The role of coronary angiography in out-of-hospital cardiac arrest patients in the absence of ST-segment elevation: A literature review.

Out-of-hospital cardiac arrest (OHCA) is a major cause of death. Although the aetiology of cardiac arrest can be diverse, the most common cause is ischaemic heart disease. Coronary angiography and percutaneous coronary intervention, if indicated, has been associated with improved long-term survival for patients with initial shockable rhythm. However, in patients without ST-segment elevation on the post-resuscitation electrocardiogram, the optimal timing of performing this invasive procedure is uncertain. One important challenge that clinicians face is to appropriately select patients that will benefit from immediate coronary angiography, yet avoid unnecessary delay of intensive care support and targeted temperature management. Observational studies have reported contradictory results and until recently, randomised trials were lacking. The Coronary Angiography after Cardiac Arrest without ST-segment elevation (COACT) was the first randomised trial that provided comparative information between coronary angiography treatment strategies. This literature review will provide the current knowledge and gaps in the literature regarding optimal care for patients successfully resuscitated from OHCA in the absence of ST-segment elevation and will primarily focus on the role and timing of coronary angiography in this high-risk patient population.

Outcome and Prognostic Impact of Surgical Staging in Serous Tubal Intraepithelial Carcinoma: A Cohort Study and Systematic Review.

The optimal management of breast cancer susceptibility gene (BRCA)1/2 carriers with isolated serous tubal intraepithelial carcinoma (STIC) found at risk-reducing salpingo-oophorectomy (RRSO) is unclear. The prevalence of occult carcinoma and STIC in a consecutive series of BRCA1/2 carriers undergoing RRSO is reported. The outcome of staging procedures in BRCA1/2 carriers with isolated STIC at RRSO as well as the relationship between staging, chemotherapy treatment and risk of recurrence was assessed via a systematic review of the literature. Our series included 235 BRCA1/2 carriers who underwent RRSO. Federation of Gynaecology and Obstetrics stage IA carcinoma or STIC was found at RRSO in three (1.3%) and two (0.9%) patients, respectively. A systematic review of the literature included 82 BRCA1/2 carriers with isolated STIC found at RRSO. In 13/82 (16%) cases with STIC, staging was reported. In none of these cases staging revealed more advanced disease. Recurrent disease was found in four of 36 patients with reported follow-up. The estimated risk of recurrence in patients with isolated STIC at RRSO was about 11% (95% confidence interval 3-26%) after a median follow-up of 42 months (range 7-138). No recurrences were reported in those patients with STIC at RRSO who underwent staging or received chemotherapy. We found 1.3% occult carcinoma and 0.9% STIC at RRSO in our cohort of BRCA1/2 carriers. A systematic review of the literature suggests that additional treatment after RRSO, i.e. staging and/or chemotherapy, is associated with a lower risk of recurrence. However, data on staging and follow-up are limited.

Epidermal growth factor receptor mutations should be considered as a prognostic factor for survival of patients with pathological fractures or painful bone metastases from non-small cell lung cancer.

AIMS: This study aims to assess first, whether mutations in the epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma (kRAS) genes are associated with overall survival (OS) in patients who present with symptomatic bone metastases from non-small cell lung cancer (NSCLC) and secondly, whether mutation status should be incorporated into prognostic models that are used when deciding on the appropriate palliative treatment for symptomatic bone metastases. PATIENTS AND METHODS: We studied 139 patients with NSCLC treated between 2007 and 2014 for symptomatic bone metastases and whose mutation status was known. The association between mutation status and overall survival was analysed and the results applied to a recently published prognostic model to determine whether including the mutation status would improve its discriminatory power. RESULTS: The median OS was 3.9 months (95% confidence interval (CI) 2.1 to 5.7). Patients with EGFR (15%) or kRAS mutations (34%) had a median OS of 17.3 months (95% CI 12.7 to 22.0) and 1.8 months (95% CI 1.0 to 2.7), respectively. Compared with EGFR-positive patients, EGFR-negative patients had a 2.5 times higher risk of death (95% CI 1.5 to 4.2). Incorporating EGFR mutation status in the prognostic model improved its discriminatory power. CONCLUSION: Survival prediction models for patients with symptomatic bone metastases are used to determine the most appropriate (surgical) treatment for painful or fractured lesions. This study shows that NSCLC should not be regarded as a single entity in such models. Cite this article: Bone Joint J 2017;99-B:516-21.

Prevalence and reproducibility of differences between home and ambulatory blood pressure and their relation with hypertensive organ damage.

