Increased risk of death associated with the use of proton-pump inhibitors in patients with dementia and controls - a pharmacoepidemiological claims data analysis.

BACKGROUND AND PURPOSE: The use of proton-pump inhibitors (PPIs) was reported to be associated with increased mortality risk and has been proposed as a potential risk factor for neurodegenerative diseases. We aimed to assess the impact of PPI use on survival in patients with dementia as compared with controls. METHODS: This register-based control-matched cohort study included 28 428 patients with dementia ascertained by the prescription of antidementia drugs and two control individuals matched by sex, age and area of residence for each patient with dementia during the study period from 1 January 2005 to 30 June 2016. Cumulative defined daily doses (DDDs) of PPIs were extracted from the health insurance prescription registries. A multivariate Cox regression model for non-proportional hazards was used to analyse mortality risk in dependence of PPI exposure, which was limited to 1 year preceding the date of cohort entry (index date) in order to avoid immortal time bias. RESULTS: The PPI exposure of 100 DDDs in the year before the index date was associated with an increased mortality risk in patients with dementia (adjusted hazard ratio, 1.07; 95% confidence intervals, 1.03-1.12), but also in controls (adjusted hazard ratio, 1.47; 95% confidence intervals, 1.31-1.64). The mortality risk in relation to PPI use was significantly lower in patients with dementia as compared with controls (P < 0.0001) and highest in the first 2 years after the index date in both cohorts. CONCLUSIONS: Our findings promote more stringent pharmacovigilance strategies to avoid PPI use in cases lacking a clear indication for therapy or where potential risks outweigh the benefits.

[Multipoint pacing-more CRT or a waste of battery power?] / MultiPoint-Pacing ­ mehr CRT oder Batterieverschwendung?

Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in patients with broad QRS complex ≥130 ms and heart failure with reduced ejection fraction despite optimal guideline-directed medical therapy. However, approximately 30% of the patients implanted with a CRT system do not show clinical benefit. Reasons for nonresponse are complex and some aspects can be addressed during follow-up. Based on quadripolar lead technology, multipoint pacing (MPP) allows left ventricular stimulation at two different sites along the lead. In particular, in scarred and fibrotic ventricular myocardium stimulation at two different sites may overcome conduction barriers and lead to homogeneous ventricular depolarization. Especially for patients that do not respond to conventional CRT, activation of MPP may present an option to increase clinical response. On the other hand, MPP may significantly decrease battery longevity.This review offers an overview of the current knowledge and data on MPP balancing the potential clinical benefit and the possible disadvantages of this therapy.

A prospective, randomised trial of pre-oxygenation strategies available in the pre-hospital environment.

Pre-oxygenation before tracheal intubation aims to increase safe apnoea duration by denitrogenation of the functional residual capacity of the lungs, and increasing oxygen stores at the onset of apnoea. Pre-oxygenation options in the pre-hospital environment are limited due to oxygen availability and equipment portability. The aim of this study was to evaluate the effectiveness of strategies available in this setting. This was a prospective, randomised, crossover study of 30 healthy volunteers who underwent 3-min periods of pre-oxygenation by tidal volume breathing with a non-rebreather mask, a bag-valve-mask and a portable ventilator. The primary outcome measure was fractional expired oxygen concentration of the first exhaled breath after each technique. The secondary outcome measure was ease of breathing, assessed using a visual analogue scale. The mean (95%CI) fractional expired oxygen concentrations achieved with the non-rebreather mask were 64 (60-68)%, bag-valve-mask 89 (86-92)% and portable ventilator 95 (94-96)%. Pre-oxygenation efficacy with the non-rebreather mask was significantly worse than with either the bag-valve-mask (p < 0.001) or ventilator (p < 0.001). No significant difference in ease of breathing was identified between the bag-valve-mask and ventilator, but both were perceived as being significantly more difficult to breathe through than the non-rebreather mask. We conclude that, in healthy volunteers, the effectiveness of pre-oxygenation by bag-valve-mask and portable ventilator was superior to pre-oxygenation with a non-rebreather mask, although the non-rebreather mask was easier to breathe through than the other pre-oxygenation devices.

[Foetal Mortality in Singleton Foetuses at and beyond Term - An Analysis of German Perinatal Data 2004-2013]. / Fetale Mortalität bei Einlingen ab Termin - eine Analyse bundesdeutscher Perinataldaten 2004-2013.

