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2.
Curr Oncol Rep ; 26(5): 504-537, 2024 May.
Article En | MEDLINE | ID: mdl-38581470

PURPOSE OF REVIEW: Patient navigation promotes access to timely treatment of chronic diseases by eliminating barriers to care. Patient navigation programs have been well-established in improving screening rates and diagnostic resolution. This systematic review aimed to characterize the multifaceted role of patient navigators within the realm of cancer treatment. RECENT FINDINGS: A comprehensive electronic literature review of PubMed and Embase databases was conducted to identify relevant studies investigating the role of patient navigators in cancer treatment from August 1, 2009 to March 27, 2023. Fifty-nine articles were included in this review. Amongst studies focused on cancer treatment initiation, 70% found a significant improvement in treatment initiation amongst patients who were enrolled in patient navigation programs, 71% of studies focused on treatment adherence demonstrated significant improvements in treatment adherence, 87% of studies investigating patient satisfaction showed significant benefits, and 81% of studies reported a positive impact of patient navigators on quality care indicators. Three palliative care studies found beneficial effects of patient navigation. Thirty-seven studies investigated disadvantaged populations, with 76% of them concluded that patient navigators made a positive impact during treatment. This systematic review provides compelling evidence supporting the value of patient navigation programs in cancer treatment. The findings suggest that patient navigation plays a crucial role in improving access to care and optimizing treatment outcomes, especially for disadvantaged cancer patients. Incorporating patient navigation into standard oncology practice can reduce disparities and improve the overall quality of cancer care.


Neoplasms , Patient Navigation , Humans , Neoplasms/therapy , Health Services Accessibility , Patient Satisfaction
3.
J Surg Oncol ; 129(6): 1150-1158, 2024 May.
Article En | MEDLINE | ID: mdl-38385654

BACKGROUND AND OBJECTIVES: This study aimed to evaluate the postoperative complications associated with administering intravenous (IV) tranexamic acid (TXA) in patients undergoing surgical fixation for neoplastic pathologic fractures of the lower extremities. METHODS: Patients ≥18 years old who underwent surgical intervention for neoplastic pathologic lower extremity fractures from 2015 to 2021 were identified using the Premier Healthcare Database. This cohort was divided by TXA receipt on the index surgery day. Patient demographics, hospital factors, patient comorbidities, and 90-day complications were assessed and compared between the cohorts. RESULTS: From 2015 to 2021, 4497 patients met inclusion criteria (769 TXA[+] and 3728 TXA[-]). Following propensity score matching, patients who received TXA had a significantly shorter length of stay than those who did not (7.6 ± 7.3 days vs. 9.0 ± 15.2, p = 0.036). Between the two cohorts, there were no significant differences in comorbidities. Regarding differences in postoperative complications, TXA(+) patients had significantly decreased odds of deep vein thrombosis (DVT) (1.87% vs. 5.46%; odds ratio [OR]:0.33; 95% confidence interval: 0.17-0.62; p = 0.001). CONCLUSION: Administration of IV TXA may be associated with a decreased risk of postoperative DVT without an increased risk of other complications. Orthopedic surgeons should consider the utilization of IV TXA in patients treated surgically for neoplastic pathologic fractures of the lower extremity.


Antifibrinolytic Agents , Postoperative Complications , Tranexamic Acid , Humans , Tranexamic Acid/administration & dosage , Male , Female , Middle Aged , Antifibrinolytic Agents/administration & dosage , Postoperative Complications/prevention & control , Retrospective Studies , Aged , Fractures, Spontaneous/prevention & control , Fractures, Spontaneous/surgery , Fractures, Spontaneous/etiology , Administration, Intravenous , Lower Extremity/surgery , Follow-Up Studies , Adult , Prognosis
4.
J Geriatr Oncol ; 15(4): 101700, 2024 May.
Article En | MEDLINE | ID: mdl-38218674

