The role of multimodal adjuvant therapy for FIGO I-II carcinosarcoma of the uterus: a systematic review.

The uterine carcinosarcoma (UCS) is a rare entity with poor prognosis. Treatment of FIGO I-II UCS usually consists of surgery with or without adjuvant treatment. Due to the high metastatic potential, aggressive combined modality adjuvant treatment approaches, consisting of chemo- and radiotherapy, have been of interest. Our systematic review aims to compare survival, disease control and toxicity profiles in patients receiving adjuvant chemoradiation to other adjuvant strategies (e.g.observation, chemotherapy or radiotherapy). A total of ten studies were included for a combined cohort size of 6520 patients. Generally, the studies showed a trend towards improved disease control and survival in patients undergoing adjuvant multimodal treatment, although statistical significance was often not reached. Selection bias and non-randomized treatment allocation pose serious challenges to extrapolate these outcomes to clinical practice. We recommend additional prospective research on the role of adjuvant chemoradiation in FIGO I-II UCS.

An atomic hydrogen etching sensor for H2 plasma diagnostics.

A simple and selective new technique for atomic hydrogen flux measurements in a hydrogen plasma environment is introduced and demonstrated in this work. This technique works by measuring the etching rate of an amorphous carbon film and translating this to an incoming hydrogen radical flux through a well-defined carbon etch yield per radical. Ions present in the plasma environment have a much higher etch yield than radicals do. For that reason, suppression of the ion flux toward the carbon film is crucial to ensure that the observed carbon etch rate is dominated by atomic hydrogen etching. It is demonstrated that this can be achieved using a simple cylindrical pipe (hereinafter "chimney") in which a bend is introduced to enforce ion-wall collisions, neutralizing the ions. The chimney is made out of Macor, a material with low catalytic surface activity, to preserve the incoming atomic hydrogen flux while effectively suppressing ions. Ultimately, the etching sensor is deployed in a radio frequency inductively coupled hydrogen plasma operated at low pressure (1-10 Pa). Atomic hydrogen fluxes are measured and compared with heat flux sensor and vacuum ultraviolet absorption spectroscopy measurements in the same setup. All sensors agreed within a factor 4 in the atomic hydrogen flux range 1019 to 1021 m-2 s-1.

The value of MRI STIR signal intensity on return to play prognosis and reinjury risk estimation in athletes with acute hamstring injuries.

OBJECTIVES: Previous studies have shown low to moderate evidence for a variety of magnetic resonance imaging (MRI) features as prognostic factors in athletes with hamstring injuries. Short-tau inversion recovery (STIR) signal intensity has not yet been investigated for assessing the prognosis of acute muscle injuries. Our aim was to explore the relationship between MRI STIR signal intensity and time to return to play (RTP) and to investigate the association between MRI STIR and reinjury risk in athletes with acute hamstring injuries. STUDY DESIGN: Case-control study. METHODS: We used MRI STIR to measure intramuscular signal intensity in patients with clinically diagnosed hamstring injuries at two time points: at injury and RTP. At injury, we calculated the association of MRI STIR signal intensity with the time to RTP and reinjury risk. At RTP, the association of MRI STIR signal intensity and reinjury risk and the change in MRI STIR signal intensity over time on reinjury risk was evaluated. RESULTS: 51 patients were included. We found increased MRI STIR signal intensity: (1) at time of injury not to be associated with time to RTP, (2) at time of injury to be associated with a slightly lower risk for reinjury: odds 0.986 (0.975-0.998, p=0.02) and (3) at RTP not to be associated with reinjury risk. (4) We found no association between the change in MRI STIR signal intensity over time and reinjury risk. CONCLUSION: Increased MRI STIR signal intensity at injury has no value in time to RTP prognosis, but is associated with a reduced reinjury risk.

Analysis of retarding field energy analyzer transmission by simulation of ion trajectories.

Retarding field energy analyzers (RFEAs) are used routinely for the measurement of ion energy distribution functions. By contrast, their ability to measure ion flux densities has been considered unreliable because of lack of knowledge about the effective transmission of the RFEA grids. In this work, we simulate the ion trajectories through a three-gridded RFEA using the simulation software SIMION. Using idealized test cases, it is shown that at high ion energy (i.e., >100 eV) the transmission is equal to the optical transmission rather than the product of the individual grid transparencies. Below 20 eV, ion trajectories are strongly influenced by the electric fields in between the grids. In this region, grid alignment and ion focusing effects contribute to fluctuations in transmission with ion energy. Subsequently the model has been used to simulate the transmission and energy resolution of an experimental RFEA probe. Grid misalignments reduce the transmission fluctuations at low energy. The model predicts the minimum energy resolution, which has been confirmed experimentally by irradiating the probe with a beam of ions with a small energy bandwidth.

