bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms and pathways to impact in public health research: a preliminary analysis of research funded by the National Institute for Health Research (NIHR)
Authors: Boulding Harriet , Kamenetzky Adam , Ghiga Ioana , Ioppolo Becky , Herrera Facundo , Parks Sarah , Manville Catriona , Guthrie Susan , Hinrichs-Krapels Saba
Published: February 2020

Background

The mechanisms and pathways to impacts from public health research in the UK have not been widely studied. Through the lens of one funder (NIHR), our aims are to map the diversity of public health research, in terms of funding mechanisms, disciplinary contributions, and public health impacts, identify examples of impacts, and pathways to impact that existing reporting mechanisms may not otherwise have captured, and provide illustrations of how public health researchers perceive the generation of non-academic impact from their work.

Methods

A total of 1386 projects were identified as ‘public health research’ by the NIHR and listed in the NIHR Public Health Overview database (2000–2016). From these, a subset of 857 projects were matched as potentially having begun reporting impacts via an external data-gathering platform (Researchfish). Data on the 857 projects were analyzed quantitatively, and nine projects were selected to investigate further through semi-structured interviews with principal investigators. Two workshops took place to validate emerging and final findings and facilitate analysis.

Results

In addition to the NIHR School for Public Health Research and the NIHR Public Health Research Programme, 89% of projects contained in the NIHR Public Health Overview portfolio as ‘public health research’ are funded via other NIHR research programmes, suggesting significant diversity in disciplines contributing to public health research and outcomes. The pathways to impact observed in our in-depth case studies include contributing to debates on what constitutes appropriate evidence for national policy change, acknowledging local ‘unintended’ impacts, building trusted relationships with stakeholders across health and non-health sectors and actors, collaborating with local authorities, and using non-academic dissemination channels.

Conclusions

Public health as a discipline contributes substantially to impact beyond academia. To support the diversity of these impacts, we need to recognise localized smaller-scale impacts, and the difference in types of evidence required for community and local authority-based impacts. This will also require building capacity and resources to enable impact to take place from public health research. Finally, support is required for engagement with local authorities and working with non-health sectors that contribute to health outcomes.
Discharge outcomes among elderly patients undergoing emergency abdominal surgery: registry study of discharge data from Irish public hospitals
Authors: McCann Aisling , Sorensen Jan , Nally Deirdre , Kavanagh Dara , McNamara Deborah A.
Published: February 2020

Background

Intra-abdominal emergency surgery is associated with high mortality risk and long length of hospital stay. The objective of this study was to explore variations in surgery rates, the relationship between admission source and discharge destination, and whether the postoperative length of stay was related to nursing home capacity in Irish counties.

Methods

Data on emergency hospital episodes for 2014–18 for patients aged over 65 years with a primary abdominal procedure code were obtained from the National Quality Assurance Improvement System. Data on population and nursing home capacity were obtained from the Central Statistics Office and the Health Information and Quality Authority. Episode rates per 100,000 were estimated for sex and age groups and compared between 26 Irish counties. The association between admission source and discharge destination was explored in terms episode numbers, length of stay and mortality. A negative binomial regression model estimated casemix adjusted excess post-operative length of stay. The correlation between excess post-operative length of stay and nursing home capacity was explored by linear regression.

Results

Overall, 4951 hospital episodes were included. The annual surgery rate ranged from 100 episodes per 100,000 65–69 years old to 250 per 100,000 85–89 year old men. 90% of the episodes were admitted from patients’ home. Four in five of these patients returned to their home while 12.7% died at hospital. The proportion of episodes where patients returned to their home reduced to two in five for those aged 85–89 years. The post-operative length of stay was 13.6 days longer (p < 0.01) for episodes admitted from home and discharged to nursing home in comparison with episodes discharged home. A negative association (p = 0.08) was found between excess post-operative length of stay and county-level nursing home capacity.

Conclusions

This study provides relevant information to support informed consent to surgery for patients and clinicians and to improve the provision of care to older patients presenting with intra-abdominal emergencies.
NASCITA Italian birth cohort study: a study protocol
Authors: Pansieri Claudia , Clavenna Antonio , Pandolfini Chiara , Zanetti Michele , Calati Maria Grazia , Miglio Daniela , Cartabia Massimo , Zanetto Federica , Bonati Maurizio
Published: February 2020

Background

Young children’s healthy development depends on nurturing care, which ensures health, nutrition, responsive caregiving, safety and security, and early learning. Infancy and childhood are characterized by rapid growth and development, and these two factors contribute largely to determining health status and well-being across the lifespan. Identification of modifiable risk factors and prognostic factors during the critical periods of life will contribute to the development of effective prevention and intervention strategies.

The NASCITA (NAscere e creSCere in ITAlia) study was created to evaluate physical, cognitive, and psychological development, health status and health resource utilization during the first six years of life in a cohort of newborns, and to evaluate potential associated factors.

Methods

NASCITA is an ongoing, dynamic, prospective, population-based birth cohort study of an expected number of more than 5000 newborns who will be recruited in 22 national geographic clusters starting in 2019. It was designed to follow children from birth to school entry age for a wide range of determinants, disorders, and diseases. Recruitment of the newborns (and their parents) will take place during the first routine well-child visit, which takes place at the office of the pediatrician assigned to them by the local health unit of residence, and which is scheduled for all newborns born in Italy within the first 45 days of their life.

Data will be web-based and collected by the family pediatricians during each of the 7 standard well-child visits scheduled for all children during their first 6 years of life. Information on every contact with the enrolled children in addition to these prescheduled visits will be also recorded.

