bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biperiden for prevention of post-traumatic epilepsy: A protocol of a double-blinded placebo-controlled randomized clinical trial (BIPERIDEN trial)
Authors: Foresti Maira Licia , Garzon Eliana , Pinheiro Carla Cristina Gomes , Pacheco Rafael Leite , Riera Rachel , Mello Luiz Eugênio 
Published: September 2022

Background
Traumatic brain injury (TBI) is one of the most important causes of acquired structural epilepsy, post-traumatic epilepsy (PTE), however, efficient preventative measures and treatment are still not available to patients. Preclinical studies indicated biperiden, an anticholinergic drug, as a potential drug to modify the epileptogenic process. The main objective of this clinical trial is to evaluate the efficacy of biperiden as an antiepileptogenic agent in patients that suffered TBI.

Methods
This prospective multicenter (n = 10) interventional study will include 312 adult patients admitted to emergency care units with a diagnosis of moderate or severe TBI. Following inclusion and exclusion criteria, patients will be randomized, using block randomization, to receive double-blind treatment with placebo or biperiden for 10 days. Follow-up will occur at specific time windows up to 2 years. Main outcomes are incidence of PTE after TBI and occurrence of severe adverse events. Other outcomes include exploratory investigation of factors that might have benefits for the treatment or might influence its results, such as genetic background, clinical progression, electroencephalographic abnormalities, health-related quality of life and neuropsychological status. Analyses will be conducted following the safety, intention-to-treat and efficacy concepts.

Discussion
We hypothesize that biperiden treatment will be effective to prevent or mitigate the development of post-traumatic epilepsy in TBI patients. Other health measures from this population also may benefit from treatment with biperiden.

Trial registration
ClinicalTrials.gov, NCT04945213. Registered on June 30, 2021.
Associations between self-reported masticatory dysfunction and frailty: A systematic review and meta-analysis
Authors: Kojima Gotaro , Taniguchi Yu , Iwasaki Masanori , Aoyama Reijiro , Urano Tomohiko 
Published: September 2022

Background
Oral health is a key factor of overall health and closely associated with well-being and quality of life. Mastication is one the most important oral functions and may deteriorate with aging. Evidence on association between masticatory dysfunction and frailty in the literature is scarce and not coherent.

Methods
A search strategy was developed to conduct a systematic review of the literature in PubMed, CINAHL, and AMED in accordance with the PRISMA 2020 guidelines. We searched for studies published in 2000 or later that examined associations between self-reported masticatory dysfunction and frailty risk. The reference lists of the relevant articles were reviewed for additional studies. We calculated pooled odds ratios (OR) of association between self-reported masticatory dysfunction and the risk of frailty by fixed-effects meta-analysis. The Joanna Briggs Institute Critical Appraisal Checklist was used to assess risk of bias. Publication bias was assessed by visually inspecting a funnel plot.

Results
A total of 285 studies were identified by the literature search. Among 5 studies selected for this review, 4 cross-sectional studies including a total of 7425 individuals were used for meta-analysis. The pooled results by a fixed-effects model showed that there was a significant association between self-reported masticatory dysfunction and frailty risk (pooled OR = 1.83, 95%CI = 1.55–2.18, p<0.00001). There was no evidence of publication bias observed.

Conclusions
This systematic review and meta-analysis highlighted pooled cross-sectional evidence that community-dwelling older people who report masticatory dysfunction are significantly more likely to be frail than those who do not. The limitations of this study are: inclusion of only cross-sectional studies, no gold standard to measure masticatory functions, self-reported information on masticatory function, and the limited number of included studies. More longitudinal studies are warranted for further understanding of the causal pathways and elucidate underlying mechanisms.
Registration: PROSPERO CRD42021277173
Economic issues of Severe Acute Respiratory Infections for influenza in Mexican children attended in a tertiary public hospital
Authors: Reyes-Lopez Alfonso , Moreno-Espinosa Sarbelio , Hernandez- Olivares Yosef Olaf , Rodolfo Norberto Jimenez-Juarez 
Published: September 2022

Background
Influenza cause a clinical and economic burden for health systems and society. It is necessary to know the cost of the disease in order to perform cost-effectiveness assessments of preventive or treatment interventions.

