bluuebunny/crossref_metadata_2025 huggingface dataset:
Finding the optimal regimen for short-term daily recombinant human erythropoietin treatment for blood-saving purpose in patients undergoing unilateral primary total hip arthroplasty: a double-blinded randomized placebo-controlled trial
Authors: Yuan Mingcheng , Tao Qifeng , Wang Duan , Wang Haoyang , Zhou Zongke
Published: March 2022

Purpose

To find the best short-term daily recombinant human erythropoietin (rhEPO)-based treatment protocols for blood-saving purpose in THA.

Method

The patients were randomized to 1 of 3 interventions: Patients in group A received 10,000 IU (150 IU/kg) of subcutaneous rhEPO (1 ml) daily from 5 days preoperatively to 3 days postoperatively (9 doses in total); Patients in group B received 1 ml of subcutaneous normal saline daily from 5 days preoperatively to 3 days preoperatively and then 10,000 IU (150 IU/kg) of subcutaneous rhEPO daily until 3 days postoperatively (6 doses in total). Patients in group C received 1 ml of subcutaneous normal saline daily from 5 days preoperatively to one day preoperatively and then 10,000 IU (150 IU/kg) of subcutaneous rhEPO daily from the day of surgery to 3 days postoperatively (4 doses in total).

Results

One hundred eighty patients were included. On postoperative day one, patients in the group A showed significantly higher Hb level (108.4 ± 11.4 g/L) than group C (103.9 ± 8.8 g/L). Group B (107.8 ± 8.4 g/L) also showed significantly higher Hb level than group C (103.9 ± 8.8 g/L) (p < 0.05). On postoperative day 3, no significant difference was found between group B and group C in Hb level (98.7 ± 10.5 and 94.9 ± 8.7 g/L, respectively) (p = 0.094), but the Hb level in group A (103.6 ± 11.0 g/L) was still markedly higher than in group B and the Hb level in group A was also markedly higher than in group C. In terms of blood loss, no markedly difference was found in intraoperative blood loss among group A, B and C (78.3 ± 22.4, 84.6 ± 29.1, and 80.3 ± 23.9 ml, respectively) (p = 0.381), but on postoperative day one, the mean blood loss in group C (522.4 ± 189.4 ml) was significantly more than group B (371.2 ± 124.6 ml), and group B was also significantly more than group A (284.8 ± 112.9 ml) with 95% confidence interval, and group B had significantly less blood loss than group C (p < 0.001). With respect to the total blood loss, the total blood loss in group C (881.6 ± 314.9 ml) was significantly more than group B (642.6 ± 232.9 ml), and group B was also significantly more than group A (514.5 ± 204.6 ml) with 95% confidence interval (Table 2). Only 2 patients in each group received allogeneic blood transfusion and each patient received 2 units of red blood cells, so, the transfusion requirements among the three groups were comparable.

Conclusions

Daily small-dose of subcutaneous rhEPO administered from 5 days before THA could significantly decrease perioperative blood loss and improve postoperative Hb levels, without increasing risks of complications, when compared with the application of rhEPO from 3 days before THA or from the day of surgery. However, surgeons should choose the regimen individually according to different patients’ personal circumstances.
A comparative study of percutaneous endoscopic interlaminar discectomy and transforaminal discectomy for L5-S1 calcified lumbar disc herniation
Authors: Cheng Yuan-Pei , Cheng Xiao-Kang , Wu Han
Published: March 2022

Background

Percutaneous endoscopic lumbar discectomy (PELD) is a relatively safe and effective minimally invasive surgery in the treatment of calcified lumbar disc herniation (CLDH). However, studies on percutaneous endoscopic interlaminar discectomy (PEID) and percutaneous endoscopic transforaminal discectomy (PETD) for CLDH have rarely been reported. This research aimed to compare the clinical efficacy of PEID and PETD for L5-S1 CLDH.

Methods

We retrospectively analyzed 54 consecutive patients with L5-S1 CLDH treated with PELD at our institution from August 2016 to August 2020. Patients were divided into PEID group (n = 28) and PETD (n = 26) group according to the surgical methods. The demographic characteristics and surgical results of the two groups were compared. Clinical outcomes were estimated by the visual analog scale (VAS) for leg pain, Oswestry disability index (ODI) and modified MacNab criteria.

Results

All patients were successfully operated on by PEID or PETD. No significant differences in the demographic characteristics, intraoperative blood loss, postoperative hospital stay and complication rate were noted between the PEID and PETD groups. The excellent and good rates in the PEID group were similar to those in the PETD group (89.29% vs 88.46%, P = 1.000), whereas the PEID group exhibited superior results for operative time (min) (64.61 ± 5.60 vs 85.58 ± 8.52, P < 0.001) and fluoroscopy times (n) (2.93 ± 0.90 vs 13.35 ± 2.30, P < 0.001) compared with the PETD group.

Conclusions

PEID has achieved good clinical efficacy as PETD for L5-S1 CLDH. Compared with PETD, PEID has the advantages of shorter operative time and a reduced number of fluoroscopy times in the treatment of CLDH.
Elderly unstable distal radius fractures a prospective cohort study of bone substitutes-augmented percutaneous pinning
Authors: Kandeel Amr Abdel-Mordy
Published: March 2022

Background

Based on debatable recommendations of using bone substitutes for filling of metaphyseal void in elderly unstable distal radius fractures; this study investigated the following question “Do bone substitutes effectively contribute to postoperative stability of k-wire fixation construct and accelerate healing in elderly unstable distal radius fractures?”.

