A Phase II Study of a Paclitaxel-Based Chemoradiation Regimen With Selective Surgical Salvage for Resectable Locoregionally Advanced Esophageal Cancer: Initial Reporting of RTOG 0246

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swisher, Stephen G., E-mail: sswisher@mdanderson.org; Winter, Kathryn A.; Komaki, Ritsuko U.

2012-04-01

Purpose: The strategy of definitive chemoradiation with selective surgical salvage in locoregionally advanced esophageal cancer was evaluated in a Phase II trial in Radiation Therapy Oncology Group (RTOG)-affiliated sites. Methods and Materials: The study was designed to detect an improvement in 1-year survival from 60% to 77.5% ({alpha} = 0.05; power = 80%). Definitive chemoradiation involved induction chemotherapy with 5-fluorouracil (5-FU) (650 mg/mg{sup 2}/day), cisplatin (15 mg/mg{sup 2}/day), and paclitaxel (200 mg/mg{sup 2}/day) for two cycles, followed by concurrent chemoradiation with 50.4 Gy (1.8 Gy/fraction) and daily 5-FU (300 mg/mg{sup 2}/day) with cisplatin (15 mg/mg{sup 2}/day) over the first 5more » days. Salvage surgical resection was considered for patients with residual or recurrent esophageal cancer who did not have systemic disease. Results: Forty-three patients with nonmetastatic resectable esophageal cancer were entered from Sept 2003 to March 2006. Forty-one patients were eligible for analysis. Clinical stage was {>=}T3 in 31 patients (76%) and N1 in 29 patients (71%), with adenocarcinoma histology in 30 patients (73%). Thirty-seven patients (90%) completed induction chemotherapy followed by concurrent chemoradiation. Twenty-eight patients (68%) experienced Grade 3+ nonhematologic toxicity. Four treatment-related deaths were noted. Twenty-one patients underwent surgery following definitive chemoradiation because of residual (17 patients) or recurrent (3 patients) esophageal cancer,and 1 patient because of choice. Median follow-up of live patients was 22 months, with an estimated 1-year survival of 71%. Conclusions: In this Phase II trial (RTOG 0246) evaluating selective surgical salvage after definitive chemoradiation in locoregionally advanced esophageal cancer, the hypothesized 1-year RTOG survival rate (77.5%) was not achieved (1 year, 71%; 95% confidence interval< 54%-82%).« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guida, K; Qamar, K; Thompson, M

Purpose: The RTOG 1005 trial offered a hypofractionated arm in delivering WBRT+SIB. Traditionally, treatments were planned at our institution using field-in-field (FiF) tangents with a concurrent 3D conformal boost. With the availability of VMAT, it is possible that a hybrid VMAT-3D planning technique could provide another avenue in treating WBRT+SIB. Methods: A retrospective study of nine patients previously treated using RTOG 1005 guidelines was performed to compare FiF+3D plans with the hybrid technique. A combination of static tangents and partial VMAT arcs were used in base-dose optimization. The hybrid plans were optimized to deliver 4005cGy to the breast PTVeval andmore » 4800cGy to the lumpectomy PTVeval over 15 fractions. Plans were optimized to meet the planning goals dictated by RTOG 1005. Results: Hybrid plans yielded similar coverage of breast and lumpectomy PTVs (average D95 of 4013cGy compared to 3990cGy for conventional), while reducing the volume of high dose within the breast; the average D30 and D50 for the hybrid technique were 4517cGy and 4288cGy, compared to 4704cGy and 4377cGy for conventional planning. Hybrid plans increased conformity as well, yielding CI95% values of 1.22 and 1.54 for breast and lumpectomy PTVeval volumes; in contrast, conventional plans averaged 1.49 and 2.27, respectively. The nearby organs at risk (OARs) received more low dose with the hybrid plans due to low dose spray from the partial arcs, but all hybrid plans did meet the acceptable constraints, at a minimum, from the protocol. Treatment planning time was also reduced, as plans were inversely optimized (VMAT) rather than forward optimized. Conclusion: Hybrid-VMAT could be a solution in delivering WB+SIB, as plans yield very conformal treatment plans and maintain clinical standards in OAR sparing. For treating breast cancer patients with a simultaneously-integrated boost, Hybrid-VMAT offers superiority in dosimetric conformity and planning time as compared to FIF techniques.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, X; Penagaricano, J; Narayanasamy, G

Purpose: Hippocampus avoidance whole brain radiotherapy (HA-WBRT) has been shown to reduce the risk of neurocognitive dysfunction. This type of treatment has the potential of insurance company payment denial due to increased cost of intensity modulated radiotherapy (IMRT), while the accepted modality for WBRT is three-dimensional conformal radiotherapy (3DCRT). The purpose of this study is to assess HA-WBRT treatment plans using 3DCRT and multi-criteria optimization (MCO) that meets the RTOG 0933 criteria. Methods: Ten patients with brain metastases at least 0.5cm away from the hippocampal avoidance region as defined in RTOG 0933 were selected in this study. HA-WBRT treatment plansmore » with MCO 3DCRT technique (MCO-3D) was generated with beam arrangements and dose constraints following the RTOG 0933 guidelines. MCO-3D plans were compared with plans using MCO IMRT techniques (MCO-IMRT) with same beam arrangements and dose constraints. Evaluation parameters included D98% D2% and dose homogeneity index of PTV, and Dmax and D100% of the hippocampi. The OAR doses were also evaluated. Results: For MCO-IMRT plans, PTV D2% and hippocampi Dmax and D100% met RTOG 0933 objectives in all ten patients (PTV D2%<37.5Gy; Hippocampi Dmax<16Gy and D100%<9Gy). One patient met the RTOG 0933 PTV D98% objective (PTV D98%>25Gy) and 9/10 patients met acceptable variation (PTV D98%<25Gy). For MCO-3D plans, PTV D2% met RTOG 0933 objective for all patients; 1/10 patient for PTV D98% and 6/10 patients for Hippocampi Dmax and 7/10 patients for hippocampi D100% met RTOG 0933 objective. All the other patients met the RTOG 0933 acceptable variation requirement. (PTV D98%<25Gy; Hippocampi Dmax<17Gy and D100%<10Gy). Conclusion: All dosimetric parameters of MCO-3D plans met the criteria of at least acceptable variation per RTOG 0933. This may be helpful in cases where there is denial of patient’s medical insurance coverage due to the use of IMRT for HA-WBRT.« less

Late Urinary Side Effects 10 Years After Low-Dose-Rate Prostate Brachytherapy: Population-Based Results From a Multiphysician Practice Treating With a Standardized Protocol and Uniform Dosimetric Goals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keyes, Mira, E-mail: mkeyes@bccancer.bc.ca; Miller, Stacy; Pickles, Tom

2014-11-01

Purpose: To determine late urinary toxicity (>12 months) in a large cohort of uniformly treated low-dose-rate prostate brachytherapy patients. Methods and Materials: From 1998 to 2009, 2709 patients with National Comprehensive Cancer Network–defined low-risk and low-tier intermediate-risk prostate cancer were treated with Iodine 125 ({sup 125}I) low-dose-rate prostate brachytherapy; 2011 patients with a minimum of 25 months of follow-up were included in the study. Baseline patients, treatment, implant factors, and late urinary toxicity (Radiation Therapy Oncology Group [RTOG] grading system and International Prostate Symptom Score [IPSS]) were recorded prospectively. Time to IPSS resolution, late RTOG genitourinary toxicity was examined with Kaplan-Meier andmore » log-rank tests. Cox proportional hazards regression was done for individual covariates and multivariable models. Results: Median follow-up was 54.5 months (range, 2-13 years). Actuarial toxicity rates reached 27% and 10% (RTOG ≥2 and ≥3, respectively) at 9-13 years. Symptoms resolved quickly in the majority of patients (88% in 6-12 months). The prevalence of RTOG 0, 1, 2, 3, and 4 toxicity with a minimum of 7 years' follow-up was 70%, 21%, 6.4%, 2.3%, and 0.08%, respectively. Patients with a larger prostate volume, higher baseline IPSS, higher D90, acute toxicity, and age >70 years had more late RTOG ≥2 toxicity (all P≤.02). The IPSS resolved slower in patients with lower baseline IPSS and larger ultrasound prostate volume, those not receiving androgen deprivation therapy, and those with higher D90. The crude rate of RTOG 3 toxicity was 6%. Overall the rate of transurethral resection of the prostate was 1.9%; strictures, 2%; incontinence, 1.3%; severe symptoms, 1.8%; late catheterization, 1.3%; and hematuria, 0.8%. The majority (80%) resolved their symptoms in 6-12 months. Conclusion: Long-term urinary toxicity after brachytherapy is low. Although actuarial rates increase with longer follow-up (27% RTOG 2 and 10% RTOG 3 at 13 years), symptoms resolve relatively quickly; between 5 and 13 years' follow-up, >90% of patients have minimal urinary toxicity. Refining patient selection criteria, planning, and treatment delivery may further reduce toxicity.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herrington, J; Price, M; Brindle, J

Purpose: To evaluate the equivalence of spine SBRT treatment plans created in Eclipse for the TrueBeam STx (Varian Medical System, Palo Alto, CA) compared to plans using CyberKnife and MultiPlan (Accuray, Sunnyvale, CA). Methods: CT data and contours for 23 spine SBRT patients previously treated using CyberKnife (CK) were exported from MultiPlan treatment planning system into Eclipse where they were planned using static IMRT 6MV coplanar beams. Plans were created according to the original prescription dose and fractionation schedule while limiting spinal dose according to the RTOG 0631 protocol and maintaining target coverage comparable to the original CK plans. Plansmore » were evaluated using new conformity index (nCI), homogeneity index (HI), dose-volume histogram data, number of MU, and estimated treatment time. To ensure all Eclipse plans were deliverable, standard clinical IMRT QA was performed. The plan results were matched with their complimentary CK plans for paired statistical analysis. Results: Plans generated in Eclipse demonstrated statistically significant (p<0.01) improvements compared to complimentary CK plans in median values of maximum spinal cord dose (17.39 vs. 18.12 Gy), RTOG spinal cord constraint dose (14.50 vs. 16.93 Gy), nCI (1.28 vs. 1.54), HI (1.13 vs. 1.27), MU (3918 vs. 36416), and estimated treatment time (8 vs. 48 min). All Eclipse generated plans passed our clinically used protocols for IMRT QA. Conclusion: CK spine SBRT replanned utilizing Eclipse for LINAC delivery demonstrated dosimetric advantages. We propose improvements in plan quality metrics reviewed in this study may be attributed to dynamic MLCs that facilitate treatment of complicated geometries as well as posterior beams ideal for centrally located and/or posterior targets afforded by gantry-based RT delivery.« less

Late Gastrointestinal Toxicity After Dose-Escalated Conformal Radiotherapy for Early Prostate Cancer: Results From the UK Medical Research Council RT01 Trial (ISRCTN47772397)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Syndikus, Isabel; Morgan, Rachel C.; Sydes, Matthew R., E-mail: ms@ctu.mrc.ac.u

2010-07-01

Purpose: In men with localized prostate cancer, dose-escalated conformal radiotherapy (CFRT) improves efficacy outcomes at the cost of increased toxicity. We present a detailed analysis to provide further information about the incidence and prevalence of late gastrointestinal side effects. Methods and Materials: The UK Medical Research Council RT01 trial included 843 men with localized prostate cancer, who were treated for 6 months with neoadjuvant radiotherapy and were randomly assigned to either 64-Gy or 74-Gy CFRT. Toxicity was evaluated before CFRT and during long-term follow-up using Radiation Therapy Oncology Group (RTOG) grading, the Late Effects on Normal Tissue: Subjective, Objective, Managementmore » (LENT/SOM) scale, and Royal Marsden Hospital assessment scores. Patients regularly completed Functional Assessment of Cancer Therapy--Prostate (FACT-P) and University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI) questionnaires. Results: In the dose-escalated group, the hazard ratio (HR) for rectal bleeding (LENT/SOM grade {>=}2) was 1.55 (95% CI, 1.17-2.04); for diarrhea (LENT/SOM grade {>=}2), the HR was 1.79 (95% CI, 1.10-2.94); and for proctitis (RTOG grade {>=}2), the HR was 1.64 (95% CI, 1.20-2.25). Compared to baseline scores, the prevalence of moderate and severe toxicities generally increased up to 3 years and than lessened. At 5 years, the cumulative incidence of patient-reported severe bowel problems was 6% vs. 8% (standard vs. escalated, respectively) and severe distress was 4% vs. 5%, respectively. Conclusions: There is a statistically significant increased risk of various adverse gastrointestinal events with dose-escalated CFRT. This remains at clinically acceptable levels, and overall prevalence ultimately decreases with duration of follow-up.« less

Delineation of Supraclavicular Target Volumes in Breast Cancer Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, Lindsay C.; Diehn, Felix E.; Boughey, Judy C.

Purpose: To map the location of gross supraclavicular metastases in patients with breast cancer, in order to determine areas at highest risk of harboring subclinical disease. Methods and Materials: Patients with axial imaging of gross supraclavicular disease were identified from an institutional breast cancer registry. Locations of the metastatic lymph nodes were transferred onto representative axial computed tomography images of the supraclavicular region and compared with the Radiation Therapy Oncology Group (RTOG) breast cancer atlas for radiation therapy planning. Results: Sixty-two patients with 161 supraclavicular nodal metastases were eligible for study inclusion. At the time of diagnosis, 117 nodal metastasesmore » were present in 44 patients. Forty-four nodal metastases in 18 patients were detected at disease recurrence, 4 of whom had received prior radiation to the supraclavicular fossa. Of the 161 nodal metastases, 95 (59%) were within the RTOG consensus volume, 4 nodal metastases (2%) in 3 patients were marginally within the volume, and 62 nodal metastases (39%) in 30 patients were outside the volume. Supraclavicular disease outside the RTOG consensus volume was located in 3 regions: at the level of the cricoid and thyroid cartilage (superior to the RTOG volume), in the posterolateral supraclavicular fossa (posterolateral to the RTOG volume), and in the lateral low supraclavicular fossa (lateral to the RTOG volume). Only women with multiple supraclavicular metastases had nodal disease that extended superiorly to the level of the thyroid cartilage. Conclusions: For women with risk of harboring subclinical supraclavicular disease warranting the addition of supraclavicular radiation, coverage of the posterior triangle and the lateral low supraclavicular region should be considered. For women with known supraclavicular disease, extension of neck coverage superior to the cricoid cartilage may be warranted.« less

SU-F-BRD-05: Dosimetric Comparison of Protocol-Based SBRT Lung Treatment Modalities: Statistically Significant VMAT Advantages Over Fixed- Beam IMRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Best, R; Harrell, A; Geesey, C

2014-06-15

Purpose: The purpose of this study is to inter-compare and find statistically significant differences between flattened field fixed-beam (FB) IMRT with flattening-filter free (FFF) volumetric modulated arc therapy (VMAT) for stereotactic body radiation therapy SBRT. Methods: SBRT plans using FB IMRT and FFF VMAT were generated for fifteen SBRT lung patients using 6 MV beams. For each patient, both IMRT and VMAT plans were created for comparison. Plans were generated utilizing RTOG 0915 (peripheral, 10 patients) and RTOG 0813 (medial, 5 patients) lung protocols. Target dose, critical structure dose, and treatment time were compared and tested for statistical significance. Parametersmore » of interest included prescription isodose surface coverage, target dose heterogeneity, high dose spillage (location and volume), low dose spillage (location and volume), lung dose spillage, and critical structure maximum- and volumetric-dose limits. Results: For all criteria, we found equivalent or higher conformality with VMAT plans as well as reduced critical structure doses. Several differences passed a Student's t-test of significance: VMAT reduced the high dose spillage, evaluated with conformality index (CI), by an average of 9.4%±15.1% (p=0.030) compared to IMRT. VMAT plans reduced the lung volume receiving 20 Gy by 16.2%±15.0% (p=0.016) compared with IMRT. For the RTOG 0915 peripheral lesions, the volumes of lung receiving 12.4 Gy and 11.6 Gy were reduced by 27.0%±13.8% and 27.5%±12.6% (for both, p<0.001) in VMAT plans. Of the 26 protocol pass/fail criteria, VMAT plans were able to achieve an average of 0.2±0.7 (p=0.026) more constraints than the IMRT plans. Conclusions: FFF VMAT has dosimetric advantages over fixed beam IMRT for lung SBRT. Significant advantages included increased dose conformity, and reduced organs-at-risk doses. The overall improvements in terms of protocol pass/fail criteria were more modest and will require more patient data to establish difference trends of more statistical significance.« less

A class solution for volumetric-modulated arc therapy planning in postprostatectomy radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Forde, Elizabeth, E-mail: eforde@tcd.ie; Bromley, Regina; Institute of Medical Physics, School of Physics, University of Sydney, New South Wales

This study is aimed to test a postprostatectomy volumetric-modulated arc therapy (VMAT) planning class solution. The solution applies to both the progressive resolution optimizer algorithm version 2 (PRO 2) and the algorithm version 3 (PRO 3), addressing the effect of an upgraded algorithm. A total of 10 radical postprostatectomy patients received 68 Gy to 95% of the planning target volume (PTV), which was planned using VMAT. Each case followed a set of planning instructions; including contouring, field setup, and predetermined optimization parameters. Each case was run through both algorithms only once, with no user interaction. Results were averaged and comparedmore » against Radiation Therapy Oncology Group (RTOG) 0534 end points. In addition, the clinical target volume (CTV) D{sub 100}, PTV D{sub 99}, and PTV mean doses were recorded, along with conformity indices (CIs) (95% and 98%) and the homogeneity index. All cases satisfied PTV D{sub 95} of 68 Gy and a maximum dose < 74.8 Gy. The average result for the PTV D{sub 99} was 64.1 Gy for PRO 2 and 62.1 Gy for PRO 3. The average PTV mean dose for PRO 2 was 71.4 Gy and 71.5 Gy for PRO 3. The CTV D{sub 100} average dose was 67.7 and 68.0 Gy for PRO 2 and PRO 3, respectively. The mean homogeneity index for both algorithms was 0.08. The average 95% CI was 1.17 for PRO 2 and 1.19 for PRO 3. For 98%, the average results were 1.08 and 1.12 for PRO 2 and PRO 3, respectively. All cases for each algorithm met the RTOG organs at risk dose constraints. A successful class solution has been established for prostate bed VMAT radiotherapy regardless of the algorithm used.« less

SU-E-T-321: Dosimetric Evaluation of Non-Coplanar Arcs in VMAT Planning for SBRT Lung Cases: A Planning Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, S; Gardner, S; Doemer, A

Purpose: Investigate use of standardized non-coplanar arcs to improve plan quality in lung Stereotactic Body Radiation Therapy(SBRT) VMAT planning. Methods: VMAT planning was performed for 9 patients previously treated with SBRT for peripheral lung tumors (tumor size:12.7cc to 32.5cc). For each patient, 7 VMAT plans (couch rotation values:0,5,10,15,20,25,and 30 deg) were generated; the coplanar plans were pushed to meet the RTOG0915 constraints and each non-coplanar plans utilized the same optimization constraints. The following plan dose metrics were used (taken from RTOG 0915): D-2cm: the maximum dose at 2 cm from the PTV, conformality index (CI), gradient index (GI), lung volumemore » receiving 5 Gy (V5) and lung volume receiving 20 Gy (V20). The couch collision clearance was checked for each plan through a dry run using the couch position from the patient’s treatment. Results: Of the 9 cases, one coplanar plan failed to meet two protocol guidelines (both gradient index and D-2cm parameter), and an additional plan failed the D-2cm parameter. When introducing at least 5 degree couch rotation, all plans met the protocol guidelines. The largest feasible couch angle available was 15 to 20 degrees due to gantry collision issues. Non-coplanar plans resulted in the average (standard deviation) reduction of the following metrics: GI by 7.3% (3.7%); lung V20 by 11.1% (3.2%); D-2cm by 12.7% (3.9%). The CI was unchanged (−0.3%±0.6%), and lung V5 increased (3.8%±8.2%). Conclusion: The use of couch rotations as little as 5 degrees allows for plan quality that will meet RTOG0915 constraints while reducing D-2cm, GI, and lung V20. Using default couch rotations while planning SBRT cases will allow for more efficient planning with the stated goal of meeting RTOG0915 criteria for all clinical cases. Gantry clearance checks in the treatment room may be necessary to ensure safe treatments for larger couch rotation values.« less

On the use of volumetric-modulated arc therapy for single-fraction thoracic vertebral metastases stereotactic body radiosurgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pokhrel, Damodar, E-mail: damodar.pokhrel@uky.edu; Sood, Sumit; McClinton, Christopher

To retrospectively evaluate quality, efficiency, and delivery accuracy of volumetric-modulated arc therapy (VMAT) plans for single-fraction treatment of thoracic vertebral metastases using image-guided stereotactic body radiosurgery (SBRS) after RTOG 0631 dosimetric compliance criteria. After obtaining credentialing for MD Anderson spine phantom irradiation validation, 10 previously treated patients with thoracic vertebral metastases with noncoplanar hybrid arcs using 1 to 2 3D-conformal partial arcs plus 7 to 9 intensity-modulated radiation therapy beams were retrospectively re-optimized with VMAT using 3 full coplanar arcs. Tumors were located between T2 and T12. Contrast-enhanced T1/T2-weighted magnetic resonance images were coregistered with planning computed tomography and planningmore » target volumes (PTV) were between 14.4 and 230.1 cc (median = 38.0 cc). Prescription dose was 16 Gy in 1 fraction with 6 MV beams at Novalis-TX linear accelerator consisting of micro multileaf collimators. Each plan was assessed for target coverage using conformality index, the conformation number, the ratio of the volume receiving 50% of the prescription dose over PTV, R50%, homogeneity index (HI), and PTV-1600 coverage per RTOG 0631 requirements. Organs-at-risk doses were evaluated for maximum doses to spinal cord (D{sub 0.03} {sub cc}, D{sub 0.35} {sub cc}), partial spinal cord (D{sub 10%}), esophagus (D{sub 0.03} {sub cc} and D{sub 5} {sub cc}), heart (D{sub 0.03} {sub cc} and D{sub 15} {sub cc}), and lung (V{sub 5}, V{sub 10}, and maximum dose to 1000 cc of lung). Dose delivery efficiency and accuracy of each VMAT-SBRS plan were assessed using quality assurance (QA) plan on MapCHECK device. Total beam-on time was recorded during QA procedure, and a clinical gamma index (2%/2 mm and 3%/3 mm) was used to compare agreement between planned and measured doses. All 10 VMAT-SBRS plans met RTOG 0631 dosimetric requirements for PTV coverage. The plans demonstrated highly conformal and homogenous coverage of the vertebral PTV with mean HI, conformality index, conformation number, and R{sub 50%} values of 0.13 ± 0.03 (range: 0.09 to 0.18), 1.03 ± 0.04 (range: 0.98 to 1.09), 0.81 ± 0.06 (range: 0.72 to 0.89), and 4.2 ± 0.94 (range: 2.7 to 5.4), respectively. All 10 patients met protocol guidelines with maximum dose to spinal cord (average: 8.83 ± 1.9 Gy, range: 5.9 to 10.9 Gy); dose to 0.35 cc of spinal cord (average: 7.62 ± 1.7 Gy, range: 5.4 to 9.6 Gy); and dose to 10% of partial spinal cord (average 6.31 ± 1.5 Gy, range: 3.5 to 8.5 Gy) less than 14, 10, and 10 Gy, respectively. For all 10 patients, the maximum dose to esophagus (average: 9.41 ± 4.3 Gy, range: 1.5 to 14.9 Gy) and dose to 5 cc of esophagus (average: 7.43 ± 3.8 Gy, range: 1.1 to 11.8 Gy) were kept less than protocol requirements 16 Gy and 11.9 Gy, respectively. In a similar manner, all 10 patients met protocol compliance criteria with maximum dose to heart (average: 4.62 ± 3.5 Gy, range: 1.3 to 10.2 Gy) and dose to 15 cc of heart (average: 2.23 ± 1.8 Gy, range: 0.3 to 5.6 Gy) less than 22 and 16 Gy, respectively. The dose to the lung was retained much lower than protocol guidelines for all 10 patients. The total number of monitor units was, on average, 6919 ± 1187. The average beam-on time was 11.5 ± 2.0 minutes. The VMAT plans demonstrated dose delivery accuracy of 95.8 ± 0.7%, on average, for clinical gamma passing rate with 2%/2 mm criteria and 98.3 ± 0.8%, on average, with 3%/3 mm criteria. All VMAT-SBRS plans were considered clinically acceptable per RTOG 0631 dosimetric compliance criteria. VMAT planning provided highly conformal and homogenous dose distributions for the lower-dose vertebral PTV and the spinal cord as well as organs-at-risk such as esophagus, heart, and lung. Higher QA pass rates and shorter beam-on time suggest that VMAT-SBRS is a clinically feasible, fast, and effective treatment option for patients with thoracic vertebral metastases.« less

SU-F-T-537: Prone Breast Accelerated Partial Breast Irradiation Using Non-Coplanar Volumetric Arc Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beninati, G; Barbiere, J; Godfrey, L

2016-06-15

Purpose: To demonstrate that Volumetric Modulated Arc Therapy (VMAT) can be an alternative technique to Brachytherapy Accelerated Partial Breast Irradiation (APBI) for treating large breasted women. The non-coplanar VMAT technique uses a commercially available couch and a small number of angles. This technique with the patient in the prone position can reduce high skin and critical structure doses in large breasted women, which are usually associated with Brachytherapy APBI. Methods: Philips Pinnacle treatment planning system with Smart Arc was used to plan a left sided laterally located excision cavity on a standard prone breast patient setup. Three thirty-degree arcs enteredmore » from the lateral side at respective couch angles of 345, 0, and 15 degrees. A fourth thirty degree arc beam entered from the medial side at a couch angle of 0 degrees. The arcs were selected to avoid critical structures as much as possible. A test run was then performed to verify that the beams did not collide with the patient nor support structures. NSABP B-39/RTOG 0413 protocol guidelines were used for dose prescription, normal tissue, and target definition. Results: Dose Volume Histogram analysis indicated that all parameters were equal or better than RTOG recommendations. Of particular note regarding the plan quality:1.(a) For a prescribed dose of 3850cGy the PTV-EVAL target volume receiving 100 percent of the dose(V100) was 93; protocol recommendation is V90 > 90 percent. (b) Maximum dose was 110 percent versus the allowed 120 percent .2. Uninvolved percentage of normal breast V100 and V50 were 17 and 47 versus allowed 35 and 60 percent respectively.3. For the skin, V100 was 5.7cc and the max dose to 0.1 cc was 4190cGy. Conclusion: Prone Breast non-coplanar VMAT APBI can achieve better skin cosmesis and lower critical structure doses than Brachytherapy APBI.« less

SU-E-T-486: Effect of the Normalized Prescription Isodose Line On Target Dose Deficiency in Lung SBRT Based On Monte Carlo Calculation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, D; Zhang, Q; Zhou, S

Purpose: To investigate the impact of normalized prescription isodose line on target dose deficiency calculated with Monte Carlo (MC) vs. pencil Beam (PB) in lung SBRT. RTOG guidelines recommend prescription lines between 60% and 90% for lung SBRT. How this affects the magnitude of MC-calculated target dose deficiency has never been studied. Methods: Under an IRB-approved protocol, four lung SBRT patients were replanned following RTOG0813 by a single physicist. For each patient, four alternative plans were generated based on PB calculation prescribing to 60–90% isodose lines, respectively. Each plan consisted of 360o coplanar dynamic conformal arcs with beam apertures manuallymore » optimized to achieve similar dose coverage and conformity for all plans of the same patient. Dose distribution was calculated with MC and compared to that with PB. PTV dose-volume endpoints were compared, including Dmin, D5, Dmean, D95, and Dmax. PTV V100 coverage, conformity index (CI), and heterogeneity index (HI) were also evaluated. Results: For all 16 plans, median (range) PTV V100 and CI were 99.7% (97.5–100%) and 1.27 (1.20–1.41), respectively. As expected, lower prescription line resulted in higher target dose heterogeneity, yielding median (range) HI of 1.26 (1.05–1.51) for all plans. Comparing MC to PB, median (range) D95, Dmean, D5 PTV dose deficiency were 18.9% (11.2–23.2%), 15.6% (10.0–22.7%), and 9.4%(5.5–13.6%) of the prescription dose, respectively. The Dmean, D5, and Dmax deficiency was found to monotonically increase with decreasing prescription line from 90% to 60%, while the Dmin deficiency monotonically decreased. D95 deficiency exhibited more complex trend, reaching the largest deficiency at 80% for all patients. Conclusion: Dependence on prescription isodose line was found for MC-calculated PTV dose deficiency of lung SBRT. When comparing reported MC dose deficiency values from different institutions, their individual selections of prescription line should be considered in addition to other factors affecting the deficiency magnitude.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harris, Victoria A.; Staffurth, John; Naismith, Olivia

Purpose: The purpose of this study was to establish reproducible guidelines for delineating the clinical target volume (CTV) of the pelvic lymph nodes (LN) by combining the freehand Royal Marsden Hospital (RMH) and Radiation Therapy Oncology Group (RTOG) vascular expansion techniques. Methods and Materials: Seven patients with prostate cancer underwent standard planning computed tomography scanning. Four different CTVs (RMH, RTOG, modified RTOG, and Prostate and pelvIs Versus prOsTate Alone treatment for Locally advanced prostate cancer [PIVOTAL] trial) were created for each patient, and 6 different bowel expansion margins (BEM) were created to assess bowel avoidance by the CTV. The resulting CTVsmore » were compared visually and by using Jaccard conformity indices. The volume of overlap between bowel and planning target volume (PTV) was measured to aid selection of an appropriate BEM to enable maximal LN yet minimal normal tissue coverage. Results: In total, 84 nodal contours were evaluated. LN coverage was similar in all groups, with all of the vascular-expansion techniques (RTOG, modified RTOG, and PIVOTAL), resulting in larger CTVs than that of the RMH technique (mean volumes: 287.3 cm{sup 3}, 326.7 cm{sup 3}, 310.3 cm{sup 3}, and 256.7 cm{sup 3}, respectively). Mean volumes of bowel within the modified RTOG PTV were 19.5 cm{sup 3} (with 0 mm BEM), 17.4 cm{sup 3} (1-mm BEM), 10.8 cm{sup 3} (2-mm BEM), 6.9 cm{sup 3} (3-mm BEM), 5.0 cm{sup 3} (4-mm BEM), and 1.4 cm{sup 3} (5-mm BEM) in comparison with an overlap of 9.2 cm{sup 3} seen using the RMH technique. Evaluation of conformity between LN-CTVs from each technique revealed similar volumes and coverage. Conclusions: Vascular expansion techniques result in larger LN-CTVs than the freehand RMH technique. Because the RMH technique is supported by phase 1 and 2 trial safety data, we proposed modifications to the RTOG technique, including the addition of a 3-mm BEM, which resulted in LN-CTV coverage similar to that of the RMH technique, with reduction in bowel and planning target volume overlap. On the basis of these findings, recommended guidelines including a detailed pelvic LN contouring atlas have been produced and implemented in the PIVOTAL trial.« less

Importance of Local Control in Early-Stage Prostate Cancer: Outcomes of Patients With Positive Post-Radiation Therapy Biopsy Results Treated in RTOG 9408

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krauss, Daniel J., E-mail: dkrauss@beaumont.edu; Hu, Chen; Bahary, Jean-Paul

Purpose: The purpose of this study was to assess the association between positive post-radiation therapy (RT) biopsy results and subsequent clinical outcomes in males with localized prostate cancer. Methods and Materials: Radiation Therapy Oncology Group study 94-08 analyzed 1979 males with prostate cancer, stage T1b-T2b and prostate-specific antigen concentrations of ≤20 ng/dL, to investigate whether 4 months of total androgen suppression (TAS) added to RT improved survival compared to RT alone. Patients randomized to receive TAS received flutamide with luteinizing hormone releasing hormone (LHRH) agonist. According to protocol, patients without evidence of clinical recurrence or initiation of additional endocrine therapy underwent repeatmore » prostate biopsy 2 years after RT completion. Statistical analysis was performed to evaluate the impact of positive post-RT biopsy results on clinical outcomes. Results: A total of 831 patients underwent post-RT biopsy, 398 were treated with RT alone and 433 with RT plus TAS. Patients with positive post-RT biopsy results had higher rates of biochemical failure (hazard ratio [HR] = 1.7; 95% confidence interval [CI] = 1.3-2.1) and distant metastasis (HR = 2.4; 95% CI = 1.3-4.4) and inferior disease-specific survival (HR = 3.8; 95% CI = 1.9-7.5). Positive biopsy results remained predictive of such outcomes after correction for potential confounders such as Gleason score, tumor stage, and TAS administration. Prior TAS therapy did not prevent elevated risk of adverse outcome in the setting of post-RT positive biopsy results. Patients with Gleason score ≥7 with a positive biopsy result additionally had inferior overall survival compared to those with a negative biopsy result (HR = 1.56; 95% CI = 1.04-2.35). Conclusions: Positive post-RT biopsy is associated with increased rates of distant metastases and inferior disease-specific survival in patients treated with definitive RT and was associated with inferior overall survival in patients with high-grade tumors.« less

Evaluating which plan quality metrics are appropriate for use in lung SBRT.

PubMed

Yaparpalvi, Ravindra; Garg, Madhur K; Shen, Jin; Bodner, William R; Mynampati, Dinesh K; Gafar, Aleiya; Kuo, Hsiang-Chi; Basavatia, Amar K; Ohri, Nitin; Hong, Linda X; Kalnicki, Shalom; Tome, Wolfgang A

2018-02-01

Several dose metrics in the categories-homogeneity, coverage, conformity and gradient have been proposed in literature for evaluating treatment plan quality. In this study, we applied these metrics to characterize and identify the plan quality metrics that would merit plan quality assessment in lung stereotactic body radiation therapy (SBRT) dose distributions. Treatment plans of 90 lung SBRT patients, comprising 91 targets, treated in our institution were retrospectively reviewed. Dose calculations were performed using anisotropic analytical algorithm (AAA) with heterogeneity correction. A literature review on published plan quality metrics in the categories-coverage, homogeneity, conformity and gradient was performed. For each patient, using dose-volume histogram data, plan quality metric values were quantified and analysed. For the study, the radiation therapy oncology group (RTOG) defined plan quality metrics were: coverage (0.90 ± 0.08); homogeneity (1.27 ± 0.07); conformity (1.03 ± 0.07) and gradient (4.40 ± 0.80). Geometric conformity strongly correlated with conformity index (p < 0.0001). Gradient measures strongly correlated with target volume (p < 0.0001). The RTOG lung SBRT protocol advocated conformity guidelines for prescribed dose in all categories were met in ≥94% of cases. The proportion of total lung volume receiving doses of 20 Gy and 5 Gy (V 20 and V 5 ) were mean 4.8% (±3.2) and 16.4% (±9.2), respectively. Based on our study analyses, we recommend the following metrics as appropriate surrogates for establishing SBRT lung plan quality guidelines-coverage % (ICRU 62), conformity (CN or CI Paddick ) and gradient (R 50% ). Furthermore, we strongly recommend that RTOG lung SBRT protocols adopt either CN or CI Padddick in place of prescription isodose to target volume ratio for conformity index evaluation. Advances in knowledge: Our study metrics are valuable tools for establishing lung SBRT plan quality guidelines.

Local control of brain metastases by stereotactic radiosurgery in relation to dose to the tumor margin.

PubMed

Vogelbaum, Michael A; Angelov, Lilyana; Lee, Shih-Yuan; Li, Liang; Barnett, Gene H; Suh, John H

2006-06-01

The maximal tolerated dose (MTD) for stereotactic radiosurgery (SRS) for brain tumors was established by the Radiation Therapy Oncology Group (RTOG) in protocol 90-05, which defined three dose groups based on the maximal tumor diameter. The goal in this retrospective study was to determine whether differences in doses to the margins of brain metastases affect the ability of SRS to achieve local control. Between 1997 and 2003, 202 patients harboring 375 tumors that met study entry criteria underwent SRS for treatment of one or multiple brain metastases. The median overall follow-up duration was 10.7 months (range 3-83 months). A dose of 24 Gy to the tumor margin had a significantly lower risk of local failure than 15 or 18 Gy (p = 0.0005; hazard ratio 0.277, confidence interval [CI] 0.134-0.573), whereas the 15- and 18-Gy groups were not significantly different from each other (p = 0.82) in this regard. The 1-year local control rate was 85% (95% CI 78-92%) in tumors treated with 24 Gy, compared with 49% (CI 30-68%) in tumors treated with 18 Gy and 45% (CI 23-67%) in tumors treated with 15 Gy. Overall patient survival was independent of dose to the tumor margin. Use of the RTOG 90-05 dosing scheme for brain metastases is associated with a variable local control rate. Tumors larger than 2 cm are less effectively controlled than smaller lesions, which can be safely treated with 24 Gy. Prospective evaluations of the relationship between dose to the tumor margin and local control should be performed to confirm these observations.

A planning comparison of 7 irradiation options allowed in RTOG 1005 for early-stage breast cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Guang-Pei, E-mail: gpchen@mcw.edu; Liu, Feng; White, Julia

2015-04-01

This study compared the 7 treatment plan options in achieving the dose-volume criteria required by the Radiation Therapy Oncology Group (RTOG) 1005 protocol. Dosimetry plans were generated for 15 representative patients with early-stage breast cancer (ESBC) based on the protocol-required dose-volume criteria for each of the following 7 treatment options: 3D conformal radiotherapy (3DCRT), whole-breast irradiation (WBI) plus 3DCRT lumpectomy boost, 3DCRT WBI plus electron boost, 3DCRT WBI plus intensity-modulated radiation therapy (IMRT) boost, IMRT WBI plus 3DCRT boost, IMRT WBI plus electron boost, IMRT WBI plus IMRT boost, and simultaneous integrated boost (SIB) with IMRT. A variety of dose-volumemore » parameters, including target dose conformity and uniformity and normal tissue sparing, were compared for these plans. For the patients studied, all plans met the required acceptable dose-volume criteria, with most of them meeting the ideal criteria. When averaged over patients, most dose-volume goals for all plan options can be achieved with a positive gap of at least a few tenths of standard deviations. The plans for all 7 options are generally comparable. The dose-volume goals required by the protocol can in general be easily achieved. IMRT WBI provides better whole-breast dose uniformity than 3DCRT WBI does, but it causes no significant difference for the dose conformity. All plan options are comparable for lumpectomy dose uniformity and conformity. Patient anatomy is always an important factor when whole-breast dose uniformity and conformity and lumpectomy dose conformity are considered.« less

The Significance of Co-Expression of Epidermal Growth Factor Receptor (EGFR) and Ki67 on Clinical Outcome in Patients with Anal Cancer Treated with Chemoradiotherapy: An Analysis of NRG Oncology RTOG 9811

PubMed Central

Doll, Corinne M.; Moughan, Jennifer; Klimowicz, Alexander; Ho, Clement K.; Kornaga, Elizabeth N.; Lees-Miller, Susan P.; Ajani, Jaffer A.; Crane, Christopher H.; Kachnic, Lisa A.; Okawara, Gordon S.; Berk, Lawrence B.; Roof, Kevin S.; Becker, Mark J.; Grisell, David L.; Ellis, Robert J; Sperduto, Paul; Marsa, Gerald; Guha, Chandan; Magliocco, Anthony

2017-01-01

Purpose To measure co-expression of EGFR and Ki67 proteins in pre-treatment tumor biopsies of anal cancer patients enrolled on NRG Oncology RTOG 9811, a phase III trial comparing 5FU/MMC/RT (Arm A) vs. 5FU/cisplatin/RT (Arm B), and to correlate expression with clinical outcome. Materials/Methods EGFR and Ki67 co-expression was measured after constructing a tissue microarray using fluorescence immunohistochemistry and automated quantitative image analysis (AQUA). Ki67 score within EGFR high vs. low areas (Ki67ratio in EGFRhigh:low) in each tumor core was analyzed at the median, quartiles and as a continuous variable. Associations between the tumor markers and clinical endpoints [overall and disease-free survival (OS, DFS), locoregional and colostomy failure (LRF, CF), and distant metastases (DM] were explored. Results 282 pre-treatment tumors were analyzed from NRG Oncology RTOG 9811. Of evaluated specimens, 183 (65%, n=89, Arm A; n=94, Arm B) were eligible and analyzable. There were no significant differences in baseline characteristics or outcomes between analyzable and unanalyzable patient cases. Median follow-up was 6.0 years. On multivariate analysis, after adjusting for gender, patients with Ki67ratio in EGFRhigh:low ≥ median had worse OS (HR=2.41, 95% C.I. = [1.38, 4.19], p=0.0019). After adjusting for N stage and largest tumor dimension, patients with Ki67ratio in EGFRhigh:low ≥ median had a higher risk of a disease-free failure (HR=1.85, 95% C.I. = [1.18, 2.92], p=0.0078). Technical validation with an independent anal cancer patient cohort was performed and shows a very similar biomarker score distribution. Conclusions High Ki67ratio in EGFRhigh:low is associated with worse clinical outcome in this subset of patients with anal cancer treated with chemoradiation on NRG Oncology RTOG 9811. Evaluation within a clinical trial will be required to determine whether patients with these tumor characteristics may specifically benefit from an EGFR targeted therapeutic agent. PMID:28126304

Quantifying Unnecessary Normal Tissue Complication Risks due to Suboptimal Planning: A Secondary Study of RTOG 0126.

PubMed

Moore, Kevin L; Schmidt, Rachel; Moiseenko, Vitali; Olsen, Lindsey A; Tan, Jun; Xiao, Ying; Galvin, James; Pugh, Stephanie; Seider, Michael J; Dicker, Adam P; Bosch, Walter; Michalski, Jeff; Mutic, Sasa

2015-06-01

The purpose of this study was to quantify the frequency and clinical severity of quality deficiencies in intensity modulated radiation therapy (IMRT) planning in the Radiation Therapy Oncology Group 0126 protocol. A total of 219 IMRT patients from the high-dose arm (79.2 Gy) of RTOG 0126 were analyzed. To quantify plan quality, we used established knowledge-based methods for patient-specific dose-volume histogram (DVH) prediction of organs at risk and a Lyman-Kutcher-Burman (LKB) model for grade ≥2 rectal complications to convert DVHs into normal tissue complication probabilities (NTCPs). The LKB model was validated by fitting dose-response parameters relative to observed toxicities. The 90th percentile (22 of 219) of plans with the lowest excess risk (difference between clinical and model-predicted NTCP) were used to create a model for the presumed best practices in the protocol (pDVH0126,top10%). Applying the resultant model to the entire sample enabled comparisons between DVHs that patients could have received to DVHs they actually received. Excess risk quantified the clinical impact of suboptimal planning. Accuracy of pDVH predictions was validated by replanning 30 of 219 patients (13.7%), including equal numbers of presumed "high-quality," "low-quality," and randomly sampled plans. NTCP-predicted toxicities were compared to adverse events on protocol. Existing models showed that bladder-sparing variations were less prevalent than rectum quality variations and that increased rectal sparing was not correlated with target metrics (dose received by 98% and 2% of the PTV, respectively). Observed toxicities were consistent with current LKB parameters. Converting DVH and pDVH0126,top10% to rectal NTCPs, we observed 94 of 219 patients (42.9%) with ≥5% excess risk, 20 of 219 patients (9.1%) with ≥10% excess risk, and 2 of 219 patients (0.9%) with ≥15% excess risk. Replanning demonstrated the predicted NTCP reductions while maintaining the volume of the PTV receiving prescription dose. An equivalent sample of high-quality plans showed fewer toxicities than low-quality plans, 6 of 73 versus 10 of 73 respectively, although these differences were not significant (P=.21) due to insufficient statistical power in this retrospective study. Plan quality deficiencies in RTOG 0126 exposed patients to substantial excess risk for rectal complications. Copyright © 2015 Elsevier Inc. All rights reserved.

Exploratory Factor Analysis of NRG Oncology's University of Washington Quality of Life Questionnaire – RTOG Modification

PubMed Central

Pugh, Stephanie L.; Wyatt, Gwen; Wong, Raimond K. W.; Sagar, Stephen M.; Yueh, Bevan; Singh, Anurag K.; Yao, Min; Nguyen-Tan, Phuc Felix; Yom, Sue S.; Cardinale, Francis S.; Sultanem, Khalil; Hodson, D. Ian; Krempl, Greg A.; Chavez, Ariel; Yeh, Alexander M.; Bruner, Deborah W.

2016-01-01

Context The 15-item University of Washington Quality of Life questionnaire – Radiation Therapy Oncology Group (RTOG) modification (UW-QOL-RTOG modification) has been used in several trials of head and neck cancer conducted by NRG Oncology such as RTOG 9709, RTOG 9901, RTOG 0244, and RTOG 0537. Objectives This study is an exploratory factor analysis (EFA) to establish validity and reliability of the instrument subscales. Methods EFA on the UW-QOL - RTOG modification was conducted using baseline data from NRG Oncology's RTOG 0537, a trial of acupuncture-like transcutaneous electrical nerve stimulation in treating radiation-induced xerostomia. Cronbach's α coefficient was calculated to measure reliability; correlation with the University of Michigan Xerostomia Related Quality of Life Scale (XeQOLS) was used to evaluate concurrent validity; and correlations between consecutive time points were used to assess test-retest reliability. Results The 15-item EFA of the modified tool resulted in 11 items split into 4 factors: mucus, eating, pain, and activities. Cronbach's α ranged from 0.71 to 0.93 for the factors and total score, consisting of all 11 items. There were strong correlations (ρ≥0.60) between consecutive time points and between total score and the XeQOLS total score (ρ>0.65). Conclusion The UW-QOL-RTOG modification is a valid tool that can be used to assess symptom burden of head and neck cancer patients receiving radiation therapy or those who have recently completed radiation. The modified tool has acceptable reliability, concurrent validity, and test-retest reliability in this patient population, as well as the advantage of having being shortened from 15 to 11 items. PMID:27899312

A planning comparison of 7 irradiation options allowed in RTOG 1005 for early-stage breast cancer.

PubMed

Chen, Guang-Pei; Liu, Feng; White, Julia; Vicini, Frank A; Freedman, Gary M; Arthur, Douglas W; Li, X Allen

2015-01-01

This study compared the 7 treatment plan options in achieving the dose-volume criteria required by the Radiation Therapy Oncology Group (RTOG) 1005 protocol. Dosimetry plans were generated for 15 representative patients with early-stage breast cancer (ESBC) based on the protocol-required dose-volume criteria for each of the following 7 treatment options: 3D conformal radiotherapy (3DCRT), whole-breast irradiation (WBI) plus 3DCRT lumpectomy boost, 3DCRT WBI plus electron boost, 3DCRT WBI plus intensity-modulated radiation therapy (IMRT) boost, IMRT WBI plus 3DCRT boost, IMRT WBI plus electron boost, IMRT WBI plus IMRT boost, and simultaneous integrated boost (SIB) with IMRT. A variety of dose-volume parameters, including target dose conformity and uniformity and normal tissue sparing, were compared for these plans. For the patients studied, all plans met the required acceptable dose-volume criteria, with most of them meeting the ideal criteria. When averaged over patients, most dose-volume goals for all plan options can be achieved with a positive gap of at least a few tenths of standard deviations. The plans for all 7 options are generally comparable. The dose-volume goals required by the protocol can in general be easily achieved. IMRT WBI provides better whole-breast dose uniformity than 3DCRT WBI does, but it causes no significant difference for the dose conformity. All plan options are comparable for lumpectomy dose uniformity and conformity. Patient anatomy is always an important factor when whole-breast dose uniformity and conformity and lumpectomy dose conformity are considered. Copyright © 2015 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Age as an independent prognostic factor in patients with glioblastoma: a Radiation Therapy Oncology Group and American College of Surgeons National Cancer Data Base comparison.

PubMed

Siker, Malika L; Wang, Meihua; Porter, Kimberly; Nelson, Diana F; Curran, Walter J; Michalski, Jeff M; Souhami, Luis; Chakravarti, Arnab; Yung, W K Alfred; Delrowe, John; Coughlin, Christopher T; Mehta, Minesh P

2011-08-01

Glioblastoma (GBM) is rare in early adulthood and little information is available on this subgroup. We investigated whether young age (18-30 years) had an independent effect on survival. We retrospectively reviewed patients from two large databases: Radiation Therapy Oncology Group (RTOG) and American College of Surgeons National Cancer Data Base (NCDB). In the RTOG evaluation, we analyzed all eligible GBM cases from 17 RTOG studies from 1974 to 2002. All patients with GBM during 1985-1998 in the NCDB were examined for comparison. Patients were divided into three cohorts: ages 18-30, 31-49, and ≥50. Overall survival, as a function of age (discreet and continuous), was assessed. The RTOG review included 3,136 patients: 112 (3.6%) were 18-30, 780 (24.9%) were 31-49, and 2,244 (71.6%) were ≥50. The median survival times of the three groups were 21.0, 13.5, and 9.1 months (P < 0.0001). Significant improvement in survival for younger patients was demonstrated with adjustment for recursive partitioning analysis (RPA) class. Of the 37,260 patients analyzed in the NCDB, 796 (2.1%) were 18-30, 5,711 (15.3%) were 31-49, and 30,753 (82.5%) were ≥50. The median survival times of the three groups were 18.0, 12.8, and 6.3 months (P < 0.0001). Data were not available for RPA class from this series. GBM is rare in young adulthood, comprising 2.1-3.6% of our patients. They have superior survival, even when adjusted for RPA class. More investigations on the unique biologic and clinical characteristics of tumors in this population are needed.

Automatic planning on hippocampal avoidance whole-brain radiotherapy.

PubMed

Wang, Shuo; Zheng, Dandan; Zhang, Chi; Ma, Rongtao; Bennion, Nathan R; Lei, Yu; Zhu, Xiaofeng; Enke, Charles A; Zhou, Sumin

2017-01-01

Mounting evidence suggests that radiation-induced damage to the hippocampus plays a role in neurocognitive decline for patients receiving whole-brain radiotherapy (WBRT). Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) has been proposed to reduce the putative neurocognitive deficits by limiting the dose to the hippocampus. However, urgency of palliation for patients as well as the complexities of the treatment planning may be barriers to protocol enrollment to accumulate further clinical evidence. This warrants expedited quality planning of HA-WBRT. Pinnacle 3 Automatic treatment planning was designed to increase planning efficiency while maintaining or improving plan quality and consistency. The aim of the present study is to evaluate the performance of the Pinnacle 3 Auto-Planning on HA-WBRT treatment planning. Ten patients previously treated for brain metastases were selected. Hippocampal volumes were contoured on T1 magnetic resonance (MR) images, and planning target volumes (PTVs) were generated based on RTOG0933. The following 2 types of plans were generated by Pinnacle 3 Auto-Planning: the one with 2 coplanar volumetric modulated arc therapy (VMAT) arcs and the other with 9-field noncoplanar intensity-modulated radiation therapy (IMRT). D 2% and D 98% of PTV were used to calculate homogeneity index (HI). HI and Paddick Conformity index (CI) of PTV as well as D 100% and D max of the hippocampus were used to evaluate the plan quality. All the auto-plans met the dose coverage and constraint objectives based on RTOG0933. The auto-plans eliminated the necessity of generating pseudostructures by the planners, and it required little manual intervention which expedited the planning process. IMRT quality assurance (QA) results also suggest that all the auto-plans are practically acceptable on delivery. Pinnacle 3 Auto-Planning generates acceptable plans by RTOG0933 criteria without time-consuming planning process. The expedited quality planning achieved by Auto-Planning (AP) may facilitate protocol enrollment of patients to further investigate the hippocampal-sparing effect and be used to ensure timely start of palliative treatment in future clinical practice. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Automatic planning on hippocampal avoidance whole-brain radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Shuo, E-mail: shuo0220@gmail.com; Zheng, Dandan; Zhang, Chi

Mounting evidence suggests that radiation-induced damage to the hippocampus plays a role in neurocognitive decline for patients receiving whole-brain radiotherapy (WBRT). Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) has been proposed to reduce the putative neurocognitive deficits by limiting the dose to the hippocampus. However, urgency of palliation for patients as well as the complexities of the treatment planning may be barriers to protocol enrollment to accumulate further clinical evidence. This warrants expedited quality planning of HA-WBRT. Pinnacle{sup 3} Automatic treatment planning was designed to increase planning efficiency while maintaining or improving plan quality and consistency. The aim of the present studymore » is to evaluate the performance of the Pinnacle{sup 3} Auto-Planning on HA-WBRT treatment planning. Ten patients previously treated for brain metastases were selected. Hippocampal volumes were contoured on T1 magnetic resonance (MR) images, and planning target volumes (PTVs) were generated based on RTOG0933. The following 2 types of plans were generated by Pinnacle{sup 3} Auto-Planning: the one with 2 coplanar volumetric modulated arc therapy (VMAT) arcs and the other with 9-field noncoplanar intensity-modulated radiation therapy (IMRT). D{sub 2%} and D{sub 98%} of PTV were used to calculate homogeneity index (HI). HI and Paddick Conformity index (CI) of PTV as well as D{sub 100%} and D{sub max} of the hippocampus were used to evaluate the plan quality. All the auto-plans met the dose coverage and constraint objectives based on RTOG0933. The auto-plans eliminated the necessity of generating pseudostructures by the planners, and it required little manual intervention which expedited the planning process. IMRT quality assurance (QA) results also suggest that all the auto-plans are practically acceptable on delivery. Pinnacle{sup 3} Auto-Planning generates acceptable plans by RTOG0933 criteria without time-consuming planning process. The expedited quality planning achieved by Auto-Planning (AP) may facilitate protocol enrollment of patients to further investigate the hippocampal-sparing effect and be used to ensure timely start of palliative treatment in future clinical practice.« less

Quantifying Unnecessary Normal Tissue Complication Risks due to Suboptimal Planning: A Secondary Study of RTOG 0126

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moore, Kevin L., E-mail: kevinmoore@ucsd.edu; Schmidt, Rachel; Moiseenko, Vitali

Purpose: The purpose of this study was to quantify the frequency and clinical severity of quality deficiencies in intensity modulated radiation therapy (IMRT) planning in the Radiation Therapy Oncology Group 0126 protocol. Methods and Materials: A total of 219 IMRT patients from the high-dose arm (79.2 Gy) of RTOG 0126 were analyzed. To quantify plan quality, we used established knowledge-based methods for patient-specific dose-volume histogram (DVH) prediction of organs at risk and a Lyman-Kutcher-Burman (LKB) model for grade ≥2 rectal complications to convert DVHs into normal tissue complication probabilities (NTCPs). The LKB model was validated by fitting dose-response parameters relative tomore » observed toxicities. The 90th percentile (22 of 219) of plans with the lowest excess risk (difference between clinical and model-predicted NTCP) were used to create a model for the presumed best practices in the protocol (pDVH{sub 0126,top10%}). Applying the resultant model to the entire sample enabled comparisons between DVHs that patients could have received to DVHs they actually received. Excess risk quantified the clinical impact of suboptimal planning. Accuracy of pDVH predictions was validated by replanning 30 of 219 patients (13.7%), including equal numbers of presumed “high-quality,” “low-quality,” and randomly sampled plans. NTCP-predicted toxicities were compared to adverse events on protocol. Results: Existing models showed that bladder-sparing variations were less prevalent than rectum quality variations and that increased rectal sparing was not correlated with target metrics (dose received by 98% and 2% of the PTV, respectively). Observed toxicities were consistent with current LKB parameters. Converting DVH and pDVH{sub 0126,top10%} to rectal NTCPs, we observed 94 of 219 patients (42.9%) with ≥5% excess risk, 20 of 219 patients (9.1%) with ≥10% excess risk, and 2 of 219 patients (0.9%) with ≥15% excess risk. Replanning demonstrated the predicted NTCP reductions while maintaining the volume of the PTV receiving prescription dose. An equivalent sample of high-quality plans showed fewer toxicities than low-quality plans, 6 of 73 versus 10 of 73 respectively, although these differences were not significant (P=.21) due to insufficient statistical power in this retrospective study. Conclusions: Plan quality deficiencies in RTOG 0126 exposed patients to substantial excess risk for rectal complications.« less

Impact of Radiation-Induced Xerostomia on Quality of Life After Primary Radiotherapy Among Patients With Head and Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jellema, Anke Petra; Department of Radiation Oncology, VU University Medical Center, Amsterdam; Slotman, Ben J.

2007-11-01

Purpose: To investigate the impact of xerostomia on overall quality of life (QoL) outcome and related dimensions among head and neck cancer patients treated with primary radiotherapy. Methods and Materials: A total of 288 patients with Stage I-IV disease without distant metastases were included. Late xerostomia according to the Radiation Therapy Oncology Group (RTOG-xerostomia) and QoL (European Organization for Research and Treatment of Cancer QLC-C30) were assessed at baseline and every 6th month from 6 months to 24 months after radiotherapy. Results: A significant association was found between RTOG-xerostomia and overall QoL outcome (effect size [ES] 0.07, p < 0.001).more » A significant relationship with global QoL, all functioning scales, and fatigue and insomnia was observed. A significant interaction term was present between RTOG-xerostomia and gender and between RTOG-xerostomia and age. In terms of gender, RTOG-xerostomia had a larger impact on overall QoL outcome in women (ES 0.13 for women vs. 0.07 for men). Furthermore, in women ES on individual scales were larger, and a marked worsening was observed with increasing RTOG-xerostomia. No different ES according to age was seen (ES 0.10 for 18-65 years vs. 0.08 for >65 years). An analysis of the impact of RTOG-xerostomia on overall QoL outcome over time showed an increase from 0.09 at 6 months to 0.22 at 24 months. With elapsing time, a worsening was found for these individual scales with increasing RTOG-xerostomia. Conclusions: The results of this prospective study are the first to show a significant impact of radiation-induced xerostomia on QoL. Although the incidence of Grade {>=}2 RTOG-xerostomia decreases with time, its impact on QoL increases. This finding emphasizes the importance of prevention of xerostomia.« less

Implementation of Remote 3-Dimensional Image Guided Radiation Therapy Quality Assurance for Radiation Therapy Oncology Group Clinical Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cui Yunfeng; Galvin, James M.; Radiation Therapy Oncology Group, American College of Radiology, Philadelphia, Pennsylvania

2013-01-01

Purpose: To report the process and initial experience of remote credentialing of three-dimensional (3D) image guided radiation therapy (IGRT) as part of the quality assurance (QA) of submitted data for Radiation Therapy Oncology Group (RTOG) clinical trials; and to identify major issues resulting from this process and analyze the review results on patient positioning shifts. Methods and Materials: Image guided radiation therapy datasets including in-room positioning CT scans and daily shifts applied were submitted through the Image Guided Therapy QA Center from institutions for the IGRT credentialing process, as required by various RTOG trials. A centralized virtual environment is establishedmore » at the RTOG Core Laboratory, containing analysis tools and database infrastructure for remote review by the Physics Principal Investigators of each protocol. The appropriateness of IGRT technique and volumetric image registration accuracy were evaluated. Registration accuracy was verified by repeat registration with a third-party registration software system. With the accumulated review results, registration differences between those obtained by the Physics Principal Investigators and from the institutions were analyzed for different imaging sites, shift directions, and imaging modalities. Results: The remote review process was successfully carried out for 87 3D cases (out of 137 total cases, including 2-dimensional and 3D) during 2010. Frequent errors in submitted IGRT data and challenges in the review of image registration for some special cases were identified. Workarounds for these issues were developed. The average differences of registration results between reviewers and institutions ranged between 2 mm and 3 mm. Large discrepancies in the superior-inferior direction were found for megavoltage CT cases, owing to low spatial resolution in this direction for most megavoltage CT cases. Conclusion: This first experience indicated that remote review for 3D IGRT as part of QA for RTOG clinical trials is feasible and effective. The magnitude of registration discrepancy between institution and reviewer was presented, and the major issues were investigated to further improve this remote evaluation process.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pokhrel, D; Sood, S; Badkul, R

Purpose: To evaluate XVMC computed rib doses for peripherally located non-small-cell-lung tumors treated with SBRT following RTOG-0915 guidelines. Methods: Twenty patients with solitary peripherally located non-small-cell-lung tumors were treated using XVMC-based SBRT to 50–54Gy in 5−3 fractions, respectively, for PTV(V100%)=95%. Based on 4D-CT, ITV was delineated on MaximumIP images and organs-at-risk(OARs) including ribs were contoured on MeanIP images. Mean PTV(ITV+5mm uniform margin) was 46.1±38.7cc (range, 11.1–163.0cc). XVMC SBRT treatment plans were generated with a combination of non-coplanar 3D-conformal arcs/beams, and were delivered by Novalis-TX consisting of HD-MLCs and a 6MV-SRS(1000MU/min) beam, following RTOG-0915 criteria. XVMC rib maximum dose and dosemore » to <1cc, <5cc, <10cc were evaluated as a function of PTV, prescription dose and 3D-distance from tumor isocenter to the most proximal rib contour. Plans were re-computed using heterogeneity-corrected pencil-beam (PB-hete) algorithm utilizing identical beam geometry/MLC positions and MUs and subsequently compared to XVMC. Results: XVMC average maximum rib dose was 50.9±6.4Gy (range, 35.1–59.3Gy). XVMC mean rib dose to <1cc was 41.6±5.6Gy (range, 27.9–47.9Gy), <5cc was 31.2±7.3Gy (range, 10.6–43.1Gy), and <10cc was 21.2±8.7Gy (range, 1.1–36Gy), respectively. For the given prescription, correlation between PTV and rib doses to <5cc (p=0.005) and <10cc (p=0.018) was observed. 3D-distance from the tumor isocenter to the proximal rib contour strongly correlated with maximum rib dose (p=0.0001). PB-hete algorithm overestimated maximum rib dose and dose to <1cc, <5cc, and <10cc of ribs by 5%, 3%, 3%, and 3%, respectively. Conclusion: PB-hete overestimates ribs dose relative to XVMC. Since all the clinical XVMC plans were generated without compromising the target coverage (per RTOG-0915), almost all patient’s ribs doses were higher than the protocol guidelines. As expected, larger tumor size and proximity to ribs received higher absolute dose to ribs. Prospective observation is needed to determine if XVMC delivered rib doses correlates with patient symptoms including chest wall pain and/or rib fractures.« less

SU-E-T-578: On Definition of Minimum and Maximum Dose for Target Volume

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gong, Y; Yu, J; Xiao, Y

Purpose: This study aims to investigate the impact of different minimum and maximum dose definitions in radiotherapy treatment plan quality evaluation criteria by using tumor control probability (TCP) models. Methods: Dosimetric criteria used in RTOG 1308 protocol are used in the investigation. RTOG 1308 is a phase III randomized trial comparing overall survival after photon versus proton chemoradiotherapy for inoperable stage II-IIIB NSCLC. The prescription dose for planning target volume (PTV) is 70Gy. Maximum dose (Dmax) should not exceed 84Gy and minimum dose (Dmin) should not go below 59.5Gy in order for the plan to be “per protocol” (satisfactory).A mathematicalmore » model that simulates the characteristics of PTV dose volume histogram (DVH) curve with normalized volume is built. The Dmax and Dmin are noted as percentage volumes Dη% and D(100-δ)%, with η and d ranging from 0 to 3.5. The model includes three straight line sections and goes through four points: D95%= 70Gy, Dη%= 84Gy, D(100-δ)%= 59.5 Gy, and D100%= 0Gy. For each set of η and δ, the TCP value is calculated using the inhomogeneously irradiated tumor logistic model with D50= 74.5Gy and γ50=3.52. Results: TCP varies within 0.9% with η; and δ values between 0 and 1. With η and η varies between 0 and 2, TCP change was up to 2.4%. With η and δ variations from 0 to 3.5, maximum of 8.3% TCP difference is seen. Conclusion: When defined maximum and minimum volume varied more than 2%, significant TCP variations were seen. It is recommended less than 2% volume used in definition of Dmax or Dmin for target dosimetric evaluation criteria. This project was supported by NIH grants U10CA180868, U10CA180822, U24CA180803, U24CA12014 and PA CURE Grant.« less

Outcomes research in cancer clinical trial cooperative groups: the RTOG model.

PubMed

Bruner, D W; Movsas, B; Konski, A; Roach, M; Bondy, M; Scarintino, C; Scott, C; Curran, W

2004-08-01

The Radiation Therapy Oncology Group (RTOG), a National Cancer Institute sponsored cancer clinical trials research cooperative, has recently formed an Outcomes Committee to assess a comprehensive array of clinical trial endpoints and factors impacting the net effect of therapy. To study outcomes in a consistent, comprehensive and coordinated manner, the RTOG Outcomes Committee developed a model to assess clinical, humanistic, and economic outcomes important in clinical trials. This paper reviews how the RTOG incorporates outcomes research into cancer clinical trials, and demonstrates utilization of the RTOG Outcomes Model to test hypotheses related to non-small-cell lung cancer (NSCLC). In this example, the clinical component of the model indicates that the addition of chemotherapy to radiotherapy (RT) improves survival but increases the risk of toxicity. The humanistic component indicates that esophagitis is the symptom impacting quality of life the greatest and may outweigh the benefits in elderly (> or =70 years) patients. The economic component of the model indicates that accounting for quality-adjusted survival, concurrent chemoRT for the treatment of NSCLC is within the range of economically acceptable recommendations. The RTOG Outcomes Model guides a comprehensive program of research that systematically measures a triad of endpoints considered important to clinical trials research.

A modified inflammatory bowel disease questionnaire and the Vaizey Incontinence questionnaire are more sensitive measures of acute gastrointestinal toxicity during pelvic radiotherapy than RTOG grading

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khalid, Usman; McGough, Camilla; Hackett, Claire

Purpose: Simple scales with greater sensitivity than Radiation Therapy Oncology Group (RTOG) grading to detect acute gastrointestinal toxicity during pelvic radiotherapy, could be clinically useful. Methods and Materials: Do questionnaires used in benign gastrointestinal diseases detect toxicity in patients undergoing radiotherapy? The patient-completed Inflammatory Bowel Disease (IBDQ) and Vaizey Incontinence questionnaires were compared prospectively at baseline and at Week 5 to physician-completed RTOG grading. Results: A total of 107 patients, median age 63 years, were recruited. After 5 weeks of treatment, patients with gynecologic and gastrointestinal cancer were more symptomatic than urologic patients (p 0.012; p = 0.014). Overall, 94%more » had altered bowel habits, 80% loose stool, 74% frequency, 65% difficult gas, 60% pain, >48% distress, 44% tenesmus, >40% restrictions in daily activity, 39% urgency, 37% fecal incontinence, and 40% required antidiarrheal medication. The median RTOG score was 1 (range, 0-2), median IBDQ score 204.5 (range, 74-224), and median Vaizey score 5 (range, 0-20). Chemotherapy preceding radiotherapy increased fecal incontinence (p 0.002). RTOG scores stabilized after 3 weeks, IBDQ scores peaked at Week 4, and Vaizey scores worsened throughout treatment. IBDQ and Vaizey scores distinguished between groups with different RTOG scores. Conclusion: The IBDQ and Vaizey questionnaires are reliable and sensitive, offering greater insight into the severity and range of symptoms compared with RTOG grading.« less

A multi-institutional study to assess adherence to lung stereotactic body radiotherapy planning goals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woerner, Andrew; Roeske, John C.; Harkenrider, Matthew M.

2015-08-15

Purpose: A multi-institutional planning study was performed to evaluate the frequency that current guidelines established by Radiation Therapy Oncology Group (RTOG) protocols and other literature for lung stereotactic body radiotherapy (SBRT) treatments are followed. Methods: A total of 300 patients receiving lung SBRT treatments in four different institutions were retrospectively reviewed. The treatments were delivered using Linac based SBRT (160 patients) or image guided robotic radiosurgery (140). Most tumors were located peripherally (250/300). Median fractional doses and ranges were 18 Gy (8–20 Gy), 12 Gy (6–15 Gy), and 10 Gy (5–12 Gy) for three, four, and five fraction treatments, respectively.more » The following planning criteria derived from RTOG trials and the literature were used to evaluate the treatment plans: planning target volumes, PTV{sub V} {sub 100} ≥ 95% and PTV{sub V} {sub 95} ≥ 99%; conformality indices, CI{sub 100%} < 1.2 and CI{sub 50%} range of 2.9–5.9 dependent on PTV; total lung-ITV: V{sub 20Gy} < 10%, V{sub 12.5Gy} < 15%, and V{sub 5Gy} < 37%; contralateral lung V{sub 5Gy} < 26%; and maximum doses for spinal cord, esophagus, trachea/bronchus, and heart and great vessels. Populations were grouped by number of fractions, and dosimetric criteria satisfaction rates (CSRs) were reported. Results: Five fraction regimens were the most common lung SBRT fractionation (46%). The median PTV was 27.2 cm{sup 3} (range: 3.8–419.5 cm{sup 3}). For all plans: mean PTV{sub V} {sub 100} was 94.5% (±5.6%, planning CSR: 69.8%), mean PTV{sub V} {sub 95} was 98.1% (±4.1%, CSR: 69.5%), mean CI{sub 100%} was 1.14 (±0.21, CSR: 79.1%, and 16.5% within minor deviation), and mean CI{sub 50%} was 5.63 (±2.8, CSR: 33.0%, and 28.0% within minor deviation). When comparing plans based on location, peripherally located tumors displayed higher PTV{sub V} {sub 100} and PTV{sub V} {sub 95} CSR (71.5% and 71.9%, respectively) than centrally located tumors (61.2% and 57.1%, respectively). Overall, the planning criteria were met for all the critical structure such as lung, heart, spinal cord, esophagus, and trachea/bronchus for at least 85% of the patients. Conclusions: Among the various parameters that were used to evaluate the SBRT plans, the CI{sub 100%} and CI{sub 50%} were the most challenging criteria to meet. Although the CSRs of organs at risk were higher among all cases, their proximity to the PTV was a significant factor.« less

Prognostic value of the Glasgow Prognostic Score for glioblastoma multiforme patients treated with radiotherapy and temozolomide.

PubMed

Topkan, Erkan; Selek, Ugur; Ozdemir, Yurday; Yildirim, Berna A; Guler, Ozan C; Ciner, Fuat; Mertsoylu, Huseyin; Tufan, Kadir

2018-04-25

To evaluate the prognostic value of the Glasgow Prognostic Score (GPS), the combination of C-reactive protein (CRP) and albumin, in glioblastoma multiforme (GBM) patients treated with radiotherapy (RT) and concurrent plus adjuvant temozolomide (GPS). Data of newly diagnosed GBM patients treated with partial brain RT and concurrent and adjuvant TMZ were retrospectively analyzed. The patients were grouped into three according to the GPS criteria: GPS-0: CRP < 10 mg/L and albumin > 35 g/L; GPS-1: CRP < 10 mg/L and albumin < 35 g/L or CRP > 10 mg/L and albumin > 35 g/L; and GPS-2: CRP > 10 mg/L and albumin < 35 g/L. Primary end-point was the association between the GPS groups and the overall survival (OS) outcomes. A total of 142 patients were analyzed (median age: 58 years, 66.2% male). There were 64 (45.1%), 40 (28.2%), and 38 (26.7%) patients in GPS-0, GPS-1, and GPS-2 groups, respectively. At median 15.7 months follow-up, the respective median and 5-year OS rates for the whole cohort were 16.2 months (95% CI 12.7-19.7) and 9.5%. In multivariate analyses GPS grouping emerged independently associated with the median OS (P < 0.001) in addition to the extent of surgery (P = 0.032), Karnofsky performance status (P = 0.009), and the Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) classification (P < 0.001). The GPS grouping and the RTOG RPA classification were found to be strongly correlated in prognostic stratification of GBM patients (correlation coefficient: 0.42; P < 0.001). The GPS appeared to be useful in prognostic stratification of GBM patients into three groups with significantly different survival durations resembling the RTOG RPA classification.

Continuing evidence for poorer treatment outcomes for single male patients: retreatment data from RTOG 97-14.

PubMed

Konski, Andre; Desilvio, Michelle; Hartsell, William; Watkins-Bruner, Deborah; Coyne, James; Scarantino, Charles; Janjan, Nora

2006-09-01

The specific aim of this study was to evaluate outcome differences by gender and partner status for patients treated on Radiation Therapy Oncology Group (RTOG) protocol 97-14. RTOG 97-14 randomized patients with metastatic breast or prostate cancer to bone to receive 8 Gy in 1 fraction or 30 Gy in 10 fractions. Retreatment rates and overall survival were made based upon gender, marital status, and Karnofsky Performance Status (KPS). The cumulative incidence method was used to estimate retreatment time at 36 months from enrollment, and Gray's test was used to test for treatment differences within the same groupings. Marital status, gender, KPS, and treatment were variables tested in a univariate Cox model evaluating the time to retreatment. Married men and women and single women receiving 30 Gy had significantly longer time to retreatment, p = 0.0067, p = 0.0052, and p = 0.0009 respectively. We failed to show a difference in retreatment rates over time in single men receiving either 30 Gy or 8 Gy. Univariate analysis of the entire group determined patients receiving 30 Gy in 10 fractions significantly less likely to receive retreatment, p < 0.0001, with a trend toward single patients less likely to be re-treated, p = 0.07. Non-disease-related variables, such as social support, might influence the results of clinical trials with subjective endpoints such as retreatment rates. The statistically nonsignificant difference in the 36-month retreatment rates observed in single male patients receiving 8 Gy may be a result of inadequate social support systems in place to facilitate additional care. Patients receiving 8 Gy in a single fraction had significantly higher retreatment rates compared with patients receiving 30 Gy in 10 fractions.

Evaluation of acute and late radiation morbidity in patients with gynaecologic malignancy using the RTOG criteria and Franco-Italian glossary.

PubMed

Yildirim, G; Ozsaran, Z; Yalman, D; Kamer, S; Aras, A

2008-01-01

The purpose of this study was to evaluate acute and late radiation morbidity in patients with gynaecologic malignancy using the RTOG criteria and Franco-Italian glossary, and to compare the usefulness and disadvantages of each system. Between February 2001 and February 2003, 107 patients with gynaecologic malignancy who received either radical or djuvant external radiotherapy +/- intracavitary brachytherapy or radiochemotherapy were enrolled in this study. The patients were evaluated before radiotherapy and weekly during radiotherapy for acute morbidity using the RTOG grading system and Franco-Italian glossary. Postradiotherapy evaluation was done one month after radiotherapy and at 3-month intervals thereafter. Median follow-up duration was 17 months. Morbidity was graded and recorded according to each scoring system. Median age was 46 years (range 37-82). Sixty-four patients (59.8%) had endometrial cancer. Radical radiotherapy was applied to 26 patients because of inoperability and 81 patients received postoperative radiotherapy. Biologically effective doses for the bladder, rectum and vagina were 98.39, 103.54 and 121.81, respectively, for late morbidity (BED3); 70.88, 72.84 and 80.92, respectively, for acute morbidity (BED10). According to the RTOG grading system acute morbidity rate for the genitourinary and gastrointestinal systems, and skin were 52.3%, 83.2% and 63.5%, respectively. Late morbidity rate for the bladder, colon-rectum, skin and vagina were 16.8%, 20.6%, 47.7% and 51.4%, respectively. The morbidity rate for the bladder, nonspecific abdominal, hematopoietic system, uterus-vulva-vagina, skin and rectum were 35.4%, 29.9%, 5.6%, 60.8%, 40.1% and 32.7%, respectively using the Franco-Italian glossary. In patients with carcinoma of the vulva--whose treatment fields were wider--acute morbidity rate according to RTOG criteria was higher (p = 0.057); photon energy (6 Mv rather than 1.25 MV) (p = 0.01) and treatment interruption of more than eight days (p = 0.019) were correlated with decreased long-term morbidity. According to the Franco-Italian glossary morbidity rates were higher in patients who received chemotherapy (p = 0.047), both external radiotherapy and brachytherapy (p = 0.022) and treatment interruption of less than eight days (p = 0.019). There is no common language between the RTOG grading system and Franco-Italian glossary for defining and scoring radiation morbidity. Up to date no standard and well-defined system has been developed for recording and reporting acute and late radiation morbidity in gynaecologic malignancy, but rather it depends on the subjective evaluation and experience of a radiation oncologist and subjective complaints of the patient, and sometimes on clinical findings. A standard and well-defined user friendly objective scoring system is needed to define and predict the morbidity rate more properly.

Impact of Gender, Partner Status, and Race on Locoregional Failure and Overall Survival in Head and Neck Cancer Patients in Three Radiation Therapy Oncology Group Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dilling, Thomas J., E-mail: Thomas.Dilling@moffitt.org; Bae, Kyounghwa; Paulus, Rebecca

Purpose: We investigated the impact of race, in conjunction with gender and partner status, on locoregional control (LRC) and overall survival (OS) in three head and neck trials conducted by the Radiation Therapy Oncology Group (RTOG). Methods and Materials: Patients from RTOG studies 9003, 9111, and 9703 were included. Patients were stratified by treatment arms. Covariates of interest were partner status (partnered vs. non-partnered), race (white vs. non-white), and sex (female vs. male). Chi-square testing demonstrated homogeneity across treatment arms. Hazards ratio (HR) was used to estimate time to event outcome. Unadjusted and adjusted HRs were calculated for all covariatesmore » with associated 95% confidence intervals (CIs) and p values. Results: A total of 1,736 patients were analyzed. Unpartnered males had inferior OS rates compared to partnered females (adjusted HR = 1.22, 95% CI, 1.09-1.36), partnered males (adjusted HR = 1.20, 95% CI, 1.09-1.28), and unpartnered females (adjusted HR = 1.20, 95% CI, 1.09-1.32). White females had superior OS compared with white males, non-white females, and non-white males. Non-white males had inferior OS compared to white males. Partnered whites had improved OS relative to partnered non-white, unpartnered white, and unpartnered non-white patients. Unpartnered males had inferior LRC compared to partnered males (adjusted HR = 1.26, 95% CI, 1.09-1.46) and unpartnered females (adjusted HR = 1.30, 95% CI, 1.05-1.62). White females had LRC superior to non-white males and females. White males had improved LRC compared to non-white males. Partnered whites had improved LRC compared to partnered and unpartnered non-white patients. Unpartnered whites had improved LRC compared to unpartnered non-whites. Conclusions: Race, gender, and partner status had impacts on both OS and locoregional failure, both singly and in combination.« less

Phase 1/2 Trials of Temozolomide, Motexafin Gadolinium, and 60-Gy Fractionated Radiation for Newly Diagnosed Supratentorial Glioblastoma Multiforme: Final Results of RTOG 0513

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brachman, David G., E-mail: david.brachman@dignityhealth.org; Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; Pugh, Stephanie L.

Purpose: The purpose of phase 1 was to determine the maximum tolerated dose (MTD) of motexafin gadolinium (MGd) given concurrently with temozolomide (TMZ) and radiation therapy (RT) in patients with newly diagnosed supratentorial glioblastoma multiforme (GBM). Phase 2 determined whether this combination improved overall survival (OS) and progression-free survival (PFS) in GBM recursive partitioning analysis class III to V patients compared to therapies for recently published historical controls. Methods and Materials: Dose escalation in phase 1 progressed through 3 cohorts until 2 of 6 patients experienced dose-limiting toxicity or a dose of 5 mg/kg was reached. Once MTD was established, amore » 1-sided 1-sample log-rank test at significance level of .1 had 85% power to detect a median survival difference (13.69 vs 18.48 months) with 60 deaths over a 12-month accrual period and an additional 18 months of follow-up. OS and PFS were estimated using the Kaplan-Meier method. Results: In phase 1, 24 patients were enrolled. The MTD established was 5 mg/kg, given intravenously 5 days a week for the first 10 RT fractions, then 3 times a week for the duration of RT. The 7 patients enrolled in the third dose level and the 94 enrolled in phase 2 received this dose. Of these 101 patients, 87 were eligible and evaluable. Median survival time was 15.6 months (95% confidence interval [CI]: 12.9-17.6 months), not significantly different from that of the historical control (P=.36). Median PFS was 7.6 months (95% CI: 5.7-9.6 months). One patient (1%) experienced a grade 5 adverse event possibly related to therapy during the concurrent phase, and none experience toxicity during adjuvant TMZ therapy. Conclusions: Treatment was well tolerated, but median OS did not reach improvement specified by protocol compared to historical control, indicating that the combination of standard RT with TMZ and MGd did not achieve a significant survival advantage.« less

Pelvic Normal Tissue Contouring Guidelines for Radiation Therapy: A Radiation Therapy Oncology Group Consensus Panel Atlas

PubMed Central

Gay, Hiram A.; Barthold, H. Joseph; O’Meara, Elizabeth; Bosch, Walter R.; El Naqa, Issam; Al-Lozi, Rawan; Rosenthal, Seth A.; Lawton, Colleen; Lee, W. Robert; Sandler, Howard; Zietman, Anthony; Myerson, Robert; Dawson, Laura A.; Willett, Christopher; Kachnic, Lisa A.; Jhingran, Anuja; Portelance, Lorraine; Ryu, Janice; Small, William; Gaffney, David; Viswanathan, Akila N.; Michalski, Jeff M.

2012-01-01

Purpose To define a male and female pelvic normal tissue contouring atlas for Radiation Therapy Oncology Group (RTOG) trials. Methods and Materials One male pelvis computed tomography (CT) data set and one female pelvis CT data set were shared via the Image-Guided Therapy QA Center. A total of 16 radiation oncologists participated. The following organs at risk were contoured in both CT sets: anus, anorectum, rectum (gastrointestinal and genitourinary definitions), bowel NOS (not otherwise specified), small bowel, large bowel, and proximal femurs. The following were contoured in the male set only: bladder, prostate, seminal vesicles, and penile bulb. The following were contoured in the female set only: uterus, cervix, and ovaries. A computer program used the binomial distribution to generate 95% group consensus contours. These contours and definitions were then reviewed by the group and modified. Results The panel achieved consensus definitions for pelvic normal tissue contouring in RTOG trials with these standardized names: Rectum, AnoRectum, SmallBowel, Colon, BowelBag, Bladder, UteroCervix, Adnexa_R, Adnexa_L, Prostate, SeminalVesc, PenileBulb, Femur_R, and Femur_L. Two additional normal structures whose purpose is to serve as targets in anal and rectal cancer were defined: AnoRectumSig and Mesorectum. Detailed target volume contouring guidelines and images are discussed. Conclusions Consensus guidelines for pelvic normal tissue contouring were reached and are available as a CT image atlas on the RTOG Web site. This will allow uniformity in defining normal tissues for clinical trials delivering pelvic radiation and will facilitate future normal tissue complication research. PMID:22483697

Elective Clinical Target Volumes for Conformal Therapy in Anorectal Cancer: A Radiation Therapy Oncology Group Consensus Panel Contouring Atlas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Myerson, Robert J.; Garofalo, Michael C.; El Naqa, Issam

2009-07-01

Purpose: To develop a Radiation Therapy Oncology Group (RTOG) atlas of the elective clinical target volume (CTV) definitions to be used for planning pelvic intensity-modulated radiotherapy (IMRT) for anal and rectal cancers. Methods and Materials: The Gastrointestinal Committee of the RTOG established a task group (the nine physician co-authors) to develop this atlas. They responded to a questionnaire concerning three elective CTVs (CTVA: internal iliac, presacral, and perirectal nodal regions for both anal and rectal case planning; CTVB: external iliac nodal region for anal case planning and for selected rectal cases; CTVC: inguinal nodal region for anal case planning andmore » for select rectal cases), and to outline these areas on individual computed tomographic images. The imaging files were shared via the Advanced Technology Consortium. A program developed by one of the co-authors (I.E.N.) used binomial maximum-likelihood estimates to generate a 95% group consensus contour. The computer-estimated consensus contours were then reviewed by the group and modified to provide a final contouring consensus atlas. Results: The panel achieved consensus CTV definitions to be used as guidelines for the adjuvant therapy of rectal cancer and definitive therapy for anal cancer. The most important difference from similar atlases for gynecologic or genitourinary cancer is mesorectal coverage. Detailed target volume contouring guidelines and images are discussed. Conclusion: This report serves as a template for the definition of the elective CTVs to be used in IMRT planning for anal and rectal cancers, as part of prospective RTOG trials.« less

High Occurrence of Aberrant Lymph Node Spread on Magnetic Resonance Lymphography in Prostate Cancer Patients With a Biochemical Recurrence After Radical Prostatectomy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meijer, Hanneke J.M., E-mail: H.Meijer@rther.umcn.nl; Lin, Emile N. van; Debats, Oscar A.

2012-03-15

Purpose: To investigate the pattern of lymph node spread in prostate cancer patients with a biochemical recurrence after radical prostatectomy, eligible for salvage radiotherapy; and to determine whether the clinical target volume (CTV) for elective pelvic irradiation in the primary setting can be applied in the salvage setting for patients with (a high risk of) lymph node metastases. Methods and Materials: The charts of 47 prostate cancer patients with PSA recurrence after prostatectomy who had positive lymph nodes on magnetic resonance lymphography (MRL) were reviewed. Positive lymph nodes were assigned to a lymph node region according to the guidelines ofmore » the Radiation Therapy Oncology Group (RTOG) for delineation of the CTV for pelvic irradiation (RTOG-CTV). We defined four lymph node regions for positive nodes outside this RTOG-CTV: the para-aortal, proximal common iliac, pararectal, and paravesical regions. They were referred to as aberrant lymph node regions. For each patient, clinical and pathologic features were recorded, and their association with aberrant lymph drainage was investigated. The distribution of positive lymph nodes was analyzed separately for patients with a prostate-specific antigen (PSA) <1.0 ng/mL. Results: MRL detected positive aberrant lymph nodes in 37 patients (79%). In 20 patients (43%) a positive lymph node was found in the pararectal region. Higher PSA at the time of MRL was associated with the presence of positive lymph nodes in the para-aortic region (2.49 vs. 0.82 ng/mL; p = 0.007) and in the proximal common iliac region (1.95 vs. 0.59 ng/mL; p = 0.009). There were 18 patients with a PSA <1.0 ng/mL. Ten of these patients (61%) had at least one aberrant positive lymph node. Conclusion: Seventy-nine percent of the PSA-recurrent patients had at least one aberrant positive lymph node. Application of the standard RTOG-CTV for pelvic irradiation in the salvage setting therefore seems to be inappropriate.« less

Neoadjuvant Interdigitated Chemoradiotherapy Using Mesna, Doxorubicin, and Ifosfamide for Large, High-grade, Soft Tissue Sarcomas of the Extremity: Improved Efficacy and Reduced Toxicity.

PubMed

Chowdhary, Mudit; Sen, Neilayan; Jeans, Elizabeth B; Miller, Luke; Batus, Marta; Gitelis, Steven; Wang, Dian; Abrams, Ross A

2018-05-18

Patients with large, high-grade extremity soft tissue sarcoma (STS) are at high risk for both local and distant recurrence. RTOG 95-14, using a regimen of neoadjuvant interdigitated chemoradiotherapy with mesna, doxorubicin, ifosfamide, and dacarbazine followed by surgery and 3 cycles of adjuvant mesna, doxorubicin, ifosfamide, and dacarbazine, demonstrated high rates of disease control at the cost of significant toxicity (83% grade 4, 5% grade 5). As such, this regimen has not been widely adopted. Herein, we report our institutional outcomes utilizing a modified interdigitated chemoradiotherapy regimen, without dacarbazine, and current radiotherapy planning and delivery techniques for high-risk STS. Adults with large (≥5 cm; median, 12.9 cm), grade 3 extremity STS who were prospectively treated as part of our institutional standard of care from 2008 to 2016 are included. Neoadjuvant chemoradiotherapy consisted of 3 cycles of mesna, doxorubicin, and ifosfamide (MAI) and 44 Gy (22 Gy in 11 fractions between cycles of MAI) after which patients underwent surgical resection and received 3 additional cycles of MAI. Twenty-six patients received the MAI treatment protocol. At a median follow-up of 47.3 months, 23 (88.5%) patients are still alive. Three year locoregional recurrence-free survival, disease-free survival, and overall survival are 95.0%, 64.0%, and 95.0%, respectively. There have been no therapy-related deaths or secondary malignancies. The nonhematologic grade 4 toxicity rate was 7.7%. Neoadjuvant interdigitated MAI radiotherapy followed by resection and 3 cycles of adjuvant MAI has resulted in acceptable and manageable toxicity and highly favorable survival in patients at greatest risk for treatment failure.

No Clinically Significant Changes in Pulmonary Function Following Stereotactic Body Radiation Therapy for Early- Stage Peripheral Non-Small Cell Lung Cancer: An Analysis of RTOG 0236

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stanic, Sinisa, E-mail: sinisa.stanic@carle.com; Paulus, Rebecca; Timmerman, Robert D.

2014-04-01

Purpose: To investigate pulmonary function test (PFT) results and arterial blood gas changes (complete PFT) following stereotactic body radiation therapy (SBRT) and to see whether baseline PFT correlates with lung toxicity and overall survival in medically inoperable patients receiving SBRT for early stage, peripheral, non-small cell lung cancer (NSCLC). Methods and Materials: During the 2-year follow-up, PFT data were collected for patients with T1-T2N0M0 peripheral NSCLC who received effectively 18 Gy × 3 in a phase 2 North American multicenter study (Radiation Therapy Oncology Group [RTOG] protocol 0236). Pulmonary toxicity was graded by using the RTOG SBRT pulmonary toxicity scale. Paired Wilcoxon signedmore » rank test, logistic regression model, and Kaplan-Meier method were used for statistical analysis. Results: At 2 years, mean percentage predicted forced expiratory volume in the first second and diffusing capacity for carbon monoxide declines were 5.8% and 6.3%, respectively, with minimal changes in arterial blood gases and no significant decline in oxygen saturation. Baseline PFT was not predictive of any pulmonary toxicity following SBRT. Whole-lung V5 (the percentage of normal lung tissue receiving 5 Gy), V10, V20, and mean dose to the whole lung were almost identical between patients who developed pneumonitis and patients who were pneumonitis-free. Poor baseline PFT did not predict decreased overall survival. Patients with poor baseline PFT as the reason for medical inoperability had higher median and overall survival rates than patients with normal baseline PFT values but with cardiac morbidity. Conclusions: Poor baseline PFT did not appear to predict pulmonary toxicity or decreased overall survival after SBRT in this medically inoperable population. Poor baseline PFT alone should not be used to exclude patients with early stage lung cancer from treatment with SBRT.« less

PSA Response After Short-Term Hormonal Therapy Plus External Beam Radiotherapy and Outcome in Patients Treated on RTOG 9413

PubMed Central

Cury, Fabio L.; Hunt, Daniel; Roach, Mack; Shipley, William; Gore, Elizabeht; Hsu, I-Chow; Krisch, Robert E.; Seider, Michael J.; Sandler, Howard; Lawton, Colleen

2013-01-01

Purpose Assess the impact of PSA-complete response (PSA-CR), measured at the end of external beam radiotherapy (EBRT) and short-term hormonal therapy (STHT), on treatment outcomes. Design The Phase III RTOG-9413 trial had as part of its original protocol the assessment of PSA-CR, i.e. PSA≤0.3ng/ml, at the end of STHT as a secondary endpoint. STHT consisted of flutamide plus an LHRH-agonist for 4 months. Kaplan-Meier method was used to estimate overall survival (OS) and disease-free survival (DFS). Cumulative incidence was used to estimate biochemical failure (BF), distant metastasis (DM), and disease-specific survival (DSS). Univariate and multivariate analyses were performed to correlate PSA-CR after STHT with all endpoints, and the following variables were considered for analysis: PSA at baseline, Gleason score, treatment arm, age, and baseline testosterone. Phoenix-consensus was used to define PSA failure. Results For 1070 evaluable patients, the median PSA at the end of STHT was 0.2ng/mL. A total of 744 patients (70%) had PSA-CR. With median follow-up of 7.2 years, failure to obtain PSA-CR was significantly associated with worse DSS (p=0.0003; hazard ratio, 2.03[95%CI, 1.38–2.97]) and DFS (p=0.003; 1.28[1.09–1.50]), as well as with a higher incidence of DM (p=0.0002; 1.92[1.37–2.69]) and BF (p<0.0001; 1.57[1.29–1.91]). The other factors associated with worse DSS were Gleason score 8–10 (p=0.0002; 3.06[1.71–5.47]) and PSA>20ng/mL (p=0.04; 1.55[1.02–2.30]). Conclusion Failure to obtain a post STHT and EBRT PSA-CR (≤0.3ng/mL) appears to be an independent predictor of unfavorable outcomes, and may help identify patients who could benefit from the addition of long-term androgen ablation. PMID:23504930

Phase I-II study of multiple daily fractions for palliation of advanced head and neck malignancies.

PubMed

Paris, K J; Spanos, W J; Lindberg, R D; Jose, B; Albrink, F

1993-03-15

To assess palliation of advance head and neck malignancies with the use of rapid hyper fractionation studies similar to the RTOG 85-02. 37 patients with 39 lesions were entered into the non-randomized Phase I-II protocol, between 1984 and 1991. Previously untreated malignancies were present in 24 lesions, primary recurrent diseases in six patients, metastasis to the head and neck in five patients and skin primaries in the remaining two cases. At presentation 15 of 37 patients (or 17 of 39 lesions) were in operable due to poor medical status, eight patients were considered technically in operable due to extent of disease, 10 patients had distant metastasis and four patients refused surgery. The protocol uses twice a day fraction (370 cGy per fraction) for 2 consecutive days totalling 1,480 cGy per course. Three courses were given at 3-week intervals for a final tumor dose of 4,440 cGy in twelve fraction over 8-9 weeks. Eleven of 39 lesions had complete response; 19 lesions had partial response; 4 lesions had no response; 3 lesions progressed under treatment. Response could not be assessed in two patients. The average survival after completion of therapy was 4.5 months ranging from 2 weeks to 31 months. Palliation was achieved in 33 of 39 lesions. The acute reactions were minimal and no late or long term complications were noted. The absence of significant complications with reasonable response in the high rate of palliation suggests that this rapid hyper fractionation palliation study should be studied for further evaluation.

A Phase II Study of Bevacizumab in Combination With Definitive Radiotherapy and Cisplatin Chemotherapy in Untreated Patients With Locally Advanced Cervical Carcinoma: Preliminary Results of RTOG 0417

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schefter, Tracey E., E-mail: tracey.schefter@ucdenver.edu; Winter, Kathryn; Kwon, Janice S.

Purpose: Concurrent cisplatin-based chemoradiotherapy (CRT) is the standard treatment for locally advanced cervical cancer. RTOG 0417 was a Phase II study exploring the safety and efficacy of the addition of bevacizumab to standard CRT. Methods and Materials: Eligible patients with bulky tumors (Stage IB-IIIB) were treated with once-weekly cisplatin (40 mg/m{sup 2}) chemotherapy and standard pelvic radiotherapy and brachytherapy. Bevacizumab was administered at 10 mg/kg intravenously every 2 weeks for three cycles. Treatment-related serious adverse event (SAE) and other adverse event (AE) rates within the first 90 days from treatment start were determined. Treatment-related SAEs were defined as any Grademore » {>=}4 vaginal bleeding or thrombotic event or Grade {>=}3 arterial event, gastrointestinal (GI) bleeding, or bowel/bladder perforation, or any Grade 5 treatment-related death. Treatment-related AEs included all SAEs and Grade 3 or 4 GI toxicity persisting for >2 weeks despite medical intervention, Grade 4 neutropenia or leukopenia persisting for >7 days, febrile neutropenia, Grade 3 or 4 other hematologic toxicity, and Grade 3 or 4 GI, renal, cardiac, pulmonary, hepatic, or neurologic AEs. All AEs were scored using the National Cancer Institute Common Terminology Criteria (CTCAE) v 3.0 (MedDRA version 6.0). Results: A total of 60 patients from 28 institutions were enrolled between 2006 and 2009, and of these, 49 patients were evaluable. The median follow-up was 12.4 months (range, 4.6-31.4 months).The median age was 45 years (range, 22-80 years). Most patients had FIGO Stage IIB (63%) and were of Zubrod performance status of 0 (67%). 80% of cases were squamous. There were no treatment-related SAEs. There were 15 (31%) protocol-specified treatment-related AEs within 90 days of treatment start; the most common were hematologic (12/15; 80%). 18 (37%) occurred during treatment or follow-up at any time. 37 of the 49 patients (76%) had cisplatin and bevacizumab administered per protocol, and 46 of the 49 (94%) had both external beam and brachytherapy administered per protocol or with acceptable variation. Conclusion: Bevacizumab in addition to standard pelvic chemoradiotherapy for locally advanced cervical cancer is feasible and safe with respect to the protocol-specified treatment-related SAEs and AEs.« less

Randomized Phase II Trial of High-Dose Melatonin and Radiation Therapy for RPA Class 2 Patients With Brain Metastases (RTOG 0119)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berk, Lawrence; Berkey, Brian; Rich, Tyvin

Purpose: To determine if high-dose melatonin for Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) Class 2 patients with brain metastases improved survival over historical controls, and to determine if the time of day melatonin was given affected its toxicity or efficacy. RTOG 0119 was a phase II randomized trial for this group of patients. Methods and Materials: RTOG RPA Class 2 patients with brain metastases were randomized to 20 mg of melatonin, given either in the morning (8-9 AM) or in the evening (8-9 PM). All patients received radiation therapy (30 Gy in 10 fractions) in the afternoon.more » Melatonin was continued until neurologic deterioration or death. The primary endpoint was overall survival time. Neurologic deterioration, as reflected by the Mini-Mental Status Examination, was also measured. Results: Neither of the randomized groups had survival distributions that differed significantly from the historic controls of patients treated with whole-brain radiotherapy. The median survivals of the morning and evening melatonin treatments were 3.4 and 2.8 months, while the RTOG historical control survival was 4.1 months. Conclusions: High-dose melatonin did not show any beneficial effect in this group of patients.« less

Pelvic Normal Tissue Contouring Guidelines for Radiation Therapy: A Radiation Therapy Oncology Group Consensus Panel Atlas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gay, Hiram A., E-mail: hgay@radonc.wustl.edu; Barthold, H. Joseph; Beth Israel Deaconess Medical Center, Boston, MA

2012-07-01

Purpose: To define a male and female pelvic normal tissue contouring atlas for Radiation Therapy Oncology Group (RTOG) trials. Methods and Materials: One male pelvis computed tomography (CT) data set and one female pelvis CT data set were shared via the Image-Guided Therapy QA Center. A total of 16 radiation oncologists participated. The following organs at risk were contoured in both CT sets: anus, anorectum, rectum (gastrointestinal and genitourinary definitions), bowel NOS (not otherwise specified), small bowel, large bowel, and proximal femurs. The following were contoured in the male set only: bladder, prostate, seminal vesicles, and penile bulb. The followingmore » were contoured in the female set only: uterus, cervix, and ovaries. A computer program used the binomial distribution to generate 95% group consensus contours. These contours and definitions were then reviewed by the group and modified. Results: The panel achieved consensus definitions for pelvic normal tissue contouring in RTOG trials with these standardized names: Rectum, AnoRectum, SmallBowel, Colon, BowelBag, Bladder, UteroCervix, Adnexa{sub R}, Adnexa{sub L}, Prostate, SeminalVesc, PenileBulb, Femur{sub R}, and Femur{sub L}. Two additional normal structures whose purpose is to serve as targets in anal and rectal cancer were defined: AnoRectumSig and Mesorectum. Detailed target volume contouring guidelines and images are discussed. Conclusions: Consensus guidelines for pelvic normal tissue contouring were reached and are available as a CT image atlas on the RTOG Web site. This will allow uniformity in defining normal tissues for clinical trials delivering pelvic radiation and will facilitate future normal tissue complication research.« less

Vitamin D Deficiency Is Associated With the Severity of Radiation-Induced Proctitis in Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ghorbanzadeh-Moghaddam, Amir; Gholamrezaei, Ali, E-mail: Gholamrezaei@med.mui.ac.ir; Poursina Hakim Research Institution, Isfahan

Purpose: Radiation-induced injury to normal tissues is a common complication of radiation therapy in cancer patients. Considering the role of vitamin D in mucosal barrier hemostasis and inflammatory responses, we investigated whether vitamin D deficiency is associated with the severity of radiation-induced acute proctitis in cancer patients. Methods and Materials: This prospective observational study was conducted in cancer patients referred for pelvic radiation therapy. Serum concentration of 25-hydroxyvitamin D was measured before radiation therapy. Vitamin D deficiency was defined as 25-hydroxyvitamin D concentrations of <35 nmol/L and <40 nmol/L in male and female patients, respectively, based on available normative data.more » Acute proctitis was assessed after 5 weeks of radiation therapy (total received radiation dose of 50 Gy) and graded from 0 to 4 using Radiation Therapy Oncology Group (RTOG) criteria. Results: Ninety-eight patients (57.1% male) with a mean age of 62.8 ± 9.1 years were studied. Vitamin D deficiency was found in 57 patients (58.1%). Symptoms of acute proctitis occurred in 72 patients (73.4%) after radiation therapy. RTOG grade was significantly higher in patients with vitamin D deficiency than in normal cases (median [interquartile range] of 2 [0.5-3] vs 1 [0-2], P=.037). Vitamin D deficiency was associated with RTOG grade of ≥2, independent of possible confounding factors; odds ratio (95% confidence interval) = 3.07 (1.27-7.50), P=.013. Conclusions: Vitamin D deficiency is associated with increased severity of radiation-induced acute proctitis. Investigating the underlying mechanisms of this association and evaluating the effectiveness of vitamin D therapy in preventing radiation-induced acute proctitis is warranted.« less

Radiotherapy induced dermatitis is a strong predictor for late fibrosis in head and neck cancer. The development of a predictive model for late fibrosis.

PubMed

Nevens, Daan; Duprez, Fréderic; Daisne, Jean Francois; Laenen, Annouschka; De Neve, Wilfried; Nuyts, Sandra

2017-02-01

To determine if the severity of radiodermatitis at the end of radio(chemo)therapy (R(C)T) for head and neck cancer (HNC) is a predictive factor for late fibrosis of the neck and to find a model to predict neck fibrosis grade⩾2 (fibrosis RTOG 2-4 ) at 6months following R(C)T for HNC. 161 patients were prospectively included. We correlated radiodermatitis at the end of RCT, age, sex, T/N stage, tumor site, concomitant chemotherapy, upfront neck dissection, neo-adjuvant chemotherapy, accelerated RT, smoking, alcohol consumption, HPV status and the dose prescribed to the elective neck with fibrosis RTOG 2-4 6months after the end of treatment. Radiodermatitis at the end of R(C)T ⩾grade 3 proved to be associated with the incidence of fibrosis RTOG 2-4 at 6months (p<0.01). Furthermore, upfront neck dissection (p<0.01), increasing N stage (p<0.01) and tumor site (p=0.02) are significantly associated in univariate analysis with fibrosis RTOG 2-4 at 6months of follow-up. Upfront neck dissection and radiodermatitis grade⩾3 at the end of R(C)T were identified by our multivariate model. Additionally, increasing N stage was selected as an independent predictor variable. The AUC for this model was 0.92. A model for the prediction of fibrosis RTOG 2-4 following R(C)T for head and neck cancer is presented with an AUC of 0.92. Interestingly, radiodermatitis grade⩾3 at the end of R(C)T is associated with RTOG 2-4 fibrosis at 6months. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Benefit From Procarbazine, Lomustine, and Vincristine in Oligodendroglial Tumors Is Associated With Mutation of IDH

PubMed Central

Cairncross, J. Gregory; Wang, Meihua; Jenkins, Robert B.; Shaw, Edward G.; Giannini, Caterina; Brachman, David G.; Buckner, Jan C.; Fink, Karen L.; Souhami, Luis; Laperriere, Normand J.; Huse, Jason T.; Mehta, Minesh P.; Curran, Walter J.

2014-01-01

Purpose Patients with 1p/19q codeleted anaplastic oligodendroglial tumors who participated in RTOG (Radiation Therapy Oncology Group) 9402 lived much longer after chemoradiotherapy (CRT) than radiation therapy (RT) alone. However, some patients with noncodeleted tumors also benefited from CRT; survival curves separated after the median had been reached, and significantly more patients lived ≥ 10 years after CRT than RT. Thus, 1p/19q status may not identify all responders to CRT. Patients and Methods Using trial data, we inquired whether an IDH mutation or germ-line polymorphism associated with IDH-mutant gliomas identified the patients in RTOG 9402 who benefited from CRT. Results IDH status was evaluable in 210 of 291 patients; 156 (74%) had mutations. rs55705857 was evaluable in 245 patients; 76 (31%) carried the G risk allele. Both were associated with longer progression-free survival after CRT, and mutant IDH was associated with longer overall survival (9.4 v 5.7 years; hazard ratio [HR], 0.59; 95% CI, 0.40 to 0.86; P = .006). For those with wild-type tumors, CRT did not prolong median survival (1.3 v 1.8 years; HR, 1.14; 95% CI, 0.63 to 2.04; P = .67) or 10-year survival rate (CRT, 6% v RT, 4%). Patients with codeleted mutated tumors (14.7 v 6.8 years; HR, 0.49; 95% CI, 0.28 to 0.85; P = .01) and noncodeleted mutated tumors (5.5 v 3.3 years; HR, 0.56; 95% CI, 0.32 to 0.99; P < .05) lived longer after CRT than RT. Conclusion IDH mutational status identified patients with oligodendroglial tumors who did (and did not) benefit from alkylating-agent chemotherapy with RT. Although patients with codeleted tumors lived longest, patients with noncodeleted IDH-mutated tumors also lived longer after CRT. PMID:24516018

The Association Between Daytime Intensivist Physician Staffing and Mortality in the Context of Other ICU Organizational Practices: A Multicenter Cohort Study.

PubMed

Costa, Deena Kelly; Wallace, David J; Kahn, Jeremy M

2015-11-01

Daytime intensivist physician staffing is associated with improved outcomes in the ICU. However, it is unclear whether this association persists in the era of interprofessional, protocol-directed critical care. We sought to reexamine the association between daytime intensivist physician staffing and ICU mortality and determine if interprofessional rounding and protocols for mechanical ventilation in part mediate this relationship. Retrospective cohort study of ICUs in the Acute Physiology and Chronic Health Evaluation clinical information system from 2009 to 2010. Forty-nine ICUs in 25 U.S. hospitals. Adults (17 yr and older) admitted to a study ICU. None. We defined high-intensity daytime intensivist staffing as either a mandatory consult or closed ICU model; interprofessional rounds as rounds that included a respiratory therapist, pharmacist, physician and nurse; and protocol use as having protocols for liberation from mechanical ventilation and lung protective mechanical ventilation. Using multivariable logistic regression, we estimated the independent effect of daytime intensivist physician staffing on in-hospital mortality controlling for interprofessional rounds and protocols for mechanical ventilation, as well as other patient and hospital characteristics. Twenty-seven ICUs (55%) reported high-intensity daytime physician staffing, 42 ICUs (85%) reported daily interprofessional rounds, and 31 (63%) reported having protocols for mechanical ventilation. There was no association between daytime intensivist physician staffing and in-hospital mortality (adjusted odds ratio, 0.86; 95% CI, 0.65-1.14). After adjusting for interprofessional rounds and protocols for mechanical ventilation, the effect of daytime intensivist physician staffing remained nonsignificant (adjusted odds ratio, 0.90; 95% CI, 0.70-1.17). High-intensity daytime physician staffing in the ICU was not significantly associated with lower mortality in a modern cohort. This association was not affected by interprofessional rounds or protocols for mechanical ventilation.

Oral health care activities performed by caregivers for institutionalized elderly in Barcelona-Spain.

PubMed

Cornejo-Ovalle, Marco; Costa-de-Lima, Kenio; Pérez, Glória; Borrell, Carme; Casals-Peidro, Elías

2013-07-01

To describe the frequency of brushing teeth and cleaning of dentures, performed by caregivers, for institutionalized elderly people. A cross-sectional study in a sample of 196 caregivers of 31 health centers in Barcelona. The dependent variables were frequency of dental brushing and frequency of cleaning of dentures of the elderly by caregivers. The independent variables were characteristics of caregivers and institutions. We performed bivariate and multivariate descriptive analyses. Robust Poisson regression models were fitted to determine factors associated with the dependent variables and to assess the strength of the association. 83% of caregivers were women, 79% worked on more than one shift, 42% worked only out of necessity, 92% were trained to care for elderly persons, 67% were trained in oral hygiene care for the elderly, and 73% recognized the existence of institutional protocols on oral health among residents. The variables explaining the lower frequency of brushing teeth by caregivers for the elderly, adjusted for the workload, were: no training in the care of elderly persons (PRa 1.7 CI95%: 1.6-1.8), not fully agreeing with the importance of oral health care of the elderly (PRa 2.5 CI95%: 1.5-4.1) and not knowing of the existence of oral health protocols (PRa 1.8 CI95% 1.2-2.6). The variables that explain the lower frequency of cleaning dentures, adjusted for the workload, were lack of training in elderly care (PRa 1.7 CI95%: 1.3-1.9) and not knowing of the existence of protocols (PRa 3.7 CI95%: 1.6-8.7). The majority of caregivers perform activities of oral health care for the elderly at least once per day. The frequency of this care depends mainly on whether caregivers are trained to perform these activities, the importance given to oral health, the workload of caregivers and the existence of institutional protocols on oral health of institutionalized elderly persons.

A phase II comparative study of gross tumor volume definition with or without PET/CT fusion in dosimetric planning for non-small-cell lung cancer (NSCLC): primary analysis of Radiation Therapy Oncology Group (RTOG) 0515.

PubMed

Bradley, Jeffrey; Bae, Kyounghwa; Choi, Noah; Forster, Ken; Siegel, Barry A; Brunetti, Jacqueline; Purdy, James; Faria, Sergio; Vu, Toni; Thorstad, Wade; Choy, Hak

2012-01-01

Radiation Therapy Oncology Group (RTOG) 0515 is a Phase II prospective trial designed to quantify the impact of positron emission tomography (PET)/computed tomography (CT) compared with CT alone on radiation treatment plans (RTPs) and to determine the rate of elective nodal failure for PET/CT-derived volumes. Each enrolled patient underwent definitive radiation therapy for non-small-cell lung cancer (≥ 60 Gy) and had two RTP datasets generated: gross tumor volume (GTV) derived with CT alone and with PET/CT. Patients received treatment using the PET/CT-derived plan. The primary end point, the impact of PET/CT fusion on treatment plans was measured by differences of the following variables for each patient: GTV, number of involved nodes, nodal station, mean lung dose (MLD), volume of lung exceeding 20 Gy (V20), and mean esophageal dose (MED). Regional failure rate was a secondary end point. The nonparametric Wilcoxon matched-pairs signed-ranks test was used with Bonferroni adjustment for an overall significance level of 0.05. RTOG 0515 accrued 52 patients, 47 of whom are evaluable. The follow-up time for all patients is 12.9 months (2.7-22.2). Tumor staging was as follows: II = 6%; IIIA = 40%; and IIIB = 54%. The GTV was statistically significantly smaller for PET/CT-derived volumes (98.7 vs. 86.2 mL; p < 0.0001). MLDs for PET/CT plans were slightly lower (19 vs. 17.8 Gy; p = 0.06). There was no significant difference in the number of involved nodes (2.1 vs. 2.4), V20 (32% vs. 30.8%), or MED (28.7 vs. 27.1 Gy). Nodal contours were altered by PET/CT for 51% of patients. One patient (2%) has developed an elective nodal failure. PET/CT-derived tumor volumes were smaller than those derived by CT alone. PET/CT changed nodal GTV contours in 51% of patients. The elective nodal failure rate for GTVs derived by PET/CT is quite low, supporting the RTOG standard of limiting the target volume to the primary tumor and involved nodes. Copyright © 2012 Elsevier Inc. All rights reserved.

