogeneous way. No data were available on quality of life nor on anxiety and depression outcomes. We classified 11 studies as having low risk of bias for the primary outcome of mortality; only four studies fulfilled all trial quality criteria.In summary, researchers reported no differences in total mortality in any comparisons of different vasopressors or combinations in any of the pre-defined analyses (evidence quality ranging from high to very low). More arrhythmias were observed in participants treated with dopamine than in those treated with norepinephrine (high-quality evidence). These findings were consistent among the few large studies and among studies with different levels of within-study bias risk. AUTHORS' CONCLUSIONS: We found no evidence of substantial differences in total mortality between several vasopressors. Dopamine increases the risk of arrhythmia compared with norepinephrine and might increase mortality. Otherwise, evidence of any other differences between any of the six vasopressors examined is insufficient. We identified low risk of bias and high-quality evidence for the comparison of norepinephrine versus dopamine and moderate to very low-quality evidence for all other comparisons, mainly because single comparisons occasionally were based on only a few participants. Increasing evidence indicates that the treatment goals most often employed are of limited clinical value. Our findings suggest that major changes in clinical practice are not needed, but that selection of vasopressors could be better individualised and could be based on clinical variables reflecting hypoperfusion.

Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation.

BACKGROUND: Good neurologic outcome after cardiac arrest is hard to achieve. Interventions during the resuscitation phase and treatment within the first hours after the event are critical. Experimental evidence suggests that therapeutic hypothermia is beneficial, and a number of clinical studies on this subject have been published. This review was originally published in 2009. OBJECTIVES: We performed a systematic review and meta-analysis to assess the effectiveness of therapeutic hypothermia in patients after cardiac arrest. Neurologic outcome, survival and adverse events were our main outcomes. We aimed to perform individual patient data analysis, if data were available, and to form subgroups according to the cardiac arrest situation. SEARCH METHODS: We searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2001, Issue 7); MEDLINE (1971 to July 2011); EMBASE (1987 to July 2011); CINAHL (1988 to July 2011); PASCAL (2000 to July 2011); and BIOSIS (1989 to July 2011). The original search was performed in January 2007. SELECTION CRITERIA: We included all randomized controlled trials assessing the effectiveness of therapeutic hypothermia in patients after cardiac arrest, without language restrictions. Studies were restricted to adult populations cooled with any cooling method, applied within six hours of cardiac arrest. DATA COLLECTION AND ANALYSIS: Validity measures, the intervention, outcomes and additional baseline variables were entered into a database. Meta-analysis was only done for a subset of comparable studies with negligible heterogeneity. For these studies, individual patient data were available. MAIN RESULTS: We included four trials and one abstract reporting on 481 patients in the systematic review. The updated search resulted in no new studies to include. Quality of the included studies was good in three out of five studies. For the three comparable studies on conventional cooling methods all authors provided individual patient data. With conventional cooling methods, patients in the hypothermia group were more likely to reach a best cerebral performance categories (CPC) score of one or two (five point scale: 1 = good cerebral performance, to 5 = brain death) during the hospital stay (individual patient data; RR 1.55; 95% CI 1.22 to 1.96) and were more likely to survive to hospital discharge (individual patient data; RR 1.35; 95% CI 1.10 to 1.65) compared to standard post-resuscitation care. Across all studies, there was no significant difference in reported adverse events between hypothermia and control. AUTHORS' CONCLUSIONS: Conventional cooling methods to induce mild therapeutic hypothermia seem to improve survival and neurologic outcome after cardiac arrest. Our review supports the current best medical practice as recommended by the International Resuscitation Guidelines.

Vasopressors for hypotensive shock.

