Hearing Loss in Children With Craniofacial Microsomia.

OBJECTIVE: To evaluate the association between craniofacial phenotype and hearing loss in children with craniofacial microsomia. DESIGN: Retrospective cohort study. SETTING: Tertiary care children's hospital. PATIENTS: Individuals with craniofacial microsomia. MAIN OUTCOME MEASURES: Ear-specific audiograms and standardized phenotypic classification of facial characteristics. RESULTS: A total of 79 participants were included in the study. The mean age was 9 years (range, 1 to 23 years) and approximately 60% were boys. Facial anomalies were bilateral in 39 participants and unilateral in 40 participants (24 right, 16 left). Microtia (hypoplasia of the ear) was the most common feature (94%), followed by mandibular hypoplasia (76%), soft tissue deficiency (60%), orbital hypoplasia or displacement (53%), and facial nerve palsy (32%). Sixty-five individuals had hearing loss (12 bilateral and 53 unilateral). Hearing loss was conductive in 73% of affected ears, mixed in 10%, sensorineural in 1%, and indeterminate in 16%. Hypoplasia of the ear or mandible was frequently associated with ipsilateral hearing loss, although contralateral hearing loss occurred in 8% of hemifaces. CONCLUSIONS: Hearing loss is strongly associated with malformations of the ipsilateral ear in craniofacial microsomia and is most commonly conductive. Hearing loss can occur contralaterally to the side with malformations in children with apparent hemifacial involvement. Children with craniofacial microsomia should receive early diagnostic hearing assessments.

Phenotypic characterization of epibulbar dermoids.

The purpose of this study was to characterize the phenotypic presentation, clinical course, and outcomes of epibulbar dermoids (EpDs) which are the most common congenital eye tumor in children. Sixty-eight dermoids were identified in 58 eyes of 48 patients of Seattle Children's Hospital between 1981 and 2014 via electronic medical record search. Patients were organized into: "EpD-Only" [patients without other congenital anomalies (n = 13)], "EpD-CFM" [patients with a craniofacial microsomia (CFM) diagnosis (n = 25)], and "EpD-Other" [patients with other congenital anomalies (n = 10)]. All EpD in the EpD-Only group were unilateral and singular, while the EpD-CFM group had six cases with multiple unilateral EpD and five cases with bilateral EpD. In the EpD-Only group, 69 % of EpD were left sided, whereas in the EpD-CFM group, there was no side predisposition. Among both groups, the majority of EpD were limbal or lipodermoids in the inferotemporal quadrant of the eye. Surgery was more common and at a younger age in the EpD-CFM group than the EpD-Only group (56 vs. 38 %, 5.2 vs. 7.0 years). Follow-up surgeries occurred only in the EpD-CFM group (21 %). EpDs were most commonly associated with preauricular tags, congenital heart defects, genitourinary, and nervous system anomalies. Whereas the location and type of EpDs did not significantly differ between the groups, the phenotype in the EpD-Only group appears to be less complex. This may indicate an important difference between EpDs in isolation and those within CFM. Additional studies will further characterize these phenotypes and outcomes.

Measuring Symmetry in Children With Unrepaired Cleft Lip: Defining a Standard for the Three-Dimensional Midfacial Reference Plane.

OBJECTIVE: Quantitative measures of facial form to evaluate treatment outcomes for cleft lip (CL) are currently limited. Computer-based analysis of three-dimensional (3D) images provides an opportunity for efficient and objective analysis. The purpose of this study was to define a computer-based standard of identifying the 3D midfacial reference plane of the face in children with unrepaired cleft lip for measurement of facial symmetry. PARTICIPANTS: The 3D images of 50 subjects (35 with unilateral CL, 10 with bilateral CL, five controls) were included in this study. INTERVENTIONS: Five methods of defining a midfacial plane were applied to each image, including two human-based (Direct Placement, Manual Landmark) and three computer-based (Mirror, Deformation, Learning) methods. MAIN OUTCOME MEASURE: Six blinded raters (three cleft surgeons, two craniofacial pediatricians, and one craniofacial researcher) independently ranked and rated the accuracy of the defined planes. RESULTS: Among computer-based methods, the Deformation method performed significantly better than the others. Although human-based methods performed best, there was no significant difference compared with the Deformation method. The average correlation coefficient among raters was .4; however, it was .7 and .9 when the angular difference between planes was greater than 6° and 8°, respectively. CONCLUSIONS: Raters can agree on the 3D midfacial reference plane in children with unrepaired CL using digital surface mesh. The Deformation method performed best among computer-based methods evaluated and can be considered a useful tool to carry out automated measurements of facial symmetry in children with unrepaired cleft lip.

