An expert consensus on managing dupilumab-related ocular surface disorders in people with atopic dermatitis 2024.

BACKGROUND: Atopic dermatitis (AD) is the most common inflammatory skin condition which affects all ages. New therapies, including the monoclonal antibody therapy dupilumab, offer excellent efficacy. However, in clinical trials, and emphasised in real-world observations, the unexpected increased frequency of ocular adverse effects became apparent. The effectiveness of dupilumab and the unpredictability of ocular adverse effects mean that clinicians need guidance on counselling patients prior to treatment and on managing them if they arise. OBJECTIVES: The British Association of Dermatologists (BAD) and Royal College of Ophthalmologists collaborated on this consensus guidance on managing dupilumab-related ocular surface disorders (DROSD). METHODS: A multidisciplinary group was formed of adult and paediatric dermatologists and ophthalmologists with DROSD expertise, patient representation, and BAD Clinical Standards Unit. A literature search was conducted, and the results reviewed. All recommendations were reviewed, discussed and voted on. RESULTS: The recommendations pertain to dermatology and ophthalmology management, and apply to all ages, unless otherwise stated. Importantly, initiation of dupilumab for AD should not be delayed for most eye disorders except acute new problems, e.g. infections, or potentially severe conditions, e.g. a history of corneal transplant (ophthalmology advice should be sought first). There is insufficient evidence to recommend lubricant drops prophylactically. Dermatologists should assess eye complaints to diagnose DROSD; a severity grading system is provided. DROSD management differs slightly in those aged <7 years as ocular complications may affect neuro-ocular development; therefore, irrespective of DROSD severity, this population should be referred for ophthalmology advice. In those aged ≥7 years, dermatologists should feel confident to trial treatment and reserve ophthalmology advice for severe or non-responding cases. Discussion about dupilumab withdrawal should be prompted by a significant impact on quality of life, threat to sight, or other complications. CONCLUSIONS: Although dupilumab is a highly effective agent for treating AD, the risk of ocular adverse effects should not inhibit clinicians or patients from using it, but clinicians should be aware of them. If a patient develops DROSD, there are clear pathways to assess severity and offer initial management; where ineffective, dermatologists should assess the urgency and seek advice from or initiate referral to ophthalmology. While the evidence reviewed for these guidelines reflects the extensive literature on dupilumab, we believe our advice has relevance for ocular surface disorders in atopic dermatitis (AD) patients treated with tralokinumab and lebrikizumab.

Defining Patient-relevant Thresholds and Change Scores for the HOOS JR and KOOS JR Anchored on the Patient-acceptable Symptom State Question.

