Periodontal inflammatory and microbial profiles in healthy young African Americans and Caucasians.

AIM: This study aimed to compare microbial and inflammatory profiles in periodontally/systemically healthy African American (AA) and Caucasian (C) individuals. MATERIALS AND METHODS: Thirty-seven C and 46 AA aged from 5 to 25 years were evaluated regarding periodontal disease, caries, microbial subgingival profile via 16-s sequencing, as well as salivary and gingival crevicular fluid (GCF) inflammatory profile via multiplex assay. RESULTS: Greater probing depth percentage was detected in AA (p = .0075), while a higher percentage of caries index (p = .0069) and decayed, missing, filled teeth (DMFT) index (p = .0089) was observed in C, after adjusting for number of teeth, sex and age. Salivary levels of IL-6, IL-8 and TNFα were higher for C, whereas GCF levels of eotaxin, IL-12p40, IL-12p70, IL-2 and MIP-1α were higher in AA (p < .05). Different microbial profiles were observed between the races (p = .02). AA presented higher abundance of periodontopathogens (such as Tanerella forsythia, Treponema denticola, Filifactor alocis, among others), and C presented more caries-associated bacteria (such as Streptococcus mutans and Prevotella species). Bacillaceae and Lactobacillus species were associated with higher DMFT index, whereas Fusobacterium and Tanerella species with periodontal disease parameters. CONCLUSIONS: A different inflammatory and bacterial profile was observed between healthy AA and C, which may predispose these races to higher susceptibility to specific oral diseases.

Combination of spironolactone and DPP-4 inhibitors for treatment of SARS-CoV-2 infection: a literature review.

Coronavirus disease 2019 (COVID-19) is still causing hospitalization and death, and vaccination appears to become less effective with each emerging variant. Spike, non-spike, and other possible unrecognized mutations have reduced the efficacy of recommended therapeutic approaches, including monoclonal antibodies, plasma transfusion, and antivirals. SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2) and probably dipeptidyl peptidase 4 (DPP-4) to initiate the process of endocytosis by employing host proteases such as transmembrane serine protease-2 (TMPRSS-2) and ADAM metallopeptidase domain 17 (ADAM17). Spironolactone reduces the amount of soluble ACE2 and antagonizes TMPRSS-2 and ADAM17. DPP-4 inhibitors play immunomodulatory roles and may block viral entry. The efficacy of treatment with a combination of spironolactone and DPP-4 inhibitors does not appear to be affected by viral mutations. Therefore, the combination of spironolactone and DPP-4 inhibitors might improve the clinical outcome for COVID-19 patients by decreasing the efficiency of SARS-CoV-2 entry into cells and providing better anti-inflammatory, antiproliferative, and antifibrotic effects than those achieved using current therapeutic approaches such as antivirals and monoclonal antibodies.

Combined Motivational Interviewing and Ecological Momentary Intervention to Reduce Hazardous Alcohol Use Among Sexual Minority Cisgender Men and Transgender Individuals: Protocol for a Randomized Controlled Trial.