Home and ambulatory blood pressure (BP) better predict cardiovascular disease than office BP, but are not interchangeable. We hypothesised that home BP may be higher than office BP because of anticipatory reactions to self-measurement and studied prevalence and reproducibility of incremental differences between home and daytime ambulatory BP and their relation with hypertensive organ damage. A total of 176 participants (mean age 57.1±12.8 years, 43.2% female) measured their BP for 2 weeks and received a 24-h ambulatory BP in between. Hypertensive organ damage was assessed by urinary albumin-to-creatinine ratio and electrocardiographic criteria for left ventricular hypertrophy. Thresholds of 10/5 and 20/10 mm Hg were used to define relevant systolic/diastolic differences between home and ambulatory BP. A higher home compared to ambulatory BP was present in 92 (52.3%) and 35 (19.1%) participants, while lower home BP values were present in 36 (20.4%) and 8 (4.5%) subjects for differences ⩾10/5 and ⩾20/10 mm Hg. Participants with higher home than ambulatory BP differences were older, had higher body mass index, higher office BP, more antihypertensive medication and lower glomerular filtration rate (P<0.01). Differences between home and ambulatory BP were highly reproducible (r=0.80 and 0.67 for systolic and diastolic BP, P<0.001). Both home and ambulatory BPs were associated with organ damage, but their difference was not. Many patients have a significantly higher home than ambulatory BP. Differences between home and ambulatory BP are reproducible, but not associated with hypertensive organ damage. Our findings suggest that ambulatory BP remains the standard of reference when positive differences between home and ambulatory BP exist.

Clinical parameters associated with collateral development in patients with chronic total coronary occlusion.

OBJECTIVE: Well-developed collaterals provide survival benefit in patients with obstructive coronary artery disease (CAD). Therefore, in this study we sought to determine which clinical variables are associated with arteriogenesis. DESIGN: Clinical and laboratory variables were collected before percutaneous coronary intervention. Multivariate analysis was performed to determine which variables are associated with the collateral flow index (CFI). PATIENTS: Data from 295 chronic total occlusion (CTO) patients (Bern, Switzerland, Amsterdam, the Netherlands and Jena, Germany) were pooled. In earlier studies, patients had varying degrees of stenosis. Therefore, different stages of development of the collaterals were used. In our study, a unique group of patients with CTO was analysed. INTERVENTIONS: Instead of angiography used earlier, we used a more accurate method to determine CFI using intracoronary pressure measurements. CFI was calculated from the occlusive pressure distal of the coronary lesion, the aortic pressure and central venous pressure. RESULTS: The mean CFI was 0.39 ± 0.14. After multivariate analysis, ß blockers, hypertension and angina pectoris duration were positively associated with CFI (B: correlation coefficient ß=0.07, SE=0.03, p=0.02, B=0.040, SE=0.02, p=0.042 and B=0.001, SE=0.000, p=0.02). Furthermore also after multivariate analysis, high serum leucocytes, prior myocardial infarction and high diastolic blood pressure were negatively associated with CFI (B=-0.01, SE=0.005, p=0.03, B=-0.04, SE=0.02, p=0.03 and B=-0.002, SE=0.001, p=0.011). CONCLUSIONS: In this unique cohort, high serum leucocytes and high diastolic blood pressure are associated with poorly developed collaterals. Interestingly, the use of ß blockers is associated with well-developed collaterals, shedding new light on the potential action mode of this drug in patients with CAD.

Estimating the 5-percentile of the species sensitivity distributions without any assumptions about the distribution.

A non-parametric method is described to estimate the hazardous concentration for p% of the species, the HCp, and the confidence limits for this value, the HCp(alpha). For this method, all observed sensitivities are ordered from high to low sensitivity. The HC5 is the k-th observation were k is the largest integer below 0.05 x (n + 1). It is described how the HCp(alpha) can be calculated. A table is presented for easy calculation of several conservative confidence limits for the HC5. For the HC5(0.05), a second table is presented which can be used to interpolate between the conservative estimate of the HC5(0.05) and the next higher observed concentration. The non-parametric HC5 and HC5(0.05) estimation is illustrated with an example of sensitivity data on malathion. For this data set, the log-normal HC5 and HC5(0.05) estimations appear to be conservative compared with the non-parametric estimate. It is stressed that HC5 and HC5(0.05) estimates will often be much more affected by the non-randomness of the species set for which sensitivity data are available than by the choice of the statistical method.

Field research for the authorisation of pesticides.

On request of the Dutch government a committee of the Health Council of the Netherlands has reviewed the role that results of field research in its broadest sense (i.e., including multi-species toxicity tests in the laboratory, research on model ecosystems et cetera) can play in ecotoxicological risk assessment for the authorisation of pesticides. The Committee believes that field research can provide valuable additional data about the exposure of non-target organisms and the resultant effects at population, community and ecosystem level. However, it frequently is unclear how these data might be used in reaching a decision about authorisation. To solve this problem, it is necessary to specify what is understood by "unacceptable damage". Both more clearly formulated protection goals of the government and a better understanding of the ecological significance of effects are needed to clarify this. Furthermore, the Committee points out that the statistical power of field trials must be sufficient to allow for the detection of changes that might be regarded as ecologically relevant. Finally, it recommends keeping a finger on the pulse in relation to authorised pesticides by monitoring their presence in environmental compartments and by investigating their role in suddenly occurring mortality among conspicuous animal species, such as birds, fish and honeybees. This kind of research forms a safety net for substances that have been wrongly authorised.