Optimizing Surgical Treatment of Internationally Adopted Children With Cleft Lip and/or Palate: Understanding the Family Experience.

OBJECTIVE: To understand the experience of families with children undergoing cleft surgery following adoption from a country outside the United States. To identify factors, including the timing of surgery, that influence family function throughout the surgical experience. DESIGN: Semistructured qualitative interviews were conducted with parents of internationally adopted children postrepair of cleft lip and/or cleft palate and coded by a multidisciplinary study team. Mixed methods were used to contextualize themes derived from the parent interviews. RESULTS: Twenty parent interviews were conducted, and four core themes were identified: (1) parental anxieties prior to surgery, (2) considerations for the timing of surgery, (3) impact of the surgical experience on the child and family, and (4) modifiable sociocontextual factors. Parents considered a strong child bond with at least one parent and the ability of the child to communicate basic needs to be important before undergoing surgery. In retrospect, parents generally felt that the surgical experience did not have a negative impact on their child or their families and that the surgical experience may have even facilitated bonding and attachment with their child. Acceleration of family bonding was expressed more often by parents of children who were adopted at older than 2 years. CONCLUSIONS: In our study, parents reported that cleft surgery soon after international adoption did not appear to impair child bonding or adjustment. Specific family and provider factors that could optimize the experience for families were identified.

Phenotypic sub-grouping in microtia using a statistical and a clinical approach.

The clinical presentation of microtia varies widely from minimal morphological abnormalities to complete absence of the ear. In this study we sought to identify and characterize sub-groups of microtia using a statistical and a clinical approach. Photographs of 86 ears were classified in relation to all the external ear components. We used cluster analysis and rater's clinical opinion to identify groups with similar phenotypes in two separate analyses. We used Cramer's Phi coefficient of association to assess the similarity among the clinician's groupings as well as among the statistical sub-phenotypic groups and each of the clinician's groupings. The cluster analysis initially divided the 86 ears into a more and a less severe group. The less severe group included two sub-groups that included ears classified as normal and a group that had very few anomalous components. The group of 48 more affected ears all had abnormalities of the helix crus; antihelix-stem, -superior crus and -inferior crus; and antitragus. These were further divided into 4 sub-phenotypes. There was a moderate degree of association among the raters' groupings (Cramer's Phi: 0.64 to 0.73). The statistical and clinical groupings had a lower degree of association (Cramer's Phi: 0.49 to 0.58). Using standardized characterization of structural abnormalities of the ear we identified six distinct phenotypic groups; correlations with clinicians' groupings were moderate. These clusters may represent groups of ear malformations associated with the same etiology, similar time of insult or target cell population during embryonic development. The results will help inform investigations on etiology.

The Furlow palatoplasty for velopharyngeal dysfunction: velopharyngeal changes, speech improvements, and where they intersect.

OBJECTIVE: We investigated how Furlow palatoplasty changes velopharyngeal morphology and speech characteristics, as well as how the anatomical and clinical results might be related. We hypothesized that Furlow palatoplasty would result in measurable velar elongation, tightening of the genu angle, and retropositioning of the levator sling and that the achievement of these modifications might be associated with clinical speech improvement. DESIGN: Retrospective analysis of preoperative and postoperative videofluoroscopic and speech data. SETTING: Tertiary care center. PATIENTS/PARTICIPANTS: A total of 29 patients with velopharyngeal insufficiency in the setting of previous cleft palate repair or submucous cleft palate. INTERVENTIONS: Furlow palatoplasty for treatment of velopharyngeal insufficiency. OUTCOME MEASURES: Lateral videofluoroscopy and perceptual speech examination were conducted preoperatively and postoperatively in order to measure velopharyngeal dimensions and speech quality. We describe anatomical and speech changes associated with the Furlow palatoplasty and undertake an exploratory analysis of the relationship between surgical changes to the velopharynx and clinical outcomes. RESULTS: Furlow palatoplasty results in significant velar elongation, increased acuity of the genu angle, and retropositioning of the levator sling. Postoperative speech improvement was identified on the three subscales of resonance, nasal emission, and stops/plosives. Speech improvement and the absence of need for reoperation were most consistently associated with tightening of the genu angle. CONCLUSIONS: Furlow palatoplasty lengthens the palate, while both tightening and retropositioning the levator sling. These changes reflect transverse recruitment of lateral velar tissues, along with transverse tightening and anterior release of the muscle fibers, respectively. Levator tightening is most consistently associated with improved speech outcomes.

