bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and nature of potential drug-drug interactions among hospitalized HIV patients presenting with suspected meningitis in Uganda
Authors: Eneh Prosperity C. , Hullsiek Katherine Huppler , Kiiza Daniel , Rhein Joshua , Meya David B. , Boulware David R. , Nicol Melanie R. 
Published: August 2020

Abstract
Background
Management of co-infections including cryptococcal meningitis, tuberculosis and other opportunistic infections in persons living with HIV can lead to complex polypharmacotherapy and increased susceptibility to drug-drug interactions (DDIs). Here we characterize the frequency and types of potential DDIs (pDDIs) in hospitalized HIV patients presenting with suspected cryptococcal or tuberculous meningitis.

Methods
In a retrospective review of three cryptococcal meningitis trials between 2010 and 2017 in Kampala, Uganda, medications received over hospitalization were documented and pDDI events were assessed. IBM Micromedex DRUGDEX® online drug reference system was used to identify and describe potential interactions as either contraindicated, major, moderate or minor. For antiretroviral DDIs, the Liverpool Drug Interactions Checker from the University of Liverpool was also used to further describe interactions observed.

Results
In 1074 patients with suspected meningitis, pDDIs were present in 959 (overall prevalence = 89.3%) during the analyzed 30 day window. In total, 278 unique interacting drug pairs were identified resulting in 4582 pDDI events. Of all patients included in this study there was a mean frequency of 4.27 pDDIs per patient. Of the 4582 pDDI events, 11.3% contraindicated, 66.4% major, 17.4% moderate and 5% minor pDDIs were observed. Among all pDDIs identified, the most prevalent drugs implicated were fluconazole (58.4%), co-trimoxazole (25.7%), efavirenz (15.6%) and rifampin (10.2%). Twenty-one percent of the contraindicated pDDIs and 27% of the major ones involved an antiretroviral drug. Increased likelihood of QT interval prolongation was the most frequent potential clinical outcome. Dissonance in drug interaction checkers was noted requiring clinicians to consult more than one database in making clinical decisions about drug combinations.

Conclusions
The overall prevalence of pDDIs in this population is high. An understanding of drug combinations likely to result in undesired clinical outcomes, such as QT interval prolongation, is paramount. This is especially important in resource limited settings where availability of therapeutic drug monitoring and laboratory follow-up are inconsistent. Adequate quantification of the increased likelihood of adverse clinical outcomes from multiple drug-drug interactions of the same kind in a single patient is needed to aid clinical decisions in this setting.
HIV-associated neurocognitive disorder and HIV-associated myelopathy in a patient with a preserved CD4, but high viral load-a rarely reported phenomenon: a case report and literature review
Authors: Ayele Biniyam Alemayehu , Amogne Wondwossen , Gemechu Lalise 
Published: August 2020

Abstract
Background
Despite widespread use of combination antiretroviral therapy (cART), HIV-associated neurocognitive disorder (HAND) and HIV-associated myelopathy (HAM) are not showing significant reduction in there occurrence. The HAM is a progressive myelopathy that often occur synchronously with severe form of the HAND in patients’ having advanced immunosuppression. However, co-existence of less severe form of the HAND and HAM in patient with relatively preserved CD4 cells is rarely reported clinical entity in post cART era.

Case presentation
We report a 16-year old male, acquired HIV infection vertically, was on second line regimen because of virological failure since 3 years. His current CD4 lymphocyte count is 835 cells/uL with viral RNA level of 33,008 copies/mL. Currently presented with progressive forgetfulness, gait imbalance, and a frequent staring episodes without loss of postural tone. Neurological examination was pertinent for cognitive dysfunction with score of 6 on International HIV Dementia Scale (motor speed = 3, psychomotor speed = 2, and memory recall = 1). Lower limbs power is 4−/5, increased deep tendon reflexes, and unsteady gait. Brain MRI revealed diffuse both cortical and white matter T2 and FLAIR hyperintense lesions. Thoracic MRI showed abnormal T2 signal prolongation spanning from mid thoracic cord to conus. Electroencephalography study showed severe generalized slowing with evidence of focal dysrhythmia in bilateral frontotemporal regions. Unremarkable serum vitamin B 12 level (286 ng/mL). Virological failure with the HAND, HAM and seizure was considered. Dolutegravir +3TC + ATV/r regimen and valproate for seizure disorder was started. On 6 months follow up evaluation, he is clinically stable with significant improvement of his symptoms related to seizure disorders and modest improvement of his cognitive dysfunction, as he is now attending his school regularly. However, less improvement was observed reading his gait abnormality.

