bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling observations with a detection limit using a truncated normal distribution with censoring
Authors: Williams Justin R. , Kim Hyung-Woo , Crespi Catherine M.
Published: June 2020

Background

When data are collected subject to a detection limit, observations below the detection limit may be considered censored. In addition, the domain of such observations may be restricted; for example, values may be required to be non-negative.

Methods

We propose a method for estimating population mean and variance from censored observations that accounts for known domain restriction. The method finds maximum likelihood estimates assuming an underlying truncated normal distribution.

Results

We show that our method, tcensReg, has lower bias, Type I error rates, and mean squared error than other methods commonly used for data with detection limits such as Tobit regression and single imputation under a range of simulation settings from mild to heavy censoring and truncation. We further demonstrate the consistency of the maximum likelihood estimators. We apply our method to analyze vision quality data collected from ophthalmology clinical trials comparing different types of intraocular lenses implanted during cataract surgery. All of the methods yield similar conclusions regarding non-inferiority, but estimates from the tcensReg method suggest that there may be greater mean differences and overall variability.

Conclusions

In the presence of detection limits, our new method tcensReg provides a way to incorporate known domain restrictions in dependent variables that substantially improves inferences.
A conceptual framework for prognostic research
Authors: Kent Peter , Cancelliere Carol , Boyle Eleanor , Cassidy J. David , Kongsted Alice
Published: June 2020

Background

Prognostic research has many important purposes, including (i) describing the natural history and clinical course of health conditions, (ii) investigating variables associated with health outcomes of interest, (iii) estimating an individual’s probability of developing different outcomes, (iv) investigating the clinical application of prediction models, and (v) investigating determinants of recovery that can inform the development of interventions to improve patient outcomes. But much prognostic research has been poorly conducted and interpreted, indicating that a number of conceptual areas are often misunderstood. Recent initiatives to improve this include the Prognosis Research Strategy (PROGRESS) and the Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD) Statement. In this paper, we aim to show how different categories of prognostic research relate to each other, to differentiate exploratory and confirmatory studies, discuss moderators and mediators, and to show how important it is to understand study designs and the differences between prediction and causation.

Main text

We propose that there are four main objectives of prognostic studies – description, association, prediction and causation. By causation, we mean the effect of prediction and decision rules on outcomes as determined by intervention studies and the investigation of whether a prognostic factor is a determinant of outcome (on the causal pathway). These either fall under the umbrella of exploratory (description, association, and prediction model development) or confirmatory (prediction model external validation and investigation of causation). Including considerations of causation within a prognostic framework provides a more comprehensive roadmap of how different types of studies conceptually relate to each other, and better clarity about appropriate model performance measures and the inferences that can be drawn from different types of prognostic studies. We also propose definitions of ‘candidate prognostic factors’, ‘prognostic factors’, ‘prognostic determinants (causal)’ and ‘prognostic markers (non-causal)’. Furthermore, we address common conceptual misunderstandings related to study design, analysis, and interpretation of multivariable models from the perspectives of association, prediction and causation.

Conclusion

This paper uses a framework to clarify some concepts in prognostic research that remain poorly understood and implemented, to stimulate discussion about how prognostic studies can be strengthened and appropriately interpreted.
Transarterial chemoembolization combined with iodine 125 seeds versus transarterial chemoembolization combined with radiofrequency ablation in the treatment of early- and intermediate-stage hepatocellular carcinoma
Authors: Chen Lei , Kan Xuefeng , Sun Tao , Ren Yanqiao , Cao Yanyan , Yan Liangliang , Liang Bin , Xiong Bin , Zheng Chuansheng
Published: June 2020

Background

Transarterial chemoembolization (TACE), radiofrequency ablation (RFA), and iodine 125 seeds implantation are optional treatments for hepatocellular carcinoma (HCC). The aim of this study is to compare the efficacy of the combined treatment of TACE with iodine 125 seeds implantation (TACE-iodine 125) with TACE with RFA (TACE-RFA) in patients with early- and intermediate-stage HCC.

Methods

The study included 112 patients who were diagnosed with early- and intermediate-stage HCC from January 1, 2014, to May 31, 2018. Among them, 38 patients were treated with TACE-Iodine 125, and 74 with TACE-RFA. The efficacy of the two treatment groups was retrospectively analyzed. To reduced the selective bias, a propensity score matching (PSM) analysis and inverse probability of treatment weighting (IPTW) method were used to compare the outcomes between the two groups.

Results

In the absence of PSM and IPTW, the median overall survival (OS) and progression-free survival (PFS) of the TACE-RFA group were slightly longer than those of the TACE-Iodine 125 group (OS: 41 months vs. 36 months; PFS: 18 months vs. 15 months). However, there were no statistically significant differences in the median OS, PFS, and objective response rate (ORR) between the two groups (P > 0.05). After adjusting the age, gender, Child-Pugh class, Barcelona Clinic Liver Cancer (BCLC) stage, and Alpha-fetoprotein (AFP), TACE-Iodine 125 treatment was not associated with a significant increasing the risks of death (HR: 0.763; 95%CI: 0.403,1.345, P = 0.320) and recurrence (HR: 1.020; 95%CI: 0.645,1.611, P = 0.934). After PSM, 35 matched pairs of patients were obtained, and there were no statistically significant differences in the median OS and PFS between the two groups. After IPTW, similar results presented.

