bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of adverse drug events in e-prescribing and administrative health data: a validation study
Authors: Habib Bettina , Tamblyn Robyn , Girard Nadyne , Eguale Tewodros , Huang Allen 
Published: April 2021

Abstract
Background
Administrative health data are increasingly used to detect adverse drug events (ADEs). However, the few studies evaluating diagnostic codes for ADE detection demonstrated low sensitivity, likely due to narrow code sets, physician under-recognition of ADEs, and underreporting in administrative data. The objective of this study was to determine if combining an expanded ICD code set in administrative data with e-prescribing data improves ADE detection.

Methods
We conducted a prospective cohort study among patients newly prescribed antidepressant or antihypertensive medication in primary care and followed for 2 months. Gold standard ADEs were defined as patient-reported symptoms adjudicated as medication-related by a clinical expert. Potential ADEs in administrative data were defined as physician, ED, or hospital visits during follow-up for known adverse effects of the study medication, as identified by ICD codes. Potential ADEs in e-prescribing data were defined as study drug discontinuations or dose changes made during follow-up for safety or effectiveness reasons.

Results
Of 688 study participants, 445 (64.7%) were female and mean age was 64.2 (SD 13.9). The study drug for 386 (56.1%) patients was an antihypertensive, and for 302 (43.9%) an antidepressant. Using the gold standard definition, 114 (16.6%) patients experienced an ADE, with 40 (10.4%) among antihypertensive users and 74 (24.5%) among antidepressant users. The sensitivity of the expanded ICD code set was 7.0%, of e-prescribing data 9.7%, and of the two combined 14.0%. Specificities were high (86.0–95.0%). The sensitivity of the combined approach increased to 25.8% when analysis was restricted to the 27% of patients who indicated having reported symptoms to a physician.

Conclusion
Combining an expanded diagnostic code set with e-prescribing data improves ADE detection. As few patients report symptoms to their physician, higher detection rates may be achieved by collecting patient-reported outcomes via emerging digital technologies such as patient portals and mHealth applications.
Cost effectiveness analysis of a polygenic risk tailored breast cancer screening programme in Singapore
Authors: Wong Jerry Zeng Yang , Chai Jia Hui , Yeoh Yen Shing , Mohamed Riza Nur Khaliesah , Liu Jenny , Teo Yik-Ying , Wee Hwee Lin , Hartman Mikael 
Published: April 2021

AbstractBackgroundThis study aimed to evaluate the cost-effectiveness of a breast cancer screening programme that incorporates genetic testing using breast cancer associated single nucleotide polymorphisms (SNPs), against the current biennial mammogram-only screening programme to aid in its implementation into the current programme in Singapore.MethodsA Markov model was used to compare the costs and health outcomes of the current screening programme, against a polygenic risk-tailored screening programme, which can advise a long-term screening strategy depending on the individual’s polygenic risk. The model took the perspective of the healthcare system, with a time horizon of 40 years, following women from the age of 35 to 74. Epidemiological and cost data were taken from Asian studies, and an annual discount rate of 3% was used. The model outcome was the incremental cost-effectiveness ratio (ICER), calculated from the difference in costs per quality-adjusted life year (QALY). Scenarios with varying risk thresholds for each polygenic risk group were examined. One-way and probabilistic sensitivity analyses were performed to assess parameter uncertainty.ResultsThe ICER for a polygenic risk-tailored breast cancer screening programme, compared with the current biennial mammogram-only screening programme, was − 3713.80 SGD/QALY, with incremental costs < 0 and incremental effects > 0. The scenario analysis of different polygenic risk cutoffs showed that the ICERs remain negative, with all ICERs falling within the south-east quadrant of the cost-effectiveness plane, indicating that tailored screening is more cost effective than mammogram-only screening, with lower costs and higher QALYs to be gained. This suggests that a polygenic risk-tailored breast cancer screening programme is cost effective, entailing lower cost than the current mammogram-only programme, while causing no additional harm to women.ConclusionResults from this cost-effectiveness analysis show that polygenic risk-tailored screening is cost effective with an ICER of − 3713.80 SGD/QALY. Tailored screening remains cost effective even across varying percentile cutoffs for each risk group. While the results look promising for incorporating polygenic risk into the current breast cancer screening programme, further studies should be conducted to address various limitations.
Exploring willingness to pay for health insurance and preferences for a benefits package from the perspective of women from low-income households of Karachi, Pakistan
Authors: Habib Shifa Salman , Zaidi Shehla 
Published: April 2021

