bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the mental effects of COVID-19-related work on depression among community health workers in Vietnam
Authors: Hoang Ngoc-Anh , Van Hoang Ngoc , Quach Ha-Linh , Nguyen Khanh Cong , Duong Luong Huy , Pham Thai Quang , Vogt Florian
Published: August 2022

Background

Community health workers (CHWs) involved in the COVID-19 response might be at increased risk of developing depression, though evidence is scarce. We investigated effects of COVID-19-related work on changes in depression levels among CHWs in Vietnam and identified sub-groups among CHWs who are at particular risk of developing severe depression.

Methods

We conducted a cross-sectional online survey among 979 CHWs who were involved in the COVID-19 response in Vietnam, in particular during the 2021 Tet holiday outbreak between January and March 2021. Respondents were asked to report depression symptoms at two-time points, before the start of the COVID-19 pandemic (average June to December 2019) and during the 2021 Tet holiday outbreak using the PHQ-9 mental health questionnaire. We estimated depression levels at both time points and developed univariate and multivariable logistic regression models to estimate odds ratios and 95% confidence intervals (95% CIs) to explore the association between deterioration to high depression levels and selected risk factors.

Results

Median depression levels among CHWs in Vietnam doubled from 3 (IQR = 2–7) before COVID-19 to 6 (IQR = 3–9) on the PHQ-9 scale during the Tet holiday outbreak. The proportion with normal/minimal levels decreased from 77.1% (95% CI = 74.4–79.7) to 50.9% (95% CI = 47.7–54) (p-value < 0.001), while the proportion of CHWs with moderate, moderately severe, and severe depression levels increased 4.3, 4.5, and five-fold, respectively. Less sleep and poor sleep quality, working in unfavorable work environments, and being involved in contact tracing and the organization of quarantine for suspected cases were associated with an increased risk of deterioration to high depression levels.

Conclusions

We found a substantial increase in overall depression levels among CHWs in Vietnam due to their COVID-19 related work and a particularly worrisome rise in CHWs suffering from severe depression. CHWs are an indispensable yet often overlooked cadre of work in many low- and middle-income countries and shoulder a heavy psychological burden during the COVID-19 pandemic. Targeted psychological support for CHWs is needed to improve their mental health and to ensure the sustainability of community-based health interventions during COVID-19 and future epidemics.
Semaphorin3f as a cardiomyocyte derived regulator of heart chamber development
Authors: Halabi Rami , Cechmanek Paula Bernice , Hehr Carrie Lynn , McFarlane Sarah
Published: August 2022

Background

During development a pool of precursors form a heart with atrial and ventricular chambers that exhibit distinct transcriptional and electrophysiological properties. Normal development of these chambers is essential for full term survival of the fetus, and deviations result in congenital heart defects. The large number of genes that may cause congenital heart defects when mutated, and the genetic variability and penetrance of the ensuing phenotypes, reveals a need to understand the molecular mechanisms that allow for the formation of chamber-specific cardiomyocyte differentiation.

Methods

We used in situ hybridization, immunohistochemistry and functional analyses to identify the consequences of the loss of the secreted semaphorin, Sema3fb, in the development of the zebrafish heart by using two sema3fb CRISPR mutant alleles.

Results

We find that in the developing zebrafish heart sema3fb mRNA is expressed by all cardiomyocytes, whereas mRNA for a known receptor Plexina3 (Plxna3) is expressed preferentially by ventricular cardiomyocytes. In sema3fb CRISPR zebrafish mutants, heart chamber development is impaired; the atria and ventricles of mutants are smaller in size than their wild type siblings, apparently because of differences in cell size and not cell numbers. Analysis of chamber differentiation indicates defects in chamber specific gene expression at the border between the ventricular and atrial chambers, with spillage of ventricular chamber genes into the atrium, and vice versa, and a failure to restrict specialized cardiomyocyte markers to the atrioventricular canal (AVC). The hypoplastic heart chambers are associated with decreased cardiac output and heart edema.

Conclusions

Based on our data we propose a model whereby cardiomyocytes secrete a Sema cue that, because of spatially restricted expression of the receptor, signals in a ventricular chamber-specific manner to establish a distinct border between atrial and ventricular chambers that is important to produce a fully functional heart.
Poly(ADP-ribosyl)ation of acetyltransferase NAT10 by PARP1 is required for its nucleoplasmic translocation and function in response to DNA damage
Authors: Liu Hong-Yi , Liu Ying-Ying , Zhang Yin-Ling , Ning Yan , Zhang Fang-Lin , Li Da-Qiang
Published: August 2022

Background

N-acetyltransferase 10 (NAT10), an abundant nucleolar protein with both lysine and RNA cytidine acetyltransferase activities, has been implicated in Hutchinson-Gilford progeria syndrome and human cancer. We and others recently demonstrated that NAT10 is translocated from the nucleolus to the nucleoplasm after DNA damage, but the underlying mechanism remains unexplored.

