Podcasts about results during

N Engl J Med 2005;353:1095-1104Background: Prior trials on revascularization in patients with acute coronary syndromes without ST-segment elevation have yielded mixed results. While FRISC II and TACTICS-TIMI 18 demonstrated a significant reduction in myocardial infarction, this benefit was not observed in RITA 3. None of these trials showed a significant reduction in mortality. Further research is needed to guide treatment strategies in this population, particularly after the introduction of early use of clopidogrel and intensive lipid-lowering therapy.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.The Invasive versus Conservative Treatment in Unstable Coronary Syndromes (ICTUS) trial sough to test the hypothesis that an early invasive strategy is superior to selective invasive strategy for patients with non-ST elevation myocardial infarction (NSTEMI).Patients: Eligible patients had to have all of the following: Worsening symptoms of ischemia or symptoms at rest with the last episode being 24 hours before randomization, elevated cardiac troponin T level (≥0.03 μg per liter); and either ischemic EKG changes (defined as ST-segment depression or transient ST-segment elevation exceeding 0.05 mV, or T-wave inversion of ≥0.2 mV in two contiguous leads) or a documented history of coronary artery disease.Patients were excluded if they were older than 80 years, had an indication for primary percutaneous coronary intervention or fibrinolytic therapy, hemodynamic instability or overt congestive heart failure, oral anticoagulant drugs use in the past 7 days, fibrinolytic treatment within the past 96 hours, percutaneous coronary intervention within the past 14 days, elevated bleeding risk, plus others.Baseline characteristics: The trial randomized 1,200 patients from 42 Dutch hospitals – 604 randomized to early invasive strategy and 596 randomized to selective invasive strategy.The average age of patients was 62 years and 74% were men. Approximately 39% had hypertension, 14% had diabetes, 35% had hyperlipidemia, 23% had prior myocardial infarction and 41% were current smokers.Approximately 48% of the patients had ST deviation equal to or greater than 0.1 mV.Procedures: Patients were randomly assigned in a 1:1 ratio to undergo early invasive vs selective invasive strategy.Patients received 300 mg of aspirin at the time of randomization, followed by at least 75 mg daily indefinitely, and enoxaparin (1 mg/kg for a maximum of 80 mg) subcutaneously twice daily for at least 48 hours. The early use of clopidogrel (300 mg immediately, followed by 75 mg daily) in addition to aspirin was recommended to the investigators after the drug was approved for acute coronary syndrome in 2002. Intensive lipid-lowering therapy, preferably atorvastatin 80 mg daily or the equivalent was recommended as soon as possible after randomization. All interventional procedures during the index admission were performed with the use of abciximab.Patients assigned to the early invasive strategy were scheduled to undergo angiography within 24 - 48 hours after randomization. Patients assigned to the selective invasive strategy underwent coronary angiography if they had refractory angina despite optimal medical therapy, hemodynamic or rhythm instability, or significant ischemia on pre-discharge exercise test.In both groups, percutaneous coronary intervention (PCI) was performed when appropriate, without providing more details in the manuscript.The level of creatine kinase MB was measured at 6-hour intervals during the first day, after each new clinical episode of ischemia, and after each percutaneous revascularization procedure.Endpoints: The primary endpoint was a composite of all-cause death, myocardial infarction, or rehospitalization for angina at 1-year.The estimated sample size to provide 80% power to detect 25% relative risk difference between the two treatment groups at 5% alpha was 1,200 patients. This assumed that 21% of the patients in the early invasive arm would experience the primary outcome.Results: During the index admission, 98% of the patients in the early invasive strategy arm underwent coronary angiogram compared to 53% in the selective invasive arm. At 1-year, 79% of the patients in the early invasive strategy arm underwent revascularization compared to 54% in the selective invasive arm.The primary outcome was not significantly different between both treatment groups (22.7% with early invasive vs 21.2% with selective invasive, RR: 1.07; 95% CI: 0.87 - 1.33; p= 0.33). All-cause death was the same in both groups (2.5%). Myocardial infarction was significantly higher with the early invasive strategy (15.0% vs. 10.0%, RR: 1.50, 95% CI: 1.10 – 2.04; p= 0.005), while rehospitalization for angina was lower with early invasive (7.4% vs. 10.9%, RR: 0.68, 95% CI: 0.47 – 0.98; p= 0.04). Most myocardial infarctions were revascularization related and these were significantly more frequent with early invasive (11.3% vs 5.4%). Spontaneous myocardial infarctions were 3.7% with early invasive and 4.6% with selective invasive and this was not statistically significant.Major bleeding, not related CABG, during the index admission was more frequent with the early invasive strategy (3.1% vs 1.7%).There were no significant subgroup interactions for the primary outcome, including based on ST deviation and troponin levels.Conclusion: In patients with NSTEMI, an early invasive strategy was not superior to selective invasive strategy in reducing the composite endpoint of all-cause death, myocardial infarction, or rehospitalization for angina at 1-year. An early invasive strategy was associated with more myocardial infarctions with a number needed to harm of 20 patients, which was secondary to revascularization related myocardial infarction. An early invasive strategy reduced rehospitalization for angina with a number needed to treat of approximately 29 patients.The ICTUS trial showed that revascularization can cause harm and highlighted how counting procedural myocardial infarctions can influence outcome estimates. While there is ongoing debate about the significance of periprocedural myocardial infarctions, evidence indicates an association with increased mortality. Whether periprocedural myocardial infarctions are 'less severe' than spontaneous myocardial infarctions remains controversial, as their impact varies based on infarct size and patient characteristics. This underscores the importance of including all-cause mortality or advanced systolic heart failure as endpoints in trials of revascularization.Patients in ICTUS received better background medical therapy compared to prior trials in this area. While this could be responsible for the divergent results compared to other prior trials. It also highlights the heterogeneity of NSTEMI patients and that an invasive strategy is not appropriate for all.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Covid 12/15/22: China's Wave Begins, published by Zvi on December 15, 2022 on LessWrong. Cases increased this week, as expected. Deaths also increased, which I did not expect so soon, indicating a bigger and faster winter wave. That was not the big event in the West this week with respect to Covid. The big event this week in the West's Covid experience was a memory of events past. Patrick McKenzie wrote a very long and very worthwhile magnum opus about his efforts in VaccinateCA to get vaccine shots into arms, and what he learned about our government and public health systems along the way. If you read one thing this week, read his story. You can also read my key facts and takeaways post, and this thread with another person's remembrances (here are Patrick's takes on that). Patrick also offers his thoughts on implications for charitable efforts at the EA Forum, which includes this gem: If I had to point at any one artifact in particular, Inadequate Equilibria is a good articulation of a larger memeplex that made me comfortable with “If the evidence of a system's operation contradicts what the Efficient Market Hypothesis counsels is the probable functioning of the system, trust the evidence. Thousands of lives savable by one dedicated team of non-specialists is actually not all that low probability.” Yes. What else happened recently? China stopped attempting to contain Covid-19. They have accepted that the costs of continuing to do this are unacceptably high. Instead, they have decided they are content to contain official case numbers while they brace for the impact of the Covid surge they have successfully put off for three years. It is their turn to have trouble staffing hospitals, to have panic buying and shortages and voluntarily deserted streets. I wish them the best of luck in getting through this as best they can. Executive Summary Patrick McKenzie wrote about VaccineCA. You should read it, and remember. China is finally experiencing the Covid wave they have postponed for three years. Cases and deaths are on the rise, the winter wave is looking a bit larger. Let's run the numbers. The Numbers Predictions Predictions from Last Week: 371k cases (+5%) and 2,240 deaths (-6%). Results: 391k cases (+10%) and 2,610 deaths (+9%). Predictions for Next Week: 435k cases (+10%) and 2,900 deaths (+10%). (Note: North Dakota dumped a lot of deaths on us after reporting no deaths at all for months, so I reduced that number to something high but not impossible.) Case number came in modestly higher than expected. Compounding the expectation there makes things likely to get substantially worse than previously expected, yet still nothing at all like what we saw last winter. Deaths being up again rather than down (despite the ND adjustment), in a way I did not expect, since the timing on it seems premature, makes it that much more clear this is a real and large winter wave, and indicates that cases have likely gone up a bunch more than the numbers show, with the extra cases not being reported. Deaths Cases Physical World Modeling and Long Covid Observational study on Paxlovid in age 50+ population (paper). Results: During the study period, 12 541 (28.1%) patients were prescribed nirmatrelvir plus ritonavir, and 32 010 (71.9%) were not. Patients prescribed nirmatrelvir plus ritonavir were more likely to be older, have more comorbidities, and be vaccinated. The composite outcome of hospitalization or death occurred in 69 (0.55%) patients who were prescribed nirmatrelvir plus ritonavir and 310 (0.97%) who were not (adjusted risk ratio, 0.56 [95% CI, 0.42 to 0.75]). Recipients of nirmatrelvir plus ritonavir had lower risk for hospitalization (adjusted risk ratio, 0.60 [CI, 0.44 to 0.81]) and death (adjusted risk ratio, 0.29 [CI, 0.12 to 0.71]). Strange to say this might be not worth th...