BACKGROUND: Foetal mortality appears to increase in postmature pregnancies. There is debate on the optimal timing of induction of labour vs. watchful waiting. The literature on retrospective analyses of secondary data is inconclusive. Different approaches to calculate foetal risk exist. Recent and relevant data are needed in order to realise an appropriate discussion. MATERIAL AND METHODS: Mortality in singleton foetuses in Germany, between 2004 and 2013 was analysed in relation to gestational age. Risk for foetal death is described comparing stillbirths per 1,000 births at a particular gestational age (GA) vs. stillbirths per 1,000 ongoing pregnancies ("fetus-at-risk" model). Access to German routine perinatal data was granted. We included all stillbirths in singleton foetuses with no malformations after 36+6 weeks gestational age from 2004 until 2013. RESULTS: 5,933,117 births fulfilled our inclusion criteria. Foetal mortality per 1,000 births during that week of pregnancy is lowest between 41+0 and 41+6 days of (0.7/1,000). Mortality then increases to 2.3/1,000 in 42+0 to 42+6 GA. With the "fetus-at-risk" model, mortality is low between 37+0 and 39+6 GA, ranging from 0.2/1,000 ongoing pregnancies, increasing to 0.6/1,000 between 41+0 and 41+6, and 2.3/1,000 in the following week. For pregnancies lasting longer than 42+6 weeks, the stillbirth risk is identical at 6.3/1,000 with both calculation methods. CONCLUSION: Fetal mortality is low until 41+6 weeks of pregnancy. Interpretation of current data does not support a policy of routine IOL before this gestational age in singleton foetuses.

Short-term changes in hormonal profiles after laparoscopic ovarian laser evaporation compared with diagnostic laparoscopy for PCOS.

STUDY QUESTION: Which reproductive endocrine changes are attributed exclusively to laparoscopic ovarian drilling in polycystic ovarian syndrome (PCOS)? SUMMARY ANSWER: Laser evaporation-specific endocrine effects were the prevention of an immediate increase in inhibin B and a sustained decrease in testosterone, androstenedione and anti-Müllarian hormone (AMH). WHAT IS KNOWN ALREADY: All ovarian drilling procedures result in reproductive endocrine changes. It is not known which of these changes are the result of ovarian drilling and which are related to the surgery per se. STUDY DESIGN, SIZE, DURATION: This prospective controlled study was performed at an outpatient academic fertility clinic. Between 2007 and 2010, a total of 21 oligo- or amenorrheic PCOS patients were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: Included were oligo- or amenorrheic PCOS patients with all three of the Rotterdam criteria and luteinizing hormone (LH) >6.5 U/l. All PCOS patients had an indication for diagnostic surgery due to subfertility. There were 12 PCOS patients who chose to undergo ovarian laser evaporation (CO2 laser, 25 W, 20 times/ovary) and 9 PCOS who chose a diagnostic laparoscopy only (controls). Reproductive endocrinology was measured before, and until 5 days after, surgery, and four gonadotrophin-releasing hormone (GnRH) 'double pulse' tests were included. The main outcome measures were changes in reproductive endocrinology and pituitary sensitivity/priming to GnRH after laser evaporation compared with diagnostic laparoscopy only. MAIN RESULTS AND THE ROLE OF CHANCE: In the first hours after surgery, both groups showed an increase in LH, follicle stimulating hormone, estrogen and a decrease in testosterone, androstenedione, AMH and insulin growth factor-1 (P < 0.05). Inhibin B increased in the laparoscopy only group (P < 0.05). In the first days after surgery, testosterone, androstenedione and AMH remained at lower than baseline levels exclusively in the laser group (P < 0.05). Pituitary sensitivity/priming to GnRH was not altered after either laser evaporation or laparoscopy only. LIMITATIONS, REASONS FOR CAUTION: The limitations of this study are the short follow-up period and the relatively small groups. WIDER IMPLICATIONS OF THE FINDINGS: The strength of this study is the integrally measured endocrine profiles in combination with an optimal control group of PCOS patients undergoing diagnostic laparoscopy only. Interestingly, most of the immediate endocrine changes after laser evaporation could be related to the surgical context and not to the ovarian drilling procedure itself. STUDY FUNDING/COMPETING INTERESTS: The study was funded by the Foundation of Scientific Research in Obstetrics and Gynaecology and the study medication, Lutrelef, was donated by Ferring, The Netherlands, Hoofdorphe There were no conflicts of interests mentioned by the authors.

