Nitrofurantoin for the treatment of uncomplicated urinary tract infection in female patients: the impact of dosing regimen, age, and renal function on drug exposure.

PURPOSE: The aim of this study is to determine nitrofurantoin exposure in female patients with different age and renal function with complaints of an uncomplicated UTI. Also the nitrofurantoin exposure in relation to the dosage regimen will be studied. METHODS: Eight general practitioners (GP) participated in the study and included 38 patients with symptoms of an uncomplicated UTI, treated either with a dose of 50 mg q6h or 100 mg q12h, upon the discretion of the GP. Nitrofurantoin exposure was quantified in the patient's 24-h urine samples by UHPLC-UV and the area under the curve was calculated. RESULTS: The 38 patients provided a range of 2-17 urine samples. The urine nitrofurantoin exposure was 1028 mg h/L for the patients receiving 50 mg q6h and 1036 mg h/L for those treated with 100 mg q12h (p = 0.97) and was not affected by age and eGFR (p = 0.64 and p = 0.34, respectively). CONCLUSION: The data obtained do not support the discouragement of nitrofurantoin use in the elderly and in patients with impaired renal function. Since only a small number of patients were included, a larger study with more patients is warranted to evaluate nitrofurantoin exposure and adverse effects.

Adherence to and usefulness of the national treatment guideline for urinary tract infections (UTI) in a risk area.

BACKGROUND: To optimize antibiotic treatment and decrease antibiotic resistance, national treatment guidelines are available for urinary tract infections (UTIs) in general practice. The usefulness of these guidelines in risk areas for antimicrobial resistance such as cross border regions or areas with dense agriculture, is unknown. METHODS: Midstream urine samples from women with symptoms of acute UTI visiting general practitioners (GPs) in the Westland area, a dense agriculture area, were microbiologically analysed, and patient characteristics, symptoms, previous and present antibiotic treatment were collected. The National Nivel data were used as reference for antibiotic resistance. RESULTS: Of 310 women with symptoms of uncomplicated UTI, 247 (80%) had a culture proven E. coli UTI. Empirical antibiotic therapy was prescribed to 148 patients (48%) in total; in 7% of women with a negative and 52% with a positive urine culture. Having more than one symptom was associated with the prescription of antibiotics; travel history or previous antibiotic use for UTI were not. The isolated uropathogens were susceptible to the empiric antibiotic therapy in 98% of patients. Resistance to co-amoxiclav was higher (22%) than reported in the national data of 2004 (12%), 2009 (13%) and 2014 (9%), as was the prevalence of extended spectrum ß-lactamase (ESBL): 3.4% in our study versus 0.1%, 1% and 2.2% in the national data respectively. CONCLUSION: The presence of environmental and socio-demographic risk factors for antibiotic resistance did not influence the empiric choice nor susceptibility for antibiotics advised by the national guidelines in women with uncomplicated UTI.

Implantable cardioverter defibrillators at the end of life: future perspectives on clinical practice.

The implantable cardioverter defibrillator (ICD) is effective in terminating life-threatening arrhythmias. However, in the last phase of life, ICD shocks may no longer be appropriate. Guidelines recommend timely discussion with the patient regarding deactivation of the shock function of the ICD. However, research shows that such conversations are scarce, and some patients experience avoidable and distressful shocks in the final days of life. Barriers such as physicians' lack of time, difficulties in finding the right time to discuss ICD deactivation, patients' reluctance to discuss the topic, and the fragmentation of care, which obscures responsibilities, prevent healthcare professionals from discussing this topic with the patient. In this point-of-view article, we argue that healthcare professionals who are involved in the care for ICD patients should be better educated on how to communicate with patients about ICD deactivation and the end of life. Optimal communication is needed to reduce the number of patients experiencing inappropriate and painful shocks in the terminal stage of their lives.

Antibiotic resistance of Escherichia coli isolated from uncomplicated UTI in general practice patients over a 10-year period.