BACKGROUND: When evaluating the results of clinical research studies, readers need to know that patients perceive effect sizes, not p values. Knowing the minimum clinically important difference (MCID) and the patient-acceptable symptom state (PASS) threshold for patient-reported outcome measures helps us to ascertain whether our interventions result in improvements that are large enough for patients to care about, and whether our treatments alleviate patient symptoms sufficiently. Prior studies have developed the MCID and PASS threshold for the Hip Disability and Osteoarthritis Outcome Score for Joint Replacement (HOOS JR) and Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS JR) anchored on satisfaction with surgery, but to our knowledge, neither the MCID nor the PASS thresholds for these instruments anchored on a single-item PASS question have been described. QUESTIONS/PURPOSES: (1) What are the MCID (defined here as the HOOS/KOOS JR change score associated with achieving PASS) and PASS threshold for the HOOS JR and KOOS JR anchored on patient responses to the single-item PASS instrument? (2) How do patient demographic factors such as age, gender, and BMI correlate with MCID and PASS thresholds using the single-item PASS instrument? METHODS: Between July 2020 and September 2021, a total of 10,970 patients underwent one primary unilateral THA or TKA and completed at least one of the three surveys (preoperative HOOS or KOOS JR, 1-year postoperative HOOS or KOOS JR, and 1-year postoperative single-item anchor) at one large, academic medical center. Of those, only patients with data for all three surveys were eligible, leaving 13% (1465 total; 783 THAs and 682 TKAs) for analysis. Despite this low percentage, the overall sample size was large, and there was little difference between completers and noncompleters in terms of demographics or baseline patient-reported outcome measure scores. Patients undergoing bilateral total joint arthroplasty or revision total joint arthroplasty and those without all three surveys at 1 year of follow-up were excluded. A receiver operating characteristic curve analysis, leveraging a 1-year, single-item PASS (that is, "Do you consider that your current state is satisfactory?" with possible answers of "yes" or "no") as the anchor was then used to establish the MCID and PASS thresholds among the 783 included patients who underwent primary unilateral THA and 682 patients who underwent primary unilateral TKA. We also explored the associations of age at the time of surgery (younger than 65 years or 65 years and older), gender (men or women), BMI (< 30 or ≥ 30 kg/m 2 ), and baseline Patient-Reported Outcome Measure Information System-10 physical and mental component scores (< 50 or ≥ 50) for each of the MCID and PASS thresholds through stratified analyses. RESULTS: For the HOOS JR, the MCID associated with the PASS was 23 (95% CI 18 to 31), with an area under the receiver operating characteristic curve of 0.75, and the PASS threshold was 81 (95% CI 77 to 85), with an area under the receiver operating characteristic curve of 0.81. For the KOOS JR, the MCID was 16 (95% CI 14 to 18), with an area under the receiver operating characteristic curve of 0.75, and the PASS threshold was 71 (95% CI 66 to 73) with an area under the receiver operating characteristic curve of 0.84. Stratified analyses indicated higher change scores and PASS threshold for younger men undergoing THA and higher PASS thresholds for older women undergoing TKA. CONCLUSION: Here, we demonstrated the utility of a single patient-centered anchor question, raising the question as to whether simply collecting a postoperative PASS is an easier way to measure success than collecting preoperative and postoperative patient-reported outcome measures and then calculating MCIDs and the substantial clinical benefit. LEVEL OF EVIDENCE: Level III, therapeutic study.

Unexpected Positive Cultures in Hip and Knee Periprosthetic Fractures.

BACKGROUND: The purpose of this study was to determine the prevalence of unexpected positive cultures noted at the time of revision surgery for periprosthetic fracture (PPF) after total hip or knee arthroplasty. Moreover, we evaluated whether this finding should be considered clinically significant and what type of treatment, if any, was required. METHODS: This was a single-center retrospective review of 270 patients undergoing surgery for PPFs from December 2010 to December 2021. Exclusion criteria included: open fractures; history of infection at fractured joint; non-operatively treated patients; and intraoperative fractures. The primary end point was the prevalence of unexpected positive cultures noted at the time of revision surgery. This was defined as one or more positive cultures in a PPF that the surgeon had preoperatively classified as aseptic according to the 2018 International Consensus Meeting. Data collection included patient demographics, medical histories, preoperative investigations, postoperative microbiology, and treatment. RESULTS: During the study period, 159 patients were admitted with PPFs of the hip and 61 with PPFs of the knee. The mean age was 70 years (range, 32 to 93 years). Unexpected positive cultures were diagnosed postoperatively in 15 patients (6.8%; 10 hips, 5 knees). The most prevalent organism was Staphylococcus epidermidis (35.0%). Of those 15 patients, 6 required a surgical revision for infection. None of the patient-related risk factors were found to be associated with an increased risk of unexpected positive cultures. The comparison between infected and noninfected patients showed a significant association between preoperative C-reactive protein >10 mg/mL (P = .04), loose implant (P = .07), and infection. CONCLUSIONS: The prevalence of unexpected positive cultures was 6.8% in our study cohort. Although surgical treatment may be required, the majority of patients seem to require no treatment. Larger series are required to investigate the clinical importance of this rare finding. LEVEL OF EVIDENCE: III.

To Stage or Not to Stage? Comparison of Patient-Reported Outcomes, Complications, and Discharge Disposition After Staged and Simultaneous Bilateral Posterior Total Hip Arthroplasty.

