Pediatric donor heart acceptance practices in the United States: What is really being considered?

BACKGROUND: Recent studies demonstrate high offer decline and organ non-utilization rates are associated with increased pediatric heart transplant waitlist mortality. We sought to determine which donor, candidate, and offer specific variables most importantly influenced these decisions using only data available at the time of each offer. METHODS: Retrospective review of pediatric (<18 years) heart donor offers made to pediatric candidates in the United States between 2010 and 2020. In addition to standard donor, candidate, and offer data available in UNOS, we extracted objective and qualitative valvar and myocardial function data from all available donor echocardiogram reports. RESULTS: During the study period, 5625 pediatric donor hearts produced 30 156 offers to 4905 unique candidates, of which 88.7% of all offers were declined and 39.2% of organs were not utilized by pediatric waitlisted candidates. Of the 60.8% utilized hearts, 89.7% had a 'cumulatively' normal echocardiogram at the time of offer acceptance; 62.9% of hearts not utilized for a pediatric candidate also had a cumulatively normal final echocardiogram. Random forest and logistic regression modeling demonstrated good predictive performance (AUROC ≥0.83) of likelihood to accept when utilizing donor, candidate, and offer specific variables. SHAP variable importance scores demonstrated number of prior offer declines and candidate institution's prior year acceptance rates as the two most important variables influencing offer decisions. CONCLUSIONS: Behavioral economics appear to play a significant role in pediatric heart transplant candidate institutions' acceptance practices, even when considering the arguably healthier pediatric donor population. Removal of prior institution's decisions from DonorNet may help increase donor utilization.

The impact and indications for Oncotype DX on adjuvant treatment recommendations when third-party funding is unavailable.

OBJECTIVES: Industry-supported decision impact studies demonstrate that Oncotype Dx (ODX) changes treatment recommendations (TR) in 24-40% of hormone receptor+/HER2- patients. ODX is not reimbursed by third-party payers in Australia, potentially resulting in more selective use. We sought to evaluate the impact of self-funded ODX on TRs. METHODS: Data collected included demographics, tumor characteristics, indication for ODX and pre- and post-recurrence score (RS) TR. Primary endpoint was frequency of TR change and associations with TR change were sought. RESULTS: Eighteen physicians contributed 382 patients (median age 54). A total of 232 (61%) of tumors were T1 and were grade 1, 2 and 3 in 49 (13%), 252 (66%) and 79 (21%). A total of 257 (67%) were node negative. Assay indications were: confirm need for chemotherapy (CT) (36%), confirm omission of CT (40%) and genuine equipoise (24%). RS was low (≤17) in 55%, intermediate (18-31) in 36% and high (≥32) in 9%. Thirty-eight percent of patients had TR change post-ODX. Sixty-five percent of patients recommended CT pre-ODX changed to hormone therapy alone (HT)-more likely if lower grade and if ER and/or PR > 10%. Fourteen percent of patients with pre-ODX TR for HT added CT-more likely if ER and/or PR ≤10% and if Ki67 > 15% Overall, TR for CT decreased from 47% to 24%. CONCLUSION: Patient-funded ODX changed TRs in 38% of patients, de-escalating 65% from CT to HT and adding CT to 14% of those recommended HT. These changes were greater than an industry-funded study suggesting that physicians can identify situations where the assay may influence decisions.

Prevalence of abdominal aortic aneurysm in patients referred for transthoracic echocardiography.

BACKGROUND: Previous studies have documented the prevalence of abdominal aortic aneurysm (AAA) during transthoracic echocardiography, but the effect of such screening on subsequent vascular interventions remains unclear. AIM: This study aimed to determine the utility of opportunistic selective screening for AAA in a contemporary large series of patients having transthoracic echocardiography. METHODS: Subjects aged 50 years or older having transthoracic echocardiography had scanning of the infrarenal aorta in a consecutive series of 10 403 men and women. RESULTS: The study subjects had a mean age of 70.2 ± 10.7 years, and 54.1% were men. There was a 3.5% (95% confidence interval (CI) 3.2-3.9%) prevalence of AAA with a median diameter of 39 mm (interquartile range 32 mm-48 mm). In males ≥ 65 years the prevalence of newly diagnosed AAA was 6.2% (95% CI 5.5-7.0%). Of those with newly diagnosed AAA, 39.7% underwent AAA repair. Age and male gender were associated with AAA prevalence. After adjustment for age and gender, echocardiographic variables associated with AAA were left ventricular end diastolic dimension (odds ratio (OR) 1.02, 95%CI 1.01-1.04), interventricular septum thickness (OR 1.11, 95% CI 1.06-1.17), left ventricular posterior wall thickness (OR 1.09, 95% CI 1.03-1.15), left atrial diameter (OR 1.04, 95% CI 1.02-1.07) and aortic root diameter (OR 1.09, 95% CI 1.06-1.11). CONCLUSIONS: This study revealed a high prevalence of newly diagnosed AAA in a group of older men having cardiac evaluation. There was a relationship of increasing age with AAA, and a significant proportion of newly diagnosed subjects were not suitable for AAA repair.

