bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between caregiver-detected delirium and symptoms of depression and anxiety in family caregivers of critically ill patients: a cross-sectional study
Authors: Rosgen Brianna K. , Krewulak Karla D. , Davidson Judy E. , Ely E. Wesley , Stelfox Henry T. , Fiest Kirsten M.
Published: April 2021

Background

Witnessing delirium can be distressing for family caregivers (i.e., relatives or friends) of critically ill patients. This study aimed to evaluate associations between caregiver-detected delirium in critically ill patients and depression and anxiety symptoms in their family caregivers.

Methods

Consecutive adult patient-caregiver dyads were enrolled from a 28-bed medical-surgical intensive care unit. Patient delirium was screened for daily by family caregivers using the Sour Seven instrument. Family caregivers completed the Patient Health Questionnaire-9 (PHQ-9) and General Anxiety Disorder-7 (GAD-7) instruments daily to assess their own depression and anxiety symptoms. Response feature analysis was used to handle repeated measures. Descriptive statistics and regression analyses were completed.

Results

One hundred forty-seven patient-caregiver dyads were enrolled. Clinically significant symptoms of depression and anxiety occurred in 27% and 35% of family caregivers, respectively. Caregiver-detected delirium occurred in 65% of patients, and was not associated with clinically significant caregiver depression (Odds Ratio [OR] 1.4, 95% Confidence Interval [95%CI] 0.6–3.1) or anxiety (OR 1.2, 95%CI 0.6–2.6) symptoms. When stratified by Sour Seven scores, scores 1–3 and 4–9 were associated with increased symptoms of anxiety (OR 3.1, 95%CI 1.3–7.0) and depression (OR 2.6, 95%CI 1.1–6.1) in family caregivers. Caregiver-detected delirium score was associated with severity of family caregiver anxiety symptoms (coefficient 0.2, 95%CI 0.1–0.4), but not depression symptoms (coefficient 0.2, 95%CI -0.0–0.3).

Conclusions

Caregiver-detected patient delirium was associated with increased depression and anxiety symptoms in family caregivers of critically ill patients. Further randomized research is required to confirm these associations.
Cigarette smoking and all-cause mortality in rural Chinese male adults: 15-year follow-up of the Anqing cohort study
Authors: Ye Lijing , Yang Jie , Li Jingyi , Cheng Nannan , Zhang Yue , Lu Xiaofan , Zhou Ziyi , Wang Zhuo , Liu Lishun , Huang Xiao , Song Yun , Xing Shibo , Wang Dongqing , Li Junnong , Wang Binyan , Tang Genfu , Qin Xianhui , Zalloua Pierre , Zhang Huisheng , Yan Fangrong , Xu Xiping
Published: April 2021

Background

According to the Global Burden of Disease Study 2017, smoking is one of the leading four risk factors contributing to deaths in China. We aimed to evaluate the associations of smoking with all-cause mortality in a Chinese rural population.

Methods

Male participants over age 45 (n = 5367) from a large familial aggregation study in rural China, were included in the current analyses. A total of 528 former smokers and 3849 current smokers accounted for 10 and 71.7% of the cohort, respectively. Generalized Estimating Equations were used to evaluate the association between baseline smoking status and mortality, adjusting for pertinent covariates.

Results

There were 579 recorded deaths during the 15-year follow-up. Current smokers (odds ratio [OR],1.60; 95% CI,1.23–2.08) had higher all-cause mortality risks than nonsmokers. Relative to nonsmokers, current smokers of more than 40 pack-years ([OR],1.85; 95% CI,1.33–2.56) had a higher all-cause mortality risk. Compared to nonsmokers, current smokers who started smoking before age 20 ([OR],1.91; 95% CI,1.43–2.54) had a higher all-cause mortality risk, and former smokers in the lower pack-year group who quit after age 41 (median) ([OR],3.19; 95% CI,1.83–5.56) also had a higher risk of death after adjustment. Furthermore, former smokers who were also former drinkers had the highest significant risk of mortality than never smokers or drinkers. (P for interaction = 0.034).

Conclusions

This study provides evidence that current smokers and former smokers have a higher mortality risk than nonsmokers and would benefit from cessation at a younger age.
Damage control strategy in perforated diverticulitis with generalized peritonitis
Authors: Sohn Maximilian , Agha Ayman , Iesalnieks Igors , Gundling Felix , Presl Jaroslav , Hochrein Alfred , Tartaglia Dario , Brillantino Antonio , Perathoner Alexander , Pratschke Johann , Aigner Felix , Ritschl Paul
Published: April 2021

Background

The best treatment for perforated colonic diverticulitis with generalized peritonitis is still under debate. Concurrent strategies are resection with primary anastomosis (PRA) with or without diverting ileostomy (DI), Hartmann’s procedure (HP), laparoscopic lavage (LL) and damage control surgery (DCS). This review intends to systematically analyze the current literature on DCS.

Methods

DCS consists of two stages. Emergency surgery: limited resection of the diseased colon, oral and aboral closure, lavage, vacuum-assisted abdominal closure. Second look surgery after 24–48 h: definite reconstruction with colorectal anastomosis (−/ + DI) or HP after adequate resuscitation. The review was conducted in accordance to the PRISMA-P Statement. PubMed/MEDLINE, Cochrane central register of controlled trials (CENTRAL) and EMBASE were searched using the following term: (Damage control surgery) AND (Diverticulitis OR Diverticulum OR Peritonitis).

