Maternal and infant touching behaviours during perturbed interactions: Associations with maternal depressive symptomatology and infant crying.

Touch is an important means through which mothers and infants co-regulate during periods of stress or perturbation. The present study examined the synchrony of maternal and infant touching behaviours among 41 mother-infant dyads, some of whom were deemed at-risk due to maternal depressive symptomatology. Mothers and their 4-month-old infants participated in the Still-Face (maternal emotional unavailability; SF) and Separation (maternal physical unavailability; SP) procedures. Infant crying was examined across procedures and investigated as a brief period of perturbation. Results revealed that mothers and infants displayed a positive pattern of tactile synchrony (coordinated, analogous changes in touch) during infant crying episodes. However, dyads in the high depression group displayed significantly less affectionate touch during instances of infant crying. Furthermore, more depressive symptoms were associated with less maternal and infant touch and lower rates of infant crying. This group of dyads may be less expressive via touch, be less affected by disruptions in their interactions, have impaired regulatory abilities, or simply require minimal amounts of touch to mutually regulate following social stressors and during brief perturbation periods. These findings enrich our limited knowledge about the dynamic interplay of maternal and infant touch and inform preventative intervention programs for at-risk groups.

Prevalence of Intracranial Atherosclerotic Disease in Patients with Low-Risk Transient or Persistent Neurologic Events.

BACKGROUND AND PURPOSE: There are limited data on the prevalence and outcome of intracranial atherosclerotic disease in patients with low-risk transient or persistent minor neurologic events. We sought to determine the prevalence and risk factors associated with intracranial atherosclerotic disease in patients with low-risk transient or persistent neurologic events. MATERIALS AND METHODS: Participants with available intracranial vascular imaging from the Diagnosis of Uncertain-Origin Benign Transient Neurologic Symptoms (DOUBT) study, a large prospective multicenter cohort study, were included in this post hoc analysis. The prevalence of intracranial atherosclerotic disease of ≥50% was determined, and the association with baseline characteristics and DWI lesions was evaluated using logistic regression. RESULTS: We included 661 patients with a median age of 62 years (interquartile range, 53-70 years), of whom 53% were women. Intracranial atherosclerotic disease was found in 81 (12.3%) patients; asymptomatic intracranial atherosclerotic disease alone, in 65 (9.8%); and symptomatic intracranial atherosclerotic disease, in 16 (2.4%). The most frequent location was in the posterior cerebral artery (29%). Age was the only factor associated with any intracranial atherosclerotic disease (adjusted OR, 1.9 for 10 years increase; 95% CI, 1.6-2.5). Multivariable logistic regression showed a strong association between intracranial atherosclerotic disease and the presence of acute infarct on MR imaging (adjusted OR, 3.47; 95% CI, 1.91-6.25). CONCLUSIONS: Intracranial atherosclerotic disease is not rare in patients with transient or persistent minor neurologic events and is independently associated with the presence of MR imaging-proved ischemia in this context. Evaluation of the intracranial arteries could be valuable in establishing the etiology of such low-risk events.

Utstein recommendation for emergency stroke care.

BACKGROUND: Recent advances in treatment for stroke give new possibilities for optimizing outcomes. To deliver these prehospital care needs to become more efficient. AIM: To develop a framework to support improved delivery of prehospital care. The recommendations are aimed at clinicians involved in prehospital and emergency health systems who will often not be stroke specialists but need clear guidance as to how to develop and deliver safe and effective care for acute stroke patients. METHODS: Building on the successful implementation program from the Global Resuscitation Alliance and the Resuscitation Academy, the Utstein methodology was used to define a generic chain of survival for Emergency Stroke Care by assembling international expertise in Stroke and Emergency Medical Services (EMS). Ten programs were identified for Acute Stroke Care to improve survival and outcomes, with recommendations for implementation of best practice. CONCLUSIONS: Efficient prehospital systems for acute stroke will be improved through public awareness, optimized prehospital triage and timely diagnostics, and quick and equitable access to acute treatments. Documentation, use of metrics and transparency will help to build a culture of excellence and accountability.

