Clinicians' evaluations of, endorsements of, and intentions to use practice guidelines change over time: a retrospective analysis from an organized guideline program

<p>Abstract</p> <p>Purpose</p> <p>Clinical practice guidelines (CPGs) can improve clinical care but uptake and application are inconsistent. Objectives were: to examine temporal trends in clinicians' evaluations of, endorsements of, and intentions to use cancer CPGs developed by an established CPG program; and to evaluate how predictor variables (clinician characteristics, beliefs, and attitudes) are associated with these trends.</p> <p>Design and methods</p> <p>Between 1999 and 2005, 756 clinicians evaluated 84 Cancer Care Ontario CPGs, yielding 4,091 surveys that targeted four CPG quality domains (rigour, applicability, acceptability, and comparative value), clinicians' endorsement levels, and clinicians' intentions to use CPGs in practice.</p> <p>Results</p> <p>Time: In contrast to the applicability and intention to use in practice scores, there were small but statistically significant annual net gains in ratings for rigour, acceptability, comparative value, and CPG endorsement measures (p < 0.05 for all rating categories). Predictors: In 17 comparisons, ratings were significantly higher among clinicians having the most favourable beliefs and most positive attitudes and lowest for those having the least favourable beliefs and most negative attitudes (p < 0.05). Interactions Time × Predictors: Over time, differences in outcomes among clinicians decreased due to positive net gains in scores by clinicians whose beliefs and attitudes were least favorable.</p> <p>Conclusion</p> <p>Individual differences among clinicians largely explain variances in outcomes measured. Continued engagement of clinicians least receptive to CPGs may be worthwhile because they are the ones showing most significant gains in CPG quality ratings, endorsement ratings, and intentions to use in practice ratings.</p

Pediatric Differentiated Thyroid Carcinoma in The Netherlands: A Nationwide Follow-Up Study

Introduction: Treatment for differentiated thyroid carcinoma (DTC) in pediatric patients is based mainly on evidence from adult series due to lack of data from pediatric cohorts. Our objective was to evaluate presentation, treatment-related complications, and long-term outcome in patients with pediatric DTC in the Netherlands. Patients and methods: In this nationwide study, presentation, complications and outcome of patients with pediatric DTC (age at diagnosis ≤18 years) treated in the Netherlands between 1970 and 2013 were assessed using medical records. Results: We identified 170 patients. Overall survival was 99.4% after median follow-up of 13.5 (range 0.3–44.7) years. Extensive follow-up data were available for 105 patients (83.8% women), treated in 39 hospitals. Median age at diagnosis was 15.6 (range 5.8–18.9) years. At initial diagnosis, 43.8% of the patients had cervical lymph node metastases; 13.3% had distant metastases. All patients underwent total thyroidectomy. Radioiodine was administered to 97.1%, with a median cumulative activity of 5.66 (range 0.74–35.15) GBq. Lifelong postoperative complications (permanent hypoparathyroidism and/or recurrent laryngeal nerve injury) were present in 32.4% of the patients. At last known follow-up, 8.6% of the patients had persistent disease and 7.6% experienced a recurrence. TSH suppression was not associated with recurrences (OR 2.00, 95% CI 0.78 to 5.17, P = 0.152). Conclusions: Survival of pediatric DTC is excellent. Therefore, minimizing treatment-related morbidity takes major priority. Our study shows a frequent occurrence of lifelong postoperative complications. Adverse effects may be reduced by centralization of care, which is crucial for children with DTC

Risk Factors of Drug Interaction between Warfarin and Nonsteroidal Anti-Inflammatory Drugs in Practical Setting

Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to interact with the oral anticoagulant warfarin and can cause a serious bleeding complication. In this study, we evaluated the risk factors for international normalized ratio (INR) increase, which is a surrogate marker of bleeding, after addition of an NSAID in a total of 98 patients who used warfarin. Patient age, sex, body mass index, maintenance warfarin dose, baseline INR, coadministered medications, underlying diseases, and liver and kidney functions were evaluated for possible risk factors with INR increase ≥15.0% as the primary end-point. Of the 98 patients, 39 (39.8%) showed an INR elevation of ≥15.0% after adding a NSAID to warfarin therapy. Multivariate analysis showed that high maintenance dose (>40 mg/week) of warfarin (P=0.001), the presence of coadministered medications (P=0.024), the use of meloxicam (P=0.025) and low baseline INR value (P=0.03) were the risk factors for INR increase in respect to NSAID-warfarin interaction. In conclusion, special caution is required when an NSAID is administered to warfarin users if patients are taking warfarin >40 mg/week and other medications interacting with warfarin

Radioimmunotherapy Improves Survival of Rats with Microscopic Liver Metastases of Colorectal Origin