BACKGROUND: Sexual minority cisgender men and transgender (SMMT) individuals, particularly emerging adults (aged 18-34 years), often report hazardous drinking. Given that alcohol use increases the likelihood of HIV risk behaviors, and HIV disproportionately affects SMMT individuals, there is a need to test interventions that reduce hazardous alcohol use and subsequent HIV risk behaviors among this population. Ecological momentary interventions (EMIs), which use mobile phones to deliver risk reduction messages based on current location and behaviors, can help to address triggers that lead to drinking in real time. OBJECTIVE: This study will test an EMI that uses motivational interviewing (MI), smartphone surveys, mobile breathalyzers, and location tracking to provide real-time messaging that addresses triggers for drinking when SMMT individuals visit locations associated with hazardous alcohol use. In addition, the intervention will deliver harm reduction messaging if individuals report engaging in alcohol use. METHODS: We will conduct a 3-arm randomized controlled trial (N=405 HIV-negative SMMT individuals; n=135, 33% per arm) comparing the following conditions: (1) Tracking and Reducing Alcohol Consumption (a smartphone-delivered 4-session MI intervention), (2) Tracking and Reducing Alcohol Consumption and Environmental Risk (an EMI combining MI with real-time messaging based on geographic locations that are triggers to drinking), and (3) a smartphone-based alcohol monitoring-only control group. Breathalyzer results and daily self-reports will be used to assess the primary and secondary outcomes of drinking days, drinks per drinking day, binge drinking episodes, and HIV risk behaviors. Additional assessments at baseline, 3 months, 6 months, and 9 months will evaluate exploratory long-term outcomes. RESULTS: The study is part of a 5-year research project funded in August 2022 by the National Institute on Alcohol Abuse and Alcoholism. The first 1.5 years of the study will be dedicated to planning and development activities, including formative research, app design and testing, and message design and testing. The subsequent 3.5 years will see the study complete participant recruitment, data collection, analyses, report writing, and dissemination. We expect to complete all study data collection in or before January 2027. CONCLUSIONS: This study will provide novel evidence about the relative efficacy of using a smartphone-delivered MI intervention and real-time messaging to address triggers for hazardous alcohol use and sexual risk behaviors. The EMI approach, which incorporates location-based preventive messaging and behavior surveys, may help to better understand the complexity of daily stressors among SMMT individuals and their impact on hazardous alcohol use and HIV risk behaviors. The tailoring of this intervention toward SMMT individuals helps to address their underrepresentation in existing alcohol use research and will be promising for informing where structural alcohol use prevention and treatment interventions are needed to support SMMT individuals. TRIAL REGISTRATION: ClinicalTrials.gov NCT05576350; https://www.clinicaltrials.gov/study/NCT05576350. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/55166.

Higher First 30-Day Dose of Buprenorphine for Opioid Use Disorder Treatment Is Associated With Decreased Mortality.

OBJECTIVE: Buprenorphine is a medication for opioid use disorder that reduces mortality. This study aims to investigate the less well-understood relationship between the dose in the early stages of treatment and the subsequent risk of death. METHODS: We used Kentucky prescription monitoring data to identify adult Kentucky residents initiating transmucosal buprenorphine medication for opioid use disorder (January 2017 to November 2019). Average daily buprenorphine dose for days covered in the first 30 days of treatment was categorized as ≤8 mg, >8 to ≤16 mg, and >16 mg. Patients were followed for 365 days after the first 30 days of buprenorphine treatment. Endpoints were opioid-involved overdose death and death from other causes. Causes and dates of death were obtained using Kentucky death certificate records. Associations were evaluated using multivariable Fine and Gray models adjusting for patient baseline characteristics. RESULTS: In the cohort of 49,857 patients, there were 227 opioid-involved overdose deaths and 459 deaths from other causes. Compared with ≤8 mg, the adjusted subdistribution hazard ratio (aSHR) of opioid-involved overdose death decreased by 55% (aSHR, 0.45; 95% confidence interval [CI], 0.34-0.60) and 64% (aSHR, 0.36; 95% CI, 0.25-0.52) for patients receiving doses of >8 to ≤16 mg and >16 mg, respectively. The incidence of death from other causes was lower in patients receiving >8 to ≤16 mg (aSHR, 0.78; 95% CI, 0.62-0.98) and >16 mg (aSHR, 0.62; 95% CI, 0.47-0.80) versus ≤8 mg dose. CONCLUSIONS: Higher first 30-day buprenorphine doses were associated with reduced opioid-involved overdose death and death from other causes, supporting benefit of higher dosing in reducing mortality.

Wastewater Surveillance for Identifying SARS-CoV-2 Infections in Long-Term Care Facilities, Kentucky, USA, 2021-2022.

