bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gender discrimination as a barrier to high-quality maternal and newborn health care in Nigeria: findings from a cross-sectional quality of care assessment
Authors: Oduenyi Chioma , Banerjee Joya , Adetiloye Oniyire , Rawlins Barbara , Okoli Ugo , Orji Bright , Ugwa Emmanuel , Ishola Gbenga , Betron Myra 
Published: March 2021

Abstract
Background
Poor reproductive, maternal, newborn, child, and adolescent health outcomes in Nigeria can be attributed to several factors, not limited to low health service coverage, a lack of quality care, and gender inequity. Providers’ gender-discriminatory attitudes, and men’s limited positive involvement correlate with poor utilization and quality of services. We conducted a study at the beginning of a large family planning (FP) and maternal, newborn, child, and adolescent health program in Kogi and Ebonyi States of Nigeria to assess whether or not gender plays a role in access to, use of, and delivery of health services.

Methods
We conducted a cross-sectional, observational, baseline quality of care assessment from April–July 2016 to inform a maternal and newborn health project in health facilities in Ebonyi and Kogi States. We observed 435 antenatal care consultations and 47 births, and interviewed 138 providers about their knowledge, training, experiences, working conditions, gender-sensitive and respectful care, and workplace gender dynamics. The United States Agency for International Development’s Gender Analysis Framework was used to analyze findings.

Results
Sixty percent of providers disagreed that a woman could choose a family planning method without a male partner’s involvement, and 23.2% of providers disagreed that unmarried clients should use family planning. Ninety-eight percent believed men should participate in health services, yet only 10% encouraged women to bring their partners. Harmful practices were observed in 59.6% of deliveries and disrespectful or abusive practices were observed in 34.0%. No providers offered clients information, services, or referrals for gender-based violence. Sixty-seven percent reported observing or hearing of an incident of violence against clients, and 7.9% of providers experienced violence in the workplace themselves. Over 78% of providers received no training on gender, gender-based violence, or human rights in the past 3 years.

Conclusion
Addressing gender inequalities that limit women’s access, choice, agency, and autonomy in health services as a quality of care issue is critical to reducing poor health outcomes in Nigeria. Inherent gender discrimination in health service delivery reinforces the critical need for gender analysis, gender responsive approaches, values clarification, and capacity building for service providers.
Low incidence of venous thrombosis but high incidence of arterial thrombotic complications among critically ill COVID-19 patients in Singapore
Authors:   on behalf of the Thrombosis Haemostasis Workgroup of Singapore Society of Haematology, Tan Chuen Wen , Fan Bingwen Eugene , Teo Winnie Z. Y. , Tung Moon Ley , Shafi Humaira , Christopher Dheepa , Zheng Shuwei , Peh Wee Ming , Chan Stephrene Seok Wei , Chong Vanessa Cui Lian , Gallardo Christian Aledia , Chang Cheng Chieh Ray , Ling Li Min , Tan Jing Yuan , Lee Ken Cheah Hooi , Phua Ghee Chee , Cherng Benjamin Pei Zhi , Low Jenny Guek Hong , Ho Vui Kian , Prasad Vishnu , Wong Lester Jung Long , Lim Cheryl Xiu Qi , Chee Yen Lin , Ong Kiat Hoe , Lee Lai Heng , Ng Heng Joo , Yap Eng Soo 
Published: March 2021

Abstract
Background
Arterial and venous thrombosis are reported to be common in critically ill COVID-19 patients.

Method and results
This is a national multicenter retrospective observational study involving all consecutive adult COVID-19 patients who required intensive care units (ICU) admission between 23 January 2020 and 30 April 2020 in Singapore. One hundred eleven patients were included and the venous and arterial thrombotic rates in ICU were 1.8% (n = 2) and 9.9% (n = 11), respectively. Major bleeding rate was 14.8% (n = 16).

