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1.
Artículo en Inglés | MEDLINE | ID: mdl-38849235

RESUMEN

AIMS: WHO Grade 3 (G3) meningiomas are rare tumours with limited data to guide management. This retrospective study documents UK management approaches across 14 centres over 11 years. MATERIALS AND METHODS: Patients with WHO G3 meningioma between 01/01/2008 and 31/12/2018 were identified. Data were collected on demographics, management strategy, adjuvant radiotherapy, approach in recurrence setting and survival. RESULTS: 84 patients were identified. 21.4% transformed from lower-grade disease. 96.4% underwent primary surgical resection, with 20.8% having evidence of residual disease on their post-op MRI. 59.3% of patients underwent adjuvant radiotherapy (RT) following surgical resection. Overall median PFS and OS were 12.6 months and 28.2 months, respectively. Median OS in the group who underwent complete surgical resection was 34.9 months, compared to 27.5 months for those who had incomplete resection (HR 0.58, 95% CI 0.27-1.23, p = 0.15). Median OS was 33.1 months for those who underwent adjuvant RT and 14.0 months for those who did not (HR 0.48, 95% CI 0.27-0.84, p = 0.004). Median adjuvant RT dose delivered was 60Gy (range 12Gy-60Gy), 45.8% of adjuvant RT was delivered using IMRT. At disease relapse, 31% underwent salvage surgery and 29.3% underwent salvage RT. Of those treated with salvage RT, 64.7% were re-treats and all were treated with hypofractionated RT. CONCLUSION: Surgery continues to be the preferred primary management strategy. Post-operative MRI within 48 hours is indicated to assess presence of residual disease and guide further surgical options. Adjuvant radiotherapy plays an important part of the management paradigm in these patients with the data supporting an attached survival advantage. Further surgery and re-irradiation is an option in the disease recurrence setting with radiosurgery frequently utilised in this context.

2.
Nat Commun ; 15(1): 2917, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38575562

RESUMEN

VISTA, an inhibitory myeloid-T-cell checkpoint, holds promise as a target for cancer immunotherapy. However, its effective targeting has been impeded by issues such as rapid clearance and cytokine release syndrome observed with previous VISTA antibodies. Here we demonstrate that SNS-101, a newly developed pH-selective VISTA antibody, addresses these challenges. Structural and biochemical analyses confirmed the pH-selectivity and unique epitope targeted by SNS-101. These properties confer favorable pharmacokinetic and safety profiles on SNS-101. In syngeneic tumor models utilizing human VISTA knock-in mice, SNS-101 shows in vivo efficacy when combined with a PD-1 inhibitor, modulates cytokine and chemokine signaling, and alters the tumor microenvironment. In summary, SNS-101, currently in Phase I clinical trials, emerges as a promising therapeutic biologic for a wide range of patients whose cancer is refractory to current immunotherapy regimens.


Asunto(s)
Neoplasias , Receptor de Muerte Celular Programada 1 , Humanos , Ratones , Animales , Antígenos B7 , Anticuerpos , Neoplasias/tratamiento farmacológico , Inmunoterapia , Concentración de Iones de Hidrógeno , Microambiente Tumoral
3.
Cell Rep ; 43(2): 113678, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38236773

RESUMEN

The DNAJ-PKAc fusion kinase is a defining feature of fibrolamellar carcinoma (FLC). FLC tumors are notoriously resistant to standard chemotherapies, with aberrant kinase activity assumed to be a contributing factor. By combining proximity proteomics, biochemical analyses, and live-cell photoactivation microscopy, we demonstrate that DNAJ-PKAc is not constrained by A-kinase anchoring proteins. Consequently, the fusion kinase phosphorylates a unique array of substrates, including proteins involved in translation and the anti-apoptotic factor Bcl-2-associated athanogene 2 (BAG2), a co-chaperone recruited to the fusion kinase through association with Hsp70. Tissue samples from patients with FLC exhibit increased levels of BAG2 in primary and metastatic tumors. Furthermore, drug studies implicate the DNAJ-PKAc/Hsp70/BAG2 axis in potentiating chemotherapeutic resistance. We find that the Bcl-2 inhibitor navitoclax enhances sensitivity to etoposide-induced apoptosis in cells expressing DNAJ-PKAc. Thus, our work indicates BAG2 as a marker for advanced FLC and a chemotherapeutic resistance factor in DNAJ-PKAc signaling scaffolds.