Link to original articleWelcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Covid 12/15/22: China's Wave Begins, published by Zvi on December 15, 2022 on LessWrong. Cases increased this week, as expected. Deaths also increased, which I did not expect so soon, indicating a bigger and faster winter wave. That was not the big event in the West this week with respect to Covid. The big event this week in the West's Covid experience was a memory of events past. Patrick McKenzie wrote a very long and very worthwhile magnum opus about his efforts in VaccinateCA to get vaccine shots into arms, and what he learned about our government and public health systems along the way. If you read one thing this week, read his story. You can also read my key facts and takeaways post, and this thread with another person's remembrances (here are Patrick's takes on that). Patrick also offers his thoughts on implications for charitable efforts at the EA Forum, which includes this gem: If I had to point at any one artifact in particular, Inadequate Equilibria is a good articulation of a larger memeplex that made me comfortable with “If the evidence of a system's operation contradicts what the Efficient Market Hypothesis counsels is the probable functioning of the system, trust the evidence. Thousands of lives savable by one dedicated team of non-specialists is actually not all that low probability.” Yes. What else happened recently? China stopped attempting to contain Covid-19. They have accepted that the costs of continuing to do this are unacceptably high. Instead, they have decided they are content to contain official case numbers while they brace for the impact of the Covid surge they have successfully put off for three years. It is their turn to have trouble staffing hospitals, to have panic buying and shortages and voluntarily deserted streets. I wish them the best of luck in getting through this as best they can. Executive Summary Patrick McKenzie wrote about VaccineCA. You should read it, and remember. China is finally experiencing the Covid wave they have postponed for three years. Cases and deaths are on the rise, the winter wave is looking a bit larger. Let's run the numbers. The Numbers Predictions Predictions from Last Week: 371k cases (+5%) and 2,240 deaths (-6%). Results: 391k cases (+10%) and 2,610 deaths (+9%). Predictions for Next Week: 435k cases (+10%) and 2,900 deaths (+10%). (Note: North Dakota dumped a lot of deaths on us after reporting no deaths at all for months, so I reduced that number to something high but not impossible.) Case number came in modestly higher than expected. Compounding the expectation there makes things likely to get substantially worse than previously expected, yet still nothing at all like what we saw last winter. Deaths being up again rather than down (despite the ND adjustment), in a way I did not expect, since the timing on it seems premature, makes it that much more clear this is a real and large winter wave, and indicates that cases have likely gone up a bunch more than the numbers show, with the extra cases not being reported. Deaths Cases Physical World Modeling and Long Covid Observational study on Paxlovid in age 50+ population (paper). Results: During the study period, 12 541 (28.1%) patients were prescribed nirmatrelvir plus ritonavir, and 32 010 (71.9%) were not. Patients prescribed nirmatrelvir plus ritonavir were more likely to be older, have more comorbidities, and be vaccinated. The composite outcome of hospitalization or death occurred in 69 (0.55%) patients who were prescribed nirmatrelvir plus ritonavir and 310 (0.97%) who were not (adjusted risk ratio, 0.56 [95% CI, 0.42 to 0.75]). Recipients of nirmatrelvir plus ritonavir had lower risk for hospitalization (adjusted risk ratio, 0.60 [CI, 0.44 to 0.81]) and death (adjusted risk ratio, 0.29 [CI, 0.12 to 0.71]). Strange to say this might be not worth th...