Methods

The NAT10 and PARP1 knockout (KO) cell lines were generated using CRISPR-Cas9 technology. Knockdown of PARP1 was performed using specific small interfering RNAs targeting PARP1. Cells were irradiated with γ-rays using a 137Cs Gammacell-40 irradiator and subjected to clonogenic survival assays. Co-localization and interaction between NAT10 and MORC2 were examined by immunofluorescent staining and immunoprecipitation assays, respectively. PARylation of NAT10 and translocation of NAT10 were determined by in vitro PARylation assays and immunofluorescent staining, respectively.

Results

Here, we provide the first evidence that NAT10 underwent covalent PARylation modification following DNA damage, and poly (ADP-ribose) polymerase 1 (PARP1) catalyzed PARylation of NAT10 on three conserved lysine (K) residues (K1016, K1017, and K1020) within its C-terminal nucleolar localization signal motif (residues 983–1025). Notably, mutation of those three PARylation residues on NAT10, pharmacological inhibition of PARP1 activity, or depletion of PARP1 impaired NAT10 nucleoplasmic translocation after DNA damage. Knockdown or inhibition of PARP1 or expression of a PARylation-deficient mutant NAT10 (K3A) attenuated the co-localization and interaction of NAT10 with MORC family CW-type zinc finger 2 (MORC2), a newly identified chromatin-remodeling enzyme involved in DNA damage response, resulting in a decrease in DNA damage-induced MORC2 acetylation at lysine 767. Consequently, expression of a PARylation-defective mutant NAT10 resulted in enhanced cellular sensitivity to DNA damage agents.

Conclusion

Collectively, these findings indicate that PARP1-mediated PARylation of NAT10 is key for controlling its nucleoplasmic translocation and function in response to DNA damage. Moreover, our findings provide novel mechanistic insights into the sophisticated paradigm of the posttranslational modification-driven cellular response to DNA damage.
Opposing roles of CLK SR kinases in controlling HIV-1 gene expression and latency
Authors: Dahal Subha , Clayton Kiera , Been Terek , Fernet-Brochu Raphaële , Ocando Alonso Villasmil , Balachandran Ahalya , Poirier Mikaël , Maldonado Rebecca Kaddis , Shkreta Lulzim , Boligan Kayluz Frias , Guvenc Furkan , Rahman Fariha , Branch Donald , Bell Brendan , Chabot Benoit , Gray-Owen Scott D. , Parent Leslie J. , Cochrane Alan
Published: August 2022

Background

The generation of over 69 spliced HIV-1 mRNAs from one primary transcript by alternative RNA splicing emphasizes the central role that RNA processing plays in HIV-1 replication. Control is mediated in part through the action of host SR proteins whose activity is regulated by multiple SR kinases (CLK1-4, SRPKs).

Methods

Both shRNA depletion and small molecule inhibitors of host SR kinases were used in T cell lines and primary cells to evaluate the role of these factors in the regulation of HIV-1 gene expression. Effects on virus expression were assessed using western blotting, RT-qPCR, and immunofluorescence.

Results

The studies demonstrate that SR kinases play distinct roles; depletion of CLK1 enhanced HIV-1 gene expression, reduction of CLK2 or SRPK1 suppressed it, whereas CLK3 depletion had a modest impact. The opposing effects of CLK1 vs. CLK2 depletion were due to action at distinct steps; reduction of CLK1 increased HIV-1 promoter activity while depletion of CLK2 affected steps after transcript initiation. Reduced CLK1 expression also enhanced the response to several latency reversing agents, in part, by increasing the frequency of responding cells, consistent with a role in regulating provirus latency. To determine whether small molecule modulation of SR kinase function could be used to control HIV-1 replication, we screened a GSK library of protein kinase inhibitors (PKIS) and identified several pyrazolo[1,5-b] pyridazine derivatives that suppress HIV-1 gene expression/replication with an EC50 ~ 50 nM. The compounds suppressed HIV-1 protein and viral RNA accumulation with minimal impact on cell viability, inhibiting CLK1 and CLK2 but not CLK3 function, thereby selectively altering the abundance of individual CLK and SR proteins in cells.

Conclusions

These findings demonstrate the unique roles played by individual SR kinases in regulating HIV-1 gene expression, validating the targeting of these functions to either enhance latency reversal, essential for “Kick-and-Kill” strategies, or to silence HIV protein expression for “Block-and-Lock” strategies.
Awareness of pubertal body changes among primary school children aged 10–14 years in Eastern Uganda; challenges and opportunities
Authors: Bunoti Sarah Nantono , Tumwesigye Nazarius Mbona , Atuyambe Lynn
Published: August 2022

Background

Globally, programs that educate young people about pubertal body changes are vital. In some communities, teaching sexual education in schools has been the subject of debate. This is probably why access to sexual and reproductive health information and resources is still a challenge to children aged 10–14 years.

Methods

We conducted a qualitative study design among school children aged 10–14 years. Data were collected from 19 focus group discussions (FGDs) in 16 primary schools purposively selected from Eastern Uganda. Data were transcribed, coded and thematically analysed.