Conclusions

The combination of TACE with iodine 125 seeds implantation may represent an effective treatment for patients with early- and intermediate-stage HCC.
Asymptomatic central line-associated bloodstream infections in children implanted with long term indwelling central venous catheters in a teaching hospital, Sri Lanka
Authors: Jayaweera J. A. A. S. , Sivakumar D.
Published: June 2020

Background

Indwelling central venous catheters (CVC) are used to provide long term hemodialysis. The commonest and the severe complication of CVC is the central line-associated bloodstream infection (CLABSI). This study was done to assess the etiology and infectious complications of CVC in children on long term hemodialysis.

Methods

Children newly undergoing hemodialysis and having indwelling CVC were included. They were followed up to a period of 2-years to assess infectious complications. Catheter bundle care approach was employed to prevent infections and other complications. Automated culture from the central catheter and peripheral vein and 2D echocardiography were done in each hemodialysis. Serial procalcitonin (PCT) was measured. Differential time of positivity (DTP) was used to detect CLABSI. During homestay in weekly telephone conversations were done to assess features of infection, and whenever having, we have asked to admit to the tertiary care unit. Logistic regression was performed, and the significant outcome variable was considered following multivariable analysis as a risk factor.

Results

Blood cultures were positive in 1090 (74.5%) out of 1462 children. According to DTP, 410 (28%) were having CLABSI, while 520 (35.6%) were having bacteremia without CLABSI. Out of 410 CLABSI patients, 79 (19.2%) were asymptomatic. Coagulase-negative Staphylococcus spp. (CoNS) bacteremia was significantly associated with asymptomatic CLABSI. Right-sided infective endocarditis (RS-IE) was significantly associated with asymptomatic CLABSI and asymptomatic bacteremia without CLABSI. CoNS was associated significantly in RS-IE following asymptomatic CLABSI and asymptomatic bacteremia. PCT was in asymptomatic CLABSI was 1.8 ± 0.9 ng/mL while in symptomatic CLABSI was 11.3 ± 2.5 ng/ml (P = 0.02). CoNS bloodstream infection, tunneled CVC, peripherally inserted central catheter, femoral site, the number of line days > 90, receipt of vancomycin, meropenem, or linezolid in the 5 days before CLABSI diagnosis and recurrent bacteremia were risk factors for asymptomatic CLABSI.

Conclusions

Asymptomatic CLABSI could be a rare occurrence. CoNS was predominantly isolated in patients with asymptomatic CLABSI. RS- IE is a well-known complication in long term indwelling CVC. CoNS was significantly associated with RS-IE following asymptomatic CLABSI. Regular procalcitonin, microbiological, and imaging studies would be essential to detect infectious complications in both symptomatic and asymptomatic patients implanted with long term indwelling CVCs.
Comparison of the clinical and MRI features of patients with hepatic hemangioma, epithelioid hemangioendothelioma, or angiosarcoma
Authors: Liu Zhuangsheng , Yi Lilei , Chen Junhao , Li Ruqiong , Liang Keming , Chen Xiangmeng , Li Ronggang , Long Wansheng
Published: June 2020

Background

Comparisons of hepatic epithelioid hemangioendothelioma (HEHE), hepatic hemangioma, and hepatic angiosarcoma (HAS) have rarely been reported. The purpose of our study was to analyze the clinical and magnetic resonance imaging (MRI) findings of these conditions.

Methods

A total of 57 patients (25 with hemangioma, 13 with HEHE, and 19 with HAS) provided hepatic vascular endothelial cell data between June 2006 and May 2017.

Results

The proportions of cases with circumscribed margins were 88% (22/25), 84.6% (11/13), and 31.6% (6/19) for hemangioma, HEHE, and HAS, respectively (P < 0.001). HAS lesions were less likely to have circumscribed margins. The proportions of lesions with hemorrhaging were 4% (1/25), 30.8% (4/13), and 36.8% (7/19) for hemangioma, HEHE, and HAS, respectively (P = 0.014). HEHE and HAS cases were more likely to show heterogeneous signals on T1-weighted (T1WI) MRI. HEHE and HAS cases were more likely to show heterogeneous signals on T2-weighted (T2WI) MRI. Centripetal enhancement was the most common pattern in vascular tumors, with proportions of 100, 46.2% (6/13), and 68.4% (13/19) for hemangioma, HEHE, and HAS, respectively. The difference in enhancement pattern between HEHE and HAS was not significant, but rim enhancement was more common for HEHE (46.2%, 6/13).

Conclusions

Our study revealed clinical and imaging differences between HEHE and HAS. The platelet count (PLT) and coagulation function of the HAS group decreased, whereas the alpha-fetoprotein (AFP) level increased. The 5-year survival rate for HAS was significantly lower than that of HEHE. A higher malignancy degree indicated a more blurred lesion margin, easier occurrence of hemorrhaging, and more heterogeneous T1WI and T2WI signals.
Prospective study of stress, depression and personality in myasthenia gravis relapses
Authors: Bogdan Anca , Barnett Carolina , Ali Abdulrahman , AlQwaifly Mohammed , Abraham Alon , Mannan Shabber , Ng Eduardo , Bril Vera
Published: June 2020

Background

Psychopathology and personality traits may influence the course of autoimmune disorders. With this prospective longitudinal cohort study, we aimed to assess personality, stress and depression in myasthenia patients who relapse and those who remain stable or improve (non-relapsers).

Method

We collected data from 155 consecutive adult patients with confirmed MG attending the Neuromuscular Clinic, Toronto General Hospital, between March 2017 and July 2018, for this study. Patients were assessed at baseline and 6 months, or at the time of MG relapse. At both visits, the patients were assessed clinically and were asked to complete self-administered questionnaires for disease severity, chronic stress and depression. Personality type was assessed at baseline only. Relapsing patients were defined as those patients with MGII score increasing by more than 5.5 points from visit 1 to visit 2.

