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1.
Nature ; 624(7992): 621-629, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38049589

RESUMO

Type 2 diabetes mellitus (T2D), a major cause of worldwide morbidity and mortality, is characterized by dysfunction of insulin-producing pancreatic islet ß cells1,2. T2D genome-wide association studies (GWAS) have identified hundreds of signals in non-coding and ß cell regulatory genomic regions, but deciphering their biological mechanisms remains challenging3-5. Here, to identify early disease-driving events, we performed traditional and multiplexed pancreatic tissue imaging, sorted-islet cell transcriptomics and islet functional analysis of early-stage T2D and control donors. By integrating diverse modalities, we show that early-stage T2D is characterized by ß cell-intrinsic defects that can be proportioned into gene regulatory modules with enrichment in signals of genetic risk. After identifying the ß cell hub gene and transcription factor RFX6 within one such module, we demonstrated multiple layers of genetic risk that converge on an RFX6-mediated network to reduce insulin secretion by ß cells. RFX6 perturbation in primary human islet cells alters ß cell chromatin architecture at regions enriched for T2D GWAS signals, and population-scale genetic analyses causally link genetically predicted reduced RFX6 expression with increased T2D risk. Understanding the molecular mechanisms of complex, systemic diseases necessitates integration of signals from multiple molecules, cells, organs and individuals, and thus we anticipate that this approach will be a useful template to identify and validate key regulatory networks and master hub genes for other diseases or traits using GWAS data.


Assuntos
Diabetes Mellitus Tipo 2 , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Predisposição Genética para Doença , Ilhotas Pancreáticas , Humanos , Estudos de Casos e Controles , Separação Celular , Cromatina/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/fisiopatologia , Redes Reguladoras de Genes/genética , Estudo de Associação Genômica Ampla , Secreção de Insulina , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/patologia , Reprodutibilidade dos Testes
2.
Am J Epidemiol ; 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38907307

RESUMO

Pharmacoepidemiological studies commonly examine the association between drug dose and adverse health outcomes. In situations where no safe dose exists, the choice of modeling strategy can lead to identification of an apparent safe low dose range in the presence of a non-linear relationship or due to the modeling strategy forcing a linear relationship through a dose of 0. We conducted a simulation study to assess the performance of several regression approaches to model the drug dose-response curve at low doses in a setting where no safe range exists, including the use of a (1) linear dose term, (2) categorical dose term, and (3) natural cubic spline terms. Additionally, we introduce and apply an expansion of prior work related to modeling dose-response curves at low and infrequently used doses in the setting of no safe dose ("spike-at-zero" and "slab-and-spline"). Furthermore, we demonstrate and empirically assess the use of these regression strategies in a practical scenario examining the association between the dose of the initial postpartum opioid prescribed after vaginal delivery and the subsequent total dose of opioids prescribed in the entire postpartum period among a cohort of opioid-naïve women with a vaginal delivery enrolled in a State Medicaid program (2007-2014).

3.
J Surg Res ; 295: 289-295, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38056355

RESUMO

INTRODUCTION: Abdominal wall reconstruction (AWR) utilizes advanced myofascial releases to perform complex ventral hernia repair (VHR). The relationship between the performance of AWR and disparities in insurance type is unknown. METHODS: The Abdominal Core Health Quality Collaborative was queried for adults who had undergone an elective VHR between 2013 and 2020 with a hernia size ≥10 cm. Patients with missing insurance data were excluded. Comparison groups were divided by insurance type: favorable (private, Medicare, Veteran's Administration, Tricare) or unfavorable (Medicaid and self-pay). Propensity score matching compared the cumulative incidence of AWR between the favorable and unfavorable insurance comparison groups. RESULTS: In total, 26,447 subjects met inclusion criteria. The majority (89%, n = 23,617) had favorable insurance, while (11%, n = 2830) had unfavorable insurance. After propensity score matching, 2821 patients with unfavorable insurance were matched to 7875 patients with favorable insurance. The rate of AWR with external oblique release or transversus abdominis release was significantly higher (23%, n = 655) among the unfavorable insurance group compared to those with favorable insurance (21%, n = 1651; P = 0.013). CONCLUSIONS: This study provides evidence that patients with unfavorable insurance may undergo AWR with external oblique or transversus abdominis release at a greater rate than similar patients with favorable insurance. Understanding the mechanisms contributing to this difference and evaluating the financial implications of these trends represent important directions for future research in elective VHR.