Results

We established that girls in rural schools were aware of their body changes than those from urban schools. Boys in urban schools were knowledgeable of pubertal body changes than those from rural schools. We further found that girls experienced pubertal-related challenges amongst themselves and boys including lack of shavers, pain while shaving, rape, bad boy–girl relationships, unwanted early pregnancies, limited funds to buy pads, menstrual pain, etc. Boys too indicated that they experienced similar challenges and these included lack of shavers, pain during and after shaving, changes in height, raping of girls, bad boy–girl relationships, peer pressure, HIV and other STIs, limited infrastructure, voice changes, bad body odour etc. Girls and boys endeavoured to overcome pubertal-related challenges by utilising advise from teachers, parents and friends.

Conclusion

Boys and girls who were knowledgeable about puberty body changes possessed opportunities that enable them to cope with pubertal-related challenges.
Barriers and facilitators to exclusive breastfeeding in rural Pakistan: a qualitative exploratory study
Authors: Riaz Atif , Bhamani Shelina , Ahmed Sheraz , Umrani Fayaz , Jakhro Sadaf , Qureshi Abdul Khaliq , Ali Syed Asad
Published: August 2022

Background

Exclusive breastfeeding (EBF) of children until six months of age is considered one of the most critical interventions in tackling childhood undernutrition. EBF rates are suboptimal in Pakistan, particularly in rural areas where child undernutrition is most prevalent. This study aimed to explore barriers to EBF in a rural context of Pakistan.

Methods

The study was conducted in the rural district Matiari of Sindh, Pakistan, during Jan-March 2020. We used a qualitative exploratory study design and conducted 36 focus group discussions (FGDs). Participants were purposively selected mothers who had not practiced EBF during their previous childbirth, their spouses and mothers-in-law, and lady health workers (LHWs) serving in the study catchment. FGDs were audio-recorded, transcribed, and translated into English from the local language and analysed using thematic content analysis.

Results

Barriers to EBF included low awareness and cultural practices of prelacteal feeds, insufficient breast milk production, undernutrition of mothers, mothers’ occupation as fieldworkers, less birth spacing, low awareness about the correct technique of breastfeeding, maternal and child ailments, abnormal breasts, and influence of in-laws to start top-up feeds. Several facilitators were identified: family support, appropriate maternal diet, maternal awareness, and support in the neighborhood.

Conclusion

Barriers to EBF are multifaceted in rural areas, and interventions aiming to improve adherence to EBFshould be multipronged. Awareness-raising alone might not be sufficient, and other interventions should be designed to address the barriers of maternal malnutrition, insufficient milk production, and socio-cultural practices. In addition, safe alternatives to breast milk may be necessary if breastfeeding is truly not feasible. Lack of breast milk substitutes is particularly challenging for poor rural women who cannot afford infant formula milk.
Examining the complementarity between the ERIC compilation of implementation strategies and the behaviour change technique taxonomy: a qualitative analysis
Authors: McHugh Sheena , Presseau Justin , Luecking Courtney T. , Powell Byron J.
Published: August 2022

Background

Efforts to generate evidence for implementation strategies are frustrated by insufficient description. The Expert Recommendations for Implementing Change (ERIC) compilation names and defines implementation strategies; however, further work is needed to describe the actions involved. One potentially complementary taxonomy is the behaviour change techniques (BCT) taxonomy. We aimed to examine the extent and nature of the overlap between these taxonomies.

Methods

Definitions and descriptions of 73 strategies in the ERIC compilation were analysed. First, each description was deductively coded using the BCT taxonomy. Second, a typology was developed to categorise the extent of overlap between ERIC strategies and BCTs. Third, three implementation scientists independently rated their level of agreement with the categorisation and BCT coding. Finally, discrepancies were settled through online consensus discussions. Additional patterns of complementarity between ERIC strategies and BCTs were labelled thematically. Descriptive statistics summarise the frequency of coded BCTs and the number of strategies mapped to each of the categories of the typology.

Results

Across the 73 strategies, 41/93 BCTs (44%) were coded, with ‘restructuring the social environment’ as the most frequently coded (n=18 strategies, 25%). There was direct overlap between one strategy (change physical structure and equipment) and one BCT (‘restructuring physical environment’). Most strategy descriptions (n=64) had BCTs that were clearly indicated (n=18), and others where BCTs were probable but not explicitly described (n=31) or indicated multiple types of overlap (n=15). For some strategies, the presence of additional BCTs was dependent on the form of delivery. Some strategies served as examples of broad BCTs operationalised for implementation. For eight strategies, there were no BCTs indicated, or they did not appear to focus on changing behaviour. These strategies reflected preparatory stages and targeted collective cognition at the system level rather than behaviour change at the service delivery level.

Conclusions

This study demonstrates how the ERIC compilation and BCT taxonomy can be integrated to specify active ingredients, providing an opportunity to better understand mechanisms of action. Our results highlight complementarity rather than redundancy. More efforts to integrate these or other taxonomies will aid strategy developers and build links between existing silos in implementation science.
Telehealth service delivery in an Australian regional mental health service during COVID-19: a mixed methods analysis
Authors: Chatterton Mary Lou , Marangu Elijah , Clancy Elizabeth M. , Mackay Matthew , Gu Eve , Moylan Steve , Langbein Amy , O’Shea Melissa
Published: August 2022

Background

COVID-19 required mental health services to quickly switch from face-to-face service delivery to telehealth (telephone and videoconferencing). This evaluation explored implementation of a telehealth mental health response in a regional public mental health provider.

