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1.
Int J Pharm Pract ; 2024 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-39401321

RESUMO

OBJECTIVES: To assess the content and frequency of advice community pharmacists (CPs) provide to pregnant women with nausea and vomiting, their confidence in providing advice, and their knowledge of the safety of medication used to manage the condition. METHODS: An online questionnaire of closed- and open-ended questions was distributed to CPs in the UK in May 2023. Closed-ended questions were analysed quantitatively, and conventional content analysis was utilised for open-ended responses. KEY FINDINGS: One hundred and eighty-one respondents completed the questionnaire, 24 responses were excluded, leaving data from 157 available for analysis. The majority (90.4%) of participants reported having experience in providing advice on nausea and vomiting with varying levels of confidence. Advice provided included using over-the-counter products, lifestyle modifications, reassurance, medication advice, and referring to other healthcare professionals. Knowledge of first-line antiemetics considered safe in pregnancy varied; cyclizine was correctly identified as safe during pregnancy by 57.3%, followed by 37.6% for promethazine and 31.2% for prochlorperazine. Self-reported confidence and having experience providing advice were related to higher medication safety identification rates. Five percent of participants reported previous training on the condition, while 70% reported wanting further education, preferably delivered via an online medium. CONCLUSIONS: This study showed that although 90% of CPs provide advice on nausea and vomiting in pregnancy, their medication safety knowledge varied. The majority of CPs reported wanting further education that would ensure women could access reliable information and evidence-based advice to optimise management of the condition.

2.
Obstet Med ; 17(3): 138-143, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39262909

RESUMO

Considerable progress has been made to explain the aetiology of intrahepatic cholestasis of pregnancy (ICP) and of the adverse pregnancy outcomes associated with high maternal total serum bile acids (TSBAs). The reported thresholds for non-fasting TSBA associated with the risk of stillbirth and spontaneous preterm birth can be used to identify pregnancies at risk of these adverse outcomes to decide on appropriate interventions and to give reassurance to women with lower concentrations of TSBA. Data also support the use of ursodeoxycholic acid to protect against the risk of spontaneous preterm birth. A previous history of ICP may be associated with higher rates of subsequent hepatobiliary disease: if there is a suspicion of underlying susceptibility, clinicians caring for women with ICP should screen for associated disorders or for genetic susceptibility and, where appropriate, refer for ongoing hepatology review.

3.
Obstet Med ; 17(3): 157-161, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39262913

RESUMO

Intrahepatic cholestasis of pregnancy (ICP) is the commonest gestational liver disorder with variable global incidence. Genetic susceptibility, combined with hormonal and environmental influences, contributes to ICP aetiology. Adverse pregnancy outcomes linked to elevated serum bile acids highlight the importance of comprehensive risk assessment. ABCB4 and ABCB11 gene variants play a significant role in about 20% of severe ICP cases. Several other genes including ATP8B1, NR1H4, ABCC2, TJP2, SERPINA1, GCKR and HNF4A have also been implicated with ICP. Additionally, ABCB4 variants elevate the risk of drug-induced intrahepatic cholestasis, gallstone disease, gallbladder and bile duct carcinoma, liver cirrhosis and abnormal liver function tests. Genetic variations, both rare and common, intricately contribute to ICP susceptibility. Leveraging genetic insights holds promise for personalised management and intervention strategies. Further research is needed to elucidate variant-specific phenotypic expressions and therapeutic implications, advancing precision medicine in ICP management.

4.
Epileptic Disord ; 2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39340449

RESUMO

OBJECTIVE: Seizures during labor are reported in 3.5% of women with epilepsy (WWE) and can result in both maternal and fetal morbidity. In response to an anecdotal increase in WWE developing seizures in labor or peripartum (up to 24 h post-partum), a review of patients managed in our service was undertaken to define the incidence of peripartum seizures and determine learning points. METHODS: A retrospective review of all cases of WWE having peripartum seizures from 2017 to 2022 in our institution was undertaken. Each case was reviewed by the multidisciplinary team (MDT) and common themes identified. RESULTS: In total, 106 WWE received pregnancy care in the study period, of whom 8/106 (7.5%) had a seizure in the peripartum period. The MDT-agreed learning points included importance of pre-pregnancy counseling, prompt up-titration of antiepileptic drugs where indicated and recommendations for the management in the peripartum period. SIGNIFICANCE: We concluded that the peripartum period remains a high-risk time for seizures in WWE. There is little evidence to support guidelines for the management of WWE in the peripartum period. In the absence of this evidence, sharing experience may help those managing such women to improve care and reduce risk during this vulnerable time.

