bluuebunny/crossref_metadata_2025 huggingface dataset:
Autoimmune encephalitis in a South Asian population
Authors: Wickramasinghe Nilanka , Dasanayake Dhanushka , Malavige Neelika , de Silva Rajiva , Chang Thashi
Published: May 2021

Background

Autoimmune encephalitis (AE) is now considered a main, potentially curable cause of encephalitis, but remains conspicuously underreported from South Asia. We studied the clinical characteristics in relation to their antibody status and outcomes of patients presenting with AE in Sri Lanka.

Methods

Patients admitting to government hospitals who were clinically suspected of AE by an on-site neurologist were prospectively recruited over a period of 12 months. Sera and cerebrospinal fluid were tested for NMDAR, AMPAR1, AMPAR2, LGI1, CASPR2, GABARB1/B2 antibodies (Ab) using commercial cell-based assays. Demographic, clinical and laboratory data were compiled into an investigator-administered proforma. Patients were reviewed at 1 year follow up either in person or via telephone.

Results

One-hundred and forty-two patients from 21 of 25 districts in Sri Lanka (median age = 20.5 years; range 1–86 years; females = 61.3%) were recruited. Of them, 65 (45.8%; median age = 19 years; range 1–86 years; females = 64.6%) fulfilled diagnostic criteria for probable NMDAR-antibody encephalitis (NMDARE) and 6 (4.2%; median age = 44 years; range 28–71 years; females = 83.3%) limbic encephalitis (LE). Abnormal behaviour (95.3%), seizures (81.5%) and movement disorders (69.2%) were the most frequent clinical manifestations of probable NMDARE. NMDAR-antibodies were detectable in 29 (44.6%) and not detectable in 36 in CSF of probable-NMDARE patients. Abnormal EEG was more frequent (p = 0.003) while a worse outcome (OR = 2.78; 95% CI = 0.88–9.09) and deaths (OR = 2.38; 95% CI = 0.67–8.33) were more likely in antibody-negative than antibody-positive probable-NMDARE. Most patients with LE had amnesia (50%) and/or confusion (100%) with agitation (83.3%) and seizures (100%) but none had detectable antibodies to any of the antigens tested.

Conclusions

NMDARE is the commonest type of AE among South Asians as is the case worldwide. Clinical presentations of NMDARAb-positive and NMDARAb-negative AE patients do not significantly differ but EEG may be a useful marker of an autoimmune basis for psychiatric symptoms.
Antenatal management and maternal/fetal outcomes associated with hyperglycaemia in pregnancy (HIP) in Uganda; a prospective cohort study
Authors: Milln Jack , Nakabuye Betty , Natamba Barnabas Kahiira , Sekitoleko Isaac , Mubiru Michael , Namara Arthur Araali , Tumwesigire Samuel , Tino Salome , Mirembe Mandy , Kakande Ayoub , Agaba Brian , Nansubuga Faridah , Zaake Daniel , Ayiko Ben , Kalema Herbert , Nakubulwa Sarah , Sekikubo Musa , Nakimuli Annettee , Webb Emily L. , Nyirenda Moffat J.
Published: May 2021

Background

Hyperglycaemia in pregnancy (HIP) is associated with complications for both mother and baby. The prevalence of the condition is likely to increase across Africa as the continent undergoes a rapid demographic transition. However, little is known about the management and pregnancy outcomes associated with HIP in the region, particularly less severe forms of hyperglycaemia. It is therefore important to generate local data so that resources may be distributed effectively. The aim of this study was to describe the antenatal management and maternal/fetal outcomes associated with HIP in Ugandan women.

Methods

A prospective cohort study of 2917 pregnant women in five major hospitals in urban/semi-urban central Uganda. Women were screened with oral glucose tolerance test (OGTT) at 24–28 weeks of gestation. Cases of gestational diabetes (GDM) and diabetes in pregnancy (DIP) were identified (WHO 2013 diagnostic criteria) and received standard care. Data was collected on maternal demographics, anthropometrics, antenatal management, umbilical cord c-peptide levels, and pregnancy outcomes.

Results

Two hundred and seventy-six women were diagnosed with HIP (237 classified as GDM and 39 DIP). Women had between one and four fasting capillary blood glucose checks during third trimester. All received lifestyle advice, one quarter (69/276) received metformin therapy, and one woman received insulin. HIP was associated with large birthweight (unadjusted relative risk 1.30, 95% CI 1.00–1.68), Caesarean delivery (RR 1.34, 95% CI 1.14–1.57) and neonatal hypoglycaemia (RR 4.37, 95% CI 1.36–14.1), but not perinatal mortality or preterm birth. Pregnancy outcomes were generally worse for women with DIP compared with GDM.

Conclusion

HIP is associated with significant adverse pregnancy outcomes in this population, particularly overt diabetes in pregnancy. However pregnancy outcomes in women with milder forms of hyperglycaemia are similar to those with normoglycaemic pregnancies. Intervention strategies are required to improve current monitoring and management practice, and more research needed to understand if this is a cost-effective way of preventing poor perinatal outcomes.
Pro-poor policies and improvements in maternal health outcomes in India
Authors: Bhatia M. , Dwivedi L. K. , Banerjee K. , Bansal A. , Ranjan M. , Dixit P.
Published: May 2021

Background

Since 2005, India has experienced an impressive 77% reduction in maternal mortality compared to the global average of 43%. What explains this impressive performance in terms of reduction in maternal mortality and improvement in maternal health outcomes? This paper evaluates the effect of household wealth status on maternal mortality in India, and also separates out the performance of the Empowered Action Group (EAG) states and the Southern states of India. The results are discussed in the light of various pro-poor programmes and policies designed to reduce maternal mortality and the existing supply side gaps in the healthcare system of India. Using multiple sources of data, this study aims to understand the trends in maternal mortality (1997–2017) between EAG and non EAG states in India and explore various household, economic and policy factors that may explain reduction in maternal mortality and improvement in maternal health outcomes in India.