Methods

A mixed methods approach, combining service use data, brief satisfaction surveys, and qualitative interviews/focus groups was undertaken. Number and types of contacts from de-identified mental health service data were compared between April–May 2020 and April–May 2019. Mental health consumers and providers completed brief online satisfaction surveys after videoconferencing sessions. Attitudes and perspectives on the implementation of telehealth were further explored by applying a descriptive qualitative framework to the analysis of interview and focus group data supplied by consumers and providers. Template thematic analysis was used to elucidate key themes relating to the barriers and enablers of telehealth uptake and future implementation recommendations.

Results

Total contacts decreased by 13% from 2019 to 2020. Face-to-face contacts decreased from 55% of total in 2019 to 24% in 2020. In 2019, 45% of contacts were by telephone, increasing to 70% in 2020. Only four videoconferencing contacts were made in 2019; increasing to 886 in 2020. Consumer surveys (n = 26) rated videoconferencing as good or excellent for technical quality (92%), overall experience (86%), and satisfaction with personal comfort (82%). Provider surveys (n = 88) rated technical quality as good or excellent (68%) and 86% could achieve assessment/treatment goals with videoconferencing. Provider focus groups/interviews (n = 32) identified that videoconferencing was well-suited to some clinical tasks. Consumers interviewed (n = 6) endorsed the ongoing availability of telehealth within a blended approach to service delivery. Both groups reflected on videoconferencing limitations due to infrastructure (laptops, phones, internet access), cumbersome platform and privacy concerns, with many reverting to telephone use.

Conclusions

While videoconferencing increased, technical and other issues led to telephone being the preferred contact method. Satisfaction surveys indicated improvement opportunities in videoconferencing. Investment in user-friendly platforms, telehealth infrastructure and organisational guidelines are needed for successful integration of videoconferencing in public mental health systems.
Effect of perioperative magnesium sulfate and labetalol infusion on peripheral perfusion and postoperative pain in nasal surgery: a randomized controlled trial
Authors: Kamel Alshaimaa Abdel Fattah , Medhat Marwa Mohamed , Salem Dina Abdelhameed Elsadek , Naby Sara Mohamed Abdel
Published: August 2022

Background

Maintenance of adequate peripheral perfusion during controlled hypotension is necessary for patient safety and improved surgical outcomes during controlled hypotension in nasal surgery. The hypothesis of this study was to investigate the effect of perioperative magnesium sulfate and labetalol infusion on peripheral perfusion and postoperative pain in patients undergoing nasal surgery.

Methods

A total of 50 patients were randomly assigned into two equal groups in this double-blind clinical study: the magnesium sulfate group; received 40 mg/kg loading dose of intravenous (IV) magnesium sulfate followed by 10–15 mg/kg/h continuous IV infusion and the labetalol group; received 0.25 mg/kg loading dose of IV labetalol followed by 0.5–1 mg/kg/h continuous IV infusion to achieve a mean arterial blood pressure (MABP) of = 55–65 mmHg. The primary outcome was to compare the effect of perioperative magnesium sulfate and labetalol infusion on peripheral perfusion during nasal surgery. The secondary outcomes were the assessment of serum lactate, postoperative pain, time to the first call for pethidine (rescue analgesic) and total pethidine consumption.

Results

PPI was comparable between the groups at baseline, intubation, and 5 min. In contrast, magnesium sulfate group had a significantly higher PPI than the labetalol group. The magnesium sulfate group had a significantly higher MABP and heart rate compared to labetalol group. The time to reach the target MABP was significantly prolonged in magnesium sulfate than the labetalol group [21.6 ± 1.7 vs 6.9 ± 1.5] min. VAS scores were significantly lower for 2 hs postoperatively in the magnesium sulfate group than the labetalol group. The time to first call of pethidine was significantly prolonged in the magnesium sulfate group compared to the labetalol group [113.1 ± 5.2 vs 28.2 ± 1.5] min.

Conclusions

Magnesium sulfate maintains wider PPI and offers better postoperative pain relief compared to labetalol during induced hypotension in nasal surgery.

Trial registration

Institutional review board approval (ref: 6601/20–12-2020).

Clinicaltrial.gov (ref:NCT04688203, date of registration: 29 -12–2020).
False-positives and false-negatives in non-invasive prenatal testing (NIPT): what can we learn from a meta-analyses on > 750,000 tests?
Authors: Liehr Thomas
Published: August 2022

Background

Non-invasive prenatal testing (NIPT) has had an incomparable triumph in prenatal diagnostics in the last decade. Over 1400 research articles have been published, predominantly praising the advantages of this test.

Methods

The present study identified among the 1400 papers 24 original and one review paper, which were suited to re-evaluate the efficacy of > 750,000 published NIPT-results. Special attention was given to false-positive and false-negative result-rates. Those were discussed under different aspects—mainly from a patient-perspective.

Results

A 27: 1 rate of false-positive compared to false-negative NIPT results was found. Besides, according to all reported, real-positive, chromosomally aberrant NIPT cases, 90% of those would have been aborted spontaneously before birth. These findings are here discussed under aspects like (i) How efficient is NIPT compared to first trimester screening? (ii) What are the differences in expectations towards NIPT from specialists and the public? and (iii) There should also be children born suffering from not by NIPT tested chromosomal aberrations; why are those never reported in all available NIPT studies?