Empirical antibiotic therapy for pneumonia in intensive care units: a multicentre, retrospective analysis of potentially pathogenic microorganisms identified by endotracheal aspirates cultures.

The purpose of this investigation was to explore the presumed relationship between the days of hospitalisation and microorganisms identified by endotracheal aspirate cultures in relation to adequate empirical treatment strategies of pneumonia in the intensive care unit (ICU). All potentially pathogenic microorganisms identified by (surveillance) cultures of endotracheal aspirates obtained in the ICUs of two Dutch teaching hospitals in 2007 and 2012 were retrospectively collected and analysed. Antibiotic susceptibilities to 11 antibiotics were calculated for several time points (days or weeks) after hospital admission and expressed per patient-day. In total, 4184 potentially pathogenic microorganisms identified in 782 patients were analysed. Prevalence of the classic early-onset pneumonia-causing microorganisms decreased from 55 % on the first four days to 34 % on days 4-6 after hospital admission (p < 0.0001). Susceptibility to amoxicillin/clavulanic acid was below 70 % on all days. Except for days 0 and 12, susceptibility to ceftriaxone was below 80 %. The overall susceptibility to piperacillin/tazobactam was 1518/1973 (77 %) in 2007 vs. 727/1008 (67 %) in 2012 (p < 0.0001). After day 8 of hospital admission, susceptibility to piperacillin/tazobactam therapy was below 80 % in 2012. After one week of hospital admission, susceptibilities to antibiotics were lower in the hospital that included that antibiotic in the local empirical treatment protocols as compared to the hospitals in which that antibiotic was not or infrequently included: 90/434 (21 %) vs. 117/398 (29 %); p = 0.004 for amoxicillin/clavulanic acid and 203/433 (47 %) vs. 253/398 (64 %); p < 0.001 for ceftriaxone. No cut-off in the number of days after hospital admission could be identified to distinguish early-onset from late-onset pneumonia. Consequently, the choice of empirical antibiotics should probably not be based on the time of onset.

[Patient safety in general dental practice 2009]. / Patiëntveiligheid in tandartspraktijken in 2009.

In recent years various studies have been published which indicate that adverse events in health care facilities are the result of structural factors. In 2009 a national study was carried out in the Netherlands to gain insight into patient safety in primary care settings, including general dental practices. In 20 randomly selected practices, patient records were investigated and oral care professionals reported, during a period of 2 weeks, adverse events which occurred. For each practice, 2 researchers screened, with the help of a checklist, 50 randomly selected patient records covering a period of 1 year. A total of 8 preventable adverse events were found in the 1000 patient records (0.8%). Anonymous reports made during the 2 weeks of the research period resulted in 7 adverse events. Practically all of the adverse events had to do with diagnostics and treatment and resulted in limited harmful consequences for patients. On the basis of these results, oral care in general dental practice would appear to be safe, but the concept 'patient safety' is not at all or only minimally active among general dental practitioners. Regarding patient safety performance, improvement in the quality of record-keeping would be desirable.

Importance of temporal-envelope cues in consonant recognition.

The role of different modulation frequencies in the speech envelope were studied by means of the manipulation of vowel-consonant-vowel (VCV) syllables. The envelope of the signal was extracted from the speech and the fine-structure was replaced by speech-shaped noise. The temporal envelopes in every critical band of the speech signal were notch filtered in order to assess the relative importance of different modulation frequency regions between 0 and 20 Hz. For this purpose notch filters around three center frequencies (8, 12, and 16 Hz) with three different notch widths (4-, 8-, and 12-Hz wide) were used. These stimuli were used in a consonant-recognition task in which ten normal-hearing subjects participated, and their results were analyzed in terms of recognition scores. More qualitative information was obtained with a multidimensional scaling method (INDSCAL) and sequential information analysis (SINFA). Consonant recognition is very robust for the removal of certain modulation frequency areas. Only when a wide notch around 8 Hz is applied does the speech signal become heavily degraded. As expected, the voicing information is lost, while there are different effects on plosiveness and nasality. Even the smallest filtering has a substantial effect on the transfer of the plosiveness feature, while on the other hand, filtering out only the low-modulation frequencies has a substantial effect on the transfer of nasality cues.

Car driver behavior at flashing light railroad grade crossings.