Methods

This prospective cohort study was conducted from October 2014 to April 2021. According to use of bone substitutes, 40 patients of elderly unstable distal radius fractures were alternately allocated into; group-(A) of bone substitutes-augmented percutaneous pinning (19 patients); and group-(B) of non-augmented percutaneous pinning (21 patients). Groups were compared for preoperative patients’ demographics and postoperative ROM, Quick-DASH and Mayo Wrist scores, radiographic parameters (palmar tilt, radial height and inclination, ulnar variance and intra-articular step-off) and duration until radiographic fracture healing.

Results

Statistically, augmented and non-augmented groups were matched in terms of patients’ demographics (mean age; 58.7 vs. 62.0 years respectively, P-value = 0.25). All included fractures have healed with insignificantly longer duration in augmented group (7.1 vs. 6.8 weeks, P-value = 0.26). At 12-week postoperative evaluation, radiographic parameters of both groups were comparably well-maintained except for intra-articular step-off which showed significantly less secondary displacement in augmented group (0.1 vs. 0.4 mm, P-value = 0.01). There were insignificant differences in 6-month postoperative ROM, and Quick-DASH and Mayo Wrist scores.

Conclusion

Compared to its bone substitutes-augmented counterpart; non-augmented percutaneous pinning of elderly unstable distal radius fractures can offer advantages of comparable healing rates and functional and radiographic outcomes, less-invasive approach, shorter operative time and lower cost.

Level of evidence

III
Assessment of oral health status in a Ghanaian population: rationale, methods, and population characteristics
Authors: Hewlett Sandra Ama , Blankson Paa-Kwesi , Aheto Justice Moses K. , Anto Francis , Danso-Appiah Tony , Sackeyfio Josephine , Koram Kwadwo , Amoah Albert G. B.
Published: March 2022

Background

Oral health surveys aid in estimating the oral health of a population and provide a projection for future oral health care needs. We report the procedures and rationale of a survey carried out to assess the oral health status and risk factors for oral disease among adults in the Greater Accra Region (GAR) of Ghana. The objective was to provide prevalence estimates on dental diseases, oral health behaviour and risk factors, and to establish baseline epidemiological data on the population’s oral health for further research.

Methods

This was a population-based cross-sectional study of adults aged 25 years and above. A random, stratified two-stage sampling method was used to select participants from rural and urban communities in three types of districts (Metropolitan, Municipal, Ordinary). A semi- structured questionnaire was used to collect data on socio-demographic characteristics, oral health behaviours and risk factors for oral disease. Anthropometric data and a full-mouth clinical examination was carried out including: soft tissue assessment, tooth count, prosthodontic status, dental caries assessment and periodontal assessment.

Results

A total of 729 participants were included in the study with a mean age of 43.9 years (SD 14.6). Majority 425 (61.0%) were females. Though the metropolitan districts had more dental clinics and personnel, along with better health insurance coverage, they had a higher prevalence of missing teeth, retained roots, severe periodontitis and poorer oral health coverage. The findings also show some significant differences in disease prevalence, within the different localities and districts.

Conclusions

Availability and access to oral health services is not the most important determinant of good oral health outcomes in this region. We recommend exploring socio-behavioral and cultural factors as well. This study provides district level data to inform policy and guide further research.
Association between social capital and oral health among adults aged 50 years and over in China: a cross-sectional study
Authors: Li Suyang , Guo Yanfei , Miao Jonasson Junmei
Published: March 2022

Background

Social capital has a potential effect in protecting oral health among population. However, no study has explored the association between social capital and oral health in the Chinese context. Due to the unique culture, political, social context in China, it is important to understand their association in the Chinese context. The study aims to investigate the association between cognitive and structural dimensions of social capital with edentulism among adults aged 50 years and over in China.

Method

The study used data from the WHO SAGE (Study on Global AGEing and Adult Health) wave 1 China component. Structural social capital was operationalized as social participation. Cognitive social capital was operationalized as perceived community trust and perceived community safety. Community-level social capital was measured by aggregating individual-level social capital into community level. Oral health was measured using a final marker of oral health status, self-reported edentulism. A 2-level multilevel logistic regression was used to evaluate the association between different dimensions of social capital and oral health.

Results

In total, 12,856 individuals were included in the study, the overall prevalence of edentulism was 9.1% (95% CI 8.3–10.0). Multilevel logistic analysis revealed that individual-level social capital and community-level social capital are independently associated with edentulism. Individuals with low structural social capital and living in areas with low structural social capital have, respectively, 1.54 (95% CI 1.18–2.01) and 2.14 (95% CI 1.47–3.12) times higher odds for edentulism, after adjustment for potential confounders (age, sex, marital status, residence locality, wealth, education level, chronic conditions) and a potential mediator(smoking).

Conclusions

Living in a community with lower structural social capital and individual with low structural social capital is associated with higher risk for edentulism among adults aged 50 years and over in China.
Impact of prior underinsurance on cervical cancer screening among Davidson County, Tennessee, women diagnosed with invasive cervical cancer, 2008–2018
Authors: Sackey Emmanuel N. S. , Pemmaraju Manideepthi , Griffin Marie R. , Castilho Jessica L.
Published: March 2022

Introduction

We sought to investigate the association between insurance coverage history and cervical cancer screening among Davidson County, Tennessee, women diagnosed with incident cervical cancer.

