bluuebunny/crossref_metadata_2025 huggingface dataset:
Explaining the experiences of nursing administrators, educators, and students about education process in the COVID-19 pandemic: a qualitative study
Authors: Farsi Zahra , Sajadi Seyedeh Azam , Afaghi Effat , Fournier Andrew , Aliyari Shahla , Ahmadi Yazdan , Hazrati Ebrahim
Published: August 2021

Background

The coronavirus disease 2019 (COVID-19) has severely influenced various aspects of human life, particularly education. This study aimed to explain the impact of the COVID-19 pandemic on nursing education from administrators, educators, and students’ perspectives.

Methods

This qualitative study with a conventional content analysis approach was conducted from June to October 2020 at a nursing school in Tehran. Thirteen participants were enrolled using purposive sampling. Data collection was through in-depth and semi-structured interviews and continued until reaching data saturation. Nursing administrators, educators, and students constructed interviews to understand nursing education changes during the pandemic. All interviews were recorded, transcribed, reviewed, coded, and analyzed using the Graneheim and Lundman methods.

Results

Interviewed respondents included administrators and professors (n = 6) and nursing students (n = 7). The respondents reported five main topic areas: (1) safe management in ambiguous situations; (2) perceived situations; (3) adaptive coping; (4) educational facilitators and challenges, and (5) continuing education in an uncertain context. The central theme was “close conflict of education with COVID-19”.

Conclusions

The current study noted instability and challenges placed on nursing education during the pandemic. Opportunities were addressed during the pandemic to improve the nursing training process using planning, scientific management, emerging technology, innovative educational opportunities, and comprehensive support from institutional stakeholders. Clear guidelines and recommendations are needed to ensure medical education safety during the pandemic.
Organizational readiness to change as a leverage point for improving safety: a national nursing home survey
Authors: Quach Emma D. , Kazis Lewis E. , Zhao Shibei , Ni Pengsheng , Clark Valerie A. , McDannold Sarah E. , Hartmann Christine W.
Published: August 2021

Background

A stronger safety climate in nursing homes may reduce avoidable adverse events. Yet efforts to strengthen safety climate may fail if nursing homes are not ready to change. To inform improvement efforts, we examined the link between organizational readiness to change and safety climate.

Methods

Seven safety climate domains and organizational readiness to change were measured with validated Community Living Center/CLC Employee Survey of Attitudes about Resident Safety and Organizational Readiness to Change Assessment. Safety climate domains comprised of safety priorities, supervisor commitment to safety, senior management commitment to safety, safety attitudes, environmental safety, coworker interactions around safety, and global rating of CLC. We specified models with and without readiness to change to explain CLC- and person-level variance in safety climate domains.

Results

One thousand three hundred ninety seven workers (frontline staff and managers) responded from 56 US Veterans Health Administration CLCs located throughout the US. Adding readiness to change reduced baseline CLC-level variance of outcomes (2.3–9.3%) by > 70% for interpersonal domains (co-workers, supervisors, and senior management). Readiness to change explained person-level variance of every safety climate domain (P < 0.05), especially for interpersonal domains.

Conclusions

Organizational readiness to change predicted safety climate. Safety climate initiatives that address readiness to change among frontline staff and managers may be more likely to succeed and eventually increase resident safety.
Characterizing rescue performance in a tertiary care medical center: a systems approach to provide management decision support
Authors: McGrath Susan P. , MacKenzie Todd , Perreard Irina , Blike George
Published: August 2021

Background

Allocation of limited resources to improve quality, patient safety, and outcomes is a decision-making challenge health care leaders face every day. While much valuable health care management research has concentrated on administrative data analysis, this approach often falls short of providing actionable information essential for effective management of specific system implementations and complex systems. This comprehensive performance analysis of a hospital-wide system illustrates application of various analysis approaches to support understanding specific system behaviors and identify leverage points for improvement. The study focuses on performance of a hospital rescue system supporting early recognition and response to patient deterioration, which is essential to reduce preventable inpatient deaths.

Methods

Retrospective analysis of tertiary care hospital inpatient and rescue data was conducted using a systems analysis approach to characterize: patient demographics; rescue activation types and locations; temporal patterns of activation; and associations of patient factors, including complications, with post-rescue care disposition and outcomes.

Results

Increases in bedside consultations (20% per year) were found with increased rescue activations during periods of resource limitations and changes (e.g., shift changes, weekends). Cardiac arrest, respiratory failure, and sepsis complications present the highest risk for rescue and death. Distributions of incidence of rescue and death by day of patient stay may suggest opportunities for earlier recognition.

Conclusions

Specific findings highlight the potential of using rescue-related risk and targeted resource deployment strategies to improve early detection of deterioration. The approach and methods applied can be used by other institutions to understand performance and allow rational incremental improvements to complex care delivery systems.
Choice of HbA1c threshold for identifying individuals at high risk of type 2 diabetes and implications for diabetes prevention programmes: a cohort study
Authors: Rodgers Lauren R. , Hill Anita V. , Dennis John M. , Craig Zoe , May Benedict , Hattersley Andrew T. , McDonald Timothy J. , Andrews Rob C. , Jones Angus , Shields Beverley M.
Published: August 2021

Background

Type 2 diabetes (T2D) is common and increasing in prevalence. It is possible to prevent or delay T2D using lifestyle intervention programmes. Entry to these programmes is usually determined by a measure of glycaemia in the ‘intermediate’ range. This paper investigated the relationship between HbA1c and future diabetes risk and determined the impact of varying thresholds to identify those at high risk of developing T2D.