BACKGROUND: Patients who have bilateral hip arthritis can be treated with bilateral total hip arthroplasty (bTHA) in either a staged or simultaneous fashion. The goal of this study was to determine whether staged and simultaneous posterior bTHA patients differ in regard to (1) patient-reported outcome measures, (2) 90-day complication rates, and (3) discharge dispositions and cumulative lengths of stay. METHODS: Patients who (1) underwent simultaneous bTHA or staged bTHA (within 12 months) using the posterior approach, and (2) completed preoperative and 1-year postoperative Hip dysfunction and Osteoarthritis Outcome Score for Joint Replacement surveys were included in the study. A total of 266 patients (87 simultaneous bTHA and 179 staged bTHA) were included. Chart review was performed to collect patient-level variables, postoperative complications, discharge dispositions, and lengths of stay. RESULTS: Staged bTHA patients had higher Hip dysfunction and Osteoarthritis Outcome Score for Joint Replacement, Lower Extremity Activity Scale, and Veterans RAND 12-Item Health Survey physical component scores compared to simultaneous bTHA patients at 6 weeks after surgery (P = .019, .006, and .008, respectively), but these differences did not meet the minimal clinically important difference threshold for any questionnaire. Simultaneous bTHA was associated with higher rate of periprosthetic fractures (P = .034) and discharge to a location other than home (P < .001). CONCLUSIONS: There were statistically significant, but likely not clinically meaningful differences in patient-reported outcomes for staged and simultaneous bTHA patients at 6 weeks after surgery. Surgeons should be aware of the higher periprosthetic fracture risk and greater likelihood of discharge to a rehabilitation facility associated with simultaneous bTHA. Further research should aim to understand which patients may benefit most from simultaneous bTHA.

Early Periprosthetic Femur Fractures After Primary Cementless Total Hip Arthroplasty: High Risk of Periprosthetic Joint Infection and Subsequent Reoperation.

BACKGROUND: Periprosthetic femur fracture (PFF) following total hip arthroplasty (THA) is a leading cause of early reoperation. The objective of this study was to compare rates of periprosthetic joint infection (PJI) and reoperation following PFFs occurring early postoperatively to those that occurred late. METHODS: We retrospectively identified 173 consecutive surgically managed PFFs following primary THA. Cases were categorized as "early" if they occurred within 90 days of THA (n = 117) or "late" if they occurred following the initial 90 days (n = 56). Mean age at time of PFF was 68 years (range, 26 to 96) and 60% were women. Mean body mass index was 29 (range, 16 to 52). Mean follow-up was 2 years (range, 0 to 13). Kaplan-Meier survival analysis estimated cumulative incidences of PJI and reoperation. RESULTS: Early PFFs had higher 2-year cumulative incidence of PJI (11% versus 0%, P < .001) and reoperation (24% versus 13%, P = .110). Following early PFF, 27 patients required reoperation (ie, 13 for PJI, 5 for instability, 2 for re-fracture, 2 for painful hardware, 2 for non-union, 1 for adverse local tissue reaction, 1 for aseptic loosening, and 1 for leg-length discrepancy). Following late PFF, 5 patients required reoperation (ie, 3 for instability, 1 for re-fracture, and 1 for non-union). CONCLUSIONS: There are greater incidences of PJIs and overall reoperations following early PFFs compared to late PFFs after THA. In addition to focusing efforts on prevention of early PFFs, surgeons should consider antiseptic interventions to mitigate the increased risk of PJI after treatment of early PFF.

Obesity Severity Does Not Associate With Rate, Timing, or Invasiveness of Early Reinterventions After Total Knee Arthroplasty.

BACKGROUND: The use of body mass index (BMI) cutoff values has been suggested for proceeding with total knee arthroplasty (TKA) in obese patients. However, the relationship between obesity severity and early reoperations after TKA is poorly defined. This study evaluated whether increased World Health Organization (WHO) obesity class was associated with risk, severity, and timing of reintervention within one year after TKA. METHODS: There were 8,674 patients from our institution who had a BMI ≥ 30 and underwent unilateral TKA for primary osteoarthritis between 2016 and 2021. Patients were grouped by WHO obesity class: 4,456 class I (51.5%), 2,527 class II (29.2%), and 1,677 class III (19.4%). A chart review was performed to determine patient characteristics and identify patients who underwent any closed or open reintervention requiring anesthesia within the first postoperative year. Regression analyses were performed to identify variables associated with increased odds ratios (ORs) for requiring a reintervention, its timing, and invasiveness. RESULTS: There were 158 patients (1.8%) who required at least one reintervention, and 15 patients (0.2%) required at least 2 reinterventions. Reintervention rates for obesity classes I, II, and III were 1.8% (n = 81), 2.0% (n = 51), and 1.4% (n = 23), respectively. There were 65 closed procedures (41.1%), 47 minor procedures (29.7%), 34 open with or without liner exchange (21.5%), and 12 revisions with component exchange (7.6%). Obesity class was not associated with reintervention rate (P = .3), timing (P = .36), or invasiveness (P = .93). Diabetes (odds ratio [OR] = 2.47; P = .008) was associated with a need for reintervention. Non-Caucasian race (OR = 1.7; P = .01) and Charlson comorbidity index (OR = 2.1; P = .008) were associated with earlier reintervention. No factors were associated with the invasiveness of reintervention. CONCLUSIONS: The WHO obesity class did not associate with rate, timing, or invasiveness of reintervention after TKA in obese patients. These findings suggest that policies that restrict the indication for elective TKA based only on a BMI limit have limited efficacy in reducing early reintervention after TKA in obese patients. LEVEL OF EVIDENCE: III.