Discussion

The NASCITA cohort study provides a framework in which children are followed from birth to six-years of age. NASCITA will broaden our understanding of the contribution of early-life factors to infant and child health and development. NASCITA provides opportunities to initiate new studies, also experimental ones, in parts of the cohort, and will contribute relevant information on determinants and health outcomes to policy and decision makers. Cohort details can be found on https://coortenascita.marionegri.it.

Trial registration

Clinicaltrials.gov: NCT03894566.

Ethics committee approval: 6 February 2019, Verbale N 59.
Application of the adenosine triphosphate sensitivity assay in infantile vascular anomalies
Authors: Li Li , Yang Bin , Wei Li , Zhang Bin , Han Xiao-feng , Xu Zi-gang , Ma Lin
Published: February 2020

Background

The term vascular anomalies include various vascular tumors and vascular malformations, among them infantile hemangiomas and capillary malformations are the most well-known associated diseases in early ages. Multiple drugs have been introduced for intervention, but susceptibility test in vitro were scarcely reported.

Objective

To evaluate the inhibition effect of different drugs by adenosine triphosphate sensitivity assay in vitro before the treatment of infantile hemangiomas and capillary malformations.

Methods

Specimens were selected from 5 cases of infantile hemangiomas and 11 cases of capillary malformations. Propranolol, rapamycin, sildenafil and itraconazole were tested for their growth inhibition effect by using the adenosine triphosphate sensitivity assay.

Results

Propranolol demonstrated inhibitory effects on infantile hemangiomas cells. Rapamycin and itraconazole both showed inhibitory effects on infantile hemangiomas cells and capillary malformations cells. Sildenafil has no growth inhibitory effect on infantile hemangiomas cells or capillary malformations cells.

Conclusion

Adenosine triphosphate sensitivity assay is a sensitive and useful testing method before the management of vascular anomalies, and individualized medication suggestions for the choice of therapeutic drugs were offered based on the testing result and together with a comprehensive evaluation of each infant.
A simple angle-measuring instrument for measuring cemented stem anteversion during total hip arthroplasty
Authors: Mitsutake Ryo , Tanino Hiromasa , Nishida Yasuhiro , Higa Masaru , Ito Hiroshi
Published: February 2020

Background

During total hip arthroplasty (THA), the accurate placement of the femoral components is an important determinant of the success of the procedure. This study assessed the accuracy of cemented stem placement using a new angle-measuring instrument. The primary objective was to investigate the accuracy of the intraoperative measurements of cemented stem anteversion obtained using the angle-measuring instrument. Our secondary objective was to evaluate the accuracy of stem positioning performed using the angle-measuring instrument.

Methods

We compared the intraoperative stem anteversion measurements obtained using the angle-measuring instrument with postoperative stem anteversion measurements obtained using computed tomography in 149 hips (measurement accuracy). We also compared the target angle and postoperative stem anteversion in 105 hips (implantation accuracy).

Results

The mean amount of intraoperative stem anteversion was 37.9° ± 10.1°, and the mean amount of postoperative stem anteversion was 37.0° ± 10.4°. The mean measurement accuracy was 0.9° ± 6.1°, and the absolute measurement accuracy was 4.9° ± 3.7°. The correlation coefficient for the relationship between the intraoperative and postoperative stem anteversion measurements was 0.824 (p = 0.000). The mean amount of target angle was 37.4° ± 7.6°, and the mean amount of postoperative stem anteversion was 35.9° ± 9.1°. The mean implantation accuracy was 1.4° ± 5.6°, and the mean absolute implantation accuracy was 4.3° ± 3.6°. The correlation coefficient for the relationship between the target angle and postoperative stem anteversion was 0.795 (p = 0.000).

Conclusions

The angle-measuring instrument measured intraoperative stem anteversion accurately, and cemented stem was implanted accurately during THA with the angle-measuring instrument.
Non-significant association between − 330 T/G polymorphism in interleukin-2 gene and chronic periodontitis: findings from a meta-analysis
Authors: da Silva Felipe Rodolfo Pereira , Galeno Juliana Gomes , Leal Alessandro Luiz Araújo Bentes , Koga Reyce Santos , Batista Nayana Yared , da Conceição Furtado Silvânia , Vasconcelos Daniel Fernando Pereira , Carvalho Marcelo Diniz , Barcellos José Fernando Marques
Published: February 2020

Background

Chronic periodontitis (CP) is an immune-inflammatory disease that promotes tissue damage around the teeth. Among the several inflammatory mediators that orchestrate the periodontitis, there is the interleukin (IL)-2. Genetic variations in IL2 gene may be associated with the risk and severity of the disease. Contrary results are available in the literature with inconclusive findings and none meta-analysis to gather these data.

Methods

A literature search was performed for studies published before June 11, 2019 in diverse scientific and educational databases. The data was extracted by two investigators and the statistical evaluation was performed by Review Manager statistical program with heterogeneity (I2) and Odds Ratio (OR) with 95% of Confidence Intervals (CI) calculations and a sensitive analysis to assess the accuracy of the obtained results. The publication bias was evaluated by Begg’ and Egger’s test with Comprehensive meta-analysis software. The value of P < 0.05 was considered as significant.