Methods

We studied 4227 participants without diabetes aged ≥ 40 years recruited to the Exeter 10,000 population cohort in South West England. HbA1c was measured at study recruitment with repeat HbA1c available as part of usual care. Absolute risk of developing diabetes within 5 years, defined by HbA1c ≥ 48 mmol/mol (6.5%), according to baseline HbA1c, was assessed by a flexible parametric survival model.

Results

The overall absolute 5-year risk (95% CI) of developing T2D in the cohort was 4.2% (3.6, 4.8%). This rose to 7.1% (6.1, 8.2%) in the 56% (n = 2358/4224) of participants classified ‘high-risk’ with HbA1c ≥ 39 mmol/mol (5.7%; ADA criteria). Under IEC criteria, HbA1c ≥ 42 mmol/mol (6.0%), 22% (n = 929/4277) of the cohort was classified high-risk with 5-year risk 14.9% (12.6, 17.2%). Those with the highest HbA1c values (44–47 mmol/mol [6.2–6.4%]) had much higher 5-year risk, 26.4% (22.0, 30.5%) compared with 2.1% (1.5, 2.6%) for 39–41 mmol/mol (5.7–5.9%) and 7.0% (5.4, 8.6%) for 42–43 mmol/mol (6.0–6.1%). Changing the entry criterion to prevention programmes from 39 to 42 mmol/mol (5.7–6.0%) reduced the proportion classified high-risk by 61%, and increased the positive predictive value (PPV) from 5.8 to 12.4% with negligible impact on the negative predictive value (NPV), 99.6% to 99.1%. Increasing the threshold further, to 44 mmol/mol (6.2%), reduced those classified high-risk by 59%, and markedly increased the PPV from 12.4 to 23.2% and had little impact on the NPV (99.1% to 98.5%).

Conclusions

A large proportion of people are identified as high-risk using current thresholds. Increasing the risk threshold markedly reduces the number of people that would be classified as high-risk and entered into prevention programmes, although this must be balanced against cases missed. Raising the entry threshold would allow limited intervention opportunities to be focused on those most likely to develop T2D.
Intellectual property and access to medicines: mapping public attitudes toward pharmaceuticals during the United States-Mexico-Canada Agreement (USMCA) negotiation process
Authors: Wong Anna S. Y. , Cole Clarke B. , Kohler Jillian C.
Published: August 2021

Background

Transparency and accountability are essential components at all stages of the trade negotiation process. This study evaluates the extent to which these principles were upheld in the United States’ public consultation process during the negotiation of the United States-Mexico-Canada Agreement (USMCA), with respect to public comments about the pharmaceutical sector and access to medicines.

Results

The public consultation process occurred before the start of official negotiations and was overseen by the Office of the United States Trade Representative (USTR). It included both written comments and oral testimony about US trade negotiation objectives. Of the written comments that specifically discussed issues relating to pharmaceuticals, the majority were submitted by private individuals, members of the pharmaceutical industry, and civil society organizations. Nearly all comments submitted by non-industry groups indicated that access to medicines was a priority issue in the renegotiated agreement, with specific reference to price affordability. By contrast, more than 50% of submissions received from members or affiliates of the pharmaceutical industry advocated for strengthened pharmaceutical intellectual property rights, greater regulatory data protections, or both.

This study reveals mixed outcomes with respect to the level of transparency achieved in the US trade negotiation process. Though input from the public at-large was actively solicited, the extent to which these comments were considered in the content of the final agreement is unclear. A preliminary comparison of the analyzed comments with the USTR’s final negotiating objectives and the final text of the USMCA shows that several provisions that were advanced exclusively by the pharmaceutical industry and ultimately adopted in the final agreement were opposed by the majority of non-industry stakeholders.

Conclusions

Negotiators could increase public transparency when choosing to advance one competing trade objective over another by actively providing the public with clear rationales for their negotiation positions, as well as details on how public comments are taken into account to form these rationales. Without greater clarity on these aspects, the public consultation process risks appearing to serve as a cursory government mechanism, lacking in accountability and undermining public trust in both the trade negotiation process and its outcomes.
Validation of the Spanish version of the Goodman score in total hip arthroplasty
Authors: Brañes Julián , Barahona Maximiliano , Carvajal Sebastián , Wulf Rodrigo , Barrientos Cristián
Published: August 2021

Purpose

Currently, patient-reported outcome measures (PROMs) are the standard instruments used to compare arthroplasty results. Goodman et al. recently published a well-constructed scale with excellent psychometric properties that can be quickly administered. The main objective of our study was to translate, culturally adapt, and validate a Spanish version of the Goodman questionnaire in patients who underwent total hip arthroplasty (THA).

Methods

The original Goodman scale was translated into Spanish and cross-culturally adapted. Then, the data from this version were tested for psychometric quality. We designed a cross-sectional study for data collection. This study enrolled 2 institutions. Patients who underwent hip replacement due to primary osteoarthritis secondary to dysplasia between 1 January 2018 and 31 December 2019 were included. A total of 153 patients were contacted twice to record the Goodman and Oxford hip scales (OHS) to assess the validity of the questionnaire. Reliability was tested using the Cronbach’s alpha, Concordance using 3 test: intraclass correlation coefficient (ICC), Lin's concordance correlation coefficient (CCC), and the Bradley-Blackwood F test. The spearman correlation was used to asses correlation between the OHS and the Spanish-adapted Goodman scale.

