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Our purpose is to explore the effect of postmastectomy radiation therapy (PMRT) modality and timing on complication rates in breast cancer patients receiving immediate 2-stages expander/implant. We reviewed the charts of 661 patients who underwent immediate 2-stages expander/implant with/without PMRT at our institution from 2000 to 2019. Patients were divided into 3 cohorts: no radiation, PMRT to expanders (RTE), and PMRT to implants after expander exchange (RTI). PMRT was delivered either with 3-dimensional conformal photon with or without chest wall boost (CWB) or proton therapy. Reconstruction complications were defined as infection/necrosis requiring debridement, capsular-contracture requiring capsulotomy, and reconstruction failure requiring prothesis removal. Logistic regression and Cox models were used to assess the effect of different radiation therapy modalities on complication rates and local control. Among 661 patients, 309 (46.7%) received PMRT, 220 of the 309 (71.2%) received RTE before exchange, and 89 (28.8%) received RTI after exchange. Seventeen out of 309 (5.5%) patients received proton therapy. The complications among RTE versus RTI cohorts were 22.7% versus 15.7% for infection/necrosis, 13.6% versus 19.1% for capsular-contracture, and 39.5% versus 31.5% for overall reconstruction failure, respectively. Among proton patients, 8/17 (47%) developed capsular contracture compared with 16.4% (24/146) and 10.3% (15/146) in CWB and non-CWB groups, respectively. Adjusted multivariable analysis showed no significant difference between RTI and RTE in terms of infection/necrosis and capsular contracture. Yet, RTE significantly increased overall reconstruction failure compared with RTI (39.5% vs 31.5%; odds ratio [OR], 2.11; P =.02). Protons significantly increased capsular contracture compared with both CWB and non-CWB groups (OR, 5.4; P =.01 and OR, 10.9; P <.001, respectively). Moreover, proton significantly increased overall reconstruction failure. The 5-year local control rates were 95.3% and 97.7% for RTE and RTI, respectively (hazard ratio, 1.2; P =.7). Early radiation to the expander before the exchange to implant significantly increased overall reconstruction failure without improving local control. Protons significantly increased capsular contracture rates and overall reconstruction failure leading to more revision surgeries. [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2007.10.024 Byline: Dalton S. McLean (a), Shmuel Ravid (b), Michael Blazing (c), Bernard Gersh (d), Amy Shui (a), Christopher P. Cannon (a) Abstract: Inflammation has been suggested as a factor in the initiation and maintenance of atrial fibrillation (AF). Several observational studies have suggested that statins, presumably through their anti-inflammatory properties, decrease the risk of AF. Author Affiliation: (a) Cardiovascular Division, Department of Medicine, Thrombolysis in Myocardial Infarction (TIMI) Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (b) Lown Cardiovascular Center, Brigham and Women's Hospital, Harvard Medical School, Brookline, MA (c) Duke Clinical Research Institute, Durham, NC (d) Mayo Clinic College of Medicine, Rochester, MN Article History: Received 20 August 2007; Accepted 19 October 2007

A network of 18 pediatric practice locations serving predominantly commercially insured patients implemented the electronic administration of the Pediatric Symptom Checklist-17 parent-report (PSC-17P) for all 5.50- to 17.99-year-old children seen for well child visits (WCVs) and wrote up the results as a quality improvement project. The current study investigated this screening over 2 years to assess its implementation and risk rates over time. Parents completed the PSC-17P electronically before the visit and the scored data were immediately available in the patient's chart. Using billing and screening data, the study tracked rates of overall and positive screening during the first-year baseline (4 months) and full implementation phases of the project in the first (8 months) and second (12 months) year. A total of 35,237 patients completed a WCV in the first year. There was a significant improvement in PSC-17P screening rates from the first-year baseline (26.3%) to full implementation (89.3%; P <.001) phases. In the second year, a total of 40,969 patients completed a WCV and 77.9% (n = 31,901) were screened, including 18,024 patients with screens in both years. PSC-17P screening rates varied significantly across the 18 locations and rates of PSC-17P risk differed significantly by practice, insurance type, sex, and age. The current study demonstrated the feasibility of routine psychosocial screening over 2 years using the electronically administered PSC-17P in a network of pediatric practices. This study also corroborated past reports that PSC-17 risk rates differed significantly by insurance type (Medicaid vs commercial), sex, and age group. [ABSTRACT FROM AUTHOR]

