bluuebunny/crossref_metadata_2025 huggingface dataset:
FC 128: Novel Glucose-Lowering Drugs and the Risk of Acute Kidney Injury in Routine Care: The Stockholm Creatinine Measurements (SCREAM) Project
Authors: Alkas Jim , Bosi Alessandro , Sjolander Arvid , Peter Barany Franz , Elinder Carl-Gustaf , Fu Edouard , Jesus Carrero Juan
Published: May 2022

BACKGROUND AND AIMS

Little is known about the comparative effects of dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1RAs) or sodium glucose cotransporter-2 inhibitors (SGLT2i) on risk of acute kidney injury (AKI) in routinely care, which may differ from the controlled setting of trials.

METHOD

We performed a population-based retrospective analysis using the Stockholm CREAtinine Measurements (SCREAM) database, with complete information on diagnoses, medication dispensation claims and laboratory test results for all Stockholm citizens accessing healthcare during 2008–2018. We used a new user active comparator design: new initiation of SGLT2i, GLP1-RA or DPP-4i. The outcome AKI was defined by ICD-10 diagnostic codes as well as KDIGO criteria for rapid creatinine elevations. A multinominal propensity score model with inverse probability treatment weights (IPTW) was used to adjust for 59 identified confounders. Weighted Cox regression was used to estimate adjusted hazard ratios and weighted Kaplan-Meier curves for adjusted absolute risks.

RESULTS

We included 17 043 participants who newly initiated DPP-4i (N = 10 345), GLP1-RA (N = 4384) or SGLT2i (N = 2314). Mean age was 63 years (38% women) and median eGFR 89 mL/min/1.73 m2. During a median follow-up of 2.5 years, 1361 participants experienced AKI. SGLT2i users had the lowest incidence rate of AKI, 17.4 per 1000 person years [95% confidence interval (95% CI) 13.3–22.4], followed by GLP1-RA users, 22.2 (95% CI 19.6–25) and DPP-4 users, 26.1 (95% CI 24.6–27.8). The adjusted 3-year absolute risk for AKI was 5.98 (95% CI 3.65–8.38) in the SGLT2i arm, compared with 6.45 (95% CI 5.26–7.62) in the GLP1-RA arm and 7.03 (95% CI 6.45–7.59) in the DPP-4i arm. The adjusted hazard ratio was 0.85 (95% CI 0.58–1.18) for SGLT2i versus DPP-4i, and 0.93 (95% CI 0.78–1.11) for GLP1-RA versus DPP-4i.

CONCLUSION

This study of routinely cared patients initiating novel glucose-lowering drugs observed similar occurrence of AKI between therapies.
MO081: Ambulatory Blood Pressure Trajectories and Blood Pressure Variability in Kidney Transplant Recipients: A Comparative Study Against Chronic Kidney Disease Patients
Authors: Korogiannou Maria , Theodorakopoulou Marieta , Sarafidis Pantelis , Eleni Alexandrou Maria , Pella Eva , Efstathios Xagas , Argyris Antonis , Protogerou Athanase , Papagianni Aikaterini , Boletis Ioannis , Marinaki Smaragdi
Published: May 2022

BACKGROUND AND AIMS

Hypertension is a major cardiovascular risk factor in both kidney transplant recipients (KTRs) and patients with chronic kidney disease (CKD). Ambulatory blood pressure monitoring (ABPM) is considered the gold standard method for hypertension management in these subjects. This is the first study evaluating in comparison the full ambulatory BP profile and short-term BP variability (BPV) in KTRs versus CKD patients without kidney replacement therapy.

METHOD

93 KTRs were matched with 93 CKD patients for age, sex and eGFR. All participants underwent 24 h ABPM; mean ambulatory BP levels, BP trajectories and BPV indices [standard deviation (SD), weighted-SD and average real variability] were compared between the two groups.

RESULTS

There were no significant between-group differences in 24-h SBP/DBP (KTRs:126.9 ± 13.1/79.1 ± 7.9 versus CKD:128.1 ± 11.2/77.9 ± 8.1 mmHg,  P = 0.522/0.293), daytime SBP/DBP and nighttime SBP; nighttime DBP was slightly higher in KTRs (KTRs:76.5 ± 8.8 versus CKD:73.8 ± 8.8 mmHg, P = 0.040). For both ambulatory SBP/DBP, repeated-measurements-ANOVA showed a significant effect of time (SBP: F = [19, 3002]=11.735, P < 0.001, partial η2 = 0.069) but not of KTR/CKD status (SBP: F = [1, 158] = 0.668, P = 0.415, partial η2 = 0.004). Ambulatory systolic/diastolic BPV indices were not different between KTRs and CKD patients, except for 24-h DBP-SD that was slightly higher in the latter (KTRs: 10.2 ± 2.2 versus CKD: 10.9 ± 2.6 mmHg, P = 0.041). No differences were noted in dipping pattern between the two groups.

CONCLUSION

Mean ambulatory BP levels, BP trajectories and short-term BPV indices are not significantly different between KTRs and CKD patients, suggesting that KTRs have a similar ambulatory BP profile compared with CKD patients without kidney replacement therapy.
MO082: Predictors of Decreased Renal Function in Patients With Arterial Hypertension and Chronic Obstructive Pulmonary Disease
Authors: Boiko Olha , Rodionova Viktoriia
Published: May 2022

BACKGROUND AND AIMS

Arterial hypertension is characterized by kidney damage as a target organ. In turn, as a result of immunological and pathophysiological processes, in patients with COPD, a decrease in renal function was revealed 1.6 times more often than in the general population. The aim of this study was to identify predictors of a decrease in GFR below 60 mL/min in the case of comorbidity of arterial hypertension and COPD.

