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In children with neurological complex chronic conditions (CCC) undergoing hip surgery we aimed to: estimate the rate of postoperative pneumonia, determine the effect of pneumonia on postoperative hospital resource use, and identify predictors of postoperative pneumonia.A retrospective cohort study was conducted utilizing the Pediatric Health Information System database for 2609 children (1081 females, 1528 males) aged 4 years and older with a neurological CCC who underwent hip surgery (i.e. reconstruction surgery or salvage procedure) between 2016 and 2018 in 41 US children's hospitals. Multivariable, mixed-effects logistic regression was used to assess patient characteristics and risk of pneumonia.Mean age at hip surgery was 10 years 1 month (SD 4y 8mo). The postoperative pneumonia rate was 1.6% (n=42). Median length of stay (LOS) was longer for children with pneumonia and the 30-day all-cause unplanned readmission rate and costs were higher. Variability in rates of pneumonia ranged from 1.1% to 2.8% across hospitals. Significant predictors of postoperative pneumonia were osteotomy type (p=0.005) and number of chronic conditions (p≤0.001).Postoperative pneumonia after hip surgery in children with a neurological CCC is associated with longer LOS, readmissions, and higher costs. Children undergoing pelvic osteotomies and who have multimorbidity need additional clinical support to prevent postoperative pneumonia and decrease resource utilization.Pneumonia is a major postoperative complication in children with neurological complex chronic conditions (CCC). Forty-two (1.6%) children with neurological CCC developed pneumonia after hip surgery. Length of stay, readmissions, and costs were significantly higher in the group with pneumonia. Variability in pneumonia rates existed across hospitals. Predictors of developing pneumonia include osteotomy type and number of CCC.

Objective To assess the performance of previously published high-intensity neurologic impairment (NI) diagnosis codes in identification of hospitalized children with clinical NI. Methods Retrospective study of 500 randomly selected discharges in 2019 from a freestanding children's hospital. All charts were reviewed for 1) NI discharge diagnosis codes and 2) documentation of clinical NI (a neurologic diagnosis and indication of functional impairment like medical technology). Test statistics of clinical NI were calculated for discharges with and without an NI diagnosis code. A sensitivity analysis varied the threshold for “substantial functional impairment.” Secondary analyses evaluated misclassified discharges and a more stringent definition for NI. Results Diagnosis codes identified clinically documented NI with 88.1% (95% confidence interval [CI]: 84.7, 91) specificity, and 79.4% (95% CI: 67.3, 88.5) sensitivity; negative predictive value (NPV) was 96.7% (95% CI: 94.8, 98.0), and positive predictive value (PPV) was 49% (95% CI: 42, 56.1). Including children with milder functional impairment (lower threshold) resulted in NPV of 95.7% and PPV of 77.5%. Restricting to children with more severe functional impairment (higher threshold) resulted in NPV of 98.2% and PPV of 44.1%. Misclassification was primarily due to inclusion of children without functional impairments. A more stringent NI definition including diagnosis codes for NI and feeding tubes had a specificity of 98.4% (95% CI: 96.7–99.3) and sensitivity of 28.6% (19.4–41.3). Conclusions All scenarios evaluated demonstrated high NPV and low-to-moderate PPV of the diagnostic code list. To maximize clinical utility, NI diagnosis codes should be used with strategies to mitigate the risk of misclassification.

Mutations assessed at VICC.

Activating NRAS mutations are found in 15% to 20% of melanomas. Immune therapies have become a mainstay in advanced melanoma treatment. We sought to evaluate whether tumor genotype (e.g., NRAS mutations) correlates with benefit from immune therapy in melanoma. We identified 229 patients with melanoma treated with immune therapies [IL2, ipilimumab, or anti-programmed cell death-1/ligand-1 (PD-1/PD-L1)] at three centers and compared clinical outcomes following immune therapy for patients with or without NRAS mutations. Of the 229 patients with melanoma, 60 had NRAS mutation, 53 had BRAF mutation, and 116 had NRAS/BRAF wild type. The NRAS-mutant cohort had superior or a trend to superior outcomes compared with the other cohorts in terms of response to first-line immune therapy (28% vs. 16%, P = 0.04), response to any line of immune therapy (32% vs. 20%, P = 0.07), clinical benefit (response + stable disease lasting ≥24 weeks; 50% vs. 31%, P < 0.01), and progression-free survival (median, 4.1 vs. 2.9 months, P = 0.09). Benefit from anti–PD-1/PD-L1 was particularly marked in the NRAS cohort (clinical benefit rate 73% vs. 35%). In an independent group of patient samples, NRAS-mutant melanoma had higher PD-L1 expression (although not statistically significant) compared with other genotypes (8/12 vs. 9/20 samples with ≥1% expression; 6/12 vs. 6/20 samples with ≥5% expression), suggesting a potential mechanism for the clinical results. This retrospective study suggests that NRAS mutations in advanced melanoma correlate with increased benefit from immune-based therapies compared with other genetic subtypes. If confirmed by prospective studies, this may be explained in part by high rates of PD-L1 expression. Cancer Immunol Res; 3(3); 288–95. ©2015 AACR.