Background: Sleep difficulties in children with autism spectrum disorders (ASD) have been well-established.Aims: To develop a model to predict sleep problems in children with ASD.Methods and Procedures: A sample of children in the Autism Speaks-Autism Treatment Network (ATN) registry without parent-reported sleep problems at baseline and with sleep problem (yes/no) data at first annual followup was randomly split into training (n = 527) and test (n = 518) samples. Model predictors were selected using the training sample, and a threshold for classifying children at risk was determined. Comparison of the predicted and true sleep problem status of the test sample yielded model performance measures.Outcomes and Results: In a multivariable model aggressive behavior among children with no sleep problems reported at baseline was associated with having more sleep problems at the first annual follow-up visit. This model performed in the test sample with high sensitivity and accurate prediction of low risk.Conclusions and Implications: Among children with ASD aggressive behavior independently predicts sleep problems. The model's high sensitivity for identifying children at risk and its accurate prediction of low risk can help with treatment and prevention of sleep problems. Further data collection may provide better prediction through methods requiring larger samples. [ABSTRACT FROM AUTHOR]

Objectives To examine the one-year course of parent-reported abdominal pain in children with autism spectrum disorder (ASD), and to determine whether anxiety and sensory over-responsivity (SOR) contribute to the onset or remission of abdominal pain. Methods Participants included 225 children (ages 2–17) with ASD enrolled in the Autism Speaks Autism Treatment Network. Primary measures included the parent-reported GI Symptom Inventory Questionnaire, Child Behavior Checklist, and Short Sensory Profile. Results One-fourth (25.8%) experienced chronic abdominal pain (duration ≥3 months) at baseline, persisting at one-year follow-up for 86.7%. New onset pain occurred for 23.8% of those without baseline pain. Anxiety, SOR, and chronic abdominal pain were associated at baseline. SOR significantly predicted new onset pain, but neither anxiety nor SOR were predictors of pain remission. Conclusions Abdominal pain appears to be common and persistent among children with ASD. The relations among SOR, anxiety and abdominal pain offer information about potential underlying mechanisms. [ABSTRACT FROM AUTHOR]

Both renal dysfunction and elevated levels of high-sensitivity C-reactive protein (CRP) are associated with a higher risk of cardiovascular (CV) outcomes. However, it remains to be established whether the prognostic value of impaired estimated glomerular filtration rate (GFR) remains after accounting for markers of inflammation. Methods and Results: Glomerular filtration rate was estimated using the Modification of Diet in Renal Disease equation in 4178 patients with non-ST or ST-elevation acute coronary syndromes, participating in the A to Z trial. The mean estimated GFR was 68 mL/min, with a median baseline CRP of 20.2 mg/L. Both an estimated GFR <60 mL/min (HR 2.13, 95% CI 1.7-2.6) and a CRP in the fourth quartile (HR 1.7, 95% CI 1.4-2.2) were strong univariate predictors of a CV event (composite of CV death, recurrent myocardial infarction, heart failure, or stroke). After adjusting for baseline CRP, GFR <60 mL/min remained a strong multivariate predictor for CV death (HR 1.82, 95% CI 1.1-2.97). Randomization to high-dose statin therapy was associated with a reduction in the CV composite (adjusted HR 0.69, 95% CI 0.5-0.95) irrespective of baseline renal function. Conclusions: In a population of patients without overt renal disease, moderate reductions in estimated GFR remain an important prognostic marker. This increased CV hazard associated with an estimated GFR <60 mL/min is independent and additive to markers of inflammation. [Copyright &y& Elsevier]