METHOD

A single-stage study included 51 patients with comorbid hypertension and COPD [mean age 59.3 (3.1) years]. The exclusion criteria were age over 80 years, primary kidney disease, diabetes mellitus, cancer, heart failure, stage III hypertension. All patients underwent determination of cystatin C in the blood, studied the composition of the body using bioimpedance and spirographic examination. To determine the predictors of kidney damage, we used regression analysis with ROC-curve estimation using the MedCalc software.

RESULTS

Total adipose tissue (P < 0.0001), BMI (P = 0.003), FEV1 (P = 0.0002) had the greatest statistical significance. In turn, the highest AUCs were also in predictors such as total adipose tissue [0.91 (0.66; 0.99)], FEV1 [0.86 (0.63; 0.98)]. The optimal value (cut-off point) of adipose tissue content, which allowed to most accurately predict a decrease in GFR < 60 mL/min in patients with hypertension and COPD was 41.3 (sensitivity: 100%, specificity: 85.7%), visceral fat: 11% (sensitivity:100%, specificity: 78.3%), BMI: 30 kg/m2 (sensitivity: 100%, specificity: 50.0%). The optimal value (cut-off point) of blood cystatin C, which allowed to most accurately predict a decrease in GFR < 60 mL/min in patients with hypertension and COPD was 1.21 mg/L (sensitivity: 75%, specificity: 87.5%), FEV1: 64.0% (sensitivity: 100%, specificity: 66.7%), ambulatory artery stiffness index: 0.43 (sensitivity: 80%, specificity: 100%)

CONCLUSION

Predictors of GFR reduction <60 mL/min in patients with hypertension and COPD were: increase in total adipose tissue >41.3%, increase in visceral fat >11%, increase in BMI >30 kg/m2 increase in Cystatin C > 1.21 mg/L and reduction of FEV1 < 64.0%.
MO091: Serum Hepatocyte Growth Factor is Associated With Albuminuria in Subjects With Optimal Blood Pressure and Untreated Arterial Hypertension
Authors: Fistrek Prlic Margareta , Knezevic Tamara , Ivkovic Vanja , Fucek Mirjana , Abramovic Baric Mirta , Brzic Ivan , Domislovic Marija , Jelakovic Bojan
Published: May 2022

BACKGROUND AND AIMS

Hepatocyte growth factor (HGF) is a pleiotropic factor that has a protective role in acute renal injury. HGF prevents the development of chronic renal fibrosis in animal models via inhibition of transforming growth factor β1 expression and consequently reduces podocyte injury and proteinuria.[1,2] Serum HGF concentration is associated with systolic arterial blood pressure (BP) and is higher in hypertensive than in normotensive individuals, especially if complications of arterial hypertension are developed.[3,4] Our aim was to determine the association of serum HGF concentration and albuminuria in normotensive subjects and subjects with untreated arterial hypertension.

METHOD

Data from 563 subjects (57.8% women, mean age 48 years) was analyzed. After clinical examination, fasting blood and urine samples were drawn. Albuminuria was normalized to urine creatinine and expressed as an albumin/creatinine ratio (ACR). HGF was measured using a commercial test. BP was measured according to ESH guidelines. Based on BP values, subjects were divided into two groups: OBP: subjects with optimal blood pressure (BP < 120/80 mmHg, N = 295), and UAH: subjects with untreated arterial hypertension (BP > 140/90 mmHg, N = 268).

RESULTS

Subjects with UAH were significantly older and had higher values of body mass index, waist circumference, serum total, and LDL-cholesterol levels, triglyceride levels, fasting glucose levels, and ACR (all P < 0.001). Serum HGF concentrations were also higher in UAH subjects, but the difference was not significant (270.8 versus 304.2 pg/mL, P = 0.651). Subjects with ACR > 30 mg/g had higher values of serum HGF concentration in comparison with subject with ACR < 30 mg/g in both groups, but the difference again was not significant (262.1 versus 527.8 pg/ml, P = 0.747 and 328.6 versus 843.5 pg/ml, P = 0.066, respectively). Serum HGF concentration showed a significant positive correlation to ACR in both groups (P < 0.05). Multivariate regression analysis showed that BP was an independent predictor of ACR increase (Beta = 0.134, P = 0.028), whereas age, sex and serum glucose were not. Serum HGF concentration was also a strong predictor of the ACR increase (Beta = 0.376, P < 0.001).

CONCLUSION

Serum HGF concentration is associated with ACR in subjects with not only untreated arterial hypertension but also optimal blood pressure. We found that HGF is an independent predictor of the ACR increase in this population.
MO346: Timing of Renal Replacement Therapy Initiation in Patients With Septic Acute Kidney Injury: A Systematic Review and Meta-Analysis
Authors: Jung Oh Hyung , Su Ku Nam , Eun Chung Yong
Published: May 2022

BACKGROUND AND AIMS

To evaluate the optimal timing of renal-replacement therapy (RRT) initiation with a systemic review and meta-analysis in the patients with septic acute kidney injury (AKI).

METHOD

Systemic searches of PubMed, Cochrane and Embase databases from their inception to June 2021 were investigated. Studies that reported original data that specifically mentioned applying RRT in septic patients with AKI were selected. And, full-text reviews were performed by two reviewers independently with the following eligibility criteria: (1) observational cohort and/or randomized clinical trial (RCT) design; (2) adult septic patients; (3) diagnosis of AKI; (4) description of factors related to the timing of RRT initiation; and (5) description of mortality outcomes.

