bluuebunny/crossref_metadata_2025 huggingface dataset:
Doubly robust estimator of risk in the presence of censoring dependent on time-varying covariates: application to a primary prevention trial for coronary events with pravastatin
Authors: Kawahara Takuya , Shinozaki Tomohiro , Matsuyama Yutaka
Published: July 2020

Background

In the presence of dependent censoring even after stratification of baseline covariates, the Kaplan–Meier estimator provides an inconsistent estimate of risk. To account for dependent censoring, time-varying covariates can be used along with two statistical methods: the inverse probability of censoring weighted (IPCW) Kaplan–Meier estimator and the parametric g-formula estimator. The consistency of the IPCW Kaplan–Meier estimator depends on the correctness of the model specification of censoring hazard, whereas that of the parametric g-formula estimator depends on the correctness of the models for event hazard and time-varying covariates.

Methods

We combined the IPCW Kaplan–Meier estimator and the parametric g-formula estimator into a doubly robust estimator that can adjust for dependent censoring. The estimator is theoretically more robust to model misspecification than the IPCW Kaplan–Meier estimator and the parametric g-formula estimator. We conducted simulation studies with a time-varying covariate that affected both time-to-event and censoring under correct and incorrect models for censoring, event, and time-varying covariates. We applied our proposed estimator to a large clinical trial data with censoring before the end of follow-up.

Results

Simulation studies demonstrated that our proposed estimator is doubly robust, namely it is consistent if either the model for the IPCW Kaplan–Meier estimator or the models for the parametric g-formula estimator, but not necessarily both, is correctly specified. Simulation studies and data application demonstrated that our estimator can be more efficient than the IPCW Kaplan–Meier estimator.

Conclusions

The proposed estimator is useful for estimation of risk if censoring is affected by time-varying risk factors.
What role does the GP play for emergency department utilizers? A qualitative exploration of respiratory patients’ perspectives in Berlin, Germany
Authors: Oslislo Sarah , Heintze Christoph , Möckel Martin , Schenk Liane , Holzinger Felix
Published: July 2020

Background

While motives for emergency department (ED) self-referrals have been investigated in a number of studies, the relevance of general practitioner (GP) care for these patients has not been comprehensively evaluated. Respiratory symptoms constitute an important utilization trigger in both EDs and in primary care. In this qualitative study, we aimed to explore the role of GP care for patients visiting EDs as outpatients for respiratory complaints and the relevance of the relationship between patient and GP in the decision making process leading up to an ED visit.

Methods

Qualitative descriptive study. Semi-structured, face-to-face interviews with a sample of 17 respiratory ED patients in Berlin, Germany. Interviews were recorded and transcribed verbatim. Qualitative content analysis was performed. The study was embedded into the EMACROSS (Emergency and Acute Care for Respiratory Diseases beyond Sectoral Separation) cohort of ED patients with respiratory symptoms, which is part of EMANet (Emergency and Acute Medicine Network for Health Care Research).

Results

Three patterns of GP utilization could be differentiated: long-term regular consulters, sporadic consulters and patients without GP. In sporadic consulters and patients without GP, an ambivalent or even aversive view of GP care was prevalent, with lack of confidence in GPs’ competence and a deficit in trust as seemingly relevant influencing factors. Regardless of utilization or relationship type, patients frequently made contact with a GP before visiting an ED.

Conclusions

With regard to respiratory symptoms, our qualitative data suggest a hypothesis of limited relevance of patients’ primary care utilization pattern and GP-patient relationship for ED consultation decisions.
Covered metallic stent for the treatment of malignant esophageal fistula combined with stricture
Authors: Bi Yonghua , Yi Mengfei , Yu Zepeng , Han Xinwei , Ren Jianzhuang
Published: July 2020

Background

Esophageal fistula and stricture is rare but life-threatening complication for esophageal cancer. The management of esophageal fistula and stricture remains challenging. We aimed to determine the safety, feasibility and efficacy of covered metallic stent and three tubes placement for the management of esophageal fistula and stricture.

Methods

Between May 2012 and March 2018, all patients with esophageal fistula and stricture were treated using three tubes or covered metallic stent placement. Patients in group A received covered stents and three tubes placement. Patients in group B only received three tubes placement. Continue abscess drainage and nutritional support was performed after procedure. Three tubes or esophageal stents were removed once esophageal fistula heals. The related medical records were retrospectively assessed.

Results

Thirty-seven consecutive patients with esophageal fistula and stricture were enrolled, including 26 patients in group A and 11 patients in group B. Stent placement procedure was technically successful in 25 patients (96.2%). A total of 42 covered stents were inserted. Seventeen esophageal stents were successfully removed from 10 patients. The median retention duration was 3.3 months and 3.4 months for stent and abscess drainage tubes, respectively. One perioperative death due to massive hemorrhage was observed 21 days after stent placement. The abscess cavity was decreased or disappeared in 17 cases and 4 cases in group A and group B, respectively. During follow up, patients in group A still showed a significant better condition of normal diet than that in group B (p < 0.05). Fourteen patients died of cancer recurrence, 3 patients died of massive digestive bleeding and 2 patients died of severe pulmonary infection. The median survivals were 14.8 months and 13.2 months for group A and group B, respectively.