Objective
Assess the costs of the care of children with influenza in a third level hospital in Mexico.

Methods
Longitudinal retrospective study based on the review of clinical files of children hospitalized with influenza. The use of resources used during their hospitalization in the emergency room, general ward, or PICU was logged, and the amount of supplies were multiplied by their corresponding prices to calculate the direct medical expenses. Descriptive statistics were used, and a GLM was adjusted in order to assess the effect of the clinical characteristics of the patients on the cost. Goodness of fit tests were performed.

Results
132 files were reviewed, out of which 95% were of subjects who had comorbidities. Subjects admitted at the PICU generates the highest cost (mean $29,608.62 USD), when analyzing the total cost summarizing the three clinical areas (Emergency room, general ward and PICU) by age group, the highest cost was for patients over age 10 (mean $49,674.53 USD). Comorbidities increase the cost of hospitalization by $10,000.00 USD.

Conclusions
Influenza causes a significant financial burden on the health system. Children with comorbidities increase the costs and children over 10 years uses a significant amount of resources and they are not a priority in immunization program. It is necessary to perform studies on the use of resources in the first and second attention levels, which represent the highest incidence of the disease.
Association between retinitis pigmentosa and an increased risk of primary angle closure glaucoma: A population-based cohort study
Authors: Hung Man-Chen , Chen Yu-Yen 
Published: September 2022

Background
Retinitis pigmentosa (RP) is the most frequent retinal hereditary dystrophy and result in blindness if progresses. Several case reports have revealed the possible association between RP and primary angle-closure glaucoma (PACG). We conducted a population-based study to explore whether RP significantly increased the risk of PACG development.

Methods
Using the Taiwan National Health Insurance Research Database, we enrolled patients with RP into the RP group from 2001 to 2013 and included a comparison group of 1:4 age- and sex-matched individuals without RP. We performed a Cox regression analysis to estimate the crude and adjusted hazard ratios (HRs) of RP for PACG after adjustment for hypertension, diabetes, hyperlipidaemia, chronic kidney disease, and lens subluxation.

Results
We enrolled 6223 subjects with RP and 24892 subjects for comparison. The mean age of the cohort was 49.0 ± 18.1 years. The RP group had significantly higher percentages of diabetes mellitus, hypertension, and hyperlipidaemia. The cumulative incidence of PACG in patients with RP was 1.61%, which was significantly higher than that in the comparison group (0.81%, p < 0.0001). According to the univariate Cox regression analysis, the hazard of PACG development was significantly greater in the RP group, with an unadjusted HR of 2.09 (95% confidence interval [CI], 1.64–2.65). The increased risk persisted after adjusting for confounders (adjusted HR = 2.18; 95% CI, 1.76–2.72).

Conclusion
This nationwide population-based cohort study showed that people with RP are at a significantly greater risk of developing PACG than individuals without RP.
Prevalence and consequences of non-adherence to an evidence-based approach for incidental pulmonary nodules
Authors: Wayne Max T. , Prescott Hallie C. , Arenberg Douglas A. 
Published: September 2022

Importance
Distinguishing benign from malignant pulmonary nodules is challenging. Evidence-based guidelines exist, but their impact on patient-centered outcomes is unknown.

Objective
To understand if the evaluation of incidental pulmonary nodules that follows an evidence-based management strategy is associated with fewer invasive procedures for benign lesions and/or fewer delays in cancer diagnosis.

Design
Retrospective cohort study.

Setting
Large academic medical center.

Participants
Adults (≥18 years age) with an incidental pulmonary nodule discovered between January 2012 and December 2014. Patients with calcified nodules, prior nodules, prior diagnosis of cancer, high suspicion for pulmonary metastasis, or limited life expectancy were excluded.

Exposure
Nodule management strategy (pre-specified based on evidence-based practices).

Outcome
Composite of any invasive procedure for a benign nodule or delay in diagnosis in patients with cancer (>3 month delay once probability of cancer was >15%).