Results

Five studies were identified in diverse ethnical groups with 1425 participants. The − 330 T/G polymorphism in IL2 gene was not significantly associated with CP in allelic evaluation (P > 0.05) as well as in the genotypic comparisons (P = 0.15). The Begg’s test and the linear regression Egger’s test did not show any evidence of publication bias risk (P > 0.05) which was corroborated by the absence of obvious asymmetry in Funnel plot graphic.

Conclusions

This meta-analysis showed a non-significant association between − 330 T/G polymorphism in IL2 gene and CP in any allelic evaluation.
Structural racism in precision medicine: leaving no one behind
Authors: Geneviève Lester Darryl , Martani Andrea , Shaw David , Elger Bernice Simone , Wangmo Tenzin
Published: February 2020

Background

Precision medicine (PM) is an emerging approach to individualized care. It aims to help physicians better comprehend and predict the needs of their patients while effectively adopting in a timely manner the most suitable treatment by promoting the sharing of health data and the implementation of learning healthcare systems. Alongside its promises, PM also entails the risk of exacerbating healthcare inequalities, in particular between ethnoracial groups. One often-neglected underlying reason why this might happen is the impact of structural racism on PM initiatives. Raising awareness as to how structural racism can influence PM initiatives is paramount to avoid that PM ends up reproducing the pre-existing health inequalities between different ethnoracial groups and contributing to the loss of trust in healthcare by minority groups.

Main body

We analyse three nodes of a process flow where structural racism can affect PM’s implementation. These are: (i) the collection of biased health data during the initial encounter of minority groups with the healthcare system and researchers, (ii) the integration of biased health data for minority groups in PM initiatives and (iii) the influence of structural racism on the deliverables of PM initiatives for minority groups. We underscore that underappreciation of structural racism by stakeholders involved in the PM ecosystem can be at odds with the ambition of ensuring social and racial justice. Potential specific actions related to the analysed nodes are then formulated to help ensure that PM truly adheres to the goal of leaving no one behind, as endorsed by member states of the United Nations for the 2030 Agenda for Sustainable Development.

Conclusion

Structural racism has been entrenched in our societies for centuries and it would be naïve to believe that its impacts will not spill over in the era of PM. PM initiatives need to pay special attention to the discriminatory and harmful impacts that structural racism could have on minority groups involved in their respective projects. It is only by acknowledging and discussing the existence of implicit racial biases and trust issues in healthcare and research domains that proper interventions to remedy them can be implemented.
The development of the evidence-based SDMMCC intervention to improve shared decision making in geriatric outpatients: the DICO study
Authors: Pel-Littel Ruth E. , van Weert Julia C. M. , Minkman Mirella M. , Scholte op Reimer Wilma J. M. , van de Pol Marjolein H. , Buurman Bianca M.
Published: February 2020

Background

Shared decision making (SDM) contributes to personalized decisions that fit the personal preferences of patients when choosing a treatment for a condition. However, older adults frequently face multiple chronic conditions (MCC). Therefore, implementing SDM requires special features. The aim of this paper is to describe the development of an intervention to improve SDM in older adults with MCC.

Methods

Following the Medical Research Council framework for developing complex interventions, the SDMMCC intervention was developed step-wise. Based on a literature review and empirical research in a co-creation process with end users, we developed training for geriatricians and a preparatory tool for older patients with MCC and informal caregivers. After assessing feasibility, the intervention was implemented in a pilot study (N = 108) in two outpatient geriatric clinics of an academic and a non-academic teaching hospital in Amsterdam, the Netherlands.

Results

Key elements of the training for geriatricians include developing skills to involve older adults with MCC and informal caregivers in SDM and following the six-step ‘Dynamic model for SDM with frail older patients’, as well as learning how to explore personal goals related to quality of life and how to form a partnership with the patient and the informal caregiver. Key elements of the preparatory tool for patients include an explicit invitation to participate in SDM, nomination that the patient’s own knowledge is valuable, invitation to form a partnership with the geriatrician, encouragement to share information about daily and social functioning and exploration of possible goals. Furthermore, the invitation of informal caregivers to share their concerns was also a key element.

Conclusions

Through a process of co-creation, both training for geriatricians and a preparatory tool for older adults and their informal caregivers were developed, tailored to the needs of the end users and based on the ‘Dynamic model of SDM with frail older patients’.
Echocardiographic evidence of left ventricular untwisting-filling interplay
Authors: Hodzic Amir , Garcia Damien , Saloux Eric , Ribeiro Paula A. B. , Ethier Amélie , Thomas James D. , Milliez Paul , Normand Hervé , Tournoux Francois
Published: February 2020

Background

Left ventricular untwisting generates an early diastolic intraventricular pressure gradient (DIVPG) than can be quantified by echocardiography. We sought to confirm the quantitative relationship between peak untwisting rate and peak DIVPG in a large adult population.

Methods

From our echocardiographic database, we retrieved all the echocardiograms with a normal left ventricular ejection fraction, for whom color Doppler M-Mode interrogation of mitral inflow was available, and left ventricular untwisting rate was measurable using speckle tracking. Standard indices of left ventricular early diastolic function were assessed by Doppler (peaks E, e’ and Vp) and speckle tracking (peak strain rate Esr). Load dependency of DIVPG and untwisting rate was evaluated using a passive leg raising maneuver.

Results

We included 154 subjects, aged between 18 to 77 years old, 63% were male. Test-retest reliability for color Doppler-derived DIVPG measurements was good, the intraclass correlation coefficients were 0.97 [0.91–0.99] and 0.97 [0.67–0.99] for intra- and inter-observer reproducibility, respectively. Peak DIVPG was positively correlated with peak untwisting rate (r = 0.73, P <  0.001). On multivariate analysis, peak DIVPG was the only diastolic parameter that was independently associated with untwisting rate. Age and gender were the clinical predictive factors for peak untwisting rate, whereas only age was independently associated with peak DIVPG. Untwisting rate and DIVPG were both load-dependent, without affecting their relationship.