How long should we continue clomiphene citrate in anovulatory women?

STUDY QUESTION: What is the effectiveness of continued treatment with clomiphene citrate (CC) in women with World Health Organization (WHO) type II anovulation who have had at least six ovulatory cycles with CC but did not conceive? SUMMARY ANSWER: When women continued CC after six treatment cycles, the cumulative incidence rate of the ongoing pregnancy rate was 54% (95% CI 37-78%) for cycles 7-12. WHAT IS KNOWN ALREADY: If women with WHO type II anovulation fail to conceive with CC within six ovulatory cycles, guidelines advise switching to gonadotrophins, which have a high risk of multiple gestation and are expensive. It is however not clear what success rate could be achieved by continued treatment with CC. STUDY DESIGN, SIZE, DURATION: We performed a retrospective cohort study of women with WHO II anovulation who visited the fertility clinics of five hospitals in the Netherlands between 1994 and 2010. We included women treated with CC who had had at least six ovulatory cycles without successful conception (n = 114) after which CC was continued using dosages varying from 50 to 150 mg per day for 5 days. PARTICIPANTS/MATERIALS, SETTING, METHODS: Follow-up was a total of 12 treatment cycles. Primary outcome was the cumulative incidence rate of an ongoing pregnancy at the end of treatment. MAIN RESULTS AND THE ROLE OF CHANCE: We recruited 114 women that had ovulated on CC for at least six cycles but had not conceived. Of these 114 women, 35 (31%) had an ongoing pregnancy resulting in a cumulative incidence rate of an ongoing pregnancy of 54% after 7-12 treatment cycles with CC. LIMITATIONS, REASONS FOR CAUTION: Limitations of our study are its retrospective approach. WIDER IMPLICATIONS OF THE FINDINGS: Randomized trials comparing continued treatment with CC with the relatively established second line treatment with gonadotrophins are justified. In the meantime, we suggest to only begin this less convenient and more expensive treatment for women who do not conceive after 12 ovulatory cycles with CC. STUDY FUNDING/COMPETING INTERESTS: None. TRIAL REGISTRATION NUMBER: Not applicable.

Heightened Prevalence of Common Hospital-Treated Infections Preceding Dementia Diagnosis with Accelerated Dementia Onset after Influenza.

BACKGROUND: Since the beginning of Alzheimer's disease research, the hypothesis that infections are to some extent associated with neurodegenerative processes has been tested repeatedly. Epidemiological studies on the associations between infections and dementia have reported conflicting results. OBJECTIVES: This study analyses common hospital-treated infections (herpes, influenza, intestinal infections, pneumonia, sepsis, urinary tract infections) and their association with subsequent dementia and time until dementia onset. DESIGN, SETTING, AND PARTICIPANTS: For this nationwide population-based case-control study, the dataset of the Austrian National Health Insurance Association was used, including dementia patients (dementia cohort) and age- and gender-matched non-demented individuals (control cohort). Only subjects with data availability of at least 10 years prior to the index date (date of dementia diagnosis or date of censoring) were included. MEASUREMENTS: The incidence of six common infections in older adults (herpes, influenza, intestinal infections, pneumonia, sepsis, and urinary tract infections) was analyzed over a period of 10 years before the censoring date. RESULTS: The study population consists of 58208 subjects (29104 per study cohort), mean age: 81 years, 54% females. Patients of the dementia cohort had suffered from infections significantly more often than patients of the control cohort (6002, 20.6% vs. 4826, 16.6%; p < 0.001). Influenza, urinary tract infections, intestinal infections, and sepsis showed independent positive associations with subsequent dementia diagnosis, irrespective of other comorbidities (odds ratios: 1.26 (95% CI: 1.06-1.49), 1.23 (95% CI: 1.16-1.30), 1.16 (95% CI: 1.07-1.27), 1.17 (95% CI: 1.01-1.37), respectively). Time from infection to dementia diagnosis was shorter after influenza compared to all other infections (median: 3.4 years (95% CI: 3.1-3.7) vs. 6.6 years (95% CI: 6.4-6.8); p < 0.001). CONCLUSION: This is the first study to assess the association between infections and dementia over such a long minimum reporting period. These results, supported by consistent data from other epidemiological studies, emphasize the critical importance of infection prevention measures, especially for older adults. Further research is crucial to better understand the nature of the relationship between infections and dementia.

