Tumour border configuration in colorectal cancer: proposal for an alternative scoring system based on the percentage of infiltrating margin.

AIMS Information on tumour border configuration (TBC) in colorectal cancer (CRC) is currently not included in most pathology reports, owing to lack of reproducibility and/or established evaluation systems. The aim of this study was to investigate whether an alternative scoring system based on the percentage of the infiltrating component may represent a reliable method for assessing TBC. METHODS AND RESULTS Two hundred and fifteen CRCs with complete clinicopathological data were evaluated by two independent observers, both 'traditionally' by assigning the tumours into pushing/infiltrating/mixed categories, and alternatively by scoring the percentage of infiltrating margin. With the pushing/infiltrating/mixed pattern method, interobserver agreement (IOA) was moderate (κ = 0.58), whereas with the percentage of infiltrating margins method, IOA was excellent (intraclass correlation coefficient of 0.86). A higher percentage of infiltrating margin correlated with adverse features such as higher grade (P = 0.0025), higher pT (P = 0.0007), pN (P = 0.0001) and pM classification (P = 0.0063), high-grade tumour budding (P < 0.0001), lymphatic invasion (P < 0.0001), vascular invasion (P = 0.0032), and shorter survival (P = 0.0008), and was significantly associated with an increased probability of lymph node metastasis (P < 0.001). CONCLUSIONS Information on TBC gives additional prognostic value to pathology reports on CRC. The novel proposed scoring system, by using the percentage of infiltrating margin, outperforms the 'traditional' way of reporting TBC. Additionally, it is reproducible and simple to apply, and can therefore be easily integrated into daily diagnostic practice.

Comparison of proximal femur and vertebral body strength improvements in the FREEDOM trial using an alternative finite element methodology

Denosumab reduced the incidence of new fractures in postmenopausal women with osteoporosis by 68% at the spine and 40% at the hip over 36 months compared with placebo in the FREEDOM study. This efficacy was supported by improvements from baseline in vertebral (18.2%) strength in axial compression and femoral (8.6%) strength in sideways fall configuration at 36 months, estimated in Newtons by an established voxel-based finite element (FE) methodology. Since FE analyses rely on the choice of meshes, material properties, and boundary conditions, the aim of this study was to independently confirm and compare the effects of denosumab on vertebral and femoral strength during the FREEDOM trial using an alternative smooth FE methodology. Unlike the previous FE study, effects on femoral strength in physiological stance configuration were also examined. QCT data for the proximal femur and two lumbar vertebrae were analyzed by smooth FE methodology at baseline, 12, 24, and 36 months for 51 treated (denosumab) and 47 control (placebo) subjects. QCT images were segmented and converted into smooth FE models to compute bone strength. L1 and L2 vertebral bodies were virtually loaded in axial compression and the proximal femora in both fall and stance configurations. Denosumab increased vertebral body strength by 10.8%, 14.0%, and 17.4% from baseline at 12, 24, and 36 months, respectively (p < 0.0001). Denosumab also increased femoral strength in the fall configuration by 4.3%, 5.1%, and 7.2% from baseline at 12, 24, and 36 months, respectively (p < 0.0001). Similar improvements were observed in the stance configuration with increases of 4.2%, 5.2%, and 5.2% from baseline (p ≤ 0.0007). Differences between the increasing strengths with denosumab and the decreasing strengths with placebo were significant starting at 12 months (vertebral and femoral fall) or 24 months (femoral stance). Using an alternative smooth FE methodology, we confirmed the significant improvements in vertebral body and proximal femur strength previously observed with denosumab. Estimated increases in strength with denosumab and decreases with placebo were highly consistent between both FE techniques.

Alternative nighttime nutrition regimens in glycogen storage disease type I: a controlled crossover study

