bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical significance of unexplained persistent sinus tachycardia in women with structurally normal heart during the peripartum period
Authors: Varrias Dimitrios , Sharma Nikhil , Hentz Roland , Ma Rosaline , Gurciullo Dillon , Kleiman Jeremy , Kossack Andrew , Wolf Eliot , Lam Betty , Bimal Tia , Ansari Umair , Coleman Kristie M. , Mountantonakis Stavros E.
Published: September 2022

Background

Persistent sinus tachycardia (ST) is frequently encountered during pregnancy and peripartum period and its etiology often remains elusive. We sought to examine the possible association between unexplained persistent ST and obstetric outcomes.

Methods

A case control study was conducted using chart review of women admitted in labor to one of 7 hospitals of Northwell Health between January 2015 to June 2021. After excluding women with structurally abnormal hearts, we identified patients with persistent ST during the peripartum period, defined as a heart rate of more than 100 bpm for more than 48 h. A control group was created by randomly subsampling those who did not meet the inclusion criteria for sinus tachycardia. Obstetric outcomes were measured as mother’s length of stay (LOS), pre-term labor (PTL), admission to the neonatal ICU (NICU), and whether she received cesarean-section (CS).

Results

Seventy-eight patients with persistent ST were identified, out of 141,769 women admitted for labor throughout the Northwell Health system. 23 patients with ST attributable to infection or hypovolemia from anemia requiring transfusion and 55 with unclear etiology were identified. After adjusting for age and parity, pregnant mothers with ST were 2.35 times more likely to have a CS than those without (95% CI: 1.46–3.81, p = 0.0005) and had 1.38 times the LOS (1.21- 1.56, p < 0.0001). Among mothers with ST, those with unexplained ST were 2.14 times more likely to have a CS (1.22–3.75, p = 0.008).

Conclusion

Among pregnant patients, patients with ST have higher rates of CS.This association is unclear, however potential mechanisms include catecholamine surge, indolent infection, hormonal fluctuations, and medications. More studies are needed to explore the mechanism of ST in pregnant woman to determine the clinical significance and appropriate management.
Relationship between serum and tear levels of tissue plasminogen activator and plasminogen activator inhibitor-1 in diabetic retinopathy
Authors: Jasmiad Nurbadriah binti , Abd Ghani Rohana binti , Agarwal Renu , Ismail Zaliha binti , Mohd Abdullah Azlindarita Aisyah , Idorus Mohd Yusri
Published: September 2022

Background

Diabetic retinopathy (DR) is a serious complication of longstanding type 2 diabetes mellitus (T2DM), a leading cause of blindness and visual disability in the world. The aim of this study is to compare the activity of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) in tears and serum of patients with DR and those without DR.

Method

Among the T2DM patients enrolled in this study, 26 patients had DR (n = 26) while 29 were without DR (n = 29). The blood and tear samples were obtained from all participants. The level of PAI-1 and tPA were measured in both the serum and tears. Anthropometric measurements, HbA1c, renal and lipid profile were also obtained.

Results

Patients with DR had significantly longer disease duration and higher systolic blood pressure compared to those without DR. Serum PAI-1 level was significantly higher in patients with DR compared to those without DR, 32.72 (IQR 32.52) vs 21.37 (IQR 14.93) ng/mL, respectively (p < 0.05). However, tear PAI-1 were comparable in both groups. Serum and tear tPA levels in both groups were also comparable (p > 0.05). Among patients with DR, there were no significant correlations between tear and serum of both biomarkers. Patients without DR showed a moderate positive correlation between serum and tear tPA levels with a coefficient of 0.363, albeit no statistical significance. Patients with DR demonstrated a significant positive correlation between levels of tears PAI-1 and BMI (r = 0.555, p = 0.026). In the group without DR, there was a statistically significant positive correlation between serum level of PAI-1 with urine albumin creatinine ratio (UACR) (r = 0.501, p = 0.013).

Conclusion

The present study demonstrated a significantly greater serum PAI-1 levels in patients with DR compared to those without DR. No significant correlations between tears and serum PAI-1 and tPA were observed. Thus, the role of tear biomarkers remains relevant for further investigations.
Minimum dietary diversity and associated factors among lactating mothers in Haryana, India: a community based cross-sectional study
Authors: Shumayla Shumayla , Irfan E. M. , Kathuria Nishtha , Rathi Suresh Kumar , Srivastava Shobhit , Mehra Sunil
Published: September 2022

Introduction

Food adequacy and dietary quality in the lactation period are fundamental for maternal and child health. Lactating mothers are vulnerable to malnutrition because of increased physiological demand, monotonous diet, lactogenesis process, and increased nutrient requirements. The micronutrient adequacy especially among women is not ensured in Indian diet. The dual course of gender bias and poverty, along with lack of knowledge about diet quality are significant impediments in maintaining minimum dietary diversity among Indian women. The study aimed to assess the prevalence of minimum dietary diversity and associated factors among lactating women.

Methodology

A community-based cross-sectional study was conducted among 1236 lactating women through a multistage sampling procedure in Haryana state, India. Data were collected in Computer-assisted personal interviewing (CAPI) using a pretested structured interview schedule. Minimum Dietary Diversity for Women by Food and Agriculture Organization (FAO) was used to calculate the minimum dietary diversity.

