bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding and Application of Daptomycin-Susceptible Dose-Dependent Category for Enterococcus: A Mixed-Methods Study
Authors: Adema Jennifer L , Lake Laurel N , Stevens Ryan W , Hogan Breann M , Schuetz Audrey N , Tande Aaron J , Mara Kristin C , Eberly Allison R , Rivera Christina G
Published: January 2022

Background

In 2018, the Clinical Microbiology Laboratory at our institution adopted updated daptomycin Enterococcus–susceptible dose-dependent breakpoints. While the introduction of susceptible dose-dependent (SDD) was intended to guide practice toward optimal dosing, the understanding and application of daptomycin SDD breakpoints for enterococci were unknown.

Methods

This mixed-methods study combined a clinician survey with a retrospective pre–post prescribing analysis. An 8-question survey was distributed to infectious diseases (ID) and internal medicine (IM) clinicians. A retrospective chart review of hospitalized adults with infections due to Enterococcus spp. was conducted before (pre-SDD) and after (post-SDD) adoption of SDD reporting for enterococci.

Results

Survey response rates were 40 of 98 (41%) for IM and 22 of 34 (65%) for ID clinicians. ID clinicians scored significantly higher than IM clinicians in knowledge of SDD. Chart review of 474 patients (225 pre- vs 249 post-SDD) showed that daptomycin dosage following susceptibility testing was significantly higher post-SDD compared with pre-SDD (8.5 mg/kg vs 6.4 mg/kg; P < .001) with no difference in empiric dosing (6.3 mg/kg vs 6.2 mg/kg; P = .67). Definitive daptomycin use varied between the pre- and post-SDD periods (35.1% vs 16.9%; P < .001).

Conclusions

The survey revealed that ID clinicians placed more importance on and had more confidence in the SDD category over IM clinicians. SDD reporting was associated with a change in definitive daptomycin dosing. ID specialist involvement is recommended in the care of infections due to enterococci for which daptomycin is reported as SDD given their expertise.
Clinical Utilization of DiaSorin Molecular Polymerase Chain Reaction in Pneumocystis Pneumonia
Authors: Damhorst Gregory L , Broder Kari J , Overton Elizabeth C , Rara Ronelio , Busch Lindsay M , Burd Eileen M , Webster Andrew S , Kraft Colleen S , Babiker Ahmed
Published: January 2022

Background

Pneumocystis jirovecii polymerase chain reaction (PCR) testing is a sensitive diagnostic tool but does not distinguish infection from colonization. Cycle threshold (CT) may correlate with fungal burden and could be considered in clinical decision making. Clinical use of PCR and significance of CT values have not previously been examined with the DiaSorin Molecular platform.

Methods

Retrospective review of P jirovecii PCR, CT values and clinical data from 18 months in a multihospital academic health system. The diagnostic performance of PCR with respect to pathology and correlation of CT with severity were examined.

Results

Ninety-nine of 1006 (9.8%) assays from 786 patients in 919 encounters were positive. Among 91 (9.9%) encounters in which P jirovecii pneumonia (PJP) was treated, 41 (45%) were influenced by positive PCR. Negative PCR influenced discontinuation of therapy in 35 cases. Sensitivity and specificity of PCR were 93% (95% CI, 68%–100%) and 94% (95% CI, 91%–96%) with respect to pathology. CT values from deep respiratory specimens were significantly different among treated patients (P = .04) and those with positive pathology results (P < .0001) compared to patients not treated and those with negative pathology, respectively, and was highly predictive of positive pathology results (area under the curve = 0.92). No significant difference was observed in comparisons based on indicators of disease severity.

Conclusions

Pneumocystis jirovecii PCR was a highly impactful tool in the diagnosis and management of PJP, and use of CT values may have value in the treatment decision process in select cases. Further investigation in a prospective manner is needed.
Binary Toxin Expression by Clostridioides difficile Is Associated With Worse Disease
Authors: Young Mary K , Leslie Jhansi L , Madden Gregory R , Lyerly David M , Carman Robert J , Lyerly Matthew W , Stewart David B , Abhyankar Mayuresh M , Petri William A
Published: January 2022

Background

The incidence of Clostridioides difficile infection (CDI) has increased over the past 2 decades and is considered an urgent threat by the Centers for Disease Control and Prevention. Hypervirulent strains such as ribotype 027, which possess genes for the additional toxin C. difficile binary toxin (CDT), are contributing to increased morbidity and mortality.