Prediction of Hemorrhage after Successful Recanalization in Patients with Acute Ischemic Stroke: Improved Risk Stratification Using Dual-Energy CT Parenchymal Iodine Concentration Ratio Relative to the Superior Sagittal Sinus.

BACKGROUND AND PURPOSE: Brain parenchymal hyperdensity on postthrombectomy CT in patients with acute stroke can be due to hemorrhage and/or contrast staining. We aimed to determine whether iodine concentration within contrast-stained parenchyma compared with an internal reference in the superior sagittal sinus on dual-energy CT could predict subsequent intracerebral hemorrhage. MATERIALS AND METHODS: Seventy-one patients with small infarct cores (ASPECTS ≥ 7) and good endovascular recanalization (modified TICI 2b or 3) for anterior circulation large-vessel occlusion were included. Brain parenchymal iodine concentration as per dual-energy CT and the percentage of contrast staining relative to the superior sagittal sinus were recorded and correlated with the development of intracerebral hemorrhage using Mann-Whitney U and Fisher exact tests. RESULTS: Forty-three of 71 patients had parenchymal hyperdensity on initial dual-energy CT. The median relative iodine concentration compared with the superior sagittal sinus was significantly higher in those with subsequent intracerebral hemorrhage (137.9% versus 109.2%, P = .007). By means of receiver operating characteristic analysis, a cutoff value of 100% (iodine concentration relative to the superior sagittal sinus) enabled identification of patients going on to develop intracerebral hemorrhage with 94.75% sensitivity, 43.4% specificity, and a likelihood ratio of 1.71. CONCLUSIONS: Within our cohort of patients, the relative percentage of iodine concentration at dual-energy CT compared with the superior sagittal sinus was a reliable predictor of intracerebral hemorrhage development and may be a useful imaging biomarker for risk stratification after endovascular treatment.

Clot Burden Score and Early Ischemia Predict Intracranial Hemorrhage following Endovascular Therapy.

BACKGROUND AND PURPOSE: Intracranial hemorrhage is a known complication following endovascular thrombectomy. The radiologic characteristics of a CT scan may assist with hemorrhage risk stratification. We assessed the radiologic predictors of intracranial hemorrhage following endovascular therapy using data from the INTERRSeCT (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography) study. MATERIALS AND METHODS: Patients undergoing endovascular therapy underwent baseline imaging, postprocedural angiography, and 24-hour follow-up imaging. The primary outcome was any intracranial hemorrhage observed on follow-up imaging. The secondary outcome was symptomatic hemorrhage. We assessed the relationship between hemorrhage occurrence and baseline patient characteristics, clinical course, and imaging factors: baseline ASPECTS, thrombus location, residual flow grade, collateralization, and clot burden score. Multivariable logistic regression with backward selection was used to adjust for relevant covariates. RESULTS: Of the 199 enrolled patients who met the inclusion criteria, 46 (23%) had an intracranial hemorrhage at 24 hours. On multivariable analysis, postprocedural hemorrhage was associated with pretreatment ASPECTS (OR, 1.56 per point lost; 95% CI, 1.12-2.15), clot burden score (OR, 1.19 per point lost; 95% CI, 1.03-1.38), and ICA thrombus location (OR, 3.10; 95% CI, 1.07-8.91). In post hoc analysis, clot burden scores of ≤3 (sensitivity, 41%; specificity, 82%; OR, 3.12; 95% CI, 1.36-7.15) and pretreatment ASPECTS ≤ 7 (sensitivity, 48%; specificity, 82%; OR, 3.17; 95% CI, 1.35-7.45) robustly predicted hemorrhage. Residual flow grade and collateralization were not associated with hemorrhage occurrence. Symptomatic hemorrhage was observed in 4 patients. CONCLUSIONS: Radiologic factors, early ischemia on CT, and increased CTA clot burden are associated with an increased risk of intracranial hemorrhage in patients undergoing endovascular therapy.