SU-E-CAMPUS-J-04: Image Guided Radiation Therapy (IGRT): Review of Technical Standards and Credentialing in Radiotherapy Clinical Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giaddui, T; Chen, W; Yu, J

2014-06-15

Purpose: To review IGRT credentialing experience and unexpected technical issues encountered in connection with advanced radiotherapy technologies as implemented in RTOG clinical trials. To update IGRT credentialing procedures with the aim of improving the quality of the process, and to increase the proportion of IGRT credentialing compliance. To develop a living disease site-specific IGRT encyclopedia. Methods: Numerous technical issues were encountered during the IGRT credentialing process. The criteria used for credentialing review were based on: image quality; anatomy included in fused data sets and shift results. Credentialing requirements have been updated according to the AAPM task group reports for IGRTmore » to ensure that all required technical items are included in the quality review process. Implementation instructions have been updated and expanded for recent protocols. Results: Technical issues observed during the credentialing review process include, but are not limited to: poor quality images; inadequate image acquisition region; poor data quality; shifts larger than acceptable; no soft tissue surrogate. The updated IGRT credentialing process will address these issues and will also include the technical items required from AAPM: TG 104; TG 142 and TG 179 reports. An instruction manual has been developed describing a remote credentialing method for reviewers. Submission requirements are updated, including images/documents as well as facility questionnaire. The review report now includes summary of the review process and the parameters that reviewers check. We have reached consensus on the minimum IGRT technical requirement for a number of disease sites. RTOG 1311(NRG-BR002A Phase 1 Study of Stereotactic Body Radiotherapy (SBRT) for the Treatment of Multiple Metastases) is an example, here; the protocol specified the minimum requirement for each anatomical sites (with/without fiducials). Conclusion: Technical issues are identified and reported. IGRT guidelines are updated, with the corresponding credentialing requirements. An IGRT encyclopedia describing site-specific implementation issues is currently in development.« less

The impact of concurrent granulocyte-macrophage colony-stimulating factor on quality of life in head and neck cancer patients: results of the randomized, placebo-controlled Radiation Therapy Oncology Group 9901 trial.

PubMed

Hoffman, Karen E; Pugh, Stephanie L; James, Jennifer L; Scarantino, Charles; Movsas, Benjamin; Valicenti, Richard K; Fortin, Andre; Pollock, JonDavid; Kim, Harold; Brachman, David G; Berk, Lawrence B; Bruner, Deborah Watkins; Kachnic, Lisa A

2014-08-01

The Radiation Therapy Oncology Group (RTOG) conducted a randomized, placebo-controlled trial evaluating the efficacy of GM-CSF in reducing mucosal injury and symptom burden from curative radiotherapy for head and neck (H&N) cancer. Eligible patients with H&N cancer receiving radiation encompassing ≥50 % of the oral cavity or oropharynx received subcutaneous GM-CSF or placebo. Quality of life (QoL) was assessed using the RTOG-modified University of Washington H&N Symptom Questionnaire at baseline 4, 13, 26, and 48 weeks from radiation initiation. Of 125 eligible patients, 114 were evaluable for QoL (58 GM-CSF, 56 placebo). Patient demographics, clinical characteristics, and baseline symptom scores were well balanced between the treatment arms. At the end of the acute period (13 weeks), patients in both arms reported negative change in total symptom score indicating increase in symptom burden relative to baseline (mean -18.4 GM-CSF, -20.8 placebo). There was no difference in change in total symptom score (p > 0.05) or change in mucous, pain, eating, or activity domain scores (p > 0.01) between patients in the GM-CSF and placebo arms. Analysis limited to patients treated per protocol or with an acceptable protocol deviation also found no difference in change in total symptom score (p > 0.05) or change in domain scores (p > 0.01) between treatment arms. Provider assessment of acute mucositis during treatment did not correlate with patient-reported mucous domain and total symptom scores (p > 0.05). GM-CSF administered concurrently during head and neck radiation does not appear to significantly improve patient-reported QoL symptom burden.

The RTOG Outcomes Model: economic end points and measures.

PubMed

Konski, Andre; Watkins-Bruner, Deborah

2004-03-01

Recognising the value added by economic evaluations of clinical trials and the interaction of clinical, humanistic and economic end points, the Radiation Therapy Oncology Group (RTOG) has developed an Outcomes Model that guides the comprehensive assessment of this triad of end points. This paper will focus on the economic component of the model. The Economic Impact Committee was founded in 1994 to study the economic impact of clinical trials of cancer care. A steep learning curve ensued with considerable time initially spent understanding the methodology of economic analysis. Since then, economic analyses have been performed on RTOG clinical trials involving treatments for patients with non-small cell lung cancer, locally-advanced head and neck cancer and prostate cancer. As the care of cancer patients evolves with time, so has the economic analyses performed by the Economic Impact Committee. This paper documents the evolution of the cost-effectiveness analyses of RTOG from performing average cost-utility analysis to more technically sophisticated Monte Carlo simulation of Markov models, to incorporating prospective economic analyses as an initial end point. Briefly, results indicated that, accounting for quality-adjusted survival, concurrent chemotherapy and radiation for the treatment of non-small cell lung cancer, more aggressive radiation fractionation schedules for head and neck cancer and the addition of hormone therapy to radiation for prostate cancer are within the range of economically acceptable recommendations. The RTOG economic analyses have provided information that can further inform clinicians and policy makers of the value added of new or improved treatments.

Compiling with Types

DTIC Science & Technology

1995-12-01

ogy and Theoretical Computer Science 1993, Bombay, New York, 1993. Springer-Verlag. Extended abstract. [17] E. Biagioni . Sequence types for functional...FOX-95-06. [18] E. Biagioni , R. Harper, P. Lee, and B. Milnes. Signatures for a network protocol stack: A systems application of Standard ML. In ACM

Dosimetric effect of multileaf collimator leaf width on volumetric modulated arc stereotactic radiotherapy for spine tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amoush, Ahmad, E-mail: aamoush@augusta.edu; Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44195; Long, Huang

This work aimed to study the dosimetric effect of multileaf collimator (MLC) leaf widths in treatment plans for patients receiving volumetric modulated arc therapy (VMAT) for spine stereotactic body radiation therapy (SBRT). Thirteen patients treated with spine SBRT were retrospectively selected for this study. The patients were treated following the protocol of the Radiation Therapy Oncology Group 0631 (RTOG 0631) for spine metastasis. The prescription dose was 16 Gy in 1 fraction to 90% of the target volume (V16 > 90%). The maximum spinal cord dose of 14 Gy and 10% of the spinal cord receiving < 10 Gy (V10) were the acceptable tolerance doses. For themore » purpose of this study, 2 dual-arc VMAT plans were created for each patient using 3 different MLC leaf widths: 2.5 mm, 4 mm, and 5 mm. The compliance with the RTOG 0631 protocol, conformity index (CI), dose gradient index (DGI), and number of monitor units (MUs) were compared. The average V16Gy of the targets was 91.8 ± 1.2%, 92.2 ± 2.1%, and 91.7 ± 2.3% for 2.5-mm, 4-mm, and 5-mm leaf widths, respectively (p = 0.78). Accordingly, the average CI was 1.45 ± 0.4, 1.47 ± 0.29, and 1.47 ± 0.31 (p = 0.98), respectively. The average DGI was 0.22 ± 0.04, 0.20 ± 0.06, and 0.22 ± 0.05, respectively (p = 0.77). The average maximum dose to the spinal cord was 12.45 ± 1.0 Gy, 12.80 ± 1.0 Gy, and 12.48 ± 1.1 (p = 0.62) and V10% of the spinal cord was 3.6 ± 2.1%, 5.6 ± 2.8%, and 5.5 ± 3.0% (p = 0.11) for 2.5-mm, 4-mm, and 5-mm leaf widths, respectively. Accordingly, the average number of MUs was 4341 ± 500 MU, 5019 ± 834 MU, and 4606 ± 691 MU, respectively (p = 0.053). The use of 2.5-mm, 4-mm, and 5-mm MLCs achieved similar VMAT plan quality as recommended by the RTOG 0631. The dosimetric parameters were also comparable for the 3 MLCs. In general, any of these leaf widths can be used for spine SBRT using VMAT.« less

Shortcomings of protocols of drug trials in relation to sponsorship as identified by Research Ethics Committees: analysis of comments raised during ethical review.

PubMed

van Lent, Marlies; Rongen, Gerard A; Out, Henk J

2014-12-10

Submission of study protocols to research ethics committees (RECs) constitutes one of the earliest stages at which planned trials are documented in detail. Previous studies have investigated the amendments requested from researchers by RECs, but the type of issues raised during REC review have not been compared by sponsor type. The objective of this study was to identify recurring shortcomings in protocols of drug trials based on REC comments and to assess whether these were more common among industry-sponsored or non-industry trials. Retrospective analysis of 226 protocols of drug trials approved in 2010-2011 by three RECs affiliated to academic medical centres in The Netherlands. For each protocol, information on sponsorship, number of participating centres, participating countries, study phase, registration status of the study drug, and type and number of subjects was retrieved. REC comments were extracted from decision letters sent to investigators after review and were classified using a predefined checklist that was based on legislation and guidelines on clinical drug research and previous literature. Most protocols received comments regarding participant information and consent forms (n = 182, 80.5%), methodology and statistical analyses (n = 160, 70.8%), and supporting documentation, including trial agreements and certificates of insurance (n = 154, 68.1%). Of the submitted protocols, 122 (54.0%) were non-industry and 104 (46.0%) were industry-sponsored trials. Non-industry trials more often received comments on subject selection (n = 44, 36.1%) than industry-sponsored trials (n = 18, 17.3%; RR, 1.58; 95% CI, 1.01 to 2.47), and on methodology and statistical analyses (n = 95, 77.9% versus n = 65, 62.5%, respectively; RR, 1.18; 95% CI, 1.01 to 1.37). Non-industry trials less often received comments on supporting documentation (n = 72, 59.0%) than industry-sponsored trials (n = 82, 78.8%; RR, 0.83; 95% CI, 0.72 to 0.95). RECs identified important ethical and methodological shortcomings in protocols of both industry-sponsored and non-industry drug trials. Investigators, especially of non-industry trials, should better prepare their research protocols in order to facilitate the ethical review process.

The activity of French research ethics committees and characteristics of biomedical research protocols involving humans: a retrospective cohort study.

PubMed

Decullier, Evelyne; Lhéritier, Véronique; Chapuis, François

2005-10-17

Clinical trials throughout the world must be evaluated by research ethics committees. No one has yet attempted to clearly quantify at the national level the activity of ethics committees and describe the characteristics of the protocols submitted. The objectives of this study were to describe 1) the workload and the activity of Research Ethics Committees in France, and 2) the characteristics of protocols approved on a nation-wide basis. Retrospective cohort of 976 protocols approved by a representative sample of 25/48 of French Research Ethics Committees in 1994. Protocols characteristics (design, study size, investigator), number of revisions requested by the ethics committee before approval, time to approval and number of amendments after approval were collected for each protocol by trained research assistant using the committee's files and archives. Thirty-one percent of protocols were approved with no modifications requested in 16 days (95% CI: 14-17). The number of revisions requested by the committee, and amendments submitted by the investigator was on average respectively 39 (95% CI: 25-53) and 37 (95% CI: 27-46), per committee and per year. When revisions were requested, the main reasons were related to information to the patient (28%) and consent modalities (18%). Drugs were the object of research in 68% of the protocols examined. The majority of the research was national (80%) with a predominance of single-centre studies. Workload per protocol has been estimated at twelve and half hours on average for administrative support and at eleven and half hours for expertise. The estimated workload justifies specific and independent administrative and financial support for Research Ethics Committees.

The impact of RTOG 0614 and RTOG 0933 trials in routine clinical practice: The US Survey of Utilization of Memantine and IMRT planning for hippocampus sparing in patients receiving whole brain radiotherapy for brain metastases.

PubMed

Slade, Alexander N; Stanic, Sinisa

2016-03-01

Two recent clinical trials, phase III RTOG 0614 and phase II RTOG 0933, showed some effectiveness of Memantine and IMRT planning for hippocampus sparing, among patients receiving whole brain radiotherapy (WBRT) for brain metastases; however, their use in routine clinical practice is unknown. A survey was sent to 1933 radiation oncologists in the US. Data collected included utilization of Memantine and hippocampus sparing, reasons for adoption and non-adoption, and demographic variables. A total of 196 radiation oncologists responded to the survey, with 64% reporting using Memantine in almost none of the patients receiving WBRT for brain metastases, and only 11% considering Memantine for <10% of their patients. The most common reason for not using Memantine was a poor patient performance status, and limited life expectancy. Likewise, 56% of radiation oncologists would not change their clinical practice to include hippocampus sparing IMRT in patients receiving WBRT based on the results of RTOG 0933. Further validation of hippocampus sparing in a phase III trial was supported by 71% of radiation oncologists, whereas further exploration of Memantine for this purpose in a phase III trial was supported by 42%. At this time, the majority of surveyed radiation oncologists in the US do not use Memantine, or IMRT planning for hippocampus sparing in patients receiving WBRT. Further validation of the hippocampus sparing concept in a phase III trial was supported, before adopting it in routine clinical practice. Copyright © 2015 Elsevier Inc. All rights reserved.

Oral health care activities performed by caregivers for institutionalized elderly in Barcelona-Spain

PubMed Central

Cornejo-Ovalle, Marco; Costa-de-Lima, Kenio; Pérez, Glória; Borrell, Carme; Casals-Peidro, Elías

2013-01-01

Objectives: To describe the frequency of brushing teeth and cleaning of dentures, performed by caregivers, for institutionalized elderly people. Methods: A cross-sectional study in a sample of 196 caregivers of 31 health centers in Barcelona. The dependent variables were frequency of dental brushing and frequency of cleaning of dentures of the elderly by caregivers. The independent variables were characteristics of caregivers and institutions. We performed bivariate and multivariate descriptive analyses. Robust Poisson regression models were fitted to determine factors associated with the dependent variables and to assess the strength of the association. Results: 83% of caregivers were women, 79% worked on more than one shift, 42% worked only out of necessity, 92% were trained to care for elderly persons, 67% were trained in oral hygiene care for the elderly, and 73% recognized the existence of institutional protocols on oral health among residents. The variables explaining the lower frequency of brushing teeth by caregivers for the elderly, adjusted for the workload, were: no training in the care of elderly persons (PRa 1.7 CI95%: 1.6-1.8), not fully agreeing with the importance of oral health care of the elderly (PRa 2.5 CI95%: 1.5-4.1) and not knowing of the existence of oral health protocols (PRa 1.8 CI95%: 1.2-2.6). The variables that explain the lower frequency of cleaning dentures, adjusted for the workload, were lack of training in elderly care (PRa 1.7 CI95%: 1.3-1.9) and not knowing of the existence of protocols (PRa 3.7 CI95%: 1.6-8.7). Conclusion: The majority of caregivers perform activities of oral health care for the elderly at least once per day. The frequency of this care depends mainly on whether caregivers are trained to perform these activities, the importance given to oral health, the workload of caregivers and the existence of institutional protocols on oral health of institutionalized elderly persons. Key words:Institutionalized elderly, caregivers, oral hygiene, long-term care, oral health. PMID:23524433

Human Papillomavirus and Overall Survival After Progression of Oropharyngeal Squamous Cell Carcinoma

PubMed Central

Fakhry, Carole; Zhang, Qiang; Nguyen-Tan, Phuc Felix; Rosenthal, David; El-Naggar, Adel; Garden, Adam S.; Soulieres, Denis; Trotti, Andy; Avizonis, Vilija; Ridge, John Andrew; Harris, Jonathan; Le, Quynh-Thu; Gillison, Maura

2014-01-01

Purpose Risk of cancer progression is reduced for patients with human papillomavirus (HPV) –positive oropharynx cancer (OPC) relative to HPV-negative OPC, but it is unknown whether risk of death after progression is similarly reduced. Patients and Methods Patients with stage III-IV OPC enrolled onto Radiation Therapy Oncology Group trials 0129 or RTOG 0522 who had known tumor p16 status plus local, regional, and/or distant progression after receiving platinum-based chemoradiotherapy were eligible for a retrospective analysis of the association between tumor p16 status and overall survival (OS) after disease progression. Rates were estimated by Kaplan-Meier method and compared by log-rank; hazard ratios (HRs) were estimated by Cox models. Tests and models were stratified by treatment protocol. Results A total of 181 patients with p16-positive (n = 105) or p16-negative (n = 76) OPC were included in the analysis. Patterns of failure and median time to progression (8.2 v 7.3 months; P = .67) were similar for patients with p16-positive and p16-negative tumors. After a median follow-up period of 4.0 years after disease progression, patients with p16-positive OPC had significantly improved survival rates compared with p16-negative patients (2-year OS, 54.6% v 27.6%; median, 2.6 v 0.8 years; P < .001). p16-positive tumor status (HR, 0.48; 95% CI, 0.31 to 0.74) and receipt of salvage surgery (HR, 0.48; 95% CI; 0.27 to 0.84) reduced risk of death after disease progression whereas distant versus locoregional progression (HR, 1.99; 95% CI, 1.28 to 3.09) increased risk, after adjustment for tumor stage and cigarette pack-years at enrollment. Conclusion Tumor HPV status is a strong and independent predictor of OS after disease progression and should be a stratification factor for clinical trials for patients with recurrent or metastatic OPC. PMID:24958820

SU-E-T-43: A Methodology for Quality Control of IMPT Treatment Plan Based On VMAT Plan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, S; Tianjin Medical University Cancer Institute and Hospital; Yang, Y

Purpose: IMPT plan design is highly dependent on planner’s experiences. VMAT plan design is relatively mature and can even be automated. The quality of IMPT plan designed by in-experienced planner could be inferior to that of VMAT plan designed by experienced planner or automatic planning software. Here we introduce a method for designing IMPT plan based on VMAT plan to ensure the IMPT plan be superior to IMRT/VMAT plan for majority clinical scenario. Methods: To design a new IMPT plan, a VMAT plan is first generated either by experienced planner or by in-house developed automatic planning system. An in-house developedmore » tool is used to generate the dose volume constrains for the IMPT plan as plan template to Eclipse TPS. The beam angles for IMPT plan are selected based on the preferred angles in the VMAT plan. IMPT plan is designed by importing the plan objectives generated from VMAT plan. Majority thoracic IMPT plans are designed using this plan approach in our center. In this work, a thoracic IMPT plan under RTOG 1308 protocol is selected to demonstrate the effectiveness and efficiency of this approach. The dosimetric indices of IMPT are compared with VMAT plan. Results: The PTV D95, lung V20, MLD, mean heart dose, esophagus D1, cord D1 are 70Gy, 31%, 17.8Gy, 25.5Gy, 73Gy, 45Gy for IMPT plan and 65.3Gy, 34%, 21.6Gy, 35Gy, 74Gy, 48Gy for VMAT plan. For majority cases, the high dose region of the normal tissue which is in proximity of PTV is comparable between IMPT and VMAT plan. The low dose region of the IMPT plan is significantly better than VMAT plan. Conclusion: Using the knowledge gained in VMAT plan design can help efficiently and effectively design high quality IMPT plan. The quality of IMPT plan can be controlled to ensure the superiority of IMPT plan compared to VMAT/IMRT plan.« less

Expression of the DNA repair gene MLH1 correlates with survival in patients who have resected pancreatic cancer and have received adjuvant chemoradiation: NRG Oncology RTOG Study 9704.

PubMed

Lawrence, Yaacov R; Moughan, Jennifer; Magliocco, Anthony M; Klimowicz, Alexander C; Regine, William F; Mowat, Rex B; DiPetrillo, Thomas A; Small, William; Simko, Jeffry P; Golan, Talia; Winter, Kathryn A; Guha, Chandan; Crane, Christopher H; Dicker, Adam P

2018-02-01

The majority of patients with pancreatic cancer who undergo curative resection experience rapid disease recurrence. In previous small studies, high expression of the mismatch-repair protein mutL protein homolog 1 (MLH1) in pancreatic cancers was associated with better outcomes. The objective of this study was to validate the association between MLH1 expression and survival in patients who underwent resection of pancreatic cancer and received adjuvant chemoradiation. Samples were obtained from the NRG Oncology Radiation Therapy Oncology Group 9704 prospective, randomized trial (clinicaltrials.gov identifier NCT00003216), which compared 2 adjuvant protocols in patients with pancreatic cancer who underwent resection. Tissue microarrays were prepared from formalin-fixed, paraffin-embedded, resected tumor tissues. MLH1 expression was quantified using fluorescence immunohistochemistry and automated quantitative analysis, and expression was dichotomized above and below the median value. Immunohistochemical staining was successfully performed on 117 patients for MLH1 (60 and 57 patients from the 2 arms). The characteristics of the participants who had tissue samples available were similar to those of the trial population as a whole. At the time of analysis, 84% of participants had died, with a median survival of 17 months. Elevated MLH1 expression levels in tumor nuclei were significantly correlated with longer disease-free and overall survival in each arm individually and in both arms combined. Two-year overall survival was 16% in patients who had low MLH1 expression levels and 53% in those who had high MLH1 expression levels (P < .0001 for both arms combined). This association remained true on a multivariate analysis that allowed for lymph node status (hazard ratio, 0.41; 95% confidence interval, 0.27-0.63; P < .0001). In the current sample, MLH1 expression was correlated with long-term survival. Further studies should assess whether MLH1 expression predicts which patients with localized pancreatic cancer may benefit most from aggressive, multimodality treatment. Cancer 2018;124:491-8. © 2017 American Cancer Society. © 2017 American Cancer Society.

FIVE-YEAR RESULTS OF ADJUVANT RADIOTHER

PubMed Central

Osa, Etin-Osa O.; DeWyngaert, Keith; Roses, Daniel; Speyer, James; Guth, Amber; Axelrod, Deborah; Kerimian, Maria Fenton; Goldberg, Judith D.; Formenti, Silvia C.

2015-01-01

Purpose/Objective A technique of prone breast radiotherapy delivered by a regimen of accelerated intensity modulated radiation therapy (IMRT) with a concurrent boost to the tumor bed, was developed at our institution. We report the five year results of this approach. Methods and Materials Between 2003–2006, 404 patients with Stage I–II breast cancer were prospectively enrolled into two consecutive protocols, institutional trials 03–30 and 05–181, that used the same regimen of 40.5Gy/15 fractions delivered to the index breast over 3 weeks, with a concomitant daily boost to the tumor bed of 0.5Gy (total dose=48Gy). All patients were treated after segmental mastectomy, had negative margins, and nodal assessment. Patients were set up prone: only if lung or heart volumes were in the field was a supine set-up attempted, and chosen if found to better spare these organs. Results 92% of patients were treated prone, 8% supine. 72% had stage I, 28% stage II invasive breast cancer. In-field lung volume ranged from 0 –228.27cc, mean: 19.65cc. In-field heart volume for left breast cancer patients ranged from 0–21.24cc, mean: 1.59cc. There was no heart in the field for right breast cancer patients. At a median follow-up of five years, the five-year cumulative incidence of isolated ipsilateral breast tumor recurrence was 0.82% (95% CI: 0.65–1.04). The five-year cumulative incidence of regional recurrence was 0.53% (95% CI:0.41–0.69) and the five-year overall cumulative death rate was 1.28% (95% CI: 0.48–3.38). 82% (95% CI: 77–85) of patients judged their final cosmetic result as excellent/good. Conclusions Prone accelerated IMRT with a concomitant boost results in excellent local control, optimal sparing of heart and lung, with good cosmesis. RTOG 10–05, a phase III, multi-institutional, randomized trial is ongoing and is evaluating the equivalence of a similar dose and fractionation approach to standard six weeks radiotherapy with a sequential boost. PMID:24867535

SU-F-BRA-14: Optimization of Dosimetric Guidelines for Accelerated Partial Breast Irradiation (APBI) Using the Strut-Adjusted Volume Implant (SAVI)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mooney, K; Altman, M; Garcia-Ramirez, J

Purpose: Treatment planning guidelines for accelerated partial breast irradiation (ABPI) using the strut-adjusted volume implant (SAVI) are inconsistent between the manufacturer and NSABP B-39/RTOG 0413 protocol. Furthermore neither set of guidelines accounts for different applicator sizes. The purpose of this work is to establish guidelines specific to the SAVI that are based on clinically achievable dose distributions. Methods: Sixty-two consecutive patients were implanted with a SAVI and prescribed to receive 34 Gy in 10 fractions twice daily using high dose-rate (HDR) Ir-192 brachytherapy. The target (PTV-EVAL) was defined per NSABP. The treatments were planned and evaluated using a combination ofmore » dosimetric planning goals provided by the NSABP, the manufacturer, and our prior clinical experience. Parameters evaluated included maximum doses to skin and ribs, and volumes of PTV-EVAL receiving 90%, 95%, 100%, 150%, and 200% of the prescription (V90, etc). All target parameters were evaluated for correlation with device size using the Pearson correlation coefficient. Revised dosimetric guidelines for target coverage and heterogeneity were determined from this population. Results: Revised guidelines for minimum target coverage (ideal in parentheses): V90≥95%(97%), V95≥90%(95%), V100≥88%(91%). The only dosimetric parameters that were significantly correlated (p<0.05) with device size were V150 and V200. Heterogeneity criteria were revised for the 6–1 Mini/6-1 applicators to V150≤30cc and V200≤15cc, and unchanged for the other sizes. Re-evaluation of patient plans showed 90% (56/62) met the revised minimum guidelines and 76% (47/62) met the ideal guidelines. All and 56/62 patients met our institutional guidelines for maximum skin and rib dose, respectively. Conclusions: We have optimized dosimetric guidelines for the SAVI applicators, and found that implementation of these revised guidelines for SAVI treatment planning yielded target coverage exceeding that required by existing guidelines while preserving heterogeneity constraints and minimizing dose to organs at risk.« less

Clinical outcomes and mortality before and after implementation of a pediatric sepsis protocol in a limited resource setting: A retrospective cohort study in Bangladesh.

PubMed

Kortz, Teresa Bleakly; Axelrod, David M; Chisti, Mohammod J; Kache, Saraswati

2017-01-01

Pediatric sepsis has a high mortality rate in limited resource settings. Sepsis protocols have been shown to be a cost-effective strategy to improve morbidity and mortality in a variety of populations and settings. At Dhaka Hospital in Bangladesh, mortality from pediatric sepsis in high-risk children previously approached 60%, which prompted the implementation of an evidenced-based protocol in 2010. The clinical effectiveness of this protocol had not been measured. We hypothesized that implementation of a pediatric sepsis protocol improved clinical outcomes, including reducing mortality and length of hospital stay. This was a retrospective cohort study of children 1-59 months old with a diagnosis of sepsis, severe sepsis or septic shock admitted to Dhaka Hospital from 10/25/2009-10/25/2011. The primary outcome was inpatient mortality pre- and post-protocol implementation. Secondary outcomes included fluid overload, heart failure, respiratory insufficiency, length of hospital stay, and protocol compliance, as measured by antibiotic and fluid bolus administration within 60 minutes of hospital presentation. 404 patients were identified by a key-word search of the electronic medical record; 328 patients with a primary diagnosis of sepsis, severe sepsis, or septic shock were included (143 pre- and185 post-protocol) in the analysis. Pre- and post-protocol mortality were similar and not statistically significant (32.17% vs. 34.59%, p = 0.72). The adjusted odds ratio (AOR) for post-protocol mortality was 1.55 (95% CI, 0.88-2.71). The odds for developing fluid overload were significantly higher post-protocol (AOR 3.45, 95% CI, 2.04-5.85), as were the odds of developing heart failure (AOR 4.52, 95% CI, 1.43-14.29) and having a longer median length of stay (AOR 1.81, 95% CI 1.10-2.96). There was no statistically significant difference in respiratory insufficiency (pre- 65.7% vs. post- 70.3%, p = 0.4) or antibiotic administration between the cohorts (pre- 16.08% vs. post- 12.43%, p = 0.42). Implementation of a pediatric sepsis protocol did not improve all-cause mortality or length of stay and may have been associated with increased fluid overload and heart failure during the study period in a large, non-governmental hospital in Bangladesh. Similar rates of early antibiotic administration may indicate poor protocol compliance. Though evidenced-based protocols are a potential cost-effective strategy to improve outcomes, future studies should focus on optimal implementation of context-relevant sepsis protocols in limited resource settings.

Effects of Boron-Based Gel on Radiation-Induced Dermatitis in Breast Cancer: A Double-Blind, Placebo-Controlled Trial.

PubMed

Aysan, Erhan; Idiz, Ufuk Oguz; Elmas, Leyla; Saglam, Esra Kaytan; Akgun, Zuleyha; Yucel, Serap Baskaya

2017-06-01

This study is aimed to evaluate the effects of boron on radiation-induced skin reactions (RISR) in breast cancer patients. After 47 patients with invasive ductal carcinoma underwent radiotherapy, 23 (49%) received a boron-based gel, and 24 (51%) received placebo. Assessments were performed according to the Radiation Therapy Oncology Group (RTOG) skin scale and a Five-Point Horizontal Scale (FPHS). At the end of the fifth week of radiotherapy, the RTOG scores in the boron group were significantly lower than those in the placebo group (p = .024). The FPHS score was higher in the placebo group than in the boron group, and this difference was not statistically significant (p = .079). Using the RTOG scoring system, we revealed that the application of a boron-based gel diminished RISR. The mechanism of action is unclear but may be related to antioxidant, wound healing, and thermal degradation effects of boron.

SU-E-J-206: Adaptive Radiotherapy for Gynecological Malignancies with MRIGuided Cobolt-60 Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lamb, J; Kamrava, M; Agazaryan, N

Purpose: Even in the IMRT era, bowel toxicity and bone marrow irradiation remain concerns with pelvic irradiation. We examine the potential gain from an adaptive radiotherapy workflow for post-operative gynecological patients treated to pelvic targets including lymph nodes using MRI-guided Co-60 radiation therapy. Methods: An adaptive workflow was developed with the intent of minimizing time overhead of adaptive planning. A pilot study was performed using retrospectively analyzed images from one patient’s treatment. The patient’s treated plan was created using conventional PTV margins. Adaptive treatment was simulated on the patient’s first three fractions. The daily PTV was created by removing non-targetmore » tissue, including bone, muscle and bowel, from the initial PTV based on the daily MRI. The number of beams, beam angles, and optimization parameters were kept constant, and the plan was re-optimized. Normal tissue contours were not adjusted for the re-optimization, but were adjusted for evaluation of plan quality. Plan quality was evaluated based on PTV coverage and normal tissue DVH points per treatment protocol. Bowel was contoured as the entire bowel bag per protocol at our institution. Pelvic bone marrow was contoured per RTOG protocol 1203. Results: For the clinically treated plan, the volume of bowel receiving 45 Gy was 380 cc, 53% of the rectum received 30 Gy, 35% of the bladder received 45 Gy, and 28% of the pelvic bone marrow received 40 Gy. For the adaptive plans, the volume of bowel receiving 45 Gy was 175–201 cc, 55–62% of the rectum received 30 Gy, 21– 27% of the bladder received 45 Gy, and 13–17% of the pelvic bone marrow received 40 Gy. Conclusion: Adaptive planning led to a large reduction of bowel and bone marrow dose in this pilot study. Further study of on-line adaptive techniques for the radiotherapy of pelvic lymph nodes is warranted. Dr. Low is a member of the scientific advisory board of ViewRay, Inc.« less

Left hippocampus sparing whole brain radiotherapy (WBRT): A planning study.

PubMed

Kazda, Tomas; Vrzal, Miroslav; Prochazka, Tomas; Dvoracek, Petr; Burkon, Petr; Pospisil, Petr; Dziacky, Adam; Nikl, Tomas; Jancalek, Radim; Slampa, Pavel; Lakomy, Radek

2017-12-01

Unilateral sparing of the dominant (left) hippocampus during whole brain radiotherapy (WBRT) could mitigate cognitive decline, especially verbal memory, similar to the widely investigated bilateral hippocampus avoidance (HA-WBRT). The aim of this planning study is dosimetrical comparison of HA-WBRT with only left hippocampus sparing (LHA-WBRT) plans. HA-WBRT plans for 10 patients were prepared in accordance with RTOG 0933 trial and served as baseline for comparisons with several LHA-WBRT plans prepared with an effort: 1) to maintain the same left hippocampus dosimetry ("BEST PTV") and 2) to maintain same dosimetry in planning target volume as in HA-WBRT ("BEST LH"). All HA-WBRT plans met RTOG 0933 protocol criteria with a mean Conformity index 1.09 and mean Homogeneity index (HI) 0.21. Mean right and left hippocampal D100% was 7.8 Gy and 8.5 Gy and mean Dmax 14.0 Gy and 13.8 Gy, respectively. "BEST PTV" plans reduced HI by 31.2% (P=0.005) which is mirrored by lower PTV_D2% (-0.8 Gy, P=0.005) and higher PTV_D98% (+1.3 Gy, P=0.005) as well as decreased optic pathway's Dmax by 1 Gy. In "BEST LH", mean D100% and Dmax for the left hippocampus were significantly reduced by 11.2% (P=0.005) and 10.9% (P=0.005) respectively. LHA-WBRT could improve target coverage and/or further decrease in dose to spared hippocampus. Future clinical trials must confirm whether statistically significant reduction in left hippocampal dose is also clinically significant.

Long-Term Results of a Phase II Trial of Ultrasound-Guided Radioactive Implantation of the Prostate for Definitive Management of Localized Adenocarcinoma of the Prostate (RTOG 98-05)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lawton, Colleen A., E-mail: clawton@mcw.edu; Hunt, Daniel; Lee, W. Robert

2011-09-01

Purpose: To evaluate the long-term effectiveness of transrectal ultrasound-guided permanent radioactive I{sup 125} implantation of the prostate for organ confined adenocarcinoma of the prostate compared with historical data of prostatectomy and external beam radiotherapy within a cooperative group setting. Methods and Materials: Patients accrued to this study had histologically confirmed, locally confined adenocarcinoma of the prostate clinical stage T1b, T1c, or T2a; no nodal or metastatic disease; prostate-specific antigen level of {<=}10 ng/ml; and a Gleason score of {<=}6. All patients underwent transrectal ultrasound-guided radioactive I{sup 125} seed implantation into the prostate. The prescribed dose was 145 Gy to themore » prostate planning target volume. Results: A total of 101 patients from 27 institutions were accrued to this protocol; by design, no single institution accrued more than 8 patients. There were 94 eligible patients. The median follow up was 8.1 years (range, 0.1-9.2 years). After 8 years, 8 patients had protocol-defined biochemical (prostate-specific antigen) failure (cumulative incidence, 8.0%); 5 patients had local failure (cumulative incidence, 5.5%); and 1 patient had distant failure (cumulative incidence, 1.1%; this patient also had biochemical failure and died of causes not related to prostate cancer). The 8-year overall survival rate was 88%. At last follow-up, no patient had died of prostate cancer or related toxicities. Three patients had maximum late toxicities of Grade 3, all of which were genitourinary. No Grade 4 or 5 toxicities were observed. Conclusions: The long-term results of this clinical trial have demonstrated that this kind of trial can be successfully completed through the RTOG and that results in terms of biochemical failure and toxicity compare very favorably with other brachytherapy published series as well as surgical and external beam radiotherapy series. In addition, the prospective, multicenter design highlights the probable generalizability of the outcomes.« less

Assessing exercise cardiac reserve using real-time cardiovascular magnetic resonance.

PubMed

Le, Thu-Thao; Bryant, Jennifer Ann; Ting, Alicia Er; Ho, Pei Yi; Su, Boyang; Teo, Raymond Choon Chye; Gan, Julian Siong-Jin; Chung, Yiu-Cho; O'Regan, Declan P; Cook, Stuart A; Chin, Calvin Woon-Loong

2017-01-23

Exercise cardiovascular magnetic resonance (ExCMR) has great potential for clinical use but its development has been limited by a lack of compatible equipment and robust real-time imaging techniques. We developed an exCMR protocol using an in-scanner cycle ergometer and assessed its performance in differentiating athletes from non-athletes. Free-breathing real-time CMR (1.5T Aera, Siemens) was performed in 11 athletes (5 males; median age 29 [IQR: 28-39] years) and 16 age- and sex-matched healthy volunteers (7 males; median age 26 [interquartile range (IQR): 25-33] years). All participants underwent an in-scanner exercise protocol on a CMR compatible cycle ergometer (Lode BV, the Netherlands), with an initial workload of 25W followed by 25W-increment every minute. In 20 individuals, exercise capacity was also evaluated by cardiopulmonary exercise test (CPET). Scan-rescan reproducibility was assessed in 10 individuals, at least 7 days apart. The exCMR protocol demonstrated excellent scan-rescan (cardiac index (CI): 0.2 ± 0.5L/min/m 2 ) and inter-observer (ventricular volumes: 1.2 ± 5.3mL) reproducibility. CI derived from exCMR and CPET had excellent correlation (r = 0.83, p < 0.001) and agreement (1.7 ± 1.8L/min/m 2 ). Despite similar values at rest (P = 0.87), athletes had increased exercise CI compared to healthy individuals (at peak exercise: 12.2 [IQR: 10.2-13.5] L/min/m 2 versus 8.9 [IQR: 7.5-10.1] L/min/m 2 , respectively; P < 0.001). Peak exercise CI, where image acquisition lasted 13-17 s, outperformed that at rest (c-statistics = 0.95 [95% confidence interval: 0.87-1.00] versus 0.48 [95% confidence interval: 0.23-0.72], respectively; P < 0.0001 for comparison) in differentiating athletes from healthy volunteers; and had similar performance as VO 2max (c-statistics = 0.84 [95% confidence interval = 0.62-1.00]; P = 0.29 for comparison). We have developed a novel in-scanner exCMR protocol using real-time CMR that is highly reproducible. It may now be developed for clinical use for physiological studies of the heart and circulation.

Penile bulb dose and impotence after three-dimensional conformal radiotherapy for prostate cancer on RTOG 9406: Findings from a prospective, multi-institutional, phase I/II dose-escalation study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roach, Mack; Winter, Kathryn; Michalski, Jeffrey M.

2004-12-01

Purpose: To assess the relationship between the dose to the bulb of the penis and the risk of impotence in men treated on Radiation Therapy Oncology Group (RTOG) 9406. Methods and materials: Men enrolled on a Phase I/II dose-escalation study, RTOG 9406, who were reported to be potent at entry and evaluable (n = 158) were selected for inclusion. Follow-up evaluations were scheduled every 3, 4, and 6 months for the first, second, and the third through fifth years, then annually. At each follow-up visit an assessment of potency status was made. Penile structures were defined by a single observermore » blinded to the potency status, using Web-based, on-line software. The dosimetry for penile structures was calculated at the Quality Assurance Center at Washington University and provided to RTOG Statistical Headquarters to determine whether there was a relationship between dose and impotence. Results: Patients whose median penile dose was {>=}52.5 Gy had a greater risk of impotence compared with those receiving <52.5 Gy (p = 0.039). In a multivariate analysis neither age, the dose to the prostate, nor the use of hormonal therapy correlated with the risk of impotence. Conclusions: Dose to the bulb of the penis seems to be associated with the risk of radiation-induced impotence.« less

Improving the consistency in cervical esophageal target volume definition by special training.

PubMed

Tai, Patricia; Van Dyk, Jake; Battista, Jerry; Yu, Edward; Stitt, Larry; Tonita, Jon; Agboola, Olusegun; Brierley, James; Dar, Rashid; Leighton, Christopher; Malone, Shawn; Strang, Barbara; Truong, Pauline; Videtic, Gregory; Wong, C Shun; Wong, Rebecca; Youssef, Youssef

2002-07-01

Three-dimensional conformal radiation therapy requires the precise definition of the target volume. Its potential benefits could be offset by the inconsistency in target definition by radiation oncologists. In a previous survey of radiation oncologists, a large degree of variation in target volume definition of cervical esophageal cancer was noted for the boost phase of radiotherapy. The present study evaluated whether special training could improve the consistency in target volume definitions. A pre-training survey was performed to establish baseline values. This was followed by a special one-on-one training session on treatment planning based on the RTOG 94-05 protocol to 12 radiation oncologists. Target volumes were redrawn immediately and at 1-2 months later. Post-training vs. pre-training target volumes were compared. There was less variability in the longitudinal positions of the target volumes post-training compared to pre-training (p < 0.05 in 5 of 6 comparisons). One case had more variability due to the lack of a visible gross tumor on CT scans. Transverse contours of target volumes did not show any significant difference pre- or post-training. For cervical esophageal cancer, this study suggests that special training on protocol guidelines may improve consistency in target volume definition. Explicit protocol directions are required for situations where the gross tumor is not easily visible on CT scans. This may be particularly important for multicenter clinical trials, to reduce the occurrences of protocol violations.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gentile, Michelle S.; Usman, Asad A.; Neuschler, Erin I.

Purpose: The purpose of this study was to identify the axillary lymph nodes on pretreatment diagnostic computed tomography (CT) of the chest to determine their position relative to the anatomic axillary borders as defined by the Radiation Therapy Oncology Group (RTOG) breast cancer atlas for radiation therapy planning. Methods and Materials: Pretreatment diagnostic CT chest scans available for 30 breast cancer patients with clinically involved lymph nodes were fused with simulation CT. Contouring of axillary levels I, II, and III according to the RTOG guidelines was performed. Measurements were made from the area of distal tumor to the anatomic bordersmore » in 6 dimensions for each level. Results: Of the 30 patients, 100%, 93%, and 37% had clinical involvement of levels I, II, and III, respectively. The mean number of lymph nodes dissected was 13.6. The mean size of the largest lymph node was 2.4 cm. Extracapsular extension was seen in 23% of patients. In 97% of patients, an aspect of the involved lymph node lay outside of the anatomic border of a level. In 80% and 83% of patients, tumor extension was seen outside the cranial (1.78 ± 1.0 cm; range, 0.28-3.58 cm) and anterior (1.27 ± 0.92 cm; range, 0.24-3.58 cm) borders of level I, respectively. In 80% of patients, tumor extension was seen outside the caudal border of level II (1.36 ± 1.0 cm, range, 0.27-3.86 cm), and 0% to 33% of patients had tumor extension outside the remaining borders of all levels. Conclusions: To cover 95% of lymph nodes at the cranial and anterior borders of level I, an additional clinical target volume margin of 3.78 cm and 3.11 cm, respectively, is necessary. The RTOG guidelines may be insufficient for coverage of axillary disease in patients with clinical nodal involvement who are undergoing neoadjuvant chemotherapy, incomplete axillary dissection, or treatment with intensity modulated radiation therapy. In patients with pretreatment diagnostic CT chest scans, fusion with simulation CT should be considered for tumor delineation.« less

Impact of Intensity-Modulated Radiation Therapy Technique for Locally Advanced Non-Small-Cell Lung Cancer: A Secondary Analysis of the NRG Oncology RTOG 0617 Randomized Clinical Trial.

PubMed

Chun, Stephen G; Hu, Chen; Choy, Hak; Komaki, Ritsuko U; Timmerman, Robert D; Schild, Steven E; Bogart, Jeffrey A; Dobelbower, Michael C; Bosch, Walter; Galvin, James M; Kavadi, Vivek S; Narayan, Samir; Iyengar, Puneeth; Robinson, Clifford G; Wynn, Raymond B; Raben, Adam; Augspurger, Mark E; MacRae, Robert M; Paulus, Rebecca; Bradley, Jeffrey D

2017-01-01

Purpose Although intensity-modulated radiation therapy (IMRT) is increasingly used to treat locally advanced non-small-cell lung cancer (NSCLC), IMRT and three-dimensional conformal external beam radiation therapy (3D-CRT) have not been compared prospectively. This study compares 3D-CRT and IMRT outcomes for locally advanced NSCLC in a large prospective clinical trial. Patients and Methods A secondary analysis was performed to compare IMRT with 3D-CRT in NRG Oncology clinical trial RTOG 0617, in which patients received concurrent chemotherapy of carboplatin and paclitaxel with or without cetuximab, and 60- versus 74-Gy radiation doses. Comparisons included 2-year overall survival (OS), progression-free survival, local failure, distant metastasis, and selected Common Terminology Criteria for Adverse Events (version 3) ≥ grade 3 toxicities. Results The median follow-up was 21.3 months. Of 482 patients, 53% were treated with 3D-CRT and 47% with IMRT. The IMRT group had larger planning treatment volumes (median, 427 v 486 mL; P = .005); a larger planning treatment volume/volume of lung ratio (median, 0.13 v 0.15; P = .013); and more stage IIIB disease (30.3% v 38.6%, P = .056). Two-year OS, progression-free survival, local failure, and distant metastasis-free survival were not different between IMRT and 3D-CRT. IMRT was associated with less ≥ grade 3 pneumonitis (7.9% v 3.5%, P = .039) and a reduced risk in adjusted analyses (odds ratio, 0.41; 95% CI, 0.171 to 0.986; P = .046). IMRT also produced lower heart doses ( P < .05), and the volume of heart receiving 40 Gy (V40) was significantly associated with OS on adjusted analysis ( P < .05). The lung V5 was not associated with any ≥ grade 3 toxicity, whereas the lung V20 was associated with increased ≥ grade 3 pneumonitis risk on multivariable analysis ( P = .026). Conclusion IMRT was associated with lower rates of severe pneumonitis and cardiac doses in NRG Oncology clinical trial RTOG 0617, which supports routine use of IMRT for locally advanced NSCLC.

SU-F-T-204: A Preliminary Approach of Reducing Contralateral Breast and Heart Dose in Left Sided Whole Breast Cancer Patients Utilizing Proton Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Islam, M; Algan, O; Jin, H

Purpose: To investigate the plan quality and feasibility of a hybrid plan utilizing proton and photon fields for superior coverage in the internal mammary (IM) and supraclavicular (S/C) regions while minimizing heart and contralateral breast dose for the left-sided whole breast cancer patient treatment. Methods: This preliminary study carried out on single left-sided intact breast patient involved IM and S/C nodes. The IM and S/C node fields of the 5-Field 3DCRT photon-electron base plan were replaced by two proton fields. These two along with two Field-in-Field tangential photon fields were optimized for comparable dose coverage. The treatment plans were donemore » using Eclipse TPS for the total dose of 46Gy in 23 fractions with 95% of the prescription dose covering 95% of the RTOG PTV. The 3DCRT photon-electron and 4-Field photon-proton hybrid plans were compared for the PTV dose coverage as well as dose to OARs. Results: The overall RTOG PTV coverage for proton-hybrid and 3DCRT plan was comparable (95% of prescription dose covers 95% PTV volume). In proton-hybrid plan, 99% of IM volume received 100% dose whereas in 3DCRT only 77% received 100% dose. For S/C regions, 97% and 77% volume received 100% prescription dose in proton-hybrid and 3DCRT plans, respectively. The heart mean dose, V3Gy(%), and V5Gy(%) was 2.2Gy, 14.4%, 9.8% for proton-hybrid vs. 4.20 Gy, 21.5%, and 39% for 3DCRT plan, respectively. The maximum dose to the contralateral breast was 39.75Gy for proton-hybrid while 56.87Gy for 3DCRT plan. The mean total lung dose, V20Gy(%), and V30Gy(%) was 5.68Gy, 11.3%, 10.5% for proton-hybrid vs. 5.90Gy, 9.8%, 7.2% for 3DCRT, respectively. Conclusion: The protonhybrid plan can offer better dose coverage to the involved lymphatic tissues while lower doses to the heart and contralateral breast. More treatment plans are currently in progress before being implemented clinically.« less

Clinical outcomes and mortality before and after implementation of a pediatric sepsis protocol in a limited resource setting: A retrospective cohort study in Bangladesh

PubMed Central

Axelrod, David M.; Chisti, Mohammod J.; Kache, Saraswati

2017-01-01

Background Pediatric sepsis has a high mortality rate in limited resource settings. Sepsis protocols have been shown to be a cost-effective strategy to improve morbidity and mortality in a variety of populations and settings. At Dhaka Hospital in Bangladesh, mortality from pediatric sepsis in high-risk children previously approached 60%, which prompted the implementation of an evidenced-based protocol in 2010. The clinical effectiveness of this protocol had not been measured. We hypothesized that implementation of a pediatric sepsis protocol improved clinical outcomes, including reducing mortality and length of hospital stay. Materials and methods This was a retrospective cohort study of children 1–59 months old with a diagnosis of sepsis, severe sepsis or septic shock admitted to Dhaka Hospital from 10/25/2009-10/25/2011. The primary outcome was inpatient mortality pre- and post-protocol implementation. Secondary outcomes included fluid overload, heart failure, respiratory insufficiency, length of hospital stay, and protocol compliance, as measured by antibiotic and fluid bolus administration within 60 minutes of hospital presentation. Results 404 patients were identified by a key-word search of the electronic medical record; 328 patients with a primary diagnosis of sepsis, severe sepsis, or septic shock were included (143 pre- and185 post-protocol) in the analysis. Pre- and post-protocol mortality were similar and not statistically significant (32.17% vs. 34.59%, p = 0.72). The adjusted odds ratio (AOR) for post-protocol mortality was 1.55 (95% CI, 0.88–2.71). The odds for developing fluid overload were significantly higher post-protocol (AOR 3.45, 95% CI, 2.04–5.85), as were the odds of developing heart failure (AOR 4.52, 95% CI, 1.43–14.29) and having a longer median length of stay (AOR 1.81, 95% CI 1.10–2.96). There was no statistically significant difference in respiratory insufficiency (pre- 65.7% vs. post- 70.3%, p = 0.4) or antibiotic administration between the cohorts (pre- 16.08% vs. post- 12.43%, p = 0.42). Conclusions Implementation of a pediatric sepsis protocol did not improve all-cause mortality or length of stay and may have been associated with increased fluid overload and heart failure during the study period in a large, non-governmental hospital in Bangladesh. Similar rates of early antibiotic administration may indicate poor protocol compliance. Though evidenced-based protocols are a potential cost-effective strategy to improve outcomes, future studies should focus on optimal implementation of context-relevant sepsis protocols in limited resource settings. PMID:28753618

Prognostic Value of p16 Status on the Development of a Complete Response in Involved Oropharynx Cancer Neck Nodes After Cisplatin-Based Chemoradiation: A Secondary Analysis of NRG Oncology RTOG 0129

DOE Office of Scientific and Technical Information (OSTI.GOV)

Galloway, Thomas J., E-mail: thomas.galloway@fccc.edu; Zhang, Qiang; Nguyen-Tan, Phuc Felix

Purpose: To determine the relationship between p16 status and the regional response of patients with node-positive oropharynx cancer treated on NRG Oncology RTOG 0129. Methods and Materials: Patients with N1-N3 oropharynx cancer and known p16 status who underwent treatment on RTOG 0129 were analyzed. Pathologic complete response (pCR) rates in patients treated with a postchemoradiation neck dissection (with p16-positive or p16-negative cancer) were compared by Fisher exact test. Patients managed expectantly were compared with those treated with a neck dissection. Results: Ninety-nine (34%) of 292 patients with node-positive oropharynx cancer and known p16 status underwent a posttreatment neck dissection (p16-positive:more » n=69; p16-negative: n=30). The remaining 193 patients with malignant lymphadenopathy at diagnosis were observed. Neck dissection was performed a median of 70 (range, 17-169) days after completion of chemoradiation. Neither the pretreatment nodal stage (P=.71) nor the postradiation, pre-neck dissection clinical/radiographic neck assessment (P=.42) differed by p16 status. A pCR was more common among p16-positive patients (78%) than p16-negative patients (53%, P=.02) and was associated with a reduced incidence of local–regional failure (hazard ratio 0.33, P=.003). On multivariate analysis of local–regional failure, a test for interaction between pCR and p16 status was not significant (P=.37). One-hundred ninety-three (66%) of 292 of initially node-positive patients were managed without a posttreatment neck dissection. Development of a clinical (cCR) was not significantly influenced by p16-status (P=.42). Observed patients with a clinical nodal CR had disease control outcomes similar to those in patients with a pCR neck dissection. Conclusions: Patients with p16-positive tumors had significantly higher pCR and locoregional control rates than those with p16-negative tumors.« less

Prognostic Value of p16 Status on the Development of a Complete Response in Involved Oropharynx Cancer Neck Nodes After Cisplatin-Based Chemoradiation: A Secondary Analysis of NRG Oncology RTOG 0129.

PubMed

Galloway, Thomas J; Zhang, Qiang Ed; Nguyen-Tan, Phuc Felix; Rosenthal, David I; Soulieres, Denis; Fortin, André; Silverman, Craig L; Daly, Megan E; Ridge, John A; Hammond, J Alexander; Le, Quynh-Thu

2016-10-01

To determine the relationship between p16 status and the regional response of patients with node-positive oropharynx cancer treated on NRG Oncology RTOG 0129. Patients with N1-N3 oropharynx cancer and known p16 status who underwent treatment on RTOG 0129 were analyzed. Pathologic complete response (pCR) rates in patients treated with a postchemoradiation neck dissection (with p16-positive or p16-negative cancer) were compared by Fisher exact test. Patients managed expectantly were compared with those treated with a neck dissection. Ninety-nine (34%) of 292 patients with node-positive oropharynx cancer and known p16 status underwent a posttreatment neck dissection (p16-positive: n=69; p16-negative: n=30). The remaining 193 patients with malignant lymphadenopathy at diagnosis were observed. Neck dissection was performed a median of 70 (range, 17-169) days after completion of chemoradiation. Neither the pretreatment nodal stage (P=.71) nor the postradiation, pre-neck dissection clinical/radiographic neck assessment (P=.42) differed by p16 status. A pCR was more common among p16-positive patients (78%) than p16-negative patients (53%, P=.02) and was associated with a reduced incidence of local-regional failure (hazard ratio 0.33, P=.003). On multivariate analysis of local-regional failure, a test for interaction between pCR and p16 status was not significant (P=.37). One-hundred ninety-three (66%) of 292 of initially node-positive patients were managed without a posttreatment neck dissection. Development of a clinical (cCR) was not significantly influenced by p16-status (P=.42). Observed patients with a clinical nodal CR had disease control outcomes similar to those in patients with a pCR neck dissection. Patients with p16-positive tumors had significantly higher pCR and locoregional control rates than those with p16-negative tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

Predictors of Radiation Therapy–Related Gastrointestinal Toxicity From Anal Cancer Dose-Painted Intensity Modulated Radiation Therapy: Secondary Analysis of NRG Oncology RTOG 0529

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olsen, Jeffrey R., E-mail: Jeffrey.R.Olsen@ucdenver.edu; Moughan, Jennifer; Myerson, Robert

Purpose: NRG Oncology RTOG 0529 assessed the feasibility of dose-painted intensity modulated radiation therapy (DP-IMRT) to reduce the acute morbidity of chemoradiation with 5-fluorouracil (5FU) and mitomycin-C (MMC) for T2-4N0-3M0 anal cancer. This secondary analysis was performed to identify patient and treatment factors associated with acute and late gastrointestinal (GI) adverse events (AEs). Methods and Materials: NRG Oncology RTOG 0529 treatment plans were reviewed to extract dose-volume data for tightly contoured small bowel, loosely contoured anterior pelvic contents (APC), and uninvolved colon outside the target volume (UC). Univariate logistic regression was performed to evaluate association between volumes of each structuremore » receiving doses ≥5 to 60 Gy (V5-V60) in 5-Gy increments between patients with and without grade ≥2 acute and late GI AEs, and grade ≥3 acute GI AEs. Additional patient and treatment factors were evaluated in multivariate logistic regression (acute AEs) or Cox proportional hazards models (late AEs). Results: Among 52 evaluable patients, grade ≥2 acute, grade ≥2 late, and grade ≥3 acute GI AEs were observed in 35, 17, and 10 patients, respectively. Trends (P<.05) toward statistically significant associations were observed between grade ≥2 acute GI AEs and small bowel dose (V20-V40), grade ≥2 late GI AEs and APC dose (V60), grade ≥3 acute GI AEs and APC dose (V5-V25), increasing age, tumor size >4 cm, and worse Zubrod performance status. Small bowel volumes of 186.0 cc, 155.0 cc, 41.0 cc, and 30.4 cc receiving doses greater than 25, 30, 35, and 40 Gy, respectively, correlated with increased risk of acute grade ≥2 GI AEs. Conclusions: Acute and late GI AEs from 5FU/MMC chemoradiation using DP-IMRT correlate with radiation dose to the small bowel and APC. Such associations will be incorporated in the dose-volume normal tissue constraint design for future NRG oncology anal cancer studies.« less

GnRH antagonist versus long agonist protocols in IVF: a systematic review and meta-analysis accounting for patient type.

PubMed

Lambalk, C B; Banga, F R; Huirne, J A; Toftager, M; Pinborg, A; Homburg, R; van der Veen, F; van Wely, M

2017-09-01

Most reviews of IVF ovarian stimulation protocols have insufficiently accounted for various patient populations, such as ovulatory women, women with polycystic ovary syndrome (PCOS) or women with poor ovarian response, and have included studies in which the agonist or antagonist was not the only variable between the compared study arms. The aim of the current study was to compare GnRH antagonist protocols versus standard long agonist protocols in couples undergoing IVF or ICSI, while accounting for various patient populations and treatment schedules. The Cochrane Menstrual Disorders and Subfertility Review Group specialized register of controlled trials and Pubmed and Embase databases were searched from inception until June 2016. Eligible trials were those that compared GnRH antagonist protocols and standard long GnRH agonist protocols in couples undergoing IVF or ICSI. The primary outcome was ongoing pregnancy rate. Secondary outcomes were: live birth rate, clinical pregnancy rate, number of oocytes retrieved and safety with regard to ovarian hyperstimulation syndrome (OHSS). Separate comparisons were performed for the general IVF population, women with PCOS and women with poor ovarian response. Pre-planned subgroup analyses were performed for various antagonist treatment schedules. We included 50 studies. Of these, 34 studies reported on general IVF patients, 10 studies reported on PCOS patients and 6 studies reported on poor responders. In general IVF patients, ongoing pregnancy rate was significantly lower in the antagonist group compared with the agonist group (RR 0.89, 95% CI 0.82-0.96). In women with PCOS and in women with poor ovarian response, there was no evidence of a difference in ongoing pregnancy between the antagonist and agonist groups (RR 0.97, 95% CI 0.84-1.11 and RR 0.87, 95% CI 0.65-1.17, respectively). Subgroup analyses for various antagonist treatment schedules compared to the long protocol GnRH agonist showed a significantly lower ongoing pregnancy rate when the oral hormonal programming pill (OHP) pretreatment was combined with a flexible protocol (RR 0.74, 95% CI 0.59-0.91) while without OHP, the RR was 0.84, 95% CI 0.71-1.0. Subgroup analysis for the fixed antagonist schedule demonstrated no evidence of a significant difference with or without OHP (RR 0.94, 95% CI 0.79-1.12 and RR 0.94, 95% CI 0.83-1.05, respectively). Antagonists resulted in significantly lower OHSS rates both in the general IVF patients and in women with PCOS (RR 0.63, 95% CI 0.50-0.81 and RR 0.53, 95% CI 0.30-0.95, respectively). No data on OHSS was available from trials in poor responders. In a general IVF population, GnRH antagonists are associated with lower ongoing pregnancy rates when compared to long protocol agonists, but also with lower OHSS rates. Within this population, antagonist treatment prevents one case of OHSS in 40 patients but results in one less ongoing pregnancy out of every 28 women treated. Thus standard use of the long GnRH agonist treatment is perhaps still the approach of choice for prevention of premature luteinization. In couples with PCOS and poor responders, GnRH antagonists do not seem to compromise ongoing pregnancy rates and are associated with less OHSS and therefore could be considered as standard treatment. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

4-step 4-h carboplatin desensitization protocol for patients with gynecological malignancies showing platinum hypersensitivity: a retrospective study.

PubMed

Takase, Naoto; Matsumoto, Koji; Onoe, Takuma; Kitao, Akihito; Tanioka, Maki; Kikukawa, Yoshitaka; Yamaguchi, Satoshi; Fujiwara, Kiyoshi; Negoro, Shunichi

2015-06-01

Platinum agents are essential for treating gynecological malignancies, particularly ovarian cancer. However, multiple carboplatin doses may cause hypersensitivity reactions (HSRs). Carboplatin desensitization prevents life-threatening HSRs and promotes the successful completion of planned chemotherapy. Since January 2010, carboplatin desensitization was performed at our institution. Solutions with 1/1000, 1/100, and 1/10 dilutions of carboplatin and an undiluted solution were prepared in 250 mL of 5% glucose. Each solution was administered as a 1-h intravenous infusion (4-step 4-h protocol). This retrospective analysis was approved by the institutional review board. From January 2010 to December 2013, 20 patients with gynecological malignancies (median age 62 years, range 43-74 years) received desensitization treatment. The International Federation of Gynecology and Obstetrics stages at presentation were I, II, III, and IV in 1, 1, 15, 13 patients, respectively. During first-line and second-line treatments, 3 and 17 patients, respectively, experienced carboplatin-induced HSRs. The median carboplatin cycle number was 11 (range 2-16). In the first desensitization cycle, 17 (85%) patients completed treatment without adverse events, 2 experienced Grade 1 HSRs but completed treatment, and 1 experienced Grade 3 HSR and discontinued treatment. The first desensitization cycle completion rate was 95%. Of 83 desensitization cycles administered, 79 (95.2%) were completed. No treatment-related deaths occurred. Most patients completed the planned chemotherapy. Our protocol could be conducted safely with shorter duration and simpler procedures than previous protocols. Carboplatin desensitization seems beneficial for patients with a history of carboplatin-induced HSRs; however, the risk of HSR recurrence still remains. Desensitization should therefore be performed only by well-trained staff.

Photographing Injuries in the Acute Care Setting: Development and Evaluation of a Standardized Protocol for Research, Forensics, and Clinical Practice

PubMed Central

Bloemen, Elizabeth M.; Rosen, Tony; Schiroo, Justina A. Cline; Clark, Sunday; Mulcare, Mary R.; Stern, Michael E.; Mysliwiec, Regina; Flomenbaum, Neal E.; Lachs, Mark S.; Hargarten, Stephen

2016-01-01

Background Photographing injuries in the acute setting allows for improved documentation as well as assessment by clinicians and others who have not personally examined a patient. This tool is important, particularly for telemedicine, tracking of wound healing, the evaluation of potential abuse, and injury research. Despite this, protocols to ensure standardization of photography in clinical practice, forensics, or research have not been published. In preparation for a study of injury patterns in elder abuse and geriatric falls, our goal was to develop and evaluate a protocol for standardized photography of injuries that may be broadly applied. Methods We conducted a literature review for techniques and standards in medical, forensic, and legal photography. We developed a novel protocol describing types of photographs and body positioning for eight body regions, including instructional diagrams. We revised it iteratively in consultation with experts in medical photography; forensics; and elder, child, and domestic abuse. The resulting protocol requires a minimum of four photos of each injury at multiple distances with and without a ruler/color guide. To evaluate the protocol’s efficacy, multiple research assistants without previous photography experience photographed injuries from a convenience sample of elderly patients presenting to a single large, urban, academic emergency department. A selection of these patients’ images were then evaluated in a blinded fashion by four nontreating emergency medicine physicians and the inter-rater reliability between these physicians was calculated. Results Among the 131 injuries, from 53 patients, photographed by 18 photographers using this protocol, photographs of 25 injuries (10 bruises, seven lacerations, and eight abrasions) were used to assess characterization of the injury. Physicians’ characterizations of the injuries were reliable for the size of the injury (κ = 0.91, 95% confidence interval [CI] = 0.77 to 1.00), side of the body (κ = 0.97, 95% CI = 0.88 to 1.00), precise location of the injury (κ = 0.74, 95% CI = 0.63 = 0.81), and type of abrasion (κ = 0.76, 95% CI = 0.45 to 1.00). The exact shape of the injury (κ = 0.44, 95% CI = 0.17 to 0.51), and the primary color of bruises (κ = 0.37, 95% CI = 0.25 to 0.48) were not as reliably characterized. Conclusions Standardizing the documentation of injuries with photographs for clinical and research assessment can be conducted by nonprofessional photographers. A photography protocol will ensure that this important mechanism for documentation is optimized. PMID:26932497

A Phase III Study of Conventional Radiation Therapy Plus Thalidomide Versus Conventional Radiation Therapy for Multiple Brain Metastases (RTOG 0118)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Knisely, Jonathan P.S.; Berkey, Brian; Chakravarti, Arnab

2008-05-01

Purpose: To compare whole-brain radiation therapy (WBRT) with WBRT combined with thalidomide for patients with brain metastases not amenable to resection or radiosurgery. Patients and Methods: Patients with Zubrod performance status 0-1, MRI-documented multiple (>3), large (>4 cm), or midbrain brain metastases arising from a histopathologically confirmed extracranial primary tumor, and an anticipated survival of >8 weeks were randomized to receive WBRT to a dose of 37.5 Gy in 15 fractions with or without thalidomide during and after WBRT. Prerandomization stratification used Radiation Therapy Oncology Group (RTOG) Recursive Partitioning Analysis (RPA) Class and whether post-WBRT chemotherapy was planned. Endpoints includedmore » overall survival, progression-free survival, time to neurocognitive progression, the cause of death, toxicities, and quality of life. A protocol-planned interim analysis documented that the trial had an extremely low probability of ever showing a significant difference favoring the thalidomide arm given the results at the time of the analysis, and it was therefore closed on the basis of predefined statistical guidelines. Results: Enrolled in the study were 332 patients. Of 183 accrued patients, 93 were randomized to receive WBRT alone and 90 to WBRT and thalidomide. Median survival was 3.9 months for both arms. No novel toxicities were seen, but thalidomide was not well tolerated in this population. Forty-eight percent of patients discontinued thalidomide because of side effects. Conclusion: Thalidomide provided no survival benefit for patients with multiple, large, or midbrain metastases when combined with WBRT; nearly half the patients discontinued thalidomide due to side effects.« less

SU-F-T-455: Is Contouring the Whole Breast Necessary for Two-Field 3D Breast Planning?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Desai, A; Ku, Eric; Fang, D

Purpose: To investigate the effect of contouring the whole breast on reducing the radiation dose to the heart and affected lung in tangential field-in-field 3D breast planning. We hypothesize that contouring the whole breast will simplify the plan normalization process, reduce dose to critical structures, while maintaining treatment plan quality and consistency. Methods: Twenty previously treated breast cancer patients using tangential field-in-field 3D planning technique were randomly selected. The affected breast was contoured following the RTOG breast atlas guideline. Breast PTV was created by shrinking 5 mm from the breast contour. The same plan has been pasted to the newmore » contour and normalized to 95% of the Breast PTV receiving the prescribed isodose line. Lung V20 Gy% and Heart V25 Gy% were the primary study endpoints. Homogeneity Index (HI) and Conformity Index (CI) were calculated based on the following equations. HI= Dmax/ D95 and Nakamura’s Conformity Index= PIV/TVPIV × TV/TVPIV. Results: The average CI for previous plans was 1.68 vs. 1.66 for the new hybrid plan: both plans were conformal to the breast with similar quality. The HI for both the previous and the new hybrid plan was 1.24. Lung V 20% slightly increased from 4.27% to 4.82%. Heart V 25% for LT breast patients slightly decreased from 0.38% to 0.29%. Heart V 25% for RT breast patients was close to zero in both cases. Conclusion: With similar conformal and homogeneity indices for the plan quality, by contouring the whole breast following RTOG breast atlas guideline will simplify the planning process. The study showed that contouring the whole breast for patients with left-sided breast cancer reduced the heart V 25%, although not significantly, while maintaining the CI and HI. There was no measurable gain seen with whole breast contour for right-sided breast cancer patients.« less

Single preoperative dose of prophylactic amoxicillin versus a 2-day postoperative course in dental implant surgery: A two-centre randomised controlled trial.

PubMed

Arduino, Paolo G; Tirone, Federico; Schiorlin, Emanuele; Esposito, Marco

2015-01-01

To evaluate the difference between a single preoperative dose versus an additional two-day postoperative course of oral amoxicillin in patients undergoing conventional dental implant placement. Two dentists in two different private practices conducted this study. One hour prior to surgery, patients had to take a single prophylactic antibiotic dose, consisting of 2 g of amoxicillin orally; after implant placement, patients were randomly allocated to two different groups: protocol A (no other antibiotic administration) and protocol B, (1 g of amoxicillin in the evening of the day of surgery and 1 g twice a day for the 2 days after). Outcome measures were prosthetic and implant failures, adverse events and early postoperative complications. Patients were followed up to 6 months after functional loading. Three hundred and sixty patients were randomised and treated (192 patients in one centre and 168 in the other). Five hundred and sixty-seven implants were placed. Protocol A was applied to 180 patients (278 implants) and protocol B also to 180 patients (289 implants). Data for 17 patients, 14 from protocol A and three from protocol B, were not available. No statistically significant differences were found for the reported outcomes. Two patients of protocol B experienced a prosthetic failure, losing four implants, while no prosthetic failures were reported for protocol A (P=0.4836; difference in proportions=-0.0110; 95% CI: -0.0412 to 0.0119). Five patients (3.0%) of protocol A lost five implants versus 5 patients (2.8%) who lost eight implants in protocol B (P=1.0000; difference in proportions=0.0020; 95% CI: -0.0384 to 0.0438). Three adverse events were observed in the total population, all occurring in protocol B (1.69%), with no statistically significant differences between the two groups (P=0.1199; difference in proportions=-0.0170; 95% CI: -0.0487 to 0.0059). However, one patient experienced a severe allergic reaction requiring therapy discontinuation and hospital admission. Early postoperative complications occurred in six patients of protocol A and in four patients of protocol B, with no statistically significant differences (P=0.5170; difference in proportions=0.0130; 95% CI: -0.0254 to 0.0568). No statistically significant differences were observed between 2 g of preoperative amoxicillin and an additional 2-day postoperative course, although adverse events were reported only in the additional 2-day postoperative group. Based on these findings, it might be sufficient to routinely administer preoperatively 2 g of amoxicillin to patients undergoing routine dental implant placement procedures rather than administering additional postoperative doses.

Using Standardized Interpretation of Chest Radiographs to Identify Adults with Bacterial Pneumonia--Guatemala, 2007-2012.

PubMed

Wortham, Jonathan M; Gray, Jennifer; Verani, Jennifer; Contreras, Carmen Lucia; Bernart, Chris; Moscoso, Fabiola; Moir, Juan Carlos; Reyes Marroquin, Emma Lissette; Castellan, Rigoberto; Arvelo, Wences; Lindblade, Kim; McCracken, John P

2015-01-01

Bacterial pneumonia is a leading cause of illness and death worldwide, but quantifying its burden is difficult due to insensitive diagnostics. Although World Health Organization (WHO) protocol standardizes pediatric chest radiograph (CXR) interpretation for epidemiologic studies of bacterial pneumonia, its validity in adults is unknown. Patients (age ≥ 15 years) admitted with respiratory infections to two Guatemalan hospitals between November 2007 and March 2012 had urine and nasopharyngeal/oropharyngeal (NP/OP) swabs collected; blood cultures and CXR were also performed at physician clinical discretion. 'Any bacterial infection' was defined as a positive urine pneumococcal antigen test, isolation of a bacterial pneumonia pathogen from blood culture, or detection of an atypical bacterial pathogen by polymerase chain reaction (PCR) of nasopharyngeal/oropharyngeal (NP/OP) specimens. 'Viral infection' was defined as detection of viral pathogens by PCR of NP/OP specimens. CXRs were interpreted according to the WHO protocol as having 'endpoint consolidation', 'other infiltrate', or 'normal' findings. We examined associations between bacterial and viral infections and endpoint consolidation. Urine antigen and/or blood culture results were available for 721 patients with CXR interpretations; of these, 385 (53%) had endpoint consolidation and 253 (35%) had other infiltrate. Any bacterial infection was detected in 119 (17%) patients, including 106 (89%) pneumococcal infections. Any bacterial infection (Diagnostic Odds Ratio [DOR] = 2.9; 95% confidence Interval (CI): 1.3-7.9) and pneumococcal infection (DOR = 3.4; 95% CI: 1.5-10.0) were associated with 'endpoint consolidation', but not 'other infiltrate' (DOR = 1.7; 95% CI: 0.7-4.9, and 1.7; 95% CI: 0.7-4.9 respectively). Viral infection was not significantly associated with 'endpoint consolidation', 'other infiltrate,' or 'normal' findings. 'Endpoint consolidation' was associated with 'any bacterial infection,' specifically pneumococcal infection. Therefore, endpoint consolidation may be a useful surrogate for studies measuring the impact of interventions, such as conjugate vaccines, against bacterial pneumonia.

Implementation of an Emergency Department Sepsis Bundle and System Redesign: A Process Improvement Initiative.

PubMed

McColl, Tamara; Gatien, Mathieu; Calder, Lisa; Yadav, Krishan; Tam, Ryan; Ong, Melody; Taljaard, Monica; Stiell, Ian

2017-03-01

In 2008-2009, the Canadian Institute for Health Information reported over 30,000 cases of sepsis hospitalizations in Canada, an increase of almost 4,000 from 2005. Mortality rates from severe sepsis and septic shock continue to remain greater than 30% in Canada and are significantly higher than other critical conditions treated in the emergency department (ED). Our group formed a multidisciplinary sepsis committee, conducted an ED process of care analysis, and developed a quality improvement protocol. The objective of this study was to evaluate the effects of this sepsis management bundle on patient mortality. This before and after study was conducted in two large Canadian tertiary care EDs and included adult patients with suspected severe infection that met at least two systemic inflammatory response syndrome (SIRS) criteria. We studied the implementation of a sepsis bundle including triage flagging, RN medical directive, education campaign, and a modified sepsis protocol. The primary outcomes were 30-day all-cause mortality and sepsis protocol use. We included a total of 167 and 185 patients in the pre- and post-intervention analysis, respectively. Compared to the pre-intervention group, mortality was significantly lower in the post-intervention group (30.7% versus 17.3%; absolute difference, 13.4%; 95% CI 9.8-17.0; p=0.006). There was also a higher rate of sepsis protocol use in the post-intervention group (20.3% versus 80.5%, absolute difference 60.2%; 95% CI 55.1-65.3; p<0.001). Additionally, we found shorter time-intervals from triage to MD assessment, fluid resuscitation, and antibiotic administration as well as lower rates of vasopressor requirements and ICU admission. Interpretation The implementation of our multidisciplinary ED sepsis bundle, including improved early identification and protocolized medical care, was associated with improved time to achieve key therapeutic interventions and a reduction in 30-day mortality. Similar low-cost initiatives could be implemented in other EDs to potentially improve outcomes for this high-risk group of patients.

Modeling the Risk of Radiation-Induced Acute Esophagitis for Combined Washington University and RTOG Trial 93-11 Lung Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Ellen X.; Bradley, Jeffrey D.; El Naqa, Issam

2012-04-01

Purpose: To construct a maximally predictive model of the risk of severe acute esophagitis (AE) for patients who receive definitive radiation therapy (RT) for non-small-cell lung cancer. Methods and Materials: The dataset includes Washington University and RTOG 93-11 clinical trial data (events/patients: 120/374, WUSTL = 101/237, RTOG9311 = 19/137). Statistical model building was performed based on dosimetric and clinical parameters (patient age, sex, weight loss, pretreatment chemotherapy, concurrent chemotherapy, fraction size). A wide range of dose-volume parameters were extracted from dearchived treatment plans, including Dx, Vx, MOHx (mean of hottest x% volume), MOCx (mean of coldest x% volume), and gEUDmore » (generalized equivalent uniform dose) values. Results: The most significant single parameters for predicting acute esophagitis (RTOG Grade 2 or greater) were MOH85, mean esophagus dose (MED), and V30. A superior-inferior weighted dose-center position was derived but not found to be significant. Fraction size was found to be significant on univariate logistic analysis (Spearman R = 0.421, p < 0.00001) but not multivariate logistic modeling. Cross-validation model building was used to determine that an optimal model size needed only two parameters (MOH85 and concurrent chemotherapy, robustly selected on bootstrap model-rebuilding). Mean esophagus dose (MED) is preferred instead of MOH85, as it gives nearly the same statistical performance and is easier to compute. AE risk is given as a logistic function of (0.0688 Asterisk-Operator MED+1.50 Asterisk-Operator ConChemo-3.13), where MED is in Gy and ConChemo is either 1 (yes) if concurrent chemotherapy was given, or 0 (no). This model correlates to the observed risk of AE with a Spearman coefficient of 0.629 (p < 0.000001). Conclusions: Multivariate statistical model building with cross-validation suggests that a two-variable logistic model based on mean dose and the use of concurrent chemotherapy robustly predicts acute esophagitis risk in combined-data WUSTL and RTOG 93-11 trial datasets.« less

The Utility of a Benign Biliary Stricture Protocol in Preventing Symptomatic Recurrence and Surgical Revision.

PubMed

Kirkpatrick, Daniel L; Hasham, Hasnain; Collins, Zachary; Johnson, Philip; Lemons, Steven; Shahzada, Hassan; Hunt, Suzanne L; Walter, Carissa; Hill, Jacqueline; Fahrbach, Thomas

2018-05-01

To determine whether treating benign biliary strictures via a stricture protocol reduced the probability of developing symptomatic recurrence and requiring surgical revision compared to nonprotocol treatment. A stricture protocol was designed to include serial upsizing of internal/external biliary drainage catheters to a target maximum dilation of 18-French, optional cholangioplasty at each upsizing, and maintenance of the largest catheter for at least 6 months. Patients were included in this retrospective analysis if they underwent biliary ductal dilation at a single institution from 2005 to 2016. Forty-two patients were included, 25 women and 17 men, with an average age of 51.9 years (standard deviation ± 14.6). Logistic regression models were used to determine the probability of symptomatic recurrence and surgical revision by stricture treatment type. Twenty-two patients received nonprotocol treatment, while 20 received treatment on a stricture protocol. After treatment, 7 (32%) patients in the nonprotocol group experienced clinical or laboratory recurrence of a benign stricture, whereas only 1 patient in the stricture protocol group experienced symptom recurrence. Patients in the protocol group were 8.9 times (95% confidence interval [CI] = 1.4-175.3) more likely to remain symptom free than patients in the nonprotocol group. Moreover, patients in the protocol group had an estimated 89% reduction in the probability of undergoing surgical revision compared to patients receiving nonprotocol treatment (odds ratio = .11, 95% CI = .01-.73). Establishing a stricture protocol may decrease the risk of stricture recurrence and the need for surgical revision when compared to a nonprotocol treatment approach. Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.

Combination of external-beam radiotherapy with intraoperative electron-beam therapy is effective in incompletely resected pediatric malignancies.

PubMed

Oertel, Susanne; Niethammer, Andreas G; Krempien, Robert; Roeder, Falk; Eble, Michael J; Baer, Claudia; Huber, Peter E; Kulozik, Andreas; Waag, Karl-Ludwig; Treiber, Martina; Debus, Juergen

2006-01-01

Intraoperative electron-beam radiotherapy (IOERT) has been applied for local dose escalation in over 1,400 patients in Heidelberg since 1991. Among these were 30 children, in 18 of whom IOERT was employed in radiation treatment with external-beam radiotherapy (EBRT) on account of incomplete resection. We address the question whether IOERT is able to compensate for microscopic or macroscopic tumor residue if employed in the overall radiation regimen. The data of the aforementioned 18 children were analyzed with regard to local recurrence, overall survival, and complication rates. All children suffered from either sarcomas or neuroblastomas. In all children, IOERT was employed for local dose escalation after or before EBRT. After a median follow-up of 60.5 months, 15 of the treated children are alive. One local failure has been observed. Six children show clinically significant late morbidity, including the loss of a treated limb (Radiation Therapy Oncology Group Grade 4 [RTOG 4]), a severe nerve lesion (RTOG 3), an orthopedic complication (RTOG 2), a ureteral stenosis (not clinically significant), and a kidney hypotrophy (not clinically significant). In 1 child a fracture due to radionecrosis (RTOG 4) was diagnosed; however, in the follow-up, local tumor relapse was diagnosed as another possible reason for the fracture. Regarding the low incidence of local failure, IOERT seems to be able to compensate incomplete tumor resection in childhood sarcoma and neuroblastoma patients. The incidence of late morbidity is low enough to justify the employment of IOERT as part of the radiation treatment regimen for pediatric patients.

Efficacy of pneumococcal nontypable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in young Latin American children: A double-blind randomized controlled trial.

PubMed

Tregnaghi, Miguel W; Sáez-Llorens, Xavier; López, Pio; Abate, Hector; Smith, Enrique; Pósleman, Adriana; Calvo, Arlene; Wong, Digna; Cortes-Barbosa, Carlos; Ceballos, Ana; Tregnaghi, Marcelo; Sierra, Alexandra; Rodriguez, Mirna; Troitiño, Marisol; Carabajal, Carlos; Falaschi, Andrea; Leandro, Ana; Castrejón, Maria Mercedes; Lepetic, Alejandro; Lommel, Patricia; Hausdorff, William P; Borys, Dorota; Ruiz Guiñazú, Javier; Ortega-Barría, Eduardo; Yarzábal, Juan P; Schuerman, Lode

2014-06-01

The relationship between pneumococcal conjugate vaccine-induced antibody responses and protection against community-acquired pneumonia (CAP) and acute otitis media (AOM) is unclear. This study assessed the impact of the ten-valent pneumococcal nontypable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) on these end points. The primary objective was to demonstrate vaccine efficacy (VE) in a per-protocol analysis against likely bacterial CAP (B-CAP: radiologically confirmed CAP with alveolar consolidation/pleural effusion on chest X-ray, or non-alveolar infiltrates and C-reactive protein ≥ 40 µg/ml); other protocol-specified outcomes were also assessed. This phase III double-blind randomized controlled study was conducted between 28 June 2007 and 28 July 2011 in Argentine, Panamanian, and Colombian populations with good access to health care. Approximately 24,000 infants received PHiD-CV or hepatitis control vaccine (hepatitis B for primary vaccination, hepatitis A at booster) at 2, 4, 6, and 15-18 mo of age. Interim analysis of the primary end point was planned when 535 first B-CAP episodes, occurring ≥2 wk after dose 3, were identified in the per-protocol cohort. After a mean follow-up of 23 mo (PHiD-CV, n = 10,295; control, n = 10,201), per-protocol VE was 22.0% (95% CI: 7.7, 34.2; one-sided p = 0.002) against B-CAP (conclusive for primary objective) and 25.7% (95% CI: 8.4%, 39.6%) against World Health Organization-defined consolidated CAP. Intent-to-treat VE was 18.2% (95% CI: 5.5%, 29.1%) against B-CAP and 23.4% (95% CI: 8.8%, 35.7%) against consolidated CAP. End-of-study per-protocol analyses were performed after a mean follow-up of 28-30 mo for CAP and invasive pneumococcal disease (IPD) (PHiD-CV, n = 10,211; control, n = 10,140) and AOM (n = 3,010 and 2,979, respectively). Per-protocol VE was 16.1% (95% CI: -1.1%, 30.4%; one-sided p = 0.032) against clinically confirmed AOM, 67.1% (95% CI: 17.0%, 86.9%) against vaccine serotype clinically confirmed AOM, 100% (95% CI: 74.3%, 100%) against vaccine serotype IPD, and 65.0% (95% CI: 11.1%, 86.2%) against any IPD. Results were consistent between intent-to-treat and per-protocol analyses. Serious adverse events were reported for 21.5% (95% CI: 20.7%, 22.2%) and 22.6% (95% CI: 21.9%, 23.4%) of PHiD-CV and control recipients, respectively. There were 19 deaths (n = 11,798; 0.16%) in the PHiD-CV group and 26 deaths (n = 11,799; 0.22%) in the control group. A significant study limitation was the lower than expected number of captured AOM cases. Efficacy was demonstrated against a broad range of pneumococcal diseases commonly encountered in young children in clinical practice. www.ClinicalTrials.gov NCT00466947.

Involving American Indians and medically underserved rural populations in cancer clinical trials.

PubMed

Guadagnolo, B Ashleigh; Petereit, Daniel G; Helbig, Petra; Koop, David; Kussman, Patricia; Fox Dunn, Emily; Patnaik, Asha

2009-12-01

To assess cancer clinical trial recruitment and reasons for nonaccrual among a rural, medically underserved population served by a community-based cancer care center. We prospectively tracked clinical trial enrollment incidence among all new patients presenting at the Rapid City Regional Cancer Care Institute. Evaluating physicians completed questionnaires for each patient regarding clinical trial enrollment status and primary reasons for nonenrollment. Patients who identified as American Indian were referred to a program where patients were assisted in navigating the medical system by trained, culturally competent staff. Between September 2006 and January 2008, 891 new cancer patients were evaluated. Seventy-eight patients (9%; 95% confidence intervals, 7-11%) were enrolled on a clinical treatment trial. For 73% (95% confidence intervals, 69-75%) of patients (646 of 891) lack of relevant protocol availability or protocol inclusion criteria restrictiveness was the reason for nonenrollment. Only 45 (5%; 95% confidence intervals, 4-7%) patients refused enrollment on a trial. Of the 78 enrolled on a trial, 6 (8%; 95% confidence intervals, 3-16%) were American Indian. Three additional American Indian patients were enrolled under a nontreatment cancer control trial, bringing the total percentage enrolled of the 94 American Indians who presented to the clinic to 10% (95% confidence intervals, 5-17%). Eligibility rates were unable to be calculated and cross validation of the number in the cohort via registries or ICD-9 codes was not performed. Clinical trial participation in this medically underserved population was low overall, but approximately 3-fold higher than reported national accrual rates. Lack of availability of protocols for common cancer sites as well as stringent protocol inclusion criteria were the primary obstacles to clinical trial enrollment. Targeted interventions using a Patient Navigation program were used to engage AI patients and may have resulted in higher clinical trial enrollment among this racial/ethnic group.

Involving American Indians and medically underserved rural populations in cancer clinical trials

PubMed Central

Guadagnolo, B Ashleigh; Petereit, Daniel G; Helbig, Petra; Koop, David; Kussman, Patricia; Dunn, Emily Fox; Patnaik, Asha

2010-01-01

Purpose To assess cancer clinical trial recruitment and reasons for nonaccrual among a rural, medically underserved population served by a community-based cancer care center. Methods We prospectively tracked clinical trial enrollment incidence among all new patients presenting at the Rapid City Regional Cancer Care Institute. Evaluating physicians completed questionnaires for each patient regarding clinical trial enrollment status and primary reasons for nonenrollment. Patients who identified as American Indian were referred to a program where patients were assisted in navigating the medical system by trained, culturally competent staff. Results Between September 2006 and January 2008, 891 new cancer patients were evaluated. Seventy-eight patients (9%; 95% confidence intervals, 7–11%) were enrolled on a clinical treatment trial. For 73% (95% confidence intervals, 69–75%) of patients (646 of 891) lack of relevant protocol availability or protocol inclusion criteria restrictiveness was the reason for nonenrollment. Only 45 (5%; 95% confidence intervals, 4–7%) patients refused enrollment on a trial. Of the 78 enrolled on a trial, 6 (8%; 95% confidence intervals, 3–16%) were American Indian. Three additional American Indian patients were enrolled under a nontreatment cancer control trial, bringing the total percentage enrolled of the 94 American Indians who presented to the clinic to 10% (95% confidence intervals, 5–17%). Limitations Eligibility rates were unable to be calculated and cross validation of the number in the cohort via registries or ICD-9 codes was not performed. Conclusion Clinical trial participation in this medically underserved population was low overall, but approximately 3-fold higher than reported national accrual rates. Lack of availability of protocols for common cancer sites as well as stringent protocol inclusion criteria were the primary obstacles to clinical trial enrollment. Targeted interventions using a Patient Navigation program were used to engage AI patients and may have resulted in higher clinical trial enrollment among this racial/ethnic group. PMID:19933720

Reporting mortality findings in trials of rofecoxib for Alzheimer disease or cognitive impairment: a case study based on documents from rofecoxib litigation.

PubMed

Psaty, Bruce M; Kronmal, Richard A

2008-04-16

Sponsors have a marketing interest to represent their products in the best light. This approach conflicts with scientific standards that require the symmetric and comparable reporting of safety and efficacy data. Selective reporting of the results of clinical trials can misrepresent the risk-benefit profile of drugs. We summarize how the sponsor represented mortality findings associated with rofecoxib in clinical trials of patients with Alzheimer disease or cognitive impairment. We reviewed documents that became available during litigation related to rofecoxib involving Merck & Co, including internal company analyses and information provided by the sponsor to the FDA. We also evaluated information in 2 published articles that reported results of these trials. In one article (reporting results of protocol 091) published in 2004, 11 "non-drug related deaths" were reported (9 deaths among 346 rofecoxib patients and 2 deaths among 346 placebo patients). In another article (reporting results of protocol 078) published in 2005, 39 deaths were reported among patients taking study treatment or within 14 days of the last dose (24 among 725 rofecoxib patients and 15 among 732 placebo patients) and an additional 22 deaths in the off-drug period (17 in rofecoxib patients and 5 in placebo patients). However, these articles did not include analyses or statistical tests of the mortality data, and the 2 articles concluded that regarding safety, rofecoxib is "well tolerated." In contrast, in April 2001, the company's internal intention-to-treat analyses of pooled data from these 2 trials identified a significant increase in total mortality (hazard ratio [HR], 4.43; 95% CI, 1.26-15.53 for protocol 091, and HR, 2.55; 95% CI, 1.17-5.56 for protocol 078), with overall mortality of 34 deaths among 1069 rofecoxib patients and 12 deaths among 1078 placebo patients (HR, 2.99; 95% CI, 1.55-5.77). These mortality analyses were neither provided to the FDA nor made public in a timely fashion. The data submitted by the sponsor to the FDA in a Safety Update Report in July 2001 used on-treatment analysis methods and reported 29 deaths (2.7%) among 1067 rofecoxib patients and 17 deaths (1.6%) among 1075 placebo patients. This on-treatment approach to reporting minimized the appearance of any mortality risk. In December 2001, when the FDA raised safety questions about the submitted safety data, the sponsor did not bring these issues to an institutional review board for review and revealed that there was no data and safety monitoring board for the protocol 078 study. The findings from this case study suggest that additional protections for human research participants, including new approaches for the conduct, oversight, and reporting of industry-sponsored trials, are necessary.

Test-retest reliability of jump execution variables using mechanography: a comparison of jump protocols.

PubMed

Fitzgerald, John S; Johnson, LuAnn; Tomkinson, Grant; Stein, Jesse; Roemmich, James N

2018-05-01

Mechanography during the vertical jump may enhance screening and determining mechanistic causes underlying physical performance changes. Utility of jump mechanography for evaluation is limited by scant test-retest reliability data on force-time variables. This study examined the test-retest reliability of eight jump execution variables assessed from mechanography. Thirty-two women (mean±SD: age 20.8 ± 1.3 yr) and 16 men (age 22.1 ± 1.9 yr) attended a familiarization session and two testing sessions, all one week apart. Participants performed two variations of the squat jump with squat depth self-selected and controlled using a goniometer to 80º knee flexion. Test-retest reliability was quantified as the systematic error (using effect size between jumps), random error (using coefficients of variation), and test-retest correlations (using intra-class correlation coefficients). Overall, jump execution variables demonstrated acceptable reliability, evidenced by small systematic errors (mean±95%CI: 0.2 ± 0.07), moderate random errors (mean±95%CI: 17.8 ± 3.7%), and very strong test-retest correlations (range: 0.73-0.97). Differences in random errors between controlled and self-selected protocols were negligible (mean±95%CI: 1.3 ± 2.3%). Jump execution variables demonstrated acceptable reliability, with no meaningful differences between the controlled and self-selected jump protocols. To simplify testing, a self-selected jump protocol can be used to assess force-time variables with negligible impact on measurement error.

RTOG GU Radiation Oncology Specialists Reach Consensus on Pelvic Lymph Node Volumes for High-Risk Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lawton, Colleen A.F.; Michalski, Jeff; El-Naqa, Issam

2009-06-01

Purpose: Radiation therapy to the pelvic lymph nodes in high-risk prostate cancer is required on several Radiation Therapy Oncology Group (RTOG) clinical trials. Based on a prior lymph node contouring project, we have shown significant disagreement in the definition of pelvic lymph node volumes among genitourinary radiation oncology specialists involved in developing and executing current RTOG trials. Materials and Methods: A consensus meeting was held on October 3, 2007, to reach agreement on pelvic lymph node volumes. Data were presented to address the lymph node drainage of the prostate. Extensive discussion ensued to develop clinical target volume (CTV) pelvic lymphmore » node consensus. Results: Consensus was obtained resulting in computed tomography image-based pelvic lymph node CTVs. Based on this consensus, the pelvic lymph node volumes to be irradiated include: distal common iliac, presacral lymph nodes (S{sub 1}-S{sub 3}), external iliac lymph nodes, internal iliac lymph nodes, and obturator lymph nodes. Lymph node CTVs include the vessels (artery and vein) and a 7-mm radial margin being careful to 'carve out' bowel, bladder, bone, and muscle. Volumes begin at the L5/S1 interspace and end at the superior aspect of the pubic bone. Consensus on dose-volume histogram constraints for OARs was also attained. Conclusions: Consensus on pelvic lymph node CTVs for radiation therapy to address high-risk prostate cancer was attained and is available as web-based computed tomography images as well as a descriptive format through the RTOG. This will allow for uniformity in evaluating the benefit and risk of such treatment.« less

The Influence of Total Nodes Examined, Number of Positive Nodes, and Lymph Node Ratio on Survival After Surgical Resection and Adjuvant Chemoradiation for Pancreatic Cancer: A Secondary Analysis of RTOG 9704

DOE Office of Scientific and Technical Information (OSTI.GOV)

Showalter, Timothy N.; Winter, Kathryn A.; Berger, Adam C., E-mail: adam.berger@jefferson.edu

2011-12-01

Purpose: Lymph node status is an important predictor of survival in pancreatic cancer. We performed a secondary analysis of Radiation Therapy Oncology Group (RTOG) 9704, an adjuvant chemotherapy and chemoradiation trial, to determine the influence of lymph node factors-number of positive nodes (NPN), total nodes examined (TNE), and lymph node ratio (LNR ratio of NPN to TNE)-on OS and disease-free survival (DFS). Patient and Methods: Eligible patients from RTOG 9704 form the basis of this secondary analysis of lymph node parameters. Actuarial estimates for OS and DFS were calculated using Kaplan-Meier methods. Cox proportional hazards models were performed to evaluatemore » associations of NPN, TNE, and LNR with OS and DFS. Multivariate Cox proportional hazards models were also performed. Results: There were 538 patients enrolled in the RTOG 9704 trial. Of these, 445 patients were eligible with lymph nodes removed. Overall median NPN was 1 (min-max, 0-18). Increased NPN was associated with worse OS (HR = 1.06, p = 0.001) and DFS (HR = 1.05, p = 0.01). In multivariate analyses, both NPN and TNE were associated with OS and DFS. TNE > 12, and >15 were associated with increased OS for all patients, but not for node-negative patients (n = 142). Increased LNR was associated with worse OS (HR = 1.01, p < 0.0001) and DFS (HR = 1.006, p = 0.002). Conclusion: In patients who undergo surgical resection followed by adjuvant chemoradiation, TNE, NPN, and LNR are associated with OS and DFS. This secondary analysis of a prospective, cooperative group trial supports the influence of these lymph node parameters on outcomes after surgery and adjuvant therapy using contemporary techniques.« less

SU-E-T-534: Dosimetric Effect of Multileaf Collimator Leaf Width On Volumetric Modulated Arc Stereotactic Radiotherapy for Spine Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amoush, A; Djemil, T; Subedi, L

2014-06-01

Purpose: To study the dosimetric impact of MLC leaf width in patients treated with Volumetric Modulated Arc Therapy (VMAT) for spine Stereotactic Body radiation Therapy (SBRT). Methods: Twelve spine SBRT patients were retrospectively selected for this study. The patients were treated with IMRT following the RTOG-0631 of spine metastasis. The prescription dose was 16 Gy in one fraction to 90% of the target volume (V16 > 90%). The maximum spinal cord dose of 14 Gy and 10% of the cord receiving < 10 Gy (V10) were set as dose constraints. For purpose of this study, three dual arc VMAT plansmore » were created for each patient using three different MLC leaf widths: 2.5 mm, 4mm, and 5mm. The compliance to RTOG 0631, conformal index (CI), dose gradient index (DGI), and number of monitor units (MUs) were compared. Results: The average V16 of the target was 91.91±1.36%, 93.73±2.38%, and 92.25±2.49% for 2.5 mm, 4 mm, and 5 mm leaf widths, respectively (p=0.39). Accordingly, the average CI was 1.36±0.39, 1.36±0.34, and 1.41±0.3 (0.96), respectively. The average DGI was 0.24 ± 0.05, 0.22 ± 0.05, and 0.23 ± 0.04, respectively (p=0.86). The average spinal cord maximum dose was 12.10 ± 0.88 Gy, 12.52 ± 1.15 Gy, and 12.05 ± 1.12 (p=0.75) and V10 was 2.69 ± 1.71 cc, 5.43 ± 2.16 cc, and 3.71 ± 2.34 cc (p=0.15) for 2.5 mm, 4 mm, and 5 mm leaf widths, respectively. According, the average number of MUs was 4255 ± 431 MU, 5049 ± 1036 MU, and 4231 ± 580 MU respectively (p=0.17). Conclusion: The use of 2.5 mm, 4 mm, and 5 mm MLCs achieved similar VMAT plan quality as recommended by RTOG-0631. The dosimetric parameters were also comparable for the three MLCs.« less

Development of a Set of Nomograms to Predict Acute Lower Gastrointestinal Toxicity for Prostate Cancer 3D-CRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valdagni, Riccardo; Rancati, Tiziana; Fiorino, Claudio

2008-07-15

Purpose: To predict acute Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) and Subjective Objective Signs Management and Analysis/Late Effect of Normal Tissue (SOMA/LENT) toxicities of the lower gastrointestinal (LGI) syndrome in patients with prostate cancer undergoing three-dimensional conformal radiotherapy using a tool (nomogram) that takes into account clinical and dosimetric variables that proved to be significant in the Italian Association for Radiation Oncology (AIRO) Group on Prostate Cancer (AIROPROS) 0102 trial. Methods and Materials: Acute rectal toxicity was scored in 1,132 patients by using both the RTOG/EORTC scoring system and a 10-item self-assessed questionnaire.more » Correlation between clinical variables/dose-volume histogram constraints and rectal toxicity was investigated by means of multivariate logistic analyses. Multivariate logistic analyses results were used to create nomograms predicting the symptoms of acute LGI syndrome. Results: Mean rectal dose was a strong predictor of Grade 2-3 RTOG/EORTC acute LGI toxicity (p 0.0004; odds ratio (OR) = 1.035), together with hemorrhoids (p = 0.02; OR 1.51), use of anticoagulants/antiaggregants (p = 0.02; OR = 0.63), and androgen deprivation (AD) (p = 0.04; OR = 0.65). Diabetes (p = 0.34; OR 1.28) and pelvic node irradiation (p = 0.11; OR = 1.56) were significant variables to adjust toxicity prediction. Bleeding was related to hemorrhoids (p = 0.02; OR = 173), AD (p = 0.17; OR = 0.67), and mean rectal dose (p 0.009; OR = 1.024). Stool frequency was related to seminal vesicle irradiation (p = 0.07; OR = 6.46), AD administered for more than 3 months (p = 0.002; OR = 0.32), and the percent volume of rectum receiving more than 60 Gy (V60Gy) V60 (p = 0.02; OR = 1.02). Severe fecal incontinence depended on seminal vesicle irradiation (p = 0.14; OR = 4.5) and V70 (p = 0.033; OR 1.029). Conclusions: To the best of our knowledge, this work presents the first set of nomograms available in the literature specific to symptoms of LGI syndrome and provides clinicians with a tailored probability of the specific outcome. Validation of the tool is in progress.« less

Efficacy of Pneumococcal Nontypable Haemophilus influenzae Protein D Conjugate Vaccine (PHiD-CV) in Young Latin American Children: A Double-Blind Randomized Controlled Trial

PubMed Central

Tregnaghi, Miguel W.; Sáez-Llorens, Xavier; López, Pio; Abate, Hector; Smith, Enrique; Pósleman, Adriana; Calvo, Arlene; Wong, Digna; Cortes-Barbosa, Carlos; Ceballos, Ana; Tregnaghi, Marcelo; Sierra, Alexandra; Rodriguez, Mirna; Troitiño, Marisol; Carabajal, Carlos; Falaschi, Andrea; Leandro, Ana; Castrejón, Maria Mercedes; Lepetic, Alejandro; Lommel, Patricia; Hausdorff, William P.; Borys, Dorota; Guiñazú, Javier Ruiz; Ortega-Barría, Eduardo; Yarzábal, Juan P.; Schuerman, Lode

2014-01-01

Background The relationship between pneumococcal conjugate vaccine–induced antibody responses and protection against community-acquired pneumonia (CAP) and acute otitis media (AOM) is unclear. This study assessed the impact of the ten-valent pneumococcal nontypable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) on these end points. The primary objective was to demonstrate vaccine efficacy (VE) in a per-protocol analysis against likely bacterial CAP (B-CAP: radiologically confirmed CAP with alveolar consolidation/pleural effusion on chest X-ray, or non-alveolar infiltrates and C-reactive protein ≥ 40 µg/ml); other protocol-specified outcomes were also assessed. Methods and Findings This phase III double-blind randomized controlled study was conducted between 28 June 2007 and 28 July 2011 in Argentine, Panamanian, and Colombian populations with good access to health care. Approximately 24,000 infants received PHiD-CV or hepatitis control vaccine (hepatitis B for primary vaccination, hepatitis A at booster) at 2, 4, 6, and 15–18 mo of age. Interim analysis of the primary end point was planned when 535 first B-CAP episodes, occurring ≥2 wk after dose 3, were identified in the per-protocol cohort. After a mean follow-up of 23 mo (PHiD-CV, n = 10,295; control, n = 10,201), per-protocol VE was 22.0% (95% CI: 7.7, 34.2; one-sided p = 0.002) against B-CAP (conclusive for primary objective) and 25.7% (95% CI: 8.4%, 39.6%) against World Health Organization–defined consolidated CAP. Intent-to-treat VE was 18.2% (95% CI: 5.5%, 29.1%) against B-CAP and 23.4% (95% CI: 8.8%, 35.7%) against consolidated CAP. End-of-study per-protocol analyses were performed after a mean follow-up of 28–30 mo for CAP and invasive pneumococcal disease (IPD) (PHiD-CV, n = 10,211; control, n = 10,140) and AOM (n = 3,010 and 2,979, respectively). Per-protocol VE was 16.1% (95% CI: −1.1%, 30.4%; one-sided p = 0.032) against clinically confirmed AOM, 67.1% (95% CI: 17.0%, 86.9%) against vaccine serotype clinically confirmed AOM, 100% (95% CI: 74.3%, 100%) against vaccine serotype IPD, and 65.0% (95% CI: 11.1%, 86.2%) against any IPD. Results were consistent between intent-to-treat and per-protocol analyses. Serious adverse events were reported for 21.5% (95% CI: 20.7%, 22.2%) and 22.6% (95% CI: 21.9%, 23.4%) of PHiD-CV and control recipients, respectively. There were 19 deaths (n = 11,798; 0.16%) in the PHiD-CV group and 26 deaths (n = 11,799; 0.22%) in the control group. A significant study limitation was the lower than expected number of captured AOM cases. Conclusions Efficacy was demonstrated against a broad range of pneumococcal diseases commonly encountered in young children in clinical practice. Trial registration www.ClinicalTrials.gov NCT00466947 Please see later in the article for the Editors' Summary PMID:24892763

Effect of Long-Term Hormonal Therapy (vs Short-Term Hormonal Therapy): A Secondary Analysis of Intermediate-Risk Prostate Cancer Patients Treated on NRG Oncology RTOG 9202

PubMed Central

Mirhadi, Amin J.; Zhang, Qiang; Hanks, Gerald E.; Lepor, Herbert; Grignon, David J.; Peters, Christopher A.; Rosenthal, Seth A.; Zeitzer, Kenneth; Radwan, John S.; Lawton, Colleen; Parliament, Matthew B.; Reznik, Robert S.; Sandler, Howard M.

2017-01-01

Purpose NRG Oncology RTOG 9202 was a randomized trial testing long-term adjuvant androgen deprivation (LTAD) versus initial androgen deprivation only (STAD) with external beam radiation therapy (RT) in mostly high-risk and some intermediate-risk prostate cancer patients. RTOG 9408 found an overall survival (OS) advantage in patients with cT1b-T2b disease and prostate-specific antigen (PSA) <20 ng/mL, with benefit observed mostly among intermediate-risk patients. It was still unknown whether intermediate-risk patients would experience an additional survival benefit with LTAD; thus, we performed a secondary analysis to explore whether LTAD had any incremental benefit beyond STAD among the intermediate-risk subset of RTOG 9202. The study endpoints were OS, disease-specific survival (DSS), and PSA failure (PSAF). Methods and Materials An analysis was performed for all patients enrolled in RTOG 9202 defined as intermediate-risk (cT2 disease, PSA<10 ng/mL, and Gleason score = 7 or cT2 disease, PSA 10-20 ng/mL, and Gleason score <7). This review yielded 133 patients: 74 (STAD) and 59 (LTAD). The Kaplan-Meier method was used to estimate OS; the cumulative incidence approach was used to estimate DSS and PSAF. A 2-sided test was used, with significance level defined to be .05. Results With over 11 years of median follow-up, 39 STAD patients were alive and 33 LTAD patients were alive. There was no difference in OS (10-year estimates, 61% STAD vs 65% LTAD; P=.53), DSS (10-year DSS, 96% vs 97%; P=.72), or PSAF (10-year PSAF, 53% vs 55%; P=.99) between groups. Conclusion LTAD did not confer a benefit in terms of OS, DSS, or PSAF rates in the intermediate-risk subset in this study. Whereas the subset was relatively small, treatment assignment was randomly applied, and a trend in favor of LTAD would have been of interest. Given the small number of disease-specific deaths observed and lack of benefit with respect to our endpoints, this secondary analysis does not suggest that exploration of longer hormonal therapy is worth testing in the intermediate-risk prostate cancer subset. PMID:28126300

Once-only sigmoidoscopy in colorectal cancer screening: follow-up findings of the Italian Randomized Controlled Trial--SCORE.

PubMed

Segnan, Nereo; Armaroli, Paola; Bonelli, Luigina; Risio, Mauro; Sciallero, Stefania; Zappa, Marco; Andreoni, Bruno; Arrigoni, Arrigo; Bisanti, Luigi; Casella, Claudia; Crosta, Cristiano; Falcini, Fabio; Ferrero, Franco; Giacomin, Adriano; Giuliani, Orietta; Santarelli, Alessandra; Visioli, Carmen Beatriz; Zanetti, Roberto; Atkin, Wendy S; Senore, Carlo

2011-09-07

A single flexible sigmoidoscopy at around the age of 60 years has been proposed as an effective strategy for colorectal cancer (CRC) screening. We conducted a randomized controlled trial to evaluate the effect of flexible sigmoidoscopy screening on CRC incidence and mortality. A questionnaire to assess the eligibility and interest in screening was mailed to 236,568 men and women, aged 55-64 years, who were randomly selected from six trial centers in Italy. Of the 56,532 respondents, interested and eligible subjects were randomly assigned to the intervention group (invitation for flexible sigmoidoscopy; n = 17,148) or the control group (no further contact; n = 17,144), between June 14, 1995, and May 10, 1999. Flexible sigmoidoscopy was performed on 9911 subjects. Intention-to-treat and per-protocol analyses were performed to compare the CRC incidence and mortality rates in the intervention and control groups. Per-protocol analysis was adjusted for noncompliance. A total of 34,272 subjects (17,136 in each group) were included in the follow-up analysis. The median follow-up period was 10.5 years for incidence and 11.4 years for mortality; 251 subjects were diagnosed with CRC in the intervention group and 306 in the control group. Overall incidence rates in the intervention and control groups were 144.11 and 176.43, respectively, per 100,000 person-years. CRC-related death was noted in 65 subjects in the intervention group and 83 subjects in the control group. Mortality rates in the intervention and control groups were 34.66 and 44.45, respectively, per 100,000 person-years. In the intention-to-treat analysis, the rate of CRC incidence was statistically significantly reduced in the intervention group by 18% (rate ratio [RR] = 0.82, 95% confidence interval [CI] = 0.69 to 0.96), and the mortality rate was non-statistically significantly reduced by 22% (RR = 0.78; 95% CI = 0.56 to 1.08) compared with the control group. In the per-protocol analysis, both CRC incidence and mortality rates were statistically significantly reduced among the screened subjects; CRC incidence was reduced by 31% (RR = 0.69; 95% CI = 0.56 to 0.86) and mortality was reduced by 38% (RR = 0.62; 95% CI = 0.40 to 0.96) compared with the control group. A single flexible sigmoidoscopy screening between ages 55 and 64 years was associated with a substantial reduction of CRC incidence and mortality.

ORAL ADMINISTRATION OF EXOGENOUS LACTASE IN TABLETS FOR PATIENTS DIAGNOSED WITH LACTOSE INTOLERANCE DUE TO PRIMARY HYPOLACTASIA.