Asunto(s)
Carcinoma Hepatocelular , Humanos , Supervivencia Celular , Carcinoma Hepatocelular/tratamiento farmacológico , Apoptosis , Proteínas HSP70 de Choque Térmico , Proteínas Proto-Oncogénicas c-bcl-2 , Chaperonas Moleculares
4.
Front Med (Lausanne) ; 10: 1089087, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37859860

RESUMEN

Background: The gold standard for gathering data from electronic health records (EHR) has been manual data extraction; however, this requires vast resources and personnel. Automation of this process reduces resource burdens and expands research opportunities. Objective: This study aimed to determine the feasibility and reliability of automated data extraction in a large registry of adult COVID-19 patients. Materials and methods: This observational study included data from sites participating in the SCCM Discovery VIRUS COVID-19 registry. Important demographic, comorbidity, and outcome variables were chosen for manual and automated extraction for the feasibility dataset. We quantified the degree of agreement with Cohen's kappa statistics for categorical variables. The sensitivity and specificity were also assessed. Correlations for continuous variables were assessed with Pearson's correlation coefficient and Bland-Altman plots. The strength of agreement was defined as almost perfect (0.81-1.00), substantial (0.61-0.80), and moderate (0.41-0.60) based on kappa statistics. Pearson correlations were classified as trivial (0.00-0.30), low (0.30-0.50), moderate (0.50-0.70), high (0.70-0.90), and extremely high (0.90-1.00). Measurements and main results: The cohort included 652 patients from 11 sites. The agreement between manual and automated extraction for categorical variables was almost perfect in 13 (72.2%) variables (Race, Ethnicity, Sex, Coronary Artery Disease, Hypertension, Congestive Heart Failure, Asthma, Diabetes Mellitus, ICU admission rate, IMV rate, HFNC rate, ICU and Hospital Discharge Status), and substantial in five (27.8%) (COPD, CKD, Dyslipidemia/Hyperlipidemia, NIMV, and ECMO rate). The correlations were extremely high in three (42.9%) variables (age, weight, and hospital LOS) and high in four (57.1%) of the continuous variables (Height, Days to ICU admission, ICU LOS, and IMV days). The average sensitivity and specificity for the categorical data were 90.7 and 96.9%. Conclusion and relevance: Our study confirms the feasibility and validity of an automated process to gather data from the EHR.

5.
Ann R Coll Surg Engl ; 105(8): 683-684, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37906974
6.
Antibodies (Basel) ; 12(3)2023 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-37753969

RESUMEN

Immune checkpoints and other immunoregulatory targets can be difficult to precisely target due to expression on non-tumor immune cells critical to maintaining immune homeostasis in healthy tissues. On-target/off-tumor binding of therapeutics results in significant pharmacokinetic and pharmacodynamic problems. Target-mediated drug disposition (TMDD) significantly limits effective intratumoral drug levels and adversely affects anti-tumor efficacy. Target engagement outside the tumor environment may lead to severe immune-related adverse events (irAEs), resulting in a narrowing of the therapeutic window, sub-optimal dosing, or cessation of drug development altogether. Overcoming these challenges has become tractable through recent advances in antibody engineering and screening approaches. Here, we review the discovery and development of conditionally active antibodies with minimal binding to target at physiologic pH but high-affinity target binding at the low pH of the tumor microenvironment by focusing on the discovery and improved properties of pH-dependent mAbs targeting two T cell checkpoints, VISTA and CTLA-4.