Health literacy and pap testing in insured women.

Several studies have found a link between health literacy and participation in cancer screening. Most, however, have relied on self-report to determine screening status. Further, until now, health literacy measures have assessed print literacy only. The purpose of this study was to examine the relationship between participation in cervical cancer screening (Papanicolaou [Pap] testing) and two forms of health literacy-reading and listening. A demographically diverse sample was recruited from a pool of insured women in Georgia, Massachusetts, Hawaii, and Colorado between June 2009 and April 2010. Health literacy was assessed using the Cancer Message Literacy Test-Listening and the Cancer Message Literacy Test-Reading. Adherence to cervical cancer screening was ascertained through electronic administrative data on Pap test utilization. The relationship between health literacy and adherence to evidence-based recommendations for Pap testing was examined using multivariate logistic regression models. Data from 527 women aged 40 to 65 were analyzed and are reported here. Of these 527 women, 397 (75 %) were up to date with Pap testing. Higher health literacy scores for listening but not reading predicted being up to date. The fact that health literacy listening was associated with screening behavior even in this insured population suggests that it has independent effects beyond those of access to care. Patients who have difficulty understanding spoken recommendations about cancer screening may be at risk for underutilizing screening as a result.

Pharmacokinetically-targeted BU and fludarabine as conditioning before allogeneic hematopoietic cell transplantation for adults with ALL in first remission.

Allogeneic hematopoietic cell transplantation offers improved survival in patients with ALL, but with regimens containing TBI, the nonrelapse mortality is 20-40%. Efforts to lessen transplant toxicities by reducing conditioning regimen intensity have led to increased relapse risk. Therefore, there is a need for less toxic regimens that maintain an anti-leukemia effect. We report here a retrospective review of 65 patients with ALL in first remission receiving grafts from allogeneic donors after fludarabine 40 mg/m(2)/day for 4 days and i.v. BU targeted to a median daily area under the concentration-time curve below 6000 µmoles min/L. At 2 years after transplantation, OS was 65% (95% confidence interval (CI): 52-77%), relapse-free survival was 61% (95% CI: 48-73%), cumulative incidence of relapse was 26% (95% CI: 17-39%) and cumulative incidence of nonrelapse mortality was 14% (95% CI: 8-26%). Age over 35 years, Ph chromosome positivity and minimal residual disease at transplant did not adversely affect outcomes. Pharmacokinetically targeted BU and fludarabine can provide intensive pre-transplant conditioning for adults with ALL in first remission, with promising relapse-free and OS rates.

Breastfeeding is negatively affected by prenatal depression and reduces postpartum depression.

BACKGROUND: This prospective cohort study explored the effects of prenatal and postpartum depression on breastfeeding and the effect of breastfeeding on postpartum depression. METHOD: The Edinburgh Postpartum Depression Scale (EPDS) was administered to 145 women at the first, second and third trimester, and at the neonatal period and 3 months postpartum. Self-report exclusive breastfeeding since birth was collected at birth and at 3, 6 and 12 months postpartum. Data analyses were performed using repeated-measures ANOVAs and logistic and multiple linear regressions. RESULTS: Depression scores at the third trimester, but not at 3 months postpartum, were the best predictors of exclusive breastfeeding duration (ß = -0.30, t = -2.08, p < 0.05). A significant decrease in depression scores was seen from childbirth to 3 months postpartum in women who maintained exclusive breastfeeding for ⩾3 months (F 1,65 = 3.73, p < 0.10, η p 2 = 0.05). CONCLUSIONS: These findings suggest that screening for depression symptoms during pregnancy can help to identify women at risk for early cessation of exclusive breastfeeding, and that exclusive breastfeeding may help to reduce symptoms of depression from childbirth to 3 months postpartum.

Race/ethnicity affects the probability of finding an HLA-A, -B, -C and -DRB1 allele-matched unrelated donor and likelihood of subsequent transplant utilization.