Results

Relapsers had higher baseline scores for depression (p = 0.01) and the change in disease severity correlated with the change in depression score (r = 0.2534, p = 0.0015, 95% CI: 0.098 0.3961). Higher levels of stress at baseline and neuroticism predicted higher relapse rates (p = 0.01 and p < .0001, respectively). In the linear regression model, with change of the MGII score as the dependent variable, change in depression scores (p = 0.0004) and age (p = 0.03) predicted change in disease severity.

Conclusions

Since emotional factors and personality type may influence MG, attention to these factors might improve care in MG patients.
A novel POLR3A genotype leads to leukodystrophy type-7 in two siblings with unusually late age of onset
Authors: Campopiano Rosa , Ferese Rosangela , Zampatti Stefania , Giardina Emiliano , Biagioni Francesca , Colonnese Claudio , Centonze Diego , Storto Marianna , Buttari Fabio , Fraviga Edoardo , Broccoli Vania , Fanelli Mirco , Fornai Francesco , Gambardella Stefano
Published: June 2020

Background

Leukodystrophies are familial heterogeneous disorders primarily affecting the white matter, which are defined as hypomyelinating or demyelinating based on disease severity as assessed at MRI. Recently, a group of clinically overlapping hypomyelinating leukodystrophies (HL) has been associated with mutations in RNA polymerase III enzymes (Pol III) subunits.

Case presentation

In this manuscript, we describe two Italian siblings carrying a novel POLR3A genotype. MRI imaging, genetic analysis, and clinical data led to diagnosing HL type 7. The female sibling, at the age of 34, is tetra-paretic and suffers from severe cognitive regression. She had a disease onset at the age of 19, characterized by slow and progressive cognitive impairment associated with gait disturbances and amenorrhea. The male sibling was diagnosed during an MRI carried out for cephalalgia at the age of 41. After 5 years, he developed mild cognitive impairment, dystonia with 4-limb hypotonia, and moderate dysmetria with balance and gait impairment.

Conclusions

The present study provides the first evidence of unusually late age of onset in HL, describing two siblings with a novel POLR3A genotype which showed the first symptoms at the age of 41 and 19, respectively. This provides a powerful insight into clinical heterogeneity and genotype-phenotype correlation in POLR3A related HL.
Associations of malaria, HIV, and coinfection, with anemia in pregnancy in sub-Saharan Africa: a population-based cross-sectional study
Authors: Ssentongo Paddy , Ba Djibril M. , Ssentongo Anna E. , Ericson Jessica E. , Wang Ming , Liao Duanping , Chinchilli Vernon M.
Published: June 2020

Background

Malaria and HIV are common infections in Africa and cause substantial morbidity and mortality in pregnant women. We aimed to assess the association of malaria with anemia in pregnant women and to explore the joint effects of malaria and HIV infection on anemia in pregnant women.

Methods

We used nationally representative, cross-sectional demographic and health surveys (DHS) that were conducted between 2012 and 2017 across 7 countries of sub-Saharan Africa (Burundi, the Democratic Republic of the Congo, Gambia, Ghana, Mali, Senegal and Togo). The outcome variables were anemia (defined as a hemoglobin concentration < 110 g/L), and hemoglobin concentration on a continuous scale, in pregnant women at the time of the interview. We used generalized linear mixed-effects models to account for the nested structure of the data. We adjusted models for individual covariates, with random effects of the primary sampling unit nested within a country.

Results

A total of 947 pregnant women, ages, 15–49 y, were analyzed.Prevalence of malaria only, HIV only, and malaria- HIV coinfection in pregnant women was 31% (95% CI: 28.5 to 34.5%,n = 293), 1.3% (95% CI: 0.77 to 2.4%,n = 13) and 0.52% (95% CI: 0.02 to 1.3%,n = 5) respectively. Overall prevalence of anemia was 48.3% (95% CI: 45.1 to 51.5%). The anemia prevalence in pregnant women with malaria infection only was 56.0% (95% CI: 50.1 to 61.7%); HIV infection only, 62.5% (95% CI: 25.9 to 89.8%); malaria- HIV coinfection, 60.0 (95% CI: 17.0–92.7%) and without either infection, 44.6% (95% CI: 40.7 to 48.6%). In the fully adjusted models, malaria infection was associated with 27% higher prevalence of anemia (95% CI of prevalence ratio: 1.12 to 1.45;p = 0.004), and 3.4 g/L lower hemoglobin concentration (95% CI: - 5.01 to − 1.79;p = 0.03) compared to uninfected pregnant women. The prevalence of HIV infection and malaria-HIV coinfection was too low to allow meaningful analysis of their association with anemia or hemoglobin concentration.

Conclusion

Malaria was associated with an increased prevalence of anemia during pregnancy.
Absence of lymphatic vessels in term placenta
Authors: Becker Jürgen , Tchagou Tchangou Gilles E. , Schmidt Sonja , Zelent Christina , Kahl Fritz , Wilting Jörg
Published: June 2020

Background

There has been debate about the existence of lymphatic vessels in placenta. Lymphatic endothelial cell (LEC) markers such as LYVE-1 and podoplanin/D2–40 have been found, although PROX1 has not been detected. The most reliable marker for LECs is the double staining for CD31 and PROX1, which has not been performed yet.