Persons living in long-term care facilities (LTCFs) were disproportionately affected by COVID-19. We used wastewater surveillance to detect SARS-CoV-2 infection in this setting by collecting and testing 24-hour composite wastewater samples 2-4 times weekly at 6 LTCFs in Kentucky, USA, during March 2021-February 2022. The LTCFs routinely tested staff and symptomatic and exposed residents for SARS-CoV-2 using rapid antigen tests. Of 780 wastewater samples analyzed, 22% (n = 173) had detectable SARS-CoV-2 RNA. The LTCFs reported 161 positive (of 16,905) SARS-CoV-2 clinical tests. The wastewater SARS-CoV-2 signal showed variable correlation with clinical test data; we observed the strongest correlations in the LTCFs with the most positive clinical tests (n = 45 and n = 58). Wastewater surveillance was 48% sensitive and 80% specific in identifying SARS-CoV-2 infections found on clinical testing, which was limited by frequency, coverage, and rapid antigen test performance.

Magnetic Resonance Imaging of Macrophage Response to Radiation Therapy.

BACKGROUND: Magnetic resonance imaging (MRI) is a non-invasive imaging modality which, in conjunction with biopsies, provide a qualitative assessment of tumor response to treatment. Intravenous injection of contrast agents such as fluorine (19F) nanoemulsions labels systemic macrophages, which can, then, be tracked in real time with MRI. This method can provide quantifiable insights into the behavior of tumor-associated macrophages (TAMs) in the tumor microenvironment and macrophage recruitment during therapy. METHODS: Female mice received mammary fat pad injections of murine breast or colon cancer cell lines. The mice then received an intravenous 19F nanoemulsion injection, followed by a baseline 19F MRI. For each cancer model, half of the mice then received 8 Gy of localized radiation therapy (RT), while others remained untreated. The mice were monitored for two weeks for tumor growth and 9F signal using MRI. RESULTS: Across both cohorts, the RT-treated groups presented significant tumor growth reduction or arrest, contrary to the untreated groups. Similarly, the fluorine signal in treated groups increased significantly as early as four days post therapy. The fluorine signal change correlated to tumor volumes irrespective of time. CONCLUSION: These results demonstrate the potential of 19F MRI to non-invasively track macrophages during radiation therapy and its prognostic value with regard to tumor growth.

Pharmacologic Inhibition of Myostatin With a Myostatin Antibody Improves the Skeletal Muscle and Bone Phenotype of Male Insulin-Deficient Diabetic Mice.

Type 1 diabetes (T1D) is associated with low bone and muscle mass, increased fracture risk, and impaired skeletal muscle function. Myostatin, a myokine that is systemically elevated in humans with T1D, negatively regulates muscle mass and bone formation. We investigated whether pharmacologic myostatin inhibition in a mouse model of insulin-deficient, streptozotocin (STZ)-induced diabetes is protective for bone and skeletal muscle. DBA/2J male mice were injected with low-dose STZ (diabetic) or vehicle (non-diabetic). Subsequently, insulin or palmitate Linbits were implanted and myostatin (REGN647-MyoAb) or control (REGN1945-ConAb) antibody was administered for 8 weeks. Body composition and contractile muscle function were assessed in vivo. Systemic myostatin, P1NP, CTX-I, and glycated hemoglobin (HbA1c) were quantified, and gastrocnemii were weighed and analyzed for muscle fiber composition and gene expression of selected genes. Cortical and trabecular parameters were analyzed (micro-computed tomography evaluations of femur) and cortical bone strength was assessed (three-point bending test of femur diaphysis). In diabetic mice, the combination of insulin/MyoAb treatment resulted in significantly higher lean mass and gastrocnemius weight compared with MyoAb or insulin treatment alone. Similarly, higher raw torque was observed in skeletal muscle of insulin/MyoAb-treated diabetic mice compared with MyoAb or insulin treatment. Additionally, muscle fiber cross-sectional area (CSA) was lower with diabetes and the combination treatment with insulin/MyoAb significantly improved CSA in type II fibers. Insulin, MyoAb, or insulin/MyoAb treatment improved several parameters of trabecular architecture (eg, bone volume fraction [BV/TV], trabecular connectivity density [Conn.D]) and cortical structure (eg, cortical bone area [Ct. Ar.], minimum moment of inertia [Imin]) in diabetic mice. Lastly, cortical bone biomechanical properties (stiffness and yield force) were also improved with insulin or MyoAb treatment. In conclusion, pharmacologic myostatin inhibition is beneficial for muscle mass, muscle function, and bone properties in this mouse model of T1D and its effects are both independent and additive to the positive effects of insulin. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Community engagement through social media: A promising low-cost strategy for rural recruitment?

