A novel technique to manage transcatheter aortic valve embolization.

We report a case of a 69-year-old male who was planned for a transcatheter aortic valve replacement (TAVR) with a 26 mm Sapien 3 Valve (Edwards Lifesciences, Irvine, California) for the treatment of symptomatic severe aortic stenosis. During rapid ventricular pacing and implantation of the TAVR valve, there was a loss of pacing capture and subsequent embolization of the valve into the aortic arch. Retrieval of the embolized valve was attempted unsuccessfully using several techniques. Finally, by using a 34 mm Evolut R Valve (Medtronic, Minneapolis, Minnesota), we were able to secure the embolized valve in the transverse segment of the aortic arch without compromising the branch vessels. To our knowledge, this is the first reported case of using a valve-in-valve approach to fixate an embolized valve in the transverse aorta.

Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG).

BACKGROUND: Sickle-cell anaemia is associated with substantial morbidity from acute complications and organ dysfunction beginning in the first year of life. Hydroxycarbamide substantially reduces episodes of pain and acute chest syndrome, admissions to hospital, and transfusions in adults with sickle-cell anaemia. We assessed the effect of hydroxycarbamide therapy on organ dysfunction and clinical complications, and examined laboratory findings and toxic effects. METHODS: This randomised trial was undertaken in 13 centres in the USA between October, 2003, and September, 2009. Eligible participants had haemoglobin SS (HbSS) or haemoglobin Sß(0)thalassaemia, were aged 9-18 months at randomisation, and were not selected for clinical severity. Participants received liquid hydroxycarbamide, 20 mg/kg per day, or placebo for 2 years. Randomisation assignments were generated by the medical coordinating centre by a pre-decided schedule. Identical appearing and tasting formulations were used for hydroxycarbamide and placebo. Patients, caregivers, and coordinating centre staff were masked to treatment allocation. Primary study endpoints were splenic function (qualitative uptake on (99)Tc spleen scan) and renal function (glomerular filtration rate by (99m)Tc-DTPA clearance). Additional assessments included blood counts, fetal haemoglobin concentration, chemistry profiles, spleen function biomarkers, urine osmolality, neurodevelopment, transcranial Doppler ultrasonography, growth, and mutagenicity. Study visits occurred every 2-4 weeks. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00006400. FINDINGS: 96 patients received hydroxycarbamide and 97 placebo, of whom 83 patients in the hydroxycarbamide group and 84 in the placebo group completed the study. Significant differences were not seen between groups for the primary endpoints (19 of 70 patients with decreased spleen function at exit in the hydroxycarbamide group vs 28 of 74 patients in the placebo group, p=0·21; and a difference in the mean increase in DTPA glomerular filtration rate in the hydroxycarbamide group versus the placebo group of 2 mL/min per 1·73 m(2), p=0·84). Hydroxycarbamide significantly decreased pain (177 events in 62 patients vs 375 events in 75 patients in the placebo group, p=0·002) and dactylitis (24 events in 14 patients vs 123 events in 42 patients in the placebo group, p<0·0001), with some evidence for decreased acute chest syndrome, hospitalisation rates, and transfusion. Hydroxyurea increased haemoglobin and fetal haemoglobin, and decreased white blood-cell count. Toxicity was limited to mild-to-moderate neutropenia. INTERPRETATION: On the basis of the safety and efficacy data from this trial, hydroxycarbamide can now be considered for all very young children with sickle-cell anaemia. FUNDING: The US National Heart, Lung, and Blood Institute; and the National Institute of Child Health and Human Development.

Abdominal ultrasound with scintigraphic and clinical correlates in infants with sickle cell anemia: baseline data from the BABY HUG trial.