Conclusions
Critically ill COVID-19 patients in Singapore have lower venous thromboembolism but higher arterial thrombosis rates and bleeding manifestations than other reported cohorts.
Minimum initial service package (MISP) for sexual and reproductive health for women in a displacement setting: a narrative review on the Syrian refugee crisis in Lebanon
Authors: Nabulsi Dana , Abou Saad Maya , Ismail Hussein , Doumit Myrna A. A. , El-Jamil Fatima , Kobeissi Loulou , Fouad Fouad M. 
Published: March 2021

Abstract
Background
Women and girls are disproportionately affected in times of conflict and forced displacement, with disturbance in access to healthcare services leading to poor sexual and reproductive health outcomes. The minimal initial service package (MISP) was created to mitigate the consequences of conflict and prevent poor sexual and reproductive health (SRH) outcomes, especially among women and girls. The aim of this narrative review was to explore the SRH response for Syrian refugee women and girls in Lebanon, with a focus on MISP implementation.

Methodology
A comprehensive literature search was conducted for peer-reviewed articles in 8 electronic databases and multiple grey literature sites for articles published from March 2011 to May 2019. The target population was Syrian refugee women in Lebanon displaced from Syria as a result of the conflict that erupted in March 2011. The selected articles addressed MISP, SRH needs and services, and barriers to service access. A narrative synthesis was conducted, guided by the six main objectives of the MISP.

Results
A total of 254 documents were retrieved, from which 12 peer-reviewed articles and 12 reports were included in the review. All identified articles were descriptive in nature and no studies evaluating MISP or other interventions or programs were found. The articles described the wide range of SRH services delivered in Lebanon to Syrian refugee women. However, access to and quality of these services remain a challenge. Multiple sources reported a lack of coordination, leading to fragmented service provision and duplication of effort. Studies reported a high level of sexual and gender-based violence, pregnancy complications and poor antenatal care compliance, and limited use of contraceptive methods. Very few studies reported on the prevalence of HIV and other STIs, reporting low levels of infection. Multiple barriers to healthcare access were identified, which included system-level, financial, informational and cultural factors, healthcare workers.

Conclusion
This study highlights the main SRH services provided, their use and access by Syrian refugee women in Lebanon. Despite the multitude of services provided, the humanitarian response remains decentralized with limited coordination and multiple barriers that limit the utilization of these services. A clear gap remains, with limited evaluation of SRH services that are pertinent to achieve the MISP objectives and the ability to transition into comprehensive services. Improving the coordination of services through a lead agency can address many of the identified barriers and allow the transition into comprehensive services.
Age-related differences in monocyte DNA methylation and immune function in healthy Kenyan adults and children
Authors: Dobbs Katherine R. , Embury Paula , Koech Emmily , Ogolla Sidney , Munga Stephen , Kazura James W. , Dent Arlene E. 
Published: March 2021

AbstractBackgroundAge-related changes in adaptive and innate immune cells have been associated with a decline in effective immunity and chronic, low-grade inflammation. Epigenetic, transcriptional, and functional changes in monocytes occur with aging, though most studies to date have focused on differences between young adults and the elderly in populations with European ancestry; few data exist regarding changes that occur in circulating monocytes during the first few decades of life or in African populations. We analyzed DNA methylation profiles, cytokine production, and inflammatory gene expression profiles in monocytes from young adults and children from western Kenya.ResultsWe identified several hypo- and hyper-methylated CpG sites in monocytes from Kenyan young adults vs. children that replicated findings in the current literature of differential DNA methylation in monocytes from elderly persons vs. young adults across diverse populations. Differentially methylated CpG sites were also noted in gene regions important to inflammation and innate immune responses. Monocytes from Kenyan young adults vs. children displayed increased production of IL-8, IL-10, and IL-12p70 in response to TLR4 and TLR2/1 stimulation as well as distinct inflammatory gene expression profiles.ConclusionsThese findings complement previous reports of age-related methylation changes in isolated monocytes and provide novel insights into the role of age-associated changes in innate immune functions.
Serum ferritin levels in inflammation: a retrospective comparative analysis between COVID-19 and emergency surgical non-COVID-19 patients
Authors: Banchini Filippo , Cattaneo Gaetano Maria , Capelli Patrizio 
Published: March 2021

Abstract
Background
SARS-CoV-2 infection has spread worldwide, and the pathogenic mechanism is still under investigation. The presence of a huge inflammatory response, defined as “cytokine storm,” is being studied in order to understand what might be the prognostic factors implicated in the progression of the infection, with ferritin being one of such markers. The role of ferritin as a marker of inflammation is already known, and whether it changes differently between COVID and non-COVID patients still remains unclear. The aim of this retrospective analysis is to understand whether the inflammatory process in these two types is different.