PubMed

Francesconi, Carlos Fernando de Magalhães; Machado, Marta Brenner; Steinwurz, Flavio; Nones, Rodrigo Bremer; Quilici, Flávio Antonio; Catapani, Wilson Roberto; Miszputen, Sender Jankiel; Bafutto, Mauro

2016-01-01

Primary hypolactasia is a common condition where a reduced lactase activity in the intestinal mucosa is present. The presence of abdominal symptoms due to poor absorption of lactose, which are present in some cases, is a characteristic of lactose intolerance. Evaluate the efficacy of a product containing exogenous lactase in tablet form compared to a reference product with proven effectiveness in patients with lactose intolerance. Multicentre, randomized, parallel group, single-blind, comparative non-inferiority study. One hundred twenty-nine (129) adult lactose intolerance patients with hydrogen breath test results consistent with a diagnosis of hypolactasia were randomly assigned to receive the experimental product (Perlatte(r) - Eurofarma Laboratórios S.A.) or the reference product (Lactaid(r) - McNeilNutritionals, USA) orally (one tablet, three times per day) for 42 consecutive days. Data from 128 patients who actually received the studied treatments were analysed (66 were treated with the experimental product and 62 with the reference product). The two groups presented with similar baseline clinical and demographic data. Mean exhaled hydrogen concentration tested at 90 minutes after the last treatment (Day 42) was significantly lower in the experimental product treated group (17±18 ppm versus 34±47 ppm) in the per protocol population. The difference between the means of the two groups was -17 ppm (95% confidence interval [95% CI]: -31.03; -3.17). The upper limit of the 95% CI did not exceed the a priori non-inferiority limit (7.5 ppm). Secondary efficacy analyses confirmed that the treatments were similar (per protocol and intention to treat population). The tolerability was excellent in both groups, and there were no reports of serious adverse events related to the study treatment. The experimental product was non-inferior to the reference product, indicating that it was an effective replacement therapy for endogenous lactase in lactose intolerance patients.

Use of cardiocerebral resuscitation or AHA/ERC 2005 Guidelines is associated with improved survival from out-of-hospital cardiac arrest: a systematic review and meta-analysis.

PubMed

Salmen, Marcus; Ewy, Gordon A; Sasson, Comilla

2012-01-01

To determine whether the use of cardiocerebral resuscitation (CCR) or AHA/ERC 2005 Resuscitation Guidelines improved patient outcomes from out-of-hospital cardiac arrest (OHCA) compared to older guidelines. Systematic review and meta-analysis. MEDLINE, EMBASE, Web of Science and the Cochrane Library databases. We also hand-searched study references and consulted experts. Design: randomised controlled trials and observational studies. OHCA patients, age >17 years. 'Control' protocol versus 'Study' protocol. 'Control' protocol defined as AHA/ERC 2000 Guidelines for cardiopulmonary resuscitation (CPR). 'Study' protocol defined as AHA/ERC 2005 Guidelines for CPR, or a CCR protocol. Survival to hospital discharge. High-quality or medium-quality studies, as measured by the Newcastle Ottawa Scale using predefined categories. Twelve observational studies met inclusion criteria. All the three studies using CCR demonstrated significantly improved survival compared to use of AHA 2000 Guidelines, as did five of the nine studies using AHA/ERC 2005 Guidelines. Pooled data demonstrate that use of a CCR protocol has an unadjusted OR of 2.26 (95% CI 1.64 to 3.12) for survival to hospital discharge among all cardiac arrest patients. Among witnessed ventricular fibrillation/ventricular tachycardia (VF/VT) patients, CCR increased survival by an OR of 2.98 (95% CI 1.92 to 4.62). Studies using AHA/ERC 2005 Guidelines showed an overall trend towards increased survival, but significant heterogeneity existed among these studies. We demonstrate an association with improved survival from OHCA when CCR protocols or AHA/ERC 2005 Guidelines are compared to use of older guidelines. In the subgroup of patients with witnessed VF/VT, there was a threefold increase in OHCA survival when CCR was used. CCR appears to be a promising resuscitation protocol for Emergency Medical Services providers in increasing survival from OHCA. Future research will need to be conducted to directly compare AHA/ERC 2010 Guidelines with the CCR approach.

The citation of relevant systematic reviews and randomised trials in published reports of trial protocols.

PubMed

Pandis, Nikolaos; Fleming, Padhraig S; Koletsi, Despina; Hopewell, Sally

2016-12-07

It is important that planned randomised trials are justified and placed in the context of the available evidence. The SPIRIT guidelines for reporting clinical trial protocols recommend that a recent and relevant systematic review should be included. The aim of this study was to assess the use of the existing evidence in order to justify trial conduct. Protocols of randomised trials published over a 1-month period (December 2015) indexed in PubMed were obtained. Data on trial characteristics relating to location, design, funding, conflict of interest and type of evidence included for trial justification was extracted in duplicate and independently by two investigators. The frequency of citation of previous research including relevant systematic reviews and randomised trials was assessed. Overall, 101 protocols for RCTs were identified. Most proposed trials were parallel-group (n = 74; 73.3%). Reference to an earlier systematic review with additional randomised trials was found in 9.9% (n = 10) of protocols and without additional trials in 30.7% (n = 31), while reference was made to randomised trials in isolation in 21.8% (n = 22). Explicit justification for the proposed randomised trial on the basis of being the first to address the research question was made in 17.8% (n = 18) of protocols. A randomised controlled trial was not cited in 10.9% (95% CI: 5.6, 18.7) (n = 11), while in 8.9% (95% CI: 4.2, 16.2) (n = 9) of the protocols a systematic review was cited but did not inform trial design. A relatively high percentage of protocols of randomised trials involves prior citation of randomised trials, systematic reviews or both. However, improvements are required to ensure that it is explicit that clinical trials are justified and shaped by contemporary best evidence.

The efficacy and safety of a chest pain protocol for short stay unit patients: A one year follow-up.

PubMed

Lee, Geraldine; Dix, Samantha; Mitra, Biswadev; Coleridge, John; Cameron, Peter

2015-10-01

The Alfred Emergency Short Stay Unit initiated a chest pain protocol for patients presenting with chest pain to risk stratify for acute coronary syndrome (ACS). A 30-day follow-up of patients discharged with low-or-intermediate risk of ACS demonstrated no deaths or ACS. The purpose of this study was to evaluate the long-term safety of the chest pain protocol, a one year follow-up was undertaken. A questionnaire was designed for the one-year follow-up and it was administered via a telephone interview by emergency nurses to document adverse cardiac events and health care utilisation. From 297 patients, 224 (75%) were contacted 12 months following discharge. There was one death from stroke (0.4%; 95% confidence interval (CI): 0.01-2.5%) and another from an unknown cause. Five patients had been diagnosed with atrial fibrillation (2.2%; 95% CI: 0.7-5.1%), two patients had an acute myocardial infarction (0.9%; 95% CI: 0.03-2.1%) and four were diagnosed with angina (1.8%; 95% CI: 0.9-3.2%). Nearly half (n=103, 46%; 95% CI: 39.5-52.5%) had returned to the emergency department (ED) for various conditions including 42 patients with further chest pain. Ninety-six patients (43%; 95% CI: 39.3-52.7%) had specialist referrals and 124 investigations were performed. Thirty-four patients had cardiology referrals (15%; 95% CI: 10.7-20.5%) and 25 patients had gastroenterology referrals (11%; 95% CI: 7.3-16.0%). Diagnostic cardiac tests were performed on 38 patients: coronary angiography (n=10), 24-hour Holter monitoring (n=17), 24-hour blood pressure (BP) monitoring (n=4), thallium scans (n=5), exercise stress test (n=1) and CT scan (n=1). Patients had a low risk of adverse events 12 months after discharge but substantial continuing health care utilization was observed. Complete assessment by health care professionals prior to discharge may help mitigate representations. © The European Society of Cardiology 2014.

Determining Reliability of a Dual-Task Functional Mobility Protocol for Individuals With Lower Extremity Amputation.

PubMed

Hunter, Susan W; Frengopoulos, Courtney; Holmes, Jeff; Viana, Ricardo; Payne, Michael W

2018-04-01

To determine the relative and absolute reliability of a dual-task functional mobility assessment. Cross-sectional study. Academic rehabilitation hospital. Individuals (N=60) with lower extremity amputation attending an outpatient amputee clinic (mean age, 58.21±12.59y; 18, 80% male) who were stratified into 3 groups: (1) transtibial amputation of vascular etiology (n=20); (2) transtibial amputation of nonvascular etiology (n=20); and (3) transfemoral or bilateral amputation of any etiology (n=20). Not applicable. Time to complete the L Test measured functional mobility under single- and dual-task conditions. The addition of a cognitive task (serial subtractions by 3's) created dual-task conditions. Single-task performance on the cognitive task was also reported. Intraclass correlation coefficients (ICCs) measured relative reliability; SEM and minimal detectable change with a 95% confidence interval (MDC 95 ) measured absolute reliability. Bland-Altman plots measured agreement between assessments. Relative reliability results were excellent for all 3 groups. Values for the dual-task L Test for those with transtibial amputation of vascular etiology (n=20; mean age, 60.36±7.84y; 19, 90% men) were ICC=.98 (95% confidence interval [CI], .94-.99), SEM=1.36 seconds, and MDC 95 =3.76 seconds; for those with transtibial amputation of nonvascular etiology (n=20; mean age, 55.85±14.08y; 17, 85% men), values were ICC=.93 (95% CI, .80-.98), SEM=1.34 seconds, and MDC 95 =3.71 seconds; and for those with transfemoral or bilateral amputation (n=20; mean age, 58.21±14.88y; 13, 65% men), values were ICC=.998 (95% CI, .996-.999), SEM=1.03 seconds, and MDC 95 =2.85 seconds. Bland-Altman plots indicated that assessments did not vary systematically for each group. This dual-task assessment protocol achieved approved levels of relative reliability values for the 3 groups tested. This protocol may be used clinically or in research settings to assess the interaction between cognition and functional mobility in the population with lower extremity amputation. Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Institutional Enrollment and Survival Among NSCLC Patients Receiving Chemoradiation: NRG Oncology Radiation Therapy Oncology Group (RTOG) 0617.

PubMed

Eaton, Bree R; Pugh, Stephanie L; Bradley, Jeffrey D; Masters, Greg; Kavadi, Vivek S; Narayan, Samir; Nedzi, Lucien; Robinson, Cliff; Wynn, Raymond B; Koprowski, Christopher; Johnson, Douglas W; Meng, Joanne; Curran, Walter J

2016-09-01

The purpose of this analysis is to evaluate the effect of institutional accrual volume on clinical outcomes among patients receiving chemoradiation for locally advanced non-small cell lung cancer (LA-NSCLC) on a phase III trial. Patients with LA-NSCLC were randomly assigned to 60 Gy or 74 Gy radiotherapy (RT) with concurrent carboplatin/paclitaxel +/- cetuximab on NRG Oncology RTOG 0617. Participating institutions were categorized as low-volume centers (LVCs) or high-volume centers (HVCs) according to the number of patients accrued (≤3 vs > 3). All statistical tests were two-sided. Range of accrual for LVCs (n = 195) vs HVCs (n = 300) was 1 to 3 vs 4 to 18 patients. Baseline characteristics were similar between the two cohorts. Treatment at a HVC was associated with statistically significantly longer overall survival (OS) and progression-free survival (PFS) compared with treatment at a LVC (median OS = 26.2 vs 19.8 months; HR = 0.70, 95% CI = 0.56 to 0.88, P = .002; median PFS: 11.4 vs 9.7 months, HR = 0.80, 95% CI = 0.65-0.99, P = .04). Patients treated at HVCs were more often treated with intensity-modulated RT (54.0% vs 39.5%, P = .002), had a lower esophageal dose (mean = 26.1 vs 28.0 Gy, P = .03), and had a lower heart dose (median = V5 Gy 38.2% vs 54.1%, P = .006; V50 Gy 3.6% vs 7.3%, P < .001). Grade 5 adverse events (AEs) (5.3% vs 9.2%, P = .09) and RT termination because of AEs (1.3% vs 4.1%, P = .07) were less common among patients treated at HVCs. HVC remained independently associated with longer OS (P = .03) when accounting for other factors. Treatment at institutions with higher clinical trial accrual volume is associated with longer OS among patients with LA-NSCLC participating in a phase III trial. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

SU-F-T-538: CyberKnife with MLC for Treatment of Large Volume Tumors: A Feasibility Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bichay, T; Mayville, A

2016-06-15

Purpose: CyberKnife is a well-documented modality for SRS and SBRT treatments. Typical tumors are small and 1–5 fractions are usually used. We determined the feasibility of using CyberKnife, with an InCise multileaf collimator option, for larger tumors undergoing standard dose and fractionation. The intent was to understand the limitation of using this modality for other external beam radiation treatments. Methods: Five tumors from different anatomical sites with volumes from 127.8 cc to 1,320.5 cc were contoured and planned on a Multiplan V5.1 workstation. The target average diameter ranged from 7 cm to 13 cm. The dose fractionation was 1.8–2.0 Gy/fractionmore » and 25–45 fractions for total doses of 45–81 Gy. The sites planned were: pancreas, head and neck, prostate, anal, and esophagus. The plans were optimized to meet conventional dose constraints based on various RTOG protocols for conventional fractionation. Results: The Multiplan treatment planning system successfully generated clinically acceptable plans for all sites studied. The resulting dose distributions achieved reasonable target coverage, all greater than 95%, and satisfactory normal tissue sparing. Treatment times ranged from 9 minutes to 38 minutes, the longest being a head and neck plan with dual targets receiving different doses and with multiple adjacent critical structures. Conclusion: CyberKnife, with the InCise multileaf collimation option, can achieve acceptable dose distributions in large volume tumors treated with conventional dose and fractionation. Although treatment times are greater than conventional accelerator time; target coverage and dose to critical structures can be kept within a clinically acceptable range. While time limitations exist, when necessary CyberKnife can provide an alternative to traditional treatment modalities for large volume tumors.« less

Publication and non-publication of clinical trials: longitudinal study of applications submitted to a research ethics committee.

PubMed

von Elm, Erik; Röllin, Alexandra; Blümle, Anette; Huwiler, Karin; Witschi, Mark; Egger, Matthias

2008-04-05

Not all clinical trials are published, which may distort the evidence that is available in the literature. We studied the publication rate of a cohort of clinical trials and identified factors associated with publication and nonpublication of results. We analysed the protocols of randomized clinical trials of drug interventions submitted to the research ethics committee of University Hospital (Inselspital) Bern, Switzerland from 1988 to 1998. We identified full articles published up to 2006 by searching the Cochrane CENTRAL database (issue 02/2006) and by contacting investigators. We analyzed factors associated with the publication of trials using descriptive statistics and logistic regression models. 451 study protocols and 375 corresponding articles were analyzed. 233 protocols resulted in at least one publication, a publication rate of 52%. A total of 366 (81%) trials were commercially funded, 47 (10%) had non-commercial funding. 346 trials (77%) were multi-centre studies and 272 of these (79%) were international collaborations. In the adjusted logistic regression model non-commercial funding (Odds Ratio [OR] 2.42, 95% CI 1.14-5.17), multi-centre status (OR 2.09, 95% CI 1.03-4.24), international collaboration (OR 1.87, 95% CI 0.99-3.55) and a sample size above the median of 236 participants (OR 2.04, 95% CI 1.23-3.39) were associated with full publication. In this cohort of applications to an ethics committee in Switzerland, only about half of clinical drug trials were published. Large multi-centre trials with non-commercial funding were more likely to be published than other trials, but most trials were funded by industry.

Hodgkin lymphoma in children, adolescents and young adults - a comparative study of clinical presentation and treatment outcome.

PubMed

Englund, Annika; Glimelius, Ingrid; Rostgaard, Klaus; Smedby, Karin E; Eloranta, Sandra; Molin, Daniel; Kuusk, Thomas; Brown, Peter de Nully; Kamper, Peter; Hjalgrim, Henrik; Ljungman, Gustaf; Hjalgrim, Lisa Lyngsie

2018-02-01

Hodgkin lymphoma (HL) treatment protocols for children, adolescents and young adults traditionally differ, but the biological and clinical justification for this remains uncertain. We compared age-dependent clinical presentation and treatment and outcome for 1072 classical HL patients 0-24 years diagnosed in Denmark (1990-2010) and Sweden (1992-2009) in pediatric (n = 315, Denmark <15 years, Sweden <18 years) or adult departments (n = 757). Distribution of clinical characteristics was assessed with Pearson's chi 2 -test and Mantel-Haenszel trend test. The Kaplan-Meier method was used for survival analyses. Hazard ratios (HR) were used to compare the different treatment groups and calculated using Cox regression. Children (0-9 years) less often presented with advanced disease than adolescents (10-17 years) and young adults (18-24 years) (stage IIB-IV: children 32% vs. adolescents 50%, and adults 55%; p < .005). No variation in overall survival (OS) was seen between pediatric and adult departments or by country. Danish pediatric patients received radiotherapy (36%) less frequently than Swedish pediatric patients (71%) (p < .0001). Ten-year event-free survival (EFS) was lower among Danish pediatric patients (0-14 years) (0.79; 95% confidence interval (CI) 0.70-0.86) than among Swedish pediatric patients (0-17 years) (0.88; 95% CI 0.83-0.92), HR (1.93; 95% CI 1.08-3.46). A similar pattern was seen between adult patients in the two countries: Denmark 10-year EFS 0.85 (95% CI 0.81-0.88), Sweden 0.88 (95% CI 0.84-0.91), adjusted HR 1.51 (95% CI 1.03-2.22). Adolescents and young adults shared similar clinical presentation suggesting a rationale of harmonized treatment for these groups. Both adult and pediatric protocols provided high OS with no significant difference between the departments. The less frequent use of radiotherapy in Danish pediatric patients corresponded to a lower EFS, but comparable OS in all groups confirmed effective rescue strategies for the relapsing patients.

Significant Reduction of Late Toxicities in Patients With Extremity Sarcoma Treated With Image-Guided Radiation Therapy to a Reduced Target Volume: Results of Radiation Therapy Oncology Group RTOG-0630 Trial.

PubMed

Wang, Dian; Zhang, Qiang; Eisenberg, Burton L; Kane, John M; Li, X Allen; Lucas, David; Petersen, Ivy A; DeLaney, Thomas F; Freeman, Carolyn R; Finkelstein, Steven E; Hitchcock, Ying J; Bedi, Manpreet; Singh, Anurag K; Dundas, George; Kirsch, David G

2015-07-10

We performed a multi-institutional prospective phase II trial to assess late toxicities in patients with extremity soft tissue sarcoma (STS) treated with preoperative image-guided radiation therapy (IGRT) to a reduced target volume. Patients with extremity STS received IGRT with (cohort A) or without (cohort B) chemotherapy followed by limb-sparing resection. Daily pretreatment images were coregistered with digitally reconstructed radiographs so that the patient position could be adjusted before each treatment. All patients received IGRT to reduced tumor volumes according to strict protocol guidelines. Late toxicities were assessed at 2 years. In all, 98 patients were accrued (cohort A, 12; cohort B, 86). Cohort A was closed prematurely because of poor accrual and is not reported. Seventy-nine eligible patients from cohort B form the basis of this report. At a median follow-up of 3.6 years, five patients did not have surgery because of disease progression. There were five local treatment failures, all of which were in field. Of the 57 patients assessed for late toxicities at 2 years, 10.5% experienced at least one grade ≥ 2 toxicity as compared with 37% of patients in the National Cancer Institute of Canada SR2 (CAN-NCIC-SR2: Phase III Randomized Study of Pre- vs Postoperative Radiotherapy in Curable Extremity Soft Tissue Sarcoma) trial receiving preoperative radiation therapy without IGRT (P < .001). The significant reduction of late toxicities in patients with extremity STS who were treated with preoperative IGRT and absence of marginal-field recurrences suggest that the target volumes used in the Radiation Therapy Oncology Group RTOG-0630 (A Phase II Trial of Image-Guided Preoperative Radiotherapy for Primary Soft Tissue Sarcomas of the Extremity) study are appropriate for preoperative IGRT for extremity STS. © 2015 by American Society of Clinical Oncology.

Transformation of Physical DVHs to Radiobiologically Equivalent Ones in Hypofractionated Radiotherapy Analyzing Dosimetric and Clinical Parameters: A Practical Approach for Routine Clinical Practice in Radiation Oncology

PubMed Central

Thrapsanioti, Zoi; Karanasiou, Irene; Platoni, Kalliopi; Efstathopoulos, Efstathios P.; Matsopoulos, George; Dilvoi, Maria; Patatoukas, George; Chaldeopoulos, Demetrios; Kelekis, Nikolaos; Kouloulias, Vassilis

2013-01-01

Purpose. The purpose of this study was to transform DVHs from physical to radiobiological ones as well as to evaluate their reliability by correlations of dosimetric and clinical parameters for 50 patients with prostate cancer and 50 patients with breast cancer, who were submitted to Hypofractionated Radiotherapy. Methods and Materials. To achieve this transformation, we used both the linear-quadratic model (LQ model) and the Niemierko model. The outcome of radiobiological DVHs was correlated with acute toxicity score according to EORTC/RTOG criteria. Results. Concerning the prostate radiotherapy, there was a significant correlation between RTOG acute rectal toxicity and D 50 (P < 0.001) and V 60 (P = 0.001) dosimetric parameters, calculated for α/β = 10 Gy. Moreover, concerning the breast radiotherapy there was a significant correlation between RTOG skin toxicity and V ≥60 dosimetric parameter, calculated for both α/β = 2.3 Gy (P < 0.001) and α/β = 10 Gy (P < 0.001). The new tool seems reliable and user-friendly. Conclusions. Our proposed model seems user-friendly. Its reliability in terms of agreement with the presented acute radiation induced toxicity was satisfactory. However, more patients are needed to extract safe conclusions. PMID:24348743

Soft and Hard Tissue Changes Following Immediate Placement or Immediate Restoration of Single-Tooth Implants in the Esthetic Zone: A Systematic Review and Meta-Analysis.

PubMed

Yan, Qi; Xiao, Li-Qun; Su, Mei-Ying; Mei, Yan; Shi, Bin

This systematic review aimed to compare immediate protocols with conventional protocols of single-tooth implants in terms of changes in the surrounding hard and soft tissue in the esthetic area. Electronic and manual searches were performed in PubMed, EMBASE, Cochrane, and other data systems for research articles published between January 2001 and December 2014. Only randomized controlled trials (RCTs) reporting on hard and or soft tissue characteristics following a single-tooth implant were included. Based on the protocol used in each study, the included studies were categorized into three groups to assess the relationships between the factors and related esthetic indexes. Variables such as marginal bone level changes (mesial, distal, and mean bone level), peri-implant soft tissue changes (papilla level, midbuccal mucosa, and probing depth), and other esthetic indices were taken into consideration. The data were analyzed using RevMan version 5.3, Stata 12, and GRADEpro 3.6.1 software. A total of 13 RCTs met the inclusion criteria. Four studies examined immediate implant placement, five studies examined immediate implant restoration, and four studies examined immediate loading. Comparing the bone level changes following immediate and conventional restoration, no significant differences were found in the bone level of the mesial site (standard mean difference [SMD] = -0.04 mm; 95% confidence interval [CI]: -0.25 to 0.17 mm), the distal site (SMD = -0.15 mm; 95% CI: -0.38 to 0.09 mm), and the mean bone level changes (SMD = 0.05 mm; 95% CI: -0.18 to 0.27 mm). The difference in the marginal bone level changes between immediate and conventional loading was also not statistically significant (SMD = -0.05 mm; 95% CI: -0.15 to 0.06 mm for the mesial site and SMD = -0.02 mm; 95% CI: -0.09 to 0.05 mm for the distal site). Soft tissue changes following immediate and conventional restoration reported no significant differences in the papillae level of the mesial site (SMD = 0.18 mm; 95% CI: -0.00 to 0.37 mm), the papillae level of the distal site (SMD = -0.12 mm; 95% CI: -0.34 to 0.09 mm), and the midbuccal mucosa (SMD = -0.22 mm; 95% CI: -1.29 to 0.85 mm). Within the limitations, it can be concluded that immediately placed, restored, or loaded single-tooth implants in the esthetic zone result in similar hard and soft tissue changes compared with conventional protocols.

Prognostic impact of HPV-associated p16-expression and smoking status on outcomes following radiotherapy for oropharyngeal cancer: The MARCH-HPV project.

PubMed

Lassen, Pernille; Lacas, Benjamin; Pignon, Jean-Pierre; Trotti, Andy; Zackrisson, Bjorn; Zhang, Qiang; Overgaard, Jens; Blanchard, Pierre

2018-01-01

Evaluate the prognostic and predictive impact of HPV-associated p16-expression and assess the combined prognostic impact of p16 and smoking on altered fractionated radiotherapy (AFRT) for oropharyngeal cancer (OPC) within the frames of the update of the Meta-Analysis of Radiotherapy in Carcinomas of Head and neck (MARCH). Patients with OPC, known tumor p16-status and smoking history were identified from the MARCH update, resulting in a dataset of 815 patients from four randomized trials (RTOG9003, DAHANCA6&7, RTOG0129, ARTSCAN). Analysis was performed using a Cox model stratified by trial and adjusted on gender, age, T-stage, N-stage, type of radiotherapy fractionation, p16, smoking. Primary endpoint was progression-free survival (PFS). In total, 465 patients (57%) had p16-positive tumors and 350 (43%) p16-negative. Compared to p16-negative, p16-positive patients had significantly better PFS (HR = 0.42 [95% CI: 0.34-0.51], 28.9% absolute increase at 10 years) and OS (HR = 0.40 [0.32-0.49], 32.1% absolute increase at 10 years). No interaction between p16-status and fractionation schedule was detected. Smoking negatively impacted outcome; in the p16-positive subgroup, never smokers had significantly better PFS than former/current smokers (HR = 0.49 [0.33-0.75], 24.2% survival benefit at 10 years). No predictive impact of p16-status on response to AFRT could be detected but the strong prognostic impact of p16-status was confirmed and especially p16-positive never smoking patients have superior outcome after RT. Copyright © 2017 Elsevier B.V. All rights reserved.

Vascular endothelial growth factor (VEGF) expression in locally advanced prostate cancer: secondary analysis of radiation therapy oncology group (RTOG) 8610.

PubMed

Pan, Larry; Baek, Seunghee; Edmonds, Pamela R; Roach, Mack; Wolkov, Harvey; Shah, Satish; Pollack, Alan; Hammond, M Elizabeth; Dicker, Adam P

2013-04-25

Angiogenesis is a key element in solid-tumor growth, invasion, and metastasis. VEGF is among the most potent angiogenic factor thus far detected. The aim of the present study is to explore the potential of VEGF (also known as VEGF-A) as a prognostic and predictive biomarker among men with locally advanced prostate cancer. The analysis was performed using patients enrolled on RTOG 8610, a phase III randomized control trial of radiation therapy alone (Arm 1) versus short-term neoadjuvant and concurrent androgen deprivation and radiation therapy (Arm 2) in men with locally advanced prostate carcinoma. Tissue samples were obtained from the RTOG tissue repository. Hematoxylin and eosin slides were reviewed, and paraffin blocks were immunohistochemically stained for VEGF expression and graded by Intensity score (0-3). Cox or Fine and Gray's proportional hazards models were used. Sufficient pathologic material was available from 103 (23%) of the 456 analyzable patients enrolled in the RTOG 8610 study. There were no statistically significant differences in the pre-treatment characteristics between the patient groups with and without VEGF intensity data. Median follow-up for all surviving patients with VEGF intensity data is 12.2 years. Univariate and multivariate analyses demonstrated no statistically significant correlation between the intensity of VEGF expression and overall survival, distant metastasis, local progression, disease-free survival, or biochemical failure. VEGF expression was also not statistically significantly associated with any of the endpoints when analyzed by treatment arm. This study revealed no statistically significant prognostic or predictive value of VEGF expression for locally advanced prostate cancer. This analysis is among one of the largest sample bases with long-term follow-up in a well-characterized patient population. There is an urgent need to establish multidisciplinary initiatives for coordinating further research in the area of human prostate cancer biomarkers.

Hand hygiene with soap and water is superior to alcohol rub and antiseptic wipes for removal of Clostridium difficile.

PubMed

Oughton, Matthew T; Loo, Vivian G; Dendukuri, Nandini; Fenn, Susan; Libman, Michael D

2009-10-01

To evaluate common hand hygiene methods for efficacy in removing Clostridium difficile. Randomized crossover comparison among 10 volunteers with hands experimentally contaminated by nontoxigenic C. difficile. Interventions included warm water with plain soap, cold water with plain soap, warm water with antibacterial soap, antiseptic hand wipes, alcohol-based handrub, and a control involving no intervention. All interventions were evaluated for mean reduction in colony-forming units (CFUs) under 2 contamination protocols: "whole hand" and "palmar surface." Results were analyzed according to a Bayesian approach, by using hierarchical models adjusted for multiple observations. Under the whole-hand protocol, the greatest adjusted mean reductions were achieved by warm water with plain soap (2.14 log(10) CFU/mL [95% credible interval (CrI), 1.74-2.54 log(10) CFU/mL]), cold water with plain soap (1.88 log(10) CFU/mL [95% CrI, 1.48-2.28 log(10) CFU/mL), and warm water with antibacterial soap (1.51 log(10) CFU/mL [95% CrI, 1.12-1.91 log(10) CFU/mL]), followed by antiseptic hand wipes (0.57 log(10) CFU/mL [95% CrI, 0.17-0.96 log(10) CFU/mL]). Alcohol-based handrub (0.06 log(10) CFU/mL [95% CrI, -0.34 to 0.45 log(10) CFU/mL]) was equivalent to no intervention. Under the palmar surface protocol, warm water with plain soap, cold water with plain soap, and warm water with antibacterial soap again yielded the greatest mean reductions, followed by antiseptic hand wipes (26.6, 26.6, 26.6, and 21.9 CFUs per plate, respectively), when compared with alcohol-based handrub. Hypothenar (odds ratio, 10.98 [95% CrI, 1.96-37.65]) and thenar (odds ratio, 6.99 [95% CrI, 1.25-23.41]) surfaces were more likely than fingertips to remain heavily contaminated after handwashing. Handwashing with soap and water showed the greatest efficacy in removing C. difficile and should be performed preferentially over the use of alcohol-based handrubs when contact with C. difficile is suspected or likely.

Comparison of toxicity associated with early morning versus late afternoon radiotherapy in patients with head-and-neck cancer: a prospective randomized trial of the National Cancer Institute of Canada Clinical Trials Group (HN3).

PubMed

Bjarnason, Georg A; Mackenzie, Robert G; Nabid, Abdenour; Hodson, Ian D; El-Sayed, Samy; Grimard, Laval; Brundage, Michael; Wright, James; Hay, John; Ganguly, Pradip; Leong, Carson; Wilson, Jane; Jordan, Richard C K; Walker, Melanie; Tu, Dongsheng; Parulekar, Wendy

2009-01-01

Based on our demonstration of a circadian rhythm in the human oral mucosa cell cycle, with most cells in the G(1) phase in the morning and M phase at night, we hypothesized that morning radiotherapy (RT) would lead to less oral mucositis than afternoon RT. A total of 216 patients were randomized to morning (8-10 AM) vs. afternoon (4-6 PM) RT and stratified by radiation dose, smoking status, and center. Patients receiving primary or postoperative RT alone were eligible. Oral mucositis was scored using the Radiation Therapy Oncology Group (RTOG) criteria and a validated scoring system. Of 205 evaluable patients, 52.9% vs. 62.4% developed RTOG Grade 3 or greater mucositis after morning vs. afternoon RT, respectively (p = 0.17). Morning RT was also associated with significantly less weight loss after 5 months (p = 0.024). In a subgroup of 111 patients treated to a dose of 66-70 Gy in 33-35 fractions, exploratory analyses revealed a significant reduction in Grade 3 or greater mucositis with morning RT (44.6% vs. 67.3%, p = 0.022) and a longer interval to the development of Grade 3 or greater mucositis (median, >7.9 vs. 5.6 weeks, p = 0.033). In 53 patients, who smoked during therapy, a significant reduction was found in Grade 3 or greater mucositis with morning RT (42.9% vs. 76%, p = 0.025). In this proof of principle study, morning RT was associated with significantly less weight loss after 5 months and an apparent reduction in oral mucositis in a subset of patients receiving >/=66 Gy and in patients who smoked during therapy.

Optimal treatment for localized esophageal cancer still uncertain.

PubMed

Lord, R V

2000-01-01

These articles both report the results of multi-institutional, randomized, phase 3 trials for the treatment of patients with localized (T1-3 N0-1 M0) esophageal squamous cell carcinoma (SCC) or esophageal adenocarcinoma. Both studies were initiated and coordinated by the Radiation Therapy Oncology Group (RTOG) but included patients enrolled by other study groups as well. Cooper et al. report late follow-up results for the RTOG 85-01 trial that was conducted between 1986 and 1990. This trial randomized patients to either radiation therapy (RT) alone (RT, 64 Gy in 32 fractions over 6.4 wk, n = 62) or combined RT and chemotherapy (50 Gy in 25 fractions over 5 wk, plus cisplatin 75 mg/m2 i.v. on first day of wk 1, 5, 8, and 11, and continuous infusion fluorouracil (5FU) 1 g/m2 per day on the first 4 days of the same weeks, n = 61). Most (82%) of the patients had SCC. Eight percent of the cohort randomly assigned to combined modality therapy experienced acute life-threatening toxic effects, and an additional 2% died as a direct consequence of treatment. The randomized trial was halted in 1990 when an interim analysis found a highly significant difference in survival favoring the combined therapy group, after which 73 consecutive patients were enrolled into a nonrandomized study offering only the combined therapy regimen. At 5-yr of follow-up, the overall survival rate for the combined therapy group in the randomized study was 26% (95% CI, 15-37%) compared with 0% for RT alone. In the nonrandomized study, the 5-yr overall survival rate was 14% (95% CI, 6-23%). The histopathological type of tumor did not significantly influence survival. Cooper et al. now report that 22% of the randomized combined modality group survived at least 8 yr after treatment, and that there were no deaths caused by esophageal cancer after 5 yr post-treatment. The study reported by Kelsen et al. included 440 patients with esophageal adenocarcinoma (n = 236) or SCC (n = 204) randomized to either preoperative chemotherapy plus esophagectomy or to esophagectomy alone. The chemotherapy regimen consisted of three cycles of preoperative cisplatin and 5FU and two cycles after operation for responding patients. Doses were higher than those used in the RTOG 85-01 trial. Although radiation therapy was not part of the treatment plan, it could be given in some circumstances. There was no significant difference in median survival (14.9 months for chemotherapy plus surgery compared with 16.1 months for surgery alone), and there were also no significant differences in 1-yr, 2-yr, 3-yr, or disease-free survival rates. There were no significant differences in survival between patients with adenocarcinoma and those with SCC. A clinical response to chemotherapy, as assessed by barium contrast radiography, was found in 19% of patients who received chemotherapy. A complete pathological response was found in 2.5% of patients. There was no significant increase in operative complications in the chemotherapy treated group.

Comparison of Outcomes before and after Ohio's Law Mandating Use of the FDA-Approved Protocol for Medication Abortion: A Retrospective Cohort Study.

PubMed

Upadhyay, Ushma D; Johns, Nicole E; Combellick, Sarah L; Kohn, Julia E; Keder, Lisa M; Roberts, Sarah C M

2016-08-01

In February 2011, an Ohio law took effect mandating use of the United States Food and Drug Administration (FDA)-approved protocol for mifepristone, which is used with misoprostol for medication abortion. Other state legislatures have passed or enacted similar laws requiring use of the FDA-approved protocol for medication abortion. The objective of this study is to examine the association of this legal change with medication abortion outcomes and utilization. We used a retrospective cohort design, comparing outcomes of medication abortion patients in the prelaw period to those in the postlaw period. Sociodemographic and clinical chart data were abstracted from all medication abortion patients from 1 y prior to the law's implementation (January 2010-January 2011) to 3 y post implementation (February 2011-October 2014) at four abortion-providing health care facilities in Ohio. Outcome data were analyzed for all women undergoing abortion at ≤49 d gestation during the study period. The main outcomes were as follows: need for additional intervention following medication abortion (such as aspiration, repeat misoprostol, and blood transfusion), frequency of continuing pregnancy, reports of side effects, and the proportion of abortions that were medication abortions (versus other abortion procedures). Among the 2,783 medication abortions ≤49 d gestation, 4.9% (95% CI: 3.7%-6.2%) in the prelaw and 14.3% (95% CI: 12.6%-16.0%) in the postlaw period required one or more additional interventions. Women obtaining a medication abortion in the postlaw period had three times the odds of requiring an additional intervention as women in the prelaw period (adjusted odds ratio [AOR] = 3.11, 95% CI: 2.27-4.27). In a mixed effects multivariable model that uses facility-months as the unit of analysis to account for lack of independence by site, we found that the law change was associated with a 9.4% (95% CI: 4.0%-18.4%) absolute increase in the rate of requiring an additional intervention. The most common subsequent intervention in both periods was an additional misoprostol dose and was most commonly administered to treat incomplete abortion. The percentage of women requiring two or more follow-up visits increased from 4.2% (95% CI: 3.0%-5.3%) in the prelaw period to 6.2% (95% CI: 5.5%-8.0%) in the postlaw period (p = 0.003). Continuing pregnancy was rare (0.3%). Overall, 12.6% of women reported at least one side effect during their medication abortion: 8.4% (95% CI: 6.8%-10.0%) in the prelaw period and 15.6% (95% CI: 13.8%-17.3%) in the postlaw period (p < 0.001). Medication abortions fell from 22% (95% CI: 20.8%-22.3%) of all abortions the year before the law went into effect (2010) to 5% (95% CI: 4.8%-5.6%) 3 y after (2014) (p < 0.001). The average patient charge increased from US$426 in 2010 to US$551 in 2014, representing a 16% increase after adjusting for inflation in medical prices. The primary limitation to the study is that it was a pre/post-observational study with no control group that was not exposed to the law. Ohio law required use of a medication abortion protocol that is associated with a greater need for additional intervention, more visits, more side effects, and higher costs for women relative to the evidence-based protocol. There is no evidence that the change in law led to improved abortion outcomes. Indeed, our findings suggest the opposite. In March 2016, the FDA-protocol was updated, so Ohio providers may now legally provide current evidence-based protocols. However, this law is still in place and bans physicians from using mifepristone based on any new developments in clinical research as best practices continue to be updated.

Mometasone Furoate Cream Reduces Acute Radiation Dermatitis in Patients Receiving Breast Radiation Therapy: Results of a Randomized Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hindley, Andrew, E-mail: andrew.hindley@lthtr.nhs.uk; Zain, Zakiyah; Wood, Lisa

Purpose: We wanted to confirm the benefit of mometasone furoate (MF) in preventing acute radiation reactions, as shown in a previous study (Boström et al, Radiother Oncol 2001;59:257-265). Methods and Materials: The study was a double-blind comparison of MF with D (Diprobase), administered daily from the start of radiation therapy for 5 weeks in patients receiving breast radiation therapy, 40 Gy in 2.67-Gy fractions daily over 3 weeks. The primary endpoint was mean modified Radiation Therapy Oncology Group (RTOG) score. Results: Mean RTOG scores were significantly less for MF than for D (P=.046). Maximum RTOG and mean erythema scores were significantly less for MFmore » than for D (P=.018 and P=.012, respectively). The Dermatology Life Quality Index (DLQI) score was significantly less for MF than for D at weeks 4 and 5 when corrected for Hospital Anxiety and Depression (HAD) questionnaire scores. Conclusions: MF cream significantly reduces radiation dermatitis when applied to the breast during and after radiation therapy. For the first time, we have shown a significantly beneficial effect on quality of life using a validated instrument (DLQI), for a topical steroid cream. We believe that application of this cream should be the standard of care where radiation dermatitis is expected.« less

Xerostomia health-related quality of life: NRG oncology RTOG 0537.

PubMed

Wyatt, Gwen; Pugh, Stephanie L; Wong, Raimond K W; Sagar, Stephen; Singh, Anurag K; Koyfman, Shlomo A; Nguyen-Tân, Phuc F; Yom, Sue S; Cardinale, Francis S; Sultanem, Khalil; Hodson, Ian; Krempl, Greg A; Lukaszczyk, Barbara; Yeh, Alexander M; Berk, Lawrence

2016-09-01

The purpose of this secondary analysis was to determine change in overall health-related quality of life (HRQOL) based on patient data obtained from NRG Oncology RTOG 0537 as measured by the RTOG-modified University of Washington Head and Neck Symptom Score (RM-UWHNSS). A multi-site prospective randomized clinical trial design stratified 137 patients with post-radiation therapy xerostomia according to prior pilocarpine (PC) treatment and time after radiation therapy and/or chemotherapy and randomized patients into two groups. Patients were assigned to acupuncture or PC. Twenty-four sessions of acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) were administered over 12 weeks, or oral PC (5 mg) three times daily over the same 12 weeks. The RM-UWHNSS was administered at baseline and at 4, 6, 9, and 15 months after the date of randomization. There were no between-arm differences in change scores on the RM-UWHNSS in the individual items, total score, or factor scores. For statistical modeling, race and time were significant for all outcomes (total and factor scores), while treatment arm was not significant. The ALTENS arm showed greater yet nonsignificant improvement in outcomes compared to the PC arm. Although no significant treatment differences were seen in this trial, patients receiving ALTENS consistently had lower scores, indicating better function, as compared to those receiving PC. Radiation-induced xerostomia improved over time for all patients.

Three-dimensional conformal radiation therapy for squamous cell carcinoma of the esophagus: a prospective phase I/II study.

PubMed

Wu, Kai-Liang; Chen, Guei-Yuan; Xu, Zhi-Yong; Fu, Xiao-Long; Qian, Hao; Jiang, Guo-Liang

2009-12-01

A prospective phase I-II study was conducted to determine the tolerance and local control rate of three-dimensional conformal radiotherapy (3-DCRT) for esophageal squamous cell carcinoma (SCC). Thirty patients underwent 3-DCRT for thoracic esophageal SCC. PTV1 composed of a 1.2-1.5 cm margin lateral around GTV and 3.0 cm margin superior/inferior of GTV. PTV2 encompassed GTV with a margin of 0.5-0.7 cm. The dose for PTV1 was 50 Gy in 2 Gy daily fractions; PTV2 received a boost of 16 Gy in 2 Gy daily fractions to a total dose of 66 Gy. Median follow-up time was 18 months. The most common acute toxicity was esophagitis in 63% of patients with RTOG grades 1-2, and in 3% with grade 3. RTOG grades 1-2 radiation pneumonitis developed in 27% of patients. One patient developed pulmonary fibrosis RTOG grade 2 and another patient experienced grade 3 pulmonary fibrosis. Two patients developed mild esophageal stricture requiring dilatation. Two-year overall survival, local disease progression-free rate, and distant metastasis-free rate were 69%, 36% and 56%, respectively. Although 3-DCRT to 66 Gy for esophageal SCC was well tolerated, the local control was disappointing. The result supports the use of chemoradiation as the standard care for esophageal SCC.

Implementation of subcutaneous insulin protocol for non-critically ill hospitalized patients in andalusian tertiary care hospitals.

PubMed

Martínez-Brocca, María Asunción; Morales, Cristóbal; Rodríguez-Ortega, Pilar; González-Aguilera, Beatriz; Montes, Cristina; Colomo, Natalia; Piédrola, Gonzalo; Méndez-Muros, Mariola; Serrano, Isabel; Ruiz de Adana, Maria Soledad; Moreno, Alberto; Fernández, Ignacio; Aguilar, Manuel; Acosta, Domingo; Palomares, Rafael

2015-02-01

In 2009, the Andalusian Society of Endocrinology and Nutrition designed a protocol for subcutaneous insulin treatment in hospitalized non-critically ill patients (HIP). To analyze implementation of HIP at tertiary care hospitals from the Andalusian Public Health System. A descriptive, multicenter study conducted in 8 tertiary care hospitals on a random sample of non-critically ill patients with diabetes/hyperglycemia (n=306) hospitalized for ≥48 hours in 5 non-surgical (SM) and 2 surgical (SQ) departments. Type 1 and other specific types of diabetes, pregnancy and nutritional support were exclusion criteria. 288 patients were included for analysis (62.5% males; 70.3±10.3 years; 71.5% SM, 28.5% SQ). A scheduled subcutaneous insulin regimen based on basal-bolus-correction protocol was started in 55.9% (95%CI: 50.5-61.2%) of patients, 63.1% SM vs. 37.8% SQ (P<.05). Alternatives to insulin regimen based on basal-bolus-correction included sliding scale insulin (43.7%), diet (31.3%), oral antidiabetic drugs (17.2%), premixed insulin (1.6%), and others (6.2%). For patients previously on oral antidiabetic drugs, in-hospital insulin dose was 0.32±0.1 IU/kg/day. In patients previously on insulin, in-hospital insulin dose was increased by 17% [-13-53], and in those on insulin plus oral antidiabetic drugs, in-hospital insulin dose was increased by 26.4% [-6-100]. Supplemental insulin doses used for<40 IU/day and 40-80 IU/day were 72.2% and 56.7% respectively. HbA1c was measured in 23.6% of patients (95CI%: 18.8-28.8); 27.7% SM vs. 13.3% SQ (P<.05). Strategies are needed to improve implementation of the inpatient subcutaneous insulin protocol, particularly in surgical departments. Sliding scale insulin is still the most common alternative to insulin regimen based on basal-bolus-correction scheduled insulin. Metabolic control assessment during hospitalization should be encouraged. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

Hypersensitivity Reactions to Oxaliplatin: Identifying the Risk Factors and Judging the Efficacy of a Desensitization Protocol.

PubMed

Okayama, Tetsuya; Ishikawa, Takeshi; Sugatani, Kazuko; Yoshida, Naohisa; Kokura, Satoshi; Matsuda, Kiyomi; Tsukamoto, Shigeru; Ihara, Norihiko; Kuriu, Yoshiaki; Nakanishi, Masayoshi; Nakamura, Terukazu; Kamada, Kazuhiro; Katada, Kazuhiro; Uchiyama, Kazuhiko; Takagi, Tomohisa; Handa, Osamu; Konishi, Hideyuki; Yagi, Nobuaki; Naito, Yuji; Otsuji, Eigo; Hosoi, Hajime; Miki, Tsuneharu; Itoh, Yoshito

2015-06-01

We examined the clinical data of patients treated with oxaliplatin to determine the risk factors of oxaliplatin-related hypersensitivity reaction (HSR). In addition, we evaluated the efficacy of rechallenging patients with HSRs with oxaliplatin using prophylactic agents or desensitization procedures. This study consisted of 162 patients with colorectal cancer (88 men and 74 women) who were treated consecutively at the outpatient chemotherapy department at University Hospital, Kyoto Prefectural University of Medicine. Patients underwent chemotherapy, including oxaliplatin, between March 2006 and June 2012. We analyzed the patients' clinical backgrounds (eg, age, sex, performance status, disease stage, and allergic history) to uncover any connections to the development of HSR to oxaliplatin. In addition, we rechallenged 10 patients who had oxaliplatin-related HSR using prophylactic agents or desensitization procedures. Of 162 patients, 28 (17.2%) developed oxaliplatin-related HSRs (16, 2, 9 and 1 patient had grade 1, 2, 3, and 4 HSRs, respectively). The total cumulative dose of oxaliplatin at the onset of the HSR was 301 to 1126 mg/m(2) (median, 582 mg/m(2)), and the first reactions developed in these patients after 5 to 17 infusions of oxaliplatin (median, 8 infusions). Logistic regression analysis indicated that sex (male: odds ratio = 3.624; 95% CI, 1.181-11.122; P = 0.024) and eosinophil count in peripheral blood (odds ratio = 35.118; 95% CI, 1.058-1166.007; P = 0.046) were independent variables for oxaliplatin-related HSRs. Rechallenging patients with prophylactic agents was successful in 2 (28.6%) of 7 patients who successfully completed their treatment. On the other hand, all 3 patients rechallenged with oxaliplatin using a desensitization protocol successfully completed their treatment without new HSRs. In this retrospective study, we observed that being male and having higher counts of peripheral eosinophil could be predictors for HSR to oxaliplatin. In addition, this study confirms that oxaliplatin desensitization protocol allows patients who developed HSRs to continue with their treatment. However, the optimum desensitization protocol for oxaliplatin administration in terms of tolerability and efficacy needs to be defined. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Effect of the Addition of Cetuximab to Paclitaxel, Cisplatin, and Radiation Therapy for Patients With Esophageal Cancer: The NRG Oncology RTOG 0436 Phase 3 Randomized Clinical Trial.

PubMed

Suntharalingam, Mohan; Winter, Kathryn; Ilson, David; Dicker, Adam P; Kachnic, Lisa; Konski, André; Chakravarthy, A Bapsi; Anker, Christopher J; Thakrar, Harish; Horiba, Naomi; Dubey, Ajay; Greenberger, Joel S; Raben, Adam; Giguere, Jeffrey; Roof, Kevin; Videtic, Gregory; Pollock, Jondavid; Safran, Howard; Crane, Christopher H

2017-11-01

The role of epidermal growth factor receptor (EGFR) inhibition in chemoradiation strategies in the nonoperative treatment of patients with esophageal cancer remains uncertain. To evaluate the benefit of cetuximab added to concurrent chemoradiation therapy for patients undergoing nonoperative treatment of esophageal carcinoma. A National Cancer Institute (NCI) sponsored, multicenter, phase 3, randomized clinical trial open to patients with biopsy-proven carcinoma of the esophagus. The study accrued 344 patients from 2008 to 2013. Patients were randomized to weekly concurrent cisplatin (50 mg/m2), paclitaxel (25 mg/m2), and daily radiation of 50.4 Gy/1.8 Gy fractions with or without weekly cetuximab (400 mg/m2 on day 1 then 250 mg/m2 weekly). Overall survival (OS) was the primary endpoint, with a study designed to detect an increase in 2-year OS from 41% to 53%; 80% power and 1-sided α = .025. Between June 30, 2008, and February 8, 2013, 344 patients were enrolled. This analysis used all data received at NRG Oncology through April 12, 2015. Sixteen patients were ineligible, resulting in 328 evaluable patients, 159 in the experimental arm and 169 in the control arm. Patients were well matched between the treatment arms for patient and tumor characteristics: 263 (80%) with T3 or T4 disease, 215 (66%) N1, and 62 (19%) with celiac nodal involvement. Incidence of grade 3, 4, or 5 treatment-related adverse events at any time was 71 (46%), 35 (23%), or 6 (4%) in the experimental arm and 83 (50%), 28 (17%), or 2 (1%) in the control arm, respectively. A clinical complete response (cCR) rate of 81 (56%) was observed in the experimental arm vs 92 (58%) in the control arm (Fisher exact test, P = .66). No differences were seen in cCR between treatment arms for either histology (adenocarcinoma or squamous cell). Median follow-up for all patients was 18.6 months. The 24- and 36-month local failure for the experimental arm was 47% (95% CI, 38%-57%) and 49% (95% CI, 40%-59%) vs 49% (95% CI, 41%-58%) and 49% (95% CI, 41%-58%) for the control arm (HR, 0.92; 95% CI, 0.66-1.28; P = .65). The 24- and 36-month OS rates for the experimental arm were 45% (95% CI, 37%-53%) and 34% (95% CI, 26%-41%) vs 44% (95% CI, 36%-51%) and 28% (95% CI, 21%-35%) for the control arm (HR, 0.90; 95% CI, 0.70-1.16; P = .47). The addition of cetuximab to concurrent chemoradiation did not improve OS. These phase 3 trial results point to little benefit to current EGFR-targeted agents in an unselected patient population, and highlight the need for predictive biomarkers in the treatment of esophageal cancer. clinicaltrials.gov Identifier: NCT00655876.

Use of cardiocerebral resuscitation or AHA/ERC 2005 Guidelines is associated with improved survival from out-of-hospital cardiac arrest: a systematic review and meta-analysis

PubMed Central

Salmen, Marcus; Ewy, Gordon A; Sasson, Comilla

2012-01-01

Objective To determine whether the use of cardiocerebral resuscitation (CCR) or AHA/ERC 2005 Resuscitation Guidelines improved patient outcomes from out-of-hospital cardiac arrest (OHCA) compared to older guidelines. Design Systematic review and meta-analysis. Data sources MEDLINE, EMBASE, Web of Science and the Cochrane Library databases. We also hand-searched study references and consulted experts. Study selection Design: randomised controlled trials and observational studies. Population OHCA patients, age >17 years. Comparators ‘Control’ protocol versus ‘Study’ protocol. ‘Control’ protocol defined as AHA/ERC 2000 Guidelines for cardiopulmonary resuscitation (CPR). ‘Study’ protocol defined as AHA/ERC 2005 Guidelines for CPR, or a CCR protocol. Outcome Survival to hospital discharge. Quality High-quality or medium-quality studies, as measured by the Newcastle Ottawa Scale using predefined categories. Results Twelve observational studies met inclusion criteria. All the three studies using CCR demonstrated significantly improved survival compared to use of AHA 2000 Guidelines, as did five of the nine studies using AHA/ERC 2005 Guidelines. Pooled data demonstrate that use of a CCR protocol has an unadjusted OR of 2.26 (95% CI 1.64 to 3.12) for survival to hospital discharge among all cardiac arrest patients. Among witnessed ventricular fibrillation/ventricular tachycardia (VF/VT) patients, CCR increased survival by an OR of 2.98 (95% CI 1.92 to 4.62). Studies using AHA/ERC 2005 Guidelines showed an overall trend towards increased survival, but significant heterogeneity existed among these studies. Conclusions We demonstrate an association with improved survival from OHCA when CCR protocols or AHA/ERC 2005 Guidelines are compared to use of older guidelines. In the subgroup of patients with witnessed VF/VT, there was a threefold increase in OHCA survival when CCR was used. CCR appears to be a promising resuscitation protocol for Emergency Medical Services providers in increasing survival from OHCA. Future research will need to be conducted to directly compare AHA/ERC 2010 Guidelines with the CCR approach. PMID:23036985

Exposure to hot and cold environmental conditions does not affect the decision making ability of soccer referees following an intermittent sprint protocol.

PubMed

Taylor, Lee; Fitch, Natalie; Castle, Paul; Watkins, Samuel; Aldous, Jeffrey; Sculthorpe, Nicholas; Midgely, Adrian; Brewer, John; Mauger, Alexis

2014-01-01

Soccer referees enforce the laws of the game and the decisions they make can directly affect match results. Fixtures within European competitions take place in climatic conditions that are often challenging (e.g., Moscow ~ -5°C, Madrid ~30°C). Effects of these temperatures on player performance are well-documented; however, little is known how this environmental stress may impair cognitive performance of soccer referees and if so, whether exercise exasperates this. The present study aims to investigate the effect of cold [COLD; -5°C, 40% relative humidity (RH)], hot (HOT; 30°C, 40% RH) and temperate (CONT; 18°C, 40% RH) conditions on decision making during soccer specific exercise. On separate occasions within each condition, 13 physically active males; either semi-professional referees or semi-professional soccer players completed three 90 min intermittent treadmill protocols that simulated match play, interspersed with 4 computer delivered cognitive tests to measure vigilance and dual task capacity. Core and skin temperature, heart rate, rating of perceived exertion (RPE) and thermal sensation (TS) were recorded throughout the protocol. There was no significant difference between conditions for decision making in either the dual task (interaction effects: FALSE p = 0.46; MISSED p = 0.72; TRACKING p = 0.22) or vigilance assessments (interaction effects: FALSE p = 0.31; HIT p = 0.15; MISSED p = 0.17) despite significant differences in measured physiological variables (skin temperature: HOT vs. CONT 95% CI = 2.6 to 3.9, p < 0.001; HOT vs. COLD 95% CI = 6.6 to 9.0, p < 0.001; CONT vs. COLD 95% CI = 3.4 to 5.7, p < 0.01). It is hypothesized that the lack of difference observed in decision making ability between conditions was due to the exercise protocol used, as it may not have elicited an appropriate and valid soccer specific internal load to alter cognitive functioning.

Protocolized treatment is associated with decreased organ dysfunction in pediatric severe sepsis

PubMed Central

Balamuth, Fran; Weiss, Scott L.; Fitzgerald, Julie C.; Hayes, Katie; Centkowski, Sierra; Chilutti, Marianne; Grundmeier, Robert W.; Lavelle, Jane; Alpern, Elizabeth R.

2016-01-01

Objective To determine whether treatment with a protocolized sepsis guideline in the emergency department (ED) was associated with a lower burden of organ dysfunction (OD) by hospital day 2 compared to non-protocolized usual care in pediatric patients with severe sepsis. Design Retrospective cohort study Setting Tertiary care children’s hospital from January 1, 2012–March 31, 2014. Measurements and Main Results Subjects with international consensus defined severe sepsis and pediatric intensive care unit (PICU) admission within 24 hours of ED arrival were included. The exposure was the use of a protocolized ED sepsis guideline. The primary outcome was complete resolution of OD by hospital day 2. One hundred eighty nine subjects were identified during the study period. Of these, 121 (64%) were treated with the protocolized ED guideline and 68 were not. There were no significant differences between the groups in age, sex, race, number of comorbid conditions, ED triage level, or OD on arrival to the ED. Patients treated with protocolized ED care were more likely to be free of OD on hospital day 2 after controlling for sex, comorbid condition, indwelling central venous catheter, PIM-2 score, and timing of antibiotics and intravenous fluids (adjusted OR 4.2, 95% CI 1.7, 10.4). Conclusions Use of a protocolized ED sepsis guideline was independently associated with resolution of OD by hospital day 2 compared to non-protocolized usual care. These data indicate that morbidity outcomes in children can be improved with the use of protocolized care. PMID:27455114

Secondary Analysis of RTOG 9508, a Phase 3 Randomized Trial of Whole-Brain Radiation Therapy Versus WBRT Plus Stereotactic Radiosurgery in Patients With 1-3 Brain Metastases; Poststratified by the Graded Prognostic Assessment (GPA)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sperduto, Paul W., E-mail: psperduto@mropa.com; Shanley, Ryan; Luo, Xianghua

2014-11-01

Purpose: Radiation Therapy Oncology Group (RTOG) 9508 showed a survival advantage for patients with 1 but not 2 or 3 brain metastasis (BM) treated with whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) versus WBRT alone. An improved prognostic index, the graded prognostic assessment (GPA) has been developed. Our hypothesis was that if the data from RTOG 9508 were poststratified by the GPA, the conclusions may vary. Methods and Materials: In this analysis, 252 of the 331 patients were evaluable by GPA. Of those, 211 had lung cancer. Breast cancer patients were excluded because the components of the breast GPAmore » are not in the RTOG database. Multiple Cox regression was used to compare survival between treatment groups, adjusting for GPA. Treatment comparisons within subgroups were performed with the log-rank test. A free online tool ( (brainmetgpa.com)) simplified GPA use. Results: The fundamental conclusions of the primary analysis were confirmed in that there was no survival benefit overall for patients with 1 to 3 metastases; however, there was a benefit for the subset of patients with GPA 3.5 to 4.0 (median survival time [MST] for WBRT + SRS vs WBRT alone was 21.0 versus 10.3 months, P=.05) regardless of the number of metastases. Among patients with GPA 3.5 to 4.0 treated with WBRT and SRS, the MST for patients with 1 versus 2 to 3 metastases was 21 and 14.1 months, respectively. Conclusions: This secondary analysis of predominantly lung cancer patients, consistent with the original analysis, shows no survival advantage for the group overall when treated with WBRT and SRS; however, in patients with high GPA (3.5-4), there is a survival advantage regardless of whether they have 1, 2, or 3 BM. This benefit did not extend to patients with lower GPA. Prospective validation of this survival benefit for patients with multiple BM and high GPA when treated with WBRT and SRS is warranted.« less

Secondary Analysis of RTOG 9508, a Phase 3 Randomized Trial of Whole-Brain Radiation Therapy Versus WBRT Plus Stereotactic Radiosurgery in Patients With 1-3 Brain Metastases; Poststratified by the Graded Prognostic Assessment (GPA)

PubMed Central

Sperduto, Paul W.; Shanley, Ryan; Luo, Xianghua; Andrews, David; Werner-Wasik, Maria; Valicenti, Richard; Bahary, Jean-Paul; Souhami, Luis; Won, Minhee; Mehta, Minesh

2015-01-01

Purpose Radiation Therapy Oncology Group (RTOG) 9508 showed a survival advantage for patients with 1 but not 2 or 3 brain metastasis (BM) treated with whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) versus WBRT alone. An improved prognostic index, the graded prognostic assessment (GPA) has been developed. Our hypothesis was that if the data from RTOG 9508 were poststratified by the GPA, the conclusions may vary. Methods and Materials In this analysis, 252 of the 331 patients were evaluable by GPA. Of those, 211 had lung cancer. Breast cancer patients were excluded because the components of the breast GPA are not in the RTOG database. Multiple Cox regression was used to compare survival between treatment groups, adjusting for GPA. Treatment comparisons within subgroups were performed with the log-rank test. A free online tool (brainmetgpa.com) simplified GPA use. Results The fundamental conclusions of the primary analysis were confirmed in that there was no survival benefit overall for patients with 1 to 3 metastases; however, there was a benefit for the subset of patients with GPA 3.5 to 4.0 (median survival time [MST] for WBRT + SRS vs WBRT alone was 21.0 versus 10.3 months, P = .05) regardless of the number of metastases. Among patients with GPA 3.5 to 4.0 treated with WBRT and SRS, the MST for patients with 1 versus 2 to 3 metastases was 21 and 14.1 months, respectively. Conclusions This secondary analysis of predominantly lung cancer patients, consistent with the original analysis, shows no survival advantage for the group overall when treated with WBRT and SRS; however, in patients with high GPA (3.5-4), there is a survival advantage regardless of whether they have 1, 2, or 3 BM. This benefit did not extend to patients with lower GPA. Prospective validation of this survival benefit for patients with multiple BM and high GPA when treated with WBRT and SRS is warranted. PMID:25304947

Secondary analysis of RTOG 9508, a phase 3 randomized trial of whole-brain radiation therapy versus WBRT plus stereotactic radiosurgery in patients with 1-3 brain metastases; poststratified by the graded prognostic assessment (GPA).

PubMed

Sperduto, Paul W; Shanley, Ryan; Luo, Xianghua; Andrews, David; Werner-Wasik, Maria; Valicenti, Richard; Bahary, Jean-Paul; Souhami, Luis; Won, Minhee; Mehta, Minesh

2014-11-01

Radiation Therapy Oncology Group (RTOG) 9508 showed a survival advantage for patients with 1 but not 2 or 3 brain metastasis (BM) treated with whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) versus WBRT alone. An improved prognostic index, the graded prognostic assessment (GPA) has been developed. Our hypothesis was that if the data from RTOG 9508 were poststratified by the GPA, the conclusions may vary. In this analysis, 252 of the 331 patients were evaluable by GPA. Of those, 211 had lung cancer. Breast cancer patients were excluded because the components of the breast GPA are not in the RTOG database. Multiple Cox regression was used to compare survival between treatment groups, adjusting for GPA. Treatment comparisons within subgroups were performed with the log-rank test. A free online tool (brainmetgpa.com) simplified GPA use. The fundamental conclusions of the primary analysis were confirmed in that there was no survival benefit overall for patients with 1 to 3 metastases; however, there was a benefit for the subset of patients with GPA 3.5 to 4.0 (median survival time [MST] for WBRT + SRS vs WBRT alone was 21.0 versus 10.3 months, P=.05) regardless of the number of metastases. Among patients with GPA 3.5 to 4.0 treated with WBRT and SRS, the MST for patients with 1 versus 2 to 3 metastases was 21 and 14.1 months, respectively. This secondary analysis of predominantly lung cancer patients, consistent with the original analysis, shows no survival advantage for the group overall when treated with WBRT and SRS; however, in patients with high GPA (3.5-4), there is a survival advantage regardless of whether they have 1, 2, or 3 BM. This benefit did not extend to patients with lower GPA. Prospective validation of this survival benefit for patients with multiple BM and high GPA when treated with WBRT and SRS is warranted. Copyright © 2014 Elsevier Inc. All rights reserved.

SU-F-T-629: Effect of Multi-Leaf Collimator (MLC) Width On Plan Quality of Single-Isocenter VMAT Intracranial Stereotactic Radiosurgery for Multiple Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kraus, J; Thomas, E; Wu, X

2016-06-15

Purpose: Single-isocenter VMAT has been shown able to create high quality plans for complex intracranial multiple metastasis SRS cases. Linacs capable of the technique are typically outfitted with an MLC that consists of a combination of 5 mm and 10 mm leaves (standard) or 2.5 mm and 5 mm leaves (high-definition). In this study, we test the hypothesis that thinner collimator leaves are associated with improved plan quality. Methods: Ten multiple metastasis cases were identified and planned for VMAT SRS using a 10 MV flattening filter free beam. Plans were created for a standard (std) and a high-definition (HD) MLC.more » Published values for leaf transmission factor and dosimetric leaf gap were utilized. All other parameters were invariant. Conformity (plan and individual target), moderate isodose spill (V50%), and low isodose spill (mean brain dose) were selected for analysis. Results: Compared to standard MLC, HD-MLC improved overall plan conformity (median: Paddick CI-HD = 0.83, Paddick CI-std = 0.79; p = 0.004 and median: RTOG CI-HD =1.18, RTOG CI-std =1.24; p = 0.01 ), improved individual lesion conformity (median: Paddick CI-HD,i =0.77, Paddick CI-std,i =0.72; p < 0.001 and median: RTOG CI-HD,i = 1.28, RTOG CI-std,i =1.35; p < 0.001), improved moderate isodose spill (median: V50%-HD = 37.0 cc, V50%-std = 45.7 cc; p = 0.002), and improved low dose spill (median: dmean-HD = 2.90 Gy, dmean-std = 3.19 Gy; p = 0.002). Conclusion: For the single-isocenter VMAT SRS of multiple metastasis plans examined, use of HD-MLC modestly improved conformity, moderate isodose, and low isodose spill compared to standard MLC. However, in all cases we were able to generate clinically acceptable plans with the standard MLC. More work is need to further quantify the difference in cases with higher numbers of small targets and to better understand any potential clinical significance. This research was supported in part by Varian Medical Systems.« less

Toxicity profile and treatment delays in NOPHO ALL2008-comparing adults and children with Philadelphia chromosome-negative acute lymphoblastic leukemia.

PubMed

Toft, Nina; Birgens, Henrik; Abrahamsson, Jonas; Griškevičius, Laimonas; Hallböök, Helene; Heyman, Mats; Klausen, Tobias Wirenfeldt; Jónsson, Ólafur Gísli; Palk, Katrin; Pruunsild, Kaie; Quist-Paulsen, Petter; Vaitkeviciene, Goda; Vettenranta, Kim; Asberg, Ann; Helt, Louise Rold; Frandsen, Thomas; Schmiegelow, Kjeld

2016-02-01

Cure rates improve when adolescents and young adults with acute lymphoblastic leukemia (ALL) are treated according to pediatric protocols. Assumed risks of toxicities and associated delays in treatment have played a role in setting upper age limits. The aim of this study was to examine the toxicity profile and treatment delays in NOPHO ALL2008 comparing children and adults. We collected information on 19 treatment-related toxicities, systematically captured at 3-month intervals throughout therapy, and time intervals between 12 consecutive treatment phases for 1076 patients aged 1-45 yrs treated according to the Nordic/Baltic ALL2008 protocol. No adults died during induction. The duration of induction therapy and postinduction treatment phases did not differ between children and adults, except for patients 18-45 yrs being significantly delayed during two of nine high-risk blocks (median number of days for patients 1-9, 10-17, and 18-45 yrs; the glucocorticosteroid/antimetabolite-based block B1: 24, 26, and 29 d, respectively, P = 0.001, and Block 5 (in most cases also a B block): 29, 29, and 37 d, respectively, P = 0.02). A higher incidence of thrombosis with increasing age was found; highest odds ratio 5.4 (95% CI: (2.6;11.0)) for patients 15-17 yrs compared with children 1-9 yrs (P < 0.0001). Risk of avascular osteonecrosis was related to age with the highest OR for patients 10-14 yrs (OR = 10.4 (95% CI: (4.4;24.9)), P < 0.0001). Adults followed and tolerated the NOPHO ALL2008 protocol virtually as well as children, although thrombosis and avascular osteonecrosis was most common among adolescents. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effectiveness of different exercises and stretching physiotherapy on pain and movement in patellofemoral pain syndrome: a randomized controlled trial.

PubMed

Moyano, F Revelles; Valenza, M C; Martin, L Martin; Caballero, Y Castellote; Gonzalez-Jimenez, E; Demet, G Valenza

2013-05-01

To compare the effectiveness of proprioceptive neuromuscular facilitation combined with exercise, classic stretching physiotherapy intervention, and educational intervention at improving patient function and pain in patients with patellofemoral pain syndrome. Randomized, controlled, blind trial over four months. Urban population, Spain. Patients undergoing primary care for retropatellar pain. Subjects were allocated on three different treatment options: a proprioceptive neuromuscular facilitation and aerobic exercise group, a classic stretching group, and a control treatment were applied over four months under the supervision of a physiotherapist. Knee Society Score, pain reported (Visual analogue scale) and knee range of motion. Assessments were completed at baseline and after four months. 74 patients were enrolled in the study and distributed between groups. Both the proprioceptive neuromuscular facilitation and classic stretching group showed significant changes in all variables after four months intervention (p < 0.001). The difference in mean Kujala knee score changes between groups (classic stretching group vs. proprioceptive neuromuscular facilitation group vs. control group) at four months was -24.05 (95% confidence interval (CI) -30.19, -17.90), p ≤ 0.001; vs. -39.03 (95% confidence interval (CI) -42.5, -35.5), p ≤ 0.001; vs. -0.238 (95% confidence interval (CI) -1.2, 0.726), p = 0.621, respectively. A proprioceptive neuromuscular facilitation intervention protocol combined with aerobic exercise showed a better outcome than a classic stretching protocol after four months.

Breast cancer brain metastases: differences in survival depending on biological subtype, RPA RTOG prognostic class and systemic treatment after whole-brain radiotherapy (WBRT).

PubMed

Niwińska, A; Murawska, M; Pogoda, K

2010-05-01

Patients with breast cancer brain metastasis are a heterogeneous group in relation to tumor biology and outcome. The group of 222 breast cancer patients with brain metastasis was divided into three biological subgroups. The propensity of biological subtypes for metastases to the brain and survivals depending on biological subtype, recursive partitioning analysis of Radiation Therapy Oncology Group (RPA RTOG) prognostic class and the use of systemic treatment after whole-brain radiotherapy were assessed. The rate of patients with triple-negative, human epidermal growth factor receptor 2 (HER2)-positive and luminal breast cancer with brain metastases was 28%, 53% and 19%, respectively. Median survival from brain metastases in triple-negative, HER2-positive and luminal subtype was 3.7, 9 and 15 months, respectively. Median survival from brain metastases in RPA RTOG prognostic class I, II and III was 15, 11 and 3 months, respectively. In the luminal and in the triple-negative subtype, systemic therapy prolonged survival from 3 to 14 months and from 3 to 4 months, respectively. In HER2-positive subtype, median survival without further treatment, after chemotherapy and after chemotherapy with targeted therapy were 3, 8 and 11 months, respectively. HER2-positive and triple-negative breast cancers have special predilection for metastases to the brain. Survival from brain metastases depended on performance status and the use of systemic treatment.

HLA-G+3027 polymorphism is associated with tumor relapse in pediatric Hodgkin's lymphoma.

PubMed

De Re, Valli; Caggiari, Laura; Mussolin, Lara; d'Amore, Emanuele Stefano; Famengo, Barbara; De Zorzi, Mariangela; Martina, Lia; Elia, Caterina; Pillon, Marta; Santoro, Nicola; Muggeo, Paola; Buffardi, Salvatore; Bianchi, Maurizio; Sala, Alessandra; Farruggia, Piero; Vinti, Luciana; Carosella, Edgardo D; Burnelli, Roberta; Mascarin, Maurizio

2017-12-01

In this study, we tested whether polymorphisms in human leukocyte antigen G (HLA-G) were associated with event-free survival (EFS) in pediatric Hodgkin's lymphoma (HL). We evaluated the association of HLA-G 3'-UTR polymorphisms with EFS in 113 pediatric HL patients treated using the AIEOP LH-2004 protocol. Patients with the +3027-C/A genotype (rs17179101, UTR-7 haplotype) showed lower EFS than those with the +3027-C/C genotype (HR= 3.23, 95%CI: 0.99-10.54, P=0.012). Female patients and systemic B symptomatic patients with the HLA-G +3027 polymorphism showed lower EFS. Multivariate analysis showed that the +3027-A polymorphism (HR 3.17, 95%CI 1.16-8.66, P=0.025) was an independent prognostic factor. Immunohistochemical analysis showed that HL cells from patients with the +3027-C/A genotype did not express HLA-G. Moreover, HLA-G +3027 polymorphism improved EFS prediction when added to the algorithm for therapeutic group classification of pediatric HL patients. Our findings suggest HLA-G +3027 polymorphism is a prognostic marker in pediatric HL patients undergoing treatment according to LH-2004 protocol.

Evaluation of the Dosimetric Feasibility of Hippocampal Sparing Intensity-Modulated Radiotherapy in Patients with Locally Advanced Nasopharyngeal Carcinoma

PubMed Central

Gan, Hua; Denniston, Kyle A.; Li, Sicong; Tan, Wenyong; Wang, Zhaohua

2014-01-01

Purpose The objective of this study was to evaluate the dosimetric feasibility of using hippocampus (HPC) sparing intensity-modulated radiotherapy (IMRT) in patients with locally advanced nasopharyngeal carcinoma (NPC). Materials/Methods Eight cases of either T3 or T4 NPC were selected for this study. Standard IMRT treatment plans were constructed using the volume and dose constraints for the targets and organs at risk (OAR) per Radiation Therapy Oncology Group (RTOG) 0615 protocol. Experimental plans were constructed using the same criteria, with the addition of the HPC as an OAR. The two dose-volume histograms for each case were compared for the targets and OARs. Results All plans achieved the protocol dose criteria. The homogeneity index, conformity index, and coverage index for the planning target volumes (PTVs) were not significantly compromised by the avoidance of the HPC. The doses to all OARs, excluding the HPC, were similar. Both the dose (Dmax, D2%, D40%, Dmean, Dmedian, D98% and Dmin) and volume (V5, V10, V15, V20, V30, V40 and V50) parameters for the HPC were significantly lower in the HPC sparing plans (p<0.05), except for Dmin (P = 0.06) and V5 (P = 0.12). Conclusions IMRT for patients with locally advanced NPC exposes the HPC to a significant radiation dose. HPC sparing IMRT planning significantly decreases this dose, with minimal impact on the therapeutic targets and other OARs. PMID:24587184

Accelerated partial breast irradiation using 3D conformal radiotherapy: toxicity and cosmetic outcome.

PubMed

Gatti, M; Ponzone, R; Bresciani, S; Panaia, R; Kubatzki, F; Maggiorotto, F; Di Virgilio, M R; Salatino, A; Baiotto, B; Montemurro, F; Stasi, M; Gabriele, P

2013-12-01

The aim of this paper is to analyze the incidence of acute and late toxicity and cosmetic outcome in breast cancer patients submitted to breast conserving surgery and three-dimensional conformal radiotherapy (3D-CRT) to deliver accelerated partial breast irradiation (APBI). 84 patients were treated with 3D-CRT for APBI. This technique was assessed in patients with low risk stage I breast cancer enrolled from September 2005 to July 2011. The prescribed dose was 34/38.5 Gy delivered in 10 fractions twice daily over 5 consecutive days. Four to five no-coplanar 6 MV beams were used. In all CT scans Gross Tumor Volume (GTV) was defined around the surgical clips. A 1.5 cm margin was added by defining a Clinical Target Volume (CTV). A margin of 1 cm was added to CTV to define the planning target volume (PTV). The dose-volume constraints were followed in accordance with the NSABP/RTOG protocol. Late toxicity was evaluated according to the RTOG grading schema. The cosmetic assessment was performed using the Harvard scale. Median patient age was 66 years (range 51-87). Median follow-up was 36.5 months (range 13-83). The overall incidence of acute skin toxicities was 46.4% for grade 1 and 1% for grade 2. The incidence of late toxicity was 16.7% for grade 1, 2.4% for grade 2 and 3.6% for grade 3. No grade 4 toxicity was observed. The most pronounced grade 2 late toxicity was telangiectasia, developed in three patients. Cosmetics results were excellent for 52%, good for 42%, fair for 5% and poor for 1% of the patients. There was no statistical correlation between toxicity rates and prescribed doses (p = 0.33) or irradiated volume (p = 0.45). APBI using 3D-CRT is technically feasible with very low acute and late toxicity. Long-term results are needed to assess its efficacy in reducing the incidence of breast relapse. Copyright © 2013 Elsevier Ltd. All rights reserved.

Seven-Year Efficacy of RTS,S/AS01 Malaria Vaccine among Young African Children.

PubMed

Olotu, Ally; Fegan, Gregory; Wambua, Juliana; Nyangweso, George; Leach, Amanda; Lievens, Marc; Kaslow, David C; Njuguna, Patricia; Marsh, Kevin; Bejon, Philip

2016-06-30

The candidate malaria vaccine RTS,S/AS01 is being evaluated in order to inform a decision regarding its inclusion in routine vaccination schedules. We conducted 7 years of follow-up in children who had been randomly assigned, at 5 to 17 months of age, to receive three doses of either the RTS,S/AS01 vaccine or a rabies (control) vaccine. The end point was clinical malaria (temperature of ≥37.5°C and infection with Plasmodium falciparum of >2500 parasites per cubic millimeter). In an analysis that was not prespecified, the malaria exposure of each child was estimated with the use of information on the prevalence of malaria among residents within a 1-km radius of the child's home. Vaccine efficacy was defined as 1 minus the hazard ratio or the incidence-rate ratio, multiplied by 100, in the RTS,S/AS01 group versus the control group. Over 7 years of follow-up, we identified 1002 episodes of clinical malaria among 223 children randomly assigned to the RTS,S/AS01 group and 992 episodes among 224 children randomly assigned to the control group. The vaccine efficacy, as assessed by negative binomial regression, was 4.4% (95% confidence interval [CI], -17.0 to 21.9; P=0.66) in the intention-to-treat analysis and 7.0% (95% CI, -14.5 to 24.6; P=0.52) in the per-protocol analysis. Vaccine efficacy waned over time (P=0.006 for the interaction between vaccination and time), including negative efficacy during the fifth year among children with higher-than-average exposure to malaria parasites (intention-to-treat analysis: -43.5%; 95% CI, -100.3 to -2.8 [P=0.03]; per-protocol analysis: -56.8%; 95% CI, -118.7 to -12.3 [P=0.008]). A three-dose vaccination with RTS,S/AS01 was initially protective against clinical malaria, but this result was offset by rebound in later years in areas with higher-than-average exposure to malaria parasites. (Funded by the PATH Malaria Vaccine Initiative and others; ClinicalTrials.gov number, NCT00872963.).

Use of C-Arm Cone Beam CT During Hepatic Radioembolization: Protocol Optimization for Extrahepatic Shunting and Parenchymal Enhancement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hoven, Andor F. van den, E-mail: a.f.vandenhoven@umcutrecht.nl; Prince, Jip F.; Keizer, Bart de

PurposeTo optimize a C-arm computed tomography (CT) protocol for radioembolization (RE), specifically for extrahepatic shunting and parenchymal enhancement.Materials and MethodsA prospective development study was performed per IDEAL recommendations. A literature-based protocol was applied in patients with unresectable and chemorefractory liver malignancies undergoing an angiography before radioembolization. Contrast and scan settings were adjusted stepwise and repeatedly reviewed in a consensus meeting. Afterwards, two independent raters analyzed all scans. A third rater evaluated the SPECT/CT scans as a reference standard for extrahepatic shunting and lack of target segment perfusion.ResultsFifty scans were obtained in 29 procedures. The first protocol, using a 6 s delaymore » and 10 s scan, showed insufficient parenchymal enhancement. In the second protocol, the delay was determined by timing parenchymal enhancement on DSA power injection (median 8 s, range 4–10 s): enhancement improved, but breathing artifacts increased (from 0 to 27 %). Since the third protocol with a 5 s scan decremented subjective image quality, the second protocol was deemed optimal. Median CNR (range) was 1.7 (0.6–3.2), 2.2 (−1.4–4.0), and 2.1 (−0.3–3.0) for protocol 1, 2, and 3 (p = 0.80). Delineation of perfused segments was possible in 57, 73, and 44 % of scans (p = 0.13). In all C-arm CTs combined, the negative predictive value was 95 % for extrahepatic shunting and 83 % for lack of target segment perfusion.ConclusionAn optimized C-arm CT protocol was developed that can be used to detect extrahepatic shunts and non-perfusion of target segments during RE.« less

Intermittent But Not Continuous Static Stretching Improves Subsequent Vertical Jump Performance In Flexibility-Trained Athletes.

PubMed

Bogdanis, Gregory C; Donti, Olyvia; Tsolakis, Charilaos; Smilios, Ilias; Bishop, David J

2017-02-23

This study examined changes in countermovement jump (CMJ) height after an intermittent or a continuous static stretching protocol of equal total duration. Sixteen male, elite-level gymnasts performed 90 s of intermittent (3 x 30 s with 30 s rest) or continuous stretching (90 s) of the quadriceps muscle. A single-leg stretching and jumping design was used, with the contra-lateral limb serving as a control. The same individuals performed both conditions with alternate legs in a randomized, counterbalanced order. One leg CMJ height was measured for the stretched and the control leg after warm-up, immediately after stretching, and at regular intervals for 10 min after stretching. Range of motion (ROM) of the hip and knee joints was measured before, after, and 10 min post-stretching. Compared to the control leg, intermittent stretching increased CMJ height by 8.1±2.0%, 4 min into recovery (+2.2±2.0 cm, 95%CI: 1.0-3.4 cm, p=0.001), while continuous stretching decreased CMJ height by 17.5±3.3% immediately after (-2.9±1.7 cm, 95%CI: -2.0 to -3.7 cm, p=0.001) and by 12.0±2.7% one min after stretching (-2.2±2.1 cm, 95%CI: -1.2 to -3.2 cm, p=0.001). The increases in hip (2.9 and 3.6, p=0.001. d=2.4) and knee joint ROM (5.1 and 6.1, p=0.001. d=0.85) after the intermittent and continuous stretching protocols were not different. The opposite effects of intermittent vs. continuous stretching on subsequent CMJ performance suggests that stretching mode is an important variable when examining the acute effects of static stretching on performance in flexibility-trained athletes.

Feasibility of ballistic strength training in sub-acute stroke: A randomized, controlled, assessor-blinded pilot study.

PubMed

Hendrey, Genevieve; Clark, Ross A; Holland, Anne E; Mentiplay, Benjamin F; Davis, Carly; Windfeld-Lund, Cristie; Raymond, Melissa J; Williams, Gavin

2018-05-30

To establish the feasibility and effectiveness of a six week ballistic strength training protocol in people with stroke. Randomized, controlled, assessor-blinded study. Sub-acute inpatient rehabilitation. Consecutively admitted inpatients with a primary diagnosis of first ever stroke with lower limb weakness, functional ambulation category score of ≥3, and ability to walk ≥14m were screened for eligibility to recruit 30 participants for randomization. Participants were randomized to standard therapy or ballistic strength training three times per week for six weeks. The primary aim was to evaluate feasibility and outcomes included recruitment rate, participant retention and attrition, feasibility of the exercise protocol, therapist burden and participant safety. Secondary outcomes included measures of mobility, lower limb muscle strength, muscle power and quality of life. Thirty participants (11% of those screened) with mean age of 50 (SD 18) years were randomized. The median number of sessions attended was 15/18 and 17/18 for the ballistic and control groups respectively. Earlier than expected discharge home (n=4) and illness (n=7) were the most common reasons for non-attendance. Participants performed the exercises safely, with no study-related adverse events. There were significant (p<0.05) between-group changes favoring the ballistic group for comfortable gait velocity (mean difference (MD) 0.31m/s, 95% confidence interval CI: 0.08 to 0.52), muscle power, as measured by peak jump height (MD 8cm, 95% CI: 3 to 13) and peak propulsive velocity (MD 64cm/s, 95% CI: 17 to 112). Ballistic training was safe and feasible in select ambulant people with stroke. Similar rates of retention and attrition suggest that ballistic training was acceptable to patients. Secondary outcomes provide promising results that warrant further investigation in a larger trial. Copyright © 2018. Published by Elsevier Inc.

COLORECTAL CANCER PREVENTION BY AN OPTIMIZED COLONOSCOPY PROTOCOL IN ROUTINE PRACTICE

PubMed Central

Xirasagar, Sudha; Li, Yi-Jhen; Hurley, Thomas G.; Tsai, Meng Han; Hardin, James W.; Hurley, Deborah M.; Hebert, James R.; de Groen, Piet C.

2014-01-01

We conducted a retrospective cohort study to investigate the colorectal cancer (CRC) incidence and mortality prevention achievable in clinical practice with an optimized colonoscopy protocol targeting near-complete polyp clearance. The protocol consisted of: a) telephonic reinforcement of bowel preparation instructions; b) active inspection for polyps throughout insertion and circumferential withdrawal; and, c) timely updating of the protocol and documentation to incorporate the latest guidelines. Of 17,312 patients provided screening colonoscopies by 59 endoscopists in South Carolina, USA from 09/2001 through 12/2008, 997 were excluded using accepted exclusion criteria. Data on 16,315 patients were merged with the South Carolina Central Cancer Registry and Vital Records Registry data from 01/1996 – 12/2009 to identify incident CRC cases and deaths, incident lung cancers and brain cancer deaths (comparison control cancers). The standardized incidence ratios (SIR) and standardized mortality ratios (SMR) relative to South Carolina and US SEER-18 population rates were calculated. Over 78,375 person-years of observation, 18 patients developed CRC vs. 104.11 expected for an SIR of 0.17, or 83% CRC protection, the rates being 68% and 91%, respectively among the adenoma- and adenoma-free subgroups (all p<0.001). Restricting the cohort to ensure minimum 5-year follow-up (mean follow-up 6.58 years) did not change the results. The CRC mortality reduction was 89% (p<0.001; 4 CRC deaths vs. 35.95 expected). The lung cancer SIR was 0.96 (p=0.67), and brain cancer SMR was 0.92 (p=0.35). Over 80% reduction in CRC incidence and mortality is achievable in routine practice by implementing key colonoscopy principles targeting near-complete polyp clearance. PMID:25242510

Association of Sick Sinus Syndrome with Incident Cardiovascular Disease and Mortality: The Atherosclerosis Risk in Communities Study and Cardiovascular Health Study

PubMed Central

Alonso, Alvaro; Jensen, Paul N.; Lopez, Faye L.; Chen, Lin Y.; Psaty, Bruce M.; Folsom, Aaron R.; Heckbert, Susan R.

2014-01-01

Background Sick sinus syndrome (SSS) is a common indication for pacemaker implantation. Limited information exists on the association of sick sinus syndrome (SSS) with mortality and cardiovascular disease (CVD) in the general population. Methods We studied 19,893 men and women age 45 and older in the Atherosclerosis Risk in Communities (ARIC) study and the Cardiovascular Health Study (CHS), two community-based cohorts, who were without a pacemaker or atrial fibrillation (AF) at baseline. Incident SSS cases were validated by review of medical charts. Incident CVD and mortality were ascertained using standardized protocols. Multivariable Cox models were used to estimate the association of incident SSS with selected outcomes. Results During a mean follow-up of 17 years, 213 incident SSS events were identified and validated (incidence, 0.6 events per 1,000 person-years). After adjustment for confounders, SSS incidence was associated with increased mortality (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.14–1.70), coronary heart disease (HR 1.72, 95%CI 1.11–2.66), heart failure (HR 2.87, 95%CI 2.17–3.80), stroke (HR 1.56, 95%CI 0.99–2.46), AF (HR 5.75, 95%CI 4.43–7.46), and pacemaker implantation (HR 53.7, 95%CI 42.9–67.2). After additional adjustment for other incident CVD during follow-up, SSS was no longer associated with increased mortality, coronary heart disease, or stroke, but remained associated with higher risk of heart failure (HR 2.00, 95%CI 1.51–2.66), AF (HR 4.25, 95%CI 3.28–5.51), and pacemaker implantation (HR 25.2, 95%CI 19.8–32.1). Conclusion Individuals who develop SSS are at increased risk of death and CVD. The mechanisms underlying these associations warrant further investigation. PMID:25285853

Immunephenotype of glomerular and interstitial infiltrating cells in protocol renal allograft biopsies and histological diagnosis.

PubMed

Moreso, F; Seron, D; O'Valle, F; Ibernon, M; Gomà, M; Hueso, M; Cruzado, J M; Bestard, O; Duarte, V; del Moral, R García; Grinyó, J M

2007-12-01

Patients with a protocol renal allograft biopsy simultaneously displaying interstitial fibrosis/tubular atrophy (IF/TA) and subclinical rejection (SCR) have a shortened graft survival than patients with a normal biopsy, or with a biopsy only displaying IF/TA or SCR. The poor outcome of these patients could be related with a more severe inflammation. We evaluate the immunophenotype of infiltrating cells in these diagnostic categories. Nonexhausted paraffin blocks from protocol biopsies done during the first year were stained with anti-CD45, CD3, CD20, CD68 and CD15 monoclonal antibodies. Glomerular and interstitial positive cells were counted. C4d deposition in peritubular capillaries was evaluated. Histological diagnoses were: normal (n = 80), SCR (n = 17), IF/TA (n = 42) and IF/TA + SCR (n = 17). Only interstitial CD20 positive cells were significantly increased in patients displaying IF/TA + SCR; normal (137 +/- 117), SCR (202 +/- 145), IF/TA (208 +/- 151) and IF/TA + SCR (307 +/- 180 cells/mm(2)), p < 0.01. The proportion of biopsies displaying C4d deposition was not different among groups. The upper tertile of CD20 positive interstitial cells was associated with a decreased death-censored graft survival (relative risk: 3.01, 95% confidence interval: 1.23-7.35; p = 0.015). These data suggest that B-cell interstitial infiltrates are associated with histological damage and outcome, but do not distinguish whether these infiltrates were the cause or the consequence of chronic tubulo-interstitial damage.

Phase 2 Study of Temozolomide-Based Chemoradiation Therapy for High-Risk Low-Grade Gliomas: Preliminary Results of Radiation Therapy Oncology Group 0424

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fisher, Barbara J., E-mail: barbara.fisher@lhsc.on.ca; Hu, Chen; Macdonald, David R.

2015-03-01

Purpose: Radiation Therapy Oncology Group (RTOG) 0424 was a phase 2 study of a high-risk low-grade glioma (LGG) population who were treated with temozolomide (TMZ) and radiation therapy (RT), and outcomes were compared to those of historical controls. This study was designed to detect a 43% increase in median survival time (MST) from 40.5 to 57.9 months and a 20% improvement in 3-year overall survival (OS) rate from 54% to 65% at a 10% significance level (1-sided) and 96% power. Methods and Materials: Patients with LGGs with 3 or more risk factors for recurrence (age ≥40 years, astrocytoma histology, bihemispherical tumor, preoperativemore » tumor diameter of ≥6 cm, or a preoperative neurological function status of >1) were treated with RT (54 Gy in 30 fractions) and concurrent and adjuvant TMZ. Results: From 2005 to 2009, 129 evaluable patients (75 males and 54 females) were accrued. Median age was 49 years; 91% had a Zubrod score of 0 or 1; and 69%, 25%, and 6% of patients had 3, 4, and 5 risk factors, respectively. Patients had median and minimum follow-up examinations of 4.1 years and 3 years, respectively. The 3-year OS rate was 73.1% (95% confidence interval: 65.3%-80.8%), which was significantly improved compared to that of prespecified historical control values (P<.001). Median survival time has not yet been reached. Three-year progression-free survival was 59.2%. Grades 3 and 4 adverse events occurred in 43% and 10% of patients, respectively. One patient died of herpes encephalitis. Conclusions: The 3-year OS rate of 73.1% for RTOG 0424 high-risk LGG patients is higher than that reported for historical controls (P<.001) and the study-hypothesized rate of 65%.« less

Evaluation of factors associated with second remission in dogs with lymphoma undergoing retreatment with a cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy protocol: 95 cases (2000-2007).

PubMed

Flory, Andrea B; Rassnick, Kenneth M; Erb, Hollis N; Garrett, Laura D; Northrup, Nicole C; Selting, Kim A; Phillips, Brenda S; Locke, Jennifer E; Chretin, John D

2011-02-15

To evaluate factors associated with second remission in dogs with lymphoma retreated with a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) protocol after relapse following initial treatment with a first-line 6-month CHOP protocol. Retrospective case series. 95 dogs with lymphoma. Medical records were reviewed. Remission duration was estimated by use of the Kaplan-Meier method. Factors potentially associated with prognosis were examined. Median remission duration after the first-line CHOP protocol was 289 days (range, 150 to 1,457 days). Overall, 78% (95% confidence interval [CI], 69% to 86%) of dogs achieved a complete remission following retreatment, with a median second remission duration of 159 days (95% CI, 126 to 212 days). Duration of time off chemotherapy was associated with likelihood of response to retreatment; median time off chemotherapy was 140 days for dogs that achieved a complete remission after retreatment and 84 days for dogs that failed to respond to retreatment. Second remission duration was associated with remission duration after initial chemotherapy; median second remission duration for dogs with initial remission duration ≥ 289 days was 214 days (95% CI, 168 to 491 days), compared with 98 days (95% CI, 70 to 144 days) for dogs with initial remission duration < 289 days. Findings suggested that retreatment with the CHOP protocol can be effective in dogs with lymphoma that successfully complete an initial 6-month CHOP protocol.

Patching vs Atropine to Treat Amblyopia in Children Aged 7 to 12 Years: A Randomized Trial

PubMed Central

2008-01-01

Objective To compare patching with atropine eye drops in the treatment of moderate amblyopia (20/40 -20/100) in children age 7 to 12 years. Methods In a randomized multi-center clinical trial, 193 children with amblyopia were randomized to weekend atropine or patching 2 hours per day of the sound eye. Main Outcome Measure Masked assessment of amblyopic eye visual acuity using the EETDRS testing protocol at 17 weeks. Results At 17 weeks, visual acuity had improved from baseline by an average of 7.6 letters in the atropine group and 8.6 letters in the patching group. The mean difference (patching minus atropine) between groups adjusted for baseline acuity was 1.2 letters (ends of complementary 1-sided 95% confidence intervals for noninferiority = -0.7 and +3.1 letters). Based on the confidence intervals this difference met the pre-specified definition for equivalence (ends of confidence intervals <5 letters). Amblyopic eye visual acuity was 20/25 or better in 15 subjects (17%) in the atropine group and 20 subjects (24%) in the patching group (difference = 7%, 95% confidence interval = -3% to 17%). Conclusions Treatment with atropine or patching leads to similar degrees of improvement in 7 to 12 year old children with moderate amblyopia. About 1 in 5 achieves 20/25 or better visual acuity in the amblyopic eye. Application to Clinical Practice Treatment of older children with unilateral amblyopia. PMID:19064841

Polymorphism of regulatory region of GHRL gene (-2531C>T) as a promising predictive factor for radiotherapy-induced oral mucositis in patients with head neck cancer.

PubMed

Brzozowska, Anna; Homa-Mlak, Iwona; Mlak, Radosław; Gołębiowski, Paweł; Mazurek, Marcin; Ciesielka, Marzanna; Małecka-Massalska, Teresa

2018-03-22

The purpose of this study was to investigate the relationship between single nucleotide polymorphisms (SNP; rs1629816) in the regulatory region (c.-2531C>T) of the ghrelin (GHRL) gene and the occurrence and severity of oral mucositis caused by radiotherapy (RT) in patients with head and neck cancer. Oral mucositis in 65 patients with head and neck cancer who underwent irradiation were assessed according to Radiation Therapy Oncology Group (RTOG)/European Organisation for Research and Treatment of Cancer (EORTC) scale. The DNA from patients with head and neck cancer was isolated from whole blood. The genotypes were determined using the minisequencing method (SNaPshot PCR). The frequency of occurrence of the GHRL gene (c.-2531C>T, rs1629816) genotypes were as follows: AA = 21.5%; GA = 40%; and GG = 38.5%. In case of AA genotype, there was a 7-fold decrease of the risk of occurrence of oral mucositis (of grades 2 and 3) in the sixth week of RT (AA vs GA or GG, respectively: 17.9% vs 82.1% patients; odds ratio [OR] 0.14; 95% confidence interval [CI] 0.02-0.98; P = .0481). No statistically significant differences were observed between the volume of oral cavity contours (V30, V40, and V50) depending on the GHRL genotype in patients with head and neck cancer. The study results have demonstrated an association between the AA genotype of the GHRL gene and the risk of more severe oral mucositis attributed to RT in patients with head and neck cancer. © 2018 Wiley Periodicals, Inc.

Patients With Proneural Glioblastoma May Derive Overall Survival Benefit From the Addition of Bevacizumab to First-Line Radiotherapy and Temozolomide: Retrospective Analysis of the AVAglio Trial.

PubMed

Sandmann, Thomas; Bourgon, Richard; Garcia, Josep; Li, Congfen; Cloughesy, Timothy; Chinot, Olivier L; Wick, Wolfgang; Nishikawa, Ryo; Mason, Warren; Henriksson, Roger; Saran, Frank; Lai, Albert; Moore, Nicola; Kharbanda, Samir; Peale, Franklin; Hegde, Priti; Abrey, Lauren E; Phillips, Heidi S; Bais, Carlos

2015-09-01

The AVAglio (Avastin in Glioblastoma) and RTOG-0825 randomized, placebo-controlled phase III trials in newly diagnosed glioblastoma reported prolonged progression-free survival (PFS), but not overall survival (OS), with the addition of bevacizumab to radiotherapy plus temozolomide. To establish whether certain patient subgroups derived an OS benefit from the addition of bevacizumab to first-line standard-of-care therapy, AVAglio patients were retrospectively evaluated for molecular subtype, and bevacizumab efficacy was assessed for each patient subgroup. A total of 349 pretreatment specimens (bevacizumab arm, n = 171; placebo arm, n = 178) from AVAglio patients (total, N = 921) were available for biomarker analysis. Samples were profiled for gene expression and isocitrate dehydrogenase 1 (IDH1) mutation status and classified into previously identified molecular subtypes. PFS and OS were assessed within each subtype. A multivariable analysis accounting for prognostic covariates revealed that bevacizumab conferred a significant OS advantage versus placebo for patients with proneural IDH1 wild-type tumors (17.1 v 12.8 months, respectively; hazard ratio, 0.43; 95% CI, 0.26 to 0.73; P = .002). This analysis also revealed an interaction between the proneural subtype biomarker and treatment arm (P = .023). The group of patients with mesenchymal and proneural tumors derived a PFS benefit from bevacizumab compared with placebo; however, this translated to an OS benefit in the proneural subset only. Retrospective analysis of AVAglio data suggests that patients with IDH1 wild-type proneural glioblastoma may derive an OS benefit from first-line bevacizumab treatment. The predictive value of the proneural subtype observed in AVAglio should be validated in an independent data set. © 2015 by American Society of Clinical Oncology.

Is heterogeneity in stage 3 non-small cell lung cancer obscuring the potential benefits of dose-escalated concurrent chemo-radiotherapy in clinical trials?

PubMed

Hudson, Andrew; Chan, Clara; Woolf, David; McWilliam, Alan; Hiley, Crispin; O'Connor, James; Bayman, Neil; Blackhall, Fiona; Faivre-Finn, Corinne

2018-04-01

The current standard of care for the management of inoperable stage 3 non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy (cCRT) using radiotherapy dose-fractionation and chemotherapy regimens that were established 3 decades ago. In an attempt to improve the chances of long-term control from cCRT, dose-escalation of the radiotherapy dose was assessed in the RTOG 0617 randomised control study comparing the standard 60 Gy in 30 fractions with a high-dose arm receiving 74 Gy in 37 fractions. Following the publication of this trial the thoracic oncology community were surprised to learn that there was worse survival in the dose-escalated arm and that for now the standard of care must remain with the lower dose. In this article we review the RTOG 0617 paper with subsequent analyses and studies to explore why the use of dose-escalated cCRT in stage 3 NSCLC has not shown the benefits that were expected. The overarching theme of this opinion piece is how heterogeneity between stage 3 NSCLC cases in terms of patient, tumour, and clinical factors may obscure the potential benefits of dose-escalation by causing imbalances in the arms of studies such as RTOG 0617. We also examine recent advances in the staging, management, and technological delivery of radiotherapy in NSCLC and how these may be employed to optimise cCRT trials in the future and ensure that any potential benefits of dose-escalation can be detected. Copyright © 2018 Elsevier B.V. All rights reserved.

Acute skin toxicity associated with a 1-week schedule of whole breast radiotherapy compared with a standard 3-week regimen delivered in the UK FAST-Forward Trial.

PubMed

Brunt, A Murray; Wheatley, Duncan; Yarnold, John; Somaiah, Navita; Kelly, Stephen; Harnett, Adrian; Coles, Charlotte; Goodman, Andrew; Bahl, Amit; Churn, Mark; Zotova, Rada; Sydenham, Mark; Griffin, Clare L; Morden, James P; Bliss, Judith M

2016-07-01

FAST-Forward is a phase 3 clinical trial testing a 1-week course of whole breast radiotherapy against the UK standard 3-week regimen after primary surgery for early breast cancer. Two acute skin toxicity substudies were undertaken to test the safety of the test schedules with respect to early skin reactions. Patients were randomly allocated to 40Gy/15 fractions (F)/3-weeks, 27Gy/5F/1-week or 26Gy/5F/1-week. Acute breast skin reactions were graded using RTOG (first substudy) and CTCAE criteria v4.03 (second substudy) weekly during treatment and for 4weeks after treatment ended. Primary endpoint was the proportion of patients within each treatment group with grade ⩾3 toxicity (RTOG and CTCAE, respectively) at any time from the start of radiotherapy to 4weeks after completion. 190 and 162 patients were recruited. In the first substudy, evaluable patients with grade 3 RTOG toxicity were: 40Gy/15F 6/44 (13.6%); 27Gy/5F 5/51 (9.8%); 26Gy/5F 3/52 (5.8%). In the second substudy, evaluable patients with grade 3 CTCAE toxicity were: 40Gy/15F 0/43; 27Gy/5F 1/41 (2.4%); 26Gy/5F 0/53. Acute breast skin reactions with two 1-week schedules of whole breast radiotherapy under test in FAST-Forward were mild. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Localized volume effects for late rectal and anal toxicity after radiotherapy for prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peeters, Stephanie T.H.; Lebesque, Joos V.; Heemsbergen, Wilma D.

2006-03-15

Purpose: To identify dosimetric parameters derived from anorectal, rectal, and anal wall dose distributions that correlate with different late gastrointestinal (GI) complications after three-dimensional conformal radiotherapy for prostate cancer. Methods and Materials: In this analysis, 641 patients from a randomized trial (68 Gy vs. 78 Gy) were included. Toxicity was scored with adapted Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer (RTOG/EORTC) criteria and five specific complications. The variables derived from dose-volume histogram of anorectal, rectal, and anal wall were as follows: % receiving {>=}5-70 Gy (V5-V70), maximum dose (D{sub max}), and mean dose (D{sub mean}).more » The anus was defined as the most caudal 3 cm of the anorectum. Statistics were done with multivariate Cox regression models. Median follow-up was 44 months. Results: Anal dosimetric variables were associated with RTOG/EORTC Grade {>=}2 (V5-V40, D{sub mean}) and incontinence (V5-V70, D{sub mean}). Bleeding correlated most strongly with anorectal V55-V65, and stool frequency with anorectal V40 and D{sub mean}. Use of steroids was weakly related to anal variables. No volume effect was seen for RTOG/EORTC Grade {>=}3 and pain/cramps/tenesmus. Conclusion: Different volume effects were found for various late GI complications. Therefore, to evaluate the risk of late GI toxicity, not only intermediate and high doses to the anorectal wall volume should be taken into account, but also the dose to the anal wall.« less

Dosimetric comparison of peripheral NSCLC SBRT using Acuros XB and AAA calculation algorithms.

PubMed

Ong, Chloe C H; Ang, Khong Wei; Soh, Roger C X; Tin, Kah Ming; Yap, Jerome H H; Lee, James C L; Bragg, Christopher M

2017-01-01

There is a concern for dose calculation in highly heterogenous environments such as the thorax region. This study compares the quality of treatment plans of peripheral non-small cell lung cancer (NSCLC) stereotactic body radiation therapy (SBRT) using 2 calculation algorithms, namely, Eclipse Anisotropic Analytical Algorithm (AAA) and Acuros External Beam (AXB), for 3-dimensional conformal radiation therapy (3DCRT) and volumetric-modulated arc therapy (VMAT). Four-dimensional computed tomography (4DCT) data from 20 anonymized patients were studied using Varian Eclipse planning system, AXB, and AAA version 10.0.28. A 3DCRT plan and a VMAT plan were generated using AAA and AXB with constant plan parameters for each patient. The prescription and dose constraints were benchmarked against Radiation Therapy Oncology Group (RTOG) 0915 protocol. Planning parameters of the plan were compared statistically using Mann-Whitney U tests. Results showed that 3DCRT and VMAT plans have a lower target coverage up to 8% when calculated using AXB as compared with AAA. The conformity index (CI) for AXB plans was 4.7% lower than AAA plans, but was closer to unity, which indicated better target conformity. AXB produced plans with global maximum doses which were, on average, 2% hotter than AAA plans. Both 3DCRT and VMAT plans were able to achieve D95%. VMAT plans were shown to be more conformal (CI = 1.01) and were at least 3.2% and 1.5% lower in terms of PTV maximum and mean dose, respectively. There was no statistically significant difference for doses received by organs at risk (OARs) regardless of calculation algorithms and treatment techniques. In general, the difference in tissue modeling for AXB and AAA algorithm is responsible for the dose distribution between the AXB and the AAA algorithms. The AXB VMAT plans could be used to benefit patients receiving peripheral NSCLC SBRT. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Comparing a volume based template approach and ultrasound guided freehand approach in multicatheter interstitial accelerated partial breast irradiation.

PubMed

Koh, Vicky Y; Buhari, Shaik A; Tan, Poh Wee; Tan, Yun Inn; Leong, Yuh Fun; Earnest, Arul; Tang, Johann I

2014-06-01

Currently, there are two described methods of catheter insertion for women undergoing multicatheter interstitial accelerated partial breast irradiation (APBI). These are a volume based template approach (template) and a non-template ultrasound guidance freehand approach (non-template). We aim to compare dosimetric endpoints between the template and non-template approach. Twenty patients, who received adjuvant multicatheter interstitial APBI between August 2008 to March 2010 formed the study cohort. Dosimetric planning was based on the RTOG 04-13 protocol. For standardization, the planning target volume evaluation (PTV-Eval) and organs at risk were contoured with the assistance of the attending surgeon. Dosimetric endpoints include D90 of the PTV-Eval, Dose Homogeneity Index (DHI), V200, maximum skin dose (MSD), and maximum chest wall dose (MCD). A median of 18 catheters was used per patient. The dose prescribed was 34 Gy in 10 fractions BID over 5 days. The average breast volume was 846 cm(3) (526-1384) for the entire cohort and there was no difference between the two groups (p = 0.6). Insertion time was significantly longer for the non-template approach (mean 150 minutes) compared to the template approach (mean: 90 minutes) (p = 0.02). The planning time was also significantly longer for the non-template approach (mean: 240 minutes) compared to the template approach (mean: 150 minutes) (p < 0.01). The template approach yielded a higher D90 (mean: 95%) compared to the non-template approach (mean: 92%) (p < 0.01). There were no differences in DHI (p = 0.14), V200 (p = 0.21), MSD (p = 0.7), and MCD (p = 0.8). Compared to the non-template approach, the template approach offered significant shorter insertion and planning times with significantly improved dosimetric PTV-Eval coverage without significantly compromising organs at risk dosimetrically.

Distribution of prostate nodes: a PET/CT-derived anatomic atlas of prostate cancer patients before and after surgical treatment.

PubMed

Hegemann, Nina-Sophie; Wenter, Vera; Spath, Sonja; Kusumo, Nadia; Li, Minglun; Bartenstein, Peter; Fendler, Wolfgang P; Stief, Christian; Belka, Claus; Ganswindt, Ute

2016-03-11

In order to define adequate radiation portals in nodal positive prostate cancer a detailed knowledge of the anatomic lymph-node distribution is mandatory. We therefore systematically analyzed the localization of Choline PET/CT positive lymph nodes and compared it to the RTOG recommendation of pelvic CTV, as well as to previous work, the SPECT sentinel lymph node atlas. Thirty-two patients being mostly high risk patients with a PSA of 12.5 ng/ml (median) received PET/CT before any treatment. Eighty-seven patients received PET/CT for staging due to biochemical failure with a median PSA of 3.12 ng/ml. Each single PET-positive lymph node was manually contoured in a "virtual" patient dataset to achieve a 3-D visualization, resulting in an atlas of the cumulative PET positive lymph node distribution. Further the PET-positive lymph node location in each patient was assessed with regard to the existence of a potential geographic miss (i.e. PET-positive lymph nodes that would not have been treated adequately by the RTOG consensus on CTV definition of pelvic lymph nodes). Seventy-eight and 209 PET positive lymph nodes were detected in patients with no prior treatment and in postoperative patients, respectively. The most common sites of PET positive lymph nodes in patients with no prior treatment were external iliac (32.1 %), followed by common iliac (23.1 %) and para-aortic (19.2 %). In postoperative patients the most common sites of PET positive lymph nodes were common iliac (24.9 %), followed by external iliac (23.0 %) and para-aortic (20.1 %). In patients with no prior treatment there were 34 (43.6 %) and in postoperative patients there were 77 (36.8 %) of all detected lymph nodes that would not have been treated adequately using the RTOG CTV. We compared the distribution of lymph nodes gained by Choline PET/CT to the preexisting SPECT sentinel lymph node atlas and saw an overall good congruence. Choline PET/CT and SPECT sentinel lymph node atlas are comparable to each other. More than one-third of the PET positive lymph nodes in patients with no prior treatment and in postoperative patients would not have been treated adequately using the RTOG CTV. To reduce geographical miss, image based definition of an individual target volume is necessary.

Feasibility of magnetic resonance imaging-guided liver stereotactic body radiation therapy: A comparison between modulated tri-cobalt-60 teletherapy and linear accelerator-based intensity modulated radiation therapy.

