bluuebunny/crossref_metadata_2025 huggingface dataset:
Interest in and use of person-centred pharmacy services - a Swiss study of people with diabetes
Authors: Bawab Noura , Zuercher Emilie , Carron Tania , Chinet Léonie , Bugnon Olivier , Berger Jérôme , Peytremann-Bridevaux Isabelle
Published: March 2021

Background

Diabetes is one of the most important chronic diseases and affects 9% of the world’s population. To support these people in the day-to-day management of their treatments, pharmacies can offer professional pharmacy services. These are defined as one or more actions organized or provided in a pharmacy to optimize the process of care, with the goal of improving health outcomes and the value of healthcare. Such services have to be tailored to the needs and interests of patients. This study aimed to evaluate interest in and use of pharmacy services among people with diabetes in the canton of Vaud, Switzerland.

Methods

This cross-sectional study analysed self-reported data from 790 people with diabetes included in the CoDiab-VD cohort. Questions focused on sociodemographic and economic characteristics, diabetes and its management, and interest in and use of pharmacy services related to (1) medication intake and adherence and (2) diabetes and general health. Descriptive analyses were first conducted. Logistic regression analyses were then performed for pharmacy services that were of interest to ≥50% of respondents.

Results

The mean age of participants was 66 years, and the sample included more males (59%) than females. The pharmacy services that interested the most respondents were individual interview, pill boxes or weekly pill boxes, treatment plans, checks of all medications, first medical opinions from pharmacists and counselling on devices. Factors significantly associated with interest in pharmacy services were being older, having a lower self-efficacy score, taking more than three medications and having a positive opinion about pharmacists.

Conclusions

This study provides key information on interest in and use of pharmacy services among patients with diabetes in Switzerland; it should help pharmacists individualize their services for patients.
Scale-up and sustainability of a personalized end-of-life care intervention: a longitudinal mixed-methods study
Authors: Takaoka Alyson , Tam Benjamin , Vanstone Meredith , Clarke France J. , Hoad Neala , Swinton Marilyn , Toledo Feli , Boyle Anne , Woods Anne , Duan Erick H. , Heels-Ansdell Diane , Waugh Lily , Soth Mark , Rudkowski Jill , Alhazzani Waleed , Perri Dan , Ligori Tania , Jaeschke Roman , Zytaruk Nicole , Cook Deborah J.
Published: March 2021

Background

Scaling-up and sustaining healthcare interventions can be challenging. Our objective was to describe how the 3 Wishes Project (3WP), a personalized end-of-life intervention, was scaled-up and sustained in an intensive care unit (ICU).

Methods

In a longitudinal mixed-methods study from January 12,013 - December 31, 2018, dying patients and families were invited to participate if the probability of patient death was > 95% or after a decision to withdraw life support. A research team member or bedside clinician learned more about each of the patients and their family, then elicited and implemented at least 3 personalized wishes for patients and/or family members. We used a qualitative descriptive approach to analyze interviews and focus groups conducted with 25 clinicians who cared for the enrolled patients. We used descriptive statistics to summarize patient, wish, and clinician characteristics, and analyzed outcome data in quarters using Statistical Process Control charts. The primary outcome was enrollment of terminally ill patients and respective families; the secondary outcome was the number of wishes per patient; tertiary outcomes included wish features and stakeholder involvement.

Results

Both qualitative and quantitative analyses suggested a three-phase approach to the scale-up of this intervention during which 369 dying patients were enrolled, having 2039 terminal wishes implemented. From a research project to clinical program to an approach to practice, we documented a three-fold increase in enrolment with a five-fold increase in total wishes implemented, without a change in cost. Beginning as a study, the protocol provided structure; starting gradually enabled frontline staff to experience and recognize the value of acts of compassion for patients, families, and clinicians. The transition to a clinical program was marked by handover from the research staff to bedside staff, whereby project catalysts mentored project champions to create staff partnerships, and family engagement became more intentional. The final transition involved empowering staff to integrate the program as an approach to care, expanding it within and beyond the organization.

Conclusions

The 3WP is an end-of-life intervention which was implemented as a study, scaled-up into a clinical program, and sustained by becoming integrated into practice as an approach to care.
The genome of the stable fly, Stomoxys calcitrans, reveals potential mechanisms underlying reproduction, host interactions, and novel targets for pest control
Authors: Olafson Pia U. , Aksoy Serap , Attardo Geoffrey M. , Buckmeier Greta , Chen Xiaoting , Coates Craig J. , Davis Megan , Dykema Justin , Emrich Scott J. , Friedrich Markus , Holmes Christopher J. , Ioannidis Panagiotis , Jansen Evan N. , Jennings Emily C. , Lawson Daniel , Martinson Ellen O. , Maslen Gareth L. , Meisel Richard P. , Murphy Terence D. , Nayduch Dana , Nelson David R. , Oyen Kennan J. , Raszick Tyler J. , Ribeiro José M. C. , Robertson Hugh M. , Rosendale Andrew J. , Sackton Timothy B. , Saelao Perot , Swiger Sonja L. , Sze Sing-Hoi , Tarone Aaron M. , Taylor David B. , Warren Wesley C. , Waterhouse Robert M. , Weirauch Matthew T. , Werren John H. , Wilson Richard K. , Zdobnov Evgeny M. , Benoit Joshua B.
Published: March 2021

Background

The stable fly, Stomoxys calcitrans, is a major blood-feeding pest of livestock that has near worldwide distribution, causing an annual cost of over $2 billion for control and product loss in the USA alone. Control of these flies has been limited to increased sanitary management practices and insecticide application for suppressing larval stages. Few genetic and molecular resources are available to help in developing novel methods for controlling stable flies.