Methods

We studied three term placentas and dissected them into three areas: i.) basal plate area, ii.) intermediate area, and iii.) chorionic plate area. We used immunofluorescence single and double staining with antibodies against CD31, PROX1, LYVE-1, VEGFR-3, D2–40/PDPN, CD34, CCBE-1, and vimentin, as well as nested PCR, qPCR, Western blot and transmission electron microscopy (TEM).

Results

At TEM level we observed structures that have previously mistakenly been interpreted as lymphatics, however, we did not find any CD31/PROX1 double-positive cells in placenta. Absence of PROX1 was also noted by nested PCR, qPCR and Western blot. Also, LEC marker VEGFR-3 was expressed only in a small number of scattered leukocytes but was absent from vessels. The LEC marker D2–40/PDPN was expressed in most stromal cells, and the LEC marker LYVE-1 was found in a considerable number of stromal cells, but not in endothelial cells, which were positive for CD31, CD34, CCBE-1 and vimentin. Additionally, vimentin was found in stromal cells.

Conclusions

Our studies clearly show absence of lymphatics in term placenta. We also show that the functional area of the mother’s endometrium is not penetrated by lymphatics in term pregnancy.
Tumor necrosis as a poor prognostic predictor on postoperative survival of patients with solitary small hepatocellular carcinoma
Authors: Ling Yi-hong , Chen Jie-wei , Wen Shi-hong , Huang Chao-yun , Li Peng , Lu Liang-he , Mei Jie , Li Shao-hua , Wei Wei , Cai Mu-yan , Guo Rong-ping
Published: June 2020

Background

Small hepatocellular carcinoma (sHCC) is a special subtype of HCC with the maximum tumor diameter ≤ 3 cm and excellent long-term outcomes. Surgical resection or radiofrequency ablation provides the greatest chance for cure; however, many patients still undergo tumor recurrence after primary treatment. To date, there is no clinical applicable method to assess biological aggressiveness in solitary sHCC.

Methods

In the current study, we retrospectively evaluated tumor necrosis of 335 patients with solitary sHCC treated with hepatectomy between December 1998 and 2010 from Sun Yat-sen University Cancer Center.

Results

The presence of tumor necrosis was observed in 157 of 335 (46.9%) sHCC patients. Further correlation analysis showed that tumor necrosis was significantly correlated with tumor size and vascular invasion (P = 0.026, 0.003, respectively). The presence of tumor necrosis was associated closely with poorer cancer-specific overall survival (OS) and recurrence-free survival (RFS) as evidenced by univariate (P <  0.001; hazard ratio, 2.821; 95% CI, 1.643–4.842) and multivariate analysis (P = 0.005; hazard ratio, 2.208; 95% CI, 1.272–3.833). Notably, the combined model by tumor necrosis, vascular invasion and tumor size can significantly stratify the risk for RFS and OS and improve the ability to discriminate sHCC patients’ outcomes (P <  0.0001 for both).

Conclusions

Our results provide evidence that tumor necrosis has the potential to be a parameter for cancer aggressiveness in solitary sHCC. The combined prognostic model may be a useful tool to identify solitary sHCC patients with worse outcomes.
Clinical analysis and predictive factors associated with improved visual acuity of infectious endophthalmitis
Authors: Gao Zhao , Zhang Yunda , Gao Xiaohong , Zhang Ximei , Ma Tao , Li Gaiyun , Wang Jingjing , Yan Hua
Published: June 2020

Background

To describe the clinical characteristics and analyze the predictive factors associated with improved visual acuity of 359 patients with infectious endophthalmitis.

Methods

This study retrospectively analyzed 359 eyes of 359 patients with infectious endophthalmitis from January 2014 to December 2018. The findings summarized some epidemiological characteristics of these patients, including age, sex, occupation, patient visit time, etiology, causative organisms, therapy, and best-corrected visual acuity. Multivariate logistic regression was performed to predict the relative factors of improved visual acuity (VA).

Results

Overall, 283 (78.83%) patients were male. The mean age was 48.0 ± 18.27 years. Ocular trauma, especially open globe injuries (246, 68.5%) was the most common etiology of infectious endophthalmitis in this study. The etiologies of infectious endophthalmitis were open globe injuries (68.5%), intraocular surgery (22.6%), and corneal ulcer-associated (6.7%) and endogenous causes (2.2%). In the etiology classification and visual acuity improvement group, had statistically significant differences in factors such as age, sex, patient visit time, pre-therapy visual acuity, etc. The average Logarithm of the Minimum Angle of Resolution (logMAR) best-corrected visual acuity on pre-therapy was 2.28 ± 0.60, and it had significantly improved to 1.67 ± 0.83 post-therapy (P < 0.05). Logistic regression analysis showed that visit time > 7 day (P = 0.034, OR = 0.522, 95% CI: 0.286–0.953), pre-therapy VA ≦logMAR 2.3 (P = 0.032, OR = 1.809, 95% CI: 1.052–3.110), post-surgical (vs. posttraumatic; P = 0.023, OR = 2.100, 95% CI: 1.109–3.974), and corneal ulcer-associated etiologies (vs. posttraumatic; P = 0.005, OR = 0.202, 95%CI: 0.066–0.621) were significantly associated with improved visual acuity after adjusting for possible confounding factors.