Reliability and validity of the Paprosky classification for acetabular bone loss based on level of orthopedic training.

BACKGROUND: Reliability and validity of the Paprosky classification for acetabular bone loss have been debated. Additionally, the relationship between surgeon training level and Paprosky classification accuracy/treatment selection is poorly defined. This study aimed to: (1) evaluate the validity of preoperative Paprosky classification/treatment selection compared to intraoperative classification/treatment selection and (2) evaluate the relationship between training level and intra-rater and inter-rater reliability of preoperative classification and treatment choice. METHODS: Seventy-four patients with intraoperative Paprosky types [I (N = 24), II (N = 27), III (N = 23)] were selected. Six raters (Residents (N = 2), Fellows (N = 2), Attendings (N = 2)) independently provided Paprosky classification and treatment using preoperative radiographs. Graders reviewed images twice, 14 days apart. Cohen's Kappa was calculated for (1) inter-rater agreement of Paprosky classification/treatment by training level (2), intra-rater reliability, (3) preoperative and intraoperative classification agreement, and (4) preoperative treatment selection and actual treatment performed. RESULTS: Inter-rater agreement between raters of the same training level was moderate (K range = 0.42-0.50), and mostly poor for treatment selection (K range = 0.02-0.44). Intra-rater agreement ranged from fair to good (K range = 0.40-0.73). Agreement between preoperative and intraoperative classifications was fair (K range = 0.25-0.36). Agreement between preoperative treatment selections and actual treatments was fair (K range = 0.21-0.39). CONCLUSION: Inter-rater reliability of Paprosky classification was poor to moderate for all training levels. Preoperative Paprosky classification showed fair agreement with intraoperative Paprosky grading. Treatment selections based on preoperative radiographs had fair agreement with actual treatments. Further research should investigate the role of advanced imaging and alternative classifications in evaluation of acetabular bone loss.

Does Acetabular Bone Loss Severity Associate With Patient-Reported Outcome Measures and Reoperation Rate in Revision Total Hip Arthroplasty?

BACKGROUND: Acetabular bone loss is a challenging clinical problem when performing revision total hip arthroplasty (rTHA). This study aimed to evaluate how acetabular bone loss severity influences (1) clinical outcomes and (2) patient-reported outcome measures (PROMs) in rTHA patients. METHODS: Patients who underwent rTHA with acetabular component revision from January 2016 to February 2022 were included. Treating surgeons determined Paprosky acetabular bone loss classification intraoperatively. Patients were grouped based on numeric classification (PI, PII, or PIII) to categorize severity. Hip disability and Osteoarthritis Outcome Score for Joint Replacement (HOOS, JR.) and Lower Extremity Activity Scale (LEAS) score were collected preoperatively and 1 year postoperatively. There were 197 patients included. Paprosky classification was PI for 47 patients (23.9%), PII for 113 patients (57.4%), and PIII for 37 patients (18.8%). Mean clinical follow-up was 29 months (range, 1 to 69). RESULTS: Reoperation rate was 0% (0 patients), 6.2% (7 patients), and 10.8% (4 patients) for PI, PII and PIII groups respectively (P = .052). Mean preoperative HOOS, JR. and LEAS for PI, PII and PIII groups were significantly different, but 1-year postoperative HOOS, JR. and LEAS did not differ significantly. Rates of HOOS, JR. minimal clinically important difference achievement differed significantly between bone loss groups. CONCLUSION: In this study of rTHA patients, greater acetabular bone loss severity was associated with worse preoperative PROMs and trended toward higher reoperation rate. Postoperative PROMs for bone loss severity groups were statistically similar. Patients who had worse acetabular bone loss were more likely to achieve HOOS, JR. minimal clinically important difference postoperatively. LEVEL OF EVIDENCE: III.