PURPOSE: For the same reasons that rural telehealth has shown promise for enhancing the provision of care in underserved environments, social media recruitment may facilitate more inclusive research engagement in rural areas. However, little research has examined social media recruitment in the rural context, and few studies have evaluated the feasibility of using a free social media page to build a network of rural community members who may be interested in a research study. Here, we describe the rationale, process, and protocols of developing and implementing a social media approach to recruit rural residents to participate in an mHealth intervention. METHODS: Informed by extensive formative research, we created a study Facebook page emphasizing community engagement in an mHealth behavioral intervention. We distributed the page to local networks and regularly posted recruitment and community messages. We collected data on the reach of the Facebook page, interaction with our messages, and initiations of our study intake survey. FINDINGS: Over 21 weeks, our Facebook page gained 429 followers, and Facebook users interacted with our social media messages 3,080 times. Compared to messages that described desirable study features, messages that described community involvement resulted in higher levels of online interaction. Social media and other recruitment approaches resulted in 225 people initiating our in-take survey, 9 enrolling in our pilot study, and 26 placing their names on a waiting list. CONCLUSIONS: A standalone social media page highlighting community involvement shows promise for recruiting in rural areas.

Periodontal Disease, Local and Systemic Inflammation in Puerto Ricans with Type 2 Diabetes Mellitus.

Periodontal disease (PD) is prevalent in type 2 diabetic condition (T2DM). OBJECTIVES: We assessed the associations between serum or gingival crevicular fluid (GCF) endothelial and inflammatory mediators and chronic PD among T2DM Hispanic adults. METHODS: We enrolled 248 Puerto Rican residents with T2DM aged 40-65 years. The exposures included serum inflammatory mediators (IL-1b, IL-6, IL-10, and TNF-α), endothelial adhesion molecules, RANKL levels, and the GCF content of these analytes from a subset of 158 samples. The outcomes included the percent of sites with a probing pocket depth (PPD) ≥ 4 mm and clinical attachment loss ≥ 4 mm. Adjusted logistic regression models were fit to the categorized outcomes. RESULTS: Increased serum IL-10 (Adj. OR: 1.10, p = 0.04), sICAM-1 (Adj. OR: 1.01; p = 0.06), and elevated serum IL-1ß (Adj. OR: 1.93; p = 0.06) were statistically significant or close to being significantly associated with a percent of sites with PPD ≥ 4 mm. An increase in GCF IL-1α (Adj. OR: 1.16; p < 0.01) and IL-1ß (Adj: 2.40; p = 0.02) was associated with periodontal parameters. CONCLUSIONS: Our findings suggested that oral and systemic endothelial and inflammatory mediators are associated with periodontal clinical parameters among Hispanic adults with T2DM.

Wastewater Surveillance for SARS-CoV-2 at Long-Term Care Facilities: Mixed Methods Evaluation.