Construction and performance of a dilution-refrigerator based spectroscopic-imaging scanning tunneling microscope.

We report on the set-up and performance of a dilution-refrigerator based spectroscopic imaging scanning tunneling microscope. It operates at temperatures below 10 mK and in magnetic fields up to 14T. The system allows for sample transfer and in situ cleavage. We present first-results demonstrating atomic resolution and the multi-gap structure of the superconducting gap of NbSe(2) at base temperature. To determine the energy resolution of our system we have measured a normal metal/vacuum/superconductor tunneling junction consisting of an aluminum tip on a gold sample. Our system allows for continuous measurements at base temperature on time scales of up to ≈170 h.

A stiff scanning tunneling microscopy head for measurement at low temperatures and in high magnetic fields.

We have developed a measurement head for scanning tunneling microscopy (STM) and specifically for spectroscopic imaging STM which is optimized for high mechanical stiffness and good thermal conductivity by choice of material. The main components of the microscope head are made of sapphire. Sapphire has been chosen from several competing possibilities based on finite element modeling of the fundamental vibrational modes of the body. We demonstrate operation of the STM head in topographic imaging and tunneling spectroscopy at temperatures down to below 2 K.

The strength of female sex as a prognostic factor in small-cell lung cancer: a pooled analysis of chemotherapy trials from the Manchester Lung Group and Medical Research Council Clinical Trials Unit.

BACKGROUND: Previous studies reported that women survive longer than men, but experience greater toxicity, when treated for small-cell lung cancer (SCLC). METHODS: Individual patient data from six randomized phase II/III chemotherapy trials, from the Manchester Lung Group and UK Medical Research Council, were pooled for analysis. End points included overall survival, response rate, toxicity, dose intensity (DI) and transfusion rates. RESULTS: Of 1707 patients analyzed, 44% were women. At baseline, women had poorer performance status (PS) (57% versus 67% Eastern Cooperative Oncology Group PS 0-1/Karnofsky PS 80-100, P = 0.0004) and more were of normal weight or underweight (57% versus 48%, P = 0.003), but fewer were anemic (25% versus 62%, P < 0.0001). Response rates between women and men were similar (77% versus 76%, P = 0.64). In univariate [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.76-0.96, P = 0.006] and multivariate (HR 0.88, 95% CI 0.79-0.99, P = 0.04) analyses, female sex predicted for longer survival. Women experienced more grade 3/4 emesis (18% versus 9%, P < 0.0001) and grade 3/4 mucositis (13% versus 8%, P = 0.005) than men. There were no differences in DI, infections, transfusions or treatment-related deaths. CONCLUSION: Data from >1700 patients in randomized SCLC chemotherapy trials confirm that women survive modestly longer than men but may experience greater toxicity.

A comparative study of high-resolution cone beam computed tomography and charge-coupled device sensors for detecting caries.