Abstract
Background
Achieving universal health coverage (UHC) and reduction in out of pocket (OOP) expenditures on health, is a critical target of the Sustainable Development Goals (SDG). In low-middle income countries, micro-health insurance (MHI) schemes have emerged as a useful financing tool for laying grounds for Universal Health Coverage. The aim of this study was to provide evidence for designing a feasible health insurance scheme targeted at urban poor, by exploring preferences for an insurance benefits package and co-payments among women from low-income households in Karachi, Pakistan.

Methods
This was a descriptive cross-sectional study, conducted using household surveys between July–August 2015. A total of 167 female beneficiaries of Benazir Income Support Programme (BISP), a large-scale cash transfer scheme targeted at low-income households, were recruited in Karachi through a mix of convenience and snowball sampling. Hypothetical insurance benefits packages for a prospective health insurance scheme were formulated to capture respondents’ preferences for health insurance benefits package and co-payments. All data was analyzed using Stata (version 13).

Results
Respondents reporting expenditure on OPD and hospitalization in the last 2 weeks were 93.4 and 11.9% respectively. The highest median expenditure was incurred on medicines. Out of the proposed benefits package, a majority (53%) of the study participants opted for the comprehensive benefits package that provided coverage for emergency care, hospitalization, OPD consultation, diagnostic tests and transportation. For the co-payment plan, 38.9% participants preferred no co-payments that is 100% insurance coverage of medicines followed by hospitalization (25.9%). Nearly half of the respondents (49.4%) chose outpatient consultation for 50% co-payment. A majority of the participants (65.3%) agreed to 100% co-payment for the transportation cost.

Conclusion
Health insurance schemes can be introduced in urban areas, against collection of micro-payments, to prevent low-income households from facing financial catastrophe. A comprehensive benefits package covering emergency care, hospitalization, OPD consultation, diagnostic tests and transportation, is the most preferred among low-income beneficiaries.
Notch signaling is a critical initiator of roof plate formation as revealed by the use of RNA profiling of the dorsal neural tube
Authors: Ofek Shai , Wiszniak Sophie , Kagan Sarah , Tondl Markus , Schwarz Quenten , Kalcheim Chaya 
Published: April 2021

AbstractBackgroundThe dorsal domain of the neural tube is an excellent model to investigate the generation of complexity during embryonic development. It is a highly dynamic and multifaceted region being first transiently populated by prospective neural crest (NC) cells that sequentially emigrate to generate most of the peripheral nervous system. Subsequently, it becomes the definitive roof plate (RP) of the central nervous system. The RP, in turn, constitutes a patterning center for dorsal interneuron development. The factors underlying establishment of the definitive RP and its segregation from NC and dorsal interneurons are currently unknown.ResultsWe performed a transcriptome analysis at trunk levels of quail embryos comparing the dorsal neural tube at premigratory NC and RP stages. This unraveled molecular heterogeneity between NC and RP stages, and within the RP itself. By implementing these genes, we asked whether Notch signaling is involved in RP development. First, we observed that Notch is active at the RP-interneuron interface. Furthermore, gain and loss of Notch function in quail and mouse embryos, respectively, revealed no effect on early NC behavior. Constitutive Notch activation caused a local downregulation of RP markers with a concomitant development of dI1 interneurons, as well as an ectopic upregulation of RP markers in the interneuron domain. Reciprocally, in mice lacking Notch activity, both the RP and dI1 interneurons failed to form and this was associated with expansion of the dI2 population.ConclusionsCollectively, our results offer a new resource for defining specific cell types, and provide evidence that Notch is required to establish the definitive RP, and to determine the choice between RP and interneuron fates, but not the segregation of RP from NC.
Homocysteine, B vitamins, and cardiovascular disease: a Mendelian randomization study
Authors: Yuan Shuai , Mason Amy M. , Carter Paul , Burgess Stephen , Larsson Susanna C. 
Published: April 2021

Abstract
Background
Whether a modestly elevated homocysteine level is causally associated with an increased risk of cardiovascular disease remains unestablished. We conducted a Mendelian randomization study to assess the associations of circulating total homocysteine (tHcy) and B vitamin levels with cardiovascular diseases in the general population.

