bluuebunny/crossref_metadata_2025 huggingface dataset:
Glomerulonephritis with severe nephrotic syndrome induced by immune complexes composed of galactose-deficient IgA1 in primary Sjögren’s syndrome: a case report
Authors: Nishioka Ryo , Hara Satoshi , Kawahara Hiroyuki , Ito Kiyoaki , Mizushima Ichiro , Hirata Masayoshi , Nagata Michio , Kawano Mitsuhiro
Published: March 2021

Background

Primary Sjögren’s syndrome (pSS) is an auto-immune disease characterized by sialadenitis and dacryoadenitis with lymphoplasmacytic cell infiltration. In pSS, not only sicca symptoms, but also extra-glandular involvement induced by immune abnormalities based on pSS occurs. Renal involvement is one such important life-threatening extra-glandular involvement. Although the aberrant glycosylated IgA in pSS as a product of over-activated B cells is a risk factor of renal involvement, its association has not been clarified. Here we report a case of glomerulonephritis (GN) induced by immune complexes (IC) composed of galactose-deficient IgA1 (Gd-IgA1) in a patient with pSS.

Case presentation

A 48-year-old Japanese woman with pSS was admitted to our hospital because of a two-month history of nephrotic syndrome. Seven years before she had been diagnosed with pSS from keratoconjunctivitis sicca, elevation of serum anti-Ro/SSA antibody titer and lymphoplasmacytic cell infiltration around salivary ducts of the small salivary glands. Renal biopsy revealed diffuse bubbling appearance in glomerular basement membrane (GBM) with scarce mesangial proliferation. Immunofluorescence showed granular IgA, C3 and Gd-IgA1 staining of GBM. Light chain staining showed no monoclonality. Electron microscopy showed electron dense deposits mainly in the intra-membranous and paramesangial areas and slightly in the subepithelial area. Additional serum analysis confirmed elevation of Gd-IgA1 (13.5 μg/mL), which was comparable with that seen in IgA nephropathy, and qualitative enzyme-linked immunosorbent assay of IgA-containing circulating immune complex (IgA-CIC) was positive. Thus, we diagnosed GN induced by IC composed of Gd-IgA1. Furthermore, retrospectively performed immunofluorescence of the small salivary gland evaluated at the diagnosis of pSS showed positive Gd-IgA1 staining of infiltrating lymphoplasmacytic cells. Therefore, we concluded that Gd-IgA1 produced by over-activated B cells in pSS formed circulating IC and thereby induced GN. After induction therapy with high dose prednisolone and mycophenolate mofetil, the nephrotic syndrome remitted within 3 weeks, the serum Gd-IgA1 level decreased to the normal range (3.8 μg/mL), and serum IgA-CIC disappeared in the 6th month after induction therapy.

Conclusions

Our findings clearly demonstrate an association between aberrant glycosylated IgA and the renal involvement seen in pSS, thereby helping to clarify the renal significance of aberrant glycosylated IgA in pSS.
Association between chronic kidney disease and the most common corneal ectasia disease (keratoconus): a nationwide cohort study
Authors: Jan Ren-Long , Weng Shih-Feng , Wang Jhi-Joung , Chang Yuh-Shin
Published: March 2021

Background

Both keratoconus (KCN) and chronic kidney disease (CKD) are multifactorial conditions with multiple aetiologies and share several common pathophysiologies. However, the few studies that have described the relationship between KCN and CKD are limited to case reports and small case series. This study aimed to evaluate the association between KCN and CKD.

Methods

The study cohort included 4,609 new-onset keratoconus patients ≥ 12 years identified by the International Classification of Diseases, Ninth Revision, Clinical Modification, code 371.6 and recruited between 2004 and 2011 from the Taiwan National Health Insurance Research Database. The age-, sex-, and comorbidity-matched control group included 27,654 non-KCN patients, selected from the Taiwan Longitudinal Health Insurance Database, 2000. Information for each patient was collected and tracked from the index date until December 2013. The incidence and risk of CKD were compared between the two groups. The adjusted hazard ratios (HRs) for CKD were calculated with Cox proportional hazard regression analysis. Kaplan–Meier analysis was used to calculate the cumulative CKD incidence rate.

Results

The incidence rate of CKD was 1.36 times higher in KCN patients than in controls without statistically significant difference (95 % confidence interval [CI] = 0.99–1.86,p = 0.06). In total, 29 male KCN patients and 90 male controls developed CKD during the follow-up period. The incidence rate of CKD was 1.92 times (95 % [CI] = 1.26–2.91;p = 0.002) higher in male KCN patients than in controls. After adjusting for potential confounders, including age, hypertension, hyperlipidaemia, and diabetes mellitus, male KCN patients were 1.75 times (adjusted HR = 1.75, 95 % [CI] = 1.14–2.68,p < 0.05) more likely to develop CKD.

Conclusions

We found that male KCN patients have an increased risk of CKD. Therefore, it is recommended that male KCN patients should be aware of CKD.
Birthweight: EN-BIRTH multi-country validation study
Authors:   EN-BIRTH Study Group, Kong Stefanie , Day Louise T. , Zaman Sojib Bin , Peven Kimberly , Salim Nahya , Sunny Avinash K. , Shamba Donat , Rahman Qazi Sadeq-ur , K.C. Ashish , Ruysen Harriet , El Arifeen Shams , Mee Paul , Gladstone Miriam E. , Blencowe Hannah , Lawn Joy E.
Published: March 2021

Background

Accurate birthweight is critical to inform clinical care at the individual level and tracking progress towards national/global targets at the population level. Low birthweight (LBW) < 2500 g affects over 20.5 million newborns annually. However, data are lacking and may be affected by heaping. This paper evaluates birthweight measurement within the Every Newborn Birth Indicators Research Tracking in Hospitals (EN-BIRTH) study.