BACKGROUND: Initial goal directed resuscitation for shock usually includes the administration of intravenous fluids, followed by initiating vasopressors. Despite obvious immediate effects of vasopressors on haemodynamics their effect on patient relevant outcomes remains controversial. This review was originally published in 2004 and was updated in 2011. OBJECTIVES: Our primary objective was to assess whether particular vasopressors reduce overall mortality, morbidity, and health-related quality of life. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 2), MEDLINE, EMBASE, PASCAL BioMed, CINAHL, BIOSIS, and PsycINFO (from inception to March 2010). The original search was performed in November 2003. We also asked experts in the field and searched meta-registries for ongoing trials. SELECTION CRITERIA: Randomized controlled trials comparing various vasopressor regimens for hypotensive shock. DATA COLLECTION AND ANALYSIS: Two authors abstracted data independently. Disagreement between the authors was discussed and resolved with a third author. We used a random-effects model for combining quantitative data. MAIN RESULTS: We identified 23 randomized controlled trials involving 3212 patients, with 1629 mortality outcomes. Six different vasopressors, alone or in combination, were studied in 11 different comparisons.All 23 studies reported mortality outcomes; length of stay was reported in nine studies. Other morbidity outcomes were reported in a variable and heterogeneous way. No data were available on quality of life or anxiety and depression outcomes. We classified 10 studies as being at low risk of bias for the primary outcome mortality; only four studies fulfilled all trial quality items.In summary, there was no difference in mortality in any of the comparisons between different vasopressors or combinations. More arrhythmias were observed in patients treated with dopamine compared to norepinephrine. Norepinephrine versus dopamine, as the largest comparison in 1400 patients from six trials, yielded almost equivalence (RR 0.95, 95% confidence interval 0.87 to 1.03). Vasopressors used as add-on therapy in comparison to placebo were not effective either. These findings were consistent among the few large studies as well as in studies with different levels of within-study bias risk. AUTHORS' CONCLUSIONS: There is some evidence of no difference in mortality between norepinephrine and dopamine. Dopamine appeared to increase the risk for arrhythmia. There is not sufficient evidence of any difference between any of the six vasopressors examined. Probably the choice of vasopressors in patients with shock does not influence the outcome, rather than any vasoactive effect per se. There is not sufficient evidence that any one of the investigated vasopressors is clearly superior over others.

Cochrane corner: hypothermia for neuroprotection in adults after cardiopulmonary resuscitation.

BACKGROUND: Good neurologic outcome after cardiac arrest is hard to achieve. Interventions during the resuscitation phase and treatment within the first hours after the event are critical. Experimental evidence suggests that therapeutic hypothermia is beneficial, and a number of clinical studies on this subject have been published. OBJECTIVES: We performed a systematic review and meta-analysis to assess the effectiveness of therapeutic hypothermia in patients after cardiac arrest. Neurologic outcome, survival and adverse events were our main outcome parameters. We aimed to perform individual patient data analysis if data were available, and to from subgroups according to the cardiac arrest situation. SEARCH STRATEGY: We searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2007 Issue 1); MEDLINE (1971 to January 2007); EMBASE (1987 to January 2007); CINAHL (1988 to January 2007); PASCAL (2000 to January 2007); and BIOSIS (1989 to January 2007). SELECTION CRITERIA: We included all randomized controlled trials assessing the effectiveness of the therapeutic hypothermia in patients after cardiac arrest without language restrictions. Studies were restricted to adult populations cooled with any cooling method applied within six hours of cardiac arrest. DATA COLLECTION AND ANALYSIS: Validity measures, the intervention, outcome parameters and additional baseline variables were entered into the database. Meta-analysis was only done for a subset of comparable studies with negligible heterogeneity. For these studies individual patient data were available. MAIN RESULTS: Four trials and one abstract reporting on 481 patients were included in the systematic review. Quality of the included studies was good in three out of five included studies. For the three comparable studies on conventional cooling methods all authors provided individual patient data. With conventional cooling methods patients in the hypothermia group were more likely to reach a best cerebral performance categories score of one or two (CPC, five point scale; 1=good cerebral performance, to 5=brain death) during hospital stay (individual patient data; RR, 1.55; 95% CI 1.22 to 1.96) and were more likely to survive to hospital discharge (individual patient data; RR, 1.35; 95% CI 1.10 to 1.65) compared to standard post-resuscitation care. Across all studies there was no significant difference in reported adverse events between hypothermia and control. AUTHORS' CONCLUSIONS: Conventional cooling methods to induce mild therapeutic hypothermia seem to improve survival and neurologic outcome after cardiac arrest. Our review supports the current best medical practice as recommended by the International Resuscitation Guidelines.

Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation.