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.30.510383v1?rss=1 Authors: Castro, C., Z Rivera, L., Prado, P., Cuadros, J., Cortes, J. P., Espinoza, V., Weinstein, A., Zanartu, M. Abstract: Purpose This study aims to describe variations in acoustic and electroencephalography measures when speaking in the presence of background noise (Lombard effect) in participants with typical voice and normal hearing. Method Twenty-one participants with typical voices and normal hearing uttered simple vocal tasks in three sequential background conditions: Baseline (in quiet), Lombard (in noise), and Recovery (five minutes after removing the noise). Acoustic and electroencephalography signals were recorded in all conditions. The noise used in the Lombard condition consisted of speech-shaped noise at 80 dB SPL sent by headphones. Acoustic measure, and ERP responses were analyzed. Results During the Lombard condition, the participants increased the intensity of their voice, accompanied by an increase in CPP, and a decrease in H1-H2. The cortical response was characterized by the increased N1-P2 complex amplitude of the ERP elicited by the subject's own vocalizations in noise, The source localization showed neural activities in frontal and temporal cortical regions. Conclusions The variation in acoustic measures due to the Lombard Effect could be modulated by temporal, and cortical regions. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.07.191213v1?rss=1 Authors: jiang, c., Zeng, J., Zeng, S., Lindström, S. Abstract: Background : The aims of this study was determine if stimulation of tibial nerve afferents could induce a prolonged modulation of the micturition reflex in the rats. Methods: Fifteen female Sprague Dawley rats (250-350 g) were fully decorticated and paralysed for the study. Tibial nerve stimulation (TNS) was delivered by inserting two pairs of needle electrodes close to the nerves at the level of the medial malleolus. Constant flow cystometries (0.07 ml/min) at about 10 min interval were performed and the micturition threshold volume (MTV) was recorded and used as the dependent variable. After 4 - 5 stable control recordings, the tibial nerves of both sides were stimulated continuously for 5 min at 10 Hz, 3 times threshold for -motor axons. Six times of same stimulation were applied repeatedly with an interval of 5 min between the stimulations. The mean MTV was compiled from several cystometries in each half hour before the TNS and during, after 6 periods TNS. Results: During the experiment, all the animals survived in a good condition with reasonably stable micturition reflexes, a significant increase in MTV was revealed after TNS. The best effect (mean 178%) occurred during the first 30 min after 6 periods of stimulation. This clear threshold increase remained for at least 5 h. Conclusions: A prolonged increase in MTV was demonstrated by a short periods of TNS repeatedly. This post stimulation modulatory effects of micturition reflex would provide a theoretical explanation for the clinical beneficial effect of TNS in patients with overactive bladder (OAB). Copy rights belong to original authors. Visit the link for more info