Conclusion
This case supports the current understanding regarding the persistent occurrence of HIV-associated neurocognitive disorder and HIV-associated myelopathy even decades after introduction of cART. Therefore, it’s important to screen HIV+ patients for the HAND and HAM even if they have relatively preserved immunity. Because patient can be easily shifted to ART drugs with better CNS penetrating potential to achieve acceptable virological suppression level, to observe sound clinical improvement.
Seroprevalence of herpes simplex virus type 1 among people living with HIV in Mbeya, Tanzania
Authors: Issakwisa Habakkuk Mwakyula , Mbwile Gloria Reginald , Mbwanji Godlove Fred , Nassoro David Daniel , Ntinginya Nyanda Elias , Nsojo Anthony Ambikile 
Published: August 2020

Abstract
Background
Despite the significant decline in the prevalence of HIV in Tanzania, the prevalence rates in Mbeya, Iringa, and Njombe regions are higher than the national average and have remained stable for years. The current stable HIV prevalence may be driven by factors such as a high incidence of sexually transmitted infections (STIs) and high-risk behaviours. In sub-Saharan Africa, it has previously been observed that up to 50% of HIV cases were attributed to herpes simplex type 2 (HSV-2) among low-risk populations. Because the proportion of sexually transmitted HSV-1 is rising, it is essential to study the interaction between HSV-1 and HIV infections.

Methods
We conducted a study in Mbeya region using the archived blood sera of participants from the recently completed EU-funded EMINI project. A specially designed questionnaire was used to obtain the social and demographic characteristics of the study participants in the database. We tested archived participants’ sera for herpes simplex virus type 1 using Virotech HSV-1 (gG1) IgG ELISA (Enzygnost, Behring, Germany). Univariate and multivariate Poisson regression models were used to identify factors associated with HSV-1.

Results
A total of 640 adults were randomly recruited after stratification by HIV status (318 were HIV positive), age, and sex. The overall seroprevalence of HSV-1 in the study population was 92.1%. The extrapolated seroprevalence estimate of herpes simplex virus type 1 in the general population was 95.0% (96.0% in males versus 94.0% in females). Males and females were equally affected by HSV-1. HSV-1 was less prevalent in HIV-positive individuals than in HIV-negative individuals.

Conclusion
People living with HIV were less likely to be HSV-1 seropositive. Further prospective studies are necessary to conclude a causal association.
Choice of dialysis modality: patients’ experiences and quality of decision after shared decision-making
Authors: Finderup Jeanette , Lomborg Kirsten , Jensen Jens Dam , Stacey Dawn 
Published: August 2020

Abstract
Background
Patients with kidney failure experience a complex decision on dialysis modality performed either at home or in hospital. The options have different levels of impact on their physical and psychological condition and social life. The purpose of this study was to evaluate the implementation of an intervention designed to achieve shared decision-making for dialysis choice. Specific objectives were: 1) to measure decision quality as indicated by patients’ knowledge, readiness and achieved preferences; and 2) to determine if patients experienced shared decision-making.