Results

The mean dietary diversity score among lactating women from the ten food groups was 6.35 ± 2.57 and the prevalence of minimum dietary diversity was 77.1%. The complete model revealed that both individual and household factors can explain the variation in dietary diversity intake. Furthermore, the result of model 2 explained that women aged 31 to 35 years (AOR 5.92,95% (1.87–18.77), graduation and above qualified women (AOR 1.98, 95% (0.96–4.09) and lactating women with high knowledge on nutrition (AOR 2.00, 95% (1.34–4.57) were the significant factors promoting minimum dietary diversity.

Conclusion

Three-fourths of the lactating women reached adequate minimum dietary diversity. Younger age, low educational level, and poor nutritional knowledge were significant constraints to achieving minimum dietary diversity. Further improvement in the minimum dietary diversity among lactating women is very much required. It is also advised that exiting platforms dispersing awareness on nutrition should be supported and strengthened.
The relationship between attachment to pets and mental health: the shared link via attachment to humans
Authors: Lass-Hennemann Johanna , Schäfer Sarah K. , Sopp M. Roxanne , Michael Tanja
Published: September 2022

Background

Several studies have investigated the relationship between emotional attachment to pets and mental health with the majority of studies finding a negative relationship between emotional attachment to pets and mental health. Interestingly, attachment to pets differs from attachment to humans with studies showing that humans with an insecure attachment style form a particularly strong emotional attachment to their companion animals. Human attachment style is also related to mental health with secure attachment being associated with superior mental health. Building on those findings, the current study aimed at exploring the role of attachment to humans in the relationship between emotional attachment to pets and mental health.

Methods

In this cross-sectional online survey (N = 610) we assessed the strength of emotional attachment to pets and attachment to humans. We further collected pet specific data as well as mental health burden in a sample of German dog owners (Mage=33.12; 92.79% women). We used a mediation model estimating the indirect link between emotional attachment to pets and mental health burden via human attachment and the direct link between emotional attachment to pets and mental health burden simultaneously.

Results

We found that attachment to humans fully mediated the positive association between emotional attachment to pets and mental health burden. A stronger emotional attachment to one’s dog was associated with lower comfort with depending on or trusting in others, whereby lower comfort with depending on or trusting in others was related to higher mental health burden. Moreover, a stronger attachment to one’s dog was also related to a greater fear of being rejected and unloved (Anxiety), which was, in turn, associated with a higher mental health burden.

Conclusion

Our findings suggest that the positive link between emotional attachment to pets and mental health burden is fully accounted for by its shared variance with insecure attachment to humans in a sample mostly comprising self-identified women. Future studies need to examine whether strong emotional bonds with pets may evolve as a compensatory strategy to buffer difficult childhood bonding experiences.
Health status of recently arrived asylum seekers in their host country: results of a cross-sectional observational study
Authors: Khouani Jérémy , Blatrix Léo , Tinland Aurélie , Jego Maeva , Gentile Gaëtan , Fond Guillaume , Loundou Anderson , Fromentin Marilou , Auquier Pascal
Published: September 2022

Background

The World Health Organization (WHO) considers that the heterogeneity of concepts and definitions of migrants is an obstacle to obtaining evidence to inform public health policies. There is no recent data on the health status of only asylum seekers who have recently arrived in their Western host country. The purpose of this study was to determine the health status of asylum seekers and search for explanatory factors for this health status.

Methods

This cross-sectional observational study screened the mental and somatic health of adult asylum seekers who had arrived in France within the past 21 days and went to the Marseille single center between March 1 and August 31, 2021. In order to study the explanatory factors of the asylum seekers' health status, a multivariate analysis was performed using a logistic regression model to predict the health status. Factors taken into account were those significantly associated with outcome (level < 0.05) in univariate analysis.

Results

In total, 419 asylum seekers were included and 96% CI95%[93;97.3] had at least one health disorder. Concerning mental health, 89% CI95% [85.1;91.4] had a mental disorder and in terms of somatic health exclusively, 66% CI95% [61.4;70.6] had at least one somatic disorder. Women were more likely to have a somatic disease OR = 1.80 [1.07; 3.05]. We found a statistically significant association between the presence of at least one disorder and sleeping in a public space OR = 3.4 [1.02;11.28] p = 0.046. This association is also found for mental disorders OR = 2.36 [1.16;4.84], p = 0.018.

Conclusions

Due to the high prevalence of health disorders our study found, asylum seekers are a population with many care needs when they arrive in their host country. The main factors linked to a poor health status seem to be related to a person’s sex, geographical origin and sleeping in a public space.
Evolution of work ability, quality of life and self-rated health in a police department after remodelling shift schedule
Authors: Velasco-Garrido Marcial , Herold Robert , Rohwer Elisabeth , Mache Stefanie , Terschürenm Claudia , Preisser Alexandra M. , Harth Volker
Published: September 2022

Background

There exists a great diversity of schedules concerning the way shift work is organized and implemented with ample agreement regarding recommendable features of a shift system. In order to adapt the shift schedule of a metropolitan police department to current recommendations, a remodelled shift schedule was introduced in 2015. The aim of this study was to evaluate the potential associations between the remodelled shift schedule and work ability, quality of life and self-rated health after one and five years.