BACKGROUND: Good neurologic outcome after cardiac arrest is hard to achieve. Interventions during the resuscitation phase and treatment within the first hours after the event are critical. Experimental evidence suggests that therapeutic hypothermia is beneficial, and a number of clinical studies on this subject have been published. OBJECTIVES: We performed a systematic review and meta-analysis to assess the effectiveness of therapeutic hypothermia in patients after cardiac arrest. Neurologic outcome, survival and adverse events were our main outcome parameters. We aimed to perform individual patient data analysis if data were available, and to from subgroups according to the cardiac arrest situation. SEARCH STRATEGY: We searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2007 Issue 1); MEDLINE (1971 to January 2007); EMBASE (1987 to January 2007); CINAHL (1988 to January 2007); PASCAL (2000 to January 2007); and BIOSIS (1989 to January 2007). SELECTION CRITERIA: We included all randomized controlled trials assessing the effectiveness of the therapeutic hypothermia in patients after cardiac arrest without language restrictions. Studies were restricted to adult populations cooled with any cooling method applied within six hours of cardiac arrest. DATA COLLECTION AND ANALYSIS: Validity measures, the intervention, outcome parameters and additional baseline variables were entered into the database. Meta-analysis was only done for a subset of comparable studies with negligible heterogeneity. For these studies individual patient data were available. MAIN RESULTS: Four trials and one abstract reporting on 481 patients were included in the systematic review. Quality of the included studies was good in three out of five included studies. For the three comparable studies on conventional cooling methods all authors provided individual patient data. With conventional cooling methods patients in the hypothermia group were more likely to reach a best cerebral performance categories score of one or two (CPC, five point scale; 1= good cerebral performance, to 5 = brain death) during hospital stay (individual patient data; RR, 1.55; 95% CI 1.22 to 1.96) and were more likely to survive to hospital discharge (individual patient data; RR, 1.35; 95% CI 1.10 to 1.65) compared to standard post-resuscitation care. Across all studies there was no significant difference in reported adverse events between hypothermia and control. AUTHORS' CONCLUSIONS: Conventional cooling methods to induce mild therapeutic hypothermia seem to improve survival and neurologic outcome after cardiac arrest. Our review supports the current best medical practice as recommended by the International Resuscitation Guidelines.

Influence of socioeconomic status and gender on stroke treatment and diagnostics.

BACKGROUND AND PURPOSE: Female patients and patients with a lower level socioeconomic status (SES) often experience less favorable health outcomes. We aimed to investigate whether gender and socioeconomic status of patients with acute ischemic stroke or transient ischemic attack are associated with different diagnostic and treatment strategies. METHODS: The risk factors of interest were gender and SES. We predefined our diagnostic and treatment end points according to current stroke guidelines and used multivariate models to adjust for age, stroke severity, and comorbidities. RESULTS: A total of 2606 patients were included in the analysis. Women were less likely to receive antiplatelet agents within the first 48 hours after admission (OR: 0.59, 95% CI: 0.53 to 0.89) and more likely to have their blood glucose measured on admission than men (OR: 1.52, 95% CI: 1.1 to 2.1). With higher SES patients were more likely to receive a TTE or TTE during hospital stay. Women were almost twice as likely to receive a prescription for antidepressants at discharge OR of 1.96 (95% CI: 1.48 to 2.59). CONCLUSIONS: Socioeconomic status and gender are associated with some diagnostic and treatment differences of acute ischemic stroke. Most pronounced were a reduced chance for women to receive antiplatelet therapy on admission and a reduced chance for a TTE and TEE with a lower level of SES, whereas the rate of thrombolysis was unbiased by gender and SES.

Strict normoglycaemic blood glucose levels in the therapeutic management of patients within 12h after cardiac arrest might not be necessary.

