bluuebunny/crossref_metadata_2025 huggingface dataset:
Early versus late surgical treatment of pelvic and acetabular fractures a five-year follow-up of 419 patients
Authors: Enocson Anders , Lundin Natalie
Published: October 2023

Background

Surgical treatment of pelvic and acetabular fractures is an advanced intervention with a high risk of subsequent complications. These patients are often polytrauma patients with multiple injuries in several organ systems. The optimal timing for the definitive surgery of these fractures has been debated. The primary aim of this study was to investigate the influence of timing of definitive surgery on the rate of unplanned reoperations. Secondary aims included its influence on the occurrence of adverse events and mortality.

Methods

All patients from 18 years with a surgically treated pelvic or acetabular fracture operated at the Karolinska University Hospital in Sweden during 2010 to 2019 were identified and included. Data was collected through review of medical records and radiographs. Logistic regression analysis was performed to evaluate factors associated with unplanned reoperations and other adverse events.

Results

A total of 419 patients with definitive surgical treatment within 1 month of a pelvic (n = 191, 46%) or an acetabular (n = 228, 54%) fracture were included. The majority of the patients were males (n = 298, 71%) and the mean (SD, range) age was 53.3 (19, 18–94) years. A total of 194 (46%) patients had their surgery within 72 h (early surgery group), and 225 (54%) later than 72 h (late surgery group) after the injury. 95 patients (23%) had an unplanned reoperation. There was no difference in the reoperation rate between early (n = 44, 23%) and late (n = 51, 23%) surgery group (p = 1.0). A total of 148 patients (35%) had any kind of adverse event not requiring reoperation. The rate was 32% (n = 62) in the early, and 38% (n = 86) in the late surgery group (p = 0.2). When adjusting for relevant factors in regression analyses, no associations were found that increased the risk for reoperation or other adverse events. The 30-day mortality was 2.1% (n = 4) for the early and 2.2% (n = 5) for the late surgery group (p = 1.0). The 1-year mortality was 4.1% (n = 8) for the early and 7.6% (n = 17) for the late surgery group (p = 0.2).

Conclusions

Early (within 72 h) definitive surgery of patients with pelvic or acetabular fractures seems safe with regard to risk for reoperation, other adverse events and mortality.
Anatomical investigation of the pelvic urogenital fascia in 10 formalin-fixed female cadavers: novel insights into the laparoscopic total mesometrial resection
Authors: Zhou Zheqi , Li Bin , Zhou Jinsong , Ma Yanbing , Zhao Yang , Tong Cong , Wang Hui , Jin Dian , Li Yujie , Yan Likun
Published: October 2023

Purpose

Previous anatomical studies of the urogenital fascia (UGF) have focused on males, and there is a lack of relevant anatomical studies on the distribution of the extraperitoneal UGF in females.

Methods

In this investigation, guided by the embryonic development of the female urogenital system, the ventral pelvic fascia structure of 10 female cadavers was dissected, and the distribution and morphology of female extraperitoneal UGF were observed, recorded in text, photographs and video, and 3D modeling was performed.

Results

We find that in the female extraperitoneal space there is a migratory fascial structure, the UGF, which surrounds the urogenital system and extends from the perinephric region to the pelvis along with the development of the urogenital organs. The two layers of the UGF are composed of loose connective tissue rich in fat that surrounds the urogenital organs, their accessory vascular structures, and the nerves of the abdominopelvic cavity. In the pelvis, it participates in the formation of the ligamentous structures around the rectum and uterus. Finally, it surrounds the bladder and gradually moves into the loose connective tissue of the medial umbilical fold.

Conclusions

Sorting out the distribution characteristics of UGF has some reference value for studying the metastasis of gynecological tumors, the biomechanical structure of the female pelvis, and the surgical methods of gynecology, colorectal surgery, and hernia surgery.
Efficacy of hyaluronic acid gel and photobiomodulation therapy on wound healing after surgical gingivectomy: a randomized controlled clinical trial
Authors: Yakout Basma Khalil , Kamel Fatma Ramzy , Khadr Maha Abd El-Aziz Abou , Heikal Lamia Ahmed Hassan , El-Kimary Gillan Ibrahim
Published: October 2023

Background

Surgical gingivectomy can be considered the gold standard treatment for gingival enlargement. The healing of wound site after gingivectomy occurs slowly by secondary intention. To accelerate the wound healing process, several studies have been conducted evaluating the effect of various treatment modalities. Photobiomodulation therapy (PBMT) was proposed to provide minimally invasive and painless treatment as well as to decrease discomfort of the patient following the surgical process. Another factor that is expected to improve the healing after surgery is topical application of chemotherapeutic agents such as Hyaluronic acid (HA). This study aims to assess the effect of topically applied HA gel after PBMT on the healing of wound site after surgical gingivectomy.

Methods

This randomized controlled clinical trial included twenty-six surgical gingivectomy wound sites, equally divided into two groups, Group-I (test group): the surgical sites after gingivectomy were irradiated with a diode laser (980 nm, 0.2 W) then covered by 2% HA gel loaded in a special custom-made soft transparent tissue guard appliance for each patient. Group II (control group): the surgical sites were irradiated with a diode laser (980 nm, 0.2 W) only. Wound healing was assessed subjectively by Landry healing index on the 3rd, 7th, 14th and 21st days after surgery, and pain perception was assessed by the patients using visual analog scale (VAS) throughout the 21 days of the follow up period. Comparisons between the two study groups were performed using Mann-Whitney U test, while comparisons between different time points were performed using Friedman test. Significance was inferred at p value < 0.05.