Assuntos
Parede Abdominal , Hérnia Ventral , Estados Unidos , Adulto , Humanos , Idoso , Parede Abdominal/cirurgia , Terapia de Liberação Miofascial , Medicare , Hérnia Ventral/cirurgia , Músculos Abdominais/cirurgia , Herniorrafia , Telas Cirúrgicas , Estudos Retrospectivos
4.
Surg Endosc ; 38(5): 2871-2878, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38609587

RESUMO

BACKGROUND: The use of mesh is standard of care for large ventral hernias repaired on an elective basis. The most used type of mesh includes synthetic polypropylene mesh; however, there has been an increase in the usage of a new polyester self-gripping mesh, and there are limited data regarding its efficacy for ventral hernia. The purpose of the study is to determine whether there is a difference in surgical site occurrence (SSO), surgical site infection (SSI), surgical site occurrence requiring procedural intervention (SSOPI), and recurrence at 30 days after ventral hernia repair (VHR) using self-gripping (SGM) versus non-self-gripping mesh (NSGM). METHODS: We performed a retrospective study from January 2014 to April 2022 using the Abdominal Core Health Quality Collaborative (ACHQC). We collected data on patients over 18 years of age who underwent elective open VHR using SGM or NSGM and whom had 30-day follow-up. Propensity matching was utilized to control for variables including hernia width, body mass index, age, ASA, and mesh location. Data were analyzed to identify differences in SSO, SSI, SSOPI, and recurrence at 30 days. RESULTS: 9038 patients were identified. After propensity matching, 1766 patients were included in the study population. Patients with SGM had similar demographic and clinical characteristics compared to NSGM. The mean hernia width to mesh width ratio was 8 cm:18 cm with NSGM and 7 cm:15 cm with SGM (p = 0.63). There was no difference in 30-day rates of recurrence, SSI or SSO. The rate of SSOPI was also found to be 5.4% in the nonself-gripping group compared to 3.1% in the self-gripping mesh group (p < .005). There was no difference in patient-reported outcomes at 30 days. CONCLUSIONS: In patients undergoing ventral hernia repair with mesh, self-gripping mesh is a safe type of mesh to use. Use of self-gripping mesh may be associated with lower rates of SSOPI when compared to nonself-gripping mesh.


Assuntos
Hérnia Ventral , Herniorrafia , Recidiva , Telas Cirúrgicas , Humanos , Hérnia Ventral/cirurgia , Estudos Retrospectivos , Masculino , Feminino , Herniorrafia/métodos , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/epidemiologia , Adulto , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
5.
Surg Endosc ; 38(6): 3433-3440, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38710888

RESUMO

INTRODUCTION: Fixation of mesh during minimally invasive inguinal hernia repair is thought to contribute to chronic post-herniorrhaphy groin pain (CGP). In contrast to permanent tacks, absorbable tacks are hypothesized to minimize the likelihood of CGP. This study aimed to compare the rates of CGP after laparoscopic inguinal hernia repair between absorbable versus permanent fixation at maximum follow-up. METHODS: This is a post hoc analysis of a randomized controlled trial in patients undergoing laparoscopic inguinal hernia repair (NCT03835351). All patients were contacted at maximum follow-up after surgery to administer EuraHS quality of life (QoL) surveys. The pain and restriction of activity subdomains of the survey were utilized. The primary outcome was rate of CGP, as defined by a EuraHS QoL pain domain score ≥ 4 measured at ≥ 1 year postoperatively. The secondary outcomes were pain and restriction of activity domain scores and hernia recurrence at maximum follow-up. RESULTS: A total of 338 patients were contacted at a mean follow-up of 28 ± 11 months. 181 patients received permanent tacks and 157 patients received absorbable tacks during their repair. At maximum follow-up, the rates of CGP (27 [15%] vs 28 [18%], P = 0.47), average pain scores (1.78 ± 4.38 vs 2.32 ± 5.40, P = 0.22), restriction of activity scores (1.39 ± 4.32 vs 2.48 ± 7.45, P = 0.18), and the number of patients who reported an inguinal bulge (18 [9.9%] vs 15 [9.5%], P = 0.9) were similar between patients with permanent versus absorbable tacks. On multivariable analysis, there was no significant difference in the odds of CGP between the two groups (OR 1.23, 95% CI [0.60, 2.50]). CONCLUSION: Mesh fixation with permanent tacks does not appear to increase the risk of CGP after laparoscopic inguinal hernia repair when compared to fixation with absorbable tacks. Prospective trials are needed to further evaluate this relationship.