Methods

We reviewed medical records of women diagnosed with invasive cervical cancer from 2008 through 2018 identified via the state's cancer registry and by active surveillance of diagnostic pathology reports for the HPV-IMPACT project. Per 2012 United States Preventive Services Task Force recommended cervical cancer screening guidelines, women were characterized into three screening history categories: “no screening”, “no follow-up” and “test/screening failure”. Multivariable logistic regression measured the association of prior inadequate insurance (underinsurance) and screening history (“no screening/no follow-up” compared to “test/screening failure”).

Results

Of 212 women, most (77%) had not undergone recommended cervical cancer screening or follow-up prior to cancer diagnosis. Overall, 28% of women had history of underinsurance in 5 years prior to diagnosis. In adjusted analyses, underinsured women were more likely to have a “no screening/no follow-up” prior to cancer diagnosis (aOR 4.26; 95% CI 1.15–15.80) compared to “test/screening failure” history. Non-white race (aOR 2.73; 95% CI 0.98–7.61), older age (aOR 1.03 per year; 95% CI 1.00–1.07), and history of smoking (aOR 4.07; 95% CI 1.54–10.74) were also associated with increased likelihood of “no screening/no follow-up”.

Conclusions

Previous underinsurance was independently associated with non-adherence to cervical cancer screening and follow-up guidelines among women with incident cervical cancer. Further study of factors contributing to inadequate cervical cancer screening and interventions to increase cervical cancer screening in high-risk populations is needed.
Creating a resident-centric rehabilitation research team
Authors: Abraham Annie M. , Chavez Audrie A. , Venkatachalam Aardhra M. , Sengupta Samarpita , Olson DaiWai M. , Bell Kathleen R. , Ifejika Nneka L.
Published: March 2022

Background

The 36-month Physical Medicine and Rehabilitation (PM&R) or Physiatry residency provides a number of multidisciplinary clinical experiences. These experiences often translate to novel research questions, which may not be pursued by residents due to several factors, including limited research exposure and uncertainty of how to begin a project.

Limited resident participation in clinical research
negatively affects the growth of Physiatry as a field and medicine as a whole. The
two largest Physiatry organizations – the Association of Academic Physiatrists
and the American Academy of Physical Medicine and Rehabilitation – participate in
the Disability and Rehabilitation Research Coalition (DRRC), seeking to improve
the state of rehabilitation and disability research through funding
opportunities by way of the National Institutes of Health (NIH), the National
Institute on Disability, Independent Living and Rehabilitation Research
(NIDILRR) and the Patient-Centered Outcomes Research Institute (PCORI). A
paucity of new Physiatry researchers neutralizes these efforts.

Results

This paper details
the creation of a novel, multidisciplinary Rehabilitation Resident Research
program that promotes resident research culture and production. Mirroring our
collaborative clinical care paradigm, this program integrates faculty
mentorship, institutional research collaborates (Neuroscience Nursing Research
Center, Neuroscience Research Development Office) and departmental resources
(Shark Tank competition) to provide resident-centric research support.

Conclusions

The resident-centric
rehabilitation research team has formed a successful research program that was
piloted from the resident perspective, facilitating academic productivity while
respecting the clinical responsibilities of the 36-month PM&R residency. Resident
research trainees are uniquely positioned to become future leaders of
multidisciplinary and multispecialty collaborative teams, with a focus on
patient function and health outcomes.
Overcoming language barriers, enhancing collaboration with interpreters – an interprofessional learning intervention (Interpret2Improve)
Authors: Krampe Franziska , Fabry Götz , Langer Thorsten
Published: March 2022

Background

Language barriers (LB) are common in patient care. They can negatively impact the quality of care, and increase costs. LB can be overcome by using interpreters. However, collaboration with interpreters is a professional activity which can and needs to be learnt. Interpret2Improve is an innovative educational intervention where medical and nursing students learn together how to address LB and effectively collaborate with interpreters.

Methods

The three-hour course has two parts: After a short introduction on the relevance of LB and resulting issues of patient safety etc., students in interprofessional teams of two practice conversations with non-German-speaking simulated patients and professional interpreters. The course is evaluated in a pre-post format with the Freiburg Questionnaire for Interprofessional Learning Evaluation which has been validated in prior studies.

Results

Fifty-one students (thirty of the participants were medical students, 21 participants were students in nursing care) participated from 11/2016–07/2018. Overall, the course was very well received (mean 1.73 (SD 0.85) on a five point scale: 1 = very good, 5 = insufficient). The evaluation by medical and nursing students differed significantly. Fourteen out of twenty-one items show a self-assessed increase in interprofessional knowledge or skills.

Conclusions

Students felt that their skills in addressing LB by effectively collaborating with interpreters increased during this interprofessional format. Further studies are needed to obtain further evidence beyond self-assessment and regarding the long-term outcomes.
Cinemeducation in medicine: a mixed methods study on students’ motivations and benefits
Authors: Rueb Mike , Siebeck Matthias , Rehfuess Eva A. , Pfadenhauer Lisa M.
Published: March 2022

Background

Cinemeducation courses are used to supplement more standard teaching formats at medical schools and tend to emphasise biopsychosocial aspects of health. The purpose of this paper is to explore why medical students attend the cinemeducation course M23 Cinema (M23C) at LMU Munich and whether a film screening with a subsequent expert and peer discussion benefits their studies and their future careers as medical doctors.