BACKGROUND: Wastewater surveillance provided early indication of COVID-19 in US municipalities. Residents of long-term care facilities (LTCFs) experienced disproportionate morbidity and mortality early in the COVID-19 pandemic. We implemented LTCF building-level wastewater surveillance for SARS-CoV-2 at 6 facilities in Kentucky to provide early warning of SARS-CoV-2 in populations considered vulnerable. OBJECTIVE: This study aims to evaluate the performance of wastewater surveillance for SARS-CoV-2 at LTCFs in Kentucky. METHODS: We conducted a mixed methods evaluation of wastewater surveillance following Centers for Disease Control and Prevention (CDC) guidelines for evaluating public health surveillance systems. Evaluation steps in the CDC guidelines were engaging stakeholders, describing the surveillance system, focusing the evaluation design, gathering credible evidence, and generating conclusions and recommendations. We purposively recruited stakeholders for semistructured interviews and undertook thematic content analysis of interview data. We integrated wastewater, clinical testing, and process data to characterize or calculate 7 surveillance system performance attributes (simplicity, flexibility, data quality, sensitivity and positive predictive value [PPV], timeliness, representativeness, and stability). RESULTS: We conducted 8 stakeholder interviews. The surveillance system collected wastewater samples (N=811) 2 to 4 times weekly at 6 LTCFs in Kentucky from March 2021 to February 2022. Synthesis of credible evidence indicated variable surveillance performance. Regarding simplicity, surveillance implementation required moderate human resource and technical capacity. Regarding flexibility, the system efficiently adjusted surveillance frequency and demonstrated the ability to detect additional pathogens of interest. Regarding data quality, software identified errors in wastewater sample metadata entry (110/3120, 3.53% of fields), technicians identified polymerase chain reaction data issues (140/7734, 1.81% of reactions), and staff entered all data corrections into a log. Regarding sensitivity and PPV, using routine LTCF SARS-CoV-2 clinical testing results as the gold standard, a wastewater SARS-CoV-2 signal of >0 RNA copies/mL was 30.6% (95% CI 24.4%-36.8%) sensitive and 79.7% (95% CI 76.4%-82.9%) specific for a positive clinical test at the LTCF. The PPV of the wastewater signal was 34.8% (95% CI 27.9%-41.7%) at >0 RNA copies/mL and increased to 75% (95% CI 60%-90%) at >250 copies/mL. Regarding timeliness, stakeholders received surveillance data 24 to 72 hours after sample collection, with delayed reporting because of the lack of weekend laboratory staff. Regarding representativeness, stakeholders identified challenges delineating the population contributing to LTCF wastewater because of visitors, unknown staff toileting habits, and the use of adult briefs by some residents preventing their waste from entering the sewer system. Regarding stability, the reoccurring cost to conduct 1 day of wastewater surveillance at 1 facility was approximately US $144.50, which included transportation, labor, and materials expenses. CONCLUSIONS: The LTCF wastewater surveillance system demonstrated mixed performance per CDC criteria. Stakeholders found surveillance feasible and expressed optimism regarding its potential while also recognizing challenges in interpreting and acting on surveillance data.

Cumulative socioeconomic status and incident type 2 diabetes among African American adults from the Jackson heart study.

Background: The cumulative socioeconomic status (SES) model posits that childhood and adult experiences accumulate to influence disease risk. While individual SES indicators such as education and income are independently associated with incident type 2 diabetes (T2D), the association of cumulative SES and incident T2D is unclear, especially in African American adults. Methods: We utilized cohort data of African American participants (n = 3681, mean age 52.6 years) enrolled in the Jackson Heart Study from 2000 to 2013 free of T2D or cardiovascular disease at baseline (2000-2004). Cumulative SES scores at baseline were derived using six SES indicators (education, wealth, income, occupation, employment status, and mother's education) categorized as low, middle, and high. Incident T2D was defined at exam 2 (2005-2008) or exam 3 (2009-2013) based on fasting glucose ≥126 mg/dL, HbA1c ≥ 6.5, reported diabetic medication use, or self-reported physician diagnosis. Proportional hazards regression, allowing for interval censoring, was used to estimate the association between cumulative SES and incident T2D (hazard ratio(HR), 95% confidence interval (CI)) after adjustment for covariates. Sex and age differences were tested using interaction terms. Results: There were 544 incident T2D cases. The association between low (versus high) cumulative SES and incident T2D was not significant (HR 1.04 [95% CI 0.85, 1.28]) and did not differ by sex (p value for interaction>0.05). However, there were differences by (age p value for interaction = 0.0052 for middle-aged adults and 0.0186 for older adults). Low (versus high) cumulative SES was associated a greater hazard of incident T2D among those 20-46 years (HR 1.12 [95% CI 1.03, 1.21]), 47-59 years (HR 1.25 [95% CI 1.06, 1.47]) and those 60-93 years (HR 1.39 [95% CI 1.09, 1.78]) after adjustment for sex and family history of diabetes. Associations attenuated after adding behavioral and lifestyle risk factors. Conclusion: The association of low cumulative SES and incident T2D differed by age, which may suggest interventionist should consider impacts of SES on T2D by age.

