bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of Extramammary Paget Disease and the Role of Reflectance Confocal Microscopy: A Prospective Study
Authors: Navarrete-Dechent Cristian , Aleissa Saud , Cordova Miguel , Hibler Brian P. , Erlendsson Andres M. , Polansky Max , Cordova Frank , Lee Erica H. , Busam Klaus J. , Hollmann Travis , Lezcano Cecilia , Moy Andrea , Pulitzer Melissa , Leitao Mario M. , Rossi Anthony M. 
Published: February 2021

BACKGROUND
Extramammary Paget disease (EMPD) poses treatment challenges. Invasive and noninvasive treatment modalities exist with variable success reported. Reflectance confocal microscopy (RCM) is emerging as an adjuvant diagnostic tool.

OBJECTIVE
To evaluate the treatment of EMPD patients and the role of RCM.

METHODS
Prospective study. Demographic and tumor characteristics were recorded. Handheld-RCM was performed and correlated with histology. Treatment, clearance, pathology, and follow-up were all recorded.

RESULTS
Thirty-six EMPD lesions in 33 patients were included. Mean age was 71.7 years, and 23 were men. Mean number of surgical stages needed to clear margins was 1.9 (SD, 0.9; 1.0–3.0 stages), and mean margin needed to clear was 1.8 cm. Reflectance confocal microscopy correlated well with scouting punch biopsies (kappa, 0.93; p < .001). Disruption of the dermoepidermal junction was associated with invasive EMPD versus in situ (83.3% vs 25.9%) on histology (p = .01).

Limitations
Relatively small sample size.

CONCLUSION
Extramammary Paget disease is challenging, and lesion demarcation is of the utmost importance. Using a staged surgical excision approach, the mean margins needed were 1.8 cm, less than previously reported. Nonsurgical modalities, including radiation therapy, imiquimod, or photodynamic therapy can be considered if surgery is not pursued. Reflectance confocal microscopy is a valuable noninvasive imaging modality for the management of EMPD.
Narcotic Use for Acute Postoperative Pain Management in Mohs Micrographic Surgery Patients With End Stage Renal Disease: A Review of the Literature
Authors: Gruber Paul J. , Scholtz Jaclyn M. , Donnelly Heidi B. 
Published: February 2021

BACKGROUND
Uncontrolled acute postoperative pain presents a significant management challenge when opioids are used in patients with end-stage renal disease (ESRD). Currently, there is a lack of quality pharmacokinetic and pharmacodynamic data regarding opioid medication use in ESRD patients to optimize safe and effective management.

OBJECTIVE
To review the published literature on pharmacologic evidence for and against the use of opioid medications for acute postoperative pain following Mohs micrographic surgery in ESRD patients.

METHODS
A search of PubMed was conducted to identify articles on the pharmacokinetic and pharmacodynamic properties of opioid pain medications in ESRD patients through March 1, 2020.

RESULTS
Seventy-five articles were reviewed. Limited data exist on opioids safe for use in ESRD and are mostly confined to small case series. Studies suggest tramadol and hydromorphone could be considered when indicated. Methadone may be a safe option, but should be reserved for treatment coordinated by a trained pain subspecialist.

CONCLUSION
Randomized clinical trials are lacking. Studies that are available are not sufficient to perform a quantitative methodologic approach. Evidence supports the judicious use of postoperative opioid medications in ESRD patients at the lowest possible dose to achieve clinically meaningful improvement in pain and function.
Sex- and Type-specific Genital Human Papillomavirus Transmission Rates Between Heterosexual Partners: A Bayesian Reanalysis of the HITCH Cohort
Authors: Malagón Talía , MacCosham Aaron , Burchell Ann N. , El-Zein Mariam , Tellier Pierre-Paul , Coutlée François , Franco Eduardo L. ,   for the HITCH Study Group
Published: February 2021

Background:
It is unclear whether sexual transmission rates of human papillomaviruses (HPV) differ between sexes and HPV types. We estimate updated transmission rates from the final HITCH cohort study and propose an estimation method that accounts for interval-censored data and infection clearance.