BACKGROUND Traditional approaches for nighttime glycemic control in glycogen storage disease type I (GSDI) include continuous tube feeding, or ingestion of uncooked corn starch (CS) at bedtime. A modified corn starch (MCS) has been shown to prolong euglycemia in some patients. The aim of this study was to evaluate whether stable nighttime glucose control can be achieved with other types of slowly digested carbohydrates in adult GSDI patients. METHODS In this cross-over study, nocturnal glucose control and fasting times were assessed with three different nocturnal nutrition regimens in five patients, using continuous glucose monitoring (CGMS) in an outpatient everyday life setting. For each patient, continuous glucose profiles were measured after ingestion of (1) CS, (2) MCS or (3) a pasta meal at bedtime, during 5 to 6 consecutive nights for each regimen. RESULTS Stable nocturnal glucose control was achieved for all patients with a pasta meal, with a mean duration of glycemia >3.5 mmol/l of 7.6 h (range 5.7-10.8), and >4 mmol/l of 7 h (5.2-9.2), similar to CS and MCS. Fasting glucose before breakfast on workdays (after 7.1 ± 0.8 h) was not significantly different between the three interventions (CS 4.1 ± 0.5 mmol/l, MCS 4.6 ± 0.7 mmol/l, pasta 4.3 ± 0.9 mmol/l). During prolonged fasting on weekends, longer duration of normoglycemia was achieved with CS or MCS than with pasta. CONCLUSION Consumption of cooked pasta is a suitable and more palatable alternative to uncooked corn starch to achieve nighttime glucose control in adult patients with GSDI.

Lordoplasty: midterm outcome of an alternative augmentation technique for vertebral fractures.

OBJECTIVE Vertebroplasty and balloon kyphoplasty are effective treatment options for osteoporotic vertebral compression fractures but are limited in correction of kyphotic deformity. Lordoplasty has been reported as an alternative, cost-effective, minimally invasive, percutaneous cement augmentation technique with good restoration of vertebral body height and alignment. The authors report on its clinical and radiological midterm results. METHODS A retrospective review was conducted of patients treated with lordoplasty from 2002 to 2014. Inclusion criteria were clinical and radiological follow-up evaluations longer than 24 months. Radiographs were accessed regarding initial correction and progressive loss of reduction. Complications and reoperations were recorded. Actual pain level, pain relief immediately after surgery, autonomy, and subjective impression of improvement of posture were assessed by questionnaire. RESULTS Sixty-five patients (46 women, 19 men, age range 38.9-86.2 years old) were treated with lordoplasty for 69 vertebral compression and insufficiency fractures. A significant correction of the vertebral kyphotic angle (mean 13°) and segmental kyphotic angle (mean 11°) over a mean follow-up of 33 months (range 24-108 months) was achieved (p < 0.001). On average, pain was relieved to 90% of the initial pain level. In 24% of the 65 patients a second spinal intervention was necessary: 16 distant (24.6%) and 7 adjacent (10.8%) new osteoporotic fractures, 4 instrumented stabilizations (6.2%), 1 new adjacent traumatic fracture (1.5%), and 1 distant microsurgical decompression (1.5%). Cement leakage occurred in 10.4% but was only symptomatic in 1 case. CONCLUSIONS Lordoplasty appeared safe and effective in midterm pain alleviation and restoration of kyphotic deformity in osteoporotic compression and insufficiency fractures. The outcomes of lordoplasty are consistent with other augmentation techniques.

The enduring effects of psychodynamic treatments vis-à-vis alternative treatments: A multilevel longitudinal meta-analysis

Although evidence suggests that the benefits of psychodynamic treatments are sustained over time, presently it is unclear whether these sustained benefits are superior to non-psychodynamic treatments. Additionally, the extant literature comparing the sustained benefits of psychodynamic treatments compared to alternative treatments is limited with methodological shortcomings. The purpose of the current study was to conduct a rigorous test of the growth of the benefits of psychodynamic treatments relative to alternative treatments across distinct domains of change (i.e., all outcome measures, targeted outcome measures, non-targeted outcome measures, and personality outcome measures). To do so, the study employed strict inclusion criteria to identify randomized clinical trials that directly compared at least one bona fide psychodynamic treatment and one bona fide non-psychodynamic treatment. Hierarchical linear modeling (Raudenbush, Bryk, Cheong, Congdon, & du Toit, 2011) was used to longitudinally model the impact of psychodynamic treatments compared to non-psychodynamic treatments at post-treatment and to compare the growth (i.e., slope) of effects beyond treatment completion. Findings from the present meta-analysis indicated that psychodynamic treatments and non-psychodynamic treatments were equally efficacious at post-treatment and at follow-up for combined outcomes (k=20), targeted outcomes (k=19), non-targeted outcomes (k=17), and personality outcomes (k=6). Clinical implications, directions for future research, and limitations are discussed.