Completion Lymph Node Dissection for Melanoma Before and After the Multicenter Selective Lymphadenectomy Trial-II in the United States.

BACKGROUND: The Multicenter Selective Lymphadenectomy Trial-II (MSLT-II) revealed completion lymph node dissection (CLND) after positive sentinel lymph node biopsy (SLNB) did not improve melanoma-specific survival compared with surveillance. Given these findings and the morbidity associated with CLND, this study investigated trends in rates and predictors of CLND after MSLT-II. METHODS: Analysis of the National Cancer Database was performed for all patients aged ≥18 years with melanoma and a positive SLNB for 2012-2019. Rates of CLND before and after publication of MSLT-II were identified and logistic regression used to identify factors associated with CLND. RESULTS: Patients undergoing CLND declined from 55.9% pre-MSLT-II (n = 9725) to 19.5% post-MSLT-II (n = 9419) (odds ratio [OR] 0.32, 95% confidence interval [CI] 0.29-0.35). CLND was less likely in females (OR 0.83; 95% CI 0.78-0.89), older patients (vs. 18-39 yr; 40-64 yr OR 0.80, 95% CI 0.65-0.98; 65-79 yr OR 0.67, 95% CI 0.53-0.84; >80 yr OR 0.38, 95% CI 0.30-0.49), sicker patients (Deyo category ≥2 OR 0.85, 95% CI 0.73-0.99), thinner primary lesions (vs. 0.01-0.79 mm; 1.01-4.00 mm OR 1.16, 95% CI 1.01-1.33; ≥4.01 mm OR 1.31, 95% CI 1.08-1.59), patients from metro areas (Rural OR 1.31, 95% CI 1.00-1.70; Urban OR 1.15, 95% CI 1.03-1.29), and those treated at lower-volume centers (vs. lowest-volume; highest-volume OR 1.31, 95% CI 1.14-1.50; high-volume OR 1.40, 95% CI 1.24-1.57). CONCLUSIONS: MSLT-II has impacted clinical care; however, male gender, thicker lesions, rural/urban residence, younger age, fewer comorbidities, and treatment at higher-volume centers confer a greater likelihood of undergoing CLND. Further investigations should focus on whether these populations benefit from more aggressive surgical care.

SARS-CoV-2 Vaccine Booster Elicits Robust Prolonged Maternal Antibody Responses and Passive Transfer Via The Placenta And Breastmilk.

