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1.
Int J Public Health ; 69: 1607104, 2024.
Article in English | MEDLINE | ID: mdl-38993179

ABSTRACT

Objectives: This study used repeated cross-sectional data from three national surveys in Vietnam to determine tobacco smoking prevalence from 2010 to 2020 and disparities among demographic and socioeconomic groups. Methods: Tobacco smoking temporal trends were estimated for individuals aged 15 and over and stratified by demographic and socioeconomic status (SES). Prevalence estimates used survey weights and 95% confidence intervals. Logistic regression models adjusted for survey sample characteristics across time were used to examine trends. Results: Tobacco smoking prevalence dropped from 23.8% in 2010 to 22.5% in 2015 and 20.8% in 2020. The adjusted OR for 2015 compared to 2010 was 0.87, and for 2020 compared to 2010 was 0.69. Smoking decreased less for employed individuals than unemployed individuals in 2020 compared to 2010. Smoking was higher in the lower SES group in all 3 years. Higher-SES households have seen a decade-long drop in tobacco use. Conclusion: This prevalence remained constant in lower SES households. This highlights the need for targeted interventions to address the specific challenges faced by lower-SES smokers and emphasizes the importance of further research to inform effective policies.


Subject(s)
Tobacco Smoking , Humans , Vietnam/epidemiology , Cross-Sectional Studies , Male , Female , Adult , Prevalence , Middle Aged , Adolescent , Young Adult , Tobacco Smoking/epidemiology , Tobacco Smoking/trends , Aged , Socioeconomic Factors , Social Class
2.
J Pediatr Surg ; 2024 May 25.
Article in English | MEDLINE | ID: mdl-38897896

ABSTRACT

BACKGROUND: Fecal incontinence is a common problem for children with repaired anorectal malformations (ARM) and has significant implications for initiating school. While sex, anatomy, and medical comorbidities are known to influence continence outcomes, the impact of socioeconomic factors and neighborhood-level disadvantage are less well understood. METHODS: We performed a single-center retrospective review of all school-aged (5-18 years) children with ARM at a longitudinal pediatric surgery clinic. Demographic, clinical, and socioeconomic variables were abstracted via chart review and geocoding was performed to obtain Area Deprivation Index (ADI) and Social Vulnerability Index (SVI) scores. Statistical analyses assessed for associations between the primary outcome of social continence (defined as no diaper usage and infrequent fecal accidents at age 5) and these variables. RESULTS: 72 patients were included; of these, 45.8% were socially continent. On bivariate analysis, social continence was significantly associated with state ADI score as well as the SVI Housing characteristics score. These associations remained significant when adjusting for sex and medical comorbidities in separate multiple logistic regression models. CONCLUSION: The relative disadvantage of the neighborhood in which a child with ARM lives may play a role in their ability to achieve continence by school age. Efforts are warranted to identify and develop targeted interventions to for this pediatric population. LEVEL OF EVIDENCE: IV.