Conclusions

Even though much research has been published on NIPT, unbiased figures concerning NIPT and first trimester screening efficacy are yet not available. While false positive rates of different NIPT tests maybe halfway accurate, reported false-negative rates are most likely too low. The latter is as NIPT-cases with negative results for tested conditions are yet not in detail followed up for cases with other genetic or teratogenic caused disorders. This promotes an image in public, that NIPT is suited to replace all invasive tests, and also to solve the problem of inborn errors in humans, if not now then in near future. Overall, it is worth discussing the usefulness of NIPT in practical clinical application. Particularly, asking for unbiased figures concerning the efficacy of first trimester-screening compared to NIPT, and for really comprehensive data on false-positive and false-negative NIPT results.
Diversity of adenosine deaminase in children with EBV-related diseases
Authors: Shi Ting , Shen Yu , Zhang Wei , Qian Meiying , Chen Xiuli , Huang Linlin , Tian Jianmei
Published: August 2022

Background

Adenosine deaminase (ADA) is an enzyme involved in purine metabolism with an important role in cellular immunity. Thus, this study investigated the association between ADA and Epstein–Barr virus (EBV)-related diseases.

Methods

We retrospectively collected data from all children admitted to the Children’s Hospital of Soochow University, Suzhou, China, between May 1, 2018, and March 31, 2019, who underwent plasma EBV-DNA polymerase chain reaction, alanine aminotransferase (ALT), and ADA testing.

Results

Of 6868 children, 1877 had an elevated level of ADA, and 4991 had a level within the normal range. Multivariate logistic regression analysis indicated that ALT (adjusted odds radio [aOR] = 1.001, 95% confidence interval [CI]: 1.001–1.002), EBV infection (aOR = 8.486, 95% CI: 6.753–10.663), inflammatory disease (aOR = 3.915, 95% CI: 3.198–4.794), autoimmune disease (aOR = 2.307, 95% CI: 1.823–2.920), and malignant disease (aOR = 1.381; 95% CI: 1.101–1.734) were risk factors for an elevated ADA level. Furthermore, the ADA levels among EBV-related diseases significantly differed, including infectious mononucleosis, atypical EBV infection, respiratory infection, malignant disease, and other diseases (P < 0.05). In addition, the ADA level positively correlated with the Epstein–Barr viral load (r = 0.501, P < 0.05).

Conclusions

This large, retrospective study identified a correlation between ADA and EBV-related diseases, which may help clinicians detect these diseases earlier based on the plasma ADA concentration.
BRCA1/2 variants and copy number alterations status in non familial triple negative breast cancer and high grade serous ovarian cancer
Authors: El Ansari Fatima Zahra , Jouali Farah , Fekkak Rim , Bakkach Joaira , Ghailani Nourouti Naima , Barakat Amina , Bennani Mechita Mohcine , Fekkak Jamal
Published: August 2022

Background

While the role of BRCA1/2 genes in familial breast and ovarian cancer is well established, their implication in the sporadic form of both cancers is still controversial. With the development of poly (ADP-ribose) polymerase (PARP) inhibitors, the exact relationship between BRCA1/2 genes and sporadic triple negative breast cancer/high grade serous carcinoma (TNBC/HGSC) needs to be further investigated. Therefore, we conducted a study in which we analyze BRCA1/2 point mutations and copy number alterations in Moroccan patients suffering from TNBC/HGSC.

Methods

To achieve our goal, we analyzed BRCA1/2 genes in the FFPE tissue blocks and blood samples of 65 TNBC/HGSC selected patients, using next generation sequencing technology.

Results

From the 65 successfully sequenced patients in our cohort, we detected five-point variants in six different patients, four variants were classified as pathogenic and one of unknown significance. Regarding copy number alterations we detected one copy number loss in BRCA1 gene and one copy number gain in BRCA2 gene. The genetic screening of BRCA1/2 genes using these patients’ genomic DNA indicated that five harbored a germline genetic alteration. While three harbored a somatic genetic alteration. To the best of our knowledge, three-point variants detected in our study have never been reported before.

Conclusion

According to the results found in the present study, in a population without a family history of cancer, the possibility of a BRCA1/2 somatic pathogenic variant in high grade serous carcinoma is 7%. While for Triple negative breast cancer somatic point variants and copy number alterations seems to be a very rare genetic event.
Evaluation of an adaptive, multimodal intervention to reduce postoperative infections following cesarean delivery in Ethiopia: study protocol of the CLEAN-CS cluster-randomized stepped wedge interventional trial
Authors: Mammo Tihitena Negussie , Feyssa Mekdes Daba , Haile Sara Taye , Fikre Tesfaneh , Shiferaw Matiyas Asrat , Woldeamanuel Habtamu , Temesgen Fikremelekot , Gebeyehu Natnael , Starr Nichole , Fernandez Katie , Henrich Natalie , Alemu Senait Bitew , Miller Kate , Weiser Thomas G.
Published: August 2022

Background

We previously developed and pilot tested Clean Cut, a program to prevent postoperative infections by improving compliance with the WHO Surgical Safety Checklist (SSC) and strengthening adherence to infection control practices. This protocol describes theCheckListExpansion forAntisepsis and iNfection Control inCesareanSection (CLEAN–CS) trial evaluating our program’s ability to reduce infections following CS and other obstetric and gynecological operations in Ethiopia.

