Radiation Therapy for HPV-Positive Oropharyngeal Squamous Cell Carcinoma: An ASTRO Clinical Practice Guideline.

PURPOSE: Human Papilloma Virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is a distinct disease from other head and neck tumors. This guideline provides evidence-based recommendations on the critical decisions in its curative treatment, including both definitive and postoperative radiation therapy (RT) management. METHODS: ASTRO convened a task force to address 5 key questions on the use of RT for management of HPV-associated OPSCC. These questions included indications for definitive and postoperative RT and chemoradiation; dose-fractionation regimens and treatment volumes; preferred RT techniques and normal tissue considerations; and posttreatment management decisions. The task force did not address indications for primary surgery versus RT. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS: Concurrent cisplatin is recommended for patients receiving definitive RT with T3-4 disease and/or 1 node >3 cm, or multiple nodes. For similar patients who are ineligible for cisplatin, concurrent cetuximab, carboplatin/5-fluorouracil, or taxane-based systemic therapy are conditionally recommended. In the postoperative setting, RT with concurrent cisplatin (either schedule) is recommended for positive surgical margins or extranodal extension. Postoperative RT alone is recommended for pT3-4 disease, >2 nodes, or a single node >3 cm. Observation is conditionally recommended for pT1-2 disease and a single node ≤3 cm without other risk factors. For patients treated with definitive RT with concurrent systemic therapy, 7000 cGy in 33 to 35 fractions is recommended, and for patients receiving postoperative RT without positive surgical margins and extranodal extension, 5600 to 6000 cGy is recommended. For all patients receiving RT, intensity modulated RT over 3-dimensional techniques with reduction in dose to critical organs at risk (including salivary and swallowing structures) is recommended. Reassessment with positron emission tomography-computed tomography is recommended approximately 3 months after definitive RT/chemoradiation, and neck dissection is recommended for convincing evidence of residual disease; for equivocal positron emission tomography-computed tomography findings, either neck dissection or repeat imaging is recommended. CONCLUSIONS: The role and practice of RT continues to evolve for HPV-associated OPSCC, and these guidelines inform best clinical practice based on the available evidence.

Social Determinants of Health Among American Indians and Alaska Natives and Tribal Communities: Comparison with Other Major Racial and Ethnic Groups in the United States, 1990-2022.

Background and Objective: Limited research exists on health inequities between American Indians and Alaska Natives (AIANs), tribal communities, and other population groups in the United States. To address this gap in research, we conducted time-trend analyses of social determinants of health and disease outcomes for AIANs as a whole and specific tribal communities and compared them with those from the other major racial/ethnic groups. Methods: We used data from the 1990-2022 National Vital Statistics System, 2015-2022 American Community Survey, and the 2018-2020 Behavioral Risk Factor Surveillance System to examine socioeconomic, health, disability, disease, and mortality patterns for AIANs. Results: In 2021, life expectancy at birth was 70.6 years for AIANs, lower than that for Asian/Pacific Islanders (APIs) (84.1), Hispanics (78.8), and non-Hispanic Whites (76.3). All racial/ethnic groups experienced a decline in life expectancy between the pre-pandemic year of 2019 and the peak pandemic year of 2021. However, the impact of COVID-19 was the greatest for AIANs and Blacks whose life expectancy decreased by 6.3 and 5.8 years, respectively. The infant mortality rate for AIANs was 8.5 per 1,000 live births, 78% higher than the rate for non-Hispanic Whites. One in five AIANs assessed their physical and mental health as poor, at twice the rate of non-Hispanic Whites or the general population. COVID-19 was the leading cause of death among AIANs in 2021. Risks of mortality from alcohol-related problems, drug overdose, unintentional injuries, and homicide were higher among AIANs than the general population. AIANs had the highest overall disability, mental and ambulatory disability, health uninsurance, unemployment, and poverty rates, with differences in these indicators varying markedly across the AIAN tribes. Conclusion and Global Health Implications: AIANs remain a disadvantaged racial/ethnic group in the US in many health and socioeconomic indicators, with poverty rates in many Native American tribal groups and reservations exceeding 40%.

Leveraging a Phage-Encoded Noncanonical Amino Acid: A Novel Pathway to Potent and Selective Epigenetic Reader Protein Inhibitors.