PubMed

Kishan, Amar U; Cao, Minsong; Wang, Pin-Chieh; Mikaeilian, Argin G; Tenn, Stephen; Rwigema, Jean-Claude M; Sheng, Ke; Low, Daniel A; Kupelian, Patrick A; Steinberg, Michael L; Lee, Percy

2015-01-01

The purpose of this study was to investigate the dosimetric feasibility of liver stereotactic body radiation therapy (SBRT) using a teletherapy system equipped with 3 rotating (60)Co sources (tri-(60)Co system) and a built-in magnetic resonance imager (MRI). We hypothesized tumor size and location would be predictive of favorable dosimetry with tri-(60)Co SBRT. The primary study population consisted of 11 patients treated with SBRT for malignant hepatic lesions whose linear accelerator (LINAC)-based SBRT plans met all mandatory Radiation Therapy Oncology Group (RTOG) 1112 organ-at-risk (OAR) constraints. The secondary study population included 5 additional patients whose plans did not meet the mandatory constraints. Patients received 36 to 60 Gy in 3 to 5 fractions. Tri-(60)Co system SBRT plans were planned with ViewRay system software. All patients in the primary study population had tri-(60)Co SBRT plans that passed all RTOG constraints, with similar planning target volume coverage and OAR doses to LINAC plans. Mean liver doses and V10Gy to the liver, although easily meeting RTOG 1112 guidelines, were significantly higher with tri-(60)Co plans. When the 5 additional patients were included in a univariate analysis, the tri-(60)Co SBRT plans were still equally able to pass RTOG constraints, although they did have inferior ability to pass more stringent liver and kidney constraints (P < .05). A multivariate analysis found the ability of a tri-(60)Co SBRT plan to meet these constraints depended on lesion location and size. Patients with smaller or more peripheral lesions (as defined by distance from the aorta, chest wall, liver dome, and relative lesion volume) were significantly more likely to have tri-(60)Co plans that spared the liver and kidney as well as LINAC plans did (P < .05). It is dosimetrically feasible to perform liver SBRT with a tri-(60)Co system with a built-in MRI. Patients with smaller or more peripheral lesions are more likely to have optimal liver and kidney sparing, with the added benefit of MRI guidance, when receiving tri-(60)Co-based SBRT. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Safety and efficacy of a cytomegalovirus glycoprotein B (gB) vaccine in adolescent girls: A randomized clinical trial.

PubMed

Bernstein, David I; Munoz, Flor M; Callahan, S Todd; Rupp, Richard; Wootton, Susan H; Edwards, Kathryn M; Turley, Christine B; Stanberry, Lawrence R; Patel, Shital M; Mcneal, Monica M; Pichon, Sylvie; Amegashie, Cyrille; Bellamy, Abbie R

2016-01-12

Cytomegalovirus (CMV) is a leading cause of congenital infection and an important target for vaccine development. CMV seronegative girls between 12 and 17 years of age received CMV glycoprotein B (gB) vaccine with MF59 or saline placebo at 0, 1 and 6 months. Blood and urine were collected throughout the study for evidence of CMV infection based on PCR and/or seroconversion to non-vaccine CMV antigens. 402 CMV seronegative subjects were vaccinated (195 vaccine, 207 placebo). The vaccine was generally well tolerated, although local and systemic adverse events were significantly more common in the vaccine group. The vaccine induced gB antibody in all vaccine recipients with a gB geometric mean titer of 13,400 EU; 95%CI 11,436, 15,700, after 3 doses. Overall, 48 CMV infections were detected (21 vaccine, 27 placebo). In the per protocol population (124 vaccine, 125 placebo) vaccine efficacy was 43%; 95%CI: -36; 76, p=0.20. The most significant difference was after 2 doses, administered as per protocol; vaccine efficacy 45%, 95%CI: -9; 72, p=0.08. The vaccine was safe and immunogenic. Although the efficacy did not reach conventional levels of significance, the results are consistent with a previous study in adult women (Pass et al. N Engl J Med 2009;360:1191) using the same formulation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Enhanced case management can be delivered for patients with EVD in Africa: Experience from a UK military Ebola treatment centre in Sierra Leone.

PubMed

Dickson, S J; Clay, K A; Adam, M; Ardley, C; Bailey, M S; Burns, D S; Cox, A T; Craig, D G; Espina, M; Ewington, I; Fitchett, G; Grindrod, J; Hinsley, D E; Horne, S; Hutley, E; Johnston, A M; Kao, R L C; Lamb, L E; Lewis, S; Marion, D; Moore, A J; Nicholson-Roberts, T C; Phillips, A; Praught, J; Rees, P S; Schoonbaert, I; Trinick, T; Wilson, D R; Simpson, A J; Wang, D; O'Shea, M K; Fletcher, T E

2018-04-01

Limited data exist describing supportive care management, laboratory abnormalities and outcomes in patients with Ebola virus disease (EVD) in West Africa. We report data which constitute the first description of the provision of enhanced EVD case management protocols in a West African setting. Demographic, clinical and laboratory data were collected by retrospective review of clinical and laboratory records of patients with confirmed EVD admitted between 5 November 2014 and 30 June 2015. A total of 44 EVD patients were admitted (median age 37 years (range 17-63), 32/44 healthcare workers), and excluding those evacuated, the case fatality rate was 49% (95% CI 33%-65%). No pregnant women were admitted. At admission 9/44 had stage 1 disease (fever and constitutional symptoms only), 12/44 had stage 2 disease (presence of diarrhoea and/or vomiting) and 23/44 had stage 3 disease (presence of diarrhoea and/or vomiting with organ failure), with case fatality rates of 11% (95% CI 1%-58%), 27% (95% CI 6%-61%), and 70% (95% CI 47%-87%) respectively (p = 0.009). Haemorrhage occurred in 17/41 (41%) patients. The majority (21/40) of patients had hypokalaemia with hyperkalaemia occurring in 12/40 patients. Acute kidney injury (AKI) occurred in 20/40 patients, with 14/20 (70%, 95% CI 46%-88%) dying, compared to 5/20 (25%, 95% CI 9%-49%) dying who did not have AKI (p = 0.01). Ebola virus (EBOV) PCR cycle threshold value at baseline was mean 20.3 (SD 4.3) in fatal cases and 24.8 (SD 5.5) in survivors (p = 0.007). Mean national early warning score (NEWS) at admission was 5.5 (SD 4.4) in fatal cases and 3.0 (SD 1.9) in survivors (p = 0.02). Central venous catheters were placed in 37/41 patients and intravenous fluid administered to 40/41 patients (median duration of 5 days). Faecal management systems were inserted in 21/41 patients, urinary catheters placed in 27/41 and blood component therapy administered to 20/41 patients. EVD is commonly associated life-threatening electrolyte imbalance and organ dysfunction. We believe that the enhanced levels of protocolized care, scale and range of medical interventions we report, offer a blueprint for the future management of EVD in resource-limited settings. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Direct plan comparison of RapidArc and CyberKnife for spine stereotactic body radiation therapy

NASA Astrophysics Data System (ADS)

Choi, Young Eun; Kwak, Jungwon; Song, Si Yeol; Choi, Eun Kyung; Ahn, Seung Do; Cho, Byungchul

2015-07-01

We compared the treatment planning performance of RapidArc (RA) vs. CyberKnife (CK) for spinal stereotactic body radiation therapy (SBRT). Ten patients with spinal lesions who had been treated with CK were re-planned with RA, which consisted of two complete arcs. Computed tomography (CT) and volumetric dose data of CK, generated using the Multiplan (Accuray) treatment planning system (TPS) and the Ray-trace algorithm, were imported to Varian Eclipse TPS in Dicom format, and the data were compared with the RA plan by using an analytical anisotropic algorithm (AAA) dose calculation. The optimized dose priorities for both the CK and the RA plans were similar for all patients. The highest priority was to provide enough dose coverage to the planned target volume (PTV) while limiting the maximum dose to the spinal cord. Plan quality was evaluated with respect to PTV coverage, conformity index (CI), high-dose spillage, intermediate-dose spillage (R50% and D2cm), and maximum dose to the spinal cord, which are criteria recommended by the RTOG 0631 spine and 0915 lung SBRT protocols. The mean CI' SD values of the PTV were 1.11' 0.03 and 1.17' 0.10 for RA and CK ( p = 0.02), respectively. On average, the maximum dose delivered to the spinal cord in CK plans was approximately 11.6% higher than that in RA plans, and this difference was statistically significant ( p < 0.001). High-dose spillages were 0.86% and 2.26% for RA and CK ( p = 0.203), respectively. Intermediate-dose spillage characterized by D2cm was lower for RA than for CK; however, R50% was not statistically different. Even though both systems can create highly conformal volumetric dose distributions, the current study shows that RA demonstrates lower high- and intermediate-dose spillages than CK. Therefore, RA plans for spinal SBRT may be superior to CK plans.

Phase III Trial of Chemoradiotherapy for Anaplastic Oligodendroglioma: Long-Term Results of RTOG 9402

PubMed Central

Cairncross, Gregory; Wang, Meihua; Shaw, Edward; Jenkins, Robert; Brachman, David; Buckner, Jan; Fink, Karen; Souhami, Luis; Laperriere, Normand; Curran, Walter; Mehta, Minesh

2013-01-01

Purpose Anaplastic oligodendrogliomas, pure (AO) and mixed (anaplastic oligoastrocytoma [AOA]), are chemosensitive, especially if codeleted for 1p/19q, but whether patients live longer after chemoradiotherapy is unknown. Patients and Methods Eligible patients with AO/AOA were randomly assigned to procarbazine, lomustine, and vincristine (PCV) plus radiotherapy (RT) versus RT alone. The primary end point was overall survival (OS). Results Two hundred ninety-one eligible patients were randomly assigned: 148 to PCV plus RT and 143 to RT. For the entire cohort, there was no difference in median survival by treatment (4.6 years for PCV plus RT v 4.7 years for RT; hazard ratio [HR] = 0.79; 95% CI, 0.60 to 1.04; P = .1). Patients with codeleted tumors lived longer than those with noncodeleted tumors (PCV plus RT: 14.7 v 2.6 years, HR = 0.36, 95% CI, 0.23 to 0.57, P < .001; RT: 7.3 v 2.7 years, HR = 0.40, 95% CI, 0.27 to 0.60, P < .001), and the median survival of those with codeleted tumors treated with PCV plus RT was twice that of patients receiving RT (14.7 v 7.3 years; HR = 0.59; 95% CI, 0.37 to 0.95; P = .03). For those with noncodeleted tumors, there was no difference in median survival by treatment arm (2.6 v 2.7 years; HR = 0.85; 95% CI, 0.58 to 1.23; P = .39). In Cox models that included codeletion status, the adjusted OS for all patients was prolonged by PCV plus RT (HR = 0.67; 95% CI, 0.50 to 0.91; P = .01). Conclusion For the subset of patients with 1p/19q codeleted AO/AOA, PCV plus RT may be an especially effective treatment, although this observation was derived from an unplanned analysis. PMID:23071247

Protocolized fluid therapy in brain-dead donors: The multi-center randomized MOnIToR trial

PubMed Central

Al-Khafaji, Ali; Elder, Michele; Lebovitz, Daniel J; Murugan, Raghavan; Souter, Michael; Stuart, Susan; Wahed, Abdus S.; Keebler, Ben; Dils, Dorrie; Mitchell, Stephanie; Shutterly, Kurt; Wilkerson, Dawn; Pearse, Rupert; Kellum, John A

2015-01-01

BACKGROUND Critical shortages of organs for transplantation jeopardize many lives. Observational data suggest that better fluid management for deceased organ donors could increase organ recovery. We conducted the first large multi-center randomized trial in brain-dead donors to determine whether protocolized fluid therapy increases organs transplanted. METHODS We randomly assigned donors to either protocolized or usual care in eight organ procurement organizations. A “protocol-guided fluid therapy” algorithm targeting cardiac index, mean arterial pressure and pulse pressure variation was used. Our primary outcome was the number of organs transplanted per donor and our primary analysis was intention-to-treat. Secondary analyses included: 1) modified intention-to-treat where only subjects able to receive the intervention were included, and 2) twelve-month survival in transplant recipients. The study was stopped early. RESULTS We enrolled 556 donors; 279 protocolized care, 277 usual care. Groups had similar characteristics at baseline. The study protocol could be implemented in 76% of subjects randomized to the intervention. There was no significant difference in mean number of organs transplanted per donor: 3.39 organs per donor, (95%CI: 3.14-3.63) with protocolized care, compared to usual care 3.29 (95%CI: 3.04-3.54) (mean difference, 0.1, 95%CI: -0.25 to 0.45; p=0.56). In modified intention-to-treat analysis the mean number of organs increased (3.52 organs per donor, 95%CI: 3.23-3.8) but was not statistically significant (mean difference, 0.23, 95%CI: -0.15-0.61; p=0.23). Among the 1430 recipients of organs from study subjects, with data available, 56 deaths (7.8%) occurred in the protocolized care arm and 56 (7.9%) in the usual care arm in the first year (Hazard Ratio: 0.97, p=0.86). CONCLUSIONS In brain-dead organ donors, protocol-guided fluid therapy compared to usual care may not increase the number of organs transplanted per donor. PMID:25583616

Volumetric-modulated arc therapy (VMAT) for whole brain radiotherapy: not only for hippocampal sparing, but also for reduction of dose to organs at risk.

PubMed

Sood, Sumit; Pokhrel, Damodar; McClinton, Christopher; Lominska, Christopher; Badkul, Rajeev; Jiang, Hongyu; Wang, Fen

2017-01-01

A prospective clinical trial, Radiation Therapy Oncology Group (RTOG) 0933, has demonstrated that whole brain radiotherapy (WBRT) using conformal radiation delivery technique with hippocampal avoidance is associated with less memory complications. Further sparing of other organs at risk (OARs) including the scalp, ear canals, cochleae, and parotid glands could be associated with reductions in additional toxicities for patients treated with WBRT. We investigated the feasibility of WBRT using volumetric-modulated arc therapy (VMAT) to spare the hippocampi and the aforementioned OARs. Ten patients previously treated with nonconformal WBRT (NC-WBRT) using opposed lateral beams were retrospectively re-planned using VMAT with hippocampal sparing according to the RTOG 0933 protocol. The OARs (scalp, auditory canals, cochleae, and parotid glands) were considered as dose-constrained structures. VMAT plans were generated for a prescription dose of 30 Gy in 10 fractions. Comparison of the dosimetric parameters achieved by VMAT and NC-WBRT plans was performed using paired t-tests using upper bound p-value of < 0.001. Average beam on time and monitor units (MUs) delivered to the patients on VMAT were compared with those obtained with NC-WBRT. All VMAT plans met RTOG 0933 dosimetric criteria including the dose to hippocampi of 100% of the volume (D 100% ) of 8.4 ± 0.3 Gy and maximum dose of 15.6 ± 0.4 Gy, respectively. A statistically significant dose reduction (p < 0.001) to all OARs was achieved. The mean and maximum scalp doses were reduced by an average of 9 Gy (32%) and 2 Gy (6%), respectively. The mean and maximum doses to the auditory canals were reduced from 29.5 ± 0.5 Gy and 31.0 ± 0.4 Gy with NC-WBRT, to 21.8 ± 1.6 Gy (26%) and 27.4 ± 1.4 Gy (12%) with VMAT. VMAT also reduced mean and maximum doses to the cochlea by an average of 4 Gy (13%) and 2 Gy (6%), respectively. The parotid glands mean and maximum doses with VMAT were 4.4 ± 1.9 Gy and 15.7 ± 5.0 Gy, compared to 12.8 ± 4.9 Gy and 30.6 ± 0.5 Gy with NC-WBRT, respectively. The average dose reduction of mean and maximum of parotid glands from VMAT were 65% and 50%, respectively. The average beam on time and MUs were 2.3minutes and 719 on VMAT, and 0.7 minutes and 350 on NC-WBRT. This study demonstrated the feasibility of WBRT using VMAT to not only spare the hippocampi, but also significantly reduce dose to OARs. These advantages of VMAT could potentially decrease the toxicities associated with NC-WBRT and improve patients' quality of life, especially for patients with favorable prognosis receiving WBRT or patients receiving prophylactic cranial irradiation (PCI). Published by Elsevier Inc.

Type 2 diabetes management in nurse-led primary healthcare settings in urban and rural Cameroon.

PubMed

Kengne, Andre Pascal; Fezeu, Leopold; Sobngwi, Eugene; Awah, Paschal Kum; Aspray, Terence J; Unwin, Nigel C; Mbanya, Jean-Claude

2009-08-01

To implement a protocol-driven primary nurse-led care for type 2 diabetes in rural and urban Cameroon. We set-up three primary healthcare clinics in Yaounde (Capital city) and two in the Bafut rural health district. Participants were 225 (17% rural) patients with known or newly diagnosed type 2 diabetes, not requiring insulin, referred either from a baseline survey (38 patients, 17%), or secondarily attracted to the clinics. Protocol-driven glucose and blood pressure control were delivered by trained nurses. The main outcomes were trajectories of fasting capillary glucose and blood pressure indices, and differences in the mean levels between baseline and final visits. The total duration of follow-up was 1110 patient-months. During follow-up, there was a significant downward trend in fasting capillary glucose overall (p<0.001) and in most subgroups of participants. Between baseline and final visits, mean fasting capillary glucose dropped by 1.6 mmol/L (95% CI: 0.8-2.3; p< or =0.001). Among those with hypertension, blood pressure also decreased significantly for systolic and marginally for diastolic blood pressure. No major significant change was noticed for body weight. Nurses may be potential alternatives to improve access to diabetes care in settings where physicians are not available.

SU-F-R-11: Designing Quality and Safety Informatics Through Implementation of a CT Radiation Dose Monitoring Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilson, JM; Samei, E; Departments of Physics, Electrical and Computer Engineering, and Biomedical Engineering, and Medical Physics Graduate Program, Duke University, Durham, NC

2016-06-15

Purpose: Recent legislative and accreditation requirements have driven rapid development and implementation of CT radiation dose monitoring solutions. Institutions must determine how to improve quality, safety, and consistency of their clinical performance. The purpose of this work was to design a strategy and meaningful characterization of results from an in-house, clinically-deployed dose monitoring solution. Methods: A dose monitoring platform was designed by our imaging physics group that focused on extracting protocol parameters, dose metrics, and patient demographics and size. Compared to most commercial solutions, which focus on individual exam alerts and global thresholds, the program sought to characterize overall consistencymore » and targeted thresholds based on eight analytic interrogations. Those were based on explicit questions related to protocol application, national benchmarks, protocol and size-specific dose targets, operational consistency, outliers, temporal trends, intra-system variability, and consistent use of electronic protocols. Using historical data since the start of 2013, 95% and 99% intervals were used to establish yellow and amber parameterized dose alert thresholds, respectively, as a function of protocol, scanner, and size. Results: Quarterly reports have been generated for three hospitals for 3 quarters of 2015 totaling 27880, 28502, 30631 exams, respectively. Four adult and two pediatric protocols were higher than external institutional benchmarks. Four protocol dose levels were being inconsistently applied as a function of patient size. For the three hospitals, the minimum and maximum amber outlier percentages were [1.53%,2.28%], [0.76%,1.8%], [0.94%,1.17%], respectively. Compared with the electronic protocols, 10 protocols were found to be used with some inconsistency. Conclusion: Dose monitoring can satisfy requirements with global alert thresholds and patient dose records, but the real value is in optimizing patient-specific protocols, balancing image quality trade-offs that dose-reduction strategies promise, and improving the performance and consistency of a clinical operation. Data plots that capture patient demographics and scanner performance demonstrate that value.« less

Nodule Classification on Low-Dose Unenhanced CT and Standard-Dose Enhanced CT: Inter-Protocol Agreement and Analysis of Interchangeability.

PubMed

Lee, Kyung Hee; Lee, Kyung Won; Park, Ji Hoon; Han, Kyunghwa; Kim, Jihang; Lee, Sang Min; Park, Chang Min

2018-01-01

To measure inter-protocol agreement and analyze interchangeability on nodule classification between low-dose unenhanced CT and standard-dose enhanced CT. From nodule libraries containing both low-dose unenhanced and standard-dose enhanced CT, 80 solid and 80 subsolid (40 part-solid, 40 non-solid) nodules of 135 patients were selected. Five thoracic radiologists categorized each nodule into solid, part-solid or non-solid. Inter-protocol agreement between low-dose unenhanced and standard-dose enhanced images was measured by pooling κ values for classification into two (solid, subsolid) and three (solid, part-solid, non-solid) categories. Interchangeability between low-dose unenhanced and standard-dose enhanced CT for the classification into two categories was assessed using a pre-defined equivalence limit of 8 percent. Inter-protocol agreement for the classification into two categories {κ, 0.96 (95% confidence interval [CI], 0.94-0.98)} and that into three categories (κ, 0.88 [95% CI, 0.85-0.92]) was considerably high. The probability of agreement between readers with standard-dose enhanced CT was 95.6% (95% CI, 94.5-96.6%), and that between low-dose unenhanced and standard-dose enhanced CT was 95.4% (95% CI, 94.7-96.0%). The difference between the two proportions was 0.25% (95% CI, -0.85-1.5%), wherein the upper bound CI was markedly below 8 percent. Inter-protocol agreement for nodule classification was considerably high. Low-dose unenhanced CT can be used interchangeably with standard-dose enhanced CT for nodule classification.

SU-E-J-81: Adaptive Radiotherapy for IMRT Head & Neck Patient in AKUH

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yousuf, A; Qureshi, B; Qadir, A

2015-06-15

Purpose: In this study we proposed Adaptive radiotherapy for IMRT patients which will brought an additional dimension to the management of patients with H&N cancer in Aga Khan University Hospital. Methods: In this study 5 Head and Neck (H&N) patients plan where selected, who’s Re-CT were done during the course of their treatment, they were simulated with IMRT technique to learn the consequence of anatomical changes that may occur during the treatment, as they are more dramatic changes can occur as compare to conventional treatment. All the organ at risk were drawn according RTOG guidelines and doses were checked asmore » per NCCN guidelines. Results: The reduction in size of Planning target volume (PTV) is more than 20% in all the cases which leads to 3 to 5 % overdose to normal tissues and Organ at Risk. Conclusion: Through this study we would like to emphasis the importance of Adaptive Radiotherapy practice in all IMRT (H&N) patients, although prospective studies are required with larger sample sizes to address the safety and the clinical effect of such approaches on patient outcome, also one need to develop protocols before implementation of this technique in practice.« less

Investigating Bordetella pertussis colonisation and immunity: protocol for an inpatient controlled human infection model

PubMed Central

de Graaf, Hans; Gbesemete, Diane; Gorringe, Andrew R.; Diavatopoulos, Dimitri A.; Kester, Kent E.; Faust, Saul N.; Read, Robert C.

2017-01-01

Introduction We summarise an ethically approved protocol for the development of an experimental human challenge colonisation model. Globally Bordetella pertussis is one of the leading causes of vaccine-preventable death. Many countries have replaced whole cell vaccines with acellular vaccines over the last 20 years during which pertussis appears to be resurgent in a number of countries in the developed world that boast high immunisation coverage. The acellular vaccine provides relatively short-lived immunity and, in contrast to whole cell vaccines, may be less effective against colonisation and subsequent transmission. To improve vaccine strategies, a greater understanding of human B. pertussis colonisation is required. This article summarises a protocol and does not contain any results. Methods and analysis A controlled human colonisation model will be developed over two phases. In phase A, a low dose of the inoculum will be given intranasally to healthy participants. This dose will be escalated or de-escalated until colonisation is achieved in approximately 70% (95% CI 47% to 93%) of the exposed volunteers without causing disease. The colonisation period, shedding and exploratory immunology will be assessed during a 17-day inpatient stay and follow-up over 1 year. The dose of inoculum that achieves 70% colonisation will then be confirmed in phase B, comparing healthy participants exposed to B. pertussis with a control group receiving a sham inoculum. Ethics and dissemination This study has been approved by the ethical committee reference: 17/SC/0006, 24 February 2017. Findings will be published in peer-reviewed open access journals as soon as possible. PMID:29025851

Optimal Outcomes in Young Class 3 Patients With Thalassemia Undergoing HLA-Identical Sibling Bone Marrow Transplantation.

PubMed

Gaziev, Javid; Isgrò, Antonella; Sodani, Pietro; Marziali, Marco; Paciaroni, Katia; Gallucci, Cristiano; De Angelis, Gioia; Andreani, Marco; Testi, Manuela; Alfieri, Cecilia; Ribersani, Michela; Galluccio, Tiziana; Battarra, Maria Rosa; Morrone, Aldo; Lucarelli, Guido

2016-04-01

Bone marrow transplantation (BMT) for class 3 patients with thalassemia is challenging due to high rates of graft rejection and transplant-related mortality. Since the first studies of BMT in the late 1980s, a number of conditioning regimens have been designed to improve outcomes, but with suboptimal results. Here we report the outcome of transplantation in class 3 patients using a modified protocol. Sixty-three patients between 5 and 16.7 years of age with class 3 thalassemia received HLA-matched sibling BMT following either the original protocol (26 patients) or the modified protocol (37 patients). Both regimens comprised preconditioning cytoreduction with hydroxyurea and azathioprine starting at -45 days pretransplant, and fludarabine from days -16 to -12. Conditioning was performed with busulfan and cyclophosphamide (original protocol) or with busulfan, thiotepa, and cyclophosphamide (modified protocol). The 2 groups showed similar patient demographics. At day 0, the degree of cytoreduction (lymphopenia, neuthropenia, and thrombocytopenia) achieved by the modified protocol was greater than the original protocol. The incidence of graft failure/rejection was significantly higher in the original group (15%; 95% confidence interval [95% CI], 5-32%) compared with the modified group (0%) (P = 0.014). The respective 5-year thalassemia-free survival rates were 73% (95% CI, 51-86%) and 92% (95% CI, 77-97%) (P = 0.047). Both groups showed similar incidences of grades II to IV acute graft-versus host disease. Modified protocol did not increase nonhematological toxicity or infectious complications. The modified treatment protocol effectively and safely prevented graft failure/rejection and significantly increased thalassemia-free survival of class 3 patients with thalassemia.

[Comparision of in vitro maturation applied in PCOS and non-PCOS patients undergo stimulated and unstimulated protocols].

PubMed

Wang, Peiyu; Zhao, Junzhao; Jin, Congcong; Yu, Rong; Lin, Jia; Zhu, Ruru; Wu, Yonggen

2014-12-01

To compare the laboratory and clinical results between unstimulated in vitro maturation (IVM) and IVM converted from in vitro fertilization (IVF) in polycystic ovarian syndrome (PCOS) and non-PCOS patients. We divided 591 IVM cycles in the First Affiliated Hospital of Wenzhou Medical Univesity from Jan. 2008 to Dec. 2013 into 4 groups: group A1B1, PCOS patients underwent unstimulated IVM protocol, 240 cycles; group A1B2, PCOS patients underwent IVM converted from conventional stimulated IVF protocol, 153 cycles; group A2B1, non-PCOS patients underwent unstimutlated IVM protocol, 103 cycles; group A2B2, non-PCOS patient underwent IVM converted from conventional stimulated IVF protocol, 95 cycles. Multiple linear regression method and binary logistic regression method were used to assess the influence of PCOS and protocols for IVM on laboratory and clinical outcomes. The mean number of oocytes retrieved was positively related with PCOS [partial regression coefficient (B) = 3.37, P < 0.01]. The maturation rate of oocytes was positively related with hCG-prime prior to oocyte aspiration (B = 0.05, P = 0.010). High-quality embryo rate was positively related with PCOS and IVM converted from IVF (B = 0.08, P = 0.010; B = 0.09, P = 0.001), as well as implantation rate related with them (B = 0.07, P = 0.010; B = 0.10, P < 0.01). PCOS and IVM converted from IVF improved hCG positive (hCG>10 U/L) rate (OR = 1.636, 95%CI: 1.113-2.204, P < 0.05; OR = 1.861, 95%CI: 1.307-2.649, P < 0.05) and the clinical pregnancy rate (OR = 1.507, 95%CI: 1.041-2.240, P < 0.05; OR = 1.881, 95%CI: 1.312-2.696, P < 0.05). IVM converted from IVF protocol decreased the spontaneous abortion rate (OR = 0.490, 95%CI: 0.245-0.978, P < 0.05). Multiple gestation rate and ectopic pregnancy rate were not affected by PCOS condition and protocol used (P > 0.05). PCOS and IVM converted from IVF protocol improved the high-quality embryo rate, implantation rate, hCG positive rate and clinical pregnancy rate. IVM converted from IVF protocol reduced the spontaneous abortion rate. PCOS patients may be more suitable for the IVM treatment. No matter PCOS or non-PCOS patients, IVM converted from IVF protocol had better pregnancy outcome than that of unstimulated cycle.

Cartographic Mapping and Travel Burden to Assess and Develop Strategies to Improve Minority Access to National Cancer Clinical Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bruner, Deborah Watkins, E-mail: deborah.w.bruner@emory.edu; Pugh, Stephanie L.; Yeager, Katherine A.

Purpose: To assess how accrual to clinical trials is related to US minority population density relative to clinical trial site location and distance traveled to Radiation Therapy Oncology Group (RTOG) clinical trial sites. Methods and Materials: Data included member site address and ZIP codes, patient accrual, and patient race or ethnicity and ZIP code. Geographic Information System maps were developed for overall, Latino, and African American accrual to trials by population density. The Kruskal-Wallis test was used to assess differences in distance traveled by site, type of trial, and race or ethnicity. Results: From 2006 to 2009, 6168 patients enrolledmore » on RTOG trials. The RTOG US site distribution is generally concordant with overall population density. Sites with highest accrual are located throughout the United States and parts of Canada and do not cluster, nor does highest minority accrual cluster in areas of highest US minority population density. Of the 4913 US patients with complete data, patients traveled a median of 11.6 miles to participate in clinical trials. Whites traveled statistically longer distances (12.9 miles; P<.0001) to participate, followed by Latinos (8.22 miles) and African Americans (5.85 miles). Patients were willing to drive longer distances to academic sites than community sites, and there was a trend toward significantly longer median travel for therapeutic versus cancer control or metastatic trials. Conclusions: Location matters, but only to a degree, for minority compared with nonminority participation in clinical trials. Geographic Information System tools help identify gaps in geographic access and travel burden for clinical trials participation. Strategies that emerged using these tools are discussed.« less

Evolving management of low grade glioma: No consensus amongst treating clinicians.

PubMed

Field, K M; Rosenthal, M A; Khasraw, M; Sawkins, K; Nowak, A K

2016-01-01

Following the widely publicized presentation of the Radiation Therapy Oncology Group (RTOG) 9802 data, we sought to understand how these data had been translated to the management of low grade gliomas (LGG) by Australian neuro-oncology clinicians. The de novo management of LGG is transitioning to include postoperative radiotherapy and chemotherapy after the RTOG 9802 study results demonstrated a survival benefit in this setting. In 2014, neurosurgeons, radiation oncologists and neuro-oncologists who were members of the Australian Cooperative Trials Group for Neuro-oncology (COGNO), as well as additional attendants of the COGNO annual scientific meeting, were surveyed. The survey presented six LGG clinical scenarios and asked respondents to select their preferred management strategy. Some additional questions included the respondents' approach to 1p/19q testing and chemotherapy preferences. The response rate was 30.2% (61/202), with the majority (77%) working in tertiary referral neuro-oncology centers. There was no consensus regarding the management approach for each scenario, with postsurgery observation alone remaining a popular strategy. Only 25% of respondents reported that their institution routinely tests for 1p/19q status in LGG, although 69% were of the opinion that all LGG patients should be tested. The majority (81%) preferred to use temozolomide rather than the procarbazine, lomustine, and vincristine combination as the first line chemotherapy for LGG, but only 44% would actually use it in this setting. Up front chemotherapy, prior to radiotherapy, would be considered by 52% of respondents for certain LGG patients. This survey assessed the management strategies for LGG since the updated RTOG 9802 data were presented. It demonstrates no consensus in the postoperative treatment approaches for LGG. Copyright © 2015 Elsevier Ltd. All rights reserved.

Feasibility of Economic Analysis of Radiation Therapy Oncology Group (RTOG) 91-11 Using Medicare Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Konski, Andre, E-mail: akonski@med.wayne.ed; Bhargavan, Mythreyi; Owen, Jean

Purpose: The specific aim of this analysis was to evaluate the feasibility of performing a cost-effectiveness analysis using Medicare data from patients treated on a randomized Phase III clinical trial. Methods and Materials: Cost data included Medicare Part A and Part B costs from all providers-inpatient, outpatient, skilled nursing facility, home health, hospice, and physicians-and were obtained from the Centers for Medicare and Medicaid Services for patients eligible for Medicare, treated on Radiation Therapy Oncology Group (RTOG) 9111 between 1992 and 1996. The 47-month expected discounted (annual discount rate of 3%) cost for each arm of the trial was calculatedmore » in 1996 dollars, with Kaplan-Meier sampling average estimates of survival probabilities for each month and mean monthly costs. Overall and disease-free survival was also discounted 3%/year. The analysis was performed from a payer's perspective. Incremental cost-effectiveness ratios were calculated comparing the chemotherapy arms to the radiation alone arm. Results: Of the 547 patients entered, Medicare cost data and clinical outcomes were available for 66 patients. Reasons for exclusion included no RTOG follow-up, Medicare HMO enrollment, no Medicare claims since trial entry, and trial entry after 1996. Differences existed between groups in tumor characteristics, toxicity, and survival, all which could affect resource utilization. Conclusions: Although we were able to test the methodology of economic analysis alongside a clinical trial using Medicare data, the results may be difficult to translate to the entire trial population because of non-random missing data. Methods to improve Medicare data capture and matching to clinical trial samples are required.« less

Efficacy and Safety of Available Protocols for Aspirin Hypersensitivity for Patients Undergoing Percutaneous Coronary Intervention: A Survey and Systematic Review.

PubMed

Bianco, Matteo; Bernardi, Alessandro; D'Ascenzo, Fabrizio; Cerrato, Enrico; Omedè, Pierluigi; Montefusco, Antonio; DiNicolantonio, James J; Zoccai, Giuseppe Biondi; Varbella, Ferdinando; Carini, Giovanni; Moretti, Claudio; Pozzi, Roberto; Gaita, Fiorenzo

2016-01-01

The most suitable approach for patients with aspirin hypersensitivity undergoing percutaneous coronary intervention remains to be assessed. Pubmed, Google Scholar, and Cochrane were systematically searched for papers describing protocols about aspirin hypersensitivity in the percutaneous coronary intervention setting. Discharge from hospital with aspirin was the primary end point, whereas rates of adverse reactions being a secondary outcome. An online international survey was performed to critically analyze rates of aspirin hypersensitivity and its medical and interventional management. Eleven studies with 283 patients were included. An endovenous desensitization protocol was performed on one of them, with high efficacy rate (98%) and a low adverse reaction rate when compared with oral administration. No significant differences were reported among the oral protocols in terms of efficacy (less versus more fractionated [95.8% {95.4%-96.2%} versus 95.9% {95.2-96.5%}]), whereas higher incidence of rash and angioedema were reported for protocols with <6 doses escalation (2.6% [1.1%-4.1%] versus 2.6% [1.9%-3.2%]). In the survey, we collected answer from 86 physician of the 100 interviewed. Fifty-six percent of them managed aspirin hypersensitivity changing the therapeutic regimen (eg, clopidogrel monotherapy and indobufen). Despite the previous safety data, desensitization protocols were adopted by only 42% of surveyed cardiologist. Available protocols for aspirin hypersensitivity are effective and safe, representing a feasible approach for patients needing dual antiplatelet therapy. © 2016 American Heart Association, Inc.

Early-stage Node-negative (T1-T2N0) Anal Cancer Treated with Simultaneous Integrated Boost Radiotherapy and Concurrent Chemotherapy.

PubMed

Franco, Pierfrancesco; Arcadipane, Francesca; Ragona, Riccardo; Mistrangelo, Massimiliano; Cassoni, Paola; Rondi, Nadia; Morino, Mario; Racca, Patrizia; Ricardi, Umberto

2016-04-01

To report clinical outcomes of a consecutive series of patients with early-stage (T1-T1N0) anal cancer treated with intensity-modulated radiotherapy (IMRT) and a simultaneous integrated boost (SIB) approach similarly to the RTOG 05-29 trial. A cohort of 43 patients underwent SIB-IMRT employing a schedule consisting of 50.4 Gy/28 fractions to the gross tumor volume and 42 Gy/28 fractions to the elective nodal volumes for cT1N0 cases, and 54 Gy/30 fractions and 45 Gy/30 fractions to the same volumes for cT2N0 cases. Chemotherapy was administered concurrently following Nigro's regimen. The primary endpoint was colostomy-free survival (CFS). Secondary endpoints were locoregional control (LRC), disease-free (DFS), cancer-specific (CSS) and overall (OS) survival. Median follow-up was 39.7 months. The actuarial 3-year CFS was 79.4% [95% confidence interval (CI)=61.4-89.7%]. Actuarial 3-year OS and CSS were 90.8% (95% CI=74.1-96.9%) and 93.8% (95% CI=77.3-98.4%), while DFS was 75.5% (95% CI=56.4-87.1%). Actuarial 3-year LRC was 86.1% (95% CI=69.6-94%). On multivariate analysis, tumor size >3 cm showed a trend towards significance in predicting CFS [hazard ratio (HR)=8.6, 95% CI=84.7-88.1%; p=0.069]. Maximum detected adverse events included: skin (G3): 18%; gastrointestinal tract (G2): 67%; genitourinary tract (G3): 3%; genitalia (G2): 30%; anemia (G2): 7%; leukopenia (G3): 26%, leukopenia (G4):7%; neutropenia (G3): 15%; neutropenia (G4): 12%; thrombocytopenia (G3): 9%. Our clinical results support the use of SIB-IMRT in the combined modality treatment of patients with anal cancer. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

106-17 Telemetry Standards Chapter 7 Packet Telemetry Downlink

DTIC Science & Technology

2017-07-31

Acronyms IP Internet Protocol IPv4 Internet Protocol, Version 4 IPv6 Internet Protocol, Version 6 LLP low-latency PTDP MAC media access control...o 4’b0101: PT Internet Protocol (IP) Packet o 4’b0110: PT Chapter 24 TmNSMessage Packet o 4’b0111 – 4’b1111: Reserved • Fragment (bits 17 – 16...packet is defined as a free -running 12-bit counter. The PT test counter packet shall consist of one 12-bit word and shall be encoded as one 24-bit

VO2max Testing in Trail Runners: Is There a Specific Exercise Test Protocol?

PubMed

Scheer, Volker; Ramme, Katharina; Reinsberger, Claus; Heitkamp, Hans-Christian

2018-06-01

Trail running places specific physiological demands on the human body due to its uphill and downhill running sections. We developed and investigated a more sport-specific trail exercise test protocol (inclination and speed incremental protocol), and compared it to two standard exercise test protocols (horizontal step and ramp protocol) in thirteen highly trained trail runners (age 31±6 years, height 179±6.4 cm, weight 69.2±7.9 kg, BMI 21.6±2.1 kg/m 2 ). The maximum oxygen uptake (VO 2 max) measured during the trail test (62.5±5.9 ml·kg -1 ·min -1 , [95% CI: 59.0-66.1]) was significantly higher compared to both the step test (60.1±5.3 ml·kg -1 ·min -1 , [95% CI: 56.8-63.3], p=0.024) and the ramp test (59.7±5.5 ml·kg -1 ·min -1 , [95% CI: 56.4-63.0], p=0.028). Time to task failure was significantly shorter in the trail test (557±73 s, [95% CI: 512-601]) compared to both the step test (1378±152 s, [95% CI: 1286-1470], p<0.001) and the ramp test (605±95, [95% CI: 547-662], p<0.001). Other physiological measurements obtained were similar. The trail test was the preferred choice in our group of trail runners. This study supports the implementation of the trail test in practice, and recommends that its validity be evaluated further. © Georg Thieme Verlag KG Stuttgart · New York.

Validation of the Omron MIT Elite blood pressure device in a pregnant population with large arm circumference.

PubMed

James, Lauren; Nzelu, Diane; Hay, Anna; Shennan, Andrew; Kametas, Nikos A

2017-04-01

The aim of this study was to evaluate the accuracy of the Omron MIT Elite automated device in pregnant women with an arm circumference of or above 32 cm, using the British Hypertension Society validation protocol. Blood pressure was measured sequentially in 46 women of any gestation requiring the use of a large cuff (arm circumference ≥32 cm) alternating between the mercury sphygmomanometer and the Omron MIT Elite device. The Omron MIT Elite achieved an overall D/D grade with a mean of the device-observer difference being 7.17±6.67 and 9.31±6.59 for systolic and diastolic blood pressure respectively. Interobserver accuracy was 94.6% for systolic and 95% for diastolic readings within 5 mmHg. The Omron MIT Elite overestimates blood pressure and has failed the British Hypertension Society protocol requirements. Therefore, it cannot be recommended for use in pregnant women with an arm circumference of or above 32 cm.

The European Centre for Disease Prevention and Control (ECDC) pilot point prevalence survey of healthcare-associated infections and antimicrobial use.

PubMed

Zarb, P; Coignard, B; Griskeviciene, J; Muller, A; Vankerckhoven, V; Weist, K; Goossens, Mm; Vaerenberg, S; Hopkins, S; Catry, B; Monnet, Dl; Goossens, H; Suetens, C

2012-11-15

A standardised methodology for a combined point prevalence survey (PPS) on healthcare-associated infections (HAIs) and antimicrobial use in European acute care hospitals developed by the European Centre for Disease Prevention and Control was piloted across Europe. Variables were collected at national, hospital and patient level in 66 hospitals from 23 countries. A patient-based and a unit-based protocol were available. Feasibility was assessed via national and hospital questionnaires. Of 19,888 surveyed patients, 7.1% had an HAI and 34.6% were receiving at least one antimicrobial agent. Prevalence results were highest in intensive care units, with 28.1% patients with HAI, and 61.4% patients with antimicrobial use. Pneumonia and other lower respiratory tract infections (2.0% of patients; 95% confidence interval (CI): 1.8–2.2%) represented the most common type (25.7%) of HAI. Surgical prophylaxis was the indication for 17.3% of used antimicrobials and exceeded one day in 60.7% of cases. Risk factors in the patient-based protocol were provided for 98% or more of the included patients and all were independently associated with both presence of HAI and receiving an antimicrobial agent. The patient-based protocol required more work than the unit-based protocol, but allowed collecting detailed data and analysis of risk factors for HAI and antimicrobial use.

Pulmonary disease in cystic fibrosis: assessment with chest CT at chest radiography dose levels.

PubMed

Ernst, Caroline W; Basten, Ines A; Ilsen, Bart; Buls, Nico; Van Gompel, Gert; De Wachter, Elke; Nieboer, Koenraad H; Verhelle, Filip; Malfroot, Anne; Coomans, Danny; De Maeseneer, Michel; de Mey, Johan

2014-11-01

To investigate a computed tomographic (CT) protocol with iterative reconstruction at conventional radiography dose levels for the assessment of structural lung abnormalities in patients with cystic fibrosis ( CF cystic fibrosis ). In this institutional review board-approved study, 38 patients with CF cystic fibrosis (age range, 6-58 years; 21 patients <18 years and 17 patients >18 years) underwent investigative CT (at minimal exposure settings combined with iterative reconstruction) as a replacement of yearly follow-up posteroanterior chest radiography. Verbal informed consent was obtained from all patients or their parents. CT images were randomized and rated independently by two radiologists with use of the Bhalla scoring system. In addition, mosaic perfusion was evaluated. As reference, the previous available conventional chest CT scan was used. Differences in Bhalla scores were assessed with the χ(2) test and intraclass correlation coefficients ( ICC intraclass correlation coefficient s). Radiation doses for CT and radiography were assessed for adults (>18 years) and children (<18 years) separately by using technical dose descriptors and estimated effective dose. Differences in dose were assessed with the Mann-Whitney U test. The median effective dose for the investigative protocol was 0.04 mSv (95% confidence interval [ CI confidence interval ]: 0.034 mSv, 0.10 mSv) for children and 0.05 mSv (95% CI confidence interval : 0.04 mSv, 0.08 mSv) for adults. These doses were much lower than those with conventional CT (median: 0.52 mSv [95% CI confidence interval : 0.31 mSv, 3.90 mSv] for children and 1.12 mSv [95% CI confidence interval : 0.57 mSv, 3.15 mSv] for adults) and of the same order of magnitude as those for conventional radiography (median: 0.012 mSv [95% CI confidence interval : 0.006 mSv, 0.022 mSv] for children and 0.012 mSv [95% CI confidence interval : 0.005 mSv, 0.031 mSv] for adults). All images were rated at least as diagnostically acceptable. Very good agreement was found in overall Bhalla score ( ICC intraclass correlation coefficient , 0.96) with regard to the severity of bronchiectasis ( ICC intraclass correlation coefficient , 0.87) and sacculations and abscesses ( ICC intraclass correlation coefficient , 0.84). Interobserver agreement was excellent ( ICC intraclass correlation coefficient , 0.86-1). For patients with CF cystic fibrosis , a dedicated chest CT protocol can replace the two yearly follow-up chest radiographic examinations without major dose penalty and with similar diagnostic quality compared with conventional CT.

Protocolized fluid therapy in brain-dead donors: the multicenter randomized MOnIToR trial.

PubMed

Al-Khafaji, Ali; Elder, Michele; Lebovitz, Daniel J; Murugan, Raghavan; Souter, Michael; Stuart, Susan; Wahed, Abdus S; Keebler, Ben; Dils, Dorrie; Mitchell, Stephanie; Shutterly, Kurt; Wilkerson, Dawn; Pearse, Rupert; Kellum, John A

2015-03-01

Critical shortages of organs for transplantation jeopardize many lives. Observational data suggest that better fluid management for deceased organ donors could increase organ recovery. We conducted the first large multicenter randomized trial in brain-dead donors to determine whether protocolized fluid therapy increases the number of organs transplanted. We randomly assigned donors to either protocolized or usual care in eight organ procurement organizations. A "protocol-guided fluid therapy" algorithm targeting the cardiac index, mean arterial pressure and pulse pressure variation was used. Our primary outcome was the number of organs transplanted per donor, and our primary analysis was intention to treat. Secondary analyses included: (1) modified intention to treat where only subjects able to receive the intervention were included and (2) 12-month survival in transplant recipients. The study was stopped early. We enrolled 556 donors: 279 protocolized care and 277 usual care. Groups had similar characteristics at baseline. The study protocol could be implemented in 76 % of subjects randomized to the intervention. There was no significant difference in mean number of organs transplanted per donor: 3.39 organs per donor (95 % CI 3.14-3.63) with protocolized care compared to 3.29 usual care (95 % CI 3.04-3.54; mean difference, 0.1, 95 % CI -0.25 to 0.45; p = 0.56). In modified intention-to-treat analysis the mean number of organs increased (3.52 organs per donor, 95 % CI 3.23-3.8), but not statistically significantly (mean difference, 0.23, 95 % CI -0.15 to 0.61; p = 0.23). Among the 1,430 recipients of organs from study subjects with data available, 56 deaths (7.8 %) occurred in the protocolized care arm and 56 (7.9 %) in the usual care arm in the first year (hazard ratio: 0.97, p = 0.86). In brain-dead organ donors, protocol-guided fluid therapy compared to usual care may not increase the number of organs transplanted per donor.

Asthma prevalence in children living in north Mexico City and a comparison with other Latin American cities and world regions.

PubMed

Del-Rio-Navarro, Blanca; Del Rio-Chivardi, Jaime Mariano; Berber, Arturo; Sienra-Monge, Juan Jose Luis; Rosas-Vargas, Miguel Angel; Baeza-Bacab, Manuel

2006-01-01

Reports of previous studies done without following the international guidelines in different cities of Mexico showed a decrease in asthma prevalence. The aim of this study was to determine the prevalence and severity of asthma symptoms in children and teenagers living in north Mexico City and compare them with those of other Latin American cities and world regions. The cross-sectional survey followed the protocol of the International Study of Asthma and Allergies in Childhood IIIb phase survey. The study population included children 6-7 years old and teenagers 13-14 years old from randomly selected primary and secondary schools. There were 1629 boys and 1582 girls in the group of 6- to 7-year-old children and 2039 boys and 1860 girls in the 13- to 14-year-old group. "Wheezing or whistling in the chest at any time in the past" was present in 19.2% (95% confidence interval [CI], 17.9, 20.6) of the children and in 17.0% (95% CI, 15.8, 18.1) of the teenagers; "wheezing or whistling in the chest in the last 12 months" was reported in 6.8% (95% CI, 5.9, 7.6) of the children and 9.9% (95% CI, 9.0, 10.8) of the teenagers; "asthma ever" was claimed in 4.5% (95% CI, 3.8, 5.2) of the children and 8.0% (95% CI, 7.1, 8.8) of the teenagers. These prevalences were low compared with other ISAAC Latin American surveys and intermediate in comparison with worldwide regional prevalences reported by ISAAC surveys. The prevalence of asthma is low in Mexico City in comparison with other surveyed locations, but the number of patients with asthma makes it an important issue for Mexican public health programs.

Measures of central hyperexcitability in chronic whiplash associated disorder--a systematic review and meta-analysis.

PubMed

Stone, Andrew M; Vicenzino, Bill; Lim, Edwin C W; Sterling, Michele

2013-04-01

To synthesise the evidence for central hyperexcitability in Chronic WAD (whiplash associated disorders) with meta-analysis, and review test protocols. Chronic WAD was compared to healthy controls. Studies were eligible if they used measures of central hyperexcitability with standardised procedure. Meta-analyses (where possible) were conducted. The search yielded 27 trials of good quality and 13 were suitable for meta-analyses. Individuals with chronic WAD showed heightened sensitivity to the following tests (p < 0.05): Pressure Pain Thresholds at Head/Neck/Upper Thoracic area (H/N/UT) (SMD (Standardised mean differences) -1.36, 95% CI (confidence intervals) -1.89 to -0.82), Upper Limb (UL) (-1.33, 95% CI -2.50 to -0.16), Lower Limb (LL) (-1.01, 95% CI -1.70 to -0.33), flexor withdrawal (-0.73, 95% CI -1.11 to -0.35), Cold Pain Threshold at H/N/UT (0.91, 95% CI 0.66-1.17) and UL (0.66, 95% CI 0.37-0.94), Heat Pain Threshold at H/N/UT (-0.58, 95% CI -0.88 to -0.28), Electrocutaneous Stimulation at H/N/UT (-1.04, 95% CI -1.63 to -0.45) and LL (-0.85, 95% CI -1.67 to -0.03), and elbow extension with the Brachial Plexus Provocation Test (SMD -0.55, 95% CI -0.76 to -0.35). There is compelling evidence for central hyperexcitability in chronic WAD. This should be considered in the management of chronic WAD. Copyright © 2012 Elsevier Ltd. All rights reserved.

Impact of cytochrome P450 2C19 polymorphisms on citalopram/escitalopram exposure: a systematic review and meta-analysis.

PubMed

Chang, Ming; Tybring, Gunnel; Dahl, Marja-Liisa; Lindh, Jonatan D

2014-09-01

Citalopram and escitalopram, selective serotonin reuptake inhibitors, are primarily metabolized by cytochrome P450 (CYP) 2C19, which is a highly polymorphic enzyme known to cause inter-individual differences in pharmacokinetics. However, the impact of CYP2C19 polymorphisms on citalopram or escitalopram exposure has yet to be fully clarified, especially with regard to the quantitative impact of the CYP2C19*17 allele. The objective of this study was to quantify the effect of functional CYP2C19 allele variants on citalopram/escitalopram exposure. We performed a systematic review and meta-analysis with a structured search algorithm and eligibility criteria for including related studies, calculating the change of citalopram or escitalopram exposure associated with CYP2C19*2, *3, and *17 as compared with CYP2C19*1 using fixed-effect and random-effects models. Assessment of publication bias was performed by means of funnel plots and sensitivity analysis using meta-regressions. The pre-defined review protocol was registered at the PROSPERO international prospective register of systematic reviews, registration number CRD42013004106. Sixteen studies from 14 publications met the inclusion criteria. Eligible studies included 847 patients from psychiatric patient trials and 140 healthy subjects from pharmacokinetic studies. Compared to subjects with the EM/EM (CYP2C19*1/*1) genotype, the exposure to (es)citalopram increased by 95 % (95 % CI 40-149, p < 0.0001) in the poor metabolizer (PM)/PM (CYP2C19*2 or *3/*2 or *3), 30 % (95 % CI 4-55, p < 0.05) in the extensive metabolizer (EM)/PM (CYP2C19*1/*2 or *3), and 25 % (95 % CI 1-49, p < 0.05) in the ultrarapid metabolizer (UM)/PM (CYP2C19*17/*2 or *3) groups. In contrast, the exposure to (es)citalopram decreased by 36 % (95 % CI 27-46, p < 0.0001) in the UM/UM (CYP2C19*17/*17) and by 14 % (95 % CI 1-27, p < 0.05) in the UM/EM (CYP2C19*17/*1). This is the first meta-analysis based on a systematic review of accumulated information that addresses the relationship between CYP2C19 genotypes and the exposure to citalopram or escitalopram. All functional CYP2C19 genotype groups demonstrated significant effects on (es)citalopram exposure. The findings based on our pooled analysis are likely to help in understanding the inter-individual variability in the exposure to citalopram and escitalopram in psychiatric patients and to facilitate dose selection, particularly for the homozygous carriers of CYP2C19*2 or *3 (loss of function) and CYP2C19*17 (gain of function) alleles. The results could improve individualization of citalopram or escitalopram therapy and could also be used for physiologically based pharmacokinetic modeling as well as pharmacokinetic/pharmacodynamic modeling.

46 CFR 95.17-1 - Application.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 4 2011-10-01 2011-10-01 false Application. 95.17-1 Section 95.17-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CARGO AND MISCELLANEOUS VESSELS FIRE PROTECTION EQUIPMENT Foam Extinguishing Systems, Details § 95.17-1 Application. (a) Where a foam extinguishing system...

46 CFR 95.17-1 - Application.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Application. 95.17-1 Section 95.17-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CARGO AND MISCELLANEOUS VESSELS FIRE PROTECTION EQUIPMENT Foam Extinguishing Systems, Details § 95.17-1 Application. (a) Where a foam extinguishing system...

Modeling recovery of Swedish ecosystems from acidification.

PubMed

Sverdrup, Harald; Martinson, Liisa; Alveteg, Mattias; Moldan, Filip; Kronnäs, Veronika; Munthe, John

2005-02-01

Dynamic models complement existing time series of observations and static critical load calculations by simulating past and future development of chemistry in forest and lake ecosystems. They are used for dynamic assessment of the acidification and to produce target load functions, that describe what combinations of nitrogen and sulfur emission reductions are needed to achieve a chemical or biological criterion in a given target year. The Swedish approach has been to apply the dynamic acidification models MAGIC, to 133 lakes unaffected by agriculture and SAFE, to 645 productive forest sites. While the long-term goal is to protect 95% of the area, implementation of the Gothenburg protocol will protect approximately 75% of forest soils in the long term. After 2030, recovery will be very slow and involve only a limited geographical area. If there had been no emission reductions after 1980, 87% of the forest area would have unwanted soil status in the long term. In 1990, approximately 17% of all Swedish lakes unaffected by agriculture received an acidifying deposition above critical load. This fraction will decrease to 10% in 2010 after implementation of the Gothenburg protocol. The acidified lakes of Sweden will recover faster than the soils. According to the MAGIC model the median pre-industrial ANC of 107 microeq L(-1) in acid sensitive lakes decreased to about 60 microeq L(-1) at the peak of the acidification (1975-1990) and increases to 80 microeq L(-1) by 2010. Further increases were small, only 2 microeq L(-1) between 2010 and 2040. Protecting 95% of the lakes will require further emission reductions below the Gothenburg protocol levels. More than 7000 lakes are limed regularly in Sweden and it is unlikely that this practice can be discontinued in the near future without adverse effects on lake chemistry and biology.

Fixed-flexion knee radiography using a new positioning device produced highly repeatable measurements of joint space width: ELSA-Brasil Musculoskeletal Study (ELSA-Brasil MSK).

PubMed

Telles, Rosa Weiss; Costa-Silva, Luciana; Machado, Luciana A C; Reis, Rodrigo Citton Padilha Dos; Barreto, Sandhi Maria

To describe the performance of a non-fluoroscopic fixed-flexion PA radiographic protocol with a new positioning device, developed for the assessment of knee osteoarthritis (OA) in Brazilian Longitudinal Study of Adult Health Musculoskeletal Study (ELSA-Brasil MSK). A test-retest design including 19 adults (38 knee images) was conducted. Feasibility of the radiographic protocol was assessed by image quality parameters and presence of radioanatomic alignment according to intermargin distance (IMD) values. Repeatability was assessed for IMD and joint space width (JSW) measured at three different locations. Approximately 90% of knee images presented excellent quality. Frequencies of nearly perfect radioanatomic alignment (IMD ≤1mm) ranged from 29% to 50%, and satisfactory alignment was found in up to 71% and 76% of the images (IMD ≤1.5mm and ≤1.7mm, respectively). Repeatability analyses yielded the following results: IMD [SD of mean difference=1.08; coefficient of variation (%CV)=54.68%; intraclass correlation coefficient (ICC) (95%CI)=0.59 (0.34-0.77)]; JSW [SD of mean difference=0.34-0.61; %CV=4.48%-9.80%; ICC (95%CI)=0.74 (0.55-0.85)-0.94 (0.87-0.97)]. Adequately reproducible measurements of IMD and JSW were found in 68% and 87% of the images, respectively. Despite the difficulty in achieving consistent radioanatomic alignment between subsequent radiographs in terms of IMD, the protocol produced highly repeatable JSW measurements when these were taken at midpoint and 10mm from the medial extremity of the medial tibial plateau. Therefore, measurements of JSW at these locations can be considered adequate for the assessment of knee OA in ELSA-Brasil MSK. Copyright © 2016. Published by Elsevier Editora Ltda.

Effectiveness and safety of a high-dose weekly vitamin D (20,000 IU) protocol in older adults living in residential care.

PubMed

Feldman, Fabio; Moore, Crystal; da Silva, Liz; Gaspard, Gina; Gustafson, Larry; Singh, Sonia; Barr, Susan I; Kitts, David D; Li, Wangyang; Weiler, Hope A; Green, Timothy J

2014-08-01

To report 25 hydroxyvitamin D (25OHD) concentrations, an indicator of vitamin D status, in older adults living in residential care 1 year after a protocol of weekly 20,000 IU of vitamin D was started. Cross-sectional. Five residential care facilities in British Columbia, Canada. Residents aged 65 and older from five facilities (N=236). Participants provided a blood sample. Demographic and health information was obtained from the medical record. Mean 25OHD was 102 nmol/L (95% confidence interval (CI)=98-106 nmol/L). Three percent of residents had a 25OHD concentration of less than 40 nmol/L, 6% <50 nmol/L, and 19% <75 nmol/L. In those who received 20,000 IU/wk or more for 6 months or longer (n=147), mean 25OHD was 112 nmol/L (95% CI=108-117 nmol/L), and none had a 25OHD level of less than 50 nmol/L. Hypercalcemia (>2.6 mmol/L), a potential consequence of too much vitamin D, was present in 14%, although 25OHD levels did not differ in those with and without hypercalcemia (108 vs 101 nmol/L; P=.17). Twelve months after implementation of a 20,000-IU/wk vitamin D protocol for older adults in residential care, mean 25OHD concentrations were high, and there was no evidence of poor vitamin D status. Given the absence of demonstrated benefit of high 25OHD concentrations to the residential care population, dosages less than 20,000 IU/wk of vitamin D are recommended. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

46 CFR 95.17-15 - Piping.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 4 2011-10-01 2011-10-01 false Piping. 95.17-15 Section 95.17-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CARGO AND MISCELLANEOUS VESSELS FIRE PROTECTION EQUIPMENT Foam Extinguishing Systems, Details § 95.17-15 Piping. (a) All piping, valves, and fittings shall meet the applicable...

46 CFR 95.17-20 - Discharge outlets.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Discharge outlets. 95.17-20 Section 95.17-20 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CARGO AND MISCELLANEOUS VESSELS FIRE PROTECTION EQUIPMENT Foam Extinguishing Systems, Details § 95.17-20 Discharge outlets. (a) Discharge outlets shall be...

46 CFR 95.17-20 - Discharge outlets.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 4 2011-10-01 2011-10-01 false Discharge outlets. 95.17-20 Section 95.17-20 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CARGO AND MISCELLANEOUS VESSELS FIRE PROTECTION EQUIPMENT Foam Extinguishing Systems, Details § 95.17-20 Discharge outlets. (a) Discharge outlets shall be...

46 CFR 95.17-15 - Piping.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Piping. 95.17-15 Section 95.17-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CARGO AND MISCELLANEOUS VESSELS FIRE PROTECTION EQUIPMENT Foam Extinguishing Systems, Details § 95.17-15 Piping. (a) All piping, valves, and fittings shall meet the applicable...

Improved Outcome of Enteric Peritonitis in Peritoneal Dialysis Patients Aged 50 Years and Older with Temporary Discontinuation of Peritoneal Dialysis and Intravenous Meropenem.

PubMed

Abrahams, Alferso C; Rüger, Wim; Ter Wee, Pieter M; van Ittersum, Frans J; Boer, Walther H

2017-01-01

♦ BACKGROUND: Peritonitis is a major cause of morbidity, mortality, and technique failure in peritoneal dialysis (PD) patients, especially when caused by enteric microorganisms (EM). We have implemented a treatment protocol specifically aimed at improving the outcome in EM peritonitis. The adapted protocol was applied in all PD patients 50 years and older presenting with peritonitis who were considered to be at risk of EM peritonitis and involves 3 interventions: 1) temporary discontinuation of PD without removing the catheter (peritoneal rest), 2) intravenous meropenem, and 3) meropenem intracatheter as lock (Mero-PerRest protocol). ♦ METHODS: In this observational study, we compared the outcome of 203 peritonitis episodes in 71 patients treated with the Mero-PerRest protocol, with 217 episodes in 104 patients treated with a more traditional intraperitoneal gentamicin-rifampicin-based regimen. ♦ RESULTS: In EM peritonitis episodes, the Mero-PerRest protocol resulted in a higher primary cure rate (90.0% vs 65.3%, adjusted odds ratio [OR] 4.54 [95% confidence interval (CI) 1.46 - 14.15]) and better technique survival (90.0% vs 69.4%, adjusted OR 3.41 [95% CI 1.07 - 10.87]). This effect was most distinct in patients with polymicrobial EM peritonitis (cure rate 87.5% vs 34.8%, p = 0.0003). Interestingly, primary cure rate (95.6% vs 84.7%, adjusted OR 3.92 [95% CI 1.37 - 11.19]) and technique survival (95.6% vs 85.6%, adjusted OR 3.60 [95% CI 1.25 - 10.32]) were also excellent in non-EM peritonitis episodes. Patient survival did not differ significantly. ♦ CONCLUSION: The poor outcome of peritonitis caused by EM in PD patients aged 50 years and older could be improved by applying a treatment protocol involving temporary discontinuation of PD without catheter removal and intravenous and intracatheter meropenem. Copyright © 2017 International Society for Peritoneal Dialysis.

Efficacy and Safety of the RTS,S/AS01 Malaria Vaccine during 18 Months after Vaccination: A Phase 3 Randomized, Controlled Trial in Children and Young Infants at 11 African Sites

PubMed Central

2014-01-01

Background A malaria vaccine could be an important addition to current control strategies. We report the safety and vaccine efficacy (VE) of the RTS,S/AS01 vaccine during 18 mo following vaccination at 11 African sites with varying malaria transmission. Methods and Findings 6,537 infants aged 6–12 wk and 8,923 children aged 5–17 mo were randomized to receive three doses of RTS,S/AS01 or comparator vaccine. VE against clinical malaria in children during the 18 mo after vaccine dose 3 (per protocol) was 46% (95% CI 42% to 50%) (range 40% to 77%; VE, p<0.01 across all sites). VE during the 20 mo after vaccine dose 1 (intention to treat [ITT]) was 45% (95% CI 41% to 49%). VE against severe malaria, malaria hospitalization, and all-cause hospitalization was 34% (95% CI 15% to 48%), 41% (95% CI 30% to 50%), and 19% (95% CI 11% to 27%), respectively (ITT). VE against clinical malaria in infants was 27% (95% CI 20% to 32%, per protocol; 27% [95% CI 21% to 33%], ITT), with no significant protection against severe malaria, malaria hospitalization, or all-cause hospitalization. Post-vaccination anti-circumsporozoite antibody geometric mean titer varied from 348 to 787 EU/ml across sites in children and from 117 to 335 EU/ml in infants (per protocol). VE waned over time in both age categories (Schoenfeld residuals p<0.001). The number of clinical and severe malaria cases averted per 1,000 children vaccinated ranged across sites from 37 to 2,365 and from −1 to 49, respectively; corresponding ranges among infants were −10 to 1,402 and −13 to 37, respectively (ITT). Meningitis was reported as a serious adverse event in 16/5,949 and 1/2,974 children and in 9/4,358 and 3/2,179 infants in the RTS,S/AS01 and control groups, respectively. Conclusions RTS,S/AS01 prevented many cases of clinical and severe malaria over the 18 mo after vaccine dose 3, with the highest impact in areas with the greatest malaria incidence. VE was higher in children than in infants, but even at modest levels of VE, the number of malaria cases averted was substantial. RTS,S/AS01 could be an important addition to current malaria control in Africa. Trial registration www.ClinicalTrials.gov NCT00866619 Please see later in the article for the Editors' Summary PMID:25072396

Performance assessment of two lysis methods for direct identification of yeasts from clinical blood cultures using MALDI-TOF mass spectrometry.

PubMed

Jeddi, Fakhri; Yapo-Kouadio, Gisèle Cha; Normand, Anne-Cécile; Cassagne, Carole; Marty, Pierre; Piarroux, Renaud

2017-02-01

In cases of fungal infection of the bloodstream, rapid species identification is crucial to provide adapted therapy and thereby ameliorate patient outcome. Currently, the commercial Sepsityper kit and the sodium-dodecyl sulfate (SDS) method coupled with MALDI-TOF mass spectrometry are the most commonly reported lysis protocols for direct identification of fungi from positive blood culture vials. However, the performance of these two protocols has never been compared on clinical samples. Accordingly, we performed a two-step survey on two distinct panels of clinical positive blood culture vials to identify the most efficient protocol, establish an appropriate log score (LS) cut-off, and validate the best method. We first compared the performance of the Sepsityper and the SDS protocols on 71 clinical samples. For 69 monomicrobial samples, mass spectrometry LS values were significantly higher with the SDS protocol than with the Sepsityper method (P < .0001), especially when the best score of four deposited spots was considered. Next, we established the LS cut-off for accurate identification at 1.7, based on specimen DNA sequence data. Using this LS cut-off, 66 (95.6%) and 46 (66.6%) isolates were correctly identified at the species level with the SDS and the Sepsityper protocols, respectively. In the second arm of the survey, we validated the SDS protocol on an additional panel of 94 clinical samples. Ninety-two (98.9%) of 93 monomicrobial samples were correctly identified at the species level (median LS = 2.061). Overall, our data suggest that the SDS method yields more accurate species identification of yeasts, than the Sepsityper protocol. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

An Individualized, Perception-Based Protocol to Investigate Human Physiological Responses to Cooling

PubMed Central

Coolbaugh, Crystal L.; Bush, Emily C.; Galenti, Elizabeth S.; Welch, E. Brian; Towse, Theodore F.

2018-01-01

Cold exposure, a known stimulant of the thermogenic effects of brown adipose tissue (BAT), is the most widely used method to study BAT physiology in adult humans. Recently, individualized cooling has been recommended to standardize the physiological cold stress applied across participants, but critical experimental details remain unclear. The purpose of this work was to develop a detailed methodology for an individualized, perception-based protocol to investigate human physiological responses to cooling. Participants were wrapped in two water-circulating blankets and fitted with skin temperature probes to estimate BAT activity and peripheral vasoconstriction. We created a thermoesthesia graphical user interface (tGUI) to continuously record the subject's perception of cooling and shivering status during the cooling protocol. The protocol began with a 15 min thermoneutral phase followed by a series of 10 min cooling phases and concluded when sustained shivering (>1 min duration) occurred. Researchers used perception of cooling feedback (tGUI ratings) to manually adjust and personalize the water temperature at each cooling phase. Blanket water temperatures were recorded continuously during the protocol. Twelve volunteers (ages: 26.2 ± 1.4 years; 25% female) completed a feasibility study to evaluate the proposed protocol. Water temperature, perception of cooling, and shivering varied considerably across participants in response to cooling. Mean clavicle skin temperature, a surrogate measure of BAT activity, decreased (−0.99°C, 95% CI: −1.7 to −0.25°C, P = 0.16) after the cooling protocol, but an increase in supraclavicular skin temperature was observed in 4 participants. A strong positive correlation was also found between thermoesthesia and peripheral vasoconstriction (ρ = 0.84, P < 0.001). The proposed individualized, perception-based protocol therefore has potential to investigate the physiological responses to cold stress applied across populations with varying age, sex, body composition, and cold sensitivity characteristics. PMID:29593558

Effect of Intensity Modulated Radiation Therapy With Concurrent Chemotherapy on Survival for Patients With Cervical Esophageal Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDowell, Lachlan J.; Huang, Shao Hui; Xu, Wei

Purpose: We evaluated the effect of consecutive protocols on overall survival (OS) for cervical esophageal carcinoma (CEC). Methods and Materials: All CEC cases that received definitive radiation therapy (RT) with or without chemotherapy from 1997 to 2013 in 3 consecutive protocols were reviewed. Protocol 1 (P1) consisted of 2-dimensional RT of 54 Gy in 20 fractions with 5-fluorouracil plus either mitomycin C or cisplatin. Protocol 2 (P2) consisted of 3-dimensional conformal RT (3DRT) of ≥60 Gy in 30 fractions plus elective nodal irradiation plus cisplatin. Protocol 3 (P3) consisted of intensity modulated RT (IMRT) of ≥60 Gy in 30 fractions plus elective nodalmore » irradiation plus cisplatin. Multivariable analyses were used to assess the effect of the treatment protocol, RT technique, and RT dose on OS, separately. Results: Of 81 cases (P1, 21; P2, 23; and P3, 37), 34 local (P1, 11 [52%]; P2, 12 [52%]; and P3, 11 [30%]), 16 regional (P1, 6 [29%]); P2, 3 [13%]; and P3, 7 [19%]), and 34 distant (P1, 10 [48%]; P2, 9 [39%]; and P3, 15 [41%]) failures were identified. After adjusting for age (P=.49) and chemotherapy (any vs none; hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.3-0.9; P=.023), multivariable analysis showed P3 had improved OS compared with P1 (HR 0.4, 95% CI 0.2-0.8; P=.005), with a trend shown for benefit compared with P2 (HR 0.6, 95% CI 0.3-1.0; P=.061). OS between P1 and P2 did not differ (P=.29). Analyzed as a continuous variable, higher RT doses were associated with a borderline improved OS (HR 0.97, 95% CI 0.95-1.0; P=.075). IMRT showed improved OS compared with non-IMRT (HR 0.57, 95% CI 0.3-0.8; P=.008). Conclusions: The present retrospective consecutive cohort study showed improved OS with our current protocol (P3; high-dose IMRT with concurrent high-dose cisplatin) compared with historical protocols. The outcomes for patients with CEC remain poor, and novel approaches to improve the therapeutic ratio are warranted.« less

Quality of Life and Performance Status From a Substudy Conducted Within a Prospective Phase 3 Randomized Trial of Concurrent Standard Radiation Versus Accelerated Radiation Plus Cisplatin for Locally Advanced Head and Neck Carcinoma: NRG Oncology RTOG 0129.

PubMed

Xiao, Canhua; Zhang, Qiang; Nguyen-Tân, Phuc Felix; List, Marcie; Weber, Randal S; Ang, K Kian; Rosenthal, David; Filion, Edith J; Kim, Harold; Silverman, Craig; Raben, Adam; Galloway, Thomas; Fortin, Andre; Gore, Elizabeth; Winquist, Eric; Jones, Christopher U; Robinson, William; Raben, David; Le, Quynh-Thu; Bruner, Deborah

2017-03-15

To analyze quality of life (QOL) and performance status (PS) for head and neck cancer (HNC) patients treated on NRG Oncology RTOG 0129 by treatment (secondary outcome) and p16 status, and to examine the association between QOL/PS and survival. Eligible patients were randomized into either an accelerated-fractionation arm or a standard-fractionation arm, and completed the Performance Status Scale for the Head and Neck (PSS-HN), the Head and Neck Radiotherapy Questionnaire (HNRQ), and the Spitzer Quality of Life Index (SQLI) at 8 time points from before treatment to 5 years after treatment. The results from the analysis of area under the curve showed that QOL/PS was not significantly different between the 2 arms from baseline to year after treatment (P ranged from .39 to .98). The results from general linear mixed models further supported the nonsignificant treatment effects until 5 years after treatment (P=.95, .90, and .84 for PSS-HN Diet, Eating, and Speech, respectively). Before treatment and after 1 year after treatment, p16-positive oropharyngeal cancer (OPC) patients had better QOL than did p16-negative patients (P ranged from .0283 to <.0001 for all questionnaires). However, QOL/PS decreased more significantly from pretreatment to the last 2 weeks of treatment in the p16-positive group than in the p16-negative group (P ranged from .0002 to <.0001). Pretreatment QOL/PS was a significant independent predictor of overall survival, progression-free survival, and local-regional failure but not of distant metastasis (P ranged from .0063 to <.0001). The results indicated that patients in both arms may have experienced similar QOL/PS. p16-positive patients had better QOL/PS at baseline and after 1 year of follow-up. Patients presenting with better baseline QOL/PS scores had better survival. Copyright © 2016 Elsevier Inc. All rights reserved.

Quality of Life and Performance Status From a Substudy Conducted Within a Prospective Phase 3 Randomized Trial of Concurrent Standard Radiation Versus Accelerated Radiation Plus Cisplatin for Locally Advanced Head and Neck Carcinoma: NRG Oncology RTOG 0129

PubMed Central

Xiao, Canhua; Zhang, Qiang; Nguyen-Tân, Phuc Felix; List, Marcie; Weber, Randal S.; Ang, K. Kian; Rosenthal, David; Filion, Edith J.; Kim, Harold; Silverman, Craig; Raben, Adam; Galloway, Thomas; Fortin, Andre; Gore, Elizabeth; Winquist, Eric; Jones, Christopher U.; Robinson, William; Raben, David; Le, Quynh-Thu; Bruner, Deborah

2016-01-01

Purpose/Objective(s) To analyze quality of life (QOL) and performance status (PS) for head and neck cancer (HNC) patients treated on NRG Oncology RTOG 0129 by treatment (secondary outcome) and p16 status, and to examine the association between QOL/PS and survival. Methods and Materials Eligible patients were randomized into either an accelerated-fractionation arm or a standard-fractionation arm, and completed the Performance Status Scale for the Head and Neck (PSS-HN), the Head and Neck Radiotherapy Questionnaire (HNRQ), and the Spitzer Quality of Life Index (SQLI) at 8 time points from before treatment to 5 years after treatment. Results The results from the analysis of area under the curve showed that QOL/PS was not significantly different between the 2 arms from baseline to year after treatment (P ranged from .39 to .98). The results from general linear mixed models further supported the nonsignificant treatment effects until 5 years after treatment (P=.95, .90, and .84 for PSS-HN Diet, Eating, and Speech, respectively). Before treatment and after 1 year after treatment, p16-positive oropharyngeal cancer (OPC) patients had better QOL than did p16-negative patients (P ranged from .0283 to <.0001 for all questionnaires). However, QOL/PS decreased more significantly from pretreatment to the last 2 weeks of treatment in the p16-positive group than in the p16-negative group (P ranged from .0002 to <.0001). Pretreatment QOL/PS was a significant independent predictor of overall survival, progression-free survival, and local-regional failure but not of distant metastasis (P ranged from .0063 to <.0001). Conclusions The results indicated that patients in both arms may have experienced similar QOL/PS. p16-positive patients had better QOL/PS at baseline and after 1 year of follow-up. Patients presenting with better baseline QOL/PS scores had better survival. PMID:27727063

A Contralateral Esophagus-Sparing Technique to Limit Severe Esophagitis Associated With Concurrent High-Dose Radiation and Chemotherapy in Patients With Thoracic Malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Al-Halabi, Hani; Paetzold, Peter; Sharp, Gregory C.

2015-07-15

Purpose: Severe (Radiation Therapy Oncology Group [RTOG] grade 3 or greater) esophagitis generally occurs in 15% to 25% of non–small cell lung cancer (NSCLC) patients undergoing concurrent chemotherapy and radiation therapy (CCRT), which may result in treatment breaks that compromise local tumor control and pose a barrier to dose escalation. Here, we report a novel contralateral esophagus-sparing technique (CEST) that uses intensity modulated radiation therapy (IMRT) to reduce the incidence of severe esophagitis. Methods and Materials: We reviewed consecutive patients with thoracic malignancies undergoing curative CCRT in whom CEST was used. The esophageal wall contralateral (CE) to the tumor wasmore » contoured as an avoidance structure, and IMRT was used to guide a rapid dose falloff gradient beyond the target volume in close proximity to the esophagus. Esophagitis was recorded based on the RTOG acute toxicity grading system. Results: We identified 20 consecutive patients treated with CCRT of at least 63 Gy in whom there was gross tumor within 1 cm of the esophagus. The median radiation dose was 70.2 Gy (range, 63-72.15 Gy). In all patients, ≥99% of the planning and internal target volumes was covered by ≥90% and 100% of prescription dose, respectively. Strikingly, no patient experienced grade ≥3 esophagitis (95% confidence limits, 0%-16%) despite the high total doses delivered. The median maximum dose, V45, and V55 of the CE were 60.7 Gy, 2.1 cc, and 0.4 cc, respectively, indicating effective esophagus cross-section sparing by CEST. Conclusion: We report a simple yet effective method to avoid exposing the entire esophagus cross-section to high doses. By using proposed CE dose constraints of V45 <2.5 cc and V55 <0.5 cc, CEST may improve the esophagus toxicity profile in thoracic cancer patients receiving CCRT even at doses above the standard 60- to 63-Gy levels. Prospective testing of CEST is warranted.« less

Comparison of clinico-microbiological profile and treatment outcome of in-house and referred post cataract surgery endophthalmitis in a tertiary care center in South India.

PubMed

Ambiya, Vikas; Das, Taraprasad; Sharma, Savitri; Chhablani, Jay; Dave, Vivek; Jalali, Subhadra; Narayanan, Raja; Joseph, Joveeta

2016-12-01

The purpose of the study is to compare the clinico-microbiological profile and treatment outcome of in-house vs referred cases of post cataract surgery endophthalmitis in a tertiary eye care facility in South India. The clinical records of 50 culture-positive cases each of in-house (group A) and referred (group B) post cataract surgery endophthalmitis were analyzed. The management protocol was similar in both groups. The time to report to the institute was longer in group B (group B 13.63 [±11.67; 95% CI, 9.95-17.31] days; group A 6.83 [±7.61; 95% CI, 4.57-9.09] days; P = 0.002). The average inflammatory scores in presentation were comparable (group A 17.85 ± 5.83; group B 18.18 ± 7.35; P = 0.243). The final visual outcome was clinically superior in group A (≥20/200-group A 60.42% and group B 44%, P = 0.11; ≤20/400-group A 37.5% and group B 52%, P = 0.62), but statistically not significant. There were more gram-positive organisms in group A (62% vs 38%; P = 0.027) and more gram-negative organisms in group B (52% vs 24%; P = 0.007). Gram-positive bacteria were mostly sensitive to vancomycin (95.24% to 96.67%), but gram-negative bacteria were partly sensitive to ceftazidime (58.33% to 64%). One could suspect gram-negative infection more often in the referred cases of endophthalmitis. While vancomycin could continue to be the antibiotic of choice in gram-positive bacteria, specific antibiotic following due sensitivity for gram-negative bacteria should replace the empiric use of ceftazidime.

[Effectiveness of short educational intervention in patients with insomnia in primary care].

PubMed

Gancedo-García, Ana; Gutiérrez-Antezana, Angélica Faviola; González-García, Pablo; Salinas-Herrero, Sally; Prieto-Merino, David; Suárez-Gil, Patricio

2014-12-01

To evaluate the effectiveness of providing an educational intervention in primary care (PC) alongside a pharmacological treatment for insomnia. Single blinded non randomised clinical trial. Two urban primary health centers in Gijón (Asturias, Spain). Patients who consulted for insomnia between July 2012-January 2013 and met the inclusion criteria (n=50) were assigned systematically to the control group (CG) or intervention group (IG). All patients initiated treatment with lorazepam 1mg in the evenings and had four weekly 15 min visits plus a follow-up visit after another month. The IG received training for control of stimuli, sleep hygiene and respiration and relaxation techniques in the four visits. The CG had only non invasive measures taken. Considering as cured those who reached a Pittsburgh Sleep Quality Index PSQI <6 or a 50% reduction from baseline level. It was also analyzed the change in the PSQI from baseline to final visit and to follow-up visit, and voluntary interruption of lorazepam. Analysis by Bayesian inference. Twelve out of recoveries after intervention against one out of 24 among control group. Mean change in PSQI to final visit and follow-up visit was: -4.7 (95%CrI:-5.9 to -3.5) and -6,3 (95%ICred: -7.5 to -5.1) in IG; -1.8 (95%ICred: -3 to -0.5) and -1.7 (95%ICred: -2.9 to -0.4) in CG. Interruption of lorazepan: in 4 controls (16,7%) and 9 (34,6%) in IG. Twenty nine patients in GI and 17 in GC completed the trial. Per protocol analysis showed similar results. The educational intervention in PC improves sleep quality and reduces the need of treatment with benzodiacepines. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Academic Difficulty and Vision Symptoms Children with Concussion

PubMed Central

Swanson, Mark W.; Weise, Katherine K.; Dreer, Laura E.; Johnston, James; Davis, Richard D.; Ferguson, Drew; Hale, M. Heath; Gould, Sara J.; Christy, Jennifer; Busettini, Claudio; Lee, Sarah D.; Swanson, Erin

2016-01-01

Purpose Academic difficulty is reported in children with prolonged post-concussive symptoms. Despite growing evidence that vestibular-ocular and vision-specific dysfunction are common in children following concussion, vision is rarely mentioned in return-to-learn protocols. The purpose of this project was to evaluate a cohort of children with prolonged post-concussive symptoms to determine if vision symptoms are associated with those reporting academic difficulty. Methods Data was obtained from the Children’s of Alabama Concussion Clinic REDCap dataset from the period January 2007 to October 2013. From this dataset of 1,033 concussion events, a cohort of 276 children aged 5–18 years with three or more concussion-related symptoms present for 10 days or more was identified. A cross-sectional cohort study was undertaken to evaluate the association of concussion symptoms, SCAT2 scores, demographic and concussion severity markers to reported educational difficulty among children with prolonged post-concussive symptoms. Univariate and multivariate logistic regression techniques were used to model the association of reported educational difficulty to self-reported vision abnormalities. Results Mean age was 13.8 years. Median time since the concussive event was 21 days, with 33% (95/276) reporting their concussion more than thirty days prior to data collection. Academic difficulty was reported by 29% (79/270) and vision abnormalities in 46% (128/274). After model reduction, vision symptoms (OR 2.17, 95% CI 1.02, 4.62), hearing disturbance (OR 2.39, 95% CI 1.06, 5.36) and concentration difficulty (OR 21.62, 95% CI 9.50, 44.47) remained associated with academic difficulty. For those with symptoms 30 days or more after concussion, only vision (OR 3.15, 95% CI 1.06, 9.38) and concentration difficulty (OR 15.33, 95% CI 4.99, 47.05) remained statistically significant. Conclusions Vision problems were commonly reported in children with concussions and were independently associated with those reporting academic difficulty. Comprehensive vision assessment should be considered in children reporting academic difficulty and in the development of return-to-learn protocols. PMID:27668641

Fast and Noninvasive Characterization of Suspicious Lesions Detected at Breast Cancer X-Ray Screening: Capability of Diffusion-weighted MR Imaging with MIPs.

PubMed

Bickelhaupt, Sebastian; Laun, Frederik B; Tesdorff, Jana; Lederer, Wolfgang; Daniel, Heidi; Stieber, Anne; Delorme, Stefan; Schlemmer, Heinz-Peter

2016-03-01

To evaluate the ability of a diagnostic abbreviated magnetic resonance (MR) imaging protocol consisting of maximum intensity projections (MIPs) from diffusion-weighted imaging with background suppression (DWIBS) and unenhanced morphologic sequences to help predict the likelihood of malignancy on suspicious screening x-ray mammograms, as compared with an abbreviated contrast material-enhanced MR imaging protocol and a full diagnostic breast MR imaging protocol. This prospective institutional review board-approved study included 50 women (mean age, 57.1 years; range, 50-69 years), who gave informed consent and who had suspicious screening mammograms and an indication for biopsy, from September 2014 to January 2015. Before biopsy, full diagnostic contrast-enhanced MR imaging was performed that included DWIBS (b = 1500 sec/mm(2)). Two abbreviated protocols (APs) based on MIPs were evaluated regarding the potential to exclude malignancy: DWIBS (AP1) and subtraction images from the first postcontrast and the unenhanced series (AP2). Diagnostic indexes of both methods were examined by using the McNemar test and were compared with those of the full diagnostic protocol and histopathologic findings. Twenty-four of 50 participants had a breast carcinoma. With AP1 (DWIBS), the sensitivity was 0.92 (95% confidence interval [CI]: 0.73, 0.98), the specificity was 0.94 (95% CI: 0.77, 0.99), the negative predictive value (NPV) was 0.92 (95% CI: 0.75, 0.99), and the positive predictive value (PPV) was 0.93 (95% CI: 0.75, 0.99). The mean reading time was 29.7 seconds (range, 4.9-110.0 seconds) and was less than 3 seconds (range, 1.2-7.6 seconds) in the absence of suspicious findings on the DWIBS MIPs. With the AP2 protocol, the sensitivity was 0.85 (95% CI: 0.78, 0.95), the specificity was 0.90 (95% CI: 0.72, 0.97), the NPV was 0.87 (95% CI: 0.69, 0.95), the PPV was 0.89 (95% CI: 0.69, 0.97), and the mean reading time was 29.6 seconds (range, 6.0-100.0 seconds). Unenhanced diagnostic MR imaging (DWIBS mammography), with an NPV of 0.92 and an acquisition time of less than 7 minutes, could help exclude malignancy in women with suspicious x-ray screening mammograms. The method has the potential to reduce unnecessary invasive procedures and emotional distress for breast cancer screening participants if it is used as a complement after the regular screening clarification procedure.

A Phase II Study of Submandibular Gland Transfer Prior to Radiation for Prevention of Radiation-induced Xerostomia in Head-and-Neck Cancer (RTOG 0244)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jha, Naresh, E-mail: naresh.jha@albertahealthservices.ca; Harris, Jonathan; Seikaly, Hadi

Purpose: We report the results of a phase II study to determine the reproducibility of a submandibular salivary gland transfer (SGT) surgical technique for prevention of radiation (XRT)-induced xerostomia in a multi-institutional setting and to assess severity of xerostomia. Methods and Materials: Eligible patients had surgery for primary, neck dissection, and SGT, followed by XRT, during which the transferred salivary gland was shielded. Intensity modulated radiation therapy, amifostine, and pilocarpine were not allowed, but postoperative chemotherapy was allowed. Each operation was reviewed by 2 reviewers and radiation by 1 reviewer. If 13 or more (of 43) were 'not per protocol,'more » then the technique would be considered not reproducible as per study design. The secondary endpoint was the rate of acute xerostomia, grade 2 or higher, and a rate of {<=}51% was acceptable. Results: Forty-four of the total 49 patients were analyzable: male (81.8%), oropharynx (63.6%), stage IV (61.4%), median age 56.5 years. SGT was 'per protocol' or within acceptable variation in 34 patients (77.3%) and XRT in 79.5%. Nine patients (20.9%) developed grade 2 acute xerostomia; 2 had grade 0-1 xerostomia (4.7%) but started on amifostine/pilocarpine. Treatment for these 11 patients (25.6%) was considered a failure for the xerostomia endpoint. Thirteen patients died; median follow-up for 31 surviving patients was 2.9 years. Two-year overall and disease-free survival rates were 76.4% and 71.7%, respectively. Conclusions: The technique of submandibular SGT is reproducible in a multicenter setting. Seventy-four percent of patients were prevented from XRT-induced acute xerostomia.« less

A phase II study of submandibular gland transfer prior to radiation for prevention of radiation-induced xerostomia in head-and-neck cancer (RTOG 0244).

PubMed

Jha, Naresh; Harris, Jonathan; Seikaly, Hadi; Jacobs, John R; McEwan, A J B; Robbins, K Thomas; Grecula, John; Sharma, Anand K; Ang, K Kian

2012-10-01

We report the results of a phase II study to determine the reproducibility of a submandibular salivary gland transfer (SGT) surgical technique for prevention of radiation (XRT)-induced xerostomia in a multi-institutional setting and to assess severity of xerostomia. Eligible patients had surgery for primary, neck dissection, and SGT, followed by XRT, during which the transferred salivary gland was shielded. Intensity modulated radiation therapy, amifostine, and pilocarpine were not allowed, but postoperative chemotherapy was allowed. Each operation was reviewed by 2 reviewers and radiation by 1 reviewer. If 13 or more (of 43) were "not per protocol," then the technique would be considered not reproducible as per study design. The secondary endpoint was the rate of acute xerostomia, grade 2 or higher, and a rate of ≤ 51% was acceptable. Forty-four of the total 49 patients were analyzable: male (81.8%), oropharynx (63.6%), stage IV (61.4%), median age 56.5 years. SGT was "per protocol" or within acceptable variation in 34 patients (77.3%) and XRT in 79.5%. Nine patients (20.9%) developed grade 2 acute xerostomia; 2 had grade 0-1 xerostomia (4.7%) but started on amifostine/pilocarpine. Treatment for these 11 patients (25.6%) was considered a failure for the xerostomia endpoint. Thirteen patients died; median follow-up for 31 surviving patients was 2.9 years. Two-year overall and disease-free survival rates were 76.4% and 71.7%, respectively. The technique of submandibular SGT is reproducible in a multicenter setting. Seventy-four percent of patients were prevented from XRT-induced acute xerostomia. Copyright © 2012 Elsevier Inc. All rights reserved.

SU-E-T-508: End to End Testing of a Prototype Eclipse Module for Planning Modulated Arc Therapy On the Siemens Platform

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, L; Sarkar, V; Spiessens, S

2014-06-01

Purpose: The latest clinical implementation of the Siemens Artiste linac allows for delivery of modulated arcs (mARC) using full-field flattening filter free (FFF) photon beams. The maximum doserate of 2000 MU/min is well suited for high dose treatments such as SBRT. We tested and report on the performance of a prototype Eclipse TPS module supporting mARC capability on the Artiste platform. Method: our spine SBRT patients originally treated with 12/13 field static-gantry IMRT (SGIMRT) were chosen for this study. These plans were designed to satisfy RTOG0631 guidelines with a prescription of 16Gy in a single fraction. The cases were re-plannedmore » as mARC plans in the prototype Eclipse module using the 7MV FFF beam and required to satisfy RTOG0631 requirements. All plans were transferred from Eclipse, delivered on a Siemens Artiste linac and dose-validated using the Delta4 system. Results: All treatment plans were straightforwardly developed, in timely fashion, without challenge or inefficiency using the prototype module. Due to the limited number of segments in a single arc, mARC plans required 2-3 full arcs to yield plan quality comparable to SGIMRT plans containing over 250 total segments. The average (3%/3mm) gamma pass-rate for all arcs was 98.5±1.1%, thus demonstrating both excellent dose prediction by the AAA dose algorithm and excellent delivery fidelity. Mean delivery times for the mARC plans(10.5±1.7min) were 50-70% lower than the SGIMRT plans(26±2min), with both delivered at 2000 MU/min. Conclusion: A prototype Eclipse module capable of planning for Burst Mode modulated arc delivery on the Artiste platform has been tested and found to perform efficiently and accurately for treatment plan development and delivered-dose prediction. Further investigation of more treatment sites is being carried out and data will be presented.« less

46 CFR 95.17-5 - Quantity of foam required.

Code of Federal Regulations, 2011 CFR

2011-10-01

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46 CFR 95.17-5 - Quantity of foam required.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Quantity of foam required. 95.17-5 Section 95.17-5... PROTECTION EQUIPMENT Foam Extinguishing Systems, Details § 95.17-5 Quantity of foam required. (a) Area... blanket of foam over the entire tank top or bilge of the space protected. The arrangement of piping shall...

46 CFR 95.17-5 - Quantity of foam required.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 4 2014-10-01 2014-10-01 false Quantity of foam required. 95.17-5 Section 95.17-5... PROTECTION EQUIPMENT Foam Extinguishing Systems, Details § 95.17-5 Quantity of foam required. (a) Area... blanket of foam over the entire tank top or bilge of the space protected. The arrangement of piping shall...

46 CFR 95.17-5 - Quantity of foam required.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 4 2013-10-01 2013-10-01 false Quantity of foam required. 95.17-5 Section 95.17-5... PROTECTION EQUIPMENT Foam Extinguishing Systems, Details § 95.17-5 Quantity of foam required. (a) Area... blanket of foam over the entire tank top or bilge of the space protected. The arrangement of piping shall...

46 CFR 95.17-5 - Quantity of foam required.

Code of Federal Regulations, 2012 CFR

2012-10-01

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46 CFR 95.17-10 - Controls.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 4 2011-10-01 2011-10-01 false Controls. 95.17-10 Section 95.17-10 Shipping COAST GUARD... Extinguishing Systems, Details § 95.17-10 Controls. (a) The foam agent, its container, and all controls and... controls and valves for the operation of the system shall be outside the space protected and shall not be...

46 CFR 95.17-10 - Controls.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Controls. 95.17-10 Section 95.17-10 Shipping COAST GUARD... Extinguishing Systems, Details § 95.17-10 Controls. (a) The foam agent, its container, and all controls and... controls and valves for the operation of the system shall be outside the space protected and shall not be...

46 CFR 95.17-10 - Controls.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 4 2013-10-01 2013-10-01 false Controls. 95.17-10 Section 95.17-10 Shipping COAST GUARD... Extinguishing Systems, Details § 95.17-10 Controls. (a) The foam agent, its container, and all controls and... controls and valves for the operation of the system shall be outside the space protected and shall not be...

46 CFR 95.17-10 - Controls.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 4 2012-10-01 2012-10-01 false Controls. 95.17-10 Section 95.17-10 Shipping COAST GUARD... Extinguishing Systems, Details § 95.17-10 Controls. (a) The foam agent, its container, and all controls and... controls and valves for the operation of the system shall be outside the space protected and shall not be...

46 CFR 95.17-10 - Controls.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 4 2014-10-01 2014-10-01 false Controls. 95.17-10 Section 95.17-10 Shipping COAST GUARD... Extinguishing Systems, Details § 95.17-10 Controls. (a) The foam agent, its container, and all controls and... controls and valves for the operation of the system shall be outside the space protected and shall not be...

Prospective assessment of diagnostic tests for pediatric penicillin allergy, from clinical history to challenge tests✰,✰✰,✰✰✰.

PubMed

Ibáñez, María Dolores; Del Río, Pablo Rodríguez; Lasa, Eva Maria; Joral, Alejandro; Ruiz-Hornillos, Javier; Muñoz, Candelaria; Traseira, Carmen Gómez; Escudero, Carmelo; Olaguibel Rivera, Jose María; Garriga-Baraut, Teresa; González-de-Olano, David; Rosado, Ana; Sanchez-García, Silvia; Bustamante, Socorro Pérez; Vilchez, Maria Antonia Padial; Montaño, Patricia Prieto; Morillo, Rocío Candón; Iglesia, Eva Macías; Vila, Angélica Feliú; Valbuena, Teresa; Lopez-Patiño, Ana; Martorell, Antonio; Sastre, Joaquín; Audícana, María Teresa

2018-05-24

Diagnostic guidelines for penicillin allergy in children recommend cumbersome protocols based partially on data from adults, which may be suboptimal for pediatric use. To assess the accuracy of tools for diagnosis of penicillin allergy in children. A prospective multicenter study was conducted in children with reported adverse events related to penicillin, excluding severe reactions. All patients underwent a uniform diagnostic protocol consisting of clinical history, skin tests, serum specific IgE, and, regardless of these results, drug provocation tests (DPT). 732 children (mean 5.5 years; 51.2% males) completed the allergy work-up, including DPT. Amoxicillin triggered 96.9% of all reactions. None of the patients with an immediate index reaction (IR) developed a reaction on DPT. Penicillin allergy was confirmed in 35 subjects (4.8%): 6(17%) immediate and 29(83%) non-immediate reactions in the DPT. No severe reactions were recorded. The allergist diagnosis based upon the clinical history was not associated with the final outcome at DPT. In 30 of 33(91%) allergic patients, all skin tests and sIgE were negative. A logistic regression model identified the following to be associated with PNC allergy (p<0.05): a family history of drug allergy (OR=3.03; 95% confidence interval (CI): 1.33-6.89), an IR lasting >3 days vs ≤24 hours (OR=8.96; 95% CI: 2.01-39.86), and IR while receiving corticosteroids (OR=2.68; 95% CI: 1.30-5.54). Conventional predictors of allergy to penicillin performed weakly. The authors propose straightforward penicillin provocation testing in controlled, experienced centers for the diagnosis of non-severe penicillin allergy in children. Copyright © 2018. Published by Elsevier Inc.

Emotional Freedom Techniques for Anxiety: A Systematic Review With Meta-analysis.

PubMed

Clond, Morgan

2016-05-01

Emotional Freedom Technique (EFT) combines elements of exposure and cognitive therapies with acupressure for the treatment of psychological distress. Randomized controlled trials retrieved by literature search were assessed for quality using the criteria developed by the American Psychological Association's Division 12 Task Force on Empirically Validated Treatments. As of December 2015, 14 studies (n = 658) met inclusion criteria. Results were analyzed using an inverse variance weighted meta-analysis. The pre-post effect size for the EFT treatment group was 1.23 (95% confidence interval, 0.82-1.64; p < 0.001), whereas the effect size for combined controls was 0.41 (95% confidence interval, 0.17-0.67; p = 0.001). Emotional freedom technique treatment demonstrated a significant decrease in anxiety scores, even when accounting for the effect size of control treatment. However, there were too few data available comparing EFT to standard-of-care treatments such as cognitive behavioral therapy, and further research is needed to establish the relative efficacy of EFT to established protocols.

Dosimetric equivalence of nonstandard HDR brachytherapy catheter patterns

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cunha, J. A. M.; Hsu, I-C.; Pouliot, J.

2009-01-15

Purpose: To determine whether alternative high dose rate prostate brachytherapy catheter patterns can result in similar or improved dose distributions while providing better access and reducing trauma. Materials and Methods: Standard prostate cancer high dose rate brachytherapy uses a regular grid of parallel needle positions to guide the catheter insertion. This geometry does not easily allow the physician to avoid piercing the critical structures near the penile bulb nor does it provide position flexibility in the case of pubic arch interference. This study used CT datasets with 3 mm slice spacing from ten previously treated patients and digitized new cathetersmore » following three hypothetical catheter patterns: conical, bi-conical, and fireworks. The conical patterns were used to accommodate a robotic delivery using a single entry point. The bi-conical and fireworks patterns were specifically designed to avoid the critical structures near the penile bulb. For each catheter distribution, a plan was optimized with the inverse planning algorithm, IPSA, and compared with the plan used for treatment. Irrelevant of catheter geometry, a plan must fulfill the RTOG-0321 dose criteria for target dose coverage (V{sub 100}{sup Prostate}>90%) and organ-at-risk dose sparing (V{sub 75}{sup Bladder}<1 cc, V{sub 75}{sup Rectum}<1 cc, V{sub 125}{sup Urethra}<<1 cc). Results: The three nonstandard catheter patterns used 16 nonparallel, straight divergent catheters, with entry points in the perineum. Thirty plans from ten patients with prostate sizes ranging from 26 to 89 cc were optimized. All nonstandard patterns fulfilled the RTOG criteria when the clinical plan did. In some cases, the dose distribution was improved by better sparing the organs-at-risk. Conclusion: Alternative catheter patterns can provide the physician with additional ways to treat patients previously considered unsuited for brachytherapy treatment (pubic arch interference) and facilitate robotic guidance of catheter insertion. In addition, alternative catheter patterns may decrease toxicity by avoidance of the critical structures near the penile bulb while still fulfilling the RTOG criteria.« less

Conventional and conformal technique of external beam radiotherapy in locally advanced cervical cancer: Dose distribution, tumor response, and side effects

NASA Astrophysics Data System (ADS)

Mutrikah, N.; Winarno, H.; Amalia, T.; Djakaria, M.

2017-08-01

The objective of this study was to compare conventional and conformal techniques of external beam radiotherapy (EBRT) in terms of the dose distribution, tumor response, and side effects in the treatment of locally advanced cervical cancer patients. A retrospective cohort study was conducted on cervical cancer patients who underwent EBRT before brachytherapy in the Radiotherapy Department of Cipto Mangunkusumo Hospital. The prescribed dose distribution, tumor response, and acute side effects of EBRT using conventional and conformal techniques were investigated. In total, 51 patients who underwent EBRT using conventional techniques (25 cases using Cobalt-60 and 26 cases using a linear accelerator (LINAC)) and 29 patients who underwent EBRT using conformal techniques were included in the study. The distribution of the prescribed dose in the target had an impact on the patient’s final response to EBRT. The complete response rate of patients to conformal techniques was significantly greater (58%) than that of patients to conventional techniques (42%). No severe acute local side effects were seen in any of the patients (Radiation Therapy Oncology Group (RTOG) grades 3-4). The distribution of the dose and volume to the gastrointestinal tract affected the proportion of mild acute side effects (RTOG grades 1-2). The urinary bladder was significantly greater using conventional techniques (Cobalt-60/LINAC) than using conformal techniques at 72% and 78% compared to 28% and 22%, respectively. The use of conformal techniques in pelvic radiation therapy is suggested in radiotherapy centers with CT simulators and 3D Radiotherapy Treatment Planning Systems (RTPSs) to decrease some uncertainties in radiotherapy planning. The use of AP/PA pelvic radiation techniques with Cobalt-60 should be limited in body thicknesses equal to or less than 18 cm. When using conformal techniques, delineation should be applied in the small bowel, as it is considered a critical organ according to RTOG consensus guidelines.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Machtay, Mitchell, E-mail: mitchell.machtay@uhhospitals.org; Moughan, Jennifer; Farach, Andrew

Purpose: Concurrent chemoradiation therapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN) increases local tumor control but at the expense of increased toxicity. We recently showed that several clinical/pretreatment factors were associated with the occurrence of severe late toxicity. This study evaluated the potential relationship between radiation dose delivered to the pharyngeal wall and toxicity. Methods and Materials: This was an analysis of long-term survivors from 3 previously reported Radiation Therapy Oncology Group (RTOG) trials of CCRT for locally advanced SCCHN (RTOG trials 91-11, 97-03, and 99-14). Severe late toxicity was defined in this secondary analysis asmore » chronic grade 3-4 pharyngeal/laryngeal toxicity and/or requirement for a feeding tube {>=}2 years after registration and/or potential treatment-related death (eg, pneumonia) within 3 years. Radiation dosimetry (2-dimensional) analysis was performed centrally at RTOG headquarters to estimate doses to 4 regions of interest along the pharyngeal wall (superior oropharynx, inferior oropharynx, superior hypopharynx, and inferior hypopharynx). Case-control analysis was performed with a multivariate logistic regression model that included pretreatment and treatment potential factors. Results: A total of 154 patients were evaluable for this analysis, 71 cases (patients with severe late toxicities) and 83 controls; thus, 46% of evaluable patients had a severe late toxicity. On multivariate analysis, significant variables correlated with the development of severe late toxicity, including older age (odds ratio, 1.062 per year; P=.0021) and radiation dose received by the inferior hypopharynx (odds ratio, 1.023 per Gy; P=.016). The subgroup of patients receiving {<=}60 Gy to the inferior hypopharynx had a 40% rate of severe late toxicity compared with 56% for patients receiving >60 Gy. Oropharyngeal dose was not associated with this outcome. Conclusions: Severe late toxicity following CCRT is common in long-term survivors. Age is the most significant factor, but hypopharyngeal dose also was associated.« less

Successful Treatment of Acute Radiation Proctitis with Aloe Vera: A Preliminary Randomized Controlled Clinical Trial.

PubMed

Sahebnasagh, Adeleh; Ghasemi, Arash; Akbari, Jafar; Alipour, Abbas; Lashkardoost, Hossein; Ala, Shahram; Salehifar, Ebrahim

2017-11-01

Acute radiation proctitis (ARP) is a common side-effect that affects up to 50% of patients receiving radiotherapy. The aim of this study was to evaluate the role of a topical preparation of Aloe vera in the treatment of ARP induced by radiotherapy of pelvic area. In this double-blind placebo-controlled trial, 20 consecutive patients with ARP after external-beam radiation therapy (46-72 Gy) of pelvic malignancies were randomized to receive either Aloe vera 3% or placebo ointment, 1 g twice daily for 4 weeks. These patients presented with at least two of the following symptoms: rectal bleeding, abdominal/rectal pain, diarrhea, or fecal urgency. These symptoms were rated by the patients in terms of their severity (grade 0-4) for each of the symptoms mentioned earlier at baseline and then weekly for 4 weeks. A symptom index was calculated by the addition of the scores (16 most symptomatic). Radiation Therapy Oncology Group (RTOG) acute toxicity criteria and psychosocial status of the patients were also recorded weekly. The lifestyle impact of the symptoms was assessed by questionnaire grading from 0 (no effect on daily activity) to 4 (afraid to leave home). There was a significant (p < 0.05) improvement in the symptom index (before treatment vs. after treatment with Aloe vera) for diarrhea (median score: 0.67 vs. 0.11), fecal urgency (median score: 0.89 vs. 0.11), clinical presentation total (median score: 4.33 vs. 1.22), RTOG total (median score: 2.89 vs. 0.89), and lifestyle (median score: 1.1 vs. 0.33). Hemorrhage and abdominal/rectal pain did not improve significantly. The odds ratios for advantage of Aloe vera over placebo for "clinical presentation total" and "RTOG total" were 3.97 (1.3-11.9) and 5.9 (1.6-21.6), respectively. A substantial number of patients with radiation proctitis seem to benefit from therapy with Aloe vera 3% ointment.

Late Toxicity and Patient Self-Assessment of Breast Appearance/Satisfaction on RTOG 0319: A Phase 2 Trial of 3-Dimensional Conformal Radiation Therapy-Accelerated Partial Breast Irradiation Following Lumpectomy for Stages I and II Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chafe, Susan, E-mail: susan.chafe@albertahealthservices.ca; Moughan, Jennifer; McCormick, Beryl

2013-08-01

Purpose: Late toxicities and cosmetic analyses of patients treated with accelerated partial breast irradiation (APBI) on RTOG 0319 are presented. Methods and Materials: Patients with stages I to II breast cancer ≤3 cm, negative margins, and ≤3 positive nodes were eligible. Patients received three-dimensional conformal external beam radiation therapy (3D-CRT; 38.5 Gy in 10 fractions twice daily over 5 days). Toxicity and cosmesis were assessed by the patient (P), the radiation oncologist (RO), and the surgical oncologist (SO) at 3, 6, and 12 months from the completion of treatment and then annually. National Cancer Institute Common Terminology Criteria for Adversemore » Events, version 3.0, was used to grade toxicity. Results: Fifty-two patients were evaluable. Median follow-up was 5.3 years (range, 1.7-6.4 years). Eighty-two percent of patients rated their cosmesis as good/excellent at 1 year, with rates of 64% at 3 years. At 3 years, 31 patients were satisfied with the treatment, 5 were not satisfied but would choose 3D-CRT again, and none would choose standard radiation therapy. The worst adverse event (AE) per patient reported as definitely, probably, or possibly related to radiation therapy was 36.5% grade 1, 50% grade 2, and 5.8% grade 3 events. Grade 3 AEs were all skin or musculoskeletal-related. Treatment-related factors were evaluated to potentially establish an association with observed toxicity. Surgical bed volume, target volume, the number of beams used, and the use of bolus were not associated with late cosmesis. Conclusions: Most patients enrolled in RTOG 0319 were satisfied with their treatment, and all would choose to have the 3D-CRT APBI again.« less

Late toxicity and patient self-assessment of breast appearance/satisfaction on RTOG 0319: a phase 2 trial of 3-dimensional conformal radiation therapy-accelerated partial breast irradiation following lumpectomy for stages I and II breast cancer.

PubMed

Chafe, Susan; Moughan, Jennifer; McCormick, Beryl; Wong, John; Pass, Helen; Rabinovitch, Rachel; Arthur, Douglas W; Petersen, Ivy; White, Julia; Vicini, Frank A

2013-08-01

Late toxicities and cosmetic analyses of patients treated with accelerated partial breast irradiation (APBI) on RTOG 0319 are presented. Patients with stages I to II breast cancer ≤3 cm, negative margins, and ≤3 positive nodes were eligible. Patients received three-dimensional conformal external beam radiation therapy (3D-CRT; 38.5 Gy in 10 fractions twice daily over 5 days). Toxicity and cosmesis were assessed by the patient (P), the radiation oncologist (RO), and the surgical oncologist (SO) at 3, 6, and 12 months from the completion of treatment and then annually. National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, was used to grade toxicity. Fifty-two patients were evaluable. Median follow-up was 5.3 years (range, 1.7-6.4 years). Eighty-two percent of patients rated their cosmesis as good/excellent at 1 year, with rates of 64% at 3 years. At 3 years, 31 patients were satisfied with the treatment, 5 were not satisfied but would choose 3D-CRT again, and none would choose standard radiation therapy. The worst adverse event (AE) per patient reported as definitely, probably, or possibly related to radiation therapy was 36.5% grade 1, 50% grade 2, and 5.8% grade 3 events. Grade 3 AEs were all skin or musculoskeletal-related. Treatment-related factors were evaluated to potentially establish an association with observed toxicity. Surgical bed volume, target volume, the number of beams used, and the use of bolus were not associated with late cosmesis. Most patients enrolled in RTOG 0319 were satisfied with their treatment, and all would choose to have the 3D-CRT APBI again. Copyright © 2013. Published by Elsevier Inc.

Mapping Patterns of Ipsilateral Supraclavicular Nodal Metastases in Breast Cancer: Rethinking the Clinical Target Volume for High-risk Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jing, Hao; Wang, Shu-Lian, E-mail: wsl20040118@yahoo.com; Li, Jing

2015-10-01

Purpose: To map the location of metastatic supraclavicular (SCV) lymph nodes (LNMs) in breast cancer patients with SCV node involvement and determine whether and where the radiation therapy clinical target volume (CTV) of this region could be modified in high-risk subsets. Methods and Materials: Fifty-five patients with metastatic SCV LNMs were eligible for geographic mapping and atlas coverage analysis. All LNMs and their epicenters were registered proportionally by referencing the surrounding landmarks onto simulation computed tomography images of a standard patient. CTVs based on selected SCV atlases, including the one by the Radiation Therapy Oncology Group (RTOG) were contoured. Amore » modified SCV CTV was tried and shown to have better involved-node coverage and thus theoretically improved prophylaxis in this setting. Results: A total of 50 (91%) and 45 (81.8%) patients had LNMs in the medial and lateral SCV subregions, respectively. Also, 36 patients (65.5%) had LNMs located at the junction of the jugular-subclavian veins. All nodes were covered in only 25.5% to 41.8% of patients by different atlases. The RTOG atlas covered all nodes in 25.5% of patients. Stratified by the nodes in all the patients as a whole, 49.2% to 81.3% were covered, and the RTOG atlas covered 62.6%. The lateral and posterior borders were the most overlooked locations. Modification by extending the borders to natural anatomic barriers allowed the new CTV to cover all the nodes in 81.8% of patients and encompass 96.1% of all the nodes. Conclusions: According to the distribution of SCV LNMs, the extent of existing atlases might not be adequate for potential metastatic sites in certain groups of patients. The extension of the lateral and posterior CTV borders in high-risk or recurrent patients might be a reasonable approach for increasing coverage. However, additional data in more homogeneous populations with localized disease are needed before routine application.« less

Dairy products and colorectal cancer in middle eastern and north African countries: a systematic review.

