Factors associated with genetic testing in a cohort of breast cancer survivors.

We examined factors associated with self-reported use of genetic testing among breast cancer survivors based on a 2015 cross-sectional survey at eight Midwestern sites. Genetic testing was reported in 39% of our 1235 study participants, with higher utilization among those aged <50 and with a triple-negative cancer. Bilateral mastectomy, having relatives with breast cancer, and younger age were associated with increased genetic testing use. Increasing income, in interaction with age, was associated with use of genetic testing among younger but not older patients. Rural residency emerged as a possible barrier for genetic testing among women with triple-negative cancer.

Effects of abaloparatide, a human parathyroid hormone-related peptide analog, on bone mineral density in postmenopausal women with osteoporosis.

CONTEXT: Abaloparatide is a novel synthetic peptide analog of parathyroid hormone-related protein (PTHrP) that is currently being developed as a potential anabolic agent in the treatment of postmenopausal osteoporosis. OBJECTIVE: This study sought to assess the effects of abaloparatide on bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck in postmenopausal women with osteoporosis. DESIGN: Multi-center, multi-national, double-blind placebo controlled trial in which postmenopausal women were randomly assigned to receive 24 weeks of treatment with daily sc injections of placebo, abaloparatide, 20, 40, or 80 µg, or teriparatide, 20 µg. A 24-week extension was also performed in a subset of subjects. PARTICIPANTS: Postmenopausal women with osteoporosis (n = 222). MAIN OUTCOME MEASURES: BMD by dual-x-ray absorptiometry and biochemical markers of bone turnover. RESULTS: At 24 weeks, lumbar spine BMD increased by 2.9, 5.2, and 6.7% in the abaloparatide, 20-, 40-, and 80-µg groups, respectively, and 5.5% in the teriparatide group. The increases in the 40- and 80-µg abaloparatide groups and the teriparatide group were significantly greater than placebo (1.6%). Femoral neck BMD increased by 2.7, 2.2, and 3.1% in abaloparatide, 20-, 40-, and 80-µg groups, respectively, and 1.1% in the teriparatide group. The increase in femoral neck BMD with abaloparatide, 80 µg was significantly greater than placebo (0.8%). Total hip BMD increased by 1.4, 2.0, and 2.6% in the abaloparatide, 20-, 40-, and 80-µg groups, respectively. The total hip increases in the 40- and 80-µg abaloparatide groups were greater than both placebo (0.4%) and teriparatide (0.5%). CONCLUSIONS: Compared with placebo, 24 weeks of daily sc abaloparatide increases BMD of the lumbar spine, femoral neck, and total hip in a dose-dependent fashion. Moreover, the abaloparatide-induced BMD increases at the total hip are greater than with the marketed dose of teriparatide. These results support the further investigation of abaloparatide as an anabolic therapy in postmenopausal osteoporosis.

Variability in intraosseous pressure induced by saline flush of an intraosseous cannula by multiple practitioners.

Intraosseous cannulation is an accepted means to achieve vascular access when peripheral venous access is not available. It is common practice to flush the intraosseous cannula with saline prior to establishing infusions. The objective of this study was to evaluate changes in intraosseous pressure during the flush procedure and to assess the variability of pressure changes induced by different practitioners. Two intraosseous cannulas were placed in an isolated cadaveric femur collected from a swine. Intraosseous pressure and the rate of change in pressure were recorded continuously during a series of saline flushes into a distal femoral intraosseous cannula by 21 members of the veterinary research staff at the authors' institution. Median peak intraosseous pressures exceeded 600 mmHg, and an inverse relationship was noted between peak intraosseous pressure and the duration of flush. Bone marrow fat emboli were grossly evident in flush effluents and their presence was confirmed by microscopic examination. Until the practitioners were informed of the pressure changes induced by the intraosseous cannula flush, few had appreciated the magnitude of the pressures that they had generated, suggesting that an instrumented intraosseous flush preparation like the one used in this study may prove useful as a training tool for flush procedures.