Methods

This study triangulates data from different rounds of Sample Registration Systems to assess the trend in maternal mortality in India. It further analysed the National Family Health Surveys (NFHS). NFHS-4, 2015–16 has gathered information on maternal mortality and pregnancy-related deaths from 601,509 households. Using logistic regression, we estimate the association of various socio-economic variables on maternal deaths in the various states of India.

Results

On an average, wealth status of the households did not have a statistically significant association with maternal mortality in India. However, our disaggregate analysis reveals, the gains in terms of maternal mortality have been unevenly distributed. Although the rich-poor gap in maternal mortality has reduced in EAG states such as Bihar, Odisha, Assam, Rajasthan, the maternal mortality has remained above the national average for many of these states. The EAG states also experience supply side shortfalls in terms of availability of PHC and PHC doctors; and availability of specialist doctors.

Conclusions

The novel contribution of the present paper is that the association of household wealth status and place of residence with maternal mortality is statistically not significant implying financial barriers to access maternal health services have been minimised. This result, and India’s impressive performance with respect to maternal health outcomes, can be attributed to the various pro-poor policies and cash incentive schemes successfully launched in recent years. Community-level involvement with pivotal role played by community health workers has been one of the major reasons for the success of many ongoing policies. Policy makers need to prioritise the underperforming states and socio-economic groups within the states by addressing both demand-side and supply-side measures simultaneously mediated by contextual factors.
Germline mutations in a clinic-based series of pregnancy associated breast cancer patients
Authors: Zografos Eleni , Korakiti Anna-Maria , Andrikopoulou Angeliki , Rellias Ioannis , Dimitrakakis Constantine , Marinopoulos Spyridon , Giannos Aris , Keramopoulos Antonios , Bredakis Nikolaos , Dimopoulos Meletios-Athanasios , Zagouri Flora
Published: May 2021

Background

Pregnancy-associated breast cancer (PABC) defined as breast cancer diagnosed during gestation, lactation or within 1 year after delivery, represents a truly challenging situation with significantly increasing incidence rate. The genomic background of PABC has only recently been addressed while the underlying mechanisms of the disease still remain unknown. This analysis aims to further elucidate the frequency of PABC cases attributable to genetic predisposition and identify specific cancer susceptibility genes characterizing PABC.

Methods

A comprehensive 94-cancer gene panel was implemented in a cohort of 20 PABC patients treated in our clinic and descriptive correlation was performed among the results and the patients’ clinicopathological data.

Results

In the present study, 35% of PABC patients tested carried pathogenic mutations in two known cancer predisposition genes (BRCA1 and CHEK2). In total, 30% of the patients carried BRCA1 pathogenic variants. An additional 5% carried pathogenic variants in the CHEK2 gene. Variants of unknown/uncertain significance (VUS) in breast cancer susceptibility genes BRCA2, CHEK2 and BRIP1 were also identified in three different PABC patients (15%). Not all patients carrying germline mutations reported known family history of cancer.

Conclusions

Genetic testing should be considered as an option for PABC patients since the disease is highly associated with genetic susceptibility among other predisposing factors. Germline mutation identification may further modify PABC management approach and improve the prognostic outcome.
MiR-3168, miR-6125, and miR-4718 as potential predictors of cisplatin-induced nephrotoxicity in patients with head and neck cancer
Authors: Quintanilha Julia C. F. , Cursino Maria A. , Borges Jessica B. , Torso Nadine G. , Bastos Larissa B. , Oliveira Juliana M. , Cobaxo Thiago S. , Pincinato Eder C. , Hirata Mario H. , Geraldo Murilo V. , Lima Carmen S. P. , Moriel Patricia
Published: May 2021

Background

No biomarker is available for identifying cancer patients at risk of developing nephrotoxicity when treated with cisplatin.

Methods

We performed microRNA (miRNA) sequencing using plasma collected 5 days after cisplatin treatment (D5) from twelve patients with head and neck cancer with and without nephrotoxicity (grade ≥ 2 increased serum creatinine). The most differentially expressed miRNAs between the two groups were selected for quantification at baseline and D5 in a larger cohort of patients. The association between miRNAs and nephrotoxicity was evaluated by calculating the odds ratio (OR) from univariate logistic regression. Receiver operating characteristic curves (ROC) were used to estimate the area under the curve (AUC), sensitivity, and specificity.

Results

MiR-3168 (p = 1.98 × 10− 8), miR-4718 (p = 4.24 × 10− 5), and miR-6125 (p = 6.60 × 10− 5) were the most differentially expressed miRNAs and were further quantified in 43, 48, and 53 patients, respectively. The baseline expression of miR-3168 (p = 0.0456, OR = 1.03, 95% CI: 1.00–1.06) and miR-4718 (p = 0.0388, OR = 1.56, 95% CI: 1.03–2.46) were associated with an increased risk of nephrotoxicity, whereas miR-6125 showed a trend (p = 0.0618, OR = 1.73, 95% CI: 0.98–3.29). MiR-4718 showed the highest AUC (0.77, 95% CI: 0.61–0.93) with sensitivity of 66.76 and specificity of 79.49.

