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Investigating genetic links between blood metabolites and preeclampsia

BMC Womens Health. 2024 Apr 5;24(1):223. doi: 10.1186/s12905-024-03000-7.

ABSTRACT

BACKGROUND: Observational studies have revealed that metabolic disorders are closely related to the development of preeclampsia (PE). However, there is still a research gap on the causal role of metabolites in promoting or preventing PE. We aimed to systematically explore the causal association between circulating metabolites and PE.

METHODS: Single nucleotide polymorphisms (SNPs) from genome-wide association study (GWAS) of 486 blood metabolites (7,824 participants) were extracted as instrumental variables (P < 1 × 10– 5), GWAS summary statistics for PE were obtained from FinnGen consortium (7,212 cases and 194,266 controls) as outcome, and a two-sample Mendelian randomization (MR) analysis was conducted. Inverse variance weighted (IVW) was set as the primary method, with MR-Egger and weighted median as auxiliary methods; the instrumental variable strength and confounding factors were also assessed. Sensitivity analyses including MR-Egger, Cochran’s Q test, MR-PRESSO and leave-one-out analysis were performed to test the robustness of the MR results. For significant associations, repeated MR and meta-analysis were performed by another metabolite GWAS (8,299 participants). Furthermore, significantly associated metabolites were subjected to a metabolic pathway analysis.

RESULTS: The instrumental variables for the metabolites ranged from 3 to 493. Primary analysis revealed a total of 12 known (e.g., phenol sulfate, citrulline, lactate and gamma-glutamylglutamine) and 11 unknown metabolites were associated with PE. Heterogeneity and pleiotropy tests verified the robustness of the MR results. Validation with another metabolite GWAS dataset revealed consistency trends in 6 of the known metabolites with preliminary analysis, particularly the finding that genetic susceptibility to low levels of arachidonate (20:4n6) and citrulline were risk factors for PE. The pathway analysis revealed glycolysis/gluconeogenesis and arginine biosynthesis involved in the pathogenesis of PE.

CONCLUSIONS: This study identifies a causal relationship between some circulating metabolites and PE. Our study presented new perspectives on the pathogenesis of PE by integrating metabolomics with genomics, which opens up avenues for more accurate understanding and management of the disease, providing new potential candidate metabolic molecular markers for the prevention, diagnosis and treatment of PE. Considering the limitations of MR studies, further research is needed to confirm the causality and underlying mechanisms of these findings.

PMID:38580943 | DOI:10.1186/s12905-024-03000-7

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Impact of burnout and professional fulfillment on intent to leave among pediatric physicians: The findings of a quality improvement initiative

BMC Health Serv Res. 2024 Apr 5;24(1):434. doi: 10.1186/s12913-024-10842-2.

ABSTRACT

BACKGROUND AND OBJECTIVES: Physician burnout is rampant, and physician retention is increasingly hard. It is unclear how burnout impacts intent to leave an organization. We sought to determine how physician burnout and professional fulfillment impact pediatric physicians’ intent to leave (ITL) an organization.

DESIGN AND METHODS: We performed 120, 1:1 semi-structured interviews of our pediatric faculty and used the themes therefrom to develop a Likert-scale based, 22-question battery of their current work experience. We created a faculty climate survey by combining those questions with a standardized instrument that assesses burnout and professional fulfillment. We surveyed pediatric and pediatric-affiliated (e.g. pediatric surgery, pediatric psychiatry, etc.) physicians between November 2 and December 9, 2022. We used standard statistical methods to analyze the data. An alpha-level of 0.05 was used to determine significance.

RESULTS: A total of 142 respondents completed the survey, 129 (91%) were Department of Pediatrics faculty. Burnout was present in 41% (58/142) of respondents, whereas 30% (42/142) were professionally fulfilled. There was an inverse relationship between professional fulfillment and ITL, p < 0.001 for the trend. Among those who were not professionally fulfilled, the odds ratio of ITL in the next three years was 3.826 [95% CI 1.575-9.291], p = 0.003. There was a direct relationship between burnout and ITL, p < 0.001 for the trend.

CONCLUSIONS: Among pediatric physicians, professional fulfillment is strongly, inversely related with ITL in the next three years. Similarly, burnout is directly related with ITL. These data suggest a lack of professional fulfillment and high burnout are strong predictors of pediatric physician turnover.

PMID:38580940 | DOI:10.1186/s12913-024-10842-2

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Incidence and factors associated with failed spinal anaesthesia among patients undergoing surgery: a multi- center prospective observational study

BMC Anesthesiol. 2024 Apr 5;24(1):129. doi: 10.1186/s12871-024-02484-y.

