Online adaptive radiotherapy compared to plan selection for rectal cancer: quantifying the benefit.

BACKGROUND: To compare online adaptive radiation therapy (ART) to a clinically implemented plan selection strategy (PS) with respect to dose to the organs at risk (OAR) for rectal cancer. METHODS: The first 20 patients treated with PS between May-September 2016 were included. This resulted in 10 short (SCRT) and 10 long (LCRT) course radiotherapy treatment schedules with a total of 300 Conebeam CT scans (CBCT). New dual arc VMAT plans were generated using auto-planning for both the online ART and PS strategy. For each fraction bowel bag, bladder and mesorectum were delineated on daily Conebeam CTs. The dose distribution planned was used to calculate daily DVHs. Coverage of the CTV was calculated, as defined by the dose received by 99% of the CTV volume (D99%). The volume of normal tissue irradiated with 95% of the prescribed fraction dose was calculated by calculating the volume receiving 95% of the prescribed fraction or more dose minus the volume of the CTV. For each fraction the difference between the plan selection and online adaptive strategy of each DVH parameter was calculated, as well as the average difference per patient. RESULTS: Target coverage remained the same for online ART. The median volume of the normal tissue irradiated with 95% of the prescribed dose dropped from 642 cm3 (PS) to 237 cm3 (online-ART)(p < 0.001). Online ART reduced dose to the OARs for all tested dose levels for SCRT and LCRT (p < 0.001). For V15Gy of the bowel bag the median difference over all fractions of all patients was - 126 cm3 in LCRT, while the average difference per patient ranged from - 206 cm3 to - 40 cm3. For SCRT the median difference was - 62 cm3, while the range of the average difference per patient was - 105 cm3 to - 51 cm3. For V15Gy of the bladder the median difference over all fractions of all patients was 26% in LCRT, while the average difference per patient ranged from - 34 to 12%. For SCRT the median difference of V95% was - 8%, while the range of the average difference per patient was - 29 to 0%. CONCLUSIONS: Online ART for rectal cancer reduces dose the OARs significantly compared to a clinically implemented plan selection strategy, without compromising target coverage. TRIAL REGISTRATION: Medical Research Involving Human Subjects Act (WMO) does not apply to this study and was retrospectively approved by the Medical Ethics review Committee of the Academic Medical Center (W19_357 # 19.420; Amsterdam University Medical Centers, Location Academic Medical Center, Amsterdam, The Netherlands).

Surrogate-free machine learning-based organ dose reconstruction for pediatric abdominal radiotherapy.

To study radiotherapy-related adverse effects, detailed dose information (3D distribution) is needed for accurate dose-effect modeling. For childhood cancer survivors who underwent radiotherapy in the pre-CT era, only 2D radiographs were acquired, thus 3D dose distributions must be reconstructed from limited information. State-of-the-art methods achieve this by using 3D surrogate anatomies. These can however lack personalization and lead to coarse reconstructions. We present and validate a surrogate-free dose reconstruction method based on Machine Learning (ML). Abdominal planning CTs (n = 142) of recently-treated childhood cancer patients were gathered, their organs at risk were segmented, and 300 artificial Wilms' tumor plans were sampled automatically. Each artificial plan was automatically emulated on the 142 CTs, resulting in 42,600 3D dose distributions from which dose-volume metrics were derived. Anatomical features were extracted from digitally reconstructed radiographs simulated from the CTs to resemble historical radiographs. Further, patient and radiotherapy plan features typically available from historical treatment records were collected. An evolutionary ML algorithm was then used to link features to dose-volume metrics. Besides 5-fold cross validation, a further evaluation was done on an independent dataset of five CTs each associated with two clinical plans. Cross-validation resulted in mean absolute errors ≤ 0.6 Gy for organs completely inside or outside the field. For organs positioned at the edge of the field, mean absolute errors ≤ 1.7 Gy for [Formula: see text], ≤ 2.9 Gy for [Formula: see text], and ≤ 13% for [Formula: see text] and [Formula: see text], were obtained, without systematic bias. Similar results were found for the independent dataset. To conclude, we proposed a novel organ dose reconstruction method that uses ML models to predict dose-volume metric values given patient and plan features. Our approach is not only accurate, but also efficient, as the setup of a surrogate is no longer needed.

Dosimetric benefit of an adaptive treatment by means of plan selection for rectal cancer patients in both short and long course radiation therapy.

