Development of a value-based healthcare burns core set for adult burn care.

BACKGROUND: Value-based healthcare (VBHC) is increasingly implemented in healthcare worldwide. Transparent measurement of the outcomes most important and relevant to patients is essential in VBHC, which is supported by a core set of most important quality indicators and outcomes. Therefore, the aim of this study was to develop a VBHC-burns core set for adult burn patients. METHODS: A three-round modified national Delphi study, including 44 outcomes and 24 quality indicators, was conducted to reach consensus among Dutch patients, burn care professionals and researchers. Items were rated on a nine-point Likert scale and selected if ≥ 70% in each group considered an item 'important'. Subsequently, instruments quantifying selected outcomes were identified based on a literature review and were chosen in a consensus meeting using recommendations from the Dutch consensus-based standard set and the Dutch Centre of Expertise on Health Disparities. Time assessment points were chosen to reflect the burn care and patient recovery process. Finally, the initial core set was evaluated in practice, leading to the adapted VBHC-burns core set. RESULTS: Twenty-seven patients, 63 burn care professionals and 23 researchers participated. Ten outcomes and four quality indicators were selected in the Delphi study, including the outcomes pain, wound healing, physical activity, self-care, independence, return to work, depression, itching, scar flexibility and return to school. Quality indicators included shared decision-making (SDM), the number of patients receiving aftercare, determination of burn depth, and assessment of active range of motion. After evaluation of its use in clinical practice, the core set included all items except SDM, which are assessed by 9 patient-reported outcome instruments or measured in clinical care. Assessment time points included are at discharge, 2 weeks, 3 months, 12 months after discharge and annually afterwards. CONCLUSION: A VBHC-burns core set was developed, consisting of outcomes and quality indicators that are important to burn patients and burn care professionals. The VBHC-burns core set is now systemically monitored and analysed in Dutch burn care to improve care and patient relevant outcomes. As improving burn care and patient relevant outcomes is important worldwide, the developed VBHC-burns core set could be inspiring for other countries.

Outcomes that matter most to burn patients: A national multicentre survey study in the Netherlands.

BACKGROUND: The use of patient-reported outcomes to improve burn care increases. Little is known on burn patients' views on what outcomes are most important, and about preferences regarding online Patient Reported Outcome Measures (PROMs). Therefore, this study assessed what outcomes matter most to patients, and gained insights into patient preferences towards the use of online PROMs. METHODS: Adult patients (≥18 years old), 3-36 months after injury completed a survey measuring importance of outcomes, separately for three time periods: during admission, short-term (<6 months) and long-term (6-24 months) after burn injury. Both open and closed-ended questions were used. Furthermore, preferences regarding the use of patient-reported outcome measures in burn care were queried. RESULTS: A total of 140 patients were included (response rate: 27%). 'Not having pain' and 'good wound healing' were identified as very important outcomes. Also, 'physical functioning at pre-injury level', 'being independent' and 'taking care of yourself' were considered very important outcomes. The top-ten of most important outcomes largely overlapped in all three time periods. Most patients (84%) had no problems with online questionnaires, and many (67%) indicated that it should take up to 15 minutes. Patients' opinions differed widely on the preferred frequency of follow-up. CONCLUSIONS: Not having pain and good wound healing were considered very important during the whole recovery of burns; in addition, physical functioning at pre-injury level, being independent, and taking care of yourself were deemed very important in the short and long-term. These outcomes are recommended to be used in burn care and research, although careful selection of outcomes remains crucial as patients prefer online questionnaires up to 15 minutes.

Latent Markov Models to Test the Strategy Use of 3-Year-Olds in a Rule-Based Feedback-Learning Task.