Results

This study examines stable fly biology by utilizing a combination of high-quality genome sequencing and RNA-Seq analyses targeting multiple developmental stages and tissues. In conjunction, 1600 genes were manually curated to characterize genetic features related to stable fly reproduction, vector host interactions, host-microbe dynamics, and putative targets for control. Most notable was characterization of genes associated with reproduction and identification of expanded gene families with functional associations to vision, chemosensation, immunity, and metabolic detoxification pathways.

Conclusions

The combined sequencing, assembly, and curation of the male stable fly genome followed by RNA-Seq and downstream analyses provide insights necessary to understand the biology of this important pest. These resources and new data will provide the groundwork for expanding the tools available to control stable fly infestations. The close relationship of Stomoxys to other blood-feeding (horn flies and Glossina) and non-blood-feeding flies (house flies, medflies, Drosophila) will facilitate understanding of the evolutionary processes associated with development of blood feeding among the Cyclorrhapha.
Effects of maternal folic acid supplementation during the second and third trimesters of pregnancy on neurocognitive development in the child: an 11-year follow-up from a randomised controlled trial
Authors: Caffrey Aoife , McNulty Helene , Rollins Mark , Prasad Girijesh , Gaur Pramod , Talcott Joel B. , Witton Caroline , Cassidy Tony , Marshall Barry , Dornan James , Moore Adrian J. , Ward Mary , Strain J. J. , Molloy Anne M. , McLaughlin Marian , Lees-Murdock Diane J. , Walsh Colum P. , Pentieva Kristina
Published: March 2021

Background

Maternal folic acid (FA) supplementation before and in early pregnancy prevents neural tube defects (NTD), but it is uncertain whether continuing FA after the first trimester has benefits on offspring health. We aimed to evaluate the effect of FA supplementation throughout pregnancy on cognitive performance and brain function in the child.

Methods

Follow-up investigation of 11-year-old children, residing in Northern Ireland, whose mothers had participated in a randomised trial of Folic Acid Supplementation in the Second and Third Trimesters (FASSTT) in pregnancy and received 400 μg/day FA or placebo from the 14th gestational week. Cognitive performance (Full Scale Intelligence Quotient, Verbal Comprehension, Working Memory, Perceptual Reasoning, and Processing Speed) was assessed using the Wechsler Intelligence Scale for Children. Neuronal function was assessed using magnetoencephalographic (MEG) brain imaging.

Results

Of 119 mother-child pairs in the FASSTT trial, 68 children were assessed for neurocognitive performance at 11-year follow-up (Dec 2017 to Nov 2018). Children of mothers randomised to FA compared with placebo scored significantly higher in two Processing Speed tests, i.e. symbol search (mean difference 2.9 points, 95% CI 0.3 to 5.5,p = 0.03) and cancellation (11.3 points, 2.5 to 20.1,p = 0.04), whereas the positive effect on Verbal Comprehension was significant in girls only (6.5 points, 1.2 to 11.8,p = 0.03). MEG assessment of neuronal responses to a language task showed increased power at the Beta (13–30 Hz,p = 0.01) and High Gamma (49–70 Hz,p = 0.04) bands in children from FA-supplemented mothers, suggesting more efficient semantic processing of language.

Conclusions

Continued FA supplementation in pregnancy beyond the early period currently recommended to prevent NTD can benefit neurocognitive development of the child. MEG provides a non-invasive tool in paediatric research to objectively assess functional brain activity in response to nutrition and other interventions.

Trial registration

ISRCTNISRCTN19917787. Registered on 15 May 2013.
Efficacy of a long-term pulmonary rehabilitation maintenance program for COPD patients in a real-life setting: a 5-year cohort study
Authors: Blervaque Léo , Préfaut Christian , Forthin Hélène , Maffre Francis , Bourrelier Marion , Héraud Nelly , Catteau Matthias , Pomiès Pascal , Jaffuel Dany , Molinari Nicolas , Hayot Maurice , Gouzi Fares
Published: March 2021

Background

Pulmonary rehabilitation (PR) improves exercise capacity, health-related quality of life (HRQoL) and dyspnea in chronic obstructive pulmonary disease (COPD) patients. Maintenance programs can sustain the benefits for 12 to 24 months. Yet, the long-term effects (> 12 months) of pragmatic maintenance programs in real-life settings remain unknown. This prospective cohort study assessed the yearly evolution in the outcomes [6-min walking distance (6MWD), HRQoL, dyspnea] of a supervised self-help PR maintenance program for COPD patients followed for 5 years. The aim was to assess the change in the outcomes and survival probability for 1 to 5 years after PR program discharge in COPD patients following a PR maintenance program supported by supervised self-help associations.

Methods

Data were prospectively collected from 144 COPD patients who followed a pragmatic multidisciplinary PR maintenance program for 1 to 5 years. They were assessed yearly for 6MWD, HRQol (VQ11) and dyspnea (MRC). The 5-year survival probability was compared to that of a control PR group without a maintenance program. A trajectory-based cluster analysis identified the determinants of long-term response.