Methods:
We enrolled young women 18–24 years old and their male sex partners ≥18 years old in Montréal, Canada, between 2005 and 2011. We followed women over 24 months and men over 4 months. We tested genital samples with Linear Array for HPV DNA detection and genotyping. We calculated infection transmission rates between partners using a multistate Markov model via a Bayesian approach. We report the posterior median and 2.5%–97.5% percentile intervals (95% PI).

Results:
We observed 166 type-specific incident HPV transmission events in 447 women and 402 men. The estimated median transmission rate from an HPV-positive to a negative partner was 4.2 (95% PI = 3.1 to 5.3) per 100 person-months. The transmission rate from men-to-women was 3.5 (95% PI = 2.5 to 4.7) and from women-to-men was 5.6 (95% PI = 3.8 to 7.0) per 100 person-months, corresponding to a rate ratio of 1.6 (95% PI = 1.0 to 2.5). Partners reporting always using condoms had a 0.22 (95% PI = 0.05 to 0.61) times lower HPV transmission rate than those reporting never using condoms. HPV16/18 did not have particularly high transmission rates relative to other HPV types.

Conclusion:
Our updated analysis supports previous research suggesting higher women-to-men than men-to-women HPV transmission rates and a protective effect of condoms in heterosexual partnerships. Our results also suggest that crude incidence rates underestimate HPV transmission rates due to interval-censoring. See video abstract at http://links.lww.com/EDE/B794.
Exposure to household air pollutants and endothelial dysfunction in rural Bangladesh
Authors: Shahriar Mohammad Hasan , Chowdhury Muhammad Ashique Haider , Ahmed Shyfuddin , Eunus Mahbubul , Kader Shirmin Bintay , Begum Bilkis A. , Islam Tariqul , Sarwar Golam , Al Shams Rabab , Raqib Rubhana , Alam Dewan S. , Parvez Faruque , Ahsan Habibul , Yunus Md 
Published: February 2021

Background:
More than one third of world’s population use biomass fuel for cooking that has been linked to an array of adverse health hazards including cardiovascular mortality and morbidity. As part of Bangladesh Global Environmental and Occupational Health (GEO Health) project, we assessed whether household air pollution (HAP) was associated with dysfunction in microvascular circulation (measured by reactive hyperemia index [RHI]).

Methods:
We measured exposure to HAP (particulate matter [PM2.5], carbon monoxide [CO], and black carbon [BC]) for 48 hours of 200 healthy nonsmoker adult females who used biomass fuel for cooking. Exposure to PM2.5 and BC were measured using personal monitor, RTI MicroPEM (RTI International, NC) with an internal filter that had been both pre- and post-weighed to capture the deposited pollutants concentration. Lascar CO logger was used to measure CO. Endothelial function was measured by forearm blood flow dilatation response to brachial artery occlusion using RHI based on peripheral artery tonometry. A low RHI score (<1.67) indicates impaired endothelial function.

Results:
Average 48 hours personal exposure to PM2.5 and BC were 144.15 μg/m3 (SD 61.26) and 6.35 μg/m3 (SD 2.18), respectively. Interquartile range for CO was 0.73 ppm (0.62–1.35 ppm). Mean logarithm of RHI (LnRHI) was 0.57 in current data. No statistically significant association was observed for LnRHI with PM2.5 (odds ratio [OR] = 0.97; 95% confidence interval [CI] = 0.92, 1.01; P = 0.16), BC (OR = 0.85; 95% CI = 0.72, 1.01; P = 0.07), and CO (OR = 0.89; 95% CI = 0.64, 1.25; P = 0.53) after adjusting for potential covariates.

Conclusions:
In conclusion, HAP was not associated with endothelial dysfunction among nonsmoking females in rural Bangladesh who used biomass fuel for cooking for years.
Spatial and intraseasonal variation in changing susceptibility to extreme heat in the United States
Authors: Spangler Keith R. , Wellenius Gregory A. 
Published: February 2021

Background:
Exposure to excessive heat is associated with a higher risk of death. Although the relative risk of death on extreme-heat days has decreased over the past several decades in the United States, the drivers of this decline have not been fully characterized. In particular, while extreme heat earlier in the warm season has been shown to confer greater risk of mortality than exposure later in the season, it is unknown whether this within-season variability in susceptibility has changed over time and whether it is modified by region, climatic changes, or social vulnerability.