Use of antihypertensive medications and breast cancer risk.

PURPOSE: Use of specific antihypertensive medications (AHTs) has been hypothesized to increase breast cancer risk, but results across published studies are inconsistent. METHODS: We re-evaluated the relationship between AHT use and breast cancer risk in a prospective cohort of 3,201 women ≥65 years of age at recruitment now with more than double the length of follow-up (12 vs. 5 years) and substantially more breast cancer diagnoses (188 compared with 75 cases). We estimated the association between AHT use overall as well as use of specific formulations (based on data collected annually) and breast cancer risk using multivariate-adjusted Cox regression. RESULTS: Compared with women who reported no use of AHTs, women who had used calcium channel blockers (CCB) within the past two years had a 1.6-fold increased risk of breast cancer (95 % confidence interval (CI): 1.0-2.5), and in particular, recent users of immediate-release CCBs had a 2.4-fold increased risk (95 % CI: 1.3-4.5). Neither ever nor recent use of any other type of AHT was associated with breast cancer risk. CONCLUSIONS: While the observed association between immediate-release CCBs and breast cancer risk is based on a small sample size and needs to be interpreted cautiously, this result is consistent with others in the literature. However, given declines in use of these preparations in favor of sustained-release CCBs, which was not related to risk, the potential clinical and public health impact of this association is limited. This study also adds to the evidence that other commonly used AHTs are not strongly related to breast cancer risk.

Interrater reliability of a phenotypic assessment tool for the ear morphology in microtia.

The Elements of Morphology Standard Terminology working group published standardized definitions for external ear morphology. The primary objective of our study was to use these descriptions to evaluate the interrater reliability for specific features associated with microtia. We invited six raters from three different subspecialities to rate 100 ear photographs on 32 features. We calculated overall and within specialty and professional experience intraclass correlation coefficients (ICC) and 95% confidence intervals. A total of 600 possible observations were recorded for each feature. The overall interrater reliability ranged from 0.04 (95% CI: 0.00-0.14) for the width of the antihelix inferior crus to 0.93 (95% CI: 0.91-0.95) for the presence of the inferior crux of the antihelix. The reliability for quantitative characteristics such as length or width of an ear structure was generally lower than the reliability for qualitative characteristics (e.g., presence or absence of an ear structure). Categories with very poor interrater reliability included anti-helix inferior crux width (0.04, 95% CI: 0.00-0.14), crux helix extension (0.17, 95% CI 0.00-0.37), and shape of the incisura (0.14, 95% CI: 0.01-0.27). There were no significant differences in reliability estimates by specialty or professional experience for most variables. Our study showed that it is feasible to systematically characterize many of structures of the ear that are affected in microtia. We incorporated these descriptions into a standardized phenotypic assessment tool (PAT-Microtia) that might be used in multicenter research studies to identify sub-phenotypes for future studies of microtia.

Risk factors and demographics for microtia in South America: a case-control analysis.

BACKGROUND: The etiopathogenesis of microtia is still unknown in the majority of the cases, particularly for individuals presenting with isolated microtia. Our aim was to evaluate potential risk factors for this condition using a case-control approach. METHODS: We analyzed data from 1,194 live births with isolated microtia enrolled in the ECLAMC study (Estudio Colaborativo Latino Americano de Malformaciones Congénitas) from 1982 to 2011 and their respective controls. Odds ratios (ORs) were estimated with logistic regression models along with 95% confidence intervals for the resulting OR estimates controlling for the effects of potential confounders (sex, maternal age, hospital, and year of birth) for an adjusted OR (aOR). RESULTS: Multiparity was associated with a higher risk of microtia compared with primiparity (aOR, 1.5; 95% confidence interval [CI], 1.2-1.8), with women who had eight or more prior pregnancies having the highest risk (aOR, 2.8; 95% CI, 1.6-5.2). Women who presented with cold-like symptoms were at higher risk for microtia (aOR, 2.2; 95% CI, 1.2-3.9) as well as those that used tobacco or alcohol during pregnancy (aOR, 1.7; 95% CI, 1.1-2.6 and aOR, 1.4; 95% CI, 0.9-2.1, respectively). The association with alcohol use appeared to be limited to those women who reported binge drinking during pregnancy (aOR, 1.4; 95% CI, 0.7-3.1). Cases from hospitals at low altitude (<2500 m) tended to have more severe types of microtia than those from hospitals at high altitude. CONCLUSION: These results support the hypothesis that, in addition to teratogens, other nongenetic risk factors contribute to the occurrence of isolated microtia.