Epigenetic reader proteins interpret histone epigenetic marks to regulate gene expression. Given their vital roles and the link between their dysfunction and various diseases, these proteins present compelling targets for therapeutic interventions. Nevertheless, designing selective inhibitors for these proteins poses significant challenges, primarily due to their unique properties such as shallow binding sites and similarities with homologous proteins. To overcome these challenges, we propose an innovative strategy that uses phage display with a genetically encoded noncanonical amino acid (ncAA) containing an epigenetic mark. This ncAA guides binding to the reader protein's active site, allowing the identification of peptide inhibitors with enhanced affinity and selectivity. In this study, we demonstrate this novel approach's effectiveness by identifying potent inhibitors for the ENL YEATS domain that plays a critical role in leukemogenesis. Our strategy involved genetically incorporating Nε-butyryl-l-lysine (BuK), known for its binding to ENL YEATS, into a phage display library for enriching the pool of potent inhibitors. One resultant hit was further optimized by substituting BuK with other pharmacophores to exploit a unique π-π-π stacking interaction with ENL YEATS. This led to the creation of selective ENL YEATS inhibitors with a KD value of 2.0 nM and a selectivity 28 times higher for ENL YEATS than its close homologue AF9 YEATS. One such inhibitor, tENL-S1f, demonstrated robust cellular target engagement and on-target effects to inhibit leukemia cell growth and suppress the expression of ENL target genes. As a pioneering study, this work opens up extensive avenues for the development of potent and selective peptidyl inhibitors for a broad spectrum of epigenetic reader proteins.

Reduced expression of chlorophyllide a oxygenase (CAO) decreases the metabolic flux for chlorophyll synthesis and downregulates photosynthesis in tobacco plants.

Chlorophyll b is synthesized from chlorophyllide a, catalyzed by chlorophyllide a oxygenase (CAO). To examine whether reduced chlorophyll b content regulates chlorophyll (Chl) synthesis and photosynthesis, we raised CAO transgenic tobacco plants with antisense CAO expression, which had lower chlorophyll b content and, thus, higher Chl a/b ratio. Further, these plants had (i) lower chlorophyll b and total Chl content, whether they were grown under low or high light; (ii) decreased steady-state levels of chlorophyll biosynthetic intermediates, due, perhaps, to a feedback-controlled reduction in enzyme expressions/activities; (iii) reduced electron transport rates in their intact leaves, and reduced Photosystem (PS) I, PS II and whole chain electron transport activities in their isolated thylakoids; (iv) decreased carbon assimilation in plants grown under low or high light. We suggest that reduced synthesis of chlorophyll b by antisense expression of CAO, acting at the end of Chl biosynthesis pathway, downregulates the chlorophyll b biosynthesis, resulting in decreased Chl b, total chlorophylls and increased Chl a/b. We have previously shown that the controlled up-regulation of chlorophyll b biosynthesis and decreased Chl a/b ratio by over expression of CAO enhance the rates of electron transport and CO2 assimilation in tobacco. Conversely, our data, presented here, demonstrate that-antisense expression of CAO in tobacco, which decreases Chl b biosynthesis and increases Chl a/b ratio, leads to reduced photosynthetic electron transport and carbon assimilation rates, both under low and high light. We conclude that Chl b modulates photosynthesis; its controlled down regulation/ up regulation decreases/ increases light-harvesting, rates of electron transport, and carbon assimilation. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01395-5.

Adult Onset Orbital Xanthogranuloma, a Variant of Adult Orbital Xanthogranulomatous Disease: An Infrequent Entity.

Adult orbital xanthogranulomatous diseases (AOXGD) present clinically with symmetrical swellings around the eyes and are collectively considered within the broader group of non-Langerhans cell histiocytosis. A 45-year-old female presented with asymptomatic progressive, skin-colored, thick raised lesions around the eyes of 1 year duration. On dermatological examination, large indurated, lobulated, skin-colored thick plaques were seen bilaterally over infraorbital areas, along with a few hard, discrete nodules over the left infraorbital area. Histopathology showed pan-dermal infiltration with foamy histiocytes, non-lipidized histiocytes, a few multinucleate giant cells, lymphocytes, and a few plasma cells, with immunohistochemistry showing CD68 and S100 positivity. Laboratory and imaging studies did not show any abnormality. Based on the above findings and the absence of internal organ involvement, the patient was diagnosed with adult-onset orbital xanthogranuloma (AOX). The patient was treated with three monthly sessions of intralesional corticosteroid injections, along with methotrexate 12.5 mg per week for 8 weeks, resulting in a moderate reduction in the size of the plaques. The patient is under regular follow-up. The present case highlights the rare case of AOX and the importance of prompt recognition and evaluation in view of its potential hematological and systemic associations.