INTRODUCTION: The incidence and mortality of cancer is increasing worldwide with studies reporting that cumulative risk of cancer rises as age increases. Against the backdrop of the increasing prevalence of cancer amongst older patients, we conducted a systematic review and meta-analysis examining the depression-mortality relationship in older adults with cancer (OAC). MATERIALS AND METHODS: This PRISMA-adherent systematic review involved a systematic search of PubMed, Medline, EMBASE, and PsycINFO for prospective and retrospective cohort studies comparing the risk of all-cause and cancer-related mortality among OAC with depression. Random effects meta-analyses and meta-regressions were used for the primary analysis. RESULTS: From 5,280 citations, we included 14 cohort studies. Meta-analyses of hazard ratios (HRs) showed an increased incidence of all-cause mortality in OAC with depression (pooled HR: 1.40; 95% confidence interval [CI]: 1.25, 1.55). Subgroup analyses of other categorical study-level characteristics were insignificant. While risk of cancer-related mortality in OAC with depression was insignificantly increased with a pooled HR of 1.21 (95% CI: 0.98, 1.49), subgroup analysis indicated that risk of cancer-related mortality in OAC with depression significantly differed with cancer type. Our systematic review found that having fewer comorbidities, a higher education level, greater socioeconomic status, and positive social supportive factors lowered risk of all-cause mortality in OAC with depression. DISCUSSION: Depression in OAC significantly increases risk of all-cause mortality and cancer-related mortality among different cancer types. It is imperative for healthcare providers and policy makers to recognize vulnerable subgroups among older adults with cancer to individualize interventions.


Depression , Neoplasms , Humans , Neoplasms/mortality , Neoplasms/psychology , Aged , Depression/epidemiology , Cause of Death , Risk Factors , Female , Male , Aged, 80 and over
5.
Arthroplast Today ; 25: 101268, 2024 Feb.
Article En | MEDLINE | ID: mdl-38235399

Background: This study aims to compare indications, patient characteristics, hospital factors, and complication rates between total hip arthroplasty (THA) patients aged 30 years or younger and those older than 30 years using a large national database. Methods: The Premier Healthcare Database was utilized to identify primary THA patients from 2015 to 2021 who were aged ≤30 or >30 years. Patient demographics, hospital factors, and primary indications were compared for each cohort. Rates of complications and readmissions were assessed for each cohort by primary indication. Differences were assessed through univariate analysis. Results: Overall, 539,173 primary THA patients were identified (age ≤30: 1849; >30: 537,234). Compared to the >30 cohort, the ≤30 cohort was more likely to be male (56.5% vs 44.9%, P < .001) and non-White (34.0% vs 14.2%, P < .001). The most common indications for THA in the ≤30 cohort were osteonecrosis (49.3%), osteoarthritis (17.8%), and congenital hip deformities (16.0%), and in the >30 cohort, they were osteoarthritis (77.0%), other arthritis (11.3%), and osteonecrosis (5.4%). Patients aged ≤30 years had lower rates of respiratory failure (0.16% vs 0.57%, P < .001), acute renal failure (0.32% vs 1.72%, P < .001), and urinary tract infection (0.38% vs 1.11%, P = .003) than those aged >30 years, but higher rates of wound dehiscence (0.59% vs 0.29%, P = .015) and transfusion (3.68% vs 2.21%, P < .001). There were no differences in 90-day readmission rates (P = .811) or 90-day in-hospital death (P = .173) between cohorts. Conclusions: Younger patients undergoing THA differed significantly in indication, patient characteristics, and hospital factors compared to the older population on univariate analysis. Despite differences in indications, the cohorts did not differ markedly with regard to complication rates in this study.

6.
Global Spine J ; : 21925682231222903, 2023 Dec 16.
Article En | MEDLINE | ID: mdl-38103012

BACKGROUND CONTEXT: Several studies have shown that factors such as insurance type and patient income are associated with different readmission rates following certain orthopaedic procedures. The literature, however, remains sparse with regard to these demographic characteristics and their associations to perioperative lumbar spine fusion outcomes. PURPOSE: The purpose of this study was to assess the associations between hospital type, insurance type, and patient median income to both 30-day complication and readmission rates following lumbar spine fusion. PATIENT SAMPLE: Patients who underwent primary lumbar spine fusion (n = 596,568) from 2010-2016 were queried from the National Readmissions Database (NRD). OUTCOME MEASURES: Incidence of 30-day complication and readmission rates. METHODS: All relevant diagnoses and procedures were identified using International Classification of Disease, 9th and 10th Edition (ICD-9, 10) codes. Hospital types were categorized as metropolitan non-teaching (n = 212,131), metropolitan teaching (n = 364,752), and rural (n = 19,685). Insurance types included: Medicare (n = 213,534), Medicaid (n = 78,520), private insurance (n = 196,648), and out-of-pocket (n = 45,025). Patient income was divided into the following quartiles: Q1 (n = 112,083), Q2 (n = 145,755), Q3 (n = 156,276), and Q4 (n = 147,289), wherein quartile 1 corresponded to lower income ranges and quartile 4 to higher ranges. Statistical analysis was conducted in R. Kruskal-Wallis tests with Dunn's pairwise comparisons were performed to analyze differences in 30-day readmission and complication rates in patients who underwent lumbar spine fusion. Complications analyzed included infection, wound injury, hematoma, neurological injury, thromboembolic event, and hardware failure. RESULTS: 30-day readmission was significantly higher in metropolitan teaching hospitals compared to metropolitan non-teaching hospitals and rural hospitals (P < .05). Patients from metropolitan teaching hospitals had significantly higher rates of infection (P < .001), wound injury (P < .001), hematoma (P = .018), and hardware failure (P < .002) compared to those treated at metropolitan non-teaching hospitals. Privately insured patients were significantly less likely to be readmitted at 30 days than those paying with Medicare or Medicaid (P < .01). Patients with private insurance also experienced significantly lower rates of hematoma formation than Medicare beneficiaries and out-of-pocket payers (P < .01), postoperative wound injury compared to Medicaid patients and out-of-pocket payers (P < .005), and infection compared to all other groups (P < .001). Patients in Quartile 4 experienced significantly greater rates of hematoma formation compared to those in Quartiles 1 and 2 and were more likely to experience a thromboembolic event compared to all other groups. CONCLUSION: Patients undergoing lumbar spine fusion at metropolitan non-teaching hospitals and paying with private insurance had significantly lower 30-day readmission rates than their counterparts. Complications within 30 days following lumbar spine fusion were significantly higher in patients treated at metropolitan teaching hospitals and in Medicare and Medicaid beneficiaries. Aside from a few exceptions, however, patient income was generally not associated with differential complication rates.