AIM OF THE STUDY: The admission blood glucose level after cardiac arrest is predictive of outcome. However the blood glucose levels in the post-resuscitation period, that are optimal remains a matter of debate. We wanted to assess an association between blood glucose levels at 12h after restoration of spontaneous circulation and neurological recovery over 6 months. MATERIALS AND METHODS: A total of 234 patients from a multi-centre trial examining the effect of mild hypothermia on neurological outcome were included. According to the serum glucose level at 12h after restoration of spontaneous circulation, quartiles (Q) were generated: Median (range) glucose concentrations were for QI 100 (67-115 mg/dl), QII 130 (116-143 mg/dl), QIII 162 (144-193 mg/dl) and QIV 265 (194-464 mg/dl). RESULTS: In univariate analysis there was a strong non-linear association between blood glucose and good neurological outcome (odds ratio compared to QIV): QI 8.05 (3.03-21.4), QII 13.41 (4.9-36.67), QIII 1.88 (0.67-5.26). After adjustment for sex, age, "no-flow" and "low-flow" time, adrenaline (epinephrine) dose, history of coronary artery disease and myocardial infarction, and therapeutic hypothermia, this association still remained strong: QI 4.55 (1.28-16.12), QII 13.02 (3.29-49.9), QIII 1.37 (0.38-5.64). CONCLUSION: There is a strong non-linear association of survival with good neurological outcome and blood glucose levels 12h after cardiac arrest even after adjusting for potential confounders. Not only strict normoglycaemia, but also blood glucose levels from 116 to 143 mg/dl were correlated with survival and good neurological outcome, which might have an important therapeutic implication.

[Generic drugs: quality, efficacy, safety and interchangeability]. / Generika: Qualität, Wirksamkeit, Sicherheit und Austauschbarkeit.

Since the introduction of generic drugs to the pharmaceutical market a sometimes emotional debate exists whether they are well-investigated and of high quality. There is some uncertainty about whether evidence of bioequivalence is enough to guarantee efficacy and safety of generic drugs. Some physicians ask the question if competent authorities are able to ascertain that the pharmaceutical quality of generics is acceptable. Doctors and patients sometimes are ill at ease about the interchangeability of innovator and generic products. This article describes how the European Union legislation ensures that a generic drug is only approved if its risk-benefit relationship is favourable and that it is essentially similar to the innovator product. In this context pharmacokinetic parameters are accepted as surrogates for clinical results because bioequivalence means therapeutic equivalence as well. For most drugs, current bioequivalence testing generally enables clinicians to routinely substitute generic for innovator products. Published findings, however, suggest that particular drugs may not be ideally suited for generic substitution when a patient is already on that drug. These are the so called critical dose medicinal products (drugs with a narrow therapeutic range). When starting a new therapy with any generic drug, however, its similarity to the innovator drug in terms of efficacy, safety and quality is guaranteed.

Efficacy and safety of endovascular cooling after cardiac arrest: cohort study and Bayesian approach.

BACKGROUND AND PURPOSE: Recently 2 randomized trials in comatose survivors of cardiac arrest documented that therapeutic hypothermia improved neurological recovery. The narrow inclusion criteria resulted in an international recommendation to cool only a restricted group of primary cardiac arrest survivors. In this retrospective cohort study we investigated the efficacy and safety of endovascular cooling in unselected survivors of cardiac arrest. METHODS: Consecutive comatose survivors of cardiac arrest, who were either cooled for 24 hours to 33 degrees C with endovascular cooling or treated with standard postresuscitation therapy, were analyzed. Complication data were obtained by retrospective chart review. RESULTS: Patients in the endovascular cooling group had 2-fold increased odds of survival (67/97 patients versus 466/941 patients; odds ratio 2.28, 95% CI, 1.45 to 3.57; P<0.001). After adjustment for baseline imbalances the odds ratio was 1.96 (95% CI, 1.19 to 3.23; P=0.008). When discounting the observational data in a Bayesian analysis by using a sceptical prior the posterior odds ratio was 1.61 (95% credible interval, 1.06 to 2.44). In the endovascular cooling group, 51/97 patients (53%) survived with favorable neurology as compared with 320/941 (34%) in the control group (odds ratio 2.15, 95% CI, 1.38 to 3.35; P=0.0003; adjusted odds ratio 2.56, 1.57 to 4.17). There was no difference in the rate of complications except for bradycardia. CONCLUSIONS: Endovascular cooling improved survival and short-term neurological recovery compared with standard treatment in comatose adult survivors of cardiac arrest. Temperature control was effective and safe with this device.