Conclusions

Among the patients with infectious endophthalmitis, middle-aged male, especially farmers and workers, accounted for a large proportion. Open globe injuries were the main cause and the gram-positive bacteria were the major causative organisms. The final visual outcomes seemed to vary according to the type of endophthalmitis, but early treatment and good initial visual acuity were important factors for visual acuity improvement.
Cost-effectiveness of immediate versus delayed sequential bilateral cataract surgery in the Netherlands (the BICAT-NL study): study design of a prospective multicenter randomised controlled trial
Authors: Spekreijse L. S. , Simons R. W. P. , Winkens B. , van den Biggelaar F. J. H. M. , Dirksen C. D. , Nuijts R. M. M. A.
Published: June 2020

Background

Cataract surgery is one of the most frequently performed types of surgery. Most patients suffer from bilateral cataract and while cataract surgery of only one eye is effective in restoring functional vision, second-eye surgery leads to further improvements in health-related quality of life, and is cost-effective. At present, most patients undergo cataract surgery in both eyes on separate days as recommended in national guidelines, referred to as delayed sequential bilateral cataract surgery (DSBCS). An alternative procedure involves operating both eyes on the same day, but as separate procedures, known as immediately sequential bilateral cataract surgery (ISBCS). The aim of this study is to evaluate the effectiveness and costs of ISBCS compared to DSBCS, in order to test the hypothesis that ISBCS is non-inferior to DSBCS in terms of effectiveness and superior to ISBCS in terms of cost-effectiveness.

Methods/design

Multicenter non-inferiority randomised controlled clinical trial. Patients (18 years or older) with bilateral cataract and an indication for bilateral cataract surgery with an expected uncomplicated intraoperative and postoperative course are included in the study. Patients are randomly assigned to either ISBCS or DSBCS. The primary endpoint is the proportion of patients with a refractive outcome in the second eye within 1.0 dioptre from the target refraction, at 4 weeks after surgery. Secondary outcomes include corrected and uncorrected distance visual acuity, complications, patient reported outcomes (PROMs), cost-effectiveness, and budget impact. Follow-up visits are planned at 1 week after first-eye surgery and 4 weeks after second-eye surgery. At 3 months after first-eye surgery, the occurrence of complications is checked and patients fill in a final questionnaire.

Discussion

This study protocol describes the design of a multicenter non-inferiority randomised controlled trial. Current studies on ISBCS often lack information on safety regarding refractive outcomes. In addition, there is a lack of well-designed cost-effectiveness studies using established methods. The BICAT-NL study will provide more insight in refractive and cost-effectiveness outcomes for ISBCS compared to DSBCS.

Trial registration

This study was prospectively registered at Clinicaltrials.gov on January 17th 2018. (Identifier:NCT03400124.
Association between wasting and food insecurity among children under five years: findings from Nepal demographic health survey 2016
Authors: Nepali Sajama , Simkhada Padam , Davies Ian Glynn
Published: June 2020

Background

Wasting is a consequence of food insecurity, inappropriate dietary practices, and inadequate caring and feeding practices. The present study assessed association between wasting and household food insecurity among under 5 years old children, along with other socio-demographic characteristics.

Methods

This study is a secondary analysis of the Nepal Demographic and Health Survey 2016. The survey is cross-sectional in design with use of standardized tools. The sampling frame used is an updated version of the frame from the 2011 National Population and Housing Census. The participants were children under 5 years of age (n = 2414). Logistic regression was carried out to identify the odds of being wasted for children belonging to different levels of food insecure households using odds ratio and 95% confidence intervals.

Results

The prevalence of wasting increased with the level of food insecurity, from mild (9.4%) to moderate (10.8%) and to severe (11.3%). The highest proportions of wasted children were in Province 2 (14.3%), from rural areas (10.1%), born to mothers with no education (12.4%) and from a richer quintile (11.3%). Children belonging to severe food insecure households had 1.36 (95%CI 0.72–2.57) adjusted odds of being wasted and those belonging to mild food insecure and moderately food insecure households had 0.98 (95%CI 0.64-1.49) and 1.13 (95%CI 0.65–1.97) odds of being wasted respectively. Province 1 (AOR 2.06, 95%CI 1.01–4.19) and Province 2 (AOR 2.45, 95%CI 1.22–4.95) were significantly associated with wasting.

Conclusion

Considering the increment in childhood wasting as per level of food insecurity, an integrated intervention should be developed in Nepal that, 1. addresses improving knowledge and behavior of community people with respect to diet and nutrition; 2. reduce the problem of food insecurity through agricultural interventions.
CARTA fellows’ scientific contribution to the African public and population Health Research agenda (2011 to 2018)
Authors: Igumbor Jude O. , Bosire Edna N. , Basera Tariro J. , Uwizeye Dieudonne , Fayehun Olufunke , Wao Hesborn , Ajuwon Ademola , Otukpa Emmanuel , Karimi Florah , Conco Daphney , Gitau Evelyn , Fonn Sharon
Published: June 2020

Background

Since its inception in 2009, the Consortium for Advanced Research Training in Africa (CARTA) program has focused on strengthening the capacity of nine African universities and four research centres to produce skilled researchers and scholars able to improve public and population health on the continent. This study describes the alignment between CARTA-supported doctoral topics and publications with the priorities articulated by the African public and population health research agenda.

Methods

We reviewed the output from CARTA PhD fellows between 2011 and 2018 to establish the volume and scope of the publications, and the degree to which the research focus coincided with the SDGs, World Bank, and African Development Bank research priority areas. We identified nine key priority areas into which the topics were classified.

Results

In total, 140 CARTA fellows published 806 articles in peer-reviewed journals over the 8 years up to 2018. All the publications considered in this paper had authors affiliated with African universities, 90% of the publications had an African university first author and 41% of the papers have CARTA fellows as the first author. The publications are available in over 6300 online versions and have been cited in over 5500 other publications. About 69% of the published papers addressed the nine African public and population health research agenda and SDG priority areas. Infectious diseases topped the list of publications (26.8%), followed by the health system and policy research (17.6%), maternal and child health (14.7%), sexual and reproductive health (14.3%).