Living alone and cancer mortality by race/ethnicity and socioeconomic status among US working-age adults.

BACKGROUND: Previous studies have shown an association between living alone and cancer mortality; however, findings by sex and race/ethnicity have generally been inconsistent, and data by socioeconomic status are sparse. The association between living alone and cancer mortality by sex, race/ethnicity, and socioeconomic status in a nationally representative US cohort was examined. METHODS: Pooled 1998-2019 data for adults aged 18-64 years at enrollment from the National Health Interview Survey linked to the National Death Index (N = 473,648) with up to 22 years of follow-up were used to calculate hazard ratios (HRs) for the association between living alone and cancer mortality. RESULTS: Compared to adults living with others, adults living alone were at a higher risk of cancer death in the age-adjusted model (HR, 1.32; 95% CI, 1.25-1.39) and after additional adjustments for multiple sociodemographic characteristics and cancer risk factors (HR, 1.10; 95% CI, 1.04-1.16). Age-adjusted models stratified by sex, poverty level, and educational attainment showed similar associations between living alone and cancer mortality, but the association was stronger among non-Hispanic White adults (HR, 1.33; 95% CI, 1.25-1.42) than non-Hispanic Black adults (HR, 1.18; 95% CI, 1.05-1.32; p value for difference < .05) and did not exist in other racial/ethnic groups. These associations were attenuated but persisted in fully adjusted models among men (HR, 1.13; 95% CI, 1.05-1.23), women (HR, 1.09; 95% CI, 1.01-1.18), non-Hispanic White adults (HR, 1.13; 95% CI, 1.05-1.20), and adults with a college degree (HR, 1.22; 95% CI, 1.07-1.39). CONCLUSIONS: In this nationally representative study in the United States, adults living alone were at a higher risk of cancer death in several sociodemographic groups.

Non-prescription antibiotics dispensing by community pharmacies: implications for antimicrobial resistance.

Introduction: The non-prescription antibiotics dispensing (NPAD) from pharmacies is on the rise in low- and middle-income countries, which contributes to the emergence of antimicrobial resistance (AMR). This study was conducted with the objective to determine the community pharmacy personnel's perspectives on NPAD and its implications for AMR. Methods: A questionnaire-based cross-sectional survey was conducted in Pakistan among 336 pharmacies. The data were analyzed using SPSS v21 and MedCalc for Windows v12.3.0. Modified Bloom's cut-off point was utilized to categorize the participants' overall knowledge, attitude, and practice. For univariable logistic regression analyses, odds ratio (OR) was calculated at 95% confidence interval (CI). For multivariable logistic regression analyses, adjusted OR was calculated at 95% CI. Spearman's rank correlation coefficient test was used to assess the relationships among knowledge, attitude, and/or practice scores. Results: The majority of the respondents were staff pharmacists (45.5%). About four-fifths (78.9%) and half (50.9%) of the participants demonstrated moderate to good knowledge and practice, respectively. However, about only one-third (33.1%) had a moderate to good attitude. Staff pharmacists had higher odds of moderate to good knowledge (OR: 2.4, 95% CI: 1.2-4.7) and practice (OR: 2.3, 95% CI: 1.4-3.8). Total knowledge and practice (Spearman's ρ: 0.280; P <0.001) and total attitude and practice (Spearman's ρ: 0.299; P <0.001) scores were significantly correlated. Conclusion: The qualified pharmacists had satisfactory knowledge, attitude, and practices toward antibiotics. However, non-pharmacist staff lacked knowledge and had probable NPAD practice, which has a negative impact on public health. Regular refresher training, seminars, and strict enforcement of rules and regulations are essential.