Influence of socioeconomic status on mortality after stroke: retrospective cohort study.

BACKGROUND AND PURPOSE: Low socioeconomic status is associated with increased morbidity and mortality from stroke. The purpose of this study was to investigate the association between 4 independent measures of socioeconomic status and mortality of patients with acute ischemic stroke and transient ischemic attack. METHODS: Socioeconomic status was assessed by taking into account levels of education, occupation, occupational status, and income. The end point was overall mortality. We used Cox proportional hazard models to adjust for age, sex, and severity of stroke on admission. RESULTS: A total of 2606 stroke patients were followed up for a median of 2.5 years. Unskilled workers had a hazard ratio of 1.87 for death after stroke (95% CI, 1.37 to 2.55) and skilled workers had a hazard ratio of 1.61 (95% CI, 1.23 to 2.11) compared with white-collar workers. Of 4 income groups, patients with the second lowest level of income had a hazard ratio of 1.60 (95% CI, 1.10 to 2.33) and patients with the third lowest level of income had a hazard ratio of 1.71 (95% CI, 1.25 to 2.32) compared with patients with the highest income. The hazard ratio for death after stroke for early retired patients was 1.75 (95% CI, 1.01 to 3.04) compared with stroke patients in the active workforce at the time of the event. CONCLUSIONS: Socioeconomic status is associated with survival of patients with acute stroke after adjustment for age, sex, and severity of stroke. The influence of socioeconomic status seems to continue to affect the outcome largely independent of stroke severity.

Heme oxygenase-1 genotype and restenosis after balloon angioplasty: a novel vascular protective factor.

OBJECTIVES: We investigated the association of the heme oxygenase-1 (HO-1) promoter genotype with the inflammatory response and restenosis after balloon angioplasty. BACKGROUND: Heme oxygenase-1, which is induced by balloon angioplasty, can inhibit neointima formation and vascular remodeling. A dinucleotide repeat in the HO-1 gene promoter shows a length polymorphism that modulates HO-1 gene transcription. Short (<25 guanosine thymidine [GT]) repeats are associated with a 10-fold greater up-regulation of HO-1 than are longer repeats. METHODS: We studied 381 consecutive patients who underwent femoropopliteal balloon angioplasty (n = 210) and comparison groups with femoropopliteal stenting (n = 68) and lower limb angiography (n = 103). C-reactive protein (CRP) was measured at baseline, 24, and 48 h. We evaluated patency at six months by duplex sonography and assessed the association of the length of GT repeats in the HO-1 gene promoter with postintervention CRP and restenosis. RESULTS: Restenosis within six months was found in 74 patients (35%) after balloon angioplasty and in 21 patients (31%) after stenting. After balloon angioplasty, carriers of the short length (<25 GT) dinucleotide repeats had a lower postintervention CRP at 24 h (p = 0.009) and 48 h (p < 0.001) and a reduced risk for restenosis (adjusted relative risk 0.43, 95% confidence interval: 0.24 to 0.71, p < 0.001) compared with patients with longer alleles. After stenting or angiography, we found no association between the HO-1 genotype with CRP or restenosis. CONCLUSIONS: The HO-1 promoter genotype that controls the degree of HO-1 up-regulation in response to stress stimuli is associated with the postintervention inflammatory response and the restenosis risk after balloon angioplasty.

Mutation of the prothrombin gene and thrombotic events in patients with polycythemia vera or essential thrombocythemia: a cohort study.

The association between a prothrombin mutation and the risk of thrombosis was analyzed in 214 patients with polycythemia vera or essential thrombocythemia. The rate for venous thrombotic events was 14.7/100 patient-years in patients with the prothrombin mutation compared to 0.8 in patients without the mutation (rate ratio 17.5).

How should abridged scientific articles be presented in journals? A survey of readers and authors.