Conclusions

Color Doppler-derived peak DIVPG was quantitatively and independently associated with peak untwisting rate. It thus provides a reliable flow-based index of early left ventricular diastolic function.
c-Met is expressed by highly autoreactive encephalitogenic CD8+ cells
Authors: Benkhoucha Mahdia , Senoner Isis , Lalive Patrice H.
Published: February 2020

Background

CD8+ T lymphocytes are critical mediators of neuroinflammatory diseases. Understanding the mechanisms that govern the function of this T cell population is crucial to better understanding central nervous system autoimmune disease pathology. We recently identified a novel population of highly cytotoxic c-Met-expressing CD8+ T lymphocytes and found that hepatocyte growth factor (HGF) limits effective murine cytotoxic T cell responses in cancer models. Here, we examined the role of c-Met-expressing CD8+ T cells by using a MOG35–55 T cell-mediated EAE model.

Methods

Mice were subcutaneously immunized with myelin oligodendrocyte glycoprotein peptide (MOG)35–55 in complete Freund’s adjuvant (CFA). Peripheral and CNS inflammation was evaluated at peak disease and chronic phase, and c-Met expression by CD8 was evaluated by flow cytometry and immunofluorescence. Molecular, cellular, and killing function analysis were performed by real-time PCR, ELISA, flow cytometry, and killing assay.

Results

In the present study, we observed that a fraction of murine effector CD8+ T cells expressed c-Met receptor (c-Met+CD8+) in an experimental autoimmune encephalitis (EAE) model. Phenotypic and functional analysis of c-Met+CD8+ T cells revealed that they recognize the encephalitogenic epitope myelin oligodendrocyte glycoprotein37–50. We demonstrated that this T cell population produces higher levels of interferon-γ and granzyme B ex vivo and that HGF directly restrains the cytolytic function of c-Met+CD8+ T cells in cell-mediated cytotoxicity reactions

Conclusions

Altogether, our findings suggest that the HGF/c-Met pathway could be exploited to modulate CD8+ T cell-mediated neuroinflammation.
Influenza vaccination in early Alzheimer’s disease rescues amyloidosis and ameliorates cognitive deficits in APP/PS1 mice by inhibiting regulatory T cells
Authors: Yang Yunjie , He Zitian , Xing Zhiwei , Zuo Zejie , Yuan Lifang , Wu Yingying , Jiang Mei , Qi Fangfang , Yao Zhibin
Published: February 2020

Background

Alzheimer’s disease (AD) is a neurodegenerative disorder strongly correlated with a dysfunctional immune system. Our previous results demonstrated that inactivated influenza vaccine (IIV) facilitates hippocampal neurogenesis and blocks lipopolysaccharide (LPS)-induced cognitive impairment. However, whether IIV improves cognitive deficits in an AD mouse model remains unclear. In addition, early interventions in AD have been encouraged in recent years. Here, we investigated whether IIV immunization at the preclinical stage of AD alters the brain pathology and cognitive deficits in an APP/ PS1 mouse model.

Methods

We assessed spatial learning and memory using Morris water maze (MWM). The brain β-amyloid (Aβ) plaque burden and activated microglia were investigated by immunohistochemistry. Furthermore, flow cytometry was utilized to analyze the proportions of Treg cells in the spleen. A cytokine antibody array was performed to measure the alteration of cytokines in the brain and peripheral immune system.

Results

Five IIV immunizations activated microglia, reduced the Aβ burden and improved the cognitive impairment. Simultaneously, the IIV-induced immune response broke peripheral immunosuppression by reducing Foxp3+ regulatory T cell (Treg) activities, whereas the restoration of Treg level in the periphery using all-trans retinoic acid (ATRA) blunted the protective effects of IIV on Aβ burden and cognitive functions. Interestingly, IIV immunization might increase proinflammatory and anti-inflammatory cytokine expression in the brain of APP/PS1 mice, enhanced microglial activation, and enhanced the clustering and phagocytosis of Aβ, thereby creating new homeostasis in the disordered immune microenvironment.

Conclusions

Altogether, our results suggest that early multiple IIV immunizations exert a beneficial immunomodulatory effect in APP/PS1 mice by breaking Treg-mediated systemic immune tolerance, maintaining the activation of microglia and removing of Aβ plaques, eventually improving cognitive deficits.
Correction to: “I feel myself incomplete, and I am inferior to people”: experiences of Sudanese women living with obstetric fistula in Khartoum, Sudan
Authors: Ahmed Salma A. E. , Thorsen Viva C.
Published: February 2020

Following publication of the original article [1], we have been notified that one of the authors’ names was mentioned twice. Currently the authors are stated as:
20-kHz alternating current stimulation: effects on motor and somatosensory thresholds
Authors: Serrano-Muñoz Diego , Avendaño-Coy Juan , Simón-Martínez Cristina , Taylor Julian , Gómez-Soriano Julio
Published: February 2020

Background

High frequency alternating current (HFAC) stimulation have been shown to produce a peripheral nerve conduction block. Currently, all the studies applying HFAC stimulation in clinical studies, have employed frequencies below 10 kHz. The main aim of this work was to investigate the neuromodulatory effect of transcutaneous 20 kHz stimulation on somatosensory and pain thresholds, and maximal handgrip strength.