• Our study sample consists of children with ASD ages 0−17 years. • Higher ASD severity is associated with shorter sleep duration. • Greater bedtime consistency is associated with longer sleep duration. • Addressing sleep problems through good sleep habits may promote healthy sleep. Sleep problems are common in individuals with ASD. This study examined the relationships between bedtime consistency, cognitive functioning, comorbid diagnoses, intervention, demographics and sleep duration in children with ASD. Cross-sectional data from 1683 children with ASD in the 2016 and 2017 National Survey of Children's Health were analyzed. The sample was 80 % male, 46 % non-Hispanic white, and mean age was 10.5 (SD 4.1) years. All data were parent report. Multiple linear regression was performed. ASD severity was associated with shorter sleep duration, and bedtime consistency was associated with longer sleep duration. Age moderated the effects of both bedtime consistency and ADD/ADHD on sleep duration. Both the positive effect of bedtime consistency and the negative effect of ADD/ADHD on sleep duration became less pronounced with age. Although the challenges related to sleep and behavior may differ by age of the child, bedtime consistency could be a good target to improve sleep duration for all children with ASD. Future studies, especially longitudinal studies, on sleep habits and sleep hygiene, in conjunction with other measures of sleep patterns (e.g., night wakings) and correlates of sleep problems, may provide further evidence for the importance of good sleep practices and guide sleep treatment in children with ASD. [ABSTRACT FROM AUTHOR]

High levels of adhesion molecules, such as soluble intercellular adhesion molecule-1 (sICAM-1), are associated with long-term risk of cardiac events in patients with and without stable coronary artery disease. The relation between sICAM-1 and long-term risk after acute coronary syndromes (ACSs) and the influence of statin treatment has not been explored. Using a nested case-control design, patients with ACS who were enrolled in the PROVE IT-TIMI 22 trial were matched for age, gender, smoking, diabetes, type of ACS presentation, and revascularization for index event (583 patients with recurrent events vs 581 controls). Patients with recurrent events were identified as such by death, myocardial infarction, or hospitalization for recurrent ACS. Soluble ICAM-1 was measured at study entry (approximately 7 days after ACS). After adjusting for statin regimen and other risk factors, patients in quartiles 2 to 4 were at a higher risk of clinical events compared with those in quartile 1 (odds ratio 1.6 for quartile 4 vs 1, 95% confidence interval 1.1 to 2.3, p = 0.02). The risk of adverse events in patients with sICAM-1 levels in quartiles 2 to 4 was most marked in subjects who were allocated to standard dose statin therapy, even after adjusting for low-density lipoprotein cholesterol and C-reactive protein at day 30. The risk in quartiles 2 to 4 was somewhat attenuated in the intensive therapy group. In conclusion, in this large study of patients with ACS, we provide evidence that increased endothelial activation after ACS is independently associated with increased long-term risk of death, myocardial infarction, or recurrent ACS. [Copyright &y& Elsevier]

Background: Insomnia and low iron stores are common in children with autism spectrum disorders, and low iron stores have been associated with sleep disturbance.Methods: We performed a randomized placebo-controlled trial of oral ferrous sulfate to treat insomnia in children with autism spectrum disorders and low normal ferritin levels. Twenty participants who met inclusion criteria and whose insomnia did not respond to sleep education were randomized to 3 mg/kg/day of ferrous sulfate (n = 9) or placebo (n = 11) for three months.Results: Iron supplementation was well tolerated, and no serious adverse events were reported. Iron supplementation improved iron status (+18.4 ng/mL active versus -1.6 ng/mL placebo, P = 0.044) but did not significantly improve the primary outcome measures of sleep onset latency (-11.0 minutes versus placebo, 95% confidence interval -28.4 to 6.4 minutes, P = 0.22) and wake time after sleep onset (-7.7 minutes versus placebo, 95% confidence interval -22.1 to 6.6 min, P = 0.29) as measured by actigraphy. Iron supplementation was associated with improvement in the overall severity score from the Sleep Clinical Global Impression Scale (-1.5 points versus placebo, P = 0.047). Changes in measures of daytime behavior did not differ between groups.Conclusion: This trial demonstrated no improvement in primary outcome measures of insomnia in subjects treated with ferrous sulfate compared with placebo. Interpretation was limited by low enrollment. [ABSTRACT FROM AUTHOR]

The article discusses a study which described early generlized overgrowth in a subgroup of children with autism spectrum disorder (ASD) given the suggestion that overgrowth may be associated with a particular pattern of cognitive and social impairment in ASD. It cites hypothesis that early generalized overgrowth may serve as a biomarker for a distinct subgroup of children with ASD.