Age-specific survival rates, causes of death, and allowable take of golden eagles in the western United States.

In the United States, the Bald and Golden Eagle Protection Act prohibits take of golden eagles (Aquila chrysaetos) unless authorized by permit, and stipulates that all permitted take must be sustainable. Golden eagles are unintentionally killed in conjunction with many lawful activities (e.g., electrocution on power poles, collision with wind turbines). Managers who issue permits for incidental take of golden eagles must determine allowable take levels and manage permitted take accordingly. To aid managers in making these decisions in the western United States, we used an integrated population model to obtain estimates of golden eagle vital rates and population size, and then used those estimates in a prescribed take level (PTL) model to estimate the allowable take level. Estimated mean annual survival rates for golden eagles ranged from 0.70 (95% credible interval = 0.66-0.74) for first-year birds to 0.90 (0.88-0.91) for adults. Models suggested a high proportion of adult female golden eagles attempted to breed and breeding pairs fledged a mean of 0.53 (0.39-0.72) young annually. Population size in the coterminous western United States has averaged ~31,800 individuals for several decades, with λ = 1.0 (0.96-1.05). The PTL model estimated a median allowable take limit of ~2227 (708-4182) individuals annually given a management objective of maintaining a stable population. We estimate that take averaged 2572 out of 4373 (59%) deaths annually, based on a representative sample of transmitter-tagged golden eagles. For the subset of golden eagles that were recovered and a cause of death determined, anthropogenic mortality accounted for an average of 74% of deaths after their first year; leading forms of take over all age classes were shooting (~670 per year), collisions (~611), electrocutions (~506), and poisoning (~427). Although observed take overlapped the credible interval of our allowable take estimate and the population overall has been stable, our findings indicate that additional take, unless mitigated for, may not be sustainable. Our analysis demonstrates the utility of the joint application of integrated population and prescribed take level models to management of incidental take of a protected species.

Printable G-Putty for Frequency- and Rate-Independent, High-Performance Strain Sensors.

While nanocomposite electromechanical sensors are expected to display reasonable conductivity and high sensitivity, little consideration is given to eliminating hysteresis and strain rate/frequency dependence from their response. For example, while G-putty, a composite of graphene and polysiloxane, has very high electromechanical sensitivity, its extreme viscoelasticity renders it completely unsuitable for real sensors due to hysteretic and rate-/frequency-dependent effects. Here it is shown that G-putty can be converted to an ink and printed into patterned thin films on elastic substrates. A partial graphene-polymer phase segregation during printing increases the thin-film conductivity by ×106 compared to bulk, while the mechanical effects of the substrate largely suppress hysteresis and completely remove strain rate and frequency dependence. This allows the fabrication of practical, high-gauge-factor, wearable sensors for pulse measurements as well as patterned sensors for low-signal vibration sensing.

Influence of molecular classes and growth hormone treatment on growth and dysmorphology in Prader-Willi syndrome: A multicenter study.

Prader-Willi syndrome (PWS) is a complex genetic disorder with three molecular classes but clinical ascertainment is based on distinctive features. The prevalence of dysmorphic features was studied in 355 PWS participants (61% deletion, 36% maternal disomy [UPD], and 3% imprinting defects) from the National Institute of Health PWS Rare Diseases Clinical Research Network. The effect of growth hormone (GH) treatment on growth and dysmorphic features was compared. Among participants, upslanting palpebral fissures were seen in 23%; strabismus in 42%; abnormal dentition in 32%; small hands in 63% and small feet in 70%; hypopigmentation in 30%; striae in 32% and skin picking in 26%. Compared to those with UPD, participants with deletions were found to be heavier (p = 0.002), had smaller head circumference (HC) (p = 0.009), higher incidence of a flat occiput (p = 0.005); low-anterior hairline (p = 0.04); abnormal dentition (p = 0.009); abdominal striae (p = 0.045), nail abnormalities (p = 0.050), and fair-haired (p < 0.001). Participants in both genetic groups receiving GH were taller (p = 0.005), had larger HCs (p = 0.005), and longer hands (p = 0.049). This study suggested that PWS genetic subtypes and GH treatment can influence growth and dysmorphic features that may impact clinical diagnosis of PWS, such as stature, head shape and appearance of the eyes, nose, and genitalia.