Methods

A randomized, crossover, single-blinded, placebo-controlled trial was conducted following recruitment of fourteen healthy volunteers. Transcutaneous stimulation at 20 kHz and sham stimulation were applied over the ulnar and median nerves of fourteen healthy volunteers for 20 min. Maximal handgrip strength (MHS), mechanical detection threshold (MDT) and pressure pain threshold (PPT) were registered prior to, during (15 min), immediately after the end (20 min), and 10 min following stimulation.

Results

The 20 kHz stimulation showed a lower MHS during the stimulation at the 15 min (30.1 kgs SE 2.8) and at 20 min (31.8 kgs, SE 2.8) when compared to sham stimulation (35.1 kgs, SE 3.4; p < 0.001 and 34.2 kgs, SE 3.4; p = 0.03, respectively). The 20 kHz stimulation resulted in a slight increase in MDT at 15 min (0.25 mN; 0.25–2.00) when compared to the sham stimulation (0.25 mN; 0.25–0.25; p = 0.02), and no effects were showed for PPT.

Conclusions

High-frequency stimulation at 20 kHz suggests a partial block of nerve activity. Studies in subjects with neurological disorders characterized by nerve hyperactivity are needed to confirm the clinical impact of this non-invasive electrical stimulation technique.

Trial registration

NCT, NCT02837458. Registered on 12 April 2017.
An assessment of medical students’ proficiency in the diagnosis and management of snakebites: a cross-sectional study from Palestine
Authors: Sulaiman Suha S. , Kharusha Isra K. , Samara Ahmad M. , Al-Jabi Samah W. , Zyoud Sa’ed H.
Published: February 2020

Background

Snakebites are emergent and life-threatening injuries that may require intensive care. Physicians face difficulties in dealing with snakebite injuries due to the knowledge gaps in the diagnosis and management of snakebites. The study aimed to assess medical students’ knowledge about the diagnosis and management of snakebite injuries, as well as their proficiency in first aid methods in case of snakebite and perception regarding snakes and snakebite injuries.

Methods

A cross-sectional study conducted among 200 medical students in their clinical years at An-Najah National University. A questionnaire was developed and distributed among those students. The questionnaire assessed the students’ knowledge regarding the diagnosis and management of snakebites and their attitude regarding snakes and snakebites. The total scores of knowledge were obtained and tested based on the participants’ demographic characteristics using the Kruskal-Wallis test and the Mann-Whitney U test.P-values of < 0.05 were considered to be statistically significant.

Results

The mean age of participating medical students was 22.2 ± 2.4 (year). Half of these medical students were in there final year of study (sixth year). After the analysis was done, we found a knowledge deficit in snakebite diagnosis and management among medical students. The mean knowledge scores regardingVipera palaestinae, signs and symptoms, laboratory investigations, anti-venom, and first aid were 3.8/13, 8.2/16, 6.1/10, 3.6/11 and 8.3/15 respectively for medical students. It was found that medical students in higher years of study had a higher knowledge of laboratory investigation, and males were more knowledgeable in the correct way for first aid methods than females (p < 0.036).

Conclusions

The level of knowledge regarding the diagnosis and management of snakebites was not good enough among most of the students. In order to improve their knowledge, snakebite diagnosis and management should be introduced and focused on in medical curriculum. Also, formal first aid training classes for medical students should be introduced in order to teach them the correct and updated methods of first aid as they will be the future health care providers and proper first aid will effectively decrease morbidity and mortality of snakebites.
Can nasal Staphylococcus aureus screening and decolonization prior to elective total joint arthroplasty reduce surgical site and prosthesis-related infections? A systematic review and meta-analysis
Authors: Zhu Xingyang , Sun Xiaobo , Zeng Yuqing , Feng Wenjun , Li Jie , Zeng Jianchun , Zeng Yirong
Published: February 2020

Background

Nasal Staphylococcus aureus (S. aureus) screening and decolonization has been widely used to reduce surgical site infections (SSIs) prior to total knee and hip arthroplasty (TKA and THA). However, it remains considerably controversial. The aim of this study was to ascertain whether this scheme could reduce SSIs and periprosthetic joint infections (PJIs) following elective primary total joint arthroplasty (TJA).

Methods

A systematic search was performed in MEDLINE, Embase, and the Cochrane Library until October, 2019. Outcomes of interest included SSI, PJI, superficial infection, and different bacterial species that caused infections. Data from eligible studies were then extracted and synthesized. Pooled odds ratios (OR) and 95% confidence intervals (CIs) were calculated. We also performed additional analyses to evaluate whether there were differences in postoperative SSIs caused by S. aureus or other bacteria.

Results

Nine studies were included in our meta-analysis. The pooled data elucidated that nasal S. aureus screening and decolonization dramatically mitigated the risk of SSI, PJI, and superficial infection compared to nondecolonization group. The analysis of bacterial species causing infection also showed that the S. aureus infections postoperative were significantly decreased in the decolonization group. However, there was no statistical difference in the SSI caused by other bacteria between the two groups.

Conclusion

S. aureus screening and decolonization prior to elective primary THA and TKA could significantly decrease the risk of SSI and PJI. However, more robust studies are needed to further evaluate the impact of S. aureus screening and decolonization on infection risk after TJA.
Acute kidney injury after primary total hip arthroplasty: a risk multiplier for complication, mortality, and healthcare utilization
Authors: Singh Jasvinder A. , Cleveland John D.
Published: February 2020

Objective

To assess whether acute kidney injury (AKI) is associated with more complications and higher healthcare utilization in people undergoing primary total hip arthroplasty (THA).