Purpose The objective of this retrospective observational study was to describe and identify clinical and demographic characteristics associated with the choice of first injectable therapy (glucagon-like peptide-1 receptor agonist [GLP-1-RA] or basal insulin) among patients with type 2 diabetes mellitus (T2DM). Methods This analysis included adults naive to injectable therapy with T2DM who initiated a GLP-1-RA or basal insulin (index date) between November 2014 and February 2016 using data from the Practice Fusion Electronic Health Record database. Patients with T2DM, ≥1 office visit between 6 and 18 months before the index date, and with ≥1 glycosylated hemoglobin (HbA 1c ) result in the 6-month preindex (baseline) period were included. A generalized boosted regression model was used to determine the patient characteristics most influential in the selection of a GLP-1-RA or basal insulin as first injectable therapy. Sensitivity analysis was performed by using bootstrapped logistic regression. Findings The study included 3546 and 7507 GLP-1-RA and basal insulin initiators, respectively. At baseline, GLP-1-RA initiators were significantly younger (mean, 58 vs 63 years), had lower HbA 1c values (mean, 8.2% vs 9.1%), lower Diabetes Complications Severity Index (DCSI) scores (mean, 1.0 vs 1.7), and a higher body mass index (BMI) (mean, 36 vs 33 kg/m 2 ) compared with basal insulin initiators. Variables selected by using the generalized boosted regression model with the highest relative importance (≥5%) in the selection of GLP-1-RA or basal insulin were HbA 1c level (20.43%), BMI (17.73%), age (12.21%), prior prescription of a sodium-glucose cotransporter-2 inhibitor (9.17%), and DCSI score (8.39%). The same variables, as well as race, were selected by using stepwise logistic regression in all the bootstrapped samples. Patients who were older (adjusted odds ratio [OR], 0.975 [95% CI, 0.971–0.979]) and had higher HbA 1c values (OR, 0.741 [95% CI, 0.721–0.761]) and DCSI scores (OR, 0.870 [95% CI, 0.848–0.892]) were significantly less likely to be prescribed a GLP-1-RA compared with basal insulin. Patients with higher BMI (OR, 1.046 [95% CI, 1.040–1.053]) and previous prescription of sodium-glucose cotransporter-2 inhibitors (OR, 2.633 [95% CI, 2.224–2.982]) were significantly more likely to be prescribed a GLP-1-RA. Implications The clinically relevant differences observed between the 2 patient populations suggest that GLP-1-RAs and basal insulin are prescribed to different types of patients with T2DM. Examining patients’ demographic and clinical characteristics may be important in assisting physicians in the choice of patient-centered injectable treatment regimens. [ABSTRACT FROM AUTHOR]