ABSTRACT

BACKGROUND: Failed spinal anaesthesia causes prolonging of operation time, insufficient analgesia for surgery and needs repeating spinal anaesthesia which in turn causes local anaesthesia toxicity, high spinal and total spinal, and conversion to general anaesthesia. However, the problem remains unexplored in Amhara regional state comprehensive specialized hospitals.

OBJECTIVE: To determine incidence and factors associated with failed spinal anaesthesia among patients undergoing surgery in selected Amhara National Regional State comprehensive specialized hospitals, Northwest Ethiopia, 2023.

METHODS: Multi-center prospective observational study was conducted. Data was collected using questionnaire and checklist. All consecutive scheduled emergency and elective patients were included in the study. Data was transformed from Epi data to SPSS and logistic regression analysis was done. Both crude and adjusted odds ratio were used to assess the strength of association. Variables with a p-value of less than 0.05 were considered as statistically significant.

RESULTS: A total of 532 patients were included in this study with a response rate of 98%. Incidence of failed spinal anaesthesia was 22.4% (CI = 19-25.9). Emergency surgery (AOR = 7.01, CI = 4.5-12.7), dose of bupivacaine of ≤ 10 mg (AOR = 3.02, CI = 1.3-10.2), work experience of anaesthetist < 2 years (AOR = 3.1, CI = 1.7-5.72), bloody CSF (AOR = 8.5, CI = 2.53-18.5), hyperbaric local anaesthetic drug (AOR = 3.3, 95% CI = 3.2-8.2) and local anaesthetist without adjuvants (AOR = 5.25, CI = 2.62-14.2) were associated failed spinal anaesthesia.

CONCLUSION AND RECOMMENDATION: The incidence of failed spinal anaesthesia was high in Amhara Region comprehensive specialized hospitals. We suggest that anaesthesia providers should minimize failure by using adjuvants and appropriate dose of local anaesthetic. Additionally, simulation training should be given for anaesthesia trainees to improve their skills and to produce competent professionals.

PMID:38580926 | DOI:10.1186/s12871-024-02484-y

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Access to a pre-sleep protein snack increases daily energy and protein intake in surgical hospitalized patients

Clin Nutr. 2024 Mar 28;43(5):1073-1078. doi: 10.1016/j.clnu.2024.03.016. Online ahead of print.

ABSTRACT

BACKGROUND & AIM: In hospitalized patients, daily protein intake remains far below WHO requirements for healthy adults (0.8 g·kg-1·d-1) as well as ESPEN guidelines for patients (1.2-1.5 g·kg-1·d-1). Providing access to a pre-sleep protein dense snack between dinner and going to bed may serve as a great opportunity to increase daily energy and protein intake in hospitalized patients. However, it remains to be assessed whether protein provision prior to sleep effectively increases protein intake, or may reduce food intake throughout the remainder of the day(s). The present study evaluated the impact of giving access to a pre-sleep snack on daily energy and protein intake in patients throughout their hospitalization.

METHODS: Patients admitted to the surgical wards of the Maastricht University Medical Centre+ were randomly allocated to usual care (n = 51) or given access to a pre-sleep snack (n = 50). The pre-sleep snack consisted of 103 g cheese cubes (30 g protein) provided between 7:30 and 9:30 PM, prior to sleep. All food provided and all food consumed was weighed and recorded throughout (2-7 days) hospitalization. Daily energy and protein intake and distribution were calculated. Data were analyzed by independent T-Tests with P < 0.05 considered as statistically significant.

RESULTS: Daily energy intake was higher in the pre-sleep group (1353 ± 424 kcal d-1) when compared to the usual care group (1190 ± 402 kcal·d-1; P = 0.049). Providing patients access to a pre-sleep snack resulted in a 17% (11 ± 9 g) higher daily protein intake (0.81 ± 0.29 g·kg-1·d-1) when compared to the usual care group (0.69 ± 0.28 g·kg-1·d-1; P = 0.045). Protein intake at breakfast, lunch, and dinner did not differ between the pre-sleep and usual care groups (all P > 0.05).

CONCLUSION: Providing access to a pre-sleep protein snack, in the form of protein dense food items such as cheese, represents an effective dietary strategy to increase daily energy and protein intake in hospitalized patients. Patients consuming pre-sleep protein snacks do not compensate by lowering energy or protein intake throughout the remainder of the days. Pre-sleep protein dense food provision should be implemented in hospital food logistics to improve the nutritional intake of patients.

TRIAL REGISTER NO: NL8507 (https://trialsearch.who.int/).