5.
Nat Commun ; 15(1): 6767, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39117683

RESUMO

The long and very long chain polyunsaturated fatty acids (LC-PUFAs) are preferentially transported by the mother to the fetus. Failure to supply LC-PUFAs is strongly linked with stillbirth, fetal growth restriction, and impaired neurodevelopmental outcomes. However, dietary supplementation during pregnancy is unable to simply reverse these outcomes, suggesting imperfectly understood interactions between dietary fatty acid intake and the molecular mechanisms of maternal supply. Here we employ a comprehensive approach combining untargeted and targeted lipidomics with transcriptional profiling of maternal and fetal tissues in mouse pregnancy. Comparison of wild-type mice with genetic models of impaired lipid metabolism allows us to describe maternal hepatic adaptations required to provide LC-PUFAs to the developing fetus. A late pregnancy-specific, selective activation of the Liver X Receptor signalling pathway dramatically increases maternal supply of LC-PUFAs within circulating phospholipids. Crucially, genetic ablation of this pathway in the mother reduces LC-PUFA accumulation by the fetus, specifically of docosahexaenoic acid (DHA), a critical nutrient for brain development.


Assuntos
Ácidos Docosa-Hexaenoicos , Ácidos Graxos Insaturados , Feto , Fígado , Fosfolipídeos , Animais , Feminino , Gravidez , Fígado/metabolismo , Fosfolipídeos/metabolismo , Ácidos Graxos Insaturados/metabolismo , Camundongos , Ácidos Docosa-Hexaenoicos/metabolismo , Feto/metabolismo , Receptores X do Fígado/metabolismo , Receptores X do Fígado/genética , Metabolismo dos Lipídeos/genética , Camundongos Endogâmicos C57BL , Transdução de Sinais , Masculino , Lipidômica , Camundongos Knockout
6.
JACC Adv ; 3(8): 101071, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39050813

RESUMO

Background: Cardiovascular disease (CVD) in pregnancy is a leading cause of maternal morbidity and mortality in the United States, with an increasing prevalence. Objectives: This study aimed to examine risk factors for adverse maternal cardiac, maternal obstetric, and neonatal outcomes as well as costs for pregnant people with CVD at delivery. Methods: Using the National Inpatient Sample 2010-2019 and the Internal Classification of Diseases diagnosis codes, all pregnant people admitted for their delivery hospitalization were included. CVD diagnoses included congenital heart disease, cardiomyopathy, ischemic heart disease, arrhythmias, and valvular disease. Multivariable regressions were used to analyze major adverse cardiovascular events (MACE), maternal and fetal complications, length of stay, and resource utilization. Results: Of the 33,639,831 birth hospitalizations included, 132,532 (0.39%) had CVD. These patients experienced more frequent MACE (8.5% vs 0.4%, P < 0.001), obstetric (24.1% vs 16.6%, P < 0.001), and neonatal complications (16.1% vs 9.5%, P < 0.001), and maternal mortality (0.16% vs 0.01%, P < 0.001). Factors associated with MACE included cardiomyopathy (adjusted OR [aOR]: 49.9, 95% CI: 45.2-55.1), congenital heart disease (aOR: 13.8, 95% CI: 12.0-15.9), Black race (aOR: 1.04, 95% CI: 1.00-1.08), low income (aOR: 1.06, 95% CI: 1.02-1.11), and governmental insurance (aOR: 1.03, 95% CI: 1.00-1.07). On adjusted analysis, CVD was associated with higher odds of maternal mortality (aOR: 9.28, 95% CI: 6.35-13.56), stillbirth (aOR: 1.66, 95% CI: 1.49-1.85), preterm birth (aOR: 1.33, 1.27-1.39), and congenital anomalies (aOR: 1.84, 95% CI: 1.69-1.99). CVD was also associated with an increase of $2,598 (95% CI: $2,419-2,777) per patient during admission for delivery. Conclusions: CVD in pregnancy is associated with higher rates of adverse outcomes. Our study highlights the association of key clinical and demographic factors with CVD during pregnancy to emphasize those at highest risk for complications.