Assuntos
Implantes Absorvíveis , Dor Crônica , Virilha , Hérnia Inguinal , Herniorrafia , Laparoscopia , Dor Pós-Operatória , Telas Cirúrgicas , Humanos , Hérnia Inguinal/cirurgia , Laparoscopia/métodos , Laparoscopia/efeitos adversos , Herniorrafia/métodos , Herniorrafia/efeitos adversos , Masculino , Dor Pós-Operatória/etiologia , Pessoa de Meia-Idade , Feminino , Virilha/cirurgia , Dor Crônica/etiologia , Idoso , Qualidade de Vida , Seguimentos , Adulto
6.
Artigo em Inglês | MEDLINE | ID: mdl-38441815

RESUMO

Attention-deficit/hyperactivity disorder (ADHD) is highly prevalent in early childhood and has long-term negative effects when left untreated. Parent-Child Interaction Therapy (PCIT) is an early intervention for children aged 2- to-7-years that has extensive evidence for treating child externalizing problems by teaching parents effective strategies to manage child behavior. However, the effect of PCIT for families with children diagnosed with ADHD is not completely understood. This meta-analysis aims to synthesize research on the use of PCIT for children with ADHD. Nine out of 711 identified studies were analyzed. Summary effect sizes were calculated using the standardized mean gain for child ADHD symptoms, child behaviors, parent stress, and parenting behaviors, and the Fail-Safe N was calculated to determine the robustness of the results. Overall, PCIT had a significant beneficial effect on child ADHD symptoms (g = 0.90), child behavior (g = 0.44), parent stress (g = 0.82), and parenting behaviors (g = 2.15). Results of this meta-analysis suggest that PCIT is an effective treatment for reducing core symptoms of ADHD.

7.
Am J Physiol Endocrinol Metab ; 324(3): E251-E267, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36696598

RESUMO

The autonomic nervous system regulates pancreatic function. Islet capillaries are essential for the extension of axonal projections into islets, and both of these structures are important for appropriate islet hormone secretion. Because beta cells provide important paracrine cues for islet glucagon secretion and neurovascular development, we postulated that beta cell loss in type 1 diabetes (T1D) would lead to a decline in intraislet capillaries and reduction of islet innervation, possibly contributing to abnormal glucagon secretion. To define morphological characteristics of capillaries and nerve fibers in islets and acinar tissue compartments, we analyzed neurovascular assembly across the largest cohort of T1D and normal individuals studied thus far. Because innervation has been studied extensively in rodent models of T1D, we also compared the neurovascular architecture between mouse and human pancreas and assembled transcriptomic profiles of molecules guiding islet angiogenesis and neuronal development. We found striking interspecies differences in islet neurovascular assembly but relatively modest differences at transcriptome level, suggesting that posttranscriptional regulation may be involved in this process. To determine whether islet neurovascular arrangement is altered after beta cell loss in T1D, we compared pancreatic tissues from non-diabetic, recent-onset T1D (<10-yr duration), and longstanding T1D (>10-yr duration) donors. Recent-onset T1D showed greater islet and acinar capillary density compared to non-diabetic and longstanding T1D donors. Both recent-onset and longstanding T1D had greater islet nerve fiber density compared to non-diabetic donors. We did not detect changes in sympathetic axons in either T1D cohort. Additionally, nerve fibers overlapped with extracellular matrix (ECM), supporting its role in the formation and function of axonal processes. These results indicate that pancreatic capillaries and nerve fibers persist in T1D despite beta cell loss, suggesting that alpha cell secretory changes may be decoupled from neurovascular components.NEW & NOTEWORTHY Defining the neurovascular architecture in the pancreas of individuals with type 1 diabetes (T1D) is crucial to understanding the mechanisms of dysregulated glucagon secretion. In the largest T1D cohort of biobanked tissues analyzed to date, we found that pancreatic capillaries and nerve fibers persist in human T1D despite beta cell loss, suggesting that alpha cell secretory changes may be decoupled from neurovascular components. Because innervation has been studied extensively in rodent T1D models, our studies also provide the first rigorous direct comparisons of neurovascular assembly in mouse and human, indicating dramatic interspecies differences.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Células Secretoras de Glucagon , Ilhotas Pancreáticas , Humanos , Camundongos , Animais , Diabetes Mellitus Tipo 1/metabolismo , Ilhotas Pancreáticas/metabolismo , Glucagon/metabolismo , Capilares/metabolismo , Células Secretoras de Glucagon/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Fibras Nervosas/metabolismo
8.
Ann Surg ; 277(4): 697-703, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35129505