Methods

Using a retrospective cohort study design, we performed multivariable-adjusted logistic regression of the 1998–2014 US National Inpatient Sample data to assess the association of AKI with complications (infection, transfusion, revision, and mortality) and healthcare utilization (total hospital charges, discharge to a rehabilitation facility, length of hospital stay) post-THA. We calculated the odds ratio (OR) and 95% confidence intervals (CI).

Results

Adjusted for age, gender, race, income, underlying diagnosis, medical comorbidity, and the insurance payer, AKI in people who underwent primary THA was associated with significantly higher OR (95% CI) of (1) implant infection, 2.34 (95% CI, 1.87, 2.93); (2) transfusion, 2.46 (95% CI, 2.37, 2.56); (3) revision, 2.54 (95% CI, 2.16, 2.98); (4) death, 8.52 (95% CI, 7.47, 9.73); (5) total hospital charges above the median, 2.29 (95% CI, 1.99, 2.65); (6) discharge to a rehabilitation facility, 2.11 (95% CI, 2.02, 2.20); and (7) hospital stay > 3 days, 4.34 (95% CI, 4.16, 4.53).

Conclusion

Quality improvement initiatives with optimization of the peri-operative care to reduce AKI and subsequently AKI-associated complications and healthcare utilization are needed. Mechanisms of AKI-associated post-THA complications need further examination.
Strong convergence of an inertial iterative algorithm for variational inequality problem, generalized equilibrium problem, and fixed point problem in a Banach space
Authors: Alansari Monairah , Ali Rehan , Farid Mohammad
Published: February 2020

We propose and analyze an inertial iterative algorithm to approximate a common solution of generalized equilibrium problem, variational inequality problem, and fixed point problem in the framework of a 2-uniformly convex and uniformly smooth real Banach space. Further, we study the convergence analysis of our proposed iterative method. Finally, we give application and a numerical example to illustrate the applicability of the main algorithm.
Role of serum biomarkers and transcranial Doppler in predicting cerebral vasospasm after aneurysmal subarachnoid hemorrhage
Authors: Abdelnaseer Maged Mohammad , Nemr Ahmed Abdelkader , Ahmed Sandra Mohammad , Aboul fotouh Alshaimaa M. , Soliman Amro Mohammad Ahmed , El-Fiki Ahmed Abdullah , Osman Safinaz Hassan
Published: February 2020

Background

Aneurysmal subarachnoid hemorrhage (aSAH) can have serious consequences related to vasospasm and delayed cerebral ischemia (DCI). Serum biomarkers have emerged as a promising assessment tool to facilitate earlier diagnosis of cerebral vasospasm (CV) and to identify pre-clinical vessel narrowing.

Objectives

Our aim was to detect the predictive value of serum biomarkers such as von Willebrand factor (vWF), vascular endothelial growth factor (VEGF) and matrix metalloproteinase9 (MMP-9) in CV after aSAH.

Subjects and methods

Thirty five patients with recent aSAH were included. Patients were divided into two groups; 19 patients (CV group) and 16 patients (non-CV group). The CV group was further subdivided into 9 symptomatic (DCI) and 10 asymptomatic patients. All patients underwent transcranial Doppler (TCD) evaluations three times a week for 2 weeks measuring the mean flow velocities. Serum level of vWF, MMP-9, and VEGF were assessed twice (at onset and within 2 weeks).

Results

A statistically significant increase in serum biomarker levels was found in the CV group. Cutoff value for vWF, MMP-9, and VEGF were > 4985 ng/ml, > 495 ng/ml, and > 184 pg/ml, respectively. Statistically significant positive correlations were found between serum levels of biomarkers and degree of vasospasm. No difference was found in the biomarkers between symptomatic CV and asymptomatic CV.

Conclusion

Serum biomarkers are a reliable tool to predict CV following aSAH, their levels reflect the severity of vascular vasospasm, yet, they cannot predict DCI. TCD has a strong role in early detection, monitoring of post subarachnoid vasospasm and successfully capturing asymptomatic DCI.
Improvement in Patient-Reported Outcomes With Intensity-Modulated Radiotherapy (RT) Compared With Standard RT: A Report From the NRG Oncology RTOG 1203 Study
Authors: Yeung Anamaria R. , Pugh Stephanie L. , Klopp Ann H. , Gil Karen M. , Wenzel Lari , Westin Shannon N. , Gaffney David K. , Small William , Thompson Spencer , Doncals Desiree E. , Cantuaria Guilherme H.C. , Yaremko Brian P. , Chang Amy , Kundapur Vijayananda , Mohan Dasarahally S. , Haas Michael L. , Kim Yong Bae , Ferguson Catherine L. , Deshmukh Snehal , Bruner Deborah W. , Kachnic Lisa A.
Published: February 2020

PURPOSE

In oncology trials, the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) is the standard tool for reporting adverse events (AEs), but it may underreport symptoms experienced by patients. This analysis of the NRG Oncology RTOG 1203 compared symptom reporting by patients and clinicians during radiotherapy (RT).

PATIENTS AND METHODS

Patients with cervical or endometrial cancer requiring postoperative RT were randomly assigned to standard 4-field RT or intensity-modulated RT (IMRT). Patients completed the 6-item patient-reported outcomes version of the CTCAE (PRO-CTCAE) for GI toxicity assessing abdominal pain, diarrhea, and fecal incontinence at various time points. Patients reported symptoms on a 5-point scale. Clinicians recorded these AEs as CTCAE grades 1 to 5. Clinician- and patient-reported AEs were compared using McNemar’s test for rates > 0%.