Methods:
We used distributed-lag nonlinear models and meta-regression to estimate the association between ambient maximum daily temperature during the early, late, and overall warm seasons and the relative risk of mortality for two decades, 1973–1982 and 1997–2006, in 186 metropolitan areas in the United States. We assessed changes in relative risk nationally, regionally, and between places with differential changes in early-season relative extreme heat and indicators of social vulnerability.

Results:
Most of the reduction in heat-related mortality nationally between the two decades is driven by decreases in late-season mortality, while substantial early-season risk remains. This difference is most apparent in the Northeast, in cities with greater increases in early-season relative extreme heat, and in places that have become more socially vulnerable.

Conclusions:
Early-season heat mortality risks have persisted despite overall adaptations, particularly in places with greater warming and increasing social vulnerability. Interventions to reduce heat mortality may need to consider greater applicability to the early warm season.
Ultrasound assessment of gastric volumes of thick fluids
Authors: Tacken Marijn C.T. , van Leest Tristan A.J. , van de Putte Peter , Keijzer Christiaan , Perlas Anahi 
Published: February 2021

BACKGROUND
Enteral nutrition is essential in the treatment of critically ill patients. Current methods to monitor enteral nutrition such as aspiration of residual volume may be inaccurate. Gastric ultrasonography estimates total gastric fluid volume using the Perlas model, but this model is validated for clear fluids only, and its accuracy for measuring thick fluids is unknown.

OBJECTIVES
The primary aim of this study was to evaluate the Perlas model for gastric volume estimation of enteral nutrition, a thick fluid product.

DESIGN
A single-centre, single blinded, randomised controlled study.

SETTING
Single university hospital, from May to July 2019.

PARTICIPANTS
Seventy-two healthy fasted volunteers were randomly allocated to different fluid volume groups.

INTERVENTION
Participants randomly ingested predetermined volumes between 50 and 400 ml of a feeding-drink (Nutricia Nutridrink). Following a standardised gastric ultrasound scanning protocol, a blinded sonographer measured the antral cross-sectional area in the supine and right-lateral decubitus positions.

MAIN OUTCOME MEASURES
Measurements were performed at baseline, 5 min postingestion and 20 min postingestion. Gastric volumes were predicted using the previously established Perlas model and compared with total gastric fluid volumes after ingestion of the study drink.

RESULTS
The Perlas model underestimated the volume of thick gastric fluid and yielded a suboptimal fit for our data. However, antral cross-sectional area and total gastric thick fluid volumes were significantly correlated (Pearson's correlation coefficient 0.73, P < 0.01). A new model was fitted to predict gastric volumes of thick fluids, using the antral cross-sectional area (cm2) in the right-lateral decubitus position: Volume (ml) = 79.38 + 13.32 x right-lateral cross-sectional area.

CONCLUSION
The Perlas model for clear gastric fluid volume estimation is suboptimal for thick fluid volume assessment and an alternative model is presented.

CLINICAL TRIAL REGISTRATION
Netherlands Trial Register Trial NL7677, Registration date: 16 April 2019; https://www.trialregister.nl/trial/7677.
Reducing the time to successful intravenous cannulation in anaesthetised children with poor vein visibility using a near-infrared device
Authors: Gras Severine , Roy-Gash Fabian , Bruneau Béatrice , Salvi Nadège , Colas Anne-Emmanuelle , Skhiri Alia , Orliaguet Gilles , Dahmani Souhayl , Devys Jean-Michel 
Published: February 2021

BACKGROUND
During inhalational induction of anaesthesia for children, severe respiratory events can occur but can be rapidly treated once intravenous access is in place. Reducing the time to successful cannulation during inhalational induction for children with poor vein visibility would improve safety.

OBJECTIVE
To study the effectiveness of a near-infrared (NIR) vascular imaging device (Veinviewer) to facilitate intravenous cannulation.

DESIGN
A prospective, multicentre, randomised, open clinical trial.

SETTING
The operating rooms of three paediatric hospitals in Paris, France, from 1 October 2012 to 31 March 2016.

PATIENTS
Children up to the age of 7 years, with poor vein visibility requiring general anaesthesia.

INTERVENTION
Inhalational anaesthesia was initiated and intravenous cannulation was performed with the standard approach or with the Veinviewer Vision.

MAIN OUTCOME MEASURES
The primary outcome was the time to successful intravenous cannulation. A secondary outcome was the proportion of successful first attempts.