3.
Radiother Oncol ; 198: 110384, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38880415

ABSTRACT

BACKGROUND: Prognosis for patients with high-risk neuroblastoma (HR-NBL) is guarded despite aggressive therapy, and few studies have characterized outcomes after radiotherapy in relation to radiation treatment fields. METHODS: Multi-institutional retrospective cohort of 293 patients with HR-NBL who received autologous stem cell transplant (ASCT) and EBRT between 1997-2021. LRR was defined as recurrence at the primary site or within one nodal echelon beyond disease present at diagnosis. Follow-up was defined from the end of EBRT. Event-free survival (EFS) and OS were analyzed by Kaplan-Meier method. Cumulative incidence of locoregional progression (CILP) was analyzed using competing risks of distant-only relapse and death with Gray's test. RESULTS: Median follow-up was 7.0 years (range: 0.01-22.4). Five-year CILP, EFS, and OS were 11.9 %, 65.2 %, and 77.5 %, respectively. Of the 31 patients with LRR and imaging review, 15 (48.4 %) had in-field recurrences (>12 Gy), 6 (19.4 %) had marginal failures (≤12 Gy), and 10 (32.3 %) had both in-field and marginal recurrences. No patients receiving total body irradiation (12 Gy) experienced marginal-only failures (p = 0.069). On multivariable analyses, MYCN amplification had higher risk of LRR (HR: 2.42, 95 % CI: 1.06-5.50, p = 0.035) and post-consolidation isotretinoin and anti-GD2 antibody therapy (HR: 0.42, 95 % CI: 0.19-0.94, p = 0.035) had lower risk of LRR. CONCLUSIONS: Despite EBRT, LRR remains a contributor to treatment failure in HR-NBL with approximately half of LRRs including a component of marginal failure. Future prospective studies are needed to explore whether radiation fields and doses should be defined based on molecular features such as MYCN amplification, and/or response to chemotherapy.

4.
Acta Pharm Sin B ; 14(5): 2349-2357, 2024 May.
Article in English | MEDLINE | ID: mdl-38799620

ABSTRACT

A titrant for the SARS-CoV-2 main protease (Mpro) was developed that enables, for the first time, the exact determination of the concentration of the enzymatically active Mpro by active-site titration. The covalent binding mode of the tetrapeptidic titrant was elucidated by the determination of the crystal structure of the enzyme-titrant complex. Four fluorogenic substrates of Mpro, including a prototypical, internally quenched Dabcyl-EDANS peptide, were compared in terms of solubility under typical assay conditions. By exploiting the new titrant, key kinetic parameters for the Mpro-catalyzed cleavage of these substrates were determined.

6.
J Med Chem ; 66(18): 12776-12811, 2023 09 28.
Article in English | MEDLINE | ID: mdl-37708384

ABSTRACT

Hypoxia-inducible factor-1α (HIF-1α) constitutes the principal mediator of cellular adaptation to hypoxia in humans. The HIF-1α protein level and activity are tightly regulated by the ubiquitin E3 ligase von Hippel-Lindau (VHL). Here, we performed a structure-guided and bioactivity-driven design of new VHL inhibitors. Our iterative and combinatorial strategy focused on chemical variability at the phenylene unit and encompassed further points of diversity. The exploitation of tailored phenylene fragments and the stereoselective installation of the benzylic methyl group provided potent VHL ligands. Three high-resolution structures of VHL-ligand complexes were determined, and bioactive conformations of these ligands were explored. The most potent inhibitor (30) exhibited dissociation constants lower than 40 nM, independently determined by fluorescence polarization and surface plasmon resonance and an enhanced cellular potency, as evidenced by its superior ability to induce HIF-1α transcriptional activity. Our work is anticipated to inspire future efforts toward HIF-1α stabilizers and new ligands for proteolysis-targeting chimera (PROTAC) degraders.


Subject(s)
Ubiquitin-Protein Ligases , Von Hippel-Lindau Tumor Suppressor Protein , Humans , Ubiquitin-Protein Ligases/metabolism , Von Hippel-Lindau Tumor Suppressor Protein/metabolism , Ligands , Hypoxia-Inducible Factor 1, alpha Subunit , Ubiquitin/metabolism , Hypoxia
7.
Asian Pac J Cancer Prev ; 24(6): 2073-2082, 2023 Jun 01.
Article in English | MEDLINE | ID: mdl-37378938