BACKGROUND: To compare target coverage and dose to the organs at risk in two approaches to rectal cancer: a clinically implemented adaptive radiotherapy (ART) strategy using plan selection, and a non-adaptive (non-ART) strategy. METHODS: The inclusion of the first 20 patients receiving adaptive radiotherapy produced 10 patients with a long treatment schedule (25x2Gy) and 10 patients with a short schedule (5X5Gy). We prepared a library of three plans with different anterior PTV margins to the upper mesorectum, and selected the most appropriate plan on daily Conebeam CT scans (CBCT). We also created a non-adaptive treatment plan with a 20 mm margin. Bowel bag, bladder and target volume were delineated on CBCT. Daily DHVs were calculated based on the dose distribution of the selected and non-adaptive plans. Coverage of the target volume was compared per fraction between the ART and non-ART plans, as was the dose to the bladder and small bowel, assessing the following dose levels: V15Gy, V30Gy, V40Gy, V15Gy and V95% for long treatment schedules, and V15Gy and V95% for short ones. RESULTS: Target volume coverage was maintained from 98.3% (non-ART) to 99.0% (ART)(p = 0.878). In the small bowel, ART appeared to have produced significant reductions in the long treatment schedule at V15Gy, V40Gy, V45Gy and V95% (p <  0.05), but with small absolute differences. The DVH parameters tested for the short treatment schedule did not differ significantly. In the bladder, all DVH parameters in both schedules showed significant reductions (p <  0.05), also with small absolute differences. CONCLUSIONS: The adaptive treatment maintained target coverage and reduced dose to the organs at risk. TRIAL REGISTRATION: Medical Research Involving Human Subjects Act (WMO) does not apply to this study and was retrospectively approved by the Medical Ethics review Committee of the Academic Medical Center, W19_194 # 19.233.

Six-year healthcare trajectories of adults with anxiety and depressive disorders: Determinants of transition to specialised mental healthcare.

BACKGROUND: To investigate potential facilitators and barriers for patients receiving specialised mental healthcare using a longitudinal design. METHODS: Longitudinal data on 701 adult participants with a depressive and/or anxiety disorder were derived from the Netherlands Study of Depression and Anxiety (NESDA). Demographic, clinical and treatment determinants at baseline were assessed with self-report questionnaires and the Composite International Diagnostic Interview (CIDI 2.1). Transition to specialised mental healthcare was assessed at one, two, four, and six-year follow-up with a self-report resource use questionnaire (TiC-P). RESULTS: 28.3% of patients with a depressive and/or anxiety disorder transitioned from receiving no care or primary mental healthcare to specialised mental health services during six-year follow-up. The multivariate Cox regression model identified suicidal ideation, younger age, higher education level, openness to experience, pharmacological treatment, prior treatment in primary mental healthcare and perceived unmet need for help as determinants of transition, explaining 8-18% of variance. LIMITATIONS: This study focused on baseline determinants of future transition to specialised mental healthcare. Recovery and remittance of depression and anxiety in relation to transition were not studied. CONCLUSIONS: Not all key clinical guideline characteristics such as severity of symptoms and comorbidity were predictive of a transition to specialised mental healthcare, while non-clinical factors, such as age and perceived unmet need for help, did influence the process.

European Psychiatric Association Guidance on psychotherapy in chronic depression across Europe.

PURPOSE: Patients with chronic depression (CD) by definition respond less well to standard forms of psychotherapy and are more likely to be high utilizers of psychiatric resources. Therefore, the aim of this guidance paper is to provide a comprehensive overview of current psychotherapy for CD. The evidence of efficacy is critically reviewed and recommendations for clinical applications and research are given. METHODS: We performed a systematic literature search to identify studies on psychotherapy in CD, evaluated the retrieved documents and developed evidence tables and recommendations through a consensus process among experts and stakeholders. RESULTS: We developed 5 recommendations which may help providers to select psychotherapeutic treatment options for this patient group. The EPA considers both psychotherapy and pharmacotherapy to be effective in CD and recommends both approaches. The best effect is achieved by combined treatment with psychotherapy and pharmacotherapy, which should therefore be the treatment of choice. The EPA recommends psychotherapy with an interpersonal focus (e.g. the Cognitive Behavioural Analysis System of Psychotherapy [CBASP]) for the treatment of CD and a personalized approach based on the patient's preferences. DISCUSSION: The DSM-5 nomenclature of persistent depressive disorder (PDD), which includes CD subtypes, has been an important step towards a more differentiated treatment and understanding of these complex affective disorders. Apart from dysthymia, ICD-10 still does not provide a separate entity for a chronic course of depression. The differences between patients with acute episodic depression and those with CD need to be considered in the planning of treatment. Specific psychotherapeutic treatment options are recommended for patients with CD. CONCLUSION: Patients with chronic forms of depression should be offered tailored psychotherapeutic treatments that address their specific needs and deficits. Combination treatment with psychotherapy and pharmacotherapy is the first-line treatment recommended for CD. More research is needed to develop more effective treatments for CD, especially in the longer term, and to identify which patients benefit from which treatment algorithm.

