Improving care for elderly patients living with polypharmacy: protocol for a pragmatic cluster randomized trial in community-based primary care practices in Canada.

BACKGROUND: Elders living with polypharmacy may be taking medications that do not benefit them. Polypharmacy can be associated with elevated risks of poor health, reduced quality of life, high care costs, and persistently complex care needs. While many medications could be problematic, this project targets medications that should be deprescribed for most elders and for which guidelines and evidence-based deprescribing tools are available. These are termed potentially inappropriate prescriptions (PIPs) and are as follows: proton pump inhibitors, benzodiazepines, antipsychotics, and sulfonylureas. Implementation strategies for deprescribing PIPs in complex older patient populations are needed. METHODS: This will be a pragmatic cluster randomized controlled trial in community-based primary care practices across Canada. Eligible practices provide comprehensive primary care and have at least one physician that consents to participate. Community-dwelling patients aged 65 years and older with ten or more unique medication prescriptions in the past year will be included. The objective is to assess whether the intervention reduces targeted PIPs for these patients compared with usual care. The intervention, Structured Process Informed by Data, Evidence and Research (SPIDER), is a collaboration between quality improvement (QI) and research programs. Primary care teams will form interprofessional Learning Collaboratives and work with QI coaches to review electronic medical record data provided by their regional Practice Based Research Networks (PBRNs), identify areas of improvement, and develop and implement changes. The study will be tested for feasibility in three PBRNs (Toronto, Montreal, and Edmonton) using prospective single-arm mixed methods. Findings will then guide a pragmatic cluster randomized controlled trial in five PBRNs (Calgary, Winnipeg, Ottawa, Montreal, and Halifax). Seven practices per PBRN will be recruited for each arm. The analysis will be by intention to treat. Ten percent of patients who have at least one PIP at baseline will be randomly selected to participate in the assessment of patient experience and self-reported outcomes. Qualitative methods will be used to explore patient and physician experience and evaluate SPIDER's processes. CONCLUSION: We are testing SPIDER in a primary care population with complex care needs. This could provide a widely applicable model for care improvement. TRIAL REGISTRATION: Clinicaltrials.gov NCT03689049 ; registered September 28, 2018.

Cistitis intersticial y enterocistoplastia de parche amplio, en Hospital Higueras de Talcahuano / Intersticial cystitis and large plaster enterocystoplsty in Hospital Higueras, Talcahuano

Se analizaron 15 casos de cistitis intersticial con múltiples tratamientos, entre abril de 1996 a marzo de 2004, del Hospital las Higueras de Talcahuano, incluyéndose a las pacientes que cumplían con criterios clínicos (NIDDK), hallazgos cistoscópicos, biopsia y registro seriado de cartilla miccional. Los tratamientos evaluados fueron la hidrodistensión, instilación de Dimetilsulfóxido (DMSO), instilación de heparina y cirugía de agrandamiento vesical con íleon con distal sin cistectomía supratrigonal. El promedio de evolución sintomática antes del diagnóstico fue de 6,7 años. Las pacientes presentaban 25 micciones promedio por día con volumen miccional promedio de 112 cc, y capacidad máxima bajo anestesia de 487 cc (rango de 120 a 900 cc). El 87 por ciento refería mejoría transitoria con la hidrodistensión, con la heparina el 75 por ciento y el 44 por ciento de mejoría transitoria con DMSO. Las cuatro pacientes que requirieron de agrandamiento vesical se encuentran sin dolor, tienen adecuado vaciamiento y han retornado a sus actividades habituales. La mayor parte de nuestras pacientes han podido ser tratadas adecuadamente con medidas simples como la distensión vesical periódica a demanda y/o la instilación de sustancias. Fue adecuado reservar la ampliación vesical para casos extremos, obteniendo óptimos resultados con la técnica elegida.

Pharmacokinetic MRI for assessment of malignant glioma response to stereotactic radiotherapy: initial results.

The purpose of this study was to assess the value of dynamic, contrast-enhanced MRI in patients with malignant glioma (a) to predict before stereotactic radiotherapy local tumor control, (b) to investigate temporal changes in tumor microcirculation after stereotactic radiotherapy, and (c) to analyze whether malignant glioma response may be predicted earlier by alterations in the tissue pharmacokinetics rather than in terms of tumor volume. Ninety MRI studies were performed of 18 patients with malignant glioma before and 6, 18, 26, 52, and 72 weeks after the end of stereotactic radiotherapy. The signal time courses of the contrast-enhanced tumors were analyzed using a pharmacokinetic two-compartment model that calculates for the parameter A, reflecting the degree of MRI signal enhancement [no units] and the exchange rate constant k21 [min(-1)]. Before radiotherapy, the amplitude A was significantly (P < .05) lower in patients with subsequent local tumor control (n = 8; mean A = .34 +/- .15) compared to patients without subsequent local tumor control (n = 10; mean A = .94 +/- .71). In the local tumor control group, early after stereotactic radiotherapy (at 6-18 weeks), there was a significant (P < .05) time-dependent decrease in the parameter k21, whereas there was still no alteration in the tumor volume. A low amplitude A before radiotherapy, combined with an early drop of k21 after stereotactic radiotherapy, reliably characterized the group of patients with subsequent tumor volume decrease. Our preliminary results suggest that two contrast-enhanced dynamic MR studies, one before and one early after stereotactic radiotherapy, offer important information on local tumor control within the first 6 to 18 weeks after stereotactic radiotherapy. Moreover, this response may be evidenced before tumor volume changes and provides a therapeutic window to broaden treatment options and to improve treatment outcome.