Methods

A controlled before-and- after study was conducted during the piloting phase (2015–2016) as well as a 5-year follow-up using paper questionnaires. Outcome parameters included work ability, quality of life and self-rated health.

Results

Work ability, quality of life and self-rated health improved after the first year of the newly implemented shift schedule among police officers working in the piloting police stations compared to those working according to the former schedule. In 5-year follow-up differences between indicators diminished.

Conclusions

The implementation of a remodelled shift schedule including more 12-h shifts accompanied by more days off and a coherent weekend off duty was not associated with detrimental effects to work ability, quality of life or self-reported health among police officers.
Health care costs and lost productivity costs related to excess weight in Belgium
Authors: Gorasso Vanessa , Moyersoen Isabelle , Van der Heyden Johan , De Ridder Karin , Vandevijvere Stefanie , Vansteelandt Stijn , De Smedt Delphine , Devleesschauwer Brecht
Published: September 2022

Background

This study aimed to estimate annual health care and lost productivity costs associated with excess weight among the adult population in Belgium, using national health data.

Methods

Health care costs and costs of absenteeism were estimated using data from the Belgian national health interview survey (BHIS) 2013 linked with individual health insurance data (2013–2017). Average yearly health care costs and costs of absenteeism were assessed by body mass index (BMI) categories – i.e., underweight (BMI < 18.5 kg/m2), normal weight (18.5 ≤ BMI < 25 kg/m2), overweight (25 ≤ BMI < 30 kg/m2) and obesity (BMI ≥ 30 kg/m2). Health care costs were also analysed by type of cost (i.e. ambulatory, hospital, reimbursed medication). The cost attributable to excess weight and the contribution of various other chronic conditions to the incremental cost of excess weight were estimated using the method of recycled prediction (a.k.a. standardisation).

Results

According to BHIS 2013, 34.7% and 13.9% of the Belgian adult population were respectively affected by overweight or obesity. They were mostly concentrated in the age-group 35–65 years and had significantly more chronic conditions compared to the normal weight population. Average total healthcare expenses for people with overweight and obesity were significantly higher than those observed in the normal weight population.

The adjusted incremental annual health care cost of excess weight in Belgium was estimated at €3,329,206,657 (€651 [95% CI: €144-€1,084] and €1,015 [95% CI: €343–€1,697] per capita for individuals with overweight and obesity respectively). The comorbidities identified to be the main drivers for these incremental health care costs were hypertension, high cholesterol, serious gloom and depression. Mean annual incremental cost of absenteeism for overweight accounted for €242 per capita but was not statistically significant, people with obesity showed a significantly higher cost (p < 0.001) compared to the normal weight population: €2,015 [95% CI: €179–€4,336] per capita. The annual total incremental costs due to absenteeism of the population affected by overweight and obesity was estimated at €1,209,552,137. Arthritis, including rheumatoid arthritis and osteoarthritis, was the most important driver of the incremental cost of absenteeism in individuals with overweight and obesity, followed by hypertension and low back pain.

Conclusions

The mean annual incremental cost of excess weight in Belgium is of concern and stresses the need for policy actions aiming to reduce excess body weight. This study can be used as a baseline to evaluate the potential savings and health benefits of obesity prevention interventions.
What matters to patients following total knee arthroplasty? A grounded theory of adapting to a knee replacement
Authors: Randall Ellen , Bryan Stirling , Black Charlyn , Goldsmith Laurie J.
Published: September 2022

Background

Globally the volume of total knee arthroplasty (TKA) is on the rise, reflecting aging populations, an associated increase in treatment of osteoarthritis, and a desire for improved quality of life. There is evidence that as high as 15 to 20% of patients are not satisfied with their TKA results and efforts need to be made to improve these rates. This study set out to identify what patients consider important when reflecting on TKA satisfaction, to pave the way to identifying service transformation opportunities that will enhance patient-centred care and satisfaction with this procedure.

Methods

Twenty-seven TKA recipients were recruited in the province of British Columbia, Canada. Semi-structured interviews were conducted about participants’ experience and satisfaction with TKA, three to four years post-surgery. Grounded theory was employed to analyze participants’ stories about what was front of mind when they reflected on satisfaction with their new knee.

Results

Participants described their post-TKA knee in terms itsadequacy: how it felt and worked, and how it matched their pre-surgical expectations. The central element of their stories was the process ofadapting,which gave rise to their perceptions of adequacy. Adapting comprises the patient experience of physically integrating and cognitively accepting their new knee. Patterns of adapting reflect the level of the new knee’s achieved adequacy and the straightforwardness of the adapting process.

Discussion

The conceptualization of adequacy and the process of adapting allow a patient-centred understanding of what patients experience following TKA. For participants who did not readily achieve the adequacy they had anticipated, the challenges they experienced during adapting dominated their stories. Participants’ adapting stories afford key insights into how the health care system could adjust to better support TKA patients, and improve rates of satisfaction with this procedure.