Results

Maintenance program patients showed significant PR benefits at 4 years for 6MWD and VQ11 and 5 years for MRC. The 5-year survival probability was higher than for PR patients without PR maintenance. Two clusters of response to long-term PR were identified, with responders being the less severe COPD patients.

Conclusions

This study provides evidence of the efficacy of a pragmatic PR maintenance program in a real-life setting for more than 3 years. In contrast to short-term PR, long-term PR maintenance appeared more beneficial in less severe COPD patients.
The new Internal Transcribed Spacer 2 diagnostic tool clarifies the taxonomic position and geographic distribution of the North American malaria vector Anopheles punctipennis
Authors: Hodge James M. , Yurchenko Andrey A. , Karagodin Dmitriy A. , Masri Reem A. , Smith Ryan C. , Gordeev Mikhail I. , Sharakhova Maria V.
Published: March 2021

Background

The malaria mosquito Anopheles punctipennis, a widely distributed species in North America, is capable of transmitting human malaria and is actively involved in the transmission of the ungulate malaria parasite Plasmodium odocoilei. However, molecular diagnostic tools based on Internal Transcribed Spacer 2 (ITS2) of ribosomal DNA are lacking for this species. Anopheles punctipennis is a former member of the Anopheles maculipennis complex but its systematic position remains unclear.

Methods

In this study, ITS2 sequences were obtained from 276 An. punctipennis specimens collected in the eastern and midwestern United States and a simple and robust Restriction Fragment Length Polymorphism approach for species identification was developed. The maximum-likelihood phylogenetic tree was constructed based on ITS2 sequences available through this study and from GenBank for 20 species of Anopheles.

Results

The analysis demonstrated a consistent ITS2 sequence length and showed no indications of intragenomic variation among the samples based on ITS2, suggesting that An. punctipennis represents a single species in the studied geographic locations. In this study, An. punctipennis was found in urban, rural, and forest settings, suggesting its potential broad role in pathogen transmission. Phylogeny based on ITS2 sequence comparison demonstrated the close relationship of this species with other members of the Maculipennis group.

Conclusions

This study developed molecular tools based on ITS2 sequences for the malaria vector An. punctipennis and clarified the phylogenetic position of the species within the Maculipennis group.
Critical appraisal of the European Union Scientific Committee on Health, Environmental and Emerging Risks (SCHEER) Preliminary Opinion on electronic cigarettes
Authors:   the Center of Excellence for the Acceleration of Harm Reduction (CoEHAR), O’Leary Renée , Polosa Riccardo , Li Volti Giovanni
Published: March 2021

Background

In preparation for the 2021 revision of the European Union Tobacco Products Directive, the Scientific Committee on Health, Environmental and Emerging Risks (SCHEER) has posted its Preliminary Opinion on Electronic Cigarettes. They concluded that e-cigarettes only achieve a sub-optimal level of protection of human health. In this paper, we provide evidence that the Opinion’s conclusions are not adequately backed up by scientific evidence and did not discuss the potential health benefits of using alternative combustion-free nicotine-containing products as substitute for tobacco cigarettes.

Methods

Searches for articles were conducted in PubMed and by citation chasing in Google Scholar. Articles were also retrieved with a review of references in major publications. Primary data from World Health Organization surveys, the conclusions of reviews, and peer-reviewed non-industry studies were cited to address errors and omissions identified in the Opinion.

Results

The Opinion omitted reporting on the individual and population health benefits of the substitution of e-cigarettes (ENDS) for cigarette smoking. Alternative hypotheses to the gateway theory were not evaluated. Its assessment of cardiovascular risk is contradicted by numerous reviews. It cites ever-use data that do not represent current patterns of use. It did not report non-nicotine use. It presented erroneous statements on trends in ENDS prevalence. It over-emphasized the role of flavours in youth ENDS initiation. It did not discuss cessation in sufficient length.

Conclusions

For the delivery of a robust and comprehensive final report, the members of the Working Group of the Scientific Committee on Health, Environmental and Emerging Risks will need to consider (1) the potential health benefits of ENDS substitution for cigarette smoking, (2) alternative hypotheses and contradictory studies on the gateway effect, (3) its assessment of cardiovascular risk, (4) the measurements of frequency of use, (5) non-nicotine use, (6) the role of flavours, and (7) a fulsome discussion of cessation.
JAK2V617F positive polycythemia vera with paroxysmal nocturnal hemoglobinuria and visceral thromboses: a case report and review of the literature
Authors: Chatzidavid Sevastianos , Giannakopoulou Nefeli , Diamantopoulos Panagiotis Theodorou , Gavriilaki Eleni , Katsiampoura Panagiota , Lakiotaki Eleftheria , Sakellariou Stratigoula , Viniou Nora-Athina , Dryllis Georgios
Published: March 2021

Background

Polycythemia vera (PV) is characterized by red cell mass expansion in the peripheral blood and can be complicated with thrombosis, bleeding, evolution to acute myeloid leukemia (AML) or a fibrotic phase. Paroxysmal nocturnal hemoglobinuria (PNH) in an acquired clonal haematopoietic stem cell disorder associated with chronic intravascular hemolysis, venous thrombosis, defective hematopoiesis, frequent episodes of infection and, rarely, leukemic transformation. Herein, we report an interesting case of a patient with coexistence of PNH clones and a JAK2V617F positive PV, with unusual thromboses without hemolysis.

