Citations

AbstractBackgroundMost research on family impacts of paediatric chronic pain has been conducted with mothers, and therefore, little is known about fathers' adjustment. However, it is well established that caring for a child with chronic pain takes a toll on caregiver well‐being. Parents of children with chronic pain have been found to experience high levels of anxiety, depression, and parenting stress. As such, the goal of this study was to examine differences between mothers and fathers of youth with chronic pain, explore interaction effects between parent gender and child variables, and compare parents' scores to national norms.MethodsParticipants included 160 matched mothers and fathers of youth with chronic pain participating in an interdisciplinary pain rehabilitation programme. At admission, parents completed the Center for Epidemiological Studies–Depression scale and SF‐36 to assess depression and health‐related quality of life. T tests and analysis of variance were used to explore differences between mothers and fathers and population norms.ResultsMothers reported experiencing significantly poorer functioning than did fathers in the domains of emotional role interference, social functioning, and vitality. Differences remained significant when controlling for other psychosocial variables using multiple regression. Child gender and depression level were found to be significant predictors of parent mental health, with mothers' mental health more negatively influenced by child depression. Additionally, mothers' scores in mental health domains were significantly lower than population norms.ConclusionsThese findings highlight the importance of identifying the ways in which chronic pain in youth may affect parents differently in order to enhance caregiver support and interventions.

Objective: To characterize agreement between administrative and registry data in the determination of patient-level comorbidities. Background: Previous research finds poor agreement between these 2 types of data in the determination of outcomes. We hypothesized that concordance between administrative and registry data would also be poor. Methods: A cohort of inpatient operations (length of stay 1 day or greater) was obtained from a consortium of 8 hospitals. Within each hospital, National Surgical Quality Improvement Program (NSQIP) data were merged with intra-institutional inpatient administrative data. Twelve different comorbidities (diabetes, hypertension, congestive heart failure, hemodialysis-dependence, cancer diagnosis, chronic obstructive pulmonary disease, ascites, sepsis, smoking, steroid, congestive heart failure, acute renal failure, and dyspnea) were analyzed in terms of agreement between administrative and NSQIP data. Results: Forty-one thousand four hundred thirty-two inpatient surgical hospitalizations were analyzed in this study. Concordance (Cohen Kappa value) between the 2 data sources varied from 0.79 (diabetes) to 0.02 (dyspnea). Hospital variation in concordance (intersite variation) was quantified using a test of homogeneity. This test found significant intersite variation at a level of P < 0.001 for each of the comorbidities except for dialysis (P = 0.07) and acute renal failure (P = 0.19). These findings imply significant differences between hospitals in their generation of comorbidity data. Conclusion: This study finds significant differences in how administrative versus registry data assess patient-level comorbidity. These differences are of concern to patients, payers, and providers, each of which had a stake in the integrity of these data. Standardized definitions of comorbidity and periodic audits are necessary to ensure data accuracy and minimize bias.