Methods

An exploratory sequential mixed methods study design was used. Qualitative research, i.e. three focus groups, four expert interviews, one group interview and one narrative interview, was conducted to inform a subsequent quantitative survey. Qualitative data was analysed using qualitative content analysis and quantitative data was analysed descriptively. The findings were integrated using the “following a thread” protocol.

Results

In total, 28 people were interviewed and 503 participants responded to the survey distributed at seven M23C screenings. Participants perceive the M23C as informal teaching where they learn about perspectives on certain health topics through the combination of film and discussion while spending time with peers. The reasons for and reported benefits of participation varied with educational background, participation frequency and gender. On average, participants gave 5.7 reasons for attending the M23C. The main reasons for participating were the film, the topic and the ability to discuss these afterwards as well as to spend an evening with peers. Attending the M23C was reported to support the students’ memory with regards to certain topics addressed in the M23C when the issues resurface at a later stage, such as during university courses, in the hospital, or in their private life.

Conclusions

The M23C is characterised by its unique combination of film and discussion that encourages participants to reflect upon their opinions, perspectives and experiences. Participating in the M23C amplified the understanding of biopsychosocial aspects of health and illness in students. Thus, cinemeducative approaches such as the M23C may contribute to enabling health professionals to develop and apply humane, empathetic and relational skills.
Clinician documentation of patient centered care in the electronic health record
Authors: Butler Jorie M. , Gibson Bryan , Patterson Olga V. , Damschroder Laura J. , Halls Corrinne H. , Denhalter Daniel W. , Samore Matthew H. , Li Haojia , Zhang Yue , DuVall Scott L.
Published: March 2022

Background

In this study we sought to explore the possibility of using patient centered care (PCC) documentation as a measure of the delivery of PCC in a health system.

Methods

We first selected 6 VA medical centers based on their scores for a measure of support for self-management subscale from a national patient satisfaction survey (the Survey for Healthcare Experience-Patients). We accessed clinical notes related to either smoking cessation or weight management consults. We then annotated this dataset of notes for documentation of PCC concepts including: patient goals, provider support for goal progress, social context, shared decision making, mention of caregivers, and use of the patient's voice. We examined the association of documentation of PCC with patients’ perception of support for self-management with regression analyses.

Results

Two health centers had < 50 notes related to either tobacco cessation or weight management consults and were removed from further analysis. The resulting dataset includes 477 notes related to 311 patients total from 4 medical centers. For a majority of patients (201 out of 311; 64.8%) at least one PCC concept was present in their clinical notes. The most common PCC concepts documented were patient goals (patients n = 126; 63% clinical notes n = 302; 63%), patient voice (patients n = 165, 82%; clinical notes n = 323, 68%), social context (patients n = 105, 52%; clinical notes n = 181, 38%), and provider support for goal progress (patients n = 124, 62%; clinical notes n = 191, 40%). Documentation of goals for weight loss notes was greater at health centers with higher satisfaction scores compared to low. No such relationship was found for notes related to tobacco cessation.

Conclusion

Providers document PCC concepts in their clinical notes. In this pilot study we explored the feasibility of using this data as a means to measure the degree to which care in a health center is patient centered. Practice Implications: clinical EHR notes are a rich source of information about PCC that could potentially be used to assess PCC over time and across systems with scalable technologies such as natural language processing.
System-level policies on appropriate opioid use, a multi-stakeholder consensus
Authors: Forget Patrice , Patullo Champika , Hill Duncan , Ambekar Atul , Baldacchino Alex , Cata Juan , Chetty Sean , Cox Felicia J. , de Boer Hans D. , Dinwoodie Kieran , Dom Geert , Eccleston Christopher , Fullen Brona , Jutila Liisa , Knaggs Roger D. , Lavand’homme Patricia , Levy Nicholas , Lobo Dileep N. , Pogatzki-Zahn Esther , Scherbaum Norbert , Smith Blair H. , van Griensven Joop , Gilbert Steve
Published: March 2022

Background

This consensus statement was developed because there are concerns about the appropriate use of opioids for acute pain management, with opposing views in the literature. Consensus statement on policies for system-level interventions may help inform organisations such as management structures, government agencies and funding bodies.

Methods

We conducted a multi-stakeholder survey using a modified Delphi methodology focusing on policies, at the system level, rather than at the prescriber or patient level. We aimed to provide consensus statements for current developments and priorities for future developments.

Results

Twenty-five experts from a variety of fields with experience in acute pain management were invited to join a review panel, of whom 23 completed a modified Delphi survey of policies designed to improve the safety and quality of opioids prescribing for acute pain in the secondary care setting. Strong agreement, defined as consistent among> 75% of panellists, was observed for ten statements.