PubMed

El Kinany, K; Deoula, M; Hatime, Z; Bennani, B; El Rhazi, K

2018-03-01

This systematic review was conducted to explain the association between dairy products and colorectal cancer (CRC) risk in Middle Eastern and North African countries (MENA). The database consulted were PubMed, Clinical Trials, and Cochrane to extract the relevant studies published till the 31stof December 2016, using inclusion and exclusion criteria according to Prisma Protocol. The characteristics of these studies comprised the consumption of all types of dairy products in relation to CRC risk. Seven studies were included in this review. For dairy products overall, no significant association was found. Regarding modern dairy products, included studies found controversial results with OR = 9.88 (95% CI: 3.80-24.65) and OR a  = 0.14 (95% CI: 0.02-0.71). A positive association was reported between traditional dairy products and CRC risk, to OR = 18.66 (95% CI: 3.06-113.86) to OR = 24 (95% CI: 1.74-330.82) to ORa = 1.42 (95% CI: 0.62-3.25), p trend  = 0.03. Calcium was inversely associated with the CRC risk with OR a  = 0.08 (95% CI: 0.04-0.17). This is the first systematic review which illustrated the association between dairy consumption and CRC risk in MENA region. The results were inconsistent and not always homogeneous. Further specified studies may be warranted to address the questions about the association between CRC and dairy products in a specific context of MENA region.

Conditional Risk of Relapse in Surveillance for Clinical Stage I Testicular Cancer.

PubMed

Nayan, Madhur; Jewett, Michael A S; Hosni, Ali; Anson-Cartwright, Lynn; Bedard, Philippe L; Moore, Malcolm; Hansen, Aaron R; Chung, Peter; Warde, Padraig; Sweet, Joan; O'Malley, Martin; Atenafu, Eshetu G; Hamilton, Robert J

2017-01-01

Patients on surveillance for clinical stage I (CSI) testicular cancer are counseled regarding their baseline risk of relapse. The conditional risk of relapse (cRR), which provides prognostic information on patients who have survived for a period of time without relapse, have not been determined for CSI testicular cancer. To determine cRR in CSI testicular cancer. We reviewed 1239 patients with CSI testicular cancer managed with surveillance at a tertiary academic centre between 1980 and 2014. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: cRR estimates were calculated using the Kaplan-Meier method. We stratified patients according to validated risk factors for relapse. We used linear regression to determine cRR trends over time. At orchiectomy, the risk of relapse within 5 yr was 42.4%, 17.3%, 20.3%, and 12.2% among patients with high-risk nonseminomatous germ cell tumor (NSGCT), low-risk NSGCT, seminoma with tumor size ≥3cm, and seminoma with tumor size <3cm, respectively. However, for patients without relapse within the first 2 yr of follow-up, the corresponding risk of relapse within the next 5 yr in the groups was 0.0%, 1.0% (95% confidence interval [CI] 0.3-1.7%), 5.6% (95% CI 3.1-8.2%), and 3.9% (95% CI 1.4-6.4%). Over time, cRR decreased (p≤0.021) in all models. Limitations include changes to surveillance protocols over time and few late relapses. After 2 yr, the risk of relapse on surveillance for CSI testicular cancer is very low. Consideration should be given to adapting surveillance protocols to individualized risk of relapse based on cRR as opposed to static protocols based on baseline factors. This strategy could reduce the intensity of follow-up for the majority of patients. Our study is the first to provide data on the future risk of relapse during surveillance for clinical stage I testicular cancer, given a patient has been without relapse for a specified period of time. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Participation in Pediatric Oncology Research Protocols: Racial/ethnic, Language and Age-based Disparities

PubMed Central

Aristizabal, Paula; Singer, Jenelle; Cooper, Renee; Wells, Kristen J.; Nodora, Jesse; Milburn, Mehrzad; Gahagan, Sheila; Schiff, Deborah E.; Martinez, Maria Elena

2015-01-01

Background Survival rates in pediatric oncology have improved dramatically, in part due to high patient participation in clinical trials. Although racial/ethnic inequalities in clinical trial participation have been reported in adults, pediatric data and studies comparing participation rates by socio-demographic characteristics are scarce. The goal of this study was to assess differences in research protocol participation for childhood cancer by age, sex, race/ethnicity, parental language, cancer type and insurance status. Procedure Data on enrollment in any protocol, biospecimen, or therapeutic protocols were collected and analyzed for newly diagnosed pediatric patients with cancer from 2008–2012 at Rady Children’s Hospital. Results Among the 353 patients included in the analysis, 304 (86.1%) were enrolled in any protocol. Enrollment in biospecimen and therapeutic protocols was 84.2% (261/310) and 81.1% (206/254), respectively. Logistic regression analyses revealed significant enrollment underrepresentation in any protocol for Hispanics compared to Non-Hispanic whites (81% vs. 91%; Odds Ratio [OR], 0.43; 95% Confidence Interval [CI], 0.21–0.90; p=0.021) and among children of Spanish-speaking vs. English-speaking parents (78% vs. 89%; OR, 0.45; 95%CI, 0.23–0.87; p=0.016). Compared to patients aged 0–4 years, significant underrepresentation was also found among patients 15–21 years old (92% vs.72%; OR, 0.21; 95% CI, 0.09–0.48; p<0.001). Similar trends were observed when analyzing enrollment in biospecimen and therapeutic protocols separately. Conclusions There was significant underrepresentation in protocol participation for Hispanics, children of Spanish-speaking parents, and patients ages 15–21. Research is urgently needed to understand barriers to research participation among these groups underrepresented in pediatric oncology clinical trials. PMID:25755225

Influence of warm-up duration on physical performance and psychological perceptions in handball players.

PubMed

Romaratezabala, Estibaliz; Nakamura, Fábio Yuzo; Castillo, Daniel; Gorostegi-Anduaga, Ilargi; Yanci, Javier

2018-01-01

The purpose of the study was to analyse the effect of two warm-up protocols of different duration on physical performance, perceived load and perception of being ready for a match in handball players. Eighteen handball players were randomly divided into two groups (Wup 34min , warm-up protocol of 34 min, Wup 17min , warm-up protocol of 17 min). Before and after the warm-up protocols, they performed a battery of physical tests and recorded their perception of feeling ready for a match. At the end of the warm-up protocols, all the players evaluated their differentiated perceived effort (dRPE). The results showed that neither of the protocols significantly modified (p > 0.05) the players' physical performance. However, the Wup 34min group showed higher values in the differentiated warm-up perceived load (dRPE-WL) (p < 0.01, TE = 0.97-1.27, high) than the Wup 17min group. The players with a greater perceived muscular load (RPE MUSC ) experienced a greater decrease in their acceleration capacity (r = 0.48-0.49, p < 0.05). In spite of the fact that neither of the warm-up protocols significantly modified the players' physical performance, a greater perceived muscular load may cause a greater decrease in acceleration capacity.

Childhood Experiences of Sexual Violence, Pregnancy, and Marriage Associated With Child Sex Trafficking Among Female Sex Workers in Two US-Mexico Border Cities.

PubMed

Boyce, Sabrina C; Brouwer, Kimberly C; Triplett, Daniel; Servin, Argentina E; Magis-Rodriguez, Carlos; Silverman, Jay G

2018-06-21

To quantitatively assess the relationships of childhood experiences of marriage, pregnancy, and sexual violence with underage sex trafficking. Cross-sectional survey data from a population-based sample of 603 female sex workers from Tijuana and Ciudad Juárez, Mexico, were collected in 2013 and 2014, and we analyzed the data to evaluate relationships between pregnancy, marriage, and sexual violence when younger than 16 years, and child sex trafficking. Adjusted odds of child sex trafficking among those who experienced pregnancy, marriage, and childhood sexual violence when younger than 16 years in combined models were 2.8 (95% confidence interval [CI] = 1.8, 4.3), 1.7 (95% CI = 0.99, 2.8), and 1.7 (95% CI = 1.01, 3.0), respectively, relative to others (n = 603). For 89.8%, 78.0%, and 97.0% of those who had an experience of pregnancy (n = 69), marriage (n = 50), or sexual violence (n = 33) when younger than 16 years, respectively, the experience occurred before or the same year as sex trafficking. These results provide empirical evidence of modifiable risk factors for child sex trafficking that could be integrated into the prevention efforts and protocols of health clinics and governmental agencies in Mexico currently working to reduce underage pregnancy, marriage, and sexual violence. (Am J Public Health. Published online ahead of print June 21, 2018: e1-e6. doi:10.2105/AJPH.2018.304455).

Patient navigation for American Indians undergoing cancer treatment: utilization and impact on care delivery in a regional healthcare center.

PubMed

Guadagnolo, B Ashleigh; Boylan, Amy; Sargent, Michele; Koop, David; Brunette, Deb; Kanekar, Shalini; Shortbull, Vanessa; Molloy, Kevin; Petereit, Daniel G

2011-06-15

A study was undertaken to assess patient navigation utilization and its impact on treatment interruptions and clinical trial enrollment among American Indian cancer patients. Between February 2004 and September 2009, 332 American Indian cancer patients received patient navigation services throughout cancer treatment. The patient navigation program provided culturally competent navigators to assist patients with navigating cancer therapy, obtaining medications, insurance issues, communicating with medical providers, and travel and lodging logistics. Data on utilization and trial enrollment were prospectively collected. Data for a historical control group of 70 American Indian patients who did not receive patient navigation services were used to compare treatment interruptions among those undergoing patient navigation during curative radiation therapy (subgroup of 123 patients). The median number of contacts with a navigator was 12 (range, 1-119). The median time spent with the navigator at first contact was 40 minutes (range, 10-250 minutes), and it was 15 minutes for subsequent contacts. Patients treated with radiation therapy with curative intent who underwent patient navigation had fewer days of treatment interruption (mean, 1.7 days; 95% confidence interval [CI], 1.1-2.2 days) than historical controls who did not receive patient navigation services (mean, 4.9 days; 95% CI, 2.9-6.9 days). Of the 332 patients, 72 (22%; 95% CI, 17%-26%) were enrolled on a clinical treatment trial or cancer control protocol. Patient navigation was associated with fewer treatment interruptions and relatively high rates of clinical trial enrollment among American Indian cancer patients compared with national reports. Copyright © 2010 American Cancer Society.

SU-E-T-370: Evaluating Plan Quality and Dose Delivery Accuracy of Tomotherapy SBRT Treatments for Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blake, S; Thwaites, D; Hansen, C

2015-06-15

Purpose: This study evaluated the plan quality and dose delivery accuracy of stereotactic body radiotherapy (SBRT) helical Tomotherapy (HT) treatments for lung cancer. Results were compared with those previously reported by our group for flattening filter (FF) and flattening filter free (FFF) VMAT treatments. This work forms part of an ongoing multicentre and multisystem planning and dosimetry audit on FFF beams for lung SBRT. Methods: CT datasets and DICOM RT structures delineating the target volume and organs at risk for 6 lung cancer patients were selected. Treatment plans were generated using the HT treatment planning system. Tumour locations were classifiedmore » as near rib, near bronchial tree or in free lung with prescribed doses of 48Gy/4fr, 50Gy/5fr and 54Gy/3fr respectively. Dose constraints were specified by a modified RTOG0915 protocol used for an Australian SBRT phase II trial. Plan quality was evaluated using mean PTV dose, PTV volume receiving 100% of the prescribed dose (V100%), target conformity (CI=VD100%/VPTV) and low dose spillage (LDS=VD50%/VPTV). Planned dose distributions were compared to those measured using an ArcCheck phantom. Delivery accuracy was evaluated using a gamma-index pass rate of 95% with 3% (of max dose) and 3mm criteria. Results: Treatment plans for all patients were clinically acceptable in terms of quality and accuracy of dose delivery. The following DVH metrics are reported as averages (SD) of all plans investigated: mean PTV dose was 115.3(2.4)% of prescription, V100% was 98.8(0.9)%, CI was 1.14(0.03) and LDS was 5.02(0.37). The plans had an average gamma-index passing rate of 99.3(1.3)%. Conclusion: The results reported in this study for HT agree within 1 SD to those previously published by our group for VMAT FF and FFF lung SBRT treatments. This suggests that HT delivers lung SBRT treatments of comparable quality and delivery accuracy as VMAT using both FF and FFF beams.« less

Time to publication for publicly funded clinical trials in Australia: an observational study.

PubMed

Strand, Linn Beate; Clarke, Philip; Graves, Nicholas; Barnett, Adrian G

2017-03-22

To examine the length of time between receiving funding and publishing the protocol and main paper for randomised controlled trials. An observational study using survival analysis. Publicly funded health and medical research in Australia. Randomised controlled trials funded by the National Health and Medical Research Council of Australia between 2008 and 2010. Time from funding to the protocol paper and main results paper. Multiple variable survival models examining whether study characteristics predicted publication times. We found 77 studies with a total funding of $A59 million. The median time to publication of the protocol paper was 6.4 years after funding (95% CI 4.1 to 8.1). The proportion with a published protocol paper 8 years after funding was 0.61 (95% CI 0.48 to 0.74). The median time to publication of the main results paper was 7.1 years after funding (95% CI 6.3 to 7.6). The proportion with a published main results paper 8 years after funding was 0.72 (95% CI 0.56 to 0.87). The HRs for how study characteristics might influence timing were generally close to one with narrow CIs, the notable exception was that a longer study length lengthened the time to the main paper (HR=0.62 per extra study year, 95% CI 0.43 to 0.89). Despite the widespread registration of clinical trials, there remain serious concerns of trial results not being published or being published with a long delay. We have found that these same concerns apply to protocol papers, which should be publishable soon after funding. Funding agencies could set a target of publishing the protocol paper within 18 months of funding. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Risk prediction score for death of traumatised and injured children

PubMed Central

2014-01-01

Background Injury prediction scores facilitate the development of clinical management protocols to decrease mortality. However, most of the previously developed scores are limited in scope and are non-specific for use in children. We aimed to develop and validate a risk prediction model of death for injured and Traumatised Thai children. Methods Our cross-sectional study included 43,516 injured children from 34 emergency services. A risk prediction model was derived using a logistic regression analysis that included 15 predictors. Model performance was assessed using the concordance statistic (C-statistic) and the observed per expected (O/E) ratio. Internal validation of the model was performed using a 200-repetition bootstrap analysis. Results Death occurred in 1.7% of the injured children (95% confidence interval [95% CI]: 1.57–1.82). Ten predictors (i.e., age, airway intervention, physical injury mechanism, three injured body regions, the Glasgow Coma Scale, and three vital signs) were significantly associated with death. The C-statistic and the O/E ratio were 0.938 (95% CI: 0.929–0.947) and 0.86 (95% CI: 0.70–1.02), respectively. The scoring scheme classified three risk stratifications with respective likelihood ratios of 1.26 (95% CI: 1.25–1.27), 2.45 (95% CI: 2.42–2.52), and 4.72 (95% CI: 4.57–4.88) for low, intermediate, and high risks of death. Internal validation showed good model performance (C-statistic = 0.938, 95% CI: 0.926–0.952) and a small calibration bias of 0.002 (95% CI: 0.0005–0.003). Conclusions We developed a simplified Thai pediatric injury death prediction score with satisfactory calibrated and discriminative performance in emergency room settings. PMID:24575982

Randomized, Double-Blinded, Placebo-Controlled Crossover Trial of Treating Erectile Dysfunction with Sildenafil After Radiotherapy and Short-Term Androgen Deprivation Therapy: Results of RTOG 0215

PubMed Central

Bruner, Deborah Watkins; James, Jennifer L.; Bryan, Charlene J.; Pisansky, Thomas M.; Rotman, Marvin; Corbett, Thomas; Speight, Joycelyn; Byhardt, Roger; Sandler, Howard; Bentzen, Søren; Kachnic, Lisa; Berk, Lawrence

2013-01-01

Introduction Erectile dysfunction (ED) may be the most commonly observed adverse event (AE) associated with the combination of radiation therapy (RT) and androgen deprivation therapy (ADT). A significant number of men are trying phosphodiesterase type 5 inhibitors (PDE5s) such as sildenafil to treat ED, yet sildenafil studies to date shed little light on the response to ED after ADT. Aim The purpose of this trial was to evaluate sildenafil in the treatment of ED in prostate cancer patients previously treated with external beam RT and neoadjuvant and concurrent ADT. Methods In this randomized, double-blinded crossover trial, eligible patients received RT/ADT for intermediate risk prostate cancer and currently had ED as defined by the International Index of Erectile Function (IIEF). Patients were randomized to 12 weeks of sildenafil or placebo followed by 1 week of no treatment then 12 weeks of the alternative. Treatment differences were evaluated using a marginal model for binary crossover data. Main Outcome Measures The primary end point was improved erectile function, as measured by the IIEF. Results The study accrued 115 patients and 61 (55%) completed all three IIEF assessments. Sildenafil effect was significant (P = 0.009) with a difference in probabilities of erectile response of 0.17 (95% confidence interval: 0.06, 0.29), and 0.21 (0.06, 0.38) for patients receiving ≤120 days of ADT. However, as few as 21% of patients had a treatment-specific response, only improving during sildenafil but not during the placebo phase. Conclusions This is the first controlled trial to suggest a positive sildenafil response for ED treatment in patients previously treated with RT/ADT, however, only a minority of patients responded to treatment. ADT duration may be associated with response and requires further study. The overall low response rate suggests the need for study of additional or preventative strategies for ED after RT/ADT for prostate cancer. PMID:21235716

Introduction of a pan-scan protocol for blunt trauma activations: what are the consequences?

PubMed

James, Melissa K; Schubl, Sebastian D; Francois, Michael P; Doughlin, Geoffrey K; Lee, Shi-Wen

2017-01-01

The aim of this study is to determine if the introduction of a pan-scan protocol during the initial assessment for blunt trauma activations would affect missed injuries, incidental findings, treatment times, radiation exposure, and cost. A 6-month prospective study was performed on patients with blunt trauma at a level 1 trauma center. During the last 3 months of the study, a pan-scan protocol was introduced to the trauma assessment. Categorical data were analyzed by Fisher exact test and continuous data were analyzed by Mann-Whitney nonparametric test. There were a total of 220 patients in the pre-pan-scan period and 206 patients during the pan-scan period. There was no significant difference in injury severity or mortality between the groups. Introduction of the pan-scan protocol substantially reduced the incidence of missed injuries from 3.2% to 0.5%, the length of stay in the emergency department by 68.2 minutes (95% confidence interval [CI], -134.4 to -2.1), and the mean time to the first operating room visit by 1465 minutes (95% CI, -2519 to -411). In contrast, fixed computed tomographic scan cost increased by $48.1 (95% CI, 32-64.1) per patient; however, total radiology cost per patient decreased by $50 (95% CI, -271.1 to 171.4). In addition, the rate of incidental findings increased by 14.4% and the average radiation exposure per patient was 8.2 mSv (95% CI, 5.0-11.3) greater during the pan-scan period. Although there are advantages to whole-body computed tomography, elucidation of the appropriate blunt trauma patient population is warranted when implementing a pan-scan protocol. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluating the tolerability and acceptability of an alcohol-based hand rub - real-life experience with the WHO protocol.

PubMed

Wolfensberger, Aline; Durisch, Nina; Mertin, Juliane; Ajdler-Schaeffler, Evelyne; Sax, Hugo

2015-01-01

Optimizing user satisfaction with alcohol-based hand rubs (ABHR) may be vital to enhance hand hygiene performance. This study tested the tolerability and acceptability of a new ABHR (EVO9; Ecolab) in healthcare workers under daily working conditions and evaluated the practicability of the corresponding WHO protocol. We strictly applied the WHO single product ABHR evaluation protocol. A trained observer assessed hand skin conditions of healthy volunteers using at least 30 ml ABHR per day during their clinical work at baseline, day 3-5 and one month (visit 1-3). Participants rated ABHR tolerability and acceptability at visit 2 and 3. Additionally, we registered study time for participants and study team. Among 46 volunteers, 76% were female; 37% nurses, 28% physicians. Skin was observer-rated "not" or "incidentally" dry in 64.4%, 77.8%, and 90.9% participants at visit 1, 2, and 3, respectively. EVO9 was scored ≥5 (progressive scale, 1-7) for appearance, intactness, moisture content, and sensation by 95.7%, 97.7%, 88.9%, and 97.8% participants at visit 3, respectively. All WHO benchmarks were exceeded except for "speed of drying" at visit 2, and "texture" at visit 2 and 3. Cumulative study time expenditure was 14 days for the observer and four days for participants. EVO9 was well tolerated and accepted according to the WHO single ABHR evaluation protocol with the potential for improvement for stickiness. The WHO protocol is feasible but requires considerable time and logistics. It does not preclude bias, in this case especially due to the necessary switch to personal dispensers.

106-17 Telemetry Management Resources Chapter 25

DTIC Science & Technology

2017-07-01

aspects of the TmNS system . There are two primary protocols for accessing the management resources: Simple Network Management Protocol (SNMP) and... management resources as well as a basic HTTP clients and servers for a more RESTful approach to system management . Both tools are available from the...Telemetry Standards, RCC Standard 106-17 Chapter 25, July 2017 i CHAPTER 25 Management Resources Acronyms

Accrual of Older Patients With Breast Cancer to Alliance Systemic Therapy Trials Over Time: Protocol A151527

PubMed Central

Foster, Jared C.; Seisler, Drew K.; Lafky, Jacqueline M.; Muss, Hyman B.; Cohen, Harvey J.; Mandelblatt, Jeanne; Winer, Eric P.; Hudis, Clifford A.; Partridge, Ann H.; Carey, Lisa A.; Cirrincione, Constance; Moreno-Aspitia, Alvaro; Kimmick, Gretchen; Jatoi, Aminah; Hurria, Arti

2017-01-01

Purpose Despite increasing awareness of accrual challenges, it is unknown if accrual of older patients to breast cancer treatment trials is improving. Methods We examined accrual of older patients to Alliance for Clinical Trials in Oncology systemic therapy breast cancer trials during 1985-2012 and compared disease characteristics and reasons for therapy cessation for older (age ≥ 65 years and ≥ 70 years) versus younger (age < 65 years and < 70 years) participants. To examine accrual trends, we modeled age as a function of time, using logistic regression. Results Overall, 17% of study participants were ≥ 65 years of age. Approximately 15%, 24%, and 24% of participants in adjuvant, neoadjuvant, and metastatic trials were age ≥ 65 years, and 7%, 15%, and 13% were age ≥ 70 years, respectively. The odds of a patient age ≥ 65 years enrolling significantly increased over time for adjuvant trials (odds ratio [OR] per year, 1.04; 95% CI, 1.04 to 1.05) but decreased significantly for neoadjuvant and metastatic trials (OR, 0.62; 95% CI, 0.58 to 0.67 and OR, 0.98, 95% CI, 0.97 to 1.00). Similar trends were seen for those age ≥ 70 years but these were statistically significant for adjuvant and neoadjuvant trials only (OR, 1.05, 95% CI, 1.04 to 1.07; and OR, 0.57, 95% CI, 0.52 to 0.62). In general, those age ≥ 65 years (v those < 65 years) in adjuvant studies had a higher mean number of lymph nodes involved and more hormone receptor-negative tumors, although tumor sizes were similar. Early protocol treatment cessation was also more frequent in those age ≥ 65 years (50%) versus < 65 years (35.9%) across trials. Conclusion Older patients with breast cancer remain largely underrepresented in cooperative group therapeutic trials. We observed some improvement in accrual to adjuvant trials but worsening of accrual for neoadjuvant/metastatic trials. Novel strategies to increase accrual of older patients are critical to meaningfully change the evidence base for this growing patient population. PMID:27992272

Accrual of Older Patients With Breast Cancer to Alliance Systemic Therapy Trials Over Time: Protocol A151527.

PubMed

Freedman, Rachel A; Foster, Jared C; Seisler, Drew K; Lafky, Jacqueline M; Muss, Hyman B; Cohen, Harvey J; Mandelblatt, Jeanne; Winer, Eric P; Hudis, Clifford A; Partridge, Ann H; Carey, Lisa A; Cirrincione, Constance; Moreno-Aspitia, Alvaro; Kimmick, Gretchen; Jatoi, Aminah; Hurria, Arti

2017-02-01

Purpose Despite increasing awareness of accrual challenges, it is unknown if accrual of older patients to breast cancer treatment trials is improving. Methods We examined accrual of older patients to Alliance for Clinical Trials in Oncology systemic therapy breast cancer trials during 1985-2012 and compared disease characteristics and reasons for therapy cessation for older (age ≥ 65 years and ≥ 70 years) versus younger (age < 65 years and < 70 years) participants. To examine accrual trends, we modeled age as a function of time, using logistic regression. Results Overall, 17% of study participants were ≥ 65 years of age. Approximately 15%, 24%, and 24% of participants in adjuvant, neoadjuvant, and metastatic trials were age ≥ 65 years, and 7%, 15%, and 13% were age ≥ 70 years, respectively. The odds of a patient age ≥ 65 years enrolling significantly increased over time for adjuvant trials (odds ratio [OR] per year, 1.04; 95% CI, 1.04 to 1.05) but decreased significantly for neoadjuvant and metastatic trials (OR, 0.62; 95% CI, 0.58 to 0.67 and OR, 0.98, 95% CI, 0.97 to 1.00). Similar trends were seen for those age ≥ 70 years but these were statistically significant for adjuvant and neoadjuvant trials only (OR, 1.05, 95% CI, 1.04 to 1.07; and OR, 0.57, 95% CI, 0.52 to 0.62). In general, those age ≥ 65 years ( v those < 65 years) in adjuvant studies had a higher mean number of lymph nodes involved and more hormone receptor-negative tumors, although tumor sizes were similar. Early protocol treatment cessation was also more frequent in those age ≥ 65 years (50%) versus < 65 years (35.9%) across trials. Conclusion Older patients with breast cancer remain largely underrepresented in cooperative group therapeutic trials. We observed some improvement in accrual to adjuvant trials but worsening of accrual for neoadjuvant/metastatic trials. Novel strategies to increase accrual of older patients are critical to meaningfully change the evidence base for this growing patient population.

A Phase 1/2 Trial of a Combination of Paclitaxel and Trastuzumab With Daily Irradiation or Paclitaxel Alone With Daily Irradiation After Transurethral Surgery for Noncystectomy Candidates With Muscle-Invasive Bladder Cancer (Trial NRG Oncology RTOG 0524)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Michaelson, M. Dror, E-mail: dmichaelson1@partners.org; Hu, Chen; Sydney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland

Purpose: Bladder preservation therapy is an effective treatment for muscle-invasive urothelial carcinoma (UC). In this study we treated noncystectomy candidates with daily radiation and weekly paclitaxel for 7 weeks. Patients whose tumors showed her2/neu overexpression were additionally treated with weekly trastuzumab. Methods and Materials: Sixty-eight evaluable patients were treated with radiation therapy and either paclitaxel + trastuzumab (group 1) or paclitaxel alone (group 2). Groups were assigned on the basis of her2/neu immunohistochemistry results. Patients received 1.8-Gy fractions to a total dose of 64.8 Gy. The primary endpoint of the study was treatment-related toxicity, and secondary endpoints included complete response (CR) rate, protocol completionmore » rate, and survival. Results: A total of 20 evaluable patients were treated in group 1 and 46 patients in group 2. Acute treatment-related adverse events (AEs) were observed in 7 of 20 patients in group 1 (35%) and 14 of 46 patients in group 2 (30.4%). Protocol therapy was completed by 60% (group 1) and 74% (group 2) of patients. Most incompletions were due to toxicity, and the majority of AEs were gastrointestinal, including 1 grade 5 AE (group 1). Two other deaths (both in group 2) were unrelated to protocol therapy. No unexpected cardiac, hematologic, or other toxicities were observed. The CR rate at 1 year was 72% for group 1 and 68% for group 2. Conclusions: In patients with muscle-invasive UC who are not candidates for cystectomy, daily radiation combined with paclitaxel is an effective treatment strategy with a high completion rate and moderate toxicity. In patients with her2/neu-positive tumors, a group generally considered to have worse outcomes, the addition of trastuzumab appears to result in comparable efficacy and toxicity. Further biomarker-driven trials should be undertaken in advancing treatment of this challenging disease.« less

SU-E-T-593: Outcomes and Toxicities From a Clinical Trial of APBI Using MERT+IMRT with the Same XMLC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jimenez-Ortega, E.; Ureba, A.; Barbeiro, A.R.

2015-06-15

Purpose: We present the results from a clinical trial of accelerated partial breast irradiation (APBI), using mixed modulated photon and electron beams (MERT+IMRT) with the same photon multileaf collimator (xMLC). Methods: Seven patients were enrolled in the first year of the APBI clinical trial. Patients were selected following the conditions included in the NSABP B-39/RTOG 0413 protocol. The targets and clinically relevant normal structures were contoured on the CT images following this protocol for APBI-EBRT. All treatments were delivered using combined modulated electron and photon beams by means of the same xMLC installed in a SIEMENS Primus linac, with amore » reduced SSD equal to 60 cm for electron beams. The plans were performed with a treatment planning system based on full Monte Carlo simulations, called CARMEN, developed by our group. Simultaneously, an alternative IMRT plan was calculated with the commercial TPS PINNACLE v8.0m (Philips), and both plans were compared. An ad-hoc breast phantom with semi-spherical geometry called NAOMI was designed for a specific QA protocol. Patients received a total dose of 38.5 Gy, delivered in 10 fractions over 5 consecutive days, with a twice-a-day hypofractionated schema.Follow-up visits during 2.5 years on average were repeated at 1 month post-treatment, every 3 months for the first year, and every 6 months for the second year. Toxicity was scored according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 3.0). Results: This APBI technique achieved high loco-regional control rates and showed low acute toxicity (grade 1 of CTCAE) and no toxicities from first month onwards. Photographic assessment of cosmesis showed skin excellent results. Conclusion: The clinical results achieved with MERT+IMRT by using the same xMLC are comparable or even better than those obtained with other APBI techniques, thanks to a software solution without any additional equipment or specific device.« less

Demonstration and Certification of Amphibian Ecological Risk Assessment Protocol. Cost and Performance Report (Version 2)

DTIC Science & Technology

2009-07-01

sediment protocol, respectively). The soil protocol evaluates impacts to adult salamanders and the sediment protocol evaluates impacts to larval tadpoles ...the sediment protocol evaluates impacts to larval tadpoles . When selecting appropriate receptors to derive ERA-based remedial goals, amphibians...Sediment tests are conducted with recently hatched tadpoles (i.e., Rana pipiens; Gosner Stages 17-20). Young tadpoles are placed in beakers

47 CFR 95.417 - (CB Rule 17) Do I identify my CB communications?

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false (CB Rule 17) Do I identify my CB communications? 95.417 Section 95.417 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND... Station § 95.417 (CB Rule 17) Do I identify my CB communications? (a) You need not identify your CB...

46 CFR 95.17-90 - Installations contracted for prior to November 19, 1952.

Code of Federal Regulations, 2010 CFR

2010-10-01

... MISCELLANEOUS VESSELS FIRE PROTECTION EQUIPMENT Foam Extinguishing Systems, Details § 95.17-90 Installations... exception of § 95.17-5(a)(2), insofar as is reasonable and practicable. A 6-inch blanket of foam in 5...

46 CFR 95.17-90 - Installations contracted for prior to November 19, 1952.

Code of Federal Regulations, 2011 CFR

2011-10-01

... MISCELLANEOUS VESSELS FIRE PROTECTION EQUIPMENT Foam Extinguishing Systems, Details § 95.17-90 Installations... exception of § 95.17-5(a)(2), insofar as is reasonable and practicable. A 6-inch blanket of foam in 5...

Factors affecting the outcome of trabeculectomy: an analysis based on combined data from two phase III studies of an antibody to transforming growth factor beta2, CAT-152.

PubMed

Grehn, Franz; Holló, Gábor; Khaw, Peng; Overton, Barry; Wilson, Rosamund; Vogel, Roger; Smith, Zaid

2007-10-01

To determine the factors affecting trabeculectomy success. Retrospective analysis of 2 randomized controlled trials comparing an antibody against transforming growth factor beta2 (TGF-beta2) with vehicle (placebo) for prevention of fibrosis after trabeculectomy, in which there was no significant difference between the treatment groups. Data were from patients (n = 726) with a diagnosis of primary open-angle glaucoma, chronic angle-closure glaucoma, pseudoexfoliative glaucoma, or pigmentary glaucoma (PG) who had an intraocular pressure (IOP) > 21 mmHg and visual field or optic disc changes characteristic of glaucoma and were taking the maximum tolerated dose of medication before trabeculectomy. Patients had trabeculectomy and 4 subconjunctival injections of a human monoclonal antibody to TGF-beta2 (CAT-152) or a placebo. The definition of trabeculectomy success in the protocols was an IOP between 6 and 16 mmHg inclusive at months 6 and 12. Analyses of success used factors identified by ophthalmic experts. Covariates analyzed included patient age, black race, gender, time since diagnosis, primary diagnosis, country, diabetes, mean defect, cup-to-disc (C/D) ratio, suture type, anesthetic, flap type, IOP at listing for surgery, suture release/lysis, needling, reformed anterior chamber, wound leak, severe bleb vascularity, and bleb microcysts. A stepwise logistic regression model found the following predictors of treatment success: PG (odds ratio [OR], 4.11; 95% confidence interval [CI], 1.41-11.99), high C/D ratio (OR, 2.84; 95% CI, 1.15-6.99), and use of a corneal traction suture (OR, 1.67; 95% CI, 1.09-2.56). A negative relationship was found for black race (OR, 0.28; 95% CI, 0.13-0.62); treatment in France (OR, 0.35; 95% CI, 0.17-0.70), Sweden (OR, 0.17; 95% CI, 0.05-0.58), Spain (OR, 0.37; 95% CI, 0.21-0.68), Poland (OR, 0.53; 95% CI, 0.32-0.88), or Hungary (OR, 0.14; 95% CI, 0.06-0.34); and suture release/lysis (OR, 0.34; 95% CI, 0.22-0.53). The effect of needling was marginally statistically significant (OR, 0.56; 95% CI, 0.31-1.01). Successful trabeculectomy outcome was associated with PG, higher C/D ratio, and corneal traction suturing. Factors associated with surgical failure were black race and suture release/lysis. Intercountry differences also were observed.

Antiretroviral treatment outcome in HIV-1-infected patients routinely followed up in capital cities and remote areas of Senegal, Mali and Guinea-Conakry.

PubMed

Diouara, Abou Abdallah Malick; Ndiaye, Halimatou Diop; Guindo, Ibrehima; Bangoura, Nestor; Cissé, Mohamed; Edmond, Tchiakpe; Bougoudogo, Flabou; Mboup, Souleymame; Peeters, Martine; Ayouba, Ahidjo; Kane, Ndèye Coumba Touré

2014-01-01

Access to antiretroviral treatment (ART) becomes more and more effective in resource-limited settings (RLS). However, this global effort would be even more profitable if the access to laboratory services especially in decentralized settings was strengthened. We report the virological outcome and HIV-1 drug resistance in three West African countries using dried blood spots (DBS) samples. We included HIV-1-infected adults on ART ≥6 months and followed up in capital cities and decentralized sites in Senegal, Mali and Guinea-Conakry. Patients were consecutively enrolled and DBS were collected in field conditions and kept at ambient temperature before transfer to the reference laboratory. Viral load (VL) was quantified using the NucliSENS EasyQ HIV-1 v1.2. Genotyping of HIV-1 pol gene was performed using in-house protocol. Of the 407 participants, 119, 152 and 136 were from Senegal, Mali and Guinea-Conakry, respectively. The median treatment duration was 36 months [IQR: 6-136]. Virological failure (VF) (VL≥3log10 copies/mL) was observed in 26% (95% confidence interval (CI), 18-35; n=31), 11% (95% CI, 6-17; n=16) and 24% (95% CI, 17-32; n=33) of patients in Senegal, Mali and Guinea-Conakry, respectively (p=0.001). Of samples presenting VL≥3log10 copies/mL (n=80), 70 were successfully genotyped. At least one drug resistance mutation (DRM) was detected in the following proportions: 70% (95% CI, 50-86; n=19), 93% (95% CI, 68-100; n=14) and 68% (95% CI, 48-84; n=19) in Senegal, Mali and Guinea-Conakry, respectively (p=0.22). Twenty-six per cent (26%; 95% CI, 16-38; n=18) of patients in VF harboured wild-type viruses, which is likely indicative of weak adherence. Phylogenetic analysis showed the predominance of CRF02_AG subtype (73%; 95% CI, 61-83; n=51). We describe the ART outcome in capital and rural settings of Senegal, Mali and Guinea-Conakry. Our results in all of the three countries highlight the need to reinforce the ART adherence in order to minimize the occurrence of drug resistance. In addition, these findings provide additional evidence that the use of DBS as a sampling support could assist virological monitoring of patients on ART in remote areas.

Diagnostic protocol for gestational diabetes mellitus (GDM) (IADPSG/ADA, 2011): influence on the occurrence of GDM and mild gestational hyperglycemia (MGH) and on the perinatal outcomes.

PubMed

Sirimarco, Mariana Pinto; Guerra, Helena Maciel; Lisboa, Eduardo Guimarães; Vernini, Joice Monalisa; Cassetari, Bianca Nicolosi; de Araujo Costa, Roberto Antonio; Rudge, Marilza Vieira Cunha; de Mattos Paranhos Calderon, Iracema

2017-01-01

In August 2011, the Specialized Center for Diabetes and Pregnancy of the Botucatu Medical School/Unesp adopted a new diagnostic protocol for gestational diabetes mellitus, recommended by the American Diabetes Association and the International Association of the Diabetes and Pregnancy Study Group. The glycemic profile was evaluated using the 75-g oral glucose tolerance test (OGTT) used to diagnose mild gestational hyperglycemia, recognized and treated in our department as gestational diabetes mellitus. The cost-effectiveness of the new guidelines and the continued need for the evaluation of the glycemic profile, as part of our Service protocol, are controversial and require further investigation. We aimed to assess the impact of the new guidelines on the evaluation of mild gestational hyperglycemia and gestational diabetes mellitus, the incidence of adverse perinatal outcomes, and the association between the 75-g OGTT and the glycemic profile for the diagnosis of mild gestational hyperglycemia. This cross-sectional study was performed identifying a convenience sample of pregnant women and their newborns. The women used our Service for diagnostic procedures, prenatal care and delivery, both before (January 2008 to August 14, 2011) and after (August 15, 2011 to December 2014) the protocol modification. The following variables were compared, following stratification according to diagnostic protocol: prevalence of gestational diabetes mellitus and mild gestational hyperglycemia, newborns large for gestational age, macrosomia, first cesarean delivery, and newborn hospital stay. Statistical analysis was performed using Poisson regression, the Student's t test, the Chi square or Fisher's exact test and risk estimate. The statistical significance threshold was set at 95% (p < 0.05). The new protocol resulted in an 85% increase in the number of women with GDM, but failed to identify 17.3% of pregnant women classified as having mild gestational hyperglycemia, despite a normal 75-g OGTT. The new guidelines did not affect perinatal outcome. These results support the validity of maintaining the glycemic profile as part of the diagnostic protocol at our hospital. Large multicenter studies with an adequate sample size are required for conclusive evidence on the cost-effectiveness of the new protocol.

Identification of PSD-95 Depalmitoylating Enzymes.

PubMed

Yokoi, Norihiko; Fukata, Yuko; Sekiya, Atsushi; Murakami, Tatsuro; Kobayashi, Kenta; Fukata, Masaki

2016-06-15

Postsynaptic density (PSD)-95, the most abundant postsynaptic scaffolding protein, plays a pivotal role in synapse development and function. Continuous palmitoylation cycles on PSD-95 are essential for its synaptic clustering and regulation of AMPA receptor function. However, molecular mechanisms for palmitate cycling on PSD-95 remain incompletely understood, as PSD-95 depalmitoylating enzymes remain unknown. Here, we isolated 38 mouse or rat serine hydrolases and found that a subset specifically depalmitoylated PSD-95 in heterologous cells. These enzymes showed distinct substrate specificity. α/β-Hydrolase domain-containing protein 17 members (ABHD17A, 17B, and 17C), showing the strongest depalmitoylating activity to PSD-95, showed different localization from other candidates in rat hippocampal neurons, and were distributed to recycling endosomes, the dendritic plasma membrane, and the synaptic fraction. Expression of ABHD17 in neurons selectively reduced PSD-95 palmitoylation and synaptic clustering of PSD-95 and AMPA receptors. Furthermore, taking advantage of the acyl-PEGyl exchange gel shift (APEGS) method, we quantitatively monitored the palmitoylation stoichiometry and the depalmitoylation kinetics of representative synaptic proteins, PSD-95, GluA1, GluN2A, mGluR5, Gαq, and HRas. Unexpectedly, palmitate on all of them did not turn over in neurons. Uniquely, most of the PSD-95 population underwent rapid palmitoylation cycles, and palmitate cycling on PSD-95 decelerated accompanied by its increased stoichiometry as synapses developed, probably contributing to postsynaptic receptor consolidation. Finally, inhibition of ABHD17 expression dramatically delayed the kinetics of PSD-95 depalmitoylation. This study suggests that local palmitoylation machinery composed of synaptic DHHC palmitoylating enzymes and ABHD17 finely controls the amount of synaptic PSD-95 and synaptic function. Protein palmitoylation, the most common lipid modification, dynamically regulates neuronal protein localization and function. Its unique reversibility is conferred by DHHC-type palmitoyl acyl transferases (palmitoylating enzymes) and still controversial palmitoyl-protein thioesterases (depalmitoylating enzymes). Here, we identified the membrane-anchored serine hydrolases, ABHD17A, 17B, and 17C, as the physiological PSD-95 depalmitoylating enzymes that regulate PSD-95 palmitoylation cycles in neurons. This study describes the first direct evidence for the neuronal depalmitoylating enzyme and provides a new aspect of the dynamic regulatory mechanisms of synaptic development and synaptic plasticity. In addition, our established APEGS assay, which provides unbiased and quantitative information about the palmitoylation state and dynamics, revealed the distinct regulatory mechanisms for synaptic palmitoylation. Copyright © 2016 Yokoi, Fukata et al.

Identification of PSD-95 Depalmitoylating Enzymes

PubMed Central

Yokoi, Norihiko; Sekiya, Atsushi; Murakami, Tatsuro; Kobayashi, Kenta

2016-01-01

Postsynaptic density (PSD)-95, the most abundant postsynaptic scaffolding protein, plays a pivotal role in synapse development and function. Continuous palmitoylation cycles on PSD-95 are essential for its synaptic clustering and regulation of AMPA receptor function. However, molecular mechanisms for palmitate cycling on PSD-95 remain incompletely understood, as PSD-95 depalmitoylating enzymes remain unknown. Here, we isolated 38 mouse or rat serine hydrolases and found that a subset specifically depalmitoylated PSD-95 in heterologous cells. These enzymes showed distinct substrate specificity. α/β-Hydrolase domain-containing protein 17 members (ABHD17A, 17B, and 17C), showing the strongest depalmitoylating activity to PSD-95, showed different localization from other candidates in rat hippocampal neurons, and were distributed to recycling endosomes, the dendritic plasma membrane, and the synaptic fraction. Expression of ABHD17 in neurons selectively reduced PSD-95 palmitoylation and synaptic clustering of PSD-95 and AMPA receptors. Furthermore, taking advantage of the acyl-PEGyl exchange gel shift (APEGS) method, we quantitatively monitored the palmitoylation stoichiometry and the depalmitoylation kinetics of representative synaptic proteins, PSD-95, GluA1, GluN2A, mGluR5, Gαq, and HRas. Unexpectedly, palmitate on all of them did not turn over in neurons. Uniquely, most of the PSD-95 population underwent rapid palmitoylation cycles, and palmitate cycling on PSD-95 decelerated accompanied by its increased stoichiometry as synapses developed, probably contributing to postsynaptic receptor consolidation. Finally, inhibition of ABHD17 expression dramatically delayed the kinetics of PSD-95 depalmitoylation. This study suggests that local palmitoylation machinery composed of synaptic DHHC palmitoylating enzymes and ABHD17 finely controls the amount of synaptic PSD-95 and synaptic function. SIGNIFICANCE STATEMENT Protein palmitoylation, the most common lipid modification, dynamically regulates neuronal protein localization and function. Its unique reversibility is conferred by DHHC-type palmitoyl acyl transferases (palmitoylating enzymes) and still controversial palmitoyl-protein thioesterases (depalmitoylating enzymes). Here, we identified the membrane-anchored serine hydrolases, ABHD17A, 17B, and 17C, as the physiological PSD-95 depalmitoylating enzymes that regulate PSD-95 palmitoylation cycles in neurons. This study describes the first direct evidence for the neuronal depalmitoylating enzyme and provides a new aspect of the dynamic regulatory mechanisms of synaptic development and synaptic plasticity. In addition, our established APEGS assay, which provides unbiased and quantitative information about the palmitoylation state and dynamics, revealed the distinct regulatory mechanisms for synaptic palmitoylation. PMID:27307232

47 CFR 9.5 - E911 Service.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 1 2014-10-01 2014-10-01 false E911 Service. 9.5 Section 9.5 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL INTERCONNECTED VOICE OVER INTERNET PROTOCOL SERVICES § 9.5 E911 Service. (a) Scope of Section. The following requirements are only applicable to providers of...

47 CFR 9.5 - E911 Service.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 1 2013-10-01 2013-10-01 false E911 Service. 9.5 Section 9.5 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL INTERCONNECTED VOICE OVER INTERNET PROTOCOL SERVICES § 9.5 E911 Service. (a) Scope of Section. The following requirements are only applicable to providers of...

47 CFR 9.5 - E911 Service.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 1 2012-10-01 2012-10-01 false E911 Service. 9.5 Section 9.5 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL INTERCONNECTED VOICE OVER INTERNET PROTOCOL SERVICES § 9.5 E911 Service. (a) Scope of Section. The following requirements are only applicable to providers of...

Prognostic Value of Abnormal p53 Expression in Locally Advanced Prostate Cancer Treated With Androgen Deprivation and Radiotherapy: A Study Based on RTOG 9202

DOE Office of Scientific and Technical Information (OSTI.GOV)

Che Mingxin; DeSilvio, Michelle; Pollack, Alan

2007-11-15

Purpose: The goal of this study was to verify the significance of p53 as a prognostic factor in Radiation Therapy Oncology Group 9202, which compared short-term androgen deprivation (STAD) with radiation therapy (RT) to long-term androgen deprivation + RT in men with locally advanced prostate cancer (Pca). Methods and Materials: Tumor tissue was sufficient for p53 analysis in 777 cases. p53 status was determined by immunohistochemistry. Abnormal p53 expression was defined as 20% or more tumor cells with positive nuclei. Univariate and multivariate Cox proportional hazards models were used to evaluate the relationships of p53 status to patient outcomes. Results:more » Abnormal p53 was detected in 168 of 777 (21.6%) cases, and was significantly associated with cause-specific mortality (adjusted hazard ratio [HR] = 1.89; 95% confidence interval (CI) 1.14 - 3.14; p = 0.014) and distant metastasis (adjusted HR = 1.72; 95% CI 1.13-2.62; p = 0.013). When patients were divided into subgroups according to assigned treatment, only the subgroup of patients who underwent STAD + RT showed significant correlation between p53 status and cause-specific mortality (adjusted HR = 2.43; 95% CI = 1.32-4.49; p = 0.0044). When patients were divided into subgroups according to p53 status, only the subgroup of patients with abnormal p53 showed significant association between assigned treatment and cause-specific mortality (adjusted HR = 3.81; 95% CI 1.40-10.37; p = 0.0087). Conclusions: Abnormal p53 is a significant prognostic factor for patients with prostate cancer who undergo short-term androgen deprivation and radiotherapy. Long-term androgen deprivation may significantly improve the cause-specific survival for those with abnormal p53.« less

Addition of docetaxel or bisphosphonates to standard of care in men with localised or metastatic, hormone-sensitive prostate cancer: a systematic review and meta-analyses of aggregate data

PubMed Central

Vale, Claire L; Burdett, Sarah; Rydzewska, Larysa H M; Albiges, Laurence; Clarke, Noel W; Fisher, David; Fizazi, Karim; Gravis, Gwenaelle; James, Nicholas D; Mason, Malcolm D; Parmar, Mahesh K B; Sweeney, Christopher J; Sydes, Matthew R; Tombal, Bertrand; Tierney, Jayne F

2016-01-01

Summary Background Results from large randomised controlled trials combining docetaxel or bisphosphonates with standard of care in hormone-sensitive prostate cancer have emerged. In order to investigate the effects of these therapies and to respond to emerging evidence, we aimed to systematically review all relevant trials using a framework for adaptive meta-analysis. Methods For this systematic review and meta-analysis, we searched MEDLINE, Embase, LILACS, and the Cochrane Central Register of Controlled Trials, trial registers, conference proceedings, review articles, and reference lists of trial publications for all relevant randomised controlled trials (published, unpublished, and ongoing) comparing either standard of care with or without docetaxel or standard of care with or without bisphosphonates for men with high-risk localised or metastatic hormone-sensitive prostate cancer. For each trial, we extracted hazard ratios (HRs) of the effects of docetaxel or bisphosphonates on survival (time from randomisation until death from any cause) and failure-free survival (time from randomisation to biochemical or clinical failure or death from any cause) from published trial reports or presentations or obtained them directly from trial investigators. HRs were combined using the fixed-effect model (Mantel-Haenzsel). Findings We identified five eligible randomised controlled trials of docetaxel in men with metastatic (M1) disease. Results from three (CHAARTED, GETUG-15, STAMPEDE) of these trials (2992 [93%] of 3206 men randomised) showed that the addition of docetaxel to standard of care improved survival. The HR of 0·77 (95% CI 0·68–0·87; p<0·0001) translates to an absolute improvement in 4-year survival of 9% (95% CI 5–14). Docetaxel in addition to standard of care also improved failure-free survival, with the HR of 0·64 (0·58–0·70; p<0·0001) translating into a reduction in absolute 4-year failure rates of 16% (95% CI 12–19). We identified 11 trials of docetaxel for men with locally advanced disease (M0). Survival results from three (GETUG-12, RTOG 0521, STAMPEDE) of these trials (2121 [53%] of 3978 men) showed no evidence of a benefit from the addition of docetaxel (HR 0·87 [95% CI 0·69–1·09]; p=0·218), whereas failure-free survival data from four (GETUG-12, RTOG 0521, STAMPEDE, TAX 3501) of these trials (2348 [59%] of 3978 men) showed that docetaxel improved failure-free survival (0·70 [0·61–0·81]; p<0·0001), which translates into a reduced absolute 4-year failure rate of 8% (5–10). We identified seven eligible randomised controlled trials of bisphosphonates for men with M1 disease. Survival results from three of these trials (2740 [88%] of 3109 men) showed that addition of bisphosphonates improved survival (0·88 [0·79–0·98]; p=0·025), which translates to 5% (1–8) absolute improvement, but this result was influenced by the positive result of one trial of sodium clodronate, and we found no evidence of a benefit from the addition of zoledronic acid (0·94 [0·83–1·07]; p=0·323), which translates to an absolute improvement in survival of 2% (−3 to 7). Of 17 trials of bisphosphonates for men with M0 disease, survival results from four trials (4079 [66%] of 6220 men) showed no evidence of benefit from the addition of bisphosphonates (1·03 [0·89–1·18]; p=0·724) or zoledronic acid (0·98 [0·82–1·16]; p=0·782). Failure-free survival definitions were too inconsistent for formal meta-analyses for the bisphosphonate trials. Interpretation The addition of docetaxel to standard of care should be considered standard care for men with M1 hormone-sensitive prostate cancer who are starting treatment for the first time. More evidence on the effects of docetaxel on survival is needed in the M0 disease setting. No evidence exists to suggest that zoledronic acid improves survival in men with M1 or M0 disease, and any potential benefit is probably small. Funding Medical Research Council UK. PMID:26718929

Sources of Variability in the Detection of B-Lines, Using Lung Ultrasound.

PubMed

Pivetta, Emanuele; Baldassa, Federico; Masellis, Serena; Bovaro, Federica; Lupia, Enrico; Maule, Milena M

2018-06-01

Lung ultrasound (LUS) is a largely employed diagnostic tool but an operational protocol for implementation has never been proposed. The lack of standardization clearly introduces variability in LUS results. We enrolled adult patients presenting for acute dyspnea with a clinical suspect of etiology related to heart failure. We calculated agreement among four providers in assessing B-lines. We varied probes, depth, evaluation time and scanning areas and we estimated the importance of each factors on B-lines assessment. Overall agreement among raters varied from a kappa of 0.70 to 0.81. The mean number of B-lines was 5.44 (95% confidence interval, CI, 4.1-6.8). This estimate did not suffer variation by the depth used (0.03, 95% CI -0.2-0.2, more B-lines, using 19 cm versus 10 cm). The use of a convex probe and expertise in LUS reduced the number of artifacts by 1.7 (95% CI 1.5-1.9) and 1.1 in comparison with a phased array probe and naive operators. Evaluation time increased estimates by 1.2 (95% CI 1-1.5) and 2.9 (95% CI 2.7-3.9) B-lines for 4" and 7" clips (reference was 2" clips). This study suggests that the probe, the evaluation time and the level of expertise might affect the results of quantitative assessment of B-lines. Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

Reliability and Validity of the Inline Skating Skill Test

PubMed Central

Radman, Ivan; Ruzic, Lana; Padovan, Viktoria; Cigrovski, Vjekoslav; Podnar, Hrvoje

2016-01-01

This study aimed to examine the reliability and validity of the inline skating skill test. Based on previous skating experience forty-two skaters (26 female and 16 male) were randomized into two groups (competitive level vs. recreational level). They performed the test four times, with a recovery time of 45 minutes between sessions. Prior to testing, the participants rated their skating skill using a scale from 1 to 10. The protocol included performance time measurement through a course, combining different skating techniques. Trivial changes in performance time between the repeated sessions were determined in both competitive females/males and recreational females/males (-1.7% [95% CI: -5.8–2.6%] – 2.2% [95% CI: 0.0–4.5%]). In all four subgroups, the skill test had a low mean within-individual variation (1.6% [95% CI: 1.2–2.4%] – 2.7% [95% CI: 2.1–4.0%]) and high mean inter-session correlation (ICC = 0.97 [95% CI: 0.92–0.99] – 0.99 [95% CI: 0.98–1.00]). The comparison of detected typical errors and smallest worthwhile changes (calculated as standard deviations × 0.2) revealed that the skill test was able to track changes in skaters’ performances. Competitive-level skaters needed shorter time (24.4–26.4%, all p < 0.01) to complete the test in comparison to recreational-level skaters. Moreover, moderate correlation (ρ = 0.80–0.82; all p < 0.01) was observed between the participant’s self-rating and achieved performance times. In conclusion, the proposed test is a reliable and valid method to evaluate inline skating skills in amateur competitive and recreational level skaters. Further studies are needed to evaluate the reproducibility of this skill test in different populations including elite inline skaters. Key points Study evaluated the reliability and construct validity of a newly developed inline skating skill test. Evaluated test is a first protocol designed to assess specific inline skating skill. Two groups of amateur skaters with different skating proficiency repeated the skill test in four separate occasions. The results suggest that evaluated test is reliable and valid to evaluate inline skating skill in amateur skaters. PMID:27803616

A novel protocol for dispatcher assisted CPR improves CPR quality and motivation among rescuers-A randomized controlled simulation study.

PubMed

Rasmussen, Stinne Eika; Nebsbjerg, Mette Amalie; Krogh, Lise Qvirin; Bjørnshave, Katrine; Krogh, Kristian; Povlsen, Jonas Agerlund; Riddervold, Ingunn Skogstad; Grøfte, Thorbjørn; Kirkegaard, Hans; Løfgren, Bo

2017-01-01

Emergency dispatchers use protocols to instruct bystanders in cardiopulmonary resuscitation (CPR). Studies changing one element in the dispatcher's protocol report improved CPR quality. Whether several changes interact is unknown and the effect of combining multiple changes previously reported to improve CPR quality into one protocol remains to be investigated. We hypothesize that a novel dispatch protocol, combining multiple beneficial elements improves CPR quality compared with a standard protocol. A novel dispatch protocol was designed including wording on chest compressions, using a metronome, regular encouragements and a 10-s rest each minute. In a simulated cardiac arrest scenario, laypersons were randomized to perform single-rescuer CPR guided with the novel or the standard protocol. a composite endpoint of time to first compression, hand position, compression depth and rate and hands-off time (maximum score: 22 points). Afterwards participants answered a questionnaire evaluating the dispatcher assistance. The novel protocol (n=61) improved CPR quality score compared with the standard protocol (n=64) (mean (SD): 18.6 (1.4)) points vs. 17.5 (1.7) points, p<0.001. The novel protocol resulted in deeper chest compressions (mean (SD): 58 (12)mm vs. 52 (13)mm, p=0.02) and improved rate of correct hand position (61% vs. 36%, p=0.01) compared with the standard protocol. In both protocols hands-off time was short. The novel protocol improved motivation among rescuers compared with the standard protocol (p=0.002). Participants guided with a standard dispatch protocol performed high quality CPR. A novel bundle of care protocol improved CPR quality score and motivation among rescuers. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Meta-analysis of breast cancer mortality benefit and overdiagnosis adjusted for adherence: improving information on the effects of attending screening mammography

PubMed Central

Jacklyn, Gemma; Glasziou, Paul; Macaskill, Petra; Barratt, Alexandra

2016-01-01

Background: Women require information about the impact of regularly attending screening mammography on breast cancer mortality and overdiagnosis to make informed decisions. To provide this information we aimed to meta-analyse randomised controlled trials adjusted for adherence to the trial protocol. Methods: Nine screening mammography trials used in the Independent UK Breast Screening Report were selected. Extending an existing approach to adjust intention-to-treat (ITT) estimates for less than 100% adherence rates, we conducted a random-effects meta-analysis. This produced a combined deattenuated prevented fraction and a combined deattenuated percentage risk of overdiagnosis. Results: In women aged 39–75 years invited to screen, the prevented fraction of breast cancer mortality at 13-year follow-up was 0.22 (95% CI 0.15–0.28) and it increased to 0.30 (95% CI 0.18–0.42) with deattenuation. In women aged 40–69 years invited to screen, the ITT percentage risk of overdiagnosis during the screening period was 19.0% (95% CI 15.2–22.7%), deattenuation increased this to 29.7% (95% CI 17.8–41.5%). Conclusions: Adjustment for nonadherence increased the size of the mortality benefit and risk of overdiagnosis by up to 50%. These estimates are more appropriate when developing quantitative information to support individual decisions about attending screening mammography. PMID:27124337

Prevention of persistent human papillomavirus infection by an HPV16/18 vaccine: a community-based randomized clinical trial in Guanacaste, Costa Rica.

PubMed

Herrero, Rolando; Wacholder, Sholom; Rodríguez, Ana C; Solomon, Diane; González, Paula; Kreimer, Aimee R; Porras, Carolina; Schussler, John; Jiménez, Silvia; Sherman, Mark E; Quint, Wim; Schiller, John T; Lowy, Douglas R; Schiffman, Mark; Hildesheim, Allan

2011-10-01

Target groups for human papillomavirus (HPV) vaccination are controversial. We evaluated vaccine efficacy (VE) against 1-year persistent infection, stratified by age and sexual behavior, among young women in Costa Rica. We randomized 7,466 healthy women 18 to 25 years of age to HPV16/18 or hepatitis A vaccine (follow-up, 50.4 months). According-to-protocol (ATP) cohorts included compliant HPV-negative women; intention-to-treat (ITT) included all randomized women. ATP VE was 90.9% (95% CI, 82.0-95.9) against HPV16/18 infections, 44.5% against HPV31/33/45 (95% CI, 17.5-63.1), and 12.4% (95% CI, -3.2 to 25.6) against any oncogenic infection. Overall ITT VE against HPV16/18 infections was 49.0%, but ATP and ITT VE almost reached 100% in year 4 of follow-up. ATP efficacy against HPV16/18 was similar by age, but ITT VE was greatest among youngest women (68.9% among those 18-19 years of age; 21.8% among those 24-25 years of age) and 79.8% among virgins. Among previously unexposed women, vaccination is highly efficacious against HPV16/18 and partially against HPV31/33/45. Vaccination is most effective in women and girls before they initiate sexual activity, with programmatic and individual decision implications.

Isolation and characterization of bacteriophages of Salmonella enterica serovar Pullorum.

PubMed

Bao, H; Zhang, H; Wang, R

2011-10-01

In this study, 2 bacteriophages of Salmonella Pullorum were isolated using an enrichment protocol and the double agar layer method. They were named PSPu-95 and PSPu-4-116, respectively, against clinical isolates of Salmonella Pullorum SPu-95 and SPu-116. The host ranges of the 2 bacteriophages were determined by performing spot tests with 20 bacteria strains. Both bacteriophages had wide host ranges. Bacteriophage PSPu-95 had a lytic effect on 17 of the 20 isolates (85%), and PSPu-4-116 produced a lytic effect on 14 isolates (70%) and was the only bacteriophage that produced a clear plaque on enterotoxigenic Escherichia coli K88. Transmission electron microscopy revealed the bacteriophages belonged to the order Caudovirales. Bacteriophage PSPu-95 was a member of the family Siphoviridae, but bacteriophage PSPu-4-116 belonged to the family Myoviridae. Both had a double-stranded DNA, which was digested with HindIII or EcoRI, that was estimated to be 58.3 kbp (PSPu-95) and 45.2 kbp (PSPu-4-116) by 1% agar electrophoresis. One-step growth kinetics showed that the latent periods were all less than 20 min, and the burst size was 77.5 pfu/cell for PSPu-95 and 86 pfu/cell for PSPu-4-116. The bacteriophages were able to survive in a pH range between 4 and 10, and they were able to survive in a treatment of 70°C for 60 min. The characterizations of these 2 bacteriophages were helpful in establishing a basis for adopting the most effective bacteriophage to control bacteria in the poultry industry.

Sustained Benefit at 2 Years for Covered Stents Versus Bare-Metal Stents in Long SFA Lesions: The VIASTAR Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lammer, Johannes, E-mail: jlammer@gmx.at, E-mail: johannes.lammer@meduniwien.ac.at; Zeller, Thomas, E-mail: thomas.zeller@universitaets-herzzentrum.de; Hausegger, Klaus A., E-mail: klaus.hausegger@lkh-klu.at

PurposeThe hypothesis that covered stents are superior to bare-metal stents (BMS) in long femoropopliteal artery disease was tested. The one-year results of the VIASTAR trial revealed a patency benefit of covered stents in the treatment-per-protocol (TPP) analysis only.MethodsA prospective, randomized, single-blind, multicenter study evaluated 141 patients with symptomatic peripheral arterial disease (PAD) after treatment with heparin-bonded covered stents (VIABAHN{sup ®} Endoprosthesis) or BMS. Clinical outcomes and patency rates were assessed at 1, 6, 12, and 24 months. Mean lesion length was 19.0 ± 6.3 cm in the VIABAHN{sup ®} versus 17.3 ± 6.6 cm in the BMS group.ResultsThe 24-month primary patency rates in the VIABAHN{sup ®} andmore » BMS group were: intention-to-treat 63.1 (95 % CI 0.52–0.76) versus 41.2 % (95 % CI 0.29–0.57; log rank p = 0.04) and TPP 69.4 (95 % CI 0.58–0.83) versus 40.0 % (95 % CI 0.28–0.56; log rank p = 0.004). Freedom from target-lesion-revascularization (TLR) was 79.4 (95 % CI 0.70–0.90) versus 73.0 % (95 % CI 0.63–0.85) for VIABAHN{sup ®} versus BMS (log rank p = 0.37). For the TPP group in lesions ≥20 cm, the 24-month patency rates were 65.2 (95 % CI 0.50–0.85) versus 26.7 % (95 % CI 0.12–0.59; log rank p = 0.004) for VIABAHN{sup ®} versus BMS, and freedom from TLR was 80.0 (95 % CI 0.68–0.94) versus 61.9 % (95 % CI 0.44–0.87; log rank p = 0.13). The ankle brachial index was 0.89 ± 0.18 versus 0.91 ± 0.17 (p = 0.76) at 24-month in the VIABAHN{sup ®} versus the BMS group, respectively.ConclusionAt 24-month, this trial in PAD patients with long femoropopliteal lesions demonstrated a significantly improved primary patency rate for heparin-bonded covered stents compared to BMS, however, without a significant impact on clinical outcomes and TLR rate (Reg. Nr. ISRCTN48164244)« less

Implementation of an Intensive Care Unit-Specific Alcohol Withdrawal Syndrome Management Protocol Reduces the Need for Mechanical Ventilation.

PubMed

Heavner, Jason J; Akgün, Kathleen M; Heavner, Mojdeh S; Eng, Claire C; Drew, Matthew; Jackson, Peter; Pritchard, David; Honiden, Shyoko

2018-05-25

Alcohol use disorders are prevalent and put patients at risk for developing alcohol withdrawal syndrome (AWS). Treatment of AWS with a symptom-triggered protocol standardizes management and may avoid AWS-related complications. The objective of this study was to evaluate whether implementation of an intensive care unit (ICU)-specific, symptom-triggered protocol for management of AWS was associated with improved clinical outcomes and, in particular, would reduce the risk of patients with AWS requiring mechanical ventilation. Retrospective pre-post-protocol implementation study. Thirty-six-bed, closed medical ICU (MICU) at a large, tertiary care, teaching hospital in an urban setting. A total of 233 adults admitted to the MICU with any diagnosis of alcohol use disorders based on International Classification of Diseases, Ninth Revision codes and who received at least one dose of any benzodiazepine; of these patients, 139 were in the pre-protocol era (August 2009-January 2010 and August 2010-January 2011), and 94 were in the post-protocol era (August 2012-January 2013), after implementation of the Yale Alcohol Withdrawal Protocol (YAWP) in April 2012. The YAWP pairs a modified Minnesota Detoxification Scale with an order set that includes benzodiazepine dosing regimens and suggests adjuvant therapies. AWS was the primary reason for ICU admission (107/233 patients [45.9%]) and did not significantly vary between eras (P=0.2). Of the 233 patients included, 81.1% were male and 67.0% were white, which did not significantly differ by study era. Severity of illness at MICU admission did not significantly differ between patients in the pre-protocol and post-protocol eras (median [interquartile range] Acute Physiology and Chronic Health Evaluation [APACHE] II scores of 12 [9-17] and 12.5 [7-16], respectively, p=0.4). Median lorazepam-equivalent dose per MICU day, duration of benzodiazepine infusion, and use of adjuvant therapy were not significantly different between eras. MICU intubation was less common in the post-protocol era (36/139 patients [25.9%] pre-protocol vs 8/94 patients [8.5%] post-protocol, p=0.0009). ICU-related pneumonia was also decreased in the post-protocol era (30/139 patients [21.6%] pre-protocol vs 10/94 patients [10.6%] post-protocol, p=0.03). After adjusting for demographics, adjuvant therapies, and Acute Physiology and Chronic Health Evaluation II scores, protocol implementation was associated with a decreased odds of MICU intubation (odds ratio 0.13; 95% confidence interval 0.04-0.39). Implementation of YAWP was associated with a decreased risk of MICU intubation in patients at risk for AWS. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Protocol deviations before and after IV tPA in community hospitals

PubMed Central

Adelman, Eric E.; Scott, Phillip A.; Skolarus, Lesli E.; Fox, Allison K.; Frederiksen, Shirley M.; Meurer, William J.

2015-01-01

Background Protocol deviations before and after tPA treatment for ischemic stroke are common. It is unclear if patient or hospital factors predict protocol deviations. We examined predictors of protocol deviations and the effects of protocol violations on symptomatic intracerebral hemorrhage. Methods We used data from the INSTINCT trial, a cluster-randomized, controlled trial evaluating the efficacy of a barrier assessment and educational intervention to increase appropriate tPA use in 24 Michigan community hospitals, to review tPA treatments between 2007 and 2010. Protocol violations were defined as deviations from the standard tPA protocol, both before and after treatment. Multi-level logistic regression models were fitted to determine if patient and hospital variables were associated with pre-treatment or post-treatment protocol deviations. Results During the study, 557 patients (mean age 70; 52% male; median NIHSS 12) were treated with tPA. Protocol deviations occurred in 233 (42%) patients: 16% had pre-treatment deviations, 35% had post-treatment deviations, and 9% had both. The most common protocol deviations included elevated post-treatment blood pressure, antithrombotic agent use within 24 hours of treatment, and elevated pre-treatment blood pressure. Protocol deviations were not associated with symptomatic intracerebral hemorrhage, stroke severity, or hospital factors. Older age was associated with pre-treatment protocol deviations (adjusted OR 0.52; 95% confidence interval 0.30-0.92). Pre-treatment deviations were associated with post-treatment deviations (adjusted OR 3.20; 95% confidence interval 1.91-5.35). Conclusions Protocol deviations were not associated with symptomatic intracerebral hemorrhage. Aside from age, patient and hospital factors were not associated with protocol deviations. PMID:26419527

A comparative study of two protocols for treadmill walking exercise testing in ambulating subjects with incomplete spinal cord injury.

PubMed

Lundgaard, E; Wouda, M F; Strøm, V

2017-10-01

This is a comparative study of two exercise testing protocols. The objective of this study was to compare maximal oxygen uptake (VO 2 max) and achieved criteria for maximal exercise testing between the Sunnaas Protocol-a newly designed treadmill exercise test protocol-and the Modified Bruce Protocol in persons with incomplete spinal cord injury (SCI). This study was conducted in Sunnaas Rehabilitation Hospital, Norway. Twenty persons (19 men) with incomplete SCI (AIS D) capable of ambulating without assistive devices performed two treadmill walking exercise tests (Sunnaas Protocol and Modified Bruce Protocol) until exhaustion 1-3 days apart. The key differences between the protocols are the smaller increments in speed and shorter duration on each workload in the Sunnaas Protocol. Cardiovascular responses were measured continuously throughout both tests. The subjects exhibited statistically significantly higher VO 2 max when using the Sunnaas Protocol (37.1±9.9 vs 35.4±9.8 ml kg -1  min -1 , P=0.01), with a mean between-test difference of 1.8 ml kg -1  min -1 (95% confidence interval: 0.49-3.16). There was no significant difference in mean maximal heart rate (HR max). Nineteen (95%) subjects achieved at least three of the four criteria for maximal oxygen uptake using the Sunnaas Protocol. Thirteen (65%) subjects achieved at least three of the criteria using a Modified Bruce protocol. The small differences in both VO 2 max and achieved criteria in favor of the Sunnaas Protocol suggest that it could be a useful alternative treadmill exercise test protocol for ambulating persons with incomplete SCI.

A stepwise protocol for the treatment of refractory gastroesophageal reflux-induced chronic cough

PubMed Central

Xu, Xianghuai; Lv, Hanjing; Yu, Li; Chen, Qiang; Liang, Siwei

2016-01-01

Background Refractory gastroesophageal reflux-induced chronic cough (GERC) is difficult to manage. The purpose of the study is to evaluate the efficacy of a novel stepwise protocol for treating this condition. Methods A total of 103 consecutive patients with suspected refractory reflux-induced chronic cough failing to a standard anti-reflux therapy were treated with a stepwise therapy. Treatment commences with high-dose omeprazole and, if necessary, is escalated to subsequent sequential treatment with ranitidine and finally baclofen. The primary end-point was overall cough resolution, and the secondary end-point was cough resolution after each treatment step. Results High-dose omeprazole eliminated or improved cough in 28.1% of patients (n=29). Further stepwise of treatment with the addition of ranitide yielded a favorable response in an additional 12.6% (n=13) of patients, and subsequent escalation to baclofen provoked response in another 36.9% (n=38) of patients. Overall, this stepwise protocol was successful in 77.6% (n=80) of patients. The diurnal cough symptom score fell from 3 [1] to 1 [0] (Z=6.316, P=0.000), and the nocturnal cough symptom score decreased from 1 [1] to 0 [1] (Z=–4.511, P=0.000), with a corresponding reduction in the Gastroesophageal Reflux Diagnostic Questionnaire score from 8.6±1.7 to 6.8±0.7 (t=3.612, P=0.000). Conversely, the cough threshold C2 to capsaicin was increased from 0.49 (0.49) µmol/L to 1.95 (2.92) µmol/L (Z=–5.892, P=0.000), and the cough threshold C5 was increased from 1.95 (2.92) µmol/L to 7.8 (5.85) µmol/L (Z=–5.171, P=0.000). Conclusions Sequential stepwise anti-reflux therapy is a useful therapeutic strategy for refractory reflux-induced chronic cough. PMID:26904227

Time-dependent relation between smoking cessation and improved exercise tolerance in apparently healthy middle-age men and women.

PubMed

Berkovitch, Anat; Kivity, Shaye; Klempfner, Robert; Segev, Shlomo; Milwidsky, Assi; Goldenberg, Ilan; Sidi, Yechezkel; Maor, Elad

2015-06-01

Smoking is an independent cardiovascular risk factor and correlates with reduced exercise tolerance. However, data on the time dependent effect of smoking cessation on exercise tolerance are limited. We investigated 17,115 men and women who were annually screened at the Institute for Medical Screening of the Chaim Sheba Medical Centre. All subjects had their smoking status documented and performed an exercise stress testing (EST) according to Bruce protocol at each visit. Subjects were divided at baseline into four groups: active smokers (N = 2858), recent quitters (smoking cessation ≤2 years before baseline EST; N = 861), remote quitters (smoking cessation >2 years before the baseline EST; N = 3856) and never smokers (N = 9810). Baseline and follow up EST duration were compared among the four groups. Recent quitters demonstrated a 2.4-fold improvement in their EST duration compared with active smokers (improvement of 24 ± 157 vs. 10 ± 157 s, respectively, p = 0.02). Multivariate logistic regression showed that recent quitters were 26% more likely to improve their exercise tolerance compared with active smokers (95% confidence interval (CI) 1.08-1.47, p = 0.003). Assessing smoking status as a time-dependent covariate during four consecutive visits demonstrated that recent quitters were 17% more likely to improve their exercise tolerance compared with active smokers (95% CI 1.02-1.34, p = 0.02), with a less pronounced benefit among remote quitters (hazard ratio = 1.11, 95% CI 1.02-1.21; p = 0.01). Smoking cessation is independently associated with improved exercise tolerance. The benefits of smoking cessation are evident within the first two years of abstinence. © The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

50 CFR 17.95 - Critical habitat-fish and wildlife.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 50 Wildlife and Fisheries 2 2011-10-01 2011-10-01 false Critical habitat-fish and wildlife. 17.95 Section 17.95 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) TAKING, POSSESSION, TRANSPORTATION, SALE, PURCHASE, BARTER, EXPORTATION, AND IMPORTATION OF WILDLIFE AND PLANTS (CONTINUED)...

50 CFR 17.95 - Critical habitat-fish and wildlife.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 2 2013-10-01 2013-10-01 false Critical habitat-fish and wildlife. 17.95 Section 17.95 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) TAKING, POSSESSION, TRANSPORTATION, SALE, PURCHASE, BARTER, EXPORTATION, AND IMPORTATION OF WILDLIFE AND PLANTS (CONTINUED)...

50 CFR 17.95 - Critical habitat-fish and wildlife.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 50 Wildlife and Fisheries 2 2012-10-01 2012-10-01 false Critical habitat-fish and wildlife. 17.95 Section 17.95 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) TAKING, POSSESSION, TRANSPORTATION, SALE, PURCHASE, BARTER, EXPORTATION, AND IMPORTATION OF WILDLIFE AND PLANTS (CONTINUED)...

50 CFR 17.95 - Critical habitat-fish and wildlife.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 50 Wildlife and Fisheries 2 2014-10-01 2014-10-01 false Critical habitat-fish and wildlife. 17.95 Section 17.95 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) TAKING, POSSESSION, TRANSPORTATION, SALE, PURCHASE, BARTER, EXPORTATION, AND IMPORTATION OF WILDLIFE AND PLANTS (CONTINUED)...

50 CFR 17.95 - Critical habitat-fish and wildlife.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 2 2010-10-01 2010-10-01 false Critical habitat-fish and wildlife. 17.95 Section 17.95 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) TAKING, POSSESSION, TRANSPORTATION, SALE, PURCHASE, BARTER, EXPORTATION, AND IMPORTATION OF WILDLIFE AND PLANTS (CONTINUED)...

Genetic landscape of extreme responders with anaplastic oligodendroglioma.

PubMed

Holdhoff, Matthias; Cairncross, Gregory J; Kollmeyer, Thomas M; Zhang, Ming; Zhang, Peixin; Mehta, Minesh P; Werner-Wasik, Maria; Souhami, Luis; Bahary, Jean-Paul; Kwok, Young; Hartford, Alan C; Chakravarti, Arnab; Yegnasubramanian, Srinivasan; Vogelstein, Bert; Papadopoulos, Nickolas; Kinzler, Kenneth; Jenkins, Robert B; Bettegowda, Chetan

2017-05-30

The NRG Oncology RTOG 9402 trial showed significant survival benefit in patients with 1p/19q co-deleted anaplastic oligodendrogliomas (AO) who received both radiation (RT) and chemotherapy (PCV regimen) versus RT alone. Substantial separation of the survival curves was only seen after 7.3 years. We aimed to determine whether there are specific genetic alterations that distinguish co-deleted AO patients who benefit from the addition of PCV from those who do not. We performed whole exome sequencing on matched tumor and normal DNA from all available short-term (STS) and long-term survivors (LTS) who received RT+PCV. hTERT status and rs55705857 genotypes (G-allele) were analyzed in both cohorts. Six STS (survival of <7.3y) and 7 LTS (survival of ≥7.3y and no progression) had sufficient material for analysis. There was no significant difference between the groups regarding age, performance status and extent of resection. On average, STS had 7 and LTS 4 mutations. Most common mutations in STS vs. LTS were: IDH1 (67 vs. 86%), CIC (50 vs. 71%) and FUBP1 (17 vs. 71%). The hTERT promoter was mutated in 83% STS and 86% LTS. Genotyping of rs55705857 showed a higher prevalence of G allele carriers in LTS than STS (43 vs. 17%). These findings confirm that IDH, CIC, FUBP1 mutations and rs55705857 genotype are common in AO. No distinct genetic signature was identified to differentiate STS and LTS.

Antimicrobial usage and risk of retreatment for mild to moderate clinical mastitis cases on dairy farms following on-farm bacterial culture and selective therapy.

PubMed

McDougall, S; Niethammer, J; Graham, E M

2018-03-01

To assess antimicrobial usage for treatment of mild to moderate clinical mastitis, and risk of retreatment, following implementation of an on-farm bacterial culture system and selective therapy based on culture results, and to assess compliance with treatment decision tree protocols and the level of agreement between results from on-farm culture and laboratory-based microbiology methods. Herdowners from seven dairy herds were asked to collect milk samples from cases of mild to moderate clinical mastitis between July 2015 and May 2016. All samples were cultured on-farm using a commercially available selective media and were also submitted for laboratory-based culture. Within sequential pairs of cows with mastitis, half were assigned to be treated without regard to culture results (Blanket group), and half were treated based on the on-farm culture results (Selective group) according to decision tree diagrams provided to the farmers. Culture results, treatments, and retreatments for clinical mastitis were recorded. The sum of the daily doses of antimicrobials used per cow, the number of retreatments and interval to first retreatment were compared between treatment groups. The geometric mean sum of daily doses for quarters assigned to the Selective (1.72 (95% CI=1.55-1.90)) group was lower than for the Blanket (2.38 (95% CI=2.17-2.60)) group (p=0.005). The percentage of cows retreated for clinical mastitis did not differ between the Selective (21.7 (95% CI=10.5-25.9)%) and Blanket (26.1 (95% CI=20.9-31.3)%) groups (p=0.13), and there was no difference between groups in the hazard that cows would be retreated within 60 days of enrolment (hazard ratio=0.82 (95% CI=0.39-1.69); p=0.59). Compliance with the treatment protocols was higher amongst quarters assigned to the Selective (199/233; 85.4%) compared with the Blanket (171/249; 68.7%) group (p<0.001), and varied between farms from 64-94%. The overall agreement between results from on-farm and laboratory culture was 188/331 (56.9%; kappa=0.31; p<0.001), but varied between farms from 44.7-88.2% (p<0.001). Use of on-farm culture with selective antimicrobial therapy resulted in approximately 25% lower antimicrobial usage, but was not associated with an increase in the proportion of cows retreated for clinical mastitis. This study has demonstrated that on-farm culture and selective therapy based on culture results can be implemented on-farm. However, farms varied in their implementation of both the treatment protocols and microbiology procedures. Where such systems are to be used on-farm, specific training and on-going monitoring is required.

Fast-track cardiac care for adult cardiac surgical patients.

PubMed

Zhu, Fang; Lee, Anna; Chee, Yee Eot

2012-10-17

Fast-track cardiac care is a complex intervention involving several components of care during cardiac anaesthesia and in the postoperative period, all with the ultimate aim of early extubation after surgery, to reduce the length of stay in the intensive care unit and in the hospital. Safe and effective fast-track cardiac care may reduce hospital costs. This is an update of a Cochrane review published in 2003. To update the evidence on the safety and effectiveness of fast-track cardiac care compared to conventional (not fast-track) care in adult patients undergoing cardiac surgery. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 3), MEDLINE (January 1966 to April 2012), EMBASE (January 1980 to April 2012), CINAHL (January 1982 to April 2012), and ISI Web of Science (January 2003 to April 2012). We searched reference lists of articles and contacted experts in the field. All randomized controlled trials of adult cardiac surgical patients (coronary artery bypass grafts, aortic valve replacement, mitral valve replacement) that compared fast-track cardiac care and conventional (not fast-track) care groups were included. We focused on the following fast-track interventions that were designed for early extubation after surgery, administration of low-dose opioid based general anaesthesia during cardiac surgery and the use of a time-directed extubation protocol after surgery. The primary outcome was the risk of mortality. Secondary outcomes included postoperative complications, reintubation within 24 hours of surgery, time to extubation, length of stay in the intensive care unit and in the hospital, quality of life after surgery and hospital costs. Two review authors independently assessed trial quality and extracted the data. Study authors were contacted for additional information. We used a random-effects model and reported relative risk (RR), mean difference (MD) and 95% confidence intervals (95% CI). Twenty-five trials involving 4118 patients were included in the review. There were two studies with a low risk of bias and nine studies with a high risk of bias. There were no differences in the risk of mortality within the first year after surgery between low-dose versus high-dose opioid based general anaesthesia groups (RR 0.58, 95% CI 0.28 to 1.18) and between early extubation protocol versus usual care groups (RR 0.84, 95% CI 0.40 to 1.75).There were no significant differences between low-dose versus high-dose opioid based anaesthesia groups for postoperative complications: myocardial infarction (RR 0.98, 95% CI 0.48 to 1.99), reintubation (RR 1.77, 95% CI 0.38 to 8.27), acute renal failure (RR 1.19, 95% CI 0.33 to 4.33), major bleeding (RR 0.48, 95% CI 0.16 to 1.44), and stroke (RR 1.17, 95% CI 0.36 to 3.78). Compared to the usual care, there were no significant differences in the risk of postoperative complications associated with early extubation: myocardial infarction (RR 0.94, 95% CI 0.55 to 1.60), reintubation (RR 1.91, 95% CI 0.90 to 4.07), acute renal failure (RR 0.77, 95% CI 0.19 to 3.10), major bleeding (RR 0.80, 95% CI 0.45 to 1.44), stroke (RR 0.87, 95% CI 0.31 to 2.46), major sepsis (RR 1.25, 95% CI 0.08 to 19.75) and wound infection (RR 0.67, 95% CI 0.25 to 1.83).Although there were high levels of heterogeneity, both low-dose opioid anaesthesia and the use of time-directed extubation protocols were associated with reductions in the time to extubation (3.0 to 10.5 hours) and in the length of stay in the intensive care unit (0.4 to 8.7 hours). However, these fast-track care interventions were not associated with reductions in the total length of stay in hospital. One high quality cost-effectiveness analysis included in a randomized controlled trial showed that early extubation was likely to be cost-effective. The use of low-dose opioid based general anaesthesia and time-directed protocols for fast-track interventions have similar risks of mortality and major postoperative complications to conventional (not fast-track) care, and therefore appear to be safe in patients considered to be at low to moderate risk. These fast-track interventions reduced the time to extubation and shortened the length of stay in the intensive care unit, but did not reduce the length of stay in the hospital.

Two Different Fatigue Protocols and Lower Extremity Motion Patterns During a Stop-Jump Task

PubMed Central

Quammen, David; Cortes, Nelson; Van Lunen, Bonnie L.; Lucci, Shawn; Ringleb, Stacie I.; Onate, James

2012-01-01

Context: Altered neuromuscular control strategies during fatigue probably contribute to the increased incidence of non-contact anterior cruciate ligament injuries in female athletes. Objective: To determine biomechanical differences between 2 fatigue protocols (slow linear oxidative fatigue protocol [SLO-FP] and functional agility short-term fatigue protocol [FAST-FP]) when performing a running-stop-jump task. Design: Controlled laboratory study. Setting: Laboratory. Patients or Other Participants: A convenience sample of 15 female soccer players (age = 19.2 ±0.8 years, height = 1.67±0.05m, mass = 61.7 + 8.1 kg) without injury participated. Intervention(s): Five successful trials of a running–stop-jump task were obtained prefatigue and postfatigue during the 2 protocols. For the SLO-FP, a peak oxygen consumption (V˙o2peak) test was conducted before the fatigue protocol. Five minutes after the conclusion of the V˙o2peak test, participants started the fatigue protocol by performing a 30-minute interval run. The FAST-FP consisted of 4 sets of a functional circuit. Repeated 2 (fatigue protocol) × 2 (time) analyses of variance were conducted to assess differences between the 2 protocols and time (prefatigue, postfatigue). Main Outcome Measure(s): Kinematic and kinetic measures of the hip and knee were obtained at different times while participants performed both protocols during prefatigue and postfatigue. Results: Internal adduction moment at initial contact (IC) was greater during FAST-FP (0.064 ±0.09 Nm/kgm) than SLO-FP (0.024±0.06 Nm/kgm) (F1,14 = 5.610, P=.03). At IC, participants had less hip flexion postfatigue (44.7°±8.1°) than prefatigue (50.1°±9.5°) (F1,14 = 16.229, P=.001). At peak vertical ground reaction force, participants had less hip flexion postfatigue (44.7°±8.4°) than prefatigue (50.4°±10.3°) (F1,14 = 17.026, P=.001). At peak vertical ground reaction force, participants had less knee flexion postfatigue (−35.9°±6.5°) than prefatigue (−38.8°±5.03°) (F1,14 = 11.537, P=.001). Conclusions: Our results demonstrated a more erect landing posture due to a decrease in hip and knee flexion angles in the postfatigue condition. The changes were similar between protocols; however, the FAST-FP was a clinically applicable 5-minute protocol, whereas the SLO-FP lasted approximately 45 minutes. PMID:22488228

Detection of Acute and Long-Term Effects of Concussion: Dual-Task Gait Balance Control Versus Computerized Neurocognitive Test.

PubMed

Howell, David R; Osternig, Louis R; Chou, Li-Shan

2018-02-16

To examine the acute (within 72h of injury) and long-term (2mo postinjury) independent associations between objective dual-task gait balance and neurocognitive measurements among adolescents and young adults with a concussion and matched controls. Longitudinal case-control. Motion analysis laboratory. A total of 95 participants completed the study: 51 who sustained a concussion (mean age, 17.5±3.3y; 71% men) and 44 controls (mean age, 17.7±2.9y; 72% men). Participants who sustained a concussion underwent a dual-task gait analysis and computerized neurocognitive testing within 72 hours of injury and again 2 months later. Uninjured controls also completed the same test protocol in similar time increments. Not applicable. We compared dual-task gait balance control and computerized neurocognitive test performance between groups using independent samples t tests. Multivariable binary logistic regression models were then constructed for each testing time to determine the association between group membership (concussion vs control), dual-task gait balance control, and neurocognitive function. Medial-lateral center-of-mass displacement during dual-task gait was independently associated with group membership at the initial test (adjusted odds ratio [aOR], 2.432; 95% confidence interval [CI], 1.269-4.661) and 2-month follow-up test (aOR, 1.817; 95% CI, 1.014-3.256) tests. Visual memory composite scores were significantly associated with group membership at the initial hour postinjury time point (aOR, .953; 95% CI, .833-.998). However, the combination of computerized neurocognitive test variables did not predict dual-task gait balance control for participants with concussion, and no single neurocognitive variable was associated with dual-task gait balance control at either testing time. Dual-task assessments concurrently evaluating gait and cognitive performance may allow for the detection of persistent deficits beyond those detected by computerized neurocognitive deficits alone. Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Time to Change Dosing of Inactivated Quadrivalent Influenza Vaccine in Young Children: Evidence From a Phase III, Randomized, Controlled Trial.

PubMed

Jain, Varsha K; Domachowske, Joseph B; Wang, Long; Ofori-Anyinam, Opokua; Rodríguez-Weber, Miguel A; Leonardi, Michael L; Klein, Nicola P; Schlichter, Gary; Jeanfreau, Robert; Haney, Byron L; Chu, Laurence; Harris, Jo-Ann S; Sarpong, Kwabena O; Micucio, Amanda C; Soni, Jyoti; Chandrasekaran, Vijayalakshmi; Li, Ping; Innis, Bruce L

2017-03-01

Children under 3 years of age may benefit from a double-dose of inactivated quadrivalent influenza vaccine (IIV4) instead of the standard-dose. We compared the only United States-licensed standard-dose IIV4 (0.25 mL, 7.5 µg hemagglutinin per influenza strain) versus double-dose IIV4 manufactured by a different process (0.5 mL, 15 µg per strain) in a phase III, randomized, observer-blind trial in children 6-35 months of age (NCT02242643). The primary objective was to demonstrate immunogenic noninferiority of the double-dose for all vaccine strains 28 days after last vaccination. Immunogenic superiority of the double-dose was evaluated post hoc. Immunogenicity was assessed in the per-protocol cohort (N = 2041), and safety was assessed in the intent-to-treat cohort (N = 2424). Immunogenic noninferiority of double-dose versus standard-dose IIV4 was demonstrated in terms of geometric mean titer (GMT) ratio and seroconversion rate difference. Superior immunogenicity against both vaccine B strains was observed with double-dose IIV4 in children 6-17 months of age (GMT ratio = 1.89, 95% confidence interval [CI] = 1.64-2.17, B/Yamagata; GMT ratio = 2.13, 95% CI = 1.82-2.50, B/Victoria) and in unprimed children of any age (GMT ratio = 1.85, 95% CI = 1.59-2.13, B/Yamagata; GMT ratio = 2.04, 95% CI = 1.79-2.33, B/Victoria). Safety and reactogenicity, including fever, were similar despite the higher antigen content and volume of the double-dose IIV4. There were no attributable serious adverse events. Double-dose IIV4 may improve protection against influenza B in some young children and simplifies annual influenza vaccination by allowing the same vaccine dose to be used for all eligible children and adults. © The Author 2017. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society

Time to Change Dosing of Inactivated Quadrivalent Influenza Vaccine in Young Children: Evidence From a Phase III, Randomized, Controlled Trial

PubMed Central

Jain, Varsha K.; Domachowske, Joseph B.; Wang, Long; Ofori-Anyinam, Opokua; Rodríguez-Weber, Miguel A.; Leonardi, Michael L.; Klein, Nicola P.; Schlichter, Gary; Jeanfreau, Robert; Haney, Byron L.; Chu, Laurence; Harris, Jo-Ann S.; Sarpong, Kwabena O.; Micucio, Amanda C.; Soni, Jyoti; Chandrasekaran, Vijayalakshmi; Li, Ping

2017-01-01

Abstract Background. Children under 3 years of age may benefit from a double-dose of inactivated quadrivalent influenza vaccine (IIV4) instead of the standard-dose. Methods. We compared the only United States-licensed standard-dose IIV4 (0.25 mL, 7.5 µg hemagglutinin per influenza strain) versus double-dose IIV4 manufactured by a different process (0.5 mL, 15 µg per strain) in a phase III, randomized, observer-blind trial in children 6–35 months of age (NCT02242643). The primary objective was to demonstrate immunogenic noninferiority of the double-dose for all vaccine strains 28 days after last vaccination. Immunogenic superiority of the double-dose was evaluated post hoc. Immunogenicity was assessed in the per-protocol cohort (N = 2041), and safety was assessed in the intent-to-treat cohort (N = 2424). Results. Immunogenic noninferiority of double-dose versus standard-dose IIV4 was demonstrated in terms of geometric mean titer (GMT) ratio and seroconversion rate difference. Superior immunogenicity against both vaccine B strains was observed with double-dose IIV4 in children 6–17 months of age (GMT ratio = 1.89, 95% confidence interval [CI] = 1.64–2.17, B/Yamagata; GMT ratio = 2.13, 95% CI = 1.82–2.50, B/Victoria) and in unprimed children of any age (GMT ratio = 1.85, 95% CI = 1.59–2.13, B/Yamagata; GMT ratio = 2.04, 95% CI = 1.79–2.33, B/Victoria). Safety and reactogenicity, including fever, were similar despite the higher antigen content and volume of the double-dose IIV4. There were no attributable serious adverse events. Conclusions. Double-dose IIV4 may improve protection against influenza B in some young children and simplifies annual influenza vaccination by allowing the same vaccine dose to be used for all eligible children and adults. PMID:28062552

Denver screening protocol for blunt cerebrovascular injury reduces the use of multi-detector computed tomography angiography.

PubMed

Beliaev, Andrei M; Barber, P Alan; Marshall, Roger J; Civil, Ian

2014-06-01

Blunt cerebrovascular injury (BCVI) occurs in 0.2-2.7% of blunt trauma patients and has up to 30% mortality. Conventional screening does not recognize up to 20% of BCVI patients. To improve diagnosis of BCVI, both an expanded battery of screening criteria and a multi-detector computed tomography angiography (CTA) have been suggested. The aim of this study is to investigate whether the use of CTA restricted to the Denver protocol screen-positive patients would reduce the unnecessary use of CTA as a pre-emptive screening tool. This is a registry-based study of blunt trauma patients admitted to Auckland City Hospital from 1998 to 2012. The diagnosis of BCVI was confirmed or excluded with CTA, magnetic resonance angiography and, if these imaging were non-conclusive, four-vessel digital subtraction angiography. Thirty (61%) BCVI and 19 (39%) non-BCVI patients met eligibility criteria. The Denver protocol applied to our cohort of patients had a sensitivity of 97% (95% confidence interval (CI): 83-100%) and a specificity of 42% (95% CI: 20-67%). With a prevalence of BCVI in blunt trauma patients of 0.2% and 2.7%, post-test odds of a screen-positive test were 0.03 (95% CI: 0.002-0.005) and 0.046 (95% CI: 0.314-0.068), respectively. Application of the CTA to the Denver protocol screen-positive trauma patients can decrease the use of CTA as a pre-emptive screening tool by 95-97% and reduces its hazards. © 2013 Royal Australasian College of Surgeons.

Single‐fraction spine SBRT end‐to‐end testing on TomoTherapy, Vero, TrueBeam, and CyberKnife treatment platforms using a novel anthropomorphic phantom

PubMed Central

Kaufman, Isaac; Powell, Rachel; Pandya, Shalini; Somnay, Archana; Bossenberger, Todd; Ramirez, Ezequiel; Reynolds, Robert; Solberg, Timothy; Burmeister, Jay

2015-01-01

Spine SBRT involves the delivery of very high doses of radiation to targets adjacent to the spinal cord and is most commonly delivered in a single fraction. Highly conformal planning and accurate delivery of such plans is imperative for successful treatment without catastrophic adverse effects. End–to‐end testing is an important practice for evaluating the entire treatment process from simulation through treatment delivery. We performed end‐to‐end testing for a set of representative spine targets planned and delivered using four different treatment planning systems (TPSs) and delivery systems to evaluate the various capabilities of each. An anthropomorphic E2E SBRT phantom was simulated and treated on each system to evaluate agreement between measured and calculated doses. The phantom accepts ion chambers in the thoracic region and radiochromic film in the lumbar region. Four representative targets were developed within each region (thoracic and lumbar) to represent different presentations of spinal metastases and planned according to RTOG 0631 constraints. Plans were created using the TomoTherapy TPS for delivery using the Hi·Art system, the iPlan TPS for delivery using the Vero system, the Eclipse TPS for delivery using the TrueBeam system in both flattened and flattening filter free (FFF), and the MultiPlan TPS for delivery using the CyberKnife system. Delivered doses were measured using a 0.007 cm3 ion chamber in the thoracic region and EBT3 GAFCHROMIC film in the lumbar region. Films were scanned and analyzed using an Epson Expression 10000XL flatbed scanner in conjunction with FilmQAPro2013. All treatment platforms met all dose constraints required by RTOG 0631. Ion chamber measurements in the thoracic targets delivered an overall average difference of 1.5%. Specifically, measurements agreed with the TPS to within 2.2%, 3.2%, 1.4%, 3.1%, and 3.0% for all three measureable cases on TomoTherapy, Vero, TrueBeam (FFF), TrueBeam (flattened), and CyberKnife, respectively. Film measurements for the lumbar targets resulted in average global gamma index passing rates of 100% at 3%/3 mm, 96.9% at 2%/2 mm, and 61.8% at 1%/1 mm, with a 10% minimum threshold for all plans on all platforms. Local gamma analysis was also performed with similar results. While gamma passing rates were consistently accurate across all platforms through 2%/2 mm, treatment beam‐on delivery times varied greatly between each platform with TrueBeam FFF being shortest, averaging 4.4 min, TrueBeam using flattened beam at 9.5 min, TomoTherapy at 30.5 min, Vero at 19 min, and CyberKnife at 46.0 min. In spite of the complexity of the representative targets and their proximity to the spinal cord, all treatment platforms were able to create plans meeting all RTOG 0631 dose constraints and produced exceptional agreement between calculated and measured doses. However, there were differences in the plan characteristics and significant differences in the beam‐on delivery time between platforms. Thus, clinical judgment is required for each particular case to determine most appropriate treatment planning/delivery platform. PACS number: 87.53.Ly PMID:25679169

Population-Based Trachoma Mapping in Six Evaluation Units of Papua New Guinea.

PubMed

Ko, Robert; Macleod, Colin; Pahau, David; Sokana, Oliver; Keys, Drew; Burnett, Anthea; Willis, Rebecca; Wabulembo, Geoffrey; Garap, Jambi; Solomon, Anthony W

2016-01-01

We sought to determine the prevalence of trachomatous inflammation - follicular (TF) in children aged 1-9 years, and trachomatous trichiasis (TT) in those aged ≥15 years, in suspected trachoma-endemic areas of Papua New Guinea (PNG). We carried out six population-based prevalence surveys using the protocol developed as part of the Global Trachoma Mapping Project. A total of 19,013 individuals were sampled for inclusion, with 15,641 (82.3%) consenting to participate. Four evaluation units had prevalences of TF in children ≥10%, above which threshold the World Health Organization (WHO) recommends mass drug administration (MDA) of azithromycin for at least three years; Western Province (South Fly/Daru) 11.2% (95% confidence interval, CI, 6.9-17.0%), Southern Highlands (East) 12.2% (95% CI 9.6-15.0%), Southern Highlands (West) 11.7% (95% CI 8.5-15.3%), and West New Britain 11.4% (95% CI 8.7-13.9%). TF prevalence was 5.0-9.9% in Madang (9.4%, 95% CI 6.1-13.0%) and National Capital District (6.0%. 95% CI 3.2-9.1%) where consideration of a single round of MDA is warranted. Cases of TT were not found outside West New Britain, in which four cases were seen, generating an estimated population-level prevalence of TT in adults of 0.10% (95% CI 0.00-0.40%) for West New Britain, below the WHO elimination threshold of 0.2% of those aged ≥15 years. Trachoma is a public health issue in PNG. However, other than in West New Britain, there are few data to support the idea that trachoma is a cause of blindness in PNG. Further research is needed to understand the stimulus for the active trachoma phenotype in these populations.

Pre-Radiation Therapy Fluorine 18 Fluorodeoxyglucose PET Helps Identify Patients with Esophageal Cancer at High Risk for Radiation Pneumonitis.

PubMed

Castillo, Richard; Pham, Ngoc; Castillo, Edward; Aso-Gonzalez, Samantha; Ansari, Sobiya; Hobbs, Brian; Palacio, Diana; Skinner, Heath; Guerrero, Thomas M

2015-06-01

To examine the association between pre-radiation therapy (RT) fluorine 18 fluorodeoxyglucose (FDG) uptake and post-RT symptomatic radiation pneumonitis (RP). In accordance with the retrospective study protocol approved by the institutional review board, 228 esophageal cancer patients who underwent FDG PET/CT before chemotherapy and RT were examined. RP symptoms were evaluated by using the Common Terminology Criteria for Adverse Events, version 4.0, from the consensus of five clinicians. By using the cumulative distribution of standardized uptake values (SUVs) within the lungs, those values greater than 80%-95% of the total lung voxels were determined for each patient. The effect of pre-chemotherapy and RT FDG uptake, dose, and patient or treatment characteristics on RP toxicity was studied by using logistic regression. The study subjects were treated with three-dimensional conformal RT (n = 36), intensity-modulated RT (n = 135), or proton therapy (n = 57). Logistic regression analysis demonstrated elevated FDG uptake at pre-chemotherapy and RT was related to expression of RP symptoms. Study subjects with elevated 95% percentile of the SUV (SUV95) were more likely to develop symptomatic RP (P < .000012); each 0.1 unit increase in SUV95 was associated with a 1.36-fold increase in the odds of symptomatic RP. Receiver operating characteristic (ROC) curve analysis resulted in area under the ROC curve of 0.676 (95% confidence interval: 0.58, 0.77), sensitivity of 60%, and specificity of 71% at the 1.17 SUV95 threshold. CT imaging and dosimetric parameters were found to be poor predictors of RP symptoms. The SUV95, a biomarker of pretreatment pulmonary metabolic activity, was shown to be prognostic of symptomatic RP. Elevation in this pretreatment biomarker identifies patients at high risk for posttreatment symptomatic RP. RSNA, 2015

Evaluation of autonomous recording units for detecting 3 species of secretive marsh birds

USGS Publications Warehouse

Sidie-Slettehahl, Anna M.; Jensen, Kent C.; Johnson, Rex R.; Arnold, Todd W.; Austin, Jane; Stafford, Joshua D.

2015-01-01

Population status and habitat use of yellow rails (Coturnicops noveboracensis), Nelson's sparrows (Ammodramus nelsoni), and Le Conte's sparrows (A. leconteii) are poorly known, so standardized surveys of these species are needed to inform conservation planning and management. A protocol for monitoring secretive marsh birds exists; however, these species regularly call at night and may be missed during early morning surveys. We tested the effectiveness of autonomous recording units (hereafter, recording units) to survey these species by analyzing recorded vocalizations using bioacoustics software. We deployed 22 recording units at 54 sites in northern Minnesota and eastern North Dakota, USA, and conducted traditional broadcast surveys during May–June, 2010 and 2011. We compared detection probabilities between recording units and standard monitoring protocols using robust-design occupancy models. On average, recording units detected 0.59 (SE = 0.11) fewer Le Conte's sparrows, 0.76 (SE = 0.15) fewer Nelson's sparrows, and 1.01 (SE = 0.14) fewer yellow rails per survey than were detected using the standard protocol. Detection probabilities using the standard protocol averaged 0.95 (yellow rail; 95% CI = 0.86–0.98), 0.93 (Le Conte's sparrow; 95% CI = 0.78–0.98), and 0.89 (Nelson's sparrow; 95% CI = 0.56–0.98), but averaged 0.71 (yellow rail; 95% CI = 0.56–0.83), 0.61 (Le Conte's sparrow; 95% CI = 0.42–0.78), and 0.51 (Nelson's sparrow; 95% CI = 0.19–0.82) using recording units. Reduced detection by recording units was likely due to the ability of human listeners to identify birds calling at greater distances. Recording units may be effective for surveying nocturnal secretive marsh birds if investigators correct for differential detectability. Reduced detectability may be outweighed by the increased spatial and temporal coverage feasible with recording units.

Lack of evidence of a beneficial effect of azathioprine in dogs treated with prednisolone for idiopathic immune-mediated hemolytic anemia: a retrospective cohort study.

PubMed

Piek, Christine J; van Spil, Willem Evert; Junius, Greet; Dekker, Aldo

2011-04-13

Azathioprine is used as an immunosuppressant in canine immune-mediated hemolytic anemia (IMHA), but this potentially toxic and carcinogenic drug has not been proven to be beneficial. The aim of this study was to determine the difference in outcome and survival of dogs with idiopathic IMHA treated with a protocol that included azathioprine and prednisolone versus a protocol that included prednisolone alone. The study included 222 dogs with a hematocrit lower than 0.30 L/L and either a positive Coombs' test or spherocytosis and no evidence of diseases that could trigger IMHA. The clinical and laboratory data at the time of diagnosis and the response to therapy and survival were compared in dogs treated according to the prednisolone and azathioprine protocol (AP protocol; n = 149) and dogs treated according to the prednisolone protocol (P protocol; n = 73). At study entry, the two groups were comparable, except that thrombocyte counts were significantly lower and clinical signs had been present significantly longer in the AP protocol group. No significant difference in survival was found between the two groups: the 1-year survival was 64% (95% CI 54 - 77%) in the P protocol group and 69% (95% CI 59-80%) in the AP protocol group, respectively. Azathioprine would appear not to be beneficial as standard treatment for all cases of IMHA; however, a blinded, randomized clinical trial is needed to establish whether outcome is different with the two treatment protocols.

Gonadotrophin-releasing hormone antagonists for assisted conception.

PubMed

Al-Inany, H G; Abou-Setta, A M; Aboulghar, M

2006-07-19

Gonadotrophin-releasing hormone antagonists produce immediate suppression of gonadotrophin secretion, hence, they can be given after starting gonadotrophin administration. This has resulted in dramatic reduction in the duration of treatment cycle. Two different regimes have been described. The multiple-dose protocol involves the administration of 0.25 mg cetrorelix (or ganirelix) daily from day six to seven of stimulation, or when the leading follicle is 14 to15 mm, until human chorionic gonadotrophin (HCG) administration and the single-dose protocol involves the single administration of 3 mg cetrorelix on day seven to eight of stimulation. Assuming comparable clinical outcome, these benefits would justify a change from the standard long protocol of GnRH agonists to the new GnRH antagonist regimens. To evaluate the evidence regarding the efficacy of gonadotrophin-releasing hormone (GnRH) antagonists with the standard long protocol of GnRH agonists for controlled ovarian hyperstimulation in assisted conception. We searched Cochrane Menstrual Disorders and Subfertility Group's Specialised Register, MEDLINE and EMBASE databases from 1987 to February 2006, and handsearched bibliographies of relevant publications and reviews, and abstracts of scientific meetings. We also contacted manufacturers in the field. Randomized controlled studies comparing different protocols of GnRH antagonists with GnRH agonists in assisted conception cycles were included in this review. Two authors independently assessed trial quality and extracted data. If relevant data were missing or unclear, the authors have been consulted Twenty seven RCTs comparing the GnRH antagonist to the long protocol of GnRH agonist fulfilled the inclusion criteria. Clinical pregnancy rate was significantly lower in the antagonist group. (OR = 0.84, 95% CI = 0.72 - 0.97). The ongoing pregnancy/ live-birth rate showed the same significant lower pregnancy in the antagonist group (P = 0.03; OR 0.82, 95% CI 0.69 to 0.98).However, there was statistically significant reduction in incidence of severe OHSS with antagonist protocol. The relative risk ratio was (P = 0.01; RR 0.61, 95% CI 0.42 to 0.89). In addition, interventions to prevent OHSS (e.g. coasting, cycle cancellation) were administered more frequently in the agonist group (P = 0.03; OR 0.44, 95% CI 0.21 to 0.93). GnRH antagonist protocol is a short and simple protocol with good clinical outcome with significant reduction in incidence of severe ovarian hyperstimulation syndrome and amount of gonadotrophins but the lower pregnancy rate compared to the GnRH agonist long protocol necessitates counseling subfertile couples before recommending change from GnRH agonist to antagonist..

Evaluation of Modified 2-Tiered Serodiagnostic Testing Algorithms for Early Lyme Disease

PubMed Central

Strle, Klemen; Nigrovic, Lise E.; Lantos, Paul M.; Lepore, Timothy J.; Damle, Nitin S.; Ferraro, Mary Jane; Steere, Allen C.

2017-01-01

Abstract Background. The conventional 2-tiered serologic testing protocol for Lyme disease (LD), an enzyme immunoassay (EIA) followed by immunoglobulin M and immunoglobulin G Western blots, performs well in late-stage LD but is insensitive in patients with erythema migrans (EM), the most common manifestation of the illness. Western blots are also complex, difficult to interpret, and relatively expensive. In an effort to improve test performance and simplify testing in early LD, we evaluated several modified 2-tiered testing (MTTT) protocols, which use 2 assays designed as first-tier tests sequentially, without the need of Western blots. Methods. The MTTT protocols included (1) a whole-cell sonicate (WCS) EIA followed by a C6 EIA; (2) a WCS EIA followed by a VlsE chemiluminescence immunoassay (CLIA); and (3) a variable major protein-like sequence, expressed (VlsE) CLIA followed by a C6 EIA. Sensitivity was determined using serum from 55 patients with erythema migrans; specificity was determined using serum from 50 patients with other illnesses and 1227 healthy subjects. Results. Sensitivity of the various MTTT protocols in patients with acute erythema migrans ranged from 36% (95% confidence interval [CI], 25%–50%) to 54% (95% CI, 42%–67%), compared with 25% (95% CI, 16%–38%) using the conventional protocol (P = .003–0.3). Among control subjects, the 3 MTTT protocols were similarly specific (99.3%–99.5%) compared with conventional 2-tiered testing (99.5% specificity; P = .6–1.0). Conclusions. Although there were minor differences in sensitivity and specificity among MTTT protocols, each provides comparable or greater sensitivity in acute EM, and similar specificity compared with conventional 2-tiered testing, obviating the need for Western blots. PMID:28329259

The role of MRI in axillary lymph node imaging in breast cancer patients: a systematic review.