Nonconcentric and Irregular Dislocations of Total Hip Arthroplasties: Radiographic Analysis and Review of the Literature.

BACKGROUND: Total hip arthroplasty (THA) is one of the most successful operations in all of medicine in improving patient pain and restoring function. However, complications do arise after primary and revision THA. Dislocation of a THA, also known as instability, occurs in 1-2% of primary THAs and up to 30% of revision THAs. Most dislocations in the United States are initially managed with closed reduction under procedural sedation in emergency departments (EDs) by on-call orthopedists or emergency medicine specialists. OBJECTIVE: In this review the characteristics of the articulations that may require closed reduction in the ED are described, as well as their radiographic findings prior to reduction. Finally, we present subtle radiographic findings associated with failed closed reductions. DISCUSSION: Due to the different types of implants that have been introduced, closed reduction can be challenging in certain cases. Iatrogenic intraprosthetic dislocations are becoming more common with the increased use of dual-mobility liners. There are also dislocations after staged revision THA cases with the use of spacers. In spacers with semi-constrained articulation, there is the possibility of partial reduction of the spacer. CONCLUSIONS: Dislocation is one of the most common mechanical complications after primary and revision THA. In the majority of the cases, acute closed reduction can be achieved successfully in the ED setting. However, there are specific dislocation types that present unique challenges to acute reduction.

Modern Internet Search Analytics and Total Joint Arthroplasty: What Are Patients Asking and Reading Online?

BACKGROUND: Patients considering total joint arthroplasty often search for information online regarding surgery; however, little is known about the specific topics that patients search for and the nature of the information provided. Google compiles frequently asked questions associated with a search term using machine learning and natural language processing. Links to individual websites are provided to answer each question. Analysis of this data may help improve understanding of patient concerns and inform more effective counseling. METHODS: Search terms were entered into Google for total hip and total knee arthroplasty. Frequently asked questions and associated websites were extracted to a database using customized software. Questions were categorized by topic; websites were categorized by type. JAMA Benchmark Criteria were used to assess website quality. Pearson's chi-squared and Student's t-tests were performed as appropriate. RESULTS: A total of 620 questions (305 total knee arthroplasties, 315 total hip arthroplasties) were extracted with 602 associated websites. The most popular question topics were Specific Activities (23.5%), Indications/Management (15.6%), and Restrictions (13.4%). Questions related to Pain were more common in the TKA group (23.0% vs 2.5%, P < .001) compared to THA. The most common website types were Academic (31.1%), Commercial (29.2%), and Social Media (17.1%). JAMA scores (0-4) were highest for Government websites (mean 3.92, P = .005). CONCLUSION: The most frequently asked questions on Google related to total joint arthroplasty are related to arthritis management, rehabilitation, and ability to perform specific tasks. A sizable proportion of health information provided originate from non-academic, non-government sources (64.4%), with 17.1% from social media websites.

Molecular genetic classification in Prader-Willi syndrome: a multisite cohort study.

BACKGROUND: Prader-Willi syndrome (PWS) is due to errors in genomic imprinting. PWS is recognised as the most common known genetic cause of life-threatening obesity. This report summarises the frequency and further characterises the PWS molecular classes and maternal age effects. METHODS: High-resolution microarrays, comprehensive chromosome 15 genotyping and methylation-specific multiplex ligation probe amplification were used to describe and further characterise molecular classes of maternal disomy 15 (UPD15) considering maternal age. RESULTS: We summarised genetic data from 510 individuals with PWS and 303 (60%) had the 15q11-q13 deletion; 185 (36%) with UPD15 and 22 (4%) with imprinting defects. We further characterised UPD15 findings into subclasses based on the presence (size, location) or absence of loss of heterozygosity (LOH). Additionally, significantly older mothers (mean age=32.5 years vs 27.7 years) were found in the UPD15 group (n=145) compared with the deletion subtype (n=200). CONCLUSIONS: We report on molecular classes in PWS using advanced genomic technology in the largest cohort to date. LOH patterns in UPD15 may impact the risk of having a second genetic condition if the mother carries a recessive mutant allele in the isodisomic region on chromosome 15. The risk of UPD15 may also increase with maternal age.