Conclusions

Covered metallic stent placement is safe, feasible and efficacious for treatment of esophageal fistula and stricture, with a better condition of normal diet than patients only received three tubes placement.
Predictive value of TNF-α, IFN-γ, and IL-10 for tuberculosis among recently exposed contacts in the United States and Canada
Authors: Reichler Mary R. , Hirsch Christina , Yuan Yan , Khan Awal , Dorman Susan E. , Schluger Neil , Sterling Timothy R. ,   the Tuberculosis Epidemiologic Studies Consortium Task Order 2 Team, Bakhtawar I. , LeDoux C. , McAuley J. , Beison J. , Fitzgerald M. , Naus M. , Nakajima M. , Schluger N. , Hirsch-Moverman Y. , Moran J. , Blumberg H. , Tapia J. , Singha L. , Hershfeld E. , Roche B. , Mangura B. , Sevilla A. , Sterling T. , Chavez-Lindell T. , Maruri F. , Dorman S. , Cronin W. , Munk E. , Khan A. , Yuan Y. , Chen B. , Yan F. , Shen Y. , Zhao H. , Zhang H. , Bessler P. , Fagley M. , Reichler M. , Sterling T. , Tapia J. , Hirsch C. , Luo C.
Published: July 2020

Background

We examined cytokine immune response profiles among contacts to tuberculosis patients to identify immunologic and epidemiologic correlates of tuberculosis.

Methods

We prospectively enrolled 1272 contacts of culture-confirmed pulmonary tuberculosis patients at 9 United States and Canadian sites. Epidemiologic characteristics were recorded. Blood was collected and stimulated with Mycobacterium tuberculosis culture filtrate protein, and tumor necrosis factor (TNF-α), interferon gamma (IFN-γ), and interleukin 10 (IL-10) concentrations were determined using immunoassays.

Results

Of 1272 contacts, 41 (3.2%) were diagnosed with tuberculosis before or < 30 days after blood collection (co-prevalent tuberculosis) and 19 (1.5%) during subsequent four-year follow-up (incident tuberculosis). Compared with contacts without tuberculosis, those with co-prevalent tuberculosis had higher median baseline TNF-α and IFN-γ concentrations (in pg/mL, TNF-α 129 versus 71, P < .01; IFN-γ 231 versus 27, P < .001), and those who subsequently developed incident tuberculosis had higher median baseline TNF-α concentrations (in pg/mL, 257 vs. 71, P < .05). In multivariate analysis, contact age < 15 years, US/Canadian birth, and IFN or TNF concentrations > the median were associated with co-prevalent tuberculosis (P < .01 for each); female sex (P = .03) and smoking (P < .01) were associated with incident tuberculosis. In algorithms combining young age, positive skin test results, and elevated CFPS TNF-α, IFN-γ, and IL-10 responses, the positive predictive values for co-prevalent and incident tuberculosis were 40 and 25%, respectively.

Conclusions

Cytokine concentrations and epidemiologic factors at the time of contact investigation may predict co-prevalent and incident tuberculosis.
Efficacy and safety of cinacalcet compared with other treatments for secondary hyperparathyroidism in patients with chronic kidney disease or end-stage renal disease: a meta-analysis
Authors: Sun Yiting , Tian Binyao , Sheng Zitong , Wan Pengzhi , Xu Tianhua , Yao Li
Published: July 2020

Background

It is controversial for the effect and safety between cinacalcet and other treatments in treating secondary hyperparathyroidism for patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD).

Methods

Embase, PubMed, and Cochrane Library were searched through Feb 2017. 21 randomized controlled trials were included. We calculated the pooled mean difference (MD), relative risk (RR) and corresponding 95% confidence interval (CI).

Result

Patients received calcimimetic agents had significantly decreased serum parathyroid hormone (MD = − 259.24 pg/mL, 95% CI: − 336.23 to − 182.25), calcium (MD = − 0.92 mg/dL, 95% CI: − 0.98 to − 0.85) and calcium phosphorus product (MD = − 5.97 mg2/dL2, 95% CI: − 9.77 to − 2.16) concentration compared with control treatment. However, the differences in cardiovascular mortality and all-cause mortality between calcimimetics agents and control group were not statistically significant. The incidence of nausea (RR = 2.13, 95% CI: 1.62 to 2.79), vomiting (RR = 1.99, 95% CI: 1.78 to 2.23) and hypocalcemia (RR = 10.10, 95% CI: 7.60 to 13.43) in CKD patients with calcimimetics agents was significantly higher than that with control treatment.

Conclusion

Cinacalcet improved the biochemical parameters in CKD patients, but did not improve all-cause mortality and cardiovascular mortality. Moreover, cinacalcet can cause some adverse events.
Evaluating different adoption scenarios for TIL-therapy and the influence on its (early) cost-effectiveness
Authors: Lindenberg Melanie , Retèl Valesca , Rohaan Maartje , van den Berg Joost , Haanen John , van Harten Wim
Published: July 2020

Background

Treatment with tumor-Infiltrating Lymphocytes (TIL) is an innovative therapy for advanced melanoma with promising clinical phase I/II study results and likely beneficial cost-effectiveness. As a randomized controlled trial on the effectiveness of TIL therapy in advanced melanoma compared to ipilimumab is still ongoing, adoption of TIL therapy by the field is confronted with uncertainty. To deal with this, scenario drafting can be used to identify potential barriers and enables the subsequent anticipation on these barriers. This study aims to inform adoption decisions of TIL by evaluating various scenarios and evaluate their effect on the cost-effectiveness.