OBJECTIVE: The purpose of this study is to perform and evaluate baseline abdominal ultrasound in infants with sickle cell anemia who participated in the BABY HUG multiinstitutional randomized placebo-controlled trial of hydroxyurea therapy and to examine the potential relationships among ultrasound results and clinical, nuclear medicine, and laboratory data. SUBJECTS AND METHODS: After local institutional review board approval and with informed guardian consent, 116 girls and 87 boys (age range, 7.5-18 months) with sickle cell anemia underwent standardized abdominal sonography at 14 institutions. Imaging was centrally reviewed by one radiologist who assessed and measured the spleen, kidneys, gallbladder, and common bile duct. Baseline physical assessment of spleen size, serum alanine aminotransferase and bilirubin levels, (99m)Tc sulfur colloid liver-spleen scans, and (99m)Tc diethylenetriaminepentaacetic acid clearance glomerular filtration rates (GFRs) were obtained. Analysis of variance and the Student test were performed to compare sonographic findings to published results in healthy children and to clinical and laboratory findings. RESULTS: The mean (± SD) spleen volume (108 ± 47 mL) was significantly greater than published normal control values (30 ± 14 mL; p < 0.0001). There was no correlation between spleen volume and function assessed by liver-spleen scan. The mean GFR (125 ± 34 mL/min/1.73 m(2)) was elevated compared with control GFRs (92 ± 18 mL/min/1.73 m(2)). Renal volumes (right kidney, 29 ± 8 mL; left kidney, 31 ± 9 mL) were significantly greater than control volumes (right kidney, 27 ± 3 mL; left kidney, 27 ± 3 mL; p < 0.0001) and were positively correlated with GFR (p = 0.0009). Five percent of patients had sonographic biliary abnormalities (sludge, n = 6; dilated common bile duct, n = 2; and cholelithiasis and thickened gallbladder wall, n = 1 each). There was no correlation between biliary sonographic findings and laboratory results. CONCLUSION: In infants with sickle cell anemia, sonographic spleen volume does not reflect function, but increased renal volume correlates with GFR and is consistent with hyperfiltration. Sonographic biliary abnormalities can occur early in life, while remaining clinically silent.

Adherence to study medication and visits: data from the BABY HUG trial.

BACKGROUND: Subject retention and adherence are essential to maintain the power and validity of the Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG). We designed a study to assess adherence with study medication administration and study visits and to evaluate socioeconomic factors (SES) that may influence these measurements of adherence. These data are important for assessing impact of adherence on BABY HUG trial outcome and defining impact of SES on adherence. METHODS: Each subject's median study medication (MedAd) and mean visit adherence (VAd) were evaluated. We examined associations of adherence with SES of participating families. RESULTS: MedAd data were available on 153 of the 191 subjects who started randomized study medication. MedAd was 101.7% of volume prescribed, with 88.9% of subjects taking at least 80% of doses. VAd data were available on 185 of the 191 subjects who started randomized study medication. VAd was 97.3%, with 82.2% of subjects having no missed visits. During dose titration, subjects had on average 12.9% higher medication adherence than subjects who were on a stable dose and had less frequent study visits. MedAd and VAd were not significantly associated with SES. CONCLUSION: Subjects in the BABY HUG trial have had excellent adherence. SES was not associated with adherence, suggesting that SES should not be used as a criterion for enrolment in clinical trials. Additional efforts are needed to maintain medication adherence, particularly when the interval between scheduled visits increases. (ClinicalTrials.gov number, NCT00006400).

Transcranial doppler ultrasonography (TCD) in infants with sickle cell anemia: baseline data from the BABY HUG trial.

BACKGROUND: Transcranial Doppler ultrasonography (TCD) is used to predict stroke risk in children with sickle cell anemia (SCA), but has not been adequately studied in children under age 2 years. PROCEDURE: TCD was performed on infants with SCA enrolled in the BABY HUG trial. Subjects were 7-17 months of age (mean 12.6 months). TCD examinations were successfully performed in 94% of subjects (n = 192). RESULTS: No patient had an abnormal TCD as defined in the older child (time averaged maximum mean TAMM velocity > or =200 cm/sec) and only four subjects (2%) had velocities in the conditional range (170-199 cm/sec). TCD velocities were inversely related to hemoglobin (Hb) concentration and directly related to increasing age. CONCLUSION: Determination of whether the TCD values in this very young cohort of infants with SCA can be used to predict stroke risk later in childhood will require analysis of exit TCD's and long-term follow-up, which is ongoing (ClinicalTrials.gov number, NCT00006400).