This study is the first to investigate how 3-year-olds learn simple rules from feedback using the Toddler Card Sorting Task (TCST). To account for intra- and inter- individual differences in the learning process, latent Markov models were fitted to the time series of accuracy responses using maximum likelihood techniques (Visser et al., 2002). In a first, exploratory study (N = 110, 3- to 5-years olds) a considerable group of 3-year olds applied a hypothesis testing learning strategy. A second study confirmed these results with a preregistered study (3-years olds, N = 60). Under supportive learning conditions, a majority of 3-year- olds was capable of hypothesis testing. Furthermore, older children and those with bigger working memory capacities were more likely to use hypothesis testing, even though the latter group perseverated more than younger children or those with smaller working memory capacities. 3-year-olds are more advanced feedback-learners than assumed.

Systematic review and meta-analysis: Diagnostic performance of DNA alterations in pancreatic juice for the detection of pancreatic cancer.

BACKGROUND AND AIMS: Pancreatic cancer has a dismal prognosis. So far, imaging has been proven incapable of establishing an early enough diagnosis. Thus, biomarkers are urgently needed for early detection and improved survival. Our aim was to evaluate the pooled diagnostic performance of DNA alterations in pancreatic juice. METHODS: A systematic literature search was performed in EMBASE, MEDLINE Ovid, Cochrane CENTRAL and Web of Science for studies concerning the diagnostic performance of DNA alterations in pancreatic juice to differentiate patients with high-grade dysplasia or pancreatic cancer from controls. Study quality was assessed using QUADAS-2. The pooled prevalence, sensitivity, specificity and diagnostic odds ratio were calculated. RESULTS: Studies mostly concerned cell-free DNA mutations (32 studies: 939 cases, 1678 controls) and methylation patterns (14 studies: 579 cases, 467 controls). KRAS, TP53, CDKN2A, GNAS and SMAD4 mutations were evaluated most. Of these, TP53 had the highest diagnostic performance with a pooled sensitivity of 42% (95% CI: 31-54%), specificity of 98% (95%-CI: 92%-100%) and diagnostic odds ratio of 36 (95% CI: 9-133). Of DNA methylation patterns, hypermethylation of CDKN2A, NPTX2 and ppENK were studied most. Hypermethylation of NPTX2 performed best with a sensitivity of 39-70% and specificity of 94-100% for distinguishing pancreatic cancer from controls. CONCLUSIONS: This meta-analysis shows that, in pancreatic juice, the presence of distinct DNA mutations (TP53, SMAD4 or CDKN2A) and NPTX2 hypermethylation have a high specificity (close to 100%) for the presence of high-grade dysplasia or pancreatic cancer. However, the sensitivity of these DNA alterations is poor to moderate, yet may increase if they are combined in a panel.

Electrode Surface Potential-Driven Protein Adsorption and Desorption through Modulation of Electrostatic, van der Waals, and Hydration Interactions.

When proteins in aqueous solutions are exposed to solid substrates, they adsorb due to the dynamic interplay of electrostatic, van der Waals, and hydration interactions and do so in a rather irreversible fashion, which makes protein recovery troublesome. Here, we use a gold electrode as the solid substrate and modulate the surface potential to systematically induce protein adsorption as well as partial desorption. We use different methods such as surface plasmon resonance, atomic force microscopy, and electrowetting and show that biasing the electrode to more negative potentials (by -0.4 V compared to the open-circuit potential at pH 6) results in an increased adsorption barrier of 6 kJ mol-1 for the negatively charged protein ß-lactoglobulin. Further, we clearly demonstrate that this is due to an increased double layer potential of -0.06 V and an increase in hydration repulsion. This indicates that an electric potential can directly influence surface interactions and thus induce partial ß-lactoglobulin desorption. These observations can be the basis for biosensors as well as separation technologies that use only one trigger to steer protein ad- and desorption, which is low in energy requirement and does not generate large waste streams, as is the case for standard protein separation technologies.

Performance of the Emprint and Amica Microwave Ablation Systems in ex vivo Porcine Livers: Sphericity and Reproducibility Versus Size.

