Patient well-being and the clinical and economic burdens associated with obesity in the United States.

Obesity is a serious, progressive, chronic disease that is associated with a spectrum of complications and poor outcomes (eg, premature death, diminished quality of life) and is a risk factor for several other diseases. Obesity increases the risk of developing type 2 diabetes, cardiovascular disease, and certain cancers. More recently, obesity was recognized as a risk factor for poor outcomes in patients with COVID-19. When experienced concurrently with a serious disease, obesity may increase the risk of negative health outcomes. Furthermore, individuals with obesity are more likely to experience social stigma and discrimination at work and in educational and health care settings; these may impact mental and physical health and contribute to increased adiposity. In the United States, the economic burden of obesity is immense-according to estimates, hundreds of billions of dollars are spent annually on direct medical needs and lost productivity associated with obesity. More severe classes of obesity greatly impact both the health of individuals and health care expenditures. As obesity becomes more prevalent, policy makers, health care professionals, and payers must consider its clinical, social, and economic implications.

Managed care considerations of weight management interventions for obesity.

The growing prevalence of obesity in the United States has presented an opportunity to increase knowledge about optimal treatment approaches based on a better understanding of patient and provider biases, health care coverage and practices, and social determinants of health. Guideline-recommended obesity treatment begins with lifestyle intervention, and weight management may be enhanced by metabolic and bariatric surgery or anti-obesity medication (AOM) use. However, patient and provider perceptions surrounding obesity and different treatment modalities may present barriers to discussion and uptake of these interventions. Furthermore, it is uncommon for all effective obesity treatments (particularly AOMs) to be covered by insurance. Limited patient access to these treatments carries the potential for negative health consequences and higher health care costs. For these reasons, managed care decision makers are encouraged to improve access to effective obesity treatments, including coverage of AOMs such as semaglutide 2.4 mg.

Probe-based fluorescence dosimetry of an antibody-dye conjugate to identify head and neck cancer as a first step to fluorescence-guided tissue preselection for pathological assessment.

BACKGROUND: Despite the rapid growth of fluorescence imaging, accurate sampling of tissue sections remains challenging. Development of novel technologies to improve intraoperative assessment of tissue is needed. METHODS: A novel contact probe-based fluorescence dosimeter device, optimized for IRDye800CW quantification, was developed. After evaluation of the device in a phantom setup, its clinical value was defined ex vivo in patients with head and neck squamous cell carcinoma who received panitumumab-IRDye800CW. RESULTS: Ten patients were enrolled with a total of 216 data points obtained. Final histopathology showed tumor in 119 spots and normal tissue in 97 spots. Fluorescence-to-excitation ratios in tumor tissue were more than three times higher than those in normal tissue. The area under the curve was 0.86 (95% CI: 0.81-0.91) for tumor detection. CONCLUSIONS: Fluorescence-guided tissue preselection using a fluorescence dosimeter could have substantial impact on tissue sampling for frozen section analysis and potentially reduce sampling errors.

Intraoperative Molecular Imaging for ex vivo Assessment of Peripheral Margins in Oral Squamous Cell Carcinoma.

Objective: Complete surgical resection is the standard of care for treatment of oral cancer although the positive margin rate remains 15-30%. Tissue sampling from the resected specimen and from the wound bed for frozen section analysis (FSA) remains the mainstay for intraoperative margin assessment but is subject to sampling error and can require the processing of multiple samples. We sought to understand if an ex vivo imaging strategy using a tumor-targeted fluorescently labeled antibody could accurately identify the closest peripheral margin on the mucosal surface of resected tumor specimen, so that this "sentinel margin" could be used to guide pathological sampling. Materials and Methods: Twenty-nine patients with oral squamous cell carcinoma scheduled for surgical resection were consented for the study and received systemic administration of a tumor-targeted fluorescently labeled antibody (Panitumumab IRDye800CW). After surgical resection, the tumor specimen was imaged using a closed-field fluorescent imaging device. Relevant pathological data was available for five patients on retrospective review. For each of these five patients, two regions of highest fluorescence intensity at the peripheral margin and one region of lowest fluorescence intensity were identified, and results were correlated with histology to determine if the region of highest fluorescence intensity along the mucosal margin (i.e., the sentinel margin) was truly the closest margin. Results: Imaging acquisition of the mucosal surface of the specimen immediately after surgery took 30 s. In all of the specimens, the region of highest fluorescence at the specimen edge had a significantly smaller margin distance than other sampled regions. The average margin distance at the closest, "sentinel," margin was 3.2 mm compared to a margin distance of 8.0 mm at other regions (p < 0.0001). Conclusions: This proof-of-concept study suggests that, when combined with routine FSA, ex vivo fluorescent specimen imaging can be used to identify the closest surgical margin on the specimen. This approach may reduce sampling error of intraoperative evaluation, which should ultimately improve the ability of the surgeon to identify the sentinel margin. This rapid sentinel margin identification improves the surgeon's orientation to areas most likely to be positive in the surgical wound bed and may expedite pathology workflow.

Neonatal hyperbilirubinaemia: a global perspective.