Genes assessed at MGH by SNaPshot Testing1.

Mutations assessed at MSKCC.

Clinical and molecular characteristics of PD-L1 staining cohort.

To describe epidemiology, interventions, outcomes, and the health services experience for a cohort of children with pulmonary hypertension (PH) who underwent tracheostomy placement and to identify risk factors for inhospital mortality and 30-day readmissions.Retrospective cohort study of the Pediatric Health Information System database.Thirty-seven freestanding U.S. children's hospitals.Patients 31 days to 21 years old who were discharged from the hospital between January 1, 2009, and December 31, 2017, with a diagnosis of primary or secondary PH, and who underwent tracheostomy placement. Outcomes were examined over a 2-year period from the time of discharge from the index encounter.None.There were 793 patients with PH who underwent tracheostomy placement. The overall inhospital mortality rate was 23.7%. Secondary PH due to congenital heart disease (CHD) was significantly associated with overall inhospital mortality (adjusted odds ratio [OR], 2.36; 95% CI, 1.38-4.04). The rate of 30-day readmissions for patients over the 2-year follow-up period was 33.3%. Tracheostomy during the index encounter and the diagnosis of secondary PH due to CHD were significantly associated with lower rates of 30-day readmissions (adjusted OR, 0.34; 95% CI, 0.19-0.61; and adjusted OR, 0.43; 95% CI, 0.24-0.77, respectively).In the context of expanding utilization of tracheostomy and long-term ventilation, children with PH are among the highest risk cohorts for extended and repeated hospitalization and death. Tracheostomy placement during the index encounter was associated with fewer 30-day readmissions over the 2-year follow-up period. Further understanding of which subgroups may benefit from earlier intervention and which subgroups are at highest risk may offer important clinical insight when considering optimal timing of tracheostomy and may enhance informed decision-making for all stakeholders.

BACKGROUND It is well established that young infants have the highest risk of severe pertussis, which often results in hospitalization. Since the 2012 recommendation of administering tetanus toxoid, diphtheria toxoid, and acellular pertussis (Tdap) vaccine for every pregnancy, evaluation of pertussis hospitalizations among young infants in the United States has been limited. METHODS In this ecological study, we used the Kids’ Inpatient Database, the largest all-payer pediatric inpatient database in the United States, to study pertussis hospitalizations among infants RESULTS The overall rate of pertussis hospitalizations before the Tdap vaccination recommendation was 5.06 per 100 000 infants (95% confidence interval, 4.36–5.76) and 2.15 per 100 000 infants (95% confidence interval, 1.49–2.81) afterward. CONCLUSIONS This study supports maternal vaccination against pertussis as an important strategy in protecting young infants, and continued evaluation is needed to assess the long-term trends in hospitalization.

Solution phase titrations are made easy by multi-nuclear FlowNMR spectroscopy with automated, continuous titre addition to give accurate insights into Brønsted acid/base, hydrogen bonding, Lewis acid/base and metal/ligand binding equilibria under native conditions.

OBJECTIVE To assess risk factors associated with 30-day hospital readmission after a prolonged neonatal intensive care stay. STUDY DESIGN Retrospective analysis of 57,035 infants discharged >14 days from the NICU between 2013 and 2016. Primary outcome was 30-day, all-cause hospital readmission. Adjusted likelihood of readmission accounting for demographic and clinical characteristics, including chronic conditions was also estimated. RESULTS The 30-day readmission rate was 10.7%. Respiratory problems accounted for most (31.0%) readmissions. In multivariable analysis, shunted hydrocephalus [OR 2.2 (95%CI 1.8-2.7)], gastrostomy tube [OR 2.0 (95%CI 1.8-2.3)], tracheostomy [OR 1.5 (95%CI 1.2-1.8)], and use of public insurance [OR 1.3 (95%CI 1.2-1.4)] had the highest likelihood of readmission. Adjusted hospital readmission rates varied significantly (p

Nutrition status plays a critical role in pressure injury (PI) healing and yet the available literature, especially in pediatric patients, is limited. Critically ill pediatric patients are at an increased risk of skin integrity compromise and PI development. Adequate nutritional intake can often be challenging to achieve in this population and immobility and illness present additional obstacles to maintaining skin integrity in this vulnerable population. Despite the unique nutritional challenges and needs of this group, there is no standardized approach to macro- and micronutrient management and monitoring. Here, several key vitamins and minerals believed to play a role in PI healing are discussed and an approach to nutritional management and monitoring for PI healing in pediatric patients is proposed. Registered dietitians (RD) are essential to assess individual patient macro and micronutrient requirements, to identify gaps and make recommendations to optimize nutritional therapy that may exist and impact wound healing. We used a scoping review to focus on the interplay of nutrition and PI healing and inform a multidisciplinary approach to PI identification and management. Through this review, we propose a strategy for the nutritional management of pediatric patients