Pain scores: are they used in sickle cell pain?

OBJECTIVES: We sought to evaluate the relationship between pain scores and time to analgesic administration in 2 patient groups: those with sickle cell disease (SCD) and those with long-bone fractures (LBFs). METHODS: Patients between the ages of 3 and 21 years who presented to a pediatric emergency department (ED) with a vaso-occlusive episode secondary to SCD or an isolated LBF during 2005 were included. A retrospective chart review was conducted for each visit. Data collected included demographics, visual analog scale (VAS) pain scores, and time analgesic intervention. In 2005, all patients with SCD received analgesic management according to protocol. RESULTS: Seventy-seven patients with SCD had 152 visits to the ED for pain, whereas 219 patients had 221 visits for isolated LBF. In the long-bone-fracture group, for every 1-point increase in the VAS score, time to analgesic administration decreased by 5.6 minutes (P = 0.003), whereas in the SCD group, there was no relationship between VAS score and time to analgesic administration (P = 0.69). CONCLUSIONS: Our data suggest that pain scores are not used in the initial decision-making process in those patients with SCD presenting to the ED; however, they are utilized for patients presenting with another painful condition.

Do children with sickle cell disease receive disparate care for pain in the emergency department?

BACKGROUND: There may be disparities in pain management practice in the emergency department (ED) for sickle cell disease patients (SCD) with vaso-occlusive episodes (VOE). OBJECTIVES: To compare pain management practice for children who presented to the ED with VOE to those with isolated long bone fractures (LBF). METHODS: Children who presented with a VOE or a LBF to a children's hospital ED during 2005 were included. A retrospective medical chart review was conducted for each patient visit. Data collected included demographics, pain scores, time from triage to analgesia, and analgesic intervention. RESULTS: Seventy-seven patients with SCD had 152 visits to the ED for pain, and 219 patients had 221 visits for LBF. Fifty-five patients (108 visits) with SCD and 123 patients (124 visits) with LBF received opiates. Subsequent analysis was done on these groups. Patients with SCD were older, less likely to be male and more likely to be African-American than the LBF group. Patients with SCD had higher triage pain scores (7.7 ± 2.5 vs. 6.7 ± 3.0, p = 0.005) and spent less time in the waiting room (7.4 ± 9.0 vs. 12.1 ± 26.8 min, p = 0.10), were given higher initial opiate doses (0.09 ± 0.03 vs. 0.07 ± 0.03 mg/kg morphine, p < 0.001); however, time from triage to analgesic intervention did not differ (69.0 ± 42.6 vs. 70.4 ± 57.1 min, p = 0.92). CONCLUSIONS: No disparities in care for children with sickle cell pain were identified. More timely administration of opiates needs to be encouraged, assuming other factors such as time of day, ED census, and acuity permit.

Laparoscopic nephrectomy in children: systematic review of transperitoneal and retroperitoneal approaches.

OBJECTIVES: To perform a systematic review of the available medical data concerning laparoscopic nephrectomy in children. For many pediatric urologists, the laparoscopic approach to nephrectomy has become the standard of care. Access can be obtained using a retroperitoneal (RP) or transperitoneal (TP) approach. Previously, debates have argued the advantage of each technique relative to the other. METHODS: We performed a data search through MEDLINE and PubMed to find reports of laparoscopic nephrectomy, nephroureterectomy, and partial nephrectomy in children. We analyzed the operative time, hospital stay, and rate of complication with each approach. Specifically, we assessed the rate of vascular, solid organ, and bowel injuries. RESULTS: We found 51 articles that reported the outcomes of 689 pediatric nephrectomies. Of these, 401 were RP and 288 were TP laparoscopic renal surgeries in children. The mean patient age for RP and TP was 5.4 years and 4.8 years, respectively. The mean operative time was 129 minutes for RP and 154 minutes for TP. The hospital stay was 2.5 days for RP and 2.3 days for TP. The overall complication rate for RP was 4.3% and for TP was 3.5% (P = .58). The number of vascular injuries for RP was 2 and for TP was 0 (P = .12). The number of bowel injuries for RP was 2 and for TP was 1 (P = .68). CONCLUSIONS: According to the available published data, no significant advantage is gained by a RP or TP approach for laparoscopic nephrectomy. Although the operative time for RP was slightly shorter than for TP, the types of cases performed were not directly matched and thus were more challenging to compare. The incidence of vascular and bowel injuries was rare for both approaches. Therefore, the choice of approach should be determined by surgeon preference, patient anatomy, or the procedure to be performed.