Case presentation

A 51-year-old woman presented with increased levels of hematocrit, multiple liver, spleen, and left kidney infarctions and ascites; further investigation revealed a JAK2V617F-positive polycythemia vera and the presence of a significant PNH population (more than 90% CD55– CD59– cells among both granulocytes and red blood cells). Interestingly, the patient has experienced severe thrombotic events without any signs or symptoms of hemolysis.

Conclusions

This case raises questions over uncharted aspects of the PNH etiopathogenesis and its potential association with myeloproliferative neoplasms (MPN) and highlights the difficulty of diagnosing and managing patients with more than one potentially thrombophilic conditions, especially with established and severe thromboses.
The V-BRCH Project: building clinical trial research capacity for HIV and noncommunicable diseases in Nigeria
Authors: Aliyu Muktar H. , Sani Mahmoud U. , Ingles Donna J. , Tsiga-Ahmed Fatimah I. , Musa Baba M. , Audet Carolyn M. , Wester C. William
Published: March 2021

Antiretroviral therapy has turned HIV into a chronic condition, with morbidity from HIV-associated noncommunicable diseases (NCDs) becoming more common as HIV-infected individuals live longer. In Nigeria, the additional challenge of an under-capacitated health system highlights the need for skilled clinical investigators who can generate evidence to tackle the double burden of HIV and NCDs. The Vanderbilt-Nigeria Building Research Capacity in HIV and Non-communicable Diseases (V-BRCH) programme is a training platform to create a cohort of skilled Nigerian investigators with the capacity to lead independent clinical trial research focused on the intersection of HIV and NCDs. V-BRCH will solidify an atmosphere of continuous mentoring and skills acquisition for physician faculty at the Aminu Kano Teaching Hospital via short- and medium-term learning opportunities, paired mentoring arrangements, and mentored research projects. Trainees will attend an annual faculty enrichment programme in Nashville, in addition to on-site workshops in Nigeria on HIV-associated NCD epidemiology, clinical trials methodology, evidence synthesis, qualitative research methods, stakeholder engagement, knowledge translation, and grant writing. Research-oriented junior faculty will undergo focused training in clinical trials administration and regulatory oversight. Scholars will share best practices through mentoring panels, regular ‘Works in Progress’ meetings, and monthly career development seminars. Competitive seed grants will be provided to mentor–mentee teams to promote targeted in-country pilot studies focused on HIV-associated NCDs. For long-term training, physician scientists will be supported to undergo enhanced Master of Public Health (MPH) training at Bayero University in Nigeria and Master of Science in Clinical Investigation (MSCI) training at Vanderbilt. Short-term regional courses, staff development workshops, and MPH curriculum refinement will help to strengthen institutional capacity in HIV-associated NCD clinical trial research. V-BRCH will create a cohort of skilled Nigerian scientists who will be able to compete for independent funding and design and implement high quality research that will generate evidence to inform policy and practice and lead to improved outcomes for Nigerians impacted by HIV-associated NCDs.
Incidence, causes, and maternofetal outcomes of obstructed labor in Ethiopia: systematic review and meta-analysis
Authors: Ayenew Asteray Assmie
Published: March 2021

Background

Obstructed labor is a preventable obstetric complication. However, it is an important cause of maternal mortality and morbidity and of adverse outcomes for newborns in resource-limited countries in which undernutrition is common resulting in a small pelvis in which there is no easy access to functioning health facilities with a capacity to carry out operative deliveries. Therefore, this systematic review and meta-analysis aimed to estimate the incidence, causes, and maternofetal outcomes of obstructed labor among mothers who gave birth in Ethiopia.

Method

for this review, we used the standard PRISMA checklist guideline. Different online databases were used for the review: PubMed, Google Scholar, EMBASE, Cochrane Library, HINARI, AFRO Library Databases, and African Online Journals. Based on the adapted PICO principles, different search terms were applied to achieve and access the essential articles. The search included all published and unpublished observational studies written only in the English language and conducted in Ethiopia. Microsoft Excel 16 was used for data entrance, and Stata version 11.0 (Stata Corporation, College Station, Texas, USA) was used for data analysis.

Results

I included sixteen (16) primary studies with twenty-eight thousand five hundred ninety-one (28,591) mothers who gave birth in Ethiopia. The pooled incidence of obstructed labor in Ethiopia was 12.93% (95% CI: 10.44–15.42, I2 = 98.0%, p < 0.001). Out of these, 67.3% (95% CI: 33.32–101.28) did not have antenatal care follow-up, 77.86% (95% CI: 63.07–92.66) were from the rural area, and 58.52% (95% CI: 35.73– 82.31) were referred from health centers and visited hospitals after 12 h of labor. The major causes of obstructed labor were cephalo-pelvic disproportion 64.65% (95% CI: 57.15– 72.14), and malpresentation and malposition in 27.24% (95% CI: 22.05–32.42) of the cases. The commonest complications were sepsis in 38.59% (95% CI: 25.49–51.68), stillbirth in 38.08% (95% CI: 29.55–46.61), postpartum hemorrhage in 33.54% (95% CI:12.06– 55.02), uterine rupture in 29.84% (95% CI: 21.09–38.58), and maternal death in 17.27% (95% CI: 13.47–48.02) of mothers who gave birth in Ethiopia.