Takotsubo cardiomyopathy shortly following pacemaker implantation-case report and review of the literature.

We describe a patient with acute heart failure shortly after pacemaker implantation. With the documentation of typical dyskinesia of the apical segments with hyperdynamic contractility of the basal segments and a normal coronary angiogram, pacemaker implantation-induced Takotsubo cardiomyopathy was diagnosed. Supportive care was administered and within several days the patient's symptoms resolved. After several weeks, the left ventricular function had fully recovered. A review of the literature on Takotsubo cardiomyopathy after pacemaker implantation is presented.

Impact of childhood life events and trauma on the course of depressive and anxiety disorders.

OBJECTIVE: Data on the impact of childhood life events and childhood trauma on the clinical course of depressive and anxiety disorders are limited. METHOD: Longitudinal data were collected from 1209 adult participants in the Netherlands Study of Depression and Anxiety (NESDA). Childhood life events and trauma at baseline were assessed with a semi-structured interview and the clinical course after 2 years with a DSM-IV-based diagnostic interview and Life Chart Interview. RESULTS: At baseline, 18.4% reported at least one childhood life event and 57.8% any childhood trauma. Childhood life events were not predictive of any measures of course trajectory. Emotional neglect, psychological and physical abuse, but not sexual abuse, were associated with persistence of both depressive and comorbid anxiety and depressive disorder at follow-up. Emotional neglect and psychological abuse were associated with a higher occurrence of a chronic course. Poor course outcomes were mediated mainly through a higher baseline severity of depressive symptoms. CONCLUSION: Childhood trauma, but not childhood life events, was associated with an increased persistence of comorbidity and chronicity in adults with anxiety and/or depressive disorders. More unfavourable clinical characteristics at baseline mediate the relationship between childhood trauma and a poorer course of depressive and anxiety disorders.

The impact of the waveguide aperture size of the 3D 70 MHz AMC-8 locoregional hyperthermia system on tumour coverage.

The 70 MHz AMC-4 system, with one ring of four waveguides, provides 2D power steering. The newly developed AMC-8 system enables 3D steering, using two rings of four 70 MHz waveguides. The current waveguide aperture size is 20.2 x 34.3 cm(2). Waveguides and water boluses cover a large area of the body, which is not ideal for short patients. The aim of this study is investigating the impact of smaller waveguides on tumour coverage, using treatment planning. Finite-difference time-domain simulations were performed at 2.5 x 2.5 x 5 mm(3) resolution. Virtual AMC-8 systems with waveguide aperture sizes of 20.5 x 34.25, 17.5 x 34.25, 14.5 x 34.25, 11.5 x 34.25, 8.5 x 34.25 cm(2) and the AMC-4 system were modelled. Simulations were performed for elliptical (36 x 24 x 100 cm(3)) tissue-equivalent phantoms and for five cervical cancer patients. For the phantoms S(ratio) (SAR(max_border)/SAR(target)) was evaluated for standard and optimized settings. For the patients, temperature distributions were evaluated after optimization of tumour temperature, while limiting normal tissue temperatures to 45 degrees C. Phantom simulations showed a favourable S(ratio) for all two-ring systems, compared to the AMC-4 system, for optimized phase-amplitude settings. Patient simulations demonstrated that the improvement in T(90) for the operational AMC-8 system was approximately 0.5 degrees C. This improvement was independent of the aperture size. The average number of imminent hot spots and their total volume was almost comparable for 8.5 and 20.5 cm wide apertures, but the locations were different. Two-ring waveguide systems with eight antennas and aperture sizes in the range from 20.5 x 34.25 cm(2) to 8.5 x 34.25 cm(2) showed a stable gain in tumour temperature compared to a single-ring four-antenna system with 20.5 x 34.25 cm(2) wide apertures.