Conclusions

Using a modified Delphi study, we found agreement among a multidisciplinary panel, including patient representation, on prioritisation of policies for system-level interventions, to improve governance, pain management, patient/consumers care, safety and engagement.
Contextual factors influencing physicians’ perception of antibiotic prescribing in primary care in Germany — a prospective observational study
Authors: Queder Annika , Arnold Christine , Wensing Michel , Poß-Doering Regina
Published: March 2022

Background

Antimicrobial resistance is a worldwide challenge for health services and systems alike. To reduce the overuse of antibiotics, multifaceted interventions are often used to achieve sustainable effects. It can be assumed that these effects are influenced by contextual factors. Embedded in the cluster randomized trial ARena (Sustainable reduction of antibiotic-induced antimicrobial resistance), the aim of this present study was to identify contextual factors associated with practitioners’ perceptions of antibiotic prescribing in German primary health care.

Methods

In a prospective observational study, data were generated in a three-wave survey study between January 2018 and July 2019. Analysis was performed using logistic regression models. The outcome of interest was the physician perceived impact of participating in the ARena project on decision-making regarding antibiotic prescribing, the independent variables of interest included individual characteristics, intervention arm allocation, primary care network (PCN) environment and characteristics of the medical practice.

Results

Forty Six point eight percent (n = 126) of participants indicated to have perceived an impact on their decision-making regarding antibiotic prescribing by participating in the ARena project. Bivariate logistic regression analyses indicated that work experience (odds ratio (OR) 1.05, 95% confidence interval (CI) 1.006–1.103), PCN environment (OR 2.06, 95% CI 1.256–3.363), structural conditions (OR 1.66, 95% CI 1.161–2.371), environment of existing processes (OR 1.46, 95% CI 1.011–2.094), and externally defined general conditions (OR 1.57, 95% CI 1.035–2.378) were associated with physicians’ perceived impact of participating in the ARena project on decision-making regarding antibiotic prescribing. In the multivariable logistic regression analysis, only work experience OR 1.05 (95% CI 1.001–1.104) continuously showed a significant influence.

Conclusions

This study indicates that contextual factors at individual, practice, and system level influence physicians’ perceptions of antibiotic prescribing. Longer work experience appeared to be a significant influencing factor to be considered in antimicrobial stewardship programs.

Trial registration

ISRCTN, ISRCTN58150046 (registered 13.09.2017).
Integrating mental health into primary care: evaluation of the Health Action for Psychiatric Problems In Nigeria including Epilepsy and SubstanceS (HAPPINESS) pilot project
Authors: Chu Casey , Roxas Nichole , Aguocha Chinyere M. , Nwefoh Emeka , Wang Katie , Dike Charles , Iheanacho Theddeus
Published: March 2022

Background

The Health Action for Psychiatric Problems In Nigeria including Epilepsy and SubstanceS (HAPPINESS) project trains non-specialist and primary health care workers in Imo State, Nigeria. This project adapted the World Health Organization’s Mental Health Gap Action Programme-Intervention Guide (mhGAP-IG), emphasizing stigma reduction among trainees. This convergent mixed-methods proof-of-concept study evaluates the HAPPINESS pilot project mhGAP-IG training’s impact on mental illness stigma among trainees and barriers, facilitators, and opportunities to consider for project improvement.

Methods

Trainees (n = 13) completed a 43-item questionnaire before and after their 5-day training to assess perceptions of mental disorders and attitudes towards people with mental illness. These responses were analyzed using paired-sample t-tests for four subscales of the questionnaire: acceptance of socializing with people with mental illness, normalizing activities and relationships with people with mental illness, supernatural causation of mental illness, and endorsement of a biopsychosocial approach to mental illness. Semi-structured key informant interviews (n = 11) with trainees, trainers, and local health officials who participated in or supported the HAPPINESS project were thematically analyzed to understand their experiences and perspectives of the project’s barriers, facilitators, and opportunities.

Results

Trainees showed significant improvements on socializing, normalizing, and supernatural causation subscales of the stigma questionnaire (p < 0.05). No significant effect was seen on the biopsychosocial subscale; however, evidence of biopsychosocial beliefs was found in interview responses. Key informant interviews revealed that the HAPPINESS project enhanced trainees’ diagnostic and treatment abilities, mental health awareness, and empathy towards patients. Misinformation, stigma, inadequate funding, and lack of road access to clinics were identified as barriers to mental health care integration into general care in Imo State. Respondents also suggested ways that the HAPPINESS project could be improved and expanded in the future.

Conclusions

This study adds to the limited evidence on the implementation of mhGAP-IG in Nigeria. Using mixed methods, it evaluates how mhGAP-IG can impact perceptions and knowledge of stigma among primary care trainees. It also highlights barriers, facilitators, and opportunities to consider for project growth. Future efforts should focus on clinical support, supervision, health outcomes, as well as scaling up and assessing the cost-effectiveness of the HAPPINESS project intervention.
Compound heterozygous variants in DYNC2H1 in a foetus with type III short rib-polydactyly syndrome and situs inversus totalis
Authors: Cheng Chen , Li Xiuxiu , Zhao Sheng , Feng Qian , Ren Xiang , Chen Xinlin
Published: March 2022

Background

Short-rib thoracic dysplasia 3 with or without polydactyly (SRTD3, OMIM: 613091) is an autosomal recessive disorder. SRTD3 presents clinically with a narrow thorax, short ribs, shortened tubular bones, and acetabular roof abnormalities. Clinical signs of SRTD3 vary among individuals. Pathogenic variants of DYNC2H1 (OMIM: 603297) have been reported to cause SRTD3.

