bluuebunny/crossref_metadata_2025_split huggingface dataset:
Olfactory and taste dysfunctions in COVID-19
Authors: Rouadi Philip W. , Idriss Samar A. , Bousquet Jean 
Published: February 2021

Purpose of review
Olfactory dysfunction (OD) can be a single and early prominent symptom of severe acute respiratory syndrome (SARS)-COV-2 infection unlike middle east respiratory syndrome (MERS) and SARS. OD data are very informative but many are not peer-reviewed, often inconclusive and may reveal variable and sometimes contradictory results. This is often due to incongruent data of subjective and objective OD testing. Mechanistic pathways of OD and taste dysfunction (TD) are slowly unveiling, not infrequently extrapolated from historical models of SARS and MERS and are still partly unclear.

Recent findings
We reviewed the literature on OD and TD during the COVID-19 pandemic analyzing current data on pathogenesis and clinical correlates including prevalence, recovery rates, risk factors, and predictive power. Also, we evaluated various methods of subjective and objective olfactory testing and discussed challenges in management of patients with OD and rhinitis during the pandemic.

Summary
Subjective evaluation of smell disturbances during COVID-19 pandemic likely underestimates true prevalence, severity, and recovery rates of OD when compared to objective testing. OD is predictive of COVID-19 infection, more so when associated with TD. Recognizing inherent limitations of both subjective and objective OD and TD testing enables us better to manage chemosensory dysfunction in COVID-19 patients. Besides, current mechanistic data suggest neurotropism of COVID-19 for olfactory neuro-epithelium and a potential role of transient receptor potential (TRP) channels. Future studies are needed to explore further the neurogenic inflammation in COVID-19.
Hemodynamic support in septic shock
Authors: García-de-Acilu Marina , Mesquida Jaume , Gruartmoner Guillem , Ferrer Ricard 
Published: February 2021

Purpose of review
The current article reviews recent findings on the monitoring and hemodynamic support of septic shock patients.

Recent findings
The ultimate goal of hemodynamic resuscitation is to restore tissue oxygenation. A multimodal approach combining global and regional markers of tissue hypoxia seems appropriate to guide resuscitation. Several multicenter clinical trials have provided evidence against an aggressive fluid resuscitation strategy. Fluid administration should be personalized and based on the evidence of fluid responsiveness. Dynamic indices have proven to be highly predictive of responsiveness. Recent data suggest that balanced crystalloids may be associated with less renal failure. When fluid therapy is insufficient, a multimode approach with different types of vasopressors has been suggested as an initial approach. Dobutamine remains the firs inotropic option in patients with persistent hypotension and decrease ventricular systolic function. Calcium sensitizer and phosphodiesterase inhibitors may be considered, but evidence is still limited. Veno-arterial extracorporeal membrane oxygenation may be considered in selected unresponsive patients, particularly with myocardial depression, and in a highly experienced center.

Summary
Resuscitation should be personalized and based on global and regional markers of tissue hypoxia as well as the fluid responsiveness indices. The beneficial effect of multimode approach with different types of vasopressors, remains to be determined.
Healthcare Patterns of Pregnant Women and Children Affected by OUD in 9 State Medicaid Populations
Authors: Jarlenski Marian , Kim Joo Yeon , Ahrens Katherine A. , Allen Lindsay , Austin Anna , Barnes Andrew J. , Crane Dushka , Lanier Paul , Mauk Rachel , Mohamoud Shamis , Pauly Nathan , Talbert Jeffrey , Zivin Kara , Donohue Julie M. 
Published: February 2021

Objectives:
State Medicaid programs are the largest single provider of healthcare for pregnant persons with opioid use disorder (OUD). Our objective was to provide comparable, multistate measures estimating the burden of OUD in pregnancy, medication for OUD (MOUD) in pregnancy, and related neonatal and child outcomes.

Methods:
Drawing on the Medicaid Outcomes Distributed Research Network (MODRN), we accessed administrative healthcare data for 1.6 million pregnancies and 1.3 million live births in 9 state Medicaid populations from 2014 to 2017. We analyzed within- and between-state prevalences and time trends in the following outcomes: diagnosis of OUD in pregnancy, initiation, and continuity of MOUD in pregnancy, Neonatal Opioid Withdrawal Syndrome (NOWS), and well-child visit utilization among children with NOWS.