RESUMO

OBJECTIVE: To describe 30-day outcomes including post-operative complications, readmissions, and quality of life score changes for older adults undergoing elective ventral hernia repair with retromuscular mesh placement and to compare rates of these outcomes for individuals undergoing robotic versus open approaches. SUMMARY OF BACKGROUND DATA: Over one third of patients presenting for elective ventral hernia repair are over the age of 65 and many have complex surgical histories that warrant intricate hernia repairs. Robotic ventral hernia repairs have gained increasing popularity in the US and in some studies have demonstrated decreased rates of postoperative complications, and less pain resulting in shorter hospital stays. However, the robotic approach has several downsides including prolonged operative times as well as the use of pneumo-peritoneum which may be risky in older patients. METHODS: We performed a retrospective review of prospectively collected data in a national hernia specific registry (the Abdominal Core Health Quality Collaborative) and identified patients over the age of 65 undergoing either an open or robotic retromuscular ventral hernia repair. After propensity score matching adjusting for demographic, clinical, and hernia related factors, logistic regression was used to compare 30-day complications, readmission, and quality of life (QoL) scores as captured by the HerQLes scale for patients undergoing each approach. RESULTS: Of 2128 patients who met inclusion criteria, 1695 (79.7%) underwent open ventral hernia repair while 433 (20.3%) underwent robotic repair. After propensity score matching, there were 350 robotic cases and 759 open cases for analysis. Patients undergoing robotic repairs demonstrated significantly shorter length of stays (1 vs 4 days, P < 0.01) and had equivalent odds of both 30-day post-operative complications (odds ratio [OR] 1.15 95% confidence interval 0.92-1.44) and readmission (OR 1.09 95% confidence interval 0.74-1.6) compared to the open approach. QoL scores were similar between groups at 30 days but were slightly better for robotic patients at 1 year (92 vs 84 P < 0.01). CONCLUSIONS: Robotic ventral hernia repair is an option for appropriately selected older patients undergoing retromuscular ventral hernia repair, demonstrating shorter hospital stays and equivalent rates of complications and readmissions in the post-operative period. However, more data is needed regarding QoL outcomes and long-term function, especially as it relates to recurrence rates, between the two approaches.


Assuntos
Hérnia Ventral , Hérnia Incisional , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Humanos , Idoso , Qualidade de Vida , Procedimentos Cirúrgicos Robóticos/métodos , Herniorrafia/métodos , Hérnia Ventral/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Telas Cirúrgicas , Hérnia Incisional/cirurgia
9.
Surg Endosc ; 37(7): 5464-5471, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37043005

RESUMO

BACKGROUND: Smoking has been shown to negatively affect surgical outcomes, so smoking cessation prior to elective operations is often recommended. However, the effects of smoking status on inguinal hernia repair outcomes have not been extensively studied. Hence, we investigated the association between smoking status and short-term adverse outcomes following inguinal hernia repair. METHODS: Abdominal Core Health Quality Collaborative database was queried for elective, clean inguinal hernia repairs, excluding those with concomitant procedures or where length of stay > 30 days. The resulting cohort was divided into three groups: current smokers, former smokers, and never smokers. Baseline patient, hernia, operative characteristics, and 30-day outcomes were compared. Multivariable logistic regression was used to evaluate the association between smoking status and overall and wound complications. RESULTS: 19,866 inguinal hernia repairs were included (current smokers = 2239, former smokers = 4064 and never smokers = 13,563). Current smokers and former smokers, compared to never smokers, had slightly higher unadjusted rates of overall complication rates (9% and 9% versus 7%, p = 0.003) and surgical site occurrences/infection (6% and 6% versus 4%, p < 0.001). However, on multivariable analysis, compared to current smokers, neither the rates of overall complications nor surgical site occurrences were significantly different in former smokers (OR = 0.93, 95% CI [0.76, 1.13] and OR = 0.92, 95% CI [0.73, 1.17]) and never smokers (OR = 0.99, 95% CI [0.83, 1.18] and OR = 0.86, 95% CI [0.70,1.06]) respectively. CONCLUSIONS: Smoking status is not associated with short-term adverse outcomes following inguinal hernia repair. Mandating smoking cessation does not appear necessary to prevent short-term adverse outcomes.


Assuntos
Hérnia Inguinal , Laparoscopia , Humanos , Hérnia Inguinal/complicações , Fumar/efeitos adversos , Fumar/epidemiologia , Herniorrafia/métodos , Infecção da Ferida Cirúrgica/etiologia , Fatores de Risco , Laparoscopia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia
10.
Surg Endosc ; 37(7): 5438-5443, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37038022