Background: Infection during pregnancy can result in adverse outcomes for both pregnant persons and offspring. Maternal vaccination is an effective mechanism to protect both mother and neonate into post-partum. However, our understanding of passive transfer of antibodies elicited by maternal SARS-CoV-2 mRNA vaccination during pregnancy remains incomplete. Objective: We aimed to evaluate the antibody responses engendered by maternal SARS-CoV-2 vaccination following initial and booster doses in maternal circulation and breastmilk to better understand passive immunization of the newborn. Study Design: We collected longitudinal blood samples from 121 pregnant women who received SARS-CoV-2 mRNA vaccines spanning from early gestation to delivery followed by collection of blood samples and breastmilk between delivery and 12 months post-partum. During the study, 70% of the participants also received a booster post-partum. Paired maternal plasma, breastmilk, umbilical cord plasma, and newborn plasma samples were tested via enzyme-linked immunosorbent assays (ELISA) to evaluate SARS-CoV-2 specific IgG antibody levels. Results: Vaccine-elicited maternal antibodies were detected in both cord blood and newborn blood, albeit at lower levels than maternal circulation, demonstrating transplacental passive immunization. Booster vaccination significantly increased spike specific IgG antibody titers in maternal plasma and breastmilk. Finally, SARS-CoV-2 specific IgG antibodies in newborn blood correlated negatively with days post initial maternal vaccine dose. Conclusion: Vaccine-induced maternal SARS-CoV-2 antibodies were passively transferred to the offspring in utero via the placenta and after birth via breastfeeding. Maternal booster vaccination, regardless of gestational age at maternal vaccination, significantly increased antibody levels in breastmilk and maternal plasma, indicating the importance of this additional dose to maximize passive protection against SARS-CoV-2 infection for neonates and infants until vaccination eligibility.

A Randomized Trial of Sitagliptin and Spironolactone With Combination Therapy in Hospitalized Adults With COVID-19.

Context: COVID-19 may cause respiratory distress syndrome and death. Treatment of COVID-19 to prevent complications remains a priority. Objective: Our investigation sought to determine whether combination of spironolactone and sitagliptin could reduce mortality for inpatients with SARS-CoV-2 infection. Methods: This single-blind, 4-arm, prospective randomized clinical trial was conducted at Shiraz and Bushehr University of Medical Sciences hospitals between December 2020 and April 2021. We randomized hospitalized adult patients with COVID-19 pneumonia into 4 groups: control, combination therapy, sitagliptin add-on, or spironolactone add-on. The primary outcome was the clinical improvement of the patients in the hospital as measured on an 8-point numerical scale. The secondary outcomes included intubation, ICU admission, end organ damages, CT findings, and paraclinical information. Results: A total of 263 admitted patients were randomly assigned to control group (87 patients), combination group (60 patients), sitagliptin group (66 patients), and spironolactone group (50 patients). There were no significant differences in baseline characteristics, except for higher age in control group. The intervention groups, especially combination therapy, had better clinical outcomes (clinical score on fifth day of admission: 3.11 ± 2.45 for controls, 1.33 ± 0.50 for combination, 1.68 ± 1.02 for sitagliptin, and 1.64 ± 0.81 for spironolactone; P = 0.004). However, the mortality rate was lower in patients who received spironolactone (21.84% control, 13.33% combination, 13.64% sitagliptin, 10.00% spironolactone; P = 0.275). Our intervention reduced lung infiltration but not the area of involvement in lungs. Conclusion: Sitagliptin and spironolactone can potentially improve clinical outcomes of hospitalized COVID-19 patients.

A parametric approach to relaxing the independence assumption in relative survival analysis.

With known cause of death (CoD), competing risk survival methods are applicable in estimating disease-specific survival. Relative survival analysis may be used to estimate disease-specific survival when cause of death is either unknown or subject to misspecification and not reliable for practical usage. This method is popular for population-based cancer survival studies using registry data and does not require CoD information. The standard estimator is the ratio of all-cause survival in the cancer cohort group to the known expected survival from a general reference population. Disease-specific death competes with other causes of mortality, potentially creating dependence among the CoD. The standard ratio estimate is only valid when death from disease and death from other causes are independent. To relax the independence assumption, we formulate dependence using a copula-based model. Likelihood-based parametric method is used to fit the distribution of disease-specific death without CoD information, where the copula is assumed known and the distribution of other cause of mortality is derived from the reference population. We propose a sensitivity analysis, where the analysis is conducted across a range of assumed dependence structures. We demonstrate the utility of our method through simulation studies and an application to French breast cancer data.

Lexicogrammatical skills in 2-year-old children with and without repaired cleft palate.