7.
bioRxiv ; 2023 Sep 28.
Article En | MEDLINE | ID: mdl-37808692

Developing therapeutic strategies against COVID-19 has gained widespread interest given the likelihood that new viral variants will continue to emerge. Here we describe one potential therapeutic strategy which involves targeting members of the glutaminase family of mitochondrial metabolic enzymes (GLS and GLS2), which catalyze the first step in glutamine metabolism, the hydrolysis of glutamine to glutamate. We show three examples where GLS expression increases during coronavirus infection of host cells, and another in which GLS2 is upregulated. The viruses hijack the metabolic machinery responsible for glutamine metabolism to generate the building blocks for biosynthetic processes and satisfy the bioenergetic requirements demanded by the 'glutamine addiction' of virus-infected host cells. We demonstrate how genetic silencing of glutaminase enzymes reduces coronavirus infection and that newer members of two classes of small molecule allosteric inhibitors targeting these enzymes, designated as SU1, a pan-GLS/GLS2 inhibitor, and UP4, which is specific for GLS, block viral replication in mammalian epithelial cells. Overall, these findings highlight the importance of glutamine metabolism for coronavirus replication in human cells and show that glutaminase inhibitors can block coronavirus infection and thereby may represent a novel class of anti-viral drug candidates. Teaser: Inhibitors targeting glutaminase enzymes block coronavirus replication and may represent a new class of anti-viral drugs.

8.
Article En | MEDLINE | ID: mdl-37736618

Freezing of gait is a serious symptom of Parkinson's disease that increases the risk of injury through falling, and reduces quality of life. Current clinical freezing of gait treatments fail to adequately address the fall risk posed by freezing of gait symptoms, and current real-time treatment systems have high false positive rates. To address this problem, we designed a closed-loop, non-intrusive, and real-time freezing of gait detection and treatment system, FoG-Finder, that automatically detects and treats freezing of gait. To evaluate FoG-Finder, we first collected 716 freezing of gait events from 11 patients. We then compared FoG-Finder against other real-time systems with our dataset. Our system was able to achieve a 13.4% higher F1 score and a 10.7% higher overall accuracy while achieving a reduction of 85.8% in the false positive treatment rate compared with other validated real-time freezing of gait detection and treatment systems. Additionally, FoG-Finder achieved an average treatment latency of 427ms and 615ms for subject-dependent and leave-one-subject-out settings, respectively, making it a viable system to treat freezing of gait in the real-world.