Summary Background Glutamate excitotoxicity might contribute to the pathophysiology of amyotrophic lateral sclerosis. In animal models, decreased excitatory aminoacid transporter 2 (EAAT2) overexpression delays disease onset and prolongs survival, and ceftriaxone increases EAAT2 activity. We aimed to assess the safety and efficacy of ceftriaxone for amyotrophic lateral sclerosis in a combined phase 1, 2, and 3 clinical trial. Methods This three-stage randomised, double-blind, placebo-controlled study was done at 59 clinical sites in the USA and Canada between Sept 4, 2006, and July 30, 2012. Eligible adult patients had amyotrophic lateral sclerosis, a vital capacity of more than 60% of that predicted for age and height, and symptom duration of less than 3 years. In stages 1 (pharmacokinetics) and 2 (safety), participants were randomly allocated (2:1) to ceftriaxone (2 g or 4 g per day) or placebo. In stage 3 (efficacy), participants assigned to ceftriaxone in stage 2 received 4 g ceftriaxone, participants assigned to placebo in stage 2 received placebo, and new participants were randomly assigned (2:1) to 4 g ceftriaxone or placebo. Participants, family members, and site staff were masked to treatment assignment. Randomisation was done by a computerised randomisation sequence with permuted blocks of 3. Participants received 2 g ceftriaxone or placebo twice daily through a central venous catheter administered at home by a trained caregiver. To minimise biliary side-effects, participants assigned to ceftriaxone also received 300 mg ursodeoxycholic acid twice daily and those assigned to placebo received matched placebo capsules. The coprimary efficacy outcomes were survival and functional decline, measured as the slope of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov , number NCT00349622 . Findings Stage 3 included 66 participants from stages 1 and 2 and 448 new participants. In total, 340 participants were randomly allocated to ceftriaxone and 173 to placebo. During stages 1 and 2, mean ALSFRS-R declined more slowly in participants who received 4 g ceftriaxone than in those on placebo (difference 0·51 units per month, 95% CI 0·02 to 1·00; p=0·0416), but in stage 3 functional decline between the treatment groups did not differ (0·09, −0·06 to 0·24; p=0·2370). No significant differences in survival between the groups were recorded in stage 3 (HR 0·90, 95% CI 0·71 to 1·15; p=0·4146). Gastrointestinal adverse events and hepatobiliary adverse events were more common in the ceftriaxone group than in the placebo group (gastrointestinal, 245 of 340 [72%] ceftriaxone vs 97 of 173 [56%] placebo, p=0·0004; hepatobiliary, 211 [62%] vs 19 [11%], p<0·0001). Significantly more participants who received ceftriaxone had serious hepatobiliary serious adverse events (41 participants [12%]) than did those who received placebo (0 participants). Interpretation Despite promising stage 2 data, stage 3 of this trial of ceftriaxone in amyotrophic lateral sclerosis did not show clinical efficacy. The adaptive design allowed for seamless transition from one phase to another, and central venous catheter use in the home setting was shown to be feasible. Funding National Institute of Neurological Disorders and Stroke. [ABSTRACT FROM AUTHOR]

Objectives: The goal of this analysis was to evaluate the association of impaired Thrombolysis In Myocardial Infarction myocardial perfusion grade (TMPG) with sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Background: Impaired TMPG after successful restoration of epicardial flow among patients treated with fibrinolytic therapy for ST-segment elevation myocardial infarction (STEMI) has been associated with adverse clinical outcomes, but its relationship to VT/VF has not been evaluated. Methods: In the CLARITY-TIMI 28 (Clopidogrel as Adjunctive Reperfusion Therapy–Thrombolysis In Myocardial Infarction 28) study, 3,491 patients underwent angiography a median of 3.5 days after fibrinolytic administration for STEMI; TMPG was assessed, and its association with VT/VF was evaluated. Results: We observed VT/VF in 4.8% of patients. Impaired myocardial perfusion (TMPG 0/1/2) was associated with an increased incidence of VT/VF (7.1% vs. 2.6% with TMPG 3; log-rank p < 0.001). Among patients with restoration of normal epicardial flow (Thrombolysis In Myocardial Infarction flow grade 3), the incidence of VT/VF was increased among patients with impaired TMPG (4.7% vs. 2.7%; p = 0.02). Among patients with left ventricular ejection fraction ≥30%, impaired TMPG remained associated with an increased incidence of VT/VF (4.7% vs. 2.5%; p = 0.03). We found that VT/VF was associated with increased mortality (25.2% vs. 3.5%; p < 0.0001). Furthermore, among patients with VT/VF, impaired TMPG was associated with increased mortality (17.1% vs. 2.3%; p = 0.02). All but 1 death among patients who had VT/VF were among patients with impaired myocardial perfusion. Conclusions: Despite restoration of normal epicardial flow or a left ventricular ejection fraction ≥30%, impaired myocardial perfusion on angiography 3.5 days after fibrinolytic administration for STEMI is associated with an increased incidence of VT/VF. [Copyright &y& Elsevier]