7.
bioRxiv ; 2023 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-37425703

RESUMEN

The DNAJ-PKAc fusion kinase is a defining feature of the adolescent liver cancer fibrolamellar carcinoma (FLC). A single lesion on chromosome 19 generates this mutant kinase by creating a fused gene encoding the chaperonin binding domain of Hsp40 (DNAJ) in frame with the catalytic core of protein kinase A (PKAc). FLC tumors are notoriously resistant to standard chemotherapies. Aberrant kinase activity is assumed to be a contributing factor. Yet recruitment of binding partners, such as the chaperone Hsp70, implies that the scaffolding function of DNAJ- PKAc may also underlie pathogenesis. By combining proximity proteomics with biochemical analyses and photoactivation live-cell imaging we demonstrate that DNAJ-PKAc is not constrained by A-kinase anchoring proteins. Consequently, the fusion kinase phosphorylates a unique array of substrates. One validated DNAJ-PKAc target is the Bcl-2 associated athanogene 2 (BAG2), a co-chaperone recruited to the fusion kinase through association with Hsp70. Immunoblot and immunohistochemical analyses of FLC patient samples correlate increased levels of BAG2 with advanced disease and metastatic recurrences. BAG2 is linked to Bcl-2, an anti-apoptotic factor that delays cell death. Pharmacological approaches tested if the DNAJ- PKAc/Hsp70/BAG2 axis contributes to chemotherapeutic resistance in AML12 DNAJ-PKAc hepatocyte cell lines using the DNA damaging agent etoposide and the Bcl-2 inhibitor navitoclax. Wildtype AML12 cells were susceptible to each drug alone and in combination. In contrast, AML12 DNAJ-PKAc cells were moderately affected by etoposide, resistant to navitoclax, but markedly susceptible to the drug combination. These studies implicate BAG2 as a biomarker for advanced FLC and a chemotherapeutic resistance factor in DNAJ-PKAc signaling scaffolds.

8.
J Dent Res ; 102(11): 1261-1271, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37475472

RESUMEN

Coordinated mineralization of soft tissue is central to organismal form and function, while dysregulated mineralization underlies several human pathologies. Oral epithelial-derived ameloblasts are polarized, secretory cells responsible for generating enamel, the most mineralized substance in the human body. Defects in ameloblast development result in enamel anomalies, including amelogenesis imperfecta. Identifying proteins critical in ameloblast development can provide insight into specific pathologies associated with enamel-related disorders or, more broadly, mechanisms of mineralization. Previous studies identified a role for MEMO1 in bone mineralization; however, whether MEMO1 functions in the generation of additional mineralized structures remains unknown. Here, we identify a critical role for MEMO1 in enamel mineralization. First, we show that Memo1 is expressed in ameloblasts and, second, that its conditional deletion from ameloblasts results in enamel defects, characterized by a decline in mineral density and tooth integrity. Histology revealed that the mineralization defects in Memo1 mutant ameloblasts correlated with a disruption in ameloblast morphology. Finally, molecular profiling of ameloblasts and their progenitors in Memo1 oral epithelial mutants revealed a disruption to cytoskeletal-associated genes and a reduction in late-stage ameloblast markers, relative to controls. Collectively, our findings integrate MEMO1 into an emerging network of molecules important for ameloblast development and provide a system to further interrogate the relationship of cytoskeletal and amelogenesis-related defects.

9.
Artículo en Inglés | MEDLINE | ID: mdl-37297557

RESUMEN

During the COVID-19 pandemic, healthcare workers (HCW) were categorized as "essential" and "non-essential", creating a division where some were "locked-in" a system with little ability to prepare for or control the oncoming crisis. Others were "locked-out" regardless of whether their skills might be useful. The purpose of this study was to systematically gather data over the course of the COVID-19 pandemic from HCW through an interprofessional lens to examine experiences of locked-out HCW. This convergent parallel mixed-methods study captured perspectives representing nearly two dozen professions through a survey, administered via social media, and video blogs. Analysis included logistic regression models of differences in outcome measures by professional category and Rapid Identification of Themes from Audio recordings (RITA) of video blogs. We collected 1299 baseline responses from 15 April 2020 to 16 March 2021. Of those responses, 12.1% reported no signs of burnout, while 21.9% reported four or more signs. Qualitative analysis identified four themes: (1) professional identity, (2) intrinsic stressors, (3) extrinsic factors, and (4) coping strategies. There are some differences in the experiences of locked-in and locked-out HCW. This did not always lead to differing reports of moral distress and burnout, and both groups struggled to cope with the realities of the pandemic.