ABSTRACT

OBJECTIVE: Alcohol abuse can cause developing cirrhosis, even liver cancer. Several single nucleotide polymorphisms (SNPs) of ADH1B, ADH1C, and ALDH2 genes have been reported to be associated with alcohol abuse and alcoholic cirrhosis (ALC). This study investigated the association between three SNPs of ADH1B rs1229984, ADH1C rs698, and ALDH2 rs671 with alcohol abuse and ALC in people living in the Northeast region of Vietnam. METHODS: 306 male participants were recruited including 206 alcoholics (106 ALC, 100 without ALC) and 100 healthy non-alcoholics. Clinical characteristics were collected by clinicians. Genotypes were identified by Sanger sequencing. Chi-Square (χ2) and Fisher-exact tests were used to assess the differences in age and clinical characteristics, Child-Pugh score, frequencies of alleles and genotypes. RESULT: Our data showed that the frequency of ALDH2*1 was significantly higher in alcoholics (88.59%) and ALC groups (93.40%) than that of healthy non-alcoholics (78.50%) with p=0.0009 and non-ALC group (83.50%) with p=0.002, respectively. We detected opposite results when examined ALDH2*2. Frequency of combined genotypes with high acetaldehyde accumulation were significantly lower in alcoholics and ALC group than those of control groups with p=0.005 and p=0.008, respectively. Meanwhile, the proportion of combined genotypes with non-acetaldehyde accumulation were significantly two times higher in the ALC group (19.98%) than those of the non-ALC group (8%) with p=0.035. These combined genotypes showed a decreasing trend in the Child-Pugh score from likely phenotype causing risk for non-acetaldehyde accumulation to high acetaldehyde accumulation. CONCLUSION: The ALDH2*1 allele was found as a risk factor for alcohol abuse and ALC, and combined genotypes of ADH1B rs1229984, ADH1C rs698, and ALDH2 rs671 with non-acetaldehyde accumulation increase ALC risk. In contrast, ALDH2*2 and the genotype combinations related to high acetaldehyde accumulation were protective factors against alcohol abuse and ALC.


Subject(s)
Alcoholism , Male , Humans , Alcoholism/genetics , Liver Cirrhosis, Alcoholic/epidemiology , Liver Cirrhosis, Alcoholic/genetics , Vietnam/epidemiology , Aldehyde Dehydrogenase, Mitochondrial/genetics , Alcohol Dehydrogenase/genetics , Polymorphism, Single Nucleotide , Genotype , Acetaldehyde , Aldehyde Dehydrogenase/genetics , Alcohol Drinking/adverse effects , Alcohol Drinking/genetics
9.
Transfus Apher Sci ; 62(3): 103656, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36863912

ABSTRACT

BACKGROUND: The role of caplacizumab in the routine treatment of immune thrombotic thrombocytopenic purpura (iTTP) remains to be established. CASE SUMMARY: A 56-year-old woman was transferred to our center with iTTP and neurologic features. At the outside hospital, she was initially diagnosed and managed as Immune Thrombocytopenia (ITP). Upon transfer to our center, daily plasma exchange, steroids, and rituximab were initiated. After an initial improvement, refractoriness became evident with a decline in platelet count and continued neurologic abnormalities. Initiation of caplacizumab resulted in rapid hematologic and clinical responses. CONCLUSION: Caplacizumab is a valuable treatment modality in iTTP, particularly in cases associated with refractoriness or neurologic features.


Subject(s)
Purpura, Thrombocytopenic, Idiopathic , Purpura, Thrombotic Thrombocytopenic , Single-Domain Antibodies , Female , Humans , Middle Aged , Purpura, Thrombotic Thrombocytopenic/drug therapy , Platelet Count , Rituximab/therapeutic use , Single-Domain Antibodies/therapeutic use , Plasma Exchange , Purpura, Thrombocytopenic, Idiopathic/drug therapy , ADAMTS13 Protein
10.
Digit Health ; 9: 20552076231163786, 2023.
Article in English | MEDLINE | ID: mdl-36937692