Retrospective evaluation of pain assessment and treatment for acute vasoocclusive episodes in children with sickle cell disease.

BACKGROUND: This study was conducted to assess the care of pediatric patients hospitalized for sickle cell disease-related vasoocclusive episodes (VOE). The aim of this research was to illustrate the course of pain scores and methods of therapeutic intervention during hospitalization. PROCEDURE: Retrospective medical chart reviews were conducted to collect pain assessment and management data about children hospitalized during a 2-year period at an urban children's hospital. T tests and Chi-square analyses were used to identify differences in demographic variables, pain scores and opiate utilization. RESULTS: There were 59 children with 134 hospitalizations for VOE in a 2-year period. 50.8% of the patients were male; the mean age was 11.5 +/- 4.9 years. The average length of hospitalization was 4.6 +/- 2.7 days (range 1-19 days). Older patients stayed in the hospital significantly longer than younger patients (P = 0.002). Pain scores remained in the moderate to severe range (> or =5 out of 10) for many days in the majority of patients. Results failed to reveal significant differences in pain scores and opiate utilization between patients who had short versus extended hospitalizations, and for those patients with frequent versus infrequent hospitalizations for pain. CONCLUSIONS: Despite opiate dosing within recommended guidelines, mean pain scores remain in the moderate to severe range for several days following hospitalization for VOE. Future research should explore the factors which influence pain scores, as well as improved pain assessment and management techniques.

Reduction of topical anesthetic onset time using ultrasound: a randomized controlled trial prior to venipuncture in young children.

BACKGROUND: Ultrasound treatment prior to topical anesthetic application has been shown to speed anesthesia onset by enhancing anesthetic penetration into the skin. OBJECTIVE: To evaluate a low-frequency ultrasound device to facilitate absorption of topical anesthetic in young children who require venipuncture. METHODS: This was a prospective controlled comparison of analgesic effect of a 5-minute application of liposomal lidocaine cream after ultrasound treatment, with a 30-minute application of liposomal lidocaine cream, in children aged 3 to 7 years undergoing venipuncture. Children rated the pain of the venipuncture using the Wong-Baker FACES Pain Rating Scale (FACES) (0 = no pain, 10 = maximal pain), and parents rated their child's pain using a 100-mm (0 = no pain, 100 = maximal pain) visual analogue scale (VAS). Venipuncture skin sites were evaluated for effect immediately posttreatment, and at 24 to 72 hours post phlebotomy. RESULTS: Seventy subjects were enrolled: the first 10 patients comprised a pilot series, receiving the ultrasonic treatment and liposomal lidocaine cream; the next 60 subjects were randomized, including 29 allocated to the ultrasound treatment group, and 31 randomized to the 30-minute control treatment with liposomal lidocaine cream. Demographics were similar between the two groups. Mean child's FACES scale results were similar: Ultrasound group 4.78 (95% CI; 3.06, 6.52), CONTROL group 4.32 (95% CI; 2.82, 5.82) (P = 0.72); and mean parent VAS scores were also the same: Ultrasound: 19.1 (95% CI; 10.3, 27.8), CONTROL: 23.2 (95% CI; 14.7, 31.7) (P = 0.87). Skin effects immediately after ultrasound were limited to minor redness in 9/39 children and significant redness in 2/29 patients. CONCLUSION: Ultrasound treatment speeds time of onset of liposomal lidocaine cream anesthesia in young children undergoing venipuncture. Side effects were mild in our population.

Family and cognitive factors: modeling risk for aggression in children with ADHD.