Recommendations of first choice antibiotic therapy need to be based on actual antibiotic susceptibility data. We determined the antibiotic susceptibility of E. coli in uncomplicated UTI among women and compared the results with 2004 and 2009. In 30 sentinel general practitioner practices of Nivel Primary Care database, urine samples were collected from women with symptoms of uncomplicated UTI. Patient characteristics, E. coli susceptibility, and ESBL production were analyzed. Six hundred eighty-nine urine samples were collected; E. coli was the most isolated uropathogen (83%). Antibiotic susceptibility was stable over time except for ciprofloxacin (96% in 2004, 97% in 2009, and 94% in 2014; P < 0.05). The susceptibility to co-amoxiclav was 88%, 87%, and 92% in 2004, 2009, and 2014, respectively. The prevalence of ESBL-producing E. coli increased from 0.1% in 2004 to 2.2% in 2014 (P < 0.05). Regional differences in antibiotic susceptibility for co-trimoxazole were found being the highest in the west (88%) and the lowest in the north (72%, P = 0.021). Ciprofloxacin susceptibility was related to antibiotic use in the past 3 months (97% no use versus 90% use, P = 0.002) and age > 70 years (P = 0.005). In 2014, prescription of fosfomycin increased compared to 2009 (14.3% versus 5.6%) at the expense of co-amoxiclav, co-trimoxazole, and fluoroquinolones (P < 0.05). The susceptibility percentages to most antimicrobial agents tested were stable over 10 years' period although the prevalence of E. coli and ESBLs significantly increased. Performance of a survey with regular intervals is warranted.

Trauma care before and after optimisation in a level I trauma Centre: Life-saving changes.

BACKGROUND: The implementation of trauma systems has led to a significant reduction in mortality and length of hospital stay. In our level I trauma centre, 24/7 in-hospital coverage was implemented, and a renovation of the trauma room took place to improve the trauma care. The aim of the present study was to examine the effect of the optimised in-hospital infrastructure in terms of mortality, processes and clinical outcomes. METHODS: We performed a retrospective cohort study of prospectively collected data. All adult trauma patients admitted to our trauma centre directly during two time periods (2010-2012 and 2014-2016) were included. Any patients below the age of 18 years and patients who underwent primary trauma screening in another hospital were excluded. Logistic and linear regression were used and adjusted for demographics and characteristics of trauma. The primary endpoint was mortality. The secondary endpoints were subgroups of earlier mortality rates and severely injured patients, processes and clinical outcomes. RESULTS: In period I, 1290 patients were included, and in period II, 2421. The adjusted mortality in the trauma room (odds ratio (OR): 0.18; CI: 0.05-0.63) and the total in-hospital mortality (OR: 0.63 CI: 0.42-0.95) showed a significant reduction in period II. The trauma room (TR) time decreased by 30 min (p < 0.001), and the time until CT decreased by 22 min (p < 0.001). The number of delayed diagnoses and complications were significantly lower in the second period, with an OR of 0.2 (CI: 0.1-0.2) and 0.4 (CI: 0.3-0.6), respectively. The hospital length of stay and ICU length of stay decreased significantly, -1.5 day (p = 0.010) and -1.8 days (p = 0.022) respectively. CONCLUSIONS: Optimisation of the in-hospital infrastructure related to trauma care resulted in improved survival rates in both severely injured patients as well as in the whole trauma population. Moreover, the processes and clinical outcomes improved, showing a shorter hospital length of stay, shorter TR time, fewer complications and fewer delayed diagnoses.

Comparison between the STENTYS self-apposing bare metal and paclitaxel-eluting coronary stents for the treatment of saphenous vein grafts (ADEPT trial).

AIMS: To describe the safety and performance of STENTYS self-expandable bare metal stents (BMS) versus paclitaxel-eluting stents (PES) in saphenous vein grafts (SVGs). METHODS AND RESULTS: A randomised controlled trial was performed in four hospitals in three European countries between December 2011 and December 2013. Patients with de novo lesions (>50% stenosis) in an SVG with a diameter between 2.5-6 mm were included. Primary endpoint was late lumen loss at 6 months. Secondary endpoints included procedural success and the occurrence of major adverse cardiac events (MACE) at 12 months. A total of 57 patients were randomised to STENTYS self-apposing BMS (n = 27) or PES (n = 30). Procedural success was obtained in 89.5%. No significant differences in late lumen loss were found between BMS and PES at 6 months (0.53 mm vs 0.47; p = 0.86). MACE rates at 12 months were comparable in both groups (BMS 22.2% vs. PES 26.7%; p = 0.70). CONCLUSIONS: Treatment of SVGs with STENTYS self-expandable stents is safe and effective. No significant differences were found in late lumen loss and MACE between BMS and PES.

Modular continuing professional development for emergency physicians - the MNSHA masterclass programme.