The behavior of car drivers at two Dutch railroad grade crossings with automatic flashing warning lights was analyzed. Car drivers were videotaped while approaching either the red flashing lights or the white flashing "safe"-signal. Approach speeds, positions, and time intervals were semiautomatically measured from videos of more than 900 drivers: 660 while confronted with the red lights and 272 while passing the white light. Of the latter group, head movements during the approach to the crossing were also registered. Red light compliance was relatively good, as no driver was observed to cross later than 6 seconds after the onset of the red lights, despite train-arrival times of well over 60 seconds. The level of red light compliance was further quantified in terms of both the deceleration and time-to-stopping-line as accepted by drivers. From a comparison with earlier research on red light compliance at signalized road intersections it appeared that red light compliance was better at railroad crossings than at road crossings. It is concluded that faulty red light compliance is not a major cause for car-train accidents and that emphasis should be placed on the ability of the present device to attract attention and to signal unambiguously. The high degree of compliance also causes unexpected driver actions, such as emergency braking and hesitations. A yellow phase may reduce these problems. Some drivers tended to proceed immediately after a train had cleared the road instead of waiting for the end of the red signal (typically some 3 to 5 seconds after the train had passed). This tendency might reveal a major cause of dramatic errors when a second train is approaching. Immediate extinction of the red signal is suggested, or even better, a separate signal to announce the arrival of the second train. Behavior during the white signal phase also showed indications of uncertainty. In some 10% of cases drivers tended to decelerate more strongly than necessary and to make extra head movements. It is recommended that the present white flashing signal be reconsidered.

Digitalis, digitalis antibodies, digitalis-like immunoreactive substances, and sodium homeostasis: a review.

Most pharmacokinetic and biologic attributes of digitalis are age dependent. They are determined in great measure by the chemical structure of the specific cardiac glycoside being used. These effects differ in the intact normal circulation and in heart failure because of the altered autonomic nervous system and hormonal control that exist in the latter. Digitalis is effective only in the presence of myocardial dysfunction, but in a clinical setting, cardiac performance may be difficult to gauge; improved tools are needed for this purpose. The dosages of digoxin recommended for infants and children have been steadily reduced in the past decade, and there is no good evidence that more favorable risk-to-benefit ratios are achieved when higher doses are used or when higher plasma concentrations are sought. Massive digitalis toxicity is a serious, often fatal, complication in young infants, especially when the drug is given parenterally; it may be difficult to diagnose early. The only reliable deterrent for this complication is the adoption of careful safety standards whenever the drug is employed. Experience with digoxin antibodies is still scarce in children, especially in infancy, but their use generally has been associated with a favorable outcome. Endogenous substances that interfere with the digoxin radioimmunoassay (DLIS) occasionally yield clinically relevant, erroneously high, plasma digoxin concentration readings in neonates. An interesting hypothesis currently being investigated is the physiologic and pathologic role of these compounds in sodium hemostasis; they may be part of a putative endogenous NaK-ATP-ase inhibitor involved in the pathogenesis of hypertension and renal diseases.

Digoxin intoxication in children and young adults.

Acute digoxin intoxication in children and young adults generally occurs in three distinct age groups: in infants, a pharmacokinetically disadvantaged age group, who are given an excessive dose parenterally and invariably die from the overdose; in toddlers, a pharmacokinetically favored age group, who ingest the drug accidentally and usually recover from the overdose, and in older children and young adults, who occupy an intermediate position with respect to pharmacokinetics and prognosis.

The pattern and frequency of congenital heart disease among blacks.

The types of cardiac malformations in 804 black patients of all ages in whom the diagnosis was confirmed by cardiac catheterization, surgery or autopsy are reported. The most frequent anomalies were ventricular septal defect, patent ductus arteriosus and tetralogy of Fallot. Among infants under 1 year of age, complete transposition of the great vessels accounted for the third-largest group of malformations. While pulmonary venous anomalies were extremely rare and hypoplastic left heart defects rare in the neonate, it is not considered that a racial predilection for differences in the frequency of various cardiac malformations exists. The frequency of coarctation of the aorta in the group as a whole was not lower than that found in studies among whites. Among black patients of all ages with heart disease (studied in a hospital environment) congenital cardiac malformations ranked as the second most common form of heart disease with a frequency of 26%. Among children aged 15 years or less, congenital heart disease ranked first with a frequency of 53%. It is suggested that a diagnosis of congenital heart disease is not made in the majority of blacks born with such malformations.

Maintenance digoxin dosage and steady-state plasma concentration in infants and children.