Circulating soluble fibroblast activation protein (FAP) levels are independent of cardiac and extra-cardiac FAP expression determined by targeted molecular imaging in patients with myocardial FAP activation.

INTRODUCTION: Tissue Fibroblast Activation Protein alpha (FAP) is overexpressed in various types of acute and chronic cardiovascular disease. A soluble form of FAP has been detected in human plasma, and low circulating FAP concentrations are associated with increased risk of death in patients with acute coronary syndrome. However, little is known about the regulation and release of FAP from fibroblasts, and whether circulating FAP concentration is associated with tissue FAP expression. This study characterizes the release of FAP in human cardiac fibroblasts (CF) and analyzes the association of circulating FAP concentrations with in vivo tissue FAP expression in patients with acute (ST-segment elevation myocardial infarction, STEMI) and chronic (severe aortic stenosis, AS) myocardial FAP expression. METHODS AND RESULTS: FAP was released from CF in a time- and concentration-dependent manner. FAP concentration was higher in supernatant of TGFß-stimulated CF, and correlated with cellular FAP concentration. Inhibition of metallo- and serine-proteases diminished FAP release in vitro. Median FAP concentrations of patients with acute (77 ng/mL) and chronic (75 ng/mL, p = 0.50 vs. STEMI) myocardial FAP expression did not correlate with myocardial nor extra-myocardial nor total FAP volume (P ≥ 0.61 in all cases) measured by whole-body FAP-targeted positron emission tomography. CONCLUSION: We describe a time- and concentration dependent, protease-mediated release of FAP from cardiac fibroblasts. Circulating FAP concentrations were not associated with increased in vivo tissue FAP expression determined by molecular imaging in patients with both chronic and acute myocardial FAP expression. These data suggest that circulating FAP and tissue FAP expression provide complementary, non-interchangeable information.

Recombinant LH supplementation to a standard GnRH antagonist protocol in women of 35 years or older undergoing IVF/ICSI: a randomized controlled multicentre study.

STUDY QUESTION: Does the addition of exogenous LH to an IVF/ICSI stimulation protocol with recombinant FSH (r-FSH) and a GnRH antagonist improve the ovarian response and pregnancy rates in women of 35 years and older? SUMMARY ANSWER: Supplementation of LH during the second half of the follicular phase has no effect on pregnancy rates, implantation rates or on ovarian response in women of 35 years and older undergoing GnRH antagonist IVF/ICSI cycles. WHAT IS KNOWN ALREADY: In IVF/ICSI stimulation protocols GnRH agonists or antagonists are administered to prevent a premature pituitary LH surge, which can have a detrimental effect on the IVF/ICSI procedure. In effect, GnRH analogues cause the levels of both gonadotrophins to drop. In order to allow follicle growth FSH is administered exogenously, whereas LH is usually not supplemented. Although GnRH analogues prevent LH surges, there is evidence that, particularly in older women, administration of GnRH analogues may cause endogenous LH levels to decrease excessively. Several studies have been performed to investigate whether the addition of recombinant LH (r-LH) to r-FSH improves cycle outcome. Only a few studies have analysed this issue in the GnRH antagonist protocol and the results of these trials obtained in older women (>35 years old) are conflicting. STUDY DESIGN, SIZE, DURATION: A multicentre RCT was performed between 2004 and 2010 in 253 couples who were undergoing IVF or ICSI. Women were 35 years or older and received ovarian stimulation in a protocol with r-FSH (Gonal-F 225 IU/day) starting from cycle day 3 and GnRH antagonist (Cetrotide 0.25 mg/day) from stimulation day 6. Randomization took place on stimulation day 6 to receive both r-FSH and r-LH (Luveris 150 IU/day) or continue with FSH alone. Randomization for r-LH supplementation was performed centrally by serially numbered, opaque, sealed envelopes, stratified by centre. PARTICIPANTS/MATERIALS, SETTING, METHODS: Of 253 subjects randomized, 125 received both r-FSH and r-LH and 128 received r-FSH only. Patients were recruited from the Division of Reproductive Medicine of the Obstetrics and Gynaecology department of four hospitals in the Netherlands. MAIN RESULTS AND THE ROLE OF CHANCE: There were no demographic or clinical differences between the groups. The intention-to-treat analysis revealed that of those receiving both r-FSH and r-LH, 35 (28.0%) had a clinical pregnancy, compared with 38 (29.7%) receiving only r-FSH (mean difference -1.5%; 95% confidence interval (CI) -9.4 to 12.7, P = 0.9). Ongoing pregnancy rates were 25 (20%) versus 28 (21.9%) (mean difference -1.9%; 95% CI -8.2 to 11.9, P = 0.9) and implantation rates 18.8 versus 20.7% (mean difference -1.9%; 95% CI -8.0 to 11.7, P = 0.6) in the 'r-FSH and r-LH' and 'r-FSH only' groups respectively. LIMITATIONS, REASONS FOR CAUTION: A limitation of our study is its early closure. This was done because the interim analysis after randomization of 250 patients indicated no benefit in any aspect of the experiment. WIDER IMPLICATIONS OF THE FINDINGS: Given previous data, including a Cochrane review, and our own results the evidence indicates that LH supplementation has no benefit on ongoing pregnancy rates in women of 35 years or older. STUDY FUNDING/COMPETING INTEREST(S): Merck Serono Netherlands, an affiliate of Merck Serono SA- Geneva, an affiliate of Merck KGaA, Darmstadt, Germany has donated the r-LH (Luveris(®)). No conflict of interest to declare. TRIAL REGISTRATION NUMBER: The trial was registered in the Dutch trial register (ISRCTN10841210).