Asunto(s)
Agotamiento Profesional , COVID-19 , Humanos , COVID-19/epidemiología , Pandemias , Adaptación Psicológica , Blogging , Personal de Salud
10.
Crit Care Explor ; 5(4): e0893, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37025303

RESUMEN

COVID-19 highlighted the need for use of real-world data (RWD) in critical care as a near real-time resource for clinical, research, and policy efforts. Analysis of RWD is gaining momentum and can generate important evidence for policy makers and regulators. Extracting high quality RWD from electronic health records (EHRs) requires sophisticated infrastructure and dedicated resources. We sought to customize freely available public tools, supporting all phases of data harmonization, from data quality assessments to de-identification procedures, and generation of robust, data science ready RWD from EHRs. These data are made available to clinicians and researchers through CURE ID, a free platform which facilitates access to case reports of challenging clinical cases and repurposed treatments hosted by the National Center for Advancing Translational Sciences/National Institutes of Health in partnership with the Food and Drug Administration. This commentary describes the partnership, rationale, process, use case, impact in critical care, and future directions for this collaborative effort.

11.
Matern Child Health J ; 27(6): 1043-1050, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36939951

RESUMEN

OBJECTIVES: We sought to identify the most common diagnostic categories linked to dispensed opioid prescriptions among children 1-36 months old and changes in patterns over the years 2000 to 2017. METHODS: This study used South Carolina's Medicaid claims data of pediatric dispensed outpatient opioid prescriptions between 2000 and 2017. The major opioid-related diagnostic category (indication) for each prescription was identified using visit primary diagnoses and the Clinical Classification System (AHRQ-CCS) software. The variables of interest were the rate of opioid prescriptions per 1,000 visits for each diagnostic category and the relative percentage of opioid prescriptions assigned to each category compared to all categories. RESULTS: Six major diagnostic categories were identified; Diseases of the respiratory system (RESP), Congenital anomalies (CONG), Injury (INJURY), Diseases of the nervous system and sense organs (NEURO), Diseases of the digestive system (GI), and Diseases of the genitourinary system (GU). The overall rate of dispensed opioid prescriptions per category declined significantly for four diagnostic categories throughout the study period, RESP by 15.13, INJURY by 8.49, NEURO by 7.33, and GI by 5.93. Two categories increased during the same time, CONG (by 9.47) and GU (by 6.98). RESP was the most prevalent category linked to a dispensed opioid prescription within 2010-2012 (almost 25%) but CONG was the most prevalent by 2014 (17.77%). CONCLUSIONS FOR PRACTICE: Among Medicaid children 1-36 months old, annual dispensed opioid prescription rates declined for most major diagnostic categories (RESP, INJURY, NEURO, and GI). Future studies should explore alternatives to current opioid dispensing practices for GU and CONG cases.


Asunto(s)
Analgésicos Opioides , Medicaid , Estados Unidos , Humanos , Niño , Lactante , Preescolar , Analgésicos Opioides/uso terapéutico , Pacientes Ambulatorios , Prescripciones de Medicamentos , Pautas de la Práctica en Medicina
12.
BMC Health Serv Res ; 23(1): 168, 2023 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-36803696

RESUMEN

BACKGROUND: Sexual and gender minorities (SGM) in the Southern United States face challenges in accessing sexual and gender affirming health care. Alternative care models, like inclusive mobile clinics, help mitigate barriers to care for SGM. There is limited data in the literature on the experience of medical referral processes for SGM individuals accessing services from mobile health clinics. AIMS AND OBJECTIVES: The purpose of this study is to describe the medical referral experiences of SGM clients and their providers at a mobile health clinic in the Southern United States. METHODS: We recruited English-speaking individuals who provided care or received care from the mobile health clinic in South Carolina between June 2019 and August 2020. Participants completed a brief demographic survey and a virtual in-depth, semi-structured individual interview. Data analysis was conducted using an iterative process to generate codes, categories, and themes. Data collection and analysis were terminated once thematic saturation was achieved. RESULTS: The findings from this study indicated that the mobile health clinic had an inconsistent referral process that was largely dependent on providers' knowledge. Furthermore, clients and providers expressed individual barriers to the referral process, such as financial barriers, and opportunities to improve the referral process, such as an opt-in follow-up from the mobile clinic and increased mobile clinic resources. CONCLUSION: The findings in this study underscore the importance of having mobile clinics create a structured referral process that all medical providers are familiar with, and the value of hiring patient navigators that can support and refer clients to care that goes beyond the mobile health clinic setting.


