Access to Care and Satisfaction in Colorectal Cancer Patients

This study described the various components of access to care for resectable colorectal cancer, and correlated the timeliness of these components with patient satisfaction. With a prospective/retrospective cohort design, all patients undergoing surgical resection for primary colorectal cancer from 2/1/01 to 15/12/01, were identified during their admission for surgery. A comprehensive, standardized method of ascertaining specific time intervals, which included a patient interview, was used. A patient satisfaction questionnaire was developed, tested, and used in consenting patients. Over the study period, 118 patients underwent colorectal cancer resection. Of these, 110 (93%) consented to participate and 101 (86%) completed the satisfaction questionnaire, including test-retest. The median time intervals (interquartile range) for the various components of access to care were as follows: symptoms to first physician visit, 32 days (10-75); first physician visit to diagnosis, 88 days (44-218); diagnosis to surgery, 19 days (10-44); surgery to chemotherapy (where applicable), 54 days (47-72). On multivariate analysis, tumor location in the rectum was associated with longer prediagnosis intervals, whereas increasing tumor stage was associated with shorter intervals from diagnosis to surgery. Variation in the time interval from diagnosis to surgery was associated with patient satisfaction (r = 0.49; P < 0.0001). Substantially less correlation was identified between patient satisfaction and the time from first physician visit to diagnosis (r = 0.25, P = 0.04). No significant correlation was identified between patient satisfaction scores and the time interval from symptoms to first physician visit (r = 0.11; P = 0.7). Despite concerns regarding surgical waitlists, the longest time intervals experienced by colorectal cancer patients precede diagnosis. However, variations in the relatively short time period from diagnosis to surgery appeared to have the most impact on patient satisfaction. Interventions which improve the timeliness of specific components of access to care may not necessarily result in improved patient satisfaction.     

Vitamin D, parathyroid hormone levels and bone mineral density in community-dwelling older women: The Rancho Bernardo Study

Vitamin D (25(OH)D) increases the efficiency of intestinal calcium absorption. Low levels of serum calcium stimulate the secretion of parathyroid hormone (PTH), which maintains serum calcium levels at the expense of increased bone turnover, bone loss and increased risk of fractures. We studied the association between 25(OH)D and PTH levels, and their associations with bone mineral density (BMD), bone loss, and prevalence of hip fractures in 615 community-dwelling postmenopausal aged 50–97 years. Mean level of 25(OH)D and PTH were 102.0 nmol/l±35.0 nmol/l and 49.4 ng/l±23.2 nmol/l, respectively; 49% of women were current hormone therapy users. The overall prevalence of vitamin D insufficiency (25(OH)D<50 nmol/l) was 2%, and prevalence of high PTH levels (>65 ng/l) was 17.4%. In multiple linear regression analyses hip BMD was negatively and independently associated with PTH levels ( p =0.04), and positively and independently associated with 25(OH)D levels ( p =0.03). There were only 23 women (3.7%) who experienced a hip fracture. In age-adjusted analyses there were no significant differences of 25(OH)D and PTH levels by hip fracture status. Across the entire range of values, the overall correlation between 25(OH)D and PTH was moderate ( r =–0.20). However, after the threshold vitamin D level of 120 nmol/l, all PTH values were below 65 ng/l. Further studies are necessary to identify the optimal vitamin D levels necessary to prevent secondary hyperparathyroidism.     

Association of 18 Confirmed Susceptibility Loci for Type 2 Diabetes With Indices of Insulin Release, Proinsulin Conversion, and Insulin Sensitivity in 5,327 Nondiabetic Finnish Men

OBJECTIVE

We investigated the effects of 18 confirmed type 2 diabetes risk single nucleotide polymorphisms (SNPs) on insulin sensitivity, insulin secretion, and conversion of proinsulin to insulin.

RESEARCH DESIGN AND METHODS

A total of 5,327 nondiabetic men (age 58 ± 7 years, BMI 27.0 ± 3.8 kg/m²) from a large population-based cohort were included. Oral glucose tolerance tests and genotyping of SNPs in or near PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, LOC387761, CDKN2B, IGF2BP2, CDKAL1, HNF1B, WFS1, JAZF1, CDC123, TSPAN8, THADA, ADAMTS9, NOTCH2, KCNQ1, and MTNR1B were performed. HNF1B rs757210 was excluded because of failure to achieve Hardy-Weinberg equilibrium.