RESULTS

Among a total of six studies including 1058 patients, the 28-day mortality rate was significantly lower in the early RRT-treated group compared with the late group [RR = 0.69; 95% confidence interval (95% CI) (0.51–0.94); P = 0.018]. Moreover, among the five studies including 938 patients, the 90-day mortality rate was also significantly lower in the early RRT-treated group than in the late group [RR = 0.61; 95% CI (0.47–0.80); P = 0.01]. In a subgroup analysis for continuous RRT (CRRT), we also found significantly lower 28- and 90-day mortality rates in the early CRRT-treated group compared with the late group.

CONCLUSION

This study showed that early initiation of RRT might reduce 28- and 90-day mortality compared with late initiation in septic AKI patients.
MO348: Methylene Blue Beneficial Effect in Treatment of Renal Calculi in Patient With Recurrent Urinary Tract Infection
Authors: Ivanov Dmitry D
Published: May 2022

BACKGROUND AND AIMS

Assessment of efficacy of fixed combination of cranberry and sage extract with methylene blue (MBC) in dose of 30 mg twice daily in the prevention and management of chronic renal calculous disease.

METHOD

In 87 patients who complained recurrent urinary tract infection (UTI)—55 pts with pyelonephritis and 32 with cystitis—at least three episodes in 12 months, the impact of 3 months treatment of MBC with on renal calculi was investigated. All patients were older than 18 years without any biochemical or congenital kidney abnormalities, coagulopathies with size of renal stone over 10 mm. Simultaneous administration of phenothiazine derivatives, SSRI, MAO, tricyclic or any other antidepressants we excluded. A total of 39 (45%) of the patients with a history of nephrolithotomy in the past were included.

RESULTS

In most cases, patients were supervised during 12 months with 2–3 courses of MBC during the year. A total of 18 pts (21%) have passed no further stones with dramatic improvement of quality of life, and 47 (54%) have improved clinically with reduction of calculi size. A total of 79 pts (91%) reported overall clinical improvement of UTI symptoms and quality of life. The main disadvantage during MBC administration could be discoloration of the urine in light blue or green color. No side or adverse effects were observed during the whole period of the trial.

CONCLUSION

Methylene blue could be a promising solution in the management of patients with multiple small renal calculi, especially with necessity to reduce the level of concomitant infection without antibiotic and may be useful in the prevention of new stone formation.
MO361: Erythropoietin Treatment in Acute Kidney Injury (EAKI): A Pragmatic Randomized Clinical Trial
Authors: Aoun Mabel , Sleilaty Ghassan , Boueri Celine , Younes Eliane , Gabriel Kim , Kahwaji Reine-Marie , Hilal Najla , Hawi Jenny , Araman Rita , Nehme Chelala Dania , Beaini Chadia
Published: May 2022

BACKGROUND AND AIMS

Treatment with erythropoietin (EPO) is well established for anemia in chronic kidney disease patients but not well studied in acute kidney injury (AKI). This study aims to assess the transfusion need, renal recovery and all-cause mortality of AKI patients with anemia whether treated or not with EPO.

METHOD

This is a multicenter, randomized, pragmatic controlled clinical trial. It included 134 hospitalized patients with anemia [hemoglobin (Hb) <11 g/dL] and AKI [serum creatinine (Scr) of 0.3 mg/dL in 48 h or 1.5 times baseline]. Patients with active bleeding were excluded. Patients received EPO 4000 UI every other day (n = 67) or standard of care (control; n = 67) during the hospitalization until discharge or death. The study got the approval of the ethics committee of Saint-Joseph University number CE-HDF1115.

The trial is registered on ClinicalTrials.gov (NCT03401710).

RESULTS

The general characteristics of both groups are summarized in Table 1. There was no statistically significant difference in transfusions, renal recovery or mortality between the treated group and the control (Table 2). A conditional regression analysis found phosphate, Hb on admission, CRP at the end of the hospitalization, the need for transfusions, the absence of renal recovery and inotrope use as factors associated with mortality (OR = 1.34, 95% CI 1.09–1.63; P = 0.004; OR = 0.61, 95% CI 0.41–0.92; P = 0.018; OR = 1.014, 95% CI 1.005–1023; P = 0.003; OR = 4.48, 95% CI 1.53–13.07; P = 0.006; OR = 22.1, 95% CI 6.36–76.74; P < 0.001; OR = 9.16, 95% CI 2.89–28.99; P < 0.001, respectively).

CONCLUSION

EPO treatment in patients with AKI and anemia has no significant impact on transfusion need, renal recovery or death.
FC078: Impact of Removing Race from the CKD-EPI Equation: Analysis of 1.6 Million Swedish Adults
Authors: Fu Edouard , Coresh Josef , Grams Morgan , M. Clase Catherine , Elinder Carl-Gustaf , Paik Julie , Ramspek Chava , Inker Lesley , Levey Andrew , W. Dekker Friedo , Jesus Carrero Juan
Published: May 2022

BACKGROUND AND AIMS

The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) recently developed a novel creatinine-based eGFR equation without a race coefficient. While American nephrology societies recommend using this novel equation, its implications are unknown.

METHOD

We included 1.6 million adult individuals with routine outpatient serum creatinine testing during 2007–2018 in Stockholm, Sweden. First, we calculated reclassification across KDIGO eGFR categories when changing from the 2009 to 2021 CKD-EPI equation. Second, for both equations, the association between eGFR and (1) kidney failure with replacement therapy (KFRT), (2) all-cause mortality, (3) cardiovascular mortality and (4) major adverse cardiovascular events was estimated with Cox regression. Third, prognostic accuracy of both eGFR equations within the Kidney Failure Risk Equation was assessed with discrimination and calibration.