Methods

First, 14 adoption scenarios for TIL-therapy were drafted using a Delphi approach with a group of involved experts. Second, the likelihood of the scenarios taking place within 5 years was surveyed among international experts using a web-based questionnaire. Third, based on the questionnaire results and recent literature, scenarios were labeled as being either “likely” or “-unlikely”. Finally, the cost-effectiveness of TIL treatment involving the “likely” scored scenarios was calculated.

Results

Twenty-nine experts from 12 countries completed the questionnaire. The scenarios showed an average likelihood ranging from 29 to 58%, indicating that future developments of TIL-therapy were surrounded with quite some uncertainty. Eight of the 14 scenarios were labeled as “likely”. The net monetary benefit per patient is presented as a measure of cost-effectiveness, where a positive value means that a scenario is cost-effective. For six of these scenarios the cost-effectiveness was calculated: “Commercialization of TIL production” (the price was assumed to be 3 times the manufacturing costs in the academic setting) (−€51,550), “Pharmaceutical companies lowering the prices of ipilimumab” (€11,420), “Using TIL-therapy combined with ipilimumab” (−€10,840), “Automatic TIL production” (€22,670), “TIL more effective” (€23,270), “Less Interleukin-2” (€20,370).

Conclusions

Incorporating possible future developments, TIL-therapy was calculated to be cost-effective compared to ipilimumab in the majority of “likely” scenarios. These scenarios could function as facilitators for adoption. Contrary, TIL therapy was expected to not be cost-effective when sold at commercial prices, or when combined with ipilimumab. These scenarios should be considered in the adoption decision as these may act as crucial barriers.
Value of peri-operative chemotherapy in patients with CINSARC high-risk localized grade 1 or 2 soft tissue sarcoma: study protocol of the target selection phase III CHIC-STS trial
Authors: Filleron Thomas , Le Guellec Sophie , Chevreau Christine , Cabarrou Bastien , Lesluyes Tom , Lodin Sabrina , Massoubre Angélique , Mounier Muriel , Poublanc Muriel , Chibon Frédéric , Valentin Thibaud
Published: July 2020

Background

The value of chemotherapy in soft tissue sarcoma (STS) remains controversial. Several expert teams consider that chemotherapy provides a survival advantage and should be proposed in high-risk (HR) patients. However, the lack of accuracy in identifying HR patients with conventional risk factors (large, deep, FNCLCC grade 3, extremity STS) is an issue that cannot be neglected. For example, while the FNCLCC grading system is a powerful tool, it has several limitations. CINSARC, a 67-gene signature, has proved to be an additional independent factor for predicting metastatic spread and outperforms histological grade. Regardless of FNCLCC grade, CINSARC stratifies patients into two separate prognostic groups: one with an excellent prognosis (low-risk (LR) CINSARC) and the other with a worse outcome (HR-CINSARC) in terms of metastatic relapse. Here we evaluate the role of chemotherapy in grade 1–2 STS patients with HR-CINSARC and assess the prognostic value of CINSARC in patients treated with standard of care.

Methods

CHIC is a parallel, randomized, open-label, multicenter study evaluating the effect on metastasis-free survival of adding perioperative chemotherapy to standard of care in patients with grade ½ STS sarcoma defined as HR by CINSARC. In this target selection design, 600 patients will be screened with CINSARC to randomize 250 HR-CINSARC patients between standard of care and standard of care plus chemotherapy (4 cycles of 3 weeks of intravenous chemotherapy with doxorubicin in combination with dacarbazine or ifosfamide according to histologic subtype). LR-CINSARC patients will be treated by standard of care according to the investigator. The primary endpoint is metastasis-free survival. Secondary endpoints include overall survival, disease-free survival and safety. Furthermore, the prognostic value of CINSARC will be evaluated by comparing LR-CINSARC patients to HR-CINSARC patients randomized in standard of care.

Discussion

CHIC is a prospective randomized phase III trial designed to comprehensively evaluate the benefit of chemotherapy in HR-CINSARC patients and to prospectively validate the prognostic value of CINSARC in grade ½ STS sarcoma patients.

Trial registration

ClinicalTrials.gov identifier: NCT04307277 Date of registration: 13 March 2020
Transient ocular surface non-perfusion during cataract phacoemulsification surgery
Authors: Hu Yijun , Qi Wei , Liu Baoyi , Yu Honghua
Published: July 2020

Background

Complete non-perfusion of the anterior segment vasculature during cataract phacoemulsification surgery is rarely reported.

Case presentation

We present two cases of transient ocular surface non-perfusion (TOSN) during cataract phacoemulsification surgery. The TOSN happened during intraocular lens (IOL) implantation with complete vanish of blood flow in the conjunctival, episcleral and limbal vessels. Reperfusion started within 30 s and part of the blood supply of the conjunctiva and episclera was restored within 2 min. However, the blood flow in the limbal vessels was not restored until 5 min later. The postoperative examination of both eyes was normal. These two rare cases are the TOSN during cataract surgery. We speculated that the significantly increased intraocular pressure during IOL implantation might be the cause of this rare phenomenon.

Conclusion

Non-perfusion of the ocular structures may occur if the IOP peak during IOL injection exceeds the perfusion pressure of the anterior vasculature.
The correlation between vitamin a status and refractory Mycoplasma Pneumoniae pneumonia (RMPP) incidence in children
Authors: Li Yuanyuan , Guo Ziyao , Zhang Guangli , Tian Xiaoyin , Li Qinyuan , Chen Dapeng , Luo Zhengxiu
Published: July 2020

Background

Vitamin A plays a pivotal role in respiratory infection, accurate estimation of vitamin A status was recommended in planning and implementing interventions. As infections affect serum vitamin A productions, the real status need to be adjusted by acute phase protein (APP).Mycoplasma pneumoniaeis an important cause of respiratory infection in children, the association between vitamin A concentrations and refractoryMycoplasma pneumoniaepneumonia (RMPP) remains unclear.