SEVERAL SCIENTIFIC AND GENERAL MEDICAL JOURNALS publish full-length articles on their Web sites and abridged versions in their print journals. We surveyed a stratified random sample of BMJ readers and authors to elicit their preferred format for the abridged print version. Each participant received a research paper abridged in 3 different formats: conventional abridged version, journalistic version and enhanced-abstract version. Overall, 45% (95% confidence interval [CI] 42%-48%) of the respondents said they liked the conventional version most, 31% (95% CI 28%-34%) preferred the journalistic version and 25% (95% CI 22%-27%) preferred the enhanced-abstract version. Twenty-eight percent (95% CI 25%-32%) indicated that use of the journalistic format for abridged articles would very likely stop them from submitting papers to BMJ, and 13% (95% CI 11%-16%) said the use of the enhanced-abstract version would stop them from submitting to BMJ. Publishers of general medical journals who publish shortened articles should consider that authors and readers prefer a more conventional style of abridged papers.

Intra-articular hyaluronic acid for the treatment of osteoarthritis of the knee: systematic review and meta-analysis.

BACKGROUND: Osteoarthritis of the knee affects up to 10% of the elderly population. The condition is frequently treated by intra-articular injection of hyaluronic acid. We performed a systematic review and meta-analysis of randomized controlled trials to assess the effectiveness of this treatment. METHODS: We searched MEDLINE, EMBASE, CINAHL, BIOSIS and the Cochrane Controlled Trial Register from inception until April 2004 using a combination of search terms for knee osteoarthritis and hyaluronic acid and a filter for randomized controlled trials. We extracted data on pain at rest, pain during or immediately after movement, joint function and adverse events. RESULTS: Twenty-two trials that reported usable quantitative information on any of the predefined end points were identified and included in the systematic review. Even though pain at rest may be improved by hyaluronic acid, the data available from these studies did not allow an appropriate assessment of this end point. Patients who received the intervention experienced a reduction in pain during movement: the mean difference on a 100-mm visual analogue scale was -3.8 mm (95% confidence interval [CI] -9.1 to 1.4 mm) after 2-6 weeks, -4.3 mm (95% CI -7.6 to -0.9 mm) after 10-14 weeks and -7.1 mm (95% CI -11.8 to -2.4 mm) after 22-30 weeks. However, this effect was not compatible with a clinically meaningful difference (expected to be about 15 mm on the visual analogue scale). Furthermore, the effect was exaggerated by trials not reporting an intention-to-treat analysis. No improvement in knee function was observed at any time point. Even so, the effect of hyaluronic acid on knee function was more favourable when allocation was not concealed. Adverse events occurred slightly more often among patients who received the intervention (relative risk 1.08, 95% CI 1.01 to 1.15). Only 4 trials explicitly reported allocation concealment, had blinded outcome assessment and presented intention-to-treat data. INTERPRETATION: According to the currently available evidence, intra-articular hyaluronic acid has not been proven clinically effective and may be associated with a greater risk of adverse events. Large trials with clinically relevant and uniform end points are necessary to clarify the benefit-risk ratio.

Clostridium difficile causing acute renal failure: case presentation and review.

AIM: Clostridium difficile infection is primarily a nosocomial infection but asymptomatic carriers of Clostridium difficile can be found in up to 5% of the general population. Ampicillin, cephalosporins and clindamycin are the antibiotics that are most frequently associated with Clostridium difficile-associated diarrhea or colitis. Little is known about acute renal failure as a consequence of Clostridium difficile-associated diarrhea. METHODS: In this case report, we describe the course of Clostridium difficile-associated diarrhea in an 82-year-old patient developing acute renal failure. Stopping the offending agent and symptomatic therapy brought a rapid improvement of diarrhea and acute renal failure, full recovery was gained 18 d after admission. In a systematic review we looked for links between the two conditions. RESULTS: The link between Clostridium difficile-associated diarrhea and acute renal failure in our patient was most likely volume depletion. However, in experimental studies a direct influence of Clostridium difficile toxins on renal duct cells could be shown. CONCLUSION: Rapid diagnosis, nonspecific supportive treatment and specific antibiotic treatment, especially in the elderly, may lower excess mortality Clostridium difficile-associated diarrhea and renal failure being possible complications.

Reporting on statistical methods to adjust for confounding: a cross-sectional survey.