Results

The overall satisfaction after THA was reported to be “very satisfied” by 137 patients (75%), and only 14 patients reported some degree of dissatisfaction (6%). The improvement in quality of life was reported to be “more than I ever dreamed possible” by 41% patients. Cronbach’s alpha was acceptable, reaching a coefficient of 0.95 (95% confidence interval, 0.82–1). No statistical difference (t test, p = 0.55) was found in the original version, with great internal validity. Test re-test concordance was optimal among the 3 tests used. A moderate correlation was found between the OHS and the Spanish-adapted Goodman scale.

Conclusion

The Spanish version of the Goodman questionnaire in THA is a reliable, consistent, and feasible scale to evaluate patient satisfaction and improvement in the quality of life in Spanish speakers.
Functional outcome and complication following THA through modified direct anterior approach correlated to cadaveric study: are there any differences in Asian hip?
Authors: Phruetthiphat Ong-art , Sangthumprateep Vasin , Trakulngernthai Songpol , Aegakkatajit Noppadol , Chotanaphuti Thanainit , Chanpoo Malee
Published: August 2021

Background

Direct anterior approach (DAA) has several advantages including shorter length of hospital stay, faster recovery, and better functional outcome while this approach may cause damage to the lateral femoral cutaneous nerve (LFCN) as high as 81% in the works of literature. Not much data has identified the LFCN pattern in the Asian population. Therefore, the purpose of our study was to identify characteristics of the LFCN patterns representing an Asian hip, which would aid to provide the most appropriate incision of modified direct anterior approach (MDAA) for total hip arthroplasty (THA), and to identify the clinical outcome and complications following THA through MDAA correlated with cadaveric hip in the Asian population.

Methods

After IRB approval, a cadaveric study was done to identify pattern and course of the LFCN in Asian population. The MDAA defined as the incision 2 fingerbreadths posteriorly to anterior superior iliac spine to avoid injury to the LFCN. The clinical phase identified 32 patients who underwent THA because of late-stage osteoarthritis of the hip. The anterolateral skin numbness was measured along tensor fascia lata between 2 weeks until 2 years. The functional outcome assessed by Harris Hip Score (HHS) and complications were evaluated in all patients.

Results

The characteristics of the LFCN from cadaveric study (phase 1) was predominantly in sartorius type (60.0%) followed by posterior type (26.6%), fan type (6.7%), and variant type (6.7%). The clinical phase demonstrated that 23 patients (71.9%) had no numbness while 9 patients (28.1%) came with numbness after undergoing THA through the MDAA. Finally, a small area of skin numbness remained in only 3 patients (9.4%) at 2 years follow-up. Additionally, there was no significant difference in functional score at 2 years follow-up (89.0 vs 91.2,p= 0.422) between those with LFCN injury and those without LFCN injury.

Conclusions

The LFCNs were divided into four types. Modified direct anterior approach, which is an alternative approach for THA, allowing for a lower rate of skin numbness and faster recovery without hip dislocation, abductor weakness, and serious nerve complication. Functional outcome was comparable with and without LFCN injury.

Level of evidence

Level II, prospective observation study
Cell-free stem cell-derived extract formulation for treatment of knee osteoarthritis: study protocol for a preliminary non-randomized, open-label, multi-center feasibility and safety study
Authors: Gupta Ashim , Maffulli Nicola , Rodriguez Hugo C. , Mistovich R. Justin , Delfino Kristin , Cady Craig , Fauser Anne-Marie , Cundiff Echo D. , Martinez Marte A. , Potty Anish G.
Published: August 2021

Background

Musculoskeletal conditions are highly prevalent, and knee OA is most common. Current treatment modalities have limitations and either fail to solve the underlying pathophysiology or are highly invasive. To address these limitations, attention has focused on the use of biologics. The efficacy of these devices is attributed to presence of growth factors (GFs), cytokines (CKs), and extracellular vesicles (EVs). With this in mind, we formulated a novel cell-free stem cell-derived extract (CCM) from human progenitor endothelial stem cells (hPESCs). A preliminary study demonstrated the presence of essential components of regenerative medicine, namely GFs, CKs, and EVs, including exosomes, in CCM. The proposed study aims to evaluate the safety and efficacy of intraarticular injection of the novel cell-free stem cell-derived extract (CCM) for the treatment of knee OA.

Methods and analysis

This is a non-randomized, open-label, multi-center, prospective study in which the safety and efficacy of intraarticular CCM in patients suffering from grade II/III knee OA will be evaluated. Up to 20 patients with grade II/III OA who meet the inclusion and exclusion criteria will be consented and screened to recruit 12 patients to receive treatment. The study will be conducted at up to 2 sites within the USA, and the 12 participants will be followed for 24 months. The study participants will be monitored for adverse reactions and assessed using Numeric Pain Rating Scale (NPRS), Patient-Reported Outcomes Measurement Information System (PROMIS) Score, Knee Injury and Osteoarthritis Outcome Score Jr. (KOOS Jr.), 36-ietm short form survey (SF-36), Single Assessment Numeric Evaluation (SANE), physical exams, plain radiography, and magnetic resonance imaging (MRI) with Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score for improvements in pain, function, satisfaction, and cartilage regeneration.