The ecotoxicity and the biodegradability of lactic acid, alkyl lactate esters and lactate salts.

The ecotoxicity of lactic acid, its alkyl esters and selected metal salts was studied experimentally with the micro alga Selenastrum capricornutum, the crustacean Daphnia magna and the fish species Brachydanio rerio and Pimephales promelas. In addition, the biodegradation of lactate esters was also studied. The aim of the study was to provide predicted environmental data for additional alkyl homologues and metal salts. The ecotoxicity data are evaluated by means of Structure Activity Relations (SAR), using literature data on a non-polar narcotic mechanism of toxicity as a baseline for comparison. Lactate salts were evaluated by comparison to the toxicity of the metal ion. For the fish and D. magna, it was evident that methyl, ethyl, propyl and to a lesser extent butyl lactate were slightly more toxic in comparison to baseline non-polar narcotic toxicity data. The toxicity tests carried out with lactate-salts demonstrated clearly that the toxicity in standard tests is only determined by the associated cation and not by the lactate part. Lactic acid and its alkyl esters were degraded for more than 60% in the ready biodegradability tests and from the data presented, it is evident that the majority of alkyl lactates are readily biodegradable. The results presented in this study indicate that alkyl lactate esters show some differences in their ecotoxicity when compared to non polar narcotic compounds in but that these differences are generally small. When aquatic toxicity is considered together with their rapid tendency to biodegrade, it is concluded that lactate esters show generally favourable environmental characteristics.

The acute toxicity of selected alkylphenols to young and adult Daphnia magna.

Differences in sensitivity toward toxicants between young and adult individuals in a population are assumed to be primarily associated with their difference in body size. This assumption plays a key role in the modeling of effects of variable concentrations of toxicants on nonhomogeneous populations. The hazard-based no-effect-concentrations (NECs), killing rates, and elimination rates, estimated from the survival data of a series of acute toxicity tests with young and adults of Daphnia magna and six alkylphenols, were used to evaluated this assumption. The results lead to the conclusion that young and adult D. magna were equally sensitive in terms of NEC and killing rate and that the observed differences in elimination rates could be explained on the basis of a difference in body size. Furthermore, it was found that elimination rates estimated on the basis of the survival data were consistently smaller than those expected on the basis of a QSAR for Daphnia pulex, a comparable species. This discrepancy was likely due to a decreased uptake and elimination during a period of immobilization prior to death. Since it is unknown to what extent immobilized individuals are able to recover from short-term exposures, the observed deviation clearly identifies a complicating factor in the modeling of effects of variable concentrations of toxicants.

Salmonella test: relation between mutagenicity and number of revertant colonies.

This paper describes a model that relates the actual effect measured in the Salmonella test, i.e., the number of revertant colonies, to the mutation rate induced by a stable test compound having no side effects and acting without a time-lag. A maximum-likelihood estimator for the mutation rate is derived. Furthermore some side effects (mortality, increase in generation time, other mutations) are included in more extensive models. Side effects can cause a non-linear dose-response relation. Factors delaying the effect of the compound lead to an apparently higher mutation rate if a higher histidine dose is applied or a smaller inoculum is used. Factors slowly decreasing the effect of the compound reverse this result. Secondary effects of the test compound on the bacteria result in a non-linear dose-response relationship.

Superparasitism as an ESS: to reject or not to reject, that is the question.

A stochastic model is formulated to determine the optimal strategy for a solitary parasitoid which has discovered an already parasitized host. The model assumes that the parasitoid can count both the number of eggs already present in a host and the number of conspecifics searching in the same patch. The survival probability of an egg is assumed to depend on the total number of eggs in a host. The decision to (super)parasitize depends both on the degree to which the discovered host already is parasitized and on the number of conspecific females searching in the same patch. We consider both the case that egg laying does not involve any costs for the parasitoid and the case that it involves some marginal costs. Uniform behaviour of all the conspecific parasitoids in a patch, i.e. laying one additional egg in all encountered larvae containing a particular number of eggs, appears to be a pure evolutionary stable strategy (ESS). If either the probability that a parasitoid emerges from a host decreases with an increasing degree of parasitism, at least from a particular number of eggs onwards, or if parasitism involves marginal costs, the maximum number of eggs for which it is still profitable to superparasitize a host once more is limited. This number increases with the number of conspecifics searching in the patch. Large marginal costs (i.e. the expected gain of not parasitizing now) decrease the profit of superparasitism. For newly emerged parasitoids the rejection of an already parasitized host is not advantageous as long as the marginal costs of parasitism are small, because the host can never contain an egg of its own.

