Association of peri-operative prescription of non-steroidal anti-inflammatory drugs with continued prescription of opioids after total knee arthroplasty: a retrospective claims-based cohort study.

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the mainstays of multimodal pain management. While effective for acute pain control, recent pre-clinical evidence has raised concerns regarding an association between NSAIDs and chronic pain and potential opioid use. Our objective was to explore the association between peri-operative use of prescription NSAIDs and the need for continued opioid prescriptions lasting 90-180 days in previously opioid-naïve patients undergoing total knee arthroplasty. A database of health claims in the USA was used to identify all opioid-naïve adult patients who underwent primary knee arthroplasty between January 2010 and October 2021. We evaluated the magnitude of association between peri-operative prescription NSAID claims and claims for opioids at 90 days postoperatively using multivariable logistic regression models. Secondary outcomes included: the magnitude of association between peri-operative NSAID prescription and claims for opioids at 180 days postoperatively; and identifying other potential factors associated with opioid claims at 90 days postoperatively. After risk adjustment using multivariable logistic regression models in the 789,736-patient cohort, the adjusted odds ratio (95%CI) for a continuous claim of opioids at 90 and 180 days postoperatively among patients with a peri-operative NSAID prescription within 30 days was 1.32 (1.30-1.35), p < 0.001; and 1.12 (1.10-1.15), p < 0.001, respectively. This estimate of effect remained robust at 90 days after accounting for known potential confounders, including pre-existing knee pain and acute postoperative pain severity. Similar analysis of other pain medications (e.g. paracetamol) did not detect such an association. This population-based cohort study suggests that peri-operative prescription NSAID use may be associated with continued opioid prescription claims at 90 and 180 days after knee arthroplasty, even after adjusting for other observed covariates for continuous opioid claims. These novel findings can inform clinical decision-making for post-surgical pain management, risk-benefit discussions with patients and future research.

Geroscience: Aging and Oral Health Research.

Research in aging has significantly advanced; scientists are now able to identify interventions that slow the biologic aging processes (i.e., the "hallmarks of aging"), thus delaying the onset and progression of multiple diseases, including oral conditions. Presentations given during the 3-part session "Geroscience: Aging and Oral Health Research," held during the 2023 American Association for Dental, Oral, and Craniofacial Research meeting, are summarized in this publication. Speakers' topics spanned the translational research spectrum. Session 1 provided an overview of the geroscience and health span (disease-free and functional health throughout life) concepts. The common molecular mechanisms between oral cancer and aging were discussed, and research was presented that showed periodontal microflora as a potential factor in Alzheimer's disease progression. Session 2 focused on behavioral and social science aspects of aging and their oral health significance. The keynote provided evidence that loneliness and isolation can have major health effects. These social conditions, along with poor oral health, tooth loss, and cognitive decline, could potentially affect healthy eating ability and systemic health in older adults. Research could help elucidate the directions and pathways connecting these seemingly disparate conditions. Session 3 focused on the delivery of oral care in different settings and the many barriers to access care faced by older adults. Research is needed to identify and implement effective technology and strategies to improve access to dental care, including new delivery and financing mechanisms, workforce models, interprofessional provider education and practice, and use of big data from medical-dental integration of electronic health records. Research to improve the "oral health span," reduce oral health disparities, and increase health equity must be tackled at all levels from biologic pathways to social determinants of health and health policies.

Pregnancy and COVID-19: pharmacologic considerations.