Results:
OUD diagnosis increased from 49.6 per 1000 to 54.1 per 1000 pregnancies, and the percentage of those with any MOUD in pregnancy increased from 53.4% to 57.9%, during our study time period. State-specific percentages of 180-day continuity of MOUD ranged from 41.2% to 84.5%. The rate of neonates diagnosed with NOWS increased from 32.7 to 37.0 per 1000 live births. State-specific percentages of children diagnosed with NOWS who had the recommended well-child visits in the first 15 months ranged from 39.3% to 62.5%.

Conclusions:
Medicaid data, which allow for longitudinal surveillance of care across different settings, can be used to monitor OUD and related pregnancy and child health outcomes. Findings highlight the need for public health efforts to improve care for pregnant persons and children affected by OUD.
Uptake of Hearing Aids and Hearing Assistive Technology in a Working Population: Longitudinal Analyses of The Netherlands Longitudinal Study on Hearing
Authors: van Leeuwen Lisette M. , Goderie Thadé P. M. , van Wier Marieke F. , Lissenberg-Witte Birgit I. , Lemke Ulrike , Kramer Sophia E. 
Published: February 2021

Objective:
To identify predictors of the 5-year uptake of hearing aids (HAs) and hearing assistive technology (HAT) in a sample of Dutch employees eligible for HAs and/or HAT. The potential predictors included demographic factors (age, sex, marital status, and living situation), education, hearing factors (ability to recognize speech in noise and self-reported hearing disability), distress, self-efficacy, and work-related factors (job demand, job control, and need for recovery).

Design:
Five-year follow-up data of the Netherlands Longitudinal Study on Hearing (NL-SH) collected until January 2019 were included. An online digit-triplet in noise test, the National Hearing Test (NHT), was used to assess speech-recognition-in-noise ability. In addition, online questionnaires on demographic, socioeconomic, self-reported hearing disability, health, and work-related characteristics were administered. Adults who worked over 12 hours per week, who had not yet taken up HAs or HAT, but who would be eligible for HAs/HAT based on their NHT score (insufficient or poor hearing ability), were included in the study. The 5-year uptake of HAs/HAT was defined as a dichotomous variable of self-reported HA/HAT use reported 5 years later. Generalized Estimating Equations analyses were performed to analyze the associations between potential predicting factors and the 5-year uptake of HAs/HAT, taking into account the repeated measurements of the predicting factors and the 5-year uptake of HAs/HAT.

Results:
Data of 218 participants were included. The cumulative incidence of the 5-year uptake of HAs/HAT was 15 to 33%, of which 52 employees took up HAs and 11 employees took up HAT. Married participants had increased odds for 5-year uptake of HAs/HAT compared with unmarried participants (odds ratio [OR] = 2.13, 95% confidence interval [CI] = 1.05 to 4.35). Higher self-reported hearing disability (per one unit, scale range 0 to 74) was associated with increased odds for 5-year uptake of HAs/HAT (OR = 1.05, 95% CI = 1.03 to 1.07). Job demand showed a significant interaction with sex (p = 0.002), and therefore, stratified analyses were performed. In male participants, participants with higher job demand scores (per one unit, scale range 12 to 48) had increased odds for 5-year uptake of HAs/HAT (OR = 1.18, 95% CI = 1.05 to 1.35). No difference was seen in females.

Conclusion:
This study confirms that factors predicting the uptake of HAs/HAT in the general or older populations, including marital status and self-reported hearing disability, also extend to the working population. The identification of job demand as a predictor of the uptake of HAs/HAT (in males only) was a novel finding. It demonstrates the importance of considering work-related factors in aural rehabilitation.
Problems, Complications, and Factors Predisposing to Failure of Fassier-Duval Rodding in Children With Osteogenesis Imperfecta: A Double-center Study
Authors: Musielak Bartosz Jan , Woźniak Łukasz , Sułko Jerzy , Oberc Artur , Jóźwiak Marek 
Published: February 2021

Background:
Although Fassier-Duval (FD) rods have been used for almost 2 decades, knowledge of factors predisposing to their failure is limited. Thus, the purpose of this study was to: (1) present the most common complications of FD rodding, (2) present tips on how to avoid or overcome them, and (3) identify factors predisposing to treatment failure.