RESULTS

Of 278 eligible patients, 234 consented and completed the PRO-CTCAE. Patients reported high-grade abdominal pain 19.1% ( P < .0001), high-grade diarrhea 38.5% ( P < .0001), and fecal incontinence 6.8% more frequently than clinicians. Similar effects were seen between grade ≥ 1 CTCAE toxicity and any-grade patient-reported toxicity. Between-arm comparison of patient-reported high-grade AEs revealed that at 5 weeks of RT, patients who received IMRT experienced fewer GI AEs than patients who received 4-field pelvic RT with regard to frequency of diarrhea (18.2% difference; P = .01), frequency of fecal incontinence (8.2% difference; P = .01), and interference of fecal incontinence (8.5% difference; P = .04).

CONCLUSION

Patient-reported AEs showed a reduction in symptoms with IMRT compared with standard RT, whereas clinician-reported AEs revealed no difference. Clinicians also underreported symptomatic GI AEs compared with patients. This suggests that patient-reported symptomatic AEs are important to assess in this disease setting.
Prostate-directed radiation therapy and overall survival for men with M1a prostate cancer.
Authors: Yang David Dewei , Butler Santino , Muralidhar Vinayak , Mahal Brandon Arvin Virgil , Martin Neil E. , Mouw Kent William , Nguyen Paul L. , King Martin T. , Orio Peter F.
Published: February 2020

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Background: A recent randomized controlled trial demonstrated that radiation therapy to the prostate improves overall survival for men with newly diagnosed metastatic prostate cancer with a low metastatic burden. Most patients in this trial had bony metastases (stage M1b). The benefit of prostate-directed radiation therapy for men with metastases limited to non-regional lymph nodes (stage M1a) is unknown. We investigated the association between prostate-directed radiation therapy and overall survival for men with M1a prostate cancer. Methods: We identified 2,079 men from the National Cancer Database who were newly diagnosed with M1a prostate adenocarcinoma from 2004 through 2014 and had data on the use of androgen deprivation therapy, chemotherapy, and radiation therapy. Median follow-up was estimated using the reverse Kaplan-Meier method. The association between radiation therapy to the prostate and overall survival was examined using multivariable Cox proportional hazards regression analysis. Results: Overall, 12.7% (264) of patients received radiation therapy to the prostate. Median follow-up was 4.6 years (95% confidence interval 4.3-4.8 years). On multivariable analysis, when accounting for the use of androgen deprivation therapy and chemotherapy, Gleason grade group, clinical tumor and nodal stage, and prostate-specific antigen level at diagnosis, the use of radiation therapy to the prostate was associated with a significant improvement in overall survival (adjusted hazard ratio 0.60, 95% confidence interval 0.49-0.74, P<0.001). Adjusted median overall survival was 3.3 years for patients who did not receive radiation therapy to the prostate compared to 5.5 years for patients who did. Conclusions: Similar to newly diagnosed M1b prostate cancer with a low metastatic burden, patients with M1a prostate cancer may also derive a significant overall survival benefit from receiving radiation therapy to the primary prostate tumor. The use of prostate-directed radiation therapy for M1a patients should be further investigated.
Overall survival using radium-223 (Ra223) in metastatic castrate-resistant prostate cancer (mCRPC) patients with and without DNA damage repair (DDR) defects.
Authors: van der Doelen Maarten J. , Isaacsson Velho Pedro , Slootbeek Peter H.J. , Pamidimarri Naga Samhita , Bormann Maren , van Helvert Sjoerd , Kroeze Leonie I. , van Oort Inge M. , Gerritsen Winald R. , Antonarakis Emmanuel S. , Mehra Niven
Published: February 2020

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Background: Ra223 is a therapeutic option for mCRPC patients (pts) with symptomatic bone metastases. DDR-defective prostate cancers, specifically those with homologous recombination deficiency (HRD), accumulate irreparable DNA damage following genotoxic treatment. This study assessed presence or absence of DDR alterations in mCRPC pts treated with Ra223, investigating the effect on efficacy and overall survival (OS). Methods: All pts included were treated with Ra223 and had genomic results from a comprehensive next-generation sequencing panel of DDR genes that directly or indirectly led to HRD, from primary or metastatic tissue. Exclusion criteria were prior platinum-based chemotherapy or treatment with poly-ADP ribose polymerase inhibitors (PARPi). Pts were grouped by presence (DDR+) or absence (DDR-) of pathogenic somatic and/or germline aberrations in DDR genes. Primary endpoint was OS, and secondary endpoints were time to alkaline phosphatase (ALP) progression, time to next systemic therapy and biochemical responses; comparing DDR+ and DDR– groups. Results: 93 pts were included in this two-centre retrospective study. Median age was 68 years. 56% received prior chemotherapy. Baseline characteristics where comparable between DDR status subgroups. 28 (30%) pts had mutations in DDR genes, most frequently occurring in ATM (8.6%), BRCA2 (6.5%), and CDK12 (4.3%) genes. DDR+ pts showed prolonged OS (median 36.3 vs. 17.0 months; HR 2.29; 95% CI 1.21-4.32; P= 0.01). Median time to alkaline phosphatase progression was 6.9 months for DDR+ pts and 5.8 months for DDR- pts (HR 1.48; 95% CI 0.87-2.50; P =0.15), and median time to next systemic therapy was 8.9 months for DDR+ pts and 7.3 months for DDR- pts (HR 1.58; 95% CI 0.94-2.64; P =0.08). A higher proportion of DDR+ pts completed Ra223 therapy (79% vs 47%; P= 0.05). No differences in biochemical (prostate-specific antigen, ALP) responses were seen. Conclusions: Pts harboring deleterious DDR aberrations more commonly completed Ra223, and derived a greater OS benefit. These findings need prospective confirmation, but support combination of Ra223 with PARPi or ATR inhibitors in DDR-defective mCRPC pts.
Surgical management versus combination radiotherapy in Gleason score 9-10 prostate cancer.
Authors: Dee Edward Christopher , King Martin T. , Butler Santino , Yu Zizi , Sha Sybil , Yang David Dewei , Mahal Brandon Arvin Virgil , Mouw Kent William , D'Amico Anthony Victor , Nguyen Paul L. , Muralidhar Vinayak
Published: February 2020