Conclusions

We have provided evidence of baseline plasmatic expression of miR-3168, miR-6125, and miR-4718 as potential predictors of cisplatin-induced nephrotoxicity.
Fusarium infection complicating rheumatic keratitis that acutely progressed to endophthalmitis during regular infusion of tocilizumab: a case report
Authors: Mitsuoka Yusuke , Soma Takeshi , Maruyama Kazuichi , Nishida Kohji
Published: May 2021

Background

Filamentous fungi are ubiquitous in plants, water, and soil. The predominant fungi that infect the human cornea include Fusarium and Aspergillus species. The onset of fungal endophthalmitis is indolent, and typically takes weeks to months to develop after corneal infection. We report a case of Fusarium infection complicating rheumatic keratitis that acutely progressed to endophthalmitis during intravenous tocilizumab therapy.

Case presentation

A 65-year-old female patient was referred to our department due to pain and decreased vision in her left eye. Slit-lamp examination showed a white focus on the upper peripheral cornea, hypopyon, anterior chamber fibrin formation, marked ciliary hyperemia, and whole corneal epithelial defects. As the corneal scraping smear was positive for filamentous fungi and Fusarium species were detected by aqueous humor polymerase chain reaction, anti-fungal therapy was started. Although the initial response to anti-fungal therapy was good, we observed corneal infiltration, worsening hypopyon, and vitreous opacity after tocilizumab infusion. Given that the infection continued to progress despite conservative therapy, we performed penetrating keratoplasty combined with vitrectomy. After removal of the white focus beneath the intraocular lens, a temporary corneal prosthesis was mounted and the dense vitreous opacity was removed. Finally, a frozen donor graft was sutured in place. The corneal infiltration, hypopyon, and vitreous opacity all disappeared after the operation.

Conclusion

The rapid progression of Fusarium keratitis to endophthalmitis in a patient who was receiving a regular infusion of tocilizumab demonstrates that ocular condition should be closely monitored during systemic tocilizumab administration due to increased risk of infection.
Reference intervals for hemoglobin and mean corpuscular volume in an ethnically diverse community sample of Canadian children 2 to 36 months
Authors: Hamid Jemila S. , Atenafu Eshetu G. , Borkhoff Cornelia M. , Birken Catherine S. , Maguire Jonathon L. , Bohn Mary Kathryn , Adeli Khosrow , Abdelhaleem Mohamed , Parkin Patricia C.
Published: May 2021

Objective

To establish reference intervals for hemoglobin and mean corpuscular volume (MCV) in an ethnically diverse community sample of Canadian children 36 months and younger.

Methods

We collected blood samples from young children at scheduled primary care health supervision visits at 2 weeks, 2, 4, 6, 9, 12, 15, 18, 24, and 36 months of age. Samples were analyzed on the Sysmex XN-9000 Hematology Analyzer. We followed the Clinical and Laboratory Standards Institute guidelines in our analysis. Data were partitioned by sex and also combined. We considered large age partitions (3 and 6 months) as well as monthly partitions. Reference intervals (lower and upper limits) and 90% confidence intervals were calculated.

Results

Data from 2106 children were included. The age range was 2 weeks to 36 months, 46% were female, 48% were European and 23% were of mixed ethnicity. For hemoglobin, from 2 to 36 months of age, we found a wide reference interval and the 90% confidence intervals indicated little difference across age groups or according to sex. For MCV, from 2 to 7 months of age there was considerable decrease in the reference interval, which was lowest during the second year of life, followed by a slight increase in the last months of the third year of life.

Conclusion

These findings suggest adoption of a single hemoglobin reference interval for children 2–36 months of age. Further studies in children under 4 months of age are needed.

Trial registration

TARGet Kids! cohort is registered at ClinicalTrials.gov. www.clinicaltrials.gov. Identifier: NCT01869530.
People’s willingness and determinants to use selected tele-consultation public health services in Mozambique
Authors: Vera Cruz Germano , Dlamini Priscilla S.
Published: May 2021

Background

To achieve universal health coverage by 2030, sub-Saharan African countries are planning to develop large scale tele-consultation public health services. However, there is a lack of knowledge regarding the level of peoples’ willingness to use this kind of tele-health services. To address this gap and inform policymakers, the present study aims at accessing the Mozambican people’s willingness to use tele-consultation public health services and the determinants associate to their willingness.

Methods

A total of 403 adults participated in the study. The material consisted of 32 vignettes (scenarios) describing realistic health problem situations in which an individual was proposed to use a tele-consultation public health service, varying as a function of five factors: consultation category, health problem category, health problem severity, physician category, and the consultation price. For each health problem situation presented in the vignettes, the participants were asked to rate their willingness to use the proposed tele-consultation service on an 11-point scale. A cluster analysis using the K-means procedure was applied to the quantitative raw data to capture the participants’ different perspectives. ANOVA, x2 and t-test analyses were also conducted to examine the effects of the different health problem situations and the sociodemographic characteristics on the participant ratings.