INTRODUCTION: Emergency physician (EP) training in the Netherlands is currently a 3-year competency-based programme. Upon its completion, many Dutch EPs feel that they lack some of the skills and the knowledge necessary to be fully prepared for the challenges of emergency medicine. We perceived a need for new methods to deliver continuing professional development (CPD). METHODS: A needs analysis survey was conducted to ascertain whether our perceived need for a new CPD programme was genuine. A new course was developed, incorporating innovative learning methods. The results of the needs analysis were incorporated into the programme. Another survey was held among participants of the first two editions of the programme. RESULTS, DISCUSSION AND CONCLUSION: Modular CPD for Emergency Physicians (Dutch: MNSHA) is a modular programme that aims to deliver CPD to Dutch EPs. It combines innovative educational methods, such as asynchronous learning in a flipped classroom, with web-based mentoring. The aim is for participants to develop effective, individualized and sustainable methods to gain and maintain knowledge and skills as a part of their ongoing professional education. The participant survey showed encouraging results, strongly suggesting an improvement in confidence. A more robust study would be required to better assess the outcomes of our programme.

[Implementation of the curriculum for specialist training in Emergency Medicine: room for improval on details]. / Implementatie van het curriculum voor de opleiding tot Spoedeisende Hulp(SEH)-arts: zoektocht naar het verborgen curriculum.

OBJECTIVE: To investigate what aspects of the new curriculum for specialist training in Emergency Medicine are actually implemented in daily practice. DESIGN: Descriptive study. METHOD: The curriculum was implemented as a pilot in 4 teaching hospitals, where a total of 32 residents in training in Emergency Medicine and 20 Emergency Medicine Program directors and Emergency physicians were surveyed using a web-based questionnaire querying the use of the different aspects of the curriculum in daily practice. RESULTS: Responses were received from 29 residents in training and 15 program directors and Emergency physicians. Both residents in training and program directors rated the patient mix seen during the training programme adequate to excellent. No great differences were observed in how residents in training, trainers and physicians working in the Emergency Department assessed the curriculum. However, the results showed that the training plan should be discussed explicitly with each residents in training. More attention should be focussed on the Society Awareness, Knowledge and Science and Organisation competencies and the Disability and Dermatology themes. Competence-based assessment methods, such as multi-source feedback, specific to this type of curriculum have not yet been sufficiently implemented. CONCLUSION: The responses to the questionnaire demonstrated how the curriculum is handled in daily practice and provided information on the progress of the implementation of the curriculum. This will enable focussed feedback to teaching hospitals.

Frequency-dependent spontaneous emission rate from CdSe and CdTe nanocrystals: influence of dark states.

We studied the rate of spontaneous emission from colloidal CdSe and CdTe nanocrystals at room temperature. The decay rate, obtained from luminescence decay curves, increases with the emission frequency in a supralinear way. This dependence is explained by the thermal occupation of dark exciton states at room temperature, giving rise to a strong attenuation of the rate of emission. The supralinear dependence is in agreement with the results of tight-binding calculations.

Controlling the dynamics of spontaneous emission from quantum dots by photonic crystals.

Control of spontaneously emitted light lies at the heart of quantum optics. It is essential for diverse applications ranging from miniature lasers and light-emitting diodes, to single-photon sources for quantum information, and to solar energy harvesting. To explore such new quantum optics applications, a suitably tailored dielectric environment is required in which the vacuum fluctuations that control spontaneous emission can be manipulated. Photonic crystals provide such an environment: they strongly modify the vacuum fluctuations, causing the decay of emitted light to be accelerated or slowed down, to reveal unusual statistics, or to be completely inhibited in the ideal case of a photonic bandgap. Here we study spontaneous emission from semiconductor quantum dots embedded in inverse opal photonic crystals. We show that the spectral distribution and time-dependent decay of light emitted from excitons confined in the quantum dots are controlled by the host photonic crystal. Modified emission is observed over large frequency bandwidths of 10%, orders of magnitude larger than reported for resonant optical microcavities. Both inhibited and enhanced decay rates are observed depending on the optical emission frequency, and they are controlled by the crystals' lattice parameter. Our experimental results provide a basis for all-solid-state dynamic control of optical quantum systems.

Macroporous germanium by electrochemical deposition.