Childhood life events and childhood trauma in adult patients with depressive, anxiety and comorbid disorders vs. controls.

OBJECTIVE: To investigate the association between childhood life events, childhood trauma and the presence of anxiety, depressive or comorbid anxiety and depressive disorders in adulthood. METHOD: Data are from 1931 adult participants in the Netherlands Study of Depression and Anxiety (NESDA). Childhood life events included divorce of parents, early parental loss and 'placed in care', whereas childhood trauma was assessed as experienced emotional neglect, psychological, physical and sexual abuse prior to age 16. RESULTS: Childhood life events were not associated with psychopathology, except for 'placed in care' in the comorbid group. All types of childhood trauma were increasingly prevalent in the following order: controls, anxiety, depression, and comorbid group (P < 0.001). The higher the score was on the childhood trauma index, the stronger the association with psychopathology (P < 0.001). CONCLUSION: Childhood trauma rather than childhood life events are related to anxiety and depressive disorders. The strong associations with the comorbid group suggest that childhood trauma contributes to the severity of psychopathology. Our study underscores the importance of heightened awareness of the possible presence of childhood trauma, especially in adult patients with comorbid anxiety and depressive disorders.

[Treatment for chronic depression: cognitive behavioral analysis system of psychotherapy (CBASP)]. / Behandeling voor chronische depressie: 'cognitive behavioral analysis system of psychotherapy' (CBASP).

BACKGROUND: Chronic depression is a common disorder in secondary care. Treatment results for this group of depressed patients are often disappointing and the existing treatment protocols are insufficiently tailored to chronic MDD. For this reason, an effective psychotherapeutic treatment will constitute a welcome addition to the range of treatments currently available for chronically depressed patients. AIM: To describe 'cognitive behavioral analysis system of psychotherapy' (CBASP), the first form of psychotherapy specifically designed for the treatment of chronic depression. METHOD: This article describes the evidence, rational and the most important techniques of CBASP. RESULTS: In the United States CBASP has proven to be effective in one trial. As a result of these findings, CBASP is recommended in the Dutch treatment guidelines as an evidence-based treatment option for chronic depression. However, the findings have not yet been replicated and little is known about possible ways of implementing CBASP in the Netherlands. For this reason a randomised controlled trial on the effectiveness of CBASP has started in three psychiatric hospitals in the Netherlands. CONCLUSION: CBASP is recommended as a treatment option for chronic depression in the Dutch treatment guidelines, but evidence should be further supported by additional research.

Improving locoregional hyperthermia delivery using the 3-D controlled AMC-8 phased array hyperthermia system: a preclinical study.

BACKGROUND: The aim of this study is preclinical evaluation of our newly developed regional hyperthermia system providing 3-D SAR control: the AMC-8 phased array consisting of two rings, each with four 70 MHz waveguides. It was designed to achieve higher tumour temperatures and improve the clinical effectiveness of locoregional hyperthermia. METHODS: The performance of the AMC-8 system was evaluated with simulations and measurements aiming at heating a centrally located target region in rectangular (30 x 30 x 110 cm) and elliptical (36 x 24 x 80 cm) homogeneous tissue equivalent phantoms. Three properties were evaluated and compared to its predecessor, the 2-D AMC-4 single ring four waveguide array: (1) spatial control and (2) size of the SAR focus, (3) the ratio between maximum SAR outside the target region and SAR in the focus. Distance and phase difference between the two rings were varied. RESULTS: (1) Phase steering provides 3-D SAR control for the AMC-8 system. (2) The SAR focus is more elongated compared to the AMC-4 system, yielding a lower SAR level in the focus when using the same total power. This is counter-balanced by (3) a superficial SAR deposition which is half of that in the AMC-4 system, yielding a more favourable ratio between normal tissue and target SAR and allowing higher total power and up to 30% more SAR in the focus for 3 cm ring distance. CONCLUSION: The AMC-8 system is capable of 3-D SAR control and its SAR distribution is more favourable than for the 2-D AMC-4 system. This result promises improvement in clinical tumour temperatures.

Agronomic and Economic Responses of Spring Wheat to Management of Fusarium Head Blight.