9.
J Clin Med ; 12(15)2023 Aug 04.
Article En | MEDLINE | ID: mdl-37568523

Medicare Advantage healthcare plans may present undue impediments that result in disparities in patient outcomes. This study aims to compare the outcomes of patients who underwent STS resection based on enrollment in either traditional Medicare (TM) or Medicare Advantage (MA) plans. The Premier Healthcare Database was utilized to identify all patients ≥65 years old who underwent surgery for resection of a lower-extremity STS from 2015 to 2021. These patients were then subdivided based on their Medicare enrollment status (i.e., TM or MA). Patient characteristics, hospital factors, and comorbidities were recorded for each cohort. Bivariable analysis was performed to assess the 90-day risk of postoperative complications. Multivariable analysis controlling for patient sex, as well as demographic and hospital factors found to be significantly different between the cohorts, was also performed. From 2015 to 2021, 1858 patients underwent resection of STS. Of these, 595 (32.0%) had MA coverage and 1048 (56.4%) had TM coverage. The only comorbidities with a significant difference between the cohorts were peripheral vascular disease (p = 0.027) and hypothyroidism (p = 0.022), both with greater frequency in MA patients. After controlling for confounders, MA trended towards having significantly higher odds of pulmonary embolism (adjusted odds ratio (aOR): 1.98, 95% confidence interval (95%-CI): 0.58-6.79), stroke (aOR: 1.14, 95%-CI: 0.20-6.31), surgical site infection (aOR: 1.59, 95%-CI: 0.75-3.37), and 90-day in-hospital death (aOR 1.38, 95%-CI: 0.60-3.19). Overall, statistically significant differences in postoperative outcomes were not achieved in this study. The authors of this study hypothesize that this may be due to study underpowering or the inability to control for other oncologic factors not available in the Premier database. Further research with higher power, such as through multi-institutional collaboration, is warranted to better assess if there truly are no differences in outcomes by Medicare subtype for this patient population.

10.
Bone Jt Open ; 4(6): 424-431, 2023 Jun 05.
Article En | MEDLINE | ID: mdl-37272304

Aims: The modern prevalence of primary tumours causing metastatic bone disease is ill-defined in the oncological literature. Therefore, the purpose of this study is to identify the prevalence of primary tumours in the setting of metastatic bone disease, as well as reported rates of pathological fracture, postoperative complications, 90-day mortality, and 360-day mortality for each primary tumour subtype. Methods: The Premier Healthcare Database was queried to identify all patients who were diagnosed with metastatic bone disease from January 2015 to December 2020. The prevalence of all primary tumour subtypes was tabulated. Rates of long bone pathological fracture, 90-day mortality, and 360-day mortality following surgical treatment of pathological fracture were assessed for each primary tumour subtype. Patient characteristics and postoperative outcomes were analyzed based upon whether patients had impending fractures treated prophylactically versus treated completed fractures. Results: In total, 407,893 unique patients with metastatic bone disease were identified. Of the 14 primary tumours assessed, metastatic bone disease most frequently originated from lung (24.8%), prostatic (19.4%), breast (19.3%), gastrointestinal (9.4%), and urological (6.5%) malignancies. The top five malignant tumours resulting in long bone pathological fracture were renal (5.8%), myeloma (3.4%), female reproductive (3.2%), lung (2.8%), and breast (2.7%). Following treatment of pathological fractures of long bones, 90-day mortality rates were greatest for lung (12.1%), central nervous system (10.5%), lymphoma (10.4%), gastrointestinal (10.1%), and non-renal urinary (10.0%) malignancies. Finally, our study demonstrates improved 90-day and 360-day survival in patients treated for impending pathological fracture compared to completed fracture, as well as significantly lower rates of deep vein thrombosis, pulmonary embolism, urinary tract infection, and blood transfusion. Conclusion: This study defines the contemporary characteristics of primary malignancies resulting in metastatic bone disease. These data should be considered by surgeons when prognosticating patient outcomes during treatment of their metastatic bone disease.

11.
G3 (Bethesda) ; 13(9)2023 08 30.
Article En | MEDLINE | ID: mdl-37279923

Conditional gene regulation in Drosophila through binary expression systems like the LexA-LexAop system provides a superb tool for investigating gene and tissue function. To increase the availability of defined LexA enhancer trap insertions, we present molecular, genetic, and tissue expression studies of 301 novel Stan-X LexA enhancer traps derived from mobilization of the index SX4 line. This includes insertions into distinct loci on the X, II, and III chromosomes that were not previously associated with enhancer traps or targeted LexA constructs, an insertion into ptc, and seventeen insertions into natural transposons. A subset of enhancer traps was expressed in CNS neurons known to produce and secrete insulin, an essential regulator of growth, development, and metabolism. Fly lines described here were generated and characterized through studies by students and teachers in an international network of genetics classes at public, independent high schools, and universities serving a diversity of students, including those underrepresented in science. Thus, a unique partnership between secondary schools and university-based programs has produced and characterized novel resources in Drosophila, establishing instructional paradigms devoted to unscripted experimental science.