Results

Eight retrospective studies including 256 patients met the inclusion criteria. No randomized trial was available. 67% of the included patients had purulent, 30% feculent peritonitis. In 3% Hinchey stage II diverticulitis was found. In 49% the Mannheim peritonitis index (MPI) was greater than 26. Colorectal anastomosis was constructed during the course of the second surgery in 73%. In 15% of the latter DI was applied. The remaining 27% received HP. Postoperative mortality was 9%, morbidity 31% respectively. The anastomotic leak rate was 13%. 55% of patients were discharged without a stoma.

Conclusion

DCS is a safe technique for the treatment of acute perforated diverticulitis with generalized peritonitis, allowing a high rate of colorectal anastomosis and stoma-free hospital discharge in more than half of the patients.
Significance of postoperative adjuvant chemotherapy with an oxaliplatin-based regimen after simultaneous curative resection for colorectal cancer and synchronous colorectal liver metastasis: a propensity score matching analysis
Authors: Sugimoto Kiichi , Sakamoto Kazuhiro , Ii Yuki , Amemiya Kota , Sugo Hiroyuki , Ito Tomoaki , Munakata Shinya , Takahashi Makoto , Kojima Yutaka , Tomiki Yuichi , Sato Koichi , Saiura Akio , Kawasaki Seiji
Published: April 2021

Background

Expansion of the indication for liver resection and new regimens for systemic chemotherapy have improved postoperative outcomes for synchronous colorectal liver metastases (CRLM). However, such cases can still have a high recurrence rate, even after curative resection. Therefore, there is a need for postoperative adjuvant chemotherapy (POAC) after liver resection in patients with CRLM. There are few studies of the efficacy of POAC with an oxaliplatin-based regimen after simultaneous resection for colorectal cancer and CRLM with curative intent. The goal of the study was to compare POAC with oxaliplatin-based and fluoropyrimidine regimens using propensity score (PS) matching analysis.

Methods

The subjects were 94 patients who received POAC after simultaneous resection for colorectal cancer and synchronous CRLM, and were enrolled retrospectively. The patients were placed in a L-OHP (+) group (POAC with an oxaliplatin-based regimen, n = 47) and a L-OHP (−) group (POAC with a fluoropyrimidine regimen, n = 47). Recurrence-free (RFS), cancer-specific (CSS), unresectable recurrence-free (URRFS), remnant liver recurrence-free (RLRFS), and extrahepatic recurrence-free (EHRFS) survival were analyzed.

Results

Before PS matching, the L-OHP (+) and (−) groups had no significant differences in RFS, CSS, URRFS, RLRFS, and EHRFS. Univariate analysis indicated significant differences in age, preoperative serum CEA (≤ 30.0 ng/mL/ > 30.0 ng/mL), differentiation of primary tumor (differentiated/undifferentiated), T classification (T1–3/T4), number of hepatic lesions and maximum diameter of the hepatic lesion between the L-OHP (+) and (−) groups. After PS matching using these confounders, RFS was significantly better among patients in the L-OHP (+) group compared with the L-OHP (−) group (HR 0.40, 95% CI 0.17–0.96, p = 0.04). In addition, there was a trend towards better RLRFS among patients in the L-OHP (+) group compared with the L-OHP (−) group (HR 0.42, 95% CI 0.17–1.02, p = 0.055). However, there were no significant differences in CSS, URRFS and EHRFS between the L-OHP (+) and (−) groups.

Conclusions

PS matching analysis demonstrated the efficacy of POAC with an oxaliplatin-based regimen in RFS and RLRFS.
Safety and efficacy of secondary mandibular reconstruction using a free osteo-cutaneous fibula flap after segmental mandibular resection: a retrospective case–control study
Authors: Yamakawa Sho , Hayashida Kenji
Published: April 2021

Background

Free osteocutaneous fibula flap (FFF) is currently considered the best option for segmental mandibular reconstruction; however, there are only a few reports comparing secondary with primary reconstructions using FFF. This study aimed to evaluate the safety and efficacy of secondary mandibular reconstruction using FFF when compared with primary mandibular reconstruction.

Methods

From October 2018 to February 2020, patients who underwent mandibular reconstruction using FFF after segmental mandibulectomy were retrospectively reviewed. The size and location of the mandibular defect, the segment length and number of osteotomies in the fibula, types of the mandibular plating system, kinds and laterality of the recipient vessels were recorded from the surgical notes. Flap survival, duration of nasogastric tube use, and implant installation after reconstruction were recorded as postoperative evaluation indices.

Results

Twelve patients underwent mandibular reconstruction using FFF during the study period. There were no significant differences in demographic characteristics other than body mass index between the primary (n = 8) and secondary (n = 4) reconstruction groups. No significant differences were observed in the size and location of defects, the segment length and number of osteotomies in the fibula, and the types of mandibular plating system. There was no significant difference in the kinds of recipient vessels; however, the laterality of recipient vessels was ipsilateral in all cases of primary reconstructions and contralateral in all cases of secondary reconstructions. Three out of eight patients with primary FFF reconstruction developed partial flap necrosis. Four patients in the secondary FFF reconstruction group achieved complete flap survival. The duration of use of the nasogastric tube and implant installation after reconstruction was comparable between the two groups.

Conclusion

Safe and effective secondary mandibular reconstruction can be performed in this clinical case study using FFF.
Anti-inflammatory effects of Morus alba Linne bark on the activation of toll-like receptors and imiquimod-induced ear edema in mice
Authors: Umeyama Lin , Hardianti Besse , Kasahara Shiori , Dibwe Dya Fita , Awale Suresh , Yokoyama Satoru , Hayakawa Yoshihiro
Published: April 2021

Background

Morus alba L. bark has been widely used in traditional medicine for treating several inflammatory diseases, such as hypertension, diabetes mellitus and coughing; however, the molecular mechanisms underlying its anti-inflammatory effects are not well understood.