Results
Of 314 patients that met inclusion criteria, median age was 61, 46.5% were men, and 66.5% had current or former tobacco use. The mean nodule size was 10.3 mm, mean probability of cancer was 11.8%, and 14.3% of nodules were malignant. Evaluation followed an evidence-based strategy in 245 patients (78.0%), and deviated in 69 patients (22%). The composite outcome occurred in 26 (8.3%) patients. Among patients whose nodule evaluation was concordant with an evidence-based evaluation, 6.1% (15/245) experienced the composite outcome versus 15.9% (11/69) of patients with an evaluation that deviated from evidence-based recommendations (P<0.01).

Conclusions and relevance
At a large academic medical center, more than 1 in 5 patients with an incidental pulmonary nodule underwent evaluation that deviated from evidence-based practice recommendations. Nodule evaluation that deviated from an evidence-based strategy was associated with biopsy of benign lesions and delays in cancer diagnosis, suggesting a need to improve guideline uptake.
Are total omega-3 and omega-6 polyunsaturated fatty acids predictors of fatal stroke in the Adventist Health Study 2 prospective cohort?
Authors: Cupino Alan , Fraser Gary , Knutsen Synnøve , Knutsen Raymond , Heskey Celine , Sabaté Joan , Shavlik David 
Published: September 2022

IntroductionThe effects of omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFA) on cerebrovascular disease remain unsettled. However, most studies have focused on marine sourced n-3 PUFA rather than total n-3 PUFA, of which the majority in the American diet is plant derived. This study therefore intended to investigate these effects in a cohort for which the vegetarian diet was more prevalent than the general public.MethodsCox proportional hazards with fatal stroke as the outcome was performed on the approximately 96,000 subject Adventist Health Study 2 prospective cohort. Stratification by race and sex was performed on models with a priori covariables, comparing 90thto 10thpercentile daily intakes of energy-adjusted total n-3 PUFA, total n-6 PUFA, and the n-6 / n-3 PUFA ratio as variables of interest.ResultsFor the main analytical group (78,335 subjects), the hazard ratio (95% confidence interval) for total n-3 PUFA was 0.65 (0.51–0.83), and for total n-6 PUFA was 1.37 (1.02–1.82), while adjusting for both fatty acids in the model. The n-6 / n-3 PUFA ratio was harmful with a HR of 1.40 (1.16–1.69), whereas the inclusion of total n-3 PUFA slightly attenuated the HR to 1.33(1.02–1.74). Effects were similar for the non-black sex-combined and sex-specific analyses.ConclusionIn most analytic groups, subjects with greater total n-3 PUFA intakes have lower risk of fatal stroke, and those with a higher n-6 / n-3 PUFA ratio had higher risk. However, the n-6 / n-3 PUFA ratio remains statistically significant even after adjusting for total n-3 PUFA or total n-6 PUFA, suggesting that the ratio is of epidemiologic interest for cerebrovascular disease research.
A retrospective review of oral cephalosporins versus fluoroquinolones for the treatment of pyelonephritis
Authors: Lin Kevin , Zahlanie Yorgo , Ortwine Jessica K. , Wei Wenjing , Mang Norman S. , Prokesch Bonnie C. 
Published: September 2022

Background
The current Infectious Diseases Society of America guidelines for the treatment of acute uncomplicated pyelonephritis (AUP) advise caution when using oral beta-lactams due to concern for potentially inferior efficacy compared to fluoroquinolones (FQs) and trimethoprim-sulfamethoxazole; however, studies specifically evaluating the efficacy of oral cephalosporins (CPs) in AUP are limited.

Objective
To assess the safety and efficacy of oral CPs versus FQs for the treatment of AUP.

Design, setting and participants
This is a retrospective, chart review study conducted at a single-center, tertiary care hospital.

Measurements
The primary endpoint was treatment failure within 30 days, defined as a change in antibiotic or return to ED or clinic due to persistent symptoms. Secondary endpoints included adverse drug reactions (ADRs) and C. difficile infection (CDI) within 30 days.