Methods/design

CLEAN-CS is a cluster-randomized stepped wedge interventional trial with five clusters (two hospitals per cluster). It aims to assess the impact of Clean Cut on six critical perioperative infection prevention standards including antiseptic practices, antibiotic administration, and routine SCC use. The trial involves baseline data collection followed by Clean Cut training and implementation in each cluster in randomized order. The intervention consists of (1) modifying and implementing the SSC to fit local practices, (2) process mapping each standard, (3) coupling data and processes with site-specific action plans for improvement, and (4) targeted training focused on process gaps. The primary outcome is 30-day CS infection rates; secondary outcomes include other patient-level complications and compliance with standards. Assuming baseline SSI incidence of 12%, an effect size of 25% absolute reduction, and the ability to recruit 80–90 patients per cluster per month, we require a sample of 8100 patients for significance. We will report our study according to CONSORT.

Discussion

A cluster-randomized stepped wedge design is well-suited for evaluating this type of surgical safety program. The targeted standards are not in doubt, yet compliance is frequently difficult. Solutions are available and may be recognized by individuals, but teams dedicated to improvement are often lacking. Clean Cut was successfully piloted but requires a more rigorous methodological assessment. We seek to understand the qualities, characteristics, and resources needed to implement the program, the magnitude of effect on processes and outcomes, and to what degree it can enhance compliance with care standards. Challenges include a fraught social and political environment, pandemic travel restrictions, and a limited budget.

Trial registration

ClinicalTrials.govNCT04812522(registered on March 23, 2021); Pan-African Clinical Trials RegistryPACTR202108717887402(registered on August 24, 2021).
Principles and recommendations for incorporating estimands into clinical study protocol templates
Authors: Lynggaard Helle , Bell James , Lösch Christian , Besseghir Amel , Rantell Khadija , Schoder Volker , Lanius Vivian
Published: August 2022

Clinical study protocols are the foundation of good clinical studies. Prospective and multidisciplinary collaboration that pays attention to the design of all components of the study protocol can ensure that a clinical study will answer the research questions posed in a reliable manner that is meaningful for decision-makers and patients. The ICH E9(R1) addendum on estimands and sensitivity analysis in clinical trials provides a framework for clinical study planning to ensure alignment between study objectives, design, conduct, and analysis. The estimand or clinical question posed can be regarded as the backbone of the study and the clinical study protocol should reflect estimands accordingly. In practice, stakeholders are still learning how to embrace the estimand framework and how it impacts studies and study documents. In this paper, we anticipate that a protocol structure centred around estimands, or objectives rather than endpoints alone will prevail for all types of studies. To assist sponsors during this paradigm shift, this paper provides discussion and guidance for implementing the estimand framework in protocol templates.
Sleep optimization to improve glycemic control in adults with type 1 diabetes: study protocol for a randomized controlled parallel intervention trial
Authors: Martyn-Nemeth Pamela , Duffecy Jennifer , Quinn Laurie , Reutrakul Sirimon , Steffen Alana D. , Burke Larisa , Clark Withington Margaret H. , Irsheed Ghada Abu , Perez Rose , Park Minsun , Saleh Adam , Mihailescu Dan , Baron Kelly Glazer
Published: August 2022

Background

Despite improvements in treatment regimens and technology, less than 20% of adults with type 1 diabetes (T1D) achieve glycemic targets. Sleep is increasingly recognized as a potentially modifiable target for improving glycemic control. Diabetes distress, poor self-management behaviors, and reduced quality of life have also been linked to sleep variability and insufficient sleep duration. A significant gap of knowledge exists regarding interventions to improve sleep and the effects of sleep optimization on glycemic control in T1D. The purpose of this study is to determine the efficacy of a T1D-specific sleep optimization intervention (Sleep-Opt) on the primary outcomes of sleep variability, sleep duration, and glycemic control (A1C); other glycemic parameters (glycemic variability, time-in-range [TIR]); diabetes distress; self-management behaviors; quality of life; and other patient-reported outcomes in adults with T1D and habitual increased sleep variability or short sleep duration.

Methods

A randomized controlled parallel-arm study will be employed in 120 adults (aged 18 to 65 years) with T1D. Participants will be screened for habitual sleep variability (> 1 h/week) or insufficient sleep duration (< 6.5 h per night). Eligible subjects will be randomized to the Sleep-Opt intervention group or healthy living attention control group for 12 weeks. A 1-week run-in period is planned, with baseline measures of sleep by actigraphy (sleep variability and duration), glycemia (A1C and related glycemic measures: glycemic variability and TIR using continuous glucose monitoring), and other secondary outcomes: diabetes distress, self-management behaviors, quality of life, and additional patient-reported outcomes. Sleep-Opt is a technology-assisted behavioral sleep intervention that we recently developed that leverages the rapidly increasing public interest in sleep tracking. Our behavioral intervention employs four elements: a wearable sleep tracker, didactic content, an interactive smartphone application, and brief telephone counseling. The attention control group will participate in a healthy living information program. Baseline measures will be repeated at midpoint, program completion, and post-program (weeks 6, 12, and 24, respectively) to determine differences between the two groups and sustainability of the intervention.