OBJECTIVE: To explore the relationships of family and cognitive factors to aggression as reported by parents and teachers. METHOD: Data regarding different types of aggressive behavior were collected from parents and teachers of 165 school-age (7-11 years old) children referred to a study of attention-deficit/hyperactivity disorder and disruptive behavior. Structural equation modeling was used to examine the differential relationships of family and cognitive factors to aggression in the home and school settings. RESULTS: Family risk factors influenced aggression reported at home and at school, whereas cognitive risk factors may exert their influence on aggression at school. Significant covariance between parent and teacher report of aggressive behavior was observed. CONCLUSIONS: Intervention at the family level may serve to reduce aggressive behaviors in both home and school environments.

Circadian temperature rhythm of laboratory swine.

The circadian temperature rhythm (CTR) profile holds promise for monitoring the domestic pig's responses to stress and illness. In the present study we quantified the CTR profile of nine growing-finishing swine using a time-series, small-group design. Temperature was monitored using a probe implanted in the ear for 5 1/2 to 9 1/2 consecutive days while the unrestrained pigs were housed singly in pens. The dominant period of the temperature data was estimated with the autocorrelation function and then used in standard cosinor analysis to compute the amplitude (half of the distance between the highest and lowest value within the period), mesor (rhythm-adjusted mean), and acrophase (timing of the cosine maximum). To examine the effect of procedural stress on CTR, we compared data from the first 3 days with those from subsequent days. Eight of the nine (89%) pigs had CTR with a mean (+/- standard error) period of 23.6 (0.5) h, amplitude of 0.18 (0.02) degrees C, mesor of 38.7 (0.24) degrees C, and acrophase at 19:44 h. Mean mesor and acrophase were not different, but amplitude was lower (P = 0.03) during the first 3 days after instrumentation than during subsequent days. We conclude that: 1) laboratory-housed, unrestrained, growing-finishing swine have CTR; 2) our ear-based instrumentation protocol imposes acute stress as reflected in attenuated CTR amplitude during the first 3 days after instrumentation; and 3) CTR adaptation to stress appears to occur over time.

Hypersensitivity to ticks and Lyme disease risk.

Although residents of Lyme disease-endemic regions describe frequent exposure to ticks, Lyme disease develops in relatively few. To determine whether people who experience cutaneous hypersensitivity against tick bite have fewer episodes of Lyme disease than those who do not, we examined several factors that might restrict the incidence of Lyme disease among residents of Block Island, Rhode Island. Of 1,498 study participants, 27% (95% confidence interval [CI] 23%-31%) reported > or = 1 tick bites, and 17% (95% CI 13%-21%) reported itch associated with tick bite in the previous year. Borrelia burgdorferi infected 23% (95% CI 20%-26%) of 135 nymphal Ixodes scapularis (I. dammini) ticks. The likelihood of Lyme disease infection decreased with >3 reports of tick-associated itch (odds ratio 0.14, 95% CI 0.94-0.03, p = 0.01). Prior exposure to uninfected vector ticks protects residents of disease-endemic sites from Lyme disease.

Adherence to antiretroviral therapy in HIV-infected pediatric patients improves with home-based intensive nursing intervention.

Adherence to combination antiretroviral therapy (ART) has been shown to be a determining factor in controlling viral replication, maintaining immunologic function and long-term survival in HIV-positive individuals. Little information is available on strategies to improve adherence in pediatric HIV-infected patients. We conducted a randomized, nonblinded, pilot study to determine if a home-based nursing intervention would improve medication adherence. The study was offered to all eligible HIV-positive patients receiving care at Connecticut Children's Medical Center's (CCMC) Pediatric and Youth HIV Program. Sixty-seven percent (37/55) of the patients and their caretakers participated. We randomized participants to either standard of care or the intervention trial. The intervention was designed to improve knowledge and understanding of HIV infection and HIV medications and to resolve or modify barriers to adherence. Both groups completed pre- and post-intervention questionnaires, assessing their knowledge and understanding of HIV, ART, and adherence. Adherence was estimated objectively from medication refill history and subjectively from a self-report score. We also inferred adherence from pre- to post-test plasma viral load and CD4+ T-cell percentages. The knowledge score (p = 0.02) and medication refill history (p = 0.002) improved significantly in the intervention group. The adherence self-report score improved, although not significantly (p = 0.07). We did not observe statistical differences in CD4+ T-cell counts or viral load between groups. We conclude that our home-based nursing intervention helped HIV-positive children and their families in better adhering to prescribed medication regimens.