RESUMO

PURPOSE: Mediumweight (MW) and heavyweight (HW) polypropylene have demonstrated similar clinical and patient-reported outcomes in the setting of open retromuscular ventral hernia repair (VHR). While MW mesh has an anecdotal risk of central mesh fracture, that phenomenon is not well-characterized. We sought to assess the incidence of and risk factors for MW polypropylene mesh fractures after VHR. METHODS: The ACHQC registry was queried for patients with CT-documented hernia recurrence after open retromuscular VHR with MW polypropylene mesh at our institution with 1-year follow-up between January 2014 and April 2022. Images were reviewed by five blinded surgeons at Cleveland Clinic to reach consensus that hernia recurrence mechanism was central mesh fracture. Patients without clinical recurrence or patient-reported bulge were used as a comparator group. RESULTS: Eighty patients were identified with radiographically documented recurrence; 28 had recurrence from mesh fractures and these were compared to 644 patients without recurrence. Incidence of MW fracture was 4.2%. Bridging of anterior fascia was more common in the group with the central mesh fracture (33.3% vs 3.3%, p < 0.001); the incidence of fracture was 30% (9/30) in patients requiring a bridged closure. Mesh fracture was associated with larger hernias (median width: 20 cm [16-26] vs 15 cm [12-18], p < 0.001,), length (25 cm [23-30] vs 23 cm [19-26], p = 0.004). CONCLUSION: MW polypropylene mechanical failures are surprisingly common, particularly in settings of bridged fascial closure and larger hernias. Use of HW polypropylene should be considered in this setting, and industry should be encouraged to create larger pieces of HW polypropylene mesh.


Assuntos
Hérnia Ventral , Polipropilenos , Humanos , Polipropilenos/efeitos adversos , Incidência , Telas Cirúrgicas/efeitos adversos , Hérnia Ventral/epidemiologia , Hérnia Ventral/etiologia , Hérnia Ventral/cirurgia , Fatores de Risco , Herniorrafia/efeitos adversos , Herniorrafia/métodos , Recidiva
11.
Anaerobe ; 80: 102699, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36702174

RESUMO

We analyzed our challenging experience with a randomized controlled trial of misoprostol for prevention of recurrent C. difficile. Despite careful prescreening and thoughtful protocol modifications to facilitate enrollment, we closed the study early after enrolling just 7 participants over 3 years. We share lessons learned, noting the importance of feasibility studies, inclusion of biomarker outcomes, and dissemination of such findings to inform future research design and implementation successes.


Assuntos
COVID-19 , Clostridioides difficile , Infecções por Clostridium , Misoprostol , Humanos , COVID-19/prevenção & controle , Misoprostol/uso terapêutico , Clostridioides , Estudos de Viabilidade , Infecções por Clostridium/prevenção & controle
12.
Adm Policy Ment Health ; 50(6): 976-998, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37691065

RESUMO

Parent-Child Interaction Therapy (PCIT) is an empirically supported treatment for childhood conduct problems, with increasing numbers of clinicians being trained in Aotearoa/New Zealand. However, ensuring sustained delivery of effective treatments by trained clinicians in routine care environments is notoriously challenging. The aims of this qualitative study were to (1) systematically examine and prioritise PCIT implementation barriers and facilitators, and (2) develop a well specified and theory-driven 're-implementation' intervention to support already-trained clinicians to resume or increase their implementation of PCIT. To triangulate and refine existing understanding of PCIT implementation determinants from an earlier cross-sectional survey, we integrated previously unanalysed qualitative survey data (54 respondents; response rate 60%) with qualitative data from six new focus groups with 15 PCIT-trained clinicians and managers in Aotearoa/New Zealand. We deductively coded data, using a directed content analysis process and the Theoretical Domains Framework, resulting in the identification of salient theoretical domains and belief statements within these. We then used the Theory and Techniques Tool to identify behaviour change techniques, possible intervention components, and their hypothesised mechanisms of action. Eight of the 14 theoretical domains were identified as influential on PCIT-trained clinician implementation behaviour (Knowledge; Social/Professional Role and Identity; Beliefs about Capabilities; Beliefs about Consequences; Memory, Attention and Decision Processes; Environmental Context and Resources; Social Influences; Emotion). Two of these appeared to be particularly salient: (1) 'Environmental Context and Resources', specifically lacking suitable PCIT equipment, with (lack of) access to a well-equipped clinic room appearing to influence implementation behaviour in several ways. (2) 'Social/Professional Role and Identity', with beliefs relating to a perception that colleagues view time-out as harmful to children, concerns that internationally-developed PCIT is not suitable for non-Maori clinicians to deliver to Indigenous Maori families, and clinicians feeling obligated yet isolated in their advocacy for PCIT delivery. In conclusion, where initial implementation has stalled or languished, re-implementation may be possible, and makes good sense, both fiscally and practically. This study suggests that re-implementation of PCIT in Aotearoa/New Zealand may be facilitated by intervention components such as ensuring access to a colleague or co-worker who is supportive of PCIT delivery, access to suitable equipment (particularly a time-out room), and targeted additional training for clinicians relating to the safety of time-out for children. The feasibility and acceptability of these intervention components will be tested in a future clinical trial.