Discussion

A better understanding of strategies to improve sleep in persons with T1D has the potential to be an important component of diabetes.

Trial registration

Clinical Trial Registration: NCT04506151.
Early essential newborn care for cesarean section newborns in China: study protocol for a multi-centered randomized controlled trial
Authors: Wang Xueyin , Zhang Xiaosong , Sobel Howard Lawrence , Li Zhao , Juan Juan , Yang Huixia
Published: August 2022

Background

Early essential newborn care (EENC) is a package of evidence-based and cost-effective interventions delivered around birth mainly including delayed cord clamping, immediate and sustained skin-to-skin contact, and early initiation of exclusive breastfeeding. EENC is proven effective in promoting breastfeeding and improving women’s and newborns’ health. However, there is little evidence on implementation of EENC on newborns born by cesarean section in China. Therefore, the objective of this study is to assess the effectiveness of EENC intervention on rates of exclusive breastfeeding and early initiation of breastfeeding for cesarean section newborns in China.

Methods

This is a multi-centered, randomized controlled trial conducted in 4 tertiary hospitals in China. A total of 720 eligible women who will receive cesarean section are being randomized into four groups: control group (n=180), intervention group 1 (skin-to-skin contact for 30 min, n=180), intervention group 2 (skin-to-skin contact for 60 min, n=180), and intervention group 3 (skin-to-skin contact for 90 min, n=180). The control group will receive routine care, whereas the intervention groups will receive EENC with different duration of skin-to-skin contact. Demographic characteristics, clinical information, and breastfeeding outcomes will be collected. The primary outcome is rates of exclusive breastfeeding and early initiation of breastfeeding, and the secondary outcomes include maternal and neonatal morbidity and admissions.

Discussion

This study will provide evidence of the impact of EENC on improvement of breastfeeding outcomes and maternal and neonatal health for cesarean section newborns in China, and evidence-based recommendation to inform optimal duration of skin-to-skin contact for cesarean deliveries. The results of this study have potential to inform national-level guidelines and policy-making for optimizing EENC implementation for cesarean section newborns.

Trial registration

Chinese Clinical Trial Registry ChiCTR2100048997. Retrospectively registered on 19 July 2021
G-CuP: the effect of a forced oral glucose intake on alcohol craving and mesolimbic cue reactivity in alcohol dependence—study protocol of a randomized, double-blind, placebo-controlled crossover study
Authors: Wetzel Lea , Pourbaix Madeleine , Riegler Alisa , Pfeifer Anna-Maria , Reinhard Iris , Hoffmann Sabine , Vollstädt-Klein Sabine , Kiefer Falk , Sommer Wolfgang , Bumb Jan Malte , Bach Patrick , Koopmann Anne
Published: August 2022

Background

Multiple studies indicate that a lower plasma level of the acetylated form of the appetite-regulating hormone ghrelin and higher plasma levels of insulin lead to a reduction in subjective alcohol craving and a reduced mesolimbic cue reactivity in functional magnetic resonance imaging (fMRI) when being exposed to alcohol-associated stimuli. The ghrelin level can physiologically be reduced by the induction of stomach distension and the ingestion of glucose or lipids.

Methods

A total of 108 alcohol-dependent patients aged between 18 and 65 years are examined in the randomized, double-blind, placebo-controlled crossover study. After collecting demographic and psychometric data, participants take part in an alcohol exposure session. Afterwards, the participants go through the intervention condition (oral glucose intake) and the control condition (placebo intake) in a randomized order on two examination days. Blood samples are taken repeatedly (every 10 min) during the study course on both measuring days to determine changes in acetylated and total ghrelin and insulin plasma levels. In parallel, subjective alcohol craving after the glucose or placebo intake as the primary outcome is assessed using the Alcohol Urge Questionnaire (AUQ) and a visual analog scale (VAS). To examine the mesolimbic cue reactivity as the secondary outcome, a fMRI measurement is conducted while being exposed to alcohol-related stimuli. Appropriate statistical analysis will be used for the evaluation of the outcomes.

Discussion

If successful, the results of this study could offer alcohol-dependent patients a new potential option for acute short-term reduction of alcohol craving and thus prevent relapses and prolong periods of abstinence in the long term.

Trial registration

German Clinical Trials Register DRKS00022419 (UTN: U1111-1278-9428). Retrospectively registered on September 15, 2020.
The effect of Tribulus terrestris supplementation on inflammation, oxidative stress, and performance of recreational runners: study protocol for a randomized placebo-controlled trial
Authors: Nejati Marzieh , Dehghan Parvin , Khani Mostafa , Sarbakhsh Parvin
Published: August 2022

Background

High intensity and endurance exercises lead to exercise-induced oxidative stress (EIOS), exercise-induced muscle damage (EIMD), and inflammation, which are the influencing factors on muscle soreness, localized swelling, and sports performance decrease. Therefore, the purpose of this study is to determine the effectiveness of Tribulus terrestris (TT) as an herbal supplement with antioxidant and anti-inflammatory properties on the nutritional, oxidative, inflammatory, and anti-inflammatory status, as well as the sports performance of recreational runners.