ABSTRACT

Objectives: This study aims to: (1) identify the information required by family caregivers of people with dementia to be targeted within our dementia family caregiver intervention and (2) test the feasibility of the intervention and methodology to underpin a fully powered randomized controlled trial. Methods: The study setting will be the Department of Geriatrics at Gia Dinh People's Hospital in Ho Chi Minh City. Inclusion criteria will be the family caregivers of people with dementia living in the community, who attend the Department and use smartphones. In phase 1, we will identify the intervention content with family caregivers of people with dementia through 20 in-depth interviews to determine what information and skills they need. In phase 2, a pilot randomized control trial design will be conducted, with 60 family caregivers of people with dementia being assigned to the intervention or control group by the block randomization method with a ratio of 1:1. The intervention will include weekly, online, psycho-educational, group sessions hosted on the Zalo app. The participants will complete questionnaires at baseline, immediately postintervention, and 3-month postintervention. The feasibility of the intervention and methodology will be assessed, including the rates of recruitment, retention, completion of assessments, and acceptability of the intervention. Results: The required information and skills in phase 1 may include dealing with worrying behavior changes in people with dementia, emotional support, and seeking support sources. The rates of recruitment, retention, completion of assessments, and acceptability of the intervention will be obtained in phase 2. The scores of symptoms of stress, depression, and anxiety in the intervention group may be lower than those in the control group at postintervention and 3-month postintervention. Conclusion: The study will provide a foundation for a fully powered clinical trial for the smartphone app-based intervention to reduce stress, depression, and anxiety among family caregivers of people with dementia in Vietnam.

11.
Dig Dis Sci ; 68(6): 2188-2195, 2023 06.
Article in English | MEDLINE | ID: mdl-36807017

ABSTRACT

BACKGROUND: Pouchitis is the most frequent complication following restorative proctocolectomy and ileal pouch anal anastomosis (RP-IPAA) in patients with Ulcerative colitis (UC). Pediatric data on nutritional status during RP-IPAA and in patients with pouchitis are limited. AIMS: We aimed to delineate nutritional changes in children undergoing 2-stage and 3-stage surgeries and to evaluate the association between nutrition and the development of recurrent or chronic pouchitis. METHODS: This single-center retrospective study involved 46 children with UC who underwent a RP-IPAA. Data were collected at each surgical stage and for up to 2-year post-ileostomy takedown. We used Wilcoxon matched-pairs signed-rank test to evaluate the differences in nutritional markers across surgical stages and logistic regression to identify the factors associated with recurrent or chronic pouchitis. RESULTS: Twenty patients (43.5%) developed recurrent or chronic pouchitis. Children who underwent a 3-stage procedure had improvements in albumin, hematocrit, and body mass index (BMI)-for-age Z-scores (p < 0.01) between the first two stages. A positive trend in BMI-for-age Z-scores (p = 0.08) was identified in children with 2-stage procedures. All patients showed sustained nutritional improvement during the follow-up period. Among patients who underwent 3-stage surgeries, BMI worsened by 0.8 standard deviations (SDs) (p = 0.24) between the initial stages in those who developed recurrent or chronic pouchitis and improved by 1.1 SDs (p = 0.04) in those who did not. CONCLUSIONS: Early improvement in BMI-for-age Z-scores following the initial stage was associated with lower rates of recurrent or chronic pouchitis. Larger prospective studies are needed to validate these findings.


Subject(s)
Colitis, Ulcerative , Pouchitis , Proctocolectomy, Restorative , Humans , Child , Pouchitis/etiology , Colitis, Ulcerative/surgery , Colitis, Ulcerative/complications , Retrospective Studies , Nutritional Status , Proctocolectomy, Restorative/adverse effects , Colectomy/adverse effects
12.
Eur J Pediatr Surg ; 33(6): 477-484, 2023 Dec.
Article in English | MEDLINE | ID: mdl-36720245