Drosophila Proteins , Drosophila , Animals , Drosophila/genetics , Drosophila/metabolism , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Gene Expression Regulation , Enhancer Elements, Genetic
12.
Oncologist ; 28(4): e198-e204, 2023 04 06.
Article En | MEDLINE | ID: mdl-36779537

INTRODUCTION: In the National University Cancer Institute, Singapore (NCIS), 2 pilot programs providing (i) surgical prehabilitation before cancer surgery and (ii) geriatric oncology support for older adults planned for chemotherapy and/or radiotherapy were merged to form the Geriatric Oncology Longitudinal End to eNd (GOLDEN) program in 2019 to support patients from the time of their cancer diagnosis, through their treatment process, to cancer survivorship. METHODS AND MATERIALS: Older adults aged ≥65 years were enrolled in either surgical prehabilitation, the geriatric medical oncology (GO) arm, or both. All patients undergo a geriatric assessment. We assessed if patients had a change in treatment plans based on GOLDEN recommendations, and the impact on patient related outcomes. RESULTS: There were 777 patients enrolled in the GOLDEN program over 2 years; 569 (73%) were enrolled in surgical prehabilitation, 308 (40%) were enrolled in the GO arm, with 100 (12.8%) enrolled in both. 56.9% were females. Median age was 73. Lower gastrointestinal (51.2%) and hepatobiliary cancers (24.1%) were the most common cancer types. 43.4% were pre-frail and 11.7% were frail. Of the 308 patients in the GO arm, 86.0% had geriatric syndromes, while 60.7% had a change in their treatment plans based on GOLDEN recommendations. 31.5% reported an improved global health status, while 38.3% maintained their global health status. 226 (73%) responded that they had benefited from the GOLDEN. CONCLUSION: More than half of the population was either pre-frail or frail. Amongst those in the GO arm, the majority had geriatric syndromes and had a change in their treatment plans based on GOLDEN recommendations. Majority reported either improvement or maintenance in global health status, with most feeling they have benefited from the program. Further evaluation of the longitudinal geriatric hematology-oncology program for cancer-related outcomes and sustainability should be carried out.


Neoplasms , Aged , Female , Humans , Male , Singapore , Feasibility Studies , Syndrome , Neoplasms/epidemiology , Neoplasms/surgery , Medical Oncology , Geriatric Assessment
13.
Gen Hosp Psychiatry ; 81: 32-42, 2023.
Article En | MEDLINE | ID: mdl-36724695

OBJECTIVE: To systematically evaluate the risk factors of depression and anxiety in older adults with cancer. METHOD: This PRISMA-adherent systematic review (PROSPERO CRD42022372747) involved a systematic database search for prospective and retrospective cohort studies. RESULTS: We included 33 cohort studies with 31 evaluating depression and seven evaluating anxiety. Systematic synthesis yielded various protective and exacerbating factors for depression and anxiety amongst older adults with cancer. These factors span a range of domains: (1) Cancer and associated treatment-related factors; (2) Medical, physical and functional factors; (3) Demographic factors and; (4) Social and lifestyle factors. At the individual-level, the most significant factors were the presence of chronic medical comorbidities, having pre-existing psychological symptoms, and poor baseline physical and functional status. Within the social unit, the degree of social support and presence of a partner were most significant. CONCLUSION: The deleterious impact comorbid psychological symptoms can have on older adults with cancer can be profound. In this review, we highlight a range of protective and exacerbating factors identified from cohort studies that may enable policymakers to tailor and individualise interventions to manage depression, anxiety and associated burden in this vulnerable population. The relative paucity of studies evaluating anxiety highlights an important research gap.


Depression , Neoplasms , Aged , Humans , Anxiety/epidemiology , Anxiety/etiology , Depression/epidemiology , Neoplasms/epidemiology , Neoplasms/psychology , Prospective Studies , Retrospective Studies
14.
Int J Geriatr Psychiatry ; 38(1): e5872, 2023 Jan.
Article En | MEDLINE | ID: mdl-36683168