135

Background: For men with Gleason score 9-10 prostate cancer, studies have demonstrated conflicting results on the outcomes from combination radiation therapy (ComboRT) with external beam radiation therapy plus brachytherapy boost versus radical prostatectomy (RP), with or without adjuvant radiation therapy (ART). Differences in patient selection and management may explain some of the disparate outcomes of prior reports. Methods: The Surveillance, Epidemiology, and End Results database identified 10,396 men managed with ComboRT versus RP (+/-ART). Competing-risks regression analysis with treatment propensity adjustment defined hazard ratios (aHR) for prostate cancer-specific mortality (PCSM), controlling for patient-specific demographic factors. To explore the possible effect of patient selection, analyses were conducted before and after excluding men from analysis if they had evidence-based indications for ART (adverse pathology, i.e. pT3-T4 or positive margins) but did not receive it. Results: Median age was 64 years; median follow-up was 69 months. Five-year PCSM was similar between patients treated with RP (with or without ART, regardless of pathologic features, N=8,934) and ComboRT (N=1,462) (6.9% vs 8.1%, aHR=0.94, 95% confidence interval [CI] 0.78–1.13, P=0.51). After excluding RP-treated men with adverse pathology who did not receive ART (N=4,527 excluded), patients treated with RP+/-ART (N=4,407) had improved 5-year PCSM compared with those treated with ComboRT (5.3% vs 8.1%, aHR=0.74, 95% CI 0.60–0.91, P=0.004). Conclusions: For Gleason 9-10 prostate cancer, ComboRT was associated with similar PCSM compared to RP, but risk-tailored surgical management may be associated with superior PCSM.
Circulating tumor cell (CTC) genomic signatures of hormone therapy resistance in men with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Gupta Santosh , Halabi Susan , Kemeny Gabor , Anand Monika , Nanus David M. , Giannakakou Paraskevi , George Daniel J. , Gregory Simon , Armstrong Andrew J.
Published: February 2020

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Background: Men with CTC AR-V7 + mCRPC have very poor outcomes when treated with enzalutamide/abiraterone. However, many men lack AR-V7. Here, we determined whether baseline or post-treatment DNA alterations in CTCs from AR-V7 negative mCRPC men could provide clinical utility in predicting outcomes with these hormonal therapies. Methods: We analyzed whole-genome copy number alterations (CNA) using array-comparative genomic hybridization (aCGH) in CTCs from 48 men (45 baseline and 28 progression), and whole-exome sequencing (WES) from 11 mCRPC men treated with abi/enza, longitudinally, and focused exclusively on AR-V7 negative men (N = 40) by the Epic-AR-V7 nuclear protein assay, and comparing those men who benefit from therapy vs. who do not. Results: We observed broad heterogeneity of CNAs between patients; common genomic alterations included gain in KDM6A (44%), FOXA1 (44%), MYCN (32%), and AR (38%), and loss in BRCA1 (30%) and PTEN (25%). Men who had the clinical benefit to abi/enza (n = 23, median PFS 10 mo) were more likely to have CTCs with genomic gains of ATM, HSD17B4, or PTEN, and loss of BRAF, ABL1, or NKX3-1. Likewise, men who did not benefit from abi/enza (n = 14, median PFS 2.6 mo) had CTCs with more copy number alterations than men who had clinical benefit (median 19.5 vs. 14, p = 0.01), and were enriched for gain of BRCA2, APC, KDM5D, SPARC, MYCN, AR, and CYP11B1, and loss of PTEN, CHD1, PHLPP1, and NCOR2. After progression on abi/enza, we observed clonal evolution of CTCs harboring gain of ATM, FOXA1, KDM6A, CYP11B1, MYC, APC, and NCOR2, and loss of NCOR1, ERG, and RUNX2. Several COSMIC-validated non-synonymous pathogenic exome mutations were detected in progressed or non-responding patients’ CTC DNA; TP53 (55 vs 27% at baseline), AKAP9 (36 vs 9%), CDK12, KMT2D, and BRAF (each 36 vs 18%), and BRD4 and SPOP (each 18 vs 0%). Conclusions: We demonstrate that specific CTC genomic profiles associated with TP53, PTEN, WNT, DNA repair, epigenetic, and AR signaling, as well as lineage plasticity pathways are associated with worse clinical outcomes in AR-V7 negative men with mCRPC treated with abi/enza. Further mechanistic and validation studies are warranted. Clinical trial information: NCT02269982.