A Clinico-Mycological and Histopathological Study of Recurrent Dermatophytosis.

Background: A few recent studies have shown fungal elements within the hair follicle epithelium, which may act as a reservoir and responsible for recurrent dermatophytosis. Objectives: To assess the clinical patterns, mycological profile, and histopathology of recurrent dermatophytosis and to determine the prevalence of fungal hyphae in the hair follicle epithelium and other appendages. Materials and Methods: One hundred and fifty clinically diagnosed cases of recurrent dermatophytic infection were included. Skin samples were taken for direct microscopy, fungal culture, and histopathological analysis. Haematoxylin and eosin and special staining with periodic acid Schiff (PAS) and Gomori's methenamine silver (GMS) were performed to detect the fungal hyphae in the skin and hair follicle epithelium. Results: The most common clinical pattern observed was tinea corporis et cruris in 64 patients (42.66%). On direct microscopy and fungal culture, positive results were obtained in 116 cases (77.33%) and 78 (52%) cases, respectively. Presence of fungal hyphae in the stratum corneum, hair follicle, and acrosyringium was seen in 107 patients (71.33%), 47 patients (31.33%), and five patients (3.33%), respectively. Out of the 52 cases with hair follicle and eccrine gland involvement, history of fixed drug combinations (FDC) cream use was present in 42 cases (80.76%) and absent in ten cases (19.24%) (P = 0.000062). Limitations: Skin samples were taken only from a single skin lesion. Higher incidence of follicular invasion may have been detected if multiple biopsy samples were taken. Conclusion: Hair follicle/eccrine sweat gland involvement was observed in nearly one-third of the patients, which may act as a reservoir and may be responsible for recurrence and chronicity. Histopathology should be considered as an important adjuvant tool in recurrent dermatophytosis to establish the extent of the infection, which guides the further management.

Peptide-Induced Fusion of Dynamic Membrane Nanodomains: Implications in a Viral Entry.

Enveloped viruses infect host cells via protein-mediated membrane fusion. However, insights into the microscopic rearrangement induced by the viral proteins and peptides have not yet emerged. Here, we report a new methodology to extract viral fusion peptide (FP)-mediated biomembrane dynamical nanodomain fusion parameter, λ, based on stimulated emission depletion microscopy coupled with fluorescence correlation spectroscopy. We also define another dynamical parameter membrane gradient, defined in terms of the ratio of average lipid diffusion coefficients across dynamic crossover length scales, ξ. Significantly, we observe that λ as well as these mobility gradients are larger in the stiffer liquid-ordered (Lo) phase compared to the liquid-disordered phase and are more effective at the smaller nanodomain interfaces, which are only present in the Lo phase. The results could possibly help to resolve a long-standing puzzle about the enhanced fusogenicity of FP in the Lo phase. Results obtained from the diffusion results have been correlated with the human immunodeficiency virus gp41 FP-induced membrane fusion.

Role of radiological corroboration in a locally aggressive inverted papilloma: a case report.

Introduction and importance: Sinonasal inverted papilloma is a rare benign tumor of the nasal cavity and paranasal sinuses (PNS). Radiological evaluation is the key to management. Case presentation: A 46-year-old male presented with complaints of right nasal congestion and occasional bleeding for 4 months. During anterior rhinoscopy, a pinkish fleshy mass occupying the right nasal cavity was seen. X-ray and computed tomography (CT) PNS view showed opacification in the right nasal cavity and maxillary sinus. An MRI of the nose and PNS revealed a peculiar convoluted striated/cerebriform pattern. Histopathology report described the features of an inverted papilloma. The patient underwent endoscopic removal of the mass under general anesthesia. Surgical resection of the tumor was performed along with adjacent normal mucosal tissues. The patient recovered well and was followed-up for recurrence. Clinical discussion: Sinonasal inverted papilloma is commonly found in males in their fifth to sixth decade of life. A CT scan is the initial modality of choice to evaluate the extent of the disease. MRI is superior to CT in distinguishing tumors from other conditions as well as to evaluate soft tissue extensions. Involvement of the frontal sinus is a risk factor for recurrence. The first option for treating an inverted papilloma is complete surgical removal with the adjacent uninvolved mucosa. Conclusion: In a biopsy-proven case, radiological assessments like CT and MRI play a pivotal role in studying the typical morphology, delineating the extension, and detecting recurrence.