RESULTS
The mean time to successful intravenous cannulation was 200 (95% CI, 143 to 295) seconds in the Veinviewer and 252 (95% CI, 194 to 328) seconds for the control group: hazard ratio 1.28 (1.02 to 1.60) (P = 0.03). The adjusted hazard ratio for known predictive factors was 1.25 (0.99 to 1.56) (P = 0.06). Success at the first attempt was 64.6% (102/158) in the ‘Veinviewer’ group vs. 55.6% (85/153) in the ‘control’ group (P = 0.10).

CONCLUSION
The Veinviewer has limited value in reducing the time to successful intravenous cannulation during inhalational anaesthesia for young children with poor vein visibility. However, there is a strong trend to reducing the delay in some cases and, given its absence of side effects, it could be part of a rescue option for a difficult venous-access strategy.

CLINICAL TRIAL REGISTRATION
NCT01685866 (http://www.clinicaltrials.gov).
Sex difference and intra-operative tidal volume
Authors: Nijbroek Sunny G. , Hol Liselotte , Swart Pien , Hemmes Sabrine N.T. , Serpa Neto Ary , Binnekade Jan M. , Hedenstierna Goran , Jaber Samir , Hiesmayr Michael , Hollmann Markus W. , Mills Gary H. , Vidal Melo Marcos F. , Putensen Christian , Schmid Werner , Severgnini Paolo , Wrigge Hermann , Gama de Abreu Marcelo , Pelosi Paolo , Schultz Marcus J. 
Published: February 2021

BACKGROUND
One key element of lung-protective ventilation is the use of a low tidal volume (V
T). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.

OBJECTIVES
The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.

DESIGN, PATIENTS AND SETTING
This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.

MAIN OUTCOME MEASURES
Women and men were compared with respect to use of LTVV, defined as V
T of 8 ml kg−1 or less predicted bodyweight (PBW). A V
T was deemed ‘default’ if the set V
T was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.

RESULTS
This analysis includes 9864 patients, of whom 5425 (55%) were women. A default V
T was often set, both in women and men; mode V
T was 500 ml. Median [IQR] V
T was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg−1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients’ height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default V
T.

CONCLUSION
In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher V
T than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.

TRIAL REGISTRATION
The study was registered at Clinicaltrials.gov, NCT01601223
Striatin genotype-based, mineralocorticoid receptor antagonist-driven clinical trial: study rationale and design
Authors: Stone Isabella B. , Green Jessica A.E.M. , Koefoed Andrew W. , Hornik Ezra S. , Williams Jonathan S. , Adler Gail K. , Williams Gordon H. 
Published: February 2021

Objectives
In human studies and genetically altered mouse studies, variants in the striatin gene (STRN) are associated with increased blood pressure (BP) and aldosterone on a liberal salt diet. This clinical trial is based on the presumed mechanism for striatin-associated HTN – increased aldosterone. It is designed to determine if participants with the STRN risk alleles will have a greater BP reduction on a liberal salt diet with a specific, mechanism-based therapy – a mineralocorticoid receptor antagonist, eplerenone – as compared with a nonspecific anti-hypertensive therapy – amlodipine.

Methods
One hundred five hypertensive adults with the STRN risk alleles (SNP rs2540923 carriers or rs888083 homozygotes) will be enrolled in a 12-week, double-blind, dose-escalation, clinical trial. After a minimum 2-week washout period and baseline assessment of BP on a liberal salt diet, participants will be randomized to either daily eplerenone or amlodipine. Participants will take daily at-home BP recordings as a safety check. After 4 and 8 weeks of drug therapy, BP will be measured by the study team and medication will be increased, if needed, to achieve a participant goal BP of <140/90 mmHg.
Anticipated results We anticipate that STRN risk allele carriers will demonstrate a greater reduction in BP with eplerenone and will require a lower dose of eplerenone to reach goal BP as compared with amlodipine.