Conclusions

The process of adapting lends itself to system intervention in support of enhanced post-TKA outcomes and satisfaction. These interventions could include the development of a care model including long-term clinical support for patients whose knees do not achieve desired results on schedule, and collaborating with patients to set and manage reasonable expectations about how their post-TKA knee will feel and function.
MIR31HG polymorphisms are related to steroid-induced osteonecrosis of femoral head among Chinese Han population
Authors: Wang Yuan , Wang Yexin , Liang Da , Hu Hongtao , Li Guangwei , Meng Xiaoguang , Zhu Bing , Zhong Wei
Published: September 2022

Backgrounds

MIR31host gene (MIR31HG) polymorphisms play important roles in the occurrence of osteonecrosis. However, the association ofMIR31HGpolymorphisms with the risk of steroid-induced osteonecrosis of the femoral head (SONFH) remains unclear. In this study, we aimed to investigate the correlation betweenMIR31HGpolymorphisms and SONFH susceptibility in the Chinese Han population.

Methods

A total of 708 volunteers were recruited to detect the effect of seven single nucleotide polymorphisms (SNPs) in the MIR31HG gene on SONFH risk in the Chinese Han population. Genotyping of MIR31HG polymorphisms was performed using the Agena MassARRAY platform. The odds ratio (OR) and 95% confidence interval (95% CI) were used to evaluate the correlation between MIR31HG polymorphisms and SONFH risk using logistic regression model.

Results

According to the results of genetic model, rs10965059 inMIR31HGwas significantly correlated with the susceptibility to SONFH (OR = 0.56,p = 0.002). Interestingly, the stratified analysis showed that rs10965059 was associated with the reduced risk of SONFH in subjects aged > 40 years (OR = 0.30,p < 0.001) and male populations (OR = 0.35,p < 0 .001). Moreover, rs10965059 was associated with the reduced risk of bilateral SONFH (OR = 0.50,p = 0.002). Finally, multi-factor dimension reduction (MDR) results showed that the combination of rs1332184, rs72703442, rs2025327, rs55683539, rs2181559, rs10965059 and rs10965064 was the best model for predicting SONFH occurrence (p < 0.0001).

Conclusion

The study indicated that rs10965059 could be involved in SONFH occurrence in the Chinese Han population, which might provide clues for investigating the role ofMIR31HGin the pathogenesis of SONFH.
Establishment of an optimized orthotopic bladder cancer model in mice
Authors: Cai Jinming , Xie Zhiwen , Yan Yilin , Huang Zhengnan , Tang Pengfei , Cao Xiangqian , Wang Zeyi , Yang Chenkai , Tan Mingyue , Zhang Fang , Shen Bing
Published: September 2022

Background

Bladder cancer (BC) is one of the most common malignancies of the genitourinary system. Animal models offer an important tool to explore tumour initiation, progression, and therapeutic mechanisms. Our aim is to construct an optimized orthotopic BC model which is predictable, reproducible, and convenient.

Methods

The optimized orthotopic BC model was constructed in male C57BL/6 mice utilizing microsyringes to inoculate them with a murine BC cell line (MB49). Anesthetised mice were inoculated with an MB49 cell suspension (10 µL) at approximately 5 × 106/mL. The whole process of modelling was observed and monitored every 3 days for 21 days utilizing HE staining and transabdominal ultrasonography (TUS).

Results

In this study, the model showed excellent success rates for tumour formation (96.67%) and metastatic rate (89.66%). Compared to the control group (sham operation), mice in the modelling group had serous cachexia, visible haematuresis and weight loss (all P < 0.05). The lungs, liver, ureter and kidneys were found to have tumour metastasis. Moreover, the average survival time (19.73 ± 1.69 d) of modelling mice was significantly shorter than that of the control mice (P < 0.05), which remained alive.

Conclusion

Our study established a method using microsyringes to inject murine BC cells into the bladder wall, creating a stable transplantable BC model in mice.
Comparative assessment of the Willems dental age estimation methods: a Chinese population-based radiographic study
Authors: Wang Jian , Fan Linfeng , Shen Shihui , Sui Meizhi , Zhou Jiaxin , Yuan Xiaoyan , Wu Yiwen , Zhong Pingping , Ji Fang , Tao Jiang
Published: September 2022

Background

The comparison of the two Willems dental age estimation methods (gender-specific (Willems I) and non-gender-specific (Willems II)) has not been fully investigated. Here we aimed to explore the applicability of the Willems dental age estimation in an Eastern Chinese population, which may cast light on the field of dental age estimation.

Methods

A total of 1211 oral panoramic radiographs (582 boys and 629 girls) of the Chinese Han population aged 11–16 years old were collected. Dental ages (DAs) were calculated using the Willems method. Statistical significance was set at a p-value < 0.05. Age differences between chronological age (CA) and dental age were analyzed by paired t-tests and mean absolute error (MAE).

Results

The differences between CA and DA determined by the Willems I method were + 0.44 and + 0.09 years for boys and girls, respectively. When using the Willems II method, these differences were + 0.57 and − 0.09. The MAEs of the Willems I method between DA and CA were 0.95 and 1.00 years in boys and girls, respectively. For Willems II, MAEs were 1.02 and 1.00 years in boys and girls.