PURPOSE: To investigate the performance of two microwave ablation (MWA) systems regarding ablation volume, ablation shape and variability. MATERIALS AND METHODS: In this ex vivo study, the Emprint and Amica MWA systems were used to ablate porcine livers at 4 different settings of time and power (3 and 5 minutes at 60 and 80 Watt). In total, 48 ablations were analysed for ablation size and shape using Vitrea Advanced Visualization software after acquisition of a 7T MRI scan. RESULTS: Emprint ablations were smaller (11,1 vs. 21,1 mL p < 0.001), more spherical (sphericity index of 0.89 vs. 0.59 p < 0.001) and showed less variability than Amica ablations. In both systems, longer ablation time and higher power resulted in significantly larger ablation volumes. CONCLUSION: Emprint ablations were more spherical, and the results showed a lower variability than those of Amica ablations. This comes at the price of smaller ablation volumes.

Do infants have the horizontal bias?

A robust set of studies show that adults make more horizontal than vertical and oblique saccades, while scanning real-world scenes. In this paper we study the horizontal bias in infants. The directions of eye movements were calculated for 41 infants (M=8.40 months, SD=3.74, range=3.48-15.47) and 47 adults (M=21.74 years, SD=4.54, range=17.89-39.84) while viewing 28 real-world scenes. Saccade directions were binned to study the proportion of saccades in the horizontal, vertical and oblique directions. In addition, saccade directions were also modeled using a mixture of Von Mises distributions, to account for the relatively large amount of variance in infants data. Horizontal bias was replicated in adults and also found in infants, using both the binning and Von Mises approach. Moreover, a developmental pattern was observed in which older infants are more precise in targeting their saccades than younger infants. That infants have a horizontal bias is important in understanding infants' eye movements. Future studies should account for the horizontal bias in their designs and analyses.

DHEAS and cortisol/DHEAS-ratio in recurrent depression: State, or trait predicting 10-year recurrence?

BACKGROUND: Major depressive disorder (MDD) has been associated with low dehydroepiandrosterone-sulphate (DHEAS), - particularly relative to high cortisol - although conflicting findings exist. Moreover, it is unclear whether low DHEAS is only present during the depressive state, or manifests as a trait that may reflect vulnerability for recurrence. Therefore, we longitudinally tested whether low DHEAS and high cortisol/DHEAS-ratio in recurrent MDD (I) reflects a trait, and/or (II) varies with depressive state. In addition, we tested associations with (III) previous MDD-episodes, (IV) prospective recurrence, and (V) effects of cognitive therapy. METHODS: At study-entry, we cross-sectionally compared morning and evening salivary DHEAS and molar cortisol/DHEAS-ratio of 187 remitted recurrent MDD-patients with 72 matched controls. Subsequently, patients participated in an 8-week randomized controlled cognitive therapy trial. We repeated salivary measures after 3 months and 2 years. We measured clinical symptoms during a 10-year follow-up. RESULTS: Remitted patients showed steeper diurnal DHEAS-decline (p<.005) and a flatter diurnal profile of cortisol/DHEAS-ratio (p<.001) than controls. We found no state-effect in DHEAS or cortisol/DHEAS-ratio throughout follow-up and no association with number of previous episodes. Higher morning cortisol/DHEAS-ratio predicted shorter time till recurrence over the 10-year follow-up in interaction with the effects of cognitive therapy (p<.05). Finally, cognitive therapy did not influence DHEAS or cortisol/DHEAS-ratio. CONCLUSIONS: Diurnal profiles of DHEAS and cortisol/DHEAS-ratio remain equally altered in between depressive episodes, and may predict future recurrence. This suggests they represent an endophenotypic vulnerability trait rather than a state-effect, which provides a new road to understand recurrent depression and its prevention. TRIAL REGISTRATION: www.isrctn.com/ISRCTN68246470.

The one-carbon-cycle and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in recurrent major depressive disorder; influence of antidepressant use and depressive state?