Purpose: To examine the etiology, clinical course, and management of recurrent peripheral facial nerve paralysis. Methods: Retrospective review at a single tertiary academic center and systematic review of the literature. Clinical presentation, laboratory and imaging findings, treatment and outcome for all cases of recurrent ipsilateral, recurrent contralateral, and bilateral simultaneous cases of facial paralysis are reviewed. Results: Between 2000 and 2017, 53 patients [41.5% men, 29 median age of onset (range 2.5 wk–75 yr)] were evaluated for recurrent facial nerve paralysis at the authors’ institution. Twenty-two (41.5%) cases presented with ipsilateral recurrences only, while the remaining 31 patients (58.5%) had at least 1 episode of contralateral recurrent paralysis. No cases of bilateral simultaneous facial nerve paralysis were observed. The median number of paretic events for all patients was 3 (range 2–20). The median nadir House–Brackmann score was 4, with a median recovery to House–Brackmann grade 1.5 over a mean recovery time of 61.8 days (range 1–420 d). Diagnostic evaluation confirmed Melkersson–Rosenthal syndrome in four (7.5%) cases, neurosarcoidosis in two (3.7%), traumatic neuroma in one (1.9%), Ramsay Hunt syndrome in one (1.9%), granulomatosis with polyangiitis in one (1.9%), and neoplastic causes in three (5.7%) cases [facial nerve schwannoma (n = 2; 3.7%), metastatic squamous cell carcinoma to the deep lobe of the parotid gland (n = 1; 1.9%)]; ultimately, 77.4% (41) of cases were deemed idiopathic. Facial nerve decompression via a middle cranial fossa approach was performed in three (5.7%) cases without subsequent episodes of paralysis. Conclusion: Recurrent facial nerve paralysis is uncommon and few studies have evaluated this unique population. Recurrent ipsilateral and contralateral episodes are most commonly attributed to idiopathic facial nerve paralysis (i.e., Bell's palsy); however, a subset harbor neoplastic causes or local manifestations of underlying systemic disease. A comprehensive diagnostic evaluation is warranted in patients presenting with recurrent facial nerve paralysis and therapeutic considerations including facial nerve decompression can be considered in select cases.

Abstract STUDY QUESTION Can asoprisnil, a selective progesterone receptor modulator, provide clinically meaningful improvements in heavy menstrual bleeding (HMB) associated with uterine fibroids with an acceptable safety profile? SUMMARY ANSWER Uninterrupted treatment with asoprisnil for 12 months effectively controlled HMB and reduced fibroid and uterine volume with few adverse events. WHAT IS KNOWN ALREADY In a 3-month study, asoprisnil (5, 10 and 25 mg) suppressed uterine bleeding, reduced fibroid and uterine volume, and improved hematological parameters in a dose-dependent manner. STUDY DESIGN, SIZE, DURATION In two Phase 3, double-blind, randomized, placebo-controlled, multicentre studies, women received oral asoprisnil 10 mg, asoprisnil 25 mg or placebo (2:2:1) once daily for up to 12 months. PARTICIPANTS/MATERIALS, SETTING, METHODS Premenopausal women ≥18 years of age in North America with HMB associated with uterine fibroids were included (N = 907). The primary efficacy endpoint was the percentage of women who met all three predefined criteria at 12 months or the final month for patients who prematurely discontinued: (1) ≥50% reduction in monthly blood loss (MBL) by menstrual pictogram, (2) hemoglobin concentration ≥11 g/dL or an increase of ≥1 g/dL, and (3) no interventional therapy for uterine fibroids. Secondary efficacy endpoints included changes in other menstrual bleeding parameters, volume of the largest fibroids, uterine volume and health-related quality of life (HRQL). MAIN RESULTS AND THE ROLE OF CHANCE In all, 90% and 93% of women in the asoprisnil 10-mg and 25-mg groups, respectively, and 35% of women in the placebo group met the primary endpoint (P &lt; 0.001). Similar results were observed at month 6 (P &lt; 0.001). The percentage of women who achieved amenorrhea in any specified month ranged from 66–78% in the asoprisnil 10-mg group and 83–93% in the asoprisnil 25-mg group, significantly higher than with placebo (3–12%, P &lt; 0.001). Hemoglobin increased rapidly (by month 2) with asoprisnil treatment and was significantly higher versus placebo throughout treatment. The primary fibroid and uterine volumes were significantly reduced from baseline through month 12 with asoprisnil 10 mg (median changes up to −48% and −28%, respectively) and 25 mg (median changes up to −63% and −39%, respectively) versus placebo (median changes up to +16% and +13%, respectively; all P &lt; 0.001). Dose-dependent, significant improvements in HRQL (Uterine Fibroid Symptom and Quality of Life instrument) were observed with asoprisnil treatment. Asoprisnil was generally well tolerated. Endometrial biopsies indicated dose- and time-dependent decreases in proliferative patterns and increases in quiescent or minimally stimulated endometrium at month 12 of treatment. Although not statistically significantly different at month 6, mean endometrial thickness at month 12 increased by ~2 mm in both asoprisnil groups compared with placebo (P &lt; 0.01). This effect was associated with cystic changes in the endometrium on MRI and ultrasonography, which led to invasive diagnostic and therapeutic procedures in some asoprisnil-treated women. LIMITATIONS, REASONS FOR CAUTION Most study participants were black; few Asian and Hispanic women participated. The study duration may have been insufficient to fully characterize the endometrial effects. WIDER IMPLICATIONS OF THE FINDINGS Daily uninterrupted treatment with asoprisnil was highly effective in controlling menstrual bleeding, improving anemia, reducing fibroid and uterine volume, and increasing HRQL in women with HMB associated with uterine fibroids. However, this treatment led to an increase in endometrial thickness and invasive diagnostic and therapeutic procedures, with potential unknown consequences. STUDY FUNDING/COMPETING INTEREST(S) This trial was funded by AbbVie Inc. (prior sponsors: TAP Pharmaceutical Products Inc., Abbott Laboratories). E.A. Stewart was a site investigator in the Phase 2 study of asoprisnil and consulted for TAP during the design and conduct of these studies while at Harvard Medical School and Brigham and Women’s Hospital. She received support from National Institutes of Health grants HD063312, HS023418 and HD074711 and research funding, paid to Mayo Clinic for patient care costs related to an NIH-funded trial from InSightec Ltd. She consulted for AbbVie, Allergan, Bayer HealthCare AG, Gynesonics, and Welltwigs. She received royalties from UpToDate and the Med Learning Group. M.P. Diamond received research funding for the conduct of the studies paid to the institution and consulted for AbbVie. He is a stockholder and board and director member of Advanced Reproductive Care. He has also received funding for study conduct paid to the institution from Bayer and ObsEva. A.R.W. Williams consulted for TAP and Repros Therapeutics Inc. He has current consultancies with PregLem SA, Gedeon Richter, HRA Pharma and Bayer. B.R. Carr consulted for and received research funding from AbbVie. E.R. Myers consulted for AbbVie, Allergan and Bayer. R.A. Feldman received compensation for serving as a principal investigator and participating in the conduct of the trial. W. Elger was co-inventor of several patents related to asoprisnil. C. Mattia-Goldberg is a former employee of AbbVie and may own AbbVie stock or stock options. B.M. Schwefel and K. Chwalisz are employees of AbbVie and may own AbbVie stock or stock options. TRIAL REGISTRATION NUMBER NCT00152269, NCT00160381 (clinicaltrials.gov). TRIAL REGISTRATION DATE 7 September 2005; 8 September 2005. DATE OF FIRST PATIENT’S ENROLMENT 12 September 2002; 6 September 2002.