Challenge is thrown! Rite of Seeking created a fun way to get social distancing done! Make a thematic deck and run through Night of the Zealot with unique ultimatums!! This session I go wrap up the Zealot Campaign. Does Finn make it out alive? Here they are! Social Distancing: Whenever you perform a Parley action, add 1 doom to the agenda. Hand Washing: At the beginning of the campaign, add Hypochondria to your deck as an additional basic weakness. Dispose Infected Items: After an enemy attacks you, you must discard an Item asset you control. Stockpile: After you draw a copy by name of a card already in your hand, shuffle the just drawn copy back into your deck. Do not draw a new card to replace it. (Stockpile does not affect your opening hand or mulligan.) Wait for Results: During the first two rounds of the game, you cannot discover clues. Finn riot Deck!! Slight of Hand x2 Well Connected x2 Backstab x2 Hard knocks x2 Dario El-Amin x2 Guts Sneak Attack x2 Finn Trusty 38 Caught red handed Smuggled Goods Meat cleaver x2 Rise to the occasion x2 Money talks x2 Investments x2 Burglary x2 Scrounging for supplies Quick thinking x2 Lone wolf x2 Liquid courage x2 Chronophobia Hypochondria Added/Removed Removed Burglary Added burglary lvl 2 Added Another a day another dollar Added Leo DeLuca lvl 1 Removed Slight of Hand Status: XP:6 Spent:6 Mental: Physical:1 Enjoy this unedited and perhaps error filled podcast of the QuarantineCon edition of NOTZ: Midnight Masks and Devourer Below! Contact me at arkhamskids@gmail.com Rite of Seeking’s QuarantineCon https://riteofseeking.com/2020/03/14/quarantinecon-quarantined-in-arkham/

QuarantineCon Challenge is thrown! Rite of Seeking created a fun way to get social distancing done! Make a thematic deck and run through Night of the Zealot with unique ultimatums!! Here they are! Social Distancing: Whenever you perform a Parley action, add 1 doom to the agenda. Hand Washing: At the beginning of the campaign, add Hypochondria to your deck as an additional basic weakness. Dispose Infected Items: After an enemy attacks you, you must discard an Item asset you control. Stockpile: After you draw a copy by name of a card already in your hand, shuffle the just drawn copy back into your deck. Do not draw a new card to replace it. (Stockpile does not affect your opening hand or mulligan.) Wait for Results: During the first two rounds of the game, you cannot discover clues. Finn riot Deck!! Slight of Hand x2 Well Connected x2 Backstab x2 Hard knocks x2 Dario El-Amin x2 Guts Sneak Attack x2 Finn Trusty 38 Caught red handed Smuggled Goods Meat cleaver x2 Rise to the occasion x2 Money talks x2 Investments x2 Burglary x2 Scrounging for supplies Quick thinking x2 Lone wolf x2 Liquid courage x2 Chronophobia Hypochondria Added/Removed Status: XP: Spent: Mental: Physical: Enjoy this unedited and perhaps error filled podcast of the QuarantineCon edition of NOTZ: The gathering! Contact me at arkhamskids@gmail.com Rite of Seeking’s QuarantineCon https://riteofseeking.com/2020/03/14/quarantinecon-quarantined-in-arkham/

Infliximab Trough Levels at Induction to Predict Treatment Failure During Maintenance. Liefferinckx C1, Minsart C, Toubeau JF, Cremer A, Amininejad L, Quertinmont E, Devière J, Gils A, van Gossum A, Franchimont D. BACKGROUND: Infliximab (IFX) is indicated for the treatment of inflammatory bowel diseases (IBD). Nevertheless, loss of response (LOR) to IFX is reported in up to 10% to 30% of patients within the first year of treatment. Our objective was to evaluate the impact of the pharmacokinetics of IFX at induction on treatment failure. METHODS: This is a longitudinal cohort study on 269 patients with IBD treated with IFX in a single center. A total of 2331 blood samples were prospectively collected from 2007 until March 2015 with a retrospective analysis of clinical data. IFX trough levels (TLs) were measured by enzyme-linked immunosorbent assay. Antibodies to IFX were measured by drug-sensitive bridging assay. RESULTS: During follow-up, patients were defined according to treatment outcome. At week 6, median IFX TL in patients requiring a switch to another treatment due to LOR (LOR switched group) (2.32 μg/mL [0.12-19.93 μg/mL]) was lower than in patients with long-term response (long-term responders) (8.66 μg/mL [0.12-12.09 μg/mL], P = ...

Infliximab Trough Levels at Induction to Predict Treatment Failure During Maintenance. Liefferinckx C1, Minsart C, Toubeau JF, Cremer A, Amininejad L, Quertinmont E, Devière J, Gils A, van Gossum A, Franchimont D. BACKGROUND: Infliximab (IFX) is indicated for the treatment of inflammatory bowel diseases (IBD). Nevertheless, loss of response (LOR) to IFX is reported in up to 10% to 30% of patients within the first year of treatment. Our objective was to evaluate the impact of the pharmacokinetics of IFX at induction on treatment failure. METHODS: This is a longitudinal cohort study on 269 patients with IBD treated with IFX in a single center. A total of 2331 blood samples were prospectively collected from 2007 until March 2015 with a retrospective analysis of clinical data. IFX trough levels (TLs) were measured by enzyme-linked immunosorbent assay. Antibodies to IFX were measured by drug-sensitive bridging assay. RESULTS: During follow-up, patients were defined according to treatment outcome. At week 6, median IFX TL in patients requiring a switch to another treatment due to LOR (LOR switched group) (2.32 μg/mL [0.12-19.93 μg/mL]) was lower than in patients with long-term response (long-term responders) (8.66 μg/mL [0.12-12.09 μg/mL], P = ...