PubMed

Kuijs, V J L; Moossdorff, M; Schipper, R J; Beets-Tan, R G H; Heuts, E M; Keymeulen, K B M I; Smidt, M L; Lobbes, M B I

2015-04-01

To assess whether MRI can exclude axillary lymph node metastasis, potentially replacing sentinel lymph node biopsy (SLNB), and consequently eliminating the risk of SLNB-associated morbidity. PubMed, Cochrane, Medline and Embase databases were searched for relevant publications up to July 2014. Studies were selected based on predefined inclusion and exclusion criteria and independently assessed by two reviewers using a standardised extraction form. Sixteen eligible studies were selected from 1,372 publications identified by the search. A dedicated axillary protocol [sensitivity 84.7 %, negative predictive value (NPV) 95.0 %] was superior to a standard protocol covering both the breast and axilla simultaneously (sensitivity 82.0 %, NPV 82.6 %). Dynamic, contrast-enhanced MRI had a lower median sensitivity (60.0 %) and NPV (80.0 %) compared to non-enhanced T1w/T2w sequences (88.4, 94.7 %), diffusion-weighted imaging (84.2, 90.6 %) and ultrasmall superparamagnetic iron oxide (USPIO)- enhanced T2*w sequences (83.0, 95.9 %). The most promising results seem to be achievable when using non-enhanced T1w/T2w and USPIO-enhanced T2*w sequences in combination with a dedicated axillary protocol (sensitivity 84.7 % and NPV 95.0 %). The diagnostic performance of some MRI protocols for excluding axillary lymph node metastases approaches the NPV needed to replace SLNB. However, current observations are based on studies with heterogeneous study designs and limited populations. • Some axillary MRI protocols approach the NPV of an SLNB procedure. • Dedicated axillary MRI is more accurate than protocols also covering the breast. • T1w/T2w protocols combined with USPIO-enhanced sequences are the most promising sequences.

A prospective observational study of a novel 2-phase infusion protocol for the administration of acetylcysteine in paracetamol poisoning.

PubMed

Isbister, Geoffrey K; Downes, Michael A; Mcnamara, Kylie; Berling, Ingrid; Whyte, Ian M; Page, Colin B

2016-01-01

The current 3-phase acetylcysteine infusion for paracetamol poisoning delivers half the dose over 15-60 min and frequently results in adverse reactions. We aimed to determine adverse reaction frequency with a modified 2-phase infusion protocol with a longer initial infusion. A prospective observational study of a modified 2-phase acetylcysteine protocol was undertaken at two hospitals. Acetylcysteine was commenced on admission and ceased if paracetamol concentrations were low-risk (below the nomogram line). The first infusion was 200 mg/kg over 4-9 h based on ingestion time or 4 h for staggered/chronic ingestions. The second infusion was 100 mg/kg over 16 h. Pre-defined outcomes were frequency of adverse reactions (systemic hypersensitivity reactions or gastrointestinal); proportion with alanine transaminase (ALT) > 1000 U/L or abnormal ALT. 654 paracetamol poisonings were treated with the new protocol; median age 29 y (15-98 y); 453 females; 576 acute and 78 staggered/chronic ingestions. In 420 (64%) acetylcysteine was stopped for low-risk paracetamol concentrations. An adverse reaction occurred in 229/654 admissions (35%; 95% CI: 31-39%): 173 (26.5%; 95% CI: 23-30%) only gastrointestinal, 50 (8%; 95% CI: 6-10%) skin only systemic hypersensitivity reactions; and three severe anaphylaxis (0.5%; 95% CI: 0.1-1.5%; all hypotension). Adverse reactions occurred in 111/231 (48%) receiving full treatment compared to 116/420 (28%) in whom the infusion was stopped early (absolute difference 20%; 95% CI: 13-28%; p < 0.0001). In 200 overdoses < 10 g, one had toxic paracetamol concentrations, but 53 developed reactions. Sixteen patients had an ALT > 1000 U/L and 24 an abnormal ALT attributable to paracetamol; all but one had treatment commenced >12 h post-ingestion. A 2-phase acetylcysteine infusion protocol results in a fewer reactions in patients with toxic paracetamol concentrations, but is not justified in patients with low-risk paracetamol concentrations.

Clonal Evaluation of Prostate Cancer by ERG/SPINK1 Status to Improve Prognosis Prediction

DTIC Science & Technology

2016-10-01

clinical oncology , cancer genetics, genomic science/bioinformatics, clinical pathology, social and behavioral sciences, and bioethics in order to...Interpret and translate sequence variants into clinical oncology setting; 5) Assess and evaluate costs associated with clinical sequencing. Role...Lethal Prostate Cancer Goal(s): Radiation Therapy Oncology Group (RTOG) 96-01 represents a phase III trial of of salvage radiation therapy (RT) alone

50 CFR 17.95 - Critical habitat-fish and wildlife. (Continued)

Code of Federal Regulations, 2012 CFR

2012-10-01

... 50 Wildlife and Fisheries 5 2012-10-01 2012-10-01 false Critical habitat-fish and wildlife. (Continued) 17.95 Section 17.95 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) TAKING, POSSESSION, TRANSPORTATION, SALE, PURCHASE, BARTER, EXPORTATION, AND IMPORTATION OF WILDLIFE AND PLANTS ...

50 CFR 17.95 - Critical habitat-fish and wildlife. (Continued)

Code of Federal Regulations, 2014 CFR

2014-10-01

... 50 Wildlife and Fisheries 4 2014-10-01 2014-10-01 false Critical habitat-fish and wildlife. (Continued) 17.95 Section 17.95 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) TAKING, POSSESSION, TRANSPORTATION, SALE, PURCHASE, BARTER, EXPORTATION, AND IMPORTATION OF WILDLIFE AND PLANTS ...

50 CFR 17.95 - Critical habitat-fish and wildlife. (Continued)

Code of Federal Regulations, 2011 CFR

2011-10-01

... 50 Wildlife and Fisheries 4 2011-10-01 2011-10-01 false Critical habitat-fish and wildlife. (Continued) 17.95 Section 17.95 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) TAKING, POSSESSION, TRANSPORTATION, SALE, PURCHASE, BARTER, EXPORTATION, AND IMPORTATION OF WILDLIFE AND PLANTS ...

50 CFR 17.95 - Critical habitat-fish and wildlife. (Continued)

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 3 2010-10-01 2010-10-01 false Critical habitat-fish and wildlife. (Continued) 17.95 Section 17.95 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) TAKING, POSSESSION, TRANSPORTATION, SALE, PURCHASE, BARTER, EXPORTATION, AND IMPORTATION OF WILDLIFE AND PLANTS ...

50 CFR 17.95 - Critical habitat-fish and wildlife. (Continued)

Code of Federal Regulations, 2011 CFR

2011-10-01

... 50 Wildlife and Fisheries 3 2011-10-01 2011-10-01 false Critical habitat-fish and wildlife. (Continued) 17.95 Section 17.95 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) TAKING, POSSESSION, TRANSPORTATION, SALE, PURCHASE, BARTER, EXPORTATION, AND IMPORTATION OF WILDLIFE AND PLANTS ...

50 CFR 17.95 - Critical habitat-fish and wildlife. (Continued)

Code of Federal Regulations, 2012 CFR

2012-10-01

... 50 Wildlife and Fisheries 3 2012-10-01 2012-10-01 false Critical habitat-fish and wildlife. (Continued) 17.95 Section 17.95 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) TAKING, POSSESSION, TRANSPORTATION, SALE, PURCHASE, BARTER, EXPORTATION, AND IMPORTATION OF WILDLIFE AND PLANTS ...

50 CFR 17.95 - Critical habitat-fish and wildlife. (Continued)

Code of Federal Regulations, 2014 CFR

2014-10-01

... 50 Wildlife and Fisheries 3 2014-10-01 2014-10-01 false Critical habitat-fish and wildlife. (Continued) 17.95 Section 17.95 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) TAKING, POSSESSION, TRANSPORTATION, SALE, PURCHASE, BARTER, EXPORTATION, AND IMPORTATION OF WILDLIFE AND PLANTS ...

50 CFR 17.95 - Critical habitat-fish and wildlife. (Continued)

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 3 2013-10-01 2013-10-01 false Critical habitat-fish and wildlife. (Continued) 17.95 Section 17.95 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) TAKING, POSSESSION, TRANSPORTATION, SALE, PURCHASE, BARTER, EXPORTATION, AND IMPORTATION OF WILDLIFE AND PLANTS ...

50 CFR 17.95 - Critical habitat-fish and wildlife. (Continued)

Code of Federal Regulations, 2014 CFR

2014-10-01

... 50 Wildlife and Fisheries 5 2014-10-01 2014-10-01 false Critical habitat-fish and wildlife. (Continued) 17.95 Section 17.95 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) TAKING, POSSESSION, TRANSPORTATION, SALE, PURCHASE, BARTER, EXPORTATION, AND IMPORTATION OF WILDLIFE AND PLANTS ...

50 CFR 17.95 - Critical habitat-fish and wildlife. (Continued)

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 5 2013-10-01 2013-10-01 false Critical habitat-fish and wildlife. (Continued) 17.95 Section 17.95 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) TAKING, POSSESSION, TRANSPORTATION, SALE, PURCHASE, BARTER, EXPORTATION, AND IMPORTATION OF WILDLIFE AND PLANTS ...

Reirradiation on recurrent cervical cancer case: Treatment response and side effects

NASA Astrophysics Data System (ADS)

Siregar, M. F.; Supriana, N.; Nuranna, L.; Prihartono, J.

2017-08-01

Management of recurrent cervical cancer by reirradiation after radiation treatment remains controversial. In Indonesia, there is currently no data about reirradiation tumor response and side effects. This study aims to assess the tumor response to and side effects of reirradiation, the effect of time interval between first radiation treatment and cancer recurrence on the tumor response and side effects, and the effect of tumor size on tumor response. A cohort retrospective study with no comparison was done with the Radiotherapy Department at Cipto Mangunkusumo General Hospital, Jakarta. Participants were recurrent cervical cancer patients undergoing reirradiation. Data was collected from patients’ medical records and follow-up phone calls. Twenty-two patients participated in this study. Nine patients (40.9%) had complete responses, 10 patients (45.5%) had partial responses, 1 patient (4.5%) had a stable response, and 2 patients (9.1%) had tumor progressions. In general, 15 patients (68.2%) had no to light side effects (grade 0-2 RTOG) and 7 patients (31.8%) had severe side effects (grade 3-4 RTOG). Four patients (18.1%) had severe gastrointestinal acute side effects, 6 patients (27.3%) had severe gastrointestinal late side effects, 2 patients (9.1%) had severe urogenital side effects, and there were no patients had severe urogenital late side effects. There was no significant difference in tumor response between patients with time interval between first radiation treatment and recurrence of <12 months vs. ≥12 months. There was no significant difference in tumor response between patients with tumor size ≤4 cm vs. >4 cm. Reirradiation can be considered as a modality in recurrent cervical cancer management since good tumor response was achieved and the majority of patients had no to light side effects (grade 0-2 RTOG). This study found no correlation between tumor response, side effects, and time gap between first radiation treatment and recurrence of <12 months vs. ≥12 months. There was also no correlation between tumor response and tumor size of ≤4 cm vs. > 4 cm.

SU-F-T-112: Long-Term Follow-Up of NSCLC Patients Treated with Lung SBRT Using the Modified Conformal Arc (MDCA) Planning Technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ku, E; Desai, A; Fang, D

2016-06-15

Purpose: To assess long-term toxicity and primary tumor changes for Stage I/II non-small cell lung carcinoma (NSCLC) patients after treatment with lung SBRT using the modified dynamic conformal arc (MDCA) planning technique. Methods: Clinical and radiograph data from electronic health records of 15 NSCLC patients treated with lung SBRT utilizing the MDCA technique between October 2011 and July 2014 were retrospectively reviewed. MDCA uses a coplanar beam arrangement, patient body center for the beam isocenter, and six partial rotation conformal arcs to target the tumor. Radiation Therapy Oncology Group (RTOG) guidelines for treatment parameters were followed. Most patients received 5more » radiation fractions (Range: 3 to 7 fractions) with 48 hours between each fraction. Median total dose was 60 Gy (range: 45 to 70 Gy). Results: Median follow-up was 18 months (range: 6–51 months). Median age was 72.5 years (range: 48–90 years). Post-treatment findings included fatigue (n = 5) and chronic chest wall pain (n=1). Seven patients reported respiratory symptoms, which included: cough (n = 4), dyspnea (n = 5), and hemoptysis (n = 1). No patients deaths or grade ≥4 toxicity were recorded. Radiographic scarring was seen on computed tomography (CT) imaging in 6 patients. Local control rate was 93.3% (n = 14) and 1 patient had local recurrence. Conclusion: Our results were very similar to RTOG 0236 findings reported by Timmerman et al. – our local control rate was 93.3% compared to their 3-year primary tumor control rate of 97.6%. Toxicity rates were also similar – RTOG 0236 constitutional symptoms and pulmonary/upper respiratory symptoms rates were 36.4% and 60.0%, respectively, while ours were 33.3% and 46.7%, respectively. We were limited by a small sample size and relatively short follow-up but our findings support the use of the MDCA technique for lung SBRT treatment of Stage I/II NSCLC.« less

Feasibility of Patient Reporting of Symptomatic Adverse Events via the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in a Chemoradiotherapy Cooperative Group Multicenter Clinical Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Basch, Ethan, E-mail: ebasch@med.unc.edu; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; Pugh, Stephanie L.

Purpose: To assess the feasibility of measuring symptomatic adverse events (AEs) in a multicenter clinical trial using the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Methods and Materials: Patients enrolled in NRG Oncology's RTOG 1012 (Prophylactic Manuka Honey for Reduction of Chemoradiation Induced Esophagitis-Related Pain during Treatment of Lung Cancer) were asked to self-report 53 PRO-CTCAE items representing 30 symptomatic AEs at 6 time points (baseline; weekly ×4 during treatment; 12 weeks after treatment). Reporting was conducted via wireless tablet computers in clinic waiting areas. Compliance was defined as the proportion of visitsmore » when an expected PRO-CTCAE assessment was completed. Results: Among 226 study sites participating in RTOG 1012, 100% completed 35-minute PRO-CTCAE training for clinical research associates (CRAs); 80 sites enrolled patients, of which 34 (43%) required tablet computers to be provided. All 152 patients in RTOG 1012 agreed to self-report using the PRO-CTCAE (median age 66 years; 47% female; 84% white). Median time for CRAs to learn the system was 60 minutes (range, 30-240 minutes), and median time for CRAs to teach a patient to self-report was 10 minutes (range, 2-60 minutes). Compliance was high, particularly during active treatment, when patients self-reported at 86% of expected time points, although compliance was lower after treatment (72%). Common reasons for noncompliance were institutional errors, such as forgetting to provide computers to participants; patients missing clinic visits; Internet connectivity; and patients feeling “too sick.” Conclusions: Most patients enrolled in a multicenter chemoradiotherapy trial were willing and able to self-report symptomatic AEs at visits using tablet computers. Minimal effort was required by local site staff to support this system. The observed causes of missing data may be obviated by allowing patients to self-report electronically between visits, and by using central compliance monitoring. These approaches are being incorporated into ongoing studies.« less

Feasibility of Patient Reporting of Symptomatic Adverse Events via the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in a Chemoradiotherapy Cooperative Group Multicenter Clinical Trial.

PubMed

Basch, Ethan; Pugh, Stephanie L; Dueck, Amylou C; Mitchell, Sandra A; Berk, Lawrence; Fogh, Shannon; Rogak, Lauren J; Gatewood, Marcha; Reeve, Bryce B; Mendoza, Tito R; O'Mara, Ann M; Denicoff, Andrea M; Minasian, Lori M; Bennett, Antonia V; Setser, Ann; Schrag, Deborah; Roof, Kevin; Moore, Joan K; Gergel, Thomas; Stephans, Kevin; Rimner, Andreas; DeNittis, Albert; Bruner, Deborah Watkins

2017-06-01

To assess the feasibility of measuring symptomatic adverse events (AEs) in a multicenter clinical trial using the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Patients enrolled in NRG Oncology's RTOG 1012 (Prophylactic Manuka Honey for Reduction of Chemoradiation Induced Esophagitis-Related Pain during Treatment of Lung Cancer) were asked to self-report 53 PRO-CTCAE items representing 30 symptomatic AEs at 6 time points (baseline; weekly ×4 during treatment; 12 weeks after treatment). Reporting was conducted via wireless tablet computers in clinic waiting areas. Compliance was defined as the proportion of visits when an expected PRO-CTCAE assessment was completed. Among 226 study sites participating in RTOG 1012, 100% completed 35-minute PRO-CTCAE training for clinical research associates (CRAs); 80 sites enrolled patients, of which 34 (43%) required tablet computers to be provided. All 152 patients in RTOG 1012 agreed to self-report using the PRO-CTCAE (median age 66 years; 47% female; 84% white). Median time for CRAs to learn the system was 60 minutes (range, 30-240 minutes), and median time for CRAs to teach a patient to self-report was 10 minutes (range, 2-60 minutes). Compliance was high, particularly during active treatment, when patients self-reported at 86% of expected time points, although compliance was lower after treatment (72%). Common reasons for noncompliance were institutional errors, such as forgetting to provide computers to participants; patients missing clinic visits; Internet connectivity; and patients feeling "too sick." Most patients enrolled in a multicenter chemoradiotherapy trial were willing and able to self-report symptomatic AEs at visits using tablet computers. Minimal effort was required by local site staff to support this system. The observed causes of missing data may be obviated by allowing patients to self-report electronically between visits, and by using central compliance monitoring. These approaches are being incorporated into ongoing studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Stereotactic Body Radiation Therapy Delivery in a Genetically Engineered Mouse Model of Lung Cancer.

PubMed

Du, Shisuo; Lockamy, Virginia; Zhou, Lin; Xue, Christine; LeBlanc, Justin; Glenn, Shonna; Shukla, Gaurav; Yu, Yan; Dicker, Adam P; Leeper, Dennis B; Lu, You; Lu, Bo

2016-11-01

To implement clinical stereotactic body radiation therapy (SBRT) using a small animal radiation research platform (SARRP) in a genetically engineered mouse model of lung cancer. A murine model of multinodular Kras-driven spontaneous lung tumors was used for this study. High-resolution cone beam computed tomography (CBCT) imaging was used to identify and target peripheral tumor nodules, whereas off-target lung nodules in the contralateral lung were used as a nonirradiated control. CBCT imaging helps localize tumors, facilitate high-precision irradiation, and monitor tumor growth. SBRT planning, prescription dose, and dose limits to normal tissue followed the guidelines set by RTOG protocols. Pathologic changes in the irradiated tumors were investigated using immunohistochemistry. The image guided radiation delivery using the SARRP system effectively localized and treated lung cancer with precision in a genetically engineered mouse model of lung cancer. Immunohistochemical data confirmed the precise delivery of SBRT to the targeted lung nodules. The 60 Gy delivered in 3 weekly fractions markedly reduced the proliferation index, Ki-67, and increased apoptosis per staining for cleaved caspase-3 in irradiated lung nodules. It is feasible to use the SARRP platform to perform dosimetric planning and delivery of SBRT in mice with lung cancer. This allows for preclinical studies that provide a rationale for clinical trials involving SBRT, especially when combined with immunotherapeutics. Copyright © 2016. Published by Elsevier Inc.

Evaluation of hand hygiene adherence in a tertiary hospital.

PubMed

Novoa, Ana M; Pi-Sunyer, Teresa; Sala, Maria; Molins, Eduard; Castells, Xavier

2007-12-01

Although hand hygiene is the most important measure in the prevention of nosocomial infection, adherence to recommendations among health care workers (HCW) is low. Evaluation of compliance with hand hygiene was carried out in a Spanish teaching hospital. In 2005, adherence to hand hygiene was evaluated hospital wide through direct observation, collecting data on hand hygiene carried out whenever indicated (opportunity for hand hygiene). Compliance was defined as handwashing/disinfection in an opportunity for hand hygiene according to hospital protocols. The results were analyzed using mixed effects models, with the HCW observed as the random effect. A total of 1254 opportunities for hand hygiene were observed in 247 HCWs. Mean compliance was 20%. Although few differences were observed among types of HCW, compliance varied according to hospital area (69% in the intensive care unit [ICU]) and timing with respect to patient contact (compliance after contact was twice that before contact). Multivariate analyses revealed a protective odds ratio (OR) for nonadherence in ICUs (OR, 0.04; 95% confidence interval (95% CI): 0.01-0.10) and after patient contact (OR, 0.25; 95% CI: 0.17-0.38). Low adherence observed suggests that new interventions should focus in modification of HCWs' habits and attitudes, working at several levels: individual and institutional.

Female Adults with Patellofemoral Pain Are Characterized by Widespread Hyperalgesia, Which Is Not Affected Immediately by Patellofemoral Joint Loading.

PubMed

Pazzinatto, Marcella Ferraz; de Oliveira Silva, Danilo; Barton, Christian; Rathleff, Michael Skovdal; Briani, Ronaldo Valdir; de Azevedo, Fábio Mícolis

2016-10-01

Compare pressure pain thresholds (PPTs) at the knee and a site remote to the knee in female adults with patellofemoral pain (PFP) to pain-free controls before and after a patellofemoral joint (PFJ) loading protocol designed to aggravate symptoms. Cross-sectional study SETTING: Participants were recruited via advertisements in fitness centers, public places for physical activity and universities. Thirty-eight females with patellofemoral pain, and 33 female pain-free controls. All participant performed a novel PFJ loading protocol involving stair negotiation with an extra load equivalent 35% of body mass. PPTs and current knee pain (measured on a visual analogue scale) was assessed before and after the loading protocol. PPTs were measured at four sites around the knee and one remote site on the upper contralateral limb. Females with PFP demonstrated significantly lower PPTs locally and remote to the knee, both before and after the PFJ loading protocol when compared to control group. Following the loading protocol, PPTs at knee were significantly reduced by 0.54 kgf (95%CI = 0.33; 0.74) for quadriceps tendon, 0.38 kgf (95%CI = 0.14; 0.63) for medial patella, and 0.44 kgf (95%CI = 0.18; 0.69) for lateral patella. No significant change in PPT remote to the knee was observed - 0.10 kgf (95%CI = -0.04; 0.24). Female adults with PFP have local and widespread hyperalgesia compared to pain free controls. A novel loading protocol designed to aggravate symptoms, lowers the PPTs locally at the knee but has no effect on PPT on the upper contralateral limb. This suggests widespread hyperalgesia is not affected by acute symptom aggravation. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A randomised-controlled trial in England of a postnatal midwifery intervention on breast-feeding duration.

PubMed

Wallace, Louise M; Dunn, Orla M; Alder, Elizabeth M; Inch, Sally; Hills, Robert K; Law, Susan M

2006-09-01

To determine whether postnatal 'hands off' care by midwives on positioning and attachment of the newborn baby improves breast-feeding duration. Mothers were randomised at the first postnatal feed to receive either care by a midwife trained in the experimental protocol or by a control midwife undertaking routine care. Eight wards in four English Midlands hospitals. 370 primiparous mothers with term babies who intended to breast feed, and could sit out of bed to do so. Experimental protocol of verbal-only advice on positioning and attachment, delivered at the first postnatal ward feed compared with routine care by a qualified midwife. Duration of breast feeding up to 17 weeks as assessed by diaries and interviews with mothers and protocol adherence from self-completed checklist by the midwife. The mothers' self-reported experience of care and support before, during and after delivery were assessed at 6 weeks, and feeding outcomes and employment status at 17 weeks. Experimental group mothers more often held the baby across their lap and received 'hands off advice', but fewer babies in the experimental than control groups attached and fed: 59% (106/180) vs. 67% (118/175), p=0.1. No significant differences were found in the numbers of mothers breast feeding at 6 or 17 weeks in the experimental and control groups (stopped exclusive breast feeding: 76% (130/172) vs. 77% (126/163) at 6 weeks; 96% (167/174) vs. 96% (161/168) at 17 weeks; odds ratio 1.02, 95% CI 0.77 to 1.22; p=0.8; stopped any breast feeding: 35% (61/172) vs. 32% (53/167) at 6 weeks; 63% (109/173) vs. 60% (101/167) at 17 weeks; odds ratio 1.10, 0.84 to 1.45; p=0.5). There were no significant differences in the incidence of problems with breast feeding and care experienced by mothers before or during hospitalisation (other than at the first postnatal ward feed), nor after discharge home. No significant beneficial effect was found on breast-feeding duration of the verbal- only advice on positioning and attachment, perhaps because aspects of the intervention are already within routine UK practice. Other care practices at subsequent feeds may negate benefits of care at earlier feeds. 'Hands off' care at the first feed may be less important to subsequent feeding than achieving a first feed under supervision in the postnatal ward. Midwives can be trained in a 4-hr workshop to achieve improved knowledge of 'hands off' positioning and attachment care, and these can be translated into clinical practice. Future studies should differentiate the elements of the care that are effective in achieving postnatal feeds, and apply this advice consistently at successive feeds.

Prevalence of stroke among Chinese, Malay, and Indian Singaporeans: a community-based tri-racial cross-sectional survey.

PubMed

Venketasubramanian, Narayanaswamy; Tan, Louis C S; Sahadevan, Suresh; Chin, Jing J; Krishnamoorthy, Ennapadam S; Hong, Ching Y; Saw, Seang M

2005-03-01

Stroke prevalence data among mixed Asian populations are lacking. Prevalence rates of stroke were studied among Singaporeans aged > or =50 years of Chinese, Malay, and Indian origin. Study participants were selected by disproportionate stratified random sampling by race. Trained interviewers performed face-to-face interviews with subjects using the World Health Organization screening protocol for neurological diseases. Data were also collected on a self-report of stroke. Subjects suspected to have had a stroke underwent a clinical evaluation to diagnose or exclude stroke. Case notes review was performed for those who were unable to come for clinical evaluation. The study involved 14 906 participants: 6734 men, 8172 women, age range 52 to 106 years, Chinese:Malay:Indian ratio 3:1:1. Participation rate was 66.9%. Six hundred and six were diagnosed to have a stroke, yielding a crude prevalence rate of 4.05% (95% CI, 3.75 to 4.38) and a World Health Organization world population age-gender-standardized rate of 3.65% (95% CI, 3.36 to 3.96). Prevalence rates rose with age (P<0.001 for trend) and were higher among men compared with women, 4.53% (95% CI, 4.05 to 5.07) versus 2.91% (95% CI, 2.57 to 3.29), P<0.01. Age and gender-standardized rates among Chinese, Malays, and Indians were 3.76% (95% CI, 3.38 to 4.17), 3.32 (95% CI, 2.72 to 4.07), and 3.62% (95% CI, 2.95 to 4.44), respectively, P>0.2. Prevalence was highest among Chinese men at 4.78% (95% CI, 4.14 to 5.50) and lowest among Malay women at 2.81% (95% CI, 2.08 to 3.81), P=0.01. There is no difference in stroke prevalence among Chinese, Malay, and Indian Singaporeans. Prevalence is highest among Chinese men and lowest among Malay women. The reasons for these differences warrant further investigation.

Failure of antiarrhythmic drugs to prevent experimental reperfusion ventricular fibrillation.

PubMed

Naito, M; Michelson, E L; Kmetzo, J J; Kaplinsky, E; Dreifus, L S

1981-01-01

Ninety-nine adult mongrel dogs underwent acute ligation of the proximal left anterior descending coronary artery. Thirty minutes later, the occlusion was released to evaluate the effectiveness of five antiarrhythmic protocols in eliminating reperfusion ventricular fibrillation. The five protocols included: protocol 1 --i.v. lidocaine, preligation and prerelease (n = 19); protocol 2 -- i.v. lidocaine, prereperfusion only (n = 22); protocol 3 -- chronic, oral, daily amiodarone for 2 weeks preligation (n = 19); protocol 4 -- i.v. procainamide, preligation and prereperfusion (n = 21); and protocol 5 -- i.v. verapamil, prereperfusion (n = 18). Each regimen was evaluated with respect to the incidence of reperfusion ventricular fibrillation in dogs that survived to reperfusion, and the results were compared to 77 control dogs that underwent identical coronary artery occlusion and release procedures without drug therapy. The incidence of reperfusion ventricular fibrillation was as follows: protocol 1 -- seven of 15 dogs (47%); protocol 2 -- six of 18 (33%); protocol 3 -- 11 of 16 dogs (69%); protocol 4 -- eight of 17 dogs (47%); and protocol 5 -- 10 of 17 dogs (59%), compared with 36 of 60 (60%) in control dogs. Using chi-square analysis, protocol 2 was beneficial (p < 0.05). The dogs were then stratified into high- and low-risk subgroups based on the arrhythmic events of the antecedent coronary artery ligation periods, and predictive risk indexes for the occurrence of reperfusion ventricular fibrillation were developed. the Mantel-Haenszel method of statistical analysis revealed that none of these protocols resulted in a statistically significant reduction in the incidence of reperfusion ventricular fibrillation. Thus, use of these predictive indexes plus appropriate statistical methods has revealed, unexpectedly, limitations in the efficacy of a spectrum of antiarrhythmic agents in preventing reperfusion ventricular fibrillation.

Androgen receptor gene status in plasma DNA associates with worse outcome on enzalutamide or abiraterone for castration-resistant prostate cancer: a multi-institution correlative biomarker study.

PubMed

Conteduca, V; Wetterskog, D; Sharabiani, M T A; Grande, E; Fernandez-Perez, M P; Jayaram, A; Salvi, S; Castellano, D; Romanel, A; Lolli, C; Casadio, V; Gurioli, G; Amadori, D; Font, A; Vazquez-Estevez, S; González Del Alba, A; Mellado, B; Fernandez-Calvo, O; Méndez-Vidal, M J; Climent, M A; Duran, I; Gallardo, E; Rodriguez, A; Santander, C; Sáez, M I; Puente, J; Gasi Tandefelt, D; Wingate, A; Dearnaley, D; Demichelis, F; De Giorgi, U; Gonzalez-Billalabeitia, E; Attard, G

2017-07-01

There is an urgent need to identify biomarkers to guide personalized therapy in castration-resistant prostate cancer (CRPC). We aimed to clinically qualify androgen receptor (AR) gene status measurement in plasma DNA using multiplex droplet digital PCR (ddPCR) in pre- and post-chemotherapy CRPC. We optimized ddPCR assays for AR copy number and mutations and retrospectively analyzed plasma DNA from patients recruited to one of the three biomarker protocols with prospectively collected clinical data. We evaluated associations between plasma AR and overall survival (OS) and progression-free survival (PFS) in 73 chemotherapy-naïve and 98 post-docetaxel CRPC patients treated with enzalutamide or abiraterone (Primary cohort) and 94 chemotherapy-naïve patients treated with enzalutamide (Secondary cohort; PREMIERE trial). In the primary cohort, AR gain was observed in 10 (14%) chemotherapy-naïve and 33 (34%) post-docetaxel patients and associated with worse OS [hazard ratio (HR), 3.98; 95% CI 1.74-9.10; P < 0.001 and HR 3.81; 95% CI 2.28-6.37; P < 0.001, respectively], PFS (HR 2.18; 95% CI 1.08-4.39; P = 0.03, and HR 1.95; 95% CI 1.23-3.11; P = 0.01, respectively) and rate of PSA decline ≥50% [odds ratio (OR), 4.7; 95% CI 1.17-19.17; P = 0.035 and OR, 5.0; 95% CI 1.70-14.91; P = 0.003, respectively]. AR mutations [2105T>A (p.L702H) and 2632A>G (p.T878A)] were observed in eight (11%) post-docetaxel but no chemotherapy-naïve abiraterone-treated patients and were also associated with worse OS (HR 3.26; 95% CI 1.47-not reached; P = 0.004). There was no interaction between AR and docetaxel status (P = 0.83 for OS, P = 0.99 for PFS). In the PREMIERE trial, 11 patients (12%) with AR gain had worse PSA-PFS (sPFS) (HR 4.33; 95% CI 1.94-9.68; P < 0.001), radiographic-PFS (rPFS) (HR 8.06; 95% CI 3.26-19.93; P < 0.001) and OS (HR 11.08; 95% CI 2.16-56.95; P = 0.004). Plasma AR was an independent predictor of outcome on multivariable analyses in both cohorts. Plasma AR status assessment using ddPCR identifies CRPC with worse outcome to enzalutamide or abiraterone. Prospective evaluation of treatment decisions based on plasma AR is now required. NCT02288936 (PREMIERE trial). © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Computer-assisted brush-biopsy analysis for the detection of dysplasia in a high-risk Barrett's esophagus surveillance population.

PubMed

Anandasabapathy, Sharmila; Sontag, Stephen; Graham, David Y; Frist, Stephen; Bratton, Joan; Harpaz, Noam; Waye, Jerome D

2011-03-01

Barrett's epithelial dysplasia, the direct precursor to esophageal adenocarcinoma, is often unapparent and frequently missed during surveillance of Barrett's esophagus with four-quadrant forceps biopsy protocol. To determine whether the detection of dysplasia is improved by adding computer-assisted brush biopsy (EndoCDx©) to four-quadrant biopsy protocol. Patients with a history of Barrett's esophagus with dysplasia scheduled for endoscopic surveillance were recruited from four academic medical centers. Patients underwent brush biopsy followed by four-quadrant biopsy every 1-2 cm. The results from brush and forceps biopsy were reviewed independently by pathologists blinded to the other's results. Among 151 patients enrolled (124 men, 27 women; mean age: 65), 117 (77.5%) had forceps and brush-biopsy specimens adequate for interpretation. The mean number of forceps biopsies was 11.9 (median 10, range 2-40) and brush biopsies was 2.0 (median 2, range 1-4). The overall yield of forceps alone was 25.2% (n = 38). Brush biopsy added an additional 16 positive cases increasing the yield of dysplasia detection by 42% (95% CI: 20.7-72.7). The number needed to test (NNT) to detect one additional case of dysplasia was 9.4 (95% CI: 6.4-17.7). There were no significant differences in results among different centers, between standard versus jumbo forceps, or between forceps biopsies taken every 1 cm versus every 2 cm. These data suggest that computer-assisted brush biopsy is a useful adjunct to standard endoscopic surveillance regimens for the identification of dysplasia in Barrett's esophagus.

Effectiveness of bevacizumab and cetuximab in metastatic colorectal cancer across selected public hospitals in Queensland.

PubMed

Chapman, Suzannah J; McKavanagh, Daniel; Burge, Matthew E; McPherson, Ian; Walpole, Euan; Hollingworth, Samantha A

2017-10-01

Metastatic colorectal cancer has a large burden of disease in Australia. Medical therapy is fundamental to extending survival and improving quality of life. The benefits of two costly medicines, bevacizumab and cetuximab, used in Australia remain unclear. The aim of this study was to retrospectively examine the use of these two medicines in metastatic colorectal cancer across five public hospitals in south east Queensland and to compare clinical outcomes to those of published clinical trials. We extracted data from the chemotherapy prescribing database for patients planned for bevacizumab or cetuximab therapy between 2009 and 2013. Median overall survival was estimated using Kaplan-Meier methods. There were 490 bevacizumab-containing protocols planned and 292 patients received at least one dose of bevacizumab. Median overall survival was 17.2 months (95% confidence interval [CI], 15.4-19.3). Of 208 planned cetuximab-containing protocols, 134 patients received at least one dose of cetuximab. Median overall survival was 9.1 months (95% CI, 7.6-12.0). Thirty-day mortality rates from date of first dose were 0.7% for bevacizumab and 7.5% for cetuximab. Overall survival of patients receiving bevacizumab and cetuximab was consistent with clinical trials, providing some assurance that benefits seen in trials are observed in usual practice. This study provides a methodology of using routinely collected health data for clinical monitoring and research. Because of the high cost of these medicines and the lack of toxicity data in this study, further analysis in the postmarketing setting should be explored. © 2016 John Wiley & Sons Australia, Ltd.

Evaluation of a single-scan protocol for radiochromic film dosimetry.

PubMed

Shimohigashi, Yoshinobu; Araki, Fujio; Maruyama, Masato; Nakaguchi, Yuji; Kuwahara, Satoshi; Nagasue, Nozomu; Kai, Yudai

2015-03-08

The purpose of this study was to evaluate a single-scan protocol using Gafchromic EBT3 film (EBT3) by comparing it with the commonly used 24-hr measurement protocol for radiochromic film dosimetry. Radiochromic film is generally scanned 24 hr after film exposure (24-hr protocol). The single-scan protocol enables measurement results within a short time using only the verification film, one calibration film, and unirradiated film. The single-scan protocol was scanned 30 min after film irradiation. The EBT3 calibration curves were obtained with the multichannel film dosimetry method. The dose verifications for each protocol were performed with the step pattern, pyramid pattern, and clinical treatment plans for intensity-modulated radiation therapy (IMRT). The absolute dose distributions for each protocol were compared with those calculated by the treatment planning system (TPS) using gamma evaluation at 3% and 3 mm. The dose distribution for the single-scan protocol was within 2% of the 24-hr protocol dose distribution. For the step pattern, the absolute dose discrepancies between the TPS for the single-scan and 24-hr protocols were 2.0 ± 1.8 cGy and 1.4 ± 1.2 cGy at the dose plateau, respectively. The pass rates were 96.0% for the single-scan protocol and 95.9% for the 24-hr protocol. Similarly, the dose discrepancies for the pyramid pattern were 3.6 ± 3.5cGy and 2.9 ± 3.3 cGy, respectively, while the pass rates for the pyramid pattern were 95.3% and 96.4%, respectively. The average pass rates for the four IMRT plans were 96.7% ± 1.8% for the single-scan protocol and 97.3% ± 1.4% for the 24-hr protocol. Thus, the single-scan protocol measurement is useful for dose verification of IMRT, based on its accuracy and efficiency.

Evaluation of a single‐scan protocol for radiochromic film dosimetry

PubMed Central

Araki, Fujio; Maruyama, Masato; Nakaguchi, Yuji; Kuwahara, Satoshi; Nagasue, Nozomu; Kai, Yudai

2015-01-01

The purpose of this study was to evaluate a single‐scan protocol using Gafchromic EBT3 film (EBT3) by comparing it with the commonly used 24‐hr measurement protocol for radiochromic film dosimetry. Radiochromic film is generally scanned 24 hr after film exposure (24‐hr protocol). The single‐scan protocol enables measurement results within a short time using only the verification film, one calibration film, and unirradiated film. The single‐scan protocol was scanned 30 min after film irradiation. The EBT3 calibration curves were obtained with the multichannel film dosimetry method. The dose verifications for each protocol were performed with the step pattern, pyramid pattern, and clinical treatment plans for intensity‐modulated radiation therapy (IMRT). The absolute dose distributions for each protocol were compared with those calculated by the treatment planning system (TPS) using gamma evaluation at 3% and 3 mm. The dose distribution for the single‐scan protocol was within 2% of the 24‐hr protocol dose distribution. For the step pattern, the absolute dose discrepancies between the TPS for the single‐scan and 24‐hr protocols were 2.0±1.8 cGy and 1.4±1.2 cGy at the dose plateau, respectively. The pass rates were 96.0% for the single‐scan protocol and 95.9% for the 24‐hr protocol. Similarly, the dose discrepancies for the pyramid pattern were 3.6±3.5 cGy and 2.9±3.3 cGy, respectively, while the pass rates for the pyramid pattern were 95.3% and 96.4%, respectively. The average pass rates for the four IMRT plans were 96.7%±1.8% for the single‐scan protocol and 97.3%±1.4% for the 24‐hr protocol. Thus, the single‐scan protocol measurement is useful for dose verification of IMRT, based on its accuracy and efficiency. PACS number: 87.55.Qr PMID:26103194

[Change of care model in natural childbirth: Implementation in La Ribera delivery room].

PubMed

Camacho-Morell, F; Romero-Martín, M J

To assess knowledge, wish for inclusion and implementation of normal childbirth care protocols at La Ribera University Hospital, the reason why they are not applied, and to assess the attendance at antepartum training activities. Cross-sectional descriptive study. They were carried out 186 surveys by convenience sampling to pregnant women attending fetal well-being control at hospital between 2014 and 2015. They were collected data about knowledge, wish for inclusion, compliance of protocols and reasons for non-compliance, and attendance at antepartum training activities. Percentages and confidence intervals were calculated. Chi-square test was used to compare categorical variables. They were collected percentages of knowledge (77%, CI95%: 75,5-78,5) and wish for inclusion (84,6%, CI 95% : 82,5-86,7). Protocol compliance ranged from 6% (nitrous oxide administration) to 91% (skin-to-skin contact). The main reasons for non-compliance were due to circumstances of childbirth process (56,3%, CI 95% : 51,1-61,5). Attendance at maternal education classes was 62%, mainly primiparous women (p=0,0001) with medium or high education level (p=0,001). Pregnant women have a high knowledge and wish for inclusion of normal childbirth care protocols. Attendance at antepartum training activities could by improved and the main reason for non-attendance is lack of information. Compliance is good enough in most protocols; when they are not applied is due to childbirth circumstances. Remaining tasks include the introduction of additional protocols and to involve pregnant women in decision-making. Copyright © 2017 SECA. Publicado por Elsevier España, S.L.U. All rights reserved.

Transdiagnostic and Transcultural: Pilot Study of Unified Protocol for Depressive and Anxiety Disorders in Japan.

PubMed

Ito, Masaya; Horikoshi, Masaru; Kato, Noriko; Oe, Yuki; Fujisato, Hiroko; Nakajima, Shun; Kanie, Ayako; Miyamae, Mitsuhiro; Takebayashi, Yoshitake; Horita, Ryo; Usuki, Masato; Nakagawa, Atsuo; Ono, Yutaka

2016-05-01

Unified protocol (UP) is a transdiagnostic cognitive behavior therapy for emotional disorders. It remains unknown whether UP is applicable for use in non-Western countries and for depressive disorders. We therefore examined its feasibility for a Japanese clinical population using this clinical trial design, which is multicentered, open-labeled, and single-armed (Clinical registry: UMIN000008322). The primary outcome was severity of anxiety symptoms, as assessed using Structured Interview Guide for the Hamilton Anxiety Rating Scale. Secondary outcomes were depressive symptoms, clinical global impression, functioning, quality of life, affectivity, emotion regulation, and adverse events. Of the 28 prospective participants, 17 were eligible and enrolled (depressive disorders=9, anxiety disorders=8). Severity of anxiety symptoms, which decreased significantly after the intervention, remained low for 3months (Hedges' g=1.29, 95% CI=0.56-2.06). Similar tendencies were observed for secondary outcome measures. No severe adverse event occurred. Two participants dropped out of the intervention. High treatment adherence and interrater reliability were confirmed. Results suggest the feasibility of UP in the Japanese context sufficient to warrant a larger clinical trial. Copyright © 2016. Published by Elsevier Ltd.

Majority of systematic reviews published in high-impact journals neglected to register the protocols: a meta-epidemiological study.

PubMed

Tsujimoto, Yasushi; Tsujimoto, Hiraku; Kataoka, Yuki; Kimachi, Miho; Shimizu, Sayaka; Ikenoue, Tatsuyoshi; Fukuma, Shingo; Yamamoto, Yosuke; Fukuhara, Shunichi

2017-04-01

To describe the registration of systematic review (SR) protocols and examine whether or not registration reduced the outcome reporting bias in high-impact journals. We searched MEDLINE via PubMed to identify SRs of randomized controlled trials of interventions. We included SRs published between August 2009 and June 2015 in the 10 general and internal medicinal journals with the highest impact factors in 2013. We examined the proportion of SR protocol registration and investigated the relationship between registration and outcome reporting bias using multivariable logistic regression. Among the 284 included reviews, 60 (21%) protocols were registered. The proportion of registration increased from 5.6% in 2009 to 27% in 2015 (P for trend <0.001). Protocol registration was not associated with outcome reporting bias (adjusted odds ratio [OR] 0.85, 95% confidence interval [CI] 0.39-1.86). The association between Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) adherence and protocol registration was not statistically significant (OR 1.09, 95% CI 0.59-2.01). Six years after the launch of the PRISMA statement, the proportion of protocol registration in high-impact journals has increased some but remains low. The present study found no evidence suggesting that protocol registration reduced outcome reporting bias. Copyright © 2017 Elsevier Inc. All rights reserved.

Immune-mediated inflammatory diseases and other comorbidities in patients with psoriasis: baseline characteristics of patients in the AQUILES study.

PubMed

Vanaclocha, F; Crespo-Erchiga, V; Jiménez-Puya, R; Puig, L; Sánchez-Carazo, J L; Ferrán, M; Sancho, C; Juliá, B; Cea-Calvo, L; Marín-Jiménez, I; García-Vicuña, R

2015-01-01

Patients with psoriasis often have comorbidities, including other immune-mediated inflammatory diseases (IMIDs), and cardiovascular risk factors. In this article we describe the baseline prevalence of comorbidities-including other IMIDs-in a cohort of patients with psoriasis. AQUILES was a prospective observational multicenter study of 3 patient cohorts (patients with psoriasis, spondyloarthritis, or inflammatory bowel disease) undertaken to investigate the prevalence of comorbidities, including other IMIDs, in these settings. The psoriasis cohort comprised patients aged at least 18 years who were seen in hospital dermatology clinics. A predefined protocol was used to collect demographic and clinical data. The study enrolled 528 patients with psoriasis (60.2% men and 39.8% women). Mean age was 46.7 years; 89.8% of the participants had plaque psoriasis, and the median Psoriasis Area Severity Index score (PASI) was 3.2 (1.5-7.4). Comorbid IMIDs were present in 82 (15.5%) of the patients (CI 95%, 12.7%-18.9%). Spondyloarthritis was observed in 14% of patients (95% CI, 11.3%-17.2%), mostly in the form of psoriatic arthritis, for which the overall prevalence was 13.1% (95% CI, 10.5%-16.2%). Inflammatory bowel disease was present in 1.3% (95% CI, 0.6%-2.7%) and uveitis in .2% (95% CI, 0.1%-1.4%). Psoriatic arthritis was associated with male sex (odds ratio, 1.75 [.98-2.98]) and a disease duration of over 8 years (OR, 4.17 [1.84-9.44] vs a duration of < 4 years). In 73.1%, at least 1 cardiovascular risk factor was identified: smoking (40.5%), obesity (26.0%), dyslipidemia (24.8%), hypertension (24.3%), and diabetes mellitus (12.3%). In patients with psoriasis the prevalence of other IMIDs was 15.5%, a level slightly higher than that found in the general population. Nearly three-quarters of these patients had at least 1 cardiovascular risk factor. Copyright © 2014 Elsevier España, S.L.U. and AEDV. All rights reserved.

The quality of reports of medical and public health research from Palestinian institutions: a systematic review

PubMed Central

Abu-Rmeileh, Niveen ME; Elessi, Khamis; Obeidallah, Mohammad; Bjertness, Espen; Chalmers, Iain

2017-01-01

Objective Over the past decade, there has been an increase in reports of health research from Palestine, but no assessment of their quality. We have assessed the quality of reports of Palestinian health research and factors associated with it. Design This is a systematic review. Inclusion criteria We searched Medline and Scopus for reports of original research relevant to human health or healthcare authored by researchers affiliated with Palestinian institutions and published between January 2000 and August 2015 inclusive. Outcomes We used international guidelines to assess report quality, classifying as adequate those with ≥50% of items completely addressed. Results Of 2383 reports identified, 497 met our inclusion criteria. Just over half (264; 55%) of these were published after 2010. 354 (71%) of first authors were affiliated with Palestinian institutions; 261 (53%) reports had coauthors from outside Palestine. The majority of the reports in our study were inadequately reported (342; 69%), and none had adequately reported all items. Of 439 observational studies, 11 (2.5%) reports provided adequate descriptions of eligibility criteria and selection procedures; 35 (8%) reported efforts to address potential sources of bias; 50 (11.4%) reported the basis for the study sample size; and funding sources were mentioned in 74 reports (17%). Higher reporting quality was associated with international affiliation of the first author (prevalence ratio (PR) 1.6 (95% CI 1.2 to 2.1)), international collaboration (PR 2.9 (95% CI 1.7 to 5.0)), international funding (PR 1.9 (95% CI1.5 to 2.5)), publication after 2005 (PR 3.9 (95% CI 1.8 to 8.5)) and four or more coauthors (PR 1.5 (95% CI 1.1 to 2.1)). Conclusion Although the quality of reports of Palestinian research has improved in recent years, it remains well below an acceptable standard. International reporting guidelines should be used to guide research design and improve the quality of reports of research. Trial registration number The systematic review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) registery (registration number: CRD42015027553). PMID:28601839

Accuracy of Reduced-Dose Computed Tomography for Ureteral Stones in Emergency Department Patients

PubMed Central

Moore, Christopher L.; Daniels, Brock; Ghita, Monica; Gunabushanam, Gowthaman; Luty, Seth; Molinaro, Annette M.; Singh, Dinesh; Gross, Cary P.

2016-01-01

Study objective Reduced-dose computed tomography (CT) scans have been recommended for diagnosis of kidney stone but are rarely used in the emergency department (ED) setting. Test characteristics are incompletely characterized, particularly in obese patients. Our primary outcome is to determine the sensitivity and specificity of a reduced-dose CT protocol for symptomatic ureteral stones, particularly those large enough to require intervention, using a protocol stratified by patient size. Methods This was a prospective, blinded observational study of 201 patients at an academic medical center. Consenting subjects underwent both regular- and reduced-dose CT, stratified into a high and low body mass index (BMI) protocol based on effective abdominal diameter. Reduced-dose CT scans were interpreted by radiologists blinded to regular-dose interpretations. Follow-up for outcome and intervention was performed at 90 days. Results CT scans with both regular and reduced doses were conducted for 201 patients, with 63% receiving the high BMI reduced-dose protocol. Ureteral stone was identified in 102 patients (50.7%) of those receiving regular-dose CT, with a ureteral stone greater than 5 mm identified in 26 subjects (12.9%). Sensitivity of the reduced-dose CT for any ureteral stone was 90.2% (95% confidence interval [CI] 82.3% to 95.0%), with a specificity of 99.0% (95% CI 93.7% to 100.0%). For stones greater than 5 mm, sensitivity was 100% (95% CI 85.0% to 100.0%). Reduced-dose CT identified 96% of patients who required intervention for ureteral stone within 90 days. Mean reduction in size-specific dose estimate was 18.6 milligray (mGy), from 21.7 mGy (SD 9.7) to 3.4 mGy (SD 0.9). Conclusion CT with substantial dose reduction was 90.2% (95% CI 82.3% to 95.0%) sensitive and 98.9% (95% CI 85.0% to 100.0%) specific for ureteral stones in ED patients with a wide range of BMIs. Reduced-dose CT was 96.0% (95% CI 80.5% to 99.3%) sensitive for ureteral stones requiring intervention within 90 days. PMID:25441242

Prescription opioid use: Patient characteristics and misuse in community pharmacy.

PubMed

Cochran, Gerald; Bacci, Jennifer L; Ylioja, Thomas; Hruschak, Valerie; Miller, Sharon; Seybert, Amy L; Tarter, Ralph

2016-01-01

Opioid pain medication misuse is a major concern for US public health. The purpose of this article is to: 1) describe the demographic and physical, behavioral, and mental health characteristics of patients who fill opioid medications in community pharmacy settings; and 2) describe the extent of opioid medication misuse behaviors among these patients. We recruited and screened a convenience sample of patients with the use of a tablet computer-based assessment protocol that examined behavioral, mental, and physical health. Descriptive and inferential statistics were calculated to describe respondents and their opioid medication misuse and health characteristics. Patients were screened in 2 urban and 2 rural community pharmacies in southwestern Pennsylvania. Survey participants were adult patients filling opioid pain medications who were not currently receiving treatment for a cancer diagnosis. None. Validated screening measures included the Prescription Opioid Misuse Index, Alcohol Use Disorders Identification Test C, Short Form 12, Drug Abuse Screening Test 10, Primary Care Post-traumatic Stress Disorder (PTSD) screen, and the Patient Health Questionnaire 2. A total of 333 patients were screened (71.2% response rate). Nearly the entire population reported pain above and general health below national norms. Hydrocodone (19.2%) and morphine (20.8%) were found to be the medications with the highest rates of misuse-with hydrocodone having more than 4 times higher odds of misuse compared with other medications (adjusted odds ratio [AOR] 4.48, 95% confidence interval [CI] 1.1-17.4). Patients with positive screens for illicit drug use (AOR 8.07, 95% CI 2.7-24.0), PTSD (AOR 5.88, 95% CI 2.3-14.7), and depression (AOR 2.44, 95% CI 1.0-5.9) also had significantly higher odds for misuse compared with those with negative screening results. These findings provide important foundational data that suggest implementation of regular opioid misuse screening protocols within community pharmacies. Such screening activities could foster a culture of prevention and overall reduction for misuse among patients filling opioid medications in community pharmacies. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Effectiveness of Homeopathic Medicines as Add-on to Institutional Management Protocol for Acute Encephalitis Syndrome in Children: An Open-Label Randomized Placebo-Controlled Trial.

PubMed

Oberai, Praveen; Varanasi, Roja; Padmanabhan, Maya; Upadhyaya, Alok; Singh, Supriya; Singh, Samarendra Pratap; Vikram, Deepika; Khan, Tariq; Prasad, Ramesh; Gupta, A K; Singh, J R; Manchanda, Raj K

2018-06-05

 Acute encephalitis syndrome (AES) is endemic to certain parts of India, with limited treatment options. In our initial exploratory comparative observational study of 151 patients with AES, there was significantly reduced mortality with adjunctive homeopathy compared to institutional management protocol (IMP). The present randomized placebo-controlled trial brings more statistical rigor to this research program.  This study was conducted at a pediatric unit from 2013 to 2015. Children aged > 6 months and ≤ 18 years and receiving IMP were randomized to receive adjunctive homeopathy ( n  = 325) or placebo as control ( n  = 323). The primary effectiveness analysis was based on Glasgow Outcome Scale (GOS). Morbidity was assessed using the Liverpool Outcome Score for Assessing Children at Follow-up. Analysis was by intention to treat.  A total of 612 children were analyzed (Homeopathy [H] = 304; Control [C] = 308). The primary outcome, GOS, differed significantly between H and C groups. There was 14.8% death/neuro-vegetative state in the H group compared to 29.8% in the C group. Relative risk was 0.49 (95% confidence interval [CI]: 0.36 to 0.68), with absolute risk reduction of 15.0% (95% CI: 8.6 to 21.6%). Number needed to treat to prevent one additional death/neuro-vegetative state was 6.6 (95% CI: 4.6 to 11.6). Proportional-odds analysis also revealed a greater effect in the H group: odds ratio, 0.40 (95% CI: 0.27 to 0.60). The most frequently used medicines were Belladonna ( n  = 116), Stramonium ( n  = 33), Arsenicum album ( n  = 25), Sulfur ( n  = 18), Opium ( n  = 17), and Nux vomica ( n  = 10).  Adjunctive homeopathic medicines may improve clinical outcomes associated with AES. Further randomized and controlled studies, using double-blinded trial design, are recommended to discover if the current findings may be corroborated. The Faculty of Homeopathy.

PRESCRIPTION OPIOID USE: PATIENT CHARACTERISTICS AND MISUSE IN COMMUNITY PHARMACY

PubMed Central

Cochran, Gerald; Bacci, Jennifer L.; Ylioja, Thomas; Hruschak, Valerie; Miller, Sharon; Seybert, Amy L.; Tarter, Ralph

2016-01-01

Objective Opioid pain medication misuse is a major concern for U.S. public health. The purpose of this article is to: 1) describe the demographic and physical, behavioral, and mental health characteristics of patients who fill opioid medications in community pharmacy settings and 2) describe the extent of opioid medication misuse behaviors among these patients. Design We recruited and screened a convenience sample of patients using a tablet computer-based assessment protocol that examined behavioral, mental, and physical health. Descriptive and inferential statistics were calculated to describe respondents and their opioid medication misuse and health characteristics. Setting Patients were screened in 2 urban and 2 rural community pharmacies in southwestern Pennsylvania. Participants Survey participants were adult patients filling opioid pain medications who were not currently receiving treatment for a cancer diagnosis. Main Outcome Measures Validated screening measures included the: Prescription Opioid Misuse Index, Alcohol Use Disorders Identification Test-C, Short-Form-12, Drug Abuse Screening Test-10, Primary Care Post-traumatic Stress Disorder (PTSD) screen, and the Patient Health Questionnaire-2. Results A total of 333 patients were screened (71.2% response rate). Nearly the entire population reported pain above and general health below national norms. Hydrocodone (19.2%) and morphine (20.8%) were found to be the medications with the highest rates of misuse—with hydrocodone having higher odds for misuse by more than four times compared to other medications (AOR=4.48; 95% CI=1.1–17.4). Patients with positive screens for illicit drug use (AOR=8.07; 95% CI=2.7–24.0), PTSD (AOR=5.88; 95% CI=2.3–14.7), and depression (AOR=2.44; 95% CI=1.0–5.9) also had significantly higher odds for misuse compared to those with negative screening results. Conclusion These findings provide important foundational data that suggest implementation of regular opioid misuse screening protocols within community pharmacies. Such screening activities could foster a culture of prevention and overall reduction for misuse among patients filling opioid medications in community pharmacies. PMID:27053277

17 CFR 9.5 - Motions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... DISCIPLINARY, ACCESS DENIAL OR OTHER ADVERSE ACTIONS General Provisions § 9.5 Motions. (a) In general. An... request reconsideration, vacation or modification of the action. (d) Dilatory motions. Frivolous or... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Motions. 9.5 Section 9.5...

17 CFR 9.5 - Motions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... DISCIPLINARY, ACCESS DENIAL OR OTHER ADVERSE ACTIONS General Provisions § 9.5 Motions. (a) In general. An... request reconsideration, vacation or modification of the action. (d) Dilatory motions. Frivolous or... 17 Commodity and Securities Exchanges 1 2011-04-01 2011-04-01 false Motions. 9.5 Section 9.5...

The self-paced VO2max test to assess maximal oxygen uptake in highly trained runners.

PubMed

Hogg, James S; Hopker, James G; Mauger, Alexis R

2015-03-01

The novel self-paced maximal-oxygen-uptake (VO2max) test (SPV) may be a more suitable alternative to traditional maximal tests for elite athletes due to the ability to self-regulate pace. This study aimed to examine whether the SPV can be administered on a motorized treadmill. Fourteen highly trained male distance runners performed a standard graded exercise test (GXT), an incline-based SPV (SPVincline), and a speed-based SPV (SPVspeed). The GXT included a plateau-verification stage. Both SPV protocols included 5×2-min stages (and a plateau-verification stage) and allowed for self-pacing based on fixed increments of rating of perceived exertion: 11, 13, 15, 17, and 20. The participants varied their speed and incline on the treadmill by moving between different marked zones in which the tester would then adjust the intensity. There was no significant difference (P=.319, ES=0.21) in the VO2max achieved in the SPVspeed (67.6±3.6 mL·kg(-1)·min(-1), 95%CI=65.6-69.7 mL·kg(-1)·min(-1)) compared with that achieved in the GXT (68.6±6.0 mL·kg(-1)·min(-1), 95%CI=65.1-72.1 mL·kg(-1)·min(-1)). Participants achieved a significantly higher VO2max in the SPVincline (70.6±4.3 mL·kg(-1)·min(-1), 95%CI=68.1-73.0 mL·kg(-1)·min(-1)) than in either the GXT (P=.027, ES=0.39) or SPVspeed (P=.001, ES=0.76). The SPVspeed protocol produces VO2max values similar to those obtained in the GXT and may represent a more appropriate and athlete-friendly test that is more oriented toward the variable speed found in competitive sport.

Evaluation of the use of automatic exposure control and automatic tube potential selection in low-dose cerebrospinal fluid shunt head CT.

PubMed

Wallace, Adam N; Vyhmeister, Ross; Bagade, Swapnil; Chatterjee, Arindam; Hicks, Brandon; Ramirez-Giraldo, Juan Carlos; McKinstry, Robert C

2015-06-01

Cerebrospinal fluid shunts are primarily used for the treatment of hydrocephalus. Shunt complications may necessitate multiple non-contrast head CT scans resulting in potentially high levels of radiation dose starting at an early age. A new head CT protocol using automatic exposure control and automated tube potential selection has been implemented at our institution to reduce radiation exposure. The purpose of this study was to evaluate the reduction in radiation dose achieved by this protocol compared with a protocol with fixed parameters. A retrospective sample of 60 non-contrast head CT scans assessing for cerebrospinal fluid shunt malfunction was identified, 30 of which were performed with each protocol. The radiation doses of the two protocols were compared using the volume CT dose index and dose length product. The diagnostic acceptability and quality of each scan were evaluated by three independent readers. The new protocol lowered the average volume CT dose index from 15.2 to 9.2 mGy representing a 39 % reduction (P < 0.01; 95 % CI 35-44 %) and lowered the dose length product from 259.5 to 151.2 mGy/cm representing a 42 % reduction (P < 0.01; 95 % CI 34-50 %). The new protocol produced diagnostically acceptable scans with comparable image quality to the fixed parameter protocol. A pediatric shunt non-contrast head CT protocol using automatic exposure control and automated tube potential selection reduced patient radiation dose compared with a fixed parameter protocol while producing diagnostic images of comparable quality.

A quasi-experimental, before-after trial examining the impact of an emergency department mechanical ventilator protocol on clinical outcomes and lung-protective ventilation in acute respiratory distress syndrome

PubMed Central

Fuller, Brian M.; Ferguson, Ian T.; Mohr, Nicholas M.; Drewry, Anne M.; Palmer, Christopher; Wessman, Brian T.; Ablordeppey, Enyo; Keeperman, Jacob; Stephens, Robert J.; Briscoe, Cristopher C.; Kolomiets, Angelina A.; Hotchkiss, Richard S.; Kollef, Marin H.

2017-01-01

Objective To evaluate the impact of an emergency department (ED) mechanical ventilation protocol on clinical outcomes and adherence to lung-protective ventilation in patients with acute respiratory distress syndrome (ARDS). Design Quasi-experimental, before-after trial. Setting ED and intensive care units (ICU) of an academic center. Patients Mechanically ventilated ED patients experiencing ARDS while in the ED or after admission to the ICU. Interventions An ED ventilator protocol which targeted parameters in need of quality improvement, as identified by prior work: 1) lung-protective tidal volume; 2) appropriate setting of positive end-expiratory pressure (PEEP); 3) oxygen weaning; and 4) head-of-bed elevation. Measurements and Main Results A total of 229 patients (186 pre-intervention group, 43 intervention group) were studied. In the ED, the intervention was associated with significant changes (P < 0.01 for all) in tidal volume, PEEP, respiratory rate, oxygen administration, and head-of-bed elevation. There was a reduction in ED tidal volume from 8.1 mL/kg PBW (7.0 – 9.1) to 6.4 mL/kg PBW (6.1 – 6.7), and an increase in lung-protective ventilation from 11.1% to 61.5%, P < 0.01. The intervention was associated with a reduction in mortality from 54.8% to 39.5% (OR 0.38, 95% CI 0.17 – 0.83, P = 0.02), and a 3.9 day increase in ventilator-free days, P = 0.01. Conclusions This before-after study of mechanically ventilated patients with ARDS demonstrates that implementing a mechanical ventilator protocol in the ED is feasible, and associated with improved clinical outcomes. PMID:28157140

Silanated Surface Treatment: Effects on the Bond Strength to Lithium Disilicate Glass-Ceramic.

PubMed

Baratto, Samantha Schaffer Pugsley; Spina, Denis Roberto Falcão; Gonzaga, Carla Castiglia; Cunha, Leonardo Fernandes da; Furuse, Adilson Yoshio; Baratto Filho, Flares; Correr, Gisele Maria

2015-10-01

The aim of this study was to evaluate the effect of silanization protocols on the bond strength of two resin cements to a lithium disilicate glass-ceramic. Thirty-two ceramic discs were assigned to 2 groups (n=16): G1 - dual-cured resin cement and G2 - light-cured resin cement. Four subgroups were evaluated according to the used silanization protocol. The glass-ceramic was etched with 10% hydrofluoric acid for 20 s and silane was applied for 1 min, as follows: CTL - according to the manufacturer's instructions; HA - dried with hot air; NWA - washed and dried with water and air at room temperature; HWA - washed and dried with hot water and hot air. Thereafter, adhesive was applied and light-cured for 20 s. Silicon molds were used to prepare resin cement cylinders (1x1 mm) on the ceramic surface. The specimens were stored in deionized water at 37 °C for 48 h and subjected to a micro-shear test. The data were submitted to statistical analysis (?#61537;=0.05). Group G1 showed higher bond strengths than G2, except for the CTL and NWA subgroups. Differences as function of the silanization protocol were only observed in G1: HWA (25.13±6.83)≥HA (22.95±7.78)≥CTL(17.44±7.24) ≥NWA(14.63±8.76). For G2 there was no difference among the subgroups. In conclusion, the silanization protocol affected the resin cement/ceramic bond strengths, depending on the material. Washing/drying with hot water and/or hot air increased only the bond strength of the dual-cured resin cement.

A Quasi-Experimental, Before-After Trial Examining the Impact of an Emergency Department Mechanical Ventilator Protocol on Clinical Outcomes and Lung-Protective Ventilation in Acute Respiratory Distress Syndrome.

PubMed

Fuller, Brian M; Ferguson, Ian T; Mohr, Nicholas M; Drewry, Anne M; Palmer, Christopher; Wessman, Brian T; Ablordeppey, Enyo; Keeperman, Jacob; Stephens, Robert J; Briscoe, Cristopher C; Kolomiets, Angelina A; Hotchkiss, Richard S; Kollef, Marin H

2017-04-01

To evaluate the impact of an emergency department mechanical ventilation protocol on clinical outcomes and adherence to lung-protective ventilation in patients with acute respiratory distress syndrome. Quasi-experimental, before-after trial. Emergency department and ICUs of an academic center. Mechanically ventilated emergency department patients experiencing acute respiratory distress syndrome while in the emergency department or after admission to the ICU. An emergency department ventilator protocol which targeted variables in need of quality improvement, as identified by prior work: 1) lung-protective tidal volume, 2) appropriate setting of positive end-expiratory pressure, 3) oxygen weaning, and 4) head-of-bed elevation. A total of 229 patients (186 preintervention group, 43 intervention group) were studied. In the emergency department, the intervention was associated with significant changes (p < 0.01 for all) in tidal volume, positive end-expiratory pressure, respiratory rate, oxygen administration, and head-of-bed elevation. There was a reduction in emergency department tidal volume from 8.1 mL/kg predicted body weight (7.0-9.1) to 6.4 mL/kg predicted body weight (6.1-6.7) and an increase in lung-protective ventilation from 11.1% to 61.5%, p value of less than 0.01. The intervention was associated with a reduction in mortality from 54.8% to 39.5% (odds ratio, 0.38; 95% CI, 0.17-0.83; p = 0.02) and a 3.9 day increase in ventilator-free days, p value equals to 0.01. This before-after study of mechanically ventilated patients with acute respiratory distress syndrome demonstrates that implementing a mechanical ventilator protocol in the emergency department is feasible and associated with improved clinical outcomes.

Improved recovery of functionally active eosinophils and neutrophils using novel immunomagnetic technology.

PubMed

Son, Kiho; Mukherjee, Manali; McIntyre, Brendan A S; Eguez, Jose C; Radford, Katherine; LaVigne, Nicola; Ethier, Caroline; Davoine, Francis; Janssen, Luke; Lacy, Paige; Nair, Parameswaran

2017-10-01

Clinically relevant and reliable reports derived from in vitro research are dependent on the choice of cell isolation protocols adopted between different laboratories. Peripheral blood eosinophils are conventionally isolated using density-gradient centrifugation followed by immunomagnetic selection (positive/negative) while neutrophils follow a more simplified dextran-sedimentation methodology. With the increasing sophistication of molecular techniques, methods are now available that promise protocols with reduced user-manipulations, improved efficiency, and better yield without compromising the purity of enriched cell populations. These recent techniques utilize immunomagnetic particles with multiple specificities against differential cell surface markers to negatively select non-target cells from whole blood, greatly reducing the cost/time taken to isolate granulocytes. Herein, we compare the yield efficiencies, purity and baseline activation states of eosinophils/neutrophils isolated using one of these newer protocols that use immunomagnetic beads (MACSxpress isolation) vs. the standard isolation procedures. The study shows that the MACSxpress method consistently allowed higher yields per mL of peripheral blood compared to conventional methods (P<0.001, n=8, Wilcoxon paired test), with high isolation purities for both eosinophils (95.0±1.7%) and neutrophils (94.2±10.1%) assessed by two methods: Wright's staining and flow cytometry. In addition, enumeration of CD63 + (marker for eosinophil activation) and CD66b + (marker for neutrophil activation) cells within freshly isolated granulocytes, respectively, confirmed that conventional protocols using density-gradient centrifugation caused cellular activation of the granulocytes at baseline compared to the MACSxpress method. In conclusion, MACSxpress isolation kits were found to be superior to conventional techniques for consistent purifications of eosinophils and neutrophils that were suitable for activation assays involving degranulation markers. Copyright © 2017 Elsevier B.V. All rights reserved.

Efficacy of two types of palliative sedation therapy defined using intervention protocols: proportional vs. deep sedation.

PubMed

Imai, Kengo; Morita, Tatsuya; Yokomichi, Naosuke; Mori, Masanori; Naito, Akemi Shirado; Tsukuura, Hiroaki; Yamauchi, Toshihiro; Kawaguchi, Takashi; Fukuta, Kaori; Inoue, Satoshi

2018-06-01

This study investigated the effect of two types of palliative sedation defined using intervention protocols: proportional and deep sedation. We retrospectively analyzed prospectively recorded data of consecutive cancer patients who received the continuous infusion of midazolam in a palliative care unit. Attending physicians chose the sedation protocol based on each patient's wish, symptom severity, prognosis, and refractoriness of suffering. The primary endpoint was a treatment goal achievement at 4 h: in proportional sedation, the achievement of symptom relief (Support Team Assessment Schedule (STAS) ≤ 1) and absence of agitation (modified Richmond Agitation-Sedation Scale (RASS) ≤ 0) and in deep sedation, the achievement of deep sedation (RASS ≤ - 4). Secondary endpoints included mean scores of STAS and RASS, deep sedation as a result, and adverse events. Among 398 patients who died during the period, 32 received proportional and 18 received deep sedation. The treatment goal achievement rate was 68.8% (22/32, 95% confidence interval 52.7-84.9) in the proportional sedation group vs. 83.3% (15/18, 66.1-100) in the deep sedation group. STAS decreased from 3.8 to 0.8 with proportional sedation at 4 h vs. 3.7 to 0.3 with deep sedation; RASS decreased from + 1.2 to - 1.7 vs. + 1.4 to - 3.7, respectively. Deep sedation was needed as a result in 31.3% (10/32) of the proportional sedation group. No fatal events that were considered as probably or definitely related to the intervention occurred. The two types of intervention protocol well reflected the treatment intention and expected outcomes. Further, large-scale cohort studies are promising.

Association of IL-17A and IL-17F polymorphisms with gastric cancer risk in Asians: a meta-analysis.

PubMed

Liu, Jingwei; Xu, Qian; Yuan, Quan; Wang, Zhenning; Xing, Chengzhong; Yuan, Yuan

2015-01-01

Increasing number of studies focused on the association of IL-17A rs2275913 and IL-17F rs763780 polymorphisms with gastric cancer (GC) risk. However, the results were inconsistent. To elucidate the exact association, we performed the present meta-analysis. Databases including PubMed, Web of knowledge and Chinese National Knowledge Infrastructure (CNKI) were systematically searched for potentially eligible literatures. Odds ratios (OR) and their 95% confidence interval (CI) were used to evaluate the strength of association. Eight studies for IL-17A rs2275913 (3345 cases and 4427 controls) and five studies for IL-17F rs763780 (1784 cases and 2592 controls) were finally included. The results indicated that individuals with AA genotype of IL-17A rs2275913 polymorphism were associated with increased GC risk compared with wild-type GG (OR=1.61, 95% CI=1.17-2.23, P=0.004); A allele was significantly associated with increased GC risk compared with G allele (OR=1.22, 95% CI=1.06-1.41, P=0.007). IL-17F rs763780 polymorphism was also significantly associated with increased GC risk (CC vs. CT: OR=1.40, 95% CI=1.04-1.88, P=0.025; CT vs. TT: OR=1.35, 95% CI=1.16-1.58, P<0.001; C allele vs. T allele: OR=1.30, 95% CI=1.15-1.47, P<0.001). In summary, IL-17A rs2275913 A/G polymorphism and IL-17F rs763780 C/T polymorphism might be associated with increased GC risk in Asians. Further large-scale studies are still required to confirm the results of this meta-analysis. Copyright © 2014. Published by Elsevier Inc.

A validity study of self-reported daily texting frequency, cell phone characteristics, and texting styles among young adults.

PubMed

Gold, Judith E; Rauscher, Kimberly J; Zhu, Motao

2015-04-02

Texting is associated with adverse health effects including musculoskeletal disorders, sleep disturbances, and traffic crashes. Many studies have relied on self-reported texting frequency, yet the validity of self-reports is unknown. Our objective was to provide some of the first data on the validity of self-reported texting frequency, cell phone characteristics including input device (e.g. touchscreen), key configuration (e.g., QWERTY), and texting styles including phone orientation (e.g., horizontal) and hands holding the phone while texting. Data were collected using a self-administered questionnaire and observation of a texting task among college students ages 18 to 24. To gauge agreement between self-reported and phone bill-derived categorical number of daily text messages sent, we calculated percent of agreement, Spearman correlation coefficient, and a linear weighted kappa statistic. For agreement between self-reported and observed cell phone characteristics and texting styles we calculated percentages of agreement. We used chi-square tests to detect significant differences (α = 0.05) by gender and study protocol. There were 106 participants; 87 of which had complete data for texting frequency analyses. Among these 87, there was 26% (95% CI: 21-31) agreement between self-reported and phone bill-derived number of daily text messages sent with a Spearman's rho of 0.48 and a weighted kappa of 0.17 (95% CI: 0.06-0.27). Among those who did not accurately report the number of daily texts sent, 81% overestimated this number. Among the full sample (n = 106), there was high agreement between self-reported and observed texting input device (96%, 95% CI: 91-99), key configuration (89%, 95% CI: 81-94), and phone orientation while texting (93%, 95% CI: 86-97). No differences were found by gender or study protocol among any items. While young adults correctly reported their cell phone's characteristics and phone orientation while texting, most incorrectly estimated the number of daily text messages they sent. This suggests that while self-reported texting frequency may be useful for studies where relative ordering is adequate, it should not be used in epidemiologic studies to identify a risk threshold. For these studies, it is recommended that a less biased measure, such as a cell phone bill, be utilized.

Cure modeling in real-time prediction: How much does it help?

PubMed

Ying, Gui-Shuang; Zhang, Qiang; Lan, Yu; Li, Yimei; Heitjan, Daniel F

2017-08-01

Various parametric and nonparametric modeling approaches exist for real-time prediction in time-to-event clinical trials. Recently, Chen (2016 BMC Biomedical Research Methodology 16) proposed a prediction method based on parametric cure-mixture modeling, intending to cover those situations where it appears that a non-negligible fraction of subjects is cured. In this article we apply a Weibull cure-mixture model to create predictions, demonstrating the approach in RTOG 0129, a randomized trial in head-and-neck cancer. We compare the ultimate realized data in RTOG 0129 to interim predictions from a Weibull cure-mixture model, a standard Weibull model without a cure component, and a nonparametric model based on the Bayesian bootstrap. The standard Weibull model predicted that events would occur earlier than the Weibull cure-mixture model, but the difference was unremarkable until late in the trial when evidence for a cure became clear. Nonparametric predictions often gave undefined predictions or infinite prediction intervals, particularly at early stages of the trial. Simulations suggest that cure modeling can yield better-calibrated prediction intervals when there is a cured component, or the appearance of a cured component, but at a substantial cost in the average width of the intervals. Copyright © 2017 Elsevier Inc. All rights reserved.

Reliability and Validity of the Inline Skating Skill Test.

PubMed

Radman, Ivan; Ruzic, Lana; Padovan, Viktoria; Cigrovski, Vjekoslav; Podnar, Hrvoje

2016-09-01

This study aimed to examine the reliability and validity of the inline skating skill test. Based on previous skating experience forty-two skaters (26 female and 16 male) were randomized into two groups (competitive level vs. recreational level). They performed the test four times, with a recovery time of 45 minutes between sessions. Prior to testing, the participants rated their skating skill using a scale from 1 to 10. The protocol included performance time measurement through a course, combining different skating techniques. Trivial changes in performance time between the repeated sessions were determined in both competitive females/males and recreational females/males (-1.7% [95% CI: -5.8-2.6%] - 2.2% [95% CI: 0.0-4.5%]). In all four subgroups, the skill test had a low mean within-individual variation (1.6% [95% CI: 1.2-2.4%] - 2.7% [95% CI: 2.1-4.0%]) and high mean inter-session correlation (ICC = 0.97 [95% CI: 0.92-0.99] - 0.99 [95% CI: 0.98-1.00]). The comparison of detected typical errors and smallest worthwhile changes (calculated as standard deviations × 0.2) revealed that the skill test was able to track changes in skaters' performances. Competitive-level skaters needed shorter time (24.4-26.4%, all p < 0.01) to complete the test in comparison to recreational-level skaters. Moreover, moderate correlation (ρ = 0.80-0.82; all p < 0.01) was observed between the participant's self-rating and achieved performance times. In conclusion, the proposed test is a reliable and valid method to evaluate inline skating skills in amateur competitive and recreational level skaters. Further studies are needed to evaluate the reproducibility of this skill test in different populations including elite inline skaters.

Resource use and costs of type 2 diabetes patients receiving managed or protocolized primary care: a controlled clinical trial.

PubMed

van der Heijden, Amber A W A; de Bruijne, Martine C; Feenstra, Talitha L; Dekker, Jacqueline M; Baan, Caroline A; Bosmans, Judith E; Bot, Sandra D M; Donker, Gé A; Nijpels, Giel

2014-06-25

The increasing prevalence of diabetes is associated with increased health care use and costs. Innovations to improve the quality of care, manage the increasing demand for health care and control the growth of health care costs are needed. The aim of this study is to evaluate the care process and costs of managed, protocolized and usual care for type 2 diabetes patients from a societal perspective. In two distinct regions of the Netherlands, both managed and protocolized diabetes care were implemented. Managed care was characterized by centralized organization, coordination, responsibility and centralized annual assessment. Protocolized care had a partly centralized organizational structure. Usual care was characterized by a decentralized organizational structure. Using a quasi-experimental control group pretest-posttest design, the care process (guideline adherence) and costs were compared between managed (n = 253), protocolized (n = 197), and usual care (n = 333). We made a distinction between direct health care costs, direct non-health care costs and indirect costs. Multivariate regression models were used to estimate differences in costs adjusted for confounding factors. Because of the skewed distribution of the costs, bootstrapping methods (5000 replications) with a bias-corrected and accelerated approach were used to estimate 95% confidence intervals (CI) around the differences in costs. Compared to usual and protocolized care, in managed care more patients were treated according to diabetes guidelines. Secondary health care use was higher in patients under usual care compared to managed and protocolized care. Compared to usual care, direct costs were significantly lower in managed care (€-1.181 (95% CI: -2.597 to -334)) while indirect costs were higher (€ 758 (95% CI: -353 to 2.701), although not significant. Direct, indirect and total costs were lower in protocolized care compared to usual care (though not significantly). Compared to usual care, managed care was significantly associated with better process in terms of diabetes care, fewer secondary care consultations and lower health care costs. The same trends were seen for protocolized care, however they were not statistically significant. Current Controlled trials: ISRCTN66124817.

Resource use and costs of type 2 diabetes patients receiving managed or protocolized primary care: a controlled clinical trial

PubMed Central

2014-01-01

Background The increasing prevalence of diabetes is associated with increased health care use and costs. Innovations to improve the quality of care, manage the increasing demand for health care and control the growth of health care costs are needed. The aim of this study is to evaluate the care process and costs of managed, protocolized and usual care for type 2 diabetes patients from a societal perspective. Methods In two distinct regions of the Netherlands, both managed and protocolized diabetes care were implemented. Managed care was characterized by centralized organization, coordination, responsibility and centralized annual assessment. Protocolized care had a partly centralized organizational structure. Usual care was characterized by a decentralized organizational structure. Using a quasi-experimental control group pretest-posttest design, the care process (guideline adherence) and costs were compared between managed (n = 253), protocolized (n = 197), and usual care (n = 333). We made a distinction between direct health care costs, direct non-health care costs and indirect costs. Multivariate regression models were used to estimate differences in costs adjusted for confounding factors. Because of the skewed distribution of the costs, bootstrapping methods (5000 replications) with a bias-corrected and accelerated approach were used to estimate 95% confidence intervals (CI) around the differences in costs. Results Compared to usual and protocolized care, in managed care more patients were treated according to diabetes guidelines. Secondary health care use was higher in patients under usual care compared to managed and protocolized care. Compared to usual care, direct costs were significantly lower in managed care (€-1.181 (95% CI: -2.597 to -334)) while indirect costs were higher (€758 (95% CI: -353 to 2.701), although not significant. Direct, indirect and total costs were lower in protocolized care compared to usual care (though not significantly). Conclusions Compared to usual care, managed care was significantly associated with better process in terms of diabetes care, fewer secondary care consultations and lower health care costs. The same trends were seen for protocolized care, however they were not statistically significant. Trial registration Current Controlled trials: ISRCTN66124817. PMID:24966055

Antiretroviral treatment outcome in HIV-1-infected patients routinely followed up in capital cities and remote areas of Senegal, Mali and Guinea-Conakry

PubMed Central

Diouara, Abou Abdallah Malick; Ndiaye, Halimatou Diop; Guindo, Ibrehima; Bangoura, Nestor; Cissé, Mohamed; Edmond, Tchiakpe; Bougoudogo, Flabou; Mboup, Souleymame; Peeters, Martine; Ayouba, Ahidjo; Kane, Ndèye Coumba Touré

2014-01-01

Introduction Access to antiretroviral treatment (ART) becomes more and more effective in resource-limited settings (RLS). However, this global effort would be even more profitable if the access to laboratory services especially in decentralized settings was strengthened. We report the virological outcome and HIV-1 drug resistance in three West African countries using dried blood spots (DBS) samples. Methods We included HIV-1-infected adults on ART ≥6 months and followed up in capital cities and decentralized sites in Senegal, Mali and Guinea-Conakry. Patients were consecutively enrolled and DBS were collected in field conditions and kept at ambient temperature before transfer to the reference laboratory. Viral load (VL) was quantified using the NucliSENS EasyQ HIV-1 v1.2. Genotyping of HIV-1 pol gene was performed using in-house protocol. Results Of the 407 participants, 119, 152 and 136 were from Senegal, Mali and Guinea-Conakry, respectively. The median treatment duration was 36 months [IQR: 6–136]. Virological failure (VF) (VL≥3log10 copies/mL) was observed in 26% (95% confidence interval (CI), 18–35; n=31), 11% (95% CI, 6–17; n=16) and 24% (95% CI, 17–32; n=33) of patients in Senegal, Mali and Guinea-Conakry, respectively (p=0.001). Of samples presenting VL≥3log10 copies/mL (n=80), 70 were successfully genotyped. At least one drug resistance mutation (DRM) was detected in the following proportions: 70% (95% CI, 50–86; n=19), 93% (95% CI, 68–100; n=14) and 68% (95% CI, 48–84; n=19) in Senegal, Mali and Guinea-Conakry, respectively (p=0.22). Twenty-six per cent (26%; 95% CI, 16–38; n=18) of patients in VF harboured wild-type viruses, which is likely indicative of weak adherence. Phylogenetic analysis showed the predominance of CRF02_AG subtype (73%; 95% CI, 61–83; n=51). Conclusions We describe the ART outcome in capital and rural settings of Senegal, Mali and Guinea-Conakry. Our results in all of the three countries highlight the need to reinforce the ART adherence in order to minimize the occurrence of drug resistance. In addition, these findings provide additional evidence that the use of DBS as a sampling support could assist virological monitoring of patients on ART in remote areas. PMID:25527333

Atezolizumab (MPDL3280A) Monotherapy for Patients With Metastatic Urothelial Cancer: Long-term Outcomes From a Phase 1 Study.

PubMed

Petrylak, Daniel P; Powles, Thomas; Bellmunt, Joaquim; Braiteh, Fadi; Loriot, Yohann; Morales-Barrera, Rafael; Burris, Howard A; Kim, Joseph W; Ding, Beiying; Kaiser, Constanze; Fassò, Marcella; O'Hear, Carol; Vogelzang, Nicholas J

2018-04-01

Atezolizumab (anti-programmed death ligand 1) has demonstrated safety and activity in advanced and metastatic urothelial carcinoma, but its long-term clinical profile remains unknown. To report long-term clinical outcomes with atezolizumab therapy for patients with metastatic urothelial carcinoma. Patients were enrolled in an expansion cohort of an ongoing, open-label, phase 1 study. Median follow-up was 37.8 months (range, >0.7 to 44.4 months). Enrollment occurred between March 2013 and August 2015 at US and European academic medical centers. Eligible patients had measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1, Eastern Cooperative Oncology Group performance status 0 to 1, and a representative tumor sample. Programmed death ligand 1 expression on immune cells was assessed (VENTANA SP142 assay). Atezolizumab was given intravenously every 3 weeks until unacceptable toxic effects, protocol nonadherence, or loss of clinical benefit. Primary outcome was safety. Secondary outcomes included objective response rate, duration of response, and progression-free survival. Response and overall survival were assessed in key baseline subgroups. Ninety-five patients were evaluable (72 [76%] male; median age, 66 years [range, 36-89 years]). Forty-five (47%) received atezolizumab as third-line therapy or greater. Nine patients (9%) had a grade 3 to 4 treatment-related adverse event, mostly within the first treatment year; no serious related adverse events were observed thereafter. One patient (1%) discontinued treatment due to a related event. No treatment-related deaths occurred. Responses occurred in 26% (95% CI, 18%-36%) of patients. Median duration of response was 22.1 months (range, 2.8 to >41.0 months), and median progression-free survival was 2.7 months (95% CI, 1.4-4.3 months). Median overall survival was 10.1 months (95% CI, 7.3-17.0 months); 3-year OS rate was 27% (95% CI, 17%-36%). Response occurred in 40% (95% CI, 26%-55%; n = 40) and 11% (95% CI, 4%-25%; n = 44) of patients with programmed death ligand 1 expression of at least 5% tumor-infiltrating immune cells (IC2/3) or less than 5% (IC0/1), respectively. Median overall survival in patients with IC2/3 and IC0/1 was 14.6 months (95% CI, 9.0 months to not estimable) and 7.6 months (95% CI, 4.7 to 13.9 months), respectively. Atezolizumab remained well tolerated and provided durable clinical benefit to a heavily pretreated metastatic urothelial carcinoma population in this long-term study. clinicaltrials.gov Identifier: NCT01375842.

First Report of Chlamydiaceae Seroprevalence in Tibetan Pigs in Tibet, China

PubMed Central

Zhang, Nian-Zhang; Zhou, Dong-Hui; Shi, Xin-Chun; Nisbet, Alasdair J.; Huang, Si-Yang; Ciren, Danba; Wu, Song-Ming

2013-01-01

Abstract The seroprevalence of Chlamydiaceae infection in Tibetan pigs in Tibet, China, was examined by indirect hemagglutination assay (IHA), between April, 2010, and December, 2010. A total of 71 of 427 serum samples (16.63%, 95% confidence interval [CI] 15.31–17.95] were positive for Chlamydiaceae antibodies. Forty Chlamydiaceae seropositives from 232 samples were recorded in sera from Nyingchi (17.24%, 95% CI 15.40–19.08) and 31 positives were recorded in 195 serum samples from Mainling (15.90%, 95% CI 14.02–17.78). The investigation showed that the prevalence in female animals was 17.61% (95% CI 15.22–20.00), and in male animals it was 12.72% (95% CI 11.07–14.37). The prevalence ranged from 0% to 20.61% (95% CI 17.81–23.48) among different age groups, with a higher prevalence in growing pigs (p<0.01). The results indicated that Chlamydiaceae infection was widespread in Tibetan pigs in Tibet, China, which is of public health concern in this region of the world. To our knowledge, this is the first report of Chlamydiaceae seroprevalence in Tibetan pigs in Tibet, China. PMID:23428089

Secondary cancers among children with acute lymphoblastic leukaemia treated by the Tokyo Children's Cancer Study Group protocols: a retrospective cohort study.

PubMed

Ishida, Yasushi; Maeda, Miho; Urayama, Kevin Y; Kiyotani, Chikako; Aoki, Yuki; Kato, Yoko; Goto, Shoko; Sakaguchi, Sachi; Sugita, Kenichi; Tokuyama, Mika; Nakadate, Naoya; Ishii, Eizaburo; Tsuchida, Masahiro; Ohara, Akira

2014-01-01

With improvement in survival, it is important to evaluate the impact of treatment on secondary cancers in acute lymphoblastic leukaemia (ALL) survivors. A retrospective cohort study comprising 2918 children diagnosed with ALL and enrolled on Tokyo Children's Cancer Study Group (TCCSG) protocols between 1984 and 2005 was conducted to evaluate the incidence of secondary cancers and associated factors including treatment protocol, cranial irradiation and other characteristics of the primary ALL. Thirty-seven patients developed secondary cancers, including acute myeloid leukaemia (n = 11), myelodysplastic syndrome (n = 5), non-Hodgkin lymphoma (n = 2), brain tumours (n = 13) and other solid carcinomas (n = 6) within a median follow-up duration of 9·5 years. The cumulative incidence of any secondary cancers was 1·0% (95% confidence interval (CI), 0·7-1·4%) at 10 years and 2·4% (95% CI, 1·5-3·7%) at 20 years, respectively. Standardized incidence rate ratio of secondary cancers was 9·3 (95% CI, 6·5-12·8). Multivariate analyses showed an increased risk of secondary cancers associated with the recent treatment protocol and cranial irradiation. There was no evidence of a reduction in secondary cancer incidence despite marked decreases in cranial irradiation use in the recent protocols. © 2013 John Wiley & Sons Ltd.

Mapping of Schistosomiasis and Soil-Transmitted Helminths in Namibia: The First Large-Scale Protocol to Formally Include Rapid Diagnostic Tests.

PubMed

Sousa-Figueiredo, José Carlos; Stanton, Michelle C; Katokele, Stark; Arinaitwe, Moses; Adriko, Moses; Balfour, Lexi; Reiff, Mark; Lancaster, Warren; Noden, Bruce H; Bock, Ronnie; Stothard, J Russell

2015-01-01

Namibia is now ready to begin mass drug administration of praziquantel and albendazole against schistosomiasis and soil-transmitted helminths, respectively. Although historical data identifies areas of transmission of these neglected tropical diseases (NTDs), there is a need to update epidemiological data. For this reason, Namibia adopted a new protocol for mapping of schistosomiasis and geohelminths, formally integrating rapid diagnostic tests (RDTs) for infections and morbidity. In this article, we explain the protocol in detail, and introduce the concept of 'mapping resolution', as well as present results and treatment recommendations for northern Namibia. This new protocol allowed a large sample to be surveyed (N = 17,896 children from 299 schools) at relatively low cost (7 USD per person mapped) and very quickly (28 working days). All children were analysed by RDTs, but only a sub-sample was also diagnosed by light microscopy. Overall prevalence of schistosomiasis in the surveyed areas was 9.0%, highly associated with poorer access to potable water (OR = 1.5, P<0.001) and defective (OR = 1.2, P<0.001) or absent sanitation infrastructure (OR = 2.0, P<0.001). Overall prevalence of geohelminths, more particularly hookworm infection, was 12.2%, highly associated with presence of faecal occult blood (OR = 1.9, P<0.001). Prevalence maps were produced and hot spots identified to better guide the national programme in drug administration, as well as targeted improvements in water, sanitation and hygiene. The RDTs employed (circulating cathodic antigen and microhaematuria for Schistosoma mansoni and S. haematobium, respectively) performed well, with sensitivities above 80% and specificities above 95%. This protocol is cost-effective and sensitive to budget limitations and the potential economic and logistical strains placed on the national Ministries of Health. Here we present a high resolution map of disease prevalence levels, and treatment regimens are recommended.

Mapping of Schistosomiasis and Soil-Transmitted Helminths in Namibia: The First Large-Scale Protocol to Formally Include Rapid Diagnostic Tests

PubMed Central

Sousa-Figueiredo, José Carlos; Stanton, Michelle C.; Katokele, Stark; Arinaitwe, Moses; Adriko, Moses; Balfour, Lexi; Reiff, Mark; Lancaster, Warren; Noden, Bruce H.; Bock, Ronnie; Stothard, J. Russell

2015-01-01

Background Namibia is now ready to begin mass drug administration of praziquantel and albendazole against schistosomiasis and soil-transmitted helminths, respectively. Although historical data identifies areas of transmission of these neglected tropical diseases (NTDs), there is a need to update epidemiological data. For this reason, Namibia adopted a new protocol for mapping of schistosomiasis and geohelminths, formally integrating rapid diagnostic tests (RDTs) for infections and morbidity. In this article, we explain the protocol in detail, and introduce the concept of ‘mapping resolution’, as well as present results and treatment recommendations for northern Namibia. Methods/Findings/Interpretation This new protocol allowed a large sample to be surveyed (N = 17 896 children from 299 schools) at relatively low cost (7 USD per person mapped) and very quickly (28 working days). All children were analysed by RDTs, but only a sub-sample was also diagnosed by light microscopy. Overall prevalence of schistosomiasis in the surveyed areas was 9.0%, highly associated with poorer access to potable water (OR = 1.5, P<0.001) and defective (OR = 1.2, P<0.001) or absent sanitation infrastructure (OR = 2.0, P<0.001). Overall prevalence of geohelminths, more particularly hookworm infection, was 12.2%, highly associated with presence of faecal occult blood (OR = 1.9, P<0.001). Prevalence maps were produced and hot spots identified to better guide the national programme in drug administration, as well as targeted improvements in water, sanitation and hygiene. The RDTs employed (circulating cathodic antigen and microhaematuria for Schistosoma mansoni and S. haematobium, respectively) performed well, with sensitivities above 80% and specificities above 95%. Conclusion/Significance This protocol is cost-effective and sensitive to budget limitations and the potential economic and logistical strains placed on the national Ministries of Health. Here we present a high resolution map of disease prevalence levels, and treatment regimens are recommended. PMID:26196386

Evaluation of the effectiveness of laser in situ keratomileusis and photorefractive keratectomy for myopia: a meta-analysis.

PubMed

Yang, Xin-Jun; Yan, Hong-Tao; Nakahori, Yutaka

2003-08-01

To evaluate the effectiveness of laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) for correcting myopia. Study selection, data extraction, and quality assessment were performed by two of authors independently. Summary odds ratios and 95% confidence intervals were calculated by DerSimonian & Laird random-effects model and Mantel-Haenszel (fixed-effects) model. All calculations were based on an intention-to-treat and per protocol analysis. Five hundred and eighty eyes (476 patients) from 5 randomized controlled trials were included in this study. At > or = 6 months follow-up, by random-effects model, the pooled odds ratios (OR, for LASIK vs. PRK) of postoperative uncorrected visual acuity (UCVA) of 20/20 or better for all trials were 1.31 (95% CI=0.77-2.22) by per protocol analysis and 1.18 (95% CI=0.74-1.88) by intention-to-treat analysis. In the refractive outcome, the pooled OR of the postoperative spherical equivalent refraction within +/-0.5 diopter (D) of emmetropia did not show any statistical significance, for which the OR were 0.75 (95% CI=0.48-1.18) by per protocol analysis and 0.70 (95% CI=0.47-1.04) by intention-to-treat analysis. LASIK and PRK were found to be similarly effective for the correction of myopia from -1.5 to -15.0 D in a greater than 6 month follow-up.

Excellent clinical outcomes and retention in care for adults with HIV-associated Kaposi sarcoma treated with systemic chemotherapy and integrated antiretroviral therapy in rural Malawi.

PubMed

Herce, Michael E; Kalanga, Noel; Wroe, Emily B; Keck, James W; Chingoli, Felix; Tengatenga, Listern; Gopal, Satish; Phiri, Atupere; Mailosi, Bright; Bazile, Junior; Beste, Jason A; Elmore, Shekinah N; Crocker, Jonathan T; Rigodon, Jonas

2015-01-01

HIV-associated Kaposi sarcoma (HIV-KS) is the most common cancer in Malawi. In 2008, the non-governmental organization, Partners In Health, and the Ministry of Health established the Neno Kaposi Sarcoma Clinic (NKSC) to treat HIV-KS in rural Neno district. We aimed to evaluate 12-month clinical outcomes and retention in care for HIV-KS patients in the NKSC, and to describe our implementation model, which featured protocol-guided chemotherapy, integrated antiretroviral therapy (ART) and psychosocial support delivered by community health workers. We conducted a retrospective cohort study using routine clinical data from 114 adult HIV-KS patients who received ART and ≥1 chemotherapy cycle in the NKSC between March 2008 and February 2012. At enrolment 97% of patients (n/N=103/106) had advanced HIV-KS (stage T1). Most patients were male (n/N=85/114, 75%) with median age 36 years (interquartile range, IQR: 29-42). Patients started ART a median of 77 days prior to chemotherapy (IQR: 36-252), with 97% (n/N=105/108) receiving nevirapine/lamivudine/stavudine. Following standardized protocols, we treated 20 patients (18%) with first-line paclitaxel and 94 patients (82%) with bleomycin plus vincristine (BV). Of the 94 BV patients, 24 (26%) failed to respond to BV requiring change to second-line paclitaxel. A Division of AIDS grade 3/4 adverse event occurred in 29% of patients (n/N=30/102). Neutropenia was the most common grade 3/4 event (n/N=17/102, 17%). Twelve months after chemotherapy initiation, 83% of patients (95% CI: 74-89%) were alive, including 88 (77%) retained in care. Overall survival (OS) at 12 months did not differ by initial chemotherapy regimen (p=0.6). Among patients with T1 disease, low body mass index (BMI) (adjusted hazard ratio, aHR=4.10, 95% CI: 1.06-15.89) and 1 g/dL decrease in baseline haemoglobin (aHR=1.52, 95% CI: 1.03-2.25) were associated with increased death or loss to follow-up at 12 months. The NKSC model resulted in infrequent adverse events, low loss to follow-up and excellent OS. Our results suggest it is safe, effective and feasible to provide standard-of-care chemotherapy regimens from the developed world, integrated with ART, to treat HIV-KS in rural Malawi. Baseline BMI and haemoglobin may represent important patient characteristics associated with HIV-KS survival in rural sub-Saharan Africa.

Evaluating the Quality of Research into a Single Prognostic Biomarker: A Systematic Review and Meta-analysis of 83 Studies of C-Reactive Protein in Stable Coronary Artery Disease

PubMed Central

Hemingway, Harry; Philipson, Peter; Chen, Ruoling; Fitzpatrick, Natalie K.; Damant, Jacqueline; Shipley, Martin; Abrams, Keith R.; Moreno, Santiago; McAllister, Kate S. L.; Palmer, Stephen; Kaski, Juan Carlos; Timmis, Adam D.; Hingorani, Aroon D.

2010-01-01

Background Systematic evaluations of the quality of research on a single prognostic biomarker are rare. We sought to evaluate the quality of prognostic research evidence for the association of C-reactive protein (CRP) with fatal and nonfatal events among patients with stable coronary disease. Methods and Findings We searched MEDLINE (1966 to 2009) and EMBASE (1980 to 2009) and selected prospective studies of patients with stable coronary disease, reporting a relative risk for the association of CRP with death and nonfatal cardiovascular events. We included 83 studies, reporting 61,684 patients and 6,485 outcome events. No study reported a prespecified statistical analysis protocol; only two studies reported the time elapsed (in months or years) between initial presentation of symptomatic coronary disease and inclusion in the study. Studies reported a median of seven items (of 17) from the REMARK reporting guidelines, with no evidence of change over time. The pooled relative risk for the top versus bottom third of CRP distribution was 1.97 (95% confidence interval [CI] 1.78–2.17), with substantial heterogeneity (I2 = 79.5). Only 13 studies adjusted for conventional risk factors (age, sex, smoking, obesity, diabetes, and low-density lipoprotein [LDL] cholesterol) and these had a relative risk of 1.65 (95% CI 1.39–1.96), I2 = 33.7. Studies reported ten different ways of comparing CRP values, with weaker relative risks for those based on continuous measures. Adjusting for publication bias (for which there was strong evidence, Egger's p<0.001) using a validated method reduced the relative risk to 1.19 (95% CI 1.13–1.25). Only two studies reported a measure of discrimination (c-statistic). In 20 studies the detection rate for subsequent events could be calculated and was 31% for a 10% false positive rate, and the calculated pooled c-statistic was 0.61 (0.57–0.66). Conclusion Multiple types of reporting bias, and publication bias, make the magnitude of any independent association between CRP and prognosis among patients with stable coronary disease sufficiently uncertain that no clinical practice recommendations can be made. Publication of prespecified statistical analytic protocols and prospective registration of studies, among other measures, might help improve the quality of prognostic biomarker research. Please see later in the article for the Editors' Summary PMID:20532236

Retrospective case-control non-inferiority analysis of intravenous lidocaine in a colorectal surgery enhanced recovery program.

PubMed

Naik, Bhiken I; Tsang, Siny; Knisely, Anne; Yerra, Sandeep; Durieux, Marcel E

2017-01-31

Enhanced recovery after surgery (ERAS) programs typically utilizes multi-modal analgesia to reduce perioperative opioid consumption. Systemic lidocaine is used in several of these ERAS algorithms and has been shown to reduce opioid use after colorectal surgery. However it is unclear how much the other components of an ERAS protocol contribute to the final outcome. Using a noninferiority analysis we sought to assess the role of perioperative lidocaine in an ERAS program for colorectal surgery, using pain and opioid consumption as outcomes. We conducted a retrospective review of patients who had received intravenous lidocaine perioperatively during colorectal surgery. We matched them with patients who were managed using a multi-component ERAS protocol, which included perioperative lidocaine. We tested a joint hypothesis of noninferiority of lidocaine infusion to ERAS protocol in postoperative pain scores and opioid consumption. We assigned a noninferiority margin of 1 point (on an 11-point numerical rating scale) difference in pain and a ratio [mean (lidocaine) / mean (ERAS)] of 1.2 in opioid consumption, respectively. Fifty-two patients in the lidocaine group were matched with patients in the ERAS group. With regards to opioid consumption, in the overall [1.68 (1.43-1.98)] [odds ratio (95% confidence interval)] analysis and on postoperative day (POD) 1 [2.38 (1.74-3.31)] lidocaine alone was inferior to multi-modal analgesia. On POD 2 and beyond, although the mean odds ratio for opioid consumption was 1.43 [1.43 (1.17-1.73)], the lower limit extended beyond the pre-defined cut-off of 1.2, rendering the outcome inconclusive. For pain scores lidocaine is non-inferior to ERAS [-0.17 (-1.08-0.74)] on POD 2 and beyond. Pain scores on POD 1 and in the overall cohort were inconclusive based on the noninferiority analysis. The addition of a multi-component ERAS protocol to intravenous lidocaine incrementally reduces opioid consumption, most evident on POD 1. For pain scores the data is inconclusive on POD 1, however on POD 2 and beyond lidocaine alone is non-inferior to an ERAS program with lidocaine. Opioid-related complications, including return of bowel function, were not different between the groups despite reduced opioid use in the ERAS group.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nielsen, Yousef W., E-mail: yujwni01@heh.regionh.d; Eiberg, Jonas P., E-mail: Eiberg@dadlnet.d; Logager, Vibeke B., E-mail: viloe@heh.regionh.d

The purpose of this study was to determine the diagnostic performance of 3T whole-body magnetic resonance angiography (WB-MRA) using a hybrid protocol in comparison with a standard protocol in patients with peripheral arterial disease (PAD). In 26 consecutive patients with PAD two different protocols were used for WB-MRA: a standard sequential protocol (n = 13) and a hybrid protocol (n = 13). WB-MRA was performed using a gradient echo sequence, body coil for signal reception, and gadoterate meglumine as contrast agent (0.3 mmol/kg body weight). Two blinded observers evaluated all WB-MRA examinations with regard to presence of stenoses, as wellmore » as diagnostic quality and degree of venous contamination in each of the four stations used in WB-MRA. Digital subtraction angiography served as the method of reference. Sensitivity for detecting significant arterial disease (luminal narrowing {>=} 50%) using standard-protocol WB-MRA for the two observers was 0.63 (95%CI: 0.51-0.73) and 0.66 (0.58-0.78). Specificities were 0.94 (0.91-0.97) and 0.96 (0.92-0.98), respectively. In the hybrid protocol WB-MRA sensitivities were 0.75 (0.64-0.84) and 0.70 (0.58-0.8), respectively. Specificities were 0.93 (0.88-0.96) and 0.95 (0.91-0.97). Interobserver agreement was good using both the standard and the hybrid protocol, with {kappa} = 0.62 (0.44-0.67) and {kappa} = 0.70 (0.59-0.79), respectively. WB-MRA quality scores were significantly higher in the lower leg using the hybrid protocol compared to standard protocol (p = 0.003 and p = 0.03, observers 1 and 2). Distal venous contamination scores were significantly lower with the hybrid protocol (p = 0.02 and p = 0.01, observers 1 and 2). In conclusion, hybrid-protocol WB-MRA shows a better diagnostic performance than standard protocol WB-MRA at 3 T in patients with PAD.« less

Reducing Office Workers' Sitting Time at Work Using Sit-Stand Protocols: Results From a Pilot Randomized Controlled Trial.

PubMed

Li, Ingrid; Mackey, Martin G; Foley, Bridget; Pappas, Evangelos; Edwards, Kate; Chau, Josephine Y; Engelen, Lina; Voukelatos, Alexander; Whelan, Anna; Bauman, Adrian; Winkler, Elisabeth; Stamatakis, Emmanuel

2017-06-01

To examine the effects of different sit-stand protocols on work-time sitting and physical activity (PA) of office workers. Participants (n = 26, 77% women, mean age 42) were randomly allocated to usual sitting (control) or one of three sit-stand protocols (intervention) facilitated by height-adjustable workstations for a 4-week period between June and August 2015. Sitting, standing, and stepping time were assessed by inclinometry (activPAL); leisure-time physical activity (LTPA) by self-report. One-way analysis of covariance (ANCOVA) and post-hoc (Bonferroni) tests explored between-group differences. Compared with baseline, intervention groups reduced work sitting time by 113 minutes/8-hour workday (95% confidence interval [CI] [-147,-79]) and increased work standing time by 96 minutes/8-hour workday (95% CI [67,125]) without significantly impacting LTPA/sleep time. Sit-stand protocols facilitated by height-adjustable workstations appear to reduce office workers' sitting time without significant adverse effects on LTPA.

Nationwide access to an Internet-based contingency management intervention to promote smoking cessation: A randomized controlled trial

PubMed Central

Dallery, Jesse; Raiff, Bethany R.; Kim, Sunny Jung; Marsch, Lisa A.; Stitzer, Maxine; Grabinski, Michael J.

2016-01-01

Background and aims Contingency management (CM) is one of the most effective behavioral interventions to promote drug abstinence, but availability of this treatment is limited. We evaluated the efficacy and acceptability of Internet-based CM relative to an Internet-based monitoring and goal setting control group in a nationwide sample of cigarette smokers. Design Randomized controlled trial with 3- and 6-month follow ups. Setting USA. Participants Smokers (n=94) from 26 states were enrolled (mean age 36, 56% female). Intervention and comparator Participants were randomized to earn financial incentives (up to $480 over 7 weeks) based on video-verified abstinence using breath carbon monoxide (CO) output (n=48; Abstinent Contingent Group, AC), or based on submitting CO samples (n=46, Submission Contingent, SC). Both groups also received the same CO-based goals. A $50 deposit was required in both groups that could be recouped from initial earnings. Measures The primary outcome was point prevalence at week 4. Secondary outcomes were point prevalence at the 3- and 6-month follow-ups, percentages of negative CO samples, adherence to the CO sampling protocol, and treatment acceptability ratings on a 0–100mm visual analog scale. Findings Abstinence rates differed at 4 weeks between the AC (39.6%) and SC (13.0%) groups (odds ratio=4.4, 95% CI=1.6–12.3), but not at the 3- (29.2% AC and 19.6% SC, odds ratio=1.7, 95% CI=.6–4.4), or 6- (22.9% AC and 13.0% SC, odds ratio=2.0, 95% CI=.7–5.9) month follow-ups. During the two main treatment phases, there were significant differences in negative COs (53.9% AC and 24.8% SC, odds ratio = 3.5, 95% CI=3.1–4.0; 43.4% AC and 24.6% SC, odds ratio = 2.3, 95% CI=1.6–3.4). Adherence to the CO submission protocol was equivalent (78% AC and 85% SC, difference = 7.0%, 95% CI = −10.3%–23.8%, x2=.75, p = .39). The lowest acceptability ratings were for the items assessing the deposit, whereas the highest ratings concerned the ease of the intervention, the graph of CO results, and earning money. Conclusions A contingency management/financial incentive program delivered via the Internet improved short-term abstinence rates compared with an internet program without the incentives. PMID:27923264

Nationwide access to an internet-based contingency management intervention to promote smoking cessation: a randomized controlled trial.

PubMed

Dallery, Jesse; Raiff, Bethany R; Kim, Sunny Jung; Marsch, Lisa A; Stitzer, Maxine; Grabinski, Michael J

2017-05-01

Contingency management (CM) is one of the most effective behavioral interventions to promote drug abstinence, but availability of this treatment is limited. We evaluated the efficacy and acceptability of internet-based CM relative to an internet-based monitoring and goal-setting control group in a nationwide sample of cigarette smokers. Randomized controlled trial with 3- and 6-month follow-ups. United States. Smokers (n = 94) from 26 states were enrolled (mean age 36, 56% female). Participants were randomized to earn financial incentives (up to $480 over 7 weeks) based on video-verified abstinence using breath carbon monoxide (CO) output (n = 48; abstinent contingent group, AC), or based on submitting CO samples (n = 46, submission contingent, SC). Both groups also received the same CO-based goals. A $50 deposit was required in both groups that could be recouped from initial earnings. The primary outcome was point prevalence at week 4. Secondary outcomes were point prevalence at the 3- and 6-month follow-ups, percentages of negative CO samples, adherence to the CO sampling protocol, and treatment acceptability ratings on a 0-100-mm visual analog scale. Abstinence rates differed at 4 weeks between the AC (39.6%) and SC (13.0%) groups [odds ratio (OR) = 4.4, 95% confidence interval (CI) = 1.6-12.3], but not at the 3- (29.2% AC and 19.6% SC, OR = 1.7, 95% CI = 0.6-4.4) or 6- (22.9% AC and 13.0% SC, OR = 2.0, 95% CI = 0.7-5.9) month follow-ups. During the two main treatment phases, there were significant differences in negative COs (53.9% AC and 24.8% SC, OR = 3.5, 95% CI = 3.1-4.0; 43.4% AC and 24.6% SC, OR = 2.3, 95% CI = 1.6-3.4). Adherence to the CO submission protocol was equivalent (78% AC and 85% SC, difference = 7.0%, 95% CI = -10.3 to 23.8 %, F < 1, P = 0.39). The lowest acceptability ratings were for the items assessing the deposit, whereas the highest ratings concerned the ease of the intervention, the graph of CO results, and earning money. A contingency management/financial incentive program delivered via the internet improved short-term abstinence rates compared with an internet program without the incentives. © 2016 Society for the Study of Addiction.