The purpose of the current research was to compare the lexical-grammatical skills of two-year-old children with and without repaired cleft palate (CP), accounting for the effect of variables such as vocabulary size at 18 months of age, maternal education level, and gender. Participants included 52 children with CP and 25 typically developing (TD) children. The CDI-WS was employed to measure vocabulary and grammatical skills. Significant differences were observed between the CP and TD groups with respect to the number of words, word forms (irregular nouns and verbs), word endings (overuse of plural (-s) and past tense (-ed) markers), the mean number of morphemes in their three longest utterances (M3L), and sentence complexity. In addition, compared to TD children, significantly smaller proportions of children with CP were observed to use words to talk about past and future events or use words to talk about an absent object. The difference between the CP and TD groups in terms of the size of vocabulary at 24 months of age remained statistically significant in the multivariable model. Among all predictors, the size of vocabulary at 18 months of age was identified as the most robust precursor of lexical and grammatical skills at 24 months of age. Gender was identified as a predictor of the M3L measure as an index for syntactic ability.

Teledentistry: Dental hygiene students' knowledge, attitudes, and curriculum recommendations.

Purpose: Research has shown an increase in dental hygiene (DH) students' knowledge and attitudes toward teledentistry (TD) after TD training in states with permissive but not restrictive DH scope of practice policies. The purpose of this study was to identify self-reported knowledge and attitudes regarding TD among the DH students at the University of North Carolina (UNC) at Chapel Hill before and after an educational intervention and student recommendations for TD curriculum placement.Methods: A faculty presentation and video demonstration, followed by small group discussions and a large group debriefing session were conducted at the UNC Adams School of Dentistry in March 2019. Participants were invited to complete a survey before and after the educational session. McNemar's matched pair test was used to compare the proportion of the participants' pre- and post-test responses.Results: Survey participants (n=30) included first year and second year DH students. There was significant difference (p<0.001) between pre and post self-reported knowledge of TD as well as a significant difference in participant's response (p= 0.012) about facilitating consultation with health care specialists through TD in NC. There was a significant difference in favorable responses (p=0.0394) that TD could increase reimbursement to dentists to enhance the provision of more services in NC. Students identified didactic courses (43%), simulated cases (47%), and integration into the DH community rotations (66%) as potential ways to incorporate TD into curriculum. Most students (93%) identified DH restricted scope of practice as a barrier to TD implementation in NC.Conclusion: The educational session resulted in increased self-reported knowledge and demonstrated positive attitudes toward the adoption of TD into multiple facets of DH curriculum. A major barrier to its adoption into practice is the DH restricted scope of practice in NC.

Emergence of Prevocalic Stop Consonants in Children With Repaired Cleft Palate.

Purpose This study determined the time course of the emergence of prevocalic stop consonants in young children with cleft palate following surgical repair. Method A total of 120 children in four cohorts from three institutions were followed from 12 to 24 months of age: (a) 24 with repaired cleft lip and palate (CLP), (b) 36 with repaired cleft palate only (CP), (c) 33 without clefts but with histories of frequent otitis media and ventilation tubes (OM), and (d) 27 typically developing (TD) children without clefts or OM. Emergence of prevocalic stops and symbolic language skills were determined during administration of the Communication and Symbolic Behavioral Scales Developmental Profile. Parametric survival models were fitted with and without covariates-recruitment site, gender, maternal education level, middle ear status, language ability, and age at surgery for children with clefts-to describe the time course of the emergence of prevocalic stops. Results The estimated age at which 80% of children demonstrated prevocalic stop emergence was 15.0, 15.3, 18.9, and 21.8 months for TD, OM, CP, and CLP groups, respectively (p < .001, unadjusted model). Both CP and CLP cohorts had a significantly longer time to stop emergence than either the TD or OM cohorts, even after adjusting for covariates. Abnormal middle ear status, lower symbolic language ability, and older age at palatal surgery were significantly associated with delayed stop emergence. Conclusions Survival model estimates show that four out of five children with repaired cleft palate will achieve emergence of prevocalic stop consonants by 19-22 months of age, corresponding to 9-12 months following palate repair. Clinical implications are discussed.