Methods

We retrospectively tested stool from 215 CDI patients for CDT by enzyme-linked immunosorbent assay (ELISA). Stratifying patients by CDT status, we assessed if disease severity and clinical outcomes correlated with CDT positivity. Additionally, we completed quantitative PCR (PCR) DNA extracted from patient stool to detect cdtB gene. Lastly, we performed 16 S rRNA gene sequencing to examine if CDT-positive samples had an altered fecal microbiota.

Results

We found that patients with CdtB, the pore-forming component of CDT, detected in their stool by ELISA, were more likely to have severe disease with higher 90-day mortality. CDT-positive patients also had higher C. difficile bacterial burden and white blood cell counts. There was no significant difference in gut microbiome diversity between CDT-positive and -negative patients.

Conclusions

Patients with fecal samples that were positive for CDT had increased disease severity and worse clinical outcomes. Utilization of PCR and testing for C. difficile toxins A and B may not reveal the entire picture when diagnosing CDI; detection of CDT-expressing strains is valuable in identifying patients at risk of more severe disease.
Metabolic-Associated Fatty Liver Disease Is Highly Prevalent in the Postacute COVID Syndrome
Authors: Milic Jovana , Barbieri Sara , Gozzi Licia , Brigo Alberto , Beghé Bianca , Verduri Alessia , Bacca Erica , Iadisernia Vittorio , Cuomo Gianluca , Dolci Giovanni , Yaacoub Dina , Aprile Emanuele , Belli Michela , Venuta Maria , Meschiari Marianna , Sebastiani Giada , Clini Enrico , Mussini Cristina , Lonardo Amedeo , Guaraldi Giovanni , Raggi Paolo
Published: January 2022

Background

A proposal has recently been advanced to change the traditional definition of nonalcoholic fatty liver disease to metabolic-associated fatty liver disease (MAFLD), to reflect the cluster of metabolic abnormalities that may be more closely associated with cardiovascular risk. Long coronavirus disease 2019 (COVID-19) is a smoldering inflammatory condition, characterized by several symptom clusters. This study aims to determine the prevalence of MAFLD in patients with postacute COVID syndrome (PACS) and its association with other PACS-cluster phenotypes.

Methods

We included 235 patients observed at a single university outpatient clinic. The diagnosis of PACS was based on ≥1 cluster of symptoms: respiratory, neurocognitive, musculoskeletal, psychological, sensory, and dermatological. The outcome was prevalence of MAFLD detected by transient elastography during the first postdischarge follow-up outpatient visit. The prevalence of MAFLD at the time of hospital admission was calculated retrospectively using the hepatic steatosis index.

Results

Of 235 patients, 162 (69%) were men (median age 61). The prevalence of MAFLD was 55.3% at follow-up and 37.3% on admission (P < .001). Insulin resistance (odds ratio [OR] = 1.5; 95% confidence interval [CI], 1.14–1.96), body mass index (OR = 1.14; 95% CI, 1.04–1.24), and the metabolic syndrome (OR = 2.54; 95% CI, 1.13–5.68) were independent predictors of MAFLD. The number of PACS clusters was inversely associated with MAFLD (OR = 0.86; 95% CI, .76–0.97). Thirty-one patients (13.2%) had MAFLD with no other associated PACS clusters. All correlations between MAFLD and other PACS clusters were weak.

Conclusions

Metabolic-associated fatty liver disease was highly prevalent after hospital discharge and may represent a specific PACS-cluster phenotype, with potential long-term metabolic and cardiovascular health implications.
High Burden of Cryptococcal Meningitis Among Antiretroviral Therapy–Experienced Human Immunodeficiency Virus–Infected Patients in Northern Uganda in the Era of “Test and Treat”: Implications for Cryptococcal Screening Programs
Authors: Okwir Mark , Link Abigail , Rhein Joshua , Obbo John Stephen , Okello James , Nabongo Betty , Alal Jimmy , Meya David , Bohjanen Paul R
Published: January 2022

Background

The impact of the “test and treat” program for human immunodeficiency virus (HIV) treatment in rural areas of Uganda on cryptococcal antigen (CrAg) screening or cryptococcal meningitis (CM) is poorly understood.