Infliximab Trough Levels at Induction to Predict Treatment Failure During Maintenance. Liefferinckx C1, Minsart C, Toubeau JF, Cremer A, Amininejad L, Quertinmont E, Devière J, Gils A, van Gossum A, Franchimont D. BACKGROUND: Infliximab (IFX) is indicated for the treatment of inflammatory bowel diseases (IBD). Nevertheless, loss of response (LOR) to IFX is reported in up to 10% to 30% of patients within the first year of treatment. Our objective was to evaluate the impact of the pharmacokinetics of IFX at induction on treatment failure. METHODS: This is a longitudinal cohort study on 269 patients with IBD treated with IFX in a single center. A total of 2331 blood samples were prospectively collected from 2007 until March 2015 with a retrospective analysis of clinical data. IFX trough levels (TLs) were measured by enzyme-linked immunosorbent assay. Antibodies to IFX were measured by drug-sensitive bridging assay. RESULTS: During follow-up, patients were defined according to treatment outcome. At week 6, median IFX TL in patients requiring a switch to another treatment due to LOR (LOR switched group) (2.32 μg/mL [0.12-19.93 μg/mL]) was lower than in patients with long-term response (long-term responders) (8.66 μg/mL [0.12-12.09 μg/mL], P = ...

Infliximab Trough Levels at Induction to Predict Treatment Failure During Maintenance. Liefferinckx C1, Minsart C, Toubeau JF, Cremer A, Amininejad L, Quertinmont E, Devière J, Gils A, van Gossum A, Franchimont D. BACKGROUND: Infliximab (IFX) is indicated for the treatment of inflammatory bowel diseases (IBD). Nevertheless, loss of response (LOR) to IFX is reported in up to 10% to 30% of patients within the first year of treatment. Our objective was to evaluate the impact of the pharmacokinetics of IFX at induction on treatment failure. METHODS: This is a longitudinal cohort study on 269 patients with IBD treated with IFX in a single center. A total of 2331 blood samples were prospectively collected from 2007 until March 2015 with a retrospective analysis of clinical data. IFX trough levels (TLs) were measured by enzyme-linked immunosorbent assay. Antibodies to IFX were measured by drug-sensitive bridging assay. RESULTS: During follow-up, patients were defined according to treatment outcome. At week 6, median IFX TL in patients requiring a switch to another treatment due to LOR (LOR switched group) (2.32 μg/mL [0.12-19.93 μg/mL]) was lower than in patients with long-term response (long-term responders) (8.66 μg/mL [0.12-12.09 μg/mL], P = ...

Background: Many studies show an effectiveness of hypnotic analgesia. It has been discussed whether the analgesic effect is mainly caused by the relaxation that is concomitant to hypnosis. This study was designed to evaluate the effects of hypnotic relaxation suggestion on different somatosensory detection and pain thresholds. Methods: Quantitative sensory testing (QST) measurements were performed before and during hypnosis in twenty-three healthy subjects on the dorsum of the right hand. Paired t-test was used to compare threshold changes. The influence of hypnotic susceptibility was evaluated by calculating correlation coefficients for threshold changes and hypnotic susceptibility (Harvard group scale). Results: During hypnosis significantly changed somatosensory thresholds (reduced function) were observed for the following sensory detection thresholds: Cold Detection Threshold (CDT), Warm Detection Threshold (WDT), Thermal Sensory Limen (TSL) and Mechanical Detection Threshold (MDT). The only unchanged sensory detection threshold was Vibration Detection Threshold (VDT). No significant changes were observed for the determined pain detection thresholds (Cold Pain Thresholds, Heat Pain Thresholds, Mechanical Pain Sensitivity, Dynamic Mechanical Allodynia, Wind-up Ratio and Pressure Pain Threshold). No correlation of hypnotic susceptibility and threshold changes were detected. Conclusion: Hypnotic relaxation without a specific analgesic suggestion results in thermal and mechanical detection, but not pain threshold changes. We thus conclude that a relaxation suggestion has no genuine effect on sensory pain thresholds.

Objective: Rotavirus (RV) gastroenteritis is a notifiable disease in Germany. The reports to the authorities contain few data concerning the severity of disease. The aims of this study were to determine incidence and outcome of very severe cases of RV disease. Methods: Cases of very severe RV disease were collected by the German Paediatric Surveillance Unit for rare diseases (Erhebungseinheit fur seltene padiatrische Erkrankungen in Deutschland) using anonymous questionnaires based on hospitalized patients between April 2009 and March 2011. Inclusion criteria were detection of RV antigen in feces, patient aged 0-16 years and 1 or more of the following criteria: intensive care treatment, hypernatremia or hyponatremia (> 155 mmol/ L or < 125 mmol/ L), clinical signs of encephalopathy (somnolence, seizures, apnea) and RV-associated death. Results: During 2 years, 130 cases of very severe RV disease were reported, 101 of 130 were verified. Seventeen patients had nosocomial infection, of whom 14 were neonates in intensive care. Among those, 12 infants had verified or suspected necrotizing enterocolitis. Eighty-four community-acquired cases were reported, median age was 10.5 months (0-108 months). The median hospital stay was 6 days, and 48 patients needed intensive care treatment. Among children less than 5 years of age, the yearly incidence of community-acquired very severe RV disease was 1.2 of 100,000 (95% confidence interval: 0.9-1.4/100,000). A total of 26 of 84 and 10 of 84 patients had severe hypernatremia or hyponatremia, respectively, and 58 of 84 patients had signs of encephalopathy. Three deaths were reported (1 nosocomial and 2 community acquired). Conclusions: RV infection in Germany can have a life-threatening course. A substantial number are nosocomial infections.