Methods

The EN-BIRTH study took place in five hospitals in Bangladesh, Nepal and Tanzania (2017–2018). Clinical observers collected time-stamped data (gold standard) for weighing at birth. We compared accuracy for two data sources: routine hospital registers and women’s report at exit interview survey. We calculated absolute differences and individual-level validation metrics. We analysed birthweight coverage and quality gaps including timing and heaping. Qualitative data explored barriers and enablers for routine register data recording.

Results

Among 23,471 observed births, 98.8% were weighed. Exit interview survey-reported weighing coverage was 94.3% (90.2–97.3%), sensitivity 95.0% (91.3–97.8%). Register-reported coverage was 96.6% (93.2–98.9%), sensitivity 97.1% (94.3–99%). Routine registers were complete (> 98% for four hospitals) and legible > 99.9%. Weighing of stillbirths varied by hospital, ranging from 12.5–89.0%. Observed LBW rate was 15.6%; survey-reported rate 14.3% (8.9–20.9%), sensitivity 82.9% (75.1–89.4%), specificity 96.1% (93.5–98.5%); register-recorded rate 14.9%, sensitivity 90.8% (85.9–94.8%), specificity 98.5% (98–99.0%). In surveys, “don’t know” responses for birthweight measured were 4.7%, and 2.9% for knowing the actual weight. 95.9% of observed babies were weighed within 1 h of birth, only 14.7% with a digital scale. Weight heaping indices were around two-fold lower using digital scales compared to analogue. Observed heaping was almost 5% higher for births during the night than day. Survey-report further increased observed birthweight heaping, especially for LBW babies. Enablers to register birthweight measurement in qualitative interviews included digital scale availability and adequate staffing.

Conclusions

Hospital registers captured birthweight and LBW prevalence more accurately than women’s survey report. Even in large hospitals, digital scales were not always available and stillborn babies not always weighed. Birthweight data are being captured in hospitals and investment is required to further improve data quality, researching of data flow in routine systems and use of data at every level.
Barriers and enablers to routine register data collection for newborns and mothers: EN-BIRTH multi-country validation study
Authors:   EN-BIRTH Study Group, Shamba Donat , Day Louise T. , Zaman Sojib Bin , Sunny Avinash K. , Tarimo Menna Narcis , Peven Kimberly , Khan Jasmin , Thakur Nishant , Talha Md. Taqbir Us Samad , K.C. Ashish , Haider Rajib , Ruysen Harriet , Mazumder Tapas , Rahman Md. Hafizur , Shaikh Md. Ziaul Haque , Sæbø Johan Ivar , Hanson Claudia , Singh Neha S. , Schellenberg Joanna , Vaz Lara M. E. , Requejo Jennifer , Lawn Joy E.
Published: March 2021

Background

Policymakers need regular high-quality coverage data on care around the time of birth to accelerate progress for ending preventable maternal and newborn deaths and stillbirths. With increasing facility births, routine Health Management Information System (HMIS) data have potential to track coverage. Identifying barriers and enablers faced by frontline health workers recording HMIS source data in registers is important to improve data for use.

Methods

The EN-BIRTH study was a mixed-methods observational study in five hospitals in Bangladesh, Nepal and Tanzania to assess measurement validity for selected Every Newborn coverage indicators. We described data elements required in labour ward registers to track these indicators. To evaluate barriers and enablers for correct recording of data in registers, we designed three interview tools: a) semi-structured in-depth interview (IDI) guide b) semi-structured focus group discussion (FGD) guide, and c) checklist assessing care-to-documentation. We interviewed two groups of respondents (January 2018–March 2019): hospital nurse-midwives and doctors who fill ward registers after birth (n = 40 IDI and n = 5 FGD); and data collectors (n = 65). Qualitative data were analysed thematically by categorising pre-identified codes. Common emerging themes of barriers or enablers across all five hospitals were identified relating to three conceptual framework categories.

Results

Similar themes emerged as both barriers and enablers. First, register design was recognised as crucial, yet perceived as complex, and not always standardised for necessary data elements. Second, register filling was performed by over-stretched nurse-midwives with variable training, limited supervision, and availability of logistical resources. Documentation complexity across parallel documents was time-consuming and delayed because of low staff numbers. Complete data were valued more than correct data. Third, use of register data included clinical handover and monthly reporting, but little feedback was given from data users.