Iron Deficiency Anemia Presenting With Pancytopenia: A Study From India.

INTRODUCTION: Iron deficiency anemia (IDA) is the most common cause of anemia worldwide. IDA is commonly associated with thrombocytosis and normal or slightly decreased leukocyte count. Sometimes it can present with thrombocytopenia, but rarely present with pancytopenia. Here we are presenting six cases of severe iron deficiency presenting with pancytopenia, which responded to iron replenishment. METHODS:  This 12-month observational study was conducted in the Department of General Medicine at a tertiary care Centre in India. All cases of pancytopenia (after exclusion of other causes) with IDA were included. IDA was established with the help of a complete blood count (CBC), peripheral smear examination, serum iron studies, and serum ferritin.  Results: In our study, CBC at four weeks later of iron transfusion without other supplementation showed significant improvement in hematological parameters. CONCLUSION:  Severe iron deficiency is a reversible etiology of pancytopenia. It should be kept as a differential diagnosis of pancytopenia if common causes of pancytopenia are ruled out.

Association of urinary albumin-to-creatinine ratio with lipid abnormalities and glycemic control in patients with type 2 diabetes mellitus.

Introduction: While proteinuria aggravates dyslipidemia in diabetic patients, dyslipidemia further worsens proteinuria via inflammatory cytokines-mediated glomerular damage. Urinary albumin creatinine ratio (ACR) is an easy and reliable method of detecting proteinuria. This study aims to determine the association of ACR with lipid abnormalities and glycemic control in the Nepalese population. Methods: This was a cross-sectional study conducted among 201 diabetes patients visiting the outpatient department of internal medicine. Based on ACR values, patients were categorized as nonalbuminuric (less than 300 µg/mg) or albuminuric (more than 300 µg/mg). An unpaired t-test was used to compare the mean of various lipoproteins in these two categories. Binary logistic regression was used to check the association of ACR with sociodemographic factors (age, sex, and education), hypertension, and glycated hemoglobin. Results: Albuminuric patients had higher mean cholesterol (192.8±53.5 vs. 184.2± 37.6; P=0.209), triglyceride (194.9±97.8 vs. 164.4±73.7; P=0.017) and low-density lipoprotein (99.9±38.4 vs. 90.0±27.4; P=0.034) but lower high-density lipoprotein (53.9±18.5 vs. 61.3±19.9; P=0.008) compared to nonalbuminuric patients. There was a significant difference in mean HbA1c values across albuminuria and nonalbuminuria groups (7.1±1.1 vs. 6.7±0.8; OR: 1.4, 95% CI=1.1-1.9, P=0.030). Conclusions: Urine ACR of more than 30 mg/gram was associated with higher triglyceride and low-density lipoprotein levels and lower high-density lipoprotein levels. The HbA1c level strongly correlates with the development of albuminuria.

Assessment of rational use of antimicrobials: a cross-sectional study among people of Nepal.

Inappropriate antimicrobial use leading to antimicrobial resistance is a matter of public health concern globally. This research was conducted with the objective of preventing antimicrobial misuse across knowledge, behavior, and practice domains among the general people of Nepal. Methods: It was a cross-sectional survey conducted among 385 participants visiting tertiary care center from all over Nepal from February 2022 to May 2022. Modified Bloom's cut-off point was utilized to categorize the participants' overall knowledge, behavior, and practice. The chi-square (χ 2) test and odds ratio (OR) using binary logistic regression at 95% CI and Spearman's rank correlation coefficient test (r) were calculated wherever appropriate. Results: More than three-fifths of the participants (248, 64.42%) demonstrated good behavior, whereas less than half of the participants showed good knowledge (137, 35.58%) and practice (161, 41.82%) about rational use of antimicrobials. Health professionals had higher knowledge (OR: 1.07, 95% CI: 0.70-1.62) and good behavior (OR: 0.42, 95% CI: 0.27-0.64) than other professionals (P<0.05). Those with higher income [≥50 000 NRS (Nepalese rupees)] had good behavior (OR: 3.37, 95% CI: 1.65-6.87) and good practice (OR: 2.58, 95% CI: 1.47-4.50) scores than those with less monthly income (P<0.05). Similarly, higher educational degrees, viz. master's and/or above, had good behavior (OR: 4.13, 95% CI: 2.62-6.49) and good practice scores (OR: 2.55, 95% CI: 1.68-3.87). Additionally, there were significant positive correlations between knowledge (K), behavior (B), and practice (P) scores (r=0.331 for K and B, r=0.259 for K and P, and r=0.618 for B and P, respectively; P<0.05). Conclusions: The findings imply the demand for effective legislature, strict enforcement of the drug act, and proper implementation of plans and policies to curb antimicrobials misuse. Lack of execution of existing laws and the unawareness of the public led to the extravagant use of antimicrobials.