Methods

We examined the effects of an extract of Morus alba L. bark (MabE) on Toll-like receptor (TLR) ligand-induced activation of RAW264.7 macrophages using a luciferase reporter assay and immunoassays. For the in vivo experiment, we used an imiquimod-induced ear edema model to examine the anti-inflammatory effects of MabE.

Results

MabE inhibited the TLR ligand-induced activation of NF-κB in RAW264.7 cells without affecting their viability. Consistent with the inhibition of NF-κB activation, MabE also inhibited the production of IL-6 and IL-1β from TLR ligand-treated RAW264.7 cells. In vivo MabE treatment inhibited the ear swelling of IMQ-treated mice, in addition to the mRNA expression of IL-17A, IL-1β and COX-2. The increases in splenic γδT cells in IMQ-treated mice and the production of IL-17A from splenocytes were significantly inhibited by MabE treatment.

Conclusion

Our study suggests that the anti-inflammatory effects of MabE on the activation of the macrophage cell line RAW246.7 by TLRs and IMQ-induced ear edema are through the inhibition of NF-κB activation and IL-17A-producing γδT cells, respectively.
Phytochemical analysis of medicinal plants of Nepal and their antibacterial and antibiofilm activities against uropathogenic Escherichia coli
Authors: Bhandari Sudip , Khadayat Karan , Poudel Sami , Shrestha Sunil , Shrestha Raju , Devkota Poonam , Khanal Santosh , Marasini Bishnu P.
Published: April 2021

Background

A biofilm is an extracellular polymeric substance (EPS) composed of polysaccharides, proteins, nucleic acids, and lipids that impede antibiotics and immune cells, thus providing a shielded environment for bacterial growth. Due to biofilm formation, some microbes can show up to 1000 fold increased resistance towards the antibiotics than the normal planktonic forms. The study was conducted to screen the crude extracts of medicinal plants used in Nepal for their in vitro antibiofilm activities.

Methods

Total phenolic and total flavonoid contents were determined by using a Folin-Ciocalteau reagent and aluminium trichloride method, respectively. Resazurin assay was used to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The initial antibiofilm activities and their inhibitory concentration (IC50) values were determined by the microtiter based modified crystal violet staining method.

Results

Out of 25 different plant extracts were used for the study, methanolic extracts of 20 plants showed a biofilm inhibition activity against five different strong biofilm producing Escherichia coli strains. Calotropis gigantea exhibited inhibition against all five different E. coli strains with IC50 values ranging from 299.7 ± 20.5 to 427.4 ± 2.7 μg/mL. Apart from that, Eclipta prostrata also showed biofilm formation inhibition, followed by Eupatorium adenophorum, Moringa oleifera, Ocimum tenuifolium, Oxalis lantifolia, Prunus persica, and Urtica parviflora. The extracts of C. gigantea, E. prostrata, Mangifera indica, O. tenuifolium, P. persica, and U. parviflora exhibited a moderate to poor MIC value ranging from 625 to 2500 μg/mL. The highest amount of phenolic content (TPC) was found in Acacia catechu followed by Morus alba, which was 38.9 and 25.1 mg gallic acid equivalents, respectively. The highest amount of flavonoid content was found in A. catechu followed by M. indica, which was 27.1 and 20.8 mg quercetin equivalents, respectively.

Conclusion

Extracts of C. gigantea, E. prostrata, P. persica, U. parviflora, and O. tenuifolium showed antibacterial as well as antibiofilm activity against pathogenic and strong biofilm producing E. coli. Thus, extracts or the pure compound from these medicinal plants could be used as antibiotics in the future.
Barriers and facilitators to implementing a longitudinal dementia education programme into undergraduate healthcare curricula: a qualitative study
Authors: Feeney Yvonne , Daley Stephanie , Flaherty Breda , Banerjee Sube
Published: April 2021

Background

As the numbers of people with dementia worldwide rises, there is a need for improved knowledge and awareness about the condition across the healthcare workforce. There are concerns that traditional models of healthcare education, which focus on short-term episodes of care, limit student understanding of long-term conditions. We therefore designed and delivered the Time for Dementia programme at five Universities in the UK. Through longitudinal contact with families living with dementia, healthcare students gain increased understanding about the experiences of living with dementia. However, implementing new educational models brings challenges. To enable implementation of similar programmes in other educational institutions, this study aimed to identify the common barriers and facilitators of implementing these types of longitudinal programmes at scale.

Methods

To understand the facilitators and barriers of implementing a longitudinal dementia educational programme, a qualitative study was completed. Between October and December 2018, twelve in-depth semi-structured interviews were completed with university teaching staff (n = 6), programme administrators (n = 4), and Alzheimer’s Society staff (n = 2) that had key responsibilities for implementing Time for Dementia. Interview questions explored participants experiences, the facilitators, and the challenges encountered when implementing the programme. Interviews were audio recorded, transcribed verbatim, and analysed using inductive thematic analysis.

Results

The analysis identified five key themes: “Leadership characteristics”, “Organisational and student buy-in”, “Perceived value and motivating factors”, “Team coalition and support”, and “Time and fit”. Implementation of the programme was enhanced by resilient leaders managing the challenges of curricular change. Their belief in the value of the programme, stakeholder buy-in, and supportive team working enabled challenges to be overcome. Workload was reduced and student buy-in increased as time progressed and as more resources became available. A flexible approach to implementation was recommended to ensure the programme fits within the established curriculum.