Conclusions

Investments by CARTA in supporting doctoral studies provides fellows with sufficient training and skills to publish their research in fields of public and population health. The number of publications is understandably uneven across Africa’s public and population priority areas. Even while low in number, fellows are publishing in areas such as non-communicable disease, health financing, neglected tropical diseases and environmental health. Violence and injury is perhaps underrepresented. There is need to keep developing research capacity in partner institutions with low research output by training more PhDs in such institutions and by facilitating enabling environments for research.
Real-life experience with benralizumab during 6 months
Authors: Padilla-Galo A. , Levy-Abitbol RCh , Olveira C. , Valencia Azcona B. , Pérez Morales M. , Rivas-Ruiz F. , Tortajada-Goitia B. , Moya-Carmona I. , Levy-Naon A.
Published: June 2020

Background

Benralizumab is a monoclonal antibody that binds to the human interleukin-5 (IL-5) receptor (IL-5R), thereby preventing IL-5 from binding to its receptor and inhibiting differentiation and maturation of eosinophils in the bone marrow. Because of its recent marketing approval, sufficient real-life evidence is lacking to confirm the efficacy and safety data from clinical trials. The purpose of this study was to evaluate the efficacy and safety of benralizumab for the treatment of severe refractory eosinophilic asthma in a real-world cohort of patients.

Methods

This was a cross-sectional multicentre study of consecutive patients with severe refractory eosinophilic asthma who received treatment with benralizumab during at least 6 months. Patient follow-up was performed in specialised severe asthma units.

Results

A total of 42 patients were enrolled and treated with benralizumab. Asthma control, as measured by the asthma control test (ACT), improved in all patients both at 3 months of treatment compared with baseline (13.9 ± 4 vs 20.1 ± 3.7,p < 0.001) and at 6 months of treatment compared with the results obtained at 3 months (20.1 ± 3.7 vs 21 ± 2.7,p = 0.037). Similarly, the number of emergency department visits decreased both at 3 months compared with baseline (1 [IR:0.7] vs 0 [IR:0.75],p < 0.001) and at 6 months compared with the results at 3 months (0 [IR:0.75] vs 0 [IR:0],p = 0.012). Reductions in the number of oral corticosteroid cycles, percentage of corticosteroid-dependent patients, and mean daily dose of oral or inhaled corticosteroid were also evidenced. Finally, mean lung function improvement was 291 mL (p < 0.001), and FEV1% improved both at 3 months compared with baseline (64.4 ± 9.3 vs 73.1 ± 9.1,p < 0.001) and at 6 months compared to 3 months (73.1 ± 9.1 vs 76.1 ± 12,p = 0.002). Side effects were mild and did not lead to treatment discontinuation.

Conclusions

This study confirms the efficacy and safety of benralizumab in a real-life setting with improved asthma control and lung function, and a reduced oral and inhaled corticosteroid use as well as fewer emergency department visits. In addition to a rapid initial improvement, it appears that patients continue to improve during the first 6 months of treatment.
Comparison of cylindrical and tapered stem designs for femoral revision hip arthroplasty
Authors: Zhang Yu , Zhang Ye , Sun Jian-Ning , Hua Zi-Jian , Chen Xiang-Yang , Feng Shuo
Published: June 2020

Background

Both cylindrical and tapered stems are commonly used in revision total hip arthroplasty. However, whether the geometry of prosthesis stem has an effect on patient prognosis is unclear. We assume that the tapered stem results in better clinical outcome than the cylindrical stem.

Methods

A multicenter review of 120 femoral revisions with Paprosky I, II, and III defects using cobalt chrome cylindrical stem (54 hips) or titanium tapered stem (66 hips) was performed with an average follow-up of 6 years. Demographic data were comparable between groups.

Results

No significant group differences were found in surgery time, bleeding volume, postoperative Harris Hip Score, level of overall satisfaction, and 8-year cumulative survival. However, intraoperative fractures occurred significantly less in the tapered group (4.5%) than in the cylindrical group (14.8%), and stem subsidence was significantly less in the tapered group (2.17 mm) than in the cylindrical group (4.17 mm). A higher ratio of bone repair and lower bone loss were observed in the tapered group compared with the cylindrical group. The postoperative thigh pain rate was higher in the cylindrical group (12.9%) than in the tapered group (4.5%).

Conclusion

Both cylindrical stem and tapered stem can achieve satisfactory mid-term clinical results in revision total hip arthroplasty. The tapered stem has better bone restoration of proximal femur, lower incidence of intraoperative fractures, and lower postoperative thigh pain rate compared with the cylindrical stem.
Experimental pain and fatigue induced by excessive chewing
Authors: Al Sayegh Samaa , Vasilatou Ioanna , Kumar Abhishek , Al Barwari Ceva , Fredriksson Lars , Grigoriadis Anastasios , Christidis Nikolaos
Published: June 2020

Background

The study was aiming to optimize excessive gum chewing as an experimental model to induce jaw muscle pain and fatigue similar to those in painful TMDs with durations that would allow immediate investigations of jaw-motor function. Further, if any sex differences would be detected in the expression of pain.

Methods

This randomized, double blinded study included 31 healthy participants of both sexes. A standardized chewing protocol of either 40- or 60-min of chewing was used with a wash-out period of 1 week. Subjective fatigue, pain characteristics and functional measures were assessed. For statistical analyses, Wilcoxon Signed Rank test, Mann–Whitney Rank Sum test and Friedman’s ANOVA with Tukey post-hoc test were used.