Factors relevant to finding a suitable unrelated donor and barriers to effective transplant utilization are incompletely understood. Among a consecutive series of unrelated searches (n=531), an 8/8 HLA-A, -B, -C and -DRB1-matched unrelated donor was available for 289 (54%) patients, 7/8 for 159 (30%) and no donor for 83 (16%). Patients of Caucasian race (P<0.0001) were more likely to find a donor. Younger age (P=0.01), Caucasian race (P=0.03), lower CIBMTR (Center for International Blood and Marrow Transplantation Research) risk (P=0.005), and 8/8 HLA matching (P=0.005) were associated with higher odds of reaching hematopoietic cell transplantation (HCT). In a univariate analysis of OS, finding a donor was associated with hazard ratio (HR) of 0.85 (95% CI 0.63-1.2), P=0.31. Karnofsky performance status (KPS) accounted for interaction between having a donor and survival. Patients with KPS 90-100 and a donor had significantly reduced hazard for death (HR 0.59, 95% CI 0.38-0.90, P=0.02). These data provide estimates of the probability to find an unrelated donor in the era of high-resolution HLA typing, and identify potentially modifiable barriers to reaching HCT. Further efforts are needed to enhance effective donor identification and transplant utilization, particularly in non-Caucasian ethnic groups.

Targeted i.v. BU and fludarabine (t-i.v. BU/Flu) provides effective control of AML in adults with reduced toxicity.

Myeloablative doses of BU and fludarabine followed by allogeneic hematopoietic cell transplantation offer effective therapy for AML. We anticipated that pharmacokinetic targeting of i.v. BU to 5300 µM/L min/day × 4 (targeted i.v. BU and fludarabine (t-i.v. BU/Flu)) would limit nonrelapse mortality (NRM) in adults up to 70 years of age. We assessed the safety and efficacy of t-i.v. BU/Flu in a series of 100 adults (median age 48, range 22-69 years) with AML in the first CR (CR1) with high risk of treatment failure (n=49), second CR (CR2, n=25), relapsed disease (REL, n=9), primary induction failure (PIF, n=16) and untreated (n=1). NRM was 3% at 100 days and 15% at 1 year. The cumulative incidence of relapse was 30.6% for CR1, 41.7% for CR2, 55.6% for REL and 58.6% for PIF. OS for primary AML in CR1 was 66% (95% confidence interval (CI): 46-80%) at 1 year, and 62% (95% CI: 42-77%) at 2 years. On multivariable modeling, remission status, moderate/severe chronic GVHD and day-90 BM chimerism ≥90% predicted improved OS. Importantly, there was no effect of age. t-i.v. BU/Flu provides effective disease control with encouraging NRM in patients up to age of 70 years.

Pharmacokinetic targeting of i.v. BU with fludarabine as conditioning before hematopoietic cell transplant: the effect of first-dose area under the concentration time curve on transplant-related outcomes.

We used pharmacokinetic (PK) targeting of BU in 145 consecutive patients treated with fludarabine and i.v. BU. BU was given once daily at 130 mg/m(2) per day on days 1 and 2; doses for days 3 and 4 were adjusted in 92 patients (63%) to an average daily area under the concentration-time curve (AUC) of 5300 µM/min. In the remaining 53 patients, the first-dose AUC was within the target range and no dosing adjustments were required. First-dose AUC, maximum concentration and clearance were not correlated with age, race, ethnicity, performance status, or hematopoietic cell transplant comorbidity index. Women had higher clearance than men (median 2.9 vs 2.5 mL/min/kg; P=0.001). BU toxicities were not associated with first-dose AUC or any other PK parameter measured. First-dose BU AUC was not associated with non-relapse mortality (NRM) or survival, but higher AUC was predictive of relapse. We did not find an increased risk of toxicity or NRM in patients with high first-dose AUC presumably because of the dose adjustment. We conclude that PK targeting of BU as described here provides a simple, safe and effective method of delivering high BU doses before transplantation in a wide variety of patients.

Metastable anions of dinitrobenzene: resonances for electron attachment and kinetic energy release.