RESULTS

Compared with the 2009 equation, the 2021 equation yielded a higher eGFR by a median (IQR) of 3.9 (2.9–4.8) mL/min/1.73 m2, decreasing prevalence of CKD G3–G5 from 5.1 to 3.8%. The 2021 equation reclassified 9.9% of the total population and 36.2% of the CKD G3–G5 population to a less severe eGFR category. Individuals who were reclassified to less severe eGFR categories were older and therefore exhibited higher crude risks of all-cause/cardiovascular death and major adverse cardiovascular events, and lower risk of kidney replacement therapy compared with nonreclassified participants of similar eGFR. eGFR by both equations strongly predicted study outcomes, with similar discrimination and calibration for the Kidney Failure Risk Equation.

CONCLUSION

Implementing the 2021 CKD-EPI equation in predominantly white European populations raises eGFR by a modest amount (larger at older age and men) and shifts a major proportion of CKD patients to a higher eGFR category, with eGFR by both equations strongly predicting outcomes.
Kidney function at 3 months after acute kidney injury is an unreliable indicator of subsequent kidney dysfunction: the NARA-AKI Cohort Study
Authors: Nishimoto Masatoshi , Murashima Miho , Kokubu Maiko , Matsui Masaru , Eriguchi Masahiro , Samejima Ken-Ichi , Akai Yasuhiro , Tsuruya Kazuhiko
Published: May 2022

Background

The relationship between kidney function at 3 months after acute kidney injury (AKI) and kidney function prognosis has not been characterized.

Methods

This retrospective cohort study included adults who underwent noncardiac surgery under general anesthesia. Exclusion criteria included obstetric or urological surgery, missing data and preoperative dialysis. Linear mixed-effects models were used to compare estimated glomerular filtration rate (eGFR) slopes in patients with and without AKI. Multivariable Cox proportional hazard models were used to examine the associations of AKI with incident chronic kidney disease (CKD) and decline in eGFR ≥30%.

Results

Among 5272 patients, 316 (6.0%) developed AKI. Among 1194 patients with follow-up creatinine values, eGFR was stable or increased in patients with and without AKI at 3 months postoperatively and declined thereafter. eGFR decline after 3 months postoperatively was faster among patients with AKI than among patients without AKI (P = .09). Among 938 patients without CKD—both at baseline and at 3 months postoperatively—226 and 161 developed incident CKD and a decline in eGFR ≥30%, respectively. Despite adjustment for eGFR at 3 months, AKI was associated with incident CKD {hazard ratio [HR] 1.73 [95% confidence interval (CI) 1.06–2.84]} and a decline in eGFR ≥30% [HR 2.41 (95% CI 1.51–3.84)].

Conclusions

AKI was associated with worse kidney outcomes, regardless of eGFR at 3 months after surgery. Creatinine-based eGFR values at 3 months after AKI might be affected by acute illness-induced loss of muscle mass. Kidney function might be more accurately evaluated much later after surgery or using cystatin C values.
Seroconversion rate after primary vaccination with two doses of BNT162b2 versus mRNA-1273 in solid organ transplant recipients: a systematic review and meta-analysis
Authors: Verleye Arno , Wijtvliet Veerle , Abrams Steven , Hellemans Rachel , Bougrea Rania , Massart Annick , Pipeleers Lissa , Wissing Karl Martin , Ariën Kevin K , De Winter Benedicte Y , Van Damme Pierre , Abramowicz Daniel , Ledeganck Kristien J
Published: May 2022

Background

In the general population, the seroconversion rate after primary vaccination with two doses of an anti-severe acute respiratory syndrome coronavirus 2 messenger RNA (mRNA) vaccine reaches nearly 100%, with significantly higher antibody titers after mRNA-1273 vaccination compared to BNT162b2 vaccination. Here we performed a systematic review and meta-analysis to compare the antibody response after two-dose mRNA-1273 versus BNT162b2 vaccination in solid organ transplant (SOT) recipients.

Methods

A systematic literature review was performed using PubMed, Web of Science and the Cochrane Library and original research papers were included for a meta-analysis to calculate vaccine-specific seroconversion rates for each of the mRNA vaccines. Next, the pooled relative seroconversion rate was estimated.

Results

Eight studies that described the development of antibodies against receptor-binding domain (RBD) and/or spike protein were eligible for meta-analysis. Two of these studies also reported antibody titers. The meta-analysis revealed lower seroconversion rates in SOT recipients vaccinated with two doses of BNT162b2 {44.3% [95% confidence interval (CI) 34.1–54.7]} as compared with patients vaccinated with two doses of mRNA-1273 [58.4% (95% CI 47.2–69.2)]. The relative seroconversion rate was 0.795 (95% CI 0.732–0.864).

Conclusions

This systematic review and meta-analysis indicates that in SOT recipients, higher seroconversion rates were observed after vaccination with mRNA-1273 compared with BNT162b2.
Brain tumor patients and COVID-19 vaccines: results of an international survey
Authors: Voisin Mathew R , Oliver Kathy , Farrimond Stuart , Chee Tess , O’Halloran Philip , Glas Martin ,   International Brain Tumour Alliance (IBTA) Senior Advisors, Arzbaecher Jean , Kruchko Carol , Maher Mary Ellen , Tse Chris , Cashman Rosemary , Daniels Maureen , Mungoshi Christine , Lamb Sharon , Granero Anita , Lovely Mary , Baker Jenifer , Payne Sally , Zadeh Gelareh
Published: May 2022

Background

As the COVID-19 pandemic continues to unfold, the advent of multiple approved vaccines has led to a milestone in the fight against the virus. While vaccination rates and side effects are well established in the general population, these are largely unknown in patients with brain tumors. The purpose of this study was to determine if brain tumor patients and their caregivers have received a COVID-19 vaccine, and explore their thoughts and opinions on these vaccines.