Methods

We retrospectively evaluated clinical factors in 212 HIV-infected patients diagnosed with CM from February of 2017 to November of 2019 at Lira Regional Referral Hospital in northern Uganda.

Results

Among 212 patients diagnosed with CM, 58.5% were male. Median age was 35 years; CD4 count and HIV viral load (VL) were 86 cells/μL and 9463 copies/mL, respectively. Only 10% of patients had a previous history of CM. We found that 190 of 209 (90.9%) patients were ART experienced and 19 (9.1%) were ART naive. Overall, 90 of 212 (42.5%) patients died while hospitalized (median time to death, 14 days). Increased risk of death was associated with altered mental status (hazard ratio [HR], 6.6 [95% confidence interval {CI}, 2.411–18.219]; P ≤ .0001) and seizures (HR, 5.23 [95% CI, 1.245–21.991]; P = .024).

Conclusions

Current guidelines recommend CrAg screening based on low CD4 counts for ART-naive patients and VL or clinical failure for ART-experienced patients. Using current guidelines for CrAg screening, some ART-experienced patients miss CrAg screening in resource-limited settings, when CD4 or VL tests are unavailable. We found that the majority of HIV-infected patients with CM were ART experienced (90.9%) at presentation. The high burden of CM in ART-experienced patients supports a need for improved CrAg screening of ART-exposed patients.
Lack of Clinical Utility of Labeled White Blood Cell Scintigraphy in Patients With Fever of Unknown Origin
Authors: Fisher Ronald E , Drews Ashley L , Palmer Edwin L
Published: January 2022

Background

Labeled white blood cell scintigraphy (WBCS) has been used for over 40 years to localize an infection source in patients with fever of unknown origin (FUO). It continues to be in widespread use for such patients in modern times, despite the tremendous advances in modern radiological imaging and laboratory medicine.

Methods

We critically evaluated the clinical contribution of WBCS performed in 132 patients with FUO at 7 hospitals from mid-2015 to the end of 2019. For each patient, all radiographic and laboratory results and all electronic clinical notes were carefully evaluated as many days before and after the scan as necessary to arrive at a final diagnosis.

Results

Although 50 WBCS (38%) showed positive findings, the majority of these were false positive (FP). Of the 19 true-positive (TP) scans, most were already known or about to become known by tests already ordered at the time of the scan. Only 2 TP scans (1.5%) contributed to the final diagnosis, and these did so only indirectly. FP scans led to 7 unnecessary procedures.

Conclusions

In FUO patients for whom an infection source is not discovered following an appropriate radiographic and laboratory workup, WBCS is not a useful procedure.
Implementing the EU Climate Law via the ‘Fit for 55’ package
Authors: Schlacke Sabine , Wentzien Helen , Thierjung Eva-Maria , Köster Miriam
Published: January 2022

To implement the European Union (EU) Climate Law’s newly established 55% greenhouse gas reduction objective for 2030, the EU Commission suggests a wave of reforms to the European energy and climate legislation. The contribution aims to describe the EU Commission’s 16 initial legislative and strategic proposals regarding the major pillars of the European energy and climate legislation and intends to give an overview on the suggested reforms. By comparing the legal status quo with the legal framework de lege ferenda as presented by the Commission’s proposals, the planned major changes to the legal structures are identified. To achieve the 55% greenhouse gas reduction objective for 2030, all existing legal climate and energy acts are planned to be tightened by amending their targets as well as scopes and revising their structures. The suggested reforms concern the existing EU emissions trading system, effort sharing system between the Member States, energy taxation, energy efficiency and renewable energies. Additionally, the implementation of new instruments, such as the second EU emissions trading system for the sectors buildings and transport, the Carbon Border Adjustment Mechanism and the Social Climate Fund, is proposed. The design of the package shows that the Commission still generally pursues a climate legislation characterized by a mix of instruments and policies being both price based and regulatory. So, even though the major proposed change—the introduction of a second separate emissions trading system—would strengthen the role of carbon pricing, the Commission still relies on a mix of instruments without defining a leading instrument.
Testing the non-circularity of the spacetime around Sagittarius A* with orbiting pulsars
Authors: Takamori Yohsuke , Naruko Atsushi , Sakurai Yusuke , Takahashi Keitaro , Yamauchi Daisuke , Yoo Chul-Moon
Published: January 2022