Conclusion

Health workers invest major time recording register data for maternal and newborn core health indicators. Improving data quality requires standardised register designs streamlined to capture only necessary data elements. Consistent implementation processes are also needed. Two-way feedback between HMIS levels is critical to improve performance and accurately track progress towards agreed health goals.
Early discontinuation of PD-1 blockade upon achieving a complete or partial response in patients with advanced melanoma: the multicentre prospective Safe Stop trial
Authors: Mulder E. E. A. P. , de Joode K. , Litière S. , ten Tije A. J. , Suijkerbuijk K. P. M. , Boers-Sonderen M. J. , Hospers G. A. P. , de Groot J. W. B. , van den Eertwegh A. J. M. , Aarts M. J. B. , Piersma D. , van Rijn R. S. , Kapiteijn E. , Vreugdenhil G. , van den Berkmortel F. W. P. J. , Hoop E. Oomen-de , Franken M. G. , Ryll B. , Rutkowski P. , Sleijfer S. , Haanen J. B. A. G. , van der Veldt A. A. M.
Published: March 2021

Background

The introduction of programmed cell death protein 1 (PD-1) blockers (i.e. nivolumab and pembrolizumab) has significantly improved the prognosis of patients with advanced melanoma. However, the long treatment duration (i.e. two years or longer) has a high impact on patients and healthcare systems in terms of (severe) toxicity, health-related quality of life (HRQoL), resource use, and healthcare costs. While durable tumour responses have been observed and PD-1 blockade is discontinued on an individual basis, no consensus has been reached on the optimal treatment duration. The objective of the Safe Stop trial is to evaluate whether early discontinuation of first-line PD-1 blockade is safe in patients with advanced and metastatic melanoma who achieve a radiological response.

Methods

The Safe Stop trial is a nationwide, multicentre, prospective, single-arm, interventional study in the Netherlands. A total of 200 patients with advanced and metastatic cutaneous melanoma and a confirmed complete response (CR) or partial response (PR) according to response evaluation criteria in solid tumours (RECIST) v1.1 will be included to early discontinue first-line monotherapy with nivolumab or pembrolizumab. The primary objective is the rate of ongoing responses at 24 months after discontinuation of PD-1 blockade. Secondary objectives include best overall and duration of response, need and outcome of rechallenge with PD-1 blockade, and changes in (serious) adverse events and HRQoL. The impact of treatment discontinuation on healthcare resource use, productivity losses, and hours of informal care will also be assessed. Results will be compared to those from patients with CR or PR who completed 24 months of treatment with PD-1 blockade and had an ongoing response at treatment discontinuation. It is hypothesised that it is safe to early stop first-line nivolumab or pembrolizumab at confirmed tumour response while improving HRQoL and reducing costs.

Discussion

From a patient, healthcare, and economic perspective, shorter treatment duration is preferred and overtreatment should be prevented. If early discontinuation of first-line PD-1 blockade appears to be safe, early discontinuation of PD-1 blockade may be implemented as the standard of care in a selected group of patients.

Trial registration

The Safe Stop trial has been registered in the Netherlands Trial Register (NTR), Trial NL7293 (old NTR ID: 7502), https://www.trialregister.nl/trial/7293. Date of registration September 30, 2018.
Analysis of PET parameters as prognosticators of survival and tumor extent in Oropharyngeal Cancer treated with surgery and postoperative radiotherapy
Authors: Choi Kyu Hye , Song Jin Ho , Park Eun Young , Hong Ji Hyun , Yoo Ie Ryung , Lee Youn Soo , Sun Dong-Il , Kim Min-Sik , Kim Yeon-Sil
Published: March 2021

Background

Positron-emission tomography (PET) is widely used to detect malignancies, but consensus on its prognostic value in oropharyngeal cancer has not been established. The purpose of this study was to analyze the PET parameters associated with tumor extent and survival in resectable oropharyngeal cancer.

Methods

The PET parameters in oropharyngeal cancer patients with regional node metastasis who underwent surgery and postoperative radiotherapy between January 2005 and January 2019 were analyzed. We calculated the SUVmax, tumor-to-liver ratio (TLR), metabolic tumor volume (MTV, volume over SUV 2.5), and total lesion glycolysis (TLG, MTV x mean SUV) of the primary lesion and metastatic nodes. Histologic findings, patient survival, and recurrence were reviewed in the medical records.

Results

Fifty patients were included, and the PET parameters were extracted for 50 primary lesions and 104 nodal lesions. In the survival analysis, MTV and TLG of the primary lesions showed significant differences in overall survival (OS) and recurrence-free survival (RFS). In the multiple regression analysis, TLG of the primary lesion was associated with the depth of invasion (DOI). MTV of the nodes was a significant factor affecting extranodal extension (ENE).

Conclusions

PET parameters could be related with OS, RFS, DOI of the primary tumor, and ENE. PET would be expected to be a useful diagnostic tool as a prognosticator of survival and pathologic findings in oropharyngeal cancer.
RGD4C peptide mediates anti-p21Ras scFv entry into tumor cells and produces an inhibitory effect on the human colon cancer cell line SW480
Authors: Huang Chen-Chen , Liu Fang-Rui , Feng Qiang , Pan Xin-Yan , Song Shu-Ling , Yang Ju-Lun
Published: March 2021

Background

We prepared an anti-p21Ras scFv which could specifically bind with mutant and wild-type p21Ras. However, it cannot penetrate the cell membrane, which prevents it from binding to p21Ras in the cytoplasm. Here, the RGD4C peptide was used to mediate the scFv penetration into tumor cells and produce antitumor effects.