Abstract Human fibrin hydrogels are a popular choice for use as a biomaterial within tissue engineered constructs because they are biocompatible, nonxenogenic, autologous use compatible, and biodegradable. We have recently demonstrated the ability to culture induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium on fibrin hydrogels. However, iPSCs themselves have relatively few substrate options (e.g., laminin) for expansion in adherent cell culture for use in cell therapy. To address this, we investigated the potential of culturing iPSCs on fibrin hydrogels for three-dimensional applications and further examined the use of fibrinogen, the soluble precursor protein, as a coating substrate for traditional adherent cell culture. iPSCs successfully adhered to and proliferated on fibrin hydrogels. The two-dimensional culture with fibrinogen allows for immediate adaption of culture models to a nonxenogeneic model. Similarly, multiple commercially available iPSC lines adhered to and proliferated on fibrinogen coated surfaces. iPSCs cultured on fibrinogen expressed similar levels of the pluripotent stem cell markers SSea4 (98.7% ± 1.8%), Oct3/4 (97.3% ± 3.8%), TRA1-60 (92.2% ± 5.3%), and NANOG (96.0% ± 3.9%) compared with iPSCs on Geltrex. Using a trilineage differentiation assay, we found no difference in the ability of iPSCs grown on fibrinogen or Geltrex to differentiate to endoderm, mesoderm, or ectoderm. Finally, we demonstrated the ability to differentiate iPSCs to endothelial cells using only fibrinogen coated plates. On the basis of these data, we conclude that human fibrinogen provides a readily available and inexpensive alternative to laminin-based products for the growth, expansion, and differentiation of iPSCs for use in research and clinical cell therapy applications. Stem Cells Translational Medicine 2019;8:512–521