Background: Dysferlinopathies are autosomal recessive disorders caused by mutations in the dysferlin (DYSF) gene encoding the dysferlin protein. DYSF mutations lead to a wide range of muscular phenotypes, with the most prominent being Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B). Methods: We assessed the one-year-natural course of dysferlinopathy, and the safety and efficacy of deflazacort treatment in a double-blind, placebo-controlled cross-over trial. After one year of natural course without intervention, 25 patients with genetically defined dysferlinopathy were randomized to receive deflazacort and placebo for six months each (1 mg/kg/day in month one, 1 mg/kg every 2nd day during months two to six) in one of two treatment sequences. Results: During one year of natural course, muscle strength declined about 2% as measured by CIDD (Clinical Investigation of Duchenne Dystrophy) score, and 76 Newton as measured by hand-held dynamometry. Deflazacort did not improve muscle strength. In contrast, there is a trend of worsening muscle strength under deflazacort treatment, which recovers after discontinuation of the study drug. During deflazacort treatment, patients showed a broad spectrum of steroid side effects. Conclusion: Deflazacort is not an effective therapy for dysferlinopathies, and off-label use is not warranted. This is an important finding, since steroid treatment should not be administered in patients with dysferlinopathy, who may be often misdiagnosed as polymyositis.

Purpose: To evaluate the efficiency of a multimodality approach consisting of transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) as bridging therapy for patients with hepatocellular carcinoma (HCC) awaiting orthotopic liver transplantation (OLT) and to evaluate the histopathological response in explant specimens. Materials and Methods: Between April 2001 and November 2011, 36 patients with 50 HCC nodules (1.4-5.0 cm, median 2.8 cm) on the waiting list for liver transplantation were treated by TACE and RFA. The drop-out rate during the follow-up period was recorded. The local efficacy was evaluated by histopathological examination of the explanted livers. Results: During a median follow-up time of 29 (4.0-95.3) months the cumulative drop-out rate for the patients on the waiting list was 0, 2.8, 5.5, 11.0, 13.9 and 16.7% at 3, 6, 12, 24, 36 and 48 months, respectively. 16 patients (with 26 HCC lesions) out of 36(44.4%) were transplanted by the end of study with a median waiting list time of 13.7 (2.5-37.8) months. The histopathological examination of the explanted specimens revealed a complete necrosis in 20 of 26 HCCs (76.9%), whereas 6 (23.1%) nodules showed viable residual tumor tissue. All transplanted patients are alive at a median time of 29.9 months. Imaging correlation showed 100% specificity and 66.7% sensitivity for the depiction of residual or recurrent tumor. Conclusion: We conclude that TACE.combined with RFA could provide an effective treatment to decrease the drop-out rate from the OLT waiting list for HCC patients. Furthermore, this combination therapy results in high rates of complete tumor necrosis as evaluated in the histopathological analysis of the explanted livers. Further randomized trials are needed to demonstrate if there is a benefit in comparison with a single-treatment approach. copyright (C) 2012 S. Karger AG, Basel

Background: Anthracyclines are agents with a well-known cardiotoxicity. The study sought to evaluate the hemodynamic response to an anthracycline using real-time continuous-wave (CW)-Doppler ultrasound cardiac output monitoring (USCOM) and echocardiography in combination with serum biomarkers. Methods: 50 patients (26 male, 24 female, median age 59 years) suffering from various types of cancer received an anthracycline-based regimen. Patients' responses were measured at different time points (T0 prior to infusion, T1 6 h post infusion, T2 after 1 day, T3 after 7 days, and T4 after 3 months) with CW-Doppler ultrasound (T0-T4) and echocardiography (T1, T4) for hemodynamic parameters such as stroke volume (SV; SVUSCOM ml) and ejection fraction (EF; EFechocardiography%) and with NT-pro-BNP and hs-Troponin T (T0-T4). Results: During the 3-month observation period, the relative decrease in the EF determined by echocardiography was -2.1% (Delta T0-T4, T0 71 +/- 7.8%, T4 69.5 +/- 7%, p = 0.04), whereas the decrease in SV observed using CW-Doppler was -6.5% (Delta T0-T4, T0 54 +/- 19.2 ml, T4 50.5 +/- 20.6 ml, p = 0.14). The kinetics for serum biomarkers were inversely correlated. Conclusions: Combining real-time CW-Doppler USCOM and serum biomarkers is feasible for monitoring the immediate and chronic hemodynamic changes during an anthracycline-based regimen; the results obtained were comparable to those from echocardiography.

Background: The majority of patients with idiopathic pulmonary arterial hypertension (IPAH) in functional classes II and III are currently being treated with non-parenteral therapies, including endothelin receptor antagonists (ERA), phosphodiesterase (PDE)-5 inhibitors, inhaled iloprost or combinations of these substances. If these treatments fail, current guidelines recommend the addition of parenteral prostanoid therapy. There is, however, limited evidence for the efficacy of parenteral prostanoids when added to combinations of non-parenteral therapies. Methods: In this retrospective, multicentre study we collected data from consecutive IPAH patients receiving intravenous iloprost in addition to optimized non-parenteral therapy between Jan 2002 and Dec 2009. Analyses included 6 min walk distance (6MWD), functional class, need for transplantation, and survival. Results: During the observation period, 50 patients were treated with intravenous iloprost in addition to non-parenteral therapy; 44% of the patients were on dual combination therapy and 52% on triple combination. Three months after initiation of iloprost, functional class had improved in 24% of the patients and the median 6MWD had increased from 289 m to 298 m (n.s.). During the observation period, 22 patients (44%) died and 14 (28%) underwent lung transplantation. The probabilities of LuTx-free survival at 1, 3 and 5 years following iloprost initiation were 38%, 17% and 17%, respectively. A 6MWD < 300 m and persistent functional class IV at 3 months after initiation of intravenous iloprost were predictors of an adverse outcome. Conclusion: In essence, late initiation of intravenous iloprost in IPAH patients who previously failed to respond to non-parenteral therapies appears to be of limited efficacy in the majority patients. Alternative therapeutic options are currently not available, underlying the need for the development of new drugs.