An amber-encoding helper phage for more efficient phage display of noncanonical amino acids.

Using an amber suppression-based noncanonical amino acid (ncAA) mutagenesis approach, the chemical space in phage display can be significantly expanded for drug discovery. In this work, we demonstrate the development of a novel helper phage, CMa13ile40, for continuous enrichment of amber obligate phage clones and efficient production of ncAA-containing phages. CMa13ile40 was constructed by insertion of a Candidatus Methanomethylophilus alvus pyrrolysyl-tRNA synthetase/PylT gene cassette into a helper phage genome. The novel helper phage allowed for a continuous amber codon enrichment strategy for two different libraries and demonstrated a 100-fold increase in packaging selectivity. CMa13ile40 was then used to create two peptide libraries containing separate ncAAs, Nϵ-tert-butoxycarbonyl-lysine and Nϵ-allyloxycarbonyl-lysine, respectively. These libraries were used to identify peptide ligands that bind to the extracellular domain of ZNRF3. Each selection showed differential enrichment of unique sequences dependent upon the ncAA used. Peptides from both selections were confirmed to have low micromolar affinity for ZNRF3 that was dependent upon the presence of the ncAA used for selection. Our results demonstrate that ncAAs in phages provide unique interactions for identification of unique peptides. As an effective tool for phage display, we believe that CMa13ile40 can be broadly applied to a wide variety of applications.

Morphometric analysis of foramen ovale, foramen spinosum, and foramen rotundum of human skull using computed tomography scan: a cross-sectional study.

There is limited literature of objective assessments of foramina of skull base using computed tomography (CT) scan. This study was carried out to analyze the dimensions of foramen ovale (FO), foramen spinosum (FS), and foramen rotundum (FR) using CT scan imaging of the human skull and their associations with sex, age, and laterality of the body. Materials and methods: A cross-sectional study was carried out in the Department of Radiodiagnosis and Imaging at BP Koirala Institute of Health Sciences (BPKIHS), Nepal using a purposive sampling method. We included 96 adult patients (≥18 years) who underwent CT scan of the head for any clinical indications. All those participants below 18 years, inadequate visualization or erosions of skull base foramina, and/or not consenting were excluded. Appropriate statistical calculations were done using the statistical package for social sciences (SPSS), version 21. The P-value of less than 0.05 was considered statistically significant. Results: The mean length, width, and area of FO was 7.79±1.10 mm, 3.68±0.64 mm, and 22.80±6.18 mm2, respectively. The mean length, width, and area of FS was 2.38±0.36 mm, 1.94±0.30 mm, and 3.69±0.95 mm2, respectively. Similarly, the mean height, width, and area of FR was 2.41±0.49 mm, 2.40±0.55 mm, and 4.58±1.49 mm2, respectively. The male participants had statistically significant higher mean dimensions of FO and FS (P<0.05) than the female participants. There were statistically insignificant correlations of dimensions of these foramina with age and between the left and right side of each foraminal dimensions (P>0.05). Conclusions: The sex-based difference in dimensions of FO and FS should be clinically considered in evaluating the pathology of these foramina. However, further studies using objective assessment of foraminal dimensions are required to draw obvious inferences.

The Differential Impact of the COVID-19 Pandemic on Prenatal Care Utilization Among US Women by Medicaid Expansion and Race and Ethnicity.