Results
Of the 343 patients included in the study, treatment failure occurred in 54/338 (16.0%) patients and was similar between oral CPs and FQs (35/229 [15.3%] vs. 19/109 [17.4%]). A higher percentage of treatment failures were observed for third generation (3GC) and first generation (1GC) CPs compared to second generation CPs (2GC) (3GC: 15/65 [23.4%]; 1GC: 11/49 [22.4%]; 2GC: 9/115 [7.8%]). Documented ADRs were low (6/343 [1.7%]) and no cases of CDI were documented.

Conclusions
Oral CPs appear to be as safe and effective as FQs for the treatment of AUP. Fewer treatment failures were noted with 2GCs as compared to 3GCs and 1GCs.
Discussing prognosis and the end of life with patients with advanced cancer or COPD: A qualitative study
Authors: Owusuaa Catherine , van Lent Liza G. G. , van ‘t Spijker Adriaan , van der Rijt Carin C. D. , van der Heide Agnes 
Published: September 2022

Objectives
To explore patients’ experiences and recommendations for discussions about their prognosis and end of life with their physicians.

Methods
Patients with advanced cancer or advanced chronic obstructive pulmonary disease (COPD) were enrolled in qualitative interviews, which were analyzed with a phenomenological and thematic approach.

Results
During interviews with fourteen patients (median age 64 years), we identified the following themes for discussion about prognosis and the end of life: topics discussed, the timing, the setting, physician–patient relationship, responsibilities for clinicians, and recommendations. Patients preferred the physician to initiate such discussion, but wanted to decide about its continuation and content. The discussions were facilitated by an established physician–patient relationship or attendance of relatives. Patients with cancer had had discussions about prognosis at rather clear-cut moments of deterioration than patients with COPD. Patients with COPD did not consider end-of-life discussions a responsibility of the pulmonologist. Patients recommended an understandable message, involvement of relatives or other clinicians, sufficient time, and sensitive non-verbal communication.

Conclusions
Patients appreciated open, sensitive, and negotiable discussions about prognosis and the end of life.

Practice implications
Patients’ recommendations could be used for communication training. Possible differences in the need for such discussions between patients with cancer or COPD warrant further research.
Cardiovascular disease risk profile and management among people 40 years of age and above in Bo, Sierra Leone: A cross-sectional study
Authors: Odland Maria Lisa , Gassama Khadija , Bockarie Tahir , Wurie Haja , Ansumana Rashid , Witham Miles D. , Oyebode Oyinlola , Hirschhorn Lisa R. , Davies Justine I. 
Published: September 2022

Introduction
Access to care for cardiovascular disease risk factors (CVDRFs) in low- and middle-income countries is limited. We aimed to describe the need and access to care for people with CVDRF and the preparedness of the health system to treat these in Bo, Sierra Leone.

Methods
Data from a 2018 household survey conducted in Bo, Sierra Leone, was analysed. Demographic, anthropometric and clinical data on CVDRF (hypertension, diabetes mellitus or dyslipidaemia) from randomly sampled individuals 40 years of age and above were collected. Future risk of CVD was calculated using the World Health Organisation–International Society of Hypertension (WHO-ISH) calculator with high risk defined as >20% risk over 10 years. Requirement for treatment was based on WHO package of essential non-communicable (PEN) disease guidelines (which use a risk-based approach) or requiring treatment for individual CVDRF; whether participants were on treatment was used to determine whether care needs were met. Multivariable regression was used to test associations between individual characteristics and outcomes. Data from the most recent WHO Service Availability and Readiness Assessment (SARA) were used to create a score reflecting health system preparedness to treat CVDRF, and compared to that for HIV.

Results
2071 individual participants were included. Most participants (n = 1715 [94.0%]) had low CVD risk; 423 (20.6%) and 431 (52.3%) required treatment based upon WHO PEN guidelines or individual CVDRF, respectively. Sixty-eight (15.8%) had met-need for treatment determined by WHO guidelines, whilst 84 (19.3%) for individual CVDRF. Living in urban areas, having education, being older, single/widowed/divorced, or wealthy were independently associated with met need. Overall facility readiness scores for CVD/CVDRF care for all facilities in Bo district was 16.8%, compared to 41% for HIV.