RESULTS

Six SNPs (TCF7L2, SLC30A8, HHEX, CDKN2B, CDKAL1, and MTNR1B) were significantly (P < 6.9 × 10⁻⁴) and two SNPs (KCNJ11 and IGF2BP2) were nominally (P < 0.05) associated with early-phase insulin release (InsAUC_0–30/GluAUC_0–30), adjusted for age, BMI, and insulin sensitivity (Matsuda ISI). Combined effects of these eight SNPs reached −32% reduction in InsAUC_0–30/GluAUC_0–30 in carriers of ≥11 vs. ≤3 weighted risk alleles. Four SNPs (SLC30A8, HHEX, CDKAL1, and TCF7L2) were significantly or nominally associated with indexes of proinsulin conversion. Three SNPs (KCNJ11, HHEX, and TSPAN8) were nominally associated with Matsuda ISI (adjusted for age and BMI). The effect of HHEX on Matsuda ISI became significant after additional adjustment for InsAUC_0–30/GluAUC_0–30. Nine SNPs did not show any associations with examined traits.

CONCLUSIONS

Eight type 2 diabetes–related loci were significantly or nominally associated with impaired early-phase insulin release. Effects of SLC30A8, HHEX, CDKAL1, and TCF7L2 on insulin release could be partially explained by impaired proinsulin conversion. HHEX might influence both insulin release and insulin sensitivity.Impaired insulin secretion and insulin resistance, two main pathophysiological mechanisms leading to type 2 diabetes, have a significant genetic component (1). Recent studies have confirmed 20 genetic loci reproducibly associated with type 2 diabetes (2–13). Three were previously known (PPARG, KCNJ11, and TCF7L2), whereas 17 loci were recently discovered either by genome-wide association studies (SLC30A8, HHEX-IDE, LOC387761, CDKN2A/2B, IGF2BP2, CDKAL1, FTO, JAZF1, CDC123/CAMK1D, TSPAN8/LGR5, THADA, ADAMTS9, NOTCH2, KCNQ1, and MTNR1B), or candidate gene approach (WFS1 and HNF1B). The mechanisms by which these genes contribute to the development of type 2 diabetes are not fully understood.PPARG is the only gene from the 20 confirmed loci previously associated with insulin sensitivity (14,15). Association with impaired β-cell function has been reported for 14 loci (KCNJ11, SLC30A8, HHEX-IDE, CDKN2A/2B, IGF2BP2, CDKAL1, TCF7L2, WFS1, HNF1B, JAZF1, CDC123/CAMK1D, TSPAN8/LGR5, KCNQ1, and MTNR1B) (6,12,13,16–38). Although associations of variants in HHEX (16–22), CDKAL1 (6,21–26), TCF7L2 (22,27–30), and MTNR1B (13,31,32) with impaired insulin secretion seem to be consistent across different studies, information concerning other genes is limited (12,18–25,27,33–38). The mechanisms by which variants in these genes affect insulin secretion are unknown. However, a few recent studies suggested that variants in TCF7L2 (22,39–42), SLC30A8 (22), CDKAL1 (22), and MTNR1B (31) might influence insulin secretion by affecting the conversion of proinsulin to insulin. Variants of FTO have been shown to confer risk for type 2 diabetes through their association with obesity (7,16) and therefore were not included in this study.Large population-based studies can help to elucidate the underlying mechanisms by which single nucleotide polymorphisms (SNPs) of different risk genes predispose to type 2 diabetes. Therefore, we investigated confirmed type 2 diabetes–related loci for their associations with insulin sensitivity, insulin secretion, and conversion of proinsulin to insulin in a population-based sample of 5,327 nondiabetic Finnish men.     

Amide proton transfer imaging of the breast at 3 T: Establishing reproducibility and possible feasibility assessing chemotherapy response

Chemical exchange saturation transfer imaging can generate contrast that is sensitive to amide protons associated with proteins and peptides (termed amide proton transfer, APT). In breast cancer, APT contrast may report on underlying changes in microstructural tissue composition. However, to date, there have been no developments or applications of APT chemical exchange saturation transfer to breast cancer. As a result, the aims of this study were to (i) experimentally explore optimal scan parameters for breast chemical exchange saturation transfer near the amide resonance at 3 T, (ii) establish the reliability of APT imaging of healthy fibroglandular tissue, and (iii) demonstrate preliminary results on APT changes in locally advanced breast cancer observed during the course of neoadjuvant chemotherapy. Chemical exchange saturation transfer measurements were experimentally optimized on cross‐linked bovine serum albumin phantoms, and the reliability of APT imaging was assessed in 10 women with no history of breast disease. The mean difference between test–retest APT values was not significantly different from zero, and the individual difference values were not dependent on the average APT value. The 95% confidence interval limits were ±0.70% (α = 0.05), and the repeatability was 1.91. APT measurements were also performed in three women before and after one cycle of chemotherapy. Following therapy, APT increased in the one patient with progressive disease and decreased in the two patients with a partial or complete response. Together, these results suggest that APT imaging may report on treatment response in these patients. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Congenital high airway obstruction syndrome: natural history and management

Background

Congenital high airway obstruction syndrome (CHAOS) is a life-threatening condition with a poorly understood natural history.