OBJECTIVES: Delirium is highly prevalent in hospitalised older adults, under-diagnosed and associated with poor outcomes. We aim to determine (i) association of frailty measured using Hospital Frailty Risk Score (HFRS) with delirium, (ii) impact of delirium on mortality, 30-days readmission, extended length of stay (eLOS) and cost (eCOST). METHODS: Retrospective cohort study was conducted on 902 older adults ≥75 years discharged from an academic tertiary hospital between March and September 2021. Data was obtained from hospital administrative database. RESULTS: Delirium was prevalent in 39.1%, 58.1% were female with mean age 85.3 ± 6.2 years. Patients with delirium were significantly older, had higher HFRS, pneumonia, urinary tract infection (UTI), E.coli and Klebsiella infection, constipation, dehydration, stroke and intracranial bleed, with comorbidities including dementia, diabetes, hypertension, hyperlipidaemia and chronic kidney disease. In-hospital mortality, 30-days mortality, 30-days readmission, median LOS and cost was significantly higher. Delirium was significantly associated with at least intermediate frailty (OR = 3.52; CI = 2.48-4.98), dementia (OR = 2.39; CI = 1.61-3.54), UTI (OR = 1.95; CI = 1.29-2.95), constipation (OR = 2.49; CI = 1.43-4.33), Klebsiella infection (OR = 3.06; CI = 1.28-7.30), dehydration (OR = 2.01; CI = 1.40 - 2.88), 30-day mortality (OR = 2.52; CI = 1.42-4.47), 30-day readmission (OR = 2.18; CI = 1.36-3.48), eLOS (OR = 1.80; CI = 1.30-2.49) and eCOST (OR = 1.67; CI = 1.20-2.35). CONCLUSIONS: Delirium was highly prevalent in older inpatients, and associated with dementia, frailty, increased cost, LOS, 30-day readmissions and mortality. Hospital Frailty Risk Score had robust association with delirium and can be auto-populated from electronic medical records. Prospective studies are needed on multicomponent delirium preventive measures in high-risk groups identified by HFRS in acute care settings.


Delirium , Dementia , Frailty , Humans , Female , Aged , Aged, 80 and over , Male , Frailty/epidemiology , Frailty/diagnosis , Retrospective Studies , Dehydration , Length of Stay , Risk Factors , Delirium/epidemiology , Delirium/diagnosis , Dementia/epidemiology , Hospitals
15.
Acc Chem Res ; 55(20): 2904-2919, 2022 10 18.
Article En | MEDLINE | ID: mdl-36153960

Atropisomerism is a conformational chirality that occurs when there is hindered rotation about a σ-bond. While atropisomerism is exemplified by biaryls, it is observed in many other pharmaceutically relevant scaffolds including heterobiaryls, benzamides, diarylamines, and anilides. As bond rotation leads to racemization, atropisomers span the gamut of stereochemical stability. LaPlante has classified atropisomers based on their half-life of racemization at 37 °C: class 1 (t1/2 < 60 s), class 2 (60 s < t1/2 < 4.5 years), and class 3 (t1/2 > 4.5 years). In general, class-3 atropisomers are considered to be suitable for drug development. There are currently four FDA-approved drugs that exist as stable atropisomers, and many others are in clinical trials or have recently appeared in the drug discovery literature. Class-1 atropisomers are more prevalent, with ∼30% of recent FDA-approved small molecules possessing at least one class-1 axis. While class-1 atropisomers do not possess the requisite stereochemical stability to meet the classical definition of atropisomerism, they often bind a given target in a specific set of chiral conformations.Over the past decade, our laboratory has embarked on a research program aimed at leveraging atropisomerism as a design feature to improve the target selectivity of promiscuous lead compounds. Our studies initially focused on introducing class-3 atropisomerism into promiscuous kinase inhibitors, resulting in a proof of principle in which the different atropisomers of a compound can have different selectivity profiles with potentially improved target selectivity. This inspired a careful analysis of the binding conformations of diverse ligands bound to different target proteins, resulting in the realization that the sampled dihedral conformations about a prospective atropisomeric axis played a key role in target binding and that preorganizing the prospective atropisomeric axis into a desired target's preferred conformational range can lead to large gains in target selectivity.As atropisomerism is becoming more prevalent in modern drug discovery, there is an increasing need for strategies for atropisomerically pure samples of pharmaceutical compounds. This has led us and other groups to develop catalytic atroposelective methodologies toward pharmaceutically privileged scaffolds. Our laboratory has contributed examples of atroposelective methodologies toward heterobiaryl systems while also exploring the chirality of less-studied atropisomers such as diarylamines and related scaffolds.This Account will detail recent encounters with atropisomerism in medicinal chemistry and how atropisomerism has transitioned from a "lurking menace" into a leverageable design strategy in order to modulate various properties of biologically active small molecules. This Account will also discuss recent advances in atroposelective synthesis, with a focus on methodologies toward pharmaceutically privileged scaffolds. We predict that a better understanding of the effects of conformational restriction about a prospective atropisomeric axis on target binding will empower chemists to rapidly "program" the selectivity of a lead molecule toward a desired target.