Methods

We performed a detailed clinical prenatal sonographic characterization of a foetus with SRTD3. Trio whole-exome sequencing was used to identify causative variants in the family. The identified variants in the families were validated by Sanger sequencing and mass spectrometry. Multiple computational tools were used to predict the harmfulness of the two variants. A minigene splicing assay was carried out to evaluate the impact of the splice-site variant.

Results

We evaluated prenatal sonographic images of the foetus with SRTD3, including abnormal rib curvature, narrow thorax, bilateral hypoplastic lungs, bilateral polydactyly, syndactyly, and foetal visceral situs inversus with mirror-image dextrocardia. We revealed novel compound variants of DYNC2H1 (NM_001377.3:c.11483T > G (p.Ile3828Arg) and c.2106 + 3A > T). Various statistical methods predicted that the variants would cause harmful effects on genes or gene products. The minigene assay findings suggested that c.2106 + 3A > T caused the skipping over exon 14, producing an exon 14 loss in the protein.

Conclusion

This study identified a foetus with SRTD3 with situs inversus totalis with mirror-image dextrocardia in a Chinese family, revealing two novel compound heterozygous dynein cytoplasmic 2 heavy chain 1 (DYNC2H1) variants, expanding the phenotypic spectrum of SRTD3. The minigene study of c.2106 + 3A > T was predicted to cause an inframe exclusion of exon 14, which was predicted to have important molecular functions. Our findings strongly supported the use of WES in prenatal diagnosis and helped to understand the correlation of genotype and phenotypes of DYNC2H1. The specific sonographic findings and the molecular diagnosis helped add experience to further our expertise in prenatal counselling for SRTD3.
Engineering microbial consortia of Elizabethkingia meningoseptica and Escherichia coli strains for the biosynthesis of vitamin K2
Authors: Yang Qiang , Zheng Zhiming , Zhao Genhai , Wang Li , Wang Han , Ding XiuMin , Jiang Chunxu , Li Chu , Ma Guoliang , Wang Peng
Published: March 2022

Background

The study and application of microbial consortia are topics of interest in the fields of metabolic engineering and synthetic biology. In this study, we report the design and optimisation of Elizabethkingia meningoseptica and Escherichia coli co-culture, which bypass certain limitations found during the molecular modification of E. meningoseptica, such as resistance to many antibiotics and fewer available molecular tools.

Results

The octaprenyl pyrophosphate synthase from E. meningoseptica sp. F2 (EmOPPS) was expressed, purified, and identified in the present study. Then, owing to the low vitamin K2 production by E. coli or E. meningoseptica sp. F2 monoculture, we introduced the E. meningoseptica and E. coli co-culture strategy to improve vitamin K2 biosynthesis. We achieved production titres of 32 mg/L by introducing vitamin K2 synthesis-related genes from E. meningoseptica sp. F2 into E. coli, which were approximately three-fold more than the titre achieved with E. meningoseptica sp. F2 monoculture. This study establishes a foundation for further engineering of MK-n (n = 4, 5, 6, 7, 8) in a co-cultivation system of E. meningoseptica and E. coli. Finally, we analysed the surface morphology, esterase activity, and membrane permeability of these microbial consortia using scanning electron microscopy, confocal laser scanning microscopy, and flow cytometry, respectively. The results showed that the co-cultured bacteria were closely linked and that lipase activity and membrane permeability improved, which may be conducive to the exchange of substances between bacteria.

Conclusions

Our results demonstrated that co-culture engineering can be a useful method in the broad field of metabolic engineering of strains with restricted molecular modifications.
LRP11-AS1 promotes the proliferation and migration of triple negative breast cancer cells via the miR-149-3p/NRP2 axis
Authors: Li Peng , Zeng Yu , Chen Yudan , Huang Peng , Chen Xinchun , Zheng Weidong
Published: March 2022

Background

Breast cancer is the most commonly diagnosed cancer in women. Triple negative breast cancer (TNBC) is the most difficult subtype of breast cancer to treat due to the deficiency in drug-targetable receptors. LRP11-AS1, a newly identified oncogenic long noncoding RNA (lncRNA) was found to be significantly overexpressed in TNBC cells. The aim of this study is to investigate the malignant roles and the oncogenic mechanisms of LRP11-AS1 in TNBC.

Methods

CCK-8, colony formation, transwell migration and transwell invasion assays were performed to study the functions of LRP11-AS1. Quantitative PCR and western blot were used to determine the gene expression. Bioinformatics analysis and dual-luciferase reporter assay were conducted to study lncRNA and miRNA interactions.

Results

LRP11-AS1 was found to be significantly overexpressed in TNBC cells compared to the non-TNBC cells and normal mammary epithelial cells. Knockdown of LRP11-AS1 could inhibit the growth and metastasis of TNBC cells and regulate cell cycle. Mechanistically, LRP11-AS1 was found to act as a competing endogenous RNA (ceRNA) to sponge miR-149-3p. Silencing of LRP11-AS1 increased the expression of miR-149-3p and overexpression of miR-149-3p suppressed the expression of LRP11-AS1. Inhibition of miR-149-3p could reverse the anticancer effect of LRP11-AS1 deficiency in TNBC cells. Moreover, Neuropilin-2 (NRP2) was found to be the target of miR-149-3p. Rescue experiments revealed that NRP2 overexpression could rescue the anticancer effect of LRP11-AS1 deficiency in TNBC cells.