Conclusion

This systematic review and meta-analysis showed that the incidence of obstructed labor was high in Ethiopia. Not having antenatal care follow-up, rural residency, and visiting hospitals after 12 h of labor increased the incidence of obstructed labor. The major causes of obstructed labor were cephalo-pelvic disproportion, and malpresentation and malpresentation. Additionally, the commonest complications were sepsis, stillbirth, postpartum hemorrhage, uterine rupture, and maternal death. Thus, promoting antenatal care service utilization, a good referral system, and availing comprehensive obstetric care in nearby health institutions are recommended to prevent the incidence of obstructed labor and its complications.
Comment: difference between assessment of upper limb movement and upper limb associated reactions during walking
Authors: Meyns Pieter
Published: March 2021

Background

While walking, people swing their arms in a specific pattern. This specific arm swing pattern during walking has shown to have a beneficial effect on gait as it reduces walking energy cost and optimizes balance. In several patient populations the arm movements can be directly affected (e.g. in patients with acquired brain injury (ABI)), which in turn has a negative effect on their gait pattern, balance and energy cost of walking.

Main
text

In
December 2019, Kahn et al. published a paper in JNER concerning the
quantification of upper limb associated reactions (ARs) during walking in people
with ABI. ARs are defined as “an effort-dependent phenomenon causing an
involuntary increase in upper limb muscle tone, with awkward and uncomfortable
postures”. These upper limb ARs appear often in patients with ABI and can have
an important effect on their gait. The authors calculated kinematic measures
using three-dimensional gait analysis relating to range of motion, variability
and mean position over the gait cycle for the different upper limb joints
(shoulder, elbow, wrist) during self-selected steady-state walking. Based on
differences they found between an ABI cohort and healthy control cohort, the
authors concluded that they were able to quantify ARs during walking in this
population. This calculation, however, is not specific for upper limb ARs. In
fact, the authors calculated general measures of arm posture (e.g. mean position
over the gait cycle) or arm movement (e.g. range of motion and variability)
during gait. Previous research has already indicated that other factors than
ARs can influence the posture or movement of the arm during gait in patients
with brain injury, such as voluntary compensations for gait instability and
contractures or spasticity of upper arm muscles. Yet, it is not possible to disentangle
the different causes of the altered arm posture during steady-state walking
based on the proposed measures.

Conclusion

The kinematic arm measures proposed by Kahn et al. (J Neuroeng Rehabil 16(1):160, 2019) are not a
direct measure of ARs, but provide a quantification of overall deviation of arm
posture or movement during gait. Depending on the specific study design these
measures may provide insights in ARs.
A nonlinear association of total cholesterol with all-cause and cause-specific mortality
Authors: He Guo-dong , Liu Xiao-cong , Liu Lin , Yu Yu-ling , Chen Chao-lei , Huang Jia-yi , Lo Kenneth , Huang Yu-qing , Feng Ying-qing
Published: March 2021

Background

The link between total cholesterol (TC) and all-cause and specific mortality has not been elucidated. Herein, we aimed to evaluate the effect of TC levels on all-cause, cardiovascular disease (CVD), and cancer mortality.

Methods

All data analyzed were obtained from the National Health and Nutrition Examination Survey 1999–2014. The relationship between levels of TC and mortality was determined through Cox proportional hazard regression analysis coupled with multivariable adjustments. Two-piecewise linear regression models and Cox models with penalized splines were applied to explore nonlinear and irregular shape relationships. Kaplan–Meier survival curve and subgroup analyses were conducted.

Results

The sample studied comprised 14,662 men and 16,025 women, categorized as 25,429 adults aged 18–65 and 5,258 adults over 65 years old. A total of 2,570 deaths were recorded. All-cause, cardiovascular, and cancer mortality showed U-curve associations after adjusting for confounding variables in the restricted cubic spline analysis. Hazard ratios (HRs) of all-cause and cancer mortality were particularly negatively related to TC levels in the lower range < 200 mg/dL, especially in the range < 120 mg/dL (HR 1.97; 95% CI 1.38, 2.83, HR 2.39; 95% CI 1.21, 4.71, respectively). However, the HRs of cardiovascular disease mortality in the range < 120 mg/dL were the lowest (HR 0.60; 95% CI 0.15, 2.42). In the upper range, a TC range of ≥ 280 mg/dL was correlated with mortality as a result of CVD and cancer (HR 1.31; 95% CI 0.87, 1.97 and HR 1.22; 95% CI 0.82, 1.79). The lowest cumulative survival rate of all-cause mortality was recorded in the lowest TC-level group, while the lowest cumulative survival rate of CVD mortality was recorded in the highest TC-level group.

Conclusions

A nonlinear association of TC level with all-cause, cancer, and CVD mortality in the American population was observed, suggesting that too low or too high serum total cholesterol levels might correlate with adverse outcomes.
Integrative proteomic and lipidomic analysis of Kaili Sour Soup-mediated attenuation of high-fat diet-induced nonalcoholic fatty liver disease in a rat model
Authors: Cong Shuo , Li Zhengchao , Yu Lei , Liu Yongmei , Hu Yaxin , Bi Ying , Cheng Mingliang
Published: March 2021

Background

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease and is characterized by excessive fat accumulation. Kaili Sour Soup, a food typical of Guizhou Province, is believed to have significant health benefits. Thus, we aimed to identify and assess the impact of Kaili Sour Soup on NAFLD and its underlying mechanism using integrative proteomic and lipidomic analysis.