Results

By the end of the follow-up period, surgical sites of the test group showed excellent healing compared to the control group. There were no significant differences in VAS scores between both groups (p > 0.05).

Conclusions

Application of 2% HA gel as an adjunctive to PBMT was found to have significant clinical effects and higher power of repair among test group when compared to that achieved by PBMT alone in control group.

Trial registration

This study was retrospectively registered on ClinicalTrials.gov and first posted on 28th of March 2023 with an identifier number: NCT05787912.
Drug take-back program: assessment of knowledge, practices, and barriers to safe disposal of unused medication among healthcare students in a Nigerian university
Authors: Akande-Sholabi Wuraola , Olaoye Damilola Q. , Adebisi Yusuff A.
Published: October 2023

Background

The safe disposal of unused medication is a critical public health issue, with risks including environmental pollution, accidental ingestion, and misuse. Inadequate adherence to proper disposal methods among healthcare students could affect the practice of safe disposal of unused medicines as future healthcare professionals. This study, conducted at a Nigerian university, aimed to assess the knowledge, adherence to safe disposal practices, and barriers faced by healthcare professional students regarding unused medication disposal.

Methods

A cross-sectional study was carried out among 930 healthcare students in a Nigerian University, comprising medical and surgery, nursing, pharmacy, physiotherapy, and medical laboratory science students. Information was gathered from respondents using a self-administered questionnaire. Multivariate analyses were used to evaluate the relationship between specific variables and participants’ knowledge and practice scores, while chi-square and logistic regression tests were used for categorical variables at p < 0.05.

Results

A total of 930 students participated in this study. The results revealed a significant gap in knowledge, with (67.7%; 630) of the participants unaware of proper disposal methods and most scoring either 0 (31.9%; 297) or 1 (46.0%; 428) out of 4 on a knowledge-based questionnaire. Pharmacy students were the most knowledgeable, with 44.4% falling into the high knowledge category. However, their knowledge did not always correspond to correct practices, with only (10.1%; 94) of participants reporting use of recommended disposal methods such as returning unused medicine to a pharmacy or a drug take-back program. Significant associations were found with course of study (χ²=12.14, p = 0.033) and awareness of correct disposal methods (χ²=4.035, p = 0.045). Those aware of the correct disposal method had a higher odds ratio of high knowledge score (OR = 1.62, 95% CI: 1.1–2.41, p = 0.018) compared to those who were not aware. In terms of disposal practices, those who had received training on safe disposal had significantly higher odds of good practice score (OR = 2.25, 95% CI: 1.36–3.74, p = 0.002). Major barriers identified included lack of access to drug take-back programs (50.4%; 469), lack of knowledge (36.8%; 342), and inconvenience (10.3%; 14).

Conclusion

A knowledge gap was revealed among the respondents regarding the safe disposal of unused medications. Despite the presence of knowledge and awareness, these do not necessarily translate into good disposal practices. This call for strategies to overcome identified barriers, with the aim to bridge the knowledge-practice gap and promote safe disposal of unused medication. The study underscores the urgent need for improved public health policies and educational programs on safe medication disposal.
Assessing anti-doping knowledge among Taiwanese pharmacists
Authors: Lee Yun-Chen , Chen Chung-Yu , Cheng Ya-Yun , Hsu Mei-Chich , Chen Ting-Ting , Chang William Chih-Wei
Published: October 2023

Background

Taiwan’s unique health behaviour, such as extensive exposure to Chinese Herbal Medicine (CHM), has introduced a risk of inadvertent doping among competing athletes. Pharmacy professionals have an imperative role in advising athletes on the safe use of medicines. This study provides an overview of anti-doping knowledge and educational needs among pharmacists in Taiwan and examines influencing factors.

Methods

A cross-sectional online questionnaire survey consisting of five domains, namely demographic characteristics, source of prohibited substances, identification of prohibited substances, understanding of doping control, and education needs on anti-doping, was distributed to the registered pharmacists in Taiwan. In total, 491 responses were included in the analyses.

Results

Respondents (65% female, aged 41.9 ± 11.4 years, with 68% having a Bachelor’s degree) reported a moderate anti-doping knowledge score of 37.2 ± 4.9, ranging from 21 to 48 (out of 51). Fifteen per cent of them had the experience of being counselled about drug use in sports. Higher knowledge scores were observed in younger respondents, showing an age-dependent effect (p < 0.001). Individuals practising in southern Taiwan (compared to northern Taiwan) and those working at clinics (compared to hospitals) exhibited lower knowledge. Most of the respondents (90%) knew that stimulant ephedrine is prohibited in sports, but few had recognised diuretic furosemide (38%) and CHM (7%) containing β2-agonist higenamine. Approximately 90% of respondents agreed with the need for anti-doping education.