Methods
Independent single nucleotide polymorphisms associated with tHcy (n = 14), folate (n = 2), vitamin B6 (n = 1), and vitamin B12 (n = 14) at the genome-wide significance level were selected as instrumental variables. Summary-level data for 12 cardiovascular endpoints were obtained from genetic consortia, the UK Biobank study, and the FinnGen consortium.

Results
Higher genetically predicted circulating tHcy levels were associated with an increased risk of stroke. For each one standard deviation (SD) increase in genetically predicted tHcy levels, the odds ratio (OR) was 1.11 (95% confidence interval (CI), 1.03, 1.21; p = 0.008) for any stroke, 1.26 (95% CI, 1.05, 1.51; p = 0.013) for subarachnoid hemorrhage, and 1.11 (95% CI, 1.03, 1.21; p = 0.011) for ischemic stroke. Higher genetically predicted folate levels were associated with decreased risk of coronary artery disease (ORSD, 0.88; 95% CI, 0.78, 1.00, p = 0.049) and any stroke (ORSD, 0.86; 95% CI, 0.76, 0.97, p = 0.012). Genetically predicted increased vitamin B6 levels were associated with a reduced risk of ischemic stroke (ORSD, 0.88; 95% CI, 0.81, 0.97, p = 0.009). None of these associations persisted after multiple testing correction. There was no association between genetically predicted vitamin B12 and cardiovascular disease.

Conclusions
This study reveals suggestive evidence that B vitamin therapy and lowering of tHcy may reduce the risk of stroke, particularly subarachnoid hemorrhage and ischemic stroke.
The prevalence of pulmonary hypertension assessed using the pulmonary vein‐to‐right pulmonary artery ratio and its association with survival in West Highland white terriers with canine idiopathic pulmonary fibrosis
Authors: Roels Elodie , Fastrès Aline , Merveille Anne-Christine , Bolen Géraldine , Teske Erik , Clercx Cécile , Mc Entee Kathleen 
Published: April 2021

Abstract
Background
Pulmonary hypertension (PH) is a known co-morbidity in West Highland white terriers (WHWTs) affected with canine idiopathic pulmonary fibrosis (CIPF). The pulmonary vein-to-right pulmonary artery ratio (PV/PA) has recently been described for the detection of pre-capillary PH in dogs. The objective of the present study was to estimate the prevalence of PH at diagnostic, in WHWTs affected with CIPF, by using PV/PA, in comparison with a group of healthy breed-matched controls (CTRLs). Additional study objective was to explore whether the presence of PH at initial diagnosis of CIPF impacted survival time in dogs treated with sildenafil.

Results
Twenty-five client-owned WHWTs presented with CIPF and 19 CTRLs were included in the study. PV/PA in either two-dimensional mode (2D) or time-motion mode or both were measured from cineloops in each dog. Dogs were classified according to PV/PA value into non/mild PH (PV/PA measured in 2D ≥ 0.7) or moderate/severe PH (PV/PA < 0.7). Survival data of WHWTs affected with CIPF were extracted from medical record to assess association between presence of PH at diagnosis and outcome. 60 % overall prevalence for moderate/severe PH was estimated in this cohort of WHWTs presented with CIPF vs. 5 % in CTRLS (P = 0.0002). The presence of moderate/severe PH at initial presentation was not associated with survival.