Asunto(s)
Unidades Móviles de Salud , Minorías Sexuales y de Género , Humanos , South Carolina , Salud Pública , Identidad de Género , Derivación y Consulta
13.
Ethn Health ; 28(4): 562-585, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-35608909

RESUMEN

OBJECTIVES: Obesity and its sequelae are an increasing problem, disproportionally affecting Maori and Pacific peoples, secondary to multifactorial systemic causes, including the effects of colonisation and the impact of globalisation. There is limited synthesised evidence on interventions to address obesity in these populations. The objective of this review is to identify evaluated interventions for prevention and management of obesity amongst Maori and Pacific adults, assess the effectiveness of these interventions, and identify enablers and barriers to their uptake. DESIGN: Systematic review of databases (Medline, PubMed, EMBASE, CINAHL, Scopus, CENTRAL), key non-indexed journals, and reference lists of included articles were searched from inception to June 2021. Eligibility criteria defined using a Population, Intervention, Control, Outcome format and study/publication characteristics. Quantitative and qualitative data were extracted and analysed using narrative syntheses. Study quality was assessed using modified GRADE approach. RESULTS: From the 8190 articles identified, 21 were included, with 18 eligible for quantitative and five for qualitative analysis. The studies were heterogenous, with most graded as low quality. Some studies reported small but statistically significant improvements in weight and body mass index. Key enablers identified were social connection, making achievable sustainable lifestyle changes, culturally-centred interventions and incentives including money and enjoyment. Barriers to intervention uptake included difficulty in maintaining adherence to a programme due to intrinsic programme factors such as lack of social support and malfunctioning or lost equipment. CONCLUSIONS: Normal weight trajectory is progressive increase over time. Modest weight loss or no weight gain after several years may have a positive outcome in lowering progression to diabetes, or improvement of glycaemic control in people with diabetes. We recommend urgent implementation of Maori and Pacific-led, culturally-tailored weight loss programmes that promote holistic, small and sustainable lifestyle changes delivered in socially appropriate contexts.


Asunto(s)
Asistencia Sanitaria Culturalmente Competente , Pueblo Maorí , Obesidad , Programas de Reducción de Peso , Adulto , Humanos , Pueblo Maorí/estadística & datos numéricos , Obesidad/epidemiología , Obesidad/prevención & control , Obesidad/terapia , Pueblos Isleños del Pacífico/estadística & datos numéricos , Apoyo Social , Asistencia Sanitaria Culturalmente Competente/métodos , Estilo de Vida Saludable , Programas de Reducción de Peso/métodos , Competencia Cultural
14.
iScience ; 25(7): 104636, 2022 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-35800760

RESUMEN

Microbial inoculants containing arbuscular mycorrhizal (AM) fungi are potential tools in increasing the sustainability of our food production systems. Given the demand for sustainable agriculture, the production of such inoculants has potential economic value and has resulted in a variety of commercial inoculants currently being advertised. However, their use is limited by inconsistent product efficacy and lack of consumer confidence. Here, we propose a framework that can be used to assess the quality and reliability of AM inoculants. First, we set out a range of basic quality criteria which are required to achieve reliable inoculants. This is followed by a standardized bioassay which can be used to test inoculum viability and efficacy under controlled conditions. Implementation of these measurements would contribute to the adoption of AM inoculants by producers with the potential to increase sustainability in food production systems.

15.
Cell Rep ; 40(2): 111073, 2022 07 12.
Artículo en Inglés | MEDLINE | ID: mdl-35830806

RESUMEN

Mutations in the catalytic subunit of protein kinase A (PKAc) drive the stress hormone disorder adrenal Cushing's syndrome. We define mechanisms of action for the PKAc-L205R and W196R variants. Proximity proteomic techniques demonstrate that both Cushing's mutants are excluded from A kinase-anchoring protein (AKAP)-signaling islands, whereas live-cell photoactivation microscopy reveals that these kinase mutants indiscriminately diffuse throughout the cell. Only cAMP analog drugs that displace native PKAc from AKAPs enhance cortisol release. Rescue experiments that incorporate PKAc mutants into AKAP complexes abolish cortisol overproduction, indicating that kinase anchoring restores normal endocrine function. Analyses of adrenal-specific PKAc-W196R knockin mice and Cushing's syndrome patient tissue reveal defective signaling mechanisms of the disease. Surprisingly each Cushing's mutant engages a different mitogenic-signaling pathway, with upregulation of YAP/TAZ by PKAc-L205R and ERK kinase activation by PKAc-W196R. Thus, aberrant spatiotemporal regulation of each Cushing's variant promotes the transmission of distinct downstream pathogenic signals.