Patient acceptability of manual versus electric vacuum aspiration for early pregnancy loss.

OBJECTIVE: To compare the safety, efficacy, postprocedure quality of life, and acceptability of manual vacuum aspiration (MVA) performed as an outpatient with electric vacuum aspiration (EVA) performed in a hospital in women experiencing a first-trimester miscarriage. METHODS: From a randomized multicenter trial comparing misoprostol with vacuum aspiration for first-trimester loss, data were extracted comparing the safety, efficacy, and acceptability of MVA in an office setting with local anesthesia with EVA in an operating room environment with spinal or general anesthesia or monitored anesthesia care (MAC). RESULTS: One hundred fifty-seven women underwent EVA or MVA. Efficacy and safety were similar in both groups. Physical and emotional role functioning scores were better in patients undergoing MVA (p=0.01), and fewer patients undergoing MVA missed work or required help at home (p<0.01). However, pain severity scores were better in the EVA arm of the study (p=0.03). There was a trend toward fewer MVA patients recommending or using this procedure again. CONCLUSIONS: In patients with early pregnancy loss, treatment with MVA as an outpatient with local anesthesia is an effective and safe alternative to EVA performed in a hospital with conscious sedation or spinal or general anesthesia. Treatment in the outpatient setting allows for a better physical and emotional quality of life postprocedure.

Factors related to successful misoprostol treatment for early pregnancy failure.

OBJECTIVE: To identify potential predictors for treatment success in medical management with misoprostol for early pregnancy failure. METHODS: We conducted a planned secondary analysis of data from a multicenter trial that compared medical and surgical management of early pregnancy failure. Medical management consisted of misoprostol 800 mug vaginally on study day 1, with a repeat dose if indicated on day 3. Women returned on days 3 and 15, and a telephone interview was conducted on day 30. Failure was defined as suction aspiration for any reason within 30 days. Demographic, historical, and outcome variables were included in univariable analyses of success. Multivariable analyses were conducted using clinical site, gestational age, and variables for which the univariable analysis resulted in a P < .1 to determine predictors of overall treatment success and first-dose success. RESULTS: Of the 491 women who received misoprostol, 485 met the criteria for this secondary analysis. Lower abdominal pain or vaginal bleeding within the last 24 hours, Rh-negative blood type, and nulliparity were predictive of overall success. However, only vaginal bleeding within the last 24 hours and parity of 0 or 1 were predictive of first-dose success. Overall success exceeds 92% in women who have localized abdominal pain within the last 24 hours, Rh-negative blood type, or the combination of vaginal bleeding in the past 24 hours and nulliparity. CONCLUSION: Misoprostol treatment for early pregnancy failure is highly successful in select women, primarily those with active bleeding and nulliparity. Clinicians and patients should be aware of these differences when considering misoprostol treatment. LEVEL OF EVIDENCE: II-2.

Hormone pattern after misoprostol administration for a nonviable first-trimester gestation.