BACKGROUND: The 2014 Medicaid expansion improved racial and ethnic equity in insurance coverage and access to maternal care among women of reproductive age. This study examines differential effects of the COVID-19 pandemic on prenatal care utilization by Medicaid expansion and by race and ethnicity. METHODS: Using the pooled 2019-2020 National Natality file (N = 7 361 190), logistic regression was used to estimate the effect of COVID-19 on prenatal care utilization among US women aged 10 to 54 years after controlling for maternal age, race, ethnicity, marital status, parity, nativity/immigrant status, education, payment type, and smoking during pregnancy. Outcome measures were having no care and delayed prenatal care (third trimester or no care). Stratified models by race/ethnicity and Medicaid expansion status yielded the differential effects of COVID-19 on prenatal care utilization. RESULTS: During the COVID-19 pandemic, the adjusted odds of having no prenatal care decreased by 4% (adjusted odds ratio [AOR] = 0.96; 95% confidence interval [CI], 0.94-0.97) in expansion states but increased by 13% (AOR = 1.13; 95% CI, 1.11-1.15) in nonexpansion states. While most racial and ethnic groups in expansion states experienced a decrease in having no prenatal care, the adjusted odds of having no prenatal care increased by 15% for non-Hispanic Whites, 9% for non-Hispanic Blacks, 33% for American Indians/Alaska Natives, 25% for Asian/Pacific Islanders, and 13% for Hispanics in nonexpansion states. Women in expansion states experienced no change in delayed prenatal care during the pandemic, but women in nonexpansion states experienced an increase in delayed care. CONCLUSIONS: Prenatal care utilization decreased during the pandemic among women in nonexpansion states, particularly for American Indians/Alaska Natives and Asian/Pacific Islanders, compared with expansion states.

Recent Trends in Medicare Payments for Outpatient Cancer Care at the End of Life.

PURPOSE: Outpatient care for patients with cancer compromises 60% to 70% of health care costs during the last 6 months of life. Recent approvals for expensive biologics and growing support for lower-cost hypofractionated radiation therapy in the palliative management of advanced cancer have introduced offsetting spending effects on end-of-life care that may shift overall expenditures for this patient cohort. METHODS AND MATERIALS: In this descriptive retrospective cohort study, end-of-life care is defined as the aggregate of medical services and supplies, including drugs, furnished to patients with cancer in the outpatient setting during the last 6 months of life. A total of 84,744 Medicare beneficiaries with a cancer diagnosis were identified as having died between January 1, 2016, and December 31, 2019. Beneficiaries with Medicare Advantage were not included in this study. Medicare Standard Analytical Files were abstracted for all paid claims for these beneficiaries during the last 6 months of life, and provider payments were summed according to service or supply category and year of death. Comparisons of service and supply utilization and costs between patient groups were performed using the Pearson χ2 test. RESULTS: The average total Medicare Part B payments per treated beneficiary during the last 6 month of life increased by 12.0% between 2016 and 2019 (from $14,487 to $16,227), with the greatest absolute cost increase observed for the medical oncology category (from $7030 to $9436 [+34.2%]). Within the medical oncology category, drug utilization shifted away from less costly chemotherapy and hormone therapy agents and toward more expensive immunotherapy agents. The increase in immunotherapy utilization and drug costs alone accounted for 84% of the increase in total Part B payments for all categories during the period. CONCLUSIONS: Although costs related to end-of-life care for nearly all cost categories have remained relatively stable, oncology drug costs overall and immunotherapy costs specifically have accelerated and account almost entirely for the observed overall increase in outpatient cost burden for Medicare.

Association of blood donor's biological characteristics on outcomes of cardiac surgery patients receiving red blood cells transfusion.