Methods

A high-fat diet and male Wistar rats were used to construct a NAFLD rat model. Haematoxylin and eosin (HE) and Oil Red O staining analyses were used to perform the histologic examination. Proteomic analysis was utilized to systematically identify the global protein profile in NAFLD with and without Kaili Sour Soup treatment. Western blot assays were used to verify the expression of proteins screened by proteomic analysis. Lipidomic analysis was performed to screen lipid metabolism in NAFLD with and without Kaili Sour Soup treatment.

Results

Kaili Sour Soup alleviated high-fat diet (HFD)-induced fatty liver and had a normalizing effect on physiological and biochemical indicators of NAFLD, including body weight, liver weight, liver index, total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and insulin resistance level of homeostasis model assessment (HOMA-IR). Kaili Sour Soup decreased the levels of 13 proteins (Tmem44, Rnaseh2b, Gstm6l, LOC100910877, Rufy4, Slc12a2, Pcif1, P4503A1, Sult1e1, Nop53, AABR07065656.4, AABR07065789.3) that were upregulated by HFD and increased the levels of 3 proteins (Sult1c2, Sult1c2a, Snrnp48) that were downregulated by HFD. Kaili Sour Soup attenuated the HFD-induced increase in acyl carnitine (AcCa) and enhanced the HFD-induced decreases in gangliosides (GM3) and lysophosphatidylserine (LPS) in the NAFLD rat model.

Conclusions

Altogether, this study revealed that Kaili Sour Soup attenuated HFD-induced fatty liver and systematically identified abnormal proteins and lipids involved in the role of Kaili Sour Soup in a NAFLD rat model.
Homocystinuria patient and caregiver survey: experiences of diagnosis and patient satisfaction
Authors: Morrison T. , Bösch F. , Landolt M. A. , Kožich V. , Huemer M. , Morris A. A. M.
Published: March 2021

Background

The main genetic causes of homocystinuria are cystathionine beta-synthase (CBS) deficiency and the remethylation defects. Many patients present in childhood but milder forms may present later in life. Some countries have newborn screening programs for the homocystinurias but these do not detect all patients.

Results

HCU Network Australia is one of the very few support groups for patients with homocystinurias. Here we report the results of its survey of 143 patients and caregivers from 22 countries, evaluating current diagnostic pathways and management for the homocystinurias. Most (110) of the responses related to patients with CBS deficiency. The diagnosis was made by newborn screening in 20% of patients and in 50% of the others within 1 year of the initial symptom but in 12.5% it took over 15 years. The delay was attributed mainly to ignorance of the disease. Physicians need to learn to measure homocysteine concentrations in children with neurodevelopmental problems, and in patients with heterogeneous symptoms such as thromboembolism, dislocation of the optic lens, haemolytic uraemic syndrome, and psychiatric disease. Even when the diagnosis is made, the way it is communicated is sometimes poor. Early-onset CBS deficiency usually requires a low-protein diet with amino acid supplements. More than a third of the participants reported problems with the availability or cost of treatment. Only half of the patients always took their amino acid mixture. In contrast, good adherence to the protein restriction was reported in 98% but 80% said it was hard, time-consuming and caused unhappiness.

Conclusions

There is often a long delay in diagnosing the homocystinurias unless this is achieved by newborn screening; this survey also highlights problems with the availability and cost of treatment and the palatability of protein substitutes.
Diuretics decrease fluid balance in patients on invasive mechanical ventilation: the randomized-controlled single blind, IRIHS study
Authors: Cinotti Raphaël , Lascarrou Jean-Baptiste , Azais Marie-Ange , Colin Gwenhaël , Quenot Jean-Pierre , Mahé Pierre-Joachim , Roquilly Antoine , Gaultier Aurélie , Asehnoune Karim , Reignier Jean
Published: March 2021

Background

Fluid overload has been associated with increased morbidity and mortality in critically ill patients. The goal of this study was to assess the efficacy and safety of a diuretic strategy to overcome positive fluid balance in patients on invasive mechanical ventilation.

Methods

Design: Multicenter, single-blind, randomized-controlled study. Patients were randomized into a diuretic (furosemide) or a control group. Patients were eligible in case of fluid overload defined as in-ICU weight increase ≥ 3%, invasive mechanical ventilation (FiO2 ≤ 60% and PEEP ≤ 10 cm H2O on inclusion) and hemodynamic stabilization. The primary outcome was fluid balance, defined as weight variation from reference weight to successful extubation. The main secondary outcome was the safety of diuretic.

Results

171 patients were randomized. After 5 exclusions, 166 patients were included in the analysis: 77 in the diuretic and 89 in the control group. Fluid balance was 1.4 [− 2.5 to 4.5] kg in the diuretic and 6.4 [0.5–11.2] kg in the control group (p < 0.001). In the multiple imputation analysis, fluid balance was significantly decreased in the diuretic group (mean difference = − 4.8 95% CI [− 7.3 to − 2.5], p < 0.001). Eleven (14%) patients died in the diuretic group and 16 (18%) patients in the control group (p = 0.5). There was a worsening of Acute Kidney Injury in 67 (75.3%) patients of the control group versus 46 (59.7%) patients in the diuretic group (p = 0.03).

Conclusions

In this multicenter randomized-controlled study, protocolized diuretic therapy reduced fluid accumulation in patients receiving mechanical ventilation and was well tolerated with a favorable safety profile.