Methods

RGD4C-EGFP and RGD4C-p21Ras-scFv recombinant expression plasmids were constructed to express fusion proteins in E. coli, then the fusion proteins were purified with HisPur Ni-NTA. RGD4C-EGFP was used as reporter to test the factors affecting RGD4C penetration into tumor cell. The immunoreactivity of RGD4C-p21Ras-scFv toward p21Ras was identified by ELISA and western blotting. The ability of RGD4C-p21Ras-scFv to penetrate SW480 cells and colocalization with Ras protein was detected by immunocytochemistry and immunofluorescence. The antitumor activity of the RGD4C-p21Ras-scFv was assessed with the MTT, TUNEL, colony formation and cell migration assays. Chloroquine (CQ) was used an endosomal escape enhancing agent to enhance endosomal escape of RGD4C-scFv.

Results

RGD4C-p21Ras-scFv fusion protein were successfully expressed and purified. We found that the RGD4C fusion protein could penetrate into tumor cells, but the tumor cell entry of was time and concentration dependent. Endocytosis inhibitors and a low temperature inhibited RGD4C fusion protein endocytosis into cells. The change of the cell membrane potential did not affect penetrability. RGD4C-p21Ras-scFv could penetrate SW480 cells, effectively inhibit the growth, proliferation and migration of SW480 cells and promote this cells apoptosis. In addition, chloroquine (CQ) could increase endosomal escape and improve antitumor activity of RGD4C-scFv in SW480 cells.

Conclusion

The RGD4C peptide can mediate anti-p21Ras scFv entry into SW480 cells and produce an inhibitory effect, which indicates that RGD4C-p21Ras-scFv may be a potential therapeutic antibody for the treatment of ras-driven cancers.
A smartphone ocular alignment measurement app in school screening for strabismus
Authors: Cheng Wenbo , Lynn Marissa H. , Pundlik Shrinivas , Almeida Cheryl , Luo Gang , Houston Kevin
Published: March 2021

Background

Strabismus is the leading risk factor for amblyopia, which should be early detected for minimized visual impairment. However, traditional school screening for strabismus can be challenged due to several factors, most notably training, mobility and cost. The purpose of our study is to evaluate the feasibility of using a smartphone application in school vision screening for detection of strabismus.

Methods

The beta smartphone application, EyeTurn, can measure ocular misalignment by computerized Hirschberg test. The application was used by a school nurse in a routine vision screening for 133 elementary school children. All app measurements were reviewed by an ophthalmologist to assess the rate of successful measurement and were flagged for in-person verification with prism alternating cover test (PACT) using a 2.4Δ threshold (root mean squared error of the app). A receiver operating characteristic (ROC) curve was used to determine the best sensitivity and specificity for an 8Δ threshold (recommended by AAPOS) with the PACT measurement as ground truth.

Results

The nurse obtained at least one successful app measurement for 93% of children (125/133). 40 were flagged for PACT, of which 6 were confirmed to have strabismus, including 4 exotropia (10△, 10△, 14△ and 18△), 1 constant esotropia (25△) and 1 accommodative esotropia (14△). Based on the ROC curve, the optimum threshold for the app to detect strabismus was determined to be 3.0△, with the best sensitivity (83.0%), specificity (76.5%). With this threshold the app would have missed one child with accommodative esotriopia, whereas conventional screening missed 3 cases of intermittent extropia.

Conclusions

Results support feasibility of use of the app by personnel without professional training in routine school screenings to improve detection of strabismus.
The severity and atypical presentations of COVID-19 infection in pediatrics
Authors: Saleh Nagwan Y. , Aboelghar Hesham M. , Salem Sherif S. , Ibrahem Reda A. , Khalil Fatma O. , Abdelgawad Ahmed S. , Mahmoud Asmaa A.
Published: March 2021

Background

Emergence of 2019-nCoV attracted global attention and WHO declared COVID-19 a public health emergency of international concern. Therefore we aimed to explore the severity and atypical manifestations of COVID-19 among children.

Methods

This is an observational cohort study conducted on 398 children with confirmed COVID-19 by using real-time reverse transcriptase polymerase chain reaction assay for detection of 2019-nCoV nucleic acid during the period from March to November 2020. Patients were subdivided regarding the severity of COVID-19 presentation into Group I (Non-severe COVID-19) was admitted into wards and Group II (Severe COVID-19) admitted into the PICU.

Results

Non- severe cases were 295cases (74.1%) and 103cases (25.9%) of severe cases. There was a significant difference between age groups of the affected children (P < 0.001) with a median (0–15 years). Boys (52%) are more affected than girls (48%) with significant differences (P < 0.001). 68.6%of confirmed cases had contact history to family members infected with COVID-19. 41.7% of severe patients needed mechanical ventilation. Death of 20.4% of severe cases. In COVID-19 patients, fever, headache, fatigue and shock were the most prominent presentations (95, 60.3, 57.8, and 21.8% respectively). 3.5% of children were manifested with atypical presentations; 1.25% manifested by pictures of acute pancreatitis, 1.25% presented by manifestations of deep venous thrombosis and 1.0% had multisystem inflammatory syndrome (MIS-C). Multivariate regression analysis showed that COVID-19 severity in children was significantly higher among children with higher levels of D-dimer, hypoxia, shock and mechanical ventilation.

Conclusion

Most children had a non-severe type of COVID-19 and children with severe type had higher levels of D-dimer, hypoxia, shock and mechanical ventilation.
Associations of sleep duration with physical fitness performance and self-perception of health: a cross-sectional study of Taiwanese adults aged 23–45
Authors: Gu Ming , Liu Chia-Chen , Hsu Chi-Chieh , Lu Chi-Jie , Lee Tian-Shyug , Chen Mingchih , Ho Chien-Chang
Published: March 2021

Background

The relationship between sleep duration and physical fitness is one aspect of sleep health. Potential factors associated with sleep duration interfere with physical fitness performance, but the impact trends on physical fitness indicators remain unclear.