OBJECTIVES: This study aimed to assess the association of blood donor variables on the outcome of patients undergoing cardiac surgery. STUDY DESIGN AND METHODS: A retrospective observational study was conducted on patients who had cardiac surgery between January 2018 and December 2020. Blood donor characteristics such as age (≤ or >30 years), sex, and body mass index (BMI) (≤ or >25 kg/m2) were analyzed for association with patient outcomes (length of hospital stay (LOS), mortality, and readmission). Sex matching was done as fully match, fully mismatch, and partial mismatch. Cox regression and Linear regression models were used to study the association with mortality and readmission, and LOS. RESULTS: During the study period, 5788 patients had cardiac surgery; receiving a total of 20,348 red cell units. Of which, 522 (9%) died, 531 (9.2%) re-admitted and median LOS was 11 days (IQR 7-18). BMI >25 kg/m2 (ß, 2.96; p = 0.000), female to male transfusion (partial mismatch: ß, 4.42; p = 0.001; fully mismatch: ß, 9.0; p = 0.02) negatively affected LOS. BMI >25 kg/m2 (HR, 2.07; p = 0.00) and partial mismatch transfusion to male patients (HR, 1.60; p = 0.01) increased mortality. Fully mismatch transfusion to female patients (HR, 1.24; p = 0.01) and partial mismatch to male patients (HR, 1.86; p = 0.01) increased readmission. No association of donor age on patient outcome was observed. DISCUSSION: Blood donor sex, and BMI can influence mortality and LOS in cardiac surgery patients. The use of computer tools to match the patient's and donor's characteristics can assist to eliminate these types of adverse consequences.

Housing and Inequalities in US Life Expectancy, Child and Youth Mortality, and All-Cause and Cause-Specific Mortality, 1979-2020: Results from the National Longitudinal Mortality Study and the National Vital Statistics System.

Background: Limited research exists on the association between housing, life expectancy, and mortality disparities in the United States (US). Using longitudinal individual-level and pooled county-level mortality data from 1979 to 2020, we examine disparities in life expectancy, child and youth mortality, and all-cause and cause-specific mortality in the US by several housing variables. Methods: Using the 1979-2011 National Longitudinal Mortality Study (N=1,313,627) and the 2011-2020 linked county-level National Mortality Database and American Community Survey, we analyzed disparities in life expectancy and all-cause and cause-specific disparities by housing tenure, household crowding, and housing stability. Multivariate Cox proportional hazards regression was used to analyze individual-level mortality differentials by housing tenure. Age-adjusted mortality rates and rate ratios were used to analyze area-level disparities in mortality by housing variables. Results: US homeowners had, on average, a 3.5-year longer life expectancy at birth than renters (74.22 vs. 70.76 years), with advantages in longevity associated with homeownership being greater for males than for females; for American Indians/Alaska Natives, non-Hispanic Whites, and non-Hispanic Blacks than for Asian/Pacific islanders and Hispanics; and for the US-born than for immigrants. Compared with renters, homeowners had 22% lower risks of all-cause mortality, 15% lower child mortality, 17% lower youth mortality, and significantly lower mortality from cardiovascular diseases, all cancers combined, stomach, liver, esophageal and cervical cancer, diabetes, influenza and pneumonia, COPD, cirrhosis, kidney disease, HIV/AIDS, infectious diseases, unintentional injuries, suicide, and homicide. Conclusion and Global Health Implications: Several aspects of housing are strongly associated with life expectancy, child and youth mortality, and all-cause and cause-specific mortality in the US. Policies that aim to provide well-designed, accessible, and affordable housing to residents of both developed and developing countries are important policy options for addressing one of the most fundamental determinants of health for disadvantaged individuals and communities and for reducing health inequities globally.

Pulsed Carrier Gas Assisted High-Quality Synthetic 3R-Phase Sword-like MoS2: A Versatile Optoelectronic Material.

Synthesizing a material with the desired polymorphic phase in a chemical vapor deposition (CVD) process requires a delicate balance among various thermodynamic variables. Here, we present a methodology to synthesize rhombohedral (3R)-phase MoS2 in a well-defined sword-like geometry having lengths up to 120 µm, uniform width of 2-3 µm and thickness of 3-7 nm by controlling the carrier gas flow dynamics from continuous mode to pulsed mode during the CVD growth process. Characteristic signatures such as high degree of circular dichroism (∼58% at 100 K), distinct evolution of low-frequency Raman peaks and increasing intensity of second harmonic signals with increasing number of layers conclusively establish the 3R-phase of the material. A high value (∼844 pm/V) of second-order susceptibility for few-layer-thick MoS2 swords signifies the potential of MoS2 to serve as an atomically thin nonlinear medium. A field effect mobility of 40 cm2/V-s and Ion/Ioff ratio of ∼106 further confirm the electronic-grade standard of this 3R-phase MoS2. These findings are significant for the development of emerging quantum electronic devices utilizing valley-based physics and nonlinear optical phenomena in layered materials.