Discussion

This prospective study will provide valuable information into the safety and efficacy of intraarticular administration of cell-free stem cell-derived extract (CCM) in patients suffering with grade II/III knee OA. The outcomes from this initial study of novel CCM will lay the foundation for a larger randomized, placebo-controlled, multi-center clinical trial of intraarticular CCM for symptomatic knee OA.

Trial registration

Registered on July 21, 2021. ClinicalTrials.gov NCT04971798
Is there a difference in the outcomes of anterior cervical discectomy and fusion among female patients with different menopausal statuses?
Authors: Wang Xing-jin , Liu Hao , He Jun-bo , Gong Quan , Hong Ying , Rong Xin , Ding Chen , Wang Bei-yu , Yang Yi , Meng Yang
Published: August 2021

Background

The surgical outcomes of anterior cervical discectomy and fusion (ACDF) in female patients according to menopausal status remain unclear. The objective of this study was to investigate the differences in these outcomes among female patients with different menopausal statuses.

Methods

Ninety-one patients undergoing single-level or consecutive two-level ACDF with a minimum 12-month postoperative follow-up were included in this study. There were 38 patients in the premenopausal group, 28 patients in the early postmenopausal group, and 25 patients in the late postmenopausal group. The clinical outcomes were evaluated by means of the neck disability index (NDI) scores, Japanese Orthopedic Association (JOA) scores, and visual analog scale (VAS) scores. Radiological parameters included cervical lordosis (CL), the functional spinal unit (FSU) angle, range of motion (ROM) of the total cervical spine, ROM of the FSU, anterior and posterior FSU height, implant subsidence, adjacent segment degeneration (ASD), and Hounsfield unit (HU) values.

Results

All groups showed significant improvements in their JOA, VAS, and NDI scores (P < 0.05). The differences in preoperative and final follow-up CL, ROM of C2-7, FSU angle, and ROM of FSU were not statistically significant among the three groups (P > 0.05). The anterior FSU height loss rate showed a significant difference (P = 0.043), while there was no difference in the posterior FSU height loss rate (P = 0.072). The fusion rates in the early and late postmenopausal groups were consistently lower than those in the premenopausal group during the follow-up period. All patients had satisfactory outcomes at the final follow-up.

Conclusion

There were no significant differences in clinical or other related outcomes of single-level or consecutive two-level ACDF in the long term among female patients with different menopausal statuses. However, the early bony fusion rates and anterior FSU height loss rates were poorer in late postmenopausal patients than in premenopausal or early postmenopausal patients. Hence, importance should be attached to the protection of late postmenopausal patients in the early postoperative period to guarantee solid bony fusion.
Mediterranean diet in axial spondyloarthritis: an observational study in an Italian monocentric cohort
Authors: Ometto Francesca , Ortolan Augusta , Farber Davide , Lorenzin Mariagrazia , Dellamaria Giulia , Cozzi Giacomo , Favero Marta , Valentini Romina , Doria Andrea , Ramonda Roberta
Published: August 2021

Background

Little evidence is available about the impact of diet on disease activity of axial spondyloarthritis (axSpA). This study evaluated the impact of a 6-month nutritional advice based on the Mediterranean diet on the disease activity of axSpA.

Methods

We prospectively collected the information of a group of axSpA patients who were offered nutritional advice for a 6-month period, who were compared to axSpA patients followed at the same center who were not on a specific diet. A nutritionist gave suggestions for dietary modification at baseline and thereafter every 2 months until month 6. Adherence to the Mediterranean diet was evaluated with the PREDIMED questionnaire ranging from 0 (no adherence) to 10 (optimal adherence); disease activity was evaluated with ASDAS-CRP. A multivariable regression analysis was conducted to identify independent predictors of PREDIMED and of ASDAS-CRP improvement (improvement ≥ 20% of each score).

Results

A total of 161 patients were included: 81 receiving nutritional advice and 80 controls; 47 in the nutritional group and 63 controls had complete information until month 6. Overall, 40 (36.4%) were females, the mean age was 51.7 ± 1.3 years, and 58 (52.7%) were affected with psoriasis. No relevant change of anthropometric or laboratory measures was observed in either group. Adherence to the Mediterranean diet was moderate (PREDIMED score 6.7 ± 1.8 at baseline; 7.6 ± 2.1 at month 6) and improved more in the nutritional group compared to controls (p= 0.020). Predictors of a PREDIMED improvement ≥ 20% were receiving nutritional advice (OR 4.53, 1.36–15.1,p= 0.014), age (per 10-year increase OR 1.05, 1.02–1.68,p= 0.007), and BMI (OR 0.77, 0.63–0.9,p= 0.006). An ASDAS-CRP improvement ≥ 20% was more frequent in the nutritional group compared to controls (p= 0.020). A PREDIMED improvement ≥ 20% was associated with a ASDAS-CRP improvement ≥ 20% (OR 6.75,1.8–25.3,p= 0.005). Psoriasis and disease duration were negatively but not significantly associated to the ASDAS-CRP improvement.

Conclusions

Improving adherence to the Mediterranean diet may have a beneficial impact on the activity of axSpA. Patients with a lower BMI and older patients are more prone to modify their diet towards the Mediterranean diet following nutritional advice. Patients with psoriasis may have a limited benefit from dietary improvement.