Methods

This study examined associations between sleep duration and physical fitness among young to middle-aged adults in Taiwan. A total of 42,781 Taiwanese adults aged 23–45 participated in the National Physical Fitness Examination Survey 2013 (NPFES-2013) in Taiwan between October 2013 and March 2014. A standardized structural questionnaire was used to record participants’ sleep duration, which was stratified as short (< 6 h/day (h/d)), moderate (6–7 h/d; 7–8 h/d; 8-9 h), and long (≥ 9 h/d) sleep duration groups. Physical fitness was assessed based on four components: body composition (body mass index [BMI], waist-to-height ratio [WHtR], and waist-to-hip ratio [WHR]), muscle strength and endurance (1-min bent-leg sit-up test [BS]), flexibility (sit-and-reach test [SR]), and cardiorespiratory endurance index (3-min step test [CEI]).

Results

By using analysis of covariance (ANCOVA), after sex grouping and age adjustment, we observed that sleep duration was significantly associated with obesity, functional fitness, and self-perception of health. The sleep duration for low obesity-related values (BMI, WHtR, and WHR) for men was 7–9 h/d, and that for women was 7–8 h/d. Sleeping more than 8 h/d showed poor functional fitness performances (BS and SR). For both sexes, sleep duration of 8–9 h/d was the optimal sleep duration for self-perceptions of health.

Conclusions

Our research found that there were wide and different associations of sleep duration with physical fitness and self-perception of health among Taiwanese adults aged 23–45, and there were differences in these associated manifestations between men and women. This study could be of great importance in regional public health management in Taiwan, and provide inspirations for clinical research on physical fitness.
Identification and characterization of a new soybean promoter induced by Phakopsora pachyrhizi, the causal agent of Asian soybean rust
Authors: Cabre L. , Peyrard S. , Sirven C. , Gilles L. , Pelissier B. , Ducerf S. , Poussereau N.
Published: March 2021

Background

Phakopsora pachyrhiziis a biotrophic fungal pathogen responsible for the Asian soybean rust disease causing important yield losses in tropical and subtropical soybean-producing countries.P. pachyrhizitriggers important transcriptional changes in soybean plants during infection, with several hundreds of genes being either up- or downregulated.

Results

Based on published transcriptomic data, we identified a predicted chitinase gene, referred to asGmCHIT1, that was upregulated in the first hours of infection. We first confirmed this early induction and showed that this gene was expressed as early as 8 h afterP. pachyrhizi inoculation. To investigate the promoter ofGmCHIT1,transgenic soybean plants expressing the green fluorescence protein (GFP) under the control of theGmCHIT1promoter were generated. Following inoculation of these transgenic plants withP. pachyrhizi, GFP fluorescence was detected in a limited area located around appressoria, the fungal penetration structures. Fluorescence was also observed after mechanical wounding whereas no variation in fluorescence of pGmCHIT1:GFP transgenic plants was detected after a treatment with an ethylene precursor or a methyl jasmonate analogue.

Conclusion

We identified a soybean chitinase promoter exhibiting an early induction byP. pachyrhizilocated in the first infected soybean leaf cells. Our results on the induction ofGmCHIT1promoter byP. pachyrhizicontribute to the identification of a new pathogen inducible promoter in soybean and beyond to the development of a strategy for the Asian soybean rust disease control using biotechnological approaches.
Knowledge, awareness, and perception of dental students, interns, and freshly graduated dentists regarding dental implant complications in Saudi Arabia: a web-based anonymous survey
Authors: Saad Islam , Salem Suzan
Published: March 2021

Background

It is necessary for dental students and freshly graduated dentists to apply their education and practice to different clinical and preclinical procedures. The implant success rate and durability are high. Therefore, this study was designed to assess the level of knowledge, awareness and perception of dental students, interns and freshly graduated students regarding dental implant complications in Saudi Arabia.

Methods

A cross-sectional study design using a web-based method was conducted at different dental institutions in Saudi Arabia from December 2019 to March 2020. Data were collected from all (n = 288) undergraduate students, interns and freshly graduated dentists using a pretested standardized self-administered web-based questionnaire that was prepared and circulated using a template provided by Google Forms (Google, Inc., USA). Descriptive statistics and chi-square tests were performed to analyse the data using SPSS (version 20).

Results

A total of 288 participants completed the questionnaire, with a response rate of 83.4%. Of the total participants, 37.5% showed a good level of knowledge regarding dental implant procedures, and 38.9% showed the same level of knowledge regarding implant complications. The most important cause of complications associated with dental implants was case selection, which accounted for 54.17%. Most participants (58.33%) chose massive bone loss related to implant failure as the most common late dental complication, while 26.39% chose postoperative infection as the most common early dental complication. In addition, 30.56% of the participants selected screw loosening as the most frequent mechanical complication. However, lack of implant primary stability was the most common hard-tissue implant complication. Based on aesthetic and reversible complications, restorations that were too buccal or too palatal and prosthetic-related, respectively, were the least common dental implant complications.