Developing an alternative response format for the script concordance test

Introduction: Clinical reasoning is essential for the practice of medicine. In theory of development of medical expertise it is stated, that clinical reasoning starts from analytical processes namely the storage of isolated facts and the logical application of the ‘rules’ of diagnosis. Then the learners successively develop so called semantic networks and illness-scripts which finally are used in an intuitive non-analytic fashion [1], [2]. The script concordance test (SCT) is an example for assessing clinical reasoning [3]. However the aggregate scoring [3] of the SCT is recognized as problematic [4]. The SCT`s scoring leads to logical inconsistencies and is likely to reflect construct-irrelevant differences in examinees’ response styles [4]. Also the expert panel judgments might lead to an unintended error of measurement [4]. In this PhD project the following research questions will be addressed: 1. How does a format look like to assess clinical reasoning (similar to the SCT but) with multiple true-false questions or other formats with unambiguous correct answers, and by this address the above mentioned pitfalls in traditional scoring of the SCT? 2. How well does this format fulfill the Ottawa criteria for good assessment, with special regards to educational and catalytic effects [5]? Methods: 1. In a first study it shall be assessed whether designing a new format using multiple true-false items to assess clinical reasoning similar to the SCT-format is arguable in a theoretically and practically sound fashion. For this study focus groups or interviews with assessment experts and students will be undertaken. 2. In an study using focus groups and psychometric data Norcini`s and colleagues Criteria for Good Assessment [5] shall be determined for the new format in a real assessment. Furthermore the scoring method for this new format shall be optimized using real and simulated data.

Role of alternative interventional procedures when endo- and epicardial catheter ablation attempts for ventricular arrhythmias fail.

BACKGROUND Ventricular tachycardia (VT) refractory to antiarrhythmic drugs and standard percutaneous catheter ablation techniques portends a poor prognosis. We characterized the reasons for ablation failure and describe alternative interventional procedures in this high-risk group. METHODS AND RESULTS Sixty-seven patients with VT refractory to 4±2 antiarrhythmic drugs and 2±1 previous endocardial/epicardial catheter ablation attempts underwent transcoronary ethanol ablation, surgical epicardial window (Epi-window), or surgical cryoablation (OR-Cryo; age, 62±11 years; VT storm in 52%). Failure of endo/epicardial ablation attempts was because of VT of intramural origin (35 patients), nonendocardial origin with prohibitive epicardial access because of pericardial adhesions (16), and anatomic barriers to ablation (8). In 8 patients, VT was of nonendocardial origin with a coexisting condition also requiring cardiac surgery. Transcoronary ethanol ablation alone was attempted in 37 patients, OR-Cryo alone in 21 patients, and a combination of transcoronary ethanol ablation and OR-Cryo (5 patients), or transcoronary ethanol ablation and Epi-window (4 patients), in the remainder. Overall, alternative interventional procedures abolished ≥1 inducible VT and terminated storm in 69% and 74% of patients, respectively, although 25% of patients had at least 1 complication. By 6 months post procedures, there was a significant reduction in defibrillator shocks (from a median of 8 per month to 1; P<0.001) and antiarrhythmic drug requirement although 55% of patients had at least 1 VT recurrence, and mortality was 17%. CONCLUSIONS A collaborative strategy of alternative interventional procedures offers the possibility of achieving arrhythmia control in high-risk patients with VT that is otherwise uncontrollable with antiarrhythmic drugs and standard percutaneous catheter ablation techniques.

Bivalirudin for Alternative Anticoagulation in Extracorporeal Membrane Oxygenation: A Systematic Review.

BACKGROUND Extracorporeal membrane oxygenation (ECMO) offers therapeutic options in refractory respiratory and/or cardiac failure. Systemic anticoagulation with heparin is routinely administered. However, in patients with heparin-induced thrombocytopenia or heparin resistance, the direct thrombin inhibitor bivalirudin is a valid option and has been increasingly used for ECMO anticoagulation. We aimed at evaluating its safety and its optimal dosing for ECMO. METHODS Systematic web-based literature search of PubMed and EMBASE performed via National Health Service Library Evidence and manually, updated until January 30, 2016. RESULTS The search revealed 8 publications relevant to the topic (5 case reports). In total, 58 patients (24 pediatrics) were reported (18 received heparin as control groups). Bivalirudin was used with or without loading dose, followed by infusion at different ranges (lowest 0.1-0.2 mg/kg/h without loading dose; highest 0.5 mg/kg/h after loading dose). The strategies for monitoring anticoagulation and optimal targets were dissimilar (activated partial thromboplastin time 45-60 seconds to 42-88 seconds; activated clotting time 180-200 seconds to 200-220 seconds; thromboelastography in 1 study). CONCLUSION Bivalirudin loading dose was not always used; infusion range and anticoagulation targets were different. In this systematic review, we discuss the reasons for this variability. Larger studies are needed to establish the optimal approach with the use of bivalirudin for ECMO.