Conclusions

This study highlights the heterogeneity of anti-doping knowledge among pharmacy professionals and provides practical relevance in organising future educational topics and research-based activities.
The muslim patient and medical treatments based on porcine ingredients
Authors: Bokek-Cohen Ya’arit , Gonen Limor D. , Tarabeih Mahdi
Published: October 2023

Porcine-derived products serve as an effective solution for a wide range of human ailments; however, there may be objections to their use due to Islamic religious prohibitions on consuming products derived from pigs. In order to enhance the cultural competence of medical practitioners who treat Muslim individuals, which constitute about one fifth of the world population, this study aimed at evaluating the knowledge and positions of Muslim patients on this subject. A questionnaire presenting 15 uses of porcine-derived materials was filled out by 809 Muslims. The level of knowledge about the permissibility of these uses and participants’ position on whether it should be approved was assessed. Findings show that Muslims are not familiar with Islamic religious jurisprudence that permits the use of porcine products to save lives after it has undergone an essential transformation known as Istihala. The respondents expressed a negative attitude towards the medical use of porcine-derived substances based on imprecise knowledge about the permissibility of use of porcine-derived materials, devices and treatments. We offer recommendations for improving the informed consent obtained from Muslim patients prior to conducting porcine-based treatments.
The future of FemTech ethics & privacy – a global perspective
Authors: Alfawzan Najd , Christen Markus
Published: October 2023

We discuss the concept of women’s empowerment in FemTech, considering cultural and legal differences, ethical concerns, and legal consequences. We claim that it is crucial to prioritize privacy, a fundamental right, especially in the case of changes in laws related to women’s health, such as Roe v. Wade in the US.
General practitioners’ attitudes towards and frequency of collaboration with pharmacists in China: a cross-sectional study
Authors: Cai Songtao , Huang Xianghui , Van Connie , Li Wanchao , Yan Ming , Lu Yiting , Li Haixin , Deng Zhiling , Lu Panpan , Xu Zhijie
Published: October 2023

Background

Building interprofessional working relationships between general practitioners (GPs) and pharmacists is essential to ensure high-quality patient care. However, there is limited Chinese literature on GP–pharmacist collaboration, and few studies have explored GPs’ experiences with pharmacist integration into general practices. This study aimed to investigate GPs’ attitudes towards and frequency of collaboration with pharmacists in China.

Methods

This cross-sectional study used an online self-administered questionnaire integrating two scales, ATCI-GP and FICI-GP, which had been translated and validated to investigate 3,248 GPs from February 15 to March 15, 2023 across Zhejiang Province, China. Descriptive analyses were used, and the factors associated with GPs’ frequency of collaboration with pharmacists were explored using logistic regression analysis.

Results

A total of 2,487 GPs (76.6%) responded and consented to participate in the survey; 52.3% were male and the mean age was 35.4 years. Most GPs agreed that they shared common goals and objectives with pharmacists when caring for patients (90.0%), and pharmacists were open to working with them on patients’ medication management (80.8%). However, half of the GPs did not change or seldom changed the patient’s medication on the pharmacist’s advice (51.4%). Logistic regression analysis showed that GPs who were older and had more years of practice were more likely to agree that pharmacists were willing to collaborate, had common goals for treatment and that they would change the patient’s medication on the advice of the pharmacist. GPs who had regular communication protocols (adjusted odds ratio1 [aOR1] = 1.88, 95% CI 1.45–2.45; aOR2 = 3.33, 95% CI 2.76–4.02), participated in joint continuing education (aOR1 = 1.87, 95% CI 1.44–2.43; aOR2 = 2.27, 95% CI 1.91–2.70), provided recommendations for medication review (aOR1 = 3.01, 95% CI 2.07–4.38; aOR2 = 3.50, 95% CI 2.51–4.86), and communicated with pharmacists during resident training (aOR1 = 2.15, 95% CI 1.78–2.60; aOR2 = 1.38, 95% CI 1.18–1.62) were associated with a more positive attitude towards and higher frequency of cooperation.

Conclusions

GPs in China displayed a positive attitude towards cooperating with pharmacists, but they did not demonstrate a similar level of practice. As environmental determinants impact interdisciplinary collaboration, healthcare managers and policy-makers need to implement measures that foster a supportive environment conducive to interdisciplinary collaboration.
Glycemic control, HbA1c variability, and major cardiovascular adverse outcomes in type 2 diabetes patients with elevated cardiovascular risk: insights from the ACCORD study
Authors: Pei Junyu , Wang Xiaopu , Pei Zeyu , Hu Xinqun
Published: October 2023

Background

Although recent guidelines advocate for HbA1c target individualization, a comprehensive criterion for patient categorization remains absent. This study aimed to categorize HbA1c variability levels and explore the relationship between glycemic control, cardiovascular outcomes, and mortality across different degrees of variability.

Methods

Action to Control Cardiovascular Risk in Diabetes study data were used. HbA1c variability was measured using the HbA1c variability score (HVS) and standard deviation (SD). K-means and K-medians clustering were used to combine the HVS and SD.

Results

K-means clustering was the most stable algorithm with the lowest clustering similarities. In the low variability group, intensive glucose-lowering treatment significantly reduced the risk of adverse cardiovascular outcomes (HR: 0·78 [95% CI: 0·63, 0·97]) without increasing mortality risk (HR: 1·07 [0.81, 1·42]); the risk of adverse cardiovascular events (HR: 1·33 [1·14, 1·56]) and all-cause mortality (HR: 1·23 [1·01,1·51]) increased with increasing mean HbA1c. In the high variability group, treatment increased the risk of cardiovascular events (HR: 2.00 [1·54, 2·60]) and mortality (HR: 2·20 [1·66, 2·92]); a higher mean HbA1c (7·86%, [7·66%, 8·06%]) had the lowest mortality risk, when the mean HbA1c was < 7·86%, a higher mean HbA1c was associated with a lower mortality risk (HR: 0·63 [0·42, 0·95]). In the medium variability group, a mean HbA1c around 7·5% was associated with the lowest risk.