7.
BJOG ; 131(9): 1218-1228, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38424005

RESUMO

OBJECTIVE: Investigation of serum bile acid profiles in pregnancies complicated by gestational diabetes mellitus (GDM) in a multi-ethnic cohort of women who are lean or obese. DESIGN: Prospective cohort study. SETTING: UK multicentre study. POPULATION: Fasting serum from participants of European or South Asian self-reported ethnicity from the PRiDE study, between 23 and 31 weeks of gestation. METHODS: Bile acids were measured using ultra-performance liquid chromatography-tandem mass spectrometry. Log-transformed data were analysed using linear regression in STATA/IC 15.0. MAIN OUTCOME MEASURES: Total bile acids (TBAs), C4, fasting glucose and insulin. RESULTS: The TBAs were 1.327-fold (1.105-1.594) increased with GDM in European women (P = 0.003). Women with GDM had 1.162-fold (1.002-1.347) increased levels of the BA synthesis marker C4 (P = 0.047). In South Asian women, obesity (but not GDM) increased TBAs 1.522-fold (1.193-1.942, P = 0.001). Obesity was associated with 1.420-fold (1.185-1.702) increased primary/secondary BA ratio (P < 0.001) related to 1.355-fold (1.140-1.611) increased primary BA concentrations (P = 0.001). TBAs were positively correlated with fasting glucose (P = 0.039) in all women, and with insulin (P = 0.001) and the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (P = 0.001) in women with GDM. CONCLUSIONS: Serum BA homeostasis in late gestation depends on body mass index and GDM in ethnicity-specific ways. This suggests ethnicity-specific aetiologies may contribute to metabolic risk in European and South Asian women, with the relationship between BAs and insulin resistance of greater importance in European women. Further studies into ethnicity-specific precision medicine for GDM are required.


Assuntos
Povo Asiático , Ácidos e Sais Biliares , Diabetes Gestacional , População Branca , Adulto , Feminino , Humanos , Gravidez , Ácidos e Sais Biliares/sangue , Glicemia/metabolismo , Glicemia/análise , Índice de Massa Corporal , Estudos de Coortes , Diabetes Gestacional/sangue , Diabetes Gestacional/etnologia , Insulina/sangue , Obesidade/sangue , Obesidade/etnologia , Estudos Prospectivos , Reino Unido/epidemiologia , População Branca/estatística & dados numéricos , População do Sul da Ásia
8.
Eur J Prev Cardiol ; 31(8): 955-965, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38294056

RESUMO

AIMS: Current guidelines advise against the use of lipid-lowering drugs during pregnancy. This is based only on previous observational evidence demonstrating an association between statin use and congenital malformations, which is increasingly controversial. In the absence of clinical trial data, we aimed to use drug-target Mendelian randomization to model the potential impact of fetal LDL-lowering, overall and through PCSK9 drug targets, on congenital malformations. METHODS AND RESULTS: Instrumental variants influencing LDL levels overall and through PCSK9-inhibitor drug targets were extracted from genome-wide association study (GWAS) summary data for LDL on 1 320 016 individuals. Instrumental variants influencing circulating PCSK9 levels (pQTLs) and liver PCSK9 gene expression levels (eQTLs) were extracted, respectively, from a GWAS on 10 186 individuals and from the genotype-tissue expression project. Gene-outcome association data was extracted from the 7th release of GWAS summary data on the FinnGen cohort (n = 342 499) for eight categories of congenital malformations affecting multiple systems. Genetically proxied LDL-lowering through PCSK9 was associated with higher odds of malformations affecting multiple systems [OR 2.70, 95% confidence interval (CI) 1.30-5.63, P = 0.018], the skin (OR 2.23, 95% CI 1.33-3.75, P = 0.007), and the vertebral, anorectal, cardiovascular, tracheo-esophageal, renal, and limb association (VACTERL) (OR 1.51, 95% CI 1.16-1.96, P = 0.007). An association was also found with obstructive defects of the renal pelvis and ureter, but this association was suggestive of horizontal pleiotropy. Lower PCSK9 pQTLs were associated with the same congenital malformations. CONCLUSION: These data provide genetic evidence supporting current manufacturer advice to avoid the use of PCSK9 inhibitors during pregnancy.