Tracing Hybrid Collectives of Illness, War, and Medicine in Twentieth- and Twenty-First Century Narratives of Illness

Thesis (Ph.D.)--University of Washington, 2016-06

Constructing and evaluating alternative prediction models for identifying clinically relevant cases in an STD clinic

Thesis (Master's)--University of Washington, 2016-06

A prospective study of the use of alternative therapies by men with localized prostate cancer

Although the use of alternative therapies is highly prevalent amongst men with prostate cancer, research about the predictors of such use is limited. The current study aimed to describe prospectively the use of alternative therapies by men diagnosed with localized prostate cancer and identify predictors of alternative therapy use. In all, 111 men newly diagnosed with localized prostate cancer (93% response) were recruited to the study prior to treatment. Men's use of alternative therapies and psychological variables including: psychological distress, orientation to health care, decisional conflict, and health locus of control, were assessed at three time points-(1) before treatment; (2) 2 months after completion of treatment; and (3) 12 months after completion of treatment. Demographic information was also obtained. The percentage of men using alternative therapies was 25, 17 and 14% before treatment, 2 and 12 months after treatment, respectively. In general, the most commonly used therapies were dietary changes, vitamins and herbal and nutrient remedies. Alternative therapy use was not related to final treatment choices. Before treatment, men who used alternative therapies were more uncertain about prostate cancer compared to men who were not using these therapies. Men who were using alternative therapies 12 months after treatment were less psychologically distressed that men who were not using these therapies. Health locus of control and orientation to health care were not found to be related to men's use of alternative therapies. In conclusion, men's use of alternative therapies after localized prostate cancer varied across time in terms of the incidence of use, the types of therapies used, and the psychological correlates of therapy use. Informational support that targets uncertainty about prostate cancer may assist men at diagnosis who are considering alternative therapy use. The potential for alternative therapies to have a supportive function in patient care requires further investigation. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

Perceptions of the influence of prescription medicine samples on prescribing by family physicians

Background: The provision of free prescription medicine samples is a common and traditional marketing strategy used by pharmaceutical companies, but concerns have been raised about their influence on physician prescribing behavior and patient safety. Objective: We sought to investigate the knowledge, attitudes, and behaviors of Australian family physicians regarding the use of sample prescription medications. Methods: Qualitative and quantitative techniques were used, including (1) mailed questionnaires to family physicians, (2) semistructured interviews with family physicians, and (3) sample cupboard inventories. Results: A number of issues about samples were identified by the questionnaires (208) and interviews (17 doctors), including insufficient labeling, poor record keeping, diversion of stock (personal use by doctors.. their families, practice staff and pharmaceutical representatives), and wasting of expired stock. Prescription medicine samples also influenced prescribing behavior. Australian doctors were less likely to provide samples to patients on financial grounds compared with a previous study in the United States on medical residents. Six sample cupboards were inventoried. Median wholesale value of sample cupboards was AUD $4959 (range $2395-$8709), with 6% of stock expired. Very little generic medicine was included in the sample cupboards. Conclusions: Better methods are needed to meet legislative requirements and to ensure quality use of medicines (and optimal public health) with respect to prescription medicine samples. Doctors and practice staff require training on the appropriate handling and storage of prescription medications. Alternative ways for distribution of sample medications need to be investigated.

Dominance hierarchies and health: Constructing personal zones of spiritual power and healing in modern medicine

Ethological studies of animals in groups and sociobiology indicate that hierarchies of dominance amongst some species ensure the survival of the group. When transferred to human groups, dominance hierarchies suggest a crucial role played by recasting the scope of such hierarchies of dominant and subordinate members to included hyper-dominant beings. A recognition of such beings as even more dominant than the socially dominant members of a hierarchy facilitates the empowerment of the socially subordinate members. Religious belief and practice works to establish such hyper-dominant beings (gods, goddesses, and so forth) as superior members of human groups. Doing so is a means of ensuring the survival of the species and, thus, enhancing healing and human health. The doctor-patient relationship is examined from such a point of view, with an emphasis on whether the hierarchy created by the relationship allows consideration of alternative and complementary forms of medical treatment.