BACKGROUND AND OBJECTIVESClinicians evaluating for herpes simplex virus (HSV) in febrile infants must balance detection with overtesting, and there is no universally accepted approach to risk stratification. We aimed to describe variation in diagnostic evaluation and empirical acyclovir treatment of infants aged 0 to 60 days presenting with fever and determine the association between testing and length of stay (LOS).METHODSIn this retrospective 44-hospital observational study, we used the Pediatric Health Information System database to identify infants aged ≤60 days evaluated for fever in emergency departments from January 2016 through December 2017. We described hospital-level variation in laboratory testing, including HSV, imaging and other diagnostic evaluations, acyclovir use, and LOS. We assessed the relationship between HSV testing and LOS using generalized linear mixed effects models adjusted for age and illness severity.RESULTSIn 24 535 encounters for fever, the median HSV testing frequency across hospitals was 35.6% (interquartile range [IQR]: 28.5%–53.5%) for infants aged 0 to 21 days and 12% (IQR: 8.6%–15.7%) for infants aged 22 to 60 days. Among HSV-tested patients, median acyclovir use across hospitals was 79.2% (IQR: 68.1%–89.7%) for those aged 0 to 21 days and 63.6% (IQR: 44.1%–73%) for those aged 22 to 60 days. The prevalence of additional testing varied substantially by hospital and age group. Risk-adjusted LOS for HSV-tested infants was significantly longer than risk-adjusted LOS for those not tested (2.6 vs 1.9 days, P < .001).CONCLUSIONSSubstantial variation exists in diagnostic evaluation and acyclovir use, and infants who received HSV testing had a longer LOS than infants who did not. This variability supports the need for further studies to help clinicians better risk-stratify febrile infants and to guide HSV testing and treatment decisions.

Aim To identify the highest-priority clinical research areas related to children with neurological impairment and medical complexity among clinicians and caregivers. Method A modified, three-stage Delphi study using online surveys and guided by a steering committee was completed. In round 1, clinicians and family caregivers suggested clinical topics and related questions that require research to support this subgroup of children. After refinement of the suggestions by the steering committee, participants contributed to 1 (family caregivers) or 2 (clinicians) subsequent rounds to develop a prioritized list. Results A diverse international expert panel consisting of 49 clinicians and 12 family caregivers provided 601 responses. Responses were distilled into 26 clinical topics comprising 126 related questions. The top clinical topics prioritized for research were irritability and pain, child mental health, disorders of tone, polypharmacy, sleep, aspiration, behavior, dysautonomia, and feeding intolerance. The clinician expert panel also prioritized 10 specific research questions. Interpretation Study findings support a research agenda for children with neurological impairment and medical complexity focused on addressing clinical questions, prioritized by an international group of clinicians and caregivers.

Anti-Wolbachia therapy has been identified as a viable treatment for combating filarial diseases. Phenotypic screening revealed a series of pyrazolopyrimidine hits with potent anti-Wolbachia activity. This paper focuses on the exploration of the SAR for this chemotype, with improvement of metabolic stability and solubility profiles using medicinal chemistry approaches. Organic synthesis has enabled functionalization of the pyrazolopyrimidine core at multiple positions, generating a library of compounds of which many analogues possess nanomolar activity against Wolbachia in vitro with improved DMPK parameters. A lead compound, 15f, was selected for in vivo pharmacokinetics (PK) profiling in mice. The combination of potent anti-Wolbachia activity in two in vitro assessments plus the exceptional oral PK profiles in mice puts this lead compound in a strong position for in vivo proof-of-concept pharmacodynamics studies and demonstrates the strong potential for further optimization and development of this series for treatment of filariasis in the future.