Results

Five different perspectives (clusters) were found: never-willing (15% of the sample), severity (26%), consultation-category (22%), undecided (16%), and price-severity (21%). These perspectives were associated with participants’ sociodemographic characteristics.

Conclusion

According to the main results, it seems that the majority of the participants (69%) were highly willing to use tele-consultation public health services in the case of mild illness, cheaper prices and follow-up consultation. In addition, the participants’ willingness was significantly affected by some of the participants’ sociodemographic characteristics.
Yam Daabo interventions’ effects on postpartum family planning use in Burkina Faso at 24 months after childbirth
Authors: Coulibaly Abou , Baguiya Adama , Garanet Franck , Tran Nguyen Toan , Millogo Tieba , Yaméogo Wambi Maurice Evariste , Meda Ivlabèhirè Bertrand , Thieba Blandine , Kouanda Séni
Published: May 2021

Introduction

After testing the interventions for improving the prevalence of contraceptive use, very few studies have measured the long-term effects thereafter the end of the implementation. This study aimed to measure Yam Daabo interventions’ effects on contraceptive use in Burkina Faso at twelve months after completion of the intervention.

Methods

Yam Daabo was a two-group, multi-intervention, single-blind, cluster randomized controlled trial. Interventions comprised refresher training for the provider, a counseling tool, supportive supervision, availability of contraceptive services 7 days a week, client appointment cards, and invitation letters for partners. We used generalized linear mixed-effects models (log Poisson) to compare the modern contraceptive prevalence at 12 months post-intervention in the two groups. We collected data between September and November 2018. We conducted an intention-to-treat analysis and adjusted the prevalence ratios on cluster effects and unbalanced baseline characteristics.

Results

Twelve months after the completion of the Yam Daabo trial, we interviewed 87.4% (485 out of 555 women with available data at 12 months, that is, 247/276 in the intervention group (89.5%) and 238/279 in the control group (85.3%). No difference was observed in the use of hormonal contraceptive methods between the intervention and control groups (adjusted prevalence ratio = 1.21; 95% confidence interval [CI] = [0.91–1.61], p = 0.191). By contrast, women in the intervention group were more likely to use long-acting reversible contraceptives (LARC) than those in the control group (adjusted prevalence ratio = 1.35; 95% CI = [1.08–1.69], p = 0.008).

Conclusion

Twelve months after completion of the intervention, we found no significant difference in hormonal contraceptive use between women in the intervention and their control group counterparts. However, women in the intervention group were significantly more likely to use long-acting reversible contraceptives than those in the control group.

Trial registration

The trial registration number at the Pan African Clinical Trials Registry is PACTR201609001784334. The date of the first registration is 27/09/2016.
Multidimensional analysis of health in Mexico: implementation of fuzzy sets
Authors: Flores-Payan Lucio , Hernández-Corona Diana Mercedes , González-Heredia Tonatiuh
Published: May 2021

Background

The national health and nutrition survey allows to know the state of health of the Mexican population, it provides data for the analysis of different factors and / or indicators of health, diseases and nutritional conditions, such as chronic degenerative diseases and depressive symptoms, which, in turn, if both occur simultaneously, they will have a negative impact on health. This article studies the four factors involved in the overall health of the population in Mexico: excess weight, diabetes, high blood pressure, and depressive symptoms, which are used to conduct a multidimensional characterization and analysis.

Methods

Two methodological resources are applied, a descriptive statistical characterization and the construction of a multidimensional health index with the use of fuzzy sets, through the National Health and Nutrition Survey (ENSANUT 2018–19 - for its acronym in Spanish) in Mexico.

Results

The results reveal a growing percentage of individuals who experience detriments to their health, that is, the factors being studied have had a negative impact and tend to follow international projections. The construction of a multidimensional index enables the interaction between the factors being studied, thus allowing for an adequate modeling for the identification of health in Mexico.

Conclusion

This study aims to elucidate the current state of health throughout the population in Mexico by using the most current data provided by the autonomous public body of statistics and geography to build a multidimensional panorama using four elementary public health indicators (diabetes, obesity, high blood pressure, and depressive symptoms).
Does systemic lupus erythematosus increase the risk of complications from total hip arthroplasty?
Authors: Cai Yongrui , Ding Zichuan , Rong Xiao , Zhou Zong Ke
Published: May 2021

Background

Patients with systemic lupus erythematosus are more likely to receive THA than the general population. However, it is controversial whether SLE increases the risk of complications from THA. The purpose of this retrospective study was to reassess the risks from THA in patients with SLE under the management model of enhanced recovery after surgery.

Methods

Patients with systemic lupus erythematosus diagnosed from December 2011 to December 2017 and treated with THA were compared with THA patients with osteoarthritis. The data were extracted from the medical record system of our department. The chi-square test and t-test were used for comparison.

Results

The postoperative blood loss in patients with SLE was significantly higher than that in the control group, and the postoperative hemoglobin (Hb) and hematocrit (Hct) in the control group were lower than those in the control group (P < 0.05). There was no significant difference in the rate of blood transfusion (9.733 vs 8.133 P = 0.3148) or other complications between the two groups (P > 0.05).