Hyperbilirubinaemia, presenting as jaundice, is a ubiquitous and frequently benign condition in newborn babies but is a leading cause of hospitalisation in the first week of life. In some infants jaundice can become severe, progressing to acute bilirubin encephalopathy and kernicterus with a substantial risk of neonatal mortality and long-term neurodevelopmental impairments. Severe hyperbilirubinaemia and its sequelae continue to occur in industrialised countries with functioning medical systems and a disproportionately high burden also persists in low-income and middle-income countries due primarily to delays in delivering effective treatments that are routinely available in high-income countries. In this Review we summarise up-to-date evidence on the epidemiology of neonatal jaundice including its global burden based on estimates of its prevalence, and both fatal and non-fatal health outcomes. We also discuss the management of severe hyperbilirubinaemia including the prevention of kernicterus, and highlight future directions for research.

Anaphylaxis in a health maintenance organization: International Classification of Diseases coding and epinephrine auto-injector prescribing.

BACKGROUND: Accurate estimates of the incidence of anaphylaxis are limited. Current International Classification of Diseases, Ninth Revision (ICD-9) codes complicate accurate diagnosis of anaphylaxis and assessment of appropriate epinephrine prescribing. OBJECTIVE: To quantify the incidence and demographic character of patients with anaphylaxis-related ICD-9 codes in a large health maintenance organization and analyze epinephrine prescribing and dispensing rates. METHODS: All patients included had at least 12 months of continuous membership over a 4-year period from January 1, 2008 to December 31, 2012 and were selected based on anaphylaxis-related ICD-9 codes (N = 159,172). This algorithm was extrapolated from a previous study that used expanded ICD-9 codes to identify more cases of anaphylaxis. Individual chart reviews found that many expanded ICD-9 codes represented unconfirmed cases of anaphylaxis and therefore were excluded, resulting in analysis of 52,405 patients. RESULTS: Incidence of anaphylaxis over 4 years was 2.07%, with female predominance (56.5%) over male predominance (43.5%). Epinephrine was prescribed in 16.2% of total cases. Highest rates of epinephrine prescription were for traditional ICD-9 codes 995.0 (other anaphylactic shock) and 995.60 to 995.69 (anaphylactic shock caused by food) at 49.3% and 58.6%, respectively. Of the cases in which an epinephrine auto-injector was prescribed, it was dispensed 95.9% of the time, independent of copayment amount. CONCLUSION: Low epinephrine auto-injector prescribing rates in cases of anaphylaxis suggest the continued difficulty in the diagnosis of anaphylaxis and could result in suboptimal treatment of potential future episodes.

BRAF inhibitor treatment of primary BRAF-mutant ameloblastoma with pathologic assessment of response.

OBJECTIVE: Molecular characterization of ameloblastoma has indicated a high frequency of driver mutations in BRAF and SMO. Preclinical data suggest that Food and Drug Administration-approved BRAF-targeted therapies may be immediately relevant for patients with ameloblastoma positive for the BRAF V600E mutation. METHODS: A neoadjuvant treatment regime of dabrafenib was given to a patient with recurrent BRAF-mutant mandibular ameloblastoma. The patient subsequently underwent left mandible composite resection of the tumor and pathologic evaluation of treatment response. RESULTS: The ameloblastoma had a slow but dramatic response with >90% tumor volume reduction. The inner areas of the tumor underwent degeneration and squamous differentiation, and intact ameloblastoma was present in the outer areas associated with bone. CONCLUSIONS: Targeted neoadjuvant therapy for ameloblastoma may be useful in certain clinical settings of primary ameloblastoma. These might include tumors of advanced local stage when a neoadjuvant reduction could alter the extent of surgery and instances of local recurrence when surgical options are limited.

A prospective study of electronic quality of life assessment using tablet devices during and after treatment of head and neck cancers.

OBJECTIVES: Electronic data collection is increasingly used for quality of life (QOL) assessments in the field of oncology. It is important to assess the feasibility of these new data capture technologies. MATERIALS AND METHODS: Patients at our institution who were 18 years or older with a pathological diagnosis of head and neck cancer were prospectively enrolled. Each patient completed two questionnaires [EORTC-QLQ-C30 and EORTC-QLQ-H&N35] administered on a touch-screen tablet device (iPad) at initial consult, during treatment, at the completion of treatment and at each subsequent follow up visit for one year after treatment. RESULTS: A total of 50 patients were included in this study. Although all patients completed the surveys at the initial consult, 86% of initially enrolled patients completed surveys at the end of radiation treatment, and 48% of initially enrolled patients completed surveys by the fourth follow-up visit. Average time to complete the survey for all patients over all time points was 9.8 min (standard deviation 6.1). Age as a continuous variable was significantly associated with time for survey completion (p<0.001), with older age associated with longer survey completion times. CONCLUSION: QOL assessment using tablet devices in head and neck cancer patients is feasible, but may be more challenging in elderly patients. Patients ⩾70 years old may benefit from more assistance with electronic forms and should be allotted more time for completing tablet-based QOL surveys.

Epinephrine autoinjector refill history in an HMO.