In this review, we summarize evidence regarding the use of routine and investigational pharmacologic interventions for pregnant and lactating patients with coronavirus disease 2019 (COVID-19). Antenatal corticosteroids may be used routinely for fetal lung maturation between 24 and 34 weeks' gestation, but decisions in those with critical illness and those < 24 or > 34 weeks' gestation should be made on a case-by-case basis. Magnesium sulfate may be used for seizure prophylaxis and fetal neuroprotection, albeit cautiously in those with hypoxia and renal compromise. There are no contraindications to using low-dose aspirin to prevent placenta-mediated pregnancy complications when indicated. An algorithm for thromboprophylaxis in pregnant patients with COVID-19 is presented, which considers disease severity, timing of delivery in relation to disease onset, inpatient vs outpatient status, underlying comorbidities and contraindications to the use of anticoagulation. Nitrous oxide may be administered for labor analgesia while using appropriate personal protective equipment. Intravenous remifentanil patient-controlled analgesia should be used with caution in patients with respiratory depression. Liberal use of neuraxial labor analgesia may reduce the need for emergency general anesthesia which results in aerosolization. Short courses of non-steroidal anti-inflammatory drugs can be administered for postpartum analgesia, but opioids should be used with caution due to the risk of respiratory depression. For mechanically ventilated pregnant patients, neuromuscular blockade should be used for the shortest duration possible and reversal agents should be available on hand if delivery is imminent. To date, dexamethasone is the only proven and recommended experimental treatment for pregnant patients with COVID-19 who are mechanically ventilated or who require supplemental oxygen. Although hydroxycholoroquine, lopinavir/ritonavir and remdesivir may be used during pregnancy and lactation within the context of clinical trials, data from non-pregnant populations have not shown benefit. The role of monoclonal antibodies (tocilizumab), immunomodulators (tacrolimus), interferon, inhaled nitric oxide and convalescent plasma in pregnancy and lactation needs further evaluation. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Renal nitrate clearance in chronic kidney disease.

BACKGROUND: Nitric oxide (NO) is rapidly oxidised in humans to nitrite and nitrate, with nitrate being present in much greater abundance. These oxidation products can be recycled back into nitric oxide via a complex entero-salivary pathway, thus preserving NO activity. Approximately 65% of circulating nitrate is excreted in the urine in 48 h, with the excretory pathway of the remainder unknown. The effect of declining renal function on nitrate clearance is unknown METHODS: Forty five subjects, 21 M, 24F, median age 69 (range 27-75 years) with renal function assessed by CKD-EPI eGFR between 9 and 89 ml/min/1.73 m2 completed the study. Following a 24 h low nitrate diet a microplate spectrophotometric method was employed to measure plasma nitrate concentration and 24 h urinary nitrate excretion were measured to determine renal nitrate clearance. RESULTS: There was a strong positive correlation between urinary nitrate clearance and eGFR, (Spearman R = 0.7665, p < 0.0001) with a moderate negative correlation between plasma nitrate concentration and CKD-EPI eGFR, (Spearman's R = -0.37, p = 0.012). There was a trend between fractional excretion of nitrate and CKD-EPI eGFR (ml/min/1.73 m2) Spearman's R 0.27, p = 0.07 though this did not reach statistical significance. Plasma nitrate concentration and serum creatinine concentration were positively correlated, Spearman's R = 0.39, p = 0.008. CONCLUSIONS: We have observed a strong positive association between renal nitrate clearance and renal function such that plasma nitrate rises as renal function falls. Fractional excretion of nitrate appears to decline as renal function falls. As such, urinary nitrate excretion is unlikely to be a reliable marker of endogenous NO synthesis in settings where renal function is altered.

Increased monocyte activation with age among HIV-infected long term non-progressor children: implications for early treatment initiation.