Methods

An anonymous 31-question online survey available in 8 languages was conducted from June 30, 2021 to August 31, 2021. The survey was open to adult brain tumor patients over the age of 18 and included both categorical and open-ended questions. Descriptive statistics and modified thematic analyses were performed for all questions as appropriate.

Results

A total of 965 unique surveys were completed from 42 countries. The vast majority of both brain tumor patients and their caregivers have been vaccinated against COVID-19 (84.5% and 89.9%, respectively). No patient reported serious adverse events from any vaccine. Less than 10% of patients decided against receiving a vaccination against COVID-19, with the most common reason being concerns over the safety of the vaccine. Patients wanted more specific information on how COVID-19 vaccines might impact their future brain tumor treatment.

Conclusions

In conclusion, the majority of brain tumor patients and their caregivers have received COVID-19 vaccines with no major side effects. Patients want more information on how COVID-19 vaccines might directly impact their brain tumor and future management.
The Differential Impact of the 2000 Canadian Graphic Warning Label Policy on Smoking Prevalence by Sex and Education: A Difference-in-Difference-in-Difference Model
Authors: Usidame Bukola , Meng Gang , Thrasher James F , Thompson Mary E , Fong Geoffrey T , Fleischer Nancy L
Published: May 2022

Introduction

Using a quasiexperimental design, we compared the impact of the 2000 Canadian introduction of graphic warning labels (GWLs) on differences in smoking prevalence by sex and education, to the United States, where no GWLs were introduced.

Methods

We pooled 1999–2004 data from the Canadian Tobacco Use Monitoring Survey and the U.S. Behavioral Risk Factor Surveillance System. We used a difference-in-difference (DD) model to assess the impact of Canadian policy introduction on smoking prevalence, and a difference-in-difference-in-difference (DDD) model to examine differences in the policy impact by sex and education, comparing Canada (the treatment group) with the United States (the control group).

Results

From 1999 to 2004, smoking prevalence decreased from 23.7% to 18.6% in Canada, and from 21.7% to 20.0% in the United States. Results from the DD regression models showed that Canadian respondents reported lower odds of being a current smoker compared to the U.S. respondents following the 2000 introduction of GWLs (OR = 0.84, 95% CI = 0.74–0.94). The DDD model showed that the impact of the Canadian GWLs versus the United States did not differ by sex or education.

Conclusions

The 2000 Canadian GWL policy reduced smoking prevalence overall, with similar reductions for males and females and across education levels. The impact of the Canadian GWLs in reducing smoking prevalence did not reduce differences by sex or education. Although beneficial for all smokers, GWLs may not serve to decrease existing disparities, especially those by socioeconomic status.

Implications

Existing evidence shows that GWL implementation is associated with reductions in smoking prevalence. But there is limited evidence from past evaluation studies on whether the impact of GWLs on smoking prevalence differs by sociodemographic subgroup. Our findings confirm existing studies that the 2000 implementation of GWLs in Canada was significantly associated with an overall reduction in smoking prevalence in Canada compared to the United States. However, our study improves existing evidence by showing that the impact of the Canadian GWLs on smoking prevalence did not differ by sex or education, and thus did not reduce existing smoking disparities by educational levels.
Non-malignant silica-related diseases in a specialized outpatient clinic
Authors: Carneiro A P S , Teixeira V d S P , Silveira A M , Araújo S C B , Algranti E
Published: May 2022

Background

Uncontrolled occupational exposure to silica is still frequent in Brazil, with several recent records in the state of Minas Gerais. However, few national studies have addressed silica-related diseases other than silicosis.

Aims

To describe the occurrence of the main non-malignant silica-related diseases: silicosis, tuberculosis (TB), chronic obstructive pulmonary disease (COPD), and autoimmune diseases in a specialized outpatient clinic.

Methods

Case series study of 1525 patients exposed to silica, seen between 1984 and 2021, with descriptive findings of clinical and occupational data from the first medical evaluation.

Results

Medians of age and exposure time were 47 and 15 years, respectively, and 97% of patients were male. The prevalence of silicosis was 44%, of which 27% had large opacities. The main occupational sectors were underground gold mining (28%), precious and semi-precious stone work (20%), and artisanal mining (9%). Spirometries were abnormal in 55%, with obstructive disorder being the most common finding. COPD (25%), active TB or sequelae (12%), and connective tissue diseases (6%) were diagnosed in patients with and without silicosis.

Conclusions

The percentage of silicosis appears to be alarming, even considering the biases of selective referrals. The patients were relatively young and already had a functional impact, caused not only by silicosis but by one or more silica-related diseases. COPD, TB, and connective tissue diseases proved to be frequent, leading to the need for specifics protocols to investigate them in individuals exposed to silica. By adopting strategies to combat silicosis, the prevention of other silica-related diseases is concomitantly promoted.
Safety and Immunogenicity of an mRNA-Based Human Metapneumovirus and Parainfluenza Virus Type 3 Combined Vaccine in Healthy Adults
Authors: August Allison , Shaw Christine A , Lee Heather , Knightly Conor , Kalidindia Shiva , Chu Laurence , Essink Brandon J , Seger William , Zaks Tal , Smolenov Igor , Panther Lori
Published: May 2022

Background

Human metapneumovirus (hMPV) and parainfluenza virus type 3 (PIV3) cause respiratory tract illness in children and the elderly. No licensed vaccines are available.