ObjectiveRheumatoid arthritis (RA) is postulated to originate at mucosal surfaces, particularly the airway mucosa. To investigate this hypothesis, we determined the association between RA and asthma, passive smoke exposure, and age at start of smoking.MethodsFor this case–control study, we identified 1,023 cases of RA (175 incident) within a single‐center biobank population, using a rules‐based algorithm that combined self‐report with 2 diagnostic codes. Exposures were self‐reported on biobank questionnaires. Logistic regression models were used to calculate the association of exposures with RA, adjusting for potential confounders. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated.ResultsAfter adjustment for allergies, urban environment, and passive smoke exposure, asthma was found to be associated with RA in the full cohort (OR 1.28 [95% CI 1.04–1.58; P = 0.02]) but not the incident RA cohort (OR 1.17 [95% CI 0.66–2.06; P = 0.60]). History of allergic disease was associated with RA in both the full cohort (OR 1.30 [95% CI 1.12–1.51; P < 0.001]) and the incident RA cohort (OR 1.61 [95% CI 1.11–2.33; P = 0.01]), especially food allergy, which was significantly associated with RA in the full cohort (OR 1.38 [95% CI 1.08–1.75; P = 0.01]) and showed a trend toward significance in the incident RA cohort (OR 1.83 [95% CI 0.97–3.45; P = 0.06]). Passive smoke exposure at home or work was not associated with RA. Finally, age at start of smoking was not associated with increased odds of developing RA in either the full cohort (OR 1.03 [95% CI 1.00–1.06; P = 0.03]) or the incident RA cohort (OR 1.00 [95% CI 0.92–1.08; P = 0.98]).ConclusionAsthma and allergies may be associated with increased risk of RA. Passive smoke exposure and early age at start of smoking do not appear to influence risk of RA.

ABSTRACTThe MLLT10 (formerly AF10) gene is the fourth most common KMT2A fusion partner across all acute leukemias and requires at least 3 breaks to form an in‐frame KMT2A/MLLT10 fusion due to the opposite orientation of each gene. A 10‐year retrospective review was performed to identify individuals from all age groups that harbor KMT2A/MLLT10 fusion obtained by our KMT2A/MLLT10 dual‐color dual‐fusion fluorescence in situ hybridization (D‐FISH) assay. Of the 60 unique individuals identified, 31 were male and 29 were female (M:F ratio, 1.1:1) with ages ranging from 3 days to 86 years (mean 21.5 years, median 5.5 years). The diagnoses included acute myeloid leukemia (AML) (49 patients, 82%), B‐ or T‐lymphoblastic leukemia/lymphoma (7 patients, 12%), myeloid sarcoma (3 patients, 5%), and a single case (2%) of undifferentiated leukemia. Twenty‐seven of 49 patients (55%) with AML were in the infant or pediatric age group. Fifty‐three of 60 patients (88%) had KMT2A/MLLT10 D‐FISH signal patterns mostly consisting of single fusions. In addition, 10 (26%) of 38 patients with conventional chromosome studies had “normal” (5 patients) or abnormal (5 patients) chromosome studies that lacked structural or numeric abnormalities involving chromosomes 10 or 11, implying cryptic cytogenetic mechanisms for KMT2A/MLLT10 fusion. Lastly, mate‐pair sequencing was performed on 4 AML cases, 2 of which had “normal” chromosome studies and cryptic KMT2A/MLLT10 fusion as detected by KMT2A/MLLT10 D‐FISH studies, and verified the multiple breaks required to generate KMT2A/MLLT10 fusion.