Conclusions

This study showed that the Willems I method was more accurate than the Willems II method in the boys’ group for predicting age from a whole scale. In comparison, Willems II is more competitive in the girls' group. Neither method may be satisfactory for 11-to-16-year-old teenagers in Eastern China.
Comparing machine learning algorithms to predict 5-year survival in patients with chronic myeloid leukemia
Authors: Shanbehzadeh Mostafa , Afrash Mohammad Reza , Mirani Nader , Kazemi-Arpanahi Hadi
Published: September 2022

Introduction

Chronic myeloid leukemia (CML) is a myeloproliferative disorder resulting from the translocation of chromosomes 19 and 22. CML includes 15–20% of all cases of leukemia. Although bone marrow transplant and, more recently, tyrosine kinase inhibitors (TKIs) as a first-line treatment have significantly prolonged survival in CML patients, accurate prediction using available patient-level factors can be challenging. We intended to predict 5-year survival among CML patients via eight machine learning (ML) algorithms and compare their performance.

Methods

The data of 837 CML patients were retrospectively extracted and randomly split into training and test segments (70:30 ratio). The outcome variable was 5-year survival with potential values of alive or deceased. The dataset for the full features and important features selected by minimal redundancy maximal relevance (mRMR) feature selection were fed into eight ML techniques, including eXtreme gradient boosting (XGBoost), multilayer perceptron (MLP), pattern recognition network, k-nearest neighborhood (KNN), probabilistic neural network, support vector machine (SVM) (kernel = linear), SVM (kernel = RBF), and J-48. The scikit-learn library in Python was used to implement the models. Finally, the performance of the developed models was measured using some evaluation criteria with 95% confidence intervals (CI).

Results

Spleen palpable, age, and unexplained hemorrhage were identified as the top three effective features affecting CML 5-year survival. The performance of ML models using the selected-features was superior to that of the full-features dataset. Among the eight ML algorithms, SVM (kernel = RBF) had the best performance in tenfold cross-validation with an accuracy of 85.7%, specificity of 85%, sensitivity of 86%, F-measure of 87%, kappa statistic of 86.1%, and area under the curve (AUC) of 85% for the selected-features. Using the full-features dataset yielded an accuracy of 69.7%, specificity of 69.1%, sensitivity of 71.3%, F-measure of 72%, kappa statistic of 75.2%, and AUC of 70.1%.

Conclusions

Accurate prediction of the survival likelihood of CML patients can inform caregivers to promote patient prognostication and choose the best possible treatment path. While external validation is required, our developed models will offer customized treatment and may guide the prescription of personalized medicine for CML patients.
Understanding complex work using an extension of the resilience CARE model: an ethnographic study
Authors: Sanford Natalie , Lavelle Mary , Markiewicz Ola , Reedy Gabriel , Rafferty Anne Marie , Darzi Ara , Anderson Janet E.
Published: September 2022

Background

Resilient Healthcare research centres on understanding and improving quality and safety in healthcare. The Concepts for Applying Resilience Engineering (CARE) model highlights the relationships between demand, capacity, work-as-done, work-as-imagined, and outcomes, all of which are central aspects of Resilient Healthcare theory. However, detailed descriptions of the nature of misalignments and the mechanisms used to adapt to them are still unknown.

Objective

The objectives were to identify and classify types of misalignments between demand and capacity and types of adaptations that were made in response to misalignments.

Methods

The study involved 88.5 hours of non-participant ethnographic observations in a large, teaching hospital in central London. The wards included in the study were: two surgical wards, an older adult ward, a critical care unit, and the Acute Assessment Unit (AAU), an extension unit created to expedite patient flow out of the Emergency Department. Data were collected via observations of routine clinical work and ethnographic interviews with healthcare professionals during the observations. Field notes were transcribed and thematically analysed using a combined deductive-inductive approach based on the CARE model.

Results

A total of 365 instances of demand-capacity misalignment were identified across the five wards included in the study. Of these, 212 had at least one observed corresponding work adaptation. Misalignments identified include equipment, staffing, process, communication, workflow, and space. Adaptations identified include process, resource redistribution, and extra-role performance. For all misalignment types observed across the five in-patient settings, process adaptations were the most frequently used adaptations. The exception to this was for staffing misalignments, which were most frequently responded to with extra-role performance adaptations. Of the three process adaptations, hospital workers most often adapted by changing how the process was done.

Conclusions

This study contributes a new version of the CARE model that includes types of misalignments and corresponding adaptations, which can be used to better understand work-as-done. This affords insight into the complexity of the system and how it might be improved by reducing misalignments via work system redesign or by enhancing adaptive capacity.
Nigerian stakeholders’ perceptions of a pilot tier accreditation system for Patent and Proprietary Medicine Vendors to expand access to family planning services
Authors: OlaOlorun Funmilola M. , Jain Aparna , Olalere Emily , Daniel-Ebune Ene , Afolabi Kayode , Okafor Emeka , Dwyer Sara Chace , Ubuane Osimhen , Akomolafe Toyin O. , Baruwa Sikiru
Published: September 2022

Background

Community Pharmacists (CPs) and Patent and Proprietary Medicine Vendors (PPMVs) are often the first point of care for many Nigerians, and when sufficiently trained, they contribute to the expansion of family planning services. Nigeria’s task shifting policy and existing regulatory and licensing bodies provide the enabling environment for PPMVs to be stratified and trained. This study explored the perceptions of stakeholders toward the pilot three-tier accreditation system instituted by the Pharmacists Council of Nigeria with support from the IntegratE project.