BACKGROUND: An important biological factor suggested in the pathophysiology of (recurrent) Major Depressive Disorder (MDD) concerns a polymorphism in a gene encoding for the MTHFR-enzyme of the one-carbon (1-C)-metabolism. Integratively investigating key 1-C-components (folate, homocysteine, vitamin B6 and B12), including the possible effects of antidepressant medication and depressive state, could provide more insight in the possible association between the MTHFR-polymorphism and recurrent MDD. METHODS: We compared the MTHFR C677T-polymorphism together with the key 1-C-components in clinically ascertained patients with recurrent MDD (n=137) to age- and gender-matched healthy controls (n=73). RESULTS: First, patients had lower folate (t=2.25; p=.025) as compared to controls; a difference that resolved after correction for demographics (t=1.22; p=.223). Second, patients that were depressed during sampling had lower vitamin B6 (t=-2.070; p=.038) and higher homocysteine (t=2.404; p=.016) compared to those in remission. Finally, current use of antidepressants had no influence on the 1-C-components. CONCLUSIONS: Despite investigation of a specific recurrently depressed patient population, we found no clear associations with the 1-C-cycle, except for higher homocysteine and lower vitamin B6 during the depressed state. This suggests that 1-C-cycle alterations in MDD are state-associated, possibly resulting from high levels of acute (psychological) stress, and may provide a treatment target to reduce cardiovascular risk in this population.

Tracheal intubation with a camera embedded in the tube tip (Vivasight(™) ).

We studied tracheal intubation in manikins and patients with a camera embedded in the tip of the tracheal tube (Vivasight(™) ). Four people in two teams and two individuals attempted intubation of a manikin through an i-gel(™) 10 times each. The tracheas of 12 patients with a Mallampati grade of 1 were intubated with a Vivasight tracheal tube through a Berman airway, passed over a Frova(™) introducer. All 60 manikin intubations were successful, taking a mean (SD) time of 1.4 (0.5) s. The fastest intubation was performed in 0.5 s. All 12 participants' tracheas were successfully intubated in a median (IQR [range]) time of 90 (70-120 [50-210]) s. Seven participants complained of a sore throat, comparable with earlier findings for standard laryngoscopy and intubation: five mild; one moderate; and one severe. Tracheal intubation with the Vivasight through the i-gel or Berman airway is an alternative to existing techniques, against which it should be compared in randomised controlled trials in human participants. It has potential as a fast airway rescue technique.

Disease course and outcome of acute disseminated encephalomyelitis is more severe in adults than in children.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) affects children more frequently than adults. Current studies investigating ADEM in different age groups are difficult to compare. OBJECTIVE: To investigate whether the clinical presentation, outcome and disease course of ADEM differ between adults and children. METHODS: Disease characteristics of 25 adults and 92 children suffering from ADEM between 1988 and 2008 were compared. RESULTS: The most common presenting symptoms of ADEM in both groups were pyramidal signs and encephalopathy. Ataxia occurred more frequently in children (p = 0.002). In general, MRI showed ill-defined and large white matter lesions in both groups, whereas periventricular lesions were more prevalent in adults (p = 0.001). In adults, duration of hospitalization was longer (p = 0.002) and intensive care unit (ICU) admission was more frequently required (p = 0.043). Three adults (12%) and one child (1%) died (p = 0.030). Fewer adults had complete motor recovery after their first clinical event (p < 0.001). In 73 patients follow-up time was ≥ 2 years and most of these patients remained monophasic. Although relapses after ADEM can occur, only one adult (5%) and five children (6%) converted to MS. CONCLUSIONS: The clinical presentations in children and adults share similarities, but the disease course and outcome of ADEM is more severe in adults with respect to hospitalization, ICU admission, recovery and mortality.

Multiple strains of Mycobacterium avium subspecies hominissuis infections associated with aborted fetuses and wasting in pigs.

A herd of pigs being reared for breeding and fattening, in which there had been incidences of abortion and wasting, reduced growth rates and an increase in mortality for the past year, were tested for Mycobacterium infection by pathological examinations, skin test, serology and Mycobacterium culture. In one placenta, and also in the lung tissues of fetuses, Ziehl-Neelsen staining revealed acid-fast bacilli in combination with infiltrations of neutrophils, macrophages and multinucleated giant cells. Acid-fast bacilli were also found in the mesenteric lymph nodes, liver and/or spleen and jejunum of pigs with wasting and in slaughtered animals. The specimen cultures were identified as Mycobacterium avium subspecies hominissuis using IS1245-specific PCR and IS1245 restriction fragment length polymorphism (RFLP). IS1245 RFLP revealed that the herd was infected with multiple M avium subspecies hominissuis strains belonging to at least two different clades. It is suggested that this infection may have played a more important role in the economic losses of the pig farm than had been assumed previously.