Methods/design

This study is a double-blind, randomized, placebo-controlled trial, which will be conducted among recreational runners of Tabriz stadiums, Iran. Thirty-four recreational runners will be selected, and participants will be assigned randomly to two groups: to receive 500 mg TT supplement or placebo capsules twice daily for 2 weeks. Both groups will do high-intensity interval training (HIIT) workouts during the study. Baseline and post-intervention body composition, muscle pain, and aerobic and anaerobic performance will be assessed. In addition, assessment of malondialdehyde (MDA), total antioxidant capacity (TAC), total oxidant status (TOS), superoxide dismutase (SOD), glutathione peroxidase (GPx), uric acid (UA), 8-iso-prostaglandin F2α (8-iso-PGF2α), protein carbonyl (PC), catalase (CAT), glutathione (GSH), nitric oxide (NO), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), creatine kinase (CK), myoglobin (MYO), lactate dehydrogenase (LDH), insulin-like growth factor-1 (IGF-1) irisin, cortisol, and brain-derived neurotrophic factor (BDNF) will be done during three blood samplings. Changes in oxidative stress, anti/inflammatory biomarkers, and sports performance will be assessed as primary outcomes.

Discussion

This study will be the first to assess the potential effects of TT on recreational runners. Our results will contribute to the growing body of knowledge regarding TT supplementation on the nutritional, oxidative, inflammatory, and anti-inflammatory status and sports performance in recreational runners.

Trial registration

Iranian Registry of Clinical Trials (www.irct.ir) (ID: IRCT20150205020965N8). Registration date: 13 February 2021.
Notes from an epicenter: navigating behavioral clinical trials on autism spectrum disorder amid the COVID-19 pandemic in the Bronx
Authors: Berruti Alaina S. , Schaaf Roseann C. , Jones Emily A. , Ridgway Elizabeth , Dumont Rachel L. , Leiby Benjamin , Sancimino Catherine , Yi Misung , Molholm Sophie
Published: August 2022

Background

The COVID-19 pandemic impacted nearly all facets of our daily lives, and clinical research was no exception. Here, we discuss the impact of the pandemic on our ongoing, three-arm randomized controlled trial (RCT) Sensory Integration Therapy (SIT) in Autism: Mechanisms and Effectiveness (NCT02536365), which investigates the immediate and sustained utility of SIT to strengthen functional daily-living skills and minimize the presence of maladaptive sensory behaviors in autistic children.

Main text

In this text, we detail how we navigated the unique challenges that the pandemic brought forth between the years 2020 and 2021, including the need to rapidly adjust our study protocol, recruitment strategy, and in-person assessment battery to allow for virtual recruitment and data collection. We further detail how we triaged participants and allocated limited resources to best preserve our primary outcome measures while prioritizing the safety of our participants and study team. We specifically note the importance of open and consistent communication with all participating families throughout the pandemic in ensuring all our protocol adjustments were successfully implemented.

Conclusions

Though the COVID-19 pandemic resulted in an unprecedented interruption to in-person clinical research, clinical trials have always been and will continue to be at risk for unforeseen interruptions, whether from world events or participants’ personal circumstances. By presenting our steps to preserving this RCT throughout the pandemic, we offer suggestions for successfully managing unexpected interruptions to research. Ideally, by taking these into account, future RCTs may be increasingly prepared to minimize the impact of these potential interruptions to research.
Clinical implications of host genetic variation and susceptibility to severe or critical COVID-19
Authors: van der Made Caspar I. , Netea Mihai G. , van der Veerdonk Frank L. , Hoischen Alexander
Published: August 2022

Since the start of the coronavirus disease 2019 (COVID-19) pandemic, important insights have been gained into virus biology and the host factors that modulate the human immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 displays a highly variable clinical picture that ranges from asymptomatic disease to lethal pneumonia. Apart from well-established general risk factors such as advanced age, male sex and chronic comorbidities, differences in host genetics have been shown to influence the individual predisposition to develop severe manifestations of COVID-19. These differences range from common susceptibility loci to rare genetic variants with strongly predisposing effects, or proven pathogenic variants that lead to known or novel inborn errors of immunity (IEI), which constitute a growing group of heterogeneous Mendelian disorders with increased susceptibility to infectious disease, auto-inflammation, auto-immunity, allergy or malignancies. The current genetic findings point towards a convergence of common and rare genetic variants that impact the interferon signalling pathways in patients with severe or critical COVID-19. Monogenic risk factors that impact IFN-I signalling have an expected prevalence between 1 and 5% in young, previously healthy individuals (<60 years of age) with critical COVID-19. The identification of these IEI such as X-linked TLR7 deficiency indicates a possibility for targeted genetic screening and personalized clinical management. This review aims to provide an overview of our current understanding of the host genetic factors that predispose to severe manifestations of COVID-19 and focuses on rare variants in IFN-I signalling genes and their potential clinical implications.