Background: Our aim was to examine whether measurement of the saliva mast cell tryptase (MCT) concentrations before and after a mucosal challenge test with the offending food would be helpful in diagnosing food allergy. Methods: We performed a retrospective analysis of 44 food challenge tests performed in 38 patients between 2006 and 2009. Patients with a suspected history of food allergy chewed the food until they developed symptoms or until the amount of time known from the patients' history to usually be required for the provocation of symptoms had passed. In 5 patients, saliva samples for the measurement of MCT were collected at minutes 0, 1, 4, 8, 11, and 16 after the first onset of symptoms. The remainder of the patients only had samples taken before chewing and 4 min after the end of the test period. Results: During repeated measurements, MCT peaked about 4 min after the onset of symptoms (p = 0.028). During 33 of the 44 tests (75.0%), we observed oral symptoms during testing; after 25 of the 33 (75.8%) tests evoking symptoms, the saliva MCT concentration increased. The MCT increase was negative in all other tests where no oral symptoms could be provoked. Conclusions: The measurement of saliva MCT 4 min after the onset of symptoms may be helpful to diagnose food allergy. Because of numerous confounding variables, however, a negative saliva MCT increase does not exclude food allergy. Copyright (C) 2011 S. Karger AG, Basel

The aim of this study is, besides the elaborate documentation of the Pelvic-Floor- Reeducation-Concept, to illustrate and discuss the short and long term efficacy of the conservative incontinence therapy that has been applied at the University Clinic Grosshadern for the last seven years. In addition, predictable factors will be discussed, which serve as a foundation to better judge the therapeutic outcome. In the objectives of research section, the short and long term effectiveness of an intensive EMG-Biofeedback-assisted pelvic floor muscle training for the treatment of female stress or mixed urinary incontinence is examined. The other purpose is the comparison of two different groups of patients (successfully completed treatment versus not completed therapy). Another question that was examined is, can factors for a successful therapy be predicted? Materials and Methods: The patients examined for this study, were all of the women that were treated for stress-urinary incontinence or mixed urinary incontinence between September 1996 and March 2003 in our clinic in the urogynecology department within the Pelvic-Floor-Reeducation-Program (PFR). For methodical reasons, the patients were divided in to three separate groups. Group 1 consisted of the patients that completed the program successfully. Group 2 consisted of the patients that had started the program, but had not completed it. Group 3 consisted of patients that did not participate in the program, but instead just had a counseling interview. The diagnostics involved: an urodynamic measurement, the stress provocation test (cough test), the determination of maximum pelvic floor muscle strength, with the help of palpatoric diagnostic (Oxford-Score, Scale 0–5), and an EMG (Maximum contraction; PERFECT-Measurement). According to the PFR concept, the patients received an extensive incontinence counseling session, instructions for individual pelvic floor exercises, and copingstrategies for dealing with incontinence in every day situations. The biofeedback therapy was done with the use of PC-controlled electromyography (ST2001, Haynl Elektronik). The follow-up consisted of 92 a standardized questionnaire. In the analysis of potential predictable factors, the following parameters were used: Age > 65, BMI ≥ 30, Parity, duration of incontinence > 5 years, SIK III,, Hypotony Urethra (≤ 25 cm H²O), weak pelvis floor contraction (Oxford < 2) and motivation for the training. Results: During the period of seven years, a total of 434 women were treated with the Pelvic-Floor-Reeducation-Program. For this study, a total of 390 of the 434 women, who suffered from either stress-urinary incontinence (79.7 %) or mixed urinary incontinence (20.3 %), were evaluated. Average age: 52, mean incontinence duration: 6.7 years. 60.4 % of the women suffered from a SIK III. 67.4 % of the women successfully completed the training, while 25.1 % did not. 82.0 % of the patients improved on the stress test. The average time for follow-up was 2.9 years. The questionnaire return was 80.0 % (N = 312). 71.0 % of the patients reported that their problems with incontinence had improved after the training, and only 13.5 % chose to have surgery for the incontinence. Therefore, the long term success rate for the treatment is 61.2 % (N = 191). In comparison to the patients that did not complete treatment, there are noticeable differences, including the number of operations, as well as the quality of life. In view of the therapeutic outcome, the following factors showed a statistically significant association, which is associated with a more negative prognosis: Age > 65 (only 50.0 % improvement) and duration of incontinence > 5 years (54.4 % improvement). Interestingly, the study showed that women who had given birth, in comparison to woman with nulliparity and women who initially had weak pelvic floor contraction strength (Oxford < 2), had better therapeutic results. Conclusion: An intensive and controlled pelvic floor training is effective, and should be generally be used before an operation is considered. Both immediately after the therapy, as well as in the long-term, the patients profited from the Pelvic-Floor-Reeducation- Program. The program can often be avoided, even in severe cases of urinary incontinence. However, the motivation to successfully complete the PFR training is an essential factor for the long-term success of the therapy.