BACKGROUND: The use of complex statistical models to adjust for confounding is common in medical research. OBJECTIVE: To determine the frequency and adequacy of adjustment for confounding in medical articles. DESIGN: Cross-sectional survey. SETTING: 34 scientific medical journals with a high impact factor. MEASUREMENTS: Frequency of reporting on methods used to adjust for confounding in 537 original research articles published in January 1998. RESULTS: Of the 537 articles, 169 specified that adjustment for confounding was used. In 1 paper in 10, it was unclear which statistical method was used or for which variables adjustment was made. In 45% of papers, it was not clear how multicategory or continuous variables were treated in the analysis. Inadequate reporting was less frequent if an author was affiliated with a department of statistics, epidemiology, or public health and if articles were published in journals with a high impact factor. CONCLUSIONS: Details of methods used to adjust for confounding are frequently not reported in original research articles.

Potential savings in prescription drug costs for hypertension, hyperlipidemia, and diabetes mellitus by equivalent drug substitution in Austria: a nationwide cohort study.

BACKGROUND: Healthcare systems spend considerable proportions of their budgets on pharmaceutical treatment of hypertension, hyperlipidemia, and diabetes mellitus. From data on almost all residents of Austria, a country with mandatory health insurance and universal health coverage, we estimated potential cost savings by substituting prescribed medicines with the cheapest medicines that were of the same chemical substance and strength, and available during the same time. METHODS: Data from 8.3 million persons (98.5 % of the total Austrian insured population) from 2009-2012 were analyzed. Real prescription costs for antihypertensive, lipid-lowering, and hypoglycemic medicines achievable by same-substance, same-strength drug substitution were computed for each active ingredient, and per gender and 1-year age category of patients. RESULTS: In 2012, health insurance providers spent 231.3 million, 77.8 million, and 91.9 million for antihypertensive, lipid-lowering, and diabetes medications, of which 52.2 million (22.6 %), 15.9 million (20.5 %), and 4.1 million (4.5 %), respectively, could have been saved by same-substance drug substitution. Highest potential savings were calculated for amlodipine (8.0 million, 65.4 %), simvastatin (12.2 million, 59.3 %), and metformin (2.4 million, 54.6 %), respectively. Higher savings for men than for women resulted from differing prescribed cumulative dosages and proportions of patients with co-payment waiver. Potential cost savings in antihypertensive and lipid-lowering drugs increased from 2009-2012. CONCLUSION: Our study highlights the cost-savings potential from arguably the most acceptable of interventions, simply switching to the cheapest available same-substance, same-strength product. In 2012, this strategy could have reduced costs for antihypertensive, lipid-lowering, and hypoglycemic treatment by up to 18.0 %.

Determination of lipid profiles and use of statins in patients with ischemic stroke or transient ischemic attack.

BACKGROUND AND PURPOSE: Statins reduce the risk of myocardial infarction and stroke in patients with vascular disease. Inappropriate serum lipid determination and underuse of statins have been documented in patients with coronary artery disease. Evaluation of hyperlipidemia and treatment with statins in patients with recent ischemic cerebrovascular events have not yet been investigated. METHODS: We determined the frequency of total cholesterol (TC) and low-density lipoprotein cholesterol measurements and the use of statins in a multicenter prospective cohort study of 1743 patients with acute ischemic stroke or transient ischemic attack (TIA). Using multivariate logistic regression analysis, we determined the influence of several clinical variables on lipid measurements and the prescription of statins at hospital discharge. RESULTS: TC was measured in 90% and low-density lipoprotein cholesterol was measured in 48% of the patients. Differences between the centers accounted for most of the observed variability in a multivariate model. Statin prescription also varied widely between the centers. The prescription of a statin at discharge was most strongly associated with statin intake before the event and with increasing TC levels; elderly patients received statins less often. Coronary artery disease, peripheral artery disease, and other manifestations of atherosclerosis were not independently associated with the use of statins; 68% of the patients with manifest atherosclerosis and TC levels >200 mg/dL were discharged without a statin. CONCLUSIONS: The determination of serum lipid profiles varies widely between different centers. Statins are highly underused in patients with recent ischemic stroke or TIA, particularly in those in whom statins are indicated according to existing recommendations (eg, patients with additional coronary artery disease and hypercholesterolemia). Currently, international guidelines concerning the use of statins are not adequately implemented in clinical practice in patients with stroke or TIA.