Study registration

Protocol No. 52723, Padova Hospital Medical Ethical Committee (October 11, 2010).
Axillary lymphadenopathy at the time of COVID-19 vaccination: ten recommendations from the European Society of Breast Imaging (EUSOBI)
Authors: Schiaffino Simone , Pinker Katja , Magni Veronica , Cozzi Andrea , Athanasiou Alexandra , Baltzer Pascal A. T. , Camps Herrero Julia , Clauser Paola , Fallenberg Eva M. , Forrai Gábor , Fuchsjäger Michael H. , Helbich Thomas H. , Kilburn-Toppin Fleur , Kuhl Christiane K. , Lesaru Mihai , Mann Ritse M. , Panizza Pietro , Pediconi Federica , Pijnappel Ruud M. , Sella Tamar , Thomassin-Naggara Isabelle , Zackrisson Sophia , Gilbert Fiona J. , Sardanelli Francesco
Published: August 2021

Unilateral axillary lymphadenopathy is a frequent mild side effect of COVID-19 vaccination. European Society of Breast Imaging (EUSOBI) proposes ten recommendations to standardise its management and reduce unnecessary additional imaging and invasive procedures: (1) in patients with previous history of breast cancer, vaccination should be performed in the contralateral arm or in the thigh; (2) collect vaccination data for all patients referred to breast imaging services, including patients undergoing breast cancer staging and follow-up imaging examinations; (3) perform breast imaging examinations preferentially before vaccination or at least 12 weeks after the last vaccine dose; (4) in patients with newly diagnosed breast cancer, apply standard imaging protocols regardless of vaccination status; (5) in any case of symptomatic or imaging-detected axillary lymphadenopathy before vaccination or at least 12 weeks after, examine with appropriate imaging the contralateral axilla and both breasts to exclude malignancy; (6) in case of axillary lymphadenopathy contralateral to the vaccination side, perform standard work-up; (7) in patients without breast cancer history and no suspicious breast imaging findings, lymphadenopathy only ipsilateral to the vaccination side within 12 weeks after vaccination can be considered benign or probably-benign, depending on clinical context; (8) in patients without breast cancer history, post-vaccination lymphadenopathy coupled with suspicious breast finding requires standard work-up, including biopsy when appropriate; (9) in patients with breast cancer history, interpret and manage post-vaccination lymphadenopathy considering the timeframe from vaccination and overall nodal metastatic risk; (10) complex or unclear cases should be managed by the multidisciplinary team.
Resistance and virulence distribution in enterococci isolated from broilers reared in two farming systems
Authors: Semedo-Lemsaddek Teresa , Bettencourt Cota João , Ribeiro Tânia , Pimentel Amélia , Tavares Luís , Bernando Fernando , Oliveira Manuela
Published: August 2021

Background

The impact of enterococci in human health has been growing for the last decades, mainly due to their resistance to several antimicrobial agents. Human consumption of contaminated meat, especially poultry, has been identified as a possible route of transmission. The aim of the present study was to evaluate and compare the antimicrobial resistance profiles and virulence genes of enterococci isolated from Portuguese conventional and free-range broiler farms.

Results

Antibiotic susceptibility testing showed high frequencies of resistance to tetracycline in both farming systems. Resistance to erythromycin and gentamicin were detected in about half of the isolates. Resistance to penicillin was the less frequently observed and no vancomycin resistant isolates were identified. The majority of the enterococcal isolates, from either farming systems, were resistant to more than one antibiotic, and no statistical associations were found, except for penicillin resistance which associated with the genetic clusters. No differences were found between farming systems regarding the prevalence of tet(M), erm(B), aac (6′)-Ie-aph (2″)-Ia and pbp5 genes, nevertheless pbp5 prevalence was associated with the different genetic clusters. Hemolytic activity was identified in 26.47% of all isolates and gelatinase activity in 50%. The gelE gene was identified in the majority of the isolates, whereas esp and agg genes were rarely detected. The cylA determinant was not detected in any of the isolates.

Conclusions

Overall, results suggest that similar resistance patterns and virulence genes can be found in both farming systems, though enterococci in free-range conditions should be less prone to acquire further resistance genes.
Access, use and disposal of antimicrobials among humans and animals in Wakiso district, Uganda: a qualitative study
Authors: Musoke David , Namata Carol , Lubega Grace Biyinzika , Kitutu Freddy Eric , Mugisha Lawrence , Amir Saba , Brandish Claire , Gonza Joviah , Ikhile Deborah , Niyongabo Filimin , Ng Bee Yean , O’Driscoll Jean , Russell-Hobbs Kate , Winter Jody , Gibson Linda
Published: August 2021

Background

Inappropriate use of antimicrobials in both humans and animals is a key driver of antimicrobial resistance (AMR). In addition, human behaviours such as poor disposal of antimicrobials in the environment can increase their exposure to microbes which can impact on humans and animals. However, evidence on access, use and disposal of antimicrobials for humans and animals at community level in Uganda is limited. This study therefore explored access, use and disposal of antimicrobials among humans and animals in Wakiso district, Uganda.

Methods

A qualitative study was conducted that involved focus group discussions (FGDs) and key informant interviews (KIIs). Participants of the FGDs were community health workers (CHWs) and farmers involved in animal husbandry, while key informants included: officials from the Ministry of Health; Ministry of Agriculture, Animal Industry and Fisheries; human and animal health professionals; district health officials; and members of the national AMR surveillance committee. Twelve FGDs were held (8 for CHWs and 4 for farmers) while 15 KIIs were conducted. Thematic analysis in NVivo (version 12) was performed.