OBJECTIVE: To evaluate serial hormone concentrations in subjects treated with vaginally administered misoprostol for early pregnancy failure. DESIGN: As part of a randomized clinical trial, serum was collected on treatment days 1, 3, 8, and 15. SETTING: Multicenter clinical trial. PATIENT(S): Women with a nonviable first-trimester pregnancy. INTERVENTION(S): Serum concentrations of human chorionic gonadotropin (hCG), progesterone, and sex hormone binding globulin (SHBG) were evaluated. MAIN OUTCOME MEASURE(S): A logistic regression model was constructed to assess the associations of percent and complete expulsion of the gestational sac and/or successful management. RESULT(S): The percent change from the day of treatment until the first follow-up visit was predictive for complete expulsion for progesterone (P) (P<.005) and hCG (P<.005), but not for SHBG. The actual value was not significantly associated with complete expulsion or successful management. A decrease (day 1-3) of 79% for both hCG and P was associated with a 90% probability of complete passage of the gestational sac. A 90% probability of successful management was noted if P decreased by 78% on day 3 or 59% on day 7, or hCG decreased by 74% on day 3 or 78% on day 7 compared with pretreatment values. CONCLUSION(S): Percent change, but not absolute change, in serial hormone values are strongly associated with both the complete expulsion of the gestational sac with one dose of misoprostol and ultimate success.

Feasibility of an innovative third-year chief resident system: an internal medicine residency leadership study.

INTRODUCTION: The role of the internal medicine chief resident includes various administrative, academic, social, and educational responsibilities, fulfillment of which prepares residents for further leadership tasks. However, the chief resident position has historically only been held by a few residents. As fourth-year chief residents are becoming less common, we considered a new model for rotating third-year residents as the chief resident. METHODS: Online surveys were given to all 29 internal medicine residents in a single university-based program after implementation of a leadership curriculum and specific job description for the third-year chief resident. Chief residents evaluated themselves on various aspects of leadership. Participation was voluntary. Descriptive statistics were generated using SPSS version 21. RESULTS: Thirteen junior (first- or second-year) resident responses reported that the chief residents elicited input from others (mean rating 6.8), were committed to the team (6.8), resolved conflict (6.7), ensured efficiency, organization and productivity of the team (6.7), participated actively (7.0), and managed resources (6.6). Responses from senior residents averaged 1 point higher for each item; this pattern repeated itself in teaching evaluations. Chief resident self-evaluators were more comfortable running a morning report (8.4) than with being chief resident (5.8). CONCLUSION: The feasibility of preparing internal medicine residents for leadership roles through a rotating PGY-3 (postgraduate year) chief residency curriculum was explored at a small internal medicine residency, and we suggest extending the study to include other programs.

Revised reference curves for bone mineral content and areal bone mineral density according to age and sex for black and non-black children: results of the bone mineral density in childhood study.

CONTEXT: Deficits in bone acquisition during growth may increase fracture risk. Assessment of bone health during childhood requires appropriate reference values relative to age, sex, and population ancestry to identify bone deficits. OBJECTIVE: The objective of this study was to provide revised and extended reference curves for bone mineral content (BMC) and areal bone mineral density (aBMD) in children. DESIGN: The Bone Mineral Density in Childhood Study was a multicenter longitudinal study with annual assessments for up to 7 yr. SETTING: The study was conducted at five clinical centers in the United States. PARTICIPANTS: Two thousand fourteen healthy children (992 males, 22% African-Americans) aged 5-23 yr participated in the study. INTERVENTION: There were no interventions. MAIN OUTCOME MEASURES: Reference percentiles for BMC and aBMD of the total body, lumbar spine, hip, and forearm were obtained using dual-energy x-ray absorptiometry for Black and non-Black children. Adjustment factors for height status were also calculated. RESULTS: Extended reference curves for BMC and aBMD of the total body, total body less head, lumbar spine, total hip, femoral neck, and forearm for ages 5-20 yr were constructed relative to sex and age for Black and non-Black children. Curves are similar to those previously published for 7-17 year olds. BMC and aBMD values were greater for Black vs. non-Black children at all measurement sites. CONCLUSIONS: We provide here dual-energy x-ray absorptiometry reference data on a well-characterized cohort of 2012 children and adolescents. These reference curves provide the most robust reference values for the assessment and monitoring of bone health in children and adolescents in the literature to date.