ABSTRACT

INTRODUCTION: The purpose of this study is to describe the long-term growth and nutrition outcomes of sutureless versus sutured gastroschisis repair. We hypothesized that weight z-score at 1 year would be affected by social determinants of health measured by the U.S. Centers for Disease Control Social Vulnerability Index (SVI). MATERIALS AND METHODS: We conducted a single-center retrospective review of patients who underwent gastroschisis repair (n = 97) from 2007 to 2018. Growth z-scores collected through 5 years of age and long-term clinical outcomes were compared based on the closure method and the type of gastroschisis (simple vs. complicated). Multiple regression analysis was performed to identify the impact of SVI themes and other covariates on weight for age z-score at 1 year. RESULTS: In total, 46 patients underwent sutureless repair and 51 underwent sutured repair with median follow-up duration of 2.5 and 1.9 years, respectively. Weight and length z-scores decreased after birth but normalized within the first year of life. Growth and long-term clinical outcomes were similar regardless of the closure method, while patients with complicated gastroschisis had higher rates of hospitalizations, small bowel obstructions, and additional abdominal surgeries. Using multiple regression, both low discharge weight and high SVI in the "minority status and language" theme were associated with lower weight for age z-scores at 1 year (p = 0.003 and p = 0.03). CONCLUSION: Sutureless and sutured gastroschisis repairs result in similar growth and long-term outcomes. Patients living in areas with greater social vulnerability may be at increased risk of poor weight gain. Patients should be followed at least through their first year to ensure appropriate growth.


Subject(s)
Gastroschisis , Humans , Gastroschisis/surgery , Gastroschisis/complications , Social Vulnerability , Treatment Outcome , Retrospective Studies , Hospitalization
13.
J Pediatr Gastroenterol Nutr ; 76(3): e61-e65, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36302247

ABSTRACT

The nutritional requirements of neonates with congenital abdominal wall defects (AWDs) remain poorly described. In particular, there is a lack of literature on the calorie, protein, and micronutrient needs of those with AWD. Nutritional therapy is a cornerstone of care in patients with burns due to the metabolic consequences of injury to the epithelial layer. Similarly, children with AWD may require specialized nutritional plans to support their growth and wound healing. This case series supports the theory that patients with ruptured omphaloceles may require higher calorie, protein, and micronutrient provisions in comparison to patients with intact omphaloceles, due to increased metabolic demand to support wound healing and skin epithelialization.


Subject(s)
Hernia, Umbilical , Nutrition Therapy , Humans , Infant , Infant, Newborn , Hernia, Umbilical/complications , Hernia, Umbilical/surgery
14.
Am J Surg ; 225(1): 122-128, 2023 01.
Article in English | MEDLINE | ID: mdl-36184328

ABSTRACT

INTRODUCTION: Area-based social determinants of health (SDoH) associated with disparities in children's surgical outcomes are not well understood, though some may be risk factors modifiable by public health interventions. METHODS: This retrospective cohort study investigated the effect of high social vulnerability index (SVI), defined as ≥90th percentile, on postoperative outcomes in children classified as ASA 1-2 who underwent surgery at a large institution participating in the National Surgical Quality Improvement Program (2015-2021). Primary outcome was serious postoperative complications, defined as postoperative death, unplanned re-operation, or readmission at 30 days after surgery. RESULTS: Among 3278 pediatric surgical procedures, 12.1% had SVI in the ≥90th percentile. Controlling for age, sex, racialization, insurance status, and language preference, serious postoperative complications were associated with high overall SVI (odds ratio [OR] 1.58, 95% confidence interval [CI] 1.02-2.44) and high socioeconomic vulnerability (SVI theme 1, OR 1.75, 95% CI 1.03-2.98). CONCLUSION: Neighborhood-level socioeconomic vulnerability is associated with worse surgical outcomes in apparently healthy children, which could serve as a target for community-based intervention.