Conclusion

Curricular change is a challenging task, yet necessary, if we are to improve care for people with long term conditions such as dementia. This study highlights the common barriers and facilitators experienced when implementing a longitudinal educational programme at scale. The findings presented in this study can be used by other educational institutions to manage curricular change efforts.
Which nurses are victims of bullying: the role of negative affect, core self-evaluations, role conflict and bullying in the nursing staff
Authors: Homayuni Atefeh , Hosseini Zahra , Aghamolaei Teamur , Shahini Shirin
Published: April 2021

Background

Bullying among nurses is a universally recognized problem that has important consequences for nurses, patients and health institutions. This research was conducted with the aim of studying the relationship between role conflict, negative affect and core self-evaluations with bullying in nurses.

Methods

In this cross-sectional study, 329 nurses were selected by census method. Data were collected using PANAS Scale (negative affect), role conflict questionnaire, Core Self-Evaluations Scale (CSES), and the Negative Acts Questionnaire-Revised (NAQ-R). Data were analyzed using t-test, one way analysis of variance, Pearson correlation coefficient and multiple regression analysis with SPSS software (v. 22).

Results

The results showed that there is a significant difference between the mean bullying scores in according to gender and ward of affiliation. The influence of other variables (marital status, education level, years of experience, age group and work position) was not meaningful. Pearson correlation analysis results indicated that there is a significant positive relationship between role conflict (r = 0.47) and negative affect (r = 0.56) with bullying. Also there is a significant negative relationship between core self-evaluations and bullying (r = − 0.39). Moreover, regression analysis results revealed that negative affect, role conflict and gender can predict 44% of bullying variance significantly.

Conclusions

Based on these findings, core self-evaluations, negative affect and role conflict are good factors in predicting bullying among nurses. Consequently, hiring nurses with low negative affect and high core self-evaluations, improving nurses’ self-esteem and self-efficacy and changing workplace conditions in order to reducing role conflict can be useful in reducing workplace bullying.
Incidence of household catastrophic and impoverishing health expenditures among patients with Breast Cancer in Iran
Authors: Ahmadi Faranak , Farrokh-Eslamlou Hamidreza , Yusefzadeh Hasan , Alinia Cyrus
Published: April 2021

Background

Breast cancer disease is the most common cancer among Iranian women and imposing a significant financial burden on the households. This study calculated out-of-pocket (OOP), catastrophic health expenditure (CHE), and impoverishing health spending attributed to breast cancer in Iran.

Methods

In this cross-sectional household study, clinical and financial information on breast cancer and also household information (expenditures and income) were obtained through face-to-face interviews and completing a questionnaire by 138 women with this disease in 2019. We applied three non-food expenditure thresholds of 40, 20, and 10% to defining the CHE. Disease costs included periodical visits, diagnostic services, hospitalization care, treatment and rehabilitation services, home, and informal care. Households were disaggregated into socioeconomic status quintiles based on their Adult Equivalent values standardized monthly consumption expenditures. To identify the factors affecting these indicators, we performed the two different multivariate logistic regression models.

Results

This study finds that each patient had a monthly average OOP payment of $US 97.87 for the requested services, leading to impoverished of 5.07% and exposed 13.77% of their households to CHE. These indicators have been mainly concentrated among the poor, as they have spent a large part of their meager income on buying the needed services, and for this purpose, most of them forced to sell their assets, borrow, or take a bank loan.

Conclusions

The patients in lower SES quintiles can be protected from impoverishing and catastrophic health spending by expanding insurance coverage, providing financial risk protection programs, and increasing access to quality and effective public sector services. Alongside, expanding inpatient coverage and adding drug benefits for the poor can significantly decrease their OOP payments.
Medical malpractice in Norway: frequency and distribution of disciplinary actions for medical doctors 2011–2018
Authors: Harbitz Martin B. , Stensland Per Steinar , Abelsen Birgit
Published: April 2021

Background

Physicians who perform unsafe practices and harm patients may be disciplined. In Norway, there are five types of disciplinary action, ranging from a warning for the least serious examples of malpractice to loss of licence for the most serious ones. Disciplinary actions always involve medical malpractice. The aims of this study were to investigate the frequency and distribution of disciplinary actions by the Norwegian Board of Health Supervision for doctors in Norway and to uncover nation-wide patient safety issues.

Methods

We retrospectively investigated all 953 disciplinary actions for doctors given by the Board between 2011 and 2018. We categorized these according to type of action, recipient’s profession, organizational factors and geographical location of the recipient. Frequencies, cross tables, rates and linear regression were used for statistical analysis.

Results

Rural general practitioners received the most disciplinary actions of all doctors and had their licence revoked or restricted 2.1 times more frequently than urban general practitioners. General practitioners and private specialists received respectively 98.7 and 91.0 disciplinary actions per 1000 doctors. Senior consultants and junior doctors working in hospitals received respectively 17.0 and 6.4 disciplinary actions per 1000 doctors. Eight times more actions were received by primary care doctors than secondary care doctors. Doctors working in primary care were given a warning 10.6 times more often and had their licence revoked or restricted 4.6 times more often than those in secondary care.