PMID:38579369 | DOI:10.1016/j.clnu.2024.03.016

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Which behaviour change techniques work best for diabetes self-management mobile apps? Results from a systematic review and meta-analysis of randomised controlled trials

EBioMedicine. 2024 Apr 4;103:105091. doi: 10.1016/j.ebiom.2024.105091. Online ahead of print.

ABSTRACT

BACKGROUND: Self-management is pivotal in addressing noncommunicable diseases, such as diabetes. The increased availability of digital behaviour change interventions (DBCIs) delivered through mobile health apps offers unprecedented opportunities to enhance self-management and improve health outcomes. However, little is known about the characteristics of DBCIs for diabetes that significantly impact glycaemic control. Therefore, our systematic review with meta-analysis aimed to summarize characteristics and behaviour change components in DBCIs for diabetes self-management and explore potential associations with metabolic outcomes.

METHODS: A systematic search was conducted in PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Scopus to identify randomized controlled trials published until November 2023. The main outcome variable was the change in the mean difference of HbA1c levels between baseline and follow-up across intervention and control groups. Random-effects meta-regression was used to explore variation in glycaemic control as a function of prespecified characteristics of study designs and app interventions.

FINDINGS: A total of 57 studies was included in the analysis, showing a statistically significant percentage point reduction in HbA1c for the intervention group compared to the control arm (-0.36, 95% CI = -0.46 to -0.26, p < 0.001). The inclusion of “self-monitoring of behaviour” as a behaviour change technique (β = -0.22, p = 0.04) and “taking medication” as a target behaviour (β = -0.20, p = 0.05) was associated with improved metabolic outcomes.

INTERPRETATION: Our analyses endorse the use of diabetes self-management apps, highlighting characteristics statistically associated with intervention effectiveness and guiding the design of more effective DBCIs.

FUNDING: This project received funding from the European Union’s Horizon 2020 programme.

PMID:38579364 | DOI:10.1016/j.ebiom.2024.105091

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The role of occipital condyle and atlas anomalies on occipital cervical fusion outcomes in Chiari malformation type I with syringomyelia: a study from the Park-Reeves Syringomyelia Research Consortium

J Neurosurg Pediatr. 2024 Apr 5:1-9. doi: 10.3171/2024.1.PEDS23229. Online ahead of print.

ABSTRACT

OBJECTIVE: Congenital anomalies of the atlanto-occipital articulation may be present in patients with Chiari malformation type I (CM-I). However, it is unclear how these anomalies affect the biomechanical stability of the craniovertebral junction (CVJ) and whether they are associated with an increased incidence of occipitocervical fusion (OCF) following posterior fossa decompression (PFD). The objective of this study was to determine the prevalence of condylar hypoplasia and atlas anomalies in children with CM-I and syringomyelia. The authors also investigated the predictive contribution of these anomalies to the occurrence of OCF following PFD (PFD+OCF).

METHODS: The authors analyzed the prevalence of condylar hypoplasia and atlas arch anomalies for patients in the Park-Reeves Syringomyelia Research Consortium database who underwent PFD+OCF. Condylar hypoplasia was defined by an atlanto-occipital joint axis angle (AOJAA) ≥ 130°. Atlas assimilation and arch anomalies were identified on presurgical radiographic imaging. This PFD+OCF cohort was compared with a control cohort of patients who underwent PFD alone. The control group was matched to the PFD+OCF cohort according to age, sex, and duration of symptoms at a 2:1 ratio.

RESULTS: Clinical features and radiographic atlanto-occipital joint parameters were compared between 19 patients in the PFD+OCF cohort and 38 patients in the PFD-only cohort. Demographic data were not significantly different between cohorts (p > 0.05). The mean AOJAA was significantly higher in the PFD+OCF group than in the PFD group (144° ± 12° vs 127° ± 6°, p < 0.0001). In the PFD+OCF group, atlas assimilation and atlas arch anomalies were identified in 10 (53%) and 5 (26%) patients, respectively. These anomalies were absent (n = 0) in the PFD group (p < 0.001). Multivariate regression analysis identified the following 3 CVJ radiographic variables that were predictive of OCF occurrence after PFD: AOJAA ≥ 130° (p = 0.01), clivoaxial angle < 125° (p = 0.02), and occipital condyle-C2 sagittal vertical alignment (C-C2SVA) ≥ 5 mm (p = 0.01). A predictive model based on these 3 factors accurately predicted OCF following PFD (C-statistic 0.95).