Methods
In this retrospective analysis, we compared 17 patients affected by SARS-CoV-2, who had been admitted between February and April 2020 (group A) along with 30 patients admitted for acute surgical disease with SARS-CoV-2 negative swab (group B). A further subgroup of Covid negative patients with leukocytosis was compared to group A.

Results
In group A, the median (interquartile range) serum ferritin was 674 (1284) ng/mL, and it was double the cutoff (300 ng/mL) in 9 out of 17 (52%). The median (IQR) value of ferritin level in the total blood samples of group B was 231, and in the subgroup with leucocytosis, 149 (145). Group A showed a significantly higher ferritin median level compared to the entire group B (two-tailed Mann-Whitney test, p < 0.0001) as well as to the subgroup with leucocytosis (p < 0.0014).

Conclusions
The role of iron metabolism appears to be directly involved in COVID infection. On the other hand, in the acute inflammation of patients admitted for surgery, and probably in other common phlogistic processes, iron modifications appear to be self-limited. However, our finding suggests the use of ferritin as a marker for COVID infection.
Intraosseous versus intravenous vascular access during cardiopulmonary resuscitation for out-of-hospital cardiac arrest: a systematic review and meta-analysis of observational studies
Authors: Hsieh Yu-Lin , Wu Meng-Che , Wolfshohl Jon , d’Etienne James , Huang Chien-Hua , Lu Tsung-Chien , Huang Edward Pei-Chuan , Chou Eric H. , Wang Chih-Hung , Chen Wen-Jone 
Published: March 2021

Abstract
Introduction
This study is aimed to investigate the association of intraosseous (IO) versus intravenous (IV) route during cardiopulmonary resuscitation (CPR) with outcomes after out-of-hospital cardiac arrest (OHCA).

Methods
We systematically searched PubMed, Embase, Cochrane Library and Web of Science from the database inception through April 2020. Our search strings included designed keywords for two concepts, i.e. vascular access and cardiac arrest. There were no limitations implemented in the search strategy. We selected studies comparing IO versus IV access in neurological or survival outcomes after OHCA. Favourable neurological outcome at hospital discharge was pre-specified as the primary outcome. We pooled the effect estimates in random-effects models and quantified the heterogeneity by the I2 statistics. Time to intervention, defined as time interval from call for emergency medical services to establishing vascular access or administering medications, was hypothesized to be a potential outcome moderator and examined in subgroup analysis with meta-regression.

Results
Nine retrospective observational studies involving 111,746 adult OHCA patients were included. Most studies were rated as high quality according to Newcastle-Ottawa Scale. The pooled results demonstrated no significant association between types of vascular access and the primary outcome (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.27–1.33; I2, 95%). In subgroup analysis, time to intervention was noted to be positively associated with the pooled OR of achieving the primary outcome (OR: 3.95, 95% CI, 1.42–11.02, p: 0.02). That is, when the studies not accounting for the variable of “time to intervention” in the statistical analysis were pooled together, the meta-analytic results between IO access and favourable outcomes would be biased toward inverse association. No obvious publication bias was detected by the funnel plot.

Conclusions
The meta-analysis revealed no significant association between types of vascular access and neurological outcomes at hospital discharge among OHCA patients. Time to intervention was identified to be an important outcome moderator in this meta-analysis of observation studies. These results call for the need for future clinical trials to investigate the unbiased effect of IO use on OHCA CPR.
Serum chitinase-3-like 1 protein is a useful biomarker to assess disease activity in ANCA-associated vasculitis: an observational study
Authors: Ahn Sung Soo , Yoon Taejun , Park Yong-Beom , Prendecki Maria , Bhangal Gurjeet , McAdoo Stephen P. , Lee Sang-Won 
Published: March 2021

Abstract
Background
To investigate whether serum chitinase-3-like 1 protein (YKL-40) is associated with disease activity in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

Methods
ELISA was performed in serum samples from AAV patients who were enrolled in our prospective observational cohort to estimate levels of YKL-40. Birmingham vasculitis activity score (BVAS) (version 3), five factor score (FFS), and short form-36 (SF-36), as well as clinical and laboratory data were collected. Kidney expression of YKL-40 was assessed by immunohistochemical staining using renal biopsy tissues from ANCA-associated glomerulonephritis patients (AAGN). Severe AAV and FFS were defined as BVAS ≥ 12 and FFS ≥ 2, and the correlations between laboratory variables, BVAS, FFS, and SF-36 score were assessed using linear regression analysis. The optimal cut-off of serum YKL-40 for severe AAV and high FFS was calculated using the receiver operator characteristic curve analysis.