Methods

181 MPP patients were enrolled in this retrospective study, adjusted vitamin A concentrations and other parameters were compared between RMPP and general-MPP (GMPP) patients. Multivariate logistic regression test was performed to evaluate the association between vitamin A levels and RMPP incidence, linear correlation tests were applied to evaluate correlation between vitamin A concentrations and fever duration, length of stay (LOS).

Results

Vitamin A concentrations in RMPP group were significantly lower than those in GMPP patients (P < 0.05), vitamin A (OR = 0.795, 95% C. I 0.669–0.946) and CRP (OR = 1.050, 95% C. I 1.014–1.087) were independently associated with RMPP incidence. Linear correlation tests found vitamin A concentrations were negatively correlated with fever duration and LOS (P < 0.001).

Conclusions

Serum vitamin A concentrations were independently associated with RMPP incidence, which may correlate with reduced incidence of RMPP.
Medication management in the context of mental illness: an exploratory study of young people living in Australia
Authors: McMillan Sara S. , Stewart Victoria , Wheeler Amanda J. , Kelly Fiona , Stapleton Helen
Published: July 2020

Background

Young people face significant challenges when managing a mental illness, such as acquiring treatment autonomy, being inexperienced users of the healthcare system and associated peer-related stigma. While medication use can be challenging in its own right, there is comparatively little information about the associated experiences and needs of young people with mental illness, particularly in the Australian context. This exploratory study will provide valuable insight into how this group is currently supported in relation to medication use.

Methods

Young people (aged 14–25 years) who had used a prescription medication for any mental illness for a minimum of 2 months were eligible to participate in this qualitative exploratory study. Semi-structured interviews were conducted between October 2017–September 2018 in consultation rooms at two youth-focused mental health support organisations in Brisbane, Queensland. Interview questions explored how participants managed their medication and related experiences. Interviews were transcribed verbatim and descriptively analysed using thematic analysis.

Results

Eighteen young people discussed their lived experience during interviews averaging 50 min in duration. Finding the right medication that reduced symptom severity with minimal side-effects was identified as a complex experience for many, particularly when there was a lack of information, support or reduced financial capacity. Young people described a range of strategies to manage medication side-effects, changes and to support routine medication use.

Conclusions

Young people persevered with taking medication to manage a mental illness within a healthcare system that does not adequately support this vulnerable population. There remains a clear directive for healthcare professionals to provide credible information that proactively engages young people as healthcare participants, and for policy makers to consider financial burden for this population with limited financial capacity.
Public engagement in the development of the National Health Insurance: a study involving patients from a central hospital in South Africa
Authors: Tandwa Lizeka Amanda , Dhai Ames
Published: July 2020

Background

The National Health Insurance (NHI) is a proposed health policy in South Africa that aims to change the structure of the current health system. Public involvement in policy making is important and it is a constitutional requirement in the legislation development process in South Africa. Patients are key stakeholders and should be engaged in NHI policy process. Before patients can be engaged, they need to be provided with sufficient information about the NHI. Therefore, the aim of this exploratory study was to examine the levels of patient awareness of the NHI, which is a requisite for meaningful engagement.

Methods

This was a cross sectional study of 244 patients from the follow-up clinics at the Department of Internal Medicine, Charlotte Maxeke Johannesburg Academic Hospital in the Gauteng Province, South Africa. The patients were interviewed using a structured interview process and a questionnaire. Descriptive statistics and logistic regression analyses were conducted.

Results

The majority (79.51%) of the participants were not aware of the proposed National Health Insurance (NHI) in South Africa even though the NHI policy process commenced in 2011. Of the participants who were aware of the NHI, 86% responded that they had not been provided with an opportunity to be involved in the policy making process of the NHI. The odds of awareness were higher for male (OR: 2.08, 95% CI: 1.11–3.9, p value: 0.02) than female participants; White (OR: 2.36, 95% CI: 1.06–5.26, p value: 0.04) and Indian (OR: 2.76, 95% CI: 0.10–7.60, p value: 0.05) participants when compared to Black participants; and retired (OR: 3.13, 95% CI: 1.35–7.25, p value: 0.008) than unemployed participants.

Conclusion

The levels of awareness of the NHI were low among the participants from Department of Internal Medicine, CMJAH. Without the awareness and information about the NHI, patients are not equipped to be involved in the NHI policy process in a meaningful way. Public patients are the intended beneficiaries of universal health coverage, therefore they should be prioritized in the NHI community engagement process to ensure that the NHI is community and patient centred.
Factors associated with unsafe work behaviours in an Iranian petrochemical company: perspectives of workers, supervisors, and safety managers
Authors: Zahiri Harsini Azita , Ghofranipour Fazlollah , Sanaeinasab Hormoz , Amin Shokravi Farkhondeh , Bohle Philip , Matthews Lynda R.
Published: July 2020

Background

The petrochemical industry is hazardous, in part because of the inherently dangerous nature of the work conducted, and incidents frequently result in significant financial and social losses. The most common immediate cause of incidents and injuries in this industry is unsafe worker behaviour. Identifying the factors encouraging unsafe work behaviours is the first step in taking action to discourage them. The aim of this study was to (a) explore workers’, supervisors’ and safety managers’ attitudes and perceptions of safety in a petrochemical company in Iran, and (b) identify the factors that discourage safe work behaviours.