Silicone breast augmentation remains one of the most common aesthetic surgery procedures, and 2022 marks the 60th anniversary of the first case. Recent studies suggest a link between double capsule (DC) formation and macro-textured devices.Between 2010 and 2015, 268 aesthetic patients underwent bilateral mammary prosthesis exchange for indications including PIP exchange, adverse capsular contracture and ultrasonographic evidence of rupture. All surgery, in the form of implant exchange and capsulectomy, was undertaken by the senior author using standard techniques. A retrospective review was undertaken, and data analysed with descriptive statistics and Fisher's exact and Mann-Whitney U tests.Of 268 patients identified, 40 (14.9%) showed some degree of capsular duplication and bilateral involvement was marginally more common (52.5%). Two macroscopic patterns of duplication were observed: complete and subtotal. Complete DCs correlated with a clinical triad of extreme firmness, mobility and minimal-to-no pain. Whilst a wide range of manufacturers was represented, macro-textured devices were associated with the highest DC prevalence (58.3% vs. 5.6%) (Fisher's exact test p0.00001). Patients with DC had been implanted for less than half the time, median 52 versus. 120 months (p = 0.0003) of those without.An elevated prevalence of duplicate capsules in macro-textured prostheses is reconfirmed in addition to a novel symptom constellation that may assist with clinical diagnosis. Our study reinforces the aetiopathogenic influence of the elastomer in DC formation and reports DC for the first time in non-macrotextured implants. Single-surgeon cohort of 268 consecutive patients with 532 implants Statistically significant association of macro-textured devices with DC Statistically significant reduced duration of implantation of macro-textured devices First report of DC in non-macro-textured devices LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

*Correspondence - Stephen Kaye: S.B.Kaye@liverpool.ac.uk INTRODUCTION:Expression levels of pcrV (T3SS needle component) from ExoU-expressing PA103 and ExoS-expressing PA76026 after 16h incubation in each antimicrobial was detected using western blotting. qRT PCR detected mRNA levels of ExoU, ExoS, pcrV and ExsA (T3SS activating factor) after PA103 and PA76026 were exposed to tobramycin and moxifloxacin. LIVE/DEAD and LDH assays after 24h evaluated how the antimicrobials influenced acute cytotoxicity in a HCE-T cell scratch and infection model.Tobramycin significantly reduced pcrV in both strains by 50.5-74.0% compared to the fluoroquinolones (p=0.001 and 0.003), even at low concentrations. Fluoroquinolones significantly increased pcrV by 57.0-81.8% (p=0.004 and 0.003). mRNA levels of ExoU, ExoS, pcrV and ExsA were reduced by tobramycin but moxifloxacin increased pcrV, ExsA and ExoS. Tobramycin, despite more bacterial expansion compared to the same relative concentrations of fluoroquinolones, reduced ExoU/ExoS cytotoxicity and allowed complete wound healing.Tobramycin downregulates T3SS expression and reduces ExoS/ExoU mediated cytotoxicity which protects infected HCE-T cells even at low concentrations. Fluoroquinolones however upregulated T3SS and do not negate the cytotoxic effects.

OBJECTIVES To compare the effectiveness of dexamethasone versus prednisone or prednisolone on hospital resource utilization for children hospitalized with acute croup. METHODS This is a retrospective cohort study of the Pediatric Health Information System database on children aged 6 months to RESULTS A total of 11 740 hospitalizations met inclusion criteria; dexamethasone was used in 95.9%; prednisone or prednisolone was used in 4.1%. In the matched cohort (n = 960), the length of stay was not significantly different between the dexamethasone and prednisone or prednisolone groups (21.3 vs 18.5 hours, P = .35). Although the rates bronchoscopy did not differ between the 2 groups, the dexamethasone cohort was more likely to require ICU transfer (P = .007). The rates of 7-day emergency department returns (2.3% vs 1.3%, P = .24) and readmissions (3.1% vs. 2.1%, P = .37) were low and not statistically different. CONCLUSIONS Hospital resource utilization did not differ significantly for children receiving dexamethasone or prednisone or prednisolone for acute croup. Both corticosteroids may be considered reasonable choices for the treatment of children hospitalized with acute croup.

Hip reconstruction surgery in patients with neurological complex chronic conditions (CCC) is associated with prolonged hospitalization and extensive resource utilization. This population is vulnerable to cognitive, developmental, and medical comorbidities which can increase length of stay (LOS). The aims of this study were to characterize barriers to discharge for a cohort of children with neurological CCC undergoing hip reconstruction surgery and to identify patient risk factors for prolonged hospitalization and delayed discharge.Retrospective chart review of nonambulatory patients with neurological CCC undergoing hip reconstruction surgery between 2007-2016 was conducted. Hospitalization ≥1 day past medical clearance was characterized as delayed discharge. Barriers were defined as unresolved issues at the time of medical clearance and categorized as pertaining to the caregiver and patient education, durable medical equipment, postdischarge transportation/placement, and patient care needs.The cohort of 116 patients was 53% male, 16% non-English speaking, and 49% Gross Motor Function Classification System (GMFCS) V with the mean age at surgery of 9.1±3.64 years. Median time from admission to medical clearance was 5 days with median LOS of 6 days. Approximately three-quarters of patients experienced delayed discharge (73%) with barriers identified for 74% of delays. Most prevalent barriers involved education (30%) and durable medical equipment (29%). Postdischarge transportation and placement accounted for 26% of barriers and 3.5 times longer delays ( P0.001). Factors associated with delayed discharge included increased medical comorbidities ( P0.05) and GMFCS V ( P0.001). Longer LOS and medical clearance times were found for female ( P =0.005), older age ( P0.001), bilateral surgery ( P =0.009), GMFCS V ( P =0.003), and non-English-speaking patients ( P0.001).Patients with neurological CCC frequently encounter postoperative barriers contributing to increased LOS and delayed discharge. Patients that may be at higher risk for prolonged hospitalization and greater resource utilization include those who are female sex, adolescent, GMFCS V, non-English speaking, have additional comorbidities, and are undergoing bilateral surgery. Standardized preoperative assessment of educational needs, perioperative equipment requirements, and posthospital transportation may decrease the LOS, reduce caregiver and patient burden/distress, cost, and ultimately reduce variation in care delivery.Level III, Retrospective Case Series.