Results
Of the included 60 patients, 32 (53.3%), 17 (28.3%), and 11 (18.3%) were classified as microscopic polyangiitis, granulomatosis with polyangiitis, and eosinophilic granulomatosis with polyangiitis. The median BVAS and FFS were 7.0 and 1.0, whereas the mean SF-36 physical and mental component scores were 50.5 and 58.3. Serum YKL-40 level was higher in patients with severe AAV and high FFS compared to those without (p = 0.007 and p < 0.001); multivariable linear regression analysis revealed that serum YKL-40 was independently associated with BVAS, FFS, and SF-36 scores. On kidney tissues obtained from AAGN patients, strong cytoplasmic staining of YKL-40 was found in cells present in inflammatory lesions. In addition, AAV patients had higher levels of serum YKL-40 compared to those with systemic lupus erythematosus, rheumatoid arthritis, osteoarthritis, and healthy control. The proportion of patients having severe AAV and high FFS was significantly higher in those with serum YKL-40 > 221.3 ng/mL and > 227.1 ng/mL than those without (relative risk 2.852 and 7.000). In 12 patients with serial YKL-40 testing, 11 patients (91.7%) exhibited a reduction in serum YKL-40 levels following a decrease in disease activity (p < 0.001).

Conclusion
Our findings suggest that serum YKL-40 may be a clinically useful biomarker to assess AAV disease activity.

Trial registration
Retrospectively registered.
Proposal of initial and maintenance dosing regimens with linezolid for renal impairment patients
Authors: Kawasuji Hitoshi , Tsuji Yasuhiro , Ogami Chika , Kimoto Kou , Ueno Akitoshi , Miyajima Yuki , Kawago Koyomi , Sakamaki Ippei , Yamamoto Yoshihiro 
Published: March 2021

Abstract
Background
Linezolid is administered as a fixed dose to all patients despite evidence of overexposure and thrombocytopenia in renal impairment. The aims of this study were to evaluate the risk of thrombocytopenia and the utility of therapeutic drug monitoring (TDM), and to propose alternate dosing regimens in patients with renal impairment.

Methods
We retrospectively reviewed patients ≥13 years old for whom serum linezolid trough concentration (Cmin) was measured during linezolid treatment. Patients with episodes of infection were divided into groups by presence of renal impairment (RI group) or absence of renal impairment (non-RI group), and by use of Cmin-based TDM (TDM group) or not (non-TDM group) during linezolid treatment.

Results
In the 108 patients examined by multivariable analyses, renal impairment was independently associated with increased risk of thrombocytopenia (OR 3.17, 95%CI 1.10–9.12) and higher Cmin. Analysis of the utility of TDM in the RI group showed that clinical failure rate was significantly lower in the TDM subgroup than in the non-TDM subgroup. Furthermore, in the RI group, dosage adjustments were needed in 90.5% of the TDM subgroup. All episodes administered a reduced dose of 300 mg every 12 h in the RI group showed Cmin ≥ 2.0 mg/L. Additional analysis of 53 episodes in which Cmin was measured within 48 h after starting administration showed that the initial standard dose for 2 days was sufficient to rapidly reach an effective therapeutic concentration in the RI group.

Conclusions
Empirical dose reduction to 300 mg every 12 h after administration of the initial fixed dose for 2 days and Cmin-based TDM may improve safety outcomes while maintaining appropriate efficacy among patients with renal impairment.
Radio-adaptive response and correlation of non-homologous end joining repair gene polymorphisms [XRRC5 (3R/2R/1R/0R), XRCC6(C/G) and XRCC7 (G/T)] in human peripheral blood mononuclear cells exposed to gamma radiation
Authors: Shelke Shridevi , Das Birajalaxmi 
Published: March 2021

Abstract
Background
Radio-adaptive response (RAR) is transient phenomena, where cells conditioned with a small dose (priming) of ionizing radiation shows significantly reduced DNA damage with a subsequent high challenging dose. The role of DNA double strand break repair gene polymorphism in RAR is not known. In the present study attempt was made to find out the influence of NHEJ repair gene polymorphisms [a VNTR; XRCC5 (3R/2R/1R/0R); two single nucleotide polymorphisms (SNPs); XRCC6 (C/G) and XRCC7 (G/T)] with DNA damage, repair and mRNA expression in human PBMCs in dose and adaptive response studies. Genomic DNA extracted from venous blood samples of 20 random healthy donors (16 adaptive and 4 non-adaptive) and genotyping of NHEJ repair genes was carried out using PCR amplified length polymorphism.