Method
A mixed methods descriptive study was conducted using both questionnaires and semi-structured interviews. Eligible participants were adults with kidney failure considering dialysis modality. The intervention, based on the Three-Talk model, consisted of a patient decision aid and decision coaching meetings provided by trained dialysis coordinators. The intervention was delivered to 349 patients as part of their clinical pathway of care. After the intervention, 148 participants completed the Shared Decision-Making Questionnaire and the Decision Quality Measurement, and 29 participants were interviewed. Concordance between knowledge, decision and preference was calculated to measure decision quality. Interview transcripts were analysed qualitatively.

Results
The participants obtained a mean score for shared decision-making of 86 out of 100. There was no significant difference between those choosing home- or hospital-based treatment (97 versus 83; p = 0.627). The participants obtained a knowledge score of 82% and a readiness score of 86%. Those choosing home-based treatment had higher knowledge score than those choosing hospital-based treatment (84% versus 75%; p = 0.006) but no significant difference on the readiness score (87% versus 84%; p = 0.908). Considering the chosen option and the knowledge score, 83% of the participants achieved a high-quality decision. No significant difference was found for decision quality between those choosing home- or hospital-based treatment (83% versus 83%; p = 0.935). Interview data informed the interpretation of these results.

Conclusions
Although there was no control group, over 80% of participants exposed to the intervention and responded to the surveys experienced shared decision-making and reached a high-quality decision. Both participants who chose home- and hospital-based treatment experienced the intervention as shared decision-making and made a high-quality decision. Qualitative findings supported the quantitative results.

Trial registration
The full trial protocol is available at ClinicalTrials. Gov (NCT03868800). The study has been registered retrospectively.
Early initiation of breastfeeding, colostrum avoidance, and their associated factors among mothers with under one year old children in rural pastoralist communities of Afar, Northeast Ethiopia: a cross sectional study
Authors: Gebretsadik Gebretsadkan Gebremedhin , Tkuwab Helen , Berhe Kidanemaryam , Mulugeta Afework , Mohammed Hajira , Gebremariam Abebe 
Published: August 2020

Abstract
Background
Early initiation of breastfeeding (EIBF) is defined as initiation of breastfeeding within 1 h of birth. This is also the time colostrum is secreted with its potential benefits. Globally, two out of five under 5 children die in the first month of life, more than a third of which being on the first day. Neonatal mortality is still a major health problem in Ethiopia. EIBF and colostrum feeding are associated with decreased neonatal morbidity and mortality. With this study, we aim to determine the magnitude and factors associated with EIBF and colostrum avoidance.

Methods
A community based cross-sectional study was conducted from May to June 2016 on 390 mothers in Afar region. Bivariate logistic regression was used to identify the association between the independent and the outcome variables. Multivariable logistic regression was used to determine the independent predictors of EIBF and colostrum avoidance. The strength of the association was measured by odds ratio and 95% confidence interval, and p-value < 0.05 was considered statistically significant. Hosmer and Lemeshow test was used to test model goodness of fitness and multi-collinearity between independent variables was checked.

Results
About 248(63.6%) respondents initiated breastfeeding within 1 h of birth. Mothers whose delivery was attended by a health professional had 4.75 times higher odds (AOR 4.75; 95% CI 1.71, 13.19) of EIBF as compared to those who were attended by others. Trust on nurses to provide pregnancy care (AOR 5.59; 95% CI 1.05, 29.8) was significantly associated with EIBF. About 300(76.9%) respondents discarded colostrum. Mothers who had no discussion with TBA on child nutrition were 6.6 times (AOR 6.63; 95% CI 1.43, 30.63) more likely to avoid colostrum than their counterparts.