Conclusions
Results of the present study confirm a high prevalence of PH at diagnosis in WHWTs affected with CIPF and highlight the utility of PV/PA as a non-invasive surrogate for assessment of PH in this population.
Consumption of meals prepared away from home is associated with inadequacy of dietary fiber, vitamin C and mineral intake among Japanese adults: analysis from the 2015 National Health and Nutrition Survey
Authors: Matsumoto Mai , Saito Aki , Okada Chika , Okada Emiko , Tajima Ryoko , Takimoto Hidemi 
Published: April 2021

AbstractBackgroundConsumption of home-prepared meals may lead to better nutritional intake. Few studies have examined the association between the frequency of consuming meals prepared away from home and the inadequacy of nutritional intake based on nutritional standards and food group intake. We therefore aimed to investigate this issue among Japanese adults.MethodsThis study was a secondary analysis of the 2015 National Health and Nutrition Survey in Japan, involving 921 men and 1300 women aged 18–64 years, conducted as a cross-sectional survey. The frequency of consuming meals prepared away from home was defined using two questions inquiring about the frequency of eating out and take-away meals. Data on dietary intake were collected using a one-day semi-weighed household dietary record. Participants were stratified into three groups based on the frequency of consuming meals prepared away from home (High, Moderate, Low). The inadequacy of each nutrient intake was assessed by comparing estimated average requirement (EAR) level for 14 nutrients and the range of the dietary goal (DG) for seven nutrients according to the 2015 version of the Dietary Reference Intakes for Japanese. Group differences in nutrients adequacy were assessed using the covariate and logistic regression analysis. Food intake was also compared across the groups by classifying each food item into 17 groups based on Standard Tables of Food Composition.ResultsThe proportion of participants who consumed home-prepared meals almost every day were 34.9% among men and 46.8% among women, and the proportion of those consuming a higher frequency of meals prepared away from home were 14.7 and 6.3%, respectively. A higher frequency of consuming meals prepared away from home was associated with inadequacy of dietary fiber, vitamin C and minerals (iron, magnesium and potassium) intake, and with lower intake of vegetables and higher intake of fat and oils.ConclusionsHigh frequency of consuming meals prepared away from home was associated with insufficient intake of dietary fiber, vitamin C and multiple minerals among Japanese adults. These nutrients may be the potential target of interventions aimed at improving nutrient intake in individuals who predominantly eat food prepared away from home.
Examining common mental health disorders in people living with HIV on methadone maintenance therapy in Hanoi, Vietnam
Authors: Mughal Anisa Y. , Stockton Melissa Ann , Bui Quynh , Go Vivian , Pence Brian W. , Ha Tran Viet , Gaynes Bradley N. 
Published: April 2021

AbstractBackgroundInjection drug use drives HIV transmission in Southeast Asia, where around a quarter of users are living with HIV. Vietnam developed Methadone Maintenance Therapy (MMT) programs to reduce unsafe drug abuse. Common mental health disorders (CMD), including depression, anxiety and post-traumatic stress disorder (PTSD), can worsen MMT outcomes and are highly prevalent among people living with HIV (PLH). We aimed to characterize HIV and CMD among MMT patients and assess the impact of HIV and CMD on MMT engagement outcomes in Hanoi, Vietnam.MethodsThis cross-sectional study was conducted at an urban MMT clinic in Hanoi. Participants were screened for CMD with the relevant sections of the Mini International Neuropsychiatric Interview (MINI). Tabular comparisons and regression models were used to understand the association of HIV and CMD with substance use and methadone compliance.ResultsOf the 400 MMT participants, 22% were living with HIV, 11% a CMD, 27% reported injection drug use, and 27% reported methadone noncompliance. Around 17% of those with HIV also had a CMD. Reporting non injection and injection drug use were each higher among those with CMD regardless of HIV status. In addition, reporting any drug use was much higher among those with both HIV and CMD than among those with neither (73% vs 31%,pvalue 0.001). While methadone noncompliance was lower among PLH than among those without HIV (16.3% vs 30.1%,pvalue 0.010), noncompliance was higher among those with CMD than among those without (40.5% vs 25.6%,pvalue 0.045). Among those without HIV, noncompliance was higher among those with CMD than among those without, but among those with HIV, the opposite relationship was observed.ConclusionThere is complex overlap between substance use and methadone noncompliance among MMT patients living with HIV, CMD or both. In this population, we found a high prevalence of CMD and substance use among PLH, and a high prevalence of substance use and methadone noncompliance among those with CMD. Prioritizing provision of mental health care services to MMT patients living with HIV can help improve engagement with substance use disorder treatment and reduce the risk of HIV transmission.
Epidemiological profile, cardiopulmonary fitness and health-related quality of life of patients with heart failure: a longitudinal study
Authors: Silva Paula Cristina , de Almeida Neto Omar Pereira , Resende Elmiro Santos 
Published: April 2021

Abstract
Background
Heart failure (HF) is a severe and self-limiting syndrome. Its signs and symptoms are believed to predict poorer health-related quality of life scores, which are mainly influenced by deterioration in physical capacity. In the present study we try to analyze the influence of clinical and socioeconomic characteristics and physical capacity on the quality of life of people with HF diagnosis.