OBJECTIVES: The key to newer therapeutic and eradication approaches often lies in understanding slow disease progression in HIV infection. The paediatric population has been poorly studied in this regard. We aimed to describe a cohort of perinatally infected long-term nonprogressor (LTNP) children living with HIV in India and to evaluate the immune biomarkers of disease progression. METHODS: LTNPs (ART-naïve, with a CD4 count ≥ 500 cells/µL at age ≥ 7 years) among the cohort of HIV-infected children were identified and monitored longitudinally, and their CD4 T-cell counts and plasma viral loads were measured every 6 months. The plasma monocyte/macrophage activation markers, namely soluble CD14 (sCD14), soluble CD163 (sCD163) and interferon-inducible protein-10 (IP-10) were measured by enzyme-linked immunosorbent assay (ELISA) in LTNPs and progressors. The Mann-Whitney U-test was used to compare the two groups and P values < 0.05 were considered statistically significant. Spearman's rank or Pearson's correlation coefficient (r) was calculated to determine the associations between variables. RESULTS: Among 378 children living with HIV-1 surveyed in our cohort, 40 (10.6%) were LTNPs. Longitudinal analysis of the LTNP data showed that both CD4 count and viral load declined significantly with age (P < 0.0001 for both). Plasma sCD14 levels were significantly (P < 0.005) higher in progressors and sCD163 levels were significantly (P < 0.0001) higher in LTNPs. CONCLUSIONS: The prevalence of LTNPs in our cohort of perinatally infected children living with HIV was 10.6%. We observed a trend for associations between the increasing sCD163 monocyte/macrophage activation marker levels, declining CD4 counts and the gradual loss of nonprogressor status with age in the LTNPs. These findings underscore the need for early antiretroviral therapy in those children with proven slow disease progression.

Empowering Women Researchers in the New Century: IADR's Strategic Direction.

Gender inequality in science, medicine, and dentistry remains a central concern for the biomedical research workforce today. Although progress in areas of inclusivity and gender diversity was reported, growth has been slow. Women still face multiple challenges in reaching higher ranks and leadership positions while maintaining holistic success in these fields. Within dental research and academia, we might observe trends toward a more balanced pipeline. However, women continue to face barriers in seeking leadership roles and achieving economic equity and scholarship recognition. In an effort to evaluate the status of women in dental research and academia, the authors examined the role of the International Association for Dental Research (IADR), a global research organization, which has improved awareness on gender inequality. The goal of this article is to review five crucial issues of gender inequality in oral health research and academics-workforce pipeline, economic inequality, workplace harassment, gender bias in scholarly productivity, and work-life balance-and to discuss proactive steps that the IADR has taken to promote gender equality. Providing networking and training opportunities through effective mentoring and coaching for women researchers, the IADR has developed a robust pipeline of women leaders while promoting gender equality for women in dental academia through a culture shift. As knowledge gaps remained on the levels of conscious and unconscious bias and sexist culture affecting women advancement in academics, as well as the intersectionality of gender with race, gender identity, ability status, sexual orientation, and cultural backgrounds, the IADR has recognized that further research is warranted.

Gender Inequalities in the Dental Workforce: Global Perspectives.

The aim of this review is to investigate the growth of diversity and inclusion in global academic dental research with a focus on gender equality. A diverse range of research methodologies were used to conduct this review, including an extensive review of the literature, engagement of key informants in dental academic leadership positions around the world, and review of current data from a variety of national and international organizations. Results provide evidence of gender inequalities that currently persist in dental academics and research. Although the gender gap among graduating dental students in North America and the two most populous countries in Europe (the United Kingdom and France) has been narrowed, women make up 30% to 40% of registered dentists in countries throughout Europe, Oceania, Asia, and Africa. In academic dentistry around the globe, greater gender inequality was found to correlate with higher ranking academic and leadership positions in the United States, United Kingdom, several countries in European Union, Japan, and Saudi Arabia. Further disparities are noted in the dental research sector, where women make up 33% of dental researchers in the European Union, 35% in North America, 55% in Brazil, and 25% in Japan. Family and societal pressures, limited access to research funding, and lack of mentoring and leadership training opportunities are reported as also contributing to gender inequalities. To continue advancing gender equality in dental academia and research, efforts should be geared toward the collection and public dissemination of data on gender-specific distributions. Such evidence-driven information will guide the selection of future strategies and best practices for promoting gender equity in the dental workforce, which provides a major pipeline of researchers and scholars for the dental profession.

Short communication: Muscle protein synthetic response to microparticulated whey protein in middle-aged men.