Antegrade Foreheadplasty: A Novel Surgical Approach for Upper Eyelid Contracture Deformities in Pediatric Patients.

The intricate and delicate structure of the periorbital region, particularly in pediatric patients, presents challenges to eyelid reconstruction. Much like the more common lower eyelid ectropion, upper eyelid ectropion can result from lack of tissue, scar contracture, or over-resection as in blepharoplasty. In burns and trauma, the cause of cicatricial ectropion is typically direct scar contracture from injuries to the eyelid. However, in some cases, extrinsic wounds involving contracture to the forehead or eyebrow can result in upper eyelid cicatricial ectropion. Direct reconstruction and skin grafting of the eyelid present complex challenges, especially in the acute inflammatory phase of traumatic injury and burn care. Furthermore, in many of these cases the periorbital and lamellae anatomy is preserved, but rather severely displaced due to scar contracture forces. The authors discuss our experience with treatment of extrinsic upper eyelid cicatricial ectropion in a series of 4 pediatric patients with burns or trauma to the forehead and periorbital regions. In all 4 cases, the antegrade foreheadplasty procedure helped to provide globe coverage, while avoiding skin matching difficulties and the intrinsic risks of operating on the eyelid during the acute phase of recovery. There is currently very limited data for the use of this technique to correct such defects. With this study, the authors hope to establish the antegrade foreheadplasty as a reconstructive option for a select patient population.

Birth seasonality studies in a large Prader-Willi syndrome cohort.

Prader-Willi syndrome (PWS) is generally due to sporadic paternal deletions of the chromosome 15q11-q13 region followed by maternal disomy 15. Advanced maternal age is more commonly seen in those with maternal disomy 15. Environmental factors (e.g., drug use, occupational chemical exposure, infectious agents, and irradiation) could account for chromosome changes. Previous evidence of differences in male and female gametogenesis could suggest an environmental role in the causation of the paternal 15q11-q13 deletion seen in PWS. Certain occupations such as hydrocarbon-exposing occupations (e.g., landscaping, farming, and painting) and viral exposure (e.g., human coronavirus 229E causing upper respiratory infections in adults with an incorporation site in the human genome at chromosome 15q11) can be seasonal in nature and contribute to chromosome damage. To assess, we reviewed birth seasonality data in a large cohort of individuals with PWS recruited nationally (N = 355) but no significant differences were seen by month between those with the 15q11-q13 deletion compared with maternal disomy 15 when analyzing quarterly seasonal patterns. Although early evidence supported birth seasonality differences in PWS, a larger number of individuals in our recent study using advanced genetic testing methods did not find this observation.

Machine Learning Enhances the Efficiency of Cognitive Screenings for Primary Care.

BACKGROUND: Incorporation of cognitive screening into the busy primary care will require the development of highly efficient screening tools. We report the convergence validity of a very brief, self-administered, computerized assessment protocol against one of the most extensively used, clinician-administered instruments-the Montreal Cognitive Assessment (MoCA). METHOD: Two hundred six participants (mean age = 67.44, standard deviation [SD] = 11.63) completed the MoCA and the computerized test. Three machine learning algorithms (ie, Support Vector Machine, Random Forest, and Gradient Boosting Trees) were trained to classify participants according to the clinical cutoff score of the MoCA (ie, < 26) from participant performance on 25 features of the computerized test. Analysis employed Synthetic Minority Oversampling TEchnic to correct the sample for class imbalance. RESULTS: Gradient Boosting Trees achieved the highest performance (accuracy = 0.81, specificity = 0.88, sensitivity = 0.74, F1 score = 0.79, and area under the curve = 0.81). A subsequent K-means clustering of the prediction features yielded 3 categories that corresponded to the unimpaired (mean = 26.98, SD = 2.35), mildly impaired (mean = 23.58, SD = 3.19), and moderately impaired (mean = 17.24, SD = 4.23) ranges of MoCA score ( F = 222.36, P < .00). In addition, compared to the MoCA, the computerized test correlated more strongly with age in unimpaired participants (ie, MoCA ≥26, n = 165), suggesting greater sensitivity to age-related changes in cognitive functioning. CONCLUSION: Future studies should examine ways to improve the sensitivity of the computerized test by expanding the cognitive domains it measures without compromising its efficiency.