Using genetic techniques to mimic the effects of PCSK9-inhibitors, a group of lipid-lowering medications, this study provides evidence to support recommendations to avoid the use of these medications in pregnancy due to potential risk of multiple malformations in the newborn.This study provides genetic evidence to support potential associations of PCSK9-inhibitor medications with newborn malformations affecting multiple organ systems, the skin, and a cluster of structural defects simultaneously affecting the spine, anus/rectum, heart, throat, kidneys, arms and legs.There was also weaker evidence of an association of PCSK9-inhibitor medications with newborn malformations resulting in blockages of the kidneys and urine system, though the evidence was less certain for these than for the other malformations.


Assuntos
LDL-Colesterol , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Inibidores de PCSK9 , Pró-Proteína Convertase 9 , Humanos , LDL-Colesterol/sangue , Feminino , Pró-Proteína Convertase 9/genética , Pró-Proteína Convertase 9/metabolismo , Gravidez , Fatores de Risco , Anormalidades Induzidas por Medicamentos/prevenção & controle , Anormalidades Induzidas por Medicamentos/etiologia , Biomarcadores/sangue , Medição de Risco , Inibidores de Serina Proteinase/uso terapêutico , Inibidores de Serina Proteinase/efeitos adversos , Predisposição Genética para Doença , Fenótipo , Polimorfismo de Nucleotídeo Único , Anticolesterolemiantes/uso terapêutico , Anticolesterolemiantes/efeitos adversos
9.
PLoS One ; 19(1): e0295767, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38165963

RESUMO

BACKGROUND: While advances in medical and surgical management have allowed >97% of congenital heart disease (CHD) patients to reach adulthood, a growing number are presenting with non-cardiovascular malignancies. Indeed, adults with CHD are reported to face a 20% increase in cancer risk, relative to others, and cancer has become the fourth leading cause of death among this population. Surgical resection remains a mainstay in management of thoracoabdominal cancers. However, outcomes following cancer resection among these patients have not been well established. Thus, we sought to characterize clinical and financial outcomes following major cancer resections among adult CHD patients. METHODS: The 2012-2020 National Inpatient Sample was queried for all adults (CHD or non-CHD) undergoing lobectomy, esophagectomy, gastrectomy, pancreatectomy, hepatectomy, or colectomy for cancer. To adjust for intergroup differences in baseline characteristics, entropy balancing was applied to generate balanced patient groups. Multivariable models were constructed to assess outcomes of interest. RESULTS: Of 905,830 patients undergoing cancer resection, 1,480 (0.2%) had concomitant CHD. The overall prevalence of such patients increased from <0.1% in 2012 to 0.3% in 2012 (P for trend<0.001). Following risk adjustment, CHD was linked with greater in-hospital mortality (AOR 2.00, 95%CI 1.06-3.76), as well as a notable increase in odds of stroke (AOR 8.94, 95%CI 4.54-17.60), but no statistically significant difference in cardiac (AOR 1.33, 95%CI 0.69-2.59) or renal complications (AOR 1.35, 95%CI 0.92-1.97). Further, CHD was associated with a +2.39 day incremental increase in duration of hospitalization (95%CI +1.04-3.74) and a +$11,760 per-patient increase in hospitalization expenditures (95%CI +$4,160-19,360). CONCLUSIONS: While a growing number of patients with CHD are undergoing cancer resection, they demonstrate inferior clinical and financial outcomes, relative to others. Novel screening, risk stratification, and perioperative management guidelines are needed for these patients to provide evidence-based recommendations for this complex and unique cohort.