Conclusion

LRP11-AS1 overexpressed in TNBC showed the oncogenic effects possibly by sponging miR-149-3p and regulating the miR-149-3p/NRP2 axis, which indicated LRP11-AS1 as a potential diagnostic biomarker and therapeutic target in TNBC.
Molecular surveillance for operationally relevant genetic polymorphisms in Plasmodium falciparum in Southern Chad, 2016–2017
Authors: Das Sukanta , Kérah-Hinzoumbé Clément , Kebféné Moundiné , Srisutham Suttipat , Nagorngar Tog-Yeum , Saralamba Naowarat , Vongpromek Ranitha , Khomvarn Teeradet , Sibley Carol H. , Guérin Philippe J. , Imwong Mallika , Dhorda Mehul
Published: March 2022

Background

Resistance to anti-malarials is a serious threat to the efforts to control and eliminate malaria. Surveillance based on simple field protocols with centralized testing to detect molecular markers associated with anti-malarial drug resistance can be used to identify locations where further investigations are needed.

Methods

Dried blood spots were collected from 398 patients (age range 5–59 years, 99% male) with Plasmodium falciparum infections detected using rapid diagnostic tests over two rounds of sample collection conducted in 2016 and 2017 in Komé, South-West Chad. Specimens were genotyped using amplicon sequencing or qPCR for validated markers of anti-malarial resistance including partner drugs used in artemisinin-based combination therapy (ACT).

Results

No mutations in the pfk13 gene known to be associated with artemisinin resistance were found but a high proportion of parasites carried other mutations, specifically K189T (190/349, 54.4%, 95%CI 49.0–59.8%). Of 331 specimens successfully genotyped for pfmdr1 and pfcrt, 52% (95%CI 46.4–57.5%) carried the NFD-K haplotype, known to be associated with reduced susceptibility to lumefantrine. Only 20 of 336 (6.0%, 95%CI 3.7–9.0%) had parasites with the pfmdr1-N86Y polymorphism associated with increased treatment failures with amodiaquine. Nearly all parasites carried at least one mutation in pfdhfr and/or pfdhps genes but ‘sextuple’ mutations in pfdhfr—pfdhps including pfdhps -A581G were rare (8/336 overall, 2.4%, 95%CI 1.2–4.6%). Only one specimen containing parasites with pfmdr1 gene amplification was detected.

Conclusions

These results provide information on the likely high efficacy of artemisinin-based combinations commonly used in Chad, but suggest decreasing levels of sensitivity to lumefantrine and high levels of resistance to sulfadoxine-pyrimethamine used for seasonal malaria chemoprevention and intermittent preventive therapy in pregnancy. A majority of parasites had mutations in the pfk13 gene, none of which are known to be associated with artemisinin resistance. A therapeutic efficacy study needs to be conducted to confirm the efficacy of artemether-lumefantrine.
A single low dose of primaquine is safe and sufficient to reduce transmission of Plasmodium falciparum gametocytes regardless of cytochrome P450 2D6 enzyme activity in Bagamoyo district, Tanzania
Authors: Mwaiswelo Richard Owden , Ngasala Billy , Msolo Dominick , Kweka Eliningaya , Mmbando Bruno P. , Mårtensson Andreas
Published: March 2022

Background

Primaquine is a pro-drug and its active metabolite is potent against mature Plasmodium falciparum gametocytes. Primaquine is metabolized by a highly polymorphic cytochrome P450 2D6 (CYP2D6) enzyme. Mutations in the gene encoding this enzyme may lead to impaired primaquine activity. This study assessed if 0.25 mg/kg single-dose primaquine is safe and sufficient to reduce transmission of gametocytes in individuals with no, reduced, or increased CYP2D6 enzyme activity.

Methods

Between June 2019 and January 2020 children aged 1–10 years, attending at Yombo dispensary, Bagamoyo district, with confirmed microcopy-determined uncomplicated P. falciparum malaria were enrolled in the study. The enrolled patients were treated with a standard artemether-lumefantrine regimen plus 0.25 mg/kg single-dose primaquine and followed up for 28 days for clinical and laboratory assessment. Primaquine was administered with the first dose of artemether-lumefantrine. Safety assessment involved direct questioning and recording of the nature and incidence of clinical signs and symptoms, and measurement of haemoglobin (Hb) concentration. Blood samples collected from 100 patients were used for assessment of post-treatment infectiousness on day 7 using mosquito membrane feeding assays. Molecular methods were used to determine CYP2D6 and glucose-6-phosphate dehydrogenase (G6PD) status. The primary outcome was the safety of 0.25 mg/kg single-dose primaquine based on CYP2D6 status.

Results

In total, 157 children [median age 6.4 (Interquartile range 4.0–8.2) years] were recruited, of whom 21.0% (33/157) and 12.7% (20/157) had reduced CYP2D6 and deficient G6PD activity, respectively. Day 3 mean absolute Hb concentration reduction was 1.50 g/dL [95% confidence interval (CI) 1.10–1.90] and 1.51 g/dL (95% CI 1.31–1.71) in reduced and normal CYP2D6 patients, respectively (t = 0.012, p = 0.990). The day 3 mean absolute Hb concentration reduction in G6PD deficient, G6PD normal and heterozygous female was 1.82 g/dL (95% CI 1.32–2.32), 1.48 g/dL (95% CI 1.30–1.67) and 1.47 g/dL (95% CI 0.76–2.18), respectively (F = 0.838, p = 0.435). Sixteen percent (16/98) of the patients each infected at least one mosquito on day 7, and of these, 10.0% (2/20) and 17.9% (14/78) had reduced and normal CYP2D6 enzyme activity, respectively (x2 = 0.736, p = 0.513).