Trial registration NCT 02345681, Registered January 26 2015, Prospectively registered, https://clinicaltrials.gov/ct2/show/NCT02345681?term=02345681&draw=2&rank=1.
Statistical consideration when adding new arms to ongoing clinical trials: the potentials and the caveats
Authors: Lee Kim May , Brown Louise C. , Jaki Thomas , Stallard Nigel , Wason James
Published: March 2021

Background

Platform trials improve the efficiency of the drug development process through flexible features such as adding and dropping arms as evidence emerges. The benefits and practical challenges of implementing novel trial designs have been discussed widely in the literature, yet less consideration has been given to the statistical implications of adding arms.

Main

We explain different statistical considerations that arise from allowing new research interventions to be added in for ongoing studies. We present recent methodology development on addressing these issues and illustrate design and analysis approaches that might be enhanced to provide robust inference from platform trials. We also discuss the implication of changing the control arm, how patient eligibility for different arms may complicate the trial design and analysis, and how operational bias may arise when revealing some results of the trials. Lastly, we comment on the appropriateness and the application of platform trials in phase II and phase III settings, as well as publicly versus industry-funded trials.

Conclusion

Platform trials provide great opportunities for improving the efficiency of evaluating interventions. Although several statistical issues are present, there are a range of methods available that allow robust and efficient design and analysis of these trials.
Association of glucocorticoid doses and emotional health in lupus low disease activity state (LLDAS): a cross-sectional study
Authors: Miyawaki Yoshia , Shimizu Sayaka , Ogawa Yusuke , Sada Ken-ei , Katayama Yu , Asano Yosuke , Hayashi Keigo , Yamamura Yuriko , Hiramatsu-Asano Sumie , Ohashi Keiji , Morishita Michiko , Watanabe Haruki , Takano-Narazaki Mariko , Matsumoto Yoshinori , Yajima Nobuyuki , Yoshimi Ryusuke , Shimojima Yasuhiro , Ohno Shigeru , Kajiyama Hiroshi , Ichinose Kunihiro , Sato Shuzo , Fujiwara Michio , Yamazaki Hajime , Yamamoto Yosuke , Wada Jun , Fukuhara Shunichi
Published: March 2021

Background

While survival of systemic lupus erythematosus (SLE) patients has improved substantially, problems remain in the management of their emotional health. Medium to high-dose glucocorticoid doses are known to worsen emotional health; the effect is unclear among patients receiving relatively low-dose glucocorticoids. This study aims to investigate the association between low glucocorticoid doses and emotional health in lupus low disease activity state (LLDAS).

Methods

This cross-sectional study drew on data from SLE patients in 10 Japanese institutions. The participants were adult patients with SLE duration of ≥ 1 year who met LLDAS criteria at the study visit from April 2018 through September 2019. The exposure was the daily glucocorticoid dose (mg oral prednisolone). The outcome was the emotional health score of the lupus patient-reported outcome scale (range: 0 to 100). Multiple linear regression analysis was performed with adjustment for confounders including disease-related damage, activity, and psychotropic drug use.

Results

Of 192 patients enrolled, 175 were included in the analysis. Their characteristics were as follows: female, 89.7%; median age, 47 years (interquartile range (IQR): 37.0, 61.0). Median glucocorticoid dose was 4.0 mg (IQR 2.0, 5.0), and median emotional health score 79.2 (IQR 58.3, 91.7). Multiple linear regression analysis showed daily glucocorticoid doses to be associated with worse emotional health (β coefficient = − 2.54 [95% confidence interval − 4.48 to − 0.60], P = 0.01).

Conclusions

Daily glucocorticoid doses were inversely associated with emotional health among SLE patients in LLDAS. Further studies are needed to determine whether glucocorticoid tapering leads to clinically significant improvements in emotional health.
Inhibition of HDAC4 by GSK3β leads to downregulation of KLF5 and ASK1 and prevents the progression of intravertebral disc degeneration
Authors: Xiao Lin , Gong Dongping , Liang Loufeng , Liang Anwei , Liang Huaxin , Xu Xiayi , Teng Hongli
Published: March 2021

Background

Intervertebral disc degeneration (IDD) is a major cause of lower back pain. This study aimed at exploring the effects of histone deacetylase 4 (HDAC4) and its upstream and downstream signaling molecules on IDD development.

Methods

A murine IDD model was established by inducing a needle puncture injury to the vertebrate, whereupon we isolated and transfected of nucleus pulposus (NP) cells. Disc height index (DHI) of the mice was determined by X-ray tomography, while the pain experienced by the IDD mice was evaluated by mechanical and thermal sensitivity tests. Next, the interaction between GSK3β and HDAC4 as well as that between HDAC4 and KLF5 acetylation was assessed by co-immunoprecipitation, while the promoter region binding was assessed identified by chromatin immunoprecipitation. By staining methods with TUNEL, Safranin O fast green, and hematoxylin and eosin, the NP cell apoptosis, degradation of extracellular matrix, and morphology of intervertebral disc tissues were measured. Furthermore, mRNA and protein expressions of GSK3β, HDAC4, KLF5, and ASK1, as well as the extent of HDAC4 phosphorylation, were determined by RT-qPCR and Western blotting.

Results

GSK3β was identified to be downregulated in the intervertebral disc tissues obtained from IDD mice, while HDAC4, KLF5, and ASK1 were upregulated. HDAC4 silencing alleviated IDD symptoms. It was also found that GSK3β promoted the phosphorylation of HDAC4 to increase its degradation, while HDAC4 promoted ASK1 expression through upregulating the expression of KLF5. In IDD mice, GSK3β overexpression resulted in increased DHI, inhibition of NP cell apoptosis, alleviation of disc degeneration, and promoted mechanical and thermal pain thresholds. However, HDAC4 overexpression reversed these effects by promoting ASK1 expression.