Methods

A qualitative study was conducted by applying the steps described by Graneheim and Lundman (2004). Twenty participants were recruited from an Iranian petrochemical company using a multi-stage approach, with initial purposive sampling followed by snowball sampling to enhance recruitment. Individual face-to-face and semi-structured interviews were conducted to gain an in-depth understanding of factors acting as barriers to safe behaviour. The interviews were recorded and transcribed in Persian and then translated into English. Conventional content analysis was performed.

Results

The main themes emerging from the interviews were: (i) poor direct safety management and supervision; (ii) unsafe workplace conditions; (iii) workers’ perceptions, skills and training; and (iv) broader organisational factors.

Conclusions

The findings give insights into practical organisational measures that can be implemented by management to promote workers’ commitment to safety and engage in safe behaviours in their workplace.

Trial registration

Iranian Registry of Clinical Trials: IRCT20170515033981N2. Retrospectively registered 19 June 2018.
Clinical outcomes of Ti-Ni shape-memory patella concentrator combined with cannulated compression screws in the treatment of C2 and C3 patella fracture: a retrospective study of 54 cases
Authors: Yao Chen , Sun Jie , Wu Jiancheng , Zhou Zhenyu , Liu Fan , Tao Ran , Zhang Yafeng
Published: July 2020

Background

Ti-Ni shape-memory patella concentrator (TNSMPC) has been designed as an alternative approach for fixation of patella fracture, which has some advantages like higher hardness, higher tenacity, better wearing resistance, excellent corrosion resistance and desired histocompatibility. The present study was to investigate the efficiency of TNSMPC combined with cannulated compression screws in the treatment of comminuted patella fractures.

Methods

Between January 2014 and December 2017, 54 patients of C2 and C3 patella fractures underwent open reduction and internal fixation with TNSMPC combined with cannulated compression screws. All the patients got standard postoperative rehabilitation programs and were regularly followed up for at least 12 months after the operation. X-rays, knee functions and life quality were evaluated during the follow-up.

Results

All the patients achieved bone healing and recovery of knee function with low incidence of complications according to outcomes of X-rays and questionnaires. The average operation time and blood loss during surgery were 77.5 ± 25.12 min and 24.25 ± 4.70 ml respectively. The Knee Outcome Survey Activities of Daily Living Scale, the range of motion and the 36-item short-form heath survey after the operation were all improved. According to the Bostman’s criteria, the excellent to good rate was 92.6%.

Conclusion

TNSMPC combined with cannulated compression screws is an effective internal fixation method for C2 and C3 patella fracture with excellent clinical outcomes. In addition, the operation does not increase extra technique difficulty or tissue damage relatively, which is worth promotion.
The ethics of DNR-decisions in oncology and hematology care: a qualitative study
Authors: Pettersson Mona , Hedström Mariann , Höglund Anna T.
Published: July 2020

Background

In cancer care, do not resuscitate (DNR) orders are common in the terminal phase of the illness, which implies that the responsible physician in advance decides that in case of a cardiac arrest neither basic nor advanced Coronary Pulmonary Rescue should be performed. Swedish regulations prescribe that DNR decisions should be made by the responsible physician, preferably in co-operation with members of the team. If possible, the patient should consent, and significant others should be informed of the decision. Previous studies have shown that physicians and nurses can experience ethical dilemmas in relation to DNR decisions, but knowledge about what ethical reasoning they perform is lacking. Therefore, the aim was to describe and explore what ethical reasoning physicians and nurses apply in relation to DNR-decisions in oncology and hematology care.

Methods

A qualitative, descriptive and explorative design was used, based on 287 free-text comments in a study-specific questionnaire, answered by 216 physicians and nurses working in 16 oncology and hematology wards in Sweden. Comments were given by 89 participants.

Results

The participants applied a situation-based ethical reasoning in relation to DNR-decisions. The reasons given for this were both deontological and utilitarian in kind. Also, expressions of care ethics were found in the material. Universal rules or guidelines were seen as problematic. Concerning the importance of the subject, nurses to a higher extent underlined the importance of discussing DNR-situations, while physicians described DNR-decisions as over-investigated and not such a big issue in their daily work.

Conclusion

The study revealed that DNR-decisions in oncology and hematology care gave rise to ethical considerations. Important ethical values described by the participants were to avoid doing harm and to secure a peaceful and “natural” death with dignity for their dying patients. A preference for the expression “allow for natural death” instead of the traditional term “do not resuscitate” was found in the material.
Preventing overuse of laboratory diagnostics: a case study into diagnosing anaemia in Dutch general practice
Authors: Kip Michelle M. A. , Oonk Martijn L. J. , Levin Mark-David , Schop Annemarie , Bindels Patrick J. E. , Kusters Ron , Koffijberg Hendrik
Published: July 2020

Background

More information is often thought to improve medical decision-making, which may lead to test overuse. This study assesses which out of 15 laboratory tests contribute to diagnosing the underlying cause of anaemia by general practitioners (GPs) and determines a potentially more efficient subset of tests for setting the correct diagnosis.

Methods

Logistic regression was performed to determine the impact of individual tests on the (correct) diagnosis. The statistically optimal test subset for diagnosing a (correct) underlying cause of anaemia by GPs was determined using data from a previous survey including cases of real-world anaemia patients.