BACKGROUND: Half of the patients with colorectal cancer develop liver metastases during the course of their disease. The aim of the present study was to assess the efficacy of radioimmunotherapy (RIT) with a radiolabeled monoclonal antibody (mAb) to treat experimental colorectal liver metastases. METHODS: Male Wag/Rij rats underwent a minilaparotomy with intraportal injection of 1 x 10(6) CC531 tumor cells. The biodistribution of (111)In-labeled MG1, 1 day after intravenous administration, was determined in vivo and compared with that of an isotype-matched control antibody (UPC-10). The maximal tolerated dose (MTD) of (177)Lu-labeled MG1 was determined and the therapeutic efficacy of (177)Lu-MG1 at MTD was compared with that of (177)Lu-UPC-10 and saline only. RIT was administered either at the day of tumor inoculation or 14 days after tumor inoculation. Primary endpoint was survival. RESULTS: (111)In-MG1 preferentially accumulated in CC531 liver tumors (9.2 +/- 3.7%ID/g), whereas (111)In-UPC-10 did not (0.8 +/- 0.1%ID/g). The MTD of (177)Lu-MG1 was 400 MBq/kg body weight. Both the administration of (177)Lu-MG1 and (177)Lu-UPC-10 had no side-effects except a transient decrease in body weight. The survival curves of the group that received (177)Lu-UPC-10 and the group that received saline only did not differ (P = 0.407). Administration of (177)Lu-MG1 RIT immediately after surgery improved survival significantly compared with administration of (177)Lu-UPC-10 (P = 0.009) whereas delayed treatment did not (P = 0.940). CONCLUSION: This study provides proof of principle that RIT can be an effective treatment modality for microscopic liver metastases, whereas RIT is not effective in larger tumors

A New Peptide Ligand for Targeting Human Carbonic Anhydrase IX, Identified through the Phage Display Technology

Carbonic anhydrase IX (CAIX) is a transmembrane enzyme found to be overexpressed in various tumors and associated with tumor hypoxia. Ligands binding this target may be used to visualize hypoxia, tumor manifestation or treat tumors by endoradiotherapy

PET Imaging of Soluble Yttrium-86-Labeled Carbon Nanotubes in Mice

The potential medical applications of nanomaterials are shaping the landscape of the nanobiotechnology field and driving it forward. A key factor in determining the suitability of these nanomaterials must be how they interface with biological systems. Single walled carbon nanotubes (CNT) are being investigated as platforms for the delivery of biological, radiological, and chemical payloads to target tissues. CNT are mechanically robust graphene cylinders comprised of sp(2)-bonded carbon atoms and possessing highly regular structures with defined periodicity. CNT exhibit unique mechanochemical properties that can be exploited for the development of novel drug delivery platforms. In order to evaluate the potential usefulness of this CNT scaffold, we undertook an imaging study to determine the tissue biodistribution and pharmacokinetics of prototypical DOTA-functionalized CNT labeled with yttrium-86 and indium-111 ((86)Y-CNT and (111)In-CNT, respectively) in a mouse model.The (86)Y-CNT construct was synthesized from amine-functionalized, water-soluble CNT by covalently attaching multiple copies of DOTA chelates and then radiolabeling with the positron-emitting metal-ion, yttrium-86. A gamma-emitting (111)In-CNT construct was similarly prepared and purified. The constructs were characterized spectroscopically, microscopically, and chromatographically. The whole-body distribution and clearance of yttrium-86 was characterized at 3 and 24 hours post-injection using positron emission tomography (PET). The yttrium-86 cleared the blood within 3 hours and distributed predominantly to the kidneys, liver, spleen and bone. Although the activity that accumulated in the kidney cleared with time, the whole-body clearance was slow. Differential uptake in these target tissues was observed following intravenous or intraperitoneal injection.The whole-body PET images indicated that the major sites of accumulation of activity resulting from the administration of (86)Y-CNT were the kidney, liver, spleen, and to a much less extent the bone. Blood clearance was rapid and could be beneficial in the use of short-lived radionuclides in diagnostic applications

Health care utilization among complementary and alternative medicine users in a large military cohort