Conclusion

Well-controlled and well-managed SLE will not increase the risk of complications in THA, but can increase the amount of perioperative blood loss. Therefore, perioperative blood management is still essential in SLE patients.
Recovery trajectories in common musculoskeletal complaints by diagnosis contra prognostic phenotypes
Authors: Aasdahl Lene , Granviken Fredrik , Meisingset Ingebrigt , Woodhouse Astrid , Evensen Kari Anne I. , Vasseljen Ottar
Published: May 2021

Background

There are large variations in symptoms and prognostic factors among patients sharing the same musculoskeletal (MSK) diagnosis, making traditional diagnostic labelling not very helpful in informing treatment or prognosis. Recently, we identified five MSK phenotypes across common MSK pain locations through latent class analysis (LCA). The aim of this study was to explore the one-year recovery trajectories for pain and functional limitations in the phenotypes and describe these in relation to the course of traditional diagnostic MSK groups.

Methods

We conducted a longitudinal observational study of 147 patients with neck, back, shoulder or complex pain in primary health care physiotherapy. Data on pain intensity and function were collected at baseline (week 0) and 1, 2, 3, 4, 6, 8, 12, 26 and 52 weeks of follow up using web-based questionnaires and mobile text messages. Recovery trajectories were described separately for the traditional diagnostic MSK groups based on pain location and the same patients categorized in phenotype groups based on prognostic factors shared among the MSK diagnostic groups.

Results

There was a general improvement in function throughout the year of follow-up for the MSK groups, while there was a more modest decrease for pain intensity. The MSK diagnoses were dispersed across all five phenotypes, where the phenotypes showed clearly different trajectories for recovery and course of symptoms over 12 months follow-up. This variation was not captured by the single trajectory for site specific MSK diagnoses.

Conclusion

Prognostic subgrouping revealed more diverse patterns in pain and function recovery over 1 year than observed in the same patients classified by traditional diagnostic groups and may better reflect the diversity in recovery of common MSK disorders.
Investigating inlay designs of class II cavity with deep margin elevation using finite element method
Authors: Chen Yung-Chung , Lin Chi-Lun , Hou Chun-Hsien
Published: May 2021

Background

This study evaluates the mechanical performance of deep margin elevation technique for carious cavities by considering the shape designs and material selections of inlay using a computational approach combined with the design of experiments method. The goal is to understand the effects of the design parameters on the deep margin elevation technique and provide design guidelines from the biomechanics perspective.

Methods

Seven geometric design parameters for defining an inlay’s shape of a premolar were specified, and the influence of cavity shape and material selection on the overall stress distribution was investigated via automated modelling. Material selection included composite resin, ceramic, and lithium disilicate. Finite element analysis was performed to evaluate the mechanical behavior of the tooth and inlay under a compressive load. Next, the analysis of variance was conducted to identify the parameters with a significant effect on the stress occurred in the materials. Finally, the response surface method was used to analyze the stress responses of the restored tooth with different design parameters.

Results

The restored tooth with a larger isthmus width demonstrated superior mechanical performance in all three types of inlay materials, while the influence of other design parameters varied with the inlay material selection. The height of the deep margin elevation layer insignificantly affected the mechanical performance of the restored tooth.

Conclusions

A proper geometric design of inlay enhances the mechanical performance of the restored tooth and could require less volume of the natural dentin to be excavated. Furthermore, under the loading conditions evaluated in this study, the deep margin elevation layer did not extensively affect the strength of the tooth structure.
Factors influencing mothers’ decisions regarding obstetrical care in Western Kenya: a mixed-methods study
Authors: Umutesi Grace , McEvoy Matthew D. , Bonnet Kemberlee , Druffner Sophie , Schlundt David G. , Atieli Harrysone E. , China Joy N. , Onyango Kennedy , Newton Mark W.
Published: May 2021

Background

Siaya County in Western Kenya has one of the highest maternal mortality rates in Kenya. We sought to elucidate factors that influence mothers’ decisions regarding where to seek obstetrical care, to inform interventions that seek to promote effective use of obstetric services and reduce maternal mortalities. To guide our research, we used the “Three Delays Model”, focusing on the first delay—seeking care. While interventions to reduce maternal mortalities have focused on addressing delays in accessing and receiving care, context-specific data on drivers of the first delay are scarce.

Methods

We used a mixed-method study to assess how maternal decision-making of birth location is influenced by personal, contextual, and cultural factors. We conducted structured interviews with women aged 14 years or older living in Siaya, Bondo, and Yala, rural districts in Western Kenya. We then conducted focus group interviews with a subset of women to elucidate this question: How do drivers of the first delay (i.e., seeking care) affect the decision to seek home versus hospital delivery, potentially negatively influencing maternal mortality.

Results

Three hundred and seven women responded to the surveys, and 67 women (22%) from this group participated in focus group interviews. Although we focused on type 1 delays, we discovered that several factors that impact type 2 and type 3 delays directly contribute to type 1 delays. Our findings highlighted that factors influencing women’s decisions to seek care are not simply medical or cultural but rather contextual, involving many elements of life, particularly in rural communities.

Conclusions

It is imperative to address multiple-level factors that influence women’s decisions to seek care and have in-hospital deliveries. To curtail maternal mortality in rural Western Kenya and comparable settings, targeted interventions must take into consideration these important influencers.
The statistical approach in trial-based economic evaluations matters: get your statistics together!
Authors: Mutubuki Elizabeth N. , El Alili Mohamed , Bosmans Judith E. , Oosterhuis Teddy , J. Snoek Frank , Ostelo Raymond W. J. G. , van Tulder Maurits W. , van Dongen Johanna M.
Published: May 2021

Background

Baseline imbalances, skewed costs, the correlation between costs and effects, and missing data are statistical challenges that are often not adequately accounted for in the analysis of cost-effectiveness data. This study aims to illustrate the impact of accounting for these statistical challenges in trial-based economic evaluations.