Attachment of free, low-energy electrons to dinitrobenzene (DNB) in the gas phase leads to DNB(-) as well as several fragment anions. DNB(-), (DNB-H)(-), (DNB-NO)(-), (DNB-2NO)(-), and (DNB-NO(2))(-) are found to undergo metastable (unimolecular) dissociation. A rich pattern of resonances in the yield of these metastable reactions versus electron energy is observed; some resonances are highly isomer-specific. Most metastable reactions are accompanied by large average kinetic energy releases (KER) that range from 0.5 to 1.32 eV, typical of complex rearrangement reactions, but (1,3-DNB-H)(-) features a resonance with a KER of only 0.06 eV for loss of NO. (1,3-DNB-NO)(-) offers a rare example of a sequential metastable reaction, namely, loss of NO followed by loss of CO to yield C(5)H(4)O(-) with a large KER of 1.32 eV. The G4(MP2) method is applied to compute adiabatic electron affinities and reaction energies for several of the observed metastable channels.

Mycophenolate mofetil for the management of steroid-refractory acute graft vs host disease.

Acute graft vs host disease (aGVHD) is a significant obstacle to successful allogeneic hematopoietic cell transplantation, as only 30-40% of those with aGVHD show complete response to front-line glucocorticoids. The role of mycophenolate mofetil (MMF) as salvage therapy in steroid-refractory aGVHD remains incompletely defined. Here, we examine outcomes of 27 patients with refractory aGVHD treated with MMF as second-line therapy. Seven (26%) patients achieved complete remission (CR) of steroid-refractory aGVHD with only the addition of MMF as salvage therapy. CR of aGVHD differed by overall grade at salvage (grade I, 1/3; grade II, 5/12; grade III 0/5; grade IV, 1/7) with odds ratio for CR in grade I/II vs III/IV of 7.3 (95% CI: 0.7-72.6, P=0.09). Overall survival (OS) at 3 years was 40%. Overall aGVHD grade at salvage (hazard ratio (HR) grade I/II vs III/IV 0.18 (95% CI: 0.06-0.57), P=0.003) and achievement of CR (HR 0.12 (95% CI: 0.04-0.39), P=0.0004) were significant predictors of OS. MMF was overall well tolerated, with only two patients requiring discontinuation for myelosuppression. MMF shows activity in the salvage of steroid-refractory, grades I-II aGVHD.

5-Azacitidine for myelodysplasia before allogeneic hematopoietic cell transplantation.

Relapse remains a leading cause for treatment failure after hematopoietic cell transplantation (HCT) in patients with intermediate- or high-risk myelodysplastic syndrome (MDS). To discern the impact of 5-azacitine treatment pretransplant on the risk for relapse after HCT, we analyzed the post transplant outcomes of all 54 consecutive patients with MDS or chronic myelomonocytic leukemia who received HCT from HLA-compatible donors according to pretransplant 5-azacitidine exposure. Thirty patients received a median of four (1-7) cycles of 5-azacitidine, and 24 patients did not receive 5-azacitidine before HCT. The 1-year estimates of overall survival, relapse-free survival and cumulative incidence of relapse were 47, 41 and 20%, for 5-azacitidine patients and 60, 51 and 32%, respectively, for non-5-azacytidine patients. These observations suggest that outcomes are similar in both groups with a trend toward decreased early relapse in patients receiving 5-azacitidine. 5-Azacitidine may be of value in stabilizing the disease, thereby allowing time for patients to reach transplant and does not appear to affect transplant outcomes.

Low-energy electron attachment to the dichlorodifluoromethane (CCl2F2) molecule.