Subject(s)
Postoperative Complications , Social Vulnerability , Child , Humans , Retrospective Studies , Risk Factors , Reoperation/adverse effects , Postoperative Complications/epidemiology , Postoperative Complications/etiology
15.
Front Public Health ; 10: 1045202, 2022.
Article in English | MEDLINE | ID: mdl-36530703

ABSTRACT

Introduction: The study aims to examine the trends of 4 metabolic NCDs risk factors including raised blood pressure, increased blood glucose, elevated blood lipids and overweight/obesity over the last 10 years in Vietnam as well as examine these trends among different sub-population by geographical area, gender, and age groups. Methods: The study combined the national representative data from three rounds of STEPs survey in Vietnam conducted in 2010, 2015, and 2020 on people aged 25-64 years. The overall prevalence of each metabolic factor together with 95% CI for each time point as well as the stratified prevalence by rural/urban, male/female, and 4 separated age groups were calculated and considered the sampling weight. Cochran-Armitage test for trend was used to test for the differences in the prevalence over time. Results: The prevalence of hypertension, overweight/obesity, hyperglycemia, and hyperlipidemia among the population aged 25-64 years old was 28.3, 20.57, 6.96, and 15.63%, respectively in the year 2020. All NCD metabolic risk factors examined in this analysis show significantly increasing trends over time. For most age groups, the increasing burden of NCD metabolic risk factors was more significant during the period 2015-2020 compared to the period 2010-2015. Male population and population aged 55-64 experienced the most dramatic changes in the burden of all NCD metabolic risk factors. Conclusion: To reverse the increasing trend of NCD metabolic factors in Vietnam, intervention, and policy need to apply a comprehensive life course approach.


Subject(s)
Noncommunicable Diseases , Male , Female , Humans , Adult , Middle Aged , Noncommunicable Diseases/epidemiology , Overweight/epidemiology , Vietnam/epidemiology , Time Factors , Cross-Sectional Studies , Risk Factors , Obesity/epidemiology
16.
PLoS Negl Trop Dis ; 16(5): e0010281, 2022 05.
Article in English | MEDLINE | ID: mdl-35507541

ABSTRACT

BACKGROUND: Dengue fever is highly endemic in Vietnam, but scrub typhus-although recognized as an endemic disease-remains underappreciated. These diseases together are likely to account for more than half of the acute undifferentiated fever burden in Vietnam. Scrub typhus (ST) is a bacterial disease requiring antimicrobial treatment, while dengue fever (DF) is of viral etiology and does not. The access to adequate diagnostics and the current understanding of empirical treatment strategies for both illnesses remain limited. In this study we aimed to contribute to the clinical decision process in the management of these two important etiologies of febrile illness in Vietnam. METHODS: Using retrospective data from 221 PCR-confirmed scrub typhus cases and 387 NS1 protein positive dengue fever patients admitted to five hospitals in Khanh Hoa province (central Vietnam), we defined predictive characteristics for both diseases that support simple clinical decision making with potential to inform decision algorithms in future. We developed models to discriminate scrub typhus from dengue fever using multivariable logistic regression (M-LR) and classification and regression trees (CART). Regression trees were developed for the entire data set initially and pruned, based on cross-validation. Regression models were developed in a training data set involving 60% of the total sample and validated in the complementary subsample. Probability cut points for the distinction between scrub typhus and dengue fever were chosen to maximise the sum of sensitivity and specificity. RESULTS: Using M-LR, following seven predictors were identified, that reliably differentiate ST from DF; eschar, regional lymphadenopathy, an occupation in nature, increased days of fever on admission, increased neutrophil count, decreased ratio of neutrophils/lymphocytes, and age over 40. Sensitivity and specificity of predictions based on these seven factors reached 93.7% and 99.5%, respectively. When excluding the "eschar" variable, the values dropped to 76.3% and 92.3%, respectively. The CART model generated one further variable; increased days of fever on admission, when eschar was included, the sensitivity and specificity was 95% and 96.9%, respectively. The model without eschar involved the following six variables; regional lymphadenopathy, increased days of fever on admission, increased neutrophil count, increased lymphocyte count, platelet count ≥ 47 G/L and age over 28 years as predictors of ST and provided a sensitivity of 77.4% and a specificity of 90.7%. CONCLUSIONS: The generated algorithms contribute to differentiating scrub typhus from dengue fever using basic clinical and laboratory parameters, supporting clinical decision making in areas where dengue and scrub typhus are co-endemic in Vietnam.