Whey protein concentrate (WPC) is a high-quality dairy ingredient that is often included in formulated food products designed to stimulate muscle anabolism. Whey protein concentrate can be affected by UHT processing, and its sensory properties are not compatible with some formulated food products. Microparticulated WPC (mWPC) is a novel ingredient that is resistant to heat treatment and has enhanced sensory properties. When 16 healthy middle-aged men consumed 20 g of either WPC or mWPC, both proteins increased plasma essential AA and leucine concentrations with no detectable difference in curve kinetics. Myofibrillar protein synthesis was increased in both groups for 90 min after ingestion with no difference between groups. Ingestion of mWPC resulted in a muscle anabolic response that was equivalent to that of WPC over the full 210-min measurement period. Formulated products incorporating mWPC or standard WPC would provoke equivalent anabolic responses.

Characterization and complete genome sequence analysis of two Myoviral bacteriophages infecting clinical carbapenem-resistant Acinetobacter baumannii isolates.

AIMS: The aim of this study was to characterize phenotypical properties, to analyse whole genomes of novel Acinetobacter baumannii phages infecting carbapenem-resistant Ac. baumannii (CRAB) and to evaluate their potential as antimicrobial alternatives to control Ac. baumannii in clinical settings. METHODS AND RESULTS: The Ac. baumannii phages, Βϕ-R1215 and Βϕ-R2315, were isolated from sewage samples. These phages were characterized by transmission electron microscopy, host spectrum, the thermal/pH stability test, the bacterial lysis assay and the whole genome analysis. Both phages lysed 21 of 45 CRAB hosts, and showed high stability at various pH (pH 4-10) and temperature (25-60°C), and were strongly active against host bacteria in vitro. The genomes of Βϕ-R1215 and Βϕ-R2315 are linear double-strands of DNA with 44·866 and 44·846 bp respectively. These two genomes revealed high similarity at the DNA level, but the organization and direction of open reading frames were different. CONCLUSIONS: The Ac. baumannii phages, Βϕ-R1215 and Βϕ-R2315, are novel lytic phages lysing CRAB strains which were isolated from respiratory samples of patients. SIGNIFICANCE AND IMPACT OF THE STUDY: In vitro and in silico data showed that these novel Ac. baumannii phages, Βϕ-R1215 and Βϕ-R2315, have potential as antimicrobial alternatives to control CRAB in healthcare settings.

Fault tolerant mobile sensor node traversal schemes based on hexagonal coverage.

Mobile sensor nodes (MSNs) are equipped with locomotive can move around after having been deployed. They are equipped with limited energy. A large portion of energy is drained during the traversal. In order to extend the life time of a MSN, the traveling distance must be minimized. Region of interest (ROI) is covered with multiple MSNs using coverage based pattern movement. When a group of MSNs are deployed to cover a given ROI, all the deployed MSNs should travel an approximately equal distance. Otherwise, the MSN which travels longer distance depletes more energy compared to the MSN which travels a shorter distance. In this work we show that, ROI partition plays great role in hole free coverage and makes the MSNs have optimized movement cost with fault tolerant support.

Harold C. Slavkin: A Transformative Leader of Our Times.

Harold (Hal) C. Slavkin, DDS, the 22nd president of the American Association for Dental, Oral, and Craniofacial Research (1993 to 1994), died on December 22, 2023. During a career that spanned almost 6 decades, Hal distinguished himself as an international authority on craniofacial biology and an advocate for oral health equity. He served as dean of the University of Southern California's dental school, founded the school's Center for Craniofacial Molecular Biology, created the nation's first PhD program in craniofacial biology, and served as the sixth director of the National Institute of Dental and Craniofacial Research. Hal's studies of the molecular and cellular underpinnings of craniofacial malformations prepared him to champion translational research later in his career, when his work with patient advocates revealed the importance of applying new discoveries to clinical practice. A visionary thinker, skilled administrator, progressive educator, compelling communicator, researcher, scholar, and mentor, Hal was known as a Renaissance leader. He rejoiced in fostering collaborative synergies among people and organizations. Throughout his life, family was his central grounding force. He and his wife, Lois, advanced a wide range of social and community initiatives and took great pride in their children, grandchildren, and great-grandchildren. We remember Hal for his indelible spirit, unflappable enthusiasm for science, fierce advocacy for social justice, and infectious zest for life. Here, we outline his multidimensional accomplishments through the lenses of academia, government, and nonprofit organizations. Although it is with heavy hearts that we bid goodbye to this remarkable man, our spirits are lightened by the many gifts he left behind.