Assuntos
Terapia Comportamental , Relações Pais-Filho , Criança , Humanos , Estudos Transversais , Povo Maori
13.
FASEB J ; 35(2): e21201, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33496989

RESUMO

In recent years, it has become apparent that the gut microbiome can influence the functioning and pathological states of organs and systems throughout the body. In this study, we tested the hypothesis that the gut microbiome has a major role in the disruption of the blood-brain barrier (BBB) in the spontaneously hypertensive stroke prone rats (SHRSP), an animal model for hypertensive cerebral small vessel disease (CSVD). Loss of BBB is thought to be an early and initiating component to the full expression of CSVD in animal models and humans. To test this hypothesis, newly born SHRSP pups were placed with foster dams of the SHRSP strain or dams of the WKY strain, the control strain that does not demonstrate BBB dysfunction or develop hypertensive CSVD. Similarly, WKY pups were placed with foster dams of the same or opposite strain. The rationale for cross fostering is that the gut microbiomes are shaped by environmental bacteria of the foster dam and the nesting surroundings. Analysis of the bacterial genera in feces, using 16S rRNA analysis, demonstrated that the gut microbiome in the rat pups was influenced by the foster dam. SHRSP offspring fostered on WKY dams had systolic blood pressures (SBPs) that were significantly decreased by 26 mmHg (P < .001) from 16-20 weeks, compared to SHRSP offspring fostered on SHRSP dams. Similarly WKY offspring fostered on SHRSP dams had significantly increased SBP compared to WKY offspring fostered on WKY dams, although the magnitude of SBP change was not as robust. At ~20 weeks of age, rats fostered on SHRSP dams showed enhanced inflammation in distal ileum regardless of the strain of the offspring. Disruption of BBB integrity, an early marker of CSVD onset, was improved in SHRSPs that were fostered on WKY dams when compared to the SHRSP rats fostered on SHRSP dams. Although SHRSP is a genetic model for CSVD, environmental factors such as the gut microbiota of the foster dam have a major influence in the loss of BBB integrity.


Assuntos
Pressão Sanguínea , Barreira Hematoencefálica/patologia , Microbioma Gastrointestinal , Animais , Barreira Hematoencefálica/metabolismo , Meio Ambiente , Íleo/microbiologia , Íleo/patologia , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY
14.
Am J Perinatol ; 2022 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-35640619

RESUMO

OBJECTIVE: Opioids are commonly prescribed to women for acute pain following childbirth. Postpartum prescription opioid exposure is associated with adverse opioid-related morbidities but the association with all-cause mortality is not well studied. This study aimed to examine the association between postpartum opioid prescription fills and the 1-year risk of all-cause mortality among women with live births. METHODS: In a retrospective cohort study of live births among women enrolled in Tennessee Medicaid (TennCare) between 2007 and 2015, we compared women who filled two or more postpartum outpatient opioid prescriptions (up to 41 days of postdelivery discharge) to women who filled one or fewer opioid prescription. Women were followed from day 42 postdelivery discharge through 365 days of follow-up or date of death. Deaths were identified using linked death certificates (2007-2016). We used Cox's proportional hazard regression and inverse probability of treatment weights to compare time to death between exposure groups while adjusting for relevant confounders. We also examined effect modification by delivery route, race, opioid use disorder, use of benzodiazepines, and mental health condition diagnosis. RESULTS: Among 264,135 eligible births, 216,762 (82.1%) had one or fewer maternal postpartum opioid fills and 47,373 (17.9%) had two or more fills. There were 182 deaths during follow-up. The mortality rate was higher in women with two or more fills (120.5 per 100,000 person-years) than in those with one or fewer (57.7 per 100,000 person-years). The risk of maternal death remained higher in participants exposed to two or more opioid fills after accounting for relevant covariates using inverse probability of treatment weighting (adjusted hazard ratio: 1.46 [95% confidence interval: 1.01, 2.09]). Findings from stratified analyses were consistent with main findings. CONCLUSION: Filling two or more opioid prescriptions during the postpartum period was associated with a significant increase in 1-year risk of death among new mothers. KEY POINTS: · Opioid prescribing in the postpartum period is common.. · Prior studies show that >1 postnatal opioid fill is associated with adverse opioid-related events.. · > 1 opioid fill within 42 days of delivery was associated with an increase in 1-year risk of death..