Results

High subjective fatigue scores that lasted up to 20 min after the end of the trial were significantly induced both in the 40- and 60-min chewing trials (P <  0.001*). Significant but mild pain was induced only in the 60-min trial (P = 0.004*) and only in men (P = 0.04*). Also, the induced pain area was significantly bigger in the 60-min trial (P = 0.009*). However, this increase in pain and pain area did not last to the first 10-min follow-up. There were no significant differences neither between the 40- and 60-min chewing trials, except regarding the pain area (P = 0.008*), nor between the sexes.

Conclusion

Taken together, excessive chewing in its current form does not seem to be a proper pain experimental model. The model needs further adjustments in order to mimic TMD-pain especially in women and to prolong the pain duration.
Impact of a health alert and its implementation on flutamide prescriptions for women: an interrupted time series analysis
Authors: Vázquez-Mourelle Raquel , Carracedo-Martínez Eduardo , Figueiras Adolfo
Published: June 2020

Background

Off-label drug use among ambulatory patients is often based on little or no scientific support. This paper reports the impact of a health warning about the risks of off-label flutamide use by women and the actions subsequently implemented by the public health service targeting such use.

Method

The study was undertaken in a region in north-west Spain. We designed a segmented regression model of an interrupted time series, in which the dependent variable was the monthly value of defined daily doses of flutamide per 1000 inhabitants/day (DDD/TID), both total and stratified by sex. The following two data sources were used: flutamide prescriptions billed to the Spanish National Health Service; and flutamide deliveries made by wholesale drug distributors to pharmacies. The intervention assessed consisted of the issue of an official health warning and the actions subsequently taken to implement it.

Results

There was an immediate reduction of 49.33% in DDD/TID billed to the Spanish National Health Service in respect of women; the mean value of the population percentage of DDD/TID of flutamide billed in respect of women fell from 34.4% pre-intervention to 23.72% post-intervention. There was an immediate reduction of 19.92% (95%CI: 6.68–33.15%) in total DDD/TID invoiced. There were no significant changes in DDD/TID billed in respect of men or in flutamide use in the private medical sector.

Conclusions

Off-label drug misuse is a reality among ambulatory patients, even after actions are implemented following a toxicity warning issued by the competent Health Authority.
The VetMAX™ M. tuberculosis complex PCR kit detects MTBC DNA in antemortem and postmortem samples from white rhinoceros (Ceratotherium simum), African elephants (Loxodonta africana) and African buffaloes (Syncerus caffer)
Authors: Goosen Wynand J. , Kerr Tanya J. , Kleynhans Léanie , Buss Peter , Cooper David , Warren Robin M. , van Helden Paul D. , Schröder Björn , Parsons Sven D. C. , Miller Michele A.
Published: June 2020

Background

Bovine tuberculosis and tuberculosis are chronic infectious diseases caused by the Mycobacterium tuberculosis complex members, Mycobacterium bovis and Mycobacterium tuberculosis, respectively. Infection with M. bovis and M. tuberculosis have significant implications for wildlife species management, public health, veterinary disease control, and conservation endeavours.

Results

Here we describe the first use of the VetMAX™ Mycobacterium tuberculosis complex (MTBC) DNA quantitative real-time polymerase chain reaction (qPCR) detection kit for African wildlife samples. DNA was extracted from tissues harvested from 48 African buffaloes and MTBC DNA was detected (test-positive) in all 26 M. bovis culture-confirmed animals with an additional 12 PCR-positive results in culture-negative buffaloes (originating from an exposed population). Of six MTBC-infected African rhinoceros tested, MTBC DNA was detected in antemortem and postmortem samples from five animals. The PCR was also able to detect MTBC DNA in samples from two African elephants confirmed to have M. bovis and M. tuberculosis infections (one each). Culture-confirmed uninfected rhinoceros and elephants’ samples tested negative in the PCR assay.

Conclusions

These results suggest this new detection kit is a sensitive screening test for the detection of MTBC-infected African buffaloes, African elephants and white rhinoceros.
In silico and in vivo anti-malarial investigation on 1-(heteroaryl)-2-((5-nitroheteroaryl)methylene) hydrazine derivatives
Authors: Tahghighi Azar , Mohamadi-Zarch Seyed-Mahdi , Rahimi Hamzeh , Marashiyan Mahya , Maleki-Ravasan Naseh , Eslamifar Ali
Published: June 2020

Background

Resistance of Plasmodium falciparum against common anti-malarial drugs emphasizes the need of alternative and more effective drugs. Synthetic derivatives of 1-(heteroaryl)-2-((5-nitroheteroaryl)methylene) hydrazine have showed in vitro anti-plasmodial activities. The present study aimed to evaluate the molecular binding and anti-plasmodial activity of synthetic compounds in vivo.

Methods

The molecular docking was used to study the binding of compounds to haem and Plasmodium falciparum lactate dehydrogenase (PfLDH). Acute toxicity of the synthetic compounds was evaluated based on the modified up & down method. The anti-plasmodial activity of the compounds was conducted by the two standard tests of Peters’ and of Rane, using chloroquine-sensitive Plasmodium berghei in mice. Also, the toxicity to the internal organs of mice was evaluated on the seventh day after the treatment in addition to the histopathology of their liver. Compound 3 that showed high activity in the lowest dose was selected for further pharmacodynamic studies.