Conclusion
The number of people who require treatment for CVDRF in Sierra Leone is substantially lower based on WHO guidelines compared to CVDRF. CVDRF care needs are not met equitably, and facility readiness to provide care is low.
Body mass index and physical frailty among older Mexican Americans: Findings from an 18-year follow up
Authors: Rutherford Megan , Downer Brian , Li Chih-Ying , Chou Lin-Na , Al Snih Soham 
Published: September 2022

Purposes
The relationship between body mass index (BMI) and frailty in older Mexican Americans has not been previously studied. The objective of this study was to examine the relationship between BMI and frailty among non-frail older Mexican Americans at baseline over 18 years of follow up.

Methods
Longitudinal population-based study of 1,648 non-institutionalized Mexican Americans aged ≥ 67 years from the Hispanic Established Population for the Epidemiologic Study of the Elderly (1995/96-2012/13). Frailty phenotype was defined as meeting three or more of the following: unintentional weight loss of >10 pounds, weakness, self-reported exhaustion, low physical activity, and slow walking speed. BMI (kg/m2) was classified as underweight (<18.5), normal weight (18.5-<25), overweight (25-< 30), obesity category I (30-<35), and obesity category II/morbid obesity (≥35). Covariates included socio-demographics, comorbidities, cognitive function, and depressive symptoms. Generalized Estimating Equation models were performed to estimate the odds ratio (OR) and 95% confidence interval (CI) of frailty as a function of BMI category.

Results
Participants with underweight or obesity category II/ morbid obesity had greater odds of frailty over time compared to those with normal weight (OR = 2.39, 95% CI = 1.29–4.44 and OR = 1.62, 95% CI = 1.07–2.44, respectively) after controlling for all covariates. Participants with BMIs in the overweight or category I obesity were at lower odds of frailty over time.

Conclusions
Mexican American older adults with BMIs in the underweight or obesity category II/morbid obesity were at higher odds of frailty over time. This indicates that maintaining a healthy weight in this population may prevent future frailty.
Correlation of alpha-1 antitrypsin levels and exosome associated neutrophil elastase endothelial injury in subjects with SARS-CoV2 infection
Authors: Lascano Jorge , Oshins Regina , Eagan Christina , Wadood Zerka , Qiang Xiao , Flagg Tammy , Scindia Yogesh , Mehrad Borna , Brantly Mark , Khodayari Nazli 
Published: September 2022

Background
Severe acute respiratory syndrome caused by a novel coronavirus 2 (SARS-CoV-2) has infected more than 18 million people worldwide. The activation of endothelial cells is a hallmark of signs of SARS-CoV-2 infection that includes altered integrity of vessel barrier and endothelial inflammation.

Objectives
Pulmonary endothelial activation is suggested to be related to the profound neutrophil elastase (NE) activity, which is necessary for sterilization of phagocytosed bacterial pathogens. However, unopposed activity of NE increases alveolocapillary permeability and extracellular matrix degradation. The uncontrolled protease activity of NE during the inflammatory phase of lung diseases might be due to the resistance of exosome associated NE to inhibition by alpha-1 antitrypsin.

Method
31 subjects with a diagnosis of SARS-CoV2 infection were recruited in the disease group and samples from 30 voluntaries matched for age and sex were also collected for control.

Results
We measured the plasma levels of exosome-associated NE in SARS-CoV-2 patients which, were positively correlated with sign of endothelial damage in those patients as determined by plasma levels of LDH. Notably, we also found strong correlation with plasma levels of alpha-1 antitrypsin and exosome-associated NE in SARS-CoV-2 patients. Using macrovascular endothelial cells, we also observed that purified NE activity is inhibited by purified alpha-1 antitrypsin while, NE associated with exosomes are resistant to inhibition and show less sensitivity to alpha-1 antitrypsin inhibitory activity, in vitro.

Conclusions
Our results point out the role of exosome-associated NE in exacerbation of endothelial injury in SARS-CoV-2 infection. We have demonstrated that exosome-associated NE could be served as a new potential therapeutic target of severe systemic manifestations of SARS-CoV-2 infection.