Here, we present a rare case of a patient who developed multiple primary melanomas within the boundaries of two nevi depigmentosa. The melanomas were excised, and as a preventive measure, the remainder of the nevi depigmentosa were removed. We performed whole-exome sequencing on excised tissue from the nevus depigmentosus, adjacent normal skin, and saliva to explain this intriguing phenomenon. We also performed a GeneTrails Comprehensive Solid Tumor Panel analysis on one of the melanoma tissues. Genetic analysis revealed germline MC1R V92M and TYR R402Q polymorphisms and a MET E168D germline mutation that may have increased the risk of melanoma development. This genetic predisposition, combined with a patient-reported history of substantial sun exposure and sunburns, which were more severe within the boundaries of the nevi depigmentosa due to the lack of photoprotective melanin, produced numerous somatic mutations in the melanocytes of the nevi depigmentosa. Fitting with this paradigm for melanoma development in chronically sun-damaged skin, the patient's melanomas harbored somatic mutations in CDKN2A (splice site), NF1, and ATRX and had a tumor mutation burden in the 90-95th percentile for melanoma.

Background Since 2011, the therapeutic landscape of melanoma has changed dramatically because of the adoption of immune checkpoint inhibitor and targeted therapies. The authors sought to quantify the effects of these changes on short-term treatment costs by comparing the first-year cancer-attributable costs in novel (2011-2015) and historical (2004-2010) treatment eras. Methods The authors estimated the first-year cancer-attributable and out-of-pocket (OOP) costs by cancer stage at diagnosis by using a case-control approach. Patients aged ≥67 years with melanoma results were used to calculate the total direct costs of treatment during the first year after the diagnosis of melanoma in the US Medicare population older than 65 years. Costs were reported in 2018 dollars. Results Costs increased with the stage at diagnosis. Average first-year cancer-attributable costs per patient for stage IV patients increased significantly by 61.7% from $45,952 to $74,297 after the adoption of novel treatments. Per-patient OOP responsibility decreased by almost 30.8% across all stages of cancer but increased by 16.5% for stage IV patients from 2004 ($7646) to 2015 ($8911). The total direct cost of treatment for persons with melanoma older than 65 years increased by $16.03 million (4.93%) from $324.68 million in 2010 to $340.71 million in 2015. The largest increase in yearly total cost, $23.64 million (56.53%), was observed among stage IV patients. Conclusions The direct cost of melanoma increased significantly in the Medicare population, particularly for advanced-stage disease. Prevention and early detection initiatives may reduce the economic burden of melanoma.

OBJECTIVE Reducing emergency department (ED) use in children with complex chronic conditions (CCC) is a national health system priority. Emergency department visits with minimal clinical intervention may be the most avoidable. We assessed characteristics associated with experiencing such a low-resource ED visit among children with a CCC. METHODS A retrospective study of 271,806 ED visits between 2014 and 2017 among patients with a CCC in the Pediatric Health Information System database was performed. The main outcome was a low-resource ED visit, where no medications, laboratory, procedures, or diagnostic tests were administered and the patient was not admitted to the hospital. χ2 Tests and generalized linear models were used to assess bivariable and multivariable relationships of patients' demographic, clinical, and health service characteristics with the likelihood of a low- versus higher-resource ED visit. RESULTS Sixteen percent (n = 44,111) of ED visits among children with CCCs were low-resource. In multivariable analysis, the highest odds of experiencing a low- versus higher-resource ED visit occurred in patients aged 0 year (vs 16+ years; odds ratio [OR], 3.9 [95% confidence interval {CI}, 3.7-4.1]), living