Conclusion

The distribution and frequency of disciplinary actions by the Norwegian Board of Health Supervision clearly varied according to type of health care facility. Private specialists and general practitioners, especially those working in rural clinics, received the most disciplinary actions. These results deserve attention from health policy-makers and warrant further studies to determine the factors that influence medical malpractice. Moreover, the supervisory authorities should assess whether their procedures for reacting to malpractice are efficient and adequate for all types of physicians working in Norway.
Protective effect of selenomethionine on T-2 toxin-induced liver injury in New Zealand rabbits
Authors: Liu Yumei , Wang Haojie , Zhang Mengyu , Wang Jiajia , Zhang Zhixiang , Wang Yuqin , Sun Yingying , Zhang Ziqiang
Published: April 2021

Background

T-2 toxin is a mycotoxin produced by Fusarium species that is highly toxic to animals. Recent studies have indicated that Selenomethionine (SeMet) have protective effect against mycotoxins-induced toxicity. The aim of the present study was to investigate the protective effect of SeMet on T-2-toxin-induced liver injury in rabbit and explore its molecular mechanism. Fifty rabbits (30 d, 0.5 ± 0.1 kg) were randomly divided into 5 groups: control group, T-2 toxin group, low, medium and high dose SeMet treatment group. The SeMet-treated group was orally pretreated with SeMet (containing selenium 0.2 mg/kg, 0.4 mg/kg and 0.6 mg/kg) for 21 days. On the 17th day, T-2 toxin group and SeMet-treated group were orally administered with T-2 toxin (0.4 mg/kg body weight) for 5 consecutive days.

Results

The results showed that low-dose SeMet significantly improved T-2 toxin-induced liver injury. We found that low-dose SeMet can reduce the level of oxidative stress and the number of hepatocyte apoptosis. Moreover, the levels of Bax, caspase-3 and caspase-9 were significantly reduced and the levels of Bcl-2 were increased.

Conclusions

Therefore, we confirmed that low-dose SeMet may protect rabbit hepatocytes from T-2 toxin by inhibiting the mitochondrial-caspase apoptosis pathway.
There is detectable variation in the lipidomic profile between stable and progressive patients with idiopathic pulmonary fibrosis (IPF)
Authors: Nambiar Shabarinath , Clynick Britt , How Bong S. , King Adam , Walters E. Haydn , Goh Nicole S. , Corte Tamera J. , Trengove Robert , Tan Dino , Moodley Yuben
Published: April 2021

Background

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease characterized by fibrosis and progressive loss of lung function. The pathophysiological pathways involved in IPF are not well understood. Abnormal lipid metabolism has been described in various other chronic lung diseases including asthma and chronic obstructive pulmonary disease (COPD). However, its potential role in IPF pathogenesis remains unclear.

Methods

In this study, we used ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) to characterize lipid changes in plasma derived from IPF patients with stable and progressive disease. We further applied a data-independent acquisition (DIA) technique called SONAR, to improve the specificity of lipid identification.

Results

Statistical modelling showed variable discrimination between the stable and progressive subjects, revealing differences in the detection of triglycerides (TG) and phosphatidylcholines (PC) between progressors and stable IPF groups, which was further confirmed by mass spectrometry imaging (MSI) in IPF tissue.

Conclusion

This is the first study to characterise lipid metabolism between stable and progressive IPF, with results suggesting disparities in the circulating lipidome with disease progression.
Quality of care for adult in-patients with malaria in a tertiary hospital in Uganda
Authors: Kiguba Ronald , Karamagi Charles , Bird Sheila M.
Published: April 2021

Background

Prompt detection and appropriate treatment of malaria prevents severe disease and death. The quality of care for adult malaria in-patients is not well documented in sub-Saharan Africa, particularly in Uganda. The study sought to describe the patterns of malaria diagnosis and treatment among adult in-patients admitted to the medical and gynaecological wards of Uganda’s 1790-bed Mulago National Referral Hospital from December 2013 to April 2014.

Methods

A prospective cohort of 762 consented in-patients aged ≥ 18 years was assembled. Proportions of in-patients who received preadmission and in-hospital anti-malarials, missed Day 1 dosing of hospital-initiated anti-malarials and/or had malaria microscopy done were determined. Multivariable logistic regression was used to identify risk-factors for missed Day 1 dosing of anti-malarials.

Results

One in five (19%, 146/762) in-patients had an admission or discharge malaria diagnosis or both; with median age of 29 years (IQR, 22–42 years). Microscopy was requested in 77% (108/141) of in-patients with an admission malaria diagnosis; results were available for 46% (50/108), of whom 42% (21/50) tested positive for Plasmodium falciparum malaria parasitaemia. Only 13% (11/83) of in-patients who received in-hospital injectable artesunate (AS) or quinine (Q) received follow-up oral artemether-lumefantrine (AL); 2 of 18 severe malaria cases received follow-up oral AL. Injectable AS only (47%, 47/100) was the most frequent hospital-initiated anti-malarial treatment followed by injectable Q only (23%, 23/100) amongst in-patients who received in-hospital anti-malarials. A quarter (25%, 25/100; 95% CI: 17–35%) of in-patients missed Day 1 dosing of hospital-initiated anti-malarials. Each additional admission diagnosis was more than two-fold likely to increase the odds of missed Day 1 dosing of in-hospital anti-malarials (aOR = 2.6, 95% CI: 1.52–4.56; P-value = 0.001).