Methods

In this phase 1, randomized, dose-ranging, first-in-human study, the safety, reactogenicity, and humoral immunogenicity of an investigational mRNA-based hMPV and PIV3 combination vaccine, mRNA-1653, were evaluated in healthy adults aged 18–49 years. Sentinel participants (n = 20) received 2 doses of mRNA-1653 (25, 75, 150, or 300 μg) in the dose escalation phase, and participants (n = 104) received 2 doses of mRNA-1653 (75, 150, or 300 μg) or placebo in the dose selection phase; injections were 28 days apart.

Results

The most common solicited reactogenicity events were injection site pain, headache, fatigue, and myalgia, the majority of which were grade 1 or 2. A single mRNA-1653 dose increased neutralization titers against hMPV and PIV3 1 month after vaccination compared with baseline. No notable increases in neutralizing antibody titers were observed with escalating dose levels after mRNA-1653, although no statistical inferences were made; a second mRNA-1653 dose had little observable impact on antibody titers. Neutralizing titers through 1 year remained above baseline for hMPV and returned to baseline for PIV3.

Conclusions

mRNA-1653 was well tolerated, with an acceptable safety profile and increased hMPV and PIV3 neutralization titers in healthy adults.
Coronavirus Disease 2019 Vaccine Dosage in Children, Adolescents, and Young Adults: Is Less More?
Authors: Tobin Nicole H , Yang Otto O
Published: May 2022

The lower efficacy of the COVID-19 mRNA vaccines in 5-11 year old children was unexpected. Neutralizing antibody titers elicited by the vaccines in children, adolescents, and young adults suggest that the lower efficacy is not due to the lower dosage. Confirming the efficacy of these vaccines in children, determining if mRNA vaccination strategies are less effective in younger children, as well as optimizing the dosage, dosing intervals, and number of doses needed in children, adolescents, and young adults are critical to improve vaccination strategies for these populations going forward.
Anti-citrullinated protein antibody specificities and pulmonary fibrosis in relation to genetic loci in early rheumatoid arthritis
Authors: Brink Mikael , Ljung Lotta , Hansson Monika , Rönnelid Johan , Holmdahl Rickard , Skriner Karl , Serre Guy , Klareskog Lars , Rantapää-Dahlqvist Solbritt
Published: May 2022

Objectives

Pulmonary manifestations in RA are common comorbidities, but the underlying mechanisms are largely unknown. The added value of a multiplex of ACPA and genetic risk markers was evaluated for the development of pulmonary fibrosis (PF) in an inception cohort.

Methods

A total of 1184 patients with early RA were consecutively included and followed prospectively from the index date until death or 31 December 2016. The presence of 21 ACPA fine specificities was analysed using a custom-made microarray chip (Thermo Fisher Scientific, Uppsala, Sweden). Three SNPs, previously found related to PF were evaluated, rs2609255 (FAM13A), rs111521887 (TOLLIP) and rs35705950 (MUC5B). ACPA and genetic data were available for 841 RA patients, of whom 50 developed radiologically defined PF.

Results

In unadjusted analyses, 11 ACPA specificities were associated with PF development. In multiple variable analyses, six ACPA specificities were associated with increased risk of PF: vimentin (Vim)60–75, fibrinogen (Fib)β62–78 (72), Fibα621–635, Bla26, collagen (C)II359–369 and F4-CIT-R (P < 0.01 to P < 0.05). The number of ACPA specificities was also related to PF development (P < 0.05 crude and adjusted models). In multiple variable models respectively adjusted for each of the SNPs, the number of ACPA specificities (P < 0.05 in all models), anti-Vim60–75 (P < 0.05, in all models), anti-Fibβ62–78 (72) (P < 0.001 to P < 0.05), anti-CII359–369 (P < 0.05 in all models) and anti-F4-CIT-R AQ4 (P < 0.01 to P < 0.05), anti-Fibα621–635 (P < 0.05 in one) and anti-Bla26 (P < 0.05 in two) were significantly associated with PF development.

Conclusion

The development of PF in an inception cohort of RA patients was associated with both presence of certain ACPA and the number of ACPA specificities and risk genes.
Patterns of body composition and alteration after treatment in patients with newly diagnosed idiopathic inflammatory myopathies
Authors: Yang Shiyi , Luo Cheng , Zheng Wei , Li Xue , Zhang Xu , Jiang Ying , Xiao Fei
Published: May 2022

Objectives

To define the pattern of body composition and alteration after treatment of patients with newly diagnosed idiopathic inflammatory myopathies (IIMs) using DXA.

Methods

DXA was used to obtain regional and whole-body measurements of fat mass and lean tissue mass (LTM) in 50 patients with newly diagnosed IIM and matched controls. The DXA indices of fat mass and LTM were calculated. The analyses included correlations between DXA indices and clinical parameters [manual muscle test (MMT), Myositis Damage Index (MDI), Myositis Intention-to-Treat Activities Index (MITAX), handgrip, percentage forced vital capacity (%FVC) and creatine kinase level], comparison between patients with IIM and controls, comparison between IIM subgroups, receiver operating characteristic (ROC) analysis, and comparison of body composition before and after treatment.

Results

DXA LTM measurements were significantly correlated with MMT, MDI-muscle, handgrip strength, and %FVC. Patients with IIM had decreased LTM of the upper limbs and appendicular region. Male patients with IIM had significantly decreased LTM in the upper and lower limbs, whereas female patients with IIM had significantly decreased LTM in the upper limbs. Patients with IIM with anti-SRP seropositivity had lower LTM than patients with anti-SRP seronegativity. In ROC analysis, the DXA LTM indices presented good diagnostic values for distinguishing patients with newly diagnosed IIM from healthy controls. After treatment, the LTM of the upper limbs and appendicular region significantly increased.