Germanium is electrodeposited in a template formed from a dried suspension of silica spheres. The germanium completely fills the pores of the silica matrix. The semiconductor, as deposited, is amorphous but can be crystallized by annealing. Selective dissolution of the silica template gives a macroporous germanium-air sphere matrix, which offers interesting possibilities for photonic applications.

Volumetric measurements of bone mineral density of the lumbar spine: comparison of three geometrical approximations using dual-energy X-ray absorptiometry (DXA)

Measurements of bone mineral density using dual-energy X-ray absorptiometry (DXA) gives area values (g cm-2) rather than true volumetric values (g cm-3). To calculate the vertebral volume using planar postero-anterior and lateral DXA values, several different geometrical approximations were used: cubic, cylindrical with a circular cross-section and cylindrical with an elliptical cross-section. The aim of this study was to compare these geometrical approximations with each other and with a reference standard, defined as the volume found on a computed tomographic (CT) scan. L2 and L3 were evaluated in a phantom study. Volume approximations by the cube or cylinder with circular cross-section geometry showed more than a 50% overestimation (range 54-74%). However, the elliptical cylinder approach showed very good agreement: 2.1% and 1.2% for L2 and L3, respectively, when compared to the CT volumes. In addition, we performed four patient studies with both CT and DXA to evaluate the elliptical cylinder estimate in a clinical setting. For L2 and L3, the mean relative difference was less than 2%. We conclude that the elliptical cylinder approach results in the most accurate bone volume estimates in both the phantom and patients.

[Experience with continuous arteriovenous hemodiafiltration for acute kidney insufficiency in intensive care patients]. / Ervaringen met continue arterioveneuze hemodiafiltratie als behandeling voor acute nierinsufficiëntie bij intensive care-patiënten.

Acute renal failure is a frequent complication at the Intensive Care Department. For this complication dialysis is often necessary. In our Intensive Care Department we have opted for continuous arteriovenous hemodiafiltration (CAVHD) as the treatment of first choice for patients with acute renal failure. We describe the results in 18 patients treated with CAVHD. In all patients an arterious and a venous catheter were placed, in most cases in the femoral artery and vein. A capillary hemofilter was placed between the catheters. In the filter a counterflow mechanism took place. All patients were successfully treated with CAVHD. Haemodynamic instability as an effect of the treatment did not appear. The fluid and electrolyte balance was perfectly under control. Renal function was recovered in 7 patients. Twelve patients died. The cause of death was never associated with the renal failure or with the CAVHD treatment.

Immune response in draining lymph nodes and spleen after intraventricular injection of antigen.

Both Fischer 344 and Sprague Dawley rats showed significant numbers of antibody forming cells (PFC) in deep cervical lymph nodes after intraventricular injection of antigens, including trinitrophenylated (TNP)-hemocyanin, TNP-B. abortus and sheep erythrocytes. This indicated that particular as well as soluble antigens drained to these lymph nodes from the spinal fluid. Other lymph nodes examined did not show increased PFC over background, but levels of PFC in the spleen were significantly elevated after intraventricular injection of each of these antigens. Comparison with dose responses in the spleen after intravenous antigen injection suggested that approximately 20% of the intraventricularly injected immunogens drained to the peripheral blood. The relevance of these findings with respect to the brain as an immunologically privileged site is discussed.

An international multi-clinic study comparing the therapeutic efficacy of colloidal bismuth subcitrate coated tablets with chewing tablets in the treatment of duodenal ulceration.

The results of a randomized, single-blind, multi-clinic study comparing the therapeutic efficacy and degree of oral staining of new colloidal bismuth subcitrate (CBS) coated tablets over 4 weeks of treatment in patients suffering from duodenal ulceration are reported. The data were collected from 9 clinics in the Netherlands, Belgium, Ireland, the United Kingdom, and Italy. The results from 94 patients treated with CBS coated tablets and 95 patients treated with CBS chewing tablets were statistically evaluated. Healing rates after 4 weeks of therapy appeared to be 76% for CBS coated tablets and 72% for CBS chewing tablets, so no statistically significant difference in therapeutic efficacy was seen. A highly significant degree of discolouration of all parts of the oral cavity was observed in patients treated with CBS chewing tablets, whereas only a few patients treated with CBS coated tablets experienced a slight staining of the tongue. Blood bismuth concentrations during the study had a range of less than or equal to 3 to 33 micrograms/l. The new CBS coated tablet form has an excellent patient compliance as compared to the chewing tablets.