Methods
A longitudinal study was conducted over 2 years with patients diagnosed with HF. To evaluate the patients the method of face-to-face visit and telephone monitoring was used. In the evaluations were applied: the Clinical and Socioeconomic Characterization Questionnaire, the Minnesota Living With Heart Failure Questionnaire (MLHFQ) for quality of life evaluation and the Veterans Specific Activity Questionnaire (VSAQ) for cardiopulmonary fitness analysis. Measures of central tendency, proportion, normality test, confidence intervals, comparison of data through paired Student t test and Wilcoxon or Mann Whitney test were performed and correlations were verified through Spearman coefficient.

Results
The study included 108 patients, most of them female (50.90%) and mean age of 66.62 ± 11.33 years. The median time of HF diagnosis was 5 ± 6 years, being Chagas’ disease the main etiologic cause for the disease (57.40%). As for the clinical condition, functional classes II (44.40%) and III (48.10%) of the New York Heart Association (NYHA) were the most frequent. There was a low cardiopulmonary fitness, with loss of capacity to perform daily activities (3 ± 1 to 3 ± 3) over the time of clinical follow-up.
There was an increase in the MLHFQ instrument scores, from 50.98 ± 15.52 to 61.76 ± 19.95, over the analysis time. The analysis of correlations demonstrated that variables such as schooling, NYHA class, echocardiographic alterations and the drug profile have a significant relationship with the constructs of quality of life and physical fitness.

Conclusion
Individuals in HF have significant impairment of cardiorespiratory capacity and tend to present worsening of QL along the evolution of the disease.
Strengthened luteal phase support for patients with low serum progesterone on the day of frozen embryo transfer in artificial endometrial preparation cycles: a large-sample retrospective trial
Authors: Gao Hongyuan , Ye Jing , Ye Hongjuan , Hong Qingqing , Sun Lihua , Chen Qiuju 
Published: April 2021

Abstract
Background
Low serum progesterone on the day of frozen embryo transfer (FET) is associated with diminished pregnancy rates in artificial endometrium preparation cycles, but there is no consensus on whether strengthened luteal phase support (LPS) benefits patients with low progesterone on the FET day in artificial cycles. This single-centre, large-sample retrospective trial was designed to investigate the contribution of strengthened LPS to pregnancy outcomes for groups with low progesterone levels on the FET day in artificial endometrium preparation cycles.

Methods
Women who had undergone the first artificial endometrium preparation cycle after a freeze-all protocol in our clinic from 2016 to 2018 were classified into two groups depending on their serum progesterone levels on the FET day. Routine LPS was administered to group B (P ≥ 10.0 ng/ml on the FET day, n = 1261), and strengthened LPS (routine LPS+ im P 40 mg daily) was administered to group A (P < 10.0 ng/ml on the FET day, n = 1295). The primary endpoint was the live birth rate, and the secondary endpoints were clinical pregnancy, miscarriage and neonatal outcomes.

Results
The results showed that the clinical pregnancy rate was significantly lower in group A than in group B (48.4% vs 53.2%, adjusted risk ratio (aRR) 0.81, 95% confidence interval (CI) 0.68, 0.96), whereas miscarriage rates were similar between the two groups (16.0% vs 14.7%, aRR 1.09, 95% CI 0.77, 1.54). The live birth rate was slightly lower in group A than in group B (39.5% vs 43.3%, aRR 0.84, 95% CI 0.70, 1.0). Birthweights and other neonatal outcomes were similar between the two groups (P > 0.05).

Conclusions
The results indicated that the serum progesterone level on the FET day was one of the risk factors predicting the chances of pregnancy in artificial endometrium preparation cycles, and strengthened LPS in patients with low progesterone on the FET day might help to provide a reasonable pregnancy outcome in artificial cycles, although further prospective evidence is needed to confirm this possibility.