Making the diagnosis: metopic ridge versus metopic craniosynostosis.

INTRODUCTION: The metopic suture is the only calvarial suture which normally closes during infancy. Upon closure, a palpable and visible ridge often forms which can be confused with metopic craniosynostosis. Metopic ridging (MR) is treated nonsurgically while metopic craniosynostosis (MCS) is treated surgically. Differentiating between the two is paramount; however, consensus is lacking about where a clear diagnostic threshold lies. The goal of this study is to describe the physical examination and CT scan characteristics which may help to differentiate between physiological closure of the metopic suture with ridging (MR) and MCS. METHODS: A retrospective chart review of all patients seen at Seattle Children's Hospital between 2004 and 2009 with the diagnosis of either MCS or MR (n = 282) was performed. Physical examination characteristics described by diagnosing practitioners were analyzed. Clinical photos were assessed by 3 expert raters to determine the importance of these characteristics. CT scan findings were abstracted and compared between the two diagnoses. RESULTS: The "classic" triad of narrow forehead, biparietal widening, and hypotelorism was present in only 14% of patients with MCS. Ninety-eight percent of patients in both groups had a palpable metopic ridge. The photographic finding of narrow forehead and pterional constriction was present in all patients with MCS, but only in 11.2% and 2.8% of patients with MR. On CT scan, the presence of 3 or more MCS findings was diagnostic of MCS in 96% of patients. Patients with MCS were more likely to present before 6 months of age (66% vs. 32%). CONCLUSIONS: Patients with MCS tend to present earlier than those with MR. Upon physical examination, the relationship between the lateral frontal bone and the lateral orbit is important in distinguishing between the two diagnoses. A CT scan can be helpful in making the diagnosis not to confirm a closed suture but to identify 3 or more MCS characteristics.

Comparison of two-dimensional and three-dimensional images for phenotypic assessment of craniofacial microsomia.

Background and Purpose : Three-dimensional surface imaging is used in many craniofacial centers. However, few data exist to indicate whether such systems justify their cost. Craniofacial microsomia is associated with wide phenotypic variability and can affect most facial features. The purpose of this study is to compare three-dimensional versus two-dimensional images for classification of facial features in individuals with craniofacial microsomia. Methods : We obtained a series of two-dimensional and three-dimensional images of 50 participants, aged 0-20 years, diagnosed with craniofacial microsomia, microtia, or Goldenhar syndrome. Three clinicians classified the craniofacial features on each image, and ratings were compared by calculating kappa statistics. We also evaluated image quality using a 5-point Likert scale. Results : Reliability estimates were high for most features using both two-dimensional and three-dimensional image data. Our three-dimensional protocol did not allow for scoring of facial animation, occlusal cant, or tongue anomalies. Image quality scores for the mandible and soft tissue assessment were higher for three-dimensional images. Raters preferred two-dimensional photographs for assessment of the ear, ear canal, and eyes. Conclusions : Both three-dimensional and two-dimensional images provide useful data for objective characterization of the craniofacial features affected in craniofacial microsomia. A series of two-dimensional images has relative advantages for assessment of some specific features, such as the ear, though three-dimensional images may have advantages for quantitative analysis and qualitative assessment of deformities of the jaw and soft tissue. These results should apply to any assessment of these features with or without a craniofacial microsomia diagnosis.

Estrogen receptor, progesterone receptor, and HER2-neu expression in first primary breast cancers and risk of second primary contralateral breast cancer.