Background: Posaconazole is a novel antifungal drug for oral application intended especially for therapy of invasive mycoses. Due to variable gastrointestinal absorption, adverse side effects, and suspected drug-drug interactions, therapeutic drug monitoring (TDM) of posaconazole is recommended. Method: A fast ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for quantification of posaconazole with a run-time

Background/Aims: Pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has been shown to inhibit growth and to induce apoptosis in human hepatocellular carcinoma (HCC) cells. However, the potential benefit of pravastatin in HCC patients has still not been characterized, which prompted us to test the efficacy of pravastatin in patients with advanced HCC. Methods: We investigated prospectively a cohort of 183 HCC patients who had been selected for palliative treatment by transarterial chemoembolization (TACE). Fifty-two patients received TACE combined with pravastatin (20-40 mg/day) and 131 patients received chemoembolization alone. Six independent predictors of survival according to the Vienna survival model for HCC were equally distributed in both groups. Results: During the observation period of up to 5 years, 31 (23.7%) out of 131 patients treated by TACE alone and 19 (36.5%) out of 52 patients treated by TACE and pravastatin survived. Median survival was significantly longer in HCC patients treated by TACE and pravastatin (20.9 months, 95% Cl 15.5-26.3, p = 0.003) than in HCC patients treated by TACE alone (12.0 months, 95% Cl 10.3-13.7). Conclusion: Combined treatment of chemoembolization and pravastatin improves survival of patients with advanced HCC in comparison to patients receiving chemoembolization alone. Copyright (C) 2008 S. Karger AG, Basel

Background: To establish an efficient prophylaxis of coronary artery disease reliable risk stratification is crucial, especially in the high risk population of patients suffering from diabetes mellitus. This prospective study determined the predictive value of coronary calcifications for future cardiovascular events in asymptomatic patients with diabetes mellitus. Methods: We included 716 patients suffering from diabetes mellitus (430 men, 286 women, age 55.2 +/- 15.2 years) in this study. On study entry all patients were asymptomatic and had no history of coronary artery disease. In addition, all patients showed no signs of coronary artery disease in ECG, stress ECG or echocardiography. Coronary calcifications were determined with the Imatron C 150 XP electron beam computed tomograph. For quantification of coronary calcifications we calculated the Agatston score. After a mean observation period of 8.1 +/- 1.1 years patients were contacted and the event rate of cardiac death (CD) and myocardial infarction (MI) was determined. Results: During the observation period 40 patients suffered from MI, 36 patients died from acute CD. The initial Agatston score in patients that suffered from MI or died from CD (475 +/- 208) was significantly higher compared to those without cardiac events (236 +/- 199, p < 0.01). An Agatston score above 400 was associated with a significantly higher annualised event rate for cardiovascular events (5.6% versus 0.7%, p < 0.01). No cardiac events were observed in patients with exclusion of coronary calcifications. Compared to the Framingham risk score and the UKPDS score the Agatston score showed a significantly higher diagnostic accuracy in the prediction of MI with an area under the ROC curve of 0.77 versus 0.68, and 0.71, respectively, p < 0.01. Conclusion: By determination of coronary calcifications patients at risk for future MI and CD could be identified within an asymptomatic high risk group of patients suffering from diabetes mellitus. On the other hand future events could be excluded in patients without coronary calcifications.

Introduction Metabolic acidosis during hemorrhagic shock is common and conventionally considered to be due to hyperlactatemia. There is increasing awareness, however, that other nonlactate, unmeasured anions contribute to this type of acidosis. Methods Eleven anesthetized dogs were hemorrhaged to a mean arterial pressure of 45 mm Hg and were kept at this level until a metabolic oxygen debt of 120 mLO(2)/kg body weight had evolved. Blood pH, partial pressure of carbon dioxide, and concentrations of sodium, potassium, magnesium, calcium, chloride, lactate, albumin, and phosphate were measured at baseline, in shock, and during 3 hours post-therapy. Strong ion difference and the amount of weak plasma acid were calculated. To detect the presence of unmeasured anions, anion gap and strong ion gap were determined. Capillary electrophoresis was used to identify potential contributors to unmeasured anions. Results During induction of shock, pH decreased significantly from 7.41 to 7.19. The transient increase in lactate concentration from 1.5 to 5.5 mEq/L during shock was not sufficient to explain the transient increases in anion gap (+ 11.0 mEq/L) and strong ion gap (+ 7.1 mEq/L), suggesting that substantial amounts of unmeasured anions must have been generated. Capillary electrophoresis revealed increases in serum concentration of acetate (2.2 mEq/L), citrate (2.2 mEq/L), alpha-ketoglutarate (35.3 mu Eq/L), fumarate (6.2 mu Eq/L), sulfate (0.1 mEq/L), and urate (55.9 mu Eq/L) after shock induction. Conclusion Large amounts of unmeasured anions were generated after hemorrhage in this highly standardized model of hemorrhagic shock. Capillary electrophoresis suggested that the hitherto unmeasured anions citrate and acetate, but not sulfate, contributed significantly to the changes in strong ion gap associated with induction of shock.