Effect of 3,4-dichloroaniline and metavanadate on Daphnia populations.

Fourteen continuously fed populations of Daphnia magna were exposed to 3,4-dichloroaniline (3,4-DCA) or metavanadate and monitored for 20 (two controls), 14 (six with metavanadate), and 8 (six with 3,4-DCA) weeks. The controls showed a damped oscillation. Low concentrations of either 3,4-DCA or metavanadate stimulated the first population peak. High concentrations of metavanadate rendered population peaks less regular, and at the highest metavanadate concentration, one population perished. High concentrations of 3,4-DCA slightly reduced population size. Four periodically fed populations of D. magna were also monitored. The more they were fed, the larger they grew. In the continuously fed populations, ephippia were formed at and just after the population peaks. No ephippia were noted in the periodically fed populations. Metavanadate promoted the formation of ephippia (NOEC 0.56 mg/liter), and 3,4-DCA depressed sexual reproduction at all concentrations tested (6, 12, and 24 micrograms/liter). The population dynamics of the controls were compared with those predicted by Kooijman's model (1986a, in The Dynamics of Physiologically Structured Populations (J.A.J. Metz and O. Diekmann, Eds.), pp. 266-297, Springer Lecture Notes in Biomathematics; 1986b, J. Math. Biol. 23, 163-185) for growth and reproduction of individual daphnids. In general, there is reasonable agreement between model predictions and observations, but some adjustments to the model may be necessary.

Coexistence of incompatible plasmids in a bacterial population living under a feast and famine regime.

A model is formulated to examine the possibility of (co)existence of plasmids of the same incompatibility and surface exclusion group in a bacterial population living under a feast-and-famine regime. The condition is given under which a growth rate decreasing plasmid can invade a bacterial population. It appears that in case only one plasmid type is present, the frequency of plasmid bearers will tend to a stable equilibrium if the food supply at each growth site gets exhausted and if both plasmid-free and plasmid-bearing bacteria need an equal quantity of food per cell division. If these two conditions are not satisfied, the frequency of plasmid-bearers might oscillate. Two plasmids will sometimes be able to coexist, but only if they follow different survival strategies; one with a high conjugational transfer rate and a lower fitness of its host, and the other with a low transfer rate and a higher host fitness. Coexistence of three plasmids of the same surface exclusion group is impossible.

Evolution of bacterial surface exclusion against incompatible plasmids.

Many conjugative transferable plasmids exhibit surface exclusion against plasmids of the same incompatibility group. A mathematical model is developed to calculate under which conditions surface exclusion against incompatible plasmids can evolve. It appears that plasmids inducing surface exclusion can evolve and even replace non-excluding plasmids if the copy number is low and the transfer rate high provided that the cost of surface exclusion is small. They can more easily expel the non-excluding plasmids if the possession of a plasmid is not very harmful for a bacterium and if the rate at which plasmids are lost is small.

The function of host discrimination and superparasitization in parasitoids.

Host discrimination, i.e. the ability to distinguish unparasitized hosts from parasitized ones, and to reject the latter for egg laying is present in many parasitic wasp species. This property is classically considered as an example of contest competition, and is supposed to have a number of functions. However, different species do not react to each other's marks and lay eggs in hosts parasitized by the other species. Apparently the marks used for recognition are specific.Multiparasitization is the best strategy when hosts are scarce and the egg supplies of the parasitoids are not limited. Interspecific host discrimination is not an ESS.Superparasitization within one species would have selective advantage if the number of unparasitized hosts is small and the wasp has a reasonable chance to lay her egg in a host that is not parasitized by herself, and if the chance for her offspring to survive the competitive battle with the first parasitoid larva is not too small. This is shown to be the case.However, marks are not individual and wasps cannot distinguish hosts parasitized by themselves from those parasitized by others. The hypothesis is tested that the egg laying strategy (i.e. the decision to superparasitize) of wasps is dependent on the number of conspecifics that is searching simultaneously for hosts, since this determines the chance that a parasitized host encountered by a wasp is parasitized by herself.It is shown that host discrimination cannot be regarded as a case of contest competition. Other aspects of superparasitization, related to interference and population regulation, sex allocation and encapsulation are briefly discussed.

A mathematical model for the co-existence of incompatible, conjugative plasmids in individual bacteria of a bacterial population.

A model is formulated to examine the possibility of coexistence of two or more plasmids of the same surface exclusion group in a bacterial chemostat culture. It appears that two plasmids are able to coexist. If two plasmids can coexist they will follow different survival strategies, one with a high conjugational transfer rate and a low fitness of its host, and other with a low transfer rate and a high host fitness. Coexistence of three plasmids of the same surface exclusion group is impossible.