Conclusions

The level of knowledge among participants regarding dental implant complications differed among the institutions participating in this study. This difference reflects a significant variation that necessitates reviewing and standardizing dental implant curricula among these institutions.
A mixed methods study to evaluate the impact of a student-run clinic on undergraduate medical education
Authors: Rockey Nathan G. , Weiskittel Taylor M. , Linder Katharine E. , Ridgeway Jennifer L. , Wieland Mark L.
Published: March 2021

Background

The purpose of this study was to evaluate the extent to which a longitudinal student-run clinic (SRC) is meeting its stated learning objectives, including providing critical community services and developing physicians who more fully appreciate the social factors affecting their patients’ health.

Methods

This was a mixed methods program evaluation of an SRC at Mayo Clinic Alix School of Medicine (MCASOM). A survey was conducted of medical students who had participated in the clinic and seven interviews and three focus groups were conducted with SRC patients, students, faculty, staff, and board members. Transcripts were coded for systematic themes and sub-themes. Major themes were reported. Survey and interview data were integrated by comparing findings and discussing areas of convergence or divergence in order to more fully understand program success and potential areas for improvement.

Results

Greater than 85% of student survey respondents (N = 90) agreed or strongly agreed that the SRC met each of its objectives: to provide a vital community service, to explore social determinants of health (SDH), to understand barriers to healthcare access and to practice patience-centered examination. Qualitative data revealed that the SRC contextualized authentic patient care experiences early in students’ medical school careers, but the depth of learning was variable between students. Furthermore, exposure to SDH through the program did not necessarily translate to student understanding of the impact of these social factors on patient’s health nor did it clearly influence students’ future practice goals.

Conclusions

The MCASOM SRC experience met core learning objectives, but opportunities to improve long-term impact on students were identified. Participation in the SRC enabled students to engage in patient care early in training that is representative of future practices. SRCs are an avenue by which students can gain exposure to real-world applications of SDH and barriers to healthcare access, but additional focus on faculty development and intentional reflection may be needed to translate this exposure to actionable student understanding of social factors that impact patient care.
Entrustability levels of general internal medicine residents
Authors: Dehghani Poudeh Mostafa , Mohammadi Aeen , Mojtahedzadeh Rita , Yamani Nikoo
Published: March 2021

Background

Entrustable professional activities (EPAs) are those activities that a health professional can perform without direct supervision in a defined environment. Bridging the gap between competencies and learning objectives, EPAs have made assessing the performances of health professional more realistic. The main objective of the present study was developing and customizing EPAs for Iranian Internal Medicine Residency Programs.

Results

After reviewing the publications, residency curricula and logbooks, and collecting experts’ ideas, the initial list of EPAs was developed. Then, in a focus group, the list was refined, the entrustability level of each residency year was determined, and finally, the EPA-competency cross-tab was established, and in the next step, through a one- round Delphi, the results were validated. Twenty-eight EPAs were developed. Some of them were definitely suitable for the higher levels of residency, such that they had to be accomplished under direct supervision until the end of the program. On the other hand, some of EPAs were those that residents, even from the first year, are expected to perform independently or under indirect supervision. Most of the EPAs cover a wide range of competencies.

Conclusion

Determining the entrustability level of each residency year in each EPA as well as the competency- EPA matrix has crucial effect on the quality of the graduates. It seems that our findings are applicable in developing countries like Iran.
Pharmacy stakeholder reports on ethical and logistical considerations in anti-opioid vaccine development
Authors: Wartenweiler Vincent , Chung Grace , Stewart Amy , Wenthur Cody
Published: March 2021

Background

As opioid use disorder (OUD) incidence and its associated deaths continue to persist at elevated rates, the development of novel treatment modalities is warranted. Recent strides in this therapeutic area include novel anti-opioid vaccine approaches. This work compares logistical and ethical considerations surrounding currently available interventions for opioid use disorder with an anti-opioid vaccine approach.

Methods

The opinions of student pharmacists and practicing pharmacists assessing knowledge, perceptions, and attitudes toward current and future OUD management strategies were characterized using a staged, multi-modal research approach incorporating a focus group, pilot survey development and refinement, and final survey deployment. Survey responses were assessed using one- and two-way parametric and non-parametric analyses where appropriate, and multi-dimensional matrix profiles were compared using z-tests following an exhaustive combinatorial sum of differences calculation between items within each compared matrix.

Results

Focus group content analysis revealed a high level of agreeableness among participants regarding anti-opioid vaccine technology and a sense of shared ownership regarding solutions to the opioid epidemic at large. Pilot survey results demonstrated subject ability to consider both pragmatic and ethical considerations related to current therapeutics and novel interventions in a single instrument, with high endurance amongst engaged subjects. Access inequality was the most concerning ethical consideration identified for anti-opioid vaccines. Support for anti-opioid vaccine implementation across various clinical scenarios was strongest for voluntary use amongst individuals in recovery, and lowest for mandatory use in at-risk individuals.

Conclusions

Ethical and logistical concerns surrounding anti-opioid vaccines were largely similar to those for current OUD therapeutics overall. Anti-opioid vaccines were endorsed as helpful potential additions to current OUD therapeutic approaches, particularly for voluntary use in the later stages of clinical progression.
Considerations for applying bioethics norms to a biopharmaceutical industry setting
Authors:   The Biopharmaceutical Bioethics Working Group, Van Campen Luann E. , Poplazarova Tatjana , Therasse Donald G. , Turik Michael
Published: March 2021

Background

The biopharmaceutical industry operates at the intersection of life sciences, clinical research, clinical care, public health, and business, which presents distinct operational and ethical challenges. This setting merits focused bioethics consideration to complement legal compliance and business ethics efforts. However, bioethics as applied to a biopharmaceutical industry setting often is construed either too broadly or too narrowly with little examination of its proper scope.