CONCLUSIONS: The authors’ results indicate that the occipital condyle-atlas joint complex might affect the biomechanical integrity of the CVJ in children with CM-I and syringomyelia. They describe the role of the AOJAA metric as an independent predictive factor for occurrence of OCF following PFD. Preoperative identification of these skeletal abnormalities may be used to guide surgical planning and treatment of patients with complex CM-I and coexistent osseous pathology.

PMID:38579359 | DOI:10.3171/2024.1.PEDS23229

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Development and validation of machine learning models to predict postoperative infarction in moyamoya disease

J Neurosurg. 2024 Apr 5:1-9. doi: 10.3171/2024.1.JNS232173. Online ahead of print.

ABSTRACT

OBJECTIVE: Cerebral infarction is a common complication in patients undergoing revascularization surgery for moyamoya disease (MMD). Although previous statistical evaluations have identified several risk factors for postoperative brain ischemia, the ability to predict its occurrence based on these limited predictors remains inadequately explored. This study aimed to assess the feasibility of machine learning algorithms for predicting cerebral infarction after revascularization surgery in patients with MMD.

METHODS: This retrospective study was conducted across two centers and harnessed data from 512 patients with MMD who had undergone revascularization surgery. The patient cohort was partitioned into internal and external datasets. Using perioperative clinical data from the internal cohort, three distinct machine learning algorithms-namely the support vector machine, random forest, and light gradient-boosting machine models-were trained and cross-validated to predict the occurrence of postoperative cerebral infarction. Predictive performance validity was subsequently assessed using an external dataset. Shapley additive explanations (SHAP) analysis was conducted to augment the prediction model’s transparency and to quantify the impact of each input variable on shaping both the aggregate and individual patient predictions.

RESULTS: In the cohort of 512 patients, 33 (6.4%) experienced postrevascularization cerebral infarction. The cross-validation outcomes revealed that, among the three models, the support vector machine model achieved the largest area under the receiver operating characteristic curve (ROC-AUC) at mean ± SD 0.785 ± 0.052. Notably, during external validation, the light gradient-boosting machine model exhibited the highest accuracy at 0.903 and the largest ROC-AUC at 0.710. The top-performing prediction model utilized five input variables: postoperative serum gamma-glutamyl transpeptidase value, positive posterior cerebral artery (PCA) involvement on preoperative MRA, infarction as the rationale for surgery, presence of an infarction scar on preoperative MRI, and preoperative modified Rankin Scale score. Furthermore, the SHAP analysis identified presence of PCA involvement, infarction as the rationale for surgery, and presence of an infarction scar on preoperative MRI as positive influences on postoperative cerebral infarction.

CONCLUSIONS: This study indicates the usefulness of employing machine learning techniques with routine perioperative data to predict the occurrence of cerebral infarction after revascularization procedures in patients with MMD.

PMID:38579355 | DOI:10.3171/2024.1.JNS232173

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Ultraviolet Excitation of M-O2 (M = Phenalenone, Fluorenone, Pyridine, & Acridine) Complexes Resulting in 1O2

J Phys Chem A. 2024 Apr 5. doi: 10.1021/acs.jpca.4c00143. Online ahead of print.

ABSTRACT

In our experiment, a trace amount of an organic molecule (M = 1H-phenalen-1-one, 9-fluorenone, pyridine, or acridine) was seeded into a gas mix consisting of 3% O2 with a rare gas buffer (He or Ar) and then supersonically expanded. We excited the resulting molecular beam with ultraviolet light at either 355 nm (1H-phenalen-1-one, 9-fluorenone, or acridine) or 266 nm (pyridine) and used resonance enhanced multiphoton ionization (REMPI) spectroscopy to probe for the formation of O2 in the a-1Δg state, 1O2. For all systems, the REMPI spectra demonstrate that ultraviolet excitation results in the formation of 1O2 and the oxygen product is confirmed to be in the ground vibrational state and with an effective rotational temperature below 80 K. We then recorded the velocity map ion image of the 1O2 product. From the ion images, we determined the center-of-mass translational energy distribution, P(ET), assuming photodissociation of a bimolecular M-O2 complex. We also report results from electronic structure calculations that allow for a determination of the M-O2 ground state binding energy. We use the complex binding energy, the energy to form 1O2, and the adiabatic triplet energy for each organic molecule to determine the available energy following photodissociation. For dissociation of a bimolecular complex, this available energy may be partitioned into either center-of-mass recoil or internal degrees of freedom of the organic moiety. We use the available energy to generate a Prior distribution, which predicts statistical energy partitioning during dissociation. For low available energies, less than 0.2 eV, we find that the statistical prediction is in reasonable agreement with the experimental observations. However, at higher available energies, the experimental distribution is biased to lower center-of-mass kinetic energies compared with the statistical prediction, which suggests the complex undergoes vibrational predissociation.