Results

Five main themes emerged from the study: access to antimicrobials in humans; access to antimicrobials in animals; use of antimicrobials in humans; use of antimicrobials in animals; and disposal of antimicrobials. Community members mainly accessed antimicrobials for humans from public health facilities such as government health centres, as well as private facilities, including drug shops and clinics. Antimicrobials for animals were obtained from veterinary practitioners and drug shops (both for humans and veterinary). Examples of inappropriate use of antimicrobials in both humans and animals was evident, such as sharing antibiotics among household members, and giving human-prescribed antimicrobials to food-producing animals as growth promoters. While some CHWs returned unused antimicrobials to public health facilities for proper disposal, community members mainly disposed of antimicrobials with general household waste including dumping in rubbish pits.

Conclusions

There is a need to increase awareness among the population on proper access, use and disposal of antimicrobials for both humans and animals. Development of a drug disposal system at community level would facilitate improved waste management of antimicrobials. Together, these measures would help prevent the rate of progression of AMR in communities.
Role of serum Nogo-B as a biomarker for diagnosis of chronic liver diseases and its severity
Authors: Fouad Ayman , Aref Wael , Elshenawy Ahmed , Hanafi Hadeel M. , Attallah Khaled M. , Alnaggar Alshaimaa Rezk L. R.
Published: August 2021

Background

Nogo-B is one of the members of the reticulon family. Nogo-B influences the proliferation of the hepatic stellate cells inducing liver fibrotic changes. We aimed at measuring the serum levels of Nogo-B in patients with chronic liver disease (CLD) with different etiologies. Ninety subjects were included, 18 of them were normal healthy individuals and 72 had liver disease (fibrosis/cirrhosis) with different etiologies: post-hepatitis C infection, post-hepatitis B infection, NASH, and autoimmune hepatitis. Serum Nogo-B was assessed using ELISA. Patients were subdivided according to the Child-Pugh score into 3 groups: group 1—Child A (24 patients); group 2—Child B (24 patients); and group 3—Child C (24 patients).

Results

Serum Nogo-B levels were found to be significantly higher in patients (1477.92 ± 1113.50) when compared with healthy control (301.28 ± 180.87) (p < 0.001). There was a statistically significant difference in serum Nogo-B level between the three sub-groups of patients (p < 0.001). A positive correlation was found between serum Nogo-B and MELD score (r = 0.46, p-value < 0.001). However, there was no correlation found between Nogo-B and FIB-4 index or APRI score. There was a significant positive correlation between serum Nogo-B level and coagulation profile and serum bilirubin. An inverse correlation was found between serum Nogo-B with serum albumin. A ROC curve was done to examine the validity of Nogo-B in the diagnosis of liver cirrhosis, and the area under the curve was found to be 0.979, a cutoff value of 600 with a sensitivity of 97.2% and a specificity of 94.4% (p-value < 0.001).

Conclusion

Nogo-B had a high value in the identification of patients with any severity of CLD. There is a highly significant correlation between Nogo-B and the synthetic function of the liver; it could be used as a measure of hepatic functional reserve.
Scientific and clinical implications of genetic and cellular heterogeneity in uveal melanoma
Authors: de Lange Mark J. , Nell Rogier J. , van der Velden Pieter A.
Published: August 2021

Here, we discuss the presence and roles of heterogeneity in the development of uveal melanoma. Both genetic and cellular heterogeneity are considered, as their presence became undeniable due to single cell approaches that have recently been used in uveal melanoma analysis. However, the presence of precursor clones and immune infiltrate in uveal melanoma have been described as being part of the tumour already decades ago. Since uveal melanoma grow in the corpus vitreous, they present a unique tumour model because every cell present in the tumour tissue is actually part of the tumour and possibly plays a role. For an effective treatment of uveal melanoma metastasis, it should be clear whether precursor clones and normal cells play an active role in progression and metastasis. We propagate analysis of bulk tissue that allows analysis of tumour heterogeneity in a clinical setting.
Biosimilar Use in Breast Cancer Treatment: A National Survey of Brazilian Oncologists' Opinions, Practices, and Concerns
Authors: Resende Heloísa M. , Ladislau Leandro , Cardoso Ana Carolina F. , Brandão Juliana Dinéia P. , Assis Biazi R. , Cardoso Paola , Marassi Pedro Henrique A. , Castilho Vivienne
Published: August 2021

PURPOSE

Breast cancer is the most common malignancy in Brazilian women, with 66,280 new cases in 2020 (with 20% overexpressing human epidermal growth factor receptor 2 [HER2]). The trastuzumab biosimilar was the first oncology biosimilar approved in Brazil for HER2-positive breast cancer treatment. This study aimed to assess the current level of knowledge of biosimilars, comfort of use, extrapolation indications, and switching of practices among oncologists in Brazil.

METHODS

A 24-question survey was developed using an online platform that sought information regarding responders' characteristics and use of biosimilars. The survey analyzed the basic knowledge of biosimilars, trastuzumab biosimilars, level of comfort with extrapolation, switching treatment regimens, and opinions concerning the cost of HER2-positive breast cancer therapy. Data were collected between July and September 2019 and included 144 oncologists from five Brazilian regions.

RESULTS

In total, 95% of respondents could identify the most appropriate definition of biosimilars and 96% felt comfortable prescribing trastuzumab biosimilars. Although 63% of respondents would use the biosimilar in all settings wherein the reference biologic was approved, 35% would use the biosimilar for cases involving metastatic disease. Although 82% of oncologists were in favor of switching from a reference biologic to a biosimilar, 18% would avoid switching regimens. The lack of studies detailing switching to other regimens and the correct timing to switch was the major concern. The cost of HER2 therapy was a significant concern for most oncologists.