Conclusion

Based on the key findings of the current study, we conclude that GSK3β can promote degradation of HDAC4, which lead to an overall downregulation of the downstream KLF5/ASK1 axis, thereby alleviating the development of IDD.
The excess costs of childhood food allergy on Canadian families: a cross-sectional study
Authors: Golding Michael A. , Simons Elinor , Abrams Elissa M. , Gerdts Jennifer , Protudjer Jennifer L. P.
Published: March 2021

Background

The impact of childhood food allergy on household costs has not been examined in Canada. The current study sought to examine differences in direct, indirect, and intangible costs among Canadian families with and without a food-allergic child.

Methods

Families with a child with a specialist-diagnosed food allergy (cases) were recruited from two tertiary pediatric allergy clinics in the Province of Manitoba, Canada, and matched, based on age and sex, to families without a food-allergic child (controls). Cost data for the two groups were collected via an adapted version of the Food Allergy Economic Questionnaire (FA-EcoQ). Consideration was given to income, defined as above vs. below the provincial annual median income.

Results

Results from 35 matched case/control pairs revealed that while total household costs did not significantly differ between cases and controls, food-allergic families did incur higher direct costs ($12,455.69 vs. $10,078.93, p = 0.02), which were largely attributed to spending on food. In contrast, cases reported lower, but not statistically significant, total indirect costs compared to controls ($10,038.76 vs. $12,294.12, p = 0.06). Families also perceived their food-allergic child as having poorer quality of life relative to their healthy peers. Lastly, stratification of the analyses by annual income revealed several differences between the higher and lower income groups.

Conclusions

Relative to families without a food-allergic child, food-allergic families incurred higher direct costs across a number of different areas.
Trisomy 5p with bilateral congenital diaphragmatic hernia: a case report
Authors: Nakamura Noriyuki , Ushida Takafumi , Moriyama Yoshinori , Imai Kenji , Nakano-Kobayashi Tomoko , Osuka Satoko , Goto Maki , Kajiyama Hiroaki , Asada Hideyuki , Hayakawa Masahiro , Kotani Tomomi
Published: March 2021

Background

Bilateral congenital diaphragmatic hernia (CDH) is very rare. A few studies have reported the pathogenic role of 5p in CDH.

Case presentation

A 23-year-old primigravida Japanese woman was referred for the following abnormal findings at 33 weeks of gestation: polyhydramnios, macroglossia, talipes equinovarus, and levocardia. A marker chromosome was detected by amniocentesis. Fluorescence in situ hybridization with whole chromosome paint 5 and nucleolus organizer region probes confirmed its origin from chromosome 5 and an acrocentric chromosome. The karyotype of the fetus was diagnosed as 47, XY, +mar. ish +mar(WCP5+). At 39 + 5 weeks, a 2462 g male infant was delivered, with a specific facial configuration. Bilateral CDH, hypoplasia of the corpus callosum, atrial septal defect, and hypothyroidism were also detected in the baby. The karyotype of the peripheral blood was consistent with that of the amniocentesis.

Conclusion

Genes coded on 5p might be associated with the pathogenesis of CDH; however, further investigation is required.
Progress and challenges in developing organoids in farm animal species for the study of reproduction and their applications to reproductive biotechnologies
Authors: Bourdon Guillaume , Cadoret Véronique , Charpigny Gilles , Couturier-Tarrade Anne , Dalbies-Tran Rozenn , Flores Maria-José , Froment Pascal , Raliou Mariam , Reynaud Karine , Saint-Dizier Marie , Jouneau Alice
Published: March 2021

Within the past decades, major progress has been accomplished in isolating germ/stem/pluripotent cells, in refining culture medium and conditions and in establishing 3-dimensional culture systems, towards developing organoids for organs involved in reproduction in mice and to some extent in humans. Haploid male germ cells were generated in vitro from primordial germ cells. So were oocytes, with additional support from ovarian cells and subsequent follicle culture. Going on with the female reproductive tract, spherical oviduct organoids were obtained from adult stem/progenitor cells. Multicellular endometrial structures mimicking functional uterine glands were derived from endometrial cells. Trophoblastic stem cells were induced to form 3-dimensional syncytial-like structures and exhibited invasive properties, a crucial point for placentation. Finally, considering the embryo itself, pluripotent embryonic cells together with additional extra-embryonic cells, could self-organize into a blastoid, and eventually into a post-implantation-like embryo. Most of these accomplishments have yet to be reached in farm animals, but much effort is devoted towards this goal. Here, we review the progress and discuss the specific challenges of developing organoids for the study of reproductive biology in these species. We consider the use of such organoids in basic research to delineate the physiological mechanisms involved at each step of the reproductive process, or to understand how they are altered by environmental factors relevant to animal breeding. We evaluate their potential in reproduction of animals with a high genetic value, from a breeding point of view or in the context of preserving local breeds with limited headcounts.
Correction to: The quality of primary care provided to the elderly in Israel
Authors: Podell Rachel , Kaufman-Shriqui Vered , Sagy Yael Wolff , Manor Orly , Ben-Yehuda Arie
Published: March 2021

An amendment to this paper has been published and can be accessed via the original article.