Aim To assess the relationship of preoperative hematology laboratory results with intraoperative estimated blood loss and transfusion volumes during posterior spinal fusion for pediatric neuromuscular scoliosis. Methods Retrospective chart review of 179 children with neuromuscular scoliosis undergoing spinal fusion at a tertiary children’s hospital between 2012 and 2017. The main outcome measure was estimated blood loss. Secondary outcomes were volumes of packed red blood cells, fresh frozen plasma, and platelets transfused intraoperatively. Independent variables were preoperative blood counts, coagulation studies, and demographic and surgical characteristics. Relationships between estimated blood loss, transfusion volumes, and independent variables were assessed using bivariable analyses. Classification and Regression Trees were used to identify variables most strongly correlated with outcomes. Results In bivariable analyses, increased estimated blood loss was significantly associated with higher preoperative hematocrit and lower preoperative platelet count but not with abnormal coagulation studies. Preoperative laboratory results were not associated with intraoperative transfusion volumes. In Classification and Regression Trees analysis, binary splits associated with the largest increase in estimated blood loss were hematocrit ≥44% vs. 9/L. Conclusions Preoperative blood counts may identify patients at risk of increased bleeding, though do not predict intraoperative transfusion requirements. Abnormal coagulation studies often prompted preoperative intervention but were not associated with increased intraoperative bleeding or transfusion needs.

ImportanceTherapy for advanced melanoma has transformed during the past decade, but early detection and prognostic assessment of cutaneous melanoma (CM) remain paramount goals. Best practices for screening and use of pigmented lesion evaluation tools and gene expression profile (GEP) testing in CM remain to be defined.ObjectiveTo provide consensus recommendations on optimal screening practices and prebiopsy diagnostic, postbiopsy diagnostic, and prognostic assessment of CM.Evidence ReviewCase scenarios were interrogated using a modified Delphi consensus method. Melanoma panelists (n = 60) were invited to vote on hypothetical scenarios via an emailed survey (n = 42), which was followed by a consensus conference (n = 51) that reviewed the literature and the rationale for survey answers. Panelists participated in a follow-up survey for final recommendations on the scenarios (n = 45).FindingsThe panelists reached consensus (≥70% agreement) in supporting a risk-stratified approach to melanoma screening in clinical settings and public screening events, screening personnel recommendations (self/partner, primary care provider, general dermatologist, and pigmented lesion expert), screening intervals, and acceptable appointment wait times. Participants also reached consensus that visual and dermoscopic examination are sufficient for evaluation and follow-up of melanocytic skin lesions deemed innocuous. The panelists reached consensus on interpreting reflectance confocal microscopy and some but not all results from epidermal tape stripping, but they did not reach consensus on use of certain pigmented lesion evaluation tools, such as electrical impedance spectroscopy. Regarding GEP scores, the panelists reached consensus that a low-risk prognostic GEP score should not outweigh concerning histologic features when selecting patients to undergo sentinel lymph node biopsy but did not reach consensus on imaging recommendations in the setting of a high-risk prognostic GEP score and low-risk histology and/or negative nodal status.Conclusions and RelevanceFor this consensus statement, panelists reached consensus on aspects of a risk-stratified approach to melanoma screening and follow-up as well as use of visual examination and dermoscopy. These findings support a practical approach to diagnosing and evaluating CM. Panelists did not reach consensus on a clearly defined role for GEP testing in clinical decision-making, citing the need for additional studies to establish the clinical use of existing GEP assays.

OBJECTIVE: To describe the prevalence and characteristics of infection-related readmissions in children and to identify opportunities for readmission reduction and estimate associated cost savings. STUDY DESIGN: Retrospective analysis of 380,067 nationally representative index hospitalizations for children using the 2014 Nationwide Readmissions Database. We compared 30-day, all-cause unplanned readmissions and costs across 22 infection categories. We used the Inpatient Essentials database to measure hospital-level readmission rates and to establish readmission benchmarks for individual infections. We then estimated the number of readmissions avoided and costs saved if hospitals achieved the 10th percentile of hospitals’ readmission rates (ie, readmission benchmark). All analyses were stratified by the presence/absence of a complex chronic condition (CCC). RESULTS: The overall 30-day readmission rate was 4.9%. Readmission rates varied substantially across infections and by presence/absence of a CCC (CCC: range, 0%-21.6%; no CCC: range, 1.5%-8.6%). Approximately 42.6% of readmissions (n = 3,576) for children with a CCC and 54.7% of readmissions (n = 5,507) for children without a CCC could have been potentially avoided if hospitals achieved infection-specific benchmark readmission rates, which could result in an estimated savings of $70.8 million and $44.5 million, respectively. Bronchiolitis, pneumonia, and upper respiratory tract infections were among infections with the greatest number of potentially avoidable readmissions and cost savings for children with and without a CCC. CONCLUSION: Readmissions following hospitalizations for infection in children vary significantly by infection type. To improve hospital resource use for infections, future preventative measures may prioritize children with complex chronic conditions and those with specific diagnoses (eg, respiratory illnesses).