Spring wheat (Triticum aestivum) crop losses in the Red River Valley of Minnesota and North Dakota caused by Fusarium head blight (FHB) epidemics incited by Fusarium graminearum are common. Fungicide application is often recommended when environments promote disease development but benefits have not been fully evaluated when environment, cultivar resistance, and economic outcome are considered. Agronomic and economic characters were determined for cultivars with various resistance levels when treated with no fungicide; propiconazole at 63 g active ingredient (a.i.)/ha applied at Feekes growth stage (FGS) 2, tebuconazole at 126 g a.i./ha applied at FGS 10.51, or propiconazole at 63 g a.i./ha applied at FGS 2 followed by tebuconazole at 126 g a.i./ha applied at FGS 10.51. Revenue returned from FHB moderately susceptible (MS) cultivars was 8% greater than moderately resistant (MR) cultivars in low-disease environs but differences were not significant when disease was moderate. Deoxynivalenol accumulation in grain of MS and MR cultivars was unchanged by fungicide treatment. MS cultivars were economically more adventitious to grow than MR cultivars in both disease environments.

Delineation of potential hot spots for hyperthermia treatment planning optimisation.

The optimal feed parameters of the generators for a complex-phased hyperthermia array system consisting of 4, 8 or even more applicators cannot be found using only the expertise of the treatment staff or using the limited amount of field and temperature data obtained during treatment. A number of strategies have been proposed to help us with the task to optimise the hyperthermia treatment, including several strategies specifically addressing the occurrence of hot spots. Each of the latter strategies strongly relies on the specification of the potential hot spots. This specification is either based on anatomy or the selection of an arbitrary number of potential hot spots. Therefore it is not guaranteed that all potential hot spots are included. This paper introduces a procedure for the delineation and visualisation of potential (SAR) hot spots. The potential hot spots are delineated by selecting those points for which the maximal SAR exceeds a specific SAR selection level. This SAR selection level is defined relative to the highest achievable SAR in the target volume for a certain fixed heating power. A larger number of potential hot spots and hot spots of larger size are delineated if the selection level is decreased. Although the procedure still includes an arbitrary selection criterion, i.e. the selection level, the selection is solely based on calculated EM-field data. As a result all potential hot spots can be delineated a priori. Three different objective functions are applied to maximise the SAR in the target. The first only maximises the SAR in the target volume for a given system power output. The other two intrinsically set a constraint on the set of potential hot spots as a whole. Additionally the SAR in each delineated potential hot spot separately can be constrained. In two patient cases the SAR in potential hot spots can be kept below the selection value applied for delineation of the potential hot spots. If assessed in terms of constraining the SAR value below the selection level while maximising target heating efficiency the combination of an objective function only maximising the SAR in the target with a separate constraint on each potential hot spots appears to be the most efficient.

Prospective treatment planning to improve locoregional hyperthermia for oesophageal cancer.

BACKGROUND: In the Academic Medical Center (AMC) Amsterdam, locoregional hyperthermia for oesophageal tumours is applied using the 70 MHz AMC-4 phased array system. Due to the occurrence of treatment-limiting hot spots in normal tissue and systemic stress at high power, the thermal dose achieved in the tumour can be sub-optimal. The large number of degrees of freedom of the heating device, i.e. the amplitudes and phases of the antennae, makes it difficult to avoid treatment-limiting hot spots by intuitive amplitude/phase steering. AIM: Prospective hyperthermia treatment planning combined with high resolution temperature-based optimization was applied to improve hyperthermia treatment of patients with oesophageal cancer. METHODS: All hyperthermia treatments were performed with 'standard' clinical settings. Temperatures were measured systemically, at the location of the tumour and near the spinal cord, which is an organ at risk. For 16 patients numerically optimized settings were obtained from treatment planning with temperature-based optimization. Steady state tumour temperatures were maximized, subject to constraints to normal tissue temperatures. At the start of 48 hyperthermia treatments in these 16 patients temperature rise (DeltaT) measurements were performed by applying a short power pulse with the numerically optimized amplitude/phase settings, with the clinical settings and with mixed settings, i.e. numerically optimized amplitudes combined with clinical phases. The heating efficiency of the three settings was determined by the measured DeltaT values and the DeltaT-ratio between the DeltaT in the tumour (DeltaToes) and near the spinal cord (DeltaTcord). For a single patient the steady state temperature distribution was computed retrospectively for all three settings, since the temperature distributions may be quite different. To illustrate that the choice of the optimization strategy is decisive for the obtained settings, a numerical optimization on DeltaT-ratio was performed for this patient and the steady state temperature distribution for the obtained settings was computed. RESULTS: A higher DeltaToes was measured with the mixed settings compared to the calculated and clinical settings; DeltaTcord was higher with the mixed settings compared to the clinical settings. The DeltaT-ratio was approximately 1.5 for all three settings. These results indicate that the most effective tumour heating can be achieved with the mixed settings. DeltaT is proportional to the Specific Absorption Rate (SAR) and a higher SAR results in a higher steady state temperature, which implies that mixed settings are likely to provide the most effective heating at steady state as well. The steady state temperature distributions for the clinical and mixed settings, computed for the single patient, showed some locations where temperatures exceeded the normal tissue constraints used in the optimization. This demonstrates that the numerical optimization did not prescribe the mixed settings, because it had to comply with the constraints set to the normal tissue temperatures. However, the predicted hot spots are not necessarily clinically relevant. Numerical optimization on DeltaT-ratio for this patient yielded a very high DeltaT-ratio ( approximately 380), albeit at the cost of excessive heating of normal tissue and lower steady state tumour temperatures compared to the conventional optimization. CONCLUSION: Treatment planning can be valuable to improve hyperthermia treatments. A thorough discussion on clinically relevant objectives and constraints is essential.