Subject(s)
Dengue , Lymphadenopathy , Orientia tsutsugamushi , Scrub Typhus , Adult , Dengue/complications , Dengue/diagnosis , Dengue/epidemiology , Fever/epidemiology , Humans , Retrospective Studies , Scrub Typhus/diagnosis , Scrub Typhus/epidemiology , Vietnam/epidemiology
17.
Med Care ; 60(6): 437-443, 2022 06 01.
Article in English | MEDLINE | ID: mdl-35315376

ABSTRACT

BACKGROUND: Access to health care continues to be a challenge, especially in remote areas. Since 2013, 70 rural hospitals have closed in the United States further exacerbating barriers to health care access in rural areas. OBJECTIVE: The objective of this study is to identify the impact of rural hospital closures on total medical spending and utilization among the commercially insured rural population. RESEARCH DESIGN: We use a pre-post study design with a comparison group. Individual-level Texas commercial claims data in 2014-2019 were linked to the Centers for Medicare & Medicaid Services (CMS) Provider of Services Current Files, Area Health Resource File, and Census American Community Survey. We performed an event study to test for pre-trends. SUBJECTS: Analysis sample included commercially insured individuals 19-64 years of age residing in Texas. MEASURES: Total medical spending and counts of health care encounters. RESULTS: Individuals residing in rural Texas areas affected by a hospital closure experienced decreases in outpatient and emergency department (ED) utilization and no statistically significant changes in total medical spending relative to the unaffected individuals. Outpatient and ED utilization decreased by 0.133 (<0.1) and 0.015 (7<0.05) visits, respectively. Heterogeneity analysis showed that individuals residing in urban Texas experienced increases in total medical spending by $12.2 per month (<0.01) as well as individual spending subcategories. CONCLUSIONS: Rural hospital closures led to significant decreases in outpatient and ED utilization while having no effect on health care spending. Close attention must be paid to rural hospital closures to ensure equitable health care access, especially for underserved populations.


Subject(s)
Health Facility Closure , Hospitals, Rural , Aged , Emergency Service, Hospital , Health Services Accessibility , Humans , Medicare , Rural Population , United States
18.
Bioorg Chem ; 121: 105676, 2022 04.
Article in English | MEDLINE | ID: mdl-35202850

ABSTRACT

A combinatorial method was devised and applied for the design and identification of substrate-analogue inhibitors of therapeutically relevant serine proteases, such as thrombin and factor Xa. We conceptualized imino acid derived diketomorpholines as generally applicable key intermediates prepared through solid-phase synthesis and prone to be cleaved with primary amines in a traceless fashion. The approach led to a compound library whose members were prepared under bioassay-compatible conditions and directly subjected to the in situ evaluation, allowing a fast prediction of hit compounds. Highly active inhibitors for serine proteases of the coagulation cascade have been identified. The most potent dual inhibitor, 16K, has a binding affinity of 23.9 nM to thrombin and 32.8 nM to factor Xa.


Subject(s)
Factor Xa , Thrombin , Factor Xa/chemistry , Factor Xa Inhibitors , Serine Endopeptidases/metabolism , Serine Proteases , Serine Proteinase Inhibitors/chemistry , Serine Proteinase Inhibitors/pharmacology
19.
J Am Coll Surg ; 234(3): 290-298, 2022 03 01.
Article in English | MEDLINE | ID: mdl-35213491