To define the relationship between digoxin dose and plasma concentration and the changes in body growth, 1181 plasma digoxin levels were measured in 644 infants and children receiving maintenance digoxin therapy. The drug was given intravenously to 166 patients and orally to 478. A significant linear correlation between dose and plasma concentration was observed (r 0.346 to 0.767 in the intravenous and 0.264 to 0.664 in the oral groups). Dosage differences explained 7% to 60% of the variability in digoxin plasma concentrations in various age and weight groups. The linear regression slope was greater in younger age groups, especially preterm infants weighing less than 1500 gm, and tended to decrease with age. The data (1) allow an approximate prediction of plasma concentrations of digoxin and their variability associated with changes in dosages in various pediatric age and weight groups, (2) permit an estimate of other pharmacokinetic determinants of digoxin plasma concentration and their changes with age, and (3) suggest that larger changes in digoxin doses in older children are necessary to achieve the same change in serum concentration that is achieved with smaller dose changes in the young infant. As a result, premature infants are more sensitive to and require smaller digoxin doses.

The frequency of different types of heart disease in South African Blacks at a cardiac referral center.

Cardiomyopathy has been considered to be the most prevalent form of heart disease amongst Blacks in Southern Africa. In the present study we evaluated 5725 patients with heart disease. Rheumatic heart disease was most prevalent accounting for 42% of cardiac diseases. Ischemic heart disease was extremely rare.

Digitalis toxicity in infants and children.

There is a narrow difference between the therapeutic and toxic ranges of cardiac glycosides. The availability in the past decade of radioimmunoassays for accurate measurement of these glycosides has resulted in an improved understanding of their pharmacokinetics and clinical use. Despite these advances, however, digitalis toxicity is still a common problem in infants and children.

Tissue concentrations at autopsy in infants and children receiving therapeutic digoxin.

Therapeutic tissue concentrations of digoxin have been reported for relatively small numbers of infants and children. In forensic medicine, knowledge of these concentration ranges is important for confirming or excluding digoxin overdosage in different age groups. In addition to age and weight, other factors such as dosage, duration of treatment, route of administration, sampling site, time of last dose, and death-autopsy interval may influence tissue concentrations. In this paper we report on tissue concentrations in 36 infants and children who received therapeutic digoxin before death.

Pathologic measurements in aortic atresia.

Detailed autopsy measurements were performed in 13 infants with hypoplastic left ventricle and aortic atresia. Emphasis was placed on the evaluation of changes in the right ventricle, since its function may be important in determining surgical survival. Other important aspects were the ascending aortic and transverse aortic arch diameter, the presence of left atrial obstruction, and the size of the left atrium. The development of improved 2DE and Doppler imaging will permit preoperative and sequential evaluation of these parameters. Measurements performed in this study may serve as a basis for selection of infants for palliative surgery; these procedures are being undertaken more frequently in this hitherto fatal lesion. The measurements may also serve as a basis for noninvasive serial studies of these infants postoperatively.

Postmortem digoxin tissue concentration and organ content in infancy and childhood.

The concentration of digoxin in tissues and the content of the drug in various organs are reported in 36 infants and children. Sixteen received the drug on a short-term basis and 20 on a long-term basis. The drug was given intravenously to 12, orally to 17, and by intramuscular injection to 7. The study was conducted to determine distribution of digoxin in infants and children and to examine the forensic implications related to digoxin overdosage. Upper therapeutic concentration thresholds for digoxin were established in various tissues. These are different for preterm and full-term neonates than for older children and adults; for example, adult and neonatal values for postmortem blood specimens are 8 and 15 ng/ml, and for ventricular myocardium are 250 and 450 ng/g, respectively. The chronically digitalized premature infant retains in most tissues a considerably larger fraction of digoxin than more mature infants and children. This is in accord with previously demonstrated lower renal digoxin levels in premature infants attributed to their reduced ability to excrete this drug.

Quantitative angiographic and morphologic aspects of aortic valve atresia.

Quantitative angiographic measurements were performed in 15 infants aged 1 to 35 days who had aortic valve atresia with intact ventricular septum and hypoplastic left ventricle. Thirteen infants had similar measurements performed at autopsy. The latter measurements were smaller than those found at angiography (because of shrinkage), but their relationship was predictable. Angiographic right ventricular (RV) volumes were 2 and 4 times normal in diastole and systole, respectively. The RV volume measured at autopsy was greater than 3 times normal. Mean RV ejection fraction was 0.40; it was below normal in 10 infants. Maximal right atrial volume was greater than 2 times normal, and mean left atrial maximal volume was two-thirds normal. The relation between circumferences of the aortic arch and ascending and descending aorta was similar at angiography and autopsy.