PMID:38579334 | DOI:10.1021/acs.jpca.4c00143

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Opioid-Sparing Nonsteroid Anti-inflammatory Drugs Protocol in Patients Undergoing Intramedullary Nailing of Tibial Shaft Fractures: A Randomized Control Trial

J Am Acad Orthop Surg. 2024 Apr 4. doi: 10.5435/JAAOS-D-23-01014. Online ahead of print.

ABSTRACT

INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective analgesics commonly used in fracture management. Although previously associated with delayed fracture healing, multiple studies have demonstrated their safety, with minimal risks of fracture healing. Given the current opioid crisis in the United States, alternate pain control modalities are essential to reduce opioid consumption. This study aims to determine whether the combination of oral acetaminophen and intravenous ketorolac is a viable alternative to opioid-based pain management in closed tibial shaft fractures treated with intramedullary nailing.

METHODS: We conducted a randomized controlled trial evaluating postoperative pain control and opioid consumption in patients with closed tibial shaft fractures who underwent intramedullary nailing. Patients were randomized into an NSAID-based pain control group (52 patients) and an opioid-based pain control group (44 patients). Visual analog scale (VAS) scores and morphine milligram equivalents (MMEs) were evaluated at 12-hour postoperative intervals during the first 48 hours after surgery. Nonunion and delayed healing rates were recorded for both groups.

RESULTS: A statistically significant decrease in MMEs was noted at every measured interval (12, 24, 36, and 48 hours) in the NSAID group compared with the opioid group (P-value 0.001, 0.001, 0.040, 0.024, respectively). No significant change in visual analog scale scores was observed at 12, 36, and 48 hours between both groups (P-value 0.215, 0.12, and 0.083, respectively). A significant decrease in VAS scores was observed at the 24-hour interval in the NSAID group compared with the opioid group (P-value 0.041). No significant differences in union rates were observed between groups (P-value 0.820).

DISCUSSION: Using an NSAID-based postoperative pain protocol led to a decrease in opioid consumption without affecting pain scores or union rates. Owing to the minimal risk of short-term NSAID use, their role in the perioperative management of tibia shaft fractures is justified, especially when they reduce opioid consumption markedly.

LEVEL OF EVIDENCE: Therapeutic Level I.

PMID:38579315 | DOI:10.5435/JAAOS-D-23-01014

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Hospital incidence, mortality, and gender disparities in patients treated for type A aortic dissections in Switzerland – a secondary data analysis of Swiss DRG statistics

Swiss Med Wkly. 2023 Dec 4;153:3499. doi: 10.57187/s.3499.

ABSTRACT

AIMS OF THE STUDY: The incidence of type A aortic dissection (TAAD) has increased in several countries in recent decades, but epidemiological data for Switzerland are lacking. Furthermore, there are conflicting data regarding a gender-disparity with higher type A aortic dissection mortality in women. This study analysed sex-specific hospital incidence and in-hospital mortality rates of TAAD in Switzerland.

METHODS: This study is a secondary data analysis of case-related hospital discharge data from the Swiss Federal Statistical Office for 2009-2018. Cases that were hospitalised and surgically treated for type A aortic dissection were included in this analysis. Standardised incidence rates were calculated using the European standard population in 2013. All-cause in-hospital mortality rates were calculated as raw values and standardised for age, sex, and the van Walraven comorbidity score.

RESULTS: A total of 2117 participants were included in this study, of whom 67.1% were male. The age-standardised cumulative hospital incidence for type A aortic dissection treatment was 3.5 per 100,000 (95% CI: 3.3-3.7) for men and 1.7 (1.6-1.8) per 100,000 for women (p <0.001). The incidence rates increased in both sexes during the observed decade. The adjusted mortality rates for treatment of TAAD decreased from 27.6% (26.7-28.5%) in 2009 to 18.5% (17.9-19.1%) in 2018 in women, and they decreased from 19.0% (18.4-19.6%) to 12.3% (11.9-12.7%) in the same period in men. Multivariable logistic regression analysis revealed that female sex was significantly associated with higher mortality, with an odds ratio of 1.39 (1.07-1.79) (p = 0.012).

CONCLUSIONS: Hospital incidence rates for the treatment of type A aortic dissection increased in both sexes over the observed decade. The mortality rate was significantly higher in women than it was in men, but it decreased in both sexes. TAAD remains a cardiovascular emergency with a high mortality rate even after emergency surgery.

PMID:38579314 | DOI:10.57187/s.3499