<p>Abstract</p> <p>Background</p> <p>Complementary and Alternative Medicine use and how it impacts health care utilization in the United States Military is not well documented. Using data from the Millennium Cohort Study we describe the characteristics of CAM users in a large military population and document their health care needs over a 12-month period. The aim of this study was to determine if CAM users are requiring more physician-based medical services than users of conventional medicine.</p> <p>Methods</p> <p>Inpatient and outpatient medical services were documented over a 12-month period for 44,287 participants from the Millennium Cohort Study. Equal access to medical services was available to anyone needing medical care during this study period. The number and types of medical visits were compared between CAM and non-CAM users. Chi square test and multivariable logistic regression was applied for the analysis.</p> <p>Results</p> <p>Of the 44,287 participants, 39% reported using at least one CAM therapy, and 61% reported not using any CAM therapies. Those individuals reporting CAM use accounted for 45.1% of outpatient care and 44.8% of inpatient care. Individuals reporting one or more health conditions were 15% more likely to report CAM use than non-CAM users and 19% more likely to report CAM use if reporting one or more health symptoms compared to non-CAM users. The unadjusted odds ratio for hospitalizations in CAM users compared to non-CAM users was 1.29 (95% CI: 1.16-1.43). The mean number of days receiving outpatient care for CAM users was 7.0 days and 5.9 days for non-CAM users (<it>p </it>< 0.001).</p> <p>Conclusions</p> <p>Our study found those who report CAM use were requiring more physician-based medical services than users of conventional medicine. This appears to be primarily the result of an increase in the number of health conditions and symptoms reported by CAM users.</p

Effectiveness and cost-effectiveness of an exposure-based return-to-work programme for patients on sick leave due to common mental disorders: design of a cluster-randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>To reduce the duration of sick leave and loss of productivity due to common mental disorders (CMDs), we developed a return-to-work programme to be provided by occupational physicians (OPs) based on the principles of exposure in vivo (RTW-E programme). This study evaluates this programme's effectiveness and cost-effectiveness by comparing it with care as usual (CAU). The three research questions we have are: 1) Is an RTW-E programme more effective in reducing the sick leave of employees with common mental disorders, compared with care as usual? 2) Is an RTW-E programme more effective in reducing sick leave for employees with anxiety disorders compared with employees with other common mental disorders? 3) From a societal perspective, is an RTW-E programme cost-effective compared with care as usual?</p> <p>Methods/design</p> <p>This study was designed as a pragmatic cluster-randomized controlled trial with a one-year follow-up and randomization on the level of OPs. We aimed for 60 OPs in order to include 200 patients. Patients in the intervention group received the RTW-E programme. Patients in the control group received care as usual. Eligible patients had been on sick leave due to common mental disorders for at least two weeks and no longer than eight weeks. As primary outcome measures, we calculated the time until full return to work and the duration of sick leave. Secondary outcome measures were time until partial return to work, prevalence rate of sick leave at 3, 6, 9, and 12 months' follow-up, and scores of symptoms of distress, anxiety, depression, somatization, and fatigue; work capacity; perceived working conditions; self-efficacy for return to work; coping behaviour; avoidance behaviour; patient satisfaction; and work adaptations. As process measures, we used indices of compliance with the intervention in the intervention group and employee-supervisor communication in both groups. Economic costs were calculated from a societal perspective. The total costs consisted of the costs of consuming health care, costs of production loss due to sick leave and reduced productivity, and out-of-pocket costs of patients for travelling to their OP.</p> <p>Discussion</p> <p>The results will be published in 2009. The strengths and weaknesses of the study protocol are discussed.</p> <p>Trial registration</p> <p>ISRCTN72643128</p

Randomised controlled trial of a psychiatric consultation model for treatment of common mental disorder in the occupational health setting

BACKGROUND: Common mental disorders are the most prevalent of all mental disorders, with the highest burden in terms of work absenteeism and utilization of health care services. Evidence-based treatments are available, but recognition and treatment could be improved, especially in the occupational health setting. The situation in this setting has recently changed in the Netherlands because of new legislation, which has resulted in reduced sickness absence. Severe mental disorder has now become one of the main causes of work absenteeism. Occupational physicians (OPs) are expected to take an active role in diagnosis and treatment, and seem to be in need of support for a new approach to handle cases of more complex mental disorders. Psychiatric consultation can be a collaborative care model to achieve this. METHODS/DESIGN: This is a two-armed cluster-randomized clinical trial, with randomization among OPs. Forty OPs in two big companies providing medical care for multiple companies will be randomized to either the intervention group, i.e. psychiatric consultation embedded in a training programme, or the control group, i.e. only training aimed at recognition and providing Care As Usual. 60 patients will be included who have been absent from work for 6–52 weeks and who, after screening and a MINI interview, are diagnosed with depressive disorder, anxiety disorder or somatoform disorder based on DSM-IV criteria. Baseline measurements and follow up measurements (at 3 months and 6 months) will be assessed with questionnaires and an interview. The primary outcome measure is level of general functioning according to the SF-20. Secondary measures are severity of the mental disorder according to the PHQ and the SCL-90, quality of life (EQ-D5), measures of Return To Work and cost-effectiveness of the treatment assessed with the TiC-P. Process measures will be adherence to the treatment plan and assessment of the treatment provided by the Psychiatric Consultant (PC) in both groups. DISCUSSION: In the current study, a psychiatric consultation model that has already proved to be effective in the primary care setting, and aimed to enhance evidence-based care for patients with work absenteeism and common mental disorder will be evaluated for its efficacy and cost-effectiveness in the occupational health setting