Conclusion

DXA is an attractive method for the evaluation of patients with newly diagnosed IIM as well as a new way of monitoring disease conditions.
The Effects of Undergraduate Financing on Advanced Degree Attainment
Authors: Witteveen Dirk
Published: May 2022

This study examines the effects of undergraduate financing on subsequent advanced degree attainment in a context characterized by a shift away from traditional grant aid programs and toward widespread student loans. Using data from the National Survey of College Graduates, 2SLS Lewbel method regressions estimate the effects of having received undergraduate grant aid and having student loan debt on the chances of attaining an advanced degree during the next ten years. Results suggest a large positive influence of receiving undergraduate grant aid on advanced degree attainment (+8.5%), thus boosting higher education attainment far beyond only an undergraduate degree across college graduation cohorts between 1986 and 2007. Conversely, having loan debt upon college graduation affected the chances of advanced degree attainment negatively. The increased reliance on loans during undergraduate studies coincided with its long-term (or “spillover”) effect on advanced degree attainment being null in the late 1980s to a substantive deficit of more than 4 percentage—points from the 2000s onward. Counterfactual projection models suggest that loan-taking after the 1992 Higher Education Act suppressed the number of advanced degree holders in the US labor market and will continue to do so given current undergraduate financing patterns.
Hypocretin-1 measurements in cerebrospinal fluid using radioimmunoassay: within and between assay reliability and limit of quantification
Authors: van der Hoeven Adrienne Elisabeth , van Waaij Kevin , Bijlenga Denise , Roelandse Frederik Willem Cornelis , Overeem Sebastiaan , Bakker Jaap Adriaan , Fronczek Rolf , Lammers Gert Jan
Published: May 2022

Study Objectives

The most sensitive and specific investigative method for the diagnosis of narcolepsy type 1 (NT1) is the determination of hypocretin-1 (orexin-A) deficiency (≤110 pg/mL) in cerebrospinal fluid using a radioimmunoassay (RIA). We aimed to assess the reliability of the Phoenix Pharmaceuticals hypocretin-1 RIA, by determining the lower limit of quantification (LLOQ), the variability around the cutoff of 110 pg/mL, and the inter- and intra-assay variability.

Methods

Raw data of 80 consecutive hypocretin-1 RIAs were used to estimate the intra- and inter-assay coefficient of variation (CV). The LLOQ was established and defined as the lowest converted concentration with a CV <25%; the conversion is performed using a harmonization sample which is internationally used to minimize variation between RIAs.

Results

The mean intra-assay CV was 4.7%, while the unconverted inter-assay CV was 28.3% (18.5% excluding 2 outliers) and 7.5% when converted to international values. The LLOQ was determined as 27.9 pg/mL. The intra-assay CV of RIAs with lower specific radioactive activity showed a median of 5.6% (n = 41, range 1.6%–17.0%), which was significantly higher than in RIAs with higher specific activity (n = 36; median 3.2%, range 0.4%–11.6%, p = .013). The CV around the 110 pg/mL cutoff was <7%.

Conclusions

Hypocretin-1 RIAs should always be harmonized using standard reference material. The specific activity of an RIA has a significant impact on its reliability, because of the decay of 125I radioactivity. Values around the hypocretin-1 cut-off can reliably be measured. Hypocretin-1 concentrations below 28 pg/mL should be reported as “undetectable” when measured with the Phoenix Pharmaceuticals RIA.

Clinical Trial Information

This study is not registered in a clinical trial register, as it has a retrospective database design
Texas panhandle beef production tour, a high-impact compressed course in animal science
Authors: Bowhay Ciana M , Wickersham Tryon A , Richardson Ra’Sheedah , Dunlap Kathrin A
Published: May 2022

Many animal science students have little exposure to working livestock production systems prior to college. As such, they can lack insight into day-to-day challenges and rationale behind decision making in these systems, opening the door for the adoption of misconceptions frequently promoted in the popular press. In addition, students identify a lack of first-hand knowledge and experience in the industry as a challenge to their educational success. Field trips stimulate interest and motivation, provide context for learning, and influence long-term career goals, but are underutilized in higher education. The potential impact of such experiences prompted the creation of the Texas Panhandle Beef Production Tour, a 2-credit hour compressed course. Students on this tour visited beef production sites in the Texas Panhandle ranging from cow-calf operations, to feedlots and packing plants. To cement learning through reflection, students responded to a series of questions before, during, and after visiting these sites to probe preconceptions, observations, and outcomes of the experience. We performed a retroactive qualitative evaluation of these reflections (n = 22) to determine cogent themes. Emergent themes included surprise at the intensive systems of data collection and management and the level of technology used at each site. Cattle were calmer and more comfortable than expected at the feedlots and packing plants. Students expressed new appreciation and understanding of course material and a desire to share their insights with others after completing the tour. Finally, participants gained a broader view of industry opportunities and returned with renewed motivation to pursue additional hands-on opportunities. Participation in this course provided valuable insight into the livestock production industry and motivated students to explore new career options and address their own preconceptions of the industry through independent inquiry. The creation of similar courses may be useful to address misconceptions, create personal connections with course material, and broaden career interests in animal science students.
Induction of polyploid Malus prunifolia and analysis of its salt tolerance
Authors: Jin Yibo , Zhao Yongjuan , Ai Shukang , Chen Xiujiao , Liu Xiaomin , Wang Hongying , Han Yunqi , Ma Fengwang , Li Chao
Published: May 2022