A disformal Kerr black hole solution is a rotating black hole solution in a modified gravity theory which breaks the circular condition of spacetime differently from the case of the Kerr spacetime. In this paper, assuming that Sagittarius A* (Sgr A*) is a disformal Kerr black hole, we examine the potential to test the spacetime geometry with a hypothetical pulsar whose orbital elements are similar to those of the S2/S0-2 star. By numerically solving the equations of motion for the pulsar and photons emitted from it, we calculate the apparent position of the pulsar and the time of arrival (TOA) of the emitted pulse signals. Our analysis shows that the magnitude of the difference in the TOAs reaches the order of 10 ms if the deviation from the Kerr spacetime is significant. The time difference is mainly caused by the non-circularity of the spacetime at the 1.5 post-Newtonian order. The accuracy of the TOA measurement by a future radio telescope named the Square Kilometer Array (SKA) is between about 0.1 ms and 10 ms for a normal pulsar. Thus, we expect that the SKA can distinguish a disformal Kerr black hole from a Kerr black hole through the non-circularity of the spacetime around Sgr A*.
Phytoplankton prey of an abundant estuarine copepod identifiedin situusing DNA metabarcoding
Authors: Holmes Ann E , Kimmerer Wim J
Published: January 2022

Plankton trophic interactions play a crucial role in ecosystem processes. Diet analysis using high-throughput sequencing methods such as metabarcoding can provide new insight where traditional methods have been limited. We used 16S ribosomal RNA gene metabarcoding to identify phytoplankton from the guts of the copepod Pseudodiaptomus forbesi and in seston from the Cache Slough Complex, a tidal freshwater reach of the San Francisco Estuary, California, USA. Cyanobacteria, assumed to have low nutritional value for copepods, were detected in all copepod samples and comprised the highest relative read abundance in metabarcoding results. Differential abundance analysis, used to compare representation of operational taxonomic units between copepod and seston samples, showed that two filamentous taxa (a streptophyte and a cyanobacterium) were most overrepresented in copepod samples, whereas cryptophytes and most ochropytes (diatoms and related taxa) were underrepresented in copepod samples. These findings could reflect unexpected feeding patterns or trophic upgrading. Understanding the capabilities and limitations of DNA metabarcoding is key to its use in diet analysis and integration with traditional approaches.
Twelve-Month Cognitive Trajectories in Individuals at Ultra-High Risk for Psychosis: A Latent Class Analysis
Authors: Allott Kelly , Schmidt Stefanie J , Yuen Hok Pan , Wood Stephen J , Nelson Barnaby , Markulev Connie , Lavoie Suzie , Brewer Warrick J , Schäfer Miriam R , Mossaheb Nilufar , Schlögelhofer Monika , Smesny Stefan , Hickie Ian B , Berger Gregor Emanuel , Chen Eric Y H , de Haan Lieuwe , Nieman Dorien H , Nordentoft Merete , Riecher-Rössler Anita , Verma Swapna , Thompson Andrew , Yung Alison R , Amminger Paul , McGorry Patrick D , Hartmann Jessica
Published: January 2022

Understanding longitudinal cognitive performance in individuals at ultra-high risk for psychosis (UHR) is important for informing theoretical models and treatment. A vital step in this endeavor is to determine whether there are UHR subgroups that have similar patterns of cognitive change over time. The aims were to: i) identify latent class trajectories of cognitive performance over 12-months in UHR individuals, ii) identify baseline demographic and clinical predictors of the resulting classes, and iii) determine whether trajectory classes were associated with transition to psychosis or functional outcomes. Cognition was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS) at baseline, 6- and 12-months (N = 288). Using Growth Mixture Modeling, a single unimpaired improving trajectory class was observed for motor function, speed of processing, verbal fluency, and BACS composite. A two-class solution was observed for executive function and working memory, showing one unimpaired and a second impaired class. A three-class solution was found for verbal learning and memory: unimpaired, mildly impaired, and initially extremely impaired, but improved (“caught up”) to the level of the mildly impaired. IQ, omega-3 index, and premorbid adjustment were associated with class membership, whereas clinical variables (symptoms, substance use), including transition to psychosis, were not. Working memory and verbal learning and memory trajectory class membership was associated with functioning outcomes. These findings suggest there is no short-term progressive cognitive decline in help-seeking UHR individuals, including those who transition to psychosis. Screening of cognitive performance may be useful for identifying UHR individuals who may benefit from targeted cognitive interventions.
A Japanese Subjective Well-Being Indicator Based on Twitter Data
Authors: CARPI Tiziana , HINO Airo , IACUS Stefano Maria , PORRO Giuseppe
Published: January 2022