Conclusions

HbA1c variability can guide glycemic control targets for patients with type 2 diabetes. For patients with low variability, the lower the HbA1c, the lower the risk. For those with medium variability, controlling HbA1c at 7·5% provides the maximum benefit. For patients with high variability, a mean HbA1c of around 7·8% presents the lowest risk of all-cause mortality, a lower HbA1c did not provide cardiovascular benefits but instead increased the mortality risk. Further studies, especially those with patients that reflect the general population with type 2 diabetes undergoing the latest therapeutic approaches, are essential to validate the conclusions of this study.
C-reactive protein during pregnancy and in the early postpartum predicts adverse metabolic health outcomes at 1 year postpartum in women with gestational diabetes
Authors: Quansah Dan Yedu , Horsch Antje , Gilbert Leah , Donath Marc Y. , Puder Jardena J. ,   the MySweetheart research group, Arhab Amar , Bovet Pascal , Chiolero Arnaud , Di Bernardo Stefano , Epure Adina Mihaela , Younes Sandrine Estoppey , Gilbert Leah , Gross Justine , Horsch Antje , Lanzi Stefano , Mayerat Seyda , Mivelaz Yvan , Puder Jardena J. , Quansah Dan Yedu , Rossel Jean-Benoit , Sekarski Nicole , Simeoni Umberto , Stuijfzand Bobby , Via. Yvan
Published: October 2023

Background

Women with gestational diabetes mellitus (GDM) have higher insulin resistance and/or reduced secretion, an increased risk of future diabetes and cardiovascular disease, which may be due to a pathological activation of the innate immune system. C-reactive protein (CRP) is induced by inflammatory cytokines and reflects innate immune activity. We investigated the prospective associations between CRP during the perinatal period with adverse metabolic outcomes at 1 year postpartum in women with previous GDM.

Methods

We analyzed data from the MySweetheart trial that included 211 women with GDM at 28–32 weeks gestational age (GA). CRP was measured during  pregnancy at 28-32 weeks GA, at 6–8 weeks and at 1 year postpartum. Metabolic outcomes at 1 year postpartum included weight, total and central body fat, measures of insulin resistance and secretion and presence of the metabolic syndrome (MetS). A 75 g oral glucose tolerance test was performed to measure glucose and insulin values every 30 min over 2 h to calculate indices of insulin resistance (MATSUDA, HOMA-IR) and of absolute (AUCins/glu, HOMA-B) and insulin resistance-adjusted insulin secretion (ISSI-2).

Results

CRP during pregnancy and at 6–8 weeks postpartum predicted increased weight, body fat and visceral adipose tissue (VAT), insulin resistance (higher HOMA-IR, lower MATSUDA), absolute insulin secretion (HOMA-B, AUCins/glu), a reduced adjusted insulin secretion (ISSI-2) and a higher prevalence of the MetS at 1 year postpartum (all p ≤ 0.036). These relationships particularly those concerning CRP during pregnancy, were independent of weight ( for VAT, insulin resistance and secretion indices, MetS; all p ≤ 0.032) and of body fat ( for VAT, MATSUDA, MetS; all p ≤ 0.038). 

Conclusion

CRP during pregnancy and in the early postpartum predicted an adverse cardio-metabolic profile in women with prior GDM at 1 year postpartum independent of weight. The prospective association of CRP with increased insulin resistance and reduced adjusted insulin secretion hint to the role of inflammation in the development of impaired metabolism after GDM and could be used as an early marker for risk stratification.
Predictive value of the stress hyperglycemia ratio in dialysis patients with acute coronary syndrome: insights from a multi-center observational study
Authors: Xie Enmin , Ye Zixiang , Wu Yaxin , Zhao Xuecheng , Li Yike , Shen Nan , Gao Yanxiang , Zheng Jingang
Published: October 2023

Background

Various studies have indicated that stress hyperglycemia ratio (SHR) can reflect true acute hyperglycemic status and is associated with poor outcomes in patients with acute coronary syndrome (ACS). However, data on dialysis patients with ACS are limited. The Global Registry of Acute Coronary Events (GRACE) risk score is a well-validated risk prediction tool for ACS patients, yet it underestimates the risk of major events in patients receiving dialysis. This study aimed to evaluate the association between SHR and adverse cardiovascular events in dialysis patients with ACS and explore the potential incremental prognostic value of incorporating SHR into the GRACE risk score.

Methods

This study enrolled 714 dialysis patients with ACS from January 2015 to June 2021 at 30 tertiary medical centers in China. Patients were stratified into three groups based on the tertiles of SHR. The primary outcome was major adverse cardiovascular events (MACE), and the secondary outcomes were all-cause mortality and cardiovascular mortality.