Breast cancer survivors have a 60 % higher risk of developing a second primary asynchronous contralateral breast cancer (CBC) compared to women's risk of developing a first primary breast cancer (FBC). However, little is known about how expression of tumor markers in first breast cancers influences CBC risk. We conducted a population-based nested case-control study among women 20-74 years of age diagnosed with a first breast cancer between 1996 and 2008 in western Washington State to evaluate the association between their tumor's estrogen receptor (ER), progesterone receptor (PR) and HER2-neu (HER2) expression, and risk of CBC. The study included 482 cases diagnosed with both a FBC and a CBC and 1,506 control women diagnosed only once with breast cancer identified through our local Surveillance, Epidemiology and End Results (SEER) cancer registry. Compared to the women whose FBC was ER+/PR+, those with ER-/PR- first tumors had a 1.6-fold (95 % confidence interval (CI): 1.2-2.3) increased risk of developing a CBC. When evaluated by joint ER/PR/HER2 status, compared to women with ER+/HER2- first cancers, those with HER2-overexpressing (ER-/HER2+) and triple-negative disease (ER-/PR-/HER2-) had 2.0-fold (95 % CI: 1.1-3.8) and 1.4-fold (95 % CI: 0.9-2.3) elevated risks of developing CBC, respectively. Beyond the known higher risks of mortality among patients diagnosed with more aggressive BC subtypes, here, we observe that they may also have increased risks of developing CBC.

Visiting the emergency department for dental problems: trends in utilization, 2001 to 2008.

OBJECTIVES: We tested the hypothesis that between 2001 and 2008, Americans increasingly relied upon emergency departments (EDs) for dental care. METHODS: Data from 2001 through 2008 were collected from the National Hospital Ambulatory Medical Care Survey (NHAMCS). Population-based visit rates for dental problems, and, for comparison, asthma, were calculated using annual US Census Bureau estimates. As part of the analysis, we described patient characteristics associated with large increases in ED dental utilization. RESULTS: Dental visit rates increased most dramatically for the following subpopulations: those aged 18 to 44 years (7.2-12.2 per 1000, P < .01); Blacks (6.0-10.4 per 1000, P < .01); and the uninsured (9.5-13.2 per 1000, P < .01). Asthma visit rates did not change although dental visit rates increased 59% from 2001 to 2008. CONCLUSIONS: There is an increasing trend in ED visits for dental issues, which was most pronounced among those aged 18 to 44 years, the uninsured, and Blacks. Dental visit rates increased significantly although there was no overall change in asthma visit rates. This suggests that community access to dental care compared with medical care is worsening over time.

Evaluation of ICD-9-CM codes for craniofacial microsomia.

BACKGROUND: Craniofacial microsomia (CFM) is a congenital condition characterized by microtia and mandibular underdevelopment. Healthcare databases and birth defects surveillance programs could be used to improve knowledge of CFM. However, no specific International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code exists for this condition, which makes standardized data collection challenging. Our aim was to evaluate the validity of existing ICD-9-CM codes to identify individuals with CFM. METHODS: Study sample eligibility criteria were developed by an expert panel and matched to 11 ICD-9-CM codes. We queried hospital discharge data from two craniofacial centers and identified a total of 12,254 individuals who had ≥1 potentially CFM-related code(s). We reviewed all (n = 799) medical records identified at the University of North Carolina (UNC) and 500 randomly selected records at Seattle Children's Hospital (SCH). Individuals were classified as a CFM case or non-case. RESULTS: Thirty-two individuals (6%) at SCH and 93 (12%) at UNC met the CFM eligibility criteria. At both centers, 59% of cases and 95% of non-cases had only one code assigned. At both centers, the most frequent codes were 744.23 (microtia), 754.0 and 756.0 (nonspecific codes), and the code 744.23 had a positive predictive value (PPV) >80% and sensitivity >70%. The code 754.0 had a sensitivity of 3% (PPV <1%) at SCH and 36% (PPV = 5%) at UNC, whereas 756.0 had a sensitivity of 38% (PPV = 5%) at SCH and 18% (PPV = 26%) at UNC. CONCLUSIONS: These findings suggest the need for a specific CFM code to facilitate CFM surveillance and research.

Nasopharyngeal airway for management of airway obstruction in infants with micrognathia.