Assuntos
Cardiopatias Congênitas , Neoplasias , Adulto , Humanos , Hospitalização , Cardiopatias Congênitas/diagnóstico , Coração , Mortalidade Hospitalar , Neoplasias/epidemiologia , Neoplasias/cirurgia , Estudos Retrospectivos
10.
Ann Thorac Surg ; 117(3): 552-559, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37182822

RESUMO

BACKGROUND: Although failure to rescue (FTR) is increasingly recognized as a quality metric, studies in congenital cardiac surgery remain sparse. Within a national cohort of children undergoing cardiac operations, we characterized the presence of center-level variation in FTR and hypothesized a strong association with mortality but not complications. METHODS: All children undergoing congenital cardiac operations were identified in the 2013 to 2019 Nationwide Readmissions Database. FTR was defined as in-hospital death after cardiac arrest, ventricular tachycardia/fibrillation, prolonged mechanical ventilation, pneumonia, stroke, venous thromboembolism, or sepsis, among other complications. Hierarchical models were used to generate hospital-specific, risk-adjusted rates of mortality, complications, and FTR. Centers in the highest decile of FTR were identified and compared with others. RESULTS: Of an estimated 74,070 patients, 1.9% died before discharge, at least 1 perioperative complication developed in 43.0%, and 4.1% experienced FTR. After multilevel modeling, decreasing age, nonelective admission, and increasing operative complexity were associated with greater odds of FTR. Variations in overall mortality and FTR exhibited a strong, positive relationship (r = 0.97), whereas mortality and complications had a negligible association (r = -0.02). Compared with others, patients at centers with high rates of FTR had similar distributions of age, sex, chronic conditions, and operative complexity. CONCLUSIONS: In the present study, center-level variations in mortality were more strongly explained by differences in FTR than complications. Our findings suggest the utility of FTR as a quality metric for congenital heart surgery, although further study is needed to develop a widely accepted definition and appropriate risk-adjustment models.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Cirurgia Torácica , Humanos , Criança , Mortalidade Hospitalar , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Fibrilação Ventricular
12.
Clinics (Sao Paulo) ; 78: 100251, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37473624

RESUMO

OBJECTIVE: While Opioid Use Disorder (OUD) has been linked to inferior clinical outcomes, studies examining the clinical outcomes and readmission of OUD patients experiencing Acute Myocardial Infarction (AMI) remain lacking. The authors analyze the clinical and financial outcomes of OUD in a contemporary cohort of AMI hospitalizations. METHODS: All non-elective adult (≥ 18 years) hospitalizations for AMI were tabulated from the 2016‒2019 Nationwide Readmissions Database using relevant International Classification of Disease codes. Patients were grouped into OUD and non-OUD cohorts. Bivariate and regression analyses were performed to identify the independent association of OUD with outcomes after non-elective admission for AMI, as well as subsequent readmission. RESULTS: Of an estimated 3,318,257 hospitalizations for AMI meeting study criteria, 36,057 (1.1%) had a concomitant diagnosis of OUD. While OUD was not significantly associated with mortality, OUD patients experienced superior cardiovascular outcomes compared to non-OUD. However, OUD was linked to increased odds of non-cardiovascular complications, length of stay, costs, non-home discharge, and 30-day non-elective readmission. CONCLUSIONS: Patients with OUD presented with AMI at a significantly younger age than non-OUD. While OUD appears to have a cardioprotective effect, it is associated with several markers of increased resource use, including readmission. The present findings underscore the need for a multifaceted approach to increasing social services and treatment for OUD at index hospitalization.


Assuntos
Infarto do Miocárdio , Transtornos Relacionados ao Uso de Opioides , Adulto , Humanos , Estados Unidos/epidemiologia , Hospitalização , Infarto do Miocárdio/terapia , Readmissão do Paciente , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Transtornos Relacionados ao Uso de Opioides/terapia , Alta do Paciente , Estudos Retrospectivos
13.
J Am Heart Assoc ; 12(10): e028653, 2023 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-37183876