Methods

Two rounds of qualitative phone interviews were conducted among stakeholders in Kaduna and Lagos states in 2020 and 2021. In addition, there were two rounds of phone interviews with CPs and PPMVs (program recipients) from Lagos and Kaduna states. All participants were purposively selected, based on their involvement in the IntegratE project activities. Interviews were recorded, transcribed, and coded using Atlas.ti software. Thematic analysis was conducted.

Results

Fifteen stakeholders and 28 program recipients and 12 stakeholders and 30 program recipients were interviewed during the first and second rounds of data collection respectively. The data are presented around three main themes: 1) the pilot three-tier accreditation system; 2) enabling environment; and 3) implementation challenges. The accreditation system that allows for the stratification and training of PPMVs to provide family planning services was perceived in a positive light by majority of participants. The integrated supportive supervision team that included representation from the licensing and regulatory body was seen as a strength. However, it was noted that the licensing process needs to be more effective. Implementation challenges that need to be addressed prior to scale up include bottlenecks in licensing procedures and the deep-rooted mistrust between CPs and PPMVs.

Conclusion

Scale up of the three-tier accreditation system has the potential to expand access to family planning services in Nigeria. In other resource-poor settings where human resources for health are in short supply and where drug shops are ubiquitous, identifying drug shop owners, training them to offer a range of family planning services, and providing the enabling environment for them to function may help to improve access to family planning services.
Safety of beta-blocker and calcium channel blocker antihypertensive drugs in pregnancy: a Mendelian randomization study
Authors: Ardissino Maddalena , Slob Eric A. W. , Rajasundaram Skanda , Reddy Rohin K. , Woolf Benjamin , Girling Joanna , Johnson Mark R. , Ng Fu Siong , Gill Dipender
Published: September 2022

Background

Beta-blocker (BB) and calcium channel blocker (CCB) antihypertensive drugs are commonly used in pregnancy. However, data on their relative impact on maternal and foetal outcomes are limited. We leveraged genetic variants mimicking BB and CCB antihypertensive drugs to investigate their effects on risk of pre-eclampsia, gestational diabetes and birthweight using the Mendelian randomization paradigm.

Methods

Genetic association estimates for systolic blood pressure (SBP) were extracted from summary data of a genome-wide association study (GWAS) on 757,601 participants. Uncorrelated single-nucleotide polymorphisms (SNPs) associated with SBP (p < 5 × 10−8) in BB and CCB drug target gene regions were selected as proxies for drug target perturbation. Genetic association estimates for the outcomes were extracted from GWASs on 4743 cases and 136,325 controls (women without a hypertensive disorder in pregnancy) for pre-eclampsia or eclampsia, 7676 cases and 130,424 controls (women without any pregnancy-related morbidity) for gestational diabetes, and 155,202 women (who have given birth at least once) for birthweight of the first child. All studies were in European ancestry populations. Mendelian randomization estimates were generated using the two-sample inverse-variance weighted model.

Results

Although not reaching the conventional threshold for statistical significance, genetically-proxied BB was associated with reduced risk of pre-eclampsia (OR per 10 mmHg SBP reduction 0.27, 95%CI 0.06–1.19, p = 0.08) and increased risk of gestational diabetes (OR per 10 mmHg SBP reduction 2.01, 95%CI 0.91–4.42, p = 0.08), and significantly associated with lower birthweight of first child (beta per 10 mmHg SBP reduction − 0.27, 95%CI − 0.39 to − 0.15, p = 1.90 × 10−5). Genetically-proxied CCB was associated with reduced risk of pre-eclampsia and eclampsia (OR 0.62, 95%CI 0.43–0.89, p = 9.33 × 10−3), and was not associated with gestational diabetes (OR 1.05, 95% CI 0.76–1.45, p = 0.76) or changes in birthweight of first child (beta per 10 mmHg SBP reduction 0.02, 95%CI − 0.04–0.07, p = 0.54).

Conclusions

While BB and CCB antihypertensive drugs may both be efficacious for lowering blood pressure in pregnancy, this genetic evidence suggests that BB use may lower birthweight. Conversely, CCB use may reduce risk of pre-eclampsia and eclampsia without impacting gestational diabetes risk or birthweight. These data support further study on the effects of BBs on birthweight.
The link between gestational diabetes and cardiovascular diseases: potential role of extracellular vesicles
Authors: Ormazabal Valeska , Nair Soumyalekshmi , Carrión Flavio , Mcintyre H. David , Salomon Carlos
Published: September 2022