Conclusion
More than one-third of infants didn’t start breastfeeding within 1 h of birth and three-fourth of the mothers discarded colostrum. Therefore, it is important to develop and/or strengthen services/advice on EIBF including colostrum feeding. Promoting delivery by health professionals, discussion on child nutrition and building trust between mothers and health professionals can be important community interventions to encourage EIBF and colostrum feeding.
Antagonists of the serotonin receptor 5A target human breast tumor initiating cells
Authors: Gwynne William D. , Shakeel Mirza S. , Girgis-Gabardo Adele , Kim Kwang H. , Ford Emily , Dvorkin-Gheva Anna , Aarts Craig , Isaac Methvin , Al-awar Rima , Hassell John A. 
Published: August 2020

Abstract
Background
Breast tumor initiating cells (BTIC) are stem-like cells that initiate and sustain tumor growth, and drive disease recurrence. Identifying therapies targeting BTIC has been hindered due primarily to their scarcity in tumors. We previously reported that BTIC frequency ranges between 15% and 50% in multiple mammary tumors of 3 different transgenic mouse models of breast cancer and that this frequency is maintained in tumor cell populations cultured in serum-free, chemically defined media as non-adherent tumorspheres. The latter enabled high-throughput screening of small molecules for their capacity to affect BTIC survival. Antagonists of several serotonin receptors (5-HTRs) were among the hit compounds. The most potent compound we identified, SB-699551, selectively binds to 5-HT5A, a Gαi/o protein coupled receptor (GPCR).

Methods
We evaluated the activity of structurally unrelated selective 5-HT5A antagonists using multiple orthogonal assays of BTIC frequency. Thereafter we used a phosphoproteomic approach to uncover the mechanism of action of SB-699551. To validate the molecular target of the antagonists, we used the CRISPR-Cas9 gene editing technology to conditionally knockout HTR5A in a breast tumor cell line.

Results
We found that selective antagonists of 5-HT5A reduced the frequency of tumorsphere initiating cells residing in breast tumor cell lines and those of patient-derived xenografts (PDXs) that we established. The most potent compound among those tested, SB-699551, reduced the frequency of BTIC in ex vivo assays and acted in concert with chemotherapy to shrink human breast tumor xenografts in vivo. Our phosphoproteomic experiments established that exposure of breast tumor cells to SB-699551 elicited signaling changes in the canonical Gαi/o-coupled pathway and the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) axis. Moreover, conditional mutation of the HTR5A gene resulted in the loss of tumorsphere initiating cells and BTIC thus mimicking the effect of SB-699551.

Conclusions
Our data provide genetic, pharmacological and phosphoproteomic evidence consistent with the on-target activity of SB-699551. The use of such agents in combination with cytotoxic chemotherapy provides a novel therapeutic approach to treat breast cancer.
Association of MTHFR C677T polymorphism with severity and localization of chronic atrophic gastritis patients without Helicobacter pylori infection: a case control study
Authors: Kong Siya , Ye Feng , Dang Yini , Hua Yifei , Zhang Guoxin 
Published: August 2020

Abstract
Background
Previous reports indicate that the methylenetetrahydrofolate reductase (MTHFR) 677C > T polymorphism plays a role in gastric cancer. However, whether it influences the development and progression of atrophic gastritis remains ambiguous. We aimed to determine the possible relationship between MTHFR C677T polymorphism and the severity of atrophic gastritis.

Methods
A total of 128 patients without Helicobacter pylori infection were included in the study. The severity of gastric atrophy was assessed by pathological diagnosis using OLGA and OLGIM Gastritis Staging System. MTHFR 677C > T genotyping was performed by digital fluorescence molecular hybridization. Categorical variables were analyzed by percentages using the χ2 test.

Results
In this study, the TT genotype was significantly more frequent among Helicobacter pylori-negative patients aged ≤44 years (age ≤ 44 years vs. > 44 years, P = 0.039). Patients with TT genotype showed a higher ratio of incisura with atrophy or intestinal metaplasia (TT vs. CC + CT, P = 0.02). Furthermore, TT genotype was associated with more severe lesions compared with the CC + CT genotypes (TT vs. CC + CT for atrophy: P = 0.07; for intestinal metaplasia: P = 0.01; for moderate-to-severe lesions: P = 0.01). OLGA and OLGIM stages III-IV were observed more frequently in patients with TT genotype compared with CC + CT genotypes (for OLGA: P = 0.003; for OLGIM: P = 0.036).