OBJECTIVES: Conventional radiographic imaging of teeth underestimates the presence of caries. The objective of this study was to compare the efficacy of high-resolution cone beam CT (CBCT) images and conventional charge-coupled device (CCD) images for detecting proximal and occlusal caries. METHODS: Non-restored, extracted human permanent premolar and molar teeth were mounted and then imaged with a 3DX Accuitomo and a CCD. We selected 92 occlusal and 100 proximal surfaces for raters to score. Of these, 36 and 25, respectively, had lesions extending into dentin. Using a five-step confidence scale, eight practising dentists evaluated the images for the presence of caries in dentin using both modalities. Actual presence and extent of caries was established with microCT imaging. RESULTS: For proximal surface lesions extending into dentin, the average sensitivity score using 3DX images (0.61) was almost twice that of CCD images (0.33) and the difference was significant. The specificity values for both systems were high and not significantly different from each other. For occlusal surfaces, raters detected significantly more lesions in the enamel or dentin when using the 3DX images than when using CCD images. However, the raters also had significantly lower average specificity scores for the 3DX images compared with the CCD images for lesions at both depths. CONCLUSIONS: Practising dentists were able to improve their detection of proximal-surface caries extending into the dentin, but not occlusal caries, using 3DX high-resolution cone beam CT images compared with CCD images.

Comparative study of image quality for MSCT and CBCT scanners for dentomaxillofacial radiology applications.

The image quality of four cone-beam computed tomography (CBCT) scanners dedicated for dentomaxillofacial imaging and one multi-slice computed tomography (MSCT) scanner was compared. For the MSCT scanner, a clinical and a low-dose protocol for oral indications were evaluated. The image quality was assessed by dedicated software that allows an automated analysis of accuracy measurements and evaluation of metal artefacts on two image quality phantoms. Bone was segmented with sub-millimetre accuracyin all scanners.

Observer performance in diagnosing osteoporosis by dental panoramic radiographs: results from the osteoporosis screening project in dentistry (OSPD).

Mandibular cortical erosion detected on dental panoramic radiographs (DPRs) may be useful for identifying women with osteoporosis, but little is known about the variation in diagnostic efficacy of observers worldwide. The purpose of this study was to measure the accuracy in identifying women at risk for osteoporosis in a worldwide group of observers using DPRs. We constructed a website that included background information about osteoporosis screening and instructions regarding the interpretation of mandibular cortical erosion. DPRs of 100 Japanese postmenopausal women aged 50 years or older who had completed skeletal bone mineral measurements by dual energy X-ray absorptiometry were digitized at 300 dpi. These were displayed on the website and used for the evaluation of diagnostic efficacy. Sixty observers aged 25 to 66 years recruited from 16 countries participated in this study. These observers classified cortical erosion into one of three groups (none, mild to moderate, and severe) on the website via the Internet, twice with an approximately 2-week interval. The diagnostic efficacy of the Osteoporosis Self-Assessment Tool (OST), a simple clinical decision rule based on age and weight, was also calculated and compared with that of cortical erosion. The overall mean sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the 60 observers in identifying women with osteoporosis by cortical erosion on DPRs were 82.5, 46.2, 46.7, and 84.0%, respectively. Those same values by the OST index were 82.9, 43.1, 43.9, and 82.4%, respectively. The intra-observer agreement in classifying cortical erosion on DPRs was sufficient (weighted kappa values>0.6) in 36 (60%) observers. This was significantly increased in observers who specialized in oral radiology (P<0.05). In the 36 observers with sufficient intra-observer agreement, the overall mean sensitivity, specificity, PPV, and NPV in identifying women with osteoporosis by any cortical erosion were 83.5, 48.7, 48.3, and 85.7%, respectively. The mean PPV and NPV were significantly higher in the 36 observers with sufficient intra-observer agreement than in the 24 observers with insufficient intra-observer agreement. Our results reconfirm the efficacy of cortical erosion findings in identifying postmenopausal women at risk for osteoporosis, among observers with sufficient intra-observer agreement. Information gathered from radiographic examination is at least as useful as that gathered from the OST index.

Gallbladder management during laparoscopic Roux-en-Y gastric bypass surgery: routine preoperative screening for gallstones and postoperative prophylactic medical treatment are not necessary.