[Campylobacter as a venereal disease in cattle]. / Campylobacter als dekinfectie bij rundvee.

Since the introduction of AI, venereal diseases caused by Tritrichomonas fetus and Campylobacter fetus subsp. venerealis haved been eradicated in The Netherlands. Campylobacter fetus subsp. fetus can cause sporadic abortion and early embryonic death. When natural breeding is practised, venereal diseases must be included in the list of differential diagnoses of fertility problems. A case study of a Campylobacter fetus subsp. fetus infection is described.

Comparison of clinical and pathological diagnoses in dogs.

Clinical and pathological diagnoses were compared in a prospective study of 145 dogs. A diagnostic work up had been performed on all dogs of which 36 (24.8%) died and 109 (75.2%) were euthanatized. In 119 dogs (82.1%) both a clinical and patholical diagnosis was made, in 20 dogs (13.8%) no pathological diagnosis could be made and in 6 dogs (4.1%) no clinical diagnosis was established. In the 119 dogs the agreement level between clinical and pathological diagnosis was scored by the referring veterinarian together with a pathologist. Total agreement was found in 61 cases (51.3%) and disagreement in 31 cases (26.0%). In the remaining cases (27=22.7%) the pathological diagnosis further specified the clinical diagnosis. Consecutive submission appeared difficult to achieve by the participating veterinarians. However, no major differences in agreement level was present between the veterinarian which succeeded in almost consecutive submissions and the other veterinarians. At necropsy 42 cases were diagnosed as neoplasia, of which 52.4% had been diagnosed clinically. As to infectious diseases 55.0% of these diseases diagnosed at necropsy had been diagnosed clinically. In about 20% of the cases the differences were of clinical significance according to the referring veterinarians. In addition, it was indicated by the clinicians that about 50% of the necropsies revealed findings which could amend future patient care. The results of the study stress the relevance of postmortem examination as crucial part of continuing education and of quality monitoring and assurance in veterinary medicine.

[Infectious bovine keratoconjunctivitis (IBK) in cows, clinical and lab review at four farms]. / Infectieuze keratoconjunctivitis bij runderen, overzicht aan de hand van kliniek- en laboratoriumonderzoek op vier bedrijven.

After several reports to the GD (Dutch Animal Health Service) from practitioners in The Netherlands concerning serious Infectious Bovine Keratoconjunctivitis (IBK) in dairy herds during summer and autumn 2003, the GD has carried out a pilot-study to determine the most responsible agent. This pilot was thought to be important because of the painfulness of the illness and problems like, (for the farmer) an intensive and difficult therapy. Also the report of a Chlamydophilae infection causing IBK in a dairy herd in the UK prompted to this study. The most frequently isolated infectious agent in our study was Moraxella, probably M. bovis. For the presence of Chlamydophila, mycoplasmata or BHV1 viruses were no indications.

Fatty acids and homocysteine levels in patients with recurrent depression: an explorative pilot study.

Major depressive disorders (MDD) and cardiovascular disease are mutually associated. They share signs and symptoms of the "metabolic syndrome". Two observations that may be causally related with the metabolic syndrome and therefore with both MDD and cardiovascular disease are a decrease in omega-3 polyunsaturated fatty acids (PUFAs) and a rise in plasma homocysteine (tHcy) levels. Both the rise in tHcy and the decrease in omega-3 PUFAs may be associated with enhanced lipid peroxidation. We exploratively studied 44 randomly chosen patients out of a cohort of 134 patients with the recurrent form of MDD (MDD-R). We measured tHcy levels together with saturated FAs, monounsaturated fatty acids (MUFAs) and PUFAs of the omega-3, omega-6 and omega-9 series in plasma and erythrocytes. Levels were compared with laboratory reference values. The main findings were a decrease in the erythrocytes of C22:5omega-3, C22:6omega-3, C24:1omega-9 and C20:3omega-9 and in the plasma a decrease in C24:1omega-9 and C20:3omega-9. The only significant association we found was between the total of omega-6 fatty acids and plasma tHcy. The FA alterations were found in patients although most of them were clinically recovered, suggesting that the alterations may represent a biological" trait" marker for recurrent depression.