Online analysis and monitoring of solution phase chemistry by way of nuclear magnetic resonance spectroscopy on a recirculating sample from an external reaction vessel (FlowNMR) has proven to be a valuable tool for understanding the dynamic behaviour of complex solution-phase systems in real time. A variety of flow cells and setups have been used at both low and high magnetic field strengths for various applications, and the choice of materials, dimensions and components can have a profound impact on the quality and relevance of the data obtained. Here we review some fundamental engineering aspects of FlowNMR setups to help avoid common pitfalls and work towards establishing good practice quality guidelines (GxP) for FlowNMR investigations in academia and industry.

PURPOSE: The need for pediatric post-acute facility care (PAC) is growing due to technological advances that extend the lives of many children, especially those with complex medical needs. The objectives were to describe [1] the types and settings of PAC; [2] the clinical characteristics of the pediatric patients requiring PAC; and [3] perceptions of PAC care delivery by clinical staff. METHODS: An online survey was administered between 6/2018 to 12/2018 to administrative leaders in PAC facilities that have licensed beds for children and who were active members of the Pediatric Complex Care Association. Survey topics included types of health services provided; pediatric patient characteristics; clinical personnel characteristics; and perceptions of pediatric PAC health care delivery. RESULTS: Leaders from 26 (54%) PAC facilities in 16 U.S. states completed the survey. Fifty-four percent identified as skilled nursing facility/long-term care, 19% intermediate care facilities, 15% respite and medical group homes, and 12% post-acute rehabilitation facilities. Sixty-nine percent of facilities had a significant increase in the medical complexity of patients over the past 10 years. Most reported capability to care for children with tracheostomy/invasive ventilation (100%), gastrostomy tubes (96%), intrathecal baclofen pump (89%), non-invasive positive pressure ventilation (85%), and other medical technology. Most facilities (72%) turned away patients for admission due to bed unavailability occasionally or always. Most facilities (62%) reported that insurance reimbursement to cover the cost of providing PAC to children was not acceptable, and most reported that it was difficult to hire clinical staff (77%) and retain staff (58%). CONCLUSION: PAC in the U.S. is provided to an increasingly medically-complex population of children. There is a critical need to investigate financially-viable solutions for PAC facilities to meet the patient demands for their services and to sufficiently reimburse and retain staff for the challenging and important care that they provide.

Children with medical complexity are at increased risk of low bone mineral density (BMD) and complications after spinal fusion compared with idiopathic scoliosis patients. Our aim was to compare treatments and outcomes of children with medical complexity undergoing spinal fusion in those who had dual-energy x-ray absorptiometry (DXA) scans versus those who did not in an effort to standardize the workup of these patients before undergoing spinal surgery.We conducted a retrospective review of patients with low BMD who underwent spinal fusion at a tertiary care pediatric hospital between 2004 and 2016. We consulted with a pediatric endocrinologist to create standard definitions for low BMD to classify each subject. Regardless of DXA status, all patients were given a clinical diagnosis of osteoporosis [at least 2 long bone or 1 vertebral pathologic fracture(s)], osteopenia (stated on radiograph or by the physician), or clinically low bone density belonging to neither category. The last classification was used for patients whose clinicians had documented low bone density not meeting the criteria for osteoporosis or osteopenia. Fifty-nine patients met the criteria, and 314 were excluded for insufficient follow-up and/or not meeting a diagnosis definition. BMD Z -scores compare bone density ascertained by DXA to an age-matched and sex-matched average. Patients who had a DXA scan were also given a DXA diagnosis of low bone density (≤-2 SD), slightly low bone density (-1.0 to -1.9 SD), or neither (-1.0 SD) based on the lowest BMD Z -score recorded.Fifty-nine patients were analyzed. Fifty-four percent had at least 1 DXA scan preoperatively. Eighty-one percent of DXA patients received some form of treatment compared with 52% of non-DXA patients ( P =0.03).Patients referred for DXA scans were more likely to be treated for low BMD, although there is no standardized system in place to determine which patients should get scans. Our research highlights the need to implement clinical protocols to optimize bone health preoperatively.Level II-retrospective prognostic study.

Antimalarials targeting the ubiquinol-oxidation (Q

Prospective cerebral palsy (CP) registry review. (1) Evaluate the incidence/risk factors of gastrointestinal (GI) complications in CP patients after spinal fusion (SF); and (2) investigate the validity of the modified Clavien–Dindo–Sink classification. Perioperative GI complications result in increased length of stay (LOS) and patient morbidity/mortality. However, none have analyzed the outcomes of GI complications using an objective classification system. A prospective/multicenter CP database identified 425 children (mean, 14.4 ± 2.9 years; range, 7.9–21 years) who underwent SF. GI complications were categorized using the modified Clavien–Dindo–Sink classification. Grades I–II were minor complications and grades III–V major. Patients with and without GI complications were compared. 87 GI complications developed in 69 patients (16.2%): 39 minor (57%) and 30 major (43%). Most common were pancreatitis (n = 45) and ileus (n = 22). Patients with preoperative G-tubes had 2.2 × odds of developing a GI complication compared to oral-only feeders (OR 2.2; 95% CI 0.98–4.78; p = 0.006). Similarly, combined G-tube/oral feeders had 6.7 × odds compared to oral-only (OR 6.7; 95% CI 3.10–14.66; p