Results

Only 9 (60%) of the laboratory tests, and patient age, contributed significantly to the GPs’ ability to diagnose an underlying cause of anaemia (CRP, ESR, ferritin, folic acid, haemoglobin, leukocytes, eGFR/MDRD, reticulocytes and serum iron). Diagnosing the correct underlying cause may require just five (33%) tests (CRP, ferritin, folic acid, MCV and transferrin), and patient age.

Conclusions

In diagnosing the underlying cause of anaemia a subset of five tests has most added value. The real-world impact of using only this subset should be further investigated. As illustrated in this case study, a statistical approach to assessing the added value of tests may reduce test overuse.
A newly identified lncRNA H1FX-AS1 targets DACT1 to inhibit cervical cancer via sponging miR-324-3p
Authors: Shi Xinghua , Huo Jinzhi , Gao Xingping , Cai Hua , Zhu Weipei
Published: July 2020

Background

Cervical cancer (CC) is the 4th most common cancer-related death in gynecological cancer worldwide. It has been reported that many lncRNAs contribute to oncogenesis although the fundamental mechanisms are basically unknown. Here, we aimed to identify a novel lncRNA H1FX-AS1 and explore a ceRNA network in CC oncogenesis and progression.

Methods

The expression level and the association with the prognosis of H1FX-AS1 in CC patients were analyzed based on Cancer Genome Atlas (TCGA) datasets, and further verified in 50 CC patients. The biological role of H1FX-AS1 was investigated in vitro and in vivo by over-expression of H1FX-AS1 in CC cells; the potential binding sites between H1FX-AS1 and miRNA, between miR-324-3p and DACT1 were predicted by LncBASE and Targetscan respectively, which were further verified by dual-luciferase reporter assay, RNA pull-down and point mutation; the relationship between genes was analyzed by Pearson correlation; the rescue experiments were used to further explore the involved molecular mechanism.

Results

Lower H1FX-AS1 expression in CC tissues was found to be associated with the poor prognosis of CC patients. Over-expression of H1FX-AS1 inhibited CC cell proliferation, migration and invasion, while induced apoptosis by sponging miR-324-3p to up-regulate the DACT1 expression level.

Conclusion

A novel lncRNA H1FX-AS1 was identified, which acted as a competing endogenous RNA (ceRNA) of miR-324-3p to inhibit DACT1 mediated CC progression. Therefore, H1FX-AS1 is a new prognostic predictor and targeting the factors in the H1FX-AS1/miR-324-3p/DACT1 axis is the novel potential therapeutic strategy for CC.
Gut microbiota-associated metabolite trimethylamine N-Oxide and the risk of stroke: a systematic review and dose–response meta-analysis
Authors: Farhangi Mahdieh Abbasalizad , Vajdi Mahdi , Asghari-Jafarabadi Mohammad
Published: July 2020

Aims

Several epidemiological studies have examined the association between trimethylamineN-Oxide (TMAO) and stroke risk; however, the results are still inconclusive. The purpose of this meta-analysis was to evaluate the relationship between TMAO concentrations and stroke risk.

Methods

PubMed, Scopus, Cochrane and ProQuest search engines were systematically searched up to 18 June 2019. All of the studies that evaluated the relationship between TMAO and stroke were included in the systematic review and eligible studies were included into the meta-analysis. Meta-regression and subgroup analysis were also employed to find the source of heterogeneity.

Results

Eight studies (two cross-sectional studies, two cohort studies, three case-control studies and one nested case-control study) with a total of 6150 participants were included in the meta-analysis. The overall result showed that being in the highest category of TMAO increased the odds of stroke by 68% (OR: 1.675; CI: 0.866–3.243;P = 0.047) and mean TMAO concentrations was 2.201 μmol/L higher in patients with stroke rather than non-stroke controls (weighted mean difference (WMD): 2.20; CI: 1.213–3.188;P < 0.001). Furthermore, we observed revealed a non-linear association between increased TMAO levels and increased odds of stroke (P- for nonlinearity < 0.001). In addition, visual inspection of the funnel plot revealed a significant asymmetry among studies examining the differences in TMAO in patients with stroke versus control group.

Conclusion

This is the first meta-analysis to show positive dose-dependent relations between circulating TMAO concentration and stroke risk. However, further interventional studies and long-term studies are needed to better explain causality.
Axes of alienation: applying an intersectional lens on the social contract during the pandemic response to protect sexual and reproductive rights and health
Authors: Dasgupta Jashodhara , Schaaf Marta , Contractor Sana Qais , Banda Amanda , Viana Marisa , Kashyntseva Oksana , Ruano Ana Lorena
Published: July 2020

While economic inequalities have been a key focus of attention through the COVID 19 pandemic, gendered relations of power at every level have undermined health rights of women, girls and gender diverse individuals. Sexual and reproductive health rights (SRHR) have always been sites of power contestations within families, societies, cultures, and politics; these struggles are exacerbated by economic, racial, religious, caste, citizenship status, and other social inequities, especially in times of crisis such as these. Policy responses to the COVID pandemic such as lockdown, quarantine, contact tracing and similar measures are premised on the existence of a social contract between the government and the people and among people, with the health sector playing a key role in preventive and curative care.

We propose the use of an intersectional lens to explore the impact of the COVID-19 pandemic on the social contract, drawing on our field experiences from different continents particularly as related to SRHR. Along with documenting the ways in which the pandemic hinders access to services, we note that it is essential to interrogate state-society relations in the context of vulnerable and marginalized groups, in order to understand implications for SRHR. Intersectional analysis takes on greater importance now than in non-pandemic times as the state exercises more police or other powers and deploys myriad ways of ‘othering’.