Comparisons of mortality and pre-discharge respiratory outcomes in small-for-gestational-age and appropriate-for-gestational-age premature infants.

BACKGROUND: There are differences in the literature regarding outcomes of premature small-for-gestational-age (SGA) and appropriate-for gestational-age (AGA) infants, possibly due to failure to take into account gestational age at birth. OBJECTIVE: To compare mortality and respiratory morbidity of SGA and AGA premature newborn infants. DESIGN/METHODS: A retrospective study was done of the 2,487 infants born without congenital anomalies at 32 wk (OR = 0.41, 95% CI 0.27 - 0.63; p < 0.01). After controlling for GA, SGA infants were observed to be at a significantly higher risk for developing chronic lung disease as compared to AGA infants (OR = 2.2, 95% CI = 1.2 - 3.9, P = 0.01). There was no significant difference between SGA and AGA infants in total days on ventilator. Among infants who survived, mean length of hospital stay was significantly higher in SGA infants born between 26-36 wks GA than AGA infants. CONCLUSIONS: Premature SGA infants have significantly higher mortality, significantly higher risk of developing chronic lung disease and longer hospital stay as compared to premature AGA infants. Even the reduced risk of RDS in infants born at >/=32 wk GA, (conferred possibly by intra-uterine stress leading to accelerated lung maturation) appears to be of transient effect and is counterbalanced by adverse effects of poor intrauterine growth on long term pulmonary outcomes such as chronic lung disease.

Cyclooxygenase-2 inhibitor treatment improves left ventricular function and mortality in a murine model of doxorubicin-induced heart failure.

BACKGROUND: Progression of heart failure after initial myocardial injury is mediated in part by various redundant inflammatory mediators, including the widely expressed cyclooxygenase-2 (COX-2). Because COX-2 inhibitors are useful in treating many inflammation-mediated diseases, we asked whether COX-2 inhibition can attenuate heart failure progression. METHODS AND RESULTS: Heart failure was experimentally induced in 100 mice by administration of doxorubicin (4 mg. kg(-1). wk(-1) for 6 weeks). Beginning at day 42, mice were fed daily with either COX-2 inhibitor-containing mice chow (n=50) or plain mice chow (controls; n=50). Left ventricular ejection fraction was evaluated as a measure of heart failure by a novel method of transthoracic echocardiography (with intravascular ultrasound catheters) at baseline and on days 42, 56, and 70. From baseline to study termination, left ventricular ejection fraction in COX-2 inhibitor-treated mice decreased significantly less than in control mice (9% versus 29%, P<0.01). Mortality was significantly lower for COX-2 inhibitor-treated mice than for control mice (18% versus 38%, P<0.01). These results were confirmed in a revalidation study in COX-2 inhibitor-treated mice (n=25) and controls (n=25). That study revealed that the hearts from control mice weighed roughly the same as hearts from COX-2 inhibitor-treated mice but showed more extensive signs of cardiomyopathy (as determined by pathological analysis by an independent, blinded observer) and higher levels of COX-2 proteins (as determined by immunoblotting [6442+/-1635 versus 4300+/-2408 arbitrary units, P<0.022]). CONCLUSIONS: COX-2 inhibitors can attenuate the progression of heart failure in a murine model of doxorubicin-induced heart failure.

Gastroesophageal reflux in infants < 32 weeks gestational age at birth: lack of relationship to chronic lung disease.