Methods

Data from two trial-based economic evaluations, the REALISE and HypoAware studies, were used. In total, 14 full cost-effectiveness analyses were performed per study, in which the four statistical challenges in trial-based economic evaluations were taken into account step-by-step. Statistical approaches were compared in terms of the resulting cost and effect differences, ICERs, and probabilities of cost-effectiveness.

Results

In the REALISE study and HypoAware study, the ICER ranged from 636,744€/QALY and 90,989€/QALY when ignoring all statistical challenges to − 7502€/QALY and 46,592€/QALY when accounting for all statistical challenges, respectively. The probabilities of the intervention being cost-effective at 0€/ QALY gained were 0.67 and 0.59 when ignoring all statistical challenges, and 0.54 and 0.27 when all of the statistical challenges were taken into account for the REALISE study and HypoAware study, respectively.

Conclusions

Not accounting for baseline imbalances, skewed costs, correlated costs and effects, and missing data in trial-based economic evaluations may notably impact results. Therefore, when conducting trial-based economic evaluations, it is important to align the statistical approach with the identified statistical challenges in cost-effectiveness data. To facilitate researchers in handling statistical challenges in trial-based economic evaluations, software code is provided.
Histone deacetylase 7 mediates endothelin-1-induced connective tissue growth factor expression in human lung fibroblasts through p300 and activator protein-1 activation
Authors: Hua Hung-Sheng , Wen Heng-Ching , Weng Chih-Ming , Lee Hong-Sheng , Chen Bing-Chang , Lin Chien-Huang
Published: May 2021

Background

Histone deacetylase (HDAC) inhibition was reported to ameliorate lung fibrosis in animal models. However, little is known about the underlying mechanism of HDAC7 in the regulation of CTGF production in lung fibroblasts.

Methods

The role of HDAC7 in CTGF production caused by ET-1 stimulation in WI-38 cells (human lung fibroblast) was examined. We also evaluated the expression of HDAC7 in the lung of ovalbumin-induced airway fibrosis model. Statistical data were shown as mean ± standard error.

Results

ET-1-stimulated CTGF and α-SMA expression was attenuated by small interfering (si)RNA interference of HDAC7. ET-1 promoted HDAC7 translocation from the cytosol to nucleus. ET-1-stimulated CTGF expression was reduced by the transfection of p300 siRNA. ET-1 induced an increase in p300 activity. Furthermore, the acetylation of c-Jun was time-dependently induced by ET-1 stimulation, which was reduced by transfection of either HDAC7 or p300 siRNA. Both transfection of HDAC7 and p300 siRNA suppressed the ET-1-increased activity of AP-1-luciferase. Moreover, the presence of HDAC7 was required for ET-1-stimulated formation of HDAC7, p300, and AP-1 complex and recruitment to the CTGF promoter region. In an ovalbumin-induced airway fibrosis model, the protein level of HDAC7 was increased in the lung tissue, and the distribution of HDAC7 was colocalized with α-SMA-positive cells in the subepithelial layer of the airway.

Conclusions

ET-1 activates HDAC7 to initiate AP-1 transcriptional activity by recruiting p300 and eventually promotes the production of CTGF. HDAC7 might play a vital role in airway fibrosis and have the potential to be developed as a therapeutic target.
Malaria prevention and treatment in migrant agricultural workers in Dangur district, Benishangul-Gumuz, Ethiopia: social and behavioural aspects
Authors: Tadesse Yehualashet , Irish Seth R. , Chibsa Sheleme , Dugassa Sisay , Lorenz Lena M. , Gebreyohannes Asfawesen , Teka Hiwot , Solomon Hiwot , Gezahegn Eshetu , Petros Yonas , Haile Mesfin , Eshetu Mesfin , Murphy Matthew
Published: May 2021

Background

Sixty percent of the Ethiopia population is at risk of malaria, with the highest prevalence reported in Gambella (6%) and Benishangul-Gumuz (3%) regions. Within these regions are large agricultural developments with high numbers of seasonal migrant workers. The migrant workers are believed to be at increased risk for malaria infection due to their poor living conditions and outdoor activities, but there is little information on their specific behaviours and health risks. This study was conducted to address this gap.

Methods

Quantitative observations were conducted from September to December 2017 in the Benishangul-Gumuz Region. The nightly routines of mobile migrant workers were observed every month for 4 consecutive months. The study team collected quantitative data including nocturnal behavioural observations of worker living conditions, malaria prevention efforts, and work activities and surveys of worker representatives. Qualitative data was collected from migrant workers, farm managers and local health providers using focus group discussions and semi-structured interviews.

Results

Migrant workers arrived in the study area during the peak malaria transmission season and the workers in focus groups reported repeated cases of malaria during their stay on the farms. Overall, less than a quarter of the migrant workers were sleeping under a mosquito net by midnight in all 4 observation months. Some work activities also took place outdoors at night. The study additionally found a lack of access to malaria prevention and treatment at the farms and challenges in utilizing local public health facilities.