Results
The dose response study revealed significant positive correlation of genotypes at XRRC5 (3R/2R/1R/0R), XRCC6(C/G) and XRCC7 (G/T) with DNA damage. Donors having genotypes with 2R allele at XRCC5 showed significant positive correlation with mRNA expression level (0R/2R: r = 0.846, P = 0.034; 1R/2R: r = 0.698, P = 0.0001 and 2R/2R: r = 0.831, P = 0.0001) for dose response. Genotypes C/C and C/G of XRCC6 showed a significant positive correlation (P = 0.0001), whereas, genotype T/T of XRCC7 showed significant negative correlation (r = − 0.376, P = 0.041) with mRNA expression.

Conclusion
Interestingly, adaptive donors having C/G genotype of XRCC6 showed significantly higher (P < 0.05) mRNA expression level in primed cells suggesting their role in RAR. In addition, NHEJ repair gene polymorphisms play crucial role with radio-sensitivity and RAR in human PBMCs.
Nivolumab and Ipilimumab as Maintenance Therapy in Extensive-Disease Small-Cell Lung Cancer: CheckMate 451
Authors: Owonikoko Taofeek K. , Park Keunchil , Govindan Ramaswamy , Ready Neal , Reck Martin , Peters Solange , Dakhil Shaker R. , Navarro Alejandro , Rodríguez-Cid Jerónimo , Schenker Michael , Lee Jong-Seok , Gutierrez Vanesa , Percent Ivor , Morgensztern Daniel , Barrios Carlos H. , Greillier Laurent , Baka Sofia , Patel Miten , Lin Wen Hong , Selvaggi Giovanni , Baudelet Christine , Baden Jonathan , Pandya Dimple , Doshi Parul , Kim Hye Ryun 
Published: March 2021

PURPOSE In extensive-disease small-cell lung cancer (ED-SCLC), response rates to first-line platinum-based chemotherapy are robust, but responses lack durability. CheckMate 451, a double-blind phase III trial, evaluated nivolumab plus ipilimumab and nivolumab monotherapy as maintenance therapy following first-line chemotherapy for ED-SCLC. METHODS Patients with ED-SCLC, Eastern Cooperative Oncology Group performance status 0-1, and no progression after ≤ 4 cycles of first-line chemotherapy were randomly assigned (1:1:1) to nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks for 12 weeks followed by nivolumab 240 mg once every 2 weeks, nivolumab 240 mg once every 2 weeks, or placebo for ≤ 2 years or until progression or unacceptable toxicity. Primary end point was overall survival (OS) with nivolumab plus ipilimumab versus placebo. Secondary end points were hierarchically tested. RESULTS Overall, 834 patients were randomly assigned. The minimum follow-up was 8.9 months. OS was not significantly prolonged with nivolumab plus ipilimumab versus placebo (hazard ratio [HR], 0.92; 95% CI, 0.75 to 1.12; P = .37; median, 9.2 v 9.6 months). The HR for OS with nivolumab versus placebo was 0.84 (95% CI, 0.69 to 1.02); the median OS for nivolumab was 10.4 months. Progression-free survival HRs versus placebo were 0.72 for nivolumab plus ipilimumab (95% CI, 0.60 to 0.87) and 0.67 for nivolumab (95% CI, 0.56 to 0.81). A trend toward OS benefit with nivolumab plus ipilimumab was observed in patients with tumor mutational burden ≥ 13 mutations per megabase. Rates of grade 3-4 treatment-related adverse events were nivolumab plus ipilimumab (52.2%), nivolumab (11.5%), and placebo (8.4%). CONCLUSION Maintenance therapy with nivolumab plus ipilimumab did not prolong OS for patients with ED-SCLC who did not progress on first-line chemotherapy. There were no new safety signals.