Results

After a median follow-up of 20.9 months, 345 (48.3%) MACE and 280 (39.2%) all-cause mortality occurred, comprising 205 cases of cardiovascular death. When the highest SHR tertile was compared to the second SHR tertile, a significantly increased risk of MACE (adjusted hazard ratio, 1.92; 95% CI, 1.48–2.49), all-cause mortality (adjusted hazard ratio, 2.19; 95% CI, 1.64–2.93), and cardiovascular mortality (adjusted hazard ratio, 2.70; 95% CI, 1.90–3.83) was identified in the multivariable Cox regression model. A similar association was observed in both diabetic and nondiabetic patients. Further restricted cubic spline analysis identified a J-shaped association between the SHR and primary and secondary outcomes, with hazard ratios for MACE and mortality significantly increasing when SHR was > 1.08. Furthermore, adding SHR to the GRACE score led to a significant improvement in its predictive accuracy for MACE and mortality, as measured by the C-statistic, net reclassification improvement, and integrated discrimination improvement, especially for those with diabetes.

Conclusions

In dialysis patients with ACS, SHR was independently associated with increased risks of MACE and mortality. Furthermore, SHR may aid in improving the predictive efficiency of the GRACE score, especially for those with diabetes. These results indicated that SHR might be a valuable tool for risk stratification and management of dialysis patients with ACS.
Novel drug delivery strategies for antidepressant active ingredients from natural medicinal plants: the state of the art
Authors: Yuan Shun , Ma Ting , Zhang Ya-Nan , Wang Ning , Baloch Zulqarnain , Ma Ke
Published: October 2023

Depression is a severe mental disorder among public health issues. Researchers in the field of mental health and clinical psychiatrists have long been faced with difficulties in slow treatment cycles, high recurrence rates, and lagging efficacy. These obstacles have forced us to seek more advanced and effective treatments. Research has shown that novel drug delivery strategies for natural medicinal plants can effectively improve the utilization efficiency of the active molecules in these plants and therefore improve their efficacy. Currently, with the development of treatment technologies and the constant updating of novel drug delivery strategies, the addition of natural medicinal antidepressant therapy has given new significance to the study of depression treatment against the background of novel drug delivery systems. Based on this, this review comprehensively evaluates and analyses the research progress in novel drug delivery systems, including nanodrug delivery technology, in intervention research strategies for neurological diseases from the perspective of natural medicines for depression treatment. This provided a new theoretical foundation for the development and application of novel drug delivery strategies and drug delivery technologies in basic and clinical drug research fields.

Graphical Abstract
“As safe as possible”: a qualitative study of opioid withdrawal and risk behavior among people who use illegal opioids
Authors: Frank David , Elliott Luther , Cleland Charles M. , Walters Suzan M. , Joudrey Paul J. , Russell Danielle M. , Meyerson Beth E. , Bennett Alex S.
Published: October 2023

Background

Opioid withdrawal is a regular occurrence among many people who use illicit opioids (PWUIO) that has also been shown to increase their willingness to engage in risk-involved behavior. The proliferation of fentanyl in the illicit opioid market may have amplified this relationship, potentially putting PWUIO at greater risk of negative health outcomes. Understanding the relationship between withdrawal and risk-involved behavior may also have important implications for the ways that problematic drug use is conceptualized, particularly in disease models of addiction, which position risk behavior as evidence of pathology that helps to justify ontological distinctions between addicts and non-addicts. Examining withdrawal, and its role in PWUIO’s willingness to engage in risk, may aid in the development of alternative theories of risk involvement and create discursive spaces for de-medicalizing and de-othering people who use illegal drugs.

Methods

This article is based on 32 semi-structured interviews with PWUIO in the New York City area who also reported recent withdrawal experience. Interviews were conducted remotely between April and August 2022 and recorded for later transcription. Data were then coded and analyzed based on a combination of inductive and deductive coding strategies and informed by the literature.

Results

Participants described a strong relationship between withdrawal and their willingness to engage in risk-involved behavior that was exacerbated by the proliferation of fentanyl. Yet, their descriptions did not align with narratives of risk as a product of bad decisions made by individuals. Rather, data demonstrated the substantial role of social and structural context, particularly drug policies like prohibition and criminalization, in the kinds of risks that PWUIO faced and their ability to respond to them.

Conclusions

Withdrawal should be taken more seriously both from an ethical perspective and as an important catalyst of risk behavior. However, theories that position activities taken to avoid withdrawal as irrational and as evidence of pathology are poorly aligned with the complexity of PWUIO’s actual lives. We recommend the use of less deterministic and less medicalized theories of risk that better account for differences between how people view the world, and for the role of socio-structural forces in the production of risk.
Live birth rates after resolution of endometrial cavity fluid in frozen embryo transfer cycles
Authors: Nguyen Vincent , Jackson Aaron , Gale Jenna
Published: October 2023

Research question

Are live birth rates affected in frozen embryo transfer cycles that develop transient endometrial cavity fluid that resolves by day of embryo transfer?

Design

The first frozen blastocyst transfer cycle between January 1st, 2016 and December 31st, 2019 were included in this retrospective cohort study at an academic fertility center. The presence or absence of endometrial cavity fluid (ECF) detected on initial ultrasound and at time of transfer was recorded. Patients who had persistent ECF at time of transfer were excluded from the study. The primary outcome was live birth rate in the group with resolved ECF relative to the group without ECF.

Results

A total of 1034 frozen blastocyst transfer cycles were included, 54 with resolved ECF and 980 without ECF. Adjusted analyses were performed using a log-binomial regression model. Live birth rates were 35.2% and 34.2%, adjusted risk ratio 1.00 [95% CI 0.70-1.50] in the two groups, respectively.