Results

According to the docking studies, the active site of PfLDH had at least four common residues, including Ala98, Ile54, Gly29, and Tyr97 to bind the compounds with the affinity, ranging from − 8.0 to − 8.4 kcal/mol. The binding mode of ligands to haem revealed an effective binding affinity, ranging from − 5.1 to − 5.5 kcal/mol. Compound 2 showed the highest  % suppression of parasitaemia (99.09%) at the dose of 125 mg/kg/day in Peters’ test. Compound 3, with 79.42% suppression, was the best in Rane’s test at the lowest dose (31 mg/kg/day). Compound 3 was confirmed by the pharmacodynamic study to have faster initial parasite elimination in the lowest concentration. The histopathology of the livers of mice did not reveal any focal necrosis of hepatocytes in the studied compounds.

Conclusions

The docking studies verified Pf LDH inhibition and the inhibitory effect on the haemozoin formation for the studied compounds. Accordingly, some compounds may provide new avenues for the development of anti-malarial drugs without liver toxicity, although further studies are required to optimize their anti-plasmodial activity.
Predictors of mortality following emergency open colectomy for ischemic colitis: a single-center experience
Authors: Beghdadi Nassiba , Reitano Elisa , Cochennec Frederic , Desgranges Pascal , Amiot Aurelien , Sobhani Iradj , Mongardon Nicolas , Langeron Olivier , Notarnicola Margherita , Mulé Sébastien , Luciani Alain , Canoui-Poitrine Florence , Laurent Alexis , Sommacale Daniele , Brunetti Francesco , de’ Angelis Nicola
Published: June 2020

Background

Ischemic colitis (IC) is a severe emergency in gastrointestinal surgery. The aim of the present study was to identify the predictors of postoperative mortality after emergent open colectomy for IC treatment. Additionally, we compared postoperative outcomes of patients undergoing emergent colectomy due to aortic surgery-related IC (AS-IC group) vs. other IC etiologies (Other-IC group).

Methods

We analyzed records of consecutive patients who underwent emergency open colectomy for IC between 2008 and 2019. Logistic regression analysis was performed to identify clinical and operative parameters associated with postoperative mortality. The AS-IC and Other-IC groups were compared for mortality, morbidity, ICU stay, hospital stay, and survival.

Results

During the study period, 94 patients (mean age, 67.4 ± 13.7 years) underwent emergent open colectomy for IC. In the majority of cases, IC involved the entire colon (53.2%) and vasopressor agents were required preoperatively (63.8%) and/or intraoperatively (78.8%). Thirty-four patients underwent surgery due to AS-IC, whereas 60 due to Other-IC causes. In the AS-IC group, 9 patients had undergone endovascular aortic repair and 25 open aortic surgery; 61.8% of patients needed aortic surgery for ruptured abdominal aortic aneurism (AAA). Overall, 66 patients (70.2%) died within 90 days from surgery. The AS-IC and Other-IC groups showed similar operative outcomes and postoperative complication rates. However, the duration of the ICU stay (19 days vs. 11 days; p = 0.003) and of the total hospital stay (22 days vs. 16 days; p = 0.016) was significantly longer for the AS-IC group than for the Other-IC group. The rate of intestinal continuity restoration at 1 year after surgery was higher for the Other-IC group than for the AS-IC group (58.8% vs. 22.2%; p = 0.05). In the multivariate model, preoperative increased lactate levels, a delay between signs/symptoms’ onset and surgery > 12 h, and the occurrence of postoperative acute kidney injury were statistically associated with postoperative mortality. Neither IC etiology (aortic surgery vs. other etiology) nor ruptured AAA was associated with postoperative mortality.

Conclusion

Emergency open colectomy for IC is associated with high postoperative mortality, which appears to be unrelated to the IC etiology. Preoperative lactate levels, > 12-h delay to surgery, and postoperative acute kidney injury are independent predictors of postoperative mortality.
Subchondral pressures and perfusion during weight bearing
Authors: Beverly Michael , Marks Barbara E. , Murray David W
Published: June 2020

Background

Joints withstand huge forces, but little is known about subchondral pressures and perfusion during loading. We developed an in vitro calf foot model to explore intraosseous pressure (IOP) and subchondral perfusion during weight bearing.

Methods

Freshly culled calf forefeet were perfused with serum. IOP was measured at three sites in the foot using intraosseous needles, pressure transducers, and digital recorders. IOP was measured during perfusion, with and without a tourniquet and with differing weights, including static loading and dynamic loading to resemble walking.

Results

IOP varied with perfusion pressure. Static loading increased subchondral IOP whether the bone was non-perfused, perfused, or perfused with a proximal venous tourniquet (p< 0.0001). Under all perfusion states, IOP was proportional to the load (R2= 0.984). Subchondral IOP often exceeded perfusion pressure. On removal of a load, IOP fell to below the pre-load value. Repetitive loading led to a falling IOP whether the foot was perfused or not.

Conclusion

Superimposed on a variable background IOP, increased perfusion and physiological loading caused a significant increase in subchondral IOP. Force was thereby transmitted through subchondral bone partly by hydraulic pressure. A falling IOP with repeat loading suggests that there is an intraosseous one-way valve. This offers a new understanding of subchondral perfusion physiology.
Correction to: Cardiac surgery in patients with Hemophilia:is it safe?
Authors: Shalabi Amjad , Kachel Erez , Kogan Alexander , Sternik Leonid , Grosman-Rimon Liza , Ben-Avi Ronny , Ghanem Diab , Ram Eilon , Raanani Ehud , Misgav Mudi
Published: June 2020

An amendment to this paper has been published and can be accessed via the original article.