RESUMO

Background Guidelines for choice of prosthetic heart valve in people of reproductive age are not well established. Although biologic heart valves (BHVs) have risk of deterioration, mechanical heart valves (MHVs) require lifelong anticoagulation. This study aimed to characterize the association of prosthetic valve type with maternal and fetal outcomes in pregnant patients. Methods and Results Using the 2008 to 2019 National Inpatient Sample, we identified all adult patients hospitalized for delivery with prior heart valve implantation. Multivariable regressions were used to analyze the primary outcome, major adverse cardiovascular events, and secondary outcomes, including maternal and fetal complications, length of stay, and costs. Among 39 871 862 birth hospitalizations, 4152 had MHVs and 874 had BHVs. Age, comorbidities, and cesarean birth rates were similar between patients with MHVs and BHVs. The presence of a prosthetic valve was associated with over 22-fold increase in likelihood of major adverse cardiovascular events (MHV: adjusted odds ratio, 22.1 [95% CI, 17.3-28.2]; BHV: adjusted odds ratio, 22.5 [95% CI, 13.9-36.5]) as well as increased duration of stay and hospitalization costs. However, patients with MHVs and BHVs had no significant difference in the odds of any maternal outcome, including major adverse cardiovascular events, hypertensive disease of pregnancy, and ante/postpartum hemorrhage. Similarly, fetal complications were more likely in patients with valve prostheses, including a 4-fold increase in odds of stillbirth, but remained comparable between MHVs and BHVs. Conclusions Patients hospitalized for delivery with prior valve replacement carry substantial risk of adverse maternal and fetal events, regardless of valve type. Our findings reveal comparable outcomes between MHVs and BHVs.


Assuntos
Bioprótese , Doenças Cardiovasculares , Próteses Valvulares Cardíacas , Gravidez , Adulto , Feminino , Humanos , Valvas Cardíacas , Próteses Valvulares Cardíacas/efeitos adversos , Cuidado Pré-Natal , Parto , Doenças Cardiovasculares/etiologia
14.
Surg Open Sci ; 13: 66-70, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37181545

RESUMO

Background: While the impact of socioeconomic status (SES) on surgical outcomes has been examined in limited series, it remains a significant determinant of healthcare outcomes at the national level. Therefore, the current study aims to determine SES disparities at three time-points: hospital accessibility, in-hospital outcomes, and post-discharge consequences. Methods: The Nationwide Readmissions Database 2010-2018 was used to isolate major elective operations. SES was assigned using previously coded median income quartiles as defined by patient zip-code, with low SES defined as the lowest quartile and high SES as the highest. Results: Of an estimated 4,816,837 patients undergoing major elective operations, 1,037,689 (21.3 %) were categorized as low SES and 1,288,618 (26.5 %) as high. On univariate analysis and compared to those of low SES, high SES patients were more frequently treated at high-volume centers (70.9 vs 55.6 %, p < 0.001), had lower rates of in-hospital complications (24.0 vs 29.0 %, p < 0.001) and mortality (0.4 vs 0.9 %, p < 0.001) as well as less frequent urgent readmissions at 30- (5.7 vs 7.1 %, p < 0.001) and 90-day timepoints (9.4 vs 10.7 %, p < 0.001). On multivariable analysis, high SES patients had higher odds of treatment at high-volume centers (Odds: 1.87, 95 % CI: 1.71-2.06), and lower odds of perioperative complications (Odds: 0.98, 95 % CI: 0.96-0.99), mortality (Odds: 0.70, 95 % CI: 0.65-0.75), and urgent readmissions at 90-days (Odds: 0.95, 95 % CI: 0.92-0.98). Conclusion: This study fills a much-needed gap in the current literature by establishing that all of the aforementioned timepoints include significant disadvantages for those of low socioeconomic status. Therefore, a multidisciplinary approach may be required for intervention to improve equity for surgical patients.

15.
Sci Rep ; 13(1): 8120, 2023 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-37208429

RESUMO

This study assessed the contribution of five genes previously known to be involved in cholestatic liver disease in British Bangladeshi and Pakistani people. Five genes (ABCB4, ABCB11, ATP8B1, NR1H4, TJP2) were interrogated by exome sequencing data of 5236 volunteers. Included were non-synonymous or loss of function (LoF) variants with a minor allele frequency < 5%. Variants were filtered, and annotated to perform rare variant burden analysis, protein structure, and modelling analysis in-silico. Out of 314 non-synonymous variants, 180 fulfilled the inclusion criteria and were mostly heterozygous unless specified. 90 were novel and of those variants, 22 were considered likely pathogenic and 9 pathogenic. We identified variants in volunteers with gallstone disease (n = 31), intrahepatic cholestasis of pregnancy (ICP, n = 16), cholangiocarcinoma and cirrhosis (n = 2). Fourteen novel LoF variants were identified: 7 frameshift, 5 introduction of premature stop codon and 2 splice acceptor variants. The rare variant burden was significantly increased in ABCB11. Protein modelling demonstrated variants that appeared to likely cause significant structural alterations. This study highlights the significant genetic burden contributing to cholestatic liver disease. Novel likely pathogenic and pathogenic variants were identified addressing the underrepresentation of diverse ancestry groups in genomic research.