Anilides , Benzamides , Pharmaceutical Preparations , Prospective Studies , Stereoisomerism
16.
Front Med (Lausanne) ; 9: 908100, 2022.
Article En | MEDLINE | ID: mdl-35733862

Introduction: While hospitalist and internist inpatient care models dominate the landscape in many countries, geriatricians and internists are at the frontlines managing hospitalized older adults in countries such as Singapore and the United Kingdom. The primary aim of this study was to determine outcomes for older patients cared for by geriatricians compared with non-geriatrician-led care teams. Materials and Methods: A retrospective cohort study of 1,486 Internal Medicine patients aged ≥75 years admitted between April and September 2021 was conducted. They were either under geriatrician or non-geriatrician (internists or specialty physicians) care. Data on demographics, primary diagnosis, comorbidities, mortality, readmission rate, Hospital Frailty Risk Score (HFRS), Age-adjusted Charlson Comorbidity Index, Length of Stay (LOS), and cost of hospital stay were obtained from the hospital database and analyzed. Results: The mean age of patients was 84.0 ± 6.3 years, 860 (57.9%) females, 1,183 (79.6%) of Chinese ethnicity, and 902 (60.7%) under the care of geriatricians. Patients under geriatrician were significantly older and had a higher prevalence of frailty, dementia, and stroke, whereas patients under non-geriatrician had a higher prevalence of diabetes and hypertension. Delirium as the primary diagnosis was significantly higher among patients under geriatrician care. Geriatrician-led care model was associated with shorter LOS, lower cost, similar inpatient mortality, and 30-day readmission rates. LOS and cost were lower for patients under geriatrician care regardless of frailty status but significant only for low and intermediate frailty groups. Geriatrician-led care was associated with significantly lower extended hospital stay (OR 0.73; 95% CI 0.56-0.95) and extended cost (OR 0.69; 95% CI 0.54-0.95). Conclusion: Geriatrician-led care model showed shorter LOS, lower cost, and was associated with lower odds of extended LOS and cost.

17.
J Arthroplasty ; 37(12): 2358-2364, 2022 12.
Article En | MEDLINE | ID: mdl-35738360

BACKGROUND: Data on the clinical impact of computer navigation (CN) and robotic assistance (RA) in total knee arthroplasty (TKA) are mixed. This study aims to describe modern utilization trends in CN-TKA, RA-TKA, and traditionally-instrumented (TD) TKA and to assess for differences in postoperative complications and opioid consumption by procedure type. METHODS: A national database was queried to identify primary, elective TKA patients from 2015 to 2020. Trends in procedural utilization rates were assessed. Differences in 90-day postoperative complications and inpatient opioid consumption were assessed. Multivariate regression analyses were performed to account for potential confounders. RESULTS: Of the 847,496 patients included, 49,317 (5.82%) and 24,460 (2.89%) underwent CN-TKA and RA-TKA, respectively. CN-TKA utilization increased from 5.64% (2015) to 6.41% (2020) and RA-TKA utilization increased from 0.84% (2015) to 5.89% (2020). After adjusting for confounders, CN-TKA was associated with lower periprosthetic joint infection (P = .001), pulmonary embolism (P < .001), and acute respiratory failure (P = .015) risk compared to traditional (TD) TKA. RA-TKA was associated with lower deep vein thrombosis (P < .001), myocardial infarction (P = .013), and pulmonary embolism (P = .001) risk than TD-TKA. Lower postoperative day 1 opioid usage was seen with CN-TKA and RA-TKA than TD-TKA (P < .001). Lower postoperative day 0 opioid consumption was also seen in RA-TKA (P < .001). CONCLUSION: From 2015 to 2020, there was a relative 13.7% and 601.2% increase in CN-TKAs and RA-TKAs, respectively. This trend was associated with reductions in hospitalization duration, postoperative complications, and opioid consumption. These data support the safety of RA-TKA and CN-TKA compared to TD-TKA. Further investigation into the specific indications for these technology-assisted TKAs is warranted.


Arthroplasty, Replacement, Knee , Pulmonary Embolism , Robotic Surgical Procedures , Humans , Arthroplasty, Replacement, Knee/adverse effects , Arthroplasty, Replacement, Knee/methods , Robotic Surgical Procedures/adverse effects , Analgesics, Opioid/therapeutic use , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Computers , Pulmonary Embolism/complications
18.
Hosp Pediatr ; 12(6): 555-560, 2022 06 01.
Article En | MEDLINE | ID: mdl-35574656