Conclusion

Live birth rates in frozen embryo transfer cycles are equivalent between patients with resolved endometrial cavity fluid compared to those who never had endometrial cavity fluid. Our findings suggest that the presence of endometrial cavity fluid is likely not detrimental to live birth rates if the fluid spontaneously resolves by the time of embryo transfer.
Venous thromboembolic disease in admitted blunt trauma patients: what matters?
Authors: Lineberry Camille , Alexis Dimitri , Mukhi Ambika , Duh Kevin , Tharakan Mathew , Vosswinkel James A. , Jawa Randeep S.
Published: October 2023

Background

Venous thromboembolic events (VTE) are a significant cause of morbidity and mortality following traumatic injury. We examined demographic characteristics, chemoprophylaxis, and outcomes of VTE patients with blunt trauma requiring hospitalization.

Methods

A retrospective review of adult blunt trauma hospitalizations with and without VTE between 2012 and 2019 was conducted. Deaths in the emergency department were excluded. Univariate and multivariable analyses, including machine learning classification algorithms for VTE, were performed.

Results

Of 10,926 admitted adult blunt trauma patients, 177 had VTE events. VTE events occurred at a median of 6 [IQR 3–11] days, with 7.3% occurring within 1 day of admission. VTE patients were more often male, and more often underwent surgery. They had higher injury severity as well as longer intensive care unit and hospital lengths of stay. While VTE occurred throughout the spectrum of injury severity, 27.7% had low injury severity (ISS < = 9). In multivariable analyses, both heparin and enoxaparin had reduced adjusted odds ratios for VTE.

Conclusion

Approximately 7.3% of VTE events occurred within one day of admission. A substantial proportion of VTE events occurred in patients with low injury severity (ISS < = 9). Subcutaneous unfractionated heparin and enoxaparin chemoprophylaxis were both inversely associated with VTE. These findings underscore the need for vigilance for VTE identification in blunt trauma patients throughout their hospitalization and VTE prevention efforts.
Supporting translation of research evidence into practice—the use of Normalisation Process Theory to assess and inform implementation within randomised controlled trials: a systematic review
Authors: Williams Allison , Lennox Laura , Harris Matthew , Antonacci Grazia
Published: October 2023

Background

The status of randomised controlled trials (RCTs) as the ‘gold standard’ for evaluating efficacy in healthcare interventions is increasingly debated among the research community, due to often insufficient consideration for implementation. Normalisation Process Theory (NPT), which focuses on the work required to embed processes into practice, offers a potentially useful framework for addressing these concerns. While the theory has been deployed in numerous RCTs to date, more work is needed to consolidate understanding of if, and how, NPT may aid implementation planning and processes within RCTs. Therefore, this review seeks to understand how NPT contributes to understanding the dynamics of implementation processes within RCTs. Specifically, this review will identify and characterise NPT operationalisation, benefits and reported challenges and limitations in RCTs.

Methods

A qualitative systematic review with narrative synthesis of peer-reviewed journal articles from eight databases was conducted. Studies were eligible for inclusion if they reported sufficient detail on the use of NPT within RCTs in a healthcare domain. A pre-specified data extraction template was developed based on the research questions of this review. A narrative synthesis was performed to identify recurrent findings.

Results

Searches identified 48 articles reporting 42 studies eligible for inclusion. Findings suggest that NPT is primarily operationalised prospectively during the data collection stage, with limited sub-construct utilisation overall. NPT is beneficial in understanding implementation processes by aiding the identification and analysis of key factors, such as understanding intervention fidelity in real-world settings. Nearly three-quarters of studies failed to report the challenges and limitations of utilising NPT, though coding difficulties and data falling outside the NPT framework are most common.

Conclusions

NPT appears to be a consistent and generalisable framework for explaining the dynamics of implementation processes within RCTs. However, operationalisation of the theory to its full extent is necessary to improve its use in practice, as it is currently deployed in varying capacities. Recommendations for future research include investigation of NPT alongside other frameworks, as well as earlier operationalisation and greater use of NPT sub-constructs.

Trial Registration

The protocol for this systematic review was accepted for public registration on PROSPERO (registration number: CRD42022345427) on 26 July 2022.
Serial assessments of cardiac output and mixed venous oxygen saturation in comatose patients after out-of-hospital cardiac arrest
Authors: Grand Johannes , Hassager Christian , Schmidt Henrik , Mølstrøm Simon , Nyholm Benjamin , Høigaard Henrik Frederiksen , Dahl Jordi S. , Meyer Martin , Beske Rasmus P. , Obling Laust , Kjaergaard Jesper , Møller Jacob E.
Published: October 2023

Aim

To assess the association with outcomes of cardiac index (CI) and mixed venous oxygen saturation (SvO2) in comatose patients resuscitated from out-of-hospital cardiac arrest (OHCA).

Methods

In the cohort study of 789 patients included in the “BOX”-trial, 565 (77%) patients were included in this hemodynamic substudy (age 62 ± 13 years, male sex 81%). Pulmonary artery catheters were inserted shortly after ICU admission. CI and SvO2 were measured as soon as possible in the ICU and until awakening or death. The endpoints were all-cause mortality at 1 year and renal failure defined as need for renal replacement therapy.