Conclusions

Half the malaria microscopy results were not available; yet, the rate of testing was high. The majority of in-patients initiated on injectable AS or Q did not receive the recommended follow-up oral AL. One in four in-patients delayed to initiate hospital anti-malarials by at least one calendar day. The hospital should encourage prompt availability of malaria test-results to promote the timely initiation and completion of anti-malarial treatment, thereby improving the quality of care for hospitalized malaria patients in Uganda.
Effect of short-term exposure to particulate air pollution on heart rate variability in normal-weight and obese adults
Authors: Li Luyi , Hu Dayu , Zhang Wenlou , Cui Liyan , Jia Xu , Yang Di , Liu Shan , Deng Furong , Liu Junxiu , Guo Xinbiao
Published: April 2021

Background

The adverse effects of particulate air pollution on heart rate variability (HRV) have been reported. However, it remains unclear whether they differ by the weight status as well as between wake and sleep.

Methods

A repeated-measure study was conducted in 97 young adults in Beijing, China, and they were classified by body mass index (BMI) as normal-weight (BMI, 18.5–24.0 kg/m2) and obese (BMI ≥ 28.0 kg/m2) groups. Personal exposures to fine particulate matter (PM2.5) and black carbon (BC) were measured with portable exposure monitors, and the ambient PM2.5/BC concentrations were obtained from the fixed monitoring sites near the subjects’ residences. HRV and heart rate (HR) were monitored by 24-h Holter electrocardiography. The study period was divided into waking and sleeping hours according to time-activity diaries. Linear mixed-effects models were used to investigate the effects of PM2.5/BC on HRV and HR in both groups during wake and sleep.

Results

The effects of short-term exposure to PM2.5/BC on HRV were more pronounced among obese participants. In the normal-weight group, the positive association between personal PM2.5/BC exposure and high-frequency power (HF) as well as the ratio of low-frequency power to high-frequency power (LF/HF) was observed during wakefulness. In the obese group, personal PM2.5/BC exposure was negatively associated with HF but positively associated with LF/HF during wakefulness, whereas it was negatively correlated to total power and standard deviation of all NN intervals (SDNN) during sleep. An interquartile range (IQR) increase in BC at 2-h moving average was associated with 37.64% (95% confidence interval [CI]: 25.03, 51.51%) increases in LF/HF during wakefulness and associated with 6.28% (95% CI: − 17.26, 6.15%) decreases in SDNN during sleep in obese individuals, and the interaction terms between BC and obesity in LF/HF and SDNN were both statistically significant (p <  0.05). The results also suggested that the effects of PM2.5/BC exposure on several HRV indices and HR differed in magnitude or direction between wake and sleep.

Conclusions

Short-term exposure to PM2.5/BC is associated with HRV and HR, especially in obese individuals. The circadian rhythm of HRV should be considered in future studies when HRV is applied.

Graphical abstract
A novel protein encoded by circMAPK1 inhibits progression of gastric cancer by suppressing activation of MAPK signaling
Authors: Jiang Tianlu , Xia Yiwen , Lv Jialun , Li Bowen , Li Ying , Wang Sen , Xuan Zhe , Xie Li , Qiu Shengkui , He Zhongyuan , Wang Linjun , Xu Zekuan
Published: April 2021

Background

A novel type of noncoding RNA, circRNA has been reported to participate in the occurrence and development of diseases through many mechanisms. The MAPK pathway is a common signal transduction pathway involved in cell proliferation, inflammation and apoptosis and plays a particularly important role in cancers. However, the role of circRNAs related to the MAPK pathway in gastric cancer has not been explored.

Methods

A bioinformatics analysis was performed to profile and identify the circRNAs involved in the MAPK pathway in gastric cancer. The tumor-suppressive role of circMAPK1 was confirmed both in vitro and in vivo. Mass spectrometry, Western blot and immunofluorescence staining assays were used to validate the existence and expression of MAPK1–109aa. The molecular mechanism of circMAPK1 was investigated by mass spectrometry and immunoprecipitation analyses.

Results

In this study, we identified that circMAPK1 (hsa_circ_0004872) was downregulated in gastric cancer tissues compared with adjacent normal tissues. Importantly, lower circMAPK1 expression predicted poor survival in GC patients. CircMAPK1 inhibited the proliferation and invasion of gastric cancer cells in vitro and in vivo. Next, we found that circMAPK1 encoded a novel protein with 109 amino acids in length. Through a series of functional experiments, we confirmed that circMAPK1 exerted a tumor-suppressing effect via the encoded protein MAPK1–109aa. Mechanistically, the tumor suppressor MAPK1–109aa inhibited the phosphorylation of MAPK1 by competitively binding to MEK1, thereby suppressing the activation of MAPK1 and its downstream factors in MAPK pathway.

Conclusions

Our study revealed that circMAPK1 inhibits the malignant biological behavior of gastric cancer cells through its encoded protein MAPK1–109aa. More importantly, circMAPK1 is a favorable predictor for gastric cancer patients and may provide a new therapeutic target in the treatment of gastric cancer.
Chemical composition of surgical smoke produced during the loop electrosurgical excision procedure when treating cervical intraepithelial neoplasia
Authors: Liu Yi , Zhao Menghuang , Shao Yongqiang , Yan Linzhi , Zhu Xueqiong
Published: April 2021

Background

As LEEP (loop electrosurgical excision procedure) is being increasingly used for the diagnosis and treatment of uterine cervical intraepithelial neoplasia, surgical smoke during LEEP has become an inevitable health issue. Therefore, in this study, exposure to the chemical substances in surgical smoke produced during LEEP was assessed.