[Morphologic MR imaging with T1-weighted sequences for radiotherapy goal volume definition of intracranial tumors. Comparison with FLASH-Turbo-FLASH and SE sequences]. / Morphologische MR-Bildgebung mit T1-gewichteten Sequenzen zur radiotherapeutischen Zielvolumendefinition von intrakraniellen Tumoren. Vergleich von FLASH- Turbo-FLASH- und SE-Sequenzen.

INTRODUCTION: The goal of this study was to compare contrast-enhanced T1-weighted Flash and Turbo-Flash sequences with conventional spin-echo sequences as a basis for planning high-precision radiotherapy. METHODS: A total of 25 consecutive patients with different intracranial tumors and a disrupted blood-brain barrier were studied. T1-weighted Flash, Turbo-Flash and conventional spin-echo images were evaluated after controlled 30-s infusion of 0.1 mmol/kg body weight of Gd-DTPA. The evaluation of the three sequences included the measurement of the spinal- and contrast-to-noise ratios, the visual inspection of the tumors and artifacts, and the measurement of tumor size. RESULTS: The signal- and contrast-to-noise ratios were significantly (P < 0.05-0.01) lower for Flash and Turbo-Flash than for conventional spin-echo sequences. However, visual inspection of the contrast-enhancing tumors revealed in 23 and 24 of 25 lesions on Flash and Turbo-Flash images, respectively, good or very good tumor visibility when compared with conventional spin-echo images with a reduction of imaging time by a factor of 7-8. Flash and Turbo-Flash sequences were more prone to susceptibility artifacts, conventional spin-echo sequences more to pulsation artifacts in the posterior fossa. Tumor sizes were comparable in all three techniques. CONCLUSION: At present, conventional spin-echo images are superior to fast Flash and ultrafast Turbo-Flash sequences as a basis for accurate target volume definition in high-precision radiotherapy. However, fast Flash and Turbo-Flash images may be a practicable alternative to conventional spin-echo images for tumors in the posterior fossa or in patients unable to tolerate a stereotactic fixation device. Despite some limitations, Turbo-Flash sequences enable fast dynamic MR imaging combined with an acceptable morphology, which may be sufficient to target volume planning in high-precision radiotherapy.

Intracranial meningeomas: time- and dose-dependent effects of irradiation on tumor microcirculation monitored by dynamic MR imaging.

The purpose of this study was the characterization of the time- and dose-dependent effects of irradiation on tumor microcirculation by means of dynamic MR imaging and correlation of the estimated data with tumor response in patients with meningeomas. Dynamic MR imaging studies were performed in 20 patients with intracranial meningeomas prior to (n = 20) and at 6 (n = 17), 18 (n = 17), and 50 wk (n = 14) after the end of radiotherapy. In seven of these patients, dynamic measurements were also performed during fractionated radiotherapy after approximate 20 Gy and 54 Gy. During and after short-time infusion of gadopentetate dimeglumine, the kinetics of lesion response was resolved using a strongly T1-weighted saturation recovery TurboFLASH (SRTF) sequence. The signal-time courses of the suspected lesions were analyzed using a pharmacokinetic two-compartment model. The calculated parameters amplitude A (reflecting gadopentetate dimeglumine accumulation in the extracellular space) and exchange rate constant k21 (depending on vascular permeability and blood flow) were displayed as color-coded images and analyzed as a function of time of therapy and radiation dose. All meningeomas showed a high exchange rate constant k21 (median, 5.7 min-1; range, 1.9-23.0 min-1) and a high amplitude A (median, 1.5 arbitrary units; range, 1.1-2.7) prior to X-ray treatment. During radiotherapy we found a dose related significant (p < .01) increase of k21 accompanied by an increase of the amplitude A as compared to the pretreatment values. Analysis of tumor volume 6, 18, and 50 wk after X-ray treatment revealed two different groups. In the responder group (n = 13) the median of the tumor volume decreased from 10.0 to 7.5 cm3. For this group, we found a significant drop (p < .01) of the median of the amplitude A and a decrease of the exchange rate constant k21. In the nonresponder group (n = 4) the median of the tumor volume increased after radiation from 3.5 to 4.5 cm3. The pharmacokinetic analysis revealed a decrease of the amplitude A-and an increase of the exchange rate constant k21. The response of meningeomas to radiotherapy is influenced by the effect of X-rays on tumor microcirculation. This effect on tumor microcirculation can be derived by analysis of pharmacokinetic maps obtained from dynamic MR images. Furthermore, these pharmacokinetic maps can possibly be used to differentiate groups of patients who respond or do not respond to radiotherapy and, thus, could benefit from another treatment modality.