Removing the effects of CSF partial voluming on fitted CBF and arterial transit times using FAIR, a pulsed arterial spin labelling technique.

FAIR, an arterial spin labelling technique, provides non-invasive, quantitative CBF values and arterial transit times deltat. This paper focuses on the negative impact of CSF partial voluming on FAIR results. To understand and solve this problem, we performed a theoretical analysis and a range of simulations. We then acquired FAIR data from a volunteer to illustrate our findings. We found that the determinant effect of CSF is a delayed zero-crossing during inversion recovery. The subtraction of magnitude inversion recovery data in FAIR generates erroneous negative data and distorted fit results: we simulated that for CSF percentages of 0-40%, CBF and deltat will be progressively overestimated by up to 50%. For higher CSF percentages the errors were found to increase steeply. We explored a straightforward solution: taking the magnitude of the FAIR data before fitting. This provided a remarkably strong antidote against the effects of CSF partial voluming: for CSF percentages of 0-40%, simulations now gave CBF values accurate within 1%, and deltat within 5%. The fit remained robust for high CSF fractions. Our analysis and simulations demonstrate that using magnitude FAIR data minimises the detrimental effects of CSF partial voluming. Data from a healthy volunteer illustrate these results.

[Treatment of patients with diabetes mellitus type 2 and coronary artery disease]. / Behandeling van patiënten met diabetes mellitus type 2 en tevens coronaire hartziekten.

Of all patients presenting with coronary, artery disease, 20-30% already have a diagnosis of diabetes mellitus type 2. Of the remaining patients, another 15-20% are found at presentation to have diabetes mellitus and 30% have glucose intolerance. Both conditions are major risk factors for the recurrence of coronary artery disease and mortality. The treatment of patients with diabetes mellitus type 2 always includes improvement in lifestyle, adequate blood-glucose control, cholesterol-lowering therapy and blood-pressure control. Furthermore, if one or more other traditional cardiovascular risk factors are present, or if the patient is over 40 years of age, acetylsalicylic acid must be added. Finally, with a prior history of coronary-artery disease, patients must be given an angiotensin converting enzyme (ACE) inhibitor. During percutaneous coronary interventions, patients with diabetes mellitus type 2 are preferably treated with a drug-eluting stent in combination with clopidogrel, and in case of an acute coronary syndrome, glycoprotein (GP) IIb/IIIa receptor antagonists are added to the standard treatment.

Cardiac complications in type 2 diabetic patients with mild anginal symptoms and documented reversible myocardial perfusion defects: Results of the MERIDIAN trial.