Capacity of boar spermatozoa to bind zona pellucida proteins in vitro in relation to fertilization rates in vivo.

The purpose of this study was to determine variation among boars in the percentage of sperm in an ejaculate that express enhanced binding of zona pellucida proteins during treatment for capacitation in vitro, and to determine whether this relates to fertilizing ability in vivo. Ejaculates (n=35) were collected from 12 boars. A sample of each ejaculate was treated for capacitation in vitro. During incubation, the zona binding ability of spermatozoa was assessed at regular intervals with fluorescein-conjugated solubilized zona pellucida proteins (FITC-sZP) and propidium iodide, using a flow cytometer. After incubation, a percentage of the sperm had enhanced FITC-sZP binding. The percentage of viable sperm with enhanced FITC-sZP binding, expressed as a percentage of the total sperm population, increased rapidly over the first 60 min and thereafter reached a plateau after 120-180 min. Averaged over all ejaculates, the percentage at 180 min was 46% (range 27-61%); this percentage was significantly different among boars. However, the variation between ejaculates within a boar was relatively small. There was no significant boar effect on the rate at which the percentage of viable cells with enhanced FITC-sZP binding reached the maximum. In ejaculates (n=14) from four boars (selected from the group of 12), we investigated the increase in the percentage of viable sperm with enhanced sZP binding during treatment for capacitation in vitro in relation to the ability to fertilize in vivo. Sows (n=44) were inseminated 4 h after ovulation with a suboptimal insemination dose (0.5x10(9) spermatozoa). Time of ovulation was determined using transrectal ultrasonography and sows were killed at 120 h after ovulation. The percentage of fertilized oocytes, embryo development, and numbers of accessory spermatozoa were determined. The percentage of spermatozoa that were viable and showed enhanced sZP binding after 180 min of incubation was 48 +/- 12% (range 28-56%). The percentage of fertilized oocytes was 85 +/- 27% and 64% of the sows had 100% fertilized oocytes. The percentage of sows with 100% fertilized oocytes correlated well (P< or =0.05, R2=0.98) with the percentage of viable spermatozoa with enhanced FITC-sZP binding after capacitation in vitro.

[A men with a Salmonella dublin-infected aneurysm of the abdominal aorta]. / Een man met een door Salmonella dublin geïnfecteerd abdominaal aneurysma aortae.

A 71-year-old male was diagnosed with a Salmonella dublin infection. He presented with abdominal pain with no diarrhoea, and sepsis, and was found to have an infected aneurysm of the infrarenal abdominal aorta. He was treated surgically with resection of the aneurysm and implantation of an extra-anatomic axillobifemoral bypass, followed by long-term antibiotic treatment. Nine months after the primary treatment, the patient died as a result of rupture of the aortic stump. S. dublin-infected aneurysm of the abdominal aorta is a rare condition with high mortality. Human S. dublin infections are associated with the consumption of unpasteurised dairy products from infected animals.

Confidence intervals for hidden Markov model parameters.

Three methods for computing confidence intervals (CIs) of hidden Markov model parameters are compared in the context of 'long' time series, T > 100, namely likelihood profiling, bootstrapping and CIs based on a finite-differences approximation to the Hessian. First it is shown that with 'long' time series computing the exact Hessian is not feasible. In simulation studies quadratic and cubic interpolation polynomials for the likelihood profiles are compared. Likelihood profiling and bootstrapping produce similar CIs, whereas the CIs from the finite-differences approximation of the Hessian are mostly too small.