Methods:
Fifty-eight rod segments in 19 patients with osteogenesis imperfecta (mainly type III) underwent analysis with a median follow-up (FU) time of 4.4 years. We assessed the total number of complications clinically and radiographically. Next, the possible predisposing factors leading to failure were assessed using the Mann-Whitney U test. In addition, we evaluated the cutoff age for the increased rate of complications using the Youden index. A P<0.05 was considered significant.

Results:
The total number of complications reached 44.8%. The most common complications included: migration of the male or female implant (45.7% and 25.7% out of the total number of complications, respectively), bone fracture with bending of the rod (8.6%), and rotational deformities (8.6%). Significant differences in patients’ ages at the time of surgery were found between the group with and without complications (P=0.04), while sex, segment treated, preceding surgeries, length of FU, FD rod diameter, and length of bisphosphonate treatment were not significant. The Youden index showed that the risk of complications rose significantly in patients treated when younger than 5.5 years of age (P<0.05).

Conclusions:
This series displays the effectiveness and utility of FD rods at a median FU of over 4 years. Complication rates were comparable with the existing literature, with a notable increase in the number of side effects observed in younger patients (below the age of 5).

Level of Evidence:
Level IV—therapeutic study.
Femoral Neck Growth and Remodeling With Free-Gliding Screw Fixation of Slipped Capital Femoral Epiphysis
Authors: Morash Kevin , Orlik Benjamin , El-Hawary Ron , Gauthier Luke , Logan Karl 
Published: February 2021

Background:
Treatment of stable slipped capital femoral epiphysis (SCFE) most commonly involves in situ fixation with a standard cannulated screw, leading to physeal arrest. Recently, Pega Medical (Laval, Canada) introduced the free-gliding (FG) SCFE screw, which employs a growth-friendly, telescopic design. This study examines femoral neck growth and remodeling over the first 2 postoperative years in stable SCFE treated with FG versus standard screws.

Methods:
We retrospectively reviewed 32 hips (19 SCFE, 13 prophylactic) in 16 patients treated with FG screws for stable SCFE. We also reviewed 102 hips (63 SCFE, 19 prophylactic, 20 controls) in 55 patients treated with standard screws. Immediate postoperative radiographs were compared with 1- and 2-year follow-up images.

Results:
For the overall study cohort, mean age at surgery was 12.2±1.9 years, with a mean slip angle of 26.9±18.0 degrees. In FG SCFE hips, the alpha angle remodeled 12.9±19.2 degrees in the first postoperative year (P=0.018) and articulotrochanteric distance decreased by 4.2±4.6 mm at 2 years (P=0.018). In standard SCFE hips, the alpha angle remodeled 4.3±11.3 degrees at 1 year (P=0.014), while articulotrochanteric distance decreased by 4.5±3.2 mm at 2 years (P<0.001). By 2 years, FG screws lengthened more in prophylactic (4.8±3.4 mm) than SCFE hips (1.7±1.8 mm, P=0.027).

Conclusions:
Greater remodeling of femoral neck cam deformity occurs when treating SCFE using an FG screw. Further research is required to measure the impact of this finding on femoroacetabular impingement and degenerative arthritis. In addition, FG screws allow ongoing growth of prophylactically treated hips, while standard screws promote coxa breva.

Level of Evidence:
Level III—retrospective comparative, therapeutic study.
Late Hip Dysplasia After Normal Ultrasound in Breech Babies: Implications on Surveillance Recommendations
Authors: Morris William Z. , Mayfield Laura , Beckwith Terri , Zepeda Erica , Jo Chan-Hee , Sucato Daniel J. 
Published: February 2021

Background:
There is significant controversy in the literature over rates of late-developing dysplasia following normal screening ultrasound in breech babies, with reported rates varying from 7% to 29%. The purpose of this study is to investigate the rates of radiographic dysplasia in breech babies after a normal ultrasound with a minimum of 1 year of radiographic follow-up.