Methods

A retrospective review of five patients with CHAOS between 1997 and 2002 was performed.

Results

All fetuses had large echogenic lungs, dilated airways, inverted diaphragms, and massive ascites. One fetus with a laryngeal cyst was terminated at 22 weeks. A twin fetus with findings suggestive of a tracheal web had progressive hydrops, which led to fetal demise. The remaining 3 patients delivered via the ex utero intrapartum treatment (EXIT) procedure survived. The first patient tolerated progressive hydrops for 12 weeks in utero. He had tracheal atresia but underwent laryngotracheoplasty successfully. He is the first long-term CHAOS survivor and is speaking at 5 years of age. The 2 patients with relatively stable lung volumes prenatally have laryngeal atresia with a pinpoint posterior laryngeal fistula. Their postnatal clinical courses were much more benign than the first survivor.

Conclusions

The prenatal natural history and postnatal course of CHAOS depends on whether the airway obstruction is complete. The EXIT procedure offers the potential for salvage of this otherwise lethal condition. Hydrops may be well tolerated prenatally for weeks with potential resolution if airway fistulization is present.     

Radiology resident interpretations of on-call imaging studies: the incidence of major discrepancies

RATIONALE AND OBJECTIVES: To determine the incidence of radiology resident preliminary interpretation errors for plain film, body computed tomography, and neuroradiology (neuro)computed tomographic examinations read on call. MATERIALS AND METHODS: We retrospectively reviewed the data in a prospectively acquired resident quality assurance (QA) database dating between January 2000 and March 2007. The database comprises all imaging studies initially interpreted by an on-call resident and later reviewed by a board-certified attending radiologist who determined the level of discrepancy between the two interpretations according to a graded scale from 0 (no discrepancy) to 3 (major discrepancy). We reviewed the data with respect to resident training level, imaging modality, and variance level. Statistical analysis was performed with chi(2) test, alpha = 0.05. We compared our results with other published series studying resident and attending accuracy. RESULTS: A total of 141,381 cases were entered into the database during the review period. Of all examinations, 95.7% had zero variance, 3.3% minor variance, and 1.0% major variance. There was a slight, statistically significant increase in overall accuracy with increased resident year from 95.4% of examinations read by first-year residents (R1s) to 96.1% by fourth-year resident (R4s) (P < .0001). Overall percentages of exams with major discrepancies were 1.0% for R1s, 1.1% for second-year residents, 1.0% for third-year residents, and 0.98% for R4s. CONCLUSIONS: The majority of preliminary resident interpretations are highly accurate. The incidence of major discrepancies is extremely low and similar, even with R1s, to that of attending radiologists published in other studies. A slight, statistically significant decrease in the error rate is detectable as residents gain experience throughout the 4 years of residency.     

The EXIT procedure: experience and outcome in 31 cases

Background: The EXIT (ex utero intrapartum treatment) procedure, although initially designed for reversal of tracheal occlusion in fetuses with congenital diaphragmatic hernias (CDH), has been adapted to treat a variety of fetal conditions. Methods: A retrospective chart review of all consecutive EXIT procedures since 1996 was conducted. Results: Thirty-one women underwent the EXIT procedure, with an average maternal age of 29 years (range, 20 to 38), and average gestational age of 34 weeks (range, 29 to 40). The indication was airway obstruction from fetal neck mass in 13, and reversal of tracheal occlusion from in utero clipping in 13. Singular indications included an EXIT-to-ECMO (extracorporeal membrane oxygenation) procedure for a fetus with CDH and a cardiac defect (n = 1), congenital high airway obstruction syndrome (CHAOS, n = 1), resection of a very large congenital cystic adenomatoid malformation of the lung (CCAM) on uteroplacental bypass (n = 1), unilateral pulmonary agenesis (n = 1), and thoracoomphalopagus conjoined twins. The mean duration on uteroplacental bypass (from uterine incision to umbilical cord clamping) was 30.3 [plusmn] 14.7 minutes (range, 8 to 66). No fetus experienced hemodynamic instability during uteroplacental bypass as recorded by fetal heart rate (FHR), pulse oximeter, and fetal echocardiography, except for one instance of reversible bradycardia from umbilical cord compression. The mean FHR and fetal saturation were 153.0 [plusmn] 38.5 beats per minute and 71.2% [plusmn] 19.9%, respectively. Five fetuses required a tracheostomy. Only 1 death occurred during an EXIT procedure because of inability to secure the airway secondary to extensive involvement by a lymphangioma. The average cord pH and pCO₂ were, respectively, 7.20 [plusmn] 0.11 and 63.2 [plusmn] 14.6. Two maternal complications occurred: bleeding from a hysterotomy site and dehiscence of an old hysterotomy scar noticed at a subsequent cesarean section. The average maternal blood loss was 848.3 [plusmn] 574.1 mL. Conclusion: The EXIT procedure was used successfully to ensure uteroplacental gas exchange and fetal hemodynamic stability during a variety of surgical procedures performed to secure the fetal airway or ensure successful transition to postnatal environment.     