We conclude that an intersectional analysis should not limit itself to the cumulative disadvantages and injustices posed by the pandemic for specific social groups, but also examine the historical inequalities, structural drivers, and damaged social contract that underlie state-society relationships. At the same time, the pandemic has questioned the status quo and in doing so it has provided opportunities for disruption; for re-imagining a social contract that reaches across sectors, and builds community resilience and solidarities while upholding human rights and gender justice. This must find place in future organizing and advocacy around SRHR.
SIRM-SIAAIC consensus, an Italian document on management of patients at risk of hypersensitivity reactions to contrast media
Authors: Costantino Maria Teresa , Romanini Laura , Gaeta Francesco , Stacul Fulvio , Valluzzi Rocco Luigi , Passamonti Matteo , Bonadonna Patrizia , Cerri Giovanni , Pucci Stefano , Ricci Paolo , Savi Eleonora , Galluzzo Michele , Mauro Marina , Grassedonio Emanuele , Yacoub Mona Rita , Reginelli Alfonso , Testi Sergio , Ridolo Erminia , Nettis Eustacchio , Di Leo Elisabetta , Rossi Oliviero , Montuschi Paolo , Incorvaia Cristoforo , Romano Antonino
Published: July 2020

Hypersensitivity reactions (HRs) to contrast media (CM) can be distinguished in immune-mediated (including allergic reactions) and non-immune-mediated reactions, even if clinical manifestations could be similar. Such manifestations range from mild skin eruptions to severe anaphylaxis, making it important for radiologists to know how to identify and manage them. A panel of experts from the Società Italiana di Radiologia Medica e Interventistica (SIRM) and the Società Italiana di Allergologia, Asma e Immunologia Clinica (SIAAIC) provided a consensus document on the management of patients who must undergo radiological investigations with CM. Consensus topics included: the risk stratification of patients, the identification of the culprit CM and of a safe alternative by an allergy workup, as well as the use of premedication and the correct procedure to safely perform an elective (i.e., scheduled) or urgent examination. The most important recommendations are: (1) in all patients, a thorough medical history must be taken by the prescribing physician and/or the radiologist to identify at-risk patients; (2) in patients with hypersensitivity reactions to CM, the radiologist must consider an alternative, non-contrast imaging study with a comparable diagnostic value, or prescribe a different investigation with another class of CM; (3) if such options are not feasible, the radiologist must address at-risk patients to a reference centre for an allergy evaluation; (4) if timely referral to an allergist is not viable, it is recommended to use a CM other than the responsible one, taking into account cross-reactivity patterns; in the case of patients with histories of severe reactions, the presence of an anesthesiologist is also recommended and a premedication is suggested.
Health-related quality of life in facial palsy: translation and validation of the Dutch version Facial Disability Index
Authors: van Veen Martinus M. , Bruins Tessa E. , Artan Madina , Mooibroek-Leeuwerke Tanja , Beurskens Carien H. G. , Werker Paul M. N. , Dijkstra Pieter U.
Published: July 2020

Purpose

Patient-reported outcome measures are essential in the evaluation of facial palsy. Aim of this study was to translate and validate the Facial Disability Index (FDI) for use in the Netherlands.

Methods

The FDI was translated into Dutch according to a forward-backward method. Construct validity was assessed by formulating 22 hypotheses regarding associations of FDI scores with the Facial Clinimetric Evaluation scale, the Synkinesis Assessment Questionnaire, the Short Form-12 and the Sunnybrook Facial Grading System. Validity was considered adequate if at least 75% (i.e. 17 out of 22) of the hypotheses were confirmed. Additionally, confirmatory factor analysis was performed. Cronbach’s α was calculated as a measure of internal consistency. Participants were asked to fill out the FDI a second time after 2 weeks to analyse test-retest reliability. Lastly, smallest detectable change was calculated.

Results

In total, 19 hypotheses (86.4%) were confirmed. Confirmatory factor analysis showed acceptable fit for the two factor structure of the original FDI (root mean square error of approximation = 0.064, standardized root mean square residual = 0.081, comparative fit index = 0.925, Chi-square = 50.22 with 34 degrees of freedom). Internal consistency for the FDI physical function scale was good (α > 0.720). Internal consistency for the FDI social/well-being scale was slightly less (α > 0.574). Test-retest reliability for both scales was good (intraclass correlation coefficients > 0.786). Smallest detectable change at the level of the individual was 17.6 points for the physical function and 17.7 points for the social/well-being function, and at group level 1.9 points for both scales.

Conclusion

The Dutch version FDI shows good psychometric properties. The relatively large values for individual smallest detectable change may limit clinical use. The translation and widespread use of the FDI in multiple languages can help to compare treatment results internationally.
ATM mutations improve radio-sensitivity in wild-type isocitrate dehydrogenase-associated high-grade glioma: retrospective analysis using next-generation sequencing data
Authors: Kim Nalee , Kim Se Hoon , Kang Seok-Gu , Moon Ju Hyung , Cho Jaeho , Suh Chang-Ok , In Yoon Hong , Chang Jong Hee
Published: July 2020

Background

To identify the association between somatic ataxia-telangiectasia mutated (ATM) mutations and improved radio-sensitivity, we retrospectively reviewed next-generation sequencing data from patients diagnosed with isocitrate dehydrogenase (IDH)-wildtype high-grade glioma.