Conclusion

Single-dose 0.25 mg/kg primaquine was safe and sufficient for reducing transmission of P. falciparum gametocytes regardless of CYP2D6 or G6PD status.

Trial registration Study registration number: NCT03352843.
Evaluation of an accelerometer-based monitor for detecting bed net use and human entry/exit using a machine learning algorithm
Authors: Koudou Guibehi B. , Monroe April , Irish Seth R. , Humes Michael , Krezanoski Joseph D. , Koenker Hannah , Malone David , Hemingway Janet , Krezanoski Paul J.
Published: March 2022

Background

Distribution of long-lasting insecticidal bed nets (LLINs) is one of the main control strategies for malaria. Improving malaria prevention programmes requires understanding usage patterns in households receiving LLINs, but there are limits to what standard cross-sectional surveys of self-reported LLIN use can provide. This study was designed to assess the performance of an accelerometer-based approach for measuring a range of LLIN use behaviours as a proof of concept for more granular LLIN-use monitoring over longer time periods.

Methods

This study was carried out under controlled conditions from May to July 2018 in Liverpool, UK. A single accelerometer was affixed to the side panel of an LLIN and participants carried out five LLIN use behaviours: (1) unfurling a net; (2) entering an unfurled net; (3) lying still as if sleeping; (4) exiting from under a net; and, (5) folding up a net. The randomForest package in R, a supervised non-linear classification algorithm, was used to train models on 20-s epochs of tagged accelerometer data. Models were compared in a validation dataset using overall accuracy, sensitivity and specificity, receiver operating curves and the area under the curve (AUC).

Results

The five-category model had overall accuracy of 82.9% in the validation dataset, a sensitivity of 0.681 for entering a net, 0.632 for exiting, 0.733 for net down, and 0.800 for net up. A simplified four-category model, combining entering/exiting a net into one category had accuracy of 94.8%, and increased sensitivity for net down (0.756) and net up (0.829). A further simplified three-category model, identifying sleeping, net up, and a combined net down/enter/exit category had accuracy of 96.2% (483/502), with an AUC of 0.997 for net down and 0.987 for net up. Models for detecting entering/exiting by adults were significantly more accurate than for children (87.8% vs 70.0%; p < 0.001) and had a higher AUC (p = 0.03).

Conclusions

Understanding how LLINs are used is crucial for planning malaria prevention programmes. Accelerometer-based systems provide a promising new methodology for studying LLIN use. Further work exploring accelerometer placement, frequency of measurements and other machine learning approaches could make these methods even more accurate in the future.
Indigenous health equity in health register ascertainment and data quality: a narrative review
Authors: Wright Karen , Tapera Rachel M. , Stott N. Susan , Sorhage Alexandra , Mackey Anna , Williams Sîan A.
Published: March 2022

Background

Health registers play an important role in monitoring distribution of disease and quality of care; however, benefit is limited if ascertainment (i.e., the process of finding and recruiting people on to a register) and data quality (i.e., the accuracy, completeness, reliability, relevance, and timeliness of data) are poor. Indigenous peoples experience significant health inequities globally, yet health data for, and about, Indigenous peoples is often of poor quality. This narrative review aimed to (i) identify perceived barriers for the ascertainment of Indigenous peoples on health registers, and (ii) collate strategies identified and used by health registers to support comprehensive ascertainment and high-quality data for Indigenous peoples.

Methods

A Kaupapa Māori theoretical framework was utilized to guide this work. Four electronic databases were systematically searched for original articles and screened for eligibility. Studies involving health registers with Indigenous population(s) identified were included if either ascertainment or data quality strategies were described. Data extraction focused on the reporting of research involving Indigenous peoples using the CONSIDER checklist domains, ascertainment, and data quality.

Results

Seventeen articles were included spanning publication between 1992 and 2020. Aspects of four of eight CONSIDER domains were identified to be included in the reporting of studies. Barriers to ascertainment were themed as relating to ‘ethnicity data collection and quality’, ‘systems and structures’, ‘health services/health professionals’, and ‘perceptions of individual and community-level barriers’. Strategies to support ascertainment were categorized as ‘collaboration’, ‘finding people’, and ‘recruitment processes’. Categorized strategies to support data quality were ‘collaboration’, ‘ethnicity data collection and quality’, ‘systems-level strategies’, and ‘health service/health professional-level strategies’.

Conclusions

Poor-quality data for Indigenous peoples in health registers prevents the achievement of health equity and exemplifies inaction in the face of need. When viewed through a critical structural determinants lens, there are visible gaps in the breadth of strategies, particularly relating to the inclusion of Indigenous peoples in health register and research governance, and actions to identify and address institutional racism. Indigenous led research, meaningful collaboration, and a sharing of knowledge and experiences between health registers is recommended to enable research and health registers that support Indigenous self-determination and health equity.