Results

First measured CI was median 1.7 (1.4–2.1) l/min/m2, and first measured SvO2 was median 67 (61–73) %. CI < median with SvO2 > median was present in 222 (39%), and low SvO2 with CI < median was present in 59 (11%). Spline analysis indicated that SvO2 value < 55% was associated with poor outcome. Low CI at admission was not significantly associated with mortality in multivariable analysis (p = 0.14). SvO2 was significantly inversely associated with mortality (hazard ratioadjusted: 0.91 (0.84–0.98) per 5% increase in SvO2, p = 0.01). SvO2 was significantly inversely associated with renal failure after adjusting for confounders (ORadjusted: 0.73 [0.62–0.86] per 5% increase in SvO2, p = 0.001). The combination of lower CI and lower SvO2 was associated with higher risk of mortality (hazard ratioadjusted: 1.54 (1.06–2.23) and renal failure (ORadjusted: 5.87 [2.34–14.73].

Conclusion

First measured SvO2 after resuscitation from OHCA was inversely associated with mortality and renal failure. If SvO2 and CI were below median, the risk of poor outcomes increased significantly.

Registration

The BOX-trial is registered at clinicaltrials.gov (NCT03141099, date 2017–30–04, retrospectively registered).

Graphical abstract
Ten-year risk assessment for cardiovascular diseases using ASCVD risk estimator plus: outcomes from hypertension and diabetes patients
Authors: Osoro Ian , Kumar Ranjeet , Sharma Amit
Published: October 2023

Background

Cardiovascular risk prediction models encompass numerous CVD risk factors. Available prediction models were developed from non-Asian cohorts hence we decided to evaluate the performance of the ASCVD risk estimator model and the associated 10-year CVD predisposing factors in Punjab.

Methods

We carried out a cross-sectional study among patients having hypertension and diabetes mellitus in a tertiary hospital in Punjab, India. 201 participants without ASCVD who were ≥ 40 years old and had been admitted to the medical ward were assessed. a pre-validated questionnaire was used to collect data on the socio-demographics and behavioral patterns. Lipid profile and blood pressure measurements were collected as per standard protocols. The respondents’ CVD risk was assessed using ASCVD Risk Estimator Plus. Data were analyzed using IBM SPSS version 26; bivariate analysis was done using Chi-square and binary logistic regression was used to identify the predictors of 10-year risk for CVD at a 5% level of significance.

Measurements.

We examined the stratification of the predicted outcomes and evaluated the associations between individual risk factors and the predicted cardiovascular events. Our study categorized the results of these outcomes into 4 categories: low category (1–5%), borderline category (6–9%) intermediate category (10–20%), and high category (21–95%).

Results

Out of the 201 participants that enrolled in our study, the majority 76 (37.8%) were in the intermediate category, 56 (27.9%) were in the high category, 41 (20.4%) were in the borderline category, 28 (13.9%) were in the low category. The median ASCVD percentage was 14.20%. Respondents who were alcoholics, smokers, and drug abusers (OR = 5.8, 95% CI 0.397–83.584) were associated with the highest likelihood of developing CVDs. Furthermore, males had a significantly higher mean predicted CVD outcome % (M = 23.18%) compared to females (M = 14.91%).

Conclusion

According to our prediction study, it was discovered that 145 (72.1%) participants were not likely to have had an ASCVD in the next 10 years. However, middle-aged males should be more cautious with their lifestyle habits, particularly in dealing with risk factors that can expose them to CVDs.
Multi-tissue epigenetic analysis identifies distinct associations underlying insulin resistance and Alzheimer’s disease at CPT1A locus
Authors: Sarnowski Chloé , Huan Tianxiao , Ma Yiyi , Joehanes Roby , Beiser Alexa , DeCarli Charles S. , Heard-Costa Nancy L. , Levy Daniel , Lin Honghuang , Liu Ching-Ti , Liu Chunyu , Meigs James B. , Satizabal Claudia L. , Florez Jose C. , Hivert Marie-France , Dupuis Josée , De Jager Philip L. , Bennett David A. , Seshadri Sudha , Morrison Alanna C.
Published: October 2023

Background

Insulin resistance (IR) is a major risk factor for Alzheimer’s disease (AD) dementia. The mechanisms by which IR predisposes to AD are not well-understood. Epigenetic studies may help identify molecular signatures of IR associated with AD, thus improving our understanding of the biological and regulatory mechanisms linking IR and AD.

Methods

We conducted an epigenome-wide association study of IR, quantified using the homeostatic model assessment of IR (HOMA-IR) and adjusted for body mass index, in 3,167 participants from the Framingham Heart Study (FHS) without type 2 diabetes at the time of blood draw used for methylation measurement. We identified DNA methylation markers associated with IR at the genome-wide level accounting for multiple testing (P < 1.1 × 10−7) and evaluated their association with neurological traits in participants from the FHS (N = 3040) and the Religious Orders Study/Memory and Aging Project (ROSMAP,N = 707). DNA methylation profiles were measured in blood (FHS) or dorsolateral prefrontal cortex (ROSMAP) using the Illumina HumanMethylation450 BeadChip. Linear regressions (ROSMAP) or mixed-effects models accounting for familial relatedness (FHS) adjusted for age, sex, cohort, self-reported race, batch, and cell type proportions were used to assess associations between DNA methylation and neurological traits accounting for multiple testing.