Epinephrine can be lifesaving in episodes of anaphylaxis, yet it is underprescribed and underused. Tracking of epinephrine refills over time for patients with a diagnosis of anaphylaxis has not been reported. This study reports on the refill history of 14,677 patients in a large HMO who received an initial dispensing of EpiPen (Dey Pharma, Basking Ridge, NJ) or EpiPen Jr between 2000 and 2006. A total of 6,776 (46%) refilled at least once. Twenty-five percent of the patients who were in the cohort for 5 years or more refilled multiple times, and 11% refilled consistently at all expected refill times. Infants through children 12 years of age were more likely to receive a refill dispensing (63%) compared with teenagers and adults (40%). The most common ICD-9 codes that were linked to the initial epinephrine dispensing were allergic disorder (37%), miscellaneous anaphylaxis/angioedema (23%), hymenoptera/insect bite or sting (14%), and specific or nonspecific food allergy (11%). A total of 79% of patients with a food-related ICD-9 code and 59% of patients with an insect sting-related ICD-9 code refilled epinephrine at least once. An opportunity exists to identify system-based as well as personal barriers in an ongoing effort to provide patients at risk with the tools and empowerment that could reduce their risk during life-threatening anaphylactic reactions.

Utilization of murine laparoscopy for continuous in-vivo assessment of the liver in multiple disease models.

BACKGROUND: Current strategies for follow up of murine models of liver disease are flawed by inability to continuously monitor disease progression in the tissue level, and necessitate sacrifice of animals for tissue sampling. AIMS: In this study we aimed at developing a safe repetitive tool for sampling livers in vivo, by utilization of a miniaturized endoscopy system for laparoscopic liver biopsies and for injection of tumor cells into livers. RESULTS: We report the development of a protocol for murine laparoscopy that allows repeated visualization of murine intra-abdominal organs. The system enables safe and repeated liver biopsies in mice and rats, yielding adequate tissue for histological staining and RNA extraction. In addition, injection of tumor cells into livers facilitates under-vision implantation of hepatic tumors in liver, followed by visualization of tumor growth. CONCLUSIONS: Murine laparoscopy may be employed as a novel imaging modality for continuous assessment and manipulation of chronic liver disease models.

Visual screening versus transcutaneous bilirubinometry for predischarge jaundice assessment.

OBJECTIVE: Comparison of visual screening with transcutaneous bilirubinometry (TcB) in identifying neonates with plasma total bilirubin (PTB) > or =75th percentile. DESIGN: In 100 paired readings PTB was 34 +/- 24 micromol/L higher than the TcB counterpart. A TcB reading of 154 micromol/L was therefore regarded as equivalent to a PTB of 188 micromol/L, corresponding to the 75th percentile at 48 h. Predischarge, all newborns were evaluated for jaundice, first by visual inspection and then transcutaneously. PTB was ordered as indicated by visual assessment or if the TcB reading was > or =154 micromol/L. RESULTS: Of 346 newborns tested, 25 (7.2%) had a PTB concentration > or =75th percentile. Forty-nine had PTB determinations based on TcB compared with 83 by visual assessment. However, a similar number of affected newborns was identified by each method (21/25 (84%) by visual screening vs. 18/25 (72%) by TcB). PTB concentrations of those who had been chosen by TcB were higher than those selected visually (202 +/- 24 micromol/L vs. 186 +/- 31 micromol/L). CONCLUSIONS: A practical method for predischarge detection of neonates with plasma total bilirubin concentration > or = 75th percentile, implementing transcutaneous bilirubinometry, is described. The transcutaneous technique required fewer blood tests than visual assessment for similar yield.

Assessment of metastatic cervical adenopathy using dynamic contrast-enhanced MR imaging.

BACKGROUND AND PURPOSE: Morphologic assessment by conventional imaging methods of lymph node metastases in patients with squamous cell carcinoma of the head and neck is, at best, insensitive. Doppler sonography has shown that lymph node metastases exhibit alterations in the number of vessels and blood flow. We assessed the ability of dynamic contrast-enhanced MR imaging to differentiate normal from diseased nodes in this patient population. METHODS: Twenty-one patients with newly diagnosed squamous cell carcinoma and no previous treatment were studied with the use of a head and neck phased array surface coil. Anatomic imaging included high resolution T1-weighted, fat-saturated fast spin-echo T2-weighted, and contrast-enhanced T1-weighted imaging (0.99-1.32 mm(3) voxels). The dynamic contrast-enhanced MR imaging was performed by using a 2D fast spoiled gradient recalled sequence with single dose bolus injection of contrast agent. Calculated values included time to peak, peak enhancement, maximum slope, and washout slope for the enhancement. All patients underwent neck dissection as part of their indicated treatment, and imaging results were correlated with pathologic findings. RESULTS: Dynamic contrast-enhanced MR imaging and pathology comparisons were obtained for 68 nodes. There was significantly longer time to peak (P <.001), lower peak enhancement (P <.05), lower maximum slope (P <.01), and slower washout slope (P <.05) in the tumor-involved nodes compared with the normal nodes. CONCLUSION: Analysis of dynamic contrast-enhanced MR imaging can differentiate normal from diseased lymph nodes in patients with squamous cell carcinoma of the head and neck.