15.
Health Promot Int ; 37(5)2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36166261

RESUMO

Modifications to the social-ecological model, such as Whole School, Whole Community, Whole Child (WSCC) frameworks, have been utilized in comprehensive school health interventions. Classroom physical activity breaks are used when implementing whole-of-school approaches. However, the onus to implement classroom physical activity breaks is on school stakeholders. This study aimed to explore teacher and principal perceptions and implementation of physical activity breaks in elementary schools. Further, this study investigated how theoretical factors representative of the social-ecological model and their interactions affect teacher and principal perceptions and utilization of classroom physical activity breaks. Interviews were conducted to understand teacher and principal perceptions and implementation. A total of 12 classroom teachers and five principals participated in semi-structured interviews which were analyzed using constant comparison and deductive analysis to identify relationships and themes coded across the social-ecological and WSCC models. To ensure fidelity individuals that led the professional development (n = 2) were also interviewed. Three main themes emerged as part of the data analysis: (i) The Connection Between Intrapersonal Knowledge and Interpersonal Professional Development, (ii) Resources, Sharing Means Caring and (iii) The Policy Level Creates Time. Teachers and principals valued knowledge and resources and felt that policy facilitated implementation. Results suggest that classroom physical activity breaks are influenced by multiple factors across varied levels of the social-ecological model. Understanding this relationship can inform future professional development to increase the provision of classroom physical activity breaks among teachers.


Global health statistics suggest that youth health is deteriorating. In response, international and national health organizations have called for school settings to adopt comprehensive school health approaches that provide youth with ample opportunities, such as physical activity across the school day, to improve their health behaviors and instill lifelong healthy habits. This study used the social­ecological model, which considers the interactions between an individual, their community, and the physical, social and political environments, to frame the exploration of how teachers and principals perceive and utilize physical activity breaks in elementary schools. Findings indicate that to foster school health, a comprehensive approach that supports teachers and their interactions while providing resources and policies is needed. Adoption of classroom physical activity breaks begins with teacher knowledge which fosters teacher interaction where best practices are built. Structural supports, including access to resources and the presence of policy, are also critical to sustained implementation because they can reinforce and support teachers' individual and shared use of health-based learning practices across the school day.


Assuntos
Pessoal de Educação , Professores Escolares , Criança , Exercício Físico , Humanos , Serviços de Saúde Escolar , Instituições Acadêmicas
16.
Epilepsy Behav ; 123: 108259, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34418639

RESUMO

OBJECTIVE: Depression and anxiety disorders are common among patients with epilepsy (PWE). These comorbidities have been shown to influence prognosis and may have a greater impact on quality of life than seizure control. Despite guideline recommendations and expert consensus to regularly screen for and treat both conditions, there is evidence that they are underdiagnosed and undertreated. Our goal was to test a novel screening method to determine if it would increase the rate of detecting and treating depression and anxiety disorders among PWE. METHOD: The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and the Brief Epilepsy Anxiety Survey Instrument (brEASI) were selected as validated screening instruments for depression and anxiety disorders, respectively. They were sent via an electronic medical record-linked patient portal to all patients of four epileptologists 48 h prior to their clinic appointment. We evaluated whether this increased the rate of detecting and treating depression and anxiety disorders relative to a historical control group. RESULTS: A total of 563 patients were included of whom 351 were sent the screening instruments. 62.7% of patients completed the screening instruments of whom 47.7% screened positive for either depression only (16.4%), anxiety disorders only (5.5%) or both (25.9%); a statistically significant increase relative to the control group. There was also a significantly increased proportion of patients for whom treatment was initiated for depression (p < 0.01), anxiety disorders (p < 0.01), or both (p < 0.01). CONCLUSIONS: We identified an easily applicable and efficient means of enhancing detection and treatment rates for depression and anxiety disorders among PWE in a busy clinic setting.


Assuntos
Depressão , Epilepsia , Adulto , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/terapia , Depressão/diagnóstico , Depressão/epidemiologia , Registros Eletrônicos de Saúde , Epilepsia/complicações , Epilepsia/diagnóstico , Epilepsia/epidemiologia , Humanos , Escalas de Graduação Psiquiátrica , Qualidade de Vida , Reprodutibilidade dos Testes
17.
Surg Endosc ; 35(7): 3818-3828, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-32613304