Conclusion
This is a proof-of-concept clinical trial. Positive results support the feasibility of performing genetically-defined, mechanistically-driven trials in HTN. Clinically, it would suggest that genetic biomarkers can identify individuals highly responsive to specific treatment.
Genome-wide association study of letrozole plasma concentrations identifies non-exonic variants that may affect CYP2A6 metabolic activity
Authors: Hertz Daniel L. , Douglas Julie A. , Kidwell Kelley M. , Gersch Christina L. , Desta Zeruesenay , Storniolo Ana-Maria , Stearns Vered , Skaar Todd C , Hayes Daniel F , Henry N. Lynn , Rae James M. 
Published: February 2021

Objectives
Letrozole is a nonsteroidal aromatase inhibitor used to treat hormone-receptor-positive breast cancer. Variability in letrozole efficacy and toxicity may be partially attributable to variable systemic drug exposure, which may be influenced by germline variants in the enzymes responsible for letrozole metabolism, including cytochrome P450 2A6 (CYP2A6). The objective of this genome-wide association study (GWAS) was to identify polymorphisms associated with steady-state letrozole concentrations.

Methods
The Exemestane and Letrozole Pharmacogenetics (ELPh) Study randomized postmenopausal patients with hormone-receptor-positive nonmetastatic breast cancer to letrozole or exemestane treatment. Germline DNA was collected pretreatment and blood samples were collected after 1 or 3 months of treatment to measure steady-state letrozole (and exemestane) plasma concentrations via HPLC/MS. Genome-wide genotyping was conducted on the Infinium Global Screening Array (>650 000 variants) followed by imputation. The association of each germline variant with age- and BMI-adjusted letrozole concentrations was tested in self-reported white patients via linear regression assuming an additive genetic model.

Results
There were 228 patients who met the study-specific inclusion criteria and had both DNA and letrozole concentration data for this GWAS. The association for one genotyped polymorphism (rs7937) with letrozole concentration surpassed genome-wide significance (P = 5.26 × 10−10), explaining 13% of the variability in untransformed steady-state letrozole concentrations. Imputation around rs7937 and in silico analyses identified rs56113850, a variant in the CYP2A6 intron that may affect CYP2A6 expression and activity. rs7937 was associated with age- and BMI-adjusted letrozole levels even after adjusting for genotype-predicted CYP2A6 metabolic phenotype (P = 3.86 × 10−10).

Conclusion
Our GWAS findings confirm that steady-state letrozole plasma concentrations are partially determined by germline polymorphisms that affect CYP2A6 activity, including variants near rs7937 such as the intronic rs56113850 variant. Further research is needed to confirm whether rs56113850 directly affects CYP2A6 activity and to integrate nonexonic variants into CYP2A6 phenotypic activity prediction systems.
Pharmacogenetics: a perspective and preparedness of Pharm-D and medical students in Jordan
Authors: Zawiah Mohammed , Yousef Al-Motassem , Al-Ashwal Fahmi Y. , Abduljabbar Rami , Al-Jamei Sayida , Hayat Khan Amer , Alkhawaldeh Batool 
Published: February 2021

Background
Pharmacogenetics (PGx) science has evolved significantly with a huge number of studies exploring the effect of genetic variants on interindividual variability of drug response. In this study, we assessed the knowledge, attitudes and preparedness of Pharm-D vs. medical students toward PGx.

Method
A paper-based cross-sectional survey was performed. A pilot-tested questionnaire consisting of 21 questions (demographics 5, knowledge 6, attitude 6, and preparedness 4) was administered to 900 healthcare students at different years of study. Descriptive and inferential analyses were used.

Results
Out of the 900 students approached, 852 (94.7%) completed the questionnaire. The overall students’ mean (SD) percentage knowledge score (PKS) was poor [46.7% (18.7)]. The mean (SD) attitude and preparedness scores for all students were 4.68 (1.32), and 1.9 (1.40), respectively, indicating overall positive attitudes, but low preparedness to apply PGx to clinical care. Pharm-D students’ overall PKS was significantly higher than medical students (P < 0.0001). However, there was no significant difference in terms of attitude and preparedness scores. Interestingly, as the year of study increased, the knowledge scores increased as well, with 6th-year students had the highest knowledge scores, while preparedness in applying PGx was higher among the junior students (the 3rd and 4th year of study).

Conclusion
Pharm-D and medical students have inadequate knowledge and low preparedness despite the overall positive attitude towards PGx. There is a need to raise knowledge and to enhance the level of preparedness of medical and Pharm-D students towards PGx and its applications in clinical practice.