OBJECTIVE: Describe airway management using nasopharyngeal airway in infants. DESIGN: Retrospective case series (1996 to 2006). SETTING: Tertiary pediatric hospital. PATIENTS, PARTICIPANTS: The craniofacial database of Seattle Children's Hospital was searched to identify patients with one of the following diagnoses: micrognathia, secondary cleft palate, branchial arch anomalies, Pierre Robin sequence (PRS), or velocardiofacial syndrome. Thirty-five (10.9%) of the 320 infants born between January 1, 1996, and March 31, 2006, identified using the criteria listed above were managed with nasopharyngeal airway (NPA) during infancy. INTERVENTIONS: Use of NPA. MAIN OUTCOME MEASURE: Summary statistics describing the distribution of the infants' demographic characteristics, duration, and timing of their NPA placement, need for tracheotomy, feeding interventions, and death. RESULTS: Of the 35 patients included in this case series, 60% (21) were male. Eighteen (51.4%) patients had the diagnosis of PRS, 13 (37.1%) had secondary cleft palate and other craniofacial anomalies, and four (11.4%) had branchial anomalies and micrognathia (nonsyndromic or syndromic). Thirty-one children (88.6%) were born at term. Mean and median age at initial NPA placement was 3.2 and 1.3 weeks, respectively; median duration of NPA was 8.0 weeks. Nine children received tracheotomies. Feeding tubes were required in 85.7% of patients. Two children died; however, neither death was attributed to airway obstruction or the use of NPA. CONCLUSIONS: NPA is one option in the management of patients with craniofacial anomalies and airway obstruction. The majority of nonsyndromic PRS patients treated with NPA during infancy did not require airway intervention beyond NPA.

What the patients and parents do not tell you-recollections from families following external LeFort III midface distraction.

OBJECTIVE: The purpose of this study was to document the experience of patients and parents of patients who had recently undergone LeFort III midface distraction using an external halo-based device. DESIGN: Cross-sectional study. SETTING: A craniofacial center in a pediatric tertiary care medical center. SUBJECTS: Eight children who had undergone midface distraction within 1 year of the interview and their caregivers. INTERVENTION: Semi-structured interview. MAIN OUTCOME MEASURE: Transcripts of the interviews were rendered anonymous and analyzed by our multi-disciplinary team. Consistent themes in the subjects' experience during and after midface distraction were identified. RESULTS: (1) Family participation in the decision to undergo distraction and pre-operative preparation was recognized as valuable, but parents identified that there are inherent limitations; (2) home-care tasks seemed daunting pre-operatively but were easier than expected; (3) discomfort, sleeping, and interaction with peers were considered well accommodated, but feeding was challenging; (4) individualized pre-operative plans for community support was important; (5) parents and patients were impressed by the change in appearance, specifically in the peri-orbital region; (6) access to team members and to parents of patients who had participated in the distraction process was invaluable. CONCLUSION: External midface distraction is a valuable clinical technique, but requires intensive preparation and support from a multi-disciplinary team. We provide suggestions for consideration by centers initiating and refining patient care plans for this surgery.

Diabetes and endometrial cancer: an evaluation of the modifying effects of other known risk factors.

To determine whether risk of endometrial cancer among women with type 2 diabetes differs with respect to other endometrial cancer risk factors, the authors used data from a population-based case-control study (1,303 cases and 1,779 controls) conducted in western Washington State during 1985-1999. History of type 2 diabetes was associated with endometrial cancer (odds ratio (OR) = 1.7, 95% confidence interval (CI): 1.2, 2.3), more strongly among women with a recent diabetes diagnosis (<5 years) (OR = 2.6, CI: 1.5, 4.7) than among those with a more distant diagnosis (> or =5 years) (OR = 1.3, CI: 0.8, 1.9). Type 2 diabetes was associated with endometrial cancer among women with a body mass index (BMI) (weight (kg)/height (m)(2)) less than 35 but not among women with a BMI of 35 or more. The observed associations persisted after finer adjustment for BMI to control for residual confounding. History of diabetes was associated with a twofold increased risk of endometrial cancer among hypertensive women, but no association was observed among nonhypertensive women. The risk associated with type 2 diabetes appeared not to vary greatly with respect to other endometrial cancer risk factors. These results support the hypothesis that type 2 diabetes is associated with endometrial cancer irrespective of the presence of other risk factors for this disease, except possibly hypertension and extreme obesity.

Long-term use of postmenopausal estrogen and progestin hormone therapies and the risk of endometrial cancer.