Conclusions
The MTHFR 677C > T TT genotype showed an increased risk of moderate-to-severe lesions by OLGA and OLGIM stages, and these results indicate that MTHFR C677T polymorphism may act as a predictive marker for precancerous gastric lesions, especially in Helicobacter pylori-negative patients aged ≤44 years.
Comparison of visual field progression in new-diagnosed primary open-angle and exfoliation glaucoma patients in Sweden
Authors: Ayala Marcelo 
Published: August 2020

Abstract
Background
The present study aimed to compare visual field progression in new-diagnosed exfoliation versus open-angle glaucoma patients.

Methods
Retrospective study. The study included patients with new-diagnosed primary open-angle and exfoliation glaucoma. All patients were followed for 3 years with reliable visual fields. At least five reliable fields were needed for inclusion. Exfoliation and open-angle glaucoma were defined based on the European Glaucoma Society guidelines. Visual field evaluation was performed using the software threshold 24–2 of the Humphrey Field Analysis. Outcomes: Visual field progression. For visual field progression, three different strategies were used: mean deviation (MD), visual field index (VFI), and the guided progression analysis (GPA).

Results
The study included 128 subjects, of the 54 in the open-angle and 74 in the exfoliation glaucoma group. The MD difference values were higher in the exfoliation (− 3.17 dB) than in the primary open-angle (− 1.25 dB) glaucoma group in the three-year follow-up period. The difference between groups was significant (t-test, p = < 0.001). The difference in VFI was calculated for the 3 years follow-up period. The difference was higher in the exfoliation (− 7.65%) than in the primary open (− 1.90%) glaucoma group (t-test, p = < 0.001). The GPA showed progression in 58% of cases in exfoliation, and 13% in primary open glaucoma group (Chi-square, p = < 0.001).

Conclusion
The present study found a more frequent and faster visual field progression in exfoliation than in primary open-angle glaucoma patients. New-diagnosed exfoliation glaucoma patients must be controlled and treated more strictly than primary open-angle glaucoma patients to avoid visual field deterioration.
Socioeconomic inequalities in food insecurity and malnutrition among under-five children: within and between-group inequalities in Zimbabwe
Authors: Lukwa Akim Tafadzwa , Siya Aggrey , Zablon Karen Nelwin , Azam James Mba , Alaba Olufunke A. 
Published: August 2020

Abstract
Background
Food insecurity and malnutrition in children are pervasive public health concerns in Zimbabwe. Previous studies only identified determinants of food insecurity and malnutrition with very little efforts done in assessing related inequalities and decomposing the inequalities across household characteristics in Zimbabwe. This study explored socioeconomic inequalities trend in child health using regression decomposition approach to compare within and between group inequalities.

Methods
The study used Demographic Health Survey (DHS) data sets of 2010\11 and 2015. Food insecurity in under-five children was determined based on the WHO dietary diversity score. Minimum dietary diversity was defined by a cut- off point of > 4 therefore, children with at least 3 of the 13 food groups were defined as food insecure. Malnutrition was assessed using weight for age (both acute and chronic under-nutrition) Z-scores. Children whose weight-for-age Z-score below minus two standard deviations (− 2 SD) from the median were considered malnourished. Concentration curves and indices were computed to understand if malnutrition was dominant among the poor or rich. The study used the Theil index and decomposed the index by population subgroups (place of residence and socioeconomic status).

Results
Over the study period, malnutrition prevalence increased by 1.03 percentage points, while food insecurity prevalence decreased by 4.35 percentage points. Prevalence of malnutrition and food insecurity increased among poor rural children. Theil indices for nutrition status showed socioeconomic inequality gaps to have widened, while food security status socioeconomic inequality gaps contracted for the period under review.

Conclusion
The study concluded that unequal distribution of household wealth and residence status play critical roles in driving socioeconomic inequalities in child food insecurity and malnutrition. Therefore, child food insecurity and malnutrition are greatly influenced by where a child lives (rural/urban) and parental wealth.