Main text

Any institution with a scientific or healthcare mission should engage bioethics norms to navigate ethical issues that arise from the conduct of biomedical research, delivery of clinical care, or implementation of public health programs. It is reasonable to assume that while bioethics norms must remain constant, their application will vary depending on the characteristics of a given setting. Context “specification” substantively refines ethics norms for a particular discipline or setting and is an expected, needed and progressive ethical activity. In order for this activity to be meaningful, the scope for bioethics application and the relevant contextual factors of the setting need to be delineated and appreciated. This paper defines biopharmaceutical bioethics as:the application of bioethics norms (concepts, principles, and rules) to the research, development, supply, commercialization, and clinical use of biopharmaceutical healthcare products. It provides commentary on this definition, and presents five contextual factors that need to be considered when applying bioethics norms to a biopharmaceutical industry setting: (1) dual missions; (2) timely and pragmatic guidance; (3) resource stewardship; (4) multiple stakeholders; and (5) operational complexity.

Conclusion

Understanding the scope of the biopharmaceutical enterprise and contextual factors of a biopharmaceutical industry setting is foundational for the application of bioethics norms. Establishing a common language and approach for biopharmaceutical bioethics will facilitate breadth and depth of discussion and subsequent implementation to benefit patients, the healthcare system and society.
The impact of the COVID-19 pandemic on child health and the provision of Care in Paediatric Emergency Departments: a qualitative study of frontline emergency care staff
Authors: Conlon Ciara , McDonnell Thérèse , Barrett Michael , Cummins Fergal , Deasy Conor , Hensey Conor , McAuliffe Eilish , Nicholson Emma
Published: March 2021

Background

The COVID-19 pandemic and subsequent public health guidance to reduce the spread of the disease have wide-reaching implications for children’s health and wellbeing. Furthermore, paediatric emergency departments (EDs) have rapidly adapted provision of care in response to the pandemic. This qualitative study utilized insight from multidisciplinary frontline staff to understand 1) the changes in paediatric emergency healthcare utilization during COVID-19 2) the experiences of working within the restructured health system.

Methods

Fifteen semi-structured interviews were conducted with frontline staff working in two paediatric EDs and two mixed adult and children EDs. Participants included emergency medicine clinicians (n = 5), nursing managerial staff (n = 6), social workers (n = 2) and nursing staff (n = 2). Thematic Analysis (TA) was applied to the data to identify key themes.

Results

The pandemic and public health restrictions have had an adverse impact on children’s health and psychosocial wellbeing, compounded by difficulty in accessing primary and community services. The impact may have been more acute for children with disabilities and chronic health conditions and has raised child protection issues for vulnerable children. EDs have shown innovation and agility in the structural and operational changes they have implemented to continue to deliver care to children, however resource limitations and other challenges must be addressed to ensure high quality care delivery and protect the wellbeing of those tasked with delivering this care.

Conclusions

The spread of COVID-19 and subsequent policies to address the pandemic has had wide-reaching implications for children’s health and wellbeing. The interruption to health and social care services is manifesting in myriad ways in the ED, such as a rise in psychosocial presentations. As the pandemic continues to progress, policy makers and service providers must ensure the continued provision of essential health and social services, including targeted responses for those with existing conditions.
Sero-epidemiology and associated risk factors of brucellosis among sheep and goat population in the south western Nepal: a comparative study
Authors: Gompo Tulsi Ram , Shah Rubina , Tiwari Ishwari , Gurung Yam Bahadur
Published: March 2021

Background

Brucellosis is a zoonotic disease caused by Brucella spp. In Nepal, the presence of brucellosis in small ruminants, namely sheep and goats, has impacted farmers’ livelihood and the food safety of consumers. A cross-sectional study was conducted in Rupandehi district of Nepal during January to March 2020 to investigate the seroepidemiology and associated risk factors of brucellosis in the sheep and goat population. Altogether, 19 sheep and 60 goat farms in the district were visited. Owners were interviewed to get information on animals, including their management and movement patterns. Three hundred fifty-seven samples (80 sheep and 277 goat samples) were collected proportionately based on farm sizes. Each serum sample was tested with Rose Bengal Test and ELISA to estimate the seropositivity of brucellosis. Logistic regression was carried out to calculate corresponding odds ratios of each variable associated with detection of brucellosis.

Results

At the farm level, 31.6% (6/19; 95% CI: 12, 54%) of sheep farms and 3.3% (2/60, 95% CI: 0.9, 11.4%) of goat farms were seropositive to brucellosis. Out of 80 sheep serum samples, 12 (15%; 95% CI: 8.79–24.41%) and out of 277 goat serum samples, three (1.1%; 95% CI: 0.37–3.14%) were seropositive to brucellosis. Age greater than 1.5 years (OR = 5.56, 95% CI: 1.39, 29.38; p = 0.02) and herd size of greater than 100 (OR = 4.74, 95% CI: 1.23, 20.32, p = 0.03) were identified as significant risk factors for seropositivity of brucellosis in the sheep population. While in the goat population, none of the variables was identified as a significant risk factor.