CONCLUSION

Oncologists demonstrated a high level of knowledge of biosimilars and encouraging levels of prescriber use; however, extrapolation and switching treatment regimens are barriers to the effective use of biosimilars in cancer treatment. Efforts should be concentrated on strategies involving medical education programs on biosimilars.
Is there any Nambu monopolium out there?
Authors: Azevedo D. O. R. , Bispo M. L. , Del Cima O. M. , Franco D. H. T. , Pereira A. R.
Published: August 2021

Magnetic monopoles have been a subject of study for more than a century since the first ideas by A. Vaschy and P. Curie, circa 1890. In 1974, Y. Nambu proposed a model for magnetic monopoles exploring a parallelism between the broken symmetry Higgs and the superconductivity Ginzburg-Landau theories in order to describe the pions quark-antiquark confinement states. There, Nambu described an energetic string where its end points behave like two magnetic monopoles with opposite magnetic charges —quark and antiquark. Consequently, not only the interaction among monopole and antimonopole, mediated by a massive vector boson (Yukawa potential), but also the energetic string (linear potential) contribute to the effective interaction potential. We propose here a monopole-antimonopole non-confining attractive interaction of the Nambu type, and then investigate the formation of bound states, the monopolium. Some necessary conditions for the existence of bound states to be fulfilled by the proposed Nambu-type potential, Kato weakness, Setô and Bargmann conditions, are verified. In the following, ground-state energies are estimated for a variety of monopolium reduced mass, from 102 MeV to 102 TeV, and Compton interaction lengths, from

am to

pm, where discussion about non-relativistic and relativistic limits validation is carried out.

Dedicated to the memory of Dr. César Augusto Parga Rodrigues (1939–2021).
Catch-up Growth and Discontinuation of Fludrocortisone Treatment in Aldosterone Synthase Deficiency
Authors: Gurpinar Tosun Busra , Kendir Demirkol Yasemin , Seven Menevse Tuba , Kaygusuz Sare Betul , Ozbek Mehmet Nuri , Altincik Selda Ayca , Mammadova Jamala , Cayir Atilla , Doger Esra , Bayramoglu Elvan , Nalbantoglu Ozlem , Yesiltepe Mutlu Gul , Aghayev AghaRza , Turan Serap , Bereket Abdullah , Guran Tulay
Published: August 2021

Background

Aldosterone synthase deficiency (ASD) caused by mutations in the CYP11B2 gene is characterized by isolated mineralocorticoid deficiency. Data are scarce regarding clinical and biochemical outcomes of the disease in the follow-up.

Objective

Assessment of the growth and steroid profiles of patients with ASD at the time of diagnosis and after discontinuation of treatment.

Design and method

Children with clinical diagnosis of ASD were included in a multicenter study. Growth and treatment characteristics were recorded. Plasma adrenal steroids were measured using liquid chromatography-mass spectrometry. Genetic diagnosis was confirmed by CYP11B2 gene sequencing and in silico analyses.

Results

Sixteen patients from 12 families were included (8 females; median age at presentation: 3.1 months, range: 0.4 to 8.1). The most common symptom was poor weight gain (56.3%). Median age of onset of fludrocortisone treatment was 3.6 months (range: 0.9 to 8.3). Catch-up growth was achieved at median 2 months (range: 0.5 to 14.5) after treatment. Fludrocortisone could be stopped in 5 patients at a median age of 6.0 years (range: 2.2 to 7.6). Plasma steroid profiles revealed reduced aldosterone synthase activity both at diagnosis and after discontinuation of treatment compared to age-matched controls. We identified 6 novel (p.Y195H, c.1200 + 1G > A, p.F130L, p.E198del, c.1122-18G > A, p.I339_E343del) and 4 previously described CYP11B2 variants. The most common variant (40%) was p.T185I.

Conclusions

Fludrocortisone treatment is associated with a rapid catch-up growth and control of electrolyte imbalances in ASD. Decreased mineralocorticoid requirement over time can be explained by the development of physiological adaptation mechanisms rather than improved aldosterone synthase activity. As complete biochemical remission cannot be achieved, a long-term surveillance of these patients is required.
Network Analyses Reveal Negative Link Between Changes in Adipose Tissue GDF15 and BMI During Dietary-induced Weight Loss
Authors: Imbert Alyssa , Vialaneix Nathalie , Marquis Julien , Vion Julie , Charpagne Aline , Metairon Sylviane , Laurens Claire , Moro Cedric , Boulet Nathalie , Walter Ondine , Lefebvre Grégory , Hager Jörg , Langin Dominique , Saris Wim H M , Astrup Arne , Viguerie Nathalie , Valsesia Armand
Published: August 2021

Context

Adipose tissue (AT) transcriptome studies provide holistic pictures of adaptation to weight and related bioclinical settings changes.

Objective

To implement AT gene expression profiling and investigate the link between changes in bioclinical parameters and AT gene expression during 3 steps of a 2-phase dietary intervention (DI).