Assuntos
Colelitíase , Colestase Intra-Hepática , Colestase , Feminino , Gravidez , Humanos , Mutação , Colestase/genética , Colestase Intra-Hepática/genética , Colestase Intra-Hepática/metabolismo , Reino Unido/epidemiologia
16.
Heart ; 109(19): 1460-1466, 2023 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-37258097

RESUMO

OBJECTIVE: To assess the reliability of 30-day non-elective readmissions as a quality metric for adult cardiac surgery. BACKGROUND: Unplanned readmissions is a quality metric for adult cardiac surgery. However, its reliability in benchmarking hospitals remains under-explored. METHODS: Adults undergoing elective isolated coronary artery bypass grafting (CABG), surgical aortic valve replacement/repair (SAVR) or mitral valve replacement/repair (MVR) were tabulated from 2019 Nationwide Readmissions Database. Multi-level regressions were developed to model the likelihood of 30-day unplanned readmissions and major adverse events (MAE). Random intercepts were estimated, and associations between hospital-specific risk-adjusted rates of readmissions and were assessed using the Pearson correlation coefficient (r). RESULTS: Of an estimated 86 024 patients meeting study criteria across 298 hospitals, 62.6% underwent CABG, 22.5% SAVR and 14.9% MVR. Unadjusted readmission rates following CABG, SAVR and MVR were 8.4%, 9.3% and 11.8%, respectively. Unadjusted MAE rates following CABG, SAVR and MVR were 35.1%, 32.3% and 37.0%, respectively. Following adjustment, interhospital differences accounted for 4.1% of explained variance in readmissions for CABG, 7.6% for SAVR and 10.0% for MVR. There was no association between readmission rates for CABG and SAVR (r=0.10, p=0.09) or SAVR and MVR (r=0.09, p=0.1). A weak association was noted between readmission rates for CABG and MVR (r=0.20, p<0.001). There was no significant association between readmission and MAE for CABG (r=0.06, p=0.2), SAVR (r=0.04, p=0.4) and MVR (r=-0.03, p=0.6). CONCLUSION: Our findings suggest that readmissions following adult cardiac surgery may not be an ideal quality measure as hospital factors do not appear to influence this outcome.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Implante de Prótese de Valva Cardíaca , Humanos , Adulto , Readmissão do Paciente , Reprodutibilidade dos Testes , Resultado do Tratamento , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ponte de Artéria Coronária/efeitos adversos , Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Fatores de Risco
17.
Surgery ; 173(6): 1405-1410, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36914511

RESUMO

BACKGROUND: A paradoxical increase in mortality following extracorporeal membrane oxygenation at high-volume centers has previously been demonstrated. We examined the association between annual hospital volume and outcomes within a contemporary, national cohort of extracorporeal membrane oxygenation patients. METHODS: All adults requiring extracorporeal membrane oxygenation for postcardiotomy syndrome, cardiogenic shock, respiratory failure, or mixed cardiopulmonary failure were identified in the 2016 to 2019 Nationwide Readmissions Database. Patients undergoing heart and/or lung transplantation were excluded. A multivariable logistic regression with hospital extracorporeal membrane oxygenation volume parametrized as restricted cubic splines was developed to characterize the risk-adjusted association between volume and mortality. The volume corresponding to the maximum of the spline (43 cases/year) was used to categorize centers as low- or high-volume. RESULTS: An estimated 26,377 patients met the study criteria, and 48.7% were managed at high-volume hospitals. Patients at low- and high-volume hospitals had similar age, sex, and rates of elective admission. Notably, patients at high-volume hospitals less frequently required extracorporeal membrane oxygenation for postcardiotomy syndrome but more commonly for respiratory failure. After risk adjustment, high-volume hospital status was associated with reduced odds of in-hospital mortality, relative to low-volume hospitals (adjusted odds ratio 0.81, 95% confidence interval 0.78-0.97). Interestingly, patients at high-volume hospitals faced a 5.2-day increment in length of stay (95% confidence interval 3.8-6.5) and $23,500 in attributable costs (95% confidence interval 8,300-38,700). CONCLUSION: The present study found that greater extracorporeal membrane oxygenation volume was associated with decreased mortality but higher resource use. Our findings may help inform policies regarding access to and centralization of extracorporeal membrane oxygenation care in the United States.