Methods

We included 39 individuals with (IDH)-wildtype high-grade glioma (diffuse astrocytoma n = 2, anaplastic astrocytoma n = 10, and glioblastoma n = 27) not subjected to gross tumor resection and undergoing radiation therapy with a median total dose of 60 Gy in 30 fractions. The mutational status of the ATM gene was obtained through next-generation sequencing using a TruSight Tumor 170 cancer panel. Disease progression was defined according to the Response Assessment in Neuro-Oncology (RANO) criteria as well as neurologic and clinical findings.

Results

Among the 39 samples, ATM mutations (ATM mut(+)) were detected in 26% of cases (n = 10). No significant differences were observed in the characteristics of the patients or tumors. Among the 10 patients in the ATM mut(+) group, there were 6 patients with glioblastoma and 4 patients with anaplastic astrocytoma. Most mutations were missense mutations (n = 8, 80%). With a median follow-up of 16.5 mo (interquartile range, 11.4–19.8), ATM mut(+) exhibited 1-year in-field control of 100% compared with 44.1% in the ATM mut(−) group (p = 0.002). There was no difference in the out-field control rate or overall survival between the two groups (p = 0.861 and p = 0.247, respectively).

Conclusions

Our results demonstrated that ATM mutations might be involved in the increased radio-sensitivity with excellent in-field control despite the aggressive nature of IDH-wildtype high-grade glioma. Further studies are necessary to uncover the potential role of ATM as a biomarker and candidate therapeutic target in high-grade gliomas.
Whole brain radiotherapy (WBRT) for leptomeningeal metastasis from NSCLC in the era of targeted therapy: a retrospective study
Authors: Zhen Junjie , Wen Lei , Lai Mingyao , Zhou Zhaoming , Shan Changguo , Li Shaoqun , Lin Tao , Wu Jie , Wang Wensheng , Xu Shaoqiang , Liu Da , Lu Ming , Zhu Dan , Chen Longhua , Cai Linbo , Zhou Cheng
Published: July 2020

Background and purpose

Leptomeningeal metastasis (LM) is a rare but detrimental complication in patients with non-small cell lung cancer (NSCLC). Although whole brain radiotherapy (WBRT) is used to eliminating cancer cells or microscopic foci, it is becoming less favorable due to the concerns over neurocognitive toxicity. This study aimed to re-evaluate the role of WBRT in the setting of modern targeted therapy.

Materials and methods

From December 2014 to March 2019, 80 NSCLC patients with cytologically and/or radiologically proven LM diagnosis were retrospectively analyzed.

Results

The median OS (mOS) after diagnosis of LM was 8.0 (95%CI: 4.4 to 11.6) months, and the one-year OS was 39.4%. The mOS for EGFR-mutated LM patients was 12.6 (3.0 to 22.2) months versus only 4.1 (2.8 to 5.4) for patients with wild-type EGFR (P < 0.001). Younger patients (< 53.5 yrs.) appeared to have a better OS than older patients (≥53.5 yrs.) (12.6 vs. 6.1, P = 0.041). No survival benefits were found in EGFR-mutated patients who received WBRT (P = 0.490). In contrast, mOS was significantly prolonged in wild-type EGFR patients with WBRT versus non-WBRT (mOS: 8.0 vs. 2.1, P = 0.002). Multivariate analysis indicated that WBRT (P = 0.025) and younger age (P = 0.048) were independent prognostic factors that predicted prolonged survival for wild-type EGFR LM patients from NSCLC.

Conclusion

Our study demonstrated that WBRT has clear survival advantages for patients with wild-type EGFR, and molecular biological stratification of LM patients for WBRT is highly recommended.
Incidence of deep venous thrombosis (DVT) of the lower extremity in patients undergoing surgeries for ankle fractures
Authors: Zixuan Luo , Chen Wei , Li Yansen , Wang Xiaomeng , Zhang Weili , Zhu Yanbin , Zhang Fengqi
Published: July 2020

Objective

To investigate the incidence of postoperative deep venous thrombosis (DVP) in patients undergoing surgeries for ankle fractures and identify the associated risk factors.

Methods

This was a retrospective study. A total of 1451 patients undergoing surgery of ankle fractures from January 2016 to June 2019 were included. The inpatient medical record system was inquired for data collection, including demographics, comorbidities, injury, and surgery-related data, and laboratory biomarkers. DVT of the lower extremity was diagnosed by routine Doppler examination. Univariate analyses and multivariate logistic regression analyses were used to identify the independent risk factors.

Results

Among the 1451 patients, DVT was confirmed in 38 cases, indicating an incidence of 2.6%. DVT involved both the operated and non-operated limbs in 8 patients (21.1%). DVT involved superficial femoral vein in 4 cases (6.6%), deep femoral vein in 2 (3.3%), popliteal vein in 5 (8.2%), posterior tibial vein in 11 (18.0%), and peroneal vein in 39 (63.9%). The median interval between operation and diagnosis of DVT was 7 days. Six risk factors were identified to be independently associated with DVT, including age (10-year increase) (OR, 1.44), preoperative stay (delay of each day) (OR, 1.11), anesthesia (general vs regional) (OR, 3.51), lower hemoglobin level (OR, 2.02), total cholesterol > 5.2 mmol/L (OR, 3.20), and reduced lymphocyte count (OR, 3.16).

Conclusion

These identified factors, although not easily modifiable, do help counsel patients about the risk of DVT and help individualized assessment of the risk factors and accordingly the risk stratification.