Clomifene citrate or low-dose FSH for the first-line treatment of infertile women with anovulation associated with polycystic ovary syndrome: a prospective randomized multinational study.

BACKGROUND: Clomifene citrate (CC) is accepted as the first-line method for ovulation induction (OI) in patients with polycystic ovary syndrome (PCOS) associated with infertility owing to anovulation. Low-dose FSH has been reserved for women failing to conceive with CC. In this RCT, we tested the hypothesis that pregnancy rate (PR) and live birth rates (LBR) are higher after OI with low-dose FSH than with CC as first-line treatment. METHODS: Infertile women (<40 years old) with PCOS-related anovulation, without prior OI treatment, attending 10 centres in Europe/South America were randomized to OI with either CC (50-150 mg/day for 5 days) or FSH (starting dose 50 IU) for up to three treatment cycles. The primary outcome was clinical PR. RESULTS: Patients (n = 302) were randomized to OI with FSH (n = 132 women; 288 cycles) or CC (n = 123; 310 cycles). Per protocol analysis revealed that reproductive outcome was superior after OI with FSH than with CC with respect to PR per first cycle [30 versus 14.6%, respectively, 95% confidence interval (CI) 5.3-25.8, P = 0.003], PR per woman, (58 versus 44% of women, 95% CI 1.5-25.8, P = 0.03), LBR per woman (52 versus 39%, 95% CI 0.4-24.6, P = 0.04), cumulative PR (52.1 versus 41.2%, P = 0.021) and cumulative LBR (47.4 versus 36.9%, P = 0.031), within three cycles of OI. CONCLUSIONS: Pregnancies and live births are achieved more effectively and faster after OI with low-dose FSH than with CC. This result has to be balanced by convenience and cost in favour of CC. FSH may be an appropriate first-line treatment for some women with PCOS and anovulatory infertility, particularly older patients.

Evaluation of PEG-L-asparaginase in asparagine suppression and anti-drug antibody development in healthy Beagle dogs: A multi-phase preclinical study.

L-asparaginase is a frequently used drug in the treatment of canine malignant lymphoma. Since production and availability of native E. coli-derived L-asparaginase are limited, PEG-L-asparaginase (PEG-ASP) is an alternative. However, recommended doses and dosing intervals are mainly empirically determined. A multi-phase clinical dose-finding study with seven healthy Beagle dogs was conducted to find the minimum effective dose and, potentially, a dosing interval for PEG-ASP in dogs. Plasma concentrations of amino acids and PEG-ASP activity were measured at various time points after administration of different doses of PEG-ASP. Anti-PEG and anti-asparaginase antibody titres were measured. Administration of 10 IU/kg PEG-ASP resulted in asparagine depletion in all dogs, albeit for various durations: for 9 days in all dogs, 15 days in five dogs, 21 days in three dogs and 29 days in one dog. Asparagine suppression occurred at PEG-ASP plasma concentrations < 25 IU/L. Subsequent administrations of a second and third dose of 20 IU/kg and 40 IU/kg PEG-ASP resulted in asparagine suppression at < 9 days in five dogs, accompanied by the development of antibodies against PEG and L-asparaginase. Two dogs with prolonged asparagine suppression after the second and third administration did not develop antibodies. Marked individual variation in the mechanism and duration of response to PEG-ASP was noted. Antibody formation against PEG-ASP was frequently observed and sometimes occurred after one injection. This study suggests that PEG-ASP doses as high as the currently used dose of 40 IU/kg might not be needed in treatment of canine malignant lymphoma.