Londrina Activities of Daily Living Protocol: Reproducibility, Validity, and Reference Values in Physically Independent Adults Age 50 Years and Older.

PubMed

Paes, Thaís; Belo, Letícia Fernandes; da Silva, Diego Rodrigues; Morita, Andrea Akemi; Donária, Leila; Furlanetto, Karina Couto; Sant'Anna, Thaís; Pitta, Fabio; Hernandes, Nidia Aparecida

2017-03-01

It is important to assess activities of daily living (ADL) in older adults due to impairment of independence and quality of life. However, there is no objective and standardized protocol available to assess this outcome. Thus, the aim of this study was to verify the reproducibility and validity of a new protocol for ADL assessment applied in physically independent adults age ≥50 y, the Londrina ADL protocol, and to establish an equation to predict reference values of the Londrina ADL protocol. Ninety-three physically independent adults age ≥50 y had their performance in ADL evaluated by registering the time spent to conclude the protocol. The protocol was performed twice. The 6-min walk test, which assesses functional exercise capacity, was used as a validation criterion. A multiple linear regression model was applied, including anthropometric and demographic variables that correlated with the protocol, to establish an equation to predict the protocol's reference values. In general, the protocol was reproducible (intraclass correlation coefficient 0.91). The average difference between the first and second protocol was 5.3%. The new protocol was valid to assess ADL performance in the studied subjects, presenting a moderate correlation with the 6-min walk test (r = -0.53). The time spent to perform the protocol correlated significantly with age (r = 0.45) but neither with weight (r = -0.17) nor with height (r = -0.17). A model of stepwise multiple regression including sex and age showed that age was the only determinant factor to the Londrina ADL protocol, explaining 21% ( P < .001) of its variability. The derived reference equation was: Londrina ADL protocol pred (s) = 135.618 + (3.102 × age [y]). The Londrina ADL protocol was reproducible and valid in physically independent adults age ≥50 y. A reference equation for the protocol was established including only age as an independent variable (r 2 = 0.21), allowing a better interpretation of the protocol's results in clinical practice. Copyright © 2017 by Daedalus Enterprises.

[Incidence of phlebitis due to peripherally inserted venous catheters: impact of a catheter management protocol].

PubMed

Ferrete-Morales, C; Vázquez-Pérez, M A; Sánchez-Berna, M; Gilabert-Cerro, I; Corzo-Delgado, J E; Pineda-Vergara, J A; Vergara-López, S; Gómez-Mateos, J

2010-01-01

To assess the impact on the incidence of PPIVC by implementing a catheter management protocol and to determine risk factors for PPIVC development in hospitalized patients. A total of 3978 episodes of venous catheterization were prospectively included from September 2002 to December 2007. A catheter management protocol was implemented during this period of time. The incidence and variables associated to the occurrence of PPIVC were determined. The incidence of PPIVC from 2002 to 2007 was 4.8%, 4.3%, 3.6%, 2.5%, 1.3% and 1.8% (p<0.001). Perfusion of amiodarone [adjusted OR (AOR) 25.97; 95% CI=7.29-92.55, p=0.0001] and cefotaxime (AOR 2.90; 95% CI=1.29-6.52, p=0.01) and the shift when the catheters were placed (AOR for morning vs. night shift 0.60; 95% CI=0.35-1.02, p=0.063) were independently associated to the development of PPIVC. A history of phlebitis was the only factor independently associated to phlebitis due to peripherally inserted central venous catheters (AOR 3.24; CI at 95% CI= 1.05-9.98, p=0.04). A catheter management protocol decreases the incidence of PPIVC in hospitalized patients. The risk of PPIVC increases for peripherally inserted central venous catheters when the patients have a history of phlebitis and for peripheral venous catheters when amiodarone or cefotaxime are infused. Catheterization of peripheral veins performed during morning shifts is associated with a lower incidence of PPIVC when compared with night shift catheterizations.

Telemetry Standards, RCC Standard 106-17. Chapter 21. Telemetry Network Standard Introduction

DTIC Science & Technology

2017-07-01

Critical RF radio frequency RFC Request for Comment SNMP Simple Network Management Protocol TA test article TCP Transmission Control Protocol...chapters might be of most interest for a particular reader. In order to guide the reader toward the chapters of further interest , the applicable... Simple Network Management Protocol (SNMP) to pass management information through the system. The SNMP management information bases (MIBs) provide

17-N-Allylamino-17-Demethoxygeldanamycin in Treating Young Patients With Relapsed or Refractory Solid Tumors or Leukemia

ClinicalTrials.gov

2013-06-03

Acute Undifferentiated Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

Comparison of intensive, pediatric-inspired therapy with non-intensive therapy in older adults aged 55-65 years with Philadelphia chromosome-negative acute lymphoblastic leukemia.

PubMed

Ribera, Josep-Maria; García, Olga; Gil, Cristina; Mercadal, Santiago; García-Cadenas, Irene; Montesinos, Pau; Barba, Pere; Vives, Susana; González-Campos, José; Tormo, Mar; Esteve, Jordi; López, Aurelio; Moreno, María José; Ribera, Jordi; Alonso, Natalia; Bermúdez, Arancha; Amigo, María Luz; Genescà, Eulàlia; García, Daniel; Vall-Llovera, Ferran; Bergua, Juan Miguel; Guàrdia, Ramon; Monteserín, María Carmen; Bernal, Teresa; Calbacho, María; Martínez, María Pilar; Feliu, Evarist

2018-05-01

The standardization of treatment of older adults with Philadelphia chromosome negative (Ph-) acute lymphoblastic leukemia (ALL) is challenging, especially in the age range of 55-65 years. This study aimed to compare intensive, pediatric-inspired therapy with non-intensive therapy in this population of patients. The outcomes of 67 patients prospectively included in two consecutive pediatric-inspired intensive protocols (ALL-HR03 and ALL-HR11) from the Spanish PETHEMA Group were compared with those from 44 patients included in a contemporary semi-intensive protocol (ALL-OLD07). Baseline patient and ALL characteristics were similar in both groups, except for a younger median age in the intensive group (medians: 58 vs. 62 years). Patients treated intensively had a higher complete remission rate (85% vs. 64%, p = 0.005), a lower cumulative incidence of relapse (39% [95%CI, 25% to 52%] vs. 60% [95%CI, 38% to 77%], p = .003), a similar cumulative incidence of treatment-related mortality (28% [95% CI, 18%, 40%] vs. 21% [95% CI, 10%, 34%]) and superior event-free survival at 2 years (37% [95%CI, 25%-49%) vs. 21% [8%-34%], p = 0.002). On multivariable analysis the type of protocol was the only variable with independent significance for event-free survival (HR [95% CI]: 2 [1.3, 3], p = .002). Compared with less intensive chemotherapy, pediatric-inspired intensive chemotherapy significantly improves the outcome of older adults with Ph-negative ALL in the age range of 55-65 years. Copyright © 2018 Elsevier Ltd. All rights reserved.

A method for meta-analysis of epidemiological studies.

PubMed

Einarson, T R; Leeder, J S; Koren, G

1988-10-01

This article presents a stepwise approach for conducting a meta-analysis of epidemiological studies based on proposed guidelines. This systematic method is recommended for practitioners evaluating epidemiological studies in the literature to arrive at an overall quantitative estimate of the impact of a treatment. Bendectin is used as an illustrative example. Meta-analysts should establish a priori the purpose of the analysis and a complete protocol. This protocol should be adhered to, and all steps performed should be recorded in detail. To aid in developing such a protocol, we present methods the researcher can use to perform each of 22 steps in six major areas. The illustrative meta-analysis confirmed previous traditional narrative literature reviews that Bendectin is not related to teratogenic outcomes in humans. The overall summary odds ratio was 1.01 (chi 2 = 0.05, p = 0.815) with a 95 percent confidence interval of 0.66-1.55. When the studies were separated according to study type, the summary odds ratio for cohort studies was 0.95 with a 95 percent confidence interval of 0.62-1.45. For case-control studies, the summary odds ratio was 1.27 with a 95 percent confidence interval of 0.83-1.94. The corresponding chi-square values were not statistically significant at the p = 0.05 level.

17 CFR 49.10 - Acceptance of data.

Code of Federal Regulations, 2014 CFR

2014-04-01

... technological protocols established by a swap data repository shall provide for the receipt of swap creation data, swap continuation data, real-time public reporting data, and all other data and information... swap data repository shall adopt policies and procedures, including technological protocols, which...

Nett Warrior C3Conflict Experiment: Measuring the Effect of Battlefield Awareness in Small Units

DTIC Science & Technology

2011-01-01

Top-level categories used to score the protocol of the soldiers’ text-based “chat” communications...17 Table 4. Subcategories for Pulls, Pushes, and Scripts used to score the protocol of the soldier’s chat

Industry Relationships Among Academic Institutional Review Board Members: Changes From 2005 Through 2014.

PubMed

Campbell, Eric G; Vogeli, Christine; Rao, Sowmya R; Abraham, Melissa; Pierson, Roz; Applebaum, Sandra

2015-09-01

For the past decade, more attention and concern has been directed toward financial relationships between the life science industry and physicians. Relationships between industry and institutional review board (IRB) members represent an important subclass that has the potential to broadly influence decisions regarding medical research. To study the nature, extent, and perceived consequences of industry relationships among IRB members in academic health centers and to compare our results with findings from 2005. A survey mailed to IRB members from the 115 most research-intensive medical schools and teaching hospitals in the United States from January 16 through May 16, 2014. The survey included questions identical to those used in 2005. Data analysis was conducted from June through October 2014. The frequency of industry relationships among IRB members and the perceived effect of those relationships on IRB-related activities. We found no significant change in the percentage of IRB members with an industry relationship from 2005 through 2014 (2005: 37.2%; 95% CI, 32.7%-42.0%; 2014: 32.1%; 95% CI, 28.0%-36.4%; P = .09). However, since 2005, the percentage of members who felt another member did not properly disclose a financial relationship decreased from 10.8% (95% CI, 8.0%-14.4%) to 6.7% (95% CI, 4.7%-9.4%) (P = .04), as did the percentage who felt pressure from their institution or department to approve a protocol (2005: 18.6%; 95% CI, 15.0%-22.9%; 2014: 10.0%; 95% CI, 7.6%-13.0%; P < .001). The percentage of members with a conflict of interest who voted on protocols with which they have a conflict has not changed, although the percentage who said they always disclose relationships increased significantly from 54.9% in 2005 (95% CI, 42.2%-66.9%) to 80.0% in 2014 (95% CI, 65.3%-89.4%) (P = .01). We also found evidence of anti-industry bias in the presentation of protocols to the IRB. The results show significant positive progress in the reporting and management of conflicts of interest among IRB members in academic health centers since 2005 after adjusting for other factors. Additional attention should be focused on deterring IRB members from inappropriately voting on or presenting protocols in a biased manner.

Modified biweekly cisplatin, docetaxel plus cetuximab (TPEx) as first-line treatment for patients with recurrent/metastatic head and neck cancer.

PubMed

Fuchs, Hannah; Pammer, Johannes; Minichsdorfer, Christoph; Posch, Doris; Kornek, Gabriela; Aretin, Marie-Bernadette; Fuereder, Thorsten

2018-02-07

Three weekly high-dose chemotherapy regimens in combination with weekly cetuximab are the treatment of choice for patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (SCCHN), although the majority of patients suffer from severe side effects. Thus, we investigated the efficacy and safety of an alternative, more convenient and less toxic biweekly modified cisplatin, docetaxel plus cetuximab (TPEx) regimen in this retrospective analysis. Thirty-eight patients receiving off-protocol cisplatin (50 mg/m 2 ) in combination with docetaxel (50 mg/m 2 ) plus cetuximab (500 mg/m 2 ) every other week were included. Data collection included baseline demographic, response rate (ORR) and toxicity data as well as disease control rate, overall survival (OS) and progression-free survival (PFS). The median age was 60 years, and the majority of patients suffered from oral cavity carcinomas (44.7%) followed by oropharyngeal (28.9%) and laryngeal (17.9%) carcinomas. The ORR was 50%, and four (10.5%) patients achieved a complete response, while 15 (39.5%) patients had a partial response. The OS and PFS were 10.8 months (95% CI 6.7-14.2) and 6.3 months (95% CI 5.7-6.8), respectively. The one-year survival rate was 44.7%. The therapy was well tolerated, and the most common grade 3/4 adverse events were myelosuppression (13.2%), hypomagnesaemia (23.7%) and acne-like rash (13.1%). In conclusion, modified biweekly TPEx is of comparable efficacy with conventional TPEx and represents a well-tolerated regimen in R/M SCCHN patients. Further evaluation of this protocol in prospective clinical trials is warranted.

Comparison of Clinical Features and Outcomes in Patients with Extraskeletal Versus Skeletal Localized Ewing Sarcoma: A Report from the Children’s Oncology Group

PubMed Central

Cash, Thomas; McIlvaine, Elizabeth; Krailo, Mark D.; Lessnick, Stephen L.; Lawlor, Elizabeth R.; Laack, Nadia; Sorger, Joel; Marina, Neyssa; Grier, Holcombe E.; Granowetter, Linda; Womer, Richard B.; DuBois, Steven G.

2016-01-01

BACKGROUND The prognostic significance of having extraskeletal vs. skeletal Ewing sarcoma in the setting of modern chemotherapy protocols is unknown. The purpose of this study was to compare the clinical characteristics, biologic features, and outcomes for patients with extraskeletal and skeletal Ewing sarcoma. METHODS Patients had localized Ewing sarcoma (ES) and were treated on two consecutive protocols using 5-drug chemotherapy (INT-0154 and AEWS0031). Patients were analyzed based on having an extraskeletal (n=213) or skeletal (n=826) site of tumor origin. Event-free survival (EFS) was estimated using the Kaplan-Meier method, compared using the log-rank test, and modeled using Cox multivariate regression. RESULTS Patients with extraskeletal Ewing Sarcoma (EES) were more likely to have axial tumors (72% vs. 55%; P < 0.001), less likely to have tumors > 8 cm (9% vs. 17%; P < 0.01), and less likely to be white (81% vs. 87%; P < 0.001) compared to patients with skeletal ES. There was no difference in key genomic features (type of EWSR1 translocation, TP53 mutation, CDKN2A mutation/loss) between groups. After controlling for age, race, and primary site, EES was associated with superior EFS [hazard ratio = 0.69; 95% CI: 0.50–0.95; P = 0.02]. Among patients with EES, age ≥ 18 years, non-white race, and elevated baseline erythrocyte sedimentation rate (ESR) were independently associated with inferior EFS. CONCLUSION Clinical characteristics, but not key tumor genomic features, differ between EES and skeletal ES. Extraskeletal origin is a favorable prognostic factor, independent of age, race, and primary site. PMID:27297500

Reclassification of serous ovarian carcinoma by a 2-tier system: a Gynecologic Oncology Group Study.

PubMed

Bodurka, Diane C; Deavers, Michael T; Tian, Chunqiao; Sun, Charlotte C; Malpica, Anais; Coleman, Robert L; Lu, Karen H; Sood, Anil K; Birrer, Michael J; Ozols, Robert; Baergen, Rebecca; Emerson, Robert E; Steinhoff, Margaret; Behmaram, Behnaz; Rasty, Golnar; Gershenson, David M

2012-06-15

A study was undertaken to use the 2-tier system to reclassify the grade of serous ovarian tumors previously classified using the International Federation of Gynecology and Obstetrics (FIGO) 3-tier system and determine the progression-free survival (PFS) and overall survival (OS) of patients treated on Gynecologic Oncology Group (GOG) Protocol 158. The authors retrospectively reviewed demographic, pathologic, and survival data of 290 patients with stage III serous ovarian carcinoma treated with surgery and chemotherapy on GOG Protocol 158, a cooperative multicenter group trial. A blinded pathology review was performed by a panel of 6 gynecologic pathologists to verify histology and regrade tumors using the 2-tier system. The association of tumor grade with PFS and OS was assessed. Of 241 cases, both systems demonstrated substantial agreement when combining FIGO grades 2 and 3 (overall agreement, 95%; kappa statistic, 0.68). By using the 2-tier system, patients with low-grade versus high-grade tumors had significantly longer PFS (45.0 vs 19.8 months, respectively; P = .01). By using FIGO criteria, median PFS for patients with grade 1, 2, and 3 tumors was 37.5, 19.8, and 20.1 months, respectively (P = .07). There was no difference in clinical outcome in patients with grade 2 or 3 tumors in multivariate analysis. Woman with high-grade versus low-grade tumors demonstrated significantly higher risk of death (hazard ratio, 2.43; 95% confidence interval, 1.17-5.04; P = .02). Women with high-grade versus low-grade serous carcinoma of the ovary are 2 distinct patient populations. Adoption of the 2-tier grading system provides a simple yet precise framework for predicting clinical outcomes. Copyright © 2011 American Cancer Society.

Maximal inspiratory pressure is influenced by intensity of the warm-up protocol.

PubMed

Arend, Mati; Kivastik, Jana; Mäestu, Jarek

2016-08-01

The aim of the study was to compare the effect of inspiratory muscle warm-up protocols with different intensities and breathing repetitions on maximal inspiratory pressure (MIP). Ten healthy and recreationally active men (183.3±5.5cm, 83.7±7.8kg, 26.4±4.1years) completed four different inspiratory muscle (IM) warm-up protocols (2×30 inspirations at 40% MIP, 2×12 inspirations at 60% MIP, 2×6 inspirations at 80% MIP, 2×30 inspirations at 15% MIP) on separate, randomly assigned visits. Pre-post values of MIP using MicroRPM (Micro Medical, Kent, UK) showed a significant increase in the mean values after the IM warm-up (POWERbreathe(®) K1, Warwickshire, UK) with 40% MIP and 60% MIP warm-up protocols, when MIP increased by 7cm H2O (95% CI: 0.10…13.89) (p=0.047) and by 6.4cm H2O (95% CI: 2.98…13.83) (p=0.027), respectively. In conclusion, a higher intensity inspiratory muscle warm-up protocol (2×12 breaths at 60% of MIP) can increase IM strength. Copyright © 2016 Elsevier B.V. All rights reserved.

Program Fidelity Measures Associated With an Effective Child Restraint Program: Buckle-Up Safely

PubMed Central

Keay, Lisa; Simpson, Judy M.; Brown, Julie; Bilston, Lynne E.; Fegan, Maureen; Cosgrove, Louise; Stevenson, Mark; Ivers, Rebecca Q.

2015-01-01

Objectives. We sought to identify the program fidelity factors associated with successful implementation of the Buckle-Up Safely program, targeting correct use of age-appropriate child car restraints. Methods. In 2010, we conducted a cluster randomized controlled trial of 830 families with children attending preschools and long day care centers in South West Sydney, New South Wales, Australia. Families received the Buckle-Up Safely program in the intervention arm of the study (13 services). Independent observers assessed the type of restraint and whether it was used correctly. Results. This detailed process evaluation showed that the multifaceted program was implemented with high fidelity. Program protocols were adhered to and messaging was consistently delivered. Results from multilevel and logistic regression analyses show that age-appropriate restraint use was associated with attendance at a parent information session hosted at the center (adjusted odd ratio [AOR] = 3.66; 95% confidence interval [CI] = 1.61, 8.29) and adversely affected by the child being aged 2 to 3 years (AOR = 0.14; 95% CI = 0.07, 0.30) or being from a family with more than 2 children (AOR = 0.34; 95% CI = 0.17, 0.67). Conclusions. Findings highlight the importance of parents receiving hands-on education regarding the proper use of age-appropriate child restraints. PMID:25602901

Impact of a Respiratory Therapy Assess-and-Treat Protocol on Adult Cardiothoracic ICU Readmissions.

PubMed

Dailey, Robert T; Malinowski, Thomas; Baugher, Mitchel; Rowley, Daniel D

2017-05-01

The purpose of this retrospective medical record review was to report on recidivism to the ICU among adult postoperative cardiac and thoracic patients managed with a respiratory therapy assess-and-treat (RTAT) protocol. Our primary null hypothesis was that there would be no difference in all-cause unexpected readmissions and escalations between the RTAT group and the physician-ordered respiratory care group. Our secondary null hypothesis was that there would be no difference in primary respiratory-related readmissions, ICU length of stay, or hospital length of stay. We reviewed 1,400 medical records of cardiac and thoracic postoperative subjects between January 2015 and October 2016. The RTAT is driven by a standardized patient assessment tool, which is completed by a registered respiratory therapist. The tool develops a respiratory severity score for each patient and directs interventions for bronchial hygiene, aerosol therapy, and lung inflation therapy based on an algorithm. The protocol period commenced on December 1, 2015, and continued through October 2016. Data relative to unplanned admissions to the ICU for all causes as well as respiratory-related causes were evaluated. There was a statistically significant difference in the all-cause unplanned ICU admission rate between the RTAT (5.8% [95% CI 4.3-7.9]) and the physician-ordered respiratory care (8.8% [95% CI 6.9-11.1]) groups ( P = .034). There was no statistically significant difference in respiratory-related unplanned ICU admissions with RTAT (36% [95% CI 22.7-51.6]) compared with the physician-ordered respiratory care (53% [95% CI 41.1-64.8]) group ( P = .09). The RTAT protocol group spent 1 d less in the ICU ( P < .001) and in the hospital ( P < .001). RTAT protocol implementation demonstrated a statistically significant reduction in all-cause ICU readmissions. The reduction in respiratory-related ICU readmissions did not reach statistical significance. Copyright © 2017 by Daedalus Enterprises.

Potential for reduced radiation‐induced toxicity using intensity‐modulated arc therapy for whole‐brain radiotherapy with hippocampal sparing

PubMed Central

Sood, Sumit; Lominska, Christopher; Kumar, Parvesh; Badkul, Rajeev; Jiang, Hongyu; Wang, Fen

2015-01-01

The purpose of this study was to retrospectively investigate the accuracy, plan quality, and efficiency of using intensity‐modulated arc therapy (IMAT) for whole brain radiotherapy (WBRT) patients with sparing not only the hippocampus (following RTOG 0933 compliance criteria) but also other organs at risk (OARs). A total of 10 patients previously treated with nonconformal opposed laterals whole‐brain radiotherapy (NC‐WBRT) were retrospectively replanned for hippocampal sparing using IMAT treatment planning. The hippocampus was volumetrically contoured on fused diagnostic T1‐weighted MRI with planning CT images and hippocampus avoidance zone (HAZ) was generated using a 5 mm uniform margin around the hippocampus. Both hippocampi were defined as one paired organ. Whole brain tissue minus HAZ was defined as the whole‐brain planning target volume (WB‐PTV). Highly conformal IMAT plans were generated in the Eclipse treatment planning system for Novalis TX linear accelerator consisting of high‐definition multileaf collimators (HD‐MLCs: 2.5 mm leaf width at isocenter) and 6 MV beam for a prescription dose of 30 Gy in 10 fractions following RTOG 0933 dosimetric criteria. Two full coplanar arcs with orbits avoidance sectors were used. In addition to RTOG criteria, doses to other organs at risk (OARs), such as parotid glands, cochlea, external/middle ear canals, skin, scalp, optic pathways, brainstem, and eyes/lens, were also evaluated. Subsequently, dose delivery efficiency and accuracy of each IMAT plan was assessed by delivering quality assurance (QA) plans with a MapCHECK device, recording actual beam‐on time and measuring planed vs. measured dose agreement using a gamma index. On IMAT plans, following RTOG 0933 dosimetric criteria, the maximum dose to WB‐PTV, mean WB‐PTV D2%, and mean WB‐PTV D98% were 34.9±0.3 Gy,33.2±0.4 Gy, and 26.0±0.4 Gy, respectively. Accordingly, WB‐PTV received the prescription dose of 30 Gy and mean V30 was 90.5%±0.5%. The D100%, and mean and maximum doses to hippocampus were 8.4±0.3 Gy,11.2±0.3 Gy, and 15.6±0.4 Gy, on average, respectively. The mean values of homogeneity index (HI) and conformity index (CI) were 0.23×0.02 and 0.96×0.02, respectively. The maximum point dose to WB‐PTV was 35.3 Gy, well below the optic pathway tolerance of 37.5 Gy. In addition, compared to NC‐WBRT, dose reduction of mean and maximum of parotid glands from IMAT were 65% and 50%, respectively. Ear canals mean and maximum doses were reduced by 26% and 12%, and mean and maximum scalp doses were reduced by 9 Gy (32%) and 2 Gy (6%), on average, respectively. The mean dose to skin was 9.7 Gy with IMAT plans compared to 16 Gy with conventional NC‐WBRT, demonstrating that absolute reduction of skin dose by a factor of 2. The mean values of the total number of monitor units (MUs) and actual beam on time were 719×44 and 2.34×0.14 min, respectively. The accuracy of IMAT QA plan delivery was (98.1±0.8) %, on average, with a 3%/3 mm gamma index passing rate criteria. All of these plans were considered clinically acceptable per RTOG 0933 criteria. IMAT planning provided highly conformal and homogenous plan with a fast and effective treatment option for WBRT patients, sparing not only hippocampi but also other OARs, which could potentially result in an additional improvement of the quality life (QoL). In the future, we plan to evaluate the clinical potential of IMAT planning and treatment option with hippocampal and other OARs avoidance in our patient's cohort and asses the QoL of the WBRT patients, as well as simultaneous integrated boost (SIB) for the brain metastases diseases. PACS number: 87 PMID:26699321

Is the standard compliance check protocol a valid measure of the accessibility of tobacco to underage smokers?

PubMed Central

DiFranza, J.; Savageau, J.; Bouchard, J.

2001-01-01

OBJECTIVE—To determine if the standard compliance check protocol is a valid measure of the experience of underage smokers when purchasing tobacco in unfamiliar communities.
SETTING—160 tobacco outlets in eight Massachusetts communities where underage tobacco sales laws are vigorously enforced.
PROCEDURE—Completed purchase rates were compared between underage smokers who behaved normally and inexperienced non-smoking youths who were not allowed to lie or present proof of age (ID).
RESULTS—The "smoker protocol" increased the likelihood of a sale nearly sixfold over that for the non-smokers (odds ratio (OR) 5.7, 95% confidence interval (CI) 1.5 to 22). When the youths presented an ID with an underage birth date, the odds of a completed sale increased dramatically (OR 27, 95% CI 3.4 to 212). Clerks judged to be under 21 years of age were seven times more likely to make an illegal sale (OR 7.6, 95% CI 2.4 to 24.0).
CONCLUSIONS—Commonly used compliance check protocols are too artificial to reflect accurately the experience of underage smokers. The validity of compliance checks might be improved by having youths present ID, and by employing either tobacco users, or non-tobacco users who are sufficiently experienced to mimic the self confidence exhibited by tobacco users in this situation. Consideration should be given to prohibiting the sale of tobacco by individuals under 21 years of age.


Keywords: compliance check protocol; underage smokers PMID:11544386

Portal Hypertension in Children With Wilms' Tumor: A Report From the National Wilms' Tumor Study Group

DOE Office of Scientific and Technical Information (OSTI.GOV)

Warwick, Anne B., E-mail: awarwick@mcw.ed; Kalapurakal, John A.; Ou, San-San

Purpose: This analysis was undertaken to determine the cumulative risk of and risk factors for portal hypertension (PHTN) in patients with Wilms' tumor (WT). Methods and Materials: Medical records were reviewed to identify cases of PHTN identified with late liver/spleen/gastric toxicities in a cohort of 5,195 patients treated with National Wilms' Tumor Studies (NWTS) protocols 1 to 4. A nested case control study (5 controls/case) was conducted to determine relationships among doxorubicin, radiation therapy (RT) dose to the liver, patient gender, and PHTN. Conditional logistic regression was used to estimate adjusted hazard ratios (HR) of PHTN associated with these factors.more » Results: Cumulative risk of PHTN at 6 years from WT diagnosis was 0.7% for patients with right-sided tumors vs. 0.1% for those with left-sided tumors (p = 0.002). Seventeen of 19 cases were evaluable for RT. The majority of cases (16/17 [94%]) received right-flank RT either alone or as part of whole-abdomen RT and received >15 Gy to the liver. Fifteen of 17 (88%) patients received a higher dose to the liver than they would have with modern WT protocols. Controlling for RT dose, the HR was 3.0 for patients who received doxorubicin (p = 0.32) and 2.8 for females (p = 0.15). Controlling for doxorubicin, the 95% lower confidence bound on the HR associating PHTN with a minimum liver RT dose of >15 Gy vs. <=15 Gy was 2.5 (p = 0.001); it was 2.4 for a maximum liver dose of >15 Gy vs. <=15 Gy (p = 0.001). Conclusions: There was a strong association between higher doses of liver RT (>15 Gy) and the development of PHTN among WT patients.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Badkul, R; Nicolai, W; Pokhrel, D

Purpose: To compare the impact of Pencil Beam(PB) and Anisotropic Analytic Algorithm(AAA) dose calculation algorithms on OARs and planning target volume (PTV) in thoracic spine stereotactic body radiation therapy (SBRT). Methods: Ten Spine SBRT patients were planned on Brainlab iPlan system using hybrid plan consisting of 1–2 non-coplanar conformal-dynamic arcs and few IMRT beams treated on NovalisTx with 6MV photon. Dose prescription varied from 20Gy to 30Gy in 5 fractions depending on the situation of the patient. PB plans were retrospectively recalculated using the Varian Eclipse with AAA algorithm using same MUs, MLC pattern and grid size(3mm).Differences in dose volumemore » parameters for PTV, spinal cord, lung, and esophagus were analyzed and compared for PB and AAA algorithms. OAR constrains were followed per RTOG-0631. Results: Since patients were treated using PB calculation, we compared all the AAA DVH values with respect to PB plan values as standard, although AAA predicts the dose more accurately than PB. PTV(min), PTV(Max), PTV(mean), PTV(D99%), PTV(D90%) were overestimated with AAA calculation on average by 3.5%, 1.84%, 0.95%, 3.98% and 1.55% respectively as compared to PB. All lung DVH parameters were underestimated with AAA algorithm mean deviation of lung V20, V10, V5, and 1000cc were 42.81%,19.83%, 18.79%, and 18.35% respectively. AAA overestimated Cord(0.35cc) by mean of 17.3%; cord (0.03cc) by 12.19% and cord(max) by 10.5% as compared to PB. Esophagus max dose were overestimated by 4.4% and 5cc by 3.26% for AAA algorithm as compared to PB. Conclusion: AAA overestimated the PTV dose values by up to 4%.The lung DVH had the greatest underestimation of dose by AAA versus PB. Spinal cord dose was overestimated by AAA versus PB. Given the critical importance of accuracy of OAR and PTV dose calculation for SBRT spine, more accurate algorithms and validation of calculated doses in phantom models are indicated.« less

SU-F-T-254: Dose Volume Histogram (DVH) Analysis of Breath Hold Vs Free Breathing Techniques for Esophageal Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Badkul, R; Doke, K; Pokhrel, D

Purpose: Lung and heart doses and associated toxicity are of concern in radiotherapy for esophageal cancer. This study evaluates the dosimetry of deep-inspiration-breath-hold (DIBH) technique as compared to freebreathing( FB) using 3D-conformal treatment(3D-CRT) of esophageal cancer. Methods: Eight patients were planned with FB and DIBH CT scans. DIBH scans were acquired using Varian RPM system. FB and DIBH CTs were contoured per RTOG-1010 to create the planning target volume(PTV) as well as organs at risk volumes(OAR). Two sets of gross target volumes(GTV) with 5cm length were contoured for each patient: proximal at the level of the carina and distal atmore » the level of gastroesophageal junction and were enlarged with appropriate margin to generate Clinical Target Volume and PTV. 3D-CRT plans were created on Eclipse planning system for 45Gy to cover 95% of PTV in 25 fractions for both proximal and distal tumors on FB and DIBH scans. For distal tumors celiac nodes were covered electively. DVH parameters for lung and heart OARs were generated and analyzed. Results: All DIBH DVH parameters were normalized to FB plan values. Average of heart-mean and heart-V40 was 0.70 and 0.66 for proximal lesions. For distal lesions ratios were 1.21 and 2.22 respectively. For DIBH total lung volume increased by 2.43 times versus FB scan. Average of lung-mean, V30, V20, V10, V5 are 0.82, 0.92, 0.76, 0.77 and 0.79 for proximal lesions and 1.17,0.66,0.87,0.93 and 1.03 for distal lesions. Heart doses were lower for breath-hold proximal lesions but higher for distal lesions as compared to free-breathing plans. Lung doses were lower for both proximal and distal breath-hold lesions except mean lung dose and V5 for distal lesions. Conclusion: This study showed improvement of OAR doses for esophageal lesions at mid-thoracic level utilizing DIBH vs FB technique but did not show consistent OAR sparing with DIBH for distal lesions.« less

California adults with elevated blood lead levels, 1987 through 1990.

PubMed Central

Maizlish, N; Rudolph, L

1993-01-01

OBJECTIVES. Follow-up of California blood lead registry reports, 95% of which are of occupationally exposed adults, can guide interventions at specific high-risk work sites and measure the impact of targeted, industry-specific interventions. METHODS. A protocol was implemented to follow up the most severe case reports (> or = 2.90 mumol/L) and establish a statistical database for descriptive analysis. RESULTS. From 1987 through 1990, the California Department of Health Services received 17,951 reports for 4069 civilian, noninstitutionalized adults employed by at least 328 companies. Of 232 incident case subjects with severe lead toxicity (> or = 2.90 mumol/L), 182 were successfully traced and interviewed. Index case subjects were mostly male (95%) and disproportionately Hispanic (46%); 35% lived with children aged 7 or younger, and 10% had been hospitalized. Ninety-four percent involved overexposures at work sites that lacked medical removal (50%), ventilation (36%), appropriate respirators (62%), training (64%), clothing changes (45%), or showering (60%). CONCLUSIONS. Well-known risk factors for occupational lead poisoning clustered at the work sites of index case subjects. Despite standards of the Occupational Safety and Health Administration, lead overexposure in California adults remains a significant public and occupational health concern. PMID:8438980

The prognostic role of hemoglobin levels in patients undergoing concurrent chemo-radiation for anal cancer.

PubMed

Franco, Pierfrancesco; Montagnani, Francesco; Arcadipane, Francesca; Casadei, Chiara; Andrikou, Kalliopi; Martini, Stefania; Iorio, Giuseppe Carlo; Scartozzi, Mario; Mistrangelo, Massimiliano; Fornaro, Lorenzo; Cassoni, Paola; Cascinu, Stefano; Ricardi, Umberto; Casadei Gardini, Andrea

2018-05-02

Concurrent chemo-radiation (CT-RT) is a standard therapy for squamous cell carcinoma of anal canal. Different clinical and biological factors may potentially affect outcome. We investigated the prognostic role of baseline hemoglobin (Hb) in a cohort of anal cancer patients submitted to CT-RT with 5-fluorouracil and mitomycin C. Up to 161 patients with clinical stage T1-T4/N0-N3/M0 were treated. Response was assessed at 6 weeks and thereafter at 3, 6 and 12 months. Two different approaches were used:a)simultaneous integrated boost following RTOG 05-29 indications;b)first sequence of 45Gy/25 fractions to the pelvis followed by 9-14.4 Gy/5-8 fractions to the macroscopic disease. Primary endpoints were progression-free survival (PFS) and overall survival (OS). On multivariate analysis, pre-treatment Hb level had a significant correlation to OS (HR:0.53;95% CI:0.33-0.87; p = 0.001), but not to PFS (HR:0.78;95% CI:0.53-1.15; p = 0.12) Patients with pre-treatment Hb ≥ 12 g/dl had 5-year PFS and OS of 82.2%, compared to 29.3% and 32.8% for those below the threshold. The likelihood to achieve a complete remission increased by 5.6% for every single-unit (g/dl) increase in baseline Hb level over 11 g/dl. On multivariate analysis, response to treatment had a significant correlation to PFS (incomplete vs complete response - HR:5.43;95% CI:2.75-10.7; p < 0.0001) and OS (HR: 6.96;95% CI:2.96-16.5; p < 0.0001). We showed that baseline Hb level is a strong indicator for poor response to RT-CT in anal cancer patients. A close clinical monitoring for incomplete response to treatment should be advised in patients with low pre-treatment Hb. The hypothesis that the preservation of adequate Hb level during treatment may lead to a better outcome needs prospective evaluation.

Variation in the Gross Tumor Volume and Clinical Target Volume for Preoperative Radiotherapy of Primary Large High-Grade Soft Tissue Sarcoma of the Extremity Among RTOG Sarcoma Radiation Oncologists

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Dian, E-mail: dwang@mcw.edu; Bosch, Walter; Kirsch, David G.

Purpose: To evaluate variability in the definition of preoperative radiotherapy gross tumor volume (GTV) and clinical target volume (CTV) delineated by sarcoma radiation oncologists. Methods and Materials: Extremity sarcoma planning CT images along with the corresponding diagnostic MRI from two patients were distributed to 10 Radiation Therapy Oncology Group sarcoma radiation oncologists with instructions to define GTV and CTV using standardized guidelines. The CT data with contours were then returned for central analysis. Contours representing statistically corrected 95% (V95) and 100% (V100) agreement were computed for each structure. Results: For the GTV, the minimum, maximum, mean (SD) volumes (mL) weremore » 674, 798, 752 {+-} 35 for the lower extremity case and 383, 543, 447 {+-} 46 for the upper extremity case. The volume (cc) of the union, V95 and V100 were 882, 761, and 752 for the lower, and 587, 461, and 455 for the upper extremity, respectively. The overall GTV agreement was judged to be almost perfect in both lower and upper extremity cases (kappa = 0.9 [p < 0.0001] and kappa = 0.86 [p < 0.0001]). For the CTV, the minimum, maximum, mean (SD) volumes (mL) were 1145, 1911, 1605 {+-} 211 for the lower extremity case and 637, 1246, 1006 {+-} 180 for the upper extremity case. The volume (cc) of the union, V95, and V100 were 2094, 1609, and 1593 for the lower, and 1533, 1020, and 965 for the upper extremity cases, respectively. The overall CTV agreement was judged to be almost perfect in the lower extremity case (kappa = 0.85 [p < 0.0001]) but only substantial in the upper extremity case (kappa = 0.77 [p < 0.0001]). Conclusions: Almost perfect agreement existed in the GTV of these two representative cases. Tshere was no significant disagreement in the CTV of the lower extremity, but variation in the CTV of upper extremity was seen, perhaps related to the positional differences between the planning CT and the diagnostic MRI.« less

Phase III randomized study of radiation and temozolomide versus radiation and nitrosourea therapy for anaplastic astrocytoma: results of NRG Oncology RTOG 9813.

PubMed

Chang, Susan; Zhang, Peixin; Cairncross, J Gregory; Gilbert, Mark R; Bahary, Jean-Paul; Dolinskas, Carol A; Chakravarti, Arnab; Aldape, Kenneth D; Bell, Erica H; Schiff, David; Jaeckle, Kurt; Brown, Paul D; Barger, Geoffrey R; Werner-Wasik, Maria; Shih, Helen; Brachman, David; Penas-Prado, Marta; Robins, H Ian; Belanger, Karl; Schultz, Christopher; Hunter, Grant; Mehta, Minesh

2017-02-01

The primary objective of this study was to compare the overall survival (OS) of patients with anaplastic astrocytoma (AA) treated with radiotherapy (RT) and either temozolomide (TMZ) or a nitrosourea (NU). Secondary endpoints were time to tumor progression (TTP), toxicity, and the effect of IDH1 mutation status on clinical outcome. Eligible patients with centrally reviewed, histologically confirmed, newly diagnosed AA were randomized to receive either RT+TMZ (n = 97) or RT+NU (n = 99). The study closed early because the target accrual rate was not met. Median follow-up time for patients still alive was 10.1 years (1.9-12.6 y); 66% of the patients died. Median survival time was 3.9 years in the RT/TMZ arm (95% CI, 3.0-7.0) and 3.8 years in the RT/NU arm (95% CI, 2.2-7.0), corresponding to a hazard ratio (HR) of 0.94 (P = .36; 95% CI, 0.67-1.32). The differences in progression-free survival (PFS) and TTP between the 2 arms were not statistically significant. Patients in the RT+NU arm experienced more grade ≥3 toxicity (75.8% vs 47.9%, P < .001), mainly related to myelosuppression. Of the 196 patients, 111 were tested for IDH1-R132H status (60 RT+TMZ and 51 RT+NU). Fifty-four patients were IDH negative and 49 were IDH positive with a better OS in IDH-positive patients (median survival time 7.9 vs 2.8 y; P = .004, HR = 0.50; 95% CI, 0.31-0.81). RT+TMZ did not appear to significantly improve OS or TTP for AA compared with RT+ NU. RT+TMZ was better tolerated. IDH1-R132H mutation was associated with longer survival. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Final Results of NRG Oncology RTOG 0246: An Organ-Preserving Selective Resection Strategy in Esophageal Cancer Patients Treated with Definitive Chemoradiation.

PubMed

Swisher, Stephen G; Moughan, Jennifer; Komaki, Ritsuko U; Ajani, Jaffer A; Wu, Tsung T; Hofstetter, Wayne L; Konski, Andre A; Willett, Christopher G

2017-02-01

The impact of selective surgical resection for patients with esophageal cancer treated with definitive chemoradiation has not been clearly evaluated long-term. NRG (National Surgical Adjuvant Breast and Bowel Project, Radiation Therapy Oncology Group, Gynecologic Oncology Group) Oncology Radiation Therapy Oncology Group 0246 was a multi-institutional, single-arm, open-label, nonrandomized phase II study that enrolled 43 patients from September 2003 to March 2008 with clinical stage T1-4N0-1M0 squamous cell or adenocarcinoma of the esophagus or gastroesophageal junction from 19 sites. Patients received induction chemotherapy with fluorouracil (650 mg/m 2 /d), cisplatin (15 mg/m 2 /d), and paclitaxel (200 mg/m 2 /d) for two cycles followed by concurrent chemoradiation consisting of 50.4 Gy of radiation (1.8 Gy per fraction) and daily fluorouracil (300 mg/m 2 /d) with cisplatin (15 mg/m 2 /d) over the first 5 days. After definitive chemoradiation, patients were evaluated for residual disease. Selective esophagectomy was considered only for patients with residual disease after chemoradiation (clinical incomplete response) or recurrent disease on surveillance. This report looks at the long-term outcome of this selective surgical strategy. With a median follow-up of 8.1 years (minimum to maximum for 12 alive patients 7.2-9.8 years), the estimated 5- and 7-year survival rates are 36.6% (95% confidence interval [CI]: 22.3-51.0) and 31.7% (95% CI: 18.3-46.0). Clinical complete response was achieved in 15 patients (37%), with 5- and 7-yearr survival rates of 53.3% (95% CI: 26.3-74.4) and 46.7% (95% CI: 21.2-68.7). Esophageal resection was not required in 20 of 41 patients (49%) on this trial. The long-term results of NRG Oncology Radiation Therapy Oncology Group 0246 demonstrate promising efficacy of a selective surgical resection strategy and suggest the need for larger randomized studies to further evaluate this organ-preserving approach. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

17 CFR 49.10 - Acceptance of data.

Code of Federal Regulations, 2012 CFR

2012-04-01

... protocols established by a swap data repository shall provide for the receipt of swap creation data, swap continuation data, real-time public reporting data, and all other data and information required to be reported... repository shall adopt policies and procedures, including technological protocols, which provide for...

17 CFR 49.10 - Acceptance of data.

Code of Federal Regulations, 2013 CFR

2013-04-01

... protocols established by a swap data repository shall provide for the receipt of swap creation data, swap continuation data, real-time public reporting data, and all other data and information required to be reported... repository shall adopt policies and procedures, including technological protocols, which provide for...

Intensity-modulated radiotherapy as primary treatment for prostate cancer: acute toxicity in 114 patients.

PubMed

De Meerleer, Gert; Vakaet, Luc; Meersschout, Sabine; Villeirs, Geert; Verbaeys, Antony; Oosterlinck, Wim; De Neve, Wilfried

2004-11-01

Dose escalation improves local control in prostate cancer. At Ghent University Hospital, intensity-modulated radiotherapy (IMRT) is used to increase the dose to the prostate and/or seminal vesicles. We report on acute toxicity in 114 patients who received IMRT for prostate cancer. Intensity-modulated radiotherapy was initiated after approval of our ethics committee. A class solution was used to plan all cases. Three beams (gantry 0 degrees , 116 degrees , and 244 degrees ) and anatomy-based segmentation were used to create an intensity-modulated dose distribution. Maximal rectal dose was set at 2 Gy per fraction. Detailed dose-volume histograms for all relevant structures were present. For all patients, we determined the pretreatment morbidity by a detailed preradiotherapy, in-house developed symptom scale. All patients were treated with 18 MV photons of an Elekta linear accelerator. Patients were seen on a weekly basis during treatment, and 1 month (M1) and 3 months (M3) thereafter. The registration of acute toxicity was standardized by a fixed questionnaire. The Radiation Therapy Oncology Group (RTOG) toxicity scale served as a basis, but additional symptoms, such as rectal blood loss, urgency, and incontinence, were scored as well. All 114 IMRT plans were delivered successfully without any interruption or technical problem. Daily treatment time was always less than 8 min and less than 6 min in 90% of the cases. Grade 1 and Grade 2 gastrointestinal (GI) toxicities were observed in 44% and 29% of the patients, respectively, during the whole period. If only the RTOG scale was used, Grade 1 and Grade 2 GI toxicities were noted in 39% and 27% of the patients, respectively, leaving 34% free of acute RTOG-scaled toxicity. Grade 3 genitourinary (GU) toxicity was seen in 8 patients (7%), all but 1 during treatment. Grade 2 and Grade 1 GU toxicities were seen in 36% and 47% of the patients, respectively, leaving only 10% free of acute GU toxicity. Anatomy-based IMRT to treat prostate cancer is incorporated into our daily routine without any problem. Acute toxicity is very low. Most of the recorded symptoms decrease over time, except for GI urgency and incontinence. The incorporation of additional symptoms makes the scoring more detailed.

Association between polymorphisms in the promoter region of miR-17-92 cluster and systemic lupus erythematosus in a Chinese population.

PubMed

Wang, Rong; Wang, Chun-Fang; Qin, Hai-Mei; Lu, Yu-Lan; Wei, Gui-Jiang; Huang, Hua-Tuo; Xiang, Yang; Wang, Jun-Li; Lan, Yan; Wei, Ye-Sheng

2018-05-16

The aim of this study was to investigate the association of genetic polymorphisms in the promoter region of miR-17-92 with systemic lupus erythematosus (SLE). The gene polymorphism was analysed using SNaPshot in 312 SLE patients and 396 controls. Relative expression of miR-17-92 was measured by quantitative real-time PCR. Association was found between rs9515692 and a decreased risk of SLE (CT vs CC: OR = 0.65, 95%CI, 0.46-0.92, P = .014; CT+TT vs CC: OR = 0.64, 95%CI, 0.46-0.90, P = .009; T vs C: OR = 0.69, 95%CI, 0.52-0.92, P = .010, respectively). Haplotype analysis showed that C-G-G, C-A-A haplotypes were associated with an increased SLE risk (OR=4.46, 95%CI, 2.17-9.17, P < 0.001; OR=2.33, 95%CI, 1.44-3.76, P < 0.001, respectively). T allele and CT+TT genotypes in rs9515692 were associated with decreased risk of anti-dsDNA in SLE (CT+TT vs CC: OR = 0.42, 95%CI = 0.24-0.72, P = .002; T vs A: OR = 0.49, 95%CI = 0.31-0.79, P = .003). Moreover, rs9515692 CT+TT genotypes had a higher level of miR-17 as compared to CC genotype (P = .017). These findings suggest that the rs9515692 CT+TT genotypes were a protective factor for the susceptibility of SLE, probably by increasing the expression of miR-17. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Partial-mouth periodontal examination protocols for the determination of the prevalence and extent of gingival bleeding in adolescents.

PubMed

Machado, Michely Ediani; Tomazoni, Fernanda; Casarin, Maísa; Ardenghi, Thiago M; Zanatta, Fabricio Batistin

2017-10-01

To compare the performance of partial-mouth periodontal examination (PMPE) protocols with different cut-off points to the full-mouth examination (FME) in the assessment of the prevalence and extent of gingival bleeding in adolescents. A cross-sectional study was conducted involving 12-year-old adolescents. Following a systematic two-stage cluster sampling process, 1134 individuals were evaluated. Different PMPE protocols were compared to the FME with six sites per tooth. Sensitivity, specificity, area under the ROC curve (AUC), intraclass correlation coefficient (ICC), relative and absolute biases and the inflation factor were assessed for each PMPE protocol with different cut-off points for the severity of gingival bleeding. The highest AUC values were found for the six-site two-diagonal quadrant (2-4) (0.97), six-site random half-mouth (0.95) and Community Periodontal Index (0.95) protocols. The assessment of three sites [mesiobuccal (MB), buccal (B) and distolingual (DL)] in two diagonal quadrants and the random half-mouth protocol had higher sensitivity and lower specificity than the same protocols with distobuccal (DB) sites. However, the use of DB sites led to better specificity and improved the balance between sensitivity and specificity, except for the two-diagonal quadrant (1-3) protocol. The ≥1 cut-off point led to the most discrepant results from the FME. Six-site two-diagonal quadrant (2-4) and random half-mouth assessments perform better in the evaluation of gingival bleeding in adolescents. However, when a faster protocol is needed, a two-diagonal quadrant assessment using only MB, B and DL sites can be used with no important loss of information. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Reliability of measuring hip abductor strength following total knee arthroplasty using a hand-held dynamometer.

PubMed

Schache, Margaret B; McClelland, Jodie A; Webster, Kate E

2016-01-01

To investigate the test-retest reliability of measuring hip abductor strength in patients with total knee arthroplasty (TKA) using a hand-held dynamometer (HHD) with two different types of resistance: belt and manual resistance. Test-retest reliability of 30 subjects (17 female, 13 male, 71.9 ± 7.4 years old), 9.2 ± 2.7 days post TKA was measured using belt and therapist resistance. Retest reliability was calculated with intra-class coefficients (ICC3,1) and 95% confidence intervals (CI) for both the group average and the individual scores. A paired t-test assessed whether a difference existed between the belt and therapist methods of resistance. ICCs were 0.82 and 0.80 for the belt and therapist resisted methods, respectively. Hip abductor strength increases of 8 N (14%) for belt resisted and 14 N (17%) for therapist resisted measurements of the group average exceeded the 95% CI and may represent real change. For individuals, hip abductor strength increases of 33 N (72%) (belt resisted) and 57 N (79%) (therapist resisted) could be interpreted as real change. Hip abductor strength can be reliably measured using HHD in the clinical setting with the described protocol. Belt resistance demonstrated slightly higher test-retest reliability. Reliable measurement of hip abductor muscle strength in patients with TKA is important to ensure deficiencies are addressed in rehabilitation programs and function is maximized. Hip abductor strength can be reliably measured with a hand-held dynamometer in the clinical setting using manual or belt resistance.

Continuous Subcutaneous Insulin Infusion in Children: A Pilot Study Validating a Protocol to Avoid Hypoglycemia at Initiation.

PubMed

Manousaki, Despoina; Deladoëy, Johnny; Geoffroy, Louis; Olivier, Patricia

2017-01-01

The occurrence of hypoglycemia and hyperglycemia during the first days after transition to continuous subcutaneous insulin infusion (CSII) in patients with type 1 diabetes has not been systematically studied in children. The aim of this prospective study was to demonstrate that the protocol applied in our diabetes clinic is safe at CSII initiation in children. We assessed 22 pediatric patients with type 1 diabetes, using continuous glucose monitoring (CGM) before and after CSII initiation (±3 days). After CSII initiation, there was no difference in the rates of hypoglycemic events expressed as relative rates (RRs) per person-reading (RR = 0.85, p  = 0.52, 95% CI 0.52-1.39), as well as in the number of prolonged hypoglycemic events (>1 h) per day (RR = 1.12, p  = 0.56, 95% CI 0.75-1.68). We observed only a trend toward prolonged episodes of hyperglycemia after pump initiation (RR = 1.52, p  = 0.06, 95% CI 0.97-2.35). Our study is the first to assess, through CGM and in a prospective way, the impact of a CSII initiation protocol on glycemic values. Our protocol provides a safe model to avoid hypoglycemia at CSII initiation in children. www.ClinicalTrials.gov, identifier NCT01840358.

Genetic polymorphisms in glutathione-S-transferases are associated with anxiety and mood disorders in nicotine dependence

PubMed Central

Pizzo de Castro, Márcia Regina; Ehara Watanabe, Maria Angelica; Losi Guembarovski, Roberta; Odebrecht Vargas, Heber; Vissoci Reiche, Edna Maria; Kaminami Morimoto, Helena; Dodd, Seetal; Berk, Michael

2014-01-01

Background Nicotine dependence is associated with an increased risk of mood and anxiety disorders and suicide. The primary hypothesis of this study was to identify whether the polymorphisms of two glutathione-S-transferase enzymes (GSTM1 and GSTT1 genes) predict an increased risk of mood and anxiety disorders in smokers with nicotine dependence. Materials and methods Smokers were recruited at the Centre of Treatment for Smokers. The instruments were a sociodemographic questionnaire, Fagerström Test for Nicotine Dependence, diagnoses of mood disorder and nicotine dependence according to DSM-IV (SCID-IV), and the Alcohol, Smoking and Substance Involvement Screening Test. Anxiety disorder was assessed based on the treatment report. Laboratory assessment included glutathione-S-transferases M1 (GSTM1) and T1 (GSTT1), which were detected by a multiplex-PCR protocol. Results Compared with individuals who had both GSTM1 and GSTT1 genes, a higher frequency of at least one deletion of the GSTM1 and GSTT1 genes was identified in anxious smokers [odds ratio (OR)=2.21, 95% confidence interval (CI)=1.05–4.65, P=0.034], but there was no association with bipolar and unipolar depression (P=0.943). Compared with nonanxious smokers, anxious smokers had a greater risk for mood disorders (OR=4.67; 95% CI=2.24–9.92, P<0.001), lung disease (OR=6.78, 95% CI=1.95–23.58, P<0.003), and suicide attempts (OR=17.01, 95% CI=2.23–129.91, P<0.006). Conclusion This study suggests that at least one deletion of the GSTM1 and GSTT1 genes represents a risk factor for anxious smokers. These two genes may modify the capacity for the detoxification potential against oxidative stress. PMID:24637631

US Emergency Department Trends in Imaging for Pediatric Nontraumatic Abdominal Pain.

PubMed

Niles, Lauren M; Goyal, Monika K; Badolato, Gia M; Chamberlain, James M; Cohen, Joanna S

2017-10-01

To describe national emergency department (ED) trends in computed tomography (CT) and ultrasound imaging for the evaluation of pediatric nontraumatic abdominal pain from 2007 through 2014. We used data from the National Hospital Ambulatory Medical Care Survey to measure trends in CT and ultrasound use among children with nontraumatic abdominal pain. We performed multivariable logistic regression to measure the strength of the association of ED type (pediatric versus general ED) with CT and ultrasound use adjusting for potential confounding variables. Of an estimated 21.1 million ED visits for nontraumatic abdominal pain, 14.6% (95% confidence interval [CI], 13.2%-16.0%) had CT imaging only, 10.9% (95% CI, 9.7%-12.1%) had ultrasound imaging only, and 1.9% (95% CI, 1.4%-2.4%) received both CT and ultrasound. The overall use of CT and ultrasound did not significantly change over the study period ( P trend .63 and .90, respectively). CT use was lower among children treated in pediatric EDs compared with general EDs (adjusted odds ratio 0.34; 95% CI, 0.17-0.69). Conversely, ultrasound use was higher among children treated in pediatric EDs compared with general EDs (adjusted odds ratio 2.14; 95% CI, 1.29-3.55). CT imaging for pediatric patients with nontraumatic abdominal pain has plateaued since 2007 after the steady increase seen in the preceding 9 years. Among this population, an increased likelihood of CT imaging was demonstrated in general EDs compared with pediatric EDs, in which there was a higher likelihood of ultrasound imaging. Dissemination of pediatric-focused radiology protocols to general EDs may help optimize radiation exposure in children. Copyright © 2017 by the American Academy of Pediatrics.

eHealth and mHealth interventions in the treatment of fatigued cancer survivors: A systematic review and meta-analysis.

PubMed

Seiler, Annina; Klaas, Vanessa; Tröster, Gerhard; Fagundes, Christopher P

2017-09-01

To (1) evaluate existing eHealth/mHealth interventions developed to help manage cancer-related fatigue (CRF); and (2) summarize the best available evidence on their effectiveness. A comprehensive literature search of PubMed, MEDLINE, EMBASE, and the Cochrane Library up to November 2016 was conducted. Study outcomes were extracted, tabulated, and summarized. Random effects meta-analyses were conducted for the primary outcome (fatigue), and the secondary outcomes quality of life and depression, yielding pooled effect sizes (r), and 95% confidence intervals (CI). For eHealth interventions, our search of published papers identified 9 completed studies and 6 protocols for funded projects underway. No studies were identified for mHealth interventions that met our inclusion criteria. A meta-analysis of the 9 completed eHealth studies revealed a statistically significant beneficial effect of eHealth interventions on CRF (r = .27, 95% CI [.1109 - .4218], P < 0.01). Therapist-guided eHealth interventions were more efficacious then self-guided interventions (r = .58, 95% CI: [.3136 - .5985, P < 0.001). Small to moderate therapeutic effects were also observed for HRQoL (r = .17, 95% CI [.0384 - .3085], P < 0.05) and depression (r = .24, 95% CI [.1431 - .3334], P < 0.001). eHealth interventions appear to be effective for managing fatigue in cancer survivors with CRF. Continuous development of eHealth interventions for the treatment of CRF in cancer survivors and their testing in long-term, large-scale efficacy outcome studies is encouraged. The degree to which mHealth interventions can change CRF in cancer survivors need to be assessed systematically and empirically. Copyright © 2017 John Wiley & Sons, Ltd.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coburn, Natalie, E-mail: natalie.coburn@swahs.health.nsw.gov.au; Beldham-Collins, Rachael; Radiation Oncology Network, Westmead Cancer Care Centre, University of Sydney, Sydney, New South Wales

Protocols commonly implemented in radiotherapy work areas may be classified as being either rigid (class solution) or flexible. Because formal evaluation of these protocol types has not occurred within the literature, we evaluated the efficiency of a rigid compared with flexible prostate planning protocol by assessing a series of completed 3D conformal prostate plans. Twenty prostate cancer patients with an average age of 70 years (range, 52-77) and sizes comprising 8 small, 10 medium, and 2 large were planned on the Phillips Pinnacle treatment planning system 6 times by radiation therapists with <2 years, 2-5 years, and >5 years ofmore » experience using a rigid and flexible protocol. Plans were critiqued using critical organ doses, confirmation numbers, and conformity index. Plans were then classified as being acceptable or not. Plans produced with the flexible protocol were 53% less likely to require modification (OR 0.47, 95% CI: 0.26, 0.84, p = 0.01). Planners with >5 years of experience were 78% more likely to produce plans requiring modification (OR 1.78, 95% CI: 1.12, 2.83, P = 0.02). Plans according to the flexible protocol took longer (112 min) compared with the time taken using a rigid protocol (68 min) (p < 0.001). The results suggest that further studies are needed; however, we propose that all radiation therapy planners should start with the same limitations, and if an acceptable plan is not reached, then flexibility should be given to improve the plan to meet the desired results.« less

High-efficiency removal of phytic acid in soy meal using two-stage temperature-induced Aspergillus oryzae solid-state fermentation.

PubMed

Chen, Liyan; Vadlani, Praveen V; Madl, Ronald L

2014-01-15

Phytic acid of soy meal (SM) could influence protein and important mineral digestion of monogastric animals. Aspergillus oryzae (ATCC 9362) solid-state fermentation was applied to degrade phytic acid in SM. Two-stage temperature fermentation protocol was investigated to increase the degradation rate. The first stage was to maximize phytase production and the second stage was to realize the maximum enzymatic degradation. In the first stage, a combination of 41% moisture, a temperature of 37 °C and inoculum size of 1.7 mL in 5 g substrate (dry matter basis) favored maximum phytase production, yielding phytase activity of 58.7 U, optimized via central composite design. By the end of second-stage fermentation, 57% phytic acid was degraded from SM fermented at 50 °C, compared with 39% of that fermented at 37 °C. The nutritional profile of fermented SM was also studied. Oligosaccharides were totally removed after fermentation and 67% of total non-reducing polysaccharides were decreased. Protein content increased by 9.5%. Two-stage temperature protocol achieved better phytic acid degradation during A. oryzae solid state fermentation. The fermented SM has lower antinutritional factors (phytic acid, oligosaccharides and non-reducing polysaccharides) and higher nutritional value for animal feed. © 2013 Society of Chemical Industry.

Effect of simulated intraoral variables on the accuracy of a photogrammetric imaging technique for complete-arch implant prostheses.

PubMed

Bratos, Manuel; Bergin, Jumping M; Rubenstein, Jeffrey E; Sorensen, John A

2018-03-17

Conventional impression techniques to obtain a definitive cast for a complete-arch implant-supported prosthesis are technique-sensitive and time-consuming. Direct optical recording with a camera could offer an alternative to conventional impression making. The purpose of this in vitro study was to test a novel intraoral image capture protocol to obtain 3-dimensional (3D) implant spatial measurement data under simulated oral conditions of vertical opening and lip retraction. A mannequin was assembled simulating the intraoral conditions of a patient having an edentulous mandible with 5 interforaminal implants. Simulated mouth openings with 2 interincisal openings (35 mm and 55 mm) and 3 lip retractions (55 mm, 75 mm, and 85 mm) were evaluated to record the implant positions. The 3D spatial orientations of implant replicas embedded in the reference model were measured using a coordinate measuring machine (CMM) (control). Five definitive casts were made with a splinted conventional impression technique of the reference model. The positions of the implant replicas for each of the 5 casts were measured with a Nobel Procera Scanner (conventional digital method). For the prototype, optical targets were secured to the implant replicas, and 3 sets of 12 images each were recorded for the photogrammetric process of 6 groups of retractions and openings using a digital camera and a standardized image capture protocol. Dimensional data were imported into photogrammetry software (photogrammetry method). The calculated and/or measured precision and accuracy of the implant positions in 3D space for the 6 groups were compared with 1-way ANOVA with an F-test (α=.05). The precision (standard error [SE] of measurement) for CMM was 3.9 μm (95% confidence interval [CI] 2.7 to 7.1 μm). For the conventional impression method, the SE of measurement was 17.2 μm (95% CI 10.3 to 49.4 μm). For photogrammetry, a grand mean was calculated for groups MinR-AvgO, MinR-MaxO, AvgR-AvgO, and MaxR-AvgO obtaining a value of 26.8 μm (95% CI 18.1 to 51.4 μm). The overall linear measurement error for accurately locating the top center points (TCP) followed a similar pattern as for precision. CMM (coordinate measurement machine) measurement represents the nonclinical gold standard, with an average error TCP distance of 4.6 μm (95% CI 3.5 to 6 μm). All photogrammetry groups presented an accuracy that ranged from 63 μm (SD 17.6) to 47 μm (SD 9.2). The grand mean of accuracy was calculated as 55.2 μm (95% CI 8.8 to 130.8 μm). The CMM group (control) demonstrated the highest levels of accuracy and precision. Most of the groups with the photogrammetric method were statistically similar to the conventional group except for groups AvgR-MaxO and MaxR-MaxO, which represented maximum opening with average retraction and maximum opening with maximum retraction. Copyright © 2017 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Population-Based Trachoma Mapping in Six Evaluation Units of Papua New Guinea

PubMed Central

Ko, Robert; Macleod, Colin; Pahau, David; Sokana, Oliver; Keys, Drew; Burnett, Anthea; Willis, Rebecca; Wabulembo, Geoffrey; Garap, Jambi; Solomon, Anthony W.

2016-01-01

ABSTRACT Purpose: We sought to determine the prevalence of trachomatous inflammation – follicular (TF) in children aged 1–9 years, and trachomatous trichiasis (TT) in those aged ≥15 years, in suspected trachoma-endemic areas of Papua New Guinea (PNG). Methods: We carried out six population-based prevalence surveys using the protocol developed as part of the Global Trachoma Mapping Project. Results: A total of 19,013 individuals were sampled for inclusion, with 15,641 (82.3%) consenting to participate. Four evaluation units had prevalences of TF in children ≥10%, above which threshold the World Health Organization (WHO) recommends mass drug administration (MDA) of azithromycin for at least three years; Western Province (South Fly/Daru) 11.2% (95% confidence interval, CI, 6.9–17.0%), Southern Highlands (East) 12.2% (95% CI 9.6–15.0%), Southern Highlands (West) 11.7% (95% CI 8.5–15.3%), and West New Britain 11.4% (95% CI 8.7–13.9%). TF prevalence was 5.0–9.9% in Madang (9.4%, 95% CI 6.1–13.0%) and National Capital District (6.0%. 95% CI 3.2–9.1%) where consideration of a single round of MDA is warranted. Cases of TT were not found outside West New Britain, in which four cases were seen, generating an estimated population-level prevalence of TT in adults of 0.10% (95% CI 0.00–0.40%) for West New Britain, below the WHO elimination threshold of 0.2% of those aged ≥15 years. Conclusion: Trachoma is a public health issue in PNG. However, other than in West New Britain, there are few data to support the idea that trachoma is a cause of blindness in PNG. Further research is needed to understand the stimulus for the active trachoma phenotype in these populations. PMID:27893297

Poststroke Aphasia Frequency, Recovery, and Outcomes: A Systematic Review and Meta-Analysis.

PubMed

Flowers, Heather L; Skoretz, Stacey A; Silver, Frank L; Rochon, Elizabeth; Fang, Jiming; Flamand-Roze, Constance; Martino, Rosemary

2016-12-01

To conduct a systematic review to elucidate the frequency, recovery, and associated outcomes for poststroke aphasia over the long-term. Using the Cochrane Stroke Strategy, we searched 10 databases, 13 journals, 3 conferences, and the gray literature. Our a priori protocol criteria included unselected samples of adult stroke patients from randomized controlled trials or consecutive cohorts. Two independent reviewers rated abstracts and articles for exclusion or inclusion, resolving discrepancies by consensus. We documented aphasia frequencies by stroke type and setting, and computed odds ratios (ORs) with their 95% confidence intervals (CIs) for outcomes. We retrieved 2168 citations, reviewed 248 articles, and accepted 50. Median frequencies for mixed stroke (ischemic and hemorrhagic) were 30% and 34% for acute and rehabilitation settings, respectively. Frequencies by stroke type were lowest for acute subarachnoid hemorrhage (9%) and highest for acute ischemic stroke (62%) when arrival to the hospital was ≤3 hours from stroke onset. Articles monitoring aphasia for 1 year demonstrated aphasia frequencies 2% to 12% lower than baseline. Negative outcomes associated with aphasia included greater odds of in-hospital death (OR=2.7; 95% CI, 2.4-3.1) and longer mean length of stay in days (mean=1.6; 95% CI, 1.0-2.3) in acute settings. Patients with aphasia had greater disability from 28 days (OR=1.5; 95% CI, 1.3-1.7) to 2 years (OR=1.7; 95% CI, 1.6-2.0) than those without aphasia. By 2 years, they used more rehabilitation services (OR=1.5; 95% CI, 1.3-1.6) and returned home less frequently (OR=1.4; 95% CI, 1.2-1.7). Reported frequencies of poststroke aphasia range widely, depending on stroke type and setting. Because aphasia is associated with mortality, disability, and use of health services, we recommend long-term interdisciplinary vigilance in the management of aphasia. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Pre–Radiation Therapy Fluorine 18 Fluorodeoxyglucose PET Helps Identify Patients with Esophageal Cancer at High Risk for Radiation Pneumonitis

PubMed Central

Castillo, Richard; Pham, Ngoc; Castillo, Edward; Aso-Gonzalez, Samantha; Ansari, Sobiya; Hobbs, Brian; Palacio, Diana; Skinner, Heath

2015-01-01

Purpose To examine the association between pre–radiation therapy (RT) fluorine 18 fluorodeoxyglucose (FDG) uptake and post-RT symptomatic radiation pneumonitis (RP). Materials and Methods In accordance with the retrospective study protocol approved by the institutional review board, 228 esophageal cancer patients who underwent FDG PET/CT before chemotherapy and RT were examined. RP symptoms were evaluated by using the Common Terminology Criteria for Adverse Events, version 4.0, from the consensus of five clinicians. By using the cumulative distribution of standardized uptake values (SUVs) within the lungs, those values greater than 80%–95% of the total lung voxels were determined for each patient. The effect of pre-chemotherapy and RT FDG uptake, dose, and patient or treatment characteristics on RP toxicity was studied by using logistic regression. Results The study subjects were treated with three-dimensional conformal RT (n = 36), intensity-modulated RT (n = 135), or proton therapy (n = 57). Logistic regression analysis demonstrated elevated FDG uptake at pre-chemotherapy and RT was related to expression of RP symptoms. Study subjects with elevated 95% percentile of the SUV (SUV95) were more likely to develop symptomatic RP (P < .000012); each 0.1 unit increase in SUV95 was associated with a 1.36-fold increase in the odds of symptomatic RP. Receiver operating characteristic (ROC) curve analysis resulted in area under the ROC curve of 0.676 (95% confidence interval: 0.58, 0.77), sensitivity of 60%, and specificity of 71% at the 1.17 SUV95 threshold. CT imaging and dosimetric parameters were found to be poor predictors of RP symptoms. Conclusion The SUV95, a biomarker of pretreatment pulmonary metabolic activity, was shown to be prognostic of symptomatic RP. Elevation in this pretreatment biomarker identifies patients at high risk for posttreatment symptomatic RP. © RSNA, 2015 PMID:25584706

HDR-192Ir intraluminal brachytherapy in treatment of malignant obstructive jaundice

PubMed Central

Chen, Yi; Wang, Xiao-Lin; Yan, Zhi-Ping; Cheng, Jie-Min; Wang, Jian-Hua; Gong, Gao-Quan; Qian, Sheng; Luo, Jian-Jun; Liu, Qing-Xin

2004-01-01

AIM: To determine the feasibility and safety of intraluminal brachytherapy in treatment of malignant obstructive jaundice (MOJ) and to evaluate the clinical effect of intraluminal brachytherapy on stent patency and patient survival. METHODS: Thirty-four patients with MOJ were included in this study. Having biliary stent placed, all patients were classified into intraluminal brachytherapy group (group A, n = 14) and control group (group B, n = 20) according to their own choice. Intraluminal brachytherapy regimen included: HDR-192Ir was used in the therapy, fractional doses of 4-7 Gy were given every 3-6 d for 3-4 times, and standard points were established at 0.5-1.0 cm. Some patients of both groups received transcatheter arterial chemoembolization (TACE) after stent placement. RESULTS: In group A, the success rate of intraluminal brachytherapy was 98.0%, RTOG grade 1 acute radiation morbidity occurred in 3 patients, RTOG/EORTC grade 1 late radiation morbidity occurred in 1 patient. Mean stent patency of group A (12.6 mo) was significantly longer than that of group B (8.3 mo) (P < 0.05). There was no significant difference in the mean survival (9.4 mo vs 6.0 mo) between the two groups. CONCLUSION: HDR-192Ir intraluminal brachytherapy is a safe palliative therapy in treating MOJ, and it may prolong stent patency and has the potentiality of extending survival of patients with MOJ. PMID:15526374

Cereals and pulse-based ready-to-use therapeutic food as an alternative to the standard milk- and peanut paste-based formulation for treating severe acute malnutrition: a noninferiority, individually randomized controlled efficacy clinical trial.

PubMed

Bahwere, Paluku; Balaluka, Bisimwa; Wells, Jonathan C K; Mbiribindi, Chobohwa N; Sadler, Kate; Akomo, Peter; Dramaix-Wilmet, Michèle; Collins, Steve

2016-04-01

The cost of current standard ready-to-use therapeutic food (RUTF) is among the major obstacles to scaling up community-based management of acute malnutrition (CMAM), an important child survival strategy. Identifying a cheaper alternative is a global public health priority. We sought to compare the efficacy of soya-maize-sorghum RUTF (SMS-RUTF) with that of standard peanut paste-based RUTF (P-RUTF). We used a nonblinded, parallel-group, simple randomized controlled trial along with a day care approach that enrolled 2 groups of children aged 6-23 and 24-59 mo, respectively, with severe acute malnutrition (SAM). Intention-to-treat (ITT) and per-protocol (PP) analyses showed noninferiority of SMS-RUTF compared with P-RUTF for the recovery rate [ITT: Δ = -2.0% (95% CI: -7.6%, 3.6%); PP: -1.9% (95% CI: -5.3%, 1.4%)], weight gain [Δ = -0.7 g · kg(-1)· d(-1)(95% CI: -1.3, 0.0 g · kg(-1)· d(-1))], and length of stay [Δ = 2.0 d (95% CI: -1.7, 5.8 d)] in children ≥24 mo of age. In children ≤23 mo of age, the recovery rate of SMS-RUTF was inferior to that of P-RUTF [ITT: Δ = -20.8% (95% CI: -29.9%, -11.7%); PP: -17.2% (95% CI: -25.6%, -8.7%)]. Treatment with SMS-RUTF resulted in a greater increase in hemoglobin [0.670 g/dL (95% CI: 0.420, 0.921 g/dL);P< 0.001]. Treatment with both RUTFs resulted in the replenishment of all of the amino acids tested except for methionine. There were no differences at discharge between RUTF groups in fat mass [Δ = 0.3 kg (95% CI: -0.6, 1.6 kg);P= 0.341] or fat mass index [Δ = 0.4 kg/m(2)(95% CI: -0.3, 1.1 kg/m(2));P= 0.262]. By contrast, comparisons of fat-free mass indicated lower concentrations than the community controls after treatment with either of the 2 RUTFs [Δ = -1.3 kg (95% CI: -2.4, -0.1 kg) andP= 0.034 for comparison between community controls and the SMS-RUTF group; Δ = -1.8 kg (95% CI: -2.9, -0.6 kg) andP= 0.003 for comparison between community controls and the P-RUTF group]. SMS-RUTF can be used to treat SAM in children aged ≥24 mo to reduce the costs of CMAM programs. More research is required to optimize SMS-RUTF for younger children. This trial was registered in the Pan African Clinical Trial Registry as PACTR201303000475166. © 2016 American Society for Nutrition.

Determination of doping peptides via solid-phase microelution and accurate-mass quadrupole time-of-flight LC-MS.

PubMed

Cuervo, Darío; Loli, Cynthia; Fernández-Álvarez, María; Muñoz, Gloria; Carreras, Daniel

2017-10-15

A complete analytical protocol for the determination of 25 doping-related peptidic drugs and 3 metabolites in urine was developed by means of accurate-mass quadrupole time-of-flight (Q-TOF) LC-MS analysis following solid-phase extraction (SPE) on microplates and conventional SPE pre-treatment for initial testing and confirmation, respectively. These substances included growth hormone releasing factors, gonadotropin releasing factors and anti-diuretic hormones, with molecular weights ranging from 540 to 1320Da. Optimal experimental conditions were stablished after investigation of different parameters concerning sample preparation and instrumental analysis. Weak cation exchange SPE followed by C18 HPLC chromatography and accurate mass detection provided the required sensitivity and selectivity for all the target peptides under study. 2mg SPE on 96-well microplates can be used in combination with full scan MS detection for the initial testing, thus providing a fast, cost-effective and high-throughput protocol for the processing of a large batch of samples simultaneously. On the other hand, extraction on 30mg SPE cartridges and subsequent target MS/MS determination was the protocol of choice for confirmatory purposes. The methodology was validated in terms of selectivity, recovery, matrix effect, precision, sensitivity (limit of detection, LOD), cross contamination, carryover, robustness and stability. Recoveries ranged from 6 to 70% (microplates) and 17-95% (cartridges), with LODs from 0.1 to 1ng/mL. The suitability of the method was assessed by analyzing different spiked or excreted urines containing some of the target substances. Copyright © 2017 Elsevier B.V. All rights reserved.

Subclinical rejection associated with chronic allograft nephropathy in protocol biopsies as a risk factor for late graft loss.

PubMed

Moreso, F; Ibernon, M; Gomà, M; Carrera, M; Fulladosa, X; Hueso, M; Gil-Vernet, S; Cruzado, J M; Torras, J; Grinyó, J M; Serón, D

2006-04-01

Chronic allograft nephropathy (CAN) in protocol biopsies is associated with graft loss while the association between subclinical rejection (SCR) and outcome has yielded contradictory results. We analyze the predictive value of SCR and/or CAN in protocol biopsies on death-censored graft survival. Since 1988, a protocol biopsy was done during the first 6 months in stable grafts with serum creatinine <300 micromol/L and proteinuria <1 g/day. Biopsies were evaluated according to Banff criteria. Borderline changes and acute rejection were grouped as SCR. CAN was defined as presence of interstitial fibrosis and tubular atrophy. Mean follow-up was 91 +/- 46 months. Sufficient tissue was obtained in 435 transplants. Biopsies were classified as normal (n = 186), SCR (n = 74), CAN (n = 110) and SCR with CAN (n = 65). Presence of SCR with CAN was associated with old donors, percentage of panel reactive antibodies and presence of acute rejection before protocol biopsy. Cox regression analysis showed that SCR with CAN (relative risk [RR]: 1.86, 95% confidence interval [CI]: 1.11-3.12; p = 0.02) and hepatitis C virus (RR: 2.27, 95% CI: 1.38-3.75; p = 0.01) were independent predictors of graft survival. In protocol biopsies, the detrimental effect of interstitial fibrosis/tubular atrophy on long-term graft survival is modulated by SCR.

A Cross-Sectional Study on the Diet and Nutritional Status of Adolescent Girls in Zambézia Province, Mozambique (the ZANE Study): Design, Methods, and Population Characteristics.

PubMed

Korkalo, Liisa; Freese, Riitta; Fidalgo, Lourdes; Selvester, Kerry; Ismael, Carina; Mutanen, Marja

2014-03-05

There is very little published work on dietary intake and nutritional status of Mozambicans. We conducted a population-based cross-sectional study on the diet and nutritional status of adolescent girls in different types of communities in Zambézia Province, Central Mozambique, in two distinct seasons. The purpose of this paper is to present the design, methods, and study population characteristics of the Estudo do Estado Nutricional e da Dieta em Raparigas Adolescentes na Zambézia (the ZANE Study). Data was collected in January-February 2010 ("hunger season") and in May-June 2010 ("harvest season"). A total of 551 girls in the age group 14-19 years old were recruited from one urban area and two districts (district towns and rural villages). The study protocol included a background interview, a 24-hour dietary recall interview, a food frequency questionnaire, anthropometric measurements, bioimpedance, hemoglobin measurement, and venous blood, urine, buccal cell, and fecal sampling. Adolescent motherhood was common in all study regions. Stunting prevalence for the total study population as a weighted percentage was 17.8% (95/549; 95% CI 14.3-22.0) with no regional differences. Overweight was found mainly in the urban area where the prevalence was 12.6% (20/159; 95% CI 7.5-17.6), thinness was rare. There were regional differences in the prevalence of malaria parasitemia and intestinal helminth infestation, but not human immunodeficiency virus. The fully analyzed data from the ZANE Study will yield results useful for setting priorities in nutrition policy and further research on the diet and nutritional status in Mozambique and other countries with similar nutritional problems. ClinicalTrials.gov: NCT01944891; http://www.clinicaltrials.gov/ct2/show/NCT01944891 (Archived by WebCite at http://www.webcitation.org/6L9OUrsq8).

A Cross-Sectional Study on the Diet and Nutritional Status of Adolescent Girls in Zambézia Province, Mozambique (the ZANE Study): Design, Methods, and Population Characteristics

PubMed Central

Freese, Riitta; Fidalgo, Lourdes; Selvester, Kerry; Ismael, Carina; Mutanen, Marja

2014-01-01

Background There is very little published work on dietary intake and nutritional status of Mozambicans. We conducted a population-based cross-sectional study on the diet and nutritional status of adolescent girls in different types of communities in Zambézia Province, Central Mozambique, in two distinct seasons. Objective The purpose of this paper is to present the design, methods, and study population characteristics of the Estudo do Estado Nutricional e da Dieta em Raparigas Adolescentes na Zambézia (the ZANE Study). Methods Data was collected in January-February 2010 ("hunger season") and in May-June 2010 ("harvest season"). A total of 551 girls in the age group 14-19 years old were recruited from one urban area and two districts (district towns and rural villages). The study protocol included a background interview, a 24-hour dietary recall interview, a food frequency questionnaire, anthropometric measurements, bioimpedance, hemoglobin measurement, and venous blood, urine, buccal cell, and fecal sampling. Results Adolescent motherhood was common in all study regions. Stunting prevalence for the total study population as a weighted percentage was 17.8% (95/549; 95% CI 14.3-22.0) with no regional differences. Overweight was found mainly in the urban area where the prevalence was 12.6% (20/159; 95% CI 7.5-17.6), thinness was rare. There were regional differences in the prevalence of malaria parasitemia and intestinal helminth infestation, but not human immunodeficiency virus. Conclusions The fully analyzed data from the ZANE Study will yield results useful for setting priorities in nutrition policy and further research on the diet and nutritional status in Mozambique and other countries with similar nutritional problems. Trial Registration ClinicalTrials.gov: NCT01944891; http://www.clinicaltrials.gov/ct2/show/NCT01944891 (Archived by WebCite at http://www.webcitation.org/6L9OUrsq8). PMID:24598035

Association of Human Leukocyte Antigen Alleles and Nevirapine Hypersensitivity in a Malawian HIV-Infected Population

PubMed Central

Carr, Daniel F.; Chaponda, Mas; Jorgensen, Andrea L.; Castro, Elena Cornejo; van Oosterhout, Joep J.; Khoo, Saye H.; Lalloo, David G.; Heyderman, Robert S.; Alfirevic, Ana; Pirmohamed, Munir

2013-01-01

Background. The nonnucleoside reverse transcriptase inhibitor nevirapine is the cornerstone of treatment for human immunodeficiency virus (HIV) in many sub-Saharan African countries. However, nevirapine is associated with a 6%–10% risk of developing a hypersensitivity reaction, with different phenotypes, including the blistering conditions Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Our aim was to identify predictive human leukocyte antigen (HLA) markers that are associated with nevirapine hypersensitivity. Methods. We identified 117 HIV-infected Malawian adults with nevirapine hypersensitivity (15 drug-induced liver injury [DILI], 33 SJS/TEN, 20 hypersensitivity syndrome, and 46 nevirapine-induced rash plus 3 with both DILI and SJS phenotype) and 155 age-, sex- and ethnicity-matched nevirapine-exposed controls. HLA typing for 5 loci (A, B, C, DRB1, and DQB1) was undertaken using a sequence-based high-resolution protocol. Logistic regression analysis included CD4+ cell count as a covariate. Results. HLA-C*04:01 was found to markedly increase the risk for SJS (odds ratio [OR] = 17.52; 95% confidence interval, 3.31–92.80) and all hypersensitivity phenotypes (OR = 2.64; 95% CI, 1.13–6.18) when compared to the baseline rare allele group in a binary logistic regression model. The OR for absolute risk of SJS/TEN associated with carriage of HLA-C*04:01 was 5.17 (95% CI, 2.39–11.18). Positive predictive value was 2.6% and negative predictive value was 99.2%. In addition, a number of alleles within the HLA-DQB1 loci protected against nevirapine-induced hypersensitivity phenotypes. Conclusions. Our study has identified HLA-C*04:01 carriage as a risk factor for nevirapine-induced SJS/TEN in a Malawian HIV cohort. Validation of these findings in a larger cohort of patients and mechanistic investigation of the pathogenesis are required. PMID:23362284

Elucidation of several neglected reactions in the GC-MS identification of sialic acids as heptafluorobutyrates calls for an urgent reassessment of previous claims.

PubMed

Rota, Paola; Anastasia, Luigi; Allevi, Pietro

2015-05-07

The current analytical protocol used for the GC-MS determination of free or 1,7-lactonized natural sialic acids (Sias), as heptafluorobutyrates, overlooks several transformations. Using authentic reference standards and by combining GC-MS and NMR analyses, flaws in the analytical protocol were pinpointed and elucidated, thus establishing the scope and limitations of the method. It was demonstrated that (a) Sias 1,7-lactones, even if present in biological samples, decompose under the acidic hydrolysis conditions used for their release; (b) Sias 1,7-lactones are unpredicted artifacts, accidentally generated from their parent acids; (c) the N-acetyl group is quantitatively exchanged with that of the derivatizing perfluorinated anhydride; (d) the partial or complete failure of the Sias esterification-step with diazomethane leads to the incorrect quantification and structure attribution of all free Sias. While these findings prompt an urgent correction and improvement of the current analytical protocol, they could be instrumental for a critical revision of many incorrect claims reported in the literature.

Therapeutic benefit of internet-based lifestyle counselling for hypertension.

PubMed

Nolan, Robert P; Liu, Sam; Shoemaker, J Kevin; Hachinski, Vladimir; Lynn, Hazel; Mikulis, David J; Wennberg, Richard A; Moy Lum-Kwong, Margaret; Zbib, Ahmad

2012-05-01

Preventive electronic (e)-counselling has been shown to reduce cardiovascular risk factors. However, heterogeneity in outcomes is commonly reported due to differences in e-protocols. We incorporated key features of an established behavioural therapy, motivational interviewing, to help standardize e-counselling in order to reduce blood pressure in patients with hypertension. Subjects (n = 387, mean age = 56 years, 59% female, 72% taking ≥ 1 antihypertensive drug) were diagnosed with stage 1 or 2 hypertension. Subjects were randomized to a 4-month protocol of e-counselling (beta version of the "Blood Pressure Action Plan", Heart and Stroke Foundation of Canada) vs waitlist control (general e-information on heart-healthy living). Outcomes were systolic, diastolic, and pulse pressures, and total lipoprotein cholesterol after treatment. Intention to treat analysis did not find a significant group difference in outcomes due to contamination across the 2 arms of this trial. However, per protocol analysis indicated that subjects receiving ≥ 8 e-counselling messages (a priori therapeutic dose) vs 0 e-counselling messages (control) demonstrated greater reduction in systolic blood pressure (mean, -8.9 mm Hg; 95% confidence interval [CI], -11.5 to -6.4 vs -5.0 mm Hg; 95% CI, -6.7 to -3.3, P = 0.03), pulse pressure (-6.1 mm Hg; 95% CI, -8.1 to -4.1 vs -3.1 mm Hg; 95% CI, -4.3 to -1.8, P = 0.02) and total cholesterol (-0.24 mmol/L; 95% CI, -0.43 to -0.06 vs 0.05 mmol/L; 95% CI, -0.06 to 0.16, P = 0.03), but not diastolic blood pressure. These findings support the merit of evaluating whether e-counselling can improve blood pressure control and reduce cardiovascular risk over the long-term. Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Parallel diurnal fluctuation of testosterone, androstenedione, dehydroepiandrosterone and 17OHprogesterone as assessed in serum and saliva: validation of a novel liquid chromatography-tandem mass spectrometry method for salivary steroid profiling.

PubMed

Mezzullo, Marco; Fazzini, Alessia; Gambineri, Alessandra; Di Dalmazi, Guido; Mazza, Roberta; Pelusi, Carla; Vicennati, Valentina; Pasquali, Renato; Pagotto, Uberto; Fanelli, Flaminia

2017-08-28

Salivary androgen testing represents a valuable source of biological information. However, the proper measurement of such low levels is challenging for direct immunoassays, lacking adequate accuracy. In the last few years, many conflicting findings reporting low correlation with the serum counterparts have hampered the clinical application of salivary androgen testing. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) makes it possible to overcome previous analytical limits, providing new insights in endocrinology practice. Salivary testosterone (T), androstenedione (A), dehydroepiandrosterone (DHEA) and 17OHprogesterone (17OHP) were extracted from 500µL of saliva, separated in 9.5 min LC-gradient and detected by positive electrospray ionization - multiple reaction monitoring. The diurnal variation of salivary and serum androgens was described by a four paired collection protocol (8 am, 12 am, 4 pm and 8 pm) in 19 healthy subjects. The assay allowed the quantitation of T, A, DHEA and 17OHP down to 3.40, 6.81, 271.0 and 23.7 pmol/L, respectively, with accuracy between 83.0 and 106.1% for all analytes. A parallel diurnal rhythm in saliva and serum was observed for all androgens, with values decreasing from the morning to the evening time points. Salivary androgen levels revealed a high linear correlation with serum counterparts in both sexes (T: R>0.85; A: R>0.90; DHEA: R>0.73 and 17OHP: R>0.89; p<0.0001 for all). Our LC-MS/MS method allowed a sensitive evaluation of androgen salivary levels and represents an optimal technique to explore the relevance of a comprehensive androgen profile as measured in saliva for the study of androgen secretion modulation and activity in physiologic and pathologic states.

Radiation-induced complications in prostate cancer patients treated with radiotherapy

NASA Astrophysics Data System (ADS)

Azuddin, A. Yusof; Rahman, I. Abdul; Siah, N. J.; Mohamed, F.; Saadc, M.; Ismail, F.

2014-09-01

The purpose of the study is to determine the relationship between radiation-induced complications with dosimetric and radiobiological parameters for prostate cancer patients that underwent the conformal radiotherapy treatment. 17 prostate cancer patients that have been treated with conformal radiotherapy were retrospectively analysed. The dosimetric data was retrieved in the form of dose-volume histogram (DVH) from Radiotherapy Treatment Planning System. The DVH was utilised to derived Normal Tissue Complication Probability (NTCP) in radiobiological data. Follow-up data from medical records were used to grade the occurrence of acute gastrointestinal (GI) and genitourinary (GU) complications using Radiation Therapy Oncology Group (RTOG) scoring system. The chi-square test was used to determine the relationship between radiation-induced complication with dosimetric and radiobiological parameters. 8 (47%) and 7 (41%) patients were having acute GI and GU complications respectively. The acute GI complication can be associated with V60rectum, rectal mean dose and NTCPrectum with p-value of 0.016, 0.038 and 0.049 respectively. There are no significant relationships of acute GU complication with dosimetric and radiobiological variables. Further study can be done by increase the sample size and follow up duration for deeper understanding of the factors that effecting the GU and GI complication in prostate cancer radiotherapy.

Aortic Center: specialized care improves outcomes and decreases mortality

PubMed Central

Sales, Marcela da Cunha; Frota Filho, José Dario; Aguzzoli, Cristiane; Souza, Leonardo Dornelles; Rösler, Álvaro Machado; Lucio, Eraldo Azevedo; Leães, Paulo Ernesto; Pontes, Mauro Ricardo Nunes; Lucchese, Fernando Antônio

2014-01-01

Objective To compare in-hospital outcomes in aortic surgery in our cardiac surgery unit, before and after foundation of our Center for Aortic Surgery (CTA). Methods Prospective cohort with non-concurrent control. Foundation of CTA required specialized training of surgical, anesthetic and intensive care unit teams, routine neurological monitoring, endovascular and hybrid facilities, training of the support personnel, improvement of the registry and adoption of specific protocols. We included 332 patients operated on between: January/2003 to December/2007 (before-CTA, n=157, 47.3%); and January/2008 to December/2010 (CTA, n=175, 52.7%). Baseline clinical and demographic data, operative variables, complications and in-hospital mortality were compared between both groups. Results Mean age was 58±14 years, with 65% male. Group CTA was older, had higher rate of diabetes, lower rates of COPD and HF, more non-urgent surgeries, endovascular procedures, and aneurysms. In the univariate analysis, CTA had lower mortality (9.7 vs. 23.0%, P=0.008), which occurred consistently across different diseases and procedures. Other outcomes which were reduced in CTA included lower rates of reinterventions (5.7 vs 11%, P=0.046), major complications (20.6 vs. 33.1%, P=0.007), stroke (4.6 vs. 10.9%, P=0.045) and sepsis (1.7 vs. 9.6%, P=0.001), as compared to before-CTA. Multivariable analysis adjusted for potential counfounders revealed that CTA was independently associated with mortality reduction (OR=0.23, IC 95% 0.08 – 0.67, P=0.007). CTA independent mortality reduction was consistent in the multivariable analysis stratified by disease (aneurysm, OR=0.18, CI 95% 0.03 – 0.98, P=0.048; dissection, OR=0.31, CI 95% 0.09 – 0.99, P=0.049) and by procedure (hybrid, OR=0.07, CI 95% 0.007 – 0.72, P=0.026; Bentall, OR=0.18, CI 95% 0.038 – 0.904, P=0.037). Additional multivariable predictors of in-hospital mortality included creatinine (OR=1.7 [1.1-2.6], P=0.008), urgent surgery (OR=5.0 [1.5-16.7], P=0.008) and thoracoabdominal aneurysm (OR=24.6 [3.1-194.1], P=0.002). Conclusion Thoracic aorta surgery in specialized center was associated with lower incidence of complications and all-cause mortality as compared to usual care. PMID:25714201

The quality of reports of medical and public health research from Palestinian institutions: a systematic review.

PubMed

Albarqouni, Loai; Abu-Rmeileh, Niveen Me; Elessi, Khamis; Obeidallah, Mohammad; Bjertness, Espen; Chalmers, Iain

2017-06-09

Over the past decade, there has been an increase in reports of health research from Palestine, but no assessment of their quality. We have assessed the quality of reports of Palestinian health research and factors associated with it. This is a systematic review. We searched Medline and Scopus for reports of original research relevant to human health or healthcare authored by researchers affiliated with Palestinian institutions and published between January 2000 and August 2015 inclusive. We used international guidelines to assess report quality, classifying as adequate those with ≥50% of items completely addressed. Of 2383 reports identified, 497 met our inclusion criteria. Just over half (264; 55%) of these were published after 2010. 354 (71%) of first authors were affiliated with Palestinian institutions; 261 (53%) reports had coauthors from outside Palestine. The majority of the reports in our study were inadequately reported (342; 69%), and none had adequately reported all items. Of 439 observational studies, 11 (2.5%) reports provided adequate descriptions of eligibility criteria and selection procedures; 35 (8%) reported efforts to address potential sources of bias; 50 (11.4%) reported the basis for the study sample size; and funding sources were mentioned in 74 reports (17%). Higher reporting quality was associated with international affiliation of the first author (prevalence ratio (PR) 1.6 (95% CI 1.2 to 2.1)), international collaboration (PR 2.9 (95% CI 1.7 to 5.0)), international funding (PR 1.9 (95% CI1.5 to 2.5)), publication after 2005 (PR 3.9 (95% CI 1.8 to 8.5)) and four or more coauthors (PR 1.5 (95% CI 1.1 to 2.1)). Although the quality of reports of Palestinian research has improved in recent years, it remains well below an acceptable standard. International reporting guidelines should be used to guide research design and improve the quality of reports of research. The systematic review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) registery (registration number: CRD42015027553). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A Receiver-Initiated Collision-Avoidance Protocol for Multi-Channel Networks

DTIC Science & Technology

2001-01-01

00-00-2001 to 00-00-2001 4. TITLE AND SUBTITLE A Receiver-Initiated Collision-Avoidance Protocol for Multi-Channel Netowrks 5a. CONTRACT NUMBER...images. 14. ABSTRACT 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 10 19a. NAME OF RESPONSIBLE

Determination of the appropriate quarantine period following smallpox exposure: an objective approach using the incubation period distribution.

PubMed

Nishiura, Hiroshi

2009-01-01

Determination of the most appropriate quarantine period for those exposed to smallpox is crucial to the construction of an effective preparedness program against a potential bioterrorist attack. This study reanalyzed data on the incubation period distribution of smallpox to allow the optimal quarantine period to be objectively calculated. In total, 131 cases of smallpox were examined; incubation periods were extracted from four different sets of historical data and only cases arising from exposure for a single day were considered. The mean (median and standard deviation (SD)) incubation period was 12.5 (12.0, 2.2) days. Assuming lognormal and gamma distributions for the incubation period, maximum likelihood estimates (and corresponding 95% confidence interval (CI)) of the 95th percentile were 16.4 (95% CI: 15.6, 17.9) and 16.2 (95% CI: 15.5, 17.4) days, respectively. Using a non-parametric method, the 95th percentile point was estimated as 16 (95% CI: 15, 17) days. The upper 95% CIs of the incubation periods at the 90th, 95th and 99th percentiles were shorter than 17, 18 and 23 days, respectively, using both parametric and non-parametric methods. These results suggest that quarantine measures can ensure non-infection among those exposed to smallpox with probabilities higher than 95-99%, if the exposed individuals are quarantined for 18-23 days after the date of contact tracing.

A randomized trial of protocol-based care for early septic shock.

PubMed

Yealy, Donald M; Kellum, John A; Huang, David T; Barnato, Amber E; Weissfeld, Lisa A; Pike, Francis; Terndrup, Thomas; Wang, Henry E; Hou, Peter C; LoVecchio, Frank; Filbin, Michael R; Shapiro, Nathan I; Angus, Derek C

2014-05-01

In a single-center study published more than a decade ago involving patients presenting to the emergency department with severe sepsis and septic shock, mortality was markedly lower among those who were treated according to a 6-hour protocol of early goal-directed therapy (EGDT), in which intravenous fluids, vasopressors, inotropes, and blood transfusions were adjusted to reach central hemodynamic targets, than among those receiving usual care. We conducted a trial to determine whether these findings were generalizable and whether all aspects of the protocol were necessary. In 31 emergency departments in the United States, we randomly assigned patients with septic shock to one of three groups for 6 hours of resuscitation: protocol-based EGDT; protocol-based standard therapy that did not require the placement of a central venous catheter, administration of inotropes, or blood transfusions; or usual care. The primary end point was 60-day in-hospital mortality. We tested sequentially whether protocol-based care (EGDT and standard-therapy groups combined) was superior to usual care and whether protocol-based EGDT was superior to protocol-based standard therapy. Secondary outcomes included longer-term mortality and the need for organ support. We enrolled 1341 patients, of whom 439 were randomly assigned to protocol-based EGDT, 446 to protocol-based standard therapy, and 456 to usual care. Resuscitation strategies differed significantly with respect to the monitoring of central venous pressure and oxygen and the use of intravenous fluids, vasopressors, inotropes, and blood transfusions. By 60 days, there were 92 deaths in the protocol-based EGDT group (21.0%), 81 in the protocol-based standard-therapy group (18.2%), and 86 in the usual-care group (18.9%) (relative risk with protocol-based therapy vs. usual care, 1.04; 95% confidence interval [CI], 0.82 to 1.31; P=0.83; relative risk with protocol-based EGDT vs. protocol-based standard therapy, 1.15; 95% CI, 0.88 to 1.51; P=0.31). There were no significant differences in 90-day mortality, 1-year mortality, or the need for organ support. In a multicenter trial conducted in the tertiary care setting, protocol-based resuscitation of patients in whom septic shock was diagnosed in the emergency department did not improve outcomes. (Funded by the National Institute of General Medical Sciences; ProCESS ClinicalTrials.gov number, NCT00510835.).

Ultrasonic Nakagami-parameter characterization of parotid-gland injury following head-and-neck radiotherapy: A feasibility study of late toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Xiaofeng; Wu, Ning; Wang, Yuefeng

Purpose: The study aims to investigate whether Nakagami parameters—estimated from the statistical distribution of the backscattered ultrasound radio-frequency (RF) signals—could provide a means for quantitative characterization of parotid-gland injury resulting from head-and-neck radiotherapy. Methods: A preliminary clinical study was conducted with 12 postradiotherapy patients and 12 healthy volunteers. Each participant underwent one ultrasound study in which ultrasound scans were performed in the longitudinal, i.e., vertical orientation on the bilateral parotids. For the 12 patients, the mean radiation dose to the parotid glands was 37.7 ± 9.5 Gy, and the mean follow-up time was 16.3 ± 4.8 months. All enrolled patientsmore » experienced grade 1 or 2 late salivary-gland toxicity (RTOG/EORTC morbidity scale). The normal parotid glands served as the control group. The Nakagami-scaling and Nakagami-shape parameters were computed from the RF data to quantify radiation-induced parotid-gland changes. Results: Significant differences in Nakagami parameters were observed between the normal and postradiotherapy parotid glands. Compared with the control group, the Nakagami-scaling parameter of the postradiotherapy group decreased by 25.8% (p < 0.001), and the Nakagami-shape parameter decreased by 31.3% (p < 0.001). The area under the receiver operating characteristic curve was 0.85 for the Nakagami-scaling parameter and was 0.95 for the Nakagami-shape parameter, which further demonstrated the diagnostic efficiency of the Nakagami parameters. Conclusions: Nakagami parameters could be used to quantitatively measure parotid-gland injury following head-and-neck radiotherapy. Moreover, the clinical feasibility was demonstrated and this study provides meaningful preliminary data for future clinical investigation.« less

Limiting the risk of cardiac toxicity with esophageal-sparing intensity modulated radiotherapy for locally advanced lung cancers.

PubMed

Woodford, Katrina; Panettieri, Vanessa; Ruben, Jeremy D; Senthi, Sashendra

2016-05-01

Intensity modulated radiotherapy (IMRT) is routinely utilized in the treatment of locally advanced non-small cell lung cancer (NSCLC). RTOG 0617 found that overall survival was impacted by increased low (5 Gy) and intermediate (30 Gy) cardiac doses. We evaluated the impact of esophageal-sparing IMRT on cardiac doses with and without the heart considered in the planning process and predicted toxicity compared to 3D-conventional radiotherapy (3DCRT). Ten consecutive patients with N2 Stage III NSCLC treated to 60 Gy in 30 fractions, between February 2012 and September 2014, were evaluated. For each patient, 3DCRT and esophageal-sparing IMRT plans were generated. IMRT plans were then created with and without the heart considered in the optimization process. To compare plans, the dose delivered to 95% and 99% of the target (D95% and D99%), and doses to the esophagus, lung and heart were compared by determining the volume receiving X dose (VXGy) and the normal tissue complication probability (NTCP) calculated. IMRT reduced maximum esophagus dose to below 60 Gy in all patients and produced significant reductions to V50Gy, V40Gy and esophageal NTCP. The cost of this reduction was a non-statistically, non-clinically significant increase in low dose (5 Gy) lung exposure that did not worsen lung NTCP. IMRT plans produced significant cardiac sparing, with the amount of improvement correlating to the amount of heart overlapping with the target. When included in plan optimization, for selected patients further sparing of the heart and improvement in heart NTCP was possible. Esophageal-sparing IMRT can significantly spare the heart even if it is not considered in the optimization process. Further sparing can be achieved if plan optimization constrains low and intermediate heart doses, without compromising lung doses.

Ultrasonic Nakagami-parameter characterization of parotid-gland injury following head-and-neck radiotherapy: A feasibility study of late toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Xiaofeng; Wu, Ning; Wang, Yuefeng

2014-02-15

Purpose: The study aims to investigate whether Nakagami parameters—estimated from the statistical distribution of the backscattered ultrasound radio-frequency (RF) signals—could provide a means for quantitative characterization of parotid-gland injury resulting from head-and-neck radiotherapy. Methods: A preliminary clinical study was conducted with 12 postradiotherapy patients and 12 healthy volunteers. Each participant underwent one ultrasound study in which ultrasound scans were performed in the longitudinal, i.e., vertical orientation on the bilateral parotids. For the 12 patients, the mean radiation dose to the parotid glands was 37.7 ± 9.5 Gy, and the mean follow-up time was 16.3 ± 4.8 months. All enrolled patientsmore » experienced grade 1 or 2 late salivary-gland toxicity (RTOG/EORTC morbidity scale). The normal parotid glands served as the control group. The Nakagami-scaling and Nakagami-shape parameters were computed from the RF data to quantify radiation-induced parotid-gland changes. Results: Significant differences in Nakagami parameters were observed between the normal and postradiotherapy parotid glands. Compared with the control group, the Nakagami-scaling parameter of the postradiotherapy group decreased by 25.8% (p < 0.001), and the Nakagami-shape parameter decreased by 31.3% (p < 0.001). The area under the receiver operating characteristic curve was 0.85 for the Nakagami-scaling parameter and was 0.95 for the Nakagami-shape parameter, which further demonstrated the diagnostic efficiency of the Nakagami parameters. Conclusions: Nakagami parameters could be used to quantitatively measure parotid-gland injury following head-and-neck radiotherapy. Moreover, the clinical feasibility was demonstrated and this study provides meaningful preliminary data for future clinical investigation.« less

Evaluating a preoperative protocol that includes magnetic resonance imaging for lymph node metastasis in the Cholangiocarcinoma Screening and Care Program (CASCAP) in Thailand.

PubMed

Songthamwat, Metha; Chamadol, Nittaya; Khuntikeo, Narong; Thinkhamrop, Jadsada; Koonmee, Supinda; Chaichaya, Nathaphop; Bethony, Jeffrey; Thinkhamrop, Bandit

2017-09-20

Treatment planning especially liver resection in cholangiocarcinoma (CCA) depends on the extension of tumor and lymph node metastasis which is included as a key criterion for operability. Magnetic resonance imaging (MRI) offers a rapid and powerful tool for the detection of lymph node metastasis (LNM) and in the current manuscript is assessed as a critical tool in the preoperative protocol for liver resection for treatment of CCA. However, the accuracy of MRI to detect LNM from CCA had yet to be comprehensively evaluated. The accuracy of MRI to detect LNM was assessed in a cohort of individuals with CCA from the Cholangiocarcinoma Screening and Care Program (CASCAP), a screening program designed to reduce CCA in Northeastern Thailand by community-based ultrasound (US) for CCA. CCA-positive individuals are referred to one of the nine tertiary centers in the study to undergo a preoperative protocol that included enhanced imaging by MRI. Additionally, these individuals also underwent lymph node biopsies for histological confirmation of LNM (the "gold standard") to determine the accuracy of the MRI results. MRI accurately detected the presence or absence of LNM in only 29 out of the 51 CCA cases (56.9%, 95% CI 42.2-70.7), resulting in a sensitivity of 57.1% (95% CI 34.0-78.2) and specificity of 56.7% (95% CI 37.4-74.5), with positive and negative predictive values of 48.0% (95% CI 27.8-68.7) and 65.4% (95% CI 44.3-82.8), respectively. The positive likelihood ratio was 1.32 (95% CI 0.76-2.29), and the negative likelihood ratio was 0.76 (95% CI 0.42-1.36). MRI showed limited sensitivity and a poor positive predictive value for the diagnosis of LNM for CCA, which is of particular concern in this resource-limited setting, where simpler detection methods could be utilized that are more cost-effective in this region of Thailand. Therefore, the inclusion of MRI, a costly imaging method, should be reconsidered as part of protocol for treatment planning of CCA, given the number of false positives, especially as it is critical in determining the operability for CCA subjects.

Spine Radiosurgery: A Dosimetric Analysis in 124 Patients Who Received 18 Gy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schipani, Stefano; Wen, Winston; Jin, Jain-Yue

2012-12-01

Purpose: To define the safely tolerated doses to organs at risk (OARs) adjacent to the target volume (TV) of spine radiosurgery (SRS) with 18-Gy in a single fraction. Methods and Materials: A total of 124 patient cases with 165 spine metastases were reviewed. An 18-Gy single-fraction regimen was prescribed to the 90% isodose line encompassing the TV. A constraint of 10 Gy to 10% of the spinal cord outlined 6 mm above and below the TV was used. Dosimetric data to OARs were analyzed. Results: A total of 124 patients (100%) were followed-up, and median follow-up time was 7 monthsmore » (1-50 months). Symptoms and local control were achieved in 114 patients (92%). Acute Radiation Therapy Oncology Group (RTOG) grade 1 oral mucositis occurred in 11 of 11 (100%) patients at risk for oropharyngeal toxicity after cervical spine treatment. There were no RTOG grade 2-4 acute or late complications. Median TV was 43.2 cc (5.3-175.4 cc) and 90% of the TV received median dose of 19 Gy (17-19.8 Gy). Median (range) of spinal cord maximum dose (Dmax), dose to spinal cord 0.35 cc (Dsc0.35), and cord volume receiving 10 Gy (Vsc10) were 13.8 Gy (5.4-21 Gy), 8.9 Gy (2.6-11.4 Gy) and 0.33 cc (0-1.6 cc), respectively. Other OARs were evaluated when in proximity to the TV. Esophagus (n=58), trachea (n=28), oropharynx (n=11), and kidneys (n=34) received median (range) V10 and V15 of 3.1 cc (0-5.8 cc) and 1.2 cc (0-2.9 cc), 2.8 cc (0-4.9 cc), and 0.8 cc (0-2.1 cc), 3.4 cc (0-6.2 cc) and 1.6 cc (0-3.2 cc), 0.3 cc (0-0.8 cc) and 0.08 cc (0-0.1 cc), respectively. Conclusions: Cord Dmax of 14 Gy and D0.35 of 10 Gy are safe dose constraints for 18-Gy single-fraction SRS. Esophagus V10 of 3 cc and V15 of 1 cc, trachea V10 of 3 cc, and V15 of 1 cc, oropharynx V10 of 3.5 cc and V15 of 1.5 cc, kidney V10 of 0.3 cc, and V15 of 0.1 cc are planning guidelines when these OARs are in proximity to the TV.« less

Association between the interleukin-17A -197G>A (rs2275913) polymorphism and risk of digestive cancer.