In the bariatric surgery literature, the optimum approach to the gallbladder is controversial. Recommendations range from concomitant cholecystectomy to selective screening and postoperative medical prophylaxis. At our institution, we have taken a highly selective approach where patients are not routinely screened for gallstones, nor are they medically treated postoperatively with bile salts. We have reviewed our experience with this approach. From January 2003 to January 2005, 407 laparoscopic Roux en Y gastric bypasses were performed at UCLA and postoperative outcomes were collected into a prospective database. Exclusion criteria included previous cholecystectomy, a follow-up period less than 6 months, or incomplete records. One hundred ninety-nine patients were included in the study. With a mean follow up period of 17.8 months, 12 (6%) patients required cholecystectomy for gallstone-induced pathology. Laparoscopic removal was performed in 11 (92%) patients. Indications for surgery included acute cholecystitis in five (2.5%) patients, gallstone pancreatitis in two (1%) patients, and biliary colic alone in another five (2.5%) patients. The incidence of symptomatic gallstones requiring cholecystectomy after laparoscopic Roux en Y gastric bypass is low. These results are similar to those from institutions where routine preoperative screening and prophylactic postoperative medical therapy is used. Routine preoperative screening or medical prophylaxis may not be necessary.

Phase II study of SPI-77 (sterically stabilised liposomal cisplatin) in advanced non-small-cell lung cancer.

To determine the efficacy and tolerability of SPI-77 (sterically stabilised liposomal cisplatin) at three dose levels in patients with advanced non-small-cell lung cancer (NSCLC). Patients had Stage IIIB or IV NSCLC and were chemo-naïve, and Eastern Oncology Cooperative Group 0-2. The first cohort received SPI-77 at 100 mg m-2, the second 200 mg m-2 and the final cohort 260 mg m-2. Patients had also pharmacokinetics and analysis of leucocyte platinum (Pt)-DNA adducts performed. Twenty-six patients were treated, with 22 patients being evaluable for response. Only one response occurred at the 200 mg m-2 dose level for an overall response rate of 4.5% (7.1% at >or=200 mg m-2). No significant toxicity was noted including nephrotoxicity or ototoxicity aside from two patients with Grade 3 nausea. No routine antiemetics or hydration was used. The pharmacokinetic profile of SPI-77 was typical for a liposomally formulated drug, and the AUC appeared to be proportional to the dose of SPI-77. Plasma Pt levels and leucocyte DNA adduct levels did not appear to rise with successive doses. SPI-77 demonstrates only modest activity in patients with NSCLC.

Change in mandibular trabecular pattern and hip fracture rate in elderly women.

OBJECTIVES: To determine if alterations of trabecular pattern, or the rate of change of jaw trabeculae, are associated with rate of hip fracture. METHODS: Participants in a population-based study of residents of a California retirement community (Leisure World Cohort Study) were asked for permission to obtain their dental radiographs. Periapical radiographs were retrieved on 598 women (average age at time of first radiograph=77 years). Several measurements of trabecular pattern (strut analysis), textural properties (run-length analysis) and Fourier analysis were made in several anatomical regions of the jaw. These trabecular features and clinical information self-reported by subjects in the early 1980s were examined for association with hip fracture rate using Cox proportional-hazard regression. RESULTS: Rate of hip fracture increased with decreasing average length of node-to-terminus struts in the mandibular incisor region. Each 0.01 mm per year decrease in the average length of node-to-terminus struts increased hip fracture rate by a factor of 2.9 (P=0.02, accuracy=73%). Inclusion of clinical parameters improved the predictive model compared with use of the radiographic parameter alone (accuracy=79%). Similar results were seen for percent change per year in this parameter. CONCLUSIONS: Changes in radiographic trabecular structure, augmented with clinical information, are predictive of hip fracture in elderly women. Further refinement of both the radiographic and clinical parameters may lead to a screening process accessible to a large number of women and to early diagnosis and treatment of osteoporosis.

Oral radiographic predictors of osteoporosis.

Osteoporosis is a systemic skeletal disease characterized by low bone mass and micro architectural deterioration of the bone scaffold that result in increased bone fragility and susceptibility to fracture. It is one of the most common disorders of the elderly and is estimated to effect 75 million people in Europe, Japan and the USA. The purpose of screening for osteoporosis is to identify individuals who are likely to benefit from treatment. The fact that dental radiographs are regularly made on a large fraction of the adult population makes their potential use as a marker of skeletal health an exciting avenue of research. In the last four decades numerous research teams have reported oral radiographic findings associated with osteoporosis. The preponderance of the evidence shows that the jaws of subjects with osteoporosis show reduced bone mass and altered morphology. Clinically useful predictions of individuals most likely to develop osteoporotic fractures will require a multifactorial model including both radiographic and clinical findings. Future efforts should continue to search for oral radiographic signs with high sensitivity and specificity for osteoporosis, identify clinical signs available in the dental office associated with osteoporosis, develop multidisciplinary classification methods including both radiographic and clinical parameters, and automate radiographic and clinical analyses as much as possible to minimize the involvement of the dentist as well as to standardize data collection.