Assuntos
Oxigenação por Membrana Extracorpórea , Insuficiência Respiratória , Adulto , Humanos , Estados Unidos/epidemiologia , Estudos Retrospectivos , Choque Cardiogênico , Hospitais com Alto Volume de Atendimentos , Mortalidade Hospitalar , Insuficiência Respiratória/terapia
18.
Pediatr Cardiol ; 44(4): 826-835, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36906870

RESUMO

A body of literature has previously highlighted the impact of health insurance on observed disparities in congenital cardiac operations. With aims of improving access to healthcare for all patients, the Affordable Care Act (ACA) expanded Medicaid coverage to nearly all eligible children in 2010. Therefore, the present population-based study aimed to examine the association of Medicaid coverage with clinical and financial outcomes in the era the ACA. Records for pediatric patients (≤ 18 years) who underwent congenital cardiac operations were abstracted from the 2010-2018 Nationwide Readmissions Database. Operations were stratified using the Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) Category. Multivariable regression models were developed to evaluate the association of insurance status on index mortality, 30-day readmissions, care fragmentation, and cumulative costs. Of an estimated 132,745 hospitalizations for congenital cardiac surgery from 2010 to 2018, 74,925 (56.4%) were insured by Medicaid. The proportion of Medicaid patients increased from 57.6 to 60.8% during the study period. On adjusted analysis, patients with Medicaid insurance were at an increased odds of mortality (1.35, 95%CI: 1.13-1.60) and 30-day unplanned readmission (1.12, 95%CI: 1.01-1.25), experienced longer lengths of stay (+ 6.5 days, 95%CI 3.7-9.3), and exhibited higher cumulative hospitalization costs (+ $21,600, 95%CI: $11,500-31,700). The total hospitalization cost-burden for patients with Medicaid and private insurance were $12.6 billion and $8.06 billion, respectively. Medicaid patients exhibited increased mortality, readmissions, care fragmentation, and costs compared to those with private insurance. Our results of outcome variation by insurance status indicate the necessity of policy changes to attempt to approach equality in surgical out comes for this high-risk cohort. Baseline characteristics, trends, and outcomes by insurance status over the ACA rollout period 2010-2018.


Assuntos
Seguro Saúde , Patient Protection and Affordable Care Act , Estados Unidos , Humanos , Criança , Medicaid , Cobertura do Seguro , Hospitalização
19.
Frontline Gastroenterol ; 14(2): 124-131, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36818790

RESUMO

Objective: Prepregnancy counselling (PPC) is an important aspect of care for women with chronic liver disease (CLD) and liver transplantation (LT), yet its impact has not been well described. This study aims to assess the experience of women attending a joint obstetric-hepatology PPC clinic in a single-centre unit. Design/methods: A retrospective questionnaire-based study in a tertiary unit within the UK where patients who attended the PPC clinic between March 2016 and July 2021 were invited to participate by filling in a questionnaire. Descriptive data and free-text content were subsequently analysed. Results: 108 women attended the PPC clinic over a 5-year period. Overall, 58/108 (54%) completed the questionnaire. Principal concerns regarding pregnancy included fears around deterioration in health (66%), maternal death (24%), pregnancy loss (66%), medication effects (60%) and disease transmission (36%). 17/58 (14%) patients felt the presence of multiple doctors was intimidating, however, perceptions improved by the end of the consultation.Overall, 44/58 (76%) respondents felt the clinic helped them reach a decision about pursuing pregnancy. Almost all respondents would recommend the clinic to others. There were no major differences in pregnancy outcomes between those that received PPC and those that did not. Conclusion: The PPC clinic facilitates a personalised approach to care and is well received by patients with CLD/LT. It is difficult to elucidate whether attendance alone impacts on pregnancy outcomes; registry data may be better placed at addressing this important question.

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