Methods

Smoke samples from patients with high-grade cervical intraepithelial neoplasia undergoing LEEP were collected by smoke-absorbing devices situated 1 m away from the operating table and near the nose of the operator during LEEP. Each plume sample was collected after 5 patients underwent LEEP, requiring 5 min for smoke collection for each patient. The chemicals of exposure to surgical smoke were assessed, and the hazard classes of these chemical components were evaluated by the International Agency for Research on Cancer.

Results

Qualitative analysis of the smoke produced during LEEP revealed a variety of potentially toxic chemicals under standard detection, such as benzene, toluene, xylene, ethylbenzene, styrene, butyl acetate, acrylonitrile, 1,2-dichloroethane, phenol, chlorine, cyanide, hydrogen cyanide and carbon monoxide. Additionally, the average concentration of carbon dioxide was 0.098 ± 0.015% during surgery and was higher than that before surgery (0.072 ± 0.007%, P < 0.001), and the concentration of formaldehyde was significantly higher during surgery (0.023 ± 0.009 mg/m3, P < 0.05) than before surgery (0.012 ± 0.001 mg/m3, P < 0.05).

Conclusions

Most of the detected chemical concentrations in smoke generated during LEEP were below the exposure limits when local exhaust ventilation procedures were efficiently used. However, the concentrations of carbon dioxide and formaldehyde found in smoke were significantly higher after surgery. Wearing a high-filtration mask and using evacuation devices routinely and consistently when performing LEEP are recommended to protect perioperative personnel.
A prospective study investigating the efficacy and toxicity of definitive ChemoRadiation and ImmunOtherapy (CRIO) in locally and/or regionally advanced unresectable cutaneous squamous cell carcinoma
Authors: Lin Charles , Ballah Trishna , Nottage Michelle , Hay Karen , Chua Benjamin , Kenny Lizbeth , Thomas Paul , Teng Michele , Keller Jacqui , Le Trang , Edmunds Jennifer , Hughes Brett
Published: April 2021

Background

Patients with unresectable advanced cutaneous squamous cell carcinoma (cSCC) are generally treated with palliative intent. Immune checkpoint blockade has significant activity in the palliative setting in patients with recurrent or metastatic cSCC. This single arm phase 2 prospective study aims to investigate the combination of curative intent chemoradiation and durvalumab (anti-PD-L1 checkpoint inhibitor) for this patient cohort.

Methods

Patients with unresectable locally and or regionally advanced pathologically confirmed cSCC (stage III-IVa) deemed fit for CRIO by consensus of the Multidisciplinary meeting will be eligible. In the first stage of a two-stage minimax design, we aim to recruit a total of 15 patients. If fewer than 7 patients achieved a complete response in the first stage, we will conclude the treatment is not more effective than standard treatment. The co-primary endpoints of CRIO are the safety of treatment (acute and late toxicities) and the rate of complete response. Secondary endpoints would include overall survival, progression free survival, and locoregional control. Translational research endpoints including biomarkers (CD73, CD39, PD-1, PD-L1) will also be explored utilising multiplex immunohistochemistry on tumour biopsy samples obtained prior to commencing treatment and during treatment (week 2). In addition, the utility of CXCR-4 PET/CT scan will be explored.

Discussion

CRIO is a novel trial evaluating the combination of curative intent chemoradiotherapy with concurrent and adjuvant durvalumab for patients with unresectable stage III-IVa cSCC.

Trial registration: Trial registered with the Australian New Zealand Clinical Trial Registry (ACTRN12618001573246)
Carrier frequency and incidence estimation of Smith–Lemli–Opitz syndrome in East Asian populations by Genome Aggregation Database (gnomAD) based analysis
Authors: Park Jong Eun , Lee Taeheon , Ha Kyeongsu , Ki Chang-Seok
Published: April 2021

Background

Smith–Lemli–Opitz syndrome (SLOS) is an autosomal, recessively inherited congenital malformation syndrome characterized by multiple congenital anomalies such as microcephaly with mental defects, distinctive facial features, genital abnormalities, and 2–3 syndactyly of the toes. SLOS is caused by defective 7-dehydrocholesterol reductase, which is encoded by the DHCR7 gene. This study aimed to analyze the carrier frequency and expected incidence of SLOS in East Asians and Koreans using exome data from the Genome Aggregation Database (gnomAD) through the 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology guideline (2015 ACMG-AMP guideline).

Methods

We analyzed 9197 exomes for East Asian populations from gnomAD, comprising 1909 Korean, 76 Japanese, and 7212 other East Asian populations. All identified variants were classified according to the 2015 ACMG-AMP guideline.

Results

According to the 2015 ACMG-AMP guideline, 15 pathogenic variant/likely pathogenic variant (PV/LPV) cases were identified in 33 East Asian individuals (33/9191 = 0.4%). Among them, four PVs/LPVs were identified in 19 Korean individuals (19/1909 = 1.0%). The predicted incidence, based upon the carrier rates of PV/LPV of DHCR7 alleles, is 1 in 310,688 in East Asians and l in 40,380 in Koreans.

Conclusions

This study is the first to identify carrier frequencies in East Asians and Koreans using gnomAD. It was confirmed that East Asians (0.4%) had a lower carrier frequency than did other ethnicities (1–3%) and Koreans (1.0%) had similar or lower carrier frequencies than other ethnicities. The variant spectrums of DHCR7 in East Asian and Korean populations differed greatly from those of other ethnic groups.
Impact of newborn screening for cystic fibrosis on clinical outcomes of pediatric patients: 10 years’ experience in Lodz Voivodship
Authors: Olszowiec-Chlebna M. , Mospinek E. , Jerzynska J.
Published: April 2021

Background

Cystic Fibrosis newborn screening (CFNBS) is the optimal method to diagnose the disease during the asymptomatic period. The aim of the study was to determine how CFNBS affects long term clinical outcomes.