AIM To assess how co-occurring conditions influence recovery after hip reconstruction surgery in children with neurological complex chronic conditions (CCCs). METHOD This was a retrospective analysis of 4058 children age 4 years or older with neurological CCCs who underwent hip reconstructive surgery between 1st January 2015 and 31st December 2018 in 49 children's hospitals. The presence of co-occurring chronic conditions was assessed using the Agency for Healthcare Research Chronic Condition Indicator system. Multivariable, hierarchical regression was used to assess the relationship between co-existing conditions and postoperative hospital length of stay (LOS), cost, and 30-day readmission rate. RESULTS The most common co-occurring conditions were digestive (60.1%) and respiratory (37.9%). As the number of co-existing conditions increased from one to four or more, median LOS increased 67% (3d [interquartile range {IQR} 2-4d] to 5d [IQR 3-8d]); median hospital cost increased 41% ($20 248 [IQR $14 921-$27 842] to $28 692 [IQR $19 236-$45 887]); and readmission rates increased 250% (5.5-13.9%), p

Background When applied to the pediatric population, the American Society of Anesthesiologists physical status (ASA-PS) classification has exhibited poor reliability due to its subjective and adult-focused definitions. This study was done to measure interrater agreement of a pediatric-adapted ASA-PS classification and to solicit multicenter perspectives to optimize the pediatric ASA-PS classification. Methods A prospective, mixed-methods study of 197 pediatric anesthesiologists from 13 academic pediatric hospitals in the United States, Europe, and Australia surveyed in May and July 2019. Participants assigned ASA-PS scores (I to V) for 15 pediatric cases with a heterogeneous mix of acute and chronic health conditions undergoing a variety of surgical and related procedures. Pediatric-adapted definitions of ASA-PS were provided. The intraclass correlation coefficient (ICC) was used to assess interrater reliability of ASA-PS scores. The ICC was estimated using 2-way mixed-effects modeling, accounting for multiple raters assigning scores for the same set of cases. Qualitative feedback on the pediatric-adapted ASA-PS classification was analyzed with line-by-line coding. Results The survey response rate was 83.8% (165 of 197). The ICC agreement among participants on ASA-PS scoring across all 15 clinical cases was 0.58 (95% confidence interval [CI], 0.42-0.77). ICC did not vary significantly by years of anesthesiology practice. ICC varied across hospitals (range: 0.34; 95% CI, 0.12-0.63 to 0.79; 95% CI, 0.66-0.91). The highest level of agreement occurred with cases most often scored as ASA-PS I, IV, and V; the lowest agreement occurred with cases most often scored ASA-PS II and III. Clarification of how well a chronic condition was controlled and presence of an acute illness were 2 common themes suggested to optimize the validity of the pediatric-adapted ASA-PS definitions. Conclusions The pediatric-adapted ASA-PS classification had moderate interrater reliability among pediatric anesthesiologists. The lower reliability of scoring for ASA-PS II and III cases, in particular, supports the need for further ASA-PS definition refinement for pediatric populations.

OBJECTIVES We sought to characterize the nature and prevalence of medication order errors (MOEs) occurring at hospital admission for children with medical complexity (CMC), as well as identify the demographic and clinical risk factors for CMC experiencing MOEs. METHODS Prospective cohort study of 1233 hospitalizations for CMC from November 1, 2015, to October 31, 2016, at 2 children's hospitals. Medication order errors at admission were identified prospectively by nurse practitioners and a pharmacist through direct patient care. The primary outcome was presence of at least one MOE at hospital admission. Statistical methods used included χ test, Fisher exact tests, and generalized linear mixed models. RESULTS Overall, 6.1% (n = 75) of hospitalizations had ≥1 MOE occurring at admission, representing 112 total identified MOEs. The most common MOEs were incorrect dose (41.1%) and omitted medication (34.8%). Baclofen and clobazam were the medications most commonly associated with MOEs. In bivariable analyses, MOEs at admission varied significantly by age, assistance with medical technology, and numbers of complex chronic conditions and medications (P < 0.05). In multivariable analysis, patients receiving baclofen had the highest adjusted odds of MOEs at admission (odds ratio, 2.2 [95% confidence interval, 1.2-3.8]). CONCLUSIONS Results from this study suggest that MOEs are common for CMC at hospital admission. Children receiving baclofen are at significant risk of experiencing MOEs, even when orders for baclofen are correct. Several limitations of this study suggest possible undercounting of MOEs during the study period. Further investigation of medication reconciliation processes for CMC receiving multiple chronic, home medications is needed to develop effective strategies for reducing MOEs in this vulnerable population.