[Testing of practical surgical teaching at a distance-Experiences with a hybrid OSCE in surgery]. / Prüfung praktisch-chirurgischer Lehre auf Distanz ­ Erfahrungen mit einem Hybrid-OSCE in der Chirurgie.

BACKGROUND: The COVID-19 pandemic has changed medical teaching worldwide. Digital teaching and examinations are successful for cognitive learning objectives, whereas practical skills had to be carried out predominantly in person under strict hygiene standards. AIM: This study presents the opportunities and challenges of using a presence objective structured clinical examination (OSCE) at a distance with digital support. METHOD: Following surgical practical teaching an OSCE was conducted in presence, where students demonstrated practical skills in one room while the examiners were connected via videoconference from another room. Students were surveyed about the OSCE and sustained learning via a standardized online questionnaire after completion of the surgical teaching. Additionally, examiners were surveyed on their experiences. RESULTS: In the online survey 40 students participated (25% of n = 157 students contacted) and 36 completed questionnaires were analyzed. Overall, the implementation of an OSCE even under pandemic conditions was perceived as very positive by the students (92% of students n = 33). In particular, the acquisition of practical skills was rated as very high. For 78% (n = 28) of the students, the acquisition of competencies through the practical examination was particularly sustainable. The vast majority of students and examiners felt safe regarding infection control because of the hygiene concept (92%, n = 33). Overall, 80 students achieved grade 1 (51%), 71 students grade 2 (45.2%) and 6 students grade 3 (3.8%) (grade 1 = very good, grade 6 = very bad). CONCLUSION: Practical examinations are essential for checking practical learning objectives and can be implemented at a distance with a well-developed hygiene concept and digital support.

Plasma pharmacokinetics of daptomycin in critically ill patients with renal failure and undergoing CVVHD.

BACKGROUND: Daptomycin is a novel antibiotic with primarily renal elimination. METHODS: In an open-label, prospective trial, the pharmacokinetics of daptomycin after single (8 mg/kg BW) and multiple intravenous doses (4 mg/kg BW) at steady state were determined in critically ill, dialysis-dependent patients treated with continuous veno-venous hemodialysis (CVVHD). Daptomycin levels were determined by HPLC. Subjects with normal renal function received one dose of 4 mg/kg BW of daptomycin. RESULTS: In the normal controls, daptomycin administration resulted in a mean maximum concentration (Cmax) of 60.7 ± 10.7 mg/l and an area under the time-versus-concentration curve from 0 to 24 h (AUC0-24) of 402 ± 56 mg × h/l. In the CVVHD-treated patients, a loading dose of 8 mg/kg lead to Cmax of 87.5 ± 15.0 mg/l, AUC0-24 of 537 ± 97 mg × h/l and AUC24-48 of 193 ± 69 mg × h/l, respectively. After multiple doses of 4 mg/kg every 48 h, Cmax was 41.8 ± 5.0 mg/l, AUC0-24 302 ± 43 mg × h/l and AUC 24-48 h 102 ± 24 mg × h/l, respectively. Approximately 40% of the daptomycin dose administered was removed by CVVHD. Mean plasma half-lives of daptomycin in patients were 2 - 3 times longer than in healthy controls. CONCLUSIONS: The dosing regimen of 4 mg/kg TBW of daptomycin administered to CVVHD patients every 48 h is inappropriate to achieve effective antimicrobial plasma concentrations of daptomycin in the second half of the dosing interval (24 - 48 h). Doses of ≥ 4 mg/kg TBW administered intravenously every 24 h are necessary in CVVHD patients to assure that plasma daptomycin levels are comparably high to subjects with normal renal function and to avoid underdosing.

How do deployed general surgeons acquire relevant skill sets and competencies and mitigate skill fade?