The objective of this study was to determine the incidence of gastroesophageal reflux (GER) as documented by extended esophageal pH monitoring in symptomatic premature infants and to identify its relationship with chronic lung disease (CLD). This was a retrospective study of 629 infants born < 32 weeks gestational age and admitted to the neonatal intensive care unit during the study period. Univariate analyses were done on the 137 infants undergoing the test for the association of the following risk factors with acid reflux: birth weight, gestational age, race, sex, length of stay, bronchopulmonary dysplasia (BPD; O2 requirement at 28 days), and severe CLD (O2 requirement at 36 weeks postmenstrual age). Eighty-seven of 137 infants were positive for GER. There was no association of GER with the risk factors studied, nor were there correlations with BPD or severe CLD. GER is common (63%) in premature infants < 32 weeks gestational age but clinical symptoms and CLD are poorly correlated with this diagnosis.

Feasibility of a porcine adult intensive care model.

A porcine adult ICU model would be useful for several avenues of investigation relevant to the care of critically ill patients. The purpose of the experiments reported here was to test the feasibility of such a model, using healthy swine. Swine (n = 4; body weight, 76 +/- 5 kg) were instrumented with endotracheal, bladder, and central arterial and venous catheters, and were admitted to the intensive care unit (ICU) while undergoing mechanical ventilation under the continuous care of nurses. Cardiopulmonary parameters were monitored continuously, and serum biochemical parameters were measured intermittently. Survival was seven days in subject 1 and five and a half days in subject 2. Subjects 3 and 4 survived an abbreviated protocol (44 and 41 h, respectively). Care of the subjects was complicated by iatrogenic hemorrhage (n = 3), pneumonia (n = 2), and acute respiratory distress syndrome (n = 1). One subject was free of complications. Critically ill swine > or = 70 kg can survive mechanical ventilation in the ICU for up to seven days. When iatrogenic injury occurs, swine respond well to clinical care protocols. Further testing is needed to develop a reproducible model and determine whether healthy swine can survive the ICU environment for longer than 41 h.

Growth hormone response to guanfacine in boys with attention deficit hyperactivity disorder: a preliminary study.

OBJECTIVE: This preliminary study evaluated a method for assessing central noradrenergic function in children via the growth hormone response to a single dose of the alpha-2 adrenergic receptor agonist guanfacine and examined whether this measure distinguishes between attention deficit hyperactivity disorder (ADHD) boys with and without reading disabilities (RD). METHODS: Plasma growth hormone was assessed before and after the oral administration of guanfacine and placebo in boys with ADHD who were divided into subgroups based on the presence (n = 3) or absence (n = 5) of RD. RESULTS: Guanfacine and placebo conditions did not differ at baseline, but peak growth hormone was significantly higher following guanfacine. The increase in growth hormone following guanfacine was significantly greater in boys without RD as compared to those with RD, with no overlap between the groups. CONCLUSIONS: Consistent with findings using peripheral measures of noradrenergic function, these preliminary data suggest that ADHD boys with and without RD may differ in central noradrenergic function.

Familial correlates of central serotonin function in children with disruptive behavior disorders.

Previous findings suggest a relationship between childhood aggression, parental history of aggression and central serotonin (5-HT) function. The present study extended these findings by examining the impact of childhood aggression and central 5-HT function on the incidence of psychopathology in first- and second-degree relatives of pre-pubertal children with disruptive behavior disorders. Family history of psychopathology was obtained for 58 aggressive and 44 non-aggressive clinically referred children who were further sub-divided based on central 5-HT function. Central 5-HT function was assessed by measuring the prolactin response to a 1 mg/kg oral dose of d,l-fenfluramine. Aggressive children with low-prolactin responses to fenfluramine had a significantly greater incidence of first- and second-degree relatives with aggressive and antisocial characteristics compared to both non-aggressive children and aggressive children with high-prolactin responses. No group differences were found in the frequency of relatives with symptoms of cognitive impairment or inattention and hyperactivity. These data suggest that there are both familial and non-familial forms of aggression in children, and that only the familial type is associated with reduced 5-HT function.