OBJECTIVE: The purpose of this study was to assess whether endometrial cancer risk among long-term users of (1) sequential estrogen plus progestin 10-24 days per month exceeds that of nonusers and (2) daily estrogen plus progestin (continuous combined hormone therapy) is below that of nonusers. STUDY DESIGN: In this population-based case-control study with 1038 endometrial cancer cases diagnosed in 1985-1999 and 1453 control subjects, exclusive users of a single form of hormone therapy were compared with never users of hormone therapy. RESULTS: For sequential therapy, only long-term use (> or = 6 years) was associated with increased risk (odds ratio, 2.0; 95% CI, 1.2-3.5). Continuous combined therapy was associated with decreased risk (odds ratio, 0.59; 95% CI, 0.40-0.88), with no increased risk among long-term users (odds ratio, 0.77; 95% CI, 0.45-1.3). CONCLUSION: These results support the hypotheses that continuous combined therapy does not increase (and may decrease) endometrial cancer risk and that long-term sequential therapy can lead to a modest increased risk. However, the collective results of all studies of these questions and their clinical implications remain unclear.

Risk Factors for Late-Onset Group B Streptococcal Disease Before and After Implementation of Universal Screening and Intrapartum Antibiotic Prophylaxis.

BACKGROUND: It is unclear whether risk factors for late-onset Group B Streptococcus disease (LOD) have changed since the introduction of universal screening and treatment in 2002. METHODS: We conducted a case-control study using linked birth certificates and hospital discharge records. All infants born in Washington State from 1992 to 2011 and hospitalized between 7 and 89 days of life with a Group B Streptococcus (GBS)-related International Classification of Diseases (ICD)-9 code were included. Controls were matched 4:1 by birth year. Multivariate logistic regression was used to evaluate the association between clinical characteristics and LOD. We compared differences in the effect of risk factors on LOD between infants born before and after 2002 using likelihood ratio tests. RESULTS: We identified 138 cases of LOD. In multivariate analyses, prematurity and young maternal age were significantly associated with risk of LOD throughout the study period; positive GBS screen was associated with LOD from 2003 to 2011. Each week of decreasing gestation was associated with a 1.24 (95% confidence interval: 1.15-1.35) times greater likelihood of LOD. We did not detect differences in the association between prematurity or young maternal age and LOD comparing infants born before and after 2002. Compared with infants of non-Hispanic white mothers, risk of LOD among infants of non-Hispanic black mothers decreased after 2002 (adjusted odds ratio [aOR] = 2.74 vs 0.64; pinteraction = 0.02), whereas risk of LOD among infants of Hispanic mothers increased (aOR = 0.80 vs 2.23; pinteraction ≤ 0.001). CONCLUSIONS: Our results confirm studies conducted before 2002, which found that prematurity and young maternal age were associated with increased risk of LOD. Ethnicity-associated LOD risk differed before and after 2002, which may be related to healthcare access.

Reliable classification of facial phenotypic variation in craniofacial microsomia: a comparison of physical exam and photographs.

BACKGROUND: Craniofacial microsomia is a common congenital condition for which children receive longitudinal, multidisciplinary team care. However, little is known about the etiology of craniofacial microsomia and few outcome studies have been published. In order to facilitate large, multicenter studies in craniofacial microsomia, we assessed the reliability of phenotypic classification based on photographs by comparison with direct physical examination. METHODS: Thirty-nine children with craniofacial microsomia underwent a physical examination and photographs according to a standardized protocol. Three clinicians completed ratings during the physical examination and, at least a month later, using respective photographs for each participant. We used descriptive statistics for participant characteristics and intraclass correlation coefficients (ICCs) to assess reliability. RESULTS: The agreement between ratings on photographs and physical exam was greater than 80 % for all 15 categories included in the analysis. The ICC estimates were higher than 0.6 for most features. Features with the highest ICC included: presence of epibulbar dermoids, ear abnormalities, and colobomas (ICC 0.85, 0.81, and 0.80, respectively). Orbital size, presence of pits, tongue abnormalities, and strabismus had the lowest ICC, values (0.17 or less). There was not a strong tendency for either type of rating, physical exam or photograph, to be more likely to designate a feature as abnormal. The agreement between photographs and physical exam regarding the presence of a prior surgery was greater than 90 % for most features. CONCLUSIONS: Our results suggest that categorization of facial phenotype in children with CFM based on photographs is reliable relative to physical examination for most facial features.