There are recognised difficulties internationally with acquisition and retention of skills among deployed military general surgeons. These are compounded by reduced trauma workload in non-deployed roles or during low tempo or limited activity deployments, and the winding-down of combat operations in Iraq and Afghanistan. We summarise the relevant military-run courses, military-civilian collaborations and potential future strategies that have been used to address skill sets and competencies of deployed surgeons. We use examples from the American, British, Danish, French, German and Swedish Armed Forces. There is variation between nations in training, with a combination of didactic lectures, simulation training and trauma placements in civilian settings at home and overseas. Data regarding effectiveness of these techniques are sparse. It is likely that combat surgical skill-set acquisition and maintenance requires a combination of employment at a high-volume trauma centre during a surgeon's non-deployed role, together with military-specific courses and high-fidelity simulation to fill skill gaps. There are multiple newer modalities of training that require further evaluation if they are to prove effective in the future. We aimed to summarise the current methods used internationally to ensure acquisition and retention of vital skill sets for these surgeons.

[National health fund and morbidity-based risk structure equalization with focus on haemophilia]. / Gesundheitsfonds und morbiditätsorientierter Risikostrukturausgleich. Funktionsweise unter besonderer Berücksichtigung der Hämophilie.

The Gesundheitsfonds (national health fund) was established in Germany on January 1st, 2009, in combination with the morbidity-based risk structure equalization (RSA) in order to manage the cash flow between the statutory health insurances. The RSA equalizes income differences due to the varying levels of contributory income of the members of a health insurance (basic wage totals) and expenditure differences due to varying distribution of morbidity risks across different health insurances, as well as the varying numbers of non-contributing insured family members. Additionally, insured persons are allocated to morbidity groups according to a classification model based upon diagnoses and prescriptions anticipating medical expenses in the subsequent year. Haemophilia falls, among 80 disease entities, in the morbidity group which generates the highest risk supplement. Matching of prescribed drugs with disease entities facilitates disease grading and improves the accuracy of risk supplements.

Retrospective study on risk factors for repeated dental treatment of children under general anaesthesia.

AIM: This retrospective study aimed to evaluate potential risk factors predicting repeated dental treatment of children under general anaesthesia. MATERIALS AND METHODS: Children below 12 years of age receiving at least one dental treatment under general anaesthesia between 03/2010 and 10/2018 were analysed (n = 935, mean age: 4.6 ± 2.4). Dental records were analysed retrospectively for anamnestic, demographic, oral health and treatment factors. Kaplan-Meier statistics was used to estimate the time to second dental treatment under general anaesthesia. Potential risk factors for repeated dental treatment underwent univariate analysis using log-rank tests and were then submitted to a multi-variate Cox-regression analysis (a = 5%). RESULTS: One hundred fifteen children (12.3%) received or were planned to receive repeated dental treatment under general anaesthesia. In children receiving repeated dental treatment, the time intervals between first and second general anaesthesia and second and third general anaesthesia amounted to 22 ± 18 and 23 ± 20 months, respectively. The use of fluoridated toothpaste (HR: 0.28, p < 0.01) and attending 2 or more recall appointments per year (HR: 0.6, p < 0.01) significantly decreased the risk for repeated dental treatment under general anaesthesia in the multivariate model. CONCLUSION: Adherence to preventive recall appointments and to oral hygiene recommendations is essential to maintain oral health and avoid repeated dental treatment under general anaesthesia.

Measuring the charge state of point defects on MgO/Ag(001).

A detailed understanding of surface defects is highly desirable, e.g. to clarify their role as active sites in catalysis. Here localized defects on the surface of MgO films deposited on Ag(001) are investigated. Since the electronic structure of color centers depends on their local position, spectroscopic signals are highly convoluted and often difficult to disentangle. In this study we aimed to obtain morphological and spectroscopic information on single color centers at a microscopic level with frequency modulated dynamic force microscopy (FM-DFM) and scanning tunneling microscopy (STM) in an ultrahigh vacuum and at low temperature. Four of the major and in literature mostly discussed defect types on MgO have been characterized by their charge state and finally identified by the complementary application of FM-DFM and STM in combination with density functional theory results.

Continuous local anaesthetic wound catheter infiltration after clamshell thoracotomy.

We report on the novel and successful use of local anaesthetic wound infusions via elastomeric pumps in a 17-year-old male who underwent emergent clamshell thoracotomy after sustaining a stab wound to the flank. This formed one component of a multi-modal analgesic regimen aimed at reducing opioid requirements and their associated side-effects. The patient was mobilising and was discharged from the intensive care unit 24 h postoperatively. There was an unplanned break in the local anaesthetic infusion during which the patient's reported pain scores increased significantly. The catheters were removed on the fifth postoperative day and he was discharged from hospital on day 7.