Results

We confirmed the strong association of blood DNA methylation with IR at three loci (cg17901584–DHCR24, cg17058475–CPT1A, cg00574958–CPT1A, and cg06500161–ABCG1). In FHS, higher levels of blood DNA methylation at cg00574958 and cg17058475 were both associated with lower IR (P = 2.4 × 10−11andP = 9.0 × 10–8), larger total brain volumes (P = 0.03 andP = 9.7 × 10−4), and smaller log lateral ventricular volumes (P = 0.07 andP = 0.03). In ROSMAP, higher levels of brain DNA methylation at the same twoCPT1Amarkers were associated with greater risk of cognitive impairment (P = 0.005 andP = 0.02) and higher AD-related indices (CERAD score:P = 5 × 10−4and 0.001; Braak stage:P = 0.004 andP = 0.01).

Conclusions

Our results suggest potentially distinct epigenetic regulatory mechanisms between peripheral blood and dorsolateral prefrontal cortex tissues underlying IR and AD atCPT1Alocus.
Progressive mechanical and structural changes in anterior cerebral arteries with Alzheimer’s disease
Authors: Liu Xiaozhu , Halvorsen Samuel , Blanke Nathan , Downs Margaret , Stein Thor D. , Bigio Irving J. , Zaia Joseph , Zhang Yanhang
Published: October 2023

Alzheimer's disease (AD) is a neurodegenerative disease and the main cause for dementia. The irreversible neurodegeneration leads to a gradual loss of brain function characterized predominantly by memory loss. Cerebrovascular changes are common neuropathologic findings in aged subjects with dementia. Cerebrovascular integrity is critical for proper metabolism and perfusion of the brain, as cerebrovascular remodeling may render the brain more susceptible to pulse pressure and may be associated with poorer cognitive performance and greater risk of cerebrovascular events. The objective of this study is to provide understanding of cerebrovascular remodeling with AD progression. Anterior cerebral arteries (ACAs) from a total of 19 brain donor participants from controls and pathologically diagnosed AD groups (early—Braak stages I-II; intermediate—Braak stages III-IV; and advanced—Braak stages V-VI) were included in this study. Mechanical testing, histology, advanced optical imaging, and mass spectrometry were performed to study the progressive structural and functional changes of ACAs with AD progression. Biaxial extension-inflation tests showed that ACAs became progressively less compliant, and the longitudinal stress in the intermediate and advanced AD groups was significantly higher than that from the control group. With pathological AD development, the inner and outer diameters of the ACAs remained almost unchanged; however, histology study revealed progressive smooth muscle cell atrophy and loss of elastic fibers which led to compromised structural integrity of the arterial wall. Multiphoton imaging demonstrated elastin degradation at the media-adventitia interface, which led to the formation of an empty band of 21.0 ± 15.4 μm and 32.8 ± 9.24 μm in width for the intermediate and advanced AD groups, respectively. Furthermore, quantitative birefringence microscopy showed disorganized adventitial collagen with AD development. Mass spectrometry analysis provided further evidence of altered collagen content and other extracellular matrix (ECM) molecule and smooth muscle cell changes that were consistent with the mechanical and structural alterations. Collectively, our study provides understanding of the mechanical and structural cerebrovascular deterioration in cerebral arteries with AD, which may be related to neurodegenration and pathology in the brain.
PACAP–Sirtuin3 alleviates cognitive impairment through autophagy in Alzheimer’s disease
Authors: Wang Qing , Wang Yue , Li Shiping , Shi Jiong
Published: October 2023

Background

Autophagy is vital in the pathogenesis of neurodegeneration. Thus far, no studies have specifically investigated the relationship between pituitary adenylate cyclase-activating polypeptide (PACAP) and autophagy, particularly in the context of Alzheimer’s disease (AD). This study used in vitro and in vivo models, along with clinical samples, to explore interactions between PACAP and autophagy in AD.

Methods

AD model mice were administered 6 μl of 0.1 mg/ml PACAP liquid intranasally for 4 weeks, then subjected to behavioral analyses to assess the benefits of PACAP treatment. The underlying mechanisms of PACAP-induced effects were investigated by methods including real-time quantitative polymerase chain reaction, RNA sequencing, immunofluorescence, and western blotting. Exosomes were extracted from human serum and subjected to enzyme-linked immunosorbent assays to examine autophagy pathways. The clinical and therapeutic implications of PACAP and autophagy were extensively investigated throughout the experiment.

Results

Impaired autophagy was a critical step in amyloid β (Aβ) and Tau deposition; PACAP enhanced autophagy and attenuated cognitive impairment. RNA sequencing revealed three pathways that may be involved in AD progression: PI3K-AKT, mTOR, and AMPK. In vivo and in vitro studies showed that sirtuin3 knockdown diminished the ability of PACAP to restore normal autophagy function, resulting in phagocytosis dysregulation and the accumulation of pTau, Tau, and Aβ. Additionally, the autophagic biomarker MAP1LC3 demonstrated a positive association with PACAP in human serum.

Conclusions

PACAP reverses AD-induced cognitive impairment through autophagy, using sirtuin3 as a key mediator. MAP1LC3 has a positive relationship with PACAP in humans. These findings provide insights regarding potential uses of intranasal PACAP and sirtuin3 agonists in AD treatment.

Trial registration

NCT04320368.