RESUMO

BACKGROUND: The postoperative management of patients undergoing laparoscopic ventral hernia repair (VHR) remains relatively unknown. The purpose of our study was to determine if patient and hernia-specific factors could be used to predict the likelihood of hospital admission following laparoscopic VHR using the Americas Hernia Society Quality Collaborative (AHSQC) database. METHODS: All patients who underwent elective, laparoscopic VHR with mesh placement from October 2015 through April 2019 were identified within the AHSQC database. Patients without clean wounds, those with chronic liver disease, and those without 30-day follow-up data were excluded from our analysis. Patient and hernia-specific variables were compared between patients who were discharged from the post-anesthesia care unit (PACU) and patients who required hospital admission. Comparisons were also made between the two groups with respect to 30-day morbidity and mortality events. RESULTS: A total of 1609 patients met inclusion criteria; 901 (56%) patients were discharged from the PACU. The proportion of patients discharged from the PACU increased with each subsequent year. Several patient comorbidities and hernia-specific factors were found to be associated with postoperative hospital admission, including older age, repair of a recurrent hernia, a larger hernia width, longer operative time, drain placement, and use of mechanical bowel preparation. Patients who required hospital admission were more likely than those discharged from the PACU to be readmitted to the hospital within 30 days (4% vs. 2%, respectively) and to experience a 30-day morbidity event (18% vs. 8%, respectively). CONCLUSIONS: Patient- and hernia-specific factors can be used to identify patients who can be safely discharged from the PACU following laparoscopic VHR. Additional studies are needed to determine if appropriate patient selection for discharge from the PACU leads to decreased healthcare costs for laparoscopic VHR over the long-term.


Assuntos
Hérnia Ventral , Laparoscopia , Idoso , Hérnia Ventral/cirurgia , Herniorrafia/efeitos adversos , Humanos , Alta do Paciente , Seleção de Pacientes , Estudos Retrospectivos , Estados Unidos
19.
Atmos Environ (1994) ; 2142019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32665763

RESUMO

Trace metal distributions are of relevance to understand sources of fine particulate matter (PM2.5), PM2.5-related health effects, and atmospheric chemistry. However, knowledge of trace metal distributions is lacking due to limited ground-based measurements and model simulations. This study develops a simulation of 12 trace metal concentrations (Si, Ca, Al, Fe, Ti, Mn, K, Mg, As, Cd, Ni and Pb) over continental North America for 2013 using the GEOS-Chem chemical transport model. Evaluation of modeled trace metal concentrations with observations indicates a spatial consistency within a factor of 2, an improvement over previous studies that were within a factor of 3-6. The spatial distribution of trace metal concentrations reflects their primary emission sources. Crustal element (Si, Ca, Al, Fe, Ti, Mn, K) concentrations are enhanced over the central US from anthropogenic fugitive dust and over the southwestern U.S. due to natural mineral dust. Heavy metal (As, Cd, Ni and Pb) concentrations are high over the eastern U.S. from industry. K is abundance in the southeast from biomass burning and high concentrations of Mg is observed along the coast from sea spray. The spatial pattern of PM2.5 mass is most strongly correlated with Pb, Ni, As and K due to their signature emission sources. Challenges remain in accurately simulating observed trace metal concentrations. Halving anthropogenic fugitive dust emissions in the 2011 National Air Toxic Assessment (NATA) inventory and doubling natural dust emissions in the default GEOS-Chem simulation was necessary to reduce biases in crustal element concentrations. A fivefold increase of anthropogenic emissions of As and Pb was necessary in the NATA inventory to reduce the national-scale bias versus observations by more than 80 %, potentially reflecting missing sources.

20.
Atmos Environ (1994) ; 214: 1-116872, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31741655

RESUMO

Previous studies have proposed that model performance statistics from earlier photochemical grid model (PGM) applications can be used to benchmark performance in new PGM applications. A challenge in implementing this approach is that limited information is available on consistently calculated model performance statistics that vary spatially and temporally over the U.S. Here, a consistent set of model performance statistics are calculated by year, season, region, and monitoring network for PM2.5 and its major components using simulations from versions 4.7.1-5.2.1 of the Community Multiscale Air Quality (CMAQ) model for years 2007-2015. The multi-year set of statistics is then used to provide quantitative context for model performance results from the 2015 simulation. Model performance for PM2.5 organic carbon in the 2015 simulation ranked high (i.e., favorable performance) in the multi-year dataset, due to factors including recent improvements in biogenic secondary organic aerosol and atmospheric mixing parameterizations in CMAQ. Model performance statistics for the Northwest region in 2015 ranked low (i.e., unfavorable performance) for many species in comparison to the 2007-2015 dataset. This finding motivated additional investigation that suggests a need for improved speciation of wildfire PM2.5emissions and modeling of boundary layer dynamics near water bodies. Several limitations were identified in the approach of benchmarking new model performance results with previous results. Since performance statistics vary widely by region and season, a simple set of national performance benchmarks (e.g., one or two targets per species and statistic) as proposed previously are inadequate to assess model performance throughout the U.S. Also, trends in model performance statistics for sulfate over the 2007 to 2015 period suggest that model performance for earlier years may not be a useful reference for assessing model performance for recent years in some cases. Comparisons of results from the 2015 base case with results from five sensitivity simulations demonstrated the importance of parameterizations of NH3 surface exchange, organic aerosol volatility and production, and emissions of crustal cations for predicting PM2.5 species concentrations.

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