Conclusion

The study provides evidence that the older sheep and the sheep from the large herds were at higher risk of brucellosis. A control program should be put in place immediately in the sheep population because they may transmit infections to other livestock as they were regularly moved for grazing and selling purposes. Also, strict biosecurity measures should be implemented among pastoralists to prevent brucellosis transmission in them. We suggest further one health-based study to reveal the transmission dynamics of brucellosis between animals and humans.
Association between cholesterol efflux capacity and peripheral artery disease in coronary heart disease patients with and without type 2 diabetes: from the CORDIOPREV study
Authors: Yubero-Serrano Elena M. , Alcalá-Diaz Juan F. , Gutierrez-Mariscal Francisco M. , Arenas-de Larriva Antonio P. , Peña-Orihuela Patricia J. , Blanco-Rojo Ruth , Martinez-Botas Javier , Torres-Peña Jose D. , Perez-Martinez Pablo , Ordovas Jose M. , Delgado-Lista Javier , Gómez-Coronado Diego , Lopez-Miranda Jose
Published: March 2021

Background

Peripheral artery disease (PAD) is recognized as a significant predictor of mortality and adverse cardiovascular outcomes in patients with coronary heart disease (CHD). In fact, coexisting PAD and CHD is strongly associated with a greater coronary event recurrence compared with either one of them alone. High-density lipoprotein (HDL)-mediated cholesterol efflux capacity (CEC) is found to be inversely associated with an increased risk of incident CHD. However, this association is not established in patients with PAD in the context of secondary prevention. In this sense, our main aim was to evaluate the association between CEC and PAD in patients with CHD and whether the concurrent presence of PAD and T2DM influences this association.

Methods

CHD patients (n = 1002) from the CORDIOPREV study were classified according to the presence or absence of PAD (ankle-brachial index, ABI ≤ 0.9 and ABI > 0.9 and < 1.4, respectively) and T2DM status. CEC was quantified by incubation of cholesterol-loaded THP-1 cells with the participants' apoB-depleted plasma was performed.

Results

The presence of PAD determined low CEC in non-T2DM and newly-diagnosed T2DM patients. Coexisting PAD and newly-diagnosed T2DM provided and additive effect providing an impaired CEC compared to non-T2DM patients with PAD. In established T2DM patients, the presence of PAD did not determine differences in CEC, compared to those without PAD, which may be restored by glucose-lowering treatment.

Conclusions

Our findings suggest an inverse relationship between CEC and PAD in CHD patients. These results support the importance of identifying underlying mechanisms of PAD, in the context of secondary prevention, that provide potential therapeutic targets, that is the case of CEC, and establishing strategies to prevent or reduce the high risk of cardiovascular events of these patients.

Trial registrationhttps://clinicaltrials.gov/ct2/show/NCT00924937. Unique Identifier: NCT00924937
Impact of type 2 diabetes mellitus on left ventricular diastolic function in patients with essential hypertension: evaluation by volume-time curve of cardiac magnetic resonance
Authors: Yan Wei-feng , Gao Yue , Zhang Yi , Guo Ying-kun , Wang Jin , Jiang Li , Li Yuan , Yang Zhi-gang
Published: March 2021

Background

Essential hypertension and type 2 diabetes mellitus (T2DM) are two common chronic diseases that often coexist, and both of these diseases can cause heart damage. However, the additive effects of essential hypertension complicated with T2DM on left ventricle (LV) diastolic function have not been fully illustrated. This study aims to investigate whether T2DM affects the diastolic function of the LV in patients with essential hypertension using the volume-time curve from cardiac magnetic resonance (CMR).

Methods

A total of 124 essential hypertension patients, including 48 with T2DM [HTN(T2DM +) group] and 76 without T2DM [HTN(T2DM-) group], and 52 normal controls who underwent CMR scans were included in this study. LV volume-time curve parameters, including the peak ejection rate (PER), time to peak ejection rate (PET), peak filling rate (PFR), time to peak filling rate from end-systole (PFT), PER normalized to end-diastolic volume (PER/EDV), and PFR normalized to EDV (PFR/EDV), were measured and compared among the three groups. Multivariate linear regression analyses were performed to determine the effects of T2DM on LV diastolic dysfunction in patients with hypertension. Pearson correlation was used to analyse the correlation between the volume-time curve and myocardial strain parameters.

Results

PFR and PFR/EDV decreased from the control group, through HTN(T2DM −), to HTN(T2DM +) group. PFT in the HTN(T2DM-) group and HTN(T2DM +) group was significantly longer than that in the control group. The LV remodelling index in the HTN(T2DM −) and HTN(T2DM +) groups was higher than that in the normal control group, but there was no significant difference between the HTN(T2DM −) and HTN(T2DM +) groups. Multiple regression analyses controlling for covariates of systolic blood pressure, age, sex, and heart rate demonstrated that T2DM was independently associated with PFR/EDV (β = 0.252, p < 0.05). The volume-time curve method has good repeatability, and there is a significant correlation between volume-time curve parameters (PER/EDV and PFR/EDV) and myocardial peak strain rate, especially circumferential peak strain rate, which exhibited the highest correlation (r = − 0.756 ~ 0.795).

Conclusions

T2DM exacerbates LV diastolic dysfunction in patients with essential hypertension. The LV filling model changes reflected by the CMR volume-time curve could provide more information for early clinical intervention.