Extracellular vesicles are critical mediators of cell communication. They encapsulate a variety of molecular cargo such as proteins, lipids, and nucleic acids including miRNAs, lncRNAs, circular RNAs, and mRNAs, and through transfer of these molecular signals can alter the metabolic phenotype in recipient cells. Emerging studies show the important role of extracellular vesicle signaling in the development and progression of cardiovascular diseases and associated risk factors such as type 2 diabetes and obesity. Gestational diabetes mellitus (GDM) is hyperglycemia that develops during pregnancy and increases the future risk of developing obesity, impaired glucose metabolism, and cardiovascular disease in both the mother and infant. Available evidence shows that changes in maternal metabolism and exposure to the hyperglycemic intrauterine environment can reprogram the fetal genome, leaving metabolic imprints that define life-long health and disease susceptibility. Understanding the factors that contribute to the increased susceptibility to metabolic disorders of children born to GDM mothers is critical for implementation of preventive strategies in GDM. In this review, we discuss the current literature on the fetal programming of cardiovascular diseases in GDM and the impact of extracellular vesicle (EV) signaling in epigenetic programming in cardiovascular disease, to determine the potential link between EV signaling in GDM and the development of cardiovascular disease in infants.
Dapagliflozin improves myocardial flow reserve in patients with type 2 diabetes: the DAPAHEART Trial: a preliminary report
Authors: Leccisotti Lucia , Cinti Francesca , Sorice Gian Pio , D’Amario Domenico , Lorusso Margherita , Guzzardi Maria Angela , Mezza Teresa , Gugliandolo Shawn , Cocchi Camilla , Capece Umberto , Indovina Luca , Ferraro Pietro Manuel , Iozzo Patricia , Crea Filippo , Giordano Alessandro , Giaccari Andrea
Published: September 2022

Objective

Cardiovascular (CV) outcome trials have shown that in patients with type 2 diabetes (T2D), treatment with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) reduces CV mortality and hospital admission rates for heart failure (HF). However, the mechanisms behind these benefits are not fully understood. This study was performed to investigate the effects of the SGLT-2i dapagliflozin on myocardial perfusion and glucose metabolism in patients with T2D and stable coronary artery disease (coronary stenosis ≥ 30% and < 80%), with or without previous percutaneous coronary intervention (> 6 months) but no HF.

Methods

This was a single-center, prospective, randomized, double-blind, controlled clinical trial including 16 patients with T2D randomized to SGLT-2i dapagliflozin (10 mg daily) or placebo. The primary outcome was to detect changes in myocardial glucose uptake (MGU) from baseline to 4 weeks after treatment initiation by [(18)F]2-deoxy-2-fluoro-D-glucose (FDG) PET/CT during hyperinsulinemic euglycemic clamp. The main secondary outcome was to assess whether the hypothetical changes in MGU were associated with changes in myocardial blood flow (MBF) and myocardial flow reserve (MFR) measured by 13N-ammonia PET/CT. The study was registered at eudract.ema.europa.eu (EudraCT No. 2016-003614-27) and ClinicalTrials.gov (NCT 03313752).

Results

16 patients were randomized to dapagliflozin (n = 8) or placebo (n = 8). The groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, renal and heart function). There was no significant change in MGU during euglycemic hyperinsulinemic clamp in the dapagliflozin group (2.22 ± 0.59 vs 1.92 ± 0.42 μmol/100 g/min, p = 0.41) compared with the placebo group (2.00 ± 0.55 vs 1.60 ± 0.45 μmol/100 g/min, p = 0.5). Dapagliflozin significantly improved MFR (2.56 ± 0.26 vs 3.59 ± 0.35 p = 0.006 compared with the placebo group 2.34 ± 0.21 vs 2.38 ± 0.24 p = 0.81; pint = 0.001) associated with a reduction in resting MBF corrected for cardiac workload (p = 0.005; pint = 0.045). A trend toward an increase in stress MBF was also detected (p = 0.054).

Conclusions

SGLT-2 inhibition increases MFR in T2D patients. We provide new insight into SGLT-2i CV benefits, as our data show that patients on SGLT-2i are more resistant to the detrimental effects of obstructive coronary atherosclerosis due to increased MFR, probably caused by an improvement in coronary microvascular dysfunction.

Trial registration EudraCT No. 2016-003614-27; ClinicalTrials.gov Identifier: NCT03313752
Structural disruption of BAF chromatin remodeller impairs neuroblastoma metastasis by reverting an invasiveness epigenomic program
Authors: Jiménez Carlos , Antonelli Roberta , Nadal-Ribelles Mariona , Devis-Jauregui Laura , Latorre Pablo , Solé Carme , Masanas Marc , Molero-Valenzuela Adrià , Soriano Aroa , Sánchez de Toledo Josep , Llobet-Navas David , Roma Josep , Posas Francesc , de Nadal Eulàlia , Gallego Soledad , Moreno Lucas , Segura Miguel F.
Published: September 2022

Background

Epigenetic programming during development is essential for determining cell lineages, and alterations in this programming contribute to the initiation of embryonal tumour development. In neuroblastoma, neural crest progenitors block their course of natural differentiation into sympathoadrenergic cells, leading to the development of aggressive and metastatic paediatric cancer. Research of the epigenetic regulators responsible for oncogenic epigenomic networks is crucial for developing new epigenetic-based therapies against these tumours. Mammalian switch/sucrose non-fermenting (mSWI/SNF) ATP-dependent chromatin remodelling complexes act genome-wide translating epigenetic signals into open chromatin states. The present study aimed to understand the contribution of mSWI/SNF to the oncogenic epigenomes of neuroblastoma and its potential as a therapeutic target.