Methods

Data from infants who were born in Lodz Voivodship, referred to CF center as a part of CFNBS according to IRT/DNA protocol were compared to the data of children with established CF diagnosis before the start of NBS in Poland (Group CF, n = 52).

Results

In 37 children (during 151 referred infants) the diagnosis of CF was established due to CF NBS (CF NBS Group, n = 37). The average time of diagnosis was 1.59 month in Group CF NBS and 45.25 months in 52 children from Group CF.

Pulmonary exacerbations occurred on average 4.2 times in Group CFNBS and they were hospitalized on average 0.5 times compared to Group CF – respectively 6.77 and 2.14 (p < 0.001).

The number of PA infected patients increased between the fifth and eighth year of age (OR = 1.16 (95% CI: 1.04–19) (P = 0.007)) regardless of the study group (P = 0.984). Patients with MRSA infection have a higher risk of PA infections in subsequent years of their life (OR = 1.45 (95% CI: 1.03–2.03) (P = 0.032)).

Conclusions

CF NBS has beneficial effects primarily on decrease of pulmonary withhope for a longer life expectancy and better and centralised treatment in multidisciplinary CF focused centres.
Efficacy and safety of sprifermin injection for knee osteoarthritis treatment: a meta-analysis
Authors: Zeng Ni , Chen Xin-Yuan , Yan Zhi-Peng , Li Jie-Ting , Liao Tao , Ni Guo-Xin
Published: April 2021

Objective

To perform a meta-analysis comparing the structural progression and clinical symptom outcomes as well as adverse events experienced from intra-articular injections of sprifermin compared to a placebo treatment for patients with knee osteoarthritis (KOA).

Method

We systematically searched the literature for studies that compared long-term outcomes between sprifermin and placebo injections for KOA treatment. Meta-analysis was performed with RevMan5.3 using an inverse variance approach with fixed or random effects models. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated.

Results

Eight studies were included. Overall, there was significantly less improvement of WOMAC total scores in patients receiving sprifermin, compared with the placebo (mean difference (MD) = 3.23, 95% CI 0.76–5.69; I2 = 0%; P = 0.01). Further, sprifermin injection patients gained more, and lost less, cartilage thickness and volume in total femorotibial joint (cartilage thickness: standardized mean differences (SMD) = 0.55, 95% CI 0.26–0.84; I2 = 78%; P = 0.0002; cartilage volume: SMD = 0.39, 95% CI 0.20–0.58; I2 = 49%; P < 0.0001). Changes in the cartilage surface morphology of the medial tibio-femoral joint (MD = −0.30, 95% CI −0.44 to −0.16; I2 = 0%; P < 0.0001) and patello-femoral joint (MD = −0.22; 95% CI −0.37 to −0.07; I2 = 0%; P = 0.004) showed a significant difference between the sprifermin and placebo injections. Moreover, there were no significant differences between sprifermin and the placebo in the risk of treatment-emergent adverse events (OR = 1.05; 95% CI 0.52–2.14; I2 = 48%; P = 0.89).

Conclusion

The data from the included studies provide strong evidence to determine the effect of intra-articular sprifermin on joint structure in individuals with KOA and show no specific adverse effects. Nevertheless, intra-articular sprifermin did not likely have any positive effect on symptom alleviation.
DNA methylation and gene expression integration in cardiovascular disease
Authors: Palou-Márquez Guillermo , Subirana Isaac , Nonell Lara , Fernández-Sanlés Alba , Elosua Roberto
Published: April 2021

Background

The integration of different layers of omics information is an opportunity to tackle the complexity of cardiovascular diseases (CVD) and to identify new predictive biomarkers and potential therapeutic targets. Our aim was to integrate DNA methylation and gene expression data in an effort to identify biomarkers related to cardiovascular disease risk in a community-based population. We accessed data from the Framingham Offspring Study, a cohort study with data on DNA methylation (Infinium HumanMethylation450 BeadChip; Illumina) and gene expression (Human Exon 1.0 ST Array; Affymetrix). Using the MOFA2 R package, we integrated these data to identify biomarkers related to the risk of presenting a cardiovascular event.

Results

Four independent latent factors (9, 19, 21—only in women—and 27), driven by DNA methylation, were associated with cardiovascular disease independently of classical risk factors and cell-type counts. In a sensitivity analysis, we also identified factor 21 as associated with CVD in women. Factors 9, 21 and 27 were also associated with coronary heart disease risk. Moreover, in a replication effort in an independent study three of the genes included in factor 27 were also present in a factor identified to be associated with myocardial infarction (CDC42BPB, MAN2A2 and RPTOR). Factor 9 was related to age and cell-type proportions; factor 19 was related to age and B cells count; factor 21 pointed to human immunodeficiency virus infection-related pathways and inflammation; and factor 27 was related to lifestyle factors such as alcohol consumption, smoking and body mass index. Inclusion of factor 21 (only in women) improved the discriminative and reclassification capacity of the Framingham classical risk function and factor 27 improved its discrimination.

Conclusions

Unsupervised multi-omics data integration methods have the potential to provide insights into the pathogenesis of cardiovascular diseases. We identified four independent factors (one only in women) pointing to inflammation, endothelium homeostasis, visceral fat, cardiac remodeling and lifestyles as key players in the determination of cardiovascular risk. Moreover, two of these factors improved the predictive capacity of a classical risk function.