Methods:
This study was an institutional review board–approved prospective study of all patients referred by their pediatrician for concern for developmental dysplasia of the hip between July 2008 and August 2014. We identified all subjects with breech presentation and excluded those with an abnormal initial examination/ultrasound or with <12 months of radiographic follow-up. Anterior-posterior pelvis films were obtained after >12 months and acetabular indices (AIs) were measured and compared with contemporary normative data. Dysplasia was diagnosed as >2 SDs above the mean.

Results:
A total of 654 patients were referred with a history of a breech presentation, and 150 (22.9%) were found to have clinical instability or sonographic evidence of dysplasia on initial presentation and were observed with serial imaging or treated. Of the remaining 504 subjects with a normal clinical examination and screening ultrasound, 133 (26.4%; 74.4% females, 25.6% males) were followed until at least 12 months of age. Of those presenting at age 12 to 14 months, the mean AI was 0.42±0.83 SD above the mean with a skew towards elevated AIs. At the final follow-up (mean: 20.7±6.7 mo), the mean AI was 0.05±0.92 SD above the mean, and only 3/133 (2.2%) patients had a dysplastic hip. No patients underwent treatment other than an observation during the study period.

Conclusions:
One in 5 breech babies have dysplasia at presentation, but late dysplasia following normal screening ultrasound may be less common than previously reported and may be due to our prolonged follow-up period. We recommend surveillance of breech babies with follow-up visits after 12 months of age since earlier visits may offer limited benefits.

Level of Evidence:
Level II—prospective prognostic study.
Etiologies and Outcomes Associated With Tacrolimus Levels Out of a Typical Range That Lead to High Variability in Kidney Transplant Recipients
Authors: Taber David J. , Hirsch Jason , Keys Alison , Su Zemin , McGillicuddy John W. 
Published: February 2021

Background:
High tacrolimus intrapatient variability (tac IPV) is associated with poor outcomes in kidney transplantation, including rejection, donor-specific antibodies, and graft loss. A common cause of high tac IPV is related to patient nonadherence, but this is yet to be conclusively demonstrated.

Methods:
This was a longitudinal cohort study comprising adult kidney recipients, who received transplants between 2015 and 2017, with follow-ups through February 2020. The goal of this study was to identify the most common etiologies of tac levels outside the typical range, which lead to high tac IPV, and assess the etiology-specific associations between high tac IPV and graft outcomes. Multivariate Cox regression was used to assess time-to-event analyses.

Results:
In total, 537 adult kidney recipients were included; 145 (27%) were identified as having a high tac IPV (>40%) 3–102 months post-transplant. Common etiologies of tac levels significantly outside the standard goal range (6–12 ng/mL) leading to high tac IPV included patient nonadherence (20%), infections (19%), tac-related toxicities (17%), and undocumented issues (27%). In multivariable Cox modeling, those with high tac IPV because of nonadherence had a 3.5 times higher risk of late acute rejection (P = 0.019) and 2.2 times higher risk of late graft loss (P = 0.044). No other etiologies in the typical tac level range were significantly associated with either acute rejection or graft loss.

Conclusions:
Although high tac IPV has many causes, only high tac IPV caused by nonadherence is consistently associated with poor allograft outcomes.
A Loading Micafungin Dose in Critically Ill Patients Undergoing Continuous Venovenous Hemofiltration or Continuous Venovenous Hemodiafiltration: A Population Pharmacokinetic Analysis
Authors: Garbez Nicolas , Mbatchi Litaty C. , Maseda Emilio , Luque Sonia , Grau Santiago , Wallis Steven C. , Muller Laurent , Lipman Jeffrey , Roberts Jason A. , Lefrant Jean-Yves , Roger Claire 
Published: February 2021

Background:
In this study, the authors aimed to compare the pharmacokinetics (PK) of micafungin in critically ill patients receiving continuous venovenous hemofiltration (CVVH, 30 mL·kg−1·h−1) with those of patients receiving equidoses of hemodiafiltration (CVVHDF, 15 mL·kg−1·h−1 + 15 mL·kg−1·h−1) and determine the optimal dosing regimen using the developed model.