The apple rootstock Malus prunifolia (Willd.) Borkh. is widely used for apple production. Because polyploid plants are often more tolerant to abiotic stress than diploids, we wondered whether polyploidy induction in M. prunifolia might improve its stress tolerance, particularly to high salinity. We used a combination of colchicine and dimethyl sulfoxide (DMSO) to induce chromosome doubling in M. prunifolia and identified the resulting polyploids by stomatal observations and flow cytometry. We found the best way to induce polyploidy in M. prunifolia was to use 2% DMSO and 0.05% colchicine for 2 days for leaves or 0.02% colchicine for stem segments. The results of hydroponic salt treatment showed that polyploid plants were more salt tolerant and had greater photosynthetic efficiency, thicker leaf epidermis and palisade tissues, and shorter but denser root systems than diploids. During salt stress, the polyploid leaves and roots accumulated less Na+, showed upregulated expression of three salt overly sensitive (SOS) pathway genes, and produced fewer reactive oxygen species. The polyploid plants also had considerably higher ABA and jasmonic acid levels than diploid plants under salt stress. Under normal growth conditions, gibberellins (GAs) levels were much lower in polyploid leaves than in diploid leaves; however, after salt treatment, polyploid leaves showed upregulation of essential GAs synthesis genes. In summary, we developed a system for the induction of polyploidy in M. prunifolia and response to salt stress of the resulting polyploids, as reflected in leaf and root morphology, changes in Na+ accumulation, antioxidant capacity and plant hormone levels.
Expert Consensus Regarding Core Outcomes for Enhanced Recovery after Cesarean Delivery Studies: A Delphi Study
Authors: Sultan Pervez , George Ron , Weiniger Carolyn F. , El-Boghdadly K. , Pandal Perman , Carvalho Brendan ,   CRADLE Study Investigators
Published: May 2022

Background

Heterogeneity among reported outcomes from enhanced recovery after cesarean delivery impact studies is high. This study aimed to develop a standardized enhanced recovery core outcome set for use in future enhanced recovery after cesarean delivery studies.

Methods

An international consensus study involving physicians, patients, and a director of midwifery and nursing services was conducted using a three-round modified Delphi approach (two rounds of electronic questionnaires and a third-round e-discussion) to produce the core outcome set. An initial list of outcomes was based on a previously published systematic review. Consensus was obtained for the final core outcome set, including definitions for key terms and preferred units of measurement. Strong consensus was defined as 70% or greater agreement and weak consensus as 50 to 69% agreement. Of the 64 stakeholders who were approached, 32 agreed to participate. All 32, 31, and 26 stakeholders completed Rounds 1, 2 and 3, respectively.

Results

The number of outcomes in the final core outcome set was reduced from 98 to 15. Strong consensus (70% or greater stakeholder agreement) was achieved for 15 outcomes. The core outcome set included length of hospital stay; compliance with enhanced recovery protocol; maternal morbidity (hospital re-admissions or unplanned consultations); provision of optimal analgesia (maternal satisfaction, compliance with analgesia, opioid consumption or requirement and incidence of nausea or vomiting); fasting times; breastfeeding success; and times to mobilization and urinary catheter removal. The Obstetric Quality of Recovery-10 item composite measure was also included in the final core outcome set. Areas identified as requiring further research included readiness for discharge and analysis of cost savings.

Conclusions

Results from an international consensus to develop a core outcome set for enhanced recovery after cesarean delivery are presented. These are outcomes that could be considered when designing future enhanced recovery studies.

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The Volume-Cost Relationship
Authors: Sarwahi Vishal , Tran Elaine , Vora Rushabh , Dowling Thomas J. , Galina Jesse , Fakhoury Jordan , Lo Yungtai , Amaral Terry , DiMauro Jon-Paul , Hasan Sayyida
Published: May 2022

Study Design:

Retrospective review.

Objective:

The objective of this study was to evaluate and compare distribution of hospital and operating room charges and outcomes during posterior spinal fusion for adolescent idiopathic scoliosis (AIS) patients by high-volume (HV) and standard-volume (SV) surgeons at one institution and examine potential cost savings.

Summary of Background Data:

Increased surgical volume has been associated with improved perioperative outcomes after spinal deformity correction. However, there is a lack of information on how this may affect hospital costs.

Methods:

Retrospective study of AIS patients undergoing posterior spinal fusion between 2013 and 2019. Demographic, x-ray, chart review and hospital costs were collected and compared between HV surgeons (≥50 AIS cases/y) and SV surgeons (<50/y). Comparative analyses were computed using Wilcoxon rank-sum, Kruskal-Wallis, and the Fisher exact tests. Average values with corresponding minimum–maximum rages were reported.

Results:

A total of 407 patients (HV: 232, SV: 175) operated by 4 surgeons (1 HV, 3 SV). Radiographic parameters were similar between the groups. HV surgeons had significantly lower estimated blood loss (385.3 vs. 655.6 mL, P<0.001), fewer intraoperative transfusions (10.8% vs. 25.1%, P<0.001), shorter surgery time (221.6 vs. 324.9 min, P<0.001), and lower radiation from intraoperative fluoroscopy (4.4 vs. 6.4 mGy, P<0.001). HV patients had a significantly lower length of stay (4.3 vs. 5.3, P<0.001) and complication rate (0.4% vs. 4%, P=0.04).

HV surgeons had significantly lower total costs ($61,716.24 vs. $72,745.93, P<0.001). This included lower transfusion costs (P<0.001), operative time costs (P<0.001), screw costs (P<0.001), hospital stay costs (P<0.001), and costs associated with 30-day emergency department returns (P<0.001).

Conclusion:

HV surgeons had significantly lower operative times, lower estimated blood loss and transfusion rates and lower perioperative complications requiring readmission or return to emergency department resulting in lower health care costs.

Level of Evidence:

Level III.