Fourier analysis reveals increased trabecular spacing in sickle cell anemia.

Sickle cell anemia may expand marrow spaces in the jaws. Fourier analysis is well-suited to the analysis of trabecular spacing in radiographs. We hypothesize that individuals with sickle cell anemia demonstrate increased intertrabecular spacing. Periapical radiographs of 18 African Americans with sickle cell disease and 18 controls were examined by one-dimensional discrete Fourier analyses in both jaws for measurement of the spatial frequency distribution of repeating trabecular structures. A strut analysis of trabeculae was also performed and the results compared. Trabecular structures in individuals with sickle cell anemia revealed increased intertrabecular distance compared with controls. Strut analysis revealed significant reductions in trabecular complexity. Fourier analysis allows for the classification of subjects with 94% sensitivity and specificity. Fourier analysis of dental radiographs is a more effective method of identifying individuals with sickle cell anemia than strut analysis.

Vertical ground reaction forces: objective measures of gait following hip arthroplasty.

After hip arthroplasty, many patients continue to exhibit abnormal gait patterns. The purpose of this study was to compare the vertical ground reaction forces of a group of 27 individuals who have undergone hip arthroplasty with a group of 35 normal control subjects. Specific force measures were determined from vertical ground reaction forces collected on a treadmill instrumented with two force plates. Symmetry indices were calculated on both groups of subjects. First and second peak forces, loading rate, impulse, and stance time were significantly less, while time to first peak force was significantly greater on the affected leg of the hip arthroplasty subjects when compared to their unaffected leg, or to the control group. The hip arthroplasty group showed greater asymmetry of ground reaction forces than the control group did. Bilateral asymmetric limb loading persists well after unilateral hip replacement surgery. Ground reaction force measures have been shown to be an effective means of quantifying the antalgic gait of hip arthroplasty patients.

Randomized phase II study of cyclophosphamide, doxorubicin, and vincristine compared with single-agent carboplatin in patients with poor prognosis small cell lung carcinoma.

BACKGROUND: Information on the effect of chemotherapy in a group of patients with poor prognosis, poor performance status small cell lung carcinoma (SCLC) is scarce. A randomized study comparing single-agent carboplatin with combination chemotherapy in this largely unreported population of SCLC patients was undertaken. METHODS: One hundred nineteen patients were allocated to four cycles of either cyclophosphamide, doxorubicin, and vincristine (CAV) or single-agent carboplatin. Patients had either a Karnofsky performance score < or = 50 and/or a prognostic score indicative of a 1-year survival rate < or = 15%. RESULTS: Grade 3-4 neutropenia and intravenous antibiotic use were significantly more common with the CAV regimen (P < 0.005). Conversely, Grade 3-4 thrombocytopenia was more common (P < 0.0009) and platelet transfusion was more frequent (P < 0.05) with carboplatin therapy. Nonhematologic toxicity was similar in both treatment arms, except for alopecia with CAV therapy (P < 0.0007). Symptom relief occurred in 48% and 41% of patients in the CAV and carboplatin treatment arms, respectively. Dyspnea was improved in 66% and 41% of patients and cough was improved in 21% and 7% of patients in the CAV and carboplatin treatment arms, respectively. CAV therapy produced a higher response rate than carboplatin (38% vs. 25%), but this was not statistically significant (P = 0.15). The median overall survival for patients in the CAV and carboplatin treatment arms was 17 weeks and 15.9 weeks, respectively, with 1-year survival rates of 12% and 6%. CONCLUSIONS: Single-agent carboplatin is a feasible treatment in patients with poor prognosis SCLC and produces response rates, relief of tumor-related symptoms, and survival similar to what is seen in patients who receive CAV chemotherapy. The lower risk of life-threatening sepsis and less need for hospitalization or intravenous antibiotic courses is advantageous in this susceptible patient population.

Effect of localized muscle fatigue on vertical ground reaction forces and ankle joint motion during running.