Conclusions

There is a need to better address malaria prevention and treatment needs among migrant workers in Ethiopia through outreach from existing healthcare infrastructure and within the farms themselves. This will help prevent malaria transmission both within this population and prevent transmission of malaria back to home communities in lower burden areas in Ethiopia.
Graphene oxide (GO)-based nanosheets with combined chemo/photothermal/photodynamic therapy to overcome gastric cancer (GC) paclitaxel resistance by reducing mitochondria-derived adenosine-triphosphate (ATP)
Authors: Guo Weihong , Chen Zhian , Feng Xiaoli , Shen Guodong , Huang Huilin , Liang Yanrui , Zhao Bingxia , Li Guoxin , Hu Yanfeng
Published: May 2021

Background

Paclitaxel (PTX) has been suggested to be a promising front-line drug for gastric cancer (GC), while P-glycoprotein (P-gp) could lead to drug resistance by pumping PTX out of GC cells. Consequently, it might be a hopeful way to combat drug resistance by inhibiting the out-pumping function of P-gp.

Results

In this study, we developed a drug delivery system incorporating PTX onto polyethylene glycol (PEG)-modified and oxidized sodium alginate (OSA)-functionalized graphene oxide (GO) nanosheets (NSs), called PTX@GO-PEG-OSA. Owing to pH/thermal-sensitive drug release properties, PTX@GO-PEG-OSA could induced more obvious antitumor effects on GC, compared to free PTX. With near infrared (NIR)-irradiation, PTX@GO-PEG-OSA could generate excessive reactive oxygen species (ROS), attack mitochondrial respiratory chain complex enzyme, reduce adenosine-triphosphate (ATP) supplement for P-gp, and effectively inhibit P-gp’s efflux pump function. Since that, PTX@GO-PEG-OSA achieved better therapeutic effect on PTX-resistant GC without evident toxicity.

Conclusions

In conclusion, PTX@GO-PEG-OSA could serve as a desirable strategy to reverse PTX’s resistance, combined with chemo/photothermal/photodynamic therapy.

Graphic Abstract
Chitosan oligosaccharide decorated liposomes combined with TH302 for photodynamic therapy in triple negative breast cancer
Authors: Ding Yinan , Yang Rui , Yu Weiping , Hu Chunmei , Zhang Zhiyuan , Liu Dongfang , An Yanli , Wang Xihui , He Chen , Liu Peidang , Tang Qiusha , Chen Daozhen
Published: May 2021

Background

Triple negative breast cancer (TNBC) is an aggressive tumor with extremely high mortality that results from its lack of effective therapeutic targets. As an adhesion molecule related to tumorigenesis and tumor metastasis, cluster of differentiation-44 (also known as CD44) is overexpressed in TNBC. Moreover, CD44 can be effectively targeted by a specific hyaluronic acid analog, namely, chitosan oligosaccharide (CO). In this study, a CO-coated liposome was designed, with Photochlor (HPPH) as the 660 nm light mediated photosensitizer and evofosfamide (also known as TH302) as the hypoxia-activated prodrug. The obtained liposomes can help diagnose TNBC by fluorescence imaging and produce antitumor therapy by synergetic photodynamic therapy (PDT) and chemotherapy.

Results

Compared with the nontargeted liposomes, the targeted liposomes exhibited good biocompatibility and targeting capability in vitro; in vivo, the targeted liposomes exhibited much better fluorescence imaging capability. Additionally, liposomes loaded with HPPH and TH302 showed significantly better antitumor effects than the other monotherapy groups both in vitro and in vivo.

Conclusion

The impressive synergistic antitumor effects, together with the superior fluorescence imaging capability, good biocompatibility and minor side effects confers the liposomes with potential for future translational research in the diagnosis and CD44-overexpressing cancer therapy, especially TNBC.

Graphic abstract
Predictors for quality of life improvement after surgery for degenerative cervical myelopathy: a prospective multi-center study
Authors: Inose Hiroyuki , Hirai Takashi , Yoshii Toshitaka , Kimura Atsushi , Takeshita Katsushi , Inoue Hirokazu , Maekawa Asato , Endo Kenji , Miyamoto Takuya , Furuya Takeo , Nakamura Akira , Mori Kanji , Kanbara Shunsuke , Imagama Shiro , Seki Shoji , Matsunaga Shunji , Okawa Atsushi
Published: May 2021

Background

Degenerative cervical myelopathy (DCM) can significantly impair a patient’s quality of life (QOL). In this study, we aimed to identify predictors associated with QOL improvement after surgery for DCM.

Methods

This study included 148 patients who underwent surgery for DCM. The European QOL-5 Dimension (EQ-5D) score, the Japanese Orthopedic Association for the assessment of cervical myelopathy (C-JOA) score, and the Nurick grade were used as outcome measures. Radiographic examinations were performed at enrollment. The associations of baseline variables with changes in EQ-5D scores from preoperative to 1-year postoperative assessment were investigated using a multivariable linear regression model.

Results

The EQ-5D and C-JOA scores and the Nurick grade improved after surgery (P < 0.001, P < 0.001, and P < 0.001, respectively). Univariable analysis revealed that preoperative EQ-5D and C-JOA scores were significantly associated with increased EQ-5D scores from preoperative assessment to 1 year after surgery (P < 0.0001 and P = 0.045). Multivariable regression analysis showed that the independent preoperative predictors of change in QOL were lumbar lordosis (LL), sacral slope (SS), and T1 pelvic angle (TPA). According to the prediction model, the increased EQ-5D score from preoperatively to 1 year after surgery = 0.308 − 0.493 × EQ-5D + 0.006 × LL − 0.008 × SS + 0.004 × TPA.