BACKGROUND/OBJECTIVE: To compare early invasive treatment with continued pharmacological treatment in patients with diabetes mellitus type 2, mild anginal symptoms and documented myocardial ischaemia. METHODS: Patients with type 2 diabetes mellitus and mild anginal symptoms underwent myocardial perfusion scintigraphy (MPS). Patients with myocardial ischaemia were randomly assigned to early invasive or continued pharmacological treatment. All patients were followed for the occurrence of MACE (death, nonfatal myocardial infarction or hospitalisation for unstable angina pectoris). RESULTS: A total of 156 patients were randomised when the sponsor (ZonMW) prematurely terminated the study because of a slow recruitment rate. With a mean follow-up of 2.1±0.6 years, 9 of 79 patients assigned to early invasive treatment developed MACE compared with 10 of 77 patients randomised to continued pharmacological treatment, annual event rate 5.4 vs. 6.3%, hazard ratio 0.89, 95% CI 0.36 to 2.20, p=0.34. Due to the limited number of included patients and the low event rate, the study did not have sufficient power for the study objective. CONCLUSION: Patients with diabetes mellitus type 2, mild anginal symptoms and documented myocardial ischaemia, under appropriate medical treatment, have a lower than anticipated annual event rate of MACE of ±5 to 6% which questions the beneficial effect of early revascularisation.

High-resolution temperature-based optimization for hyperthermia treatment planning.

In regional hyperthermia, optimization techniques are valuable in order to obtain amplitude/phase settings for the applicators to achieve maximal tumour heating without toxicity to normal tissue. We implemented a temperature-based optimization technique and maximized tumour temperature with constraints on normal tissue temperature to prevent hot spots. E-field distributions are the primary input for the optimization method. Due to computer limitations we are restricted to a resolution of 1 x 1 x 1 cm3 for E-field calculations, too low for reliable treatment planning. A major problem is the fact that hot spots at low-resolution (LR) do not always correspond to hot spots at high-resolution (HR), and vice versa. Thus, HR temperature-based optimization is necessary for adequate treatment planning and satisfactory results cannot be obtained with LR strategies. To obtain HR power density (PD) distributions from LR E-field calculations, a quasi-static zooming technique has been developed earlier at the UMC Utrecht. However, quasi-static zooming does not preserve phase information and therefore it does not provide the HR E-field information required for direct HR optimization. We combined quasi-static zooming with the optimization method to obtain a millimetre resolution temperature-based optimization strategy. First we performed a LR (1 cm) optimization and used the obtained settings to calculate the HR (2 mm) PD and corresponding HR temperature distribution. Next, we performed a HR optimization using an estimation of the new HR temperature distribution based on previous calculations. This estimation is based on the assumption that the HR and LR temperature distributions, though strongly different, respond in a similar way to amplitude/phase steering. To verify the newly obtained settings, we calculate the corresponding HR temperature distribution. This method was applied to several clinical situations and found to work very well. Deviations of this estimation method for the AMC-4 system were typically smaller than 0.2 degrees C in the volume of interest, which is accurate enough for treatment planning purposes.

Duodenal motility during a run-bike-run protocol: the effect of a sports drink.

OBJECTIVE: To examine the effect of a sports drink during strenuous exercise on duodenal motility and gastrointestinal symptoms. METHODS: In a cross-over design, seven male triathletes performed two 170-min run-bike-run tests at about 70% peak oxygen uptake (O(2peak)), with either a 7% carbohydrate (CHO) sports drink or tap water. Antroduodenal motility (phase III of the migrating motor complex; MMC) was measured with an ambulant manometry system. The effect of the two exercise trials on the first appearance of the MMC was assessed in the postprandial period. RESULTS: Exercise heart rate, percentage O(2peak) and loss of body mass did not differ significantly between the two trials. After the start of the exercise, the expected time before the first phase III occurrence, based on the actual energy intake of the last meal in the morning before exercise (1048 +/- 294 kcal), a fixed gastric emptying rate and a lag phase for solid food, was 183 +/- 113 min (mean +/- standard deviation [SD]). The real time period between the start of the exercise with CHO and the first phase III was 63 +/- 61 min, which was significantly shorter than that observed with tap water (152 +/- 59 min). Both real time periods were shorter than the expected time period of 183 +/- 113 min (P < 0.05). During exercise, the number of subjects with a phase III was higher with CHO than with tap water (n =6 v. n =1; P < 0.05). Also, the median number of phases III per hour with CHO was higher than with tap water (0.4 v. 0.0; P < 0.05). During cycling, significantly more phases III per hour (0.9) were measured than during running (0.2). All subjects reported one or more gastrointestinal symptoms during exercise, however, without a clear association with the mode of exercise or supplementation. CONCLUSIONS: Prolonged exercise results in gastrointestinal symptoms and a significant interruption of postprandial motility. Only the latter phenomenon depends on the mode of exercise and supplementation.