This study presents for the first time the SWB-J index, a subjective well-being indicator for Japan based on Twitter data. The index is composed by eight dimensions of subjective well-being and is estimated relying on Twitter data by using human supervised sentiment analysis. The index is then compared with the analogous SWB-I index for Italy in order to verify possible analogies and cultural differences. Further, through structural equation models, we investigate the relationship between economic and health conditions of the country and the well-being latent variable and illustrate how this latent dimension affects the SWB-J and SWB-I indicators. It turns out that, as expected, economic and health welfare is only one aspect of the multidimensional well-being that is captured by the Twitter-based indicator.
Phylogenomics of Bony-Tongue Fishes (Osteoglossomorpha) Shed Light on the Craniofacial Evolution and Biogeography of the Weakly Electric Clade (Mormyridae)
Authors: Peterson Rose D , Sullivan John P , Hopkins Carl D , Santaquiteria Aintzane , Dillman Casey B , Pirro Stacy , Betancur-R Ricardo , Arcila Dahiana , Hughes Lily C , Ortí Guillermo
Published: January 2022

Bonytongues (Osteoglossomorpha) constitute an ancient clade of teleost fishes distributed in freshwater habitats throughout the world. The group includes well-known species such as arowanas, featherbacks, pirarucus, and the weakly electric fishes in the family Mormyridae. Their disjunct distribution, extreme morphologies, and electrolocating capabilities (Gymnarchidae and Mormyridae) have attracted much scientific interest, but a comprehensive phylogenetic framework for comparative analysis is missing, especially for the species-rich family Mormyridae. Of particular interest are disparate craniofacial morphologies among mormyrids which might constitute an exceptional model system to study convergent evolution. We present a phylogenomic analysis based on 546 exons of 179 species (out of 260), 28 out of 29 genera, and all six families of extant bonytongues. Based on a recent reassessment of the fossil record of osteoglossomorphs, we inferred dates of divergence among transcontinental clades and the major groups. The estimated ages of divergence among extant taxa (e.g., Osteoglossomorpha, Osteoglossiformes, and Mormyroidea) are older than previous reports, but most of the divergence dates obtained for clades on separate continents are too young to be explained by simple vicariance hypotheses. Biogeographic analysis of mormyrids indicates that their high species diversity in the Congo Basin is a consequence of range reductions of previously widespread ancestors and that the highest diversity of craniofacial morphologies among mormyrids originated in this basin. Special emphasis on a taxon-rich representation for mormyrids revealed pervasive misalignment between our phylogenomic results and mormyrid taxonomy due to repeated instances of convergence for extreme craniofacial morphologies. Estimation of ancestral phenotypes revealed contingent evolution of snout elongation and unique projections from the lower jaw to form the distinctive Schnauzenorgan. Synthesis of comparative analyses suggests that the remarkable craniofacial morphologies of mormyrids evolved convergently due to niche partitioning, likely enabled by interactions between their exclusive morphological and electrosensory adaptations. [Africa; ancestral state estimation; diversity; exon capture; freshwater fishes; Phylogenomics.]
Measuring Graduate Medical Education Outcomes to Honor the Social Contract
Authors: Phillips Robert L. , George Brian C. , Holmboe Eric S. , Bazemore Andrew W. , Westfall John M. , Bitton Asaf
Published: January 2022