Spatial Multi-omics Reveals the Role of the Wnt Modulator, Dkk2, in Palatogenesis'.

Multiple genetic and environmental etiologies contribute to the pathogenesis of cleft palate, which is the most common of the inherited disorders of the craniofacial complex. Insights into the molecular mechanisms regulating osteogenic differentiation and patterning in the palate during embryogenesis are limited and needed for the development of innovative diagnostics and cures. This study used the Pax9-/- mouse model with a consistent phenotype of cleft secondary palate to investigate the role of Pax9 in the process of palatal osteogenesis. Although prior research has identified the upregulation of Wnt pathway modulators Dkk1 and Dkk2 in Pax9-/- palate mesenchyme, limitations of spatial resolution and technology restricted a more robust analysis. Here, data from single-nucleus transcriptomics and chromatin accessibility assays validated by in situ highly multiplex targeted single-cell spatial profiling technology suggest a distinct relationship between Pax9+ and osteogenic populations. Loss of Pax9 results in spatially restricted osteogenic domains bounded by Dkk2, which normally interfaces with Pax9 in the mesenchyme. Moreover, the loss of Pax9 leads to a disruption in the normal osteodifferentiaion of palatal osteogenic mesenchymal cells. These results suggest that Pax9-dependent Wnt signaling modulators influence osteogenic programming during palate formation, potentially contributing to the observed cleft palate phenotype.

Loss of dentin sialophosphoprotein leads to periodontal diseases in mice.

BACKGROUND AND OBJECTIVE: Dentin sialophosphoprotein (DSPP) and its cleaved products, dentin phosphoprotein (DPP) and dentin sialoprotein (DSP), play important roles in biomineralization. Recently, we observed that DSPP is highly expressed in the alveolar bone and cementum, indicating that this molecule may play an important role in the formation and maintenance of a healthy periodontium, and its deletion may cause increased susceptibility to periodontal diseases. The objective of this investigation was to study the effects of Dspp ablation on periodontal tissues by analyzing Dspp null mice. MATERIAL AND METHODS: Newborn to 6-mo-old Dspp null mice were examined, and the 3- and 6-mo-old Dspp null mice were characterized in detail using X-ray radiography, histology and scanning electron microscopy (backscattered as well as resin-infiltrating). Wild-type mice of the same age groups served as the normal controls. RESULTS: The Dspp null mice showed significant loss of alveolar bone and cementum, particularly in the furcation and interproximal regions of the molars. The alveolar bone appeared porous while the quantity of cementum was reduced in the apical region. The canalicular systems and osteocytes in the alveolar bone were abnormal, with reduced numbers of canaliculi and altered osteocyte morphology. The loss of alveolar bone and cementum along with the detachment of the periodontal ligaments (PDL) led to the apical migration of the epithelial attachment and formation of periodontal pockets. CONCLUSION: Inactivation of DSPP leads to the loss of alveolar bone and cementum and increased susceptibility to bacterial infections in PDL of Dspp null mice. The fact that the loss of DSPP results in periodontal diseases indicates that this molecule plays a vital role in maintaining the health of the periodontium.

Successful use of extracorporeal membrane oxygenation in a patient with combined pulmonary and systemic embolisation.

We present a highly unusual case of massive pulmonary embolism with secondary paradoxical systemic embolisation that was successfully resuscitated with veno-arterial extracorporeal membrane oxygenation (ECMO). This enabled subsequent successful bridging to pulmonary embolectomy.