The natural history of prenatally diagnosed conjoined twins

Background/Purpose: Accurate prenatal diagnosis of complex anatomic connections and associated anomalies has only been possible recently with the use of ultrasonography, echocardiography, and fetal magnetic resonance imaging (MRI). To assess the impact of improved antenatal diagnosis in the management and outcome of conjoined twins, the authors reviewed their experience with 14 cases. Methods: A retrospective review of prenatally diagnosed conjoined twins referred to our institution from 1996 to present was conducted. Results: In 14 sets of conjoined twins, there were 10 thoracoomphalopagus, 2 dicephalus tribrachius dipus, 1 ischiopagus, and 1 ischioomphalopagus. The earliest age at diagnosis was 9 weeks' gestation (range, 9 to 29; mean, 20). Prenatal imaging with ultrasonography, echocardiography, and ultrafast fetal MRI accurately defined the shared anatomy in all cases. Associated anomalies included cardiac malformations (11 of 14), congenital diaphragmatic hernia (4 of 14), abdominal wall defects (2 of 14), and imperforate anus (2 of 14). Three sets of twins underwent therapeutic abortion, 1 set of twins died in utero, and 10 were delivered via cesarean section at a mean gestational age of 34 weeks. There were 5 individual survivors in the series after separation (18%). In one case, in which a twin with a normal heart perfused the cotwin with a rudimentary heart, the ex utero intrapartum treatment procedure (EXIT) was utilized because of concern that the normal twin would suffer immediate cardiac decompensation at birth. This EXIT-to-separation strategy allowed prompt control of the airway and circulation before clamping the umbilical cord and optimized control over a potentially emergent situation, leading to survival of the normal cotwin. In 2 sets of twins in which each twin had a normal heart, tissue expanders were inserted before separation. Conclusions: Advances in prenatal diagnosis allow detailed, accurate evaluations of conjoined twins. Careful prenatal studies may uncover cases in which emergent separation at birth is lifesaving.     

Altered swelling behavior of femoral cartilage following joint immobilization in a canine model.

Periods of reduced joint loading have been shown to induce changes in the biochemical composition. metabolism and mechanics of articular cartilage. In this study, changes in cartilage swelling behavior were studied following a 4-week period of joint immobilization, using a recently developed osmotic loading technique [J. Biomech, 32 (1999) 401-408]. The magnitude and distribution of swelling strains were measured in cartilage-bone samples equilibrated in physiological and hypotonic saline, relative to a hypertonic reference NaCl solution. Physicochemical parameters (glycosaminoglycan fixed charge density and water volume fraction) were determined in site-matched cartilage samples. The experimental data for swelling strains, fixed charge density and water volume fraction were used with a triphasic mechano-chemical theory [J. Biomech. Eng. 113 (1991) 245-258] to determine the effect of joint immobilization on the tensile modulus of the cartilage solid matrix. Four weeks of immobilization resulted in a significant increase in the magnitude of swelling-induced strains, and a significant decrease in fixed charge density in cartilage, as compared with the contralateral controls. Joint immobilization also resulted in decreases in values for the modulus of cartilage, as compared with the contralateral controls. Our results suggest that 4 weeks of joint immobilization had a significant effect on cartilage mechanical function that may be linked to collagen changes in the cartilage extracellular matrix.     

Progressive slippage after pinning for slipped capital femoral epiphysis

The authors retrospectively reviewed seven cases of progressive slipped capital femoral epiphysis after screw fixation. All seven patients initially presented with chronic symptoms, and five had an acute exacerbation of symptoms with the appearance of an acute-on-chronic slip. Of the other two, one had obvious motion at the proximal femoral physis and the other had increased symptoms but did not have an obvious acute slip radiographically. All underwent percutaneous screw fixation. In four patients a single screw was placed, and in three patients two screws were placed. No patient became symptom-free after surgery. Slip progression was noted on average 5 months after treatment. Radiographs in all patients revealed an increase in slip severity and loss of screw purchase in the femoral neck while fixation in the proximal femoral epiphysis remained secure. One patient had hypothyroidism and another Cushing disease, both diagnosed after the slipped epiphysis. Slips occurring in children with underlying endocrinopathies, and unstable slips in children with a history of antecedent knee or hip pain (commonly called an acute-on-chronic slip) may be susceptible to screw fixation failure. In such patients, close radiographic follow-up, particularly in the presence of continued symptoms, is required to document slip progression and fixation failure as soon as possible.