Methods

Functional characterisation of the mSWI/SNF complexes was performed in neuroblastoma cells using proteomic approaches, loss-of-function experiments, transcriptome and chromatin accessibility analyses, and in vitro and in vivo assays.

Results

Neuroblastoma cells contain three main mSWI/SNF subtypes, but only BRG1-associated factor (BAF) complex disruption through silencing of its key structural subunits, ARID1A and ARID1B, impairs cell proliferation by promoting cell cycle blockade. Genome-wide chromatin remodelling and transcriptomic analyses revealed that BAF disruption results in the epigenetic repression of an extensive invasiveness-related expression program involving integrins, cadherins, and key mesenchymal regulators, thereby reducing adhesion to the extracellular matrix and the subsequent invasion in vitro and drastically inhibiting the initiation and growth of neuroblastoma metastasis in vivo.

Conclusions

We report a novel ATPase-independent role for the BAF complex in maintaining an epigenomic program that allows neuroblastoma invasiveness and metastasis, urging for the development of new BAF pharmacological structural disruptors for therapeutic exploitation in metastatic neuroblastoma.
Neutrophil to high-density lipoprotein cholesterol ratio predicts adverse cardiovascular outcomes in subjects with pre-diabetes: a large cohort study from China
Authors: Liu Shuo-Lin , Feng Bao-Yu , Song Qi-Rui , Zhang Ying-Mei , Wu Shuo-Ling , Cai Jun
Published: September 2022

Background

This study aimed to examine whether the neutrophil to high-density lipoprotein cholesterol ratio (NHR) can predict cardiovascular outcomes in normoglycemic individuals with elevated fasting glucose levels.

Methods

A total of 130,801 participants with normal blood glucose levels were enrolled in the Kailuan study. Participants were categorized according to NHR quartiles and further divided into normal glucose regulation (NGR) and pre-diabetes (pre-DM) subgroups. The follow-up endpoint was major adverse cardiovascular events (CVE), including stroke and myocardial infarction.

Results

Over a median of 12.53 (8.95–13.08) years of follow-up, subjects with NHR levels in the highest quartile experienced more CVE than those with NHR levels in the lowest quartile. Multivariate Cox analyses showed that continuous changes in NHR (hazard ratio, 1.21; 95% confidence interval [CI], 1.15–1.28) and the highest quartile of NHR (hazard ratio, 1.30; 95% CI, 1.21–1.39) were independent predictors of CVE (all P < 0.001). Furthermore, when participants were categorized by both NHR quartile and glucose metabolism status, the NHR level in the highest quartile plus pre-DM group was associated with a 1.60-fold (95% CI, 1.38–1.86; P < 0.001] higher risk of CVE than that in the lowest quartile plus normoglycemic group. Significantly, the addition of NHR only, presence of pre-DM only, or combination of NHR and pre-DM to the prediction algorithm, including traditional risk factors, improved the C-statistic by 0.19, 0.05, and 0.23 (all P < 0.001).

Conclusions

Elevated NHR or fasting blood glucose level were independently associated with a higher risk of CVE among normoglycemic individuals. Moreover, pre-DM participants with high NHR levels tended to have worse prognosis, suggesting that NHR could provide greater risk stratification value than traditional risk factors for subjects with pre-DM.
A case of Vp4 hepatocellular carcinoma with tumor thrombosis extending into the confluence of the splenic/portal vein achieved a good prognosis with emergent hepatectomy and postoperative adjuvant therapy with lenvatinib
Authors: Kato Hiroyuki , Asano Yukio , Ito Masahiro , Arakawa Satoshi , Shimura Masahiro , Koike Daisuke , Ochi Takayuki , Yasuoka Hironobu , Kawai Toki , Higashiguchi Takahiko , Tani Hiroki , Kunimura Yoshiki , Kondo Yuka , Nagata Hidetoshi , Sato Harunobu , Horiguchi Akihiko
Published: September 2022

In this report, we describe a case of highly advanced hepatocellular carcinoma with tumor thrombosis extending into the main portal vein of the pancreas that was successfully treated with adjuvant lenvatinib after right hepatic resection with thrombectomy. A 70-year-old woman was referred from the clinic because of elevated hepatobiliary enzymes. The patient was positive for the hepatitis B virus antigen at our hospital. The tumor markers were highly elevated with alpha-fetoprotein (14.5 U/mL) and protein induced by vitamin K absence (PIVKAII) (1545 ng/mL), suggesting hepatocellular carcinoma. Dynamic abdominal computed tomography showed an early enhanced tumor approximately 6 cm in size and portal vein tumor thrombosis filling the main portal vein, but not extending into the splenic or superior mesenteric vein (SMV). On magnetic resonance imaging 1 week after CT, portal vein tumor thrombosis had extended to the confluence of the splenic vein with the SMV, indicating rapid tumor growth. Thus, we performed emergent right hepatectomy with tumor thrombectomy. Postoperatively, we treated the patient with lenvatinib for a tumor reduction surgery. Fortunately, the patient was alive 2 years postoperatively without recurrence. This case report suggests that a favorable outcome may be achieved with multidisciplinary treatment including resection and postoperative treatment with lenvatinib.