Reactogenicity, pregnancy outcomes, and SARS-CoV-2 infection following COVID-19 vaccination during pregnancy in Canada: A national prospective cohort study.

OBJECTIVE: To describe self-reported reactogenicity, pregnancy outcomes, and SARS-CoV-2 infection following COVID-19 vaccination during pregnancy. DESIGN: National, prospective cohort study. SETTING: Participants across Canada were enrolled from July 2021 until June 2022. POPULATION: Individuals pregnant during the COVID-19 pandemic, regardless of vaccination status, were included. METHODS: The Canadian COVID-19 Vaccine Registry for Pregnant and Lactating Individuals (COVERED) was advertised through traditional and social media. Surveys were administered at baseline, following each vaccine dose if vaccinated, pregnancy conclusion, and every two months for 14 months. Changes to pregnancy or vaccination status, SARS-CoV-2 infections, or significant health events were recorded. MAIN OUTCOME MEASURES: Reactogenicity (local and systemic adverse events, and serious adverse events) within 1 week post-vaccination, pregnancy and neonatal outcomes, and subsequent SARS-CoV-2 infection. RESULTS: Among 2868 participants who received 1-2 doses of a COVID-19 vaccine during pregnancy, adverse events described included: headache (19.5-33.9%), nausea (4.8-13.8%), fever (2.7-10.2%), and myalgia (33.4-42.2%). Reactogenicity was highest after the 2nd dose of vaccine in pregnancy. Compared to 1660 unvaccinated participants, there were no statistically significant differences in adverse pregnancy or infant outcomes, aside from an increased risk of NICU admission ≥ 24 h among the unvaccinated group. During follow-up, there was a higher rate of participant-reported SARS-CoV-2 infection in the unvaccinated compared to the vaccinated group (18[47.4%] vs. 786[27.3%]). CONCLUSIONS: Participant-reported reactogenicity was similar to reports from non-pregnant adults. There was no increase in adverse pregnancy and birth outcomes among vaccinated vs. unvaccinated participants and lower rates of SARS-CoV-2 infection were reported in vaccinated participants. TWEETABLE ABSTRACT: No significant increase in adverse pregnancy or infant outcomes among vaccinated versus unvaccinated pregnant women in Canada.

A comparison of the colorectal surgical research across Europe, USA and Australasia.

AIM: The annual scientific meetings of the Association of Coloproctology of Great Britain and Ireland (ACPGBI), the American Society of Colon and Rectal Surgeons (ASCRS), the European Society of Coloproctology (ESCP) and the Royal Australasian College of Surgeons (RACS) are the major fora for presentation of colorectal surgical research. Thus, their content could be a proxy of the content and quality of colorectal surgical research worldwide. We aimed to critically appraise the quantity, quality and topics of colorectal surgical research over the previous 5 years for the above meetings. METHOD: All published abstracts from the ACPGBI, ASCRS, ESCP and the colorectal-specific component of the RACS from 2006 to 2010 were appraised. Abstracts were coded by predefined categories pertaining to study type and topic. RESULTS: Level 1 evidence (systematic reviews/meta-analyses) and level 2 evidence (randomized controlled trials) comprised 3% (95% CI 1-9%) and 5% (95% CI 2-11%), respectively, of research presented at the meetings. There was a predominance of level 4 evidence (retrospective studies) across all years (mean 54%, 95% CI 44-68%). Operative management was most commonly studied (mean 43%, 95% CI 36-49%). There was minimal research in perioperative care (mean 6%, 95% CI 2-13%) and basic surgical science (mean 6%, 95% CI 2-11%). Research related to perioperative care was significantly higher at the ACPGBI and RACS meetings than the ASCRS and ESCP meetings (P<0.01). CONCLUSION: The research at these meetings consists largely of retrospective reviews exploring operative management with minimal high quality scientific content. Active steps need to be taken to increase the quantity of high level evidence especially in topics other than operative management.