Methods

AT transcriptome profiling was obtained from sequencing 1051 samples, corresponding to 556 distinct individuals enrolled in a weight loss intervention (8-week low-calorie diet (LCD) at 800 kcal/day) followed with a 6-month ad libitum randomized DI. Transcriptome profiles obtained with QuantSeq sequencing were benchmarked against Illumina RNAseq. Reverse transcription quantitative polymerase chain reaction was used to further confirm associations. Cell specificity was assessed using freshly isolated cells and THP-1 cell line.

Results

During LCD, 5 modules were found, of which 3 included at least 1 bioclinical variable. Change in body mass index (BMI) connected with changes in mRNA level of genes with inflammatory response signature. In this module, change in BMI was negatively associated with changes in expression of genes encoding secreted protein (GDF15, CCL3, and SPP1). Through all phases of the DI, change in GDF15 was connected to changes in SPP1, CCL3, LIPA and CD68. Further characterization showed that these genes were specific to macrophages (with LIPA, CD68 and GDF15 expressed in anti-inflammatory macrophages) and GDF15 also expressed in preadipocytes.

Conclusion

Network analyses identified a novel AT feature with GDF15 upregulated with calorie restriction induced weight loss, concomitantly to macrophage markers. In AT, GDF15 was expressed in preadipocytes and macrophages where it was a hallmark of anti-inflammatory cells.
Sobp modulates the transcriptional activation of Six1 target genes and is required during craniofacial development
Authors: Tavares Andre L. P. , Jourdeuil Karyn , Neilson Karen M. , Majumdar Himani D. , Moody Sally A.
Published: August 2021

Branchio-oto-renal syndrome (BOR) is a disorder characterized by hearing loss, and craniofacial and/or renal defects. Variants in the transcription factor Six1 and its co-factor Eya1, both of which are required for otic development, are linked to BOR. We previously identified Sobp as a potential Six1 co-factor, and SOBP variants in mouse and humans cause otic phenotypes; therefore, we asked whether Sobp interacts with Six1 and thereby may contribute to BOR. Co-immunoprecipitation and immunofluorescence experiments demonstrate that Sobp binds to and colocalizes with Six1 in the cell nucleus. Luciferase assays show that Sobp interferes with the transcriptional activation of Six1+Eya1 target genes. Experiments in Xenopus embryos that either knock down or increase expression of Sobp show that it is required for formation of ectodermal domains at neural plate stages. In addition, altering Sobp levels disrupts otic vesicle development and causes craniofacial cartilage defects. Expression of Xenopus Sobp containing the human variant disrupts the pre-placodal ectoderm similar to full-length Sobp, but other changes are distinct. These results indicate that Sobp modifies Six1 function and is required for vertebrate craniofacial development, and identify Sobp as a potential candidate gene for BOR.
Local DNA synthesis is critical for DNA repair during oocyte maturation
Authors: Singh Ajay K. , Kumar S. Lava , Beniwal Rohit , Mohanty Aradhana , Kushwaha Bhawna , Rao H. B. D. Prasada
Published: August 2021

Mammalian oocytes can be very long-lived cells and thereby are very likely to encounter DNA damage during their lifetime. Defective DNA repair may result in oocytes that are developmentally incompetent or give rise to progeny with congenital disorders. During oocyte maturation, damaged DNA is repaired primarily by non-homologous end joining (NHEJ) or homologous recombination (HR). Although these repair pathways have been studied extensively, the associated DNA synthesis is poorly characterized. Here, using porcine oocytes, we demonstrate that the DNA synthesis machinery is present during oocyte maturation and dynamically recruited to sites of DNA damage. DNA polymerase δ is identified as being crucial for oocyte DNA synthesis. Furthermore, inhibiting synthesis causes DNA damage to accumulate and delays the progression of oocyte maturation. Importantly, inhibition of the spindle assembly checkpoint (SAC) bypassed the delay of oocyte maturation caused by DNA synthesis inhibition. Finally, we found that ∼20% of unperturbed oocytes experienced spontaneously arising damage during maturation. Cumulatively, our findings indicate that oocyte maturation requires damage-associated DNA synthesis that is monitored by the SAC.

This article has an associated First Person interview with the first author of the paper.
Practical Recommendations for High-Intensity Interval Training for Adults with Cardiovascular Disease
Authors: Way Kimberley L. , Terada Tasuku , O’Neill Carley D. , Vidal-Almela Sol , Keech Andrew , Reed Jennifer L.
Published: August 2021

Apply It!

• High-intensity interval training (HIIT) can be implemented safely in adults with cardiovascular disease (CVD) after a graded exercise test assessing exercise responses at a high intensity (e.g., to 85% heart rate peak [HRpeak] or a rating of perceived exertion [RPE] of 15).

• Always involve the patient in the decision-making process for selecting the mode of exercise to perform HIIT to increase adherence, compliance, and enjoyment to the exercise program.

• Given the low exercise tolerance that is typically experienced by patients with CVD, short duration high-intensity bouts (e.g., 30 seconds to 1 minute) may be necessary to increase exercise tolerance and self-efficacy. Active or passive recovery interspersed between high-intensity intervals should be equal to or greater than the duration of the high-intensity intervals. Passive recoveries should be avoided if a person experiences vasovagal symptoms/events.
Introduction to High-Intensity Interval Training and Chronic Diseases
Authors: Fountaine Charles J.
Published: August 2021

Apply It!

From this article, the reader will be introduced to this specially themed issue of ACSM’s Health & Fitness Journal
® on high intensity interval training and chronic disease. The reader also will be made aware of the terms and definitions used throughout this themed issue.