Thrombocytopenia is associated with an increased risk for adverse cardiac events and bleeding in patients presenting with acute coronary syndromes (ACS) treated with unfractionated heparin (UFH). Enoxaparin has been shown to improve outcomes in ACS; however, its effect on the development of thrombocytopenia in this population is not well documented. This study was conducted to examine the incidence and clinical importance of thrombocytopenia in patients presenting with non–ST-elevation ACS randomized to treatment with enoxaparin or UFH. Thrombocytopenia was defined as a platelet count <100 × 109/L or a >50% decrease from baseline. Thrombocytopenia developed in a total of 93 of 3,910 patients during the follow-up period of 14 days; the incidence was similar between study arms. The development of thrombocytopenia was associated with more frequent death, nonfatal myocardial infarction, and urgent revascularization during the study period (odds ratio 2.96, p = 0.001). This association was independent of assignment to treatment with enoxaparin or UFH (p for interaction = 0.47). Major bleeding was also more common in patients with thrombocytopenia regardless of treatment. In conclusion, thrombocytopenia is a significant correlate of adverse events in patients presenting with non–ST-elevation ACS treated with either enoxaparin or UFH. [Copyright &y& Elsevier]

Objectives: We aimed to determine whether intensive statin therapy reduces hospitalization for heart failure (HF) in high-risk patients. Background: While the relationship between intensive statin therapy and ischemic events is well established, its relationship to the risk of HF after an acute coronary syndrome (ACS) is not well defined. Methods: The Pravastatin or Atorvastatin Evaluation and Infection Trial–Thrombolysis In Myocardial Infarction 22 (PROVE IT–TIMI 22) study randomized 4,162 patients, stabilized after ACS, to either intensive statin therapy (atorvastatin 80 mg) or moderate statin therapy (pravastatin 40 mg). Hospitalization for HF occurring more than 30 days after randomization was determined during a mean follow-up of 24 months. B-type natriuretic peptide (BNP) levels were measured at baseline (median seven days after randomization). Results: Treatment with atorvastatin 80 mg significantly reduced the rate of hospitalization for HF (1.6% vs. 3.1%, hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.35 to 0.85, p = 0.008) independently of a recurrent myocardial infarction or prior history of HF. The risk of HF increased steadily with increasing quartiles of BNP (HR 2.6, 95% CI 1.2 to 5.5, p = 0.016 for the highest quartile compared with the lowest). Among patients with elevated levels of BNP (>80 pg/ml), treatment with atorvastatin significantly reduced the risk of HF compared with pravastatin (HR 0.32, 95% CI 0.13 to 0.8, p = 0.014). A meta-analysis of four trials that included 27,546 patients demonstrates a 27% reduction in the odds of hospitalization for HF with intensive statin therapy. Conclusions: Intensive statin therapy reduces the risk of hospitalization for HF after ACS with the most gain in patients with elevated levels of BNP. [Copyright &y& Elsevier]

Distal embolization of atherothrombotic material during primary percutaneous coronary intervention (PCI) is associated with impaired myocardial perfusion, abnormal left ventricular function, and higher mortality. At high local concentrations, glycoprotein IIb/IIIa receptor antagonists have been demonstrated to promote clot disaggregation in vitro. Intracoronary administration of eptifibatide in vivo may increase local drug concentration by several orders of magnitude and promote clot disaggregation with a minimal increase in systemic drug concentrations. We hypothesized that intracoronary administration of eptifibatide before primary PCI for ST-elevation myocardial infarction would be safe and would be associated with high rates of normal myocardial perfusion. Clinical and angiographic data were pooled from patients who underwent primary PCI and received intracoronary eptifibatide as part of clinical practice. In-hospital adverse events were collected retrospectively. No deaths, urgent revascularizations, or reinfarctions were observed among the 59 patients who were treated with intracoronary eptifibatide. There were no Thrombolysis In Myocardial Infarction (TIMI) major bleeding events. Two TIMI minor bleeding events were noted. Normal TIMI myocardial perfusion grade 3 flow after PCI was noted in 54.4% of patients. No adverse events. including arrhythmias, were noted during intracoronary eptifibatide administration. In conclusion, intracoronary eptifibatide can be administered safely during primary PCI and is associated with few adverse events. Relatively high rates of normal myocardial perfusion were observed after primary PCI with adjunctive intracoronary eptifibatide. Further prospective randomized trials are warranted to evaluate the efficacy and safety of intracoronary eptifibatide. [Copyright &y& Elsevier]