Conclusions

Preoperative LL, SS, and TPA significantly impacted the QOL of patients who underwent surgery for DCM. Less improvement in QOL after surgery was achieved in patients with smaller LL and TPA and larger SS values. Patients with these risk factors may therefore require additional support to experience adequate improvement in QOL.
Attracting and retaining physicians in less attractive specialties: the role of continuing medical education
Authors: Thi Nguyen Van Anh , Könings Karen D. , Scherpbier Albert J. J. A. , van Merriënboer Jeroen J. G.
Published: May 2021

Background

Less attractive specialties in medicine are struggling to recruit and retain physicians. When properly organized and delivered, continuing medical education (CME) activities that include short courses, coaching in the workplace, and communities of practice might offer a solution to this problem. This position paper discusses how educationalists can create CME activities based on the self-determination theory that increase physicians’ intrinsic motivation to work in these specialties.

Main content

The authors propose a set of guidelines for the design of CME activities that offer physicians meaningful training experiences within the limits of the available resources and support. First, to increase physicians’ sense of professional relatedness, educationalists must conduct a learner needs assessment, evaluate CME’s long-term outcomes in work-based settings, create social learning networks, and involve stakeholders in every step of the CME design and implementation process. Moreover, providing accessible, practical training formats and giving informative performance feedback that authentically connects to learners' working life situation increases physicians’ competence and autonomy, so that they can confidently and independently manage the situations in their practice contexts. For each guideline, application methods and instruments are proposed, making use of relevant literature and connecting to the self-determination theory.

Conclusions

By reducing feelings of professional isolation and reinforcing feelings of competence and autonomy in physicians, CME activities show promise as a strategy to recruit and retain physicians in less attractive specialties.
Ethylmalonic encephalopathy and liver transplantation: long-term outcome of the first treated patient
Authors: Olivieri Giorgia , Martinelli Diego , Longo Daniela , Grimaldi Chiara , Liccardo Daniela , Di Meo Ivano , Pietrobattista Andrea , Sidorina Anna , Semeraro Michela , Dionisi-Vici Carlo
Published: May 2021

Background

Ethylmalonic encephalopathy (EE) is a severe intoxication-type metabolic disorder with multisystem clinical features and leading to early death. In 2014, based on the promising results obtained by liver-targeted gene therapy in Ethe1−/− mouse model, we successfully attempted liver transplantation in a 9-month-old EE girl. Here we report her long-term follow-up, lasting over 6 years, with a comprehensive evaluation of clinical, instrumental and biochemical assessments.

Results

Neurological signs initially reverted, with a clinical stabilization during the entire follow-up course. Accordingly, gross motor functions improved and then stabilized. Psychomotor evaluations documented an increasing communicative intent, the acquisition of new social skills and the capability to carry out simple orders. Neurophysiological assessments, which included EEG, VEP/ERG and BAEPs, remained unchanged. Brain MRI also stabilized, showing no further lesions and cerebral atrophy improvement. Compared to pre-transplant assessments, urinary ethylmalonic acid strikingly reduced, and plasma thiosulphate fully normalized. The child maintained good clinical conditions and never experienced metabolic crises nor epileptic seizures.

Conclusions

The long-term follow-up of the first EE transplanted patient demonstrates that liver transplantation stabilizes, or even improves, disease course, therefore representing a potentially elective option especially in early-diagnosed patients, such as those detected by newborn screening, before irreversible neurological damage occurs.
Super-enhancers: a new frontier for epigenetic modifiers in cancer chemoresistance
Authors: Li Guo-Hua , Qu Qiang , Qi Ting-Ting , Teng Xin-Qi , Zhu Hai-Hong , Wang Jiao-Jiao , Lu Qiong , Qu Jian
Published: May 2021

Although new developments of surgery, chemotherapy, radiotherapy, and immunotherapy treatments for cancer have improved patient survival, the emergence of chemoresistance in cancer has significant impacts on treatment effects. The development of chemoresistance involves several polygenic, progressive mechanisms at the molecular and cellular levels, as well as both genetic and epigenetic heterogeneities. Chemotherapeutics induce epigenetic reprogramming in cancer cells, converting a transient transcriptional state into a stably resistant one. Super-enhancers (SEs) are central to the maintenance of identity of cancer cells and promote SE-driven-oncogenic transcriptions to which cancer cells become highly addicted. This dependence on SE-driven transcription to maintain chemoresistance offers an Achilles’ heel for chemoresistance. Indeed, the inhibition of SE components dampens oncogenic transcription and inhibits tumor growth to ultimately achieve combined sensitization and reverse the effects of drug resistance. No reviews have been published on SE-related mechanisms in the cancer chemoresistance. In this review, we investigated the structure, function, and regulation of chemoresistance-related SEs and their contributions to the chemotherapy via regulation of the formation of cancer stem cells, cellular plasticity, the microenvironment, genes associated with chemoresistance, noncoding RNAs, and tumor immunity. The discovery of these mechanisms may aid in the development of new drugs to improve the sensitivity and specificity of cancer cells to chemotherapy drugs.