OBJECTIVE: To date, there is little in the literature that describes any relationship between newborn circumcision, its timing, and breastfeeding outcomes. We sought to determine if the timing of circumcision in term, healthy newborns affects exclusive breastfeeding rates during the first 6 months of life. METHODS: One hundred and forty-eight maternal-infant dyads were enrolled in a randomized, multicenter, clinical trial between June 2016 and July 2019. Study participants included parent-infant dyads who desired both circumcision and breastfeeding. Newborns were randomized into 3 groups for circumcision: "early," circumcised within 24 hours of delivery; "intermediate," circumcised between 24 to 72 hours of age; and "late," circumcised between 1 and 3 weeks of age. The primary outcome was exclusive breastfeeding duration, assessed at discharge, 2 weeks, and 2, 4, and 6 months. RESULTS: Baseline characteristics between groups were similar. Exclusive breastfeeding decreased more rapidly over 6 months in the intermediate group (by 74%, 89% to 23%), as compared to the early (by 34%, 81% to 53%) or late (by 50%, 88% to 44%) groups (P = .04). Exclusive breastfeeding was less common in the intermediate group (circumcision between 24 and 72 hours), as compared to the early and late circumcision groups, at each measured time point beyond 2 weeks of age. CONCLUSIONS: Circumcision before 24 hours of age may be advantageous with respect to increased exclusive breastfeeding throughout the first 6 months of life. Deferral of circumcision beyond the immediate newborn period was not superior to performing the procedure within the first 24 hours.


Breast Feeding , Circumcision, Male , Female , Humans , Infant , Infant, Newborn , Male
19.
J Multidiscip Healthc ; 15: 921-939, 2022.
Article En | MEDLINE | ID: mdl-35519152

Background: Chronic heart failure (CHF) is a debilitating condition that affects millions worldwide. It is accompanied by a myriad of adverse consequences, such asdiminishing of quality of life and deterioration of mental health. Caregivers play a pivotal role in helping CHF patients manage their conditions and symptoms, as a result the physical, mental and emotional state of caregivers have a direct impact on CHF patients and the management of this condition. Purpose: This systematic review aims to synthesize data about the effectiveness of behavioral interventions targeted at patients with chronic heart failure (CHF) and/or informal caregivers of CHF patients to improve overall management and treatment of CHF in the population. Patients and Methods: Three databases were searched for published studies and studies that included evaluated outcomes of interventions that targeted CHF patients or informal caregivers. All randomized controlled trials, trials of either experimental or quasi-experimental design were included. Studies that only involved formal caregivers, patient populations of adolescents/young adults and patients with non-chronic conditions were excluded. Results: Across the 21 included studies, no study reported a significant improvement in all three domains of quality of life (QoL), depression and loneliness of caregivers while only three studies reported a significant improvement in two outcomes. Within each domain, heterogeneity in measures limited quantitative pooling. Conclusion: This review provides data on the efficacy of interventions targeted at CHF patients and/or informal caregivers. It also highlights successful interventions and its features. Following this, additional resources need to be invested and directed towards implementing these interventions.

20.
Psychogeriatrics ; 22(4): 460-468, 2022 Jul.
Article En | MEDLINE | ID: mdl-35577347

BACKGROUND: The Montreal Cognitive Assessment (MoCA) was developed as a screening tool for mild cognitive impairment (MCI). Given the need for a rapid screening test in settings such as primary care, we compare the validity of the Rapid Cognitive Screen (RCS) against the MoCA, and determine cut-off scores in the old and old-old. METHODS: Cross-sectional study involving community-dwelling 'old' (65 to 79 years old) and 'old-old' (≥ 80 years old) without dementia. Cognitive impairment was defined by MoCA score 17 to 22. Validation was done using the receiver operating characteristic (ROC) curve analysis: area under the curve (AUC), sensitivity (Sn), and specificity (Sp). RESULTS: Of the 183 participants (mean age 72.1 ± 5.2 years),15.8% (n = 29) were classified as cognitively impaired. The overall ROC curve had an AUC of 0.82 (95% CI 0.75-0.90, P < 0.01) with an optimal cut-off of 7/8 on RCS (Sn 0.77, Sp 0.72). The 'old' and 'old-old' group had AUC of 0.82 (95% CI 0.74-0.91, P < 0.01) with 8/9 as optimal cut-off (Sn 0.51, Sp 0.96) and AUC of 0.85 (95% CI 0.66-1.03, P < 0.01) with 7/8 as optimal cut-off (Sn 0.71, Sp 1.00) respectively. In multivariate analysis, age was associated with 0.05 (95% CI -0.10-0.00, P < 0.04) point decrement, while >6 years of education was associated with 0.82 (95% CI 0.32-1.33, P < 0.01) point increment in RCS scores. CONCLUSION: The three-item RCS is quick and easy to administer. Although RCS met the criterion for good validity against MoCA in predicting cognitive impairment, its utility as a first-line screening tool needs to be further validated in a large-scale population study.


Cognitive Dysfunction , Aged , Aged, 80 and over , Cognition , Cognitive Dysfunction/psychology , Cross-Sectional Studies , Humans , Mental Status and Dementia Tests , Neuropsychological Tests , ROC Curve , Reproducibility of Results , Sensitivity and Specificity
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