Methods:
Patients with septic shock undergoing continuous renal replacement therapy and receiving a conventional dose of 100 mg micafungin once daily were eligible for inclusion. Total micafungin plasma concentrations from 8 CVVH sessions and 8 CVVHDF sessions were subjected to a population PK analysis using Pmetrics. Validation of the model performance was reinforced by external validation. Monte Carlo simulations were performed considering the total ratio of free drug area under the curve (AUC) over 24 hours to the minimum inhibitory concentration (MIC) (AUC0-24/MIC) in plasma.

Results:
The median total body weight (min–max) was 94.8 (66–138) kg. Micafungin concentrations were best described by a 2-compartmental PK model. No covariates, including continuous renal replacement therapy modality (CVVH or CVVHDF), were retained in the final model. The mean parameter estimates (SD) were 0.96 (0.32) L/h for clearance and 14.8 (5.3) L for the central compartment volume. External validation confirmed the performance of the developed PK model. Dosing simulations did not support the use of standard 100 mg daily dosing, except for Candida albicans on the second day of therapy. A loading dose of 150 mg followed by 100 mg daily reached the probability of target attainment for all C. albicans and C. glabrata, but not for C. krusei and C. parapsilosis.

Conclusions:
No difference was observed in micafungin PK between equidoses of CVVH and CVVHDF. A loading dose of 150 mg is required to achieve the PK/PD target for less susceptible Candida species from the first day of therapy.
Improving uptake of perinatal autopsy
Authors: Lewis Celine , Simcock Ian C. , Arthurs Owen J. 
Published: February 2021

Purpose of review
Uptake of perinatal autopsy has declined in the West over the past 30 years, largely because of reduced parental acceptance of a traditional invasive autopsy. Several studies have recently investigated the decline to identify the key factors and how they may be mitigated.

Recent findings
Three main themes were identified that have been found to improve uptake of perinatal autopsy: improved communication, in particular ensuring the consent process was conducted as a conversation with time spent talking through the procedure and allowing time for questions; health professional training to ensure staff discussing autopsy with parents have adequate understanding of the procedure and are able to convey confidence and empathy; and availability of less invasive autopsy, including noninvasive as well as minimally invasive options. These should be offered alongside standard autopsy, which some parents may still prefer.

Summary
This review highlights that the discussions that take place, and the options that are available to parents, can profoundly impact whether or not they consent to autopsy investigation. Further research should focus on the impact of offering less invasive options as well as evaluating the training and support materials that have recently been developed.
SURGICAL RETINAL EXPLANTS AS A SOURCE OF RETINAL PROGENITOR CELLS
Authors: Too Lay Khoon , Shen Weiyong , Mammo Zaid , Osaadon Perach , Gillies Mark C. , Simunovic Matthew P. 
Published: February 2021

Purpose:
To describe the novel observation of spontaneously migrating retinal cells from living donor surgical retinal explants that express progenitor cell markers in the absence of exogenous growth factors.

Methods:
Surgical retinal explants were harvested from 5 consecutive patients undergoing 23 G pars plana vitrectomy for the management of rhegmatogenous detachment. During surgery, equatorial flap tears were trimmed with the vitreous cutter and aspirated. Excised tissue was then regurgitated into a syringe containing balanced salt solution and immediately transferred to tissue culture. Migrating cells subsequently underwent immunohistochemical staining and their characteristics were compared with those of a spontaneously immortalized Müller stem cell line.

Results:
Spontaneously migrating cells were observed from samples taken from all 5 patients from Day 2 to 10 after transfer to culture. These cells were found to express embryonic cell markers, including paired box 6 (Pax6), sex-determining region Y-box 2 (Sox-2), nestin, cone-rod homeobox, and cyclin-dependent kinase inhibitor 1B (p27Kip1) as well as proteins consistent with early or retained differentiation down the Müller cell lineage, including glial fibrillary acidic protein and glutamine synthetase.

Conclusion:
After injury, the human equatorial retina is capable of spontaneously producing cells that demonstrate migration and that express progenitor cell markers. In addition, these cells express proteins consistent with Müller cell lineage. These initial observations support the assertion that the human retina may possess the potential for regeneration and that surgical retinal explants could also act as a ready source of retinal progenitor cells.