PubMed

Duan, Yin; Shi, Ji-Nan; Pan, Chi; Chen, Hai-Long; Zhang, Su-Zhan

2014-01-01

Interleukin-17A (IL-17A) is a multifunctional cytokine which plays a crucial role in the initiation and progression of cancer. To date, several studies have investigated associations between IL-17A -197G>A (rs2275913) polymorphism and digestive cancer risk, but the results remain conflicting. We here aimed to confirm the role of this single nucleotide polymorphism (SNP) in susceptibility to digestive cancer through a systemic review and meta-analysis. Ten eligible case-control studies were identified by searching electronic databases, involving 3,087 cases and 3,815 controls. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to estimate the strength of the association. The results of overall analyses indicated that the variant A allele was associated with an increased risk of digestive cancer (AA vs GG: OR=1.51, 95%CI=1.18-1.93; AA vs GG+GA: OR=1.45, 95%CI=1.12-1.87; A vs G: OR=1.21, 95%CI=1.05-1.39). In subgroup analysis stratified by specific cancer type, elevated risk among studies of gastric cancer was found (AA vs GG: OR=1.68, 95%CI=1.24-2.28; AA vs GG+GA: OR=1.62, 95%CI=1.16-2.26; A vs G: OR=1.23, 95%CI=1.04-1.46). According to ethnicity, there was evidence in the Asian populations for an association between this polymorphism and cancer risk (GA vs GG: OR=1.19, 95%CI=1.05-1.36; AA vs GG: OR=1.56, 95%CI=1.15-2.12; AA+GA vs GG: OR=1.28, 95%CI=1.13- 1.44; AA vs GG+GA: OR=1.42, 95%CI=1.01-2.00; A vs G: OR=1.24, 95%CI=1.08-1.44), while in the Caucasian populations an association was found in the recessive model (AA vs GG+GA: OR=1.62, 95%CI=1.17-2.24). In conclusion, the results of this meta-analysis suggest that the IL-17A -197G>A polymorphism contributes to an increased risk of human digestive cancer, both in the Asian and Caucasian populations and especially for gastric cancer.

46 CFR 95.17-25 - Additional protection required.

Code of Federal Regulations, 2011 CFR

2011-10-01

... FIRE PROTECTION EQUIPMENT Foam Extinguishing Systems, Details § 95.17-25 Additional protection required. (a) In order that any residual fires above the floor plates may be extinguished when a foam system is...

46 CFR 95.17-25 - Additional protection required.

Code of Federal Regulations, 2010 CFR

2010-10-01

... FIRE PROTECTION EQUIPMENT Foam Extinguishing Systems, Details § 95.17-25 Additional protection required. (a) In order that any residual fires above the floor plates may be extinguished when a foam system is...

Frequency of "Pocket" Hematoma in Patients Receiving Vitamin K Antagonist and Antiplatelet Therapy at the Time of Pacemaker or Cardioverter Defibrillator Implantation (from the POCKET Study).

PubMed

Malagù, Michele; Trevisan, Filippo; Scalone, Antonella; Marcantoni, Lina; Sammarco, Giuseppe; Bertini, Matteo

2017-04-01

In patients undergoing cardiac device implantation, anticoagulant and antiplatelet therapy are associated with an increased risk of pocket hematoma. In case of vitamin K antagonist therapy, a strategy of continued warfarin with no heparin bridge showed a reduction of pocket hematoma. Evidence regarding antiplatelet therapy management is limited. This is a single-center observational study which reflects our systematic approach to the problem. In 2012, we proposed an improved management protocol for anticoagulant and antiplatelet therapy (no-bridge protocol) based on individual thromboembolic risk stratification, noninterruption of oral anticoagulation, no bridge with heparin and elastic adherence compression bandage. The primary end point was the incidence of clinically significant pocket hematoma in the first 30 days after implantation. A total of 1,035 patients were enrolled, of whom 522 received the standard management and 513 the new protocol. The primary end point occurred in 34 patients of the standard management group and 8 patients of the no-bridge protocol group (6.5% vs 1.6%, p <0.001). Patients in the standard management group had a higher incidence of pocket infections (2.3% vs 0.6%, p = 0.02), lead dislodgements (4.8% vs 2.1%, p = 0.02), and thromboembolic events (1.3% vs 0.0%, p <0.01). On a multivariate analysis, heparin and coronary artery disease were independent predictors of pocket hematoma (relative risk [RR] 3.48, 95% confidence interval [CI] 1.55 to 7.83 and RR 2.43, 95% CI 1.25 to 4.76, respectively), whereas the no-bridge protocol was associated with a reduction of pocket hematoma (RR 0.33, 95% CI 0.14 to 0.76). New anticoagulant and antiplatelet therapy management protocol was associated with a reduced incidence of clinically significant pocket hematomas, thromboembolic events, pocket infections, and lead dislodgements. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of individually body weight adapted contrast media injection in coronary CT-angiography.

PubMed

Mihl, Casper; Kok, Madeleine; Altintas, Sibel; Kietselaer, Bas L J H; Turek, Jakub; Wildberger, Joachim E; Das, Marco

2016-04-01

Contrast media (CM) injection protocols should be customized to the individual patient. Aim of this study was to determine if software tailored CM injections result in diagnostic enhancement of the coronary arteries in computed tomography angiography (CTA) and if attenuation values were comparable between different weight categories. 265 consecutive patients referred for routine coronary CTA were scanned on a 2nd generation dual-source CT. Group 1 (n=141) received an individual CM bolus based on weight categories (39-59 kg; 60-74 kg; 75-94 kg; 95-109 kg) and scan duration ('high-pitch: 1s; "dual-step prospective triggering": 7s), as determined by contrast injection software (Certegra™ P3T, Bayer, Berlin, Germany). Group 2 (n=124) received a standard fixed CM bolus; Iopromide 300 mgI/ml; volume: 75 ml; flow rate: 7.2 ml/s. Contrast enhancement was measured in all proximal and distal coronary segments. Subjective and objective image quality was evaluated. Statistical analysis was performed using SPSS (IBM, version 20.0). For group 1, mean attenuation values of all segments were diagnostic (>325 HU) without statistical significant differences between different weight categories (p>0.17), proximal vs. distal: 449 ± 65-373 ± 58 HU (39-59 kg); 443 ± 69-367 ± 81 HU (60-74 kg); 427 ± 59-370 ± 61 HU (75-94 kg); 427 ± 73-347 ± 61 HU (95-109 kg). Mean CM volumes were: 55 ± 6 ml (39-59 kg); 61 ± 7 ml (60-74 kg); 71 ± 8 ml (75-94 kg); 84 ± 9 ml (95-109 kg). For group 2, mean attenuation values were not all diagnostic with differences between weight categories (p<0.01), proximal vs. distal: 611 ± 142-408 ± 69 HU (39-59 kg); 562 ± 135-389 ± 98 HU (60-74 kg); 481 ± 83-329 ± 81 HU (75-94 kg); 420 ± 73-305 ± 35 HU (95-109 kg). Comparable image noise and image quality were found between groups (p ≥ 0.330). Individually tailored CM injection protocols yield diagnostic attenuation and a more homogeneous enhancement pattern between different weight groups. CM volumes could be reduced for the majority of patients utilizing individualized CM bolus application. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Schroth Physiotherapeutic Scoliosis-Specific Exercises Added to the Standard of Care Lead to Better Cobb Angle Outcomes in Adolescents with Idiopathic Scoliosis - an Assessor and Statistician Blinded Randomized Controlled Trial.

PubMed

Schreiber, Sanja; Parent, Eric C; Khodayari Moez, Elham; Hedden, Douglas M; Hill, Douglas L; Moreau, Marc; Lou, Edmond; Watkins, Elise M; Southon, Sarah C

2016-01-01

The North American non-surgical standard of care for adolescent idiopathic scoliosis (AIS) includes observation and bracing, but not exercises. Schroth physiotherapeutic scoliosis-specific exercises (PSSE) showed promise in several studies of suboptimal methodology. The Scoliosis Research Society calls for rigorous studies supporting the role of exercises before including it as a treatment recommendation for scoliosis. To determine the effect of a six-month Schroth PSSE intervention added to standard of care (Experimental group) on the Cobb angle compared to standard of care alone (Control group) in patients with AIS. Fifty patients with AIS aged 10-18 years, with curves of 10°-45° and Risser grade 0-5 were recruited from a single pediatric scoliosis clinic and randomized to the Experimental or Control group. Outcomes included the change in the Cobb angles of the Largest Curve and Sum of Curves from baseline to six months. The intervention consisted of a 30-45 minute daily home program and weekly supervised sessions. Intention-to-treat and per protocol linear mixed effects model analyses are reported. In the intention-to-treat analysis, after six months, the Schroth group had significantly smaller Largest Curve than controls (-3.5°, 95% CI -1.1° to -5.9°, p = 0.006). Likewise, the between-group difference in the square root of the Sum of Curves was -0.40°, (95% CI -0.03° to -0.8°, p = 0.046), suggesting that an average patient with 51.2° at baseline, will have a 49.3° Sum of Curves at six months in the Schroth group, and 55.1° in the control group with the difference between groups increasing with severity. Per protocol analyses produced similar, but larger differences: Largest Curve = -4.1° (95% CI -1.7° to -6.5°, p = 0.002) and [Formula: see text] (95% CI -0.8 to 0.2, p = 0.006). Schroth PSSE added to the standard of care were superior compared to standard of care alone for reducing the curve severity in patients with AIS. NCT01610908.

Schroth Physiotherapeutic Scoliosis-Specific Exercises Added to the Standard of Care Lead to Better Cobb Angle Outcomes in Adolescents with Idiopathic Scoliosis – an Assessor and Statistician Blinded Randomized Controlled Trial

PubMed Central

Parent, Eric C.; Khodayari Moez, Elham; Hedden, Douglas M.; Hill, Douglas L.; Moreau, Marc; Lou, Edmond; Watkins, Elise M.; Southon, Sarah C.

2016-01-01

Background The North American non-surgical standard of care for adolescent idiopathic scoliosis (AIS) includes observation and bracing, but not exercises. Schroth physiotherapeutic scoliosis-specific exercises (PSSE) showed promise in several studies of suboptimal methodology. The Scoliosis Research Society calls for rigorous studies supporting the role of exercises before including it as a treatment recommendation for scoliosis. Objectives To determine the effect of a six-month Schroth PSSE intervention added to standard of care (Experimental group) on the Cobb angle compared to standard of care alone (Control group) in patients with AIS. Methods Fifty patients with AIS aged 10–18 years, with curves of 10°-45° and Risser grade 0–5 were recruited from a single pediatric scoliosis clinic and randomized to the Experimental or Control group. Outcomes included the change in the Cobb angles of the Largest Curve and Sum of Curves from baseline to six months. The intervention consisted of a 30–45 minute daily home program and weekly supervised sessions. Intention-to-treat and per protocol linear mixed effects model analyses are reported. Results In the intention-to-treat analysis, after six months, the Schroth group had significantly smaller Largest Curve than controls (-3.5°, 95% CI -1.1° to -5.9°, p = 0.006). Likewise, the between-group difference in the square root of the Sum of Curves was -0.40°, (95% CI -0.03° to -0.8°, p = 0.046), suggesting that an average patient with 51.2° at baseline, will have a 49.3° Sum of Curves at six months in the Schroth group, and 55.1° in the control group with the difference between groups increasing with severity. Per protocol analyses produced similar, but larger differences: Largest Curve = -4.1° (95% CI -1.7° to -6.5°, p = 0.002) and Sum of Curves=−0.5° (95% CI -0.8 to 0.2, p = 0.006). Conclusion Schroth PSSE added to the standard of care were superior compared to standard of care alone for reducing the curve severity in patients with AIS. Trial Registration NCT01610908 PMID:28033399

Effects of different impact exercise modalities on bone mineral density in premenopausal women: a meta-analysis.

PubMed

Martyn-St James, Marrissa; Carroll, Sean

2010-05-01

Our objective was to assess the effects of differing modes of impact exercise on bone density at the hip and spine in premenopausal women through systematic review and meta-analysis. Electronic databases, key journals and reference lists were searched for controlled trials investigating the effects of impact exercise interventions on lumbar spine (LS), femoral neck (FN) and total hip (TH) bone mineral density (BMD) in premenopausal women. Exercise protocols were categorised according to impact loading characteristics. Weighted mean difference (WMD) meta-analyses were undertaken. Heterogeneity amongst trials was assessed. Fixed and random effects models were applied. Inspection of funnel plot symmetry was performed. Trial quality assessment was also undertaken. Combined protocols integrating odd- or high-impact exercise with high-magnitude loading (resistance exercises), were effective in increasing BMD at both LS and FN [WMD (fixed effect) 0.009 g cm(-2) 95% CI (0.002-0.015) and 0.007 g cm(-2) 95% CI (0.001-0.013); P = 0.011 and 0.017, respectively]. High-impact only protocols were effective on femoral neck BMD [WMD (fixed effect) 0.024 g cm(-2) 95% CI (0.002-0.027); P < 0.00001]. Funnel plots showed some asymmetry for positive BMD outcomes. Insufficient numbers of protocols assessing TH BMD were available for assessment. Exercise programmes that combine odd- or high-impact activity with high-magnitude resistance training appear effective in augmenting BMD in premenopausal women at the hip and spine. High-impact-alone protocols are effective only on hip BMD in this group. However, diverse methodological and reporting discrepancies are evident in published trials.

Evaluation of a focussed protocol for hand-held echocardiography and computer-assisted auscultation in detecting latent rheumatic heart disease in scholars.

PubMed

Zühlke, Liesl J; Engel, Mark E; Nkepu, Simpiwe; Mayosi, Bongani M

2016-08-01

Introduction Echocardiography is the diagnostic test of choice for latent rheumatic heart disease. The utility of echocardiography for large-scale screening is limited by high cost, complex diagnostic protocols, and time to acquire multiple images. We evaluated the performance of a brief hand-held echocardiography protocol and computer-assisted auscultation in detecting latent rheumatic heart disease with or without pathological murmur. A total of 27 asymptomatic patients with latent rheumatic heart disease based on the World Heart Federation criteria and 66 healthy controls were examined by standard cardiac auscultation to detect pathological murmur. Hand-held echocardiography using a focussed protocol that utilises one view - that is, the parasternal long-axis view - and one measurement - that is, mitral regurgitant jet - and a computer-assisted auscultation utilising an automated decision tool were performed on all patients. The sensitivity and specificity of computer-assisted auscultation in latent rheumatic heart disease were 4% (95% CI 1.0-20.4%) and 93.7% (95% CI 84.5-98.3%), respectively. The sensitivity and specificity of the focussed hand-held echocardiography protocol for definite rheumatic heart disease were 92.3% (95% CI 63.9-99.8%) and 100%, respectively. The test reliability of hand-held echocardiography was 98.7% for definite and 94.7% for borderline disease, and the adjusted diagnostic odds ratios were 1041 and 263.9 for definite and borderline disease, respectively. Computer-assisted auscultation has extremely low sensitivity but high specificity for pathological murmur in latent rheumatic heart disease. Focussed hand-held echocardiography has fair sensitivity but high specificity and diagnostic utility for definite or borderline rheumatic heart disease in asymptomatic patients.

The impact of perioperative fluid therapy on short-term outcomes and 5-year survival among patients undergoing colorectal cancer surgery - A prospective cohort study within an ERAS protocol.

PubMed

Asklid, D; Segelman, J; Gedda, C; Hjern, F; Pekkari, K; Gustafsson, U O

2017-08-01

Restricted perioperative fluid therapy is one of several interventions in the enhanced recovery after surgery (ERAS) protocol, designed to reduce morbidity and hospital stay after surgery. The impact of this single intervention on short and long term outcome after colorectal surgery is unknown. This cohort study includes all consecutive patients operated with abdominal resection of colorectal cancer 2002-2007 at Ersta Hospital, Stockholm, Sweden. All patients were treated within an ERAS protocol and registered in the ERAS-database. Compliance to interventions in the ERAS protocol was analysed. The impact of a restrictive perioperative fluid therapy (≤3000 ml on the day of surgery) protocol on short-term outcomes as well as 5-year survival was assessed with multivariable analysis adjusted for confounding factors. Nine hundred and eleven patients were included. Patients receiving ≤3000 ml of intravenous fluids on the day of surgery had a lower risk of complications OR 0.44 (95% C I 0.28-0.71), symptoms delaying discharge OR 0.47(95% C I 0.32-0.70) and shorter length of stay compared with patients receiving >3000 ml. In cox regression analysis, the risk of cancer specific death was reduced with 55% HR 0.45(95% C I 0.25-0.81) for patients receiving ≤ 3000 ml compared with patients receiving >3000 ml. A restrictive compared with a non-restrictive perioperative fluid therapy on the day of surgery may be associated with lower short-term complication rates, faster recovery, shorter length of stay and improved 5-year survival. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Baseline immunosuppression is associated with histological findings in early protocol biopsies.

PubMed

Moreso, Francesc; Serón, Daniel; Carrera, Marta; Gil-Vernet, Salvador; Cruzado, Josep M; Hueso, Miguel; Fulladosa, Xavier; Ramos, Rosa; Ibernon, Meritxell; Castelao, Alberto M; Grinyó, Josep M

2004-10-15

Protocol biopsies performed in stable renal allografts show different degrees of acute and chronic lesions that have been related with graft outcome. However, the utility of protocol biopsies to manage baseline immunosuppression has not been well characterized. We performed a case-control study to compare histological lesions observed in protocol biopsies in 49 patients treated with tacrolimus (TAC), mycophenolate mofetil (MMF), and prednisone to 49 patients treated with cyclosporine Neoral (CsA), MMF, and prednisone. Histological lesions were graded according to 1997 Banff criteria. The analysis was done according to an intention-to-treat basis. Patients treated with TAC displayed in the protocol biopsy a lower acute score (0.61+/-1.01 vs. 1.26+/-1.45; P=0.0115) and a similar chronic score (1.57+/-1.97 vs. 1.51+/-1.59; P=NS). Transplant glomerulopathy was also lower in TAC treated patients (0.02+/-0.14 vs. 0.20+/-0.41; P=0.0037). Univariate and multivariate logistic regression analysis showed that the presence of acute inflammation was associated with tacrolimus treatment (relative risk [RR]: 0.30, 95% confidence interval [CI]: 0.11-0.84; P=0.0211) and the time of biopsy (RR per month: 0.56, 95% CI: 0.32-0.97; P=0.0394). The presence of chronic lesions was only associated with serum creatinine at the time of biopsy (RR: 1.01, 95% CI: 1.00-1.02; P=0.0439). The incidence of inflammatory lesions and transplant glomerulopathy is lower in patients treated with TAC than in patients treated with CsA. These data suggest that baseline immunosuppression could influence the severity of histological lesions in stable grafts.

Risk of multiple myeloma in a case-spouse study.

PubMed

Andreotti, Gabriella; Katz, Michael; Hoering, Antje; Van Ness, Brian; Crowley, John; Morgan, Gareth; Hoover, Robert N; Baris, Dalsu; Durie, Brian

2016-01-01

This study examined lifestyle, occupation, medical history and medication use with multiple myeloma risk in a case-spouse study (481 patients, 351 spouses). Odds ratios (ORs) and 95% confidence intervals (CI) were calculated using logistic regression. Compared to spouse controls, cases were more likely to have a family history of multiple myeloma (OR = 2.8, 95% CI = 1.2-6.4) and smoked cigarettes (OR = 1.7, 95% CI = 1.2-2.5), but less likely to have consumed alcohol (OR = 0.6, 95% CI = 0.4-0.9). Nurse/health practitioners (OR = 2.8, 95% CI = 1.3-6.2) and production workers (OR = 3.7, 95% CI = 1.0-13.7) had significantly increased risks; and some occupations linked to diesel exhaust had elevated, but non-significant, risks. History of herpes simplex (OR = 1.7, 95% CI = 1.2-2.4), shingles (OR = 1.7, 95% CI = 1.1-2.7), sexually transmitted diseases (OR = 2.0, 95% CI = 1.0-3.7) and medication allergies (OR = 1.7, 95% CI = 1.2-2.4) were associated with higher risks. Use of angiotensin-converting enzyme inhibitors, anti-convulsants, antidepressants, statins and diuretics were associated with reduced risks. The results are consistent with previous population-based studies and support the utility of patient databanks and spouse controls as a resource in epidemiologic research.

Cladribine in a weekly versus daily schedule for untreated active hairy cell leukemia: final report from the Polish Adult Leukemia Group (PALG) of a prospective, randomized, multicenter trial.

PubMed

Robak, Tadeusz; Jamroziak, Krzysztof; Gora-Tybor, Joanna; Blonski, Jerzy Z; Kasznicki, Marek; Dwilewicz-Trojaczek, Jadwiga; Wiater, Elzbieta; Zdunczyk, Andrzej; Dybowicz, Jacek; Dmoszynska, Anna; Wojtaszko, Maria; Zdziarska, Barbara; Calbecka, Malgorzata; Kostyra, Aleksandra; Hellmann, Andrzej; Lewandowski, Krzysztof; Stella-Holowiecka, Beata; Sulek, Kazimierz; Gawronski, Krzysztof; Skotnicki, Aleksander B; Nowak, Wieslaw; Zawilska, Krystyna; Molendowicz-Portala, Lucyna; Kloczko, Janusz; Sokolowski, Jaroslaw; Warzocha, Krzysztof; Seferynska, Ilona; Ceglarek, Bernardeta; Konopka, Lech

2007-05-01

Cladribine (2-chlorodeoxyadenosine, 2-CdA) treatment-associated infections may shorten potentially long-term survival in hairy cell leukemia (HCL). In search of the optimal mode of 2-CdA administration, 132 patients with untreated HCL were randomized to receive either standard 5-day 2-CdA protocol or a novel schedule of 6 weekly 2-CdA infusions suggested to be less toxic. Analysis of treatment response confirmed similar complete remission rates, overall response rates, progression-free survival, and overall survival in both 2-CdA protocols. However, we did not observe lower toxicity in the weekly schedule. Of special interest, no significant differences were found in the rate of grade 3/4 infections (18% for daily and 26% for weekly protocol, difference -8.2%; 95% confidence interval [CI] -23.2% to 6.9%; P = .28) and the rate of septic deaths (3% for daily and 2% for weekly protocol, difference 1.4%; 95% CI -4.3% to 7.0%; P = .64). In conclusion, HCL treatment with weekly 2-CdA infusions is equally effective but no safer than the standard 5-day 2-CdA protocol.

Families of quantum fingerprinting protocols

NASA Astrophysics Data System (ADS)

Lovitz, Benjamin; Lütkenhaus, Norbert

2018-03-01

We introduce several families of quantum fingerprinting protocols to evaluate the equality function on two n -bit strings in the simultaneous message passing model. The original quantum fingerprinting protocol uses a tensor product of a small number of O (logn ) -qubit high-dimensional signals [H. Buhrman et al., Phys. Rev. Lett. 87, 167902 (2001), 10.1103/PhysRevLett.87.167902], whereas a recently proposed optical protocol uses a tensor product of O (n ) single-qubit signals, while maintaining the O (logn ) information leakage of the original protocol [J. M. Arazola and N. Lütkenhaus, Phys. Rev. A 89, 062305 (2014), 10.1103/PhysRevA.89.062305]. We find a family of protocols which interpolate between the original and optical protocols while maintaining the O (logn ) information leakage, thus demonstrating a tradeoff between the number of signals sent and the dimension of each signal. There has been interest in experimental realization of the recently proposed optical protocol using coherent states [F. Xu et al., Nat. Commun. 6, 8735 (2015), 10.1038/ncomms9735; J.-Y. Guan et al., Phys. Rev. Lett. 116, 240502 (2016), 10.1103/PhysRevLett.116.240502], but as the required number of laser pulses grows linearly with the input size n , eventual challenges for the long-time stability of experimental setups arise. We find a coherent state protocol which reduces the number of signals by a factor 1/2 while also reducing the information leakage. Our reduction makes use of a simple modulation scheme in optical phase space, and we find that more complex modulation schemes are not advantageous. Using a similar technique, we improve a recently proposed coherent state protocol for evaluating the Euclidean distance between two real unit vectors [N. Kumar et al., Phys. Rev. A 95, 032337 (2017), 10.1103/PhysRevA.95.032337] by reducing the number of signals by a factor 1/2 and also reducing the information leakage.

Impact of peer counselling breast-feeding support programme protocols on any and exclusive breast-feeding discontinuation in low-income women.

PubMed

Rozga, Mary R; Kerver, Jean M; Olson, Beth H

2015-02-01

Peer counselling (PC) programmes have been shown to improve breast-feeding outcomes in populations at risk for early discontinuation. Our objective was to describe associations between programme components (individual and combinations) and breast-feeding outcomes (duration and exclusivity) in a PC programme for low-income women. Secondary analysis of programme data. Multivariable-adjusted Cox proportional hazards models were used to examine associations between type and quantity of peer contacts with breast-feeding outcomes. Types of contacts included in-person (hospital or home), phone or other (e.g. mail, text). Quantities of contacts were considered 'optimal' if they adhered to standard programme guidelines. Programme data collected from 2005 to 2011 in Michigan's Breastfeeding Initiative Peer Counseling Program. Low-income (n 5886) women enrolled prenatally. For each additional home, phone and other PC contact there was a significant reduction in the hazard of discontinuing any breast-feeding by 6 months (hazard ratio (HR)=0·90 (95% CI 0·88, 0·92); HR=0·89 (95% CI 0·87, 0·90); and HR=0·93 (95% CI 0·90, 0·96), respectively) and exclusive breast-feeding by 3 months (HR=0·92 (95% CI 0·89, 0·95); HR=0·90 (95% CI 0·88, 0·91); and HR=0·93 (95% CI 0·89, 0·97), respectively). Participants receiving greater than optimal in-person and less than optimal phone contacts had a reduced hazard of any and exclusive breast-feeding discontinuation compared with those who were considered to have optimum quantities of contacts (HR=0·17 (95% CI 0·14, 0·20) and HR=0·28 (95% CI 0·23, 0·35), respectively). Specific components of a large PC programme appeared to have an appreciable impact on breast-feeding outcomes. In-person contacts were essential to improving breast-feeding outcomes, but defining optimal programme components is complex.

Blood Product Utilization Among Trauma and Nontrauma Massive Transfusion Protocols at an Urban Academic Medical Center.

PubMed

Patel, Eshan U; Ness, Paul M; Marshall, Christi E; Gniadek, Thomas; Efron, David T; Miller, Peter M; Zeitouni, Joseph A; King, Karen E; Bloch, Evan M; Tobian, Aaron A R

2017-09-01

Hospital-wide massive transfusion protocols (MTPs) primarily designed for trauma patients may lead to excess blood products being prepared for nontrauma patients. This study characterized blood product utilization among distinct trauma and nontrauma MTPs at a large, urban academic medical center. A retrospective study of blood product utilization was conducted in patients who required an MTP activation between January 2011 and December 2015 at an urban academic medical center. Trauma MTP containers included 6 red blood cell (RBC) units, 5 plasma units, and 1 unit of apheresis platelets. Nontrauma MTP containers included 6 RBC and 3 plasma units. There were 334 trauma MTP activations, 233 nontrauma MTP activations, and 77 nontrauma MTP activations that subsequently switched to a trauma MTP ("switched activations"). All nontrauma MTP activations were among bleeding patients who did not have a traumatic injury (100% [233/233]). Few patients with a nontrauma activation required ad hoc transfusion of RBC units (1.3% [95% confidence interval {CI}, 0.3%-3.7%]) or plasma (3.4% [95% CI, 1.5%-6.7%]), and only 45.5% (95% CI, 39.0%-52.1%) required ad hoc transfusion of apheresis platelets. Compared to trauma and switched activations, nontrauma activations transfused a lower median number of RBC, plasma, and apheresis platelet units (P < .001 for all comparisons). There was also a lower median number of prepared but unused plasma units for nontrauma activations (3; [interquartile range {IQR}, 3-5]) compared to trauma (7; [IQR, 5-10]; P < .001) and switched activations (8; [IQR, 5-11]; P < .001). The median number of unused apheresis platelet units was 1 (IQR, 1-2) for trauma activations and 0 (IQR, 0-1) for switched activations. There was a high proportion of trauma and switched activations in which all of the prepared apheresis platelet units were unused (28.1% [95% CI, 23.4%-33.3%] and 9.1% [95% CI, 3.7%-17.8%], respectively). The majority of initial nontrauma MTP activations did not require a switch to a trauma MTP. Patients remaining under a nontrauma MTP activation were associated with a lower number of transfused and unused plasma and apheresis platelet units. Future studies evaluating the use of hospital-wide nontrauma MTPs are warranted since an MTP designed for nontrauma patient populations may yield a key strategy to optimize blood product utilization in comparison to a universal MTP for both trauma and nontrauma patients.

Traditional Chinese medicine compound ShengJinRunZaoYangXue granules for treatment of primary Sjögren's syndrome: a randomized, double-blind, placebo-controlled clinical trial.

PubMed

Hu, Wei; Qian, Xian; Guo, Feng; Zhang, Miaojia; Lyu, Chengyin; Tao, Juan; Gao, Zhong'en; Zhou, Zhengqiu

2014-01-01

Traditional Chinese medical treatment of primary Sjögren's syndrome has advantages over Western medicine in terms of fewer side effects and improved patient conditions. This study was a multicenter, randomized, double-blind, placebo-controlled clinical trial of the efficacy and safety of ShengJinRunZaoYangXue granules for the treatment of primary Sjögren's syndrome, including the symptoms of dry mouth and dry eye. We undertook a 6-week, double-blind, randomized trial involving 240 patients with primary Sjögren's syndrome at five centers in East China. A computer-generated randomization schedule assigned patients at a 2:1 ratio to receive either ShengJinRunZaoYangXue granules or placebo once daily. Patients and investigators were blinded to treatment allocation. The primary endpoints were the salivary flow rate, Schirmer test results, and sugar test results. Intention-to-treat and per-protocol analyses were performed. All 240 patients were randomly allocated to either the treatment group (n = 160, ShengJinRunZaoYangXue granules) or placebo group (n = 80) and were included in the intention-to-treat analysis. After program violation and loss to follow-up, a total of 199 patients were included in the per-protocol analysis. At six week, intention-to-treat and per-protocol analyses of the left-eye Schirmer I test results showed an improved difference of 1.36 mm/5 min (95% CI: 0.03 to 2.69 mm/5 min) and 1.35 mm/5 min (95% CI: 0.04 to 2.73 mm/5 min), respectively, and those of the right-eye Schirmer I test results showed an improved difference of 1.12 mm/5 min (95% CI: 0.02 to 2.22 mm/5 min) and 1.12 mm/5 min (95% CI: -0.02 to 2.27 mm/5 min), respectively. There was no significant difference between the two groups before treatment. After treatment, the between-group and within-group before-and-after paired comparison results were statistically significant (P < 0.05). Intention-to-treat and per-protocol analyses showed an improved salivary flow rate by 0.04 ml/15 min (95% CI: -0.49 to 0.58 ml/15 min) and 0.04 ml/15 min (95% CI: -0.52 to 0.60 ml/15 min), respectively, but the differences were not significant. Intention-to-treat and per-protocol analyses showed that the sugar test results were improved by 1.77 minutes (95% CI: 0.11 to 3.44 minutes) and 1.84 minutes (95% CI: 0.12 to 3.55 minutes), respectively, but the differences were not significant. For the secondary endpoint, intention-to-treat and per-protocol analyses showed significant improvement in the integrated evaluation of treated patients with dry eye and dry mouth after six weeks of treatment. The incidence of adverse events was 15.6% in the treatment group and 10.0% in the placebo group. Most (94%) adverse events were mild to moderate in the two groups, and only two cases of serious adverse events occurred in the treatment group; both were caused by autoimmune liver disease. Six-week treatment with ShengJinRun ZaoYangXue granules for primary Sjögren's syndrome in this large-scale study improved the symptoms of dry mouth, dry eyes, and low tear flow rate with minimal adverse events.

High-Bandwidth Tactical-Network Data Analysis in a High-Performance-Computing (HPC) Environment: Transport Protocol (Transmission Control Protocol/User Datagram Protocol [TCP/UDP]) Analysis

DTIC Science & Technology

2015-09-01

the network Mac8 Medium Access Control ( Mac ) (Ethernet) address observed as destination for outgoing packets subsessionid8 Zero-based index of...15. SUBJECT TERMS tactical networks, data reduction, high-performance computing, data analysis, big data 16. SECURITY CLASSIFICATION OF: 17...Integer index of row cts_deid Device (instrument) Identifier where observation took place cts_collpt Collection point or logical observation point on

Measuring prefrontal cortical activity during dual task walking in patients with Parkinson's disease: feasibility of using a new portable fNIRS device.

PubMed

Nieuwhof, Freek; Reelick, Miriam F; Maidan, Inbal; Mirelman, Anat; Hausdorff, Jeffrey M; Olde Rikkert, Marcel G M; Bloem, Bastiaan R; Muthalib, Makii; Claassen, Jurgen A H R

2016-01-01

Many patients with Parkinson's disease (PD) have difficulties in performing a second task during walking (i.e., dual task walking). Functional near-infrared spectroscopy (fNIRS) is a promising approach to study the presumed contribution of dysfunction within the prefrontal cortex (PFC) to such difficulties. In this pilot study, we examined the feasibility of using a new portable and wireless fNIRS device to measure PFC activity during different dual task walking protocols in PD. Specifically, we tested whether PD patients were able to perform the protocol and whether we were able to measure the typical fNIRS signal of neuronal activity. We included 14 PD patients (age 71.2 ± 5.4 years, Hoehn and Yahr stage II/III). The protocol consisted of five repetitions of three conditions: walking while (i) counting forwards, (ii) serially subtracting, and (iii) reciting digit spans. Ability to complete this protocol, perceived exertion, burden of the fNIRS devices, and concentrations of oxygenated (O 2 Hb) and deoxygenated (HHb) hemoglobin from the left and right PFC were measured. Two participants were unable to complete the protocol due to fatigue and mobility safety concerns. The remaining 12 participants experienced no burden from the two fNIRS devices and completed the protocol with ease. Bilateral PFC O 2 Hb concentrations increased during walking while serially subtracting (left PFC 0.46 μmol/L, 95 % confidence interval (CI) 0.12-0.81, right PFC 0.49 μmol/L, 95 % CI 0.14-0.84) and reciting digit spans (left PFC 0.36 μmol/L, 95 % CI 0.03-0.70, right PFC 0.44 μmol/L, 95 % CI 0.09-0.78) when compared to rest. HHb concentrations did not differ between the walking tasks and rest. These findings suggest that a new wireless fNIRS device is a feasible measure of PFC activity in PD during dual task walking. Future studies should reduce the level of noise and inter-individual variability to enable measuring differences in PFC activity between different dual walking conditions and across health states.

Physician discretion is safe and may lower stress test utilization in emergency department chest pain unit patients.

PubMed

Napoli, Anthony M; Arrighi, James A; Siket, Matthew S; Gibbs, Frantz J

2012-03-01

Chest pain unit (CPU) observation with defined stress utilization protocols is a common management option for low-risk emergency department patients. We sought to evaluate the safety of a joint emergency medicine and cardiology staffed CPU. Prospective observational trial of consecutive patients admitted to an emergency department CPU was conducted. A standard 6-hour observation protocol was followed by cardiology consultation and stress utilization largely at their discretion. Included patients were at low/intermediate risk by the American Heart Association, had nondiagnostic electrocardiograms, and a normal initial troponin. Excluded patients were those with an acute comorbidity, age >75, and a history of coronary artery disease, or had a coexistent problem restricting 24-hour observation. Primary outcome was 30-day major adverse cardiovascular events-defined as death, nonfatal acute myocardial infarction, revascularization, or out-of-hospital cardiac arrest. A total of 1063 patients were enrolled over 8 months. The mean age of the patients was 52.8 ± 11.8 years, and 51% (95% confidence interval [CI], 48-54) were female. The mean thrombolysis in myocardial infarction and Diamond & Forrester scores were 0.6% (95% CI, 0.51-0.62) and 33% (95% CI, 31-35), respectively. In all, 51% (95% CI, 48-54) received stress testing (52% nuclear stress, 39% stress echocardiogram, 5% exercise, 4% other). In all, 0.9% patients (n = 10, 95% CI, 0.4-1.5) were diagnosed with a non-ST elevation myocardial infarction and 2.2% (n = 23, 95% CI, 1.3-3) with acute coronary syndrome. There was 1 (95% CI, 0%-0.3%) case of a 30-day major adverse cardiovascular events. The 51% stress test utilization rate was less than the range reported in previous CPU studies (P < 0.05). Joint emergency medicine and cardiology management of patients within a CPU protocol is safe, efficacious, and may safely reduce stress testing rates.

Effect of a Community Health Worker-Led Multicomponent Intervention on Blood Pressure Control in Low-income Patients in Argentina: A Randomized Clinical Trial

PubMed Central

He, Jiang; Irazola, Vilma; Mills, Katherine T.; Poggio, Rosana; Beratarrechea, Andrea; Dolan, Jacquelyn; Chen, Chung-Shiuan; Gibbons, Luz; Krousel-Wood, Marie; Bazzano, Lydia A.; Nejamis, Analia; Gulayin, Pablo; Santero, Marilina; Augustovski, Federico; Chen, Jing; Rubinstein, Adolfo

2017-01-01

Importance Despite extensive knowledge of hypertension treatment, the prevalence of uncontrolled hypertension is high and increasing in low- and middle-income countries. Objective To test whether a community health worker (CHW)-led multicomponent intervention would improve blood pressure (BP) control among low-income patients with hypertension. Design, Setting, and Participants A cluster randomized trial was conducted in 18 centers for primary healthcare within a national public system providing free medications and healthcare to uninsured patients in Argentina. A total of 1,432 low-income adult patients with uncontrolled hypertension were recruited between June 2013 and April 2015 and followed to October 2016. Intervention Nine centers (743 patients) were randomized to the multicomponent intervention, which included a CHW-led home intervention (health coaching, home BP monitoring, and BP audit and feedback), a physician intervention, and a text-messaging intervention over 18 months. Nine centers (689 patients) were randomized to usual care without study intervention. Main Outcomes and Measures The co-primary outcomes were the differences between the intervention and control groups in systolic and diastolic BP changes from baseline to end of follow-up in patients with hypertension. Secondary outcomes included the proportion of patients with controlled hypertension (BP<140/90 mmHg). Three BP measurements were obtained at each of two baseline and two termination visits using a standard protocol, and the means were used for analyses. Results Among 1,432 participants (mean age, 55.8 years; 772 [53.0%] women), 1,357 (94.8%) completed the trial. Baseline mean BP was 151.7 and 149.8 mmHg for systolic, and 92.2 and 90.1 mmHg for diastolic in the intervention and control groups, respectively. Systolic BP reduction from baseline to month 18 was 19.3 mmHg (95% confidence interval [CI]: 17.9, 20.8) in the intervention group and 12.7 mmHg (95% CI: 11.3, 14.2) in the control group; difference in the reduction was 6.6 mmHg (95% CI: 4.6, 8.6; p<0.001). Diastolic BP decreased by 12.2 mmHg (95% CI: 11.2, 13.2) in the intervention group and 6.9 mmHg (95% CI: 5.9, 7.8) in the control group; difference in the reduction was 5.4 mmHg (95% CI: 4.0, 6.8; p<0.001). The proportion of controlled hypertension increased from 17.0% at baseline to 72.9% at 18 months in the intervention group and from 17.6% to 52.2% in the control group; difference in the increase was 20.6% (95% CI: 15.4, 25.9%; p<0.001). No adverse events were reported. Conclusion and Relevance Among low-income patients with uncontrolled hypertension in Argentina, a CHW-led multicomponent intervention compared with usual care resulted in a greater decrease in systolic and diastolic BP over 18 months. Further research is needed to assess generalizability and cost-effectiveness of this intervention, and to understand which components may have contributed most to the outcome. Trial Registration clinicaltrials.gov Identifier: NCT01834131 PMID:28975305

[Acute lymphoblastic leukemia: experience in adult patients treated with hyperCVAD and 0195 Protocol, at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. Cohort 2003-2007].

PubMed

Arteaga-Ortiz, Luis; Buitrón-Santiago, Natalie; Rosas-López, Adriana; Rosas-Arzate, Guadalupe; Armengolt-Jiménez, Alicia; Aguayo, Alvaro; López-Karpovitch, Xavier; Crespo-Solís, Erick

2008-01-01

Despite therapeutic advances, acute lymphoblastic leukemia (ALL) in adults remains a disease with poor long term outcome and survival rates. Developing countries lack of information about this disease. On the other hand, infections are frequent complications related to mortality and some research studies do not show accurate rates of septic shock or other related factors. To describe characteristics of adults with acute lymphoblastic leukemia, response to treatment, complications and to evaluate further survival related factors and to compare our experience with other reports of literature. Between September 2003 to November 2007, the entire cohort of patients with diagnosis of ALL was included. The treatment regimens used were MDACC HyperCVAD (HCVAD) and 0195 (institutional regimen). Of 40 patients included with the diagnosis of ALL, 92% was B phenotype and 8%, T phenotype, with a median age of 27 years. The median follow up was 28.5 months. Initially, 14% showed central nervous system infiltration; of 51% with available cytogenetics, 16.7% was Philadelphia chromosome positive. There were 36 patients who received treatment: 13 received HCVAD and 23 the 0195 protocol; 78% achieved global complete remission, 85% for the patients with HCVAD and 74% with 0195. The induction death rate was 2.8%. The median disease-free survival was 11.6 months (IC 95%, 2.5-20.8 months) and overall survival was 15 months (IC 95%, 10.6-19.4 months). In 95% of patients, no prophylactic antibiotic therapy was used and treatment related death was 8.4% (2.8% during induction and 5.6% during the rest of treatment). Factors associated with worse survival rate were hyperleukocytosis, T phenotype and lack of early complete remission. During induction, grade 3 to 4 non hematopoietic toxicity was 17%. Incidence of neutropenic febrile episodes was 61% and septic shock was 11%. With HCVAD, we observed worse complete remission, disease-free survival and overall survival rates compared with the original MDACC reports. Chemotherapy related death rates are similar to other early reports, despite prophylactic antibiotic was not used during myelosuppression.

40 CFR Appendix J to Subpart A of... - [Reserved

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 17 2010-07-01 2010-07-01 false [Reserved] J Appendix J to Subpart A of Part 82-Parties to the Montreal Protocol Classied Under Article 5(1) That Have Banned the Import... Montreal Protocol Classied Under Article 5(1) That Have Banned the Import of Controlled Products That Rely...

40 CFR Appendix J to Subpart A of... - [Reserved

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 17 2011-07-01 2011-07-01 false [Reserved] J Appendix J to Subpart A of Part 82-Parties to the Montreal Protocol Classied Under Article 5(1) That Have Banned the Import... Montreal Protocol Classied Under Article 5(1) That Have Banned the Import of Controlled Products That Rely...

Digital Breast Tomosynthesis: Observer Performance of Clustered Microcalcification Detection on Breast Phantom Images Acquired with an Experimental System Using Variable Scan Angles, Angular Increments, and Number of Projection Views

PubMed Central

Goodsitt, Mitchell M.; Helvie, Mark A.; Zelakiewicz, Scott; Schmitz, Andrea; Noroozian, Mitra; Paramagul, Chintana; Roubidoux, Marilyn A.; Nees, Alexis V.; Neal, Colleen H.; Carson, Paul; Lu, Yao; Hadjiiski, Lubomir; Wei, Jun

2014-01-01

Purpose To investigate the dependence of microcalcification cluster detectability on tomographic scan angle, angular increment, and number of projection views acquired at digital breast tomosynthesis (DBTdigital breast tomosynthesis). Materials and Methods A prototype DBTdigital breast tomosynthesis system operated in step-and-shoot mode was used to image breast phantoms. Four 5-cm-thick phantoms embedded with 81 simulated microcalcification clusters of three speck sizes (subtle, medium, and obvious) were imaged by using a rhodium target and rhodium filter with 29 kV, 50 mAs, and seven acquisition protocols. Fixed angular increments were used in four protocols (denoted as scan angle, angular increment, and number of projection views, respectively: 16°, 1°, and 17; 24°, 3°, and nine; 30°, 3°, and 11; and 60°, 3°, and 21), and variable increments were used in three (40°, variable, and 13; 40°, variable, and 15; and 60°, variable, and 21). The reconstructed DBTdigital breast tomosynthesis images were interpreted by six radiologists who located the microcalcification clusters and rated their conspicuity. Results The mean sensitivity for detection of subtle clusters ranged from 80% (22.5 of 28) to 96% (26.8 of 28) for the seven DBTdigital breast tomosynthesis protocols; the highest sensitivity was achieved with the 16°, 1°, and 17 protocol (96%), but the difference was significant only for the 60°, 3°, and 21 protocol (80%, P < .002) and did not reach significance for the other five protocols (P = .01–.15). The mean sensitivity for detection of medium and obvious clusters ranged from 97% (28.2 of 29) to 100% (24 of 24), but the differences fell short of significance (P = .08 to >.99). The conspicuity of subtle and medium clusters with the 16°, 1°, and 17 protocol was rated higher than those with other protocols; the differences were significant for subtle clusters with the 24°, 3°, and nine protocol and for medium clusters with 24°, 3°, and nine; 30°, 3°, and 11; 60°, 3° and 21; and 60°, variable, and 21 protocols (P < .002). Conclusion With imaging that did not include x-ray source motion or patient motion during acquisition of the projection views, narrow-angle DBTdigital breast tomosynthesis provided higher sensitivity and conspicuity than wide-angle DBTdigital breast tomosynthesis for subtle microcalcification clusters. © RSNA, 2014 PMID:25007048

Identification of the Optimal Protocol for Automated Office Blood Pressure Measurement Among Patients With Treated Hypertension.

PubMed

Moore, Myles N; Schultz, Martin G; Nelson, Mark R; Black, J Andrew; Dwyer, Nathan B; Hoban, Ella; Jose, Matthew D; Kosmala, Wojciech; Przewlocka-Kosmala, Monika; Zachwyc, Jowita; Otahal, Petr; Picone, Dean S; Roberts-Thomson, Philip; Veloudi, Panagiota; Sharman, James E

2018-02-09

Automated office blood pressure (AOBP) involving repeated, unobserved blood pressure (BP) readings during one clinic visit is recommended for in-office diagnosis and assessment of hypertension. However, the optimal AOBP protocol to determine BP control in the least amount of time with the fewest BP readings is yet to be determined and was the aim of this study. One hundred and eighty-nine patients (mean age 62.8 ± 12.1 years; 50.3% female) with treated hypertension referred to specialist clinics at 2 sites underwent AOBP in a quiet room alone. Eight BP measurements were taken starting immediately after sitting and then at 2-minute intervals (15 minutes total). The optimal AOBP protocol was defined by the smallest mean difference and highest intraclass correlation coefficient (ICC) compared with daytime ambulatory BP (ABP). The same BP device (Mobil-o-graph, IEM) was used for both AOBP and daytime ABP. Average 15-minute AOBP and daytime ABP were 134 ± 22/82 ± 13 and 137 ± 17/83 ± 11 mm Hg, respectively. The optimal AOBP protocol was derived within a total duration of 6 minutes from the average of 2 measures started after 2 and 4 minutes of seated rest (systolic BP: mean difference (95% confidence interval) 0.004(-2.21, 2.21) mm Hg, P = 1.0; ICC = 0.81; diastolic BP: mean difference 0.37(-0.90, 1.63) mm Hg, P = 0.57; ICC = 0.86). AOBP measures taken after 8 minutes tended to underestimate daytime ABP (whether as a single BP or the average of more than 1 BP reading). Only 2 AOBP readings taken over 6 minutes (excluding an initial reading immediately after sitting) may be needed to be comparable with daytime ABP. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Early subclinical rejection as a risk factor for late chronic humoral rejection.

PubMed

Moreso, Francesc; Carrera, Marta; Goma, Montse; Hueso, Miguel; Sellares, Joana; Martorell, Jaume; Grinyó, Josep M; Serón, Daniel

2012-01-15

Subclinical rejection and interstitial fibrosis and tubular atrophy (IF/TA) in protocol biopsies are associated with outcome. We study the relationship between histologic lesions in early protocol biopsies and histologic diagnoses in late biopsies for cause. Renal transplants with a protocol biopsy performed within the first 6 months posttransplant between 1988 and 2006 were reviewed. Biopsies were evaluated according to Banff criteria, and C4d staining was available in biopsies for cause. Of the 517 renal transplants with a protocol biopsy, 109 had a subsequent biopsy for cause which showed the following histological diagnoses: chronic humoral rejection (CHR) (n=44), IF/TA (n=42), recurrence of the primary disease (n=11), de novo glomerulonephritis (n=7), T-cell-mediated rejection (n=4), and polyoma virus nephropathy (n=1). The proportion of retransplants (15.9% vs. 2.3%, P=0.058) and the prevalence of subclinical rejection were higher in patients with CHR than in patients with IF/TA (52.3% vs. 28.6%, P=0.0253). Demographic donor and recipient characteristics and clinical data at the time of protocol biopsy were not different between groups. Logistic regression analysis showed that subclinical rejection (relative risk, 2.52; 95% confidence interval, 1.1-6.3; P=0.047) but not retransplantation (relative risk, 6.7; 95% confidence interval, 0.8-58.8; P=0.085) was associated with CHR. Subclinical rejection in early protocol biopsies is associated with late appearance of CHR.

Prophylactic amnioinfusion for intrapartum oligohydramnios: a meta-analysis of randomized controlled trials.

PubMed

Pitt, C; Sanchez-Ramos, L; Kaunitz, A M; Gaudier, F

2000-11-01

To evaluate the effectiveness of intrapartum prophylactic amnioinfusion in pregnancies complicated by oligohydramnios. Randomized controlled trials of prophylactic amnioinfusion in women with oligohydramnios were identified using computerized databases, index reviews, and references cited in original studies and review articles. We evaluated, abstracted data from, and analyzed randomized studies of prophylactic intrapartum amnioinfusion in women with oligohydramnios. In every study the group allocation was based exclusively on presence of oligohydramnios. Only published studies with clearly documented outcome data were included. The quality of each trial was evaluated for methodology, inclusion and exclusion criteria, adequacy of randomization, amnioinfusion protocols, definition of outcomes, and statistical analyses. The trials were evaluated concerning cesarean deliveries for fetal heart rate (FHR) abnormalities, overall cesarean rates, acidemia at birth, intrapartum fetal heart rate abnormalities, Apgar scores under 7 at 5 minutes, and postpartum endometritis. Thirty-five studies were identified, of which 14 met the inclusion criteria for this systematic review. They included 1533 patients, 793 in the amnioinfusion group, and 740 controls. Odds ratios (OR) with their 95% confidence intervals (CI) for each outcome were calculated. We calculated an estimate of the OR and risk difference for dichotomous outcomes using random and fixed-effects models. A test of homogeneity was done across studies. Women with oligohydramnios who received intrapartum amnioinfusion had lower incidence of cesarean for FHR abnormalities (OR 0.23; 95% CI 0.15, 0.35). Intrapartum amnioinfusion also was associated with lower overall rates of cesarean deliveries (OR 0.52; 95% CI 0.40, 0. 68), acidemia at birth (OR 0.40; 95% CI 0.30, 0.55), FHR abnormalities during labor (OR 0.24; 95% CI 0.17, 0.34), and Apgar scores under 7 at 5 minutes (OR 0.52; 95% CI 0.29, 0.91). Postpartum endometritis rates were similar among the study groups. In the presence of oligohydramnios, prophylactic intrapartum amnioinfusion significantly improves neonatal outcome and lessens the rate of cesarean delivery, without increasing the rate of postpartum endometritis.

Effects of low-volume high-intensity interval training in a community setting: a pilot study.

PubMed

Reljic, Dejan; Wittmann, Felix; Fischer, Joachim E

2018-06-01

High-intensity interval training (HIIT) is emerging as an effective and time-efficient exercise strategy for health promotion. However, most HIIT studies are conducted in laboratory settings and evidence regarding the efficacy of time-efficient "low-volume" HIIT is based mainly on demanding "all-out" protocols. Thus, the aim of this pilot study was to assess the feasibility and efficacy of two low-volume (≤ 30 min time-effort/week), non-all-out HIIT protocols, performed 2 ×/week over 8 weeks in a community-based fitness centre. Thirty-four sedentary men and women were randomised to either 2 × 4-min HIIT (2 × 4-HIIT) or 5 × 1-min HIIT (5 × 1-HIIT) at 85-95% maximal heart rate (HR max ), or an active control group performing moderate-intensity continuous training (MICT, 76 min/week) at 65-75% HR max . The exercise protocols were well tolerated and no adverse events occurred. 2 × 4-HIIT and 5 × 1-HIIT exhibited lower dropout rates (17 and 8 vs. 30%) than MICT. All training modes improved VO 2max (2 × 4-HIIT: + 20%, P < 0.01; 5 × 1-HIIT: + 27%, P < 0.001; MICT: + 16%, P < 0.05), but the HIIT protocols required 60% less time commitment. Both HIIT protocols and MICT had positive impact on cholesterol profiles. Only 5 × 1-HIIT significantly improved waist circumference (P < 0.05) and subjective work ability (P < 0.05). The present study indicates that low-volume HIIT can be feasibly implemented in a community-based setting. Moreover, our data suggest that practical (non-all-out) HIIT that requires as little as 30 min/week, either performed as 2 × 4-HIIT or 5 × 1-HIIT, may induce significant improvements in VO 2max and cardiometabolic risk markers.

Effect of Xenon Anesthesia Compared to Sevoflurane and Total Intravenous Anesthesia for Coronary Artery Bypass Graft Surgery on Postoperative Cardiac Troponin Release: An International, Multicenter, Phase 3, Single-blinded, Randomized Noninferiority Trial.

PubMed

Hofland, Jan; Ouattara, Alexandre; Fellahi, Jean-Luc; Gruenewald, Matthias; Hazebroucq, Jean; Ecoffey, Claude; Joseph, Pierre; Heringlake, Matthias; Steib, Annick; Coburn, Mark; Amour, Julien; Rozec, Bertrand; Liefde, Inge de; Meybohm, Patrick; Preckel, Benedikt; Hanouz, Jean-Luc; Tritapepe, Luigi; Tonner, Peter; Benhaoua, Hamina; Roesner, Jan Patrick; Bein, Berthold; Hanouz, Luc; Tenbrinck, Rob; Bogers, Ad J J C; Mik, Bert G; Coiffic, Alain; Renner, Jochen; Steinfath, Markus; Francksen, Helga; Broch, Ole; Haneya, Assad; Schaller, Manuella; Guinet, Patrick; Daviet, Lauren; Brianchon, Corinne; Rosier, Sebastien; Lehot, Jean-Jacques; Paarmann, Hauke; Schön, Julika; Hanke, Thorsten; Ettel, Joachym; Olsson, Silke; Klotz, Stefan; Samet, Amir; Laurinenas, Giedrius; Thibaud, Adrien; Cristinar, Mircea; Collanges, Olivier; Levy, François; Rossaint, Rolf; Stevanovic, Ana; Schaelte, Gereon; Stoppe, Christian; Hamou, Nora Ait; Hariri, Sarah; Quessard, Astrid; Carillion, Aude; Morin, Hélène; Silleran, Jacqueline; Robert, David; Crouzet, Anne-Sophie; Zacharowski, Kai; Reyher, Christian; Iken, Sonja; Weber, Nina C; Hollmann, Marcus; Eberl, Susanne; Carriero, Giovanni; Collacchi, Daria; Di Persio, Alessandra; Fourcade, Olivier; Bergt, Stefan; Alms, Angela

2017-12-01

Ischemic myocardial damage accompanying coronary artery bypass graft surgery remains a clinical challenge. We investigated whether xenon anesthesia could limit myocardial damage in coronary artery bypass graft surgery patients, as has been reported for animal ischemia models. In 17 university hospitals in France, Germany, Italy, and The Netherlands, low-risk elective, on-pump coronary artery bypass graft surgery patients were randomized to receive xenon, sevoflurane, or propofol-based total intravenous anesthesia for anesthesia maintenance. The primary outcome was the cardiac troponin I concentration in the blood 24 h postsurgery. The noninferiority margin for the mean difference in cardiac troponin I release between the xenon and sevoflurane groups was less than 0.15 ng/ml. Secondary outcomes were the safety and feasibility of xenon anesthesia. The first patient included at each center received xenon anesthesia for practical reasons. For all other patients, anesthesia maintenance was randomized (intention-to-treat: n = 492; per-protocol/without major protocol deviation: n = 446). Median 24-h postoperative cardiac troponin I concentrations (ng/ml [interquartile range]) were 1.14 [0.76 to 2.10] with xenon, 1.30 [0.78 to 2.67] with sevoflurane, and 1.48 [0.94 to 2.78] with total intravenous anesthesia [per-protocol]). The mean difference in cardiac troponin I release between xenon and sevoflurane was -0.09 ng/ml (95% CI, -0.30 to 0.11; per-protocol: P = 0.02). Postoperative cardiac troponin I release was significantly less with xenon than with total intravenous anesthesia (intention-to-treat: P = 0.05; per-protocol: P = 0.02). Perioperative variables and postoperative outcomes were comparable across all groups, with no safety concerns. In postoperative cardiac troponin I release, xenon was noninferior to sevoflurane in low-risk, on-pump coronary artery bypass graft surgery patients. Only with xenon was cardiac troponin I release less than with total intravenous anesthesia. Xenon anesthesia appeared safe and feasible.

Impact of a modified Broviac maintenance care bundle on bloodstream infections in paediatric cancer patients

PubMed Central

Furtwängler, Rhoikos; Laux, Carolin; Graf, Norbert; Simon, Arne

2015-01-01

Background: During intensive chemotherapy, bloodstream infection (BSI) represents an important complication in paediatric cancer patients. Most patients carry a long-term central venous access device (CVAD). Improved maintenance care of these vascular catheters may decrease the risk of BSI. Methods: Intervention study (adapted CVAD prevention protocol) with two observation periods (P1: 09-2009 until 05-2011; P2: 09-2011 until 05-2013); prospective surveillance of all laboratory confirmed BSIs. In P2, ready to use sterile NaCl 0.9% syringes were used for CVAD flushing and octenidine/isopropanol for the disinfection of catheter hubs and 3-way stopcocks. Results: During P1, 84 patients were included versus 81 patients during P2. There were no significant differences between the two patient populations in terms of median age, gender, underlying malignancy or disease status (first illness or relapse). Nearly all CVADs were Broviac catheters. The median duration from implantation to removal of the CVAD was 192 days (Inter-quartile-range (IQR); 110–288 days) in P1 and 191 days (IQR; 103–270 days) in P2. 28 BSI were diagnosed in 22 patients in P1 (26% of all patients experienced at least one BSI) and 15 BSI in 12 patients in P2 (15% of all patients). The corresponding results for incidence density (ID) were 0.44 (CI95 0.29–0.62) for P1 vs. 0.34 (0.19–0.53) BSI per 100 inpatient days for P2 and for incidence rate (IR) 7.76 (5.16–10.86) in P1 vs. 4.75 (2.66–7.43) BSI per 1,000 inpatient CVAD utilization days. In P1, 9 BSI were caused by CoNS vs. only 2 in P2 (IR 2.49; CI95 0.17–4.17 vs. 0.63; CI95 0.08–1.72). In P1 two BSI (7%) lead to early removal of the device. During P2 one CVAD was prematurely removed due to a Broviac-related BSI (6.7%). Conclusion: The preventive protocol investigated in this study led to a reduction of BSI in paediatric cancer patients. This result was clinically relevant but – due to insufficient power in a single centre observation – the difference did not reach statistical significance. The most pronounced trend in BSI reduction was observed for CoNS infections. Thus, improving maintenance care of the CVAD may result in lower CVAD-linked infection rates. The higher acquisition cost of the ready to use NaCl 0.9% flushing syringes and octenidine/propanol hub disinfection were probably balanced by cost savings in the intervention period. PMID:26605135

Adult Arabs have higher risk for diabetes mellitus than Jews in Israel

PubMed Central

Giveon, Shmuel; Wulffhart, Liat; Oberman, Bernice; Baidousi, Maslama; Ziv, Arnona; Kalter-Leibovici, Ofra

2017-01-01

Objective Diabetes mellitus is an emerging epidemic in the Arab world. Although high diabetes prevalence is documented in Israeli Arabs, information from cohort studies is scant. Methods This is a population study, based on information derived between 2007–2011, from the electronic database of the largest health fund in Israel, among Arabs and Jews. Prevalence, 4-year-incidence and diabetes hazard ratios [HRs], adjusted for sex and the metabolic-syndrome [MetS]-components, were determined in 3 age groups (<50 years, 50–59 years, and ≥60 years). Results The study cohort included 17,044 Arabs (males: 49%, age: 39.4±17.3) and 16,012 Jews (males: 50%, age: 40.5 ±17.6). The overall age and sex-adjusted diabetes prevalence rates were much higher among Arabs 18.4% (95%CI: 17.6–19.1); and 10.3% (95%CI: 9.7–10.9) among Jews. Arab females had higher prevalence rates 20.0% (95%CI: 19–21) than Arab males 16.7% (95%CI: 15.7–17.8). Annual incidence rates were also significantly higher among Arabs 2.9% (95%CI: 2.7–3.1) than among Jews 1.7% (95%CI: 1.6–1.8). This held true across all age and sex subgroups. Adjustment for body mass index [BMI] attenuated HR estimates associated with Arab ethnicity across all age subgroups, mainly in the <50yrs age group from HR 2.04 (95%CI: 1.74–2.40) to 1.64 (95%CI: 1.40–1.92). BMI at incident diabetes among females was higher in Arabs than Jews. Males, however, did not differ by ethnicity. Conclusion Arabs, mainly female, have high incidence and prevalence of diabetes. This excess risk is only partially explained by the high prevalence of obesity. Effective culturally-congruent diabetes prevention and treatment and an effective engagement partnership with the Arab community are of paramount need. PMID:28481942

Adult Arabs have higher risk for diabetes mellitus than Jews in Israel.

PubMed

Jaffe, Anat; Giveon, Shmuel; Wulffhart, Liat; Oberman, Bernice; Baidousi, Maslama; Ziv, Arnona; Kalter-Leibovici, Ofra

2017-01-01

Diabetes mellitus is an emerging epidemic in the Arab world. Although high diabetes prevalence is documented in Israeli Arabs, information from cohort studies is scant. This is a population study, based on information derived between 2007-2011, from the electronic database of the largest health fund in Israel, among Arabs and Jews. Prevalence, 4-year-incidence and diabetes hazard ratios [HRs], adjusted for sex and the metabolic-syndrome [MetS]-components, were determined in 3 age groups (<50 years, 50-59 years, and ≥60 years). The study cohort included 17,044 Arabs (males: 49%, age: 39.4±17.3) and 16,012 Jews (males: 50%, age: 40.5 ±17.6). The overall age and sex-adjusted diabetes prevalence rates were much higher among Arabs 18.4% (95%CI: 17.6-19.1); and 10.3% (95%CI: 9.7-10.9) among Jews. Arab females had higher prevalence rates 20.0% (95%CI: 19-21) than Arab males 16.7% (95%CI: 15.7-17.8). Annual incidence rates were also significantly higher among Arabs 2.9% (95%CI: 2.7-3.1) than among Jews 1.7% (95%CI: 1.6-1.8). This held true across all age and sex subgroups. Adjustment for body mass index [BMI] attenuated HR estimates associated with Arab ethnicity across all age subgroups, mainly in the <50yrs age group from HR 2.04 (95%CI: 1.74-2.40) to 1.64 (95%CI: 1.40-1.92). BMI at incident diabetes among females was higher in Arabs than Jews. Males, however, did not differ by ethnicity. Arabs, mainly female, have high incidence and prevalence of diabetes. This excess risk is only partially explained by the high prevalence of obesity. Effective culturally-congruent diabetes prevention and treatment and an effective engagement partnership with the Arab community are of paramount need.

Investigating the level of agreement of two positioning protocols when using dual energy X-ray absorptiometry in the assessment of body composition.

PubMed

Shiel, Flinn; Persson, Carl; Simas, Vini; Furness, James; Climstein, Mike; Schram, Ben

2017-01-01

Dual energy X-ray absorptiometry (DXA) is a commonly used instrument for analysing segmental body composition (BC). The information from the scan guides the clinician in the treatment of conditions such as obesity and can be used to monitor recovery of lean mass following injury. Two commonly used DXA positioning protocols have been identified-the Nana positioning protocol and the National Health and Nutrition Examination Survey (NHANES). Both protocols have been shown to be reliable. However, only one study has assessed the level of agreement between the protocols and ascertained the participants' preference of protocol based upon comfort. Given the paucity of research in the field and the growing use of DXA in both healthy and pathological populations further research determining the most appropriate positioning protocol is warranted. Therefore, the aims of this study were to assess the level of agreement between results from the NHANES protocol and Nana protocol, and the participants' preference of protocol based on comfort. Thirty healthy participants (15 males, 15 females, aged 23-59 years) volunteered to participate in this study. These participants underwent two whole body DXA scans in a single morning (Nana positioning protocol and NHANES positioning protocol), in a randomised order. Each participant attended for scanning wearing minimal clothing and having fasted overnight, refrained from exercise in the past 24 h and voided their bladders. Level of agreement, comparing NAHNES to Nana protocol was assessed using an intra-class correlation coefficient (ICC), concordance correlation coefficient (CCC) and percentage change in mean. Limit of agreement comparing the two protocols were assessed using plots, mean difference and confidence limits. Participants were asked to indicate the protocol they found most comfortable. When assessing level of agreement between protocols both the ICC and CCC scores were very high and ranged from 0.987 to 0.997 for whole body composition, indicating excellent agreement between the Nana and NHANES protocols. Regional analysis (arms, legs, trunk) ICC scores, ranged between 0.966 and 0.996, CCC ranged between 0.964 and 0.997, change in mean percentage ranged between -0.58% and 0.37% which indicated a very high level of agreement. Limit of agreement analysis using mean difference ranged between -0.223 and 0.686 kg and 95% CL produced results ranging between -1.262 kg and 1.630 kg. The majority (80%) of participants found the NHANES positioning protocol more comfortable. This study reveals a strong level of agreement as illustrated by high ICC's and CCC's between the positioning protocols, however systematic bias within limit of agreement plot and a large difference in 95% confidence limits indicates that the protocols should not be interchanged when assessing an individual. The NHANES protocol affords greater participant comfort.

An improved in-house lysis-filtration protocol for bacterial identification from positive blood culture bottles with high identification rates by MALDI-TOF MS.

PubMed

Tsuchida, Sachio; Murata, Syota; Miyabe, Akiko; Satoh, Mamoru; Takiwaki, Masaki; Matsushita, Kazuyuki; Nomura, Fumio

2018-05-01

Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) is now a well-established method for identification of microorganisms from positive blood cultures. Pretreatments to effectively remove non-bacterial proteins are a prerequisite for successful identification, and a variety of protocols have been reported. Although commercially available kits, mainly the Sepsityper Kit, are increasingly used, the identification rates reported often are not satisfactory, particularly for Gram-positive isolates. We developed a new, in-house lysis-filtration protocol and prospectively evaluated its performance compared to the Sepsityper kit. The in-house protocol consists of three simple steps: lysis by ammonium chloride, aspiration with a syringe fitted with a 0.45-μm membrane, and centrifugation to collect microbes. The novel protocol requires only 20 min. Performance of the in-house protocol was evaluated using a total of 117 monomicrobial cases of positive blood culture. Medium from blood culture bottles was pretreated by the in-house protocol or the commercial kit, and isolated cells were subjected to direct identification by mass spectrometry fingerprinting in parallel with conventional subculturing for reference identification. The overall MALDI-TOF MS-based identification rates with score > 1.7 and > 2.0 obtained using the in-house protocol were 99.2% and 85.5%, respectively, whereas those obtained using the Sepsityper Kit were 85.4% and 61.5%, respectively. For Gram-positive cases, the in-house protocol yielded scores >1.7 and > 2.0 at 98.5% and 76.1%, respectively, whereas the commercial kit yielded these scores at 76.1% and 43.3%, respectively. Although these are preliminary results, these values suggest that this easy lysis-filtration protocol deserves assessment in a larger-scale test. Copyright © 2018 Elsevier B.V. All rights reserved.

A mechanical protocol to replicate impact in walking footwear.

PubMed

Price, Carina; Cooper, Glen; Graham-Smith, Philip; Jones, Richard

2014-01-01

Impact testing is undertaken to quantify the shock absorption characteristics of footwear. The current widely reported mechanical testing method mimics the heel impact in running and therefore applies excessive energy to walking footwear. The purpose of this study was to modify the ASTM protocol F1614 (Procedure A) to better represent walking gait. This was achieved by collecting kinematic and kinetic data while participants walked in four different styles of walking footwear (trainer, oxford shoe, flip-flop and triple-density sandal). The quantified heel-velocity and effective mass at ground-impact were then replicated in a mechanical protocol. The kinematic data identified different impact characteristics in the footwear styles. Significantly faster heel velocity towards the floor was recorded walking in the toe-post sandals (flip-flop and triple-density sandal) compared with other conditions (e.g. flip-flop: 0.36±0.05 ms(-1) versus trainer: 0.18±0.06 ms(-1)). The mechanical protocol was adapted by altering the mass and drop height specific to the data captured for each shoe (e.g. flip-flop: drop height 7 mm, mass 16.2 kg). As expected, the adapted mechanical protocol produced significantly lower peak force and accelerometer values than the ASTM protocol (p<.001). The mean difference between the human and adapted protocol was 12.7±17.5% (p<.001) for peak acceleration and 25.2±17.7% (p=.786) for peak force. This paper demonstrates that altered mechanical test protocols can more closely replicate loading on the lower limb in walking. This therefore suggests that testing of material properties of footbeds not only needs to be gait style specific (e.g. running versus walking), but also footwear style specific. Copyright © 2014 Elsevier B.V. All rights reserved.

Low-cost Cognitive Electronics Technology for Enhanced Communications and Situational Awareness for Networks of Small Unmanned Aerial Vehicles (UAV)

DTIC Science & Technology

2013-03-01

series of checkpoints in a complex route network,” while observing standard traffic etiquette and regulations [17]. The rules for the 2012 RoboCup...structure or protocols above the PHY. To support AVEP operation, we developed a packet structure based on the transmission control protocol (TCP...Control Protocol .” 1981. [37] F. Ge, Q. Chen, Y. Wang, C. W. Bostian, T. W. Rondeau, and B. Le, “Cognitive radio: from spectrum sharing to adaptive

Vaginal progesterone vs intramuscular 17α-hydroxyprogesterone caproate for prevention of recurrent spontaneous preterm birth in singleton gestations: systematic review and meta-analysis of randomized controlled trials.

PubMed

Saccone, G; Khalifeh, A; Elimian, A; Bahrami, E; Chaman-Ara, K; Bahrami, M A; Berghella, V

2017-03-01

Randomized controlled trials (RCTs) have recently compared intramuscular 17α-hydroxyprogesterone caproate (17-OHPC) with vaginal progesterone for reducing the risk of spontaneous preterm birth (SPTB) in singleton gestations with prior SPTB. The aim of this systematic review and meta-analysis was to evaluate the efficacy of vaginal progesterone compared with 17-OHPC in prevention of SPTB in singleton gestations with prior SPTB. Searches of electronic databases were performed to identify all RCTs of asymptomatic singleton gestations with prior SPTB that were randomized to prophylactic treatment with either vaginal progesterone (intervention group) or intramuscular 17-OHPC (comparison group). No restrictions for language or geographic location were applied. The primary outcome was SPTB < 34 weeks. Secondary outcomes were SPTB < 37 weeks, < 32 weeks, < 28 weeks and < 24 weeks, maternal adverse drug reaction and neonatal outcomes. The summary measures were reported as relative risk (RR) with 95% CI. Risk of bias for each included study was assessed. Three RCTs (680 women) were included. The mean gestational age at randomization was about 16 weeks. Women were given progesterone until 36 weeks or delivery. Regarding vaginal progesterone, one study used 90 mg gel daily, one used 100 mg suppository daily and one used 200 mg suppository daily. All included RCTs used 250 mg intramuscular 17-OHPC weekly in the comparison group. Women who received vaginal progesterone had significantly lower rates of SPTB < 34 weeks (17.5% vs 25.0%; RR, 0.71 (95% CI, 0.53-0.95); low quality of evidence) and < 32 weeks (8.9% vs 14.5%; RR, 0.62 (95% CI, 0.40-0.94); low quality of evidence) compared with women who received 17-OHPC. There were no significant differences in the rates of SPTB < 37 weeks, < 28 weeks and < 24 weeks. The rate of women who reported adverse drug reactions was significantly lower in the vaginal progesterone group compared with the 17-OHPC group (7.1% vs 13.2%; RR, 0.53 (95% CI, 0.31-0.91); very low quality of evidence). Regarding neonatal outcomes, vaginal progesterone was associated with a lower rate of neonatal intensive care unit admission compared with 17-OHPC (18.7% vs 23.5%; RR, 0.63 (95% CI, 0.47-0.83); low quality of evidence). For the comparison of 17-OHPC vs vaginal progesterone, the quality of evidence was downgraded for all outcomes by at least one degree due to imprecision (the optimal information size was not reached) and by at least one degree due to indirectness (different interventions). Daily vaginal progesterone (either suppository or gel) started at about 16 weeks' gestation is a reasonable, if not better, alternative to weekly 17-OHPC injection for prevention of SPTB in women with singleton gestations and prior SPTB. However, the quality level of the summary estimates was low or very low as assessed by GRADE, indicating that the true effect may be, or is likely to be, substantially different from the estimate of the effect. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. COMPARACIÓN ENTRE LA PROGESTERONA VAGINAL Y EL 17Α-HIDROXIPROGESTERONA CAPROATO INTRAMUSCULAR PARA LA PREVENCIÓN DEL PARTO PRETÉRMINO ESPONTÁNEO RECURRENTE EN EMBARAZOS CON FETO ÚNICO: REVISIÓN SISTEMÁTICA Y METAANÁLISIS DE ENSAYOS CONTROLADOS ALEATORIOS: RESUMEN OBJETIVO: Recientemente se han realizado varios ensayos controlados aleatorios (ECA) que comparaban el caproato de 17α-hidroxiprogesterona (17-OHPC, por sus siglas en inglés) por vía intramuscular con la progesterona por vía vaginal para la reducción del riesgo de parto pretérmino espontáneo (PPTE) en embarazos con feto único de gestantes con historial de PPTE. El objetivo de esta revisión sistemática y metaanálisis fue evaluar la eficacia de la progesterona vaginal en comparación con la 17-OHPC en la prevención de embarazos con feto único de gestantes con historial de PPTE. MÉTODOS: Se realizaron búsquedas en bases de datos electrónicas para identificar todos los ECA con embarazos de feto único asintomáticos con historial de PPTE antes de ser asignados al azar a un tratamiento profiláctico, ya fuera con progesterona vaginal (grupo de intervención) o con 17-OHPC intramuscular (grupo de control). No se aplicaron restricciones respecto al idioma o la ubicación geográfica. El resultado primario fue PPTE < 34 semanas. Los resultados secundarios fueron PPTE <37 semanas, < 32 semanas, < 28 semanas y < 24 semanas, la reacción materna adversa al fármaco y los resultados neonatales. Las medidas del resumen se reportaron como riesgo relativo (RR) con IC del 95%. Para cada estudio incluido se evaluó el riesgo de sesgo. Se incluyeron tres ECA (680 mujeres). La media de la edad gestacional en el momento de la aleatorización fue de 16 semanas. A las mujeres se les administró progesterona hasta la semana 36 o hasta el parto. Con respecto a la progesterona vaginal, un estudio utilizó gel de 90 mg diariamente, otro utilizó un supositorio diario de 100 mg y el otro utilizó un supositorio diario de 200 mg. Todos los ECA incluidos en el grupo de comparación utilizaron 250 mg semanales de 17-OHPC por vía intramuscular. Las mujeres que recibieron progesterona vaginal tuvieron tasas significativamente más bajas de PPTE < 34 semanas (17,5% vs. 25,0%; RR 0,71 (IC 95%, 0,53-0,95); calidad de la evidencia baja) y < 32 semanas (8,9% vs. 14,5%; RR 0,62 (IC 95%, 0,40-0,94); calidad de evidencia baja), en comparación con las mujeres que recibieron 17-OHPC. No hubo diferencias significativas en las tasas de PPTE < 37 semanas, < 28 semanas y < 24 semanas. La tasa de mujeres que reportaron reacciones adversas a los medicamentos fue significativamente menor en el grupo de progesterona vaginal en comparación con el grupo de 17-OHPC (7,1% vs. 13,2%; RR 0,53 (IC 95%, 0,31-0,91); calidad de la evidencia muy baja). En cuanto a los resultados neonatales, la progesterona vaginal se asoció a una menor tasa de admisiones en la unidad neonatal de cuidados intensivos en comparación con la 17-OHPC (18,7% vs. 23,5%; RR 0,63 (IC 95%, 0,47-0,83); calidad de evidencia baja). Para la comparación del 17-OHPC con la progesterona vaginal se rebajó la calidad de las pruebas para todos los resultados en al menos un grado debido a imprecisiones (no se alcanzó el tamaño óptimo de la información) y en al menos un grado debido al carácter indirecto de los estudios (diferentes intervenciones). La progesterona vaginal administrada diariamente (ya fuera como supositorio o como gel) desde la semana 16 de gestación es una alternativa razonable, si no mejor, a una inyección semanal de 17-OHPC para la prevención de PPTE en mujeres con embarazos de feto único e historial de PPTE. Sin embargo, el nivel de calidad de las estimaciones del resumen fue bajo o muy bajo según lo evaluado por GRADE, lo que indica que el verdadero efecto puede ser, o es probable que sea, sustancialmente diferente de la estimación del efecto. 17Α-:META: : (randomized controlled trials,RCTs)(spontaneous preterm birth,SPTB)17α-(intramuscular 17α-hydroxyprogesterone caproate,17-OHPC)SPTB。metaSPTB17-OHPCSPTB。 : ,SPTBRCTs,RCTs()17-OHPC()。。34SPTB。37、32、2824SPTB,。(relative risk,RR)95%CI。。 : 3RCTs(680)。16。,36。,90 mg,100 mg,200 mg。,RCTs250 mg 17-OHPC。17-OHPC,34 [17.5%25.0%;RR,0.71(95% CI,0.53 ~ 0.95);]32[8.9%14.5%;RR,0.62(95% CI,0.40 ~ 0.94);]SPTB。37、2824SPTB。17-OHPC,[7.1%13.2%;RR,0.53(95% CI,0.31 ~ 0.91);]。,17-OHPC,[18.7%23.5%;RR,0.63(95% CI,0.47 ~ 0.83);]。17-OHPC,(),()。 : SPTBSPTB,16()17-OHPC,。,GRADE,,。. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

EVALUATION OF THE EFFECTS OF A PROGRAMME PROMOTING ADEQUATE AND HEALTHY EATING ON ADOLESCENT HEALTH MARKERS: AN INTERVENTIONAL STUDY.

PubMed

Brito Beck da Silva, Karine; Leovigildo Fiaccone, Rosemeire; Couto, Ricardo David; Ribeiro-Silva, Rita de Cássia

2015-10-01

to evaluate the effects of a protocol promoting adequate and healthy eating on adolescent health parameters. this controlled intervention study was conducted for 9 months, with the participation of adolescents enrolled in two schools (intervention/control) located in a poor neighbourhood in the city of Salvador (Bahia), Brazil. For the intervention school, activities promoting adequate and healthy eating were designed based on the Food Guide for the Brazilian Population (Guia Alimentar para a População Brasileira). Students underwent biochemical, sexual maturation and anthropometric tests at baseline and at the end of the 9-month period. In addition, students answered a questionnaire on food consumption, physical activity and sedentary behaviour. Information on the socioeconomic status of their family was also obtained. Generalized Estimating Equation (GEE) analysis was chosen to evaluate the associations of interest. students under intervention presented decreases of 7.64 mg/dL in mean total cholesterol (TC) (p = 0.009) and 7.77 mg/dL in mean low-density lipoprotein cholesterol (LDLc) (p = 0.003) and increases of 18% in legume consumption (odds ratio [OR] = 1.18; 95% confidence interval [CI] 1.03-1.37) and 17% in vegetable consumption (OR = 1.17; 95%CI 1.01-1.35) compared with students who did not undergo intervention. No differences were observed in the anthropometric parameters analysed. the results showed a positive effect of activities promoting adequate and healthy eating on reducing TC and LDLc and on increasing the consumption of vegetables and legumes, evidencing that the intervention model was able to prevent and/or treat cardiovascular risk factors in adolescents. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Influence of Cranial Radiotherapy on Outcome in Children With Acute Lymphoblastic Leukemia Treated With Contemporary Therapy

PubMed Central

Andreano, Anita; Pui, Ching-Hon; Hunger, Stephen P.; Schrappe, Martin; Moericke, Anja; Biondi, Andrea; Escherich, Gabriele; Silverman, Lewis B.; Goulden, Nicholas; Taskinen, Mervi; Pieters, Rob; Horibe, Keizo; Devidas, Meenakshi; Locatelli, Franco; Valsecchi, Maria Grazia

2016-01-01

Purpose We sought to determine whether cranial radiotherapy (CRT) is necessary to prevent relapse in any subgroup of children with acute lymphoblastic leukemia (ALL). Patients and Methods We obtained aggregate data on relapse and survival outcomes for 16,623 patients age 1 to 18 years old with newly diagnosed ALL treated between 1996 and 2007 by 10 cooperative study groups from around the world. The proportion of patients eligible for prophylactic CRT varied from 0% to 33% by trial and was not related to the proportion eligible for allogeneic stem-cell transplantation in first complete remission. Using a random effects model, with CRT as a dichotomous covariate, we performed a single-arm meta-analysis to compare event-free survival and cumulative incidence of isolated or any CNS relapse and isolated bone marrow relapse in high-risk subgroups of patients who either did or did not receive CRT. Results Although there was significant heterogeneity in all outcome end points according to trial, CRT was associated with a reduced risk of relapse only in the small subgroup of patients with overt CNS disease at diagnosis, who had a significantly lower risk of isolated CNS relapse (4% with CRT v 17% without CRT; P = .02) and a trend toward lower risk of any CNS relapse (7% with CRT v 17% without CRT; P = .09). However, this group had a relatively high rate of events regardless of whether or not they received CRT (32% [95% CI, 26% to 39%] v 34% [95% CI, 19% to 54%]; P = .8). Conclusion CRT does not have an impact on the risk of relapse in children with ALL treated on contemporary protocols. PMID:26755523

Long-term outcomes of kidney transplantation across a positive complement-dependent cytotoxicity crossmatch.

PubMed

Riella, Leonardo V; Safa, Kassem; Yagan, Jude; Lee, Belinda; Azzi, Jamil; Najafian, Nader; Abdi, Reza; Milford, Edgar; Mah, Helen; Gabardi, Steven; Malek, Sayeed; Tullius, Stefan G; Magee, Colm; Chandraker, Anil

2014-06-27

More than 30% of potential kidney transplant recipients have pre-existing anti-human leukocyte antigen antibodies. This subgroup has significantly lower transplant rates and increased mortality. Desensitization has become an important tool to overcome this immunological barrier. However, limited data is available regarding long-term outcomes, in particular for the highest risk group with a positive complement-dependent cytotoxicity crossmatch (CDC XM) before desensitization. Between 2002 and 2010, 39 patients underwent living-kidney transplantation across a positive CDC XM against their donors at our center. The desensitization protocol involved pretransplant immunosuppression, plasmapheresis, and low-dose intravenous immunoglobulin±rituximab. Measured outcomes included patient survival, graft survival, renal function, rates of rejection, infection, and malignancy. The mean and median follow-up was 5.2 years. Patient survival was 95% at 1 year, 95% at 3 years, and 86% at 5 years. Death-censored graft survival was 94% at 1 year, 88% at 3 years, and 84% at 5 years. Uncensored graft survival was 87% at 1 year, 79% at 3 years, and 72% at 5 years. Twenty-four subjects (61%) developed acute antibody-mediated rejection of the allograft and one patient lost her graft because of hyperacute rejection. Infectious complications included pneumonia (17%), BK nephropathy (10%), and CMV disease (5%). Skin cancer was the most prevalent malignancy in 10% of patients. There were no cases of lymphoproliferative disorder. Mean serum creatinine was 1.7±1 mg/dL in functioning grafts at 5 years after transplantation. Despite high rates of early rejection, desensitization in living-kidney transplantation results in acceptable 5-year patient and graft survival rates.

Feasibility and safety of early combined cognitive and physical therapy for critically ill medical and surgical patients: the Activity and Cognitive Therapy in ICU (ACT-ICU) trial.

PubMed

Brummel, N E; Girard, T D; Ely, E W; Pandharipande, P P; Morandi, A; Hughes, C G; Graves, A J; Shintani, A; Murphy, E; Work, B; Pun, B T; Boehm, L; Gill, T M; Dittus, R S; Jackson, J C

2014-03-01

Cognitive impairment after critical illness is common and debilitating. We developed a cognitive therapy program for critically ill patients and assessed the feasibility and safety of administering combined cognitive and physical therapy early during a critical illness. We randomized 87 medical and surgical ICU patients with respiratory failure and/or shock in a 1:1:2 manner to three groups: usual care, early once-daily physical therapy, or early once-daily physical therapy plus a novel, progressive, twice-daily cognitive therapy protocol. Cognitive therapy included orientation, memory, attention, and problem-solving exercises, and other activities. We assessed feasibility outcomes of the early cognitive plus physical therapy intervention. At 3 months, we also assessed cognitive, functional, and health-related quality of life outcomes. Data are presented as median (interquartile range) or frequency (%). Early cognitive therapy was a delivered to 41/43 (95%) of cognitive plus physical therapy patients on 100% (92-100%) of study days beginning 1.0 (1.0-1.0) day following enrollment. Physical therapy was received by 17/22 (77%) of usual care patients, by 21/22 (95%) of physical therapy only patients, and 42/43 (98%) of cognitive plus physical therapy patients on 17% (10-26%), 67% (46-87%), and 75% (59-88%) of study days, respectively. Cognitive, functional, and health-related quality of life outcomes did not differ between groups at 3-month follow-up. This pilot study demonstrates that early rehabilitation can be extended beyond physical therapy to include cognitive therapy. Future work to determine optimal patient selection, intensity of treatment, and benefits of cognitive therapy in the critically ill is needed.

Feasibility and safety of early combined cognitive and physical therapy for critically ill medical and surgical patients: the Activity and Cognitive Therapy in ICU (ACT-ICU) trial

PubMed Central

Brummel, N.E.; Girard, T.D.; Ely, E.W.; Pandharipande, P.P.; Morandi, A.; Hughes, C.G.; Graves, A.J.; Shintani, A.K.; Murphy, E.; Work, B.; Pun, B.T.; Boehm, L.; Gill, T.M.; Dittus, R.S.; Jackson, J.C.

2013-01-01

PURPOSE Cognitive impairment after critical illness is common and debilitating. We developed a cognitive therapy program for critically ill patients and assessed the feasibility and safety of administering combined cognitive and physical therapy early during a critical illness. METHODS We randomized 87 medical and surgical ICU patients with respiratory failure and/or shock in a 1:1:2 manner to three groups: usual care, early once-daily physical therapy, or early once-daily physical therapy plus a novel, progressive, twice-daily cognitive therapy protocol. Cognitive therapy included orientation, memory, attention, and problem solving exercises, and other activities. We assessed feasibility outcomes of the early cognitive plus physical therapy intervention. At 3-months, we also assessed cognitive, functional and health-related quality of life outcomes. Data are presented as median [interquartile range] or frequency (%). RESULTS Early cognitive therapy was a delivered to 41/43 (95%) of cognitive plus physical therapy patients on 100% [92–100%] of study days beginning 1.0 [1.0–1.0] day following enrollment. Physical therapy was received by 17/22 (77%) of usual care patients, by 21/22 (95%) of physical therapy only patients and 42/43 (98%) of cognitive plus physical therapy patients on 17% [10–26%], 67% [46–87%] and 75% [59–88%] of study days, respectively. Cognitive, functional and health-related quality of life outcomes did not differ between groups at 3-month follow-up. CONCLUSIONS This pilot study demonstrates that early rehabilitation can be extended beyond physical therapy to include cognitive therapy. Future work to determine optimal patient selection, intensity of treatment and benefits of cognitive therapy in the critically ill is needed. PMID:24257969

Effect of microdose transdermal 17beta-estradiol compared with raloxifene in the prevention of bone loss in healthy postmenopausal women: a 2-year, randomized, double-blind trial.

PubMed

Schaefers, Matthias; Muysers, Christoph; Alexandersen, Peter; Christiansen, Claus

2009-01-01

Declining estrogen levels after menopause result in bone loss and increased fracture risk. This study investigated whether transdermal microdose 17beta-estradiol (E2) has efficacy and safety comparable to those of raloxifene, a selective estrogen-receptor modulator approved for the prevention and treatment of postmenopausal osteoporosis. This study involved a multicenter, randomized, double-blind, active-controlled, noninferiority trial in 500 osteopenic postmenopausal women comparing transdermal microdose E2 (0.014 mg/d) versus oral raloxifene (60 mg/d), administered for 2 years. Percent change from baseline in bone mineral density at the lumbar spine was measured after 2 years of treatment. Secondary endpoints included proportion of women with no loss of bone mineral density in lumbar spine, change in bone mineral density at hip, biochemical markers of bone turnover, and safety parameters. In the per protocol set, lumbar spine bone mineral density increased by 2.4% (95% CI, 1.9-2.9) with microdose E2 versus 3.0% (95% CI, 2.5-3.5) with raloxifene after 2 years; 77.3% of E2 recipients and 80.5% of those taking raloxifene had no bone loss in the lumbar spine. Both treatments were well tolerated. Most women (99% in the E2 group and 100% in the raloxifene group) showed no histological evidence of endometrial stimulation after 2 years. Mean dense area in breast mammograms was 19.8% in the E2 group versus 19.0% in the raloxifene group after 2 years. Transdermal microdose E2 was similarly effective as raloxifene in preventing bone loss at the lumbar spine. Both treatments were well tolerated, with no clinically significant effect on endometrium or breast density.

Intravenous oxytocin alone for cervical ripening and induction of labour

PubMed Central

Alfirevic, Zarko; Kelly, Anthony J; Dowswell, Therese

2014-01-01

Background Oxytocin is the commonest induction agent used worldwide. It has been used alone, in combination with amniotomy or following cervical ripening with other pharmacological or non-pharmacological methods. Objectives To determine the effects of oxytocin alone for third trimester cervical ripening and induction of labour in comparison with other methods of induction of labour or placebo/no treatment. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (January 2009) and bibliographies of relevant papers. Selection criteria Randomised and quasi-randomised trials comparing intravenous oxytocin with placebo or no treatment, or with prostaglandins (vaginal or intracervical) for third trimester cervical ripening or labour induction. Data collection and analysis Two review authors independently assessed eligibility and carried out data extraction. Main results Sixty-one trials (12,819 women) are included. When oxytocin inductions were compared with expectant management, fewer women failed to deliver vaginally within 24 hours (8.4% versus 53.8%, risk ratio (RR) 0.16, 95% confidence interval (CI) 0.10 to 0.25). There was a significant increase in the number of women requiring epidural analgesia (RR 1.10, 95% CI 1.04 to 1.17). Fewer women were dissatisfied with oxytocin induction in the one trial reporting this outcome (5.9% versus 13.7%, RR 0.43, 95% CI 0.33 to 0.56). Compared with vaginal prostaglandins, oxytocin increased unsuccessful vaginal delivery within 24 hours in the two trials reporting this outcome (70% versus 21%, RR 3.33, 95% CI 1.61 to 6.89). There was a small increase in epidurals when oxytocin alone was used (RR 1.09, 95% CI 1.01 to 1.17). Most of the studies included women with ruptured membranes, and there was some evidence that vaginal prostaglandin increased infection in mothers (chorioamnionitis RR 0.66, 95% CI 0.47 to 0.92) and babies (use of antibiotics RR 0.68, 95% CI 0.53 to 0.87). These data should be interpreted cautiously as infection was not pre-specified in the original review protocol. When oxytocin was compared with intracervical prostaglandins, there was an increase in unsuccessful vaginal delivery within 24 hours (50.4% versus 34.6%, RR 1.47, 95% CI 1.10 to 1.96) and an increase in caesarean sections (19.1% versus 13.7%, RR 1.37, 95% CI 1.08 to 1.74) in the oxytocin group. Authors’ conclusions Comparison of oxytocin with either intravaginal or intracervical PGE2 reveals that the prostaglandin agents probably increase the chances of achieving vaginal birth within 24 hours. Oxytocin induction may increase the rate of interventions in labour. A suggestion that for women with prelabour rupture of membranes induction with vaginal prostaglandin may increase risk of infection for mother and baby warrants further study. PMID:19821304

Validation of the AVITA BPM17 wrist blood pressure monitor for home blood pressure monitoring according to the European Society of Hypertension International Protocol revision 2010.

PubMed

Kang, Yuan-Yuan; Chen, Qi; Liu, Chang-Yuan; Li, Yan; Wang, Ji-Guang

2017-08-01

The aim of the present study was to evaluate the accuracy of the automated oscillometric wrist blood pressure monitor AVITA BPM17 for home blood pressure monitoring according to the International Protocol of the European Society of Hypertension revision 2010. Systolic and diastolic blood pressures were sequentially measured in 33 adult Chinese (19 men, 45.7 years of mean age) using a mercury sphygmomanometer (two observers) and the AVITA BPM17 device (one supervisor). Ninety-nine pairs of comparisons were obtained from 33 participants for judgments in two parts with three grading phases. The AVITA BPM17 device achieved the targets in part 1 of the validation study. The number of absolute differences between device and observers within 5, 10, and 15 mmHg was 94/99, 98/99, and 98/99, respectively, for systolic blood pressure and 92/99, 99/99, and 99/99, respectively, for diastolic blood pressure. The device also fulfilled the criteria in part 2 of the validation study. Overall, 32 participants for both systolic and diastolic blood pressure, respectively, had at least two of the three device-observerss differences within 5 mmHg (required ≥24). None had all the three device-observers comparisons greater than 5 mmHg for systolic and diastolic blood pressure. The AVITA wrist blood pressure monitor BPM17 has passed the requirements of the International Protocol revision 2010, and hence can be recommended for home use in adults.

Correlation of High-Risk Soft Tissue Sarcoma Biomarker Expression Patterns with Outcome following Neoadjuvant Chemoradiation

PubMed Central

Magliocco, Anthony; Zhang, Qiang; Wang, Dian; Klimowicz, Alex; Harris, Jonathan; Simko, Jeff; DeLaney, Thomas; Kraybill, William; Kirsch, David G.

2018-01-01

Background Sarcoma mortality remains high despite adjuvant chemotherapy. Biomarker predictors of treatment response and outcome could improve treatment selection. Methods Tissue microarrays (TMAs) were created using pre- and posttreatment tumor from two prospective trials (MGH pilot and RTOG 9514) of neoadjuvant/adjuvant MAID chemotherapy and preoperative radiation. Biomarkers were measured using automated computerized imaging (AQUA or ACIS). Expression was correlated with disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS). Results Specimens from 60 patients included 23 pretreatment (PRE), 40 posttreatment (POST), and 12 matched pairs (MPs). In the MP set, CAIX, GLUT1, and PARP1 expression significantly decreased following neoadjuvant therapy, but p53 nuclear/cytoplasmic (N/C) ratio increased. In the PRE set, no biomarker expression was associated with DFS, DDFS, or OS. In the POST set, increased p53 N/C ratio was associated with a significantly decreased DFS and DDFS (HR 4.13, p=0.017; HR 4.16, p=0.016), while increased ERCC1 and XPF expression were associated with an improved DFS and DDFS. No POST biomarkers were associated with OS. Conclusions PRE biomarker expression did not predict survival outcomes. Expression pattern changes after neoadjuvant chemoradiation supports the concepts of tumor reoxygenation, altered HIF-1α signaling, and a p53 nuclear accumulation DNA damage response. Clinical Trial Registration NRG Oncology RTOG 9514 is registered with ClinicalTrials.gov. The ClinicalTrials.gov Identifier is NCT00002791. PMID:29681762

A pilot study using dynamic contrast enhanced-MRI as a response biomarker of the radioprotective effect of memantine in patients receiving whole brain radiotherapy

PubMed Central

Wong, Philip; Leppert, Ilana R.; Roberge, David; Boudam, Karim; Brown, Paul D.; Muanza, Thierry; Pike, G. Bruce; Chankowsky, Jeffrey; Mihalcioiu, Catalin

2016-01-01

Purpose This pilot prospective study sought to determine whether dynamic contrast enhanced MRI (DCE-MRI) could be used as a clinical imaging biomarker of tissue toxicity from whole brain radiotherapy (WBRT). Method 14 patients who received WBRT were imaged using dynamic contrast enhanced DCE-MRI prior to and at 8-weeks, 16-weeks and 24-weeks after the initiation of WBRT. Twelve of the patients were also enrolled in the RTOG 0614 trial, which randomized patients to the use of placebo or memantine. After the unblinding of the treatments received by RTOG 0614 patients, DCE-MRI measures of tumor tissue and normal appearing white matter (NAWM) vascular permeability (Initial Area Under the Curve (AUC) Blood Adjusted) was analyzed. Cognitive, quality-of-life (QOL) assessment and blood samples were collected according to the patient's ability to tolerate the exams. Circulating endothelial cells (CEC) were measured using flow cytometry. Results Following WBRT, there was an increasing trend in the vascular permeability of tumors (p=0.09) and NAWM (p=0.06) with time. Memantine significantly (p=0.01) reduced NAWM AUC changes following radiotherapy. Patients on memantine retained (COWA p= 0.03) better cognitive functions than those on placebo. No association was observed between the level of CEC and DCE-MRI changes, time from radiotherapy or memantine use. Conclusions DCE-MRI can detect vascular damage secondary to WBRT. Our data suggests that memantine reduces WBRT-induced brain vasculature damages. PMID:27248467

Racial Differences in CYP3A4 Genotype and Survival Among Men Treated on Radiation Therapy Oncology Group (RTOG) 9202: A Phase III Randomized Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roach, Mack; Silvio, Michelle de; Rebbick, Timothy

2007-09-01

Purpose: Inherited genotypes may explain the inferior outcomes of African American (AA) men with prostate cancer. To understand how variation in CYP3A4 correlated with outcomes, a retrospective examination of the CYP3A4*1B genotype was performed on men treated with Radiation Therapy Oncology Group (RTOG) 92-02. Methods and Materials: From 1,514 cases, we evaluated 56 (28.4%) of 197 AA and 54 (4.3%) of 1,274 European American (EA) patients. All patients received goserelin and flutamide for 2 months before and during RT (STAD-RT) {+-} 24 months of goserelin (long-term androgen deprivation plus radiation [LTAD-RT]). Events studied included overall survival and biochemical progression usingmore » American Society for Therapeutic Radiology and Oncology consensus guidelines. Results: There were no differences in outcome in patients in with or without CYP3A4 data. There was an association between race and CYP3A4 polymorphisms with 75% of EAs having the Wild Type compared to only 25% of AA men (p <0.0001). There was no association between CYP3A4 classification or race and survival or progression. Conclusions: The samples analyzed support previously reported observations about the distribution of CYP3A4*1B genotype by race, but race was not associated with poorer outcome. However, patient numbers were limited, and selection bias cannot be completely ruled out.« less

A pilot study using dynamic contrast enhanced-MRI as a response biomarker of the radioprotective effect of memantine in patients receiving whole brain radiotherapy.

PubMed

Wong, Philip; Leppert, Ilana R; Roberge, David; Boudam, Karim; Brown, Paul D; Muanza, Thierry; Pike, G Bruce; Chankowsky, Jeffrey; Mihalcioiu, Catalin

2016-08-09

This pilot prospective study sought to determine whether dynamic contrast enhanced MRI (DCE-MRI) could be used as a clinical imaging biomarker of tissue toxicity from whole brain radiotherapy (WBRT). 14 patients who received WBRT were imaged using dynamic contrast enhanced DCE-MRI prior to and at 8-weeks, 16-weeks and 24-weeks after the initiation of WBRT. Twelve of the patients were also enrolled in the RTOG 0614 trial, which randomized patients to the use of placebo or memantine. After the unblinding of the treatments received by RTOG 0614 patients, DCE-MRI measures of tumor tissue and normal appearing white matter (NAWM) vascular permeability (Initial Area Under the Curve (AUC) Blood Adjusted) was analyzed. Cognitive, quality-of-life (QOL) assessment and blood samples were collected according to the patient's ability to tolerate the exams. Circulating endothelial cells (CEC) were measured using flow cytometry. Following WBRT, there was an increasing trend in the vascular permeability of tumors (p=0.09) and NAWM (p=0.06) with time. Memantine significantly (p=0.01) reduced NAWM AUC changes following radiotherapy. Patients on memantine retained (COWA p= 0.03) better cognitive functions than those on placebo. No association was observed between the level of CEC and DCE-MRI changes, time from radiotherapy or memantine use. DCE-MRI can detect vascular damage secondary to WBRT. Our data suggests that memantine reduces WBRT-induced brain vasculature damages.

Clinical study of concurrent chemoradiotherapy or radiotherapy alone for esophageal cancer patients with positive lymph node metastasis.

PubMed

Han, Jihua; Zhu, Weiguo; Yu, Changhua; Zhou, Xilei; Li, Tao; Zhang, Xiaoye

2012-01-01

Esophageal cancer patients with pathologic lymph node involvement generally have a poor prognosis. Many randomized controlled trials have not achieved consistent results similar to those of the RTOG8501 trial, and the long-term survival rate has not increased. The present study aimed to compare the efficacy and toxic side effects of concurrent chemoradiotherapy and radiotherapy alone to treat N1 esophageal carcinoma. A total of 130 N1 esophageal carcinoma patients were enrolled and randomly divided into two groups: concurrent chemoradiotherapy group (n = 65) and radiotherapy group (n = 65). Both groups received three-dimensional conformal radiotherapy with a total dose of 64-66 Gy. Meanwhile, to the concurrent chemoradiotherapy group, an additional chemotherapy protocol (nedaplatin, 20 mg/m²/d, 5-FU, 500 mg/m²/d for four days) was given from day 1, and such treatment was repeated until day 29. From day 21 after radiotherapy, two cycles of a consolidated chemotherapy protocol were given at an interval of 28 days. The survival rates at one, two, and three years were 72.3%, 55.3%, and 40% in the concurrent chemoradiotherapy group, respectively, and 75.3%, 38.5%, and 18.5% in the radiotheray group (P = 0.007), respectively. The survival rates of the patients in the concurrent chemoradiotherapy group who completed one to two cycles and three to four cycles at one, two, and three years were 70%, 53.3%, and 30%, and 74.2%, 57.1%, 48.6% (P = 0.128), respectively. Three-year distant metastasis rates were 10.7% in the concurrent chemoradiotherapy group and 16.9% in the radiotherapy group. Acute toxicity in the concurrent chemoradiotherapy group was higher than in the radiotherapy group. Late toxic side effects were similar in the two groups. Compared with radiotherapy alone, concurrent chemoradiotherapy in the treatment of esophageal carcinoma with local lymph node enlargement can improve the three-year survival rate. Moreover, completion of three to four cycles of chemotherapy may have better efficacy than one to two cycles.

40 CFR Appendix E to Part 75 - Optional NOX Emissions Estimation Protocol for Gas-Fired Peaking Units and Oil-Fired Peaking Units

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 17 2013-07-01 2013-07-01 false Optional NOX Emissions Estimation Protocol for Gas-Fired Peaking Units and Oil-Fired Peaking Units E Appendix E to Part 75 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTINUOUS EMISSION...

40 CFR Appendix E to Part 75 - Optional NOX Emissions Estimation Protocol for Gas-Fired Peaking Units and Oil-Fired Peaking Units

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 17 2014-07-01 2014-07-01 false Optional NOX Emissions Estimation Protocol for Gas-Fired Peaking Units and Oil-Fired Peaking Units E Appendix E to Part 75 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTINUOUS EMISSION...

Delivery of Vaccines By Biodegradable Polymeric Microcapsules with Bioadherence Properties. Phase 1.

DTIC Science & Technology

1995-10-01

DAMD17-95-C-5061 TITLE: Delivery of Vaccines by Biodegradable Polymeric Microcapsules with Bioadherence Properties PRINCIPAL INVESTIGATOR: Robert L...SUBTITLE 5. FUNDING NUMBERS Delivery of Vaccines By Biodegradable Polymeric Microcapsules with Bioadherence Properties DAMD17-95-C-5061 6. AUTHOR(S...SUBJECT TERMS 15. NUMBER OF PAGES Polymer microspheres 27 Microencapsulated vaccines 16. PRICE CODE 17. SECURITY CLASSIFICATION 18. SECURITY

Impact of a standardized nurse observation protocol including MEWS after Intensive Care Unit discharge.

PubMed

De Meester, K; Das, T; Hellemans, K; Verbrugghe, W; Jorens, P G; Verpooten, G A; Van Bogaert, P

2013-02-01

Analysis of in-hospital mortality after serious adverse events (SAE's) in our hospital showed the need for more frequent observation in medical and surgical wards. We hypothesized that the incidence of SAE's could be decreased by introducing a standard nurse observation protocol. To investigate the effect of a standard nurse observation protocol implementing the Modified Early Warning Score (MEWS) and a color graphic observation chart. Pre- and post-intervention study by analysis of patients records for a 5-day period after Intensive Care Unit (ICU) discharge to 14 medical and surgical wards before (n=530) and after (n=509) the intervention. For the total study population the mean Patient Observation Frequency Per Nursing Shift (POFPNS) during the 5-day period after ICU discharge increased from .9993 (95% C.I. .9637-1.0350) in the pre-intervention period to 1.0732 (95% C.I. 1.0362-1.1101) (p=.005) in the post-intervention period. There was an increased risk of a SAE in patients with MEWS 4 or higher in the present nursing shift (HR 8.25; 95% C.I. 2.88-23.62) and the previous nursing shift (HR 12.83;95% C.I. 4.45-36.99). There was an absolute risk reduction for SAE's within 120h after ICU discharge of 2.2% (95% C.I. -0.4-4.67%) from 5.7% to 3.5%. The intervention had a positive impact on the observation frequency. MEWS had a predictive value for SAE's in patients after ICU discharge. The drop in SAE's was substantial but did not reach statistical significance. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Development of a method to assess compliance with ergonomic posture in dental students

PubMed Central

Garcia, Patrícia Petromilli Nordi Sasso; Wajngarten, Danielle; Campos, Juliana Alvares Duarte Bonini

2018-01-01

CONTEXT: The ergonomic posture protocol is extremely important for the maintenance of occupational health in dentistry. The lack of compliance with this protocol results in a high risk of developing musculoskeletal disorders. AIMS: This study developed a direct observation method for the evaluation of dental student compliance with ergonomic posture protocol. SUBJECTS AND METHODS: The method is named compliance assessment of dental ergonomic posture requirements (CADEP). During the development of the method, 14 items were elaborated considering the theory of dental ergonomics. Each item should be classified as appropriate, partially appropriate, or inappropriate. After evaluation, all item values should be added, and the final score expressed as the percent of compliance with correct postures, with a score range of 0%–100%. STATISTICAL ANALYSIS USED: The reliability of CADEP was assessed through intra- and interobserver reproducibility. For the CADEP application, 73 senior year students from the undergraduate course in dentistry were evaluated. The intra- and interexaminer concordance was estimated using the intraclass correlation coefficient (ρ). A descriptive statistical analysis was performed. RESULTS: The reproducibility of evaluator 1 (ρ =0.90; confidence interval [CI] 95%: 0.83–0.94), evaluator 2 (ρ = 0.83; CI 95%: 0.70–0.90), the interexaminer in the first evaluation (ρ = 0.81; CI 95%:0.67–0.89), and in the second one (ρ = 0.76; CI 95%: 0.59–0.87) was classified as good. In the analysis of the compliance, it was verified that moderate compliance was the most prevalent among the evaluated students (65.6%, CI 95%: 60.3%–70.7%). CONCLUSIONS: CADEP was valid and reliable for the assessment of dentistry students’ compliance regarding ergonomic posture requirements. PMID:29693025

Heparin-bonded covered stents versus bare-metal stents for complex femoropopliteal artery lesions: the randomized VIASTAR trial (Viabahn endoprosthesis with PROPATEN bioactive surface [VIA] versus bare nitinol stent in the treatment of long lesions in superficial femoral artery occlusive disease).

PubMed

Lammer, Johannes; Zeller, Thomas; Hausegger, Klaus A; Schaefer, Philipp J; Gschwendtner, Manfred; Mueller-Huelsbeck, Stefan; Rand, Thomas; Funovics, Martin; Wolf, Florian; Rastan, Aljoscha; Gschwandtner, Michael; Puchner, Stefan; Ristl, Robin; Schoder, Maria

2013-10-08

The hypothesis that endovascular treatment with covered stents has equal risks but higher efficacy than bare-metal stents (BMS) in long femoropopliteal artery disease was tested. Although endovascular treatment of short superficial femoral artery lesions revealed excellent results, efficacy in long lesions remains unsatisfactory. In a prospective, randomized, single-blind, multicenter study, 141 patients with symptomatic peripheral arterial disease were assigned to treatment with heparin-bonded, covered stents (Viabahn 72 patients) or BMS (69 patients). Clinical outcomes and patency rates were assessed at 1, 6, and 12 months. Mean ± SD lesion length was 19.0 ± 6.3 cm in the Viabahn group and 17.3 ± 6.6 cm in the BMS group. Major complications within 30 days were observed in 1.4%. The 12-month primary patency rates in the Viabahn and BMS groups were: intention-to-treat (ITT) 70.9% (95% confidence interval [CI]: 0.58 to 0.80) and 55.1% (95% CI: 0.41 to 0.67) (log-rank test p = 0.11); treatment per-protocol (TPP) 78.1% (95% CI: 0.65 to 0.86) and 53.5% (95% CI: 0.39 to 0.65) (hazard ratio: 2.23 [95% CI: 1.14 to 4.34) (log-rank test p = 0.009). In lesions ≥20 cm, (TransAtlantic Inter-Society Consensus class D), the 12-month patency rate was significantly longer in VIA patients in the ITT analysis (VIA 71.3% vs. BMS 36.8%; p = 0.01) and the TPP analysis (VIA 73.3% vs. BMS 33.3%; p = 0.004). Freedom from target lesion revascularization was 84.6% for Viabahn (95% CI: 0.72 to 0.91) versus 77.0% for BMS (95% CI: 0.63 to 0.85; p = 0.37). The ankle-brachial index in the Viabahn group significantly increased to 0.94 ± 0.23 compared with the BMS group (0.85 ± 0.23; p < 0.05) at 12 months. This randomized trial in symptomatic patients with peripheral arterial disease who underwent endovascular treatment for long femoropopliteal lesions demonstrated significant clinical and patency benefits for heparin-bonded covered stents compared with BMS in lesions ≥20 cm and for all lesions in the TPP analysis. In the ITT analysis for all lesions, which was flawed by major protocol deviations in 8.5% of the patients, the difference was not significant. (GORE VIABAHN® endoprosthesis with bioactive propaten surface versus bare nitinol stent in the treatment of TASC B, C and D lesions in superficial femoral artery occlusive disease; ISRCTN48164244). Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.