Results from a joint experimental study of electron attachment to dichlorodifluoromethane (CCl(2)F(2)) molecules in the gas phase are reported. In a high resolution electron beam experiment involving two versions of the laser photoelectron attachment method, the relative cross section for formation of the dominant anion Cl(-) was measured over the energy range 0.001-1.8 eV at the gas temperature T(G) = 300 K. It exhibits cusp structure at thresholds for vibrational excitation of the nu(3)(a(1)) mode due to interaction with the attachment channels. With reference to the thermal attachment rate coefficient k(T = 300 K) = 2.2(8) x 10(-9) cm(3) s(-1) (fitted average from several data), a new highly resolved absolute attachment cross section for T(G) = 300 K was determined. Partial cross sections for formation of the anions Cl(-), Cl(2)(-), F(-), ClF(-), and CCl(2)F(-) were measured over the range 0-12 eV, using three different electron beam experiments of medium energy resolution. The dependence of the attachment rate coefficient k(T(e);T(G) = 300 K) on electron temperature T(e) was calculated over the range 50-15 000 K, based on a newly constructed total cross section for anion formation at T(G) = 300 K. R-matrix calculations for Cl(-) production have been carried out for comparison with the experimental data. The R-matrix results are in line with the main experimental observations and predict the dependence of the DEA cross section on the initial vibrational level nu(3)() and on the vibrational temperature. Furthermore, the cross section for vibrational excitation of the nu(3) mode has been computed.

Sirolimus for treatment of steroid-refractory acute graft-versus-host disease.

Acute GVHD (aGVHD) is a major cause of morbidity and mortality in hematopoietic allograft recipients. The best therapy for patients failing to respond, or not tolerating, systemic glucocorticoids remains undefined. We evaluated the efficacy of sirolimus in 34 patients, median age of 49 (23-67) years, with steroid-refractory (n=31) or steroid-intolerant (n=3) aGVHD. aGVHD was diagnosed at a median of 34 (7-1042) days post allografting, and confirmed by biopsy in all cases. Initial aGVHD treatment consisted of prednisone up to 2 mg/kg. Sirolimus was initiated at a median of 9 (1-255) days after glucocorticoid initiation. A sirolimus loading dose was administered to 19 (56%) of 34 patients, median 6 (3-8) mg, followed by maintenance of 1-2 mg/day to target therapeutic trough levels between 4 and 12 ng/ml. Overall response rate was 76%. Fifteen (44%) of 34 patients achieved CR, defined as complete resolution of aGVHD sustained for at least 1 month, after sirolimus initiation without additional immunosuppressive agents. CR was achieved in 11 (42%) of 31 steroid-refractory and 2 (67%) of 3 steroid-intolerant patients. Median OS after initiation of sirolimus was 5.6 months, and 1-year OS was 44% (95% CI: 27-60%). Sirolimus is effective in controlling steroid-refractory aGVHD.

Voriconazole provides effective prophylaxis for invasive fungal infection in patients receiving glucocorticoid therapy for GVHD.

Patients on systemic glucocorticoids for GVHD after hematopoietic cell transplant are susceptible to invasive fungal infections (IFI), which greatly contribute to morbidity and mortality. We evaluated the efficacy of prophylactic treatment options (voriconazole or fluconazole vs itraconazole) for IFI by performing a retrospective review of patients on glucocorticoids for GVHD who were administered voriconazole (n=97), fluconazole (n=36) or itraconazole (n=36). IFI developed in 7/72 (10%) patients on fluconazole/itraconazole vs 2/97 (2%) on voriconazole (P=0.03) within the first 100 days of glucocorticoids. Five (7%) patients developed Aspergillus IFI on fluconazole/itraconazole, compared with none on voriconazole (0%) (P=0.008); Aspergillus IFI resulted in death in all five patients. We found that IFI occurred in patients who received an initial dose of at least 2 mg/kg/day of prednisone or equivalent; when the analysis was restricted to these patients, the hazard ratio (0.39; 95% confidence interval: 0.08-1.86) was consistent with a protective effect of voriconazole compared with fluconazole/itraconazole, although this subset analysis did not reach significance. OS at 100 days after start of glucocorticoids was 77% in patients administered fluconazole/itraconazole and 85% in those administered voriconazole (P=0.22). Our results suggest that voriconazole is more effective than fluconazole/itraconazole in preventing IFI, especially aspergillosis, in patients receiving glucocorticoids post transplant.