Bushmeat Hunting and Zoonotic Transmission of Simian T-Lymphotropic Virus 1 in Tropical West and Central Africa.

Simian T-lymphotropic virus 1 (STLV-1) enters human populations through contact with nonhuman primate (NHP) bushmeat. We tested whether differences in the extent of contact with STLV-1-infected NHP bushmeat foster regional differences in prevalence of human T-lymphotropic virus 1 (HTLV-1). Using serological and PCR assays, we screened humans and NHPs at two Sub-Saharan African sites where subsistence hunting was expected to be less (Taï region, Côte d'Ivoire [CIV]) or more (Bandundu region, Democratic Republic of the Congo [DRC]) developed. Only 0.7% of human participants were infected with HTLV-1 in CIV (n = 574), and 1.3% of humans were infected in DRC (n = 302). Two of the Ivorian human virus sequences were closely related to simian counterparts, indicating ongoing zoonotic transmission. Multivariate analysis of human demographic parameters and behavior confirmed that participants from CIV were less often exposed to NHPs than participants from DRC through direct contact, e.g., butchering. At the same time, numbers of STLV-1-infected NHPs were higher in CIV (39%; n = 111) than in DRC (23%; n = 39). We conclude that similar ultimate risks of zoonotic STLV-1 transmission-defined as the product of prevalence in local NHP and human rates of contact to fresh NHP carcasses-contribute to the observed comparable rates of HTLV-1 infection in humans in CIV and DRC. We found that young adult men and mature women are most likely exposed to NHPs at both sites. In view of the continued difficulties in controlling zoonotic disease outbreaks, the identification of such groups at high risk of NHP exposure may guide future prevention efforts.IMPORTANCE Multiple studies report a high risk for zoonotic transmission of blood-borne pathogens like retroviruses through contact with NHPs, and this risk seems to be particularly high in tropical Africa. Here, we reveal high levels of exposure to NHP bushmeat in two regions of Western and Central tropical Africa. We provide evidence for continued zoonotic origin of HTLV-1 in humans at CIV, and we found that young men and mature women represent risk groups for zoonotic transmission of pathogens from NHPs. Identifying such risk groups can contribute to mitigation of not only zoonotic STLV-1 transmission but also transmission of any blood-borne pathogen onto humans in Sub-Saharan Africa.

Prader-Willi syndrome and early-onset morbid obesity NIH rare disease consortium: A review of natural history study.

We describe the National Institutes of Health rare disease consortium for Prader-Willi syndrome (PWS) developed to address concerns regarding medical care, diagnosis, growth and development, awareness, and natural history. PWS results from errors in genomic imprinting leading to loss of paternally expressed genes due to 15q11-q13 deletion, maternal disomy 15 or imprinting defects. The 8 year study was conducted at four national sites on individuals with genetically confirmed PWS and early-onset morbid obesity (EMO) with data accumulated to gain a better understanding of the natural history, cause and treatment of PWS. Enrollment of 355 subjects with PWS and 36 subjects with EMO began in September 2006 with study completion in July 2014. Clinical, genetic, cognitive, behavior, and natural history data were systematically collected along with PWS genetic subtypes, pregnancy and birth history, mortality, obesity, and cognitive status with study details as important endpoints in both subject groups. Of the 355 individuals with PWS, 217 (61%) had the 15q11-q13 deletion, 127 (36%) had maternal disomy 15, and 11 (3%) had imprinting defects. Six deaths were reported in our PWS cohort with 598 cumulative years of study exposure and one death in the EMO group with 42 years of exposure. To our knowledge, this description of a longitudinal study in PWS represents the largest and most comprehensive cohort useful for investigators in planning comparable studies in other rare disorders. Ongoing studies utilizing this database should have a direct impact on care and services, diagnosis, treatment, genotype-phenotype correlations, and clinical outcomes in PWS.