Asunto(s)
Síndrome de Cushing , Animales , Dominio Catalítico/genética , Síndrome de Cushing/genética , Síndrome de Cushing/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Hidrocortisona/metabolismo , Ratones , Proteómica
16.
J Pain Symptom Manage ; 64(4): 359-369, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35764202

RESUMEN

CONTEXT: The COVID-19 pandemic has highlighted variability in intensity of care. We aimed to characterize intensity of care among hospitalized patients with COVID-19. OBJECTIVES: Examine the prevalence and predictors of admission code status, palliative care consultation, comfort-measures-only orders, and cardiopulmonary resuscitation (CPR) among patients hospitalized with COVID-19. METHODS: This cross-sectional study examined data from an international registry of hospitalized patients with COVID-19. A proportional odds model evaluated predictors of more aggressive code status (i.e., Full Code) vs. less (i.e., Do Not Resuscitate, DNR). Among decedents, logistic regression was used to identify predictors of palliative care consultation, comfort measures only, and CPR at time of death. RESULTS: We included 29,923 patients across 179 sites. Among those with admission code status documented, Full Code was selected by 90% (n = 15,273). Adjusting for site, Full Code was more likely for patients who were of Black or Asian race (ORs 1.82, 95% CIs 1.5-2.19; 1.78, 1.15-3.09 respectively, relative to White race), Hispanic ethnicity (OR 1.89, CI 1.35-2.32), and male sex (OR 1.16, CI 1.0-1.33). Of the 4951 decedents, 29% received palliative care consultation, 59% transitioned to comfort measures only, and 29% received CPR, with non-White racial and ethnic groups less likely to receive comfort measures only and more likely to receive CPR. CONCLUSION: In this international cohort of patients with COVID-19, Full Code was the initial code status in the majority, and more likely among patients who were Black or Asian race, Hispanic ethnicity or male. These results provide direction for future studies to improve these disparities in care.


Asunto(s)
COVID-19 , Cuidado Terminal , COVID-19/terapia , Estudios Transversales , Humanos , Masculino , Pandemias , Órdenes de Resucitación , Estudios Retrospectivos
17.
Ann R Coll Surg Engl ; 104(5): 392, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35491680

RESUMEN

CORESS is an independent charity, supported by the AXA Health, the MDU and the WPA Benevolent Foundation We are grateful to those who have provided the material for these reports. The online reporting form is available on the website (www.coress.org.uk), which also includes previous Feedback reports. Published cases will be acknowledged by a Certificate of Contribution, which may be included in the contributor's record of continuing professional development or may form part of appraisal or annual review of competence progression (ARCP) portfolio documentation. Trainee contributions are particularly welcome.


Asunto(s)
Documentación , Retroalimentación , Humanos
18.
World J Crit Care Med ; 11(2): 102-111, 2022 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-35433315

RESUMEN

BACKGROUND: The coronavirus disease 2019 (COVID-19) course may be affected by environmental factors. Ecological studies previously suggested a link between climatological factors and COVID-19 fatality rates. However, individual-level impact of these factors has not been thoroughly evaluated yet. AIM: To study the association of climatological factors related to patient location with unfavorable outcomes in patients. METHODS: In this observational analysis of the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study: COVID-19 Registry cohort, the latitudes and altitudes of hospitals were examined as a covariate for mortality within 28 d of admission and the length of hospital stay. Adjusting for baseline parameters and admission date, multivariable regression modeling was utilized. Generalized estimating equations were used to fit the models. RESULTS: Twenty-two thousand one hundred eight patients from over 20 countries were evaluated. The median age was 62 (interquartile range: 49-74) years, and 54% of the included patients were males. The median age increased with increasing latitude as well as the frequency of comorbidities. Contrarily, the percentage of comorbidities was lower in elevated altitudes. Mortality within 28 d of hospital admission was found to be 25%. The median hospital-free days among all included patients was 20 d. Despite the significant linear relationship between mortality and hospital-free days (adjusted odds ratio (aOR) = 1.39 (1.04, 1.86), P = 0.025 for mortality within 28 d of admission; aOR = -1.47 (-2.60, -0.33), P = 0.011 for hospital-free days), suggesting that adverse patient outcomes were more common in locations further away from the Equator; the results were no longer significant when adjusted for baseline differences (aOR = 1.32 (1.00, 1.74), P = 0.051 for 28-day mortality; aOR = -1.07 (-2.13, -0.01), P = 0.050 for hospital-free days). When we looked at the altitude's effect, we discovered that it demonstrated a non-linear association with mortality within 28 d of hospital admission (aOR = 0.96 (0.62, 1.47), 1.04 (0.92, 1.19), 0.49 (0.22, 0.90), and 0.51 (0.27, 0.98), for the altitude points of 75 MASL, 125 MASL, 400 MASL, and 600 MASL, in comparison to the reference altitude of 148 m.a.s.l, respectively. P = 0.001). We detected an association between latitude and 28-day mortality as well as hospital-free days in this worldwide study. When the baseline features were taken into account, however, this did not stay significant. CONCLUSION: Our findings suggest that differences observed in previous epidemiological studies may be due to ecological fallacy rather than implying a causal relationship at the patient level.