The purpose of this study was to examine the changes in the vertical ground reaction force (VGRF) and ankle joint motion during the first 50% of the stance phase of running following fatiguing exercise of either the dorsiflexors or the invertors of the foot. VGRFs, sagittal and rearfoot kinematic data were collected from 11 female recreational runners running at 2.9 m/second on a treadmill prior to and following localized muscle fatigue of either the invertors or dorsiflexors of the right foot. Loading rate of the impact peak force significantly increased following fatiguing exercise of the dorsiflexors, while the peak magnitudes of the impact and push-off forces remained unchanged. There were significant decreases in dorsiflexion at heel contact, but no significant difference in any rearfoot motion parameters tested following dorsiflexor fatigue. Following fatiguing exercise of the invertors, impact peak magnitude, push-off peak magnitude and the rate of decline of the impact peak force significantly decreased; there was no change in the loading rate of the impact peak force. Invertor fatigue also resulted in a less inverted foot position at heel contact, but there were no significant differences in any other kinematic parameters tested. The results demonstrate that localized muscle fatigue of either the invertors or dorsiflexors can have a significant effect on the loading rates, peak magnitudes and ankle joint motion seen during running. These changes, due to localized muscle fatigue, may play a role in many common lower extremity running injuries.

Parameters of radiologic care: An official report of the American Academy of Oral and Maxillofacial Radiology.

The American Academy of Oral and Maxillofacial Radiology developed these Parameters of Care to provide national guidelines for the use of radiographs prescribed for the diagnosis of disease, treatment planning, and follow-up care of patients with abnormalities of the oral and maxillofacial region. The Parameters cover radiographic techniques, imaging of the temporomandibular joint, imaging of diseases of the jaws, and imaging of dental implant sites.

Digital analysis of trabecular pattern in jaws of patients with sickle cell anemia.

OBJECTIVES: To characterize how the morphological features of the cancellous bone of the maxilla and mandible differ in patients with sickle cell anemia compared with normal subjects. METHODS: Periapical radiographs of 18 young African American patients with sickle cell anemia and 18 control African Americans were digitized at 600 d.p.i. A customized computer program measured 24 morphological features of the trabecular and marrow architecture in the anterior maxilla and mandible. The mean values for each of the features were determined for the sickle cell and control groups and compared by anatomical site. RESULTS: Patients with sickle cell anemia have a significant increase in area of the marrow (53% compared with 47% in controls) and a less complex trabecular structure as evidenced by fewer skeletal branch points per square cm (451 compared with 584 in controls in the anterior maxilla and, 553 compared with 678 in controls in the anterior mandible). All values are significantly different (P < 0.001). CONCLUSIONS: The data support the hypothesis that an automated image-interpretation program can distinguish patients with sickle cell anemia from normal individuals.

Randomised phase II study of cisplatin-etoposide versus infusional carboplatin in advanced non-small-cell lung cancer and mesothelioma.

BACKGROUND: A randomised phase II study was performed to compare standard combination chemotherapy containing cisplatin and etoposide with infusional carboplatin. PATIENTS AND METHODS: One hundred twenty patients with locally advanced/metastatic non-small-cell lung cancer or mesothelioma were enrolled. All were chemotherapy-naïve and had a Karnofsky performance status of > or = 50. Patients were randomised to either four cycles of bolus therapy of cisplatin 80 mg/m2 day 1, etoposide 120 mg/m2 day 1-3, or continuous infusion of carboplatin 100/mg/m2/week for six weeks. RESULTS: No patients on infusional therapy incurred grade 3-4 toxicity while in the bolus arm, grade 3 and grade 4 leucopenia occurred in 17% and 35% of patients, respectively. Grade 4 thrombocytopenia occurred in 8% of patients and there were two instances of grade 3 renal toxicity. No responses occurred in the pump arm. Eight of forty-six patients with non-small-cell lung cancer responded to treatment (response rate 17.3%) with two complete responses and six partial responses. Only one patient with mesothelioma responded to bolus therapy. There was no difference in survival for the subset of NSCLC patients. Survival for mesothelioma patients in the pump arm was superior but this was likely to be a result of early deaths in the bolus arm. CONCLUSIONS: The pump arm was well-tolerated but not active, whilst combination platinum-based therapy demonstrated activity but significantly more toxicity than the pump arm. Further studies of infusional carboplatin with this schedule are not warranted.