ABSTRACT

BACKGROUND: There is wide variation in opioid prescribing after appendectomy in children and adolescents, with recent increases noted in opioid-related pediatric deaths from prescription and illicit opioids. The goal of this project was to minimize opioid prescribing at the time of discharge for children undergoing appendectomy by using Quality Improvement (QI) methodology. STUDY DESIGN: Children (18 years of age or less) who underwent appendectomy were evaluated from January to December 2019 using NSQIP-Pediatric at 10 children's hospitals within the Western Pediatric Surgery Research Consortium. Before project initiation, 5 hospitals did not routinely prescribe opioids after appendectomy (protocol). At the remaining 5 hospitals, prescribing was not standardized and varied by surgeon (no-protocol). A prospective multi-institutional QI project was used to minimize outpatient opioid prescriptions for children after appendectomy. The proportion of children at each hospital receiving an opioid prescription at discharge was compared for 6 months before and after the intervention using chi-square analysis. RESULTS: Overall, 1,524 children who underwent appendectomy were evaluated from January to December 2019. After the QI intervention, overall opioid prescribing decreased from 18.2% to 4.0% (p < 0.001), with significant decreases in protocol hospitals (2.7% vs 0.8%, p = 0.038) and no-protocol hospitals (37.9% vs 8.8%, p < 0.001). The proportion of 30-day emergency room visits did not change after the QI intervention (8.9% vs 9.9%, p = 0.54) and mean postintervention pain management satisfaction scores were high. CONCLUSION: Opioid prescribing can be minimized in children after appendectomy without increasing emergency room visits or decreasing patient satisfaction. Furthermore, NSQIP-Pediatric can be used as a platform for multi-institutional collaboration for successful implementation of QI projects.


Subject(s)
Analgesics, Opioid , Appendectomy , Adolescent , Analgesics, Opioid/therapeutic use , Child , Humans , Pain, Postoperative/drug therapy , Pain, Postoperative/prevention & control , Practice Patterns, Physicians' , Prospective Studies , Quality Improvement
20.
Dysphagia ; 37(5): 1305-1313, 2022 10.
Article in English | MEDLINE | ID: mdl-34981254

ABSTRACT

Infants with congenital diaphragmatic hernia (CDH) who require non-invasive positive pressure ventilation or high flow nasal cannula are at risk for aspiration and delayed initiation of oral feeding. We developed a dysphagia provider-led protocol that involved early consultation with an occupational therapist or speech/language pathologist and modified barium swallow study (MBSS) to assess for readiness for oral feeding initiation/advancement on non-invasive positive pressure ventilation. The objective of this study was to retrospectively compare this intervention cohort to a historical control cohort to evaluate the protocol's impact on the time to initiate oral feeding. We describe the development and implementation of the protocol, the MBSS findings of the intervention cohort, and compared the control (n = 64) and intervention (n = 37) cohorts using Fischer's exact test and Mann-Whitney test. We found that both cohorts had similar prenatal and neonatal characteristics including age at extubation. Significantly more infants in the intervention cohort were on non-invasive positive pressure ventilation or high flow nasal cannula at the time of oral feeding initiation (84% vs. 28%, p < 0.0001). None of the control cohort infants underwent MBSS while on respiratory support. Of the intervention cohort, 15 infants underwent a MBSS while on non-invasive positive pressure ventilation; 6 had no evidence of laryngeal penetration and/or aspiration during swallowing. Infants in the control cohort initiated oral feeds significantly sooner after extubation (6 versus 11 days, p = 0.001) and attained full oral feeds earlier (20 days versus 28 days, p = 0.02) than the intervention group. There was no difference in the rate of gastrostomy tube placement (38%). Appropriate monitoring by a dysphagia provider and evaluation with clinical and radiological means are crucial to determine the safety of initiating oral feeding in term infants with CDH. Continued surveillance is needed to determine the long-term impact on oral feeding progression in this population.


Subject(s)
Deglutition Disorders , Hernias, Diaphragmatic, Congenital , Deglutition , Deglutition Disorders/epidemiology , Deglutition Disorders/etiology , Deglutition Disorders/therapy , Hernias, Diaphragmatic, Congenital/complications , Humans , Infant , Infant, Newborn , Positive-Pressure Respiration/methods , Retrospective Studies
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