19.
Acad Pediatr ; 22(4): 631-639, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35257927

RESUMEN

OBJECTIVE: To examine dispensed opioid prescription patterns for limb fractures across racial/ethnic groups in a pediatric population. METHODS: We used South Carolina's Medicaid claims data 2000 to 2018 for pediatric limb fracture cases (under age 19) discharged from the emergency department. The key independent variable was the child's race/ethnicity. The outcomes were: 1) whether the patient had a dispensed opioid prescription; and 2) whether dispensed opioid supply was longer than 5 days among cases with any dispensed opioid prescriptions. Logistic regression models were used to test the association between race/ethnicity and the outcomes. Covariates included age-at-service, gender, service year, and having multiple fracture injuries. RESULTS: Compared with non-Hispanic White cases (NHW), the odds of receiving dispensed opioid prescriptions were lower for cases of non-Hispanic Black (NHB) (OR = 0.73; 95% confidence interval [CI]: 0.71, 0.75), Asian (OR = 0.69; CI: 0.53, 0.90), Other/Unknown (OR = 0.86; CI: 0.80, 0.92), and Hispanic (OR = 0.84; CI: 0.79, 0.90) race/ethnicity. The odds of receiving >5 days of dispensed opioid prescription supply did not differ significantly among race/ethnic categories. CONCLUSIONS: Our study confirms previous findings that as compared to NHW, the NHB children were less likely to receive dispensed opioid prescriptions. Also, it reveals that the different minority race/ethnic groups are not homogenous in their likelihoods of receiving dispensed opioid prescriptions after a limb fracture compared to NHW, findings underreported in previous studies. Children in the Other/Unknown race/ethnicity category have prescribing patterns different from those of other minority race/ethnic groups and should be analyzed separately.


Asunto(s)
Analgésicos Opioides , Fracturas Óseas , Adulto , Analgésicos Opioides/uso terapéutico , Niño , Etnicidad , Fracturas Óseas/tratamiento farmacológico , Fracturas Óseas/epidemiología , Humanos , Medicaid , Pautas de la Práctica en Medicina , Prescripciones , South Carolina , Estados Unidos , Adulto Joven
20.
Am J Public Health ; 112(1): 34-37, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34936400

RESUMEN

We implemented the HIV preexposure prophylaxis (PrEP) care continuum among individuals receiving medication for opioid use disorder (MOUD). We screened HIV-negative MOUD participants for PrEP eligibility by assessing injection drug use risk factors and sexual behaviors. Implementation of the PrEP care continuum was challenging; less than a third of MOUD participants were aware of PrEP, and very few initiated PrEP. Findings should promote the development of effective interventions to increase engagement in PrEP during MOUD treatment. (Am J Public Health. 2022;112(1):34-37. https://doi.org/10.2105/AJPH.2021.306566).


Asunto(s)
Continuidad de la Atención al Paciente , Infecciones por VIH/prevención & control , Tratamiento de Sustitución de Opiáceos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Profilaxis Pre-Exposición , Adulto , Humanos , Cumplimiento de la Medicación , Medición de Riesgo/métodos , South Carolina/epidemiología
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