The graduate medical education (GME) system is heavily subsidized by the public in return for producing physicians who meet society’s needs. Under the terms of this implicit social contract, decisions about how this funding is allocated are deferred to the individual training sites. Institutions receiving public funding face potential conflicts of interest, which have at times prioritized institutional purposes and needs over societal needs, highlighting that there is little public accountability for how such funding is used. The cost and institutional burden of assessing many fundamental GME outcomes, such as specialty, geographic physician distribution, training-imprinted cost behaviors, and populations served, could be mitigated as data sources and methods for assessing GME outcomes and guiding training improvement already exist. This new capacity to assess system-level outcomes could help institutions and policymakers strategically address the greatest public needs. Measurement of educational outcomes can also be used to guide training improvement at every level of the educational system (i.e., the individual trainee, individual teaching institution, and collective GME system levels). There are good examples of institutions, states, and training consortia that are already assessing and using GME outcomes in these ways. The ultimate outcome could be a GME system that better meets the needs of society and better honors what is now only an implicit social contract.
Role of blood pressure on stroke-related mortality: a 45-year follow-up study in China
Authors: Wang Shengshu , Yang Shanshan , Jia Wangping , Han Ke , Song Yang , Zeng Jing , Cao Wenzhe , Liu Shaohua , Chen Shimin , Li Zhiqiang , Li Xuehang , Tai Penggang , Kou Fuyin , He Yao , Liu Miao
Published: January 2022

Background:

Hypertension is associated with stroke-related mortality. However, the long-term association of blood pressure (BP) and the risk of stroke-related mortality and the influence path of BP on stroke-related death remain unknown. The current study aimed to estimate the long-term causal associations between BP and stroke-related mortality and the potential mediating and moderated mediating model of the associations.

Methods:

This is a 45-year follow-up cohort study and a total of 1696 subjects were enrolled in 1976 and 1081 participants died by the latest follow-up in 2020. COX proportional hazard model was used to explore the associations of stroke-related death with baseline systolic blood pressure (SBP)/diastolic blood pressure (DBP) categories and BP changes from 1976 to 1994. The mediating and moderated mediating effects were performed to detect the possible influencing path from BP to stroke-related deaths. E value was calculated in the sensitivity analysis.

Results:

Among 1696 participants, the average age was 44.38 ± 6.10 years, and 1124 were men (66.3%). After a 45-year follow-up, a total of 201 (11.9%) stroke-related deaths occurred. After the adjustment, the COX proportional hazard model showed that among the participants with SBP ≥ 160 mmHg or DBP ≥ 100 mmHg in 1976, the risk of stroke-related death increased by 217.5% (hazard ratio [HR] = 3.175, 95% confidence interval [CI]: 2.297–4.388), and the adjusted HRs were higher in male participants. Among the participants with hypertension in 1976 and 1994, the risk of stroke-related death increased by 110.4% (HR = 2.104, 95% CI: 1.632–2.713), and the adjusted HRs of the BP changes were higher in male participants. Body mass index (BMI) significantly mediated the association of SBP and stroke-related deaths and this mediating effect was moderated by gender.

Conclusions:

In a 45-year follow-up, high BP and persistent hypertension are associated with stroke-related death, and these associations were even more pronounced in male participants. The paths of association are mediated by BMI and moderated by gender.
Antecedents of geographical expansion: The case of federally qualified health centers
Authors: Choi Seongwon , Weech-Maldonado Robert , Powers Thomas L. , Hearld Larry R.
Published: January 2022

Background

Federally qualified health centers (FQHCs) are pivotal safety net primary care providers for the medically underserved. FQHCs have complex organizational designs, with many FQHCs providing care at multiple physical locations (“sites”). The number of sites, however, varies considerably between FQHCs, which can have important implications for differential access that may perpetuate disparities in quality of care.

Purpose

The objective of this study is to explore the organizational and environmental antecedents of the number of sites operated by each FQHC. The findings of this study contribute to a better understanding of FQHCs’ expansion that has vital implications for cost and access outcomes.

Methodology/Approach

The study is based on data between the years 2012 and 2018. Using multivariate growth curve modeling, we analyzed the final sample, consisting of 5,482 FQHC-years.

Results

The level of competition, measured as the number of FQHC sites in the Primary Care Service Area (PCSA) and the number of primary care physicians per 1,000 PCSA residents, was positively associated with the number of FQHC sites. The number of patients, the level of federal grant, and the year were also positively associated with the number of FQHC sites, whereas percentage of Medicaid patients; workforce supply, measured as primary care physician assistants per 1,000 PCSA residents; Medicaid expansion; and state/local funding available for FQHCs were not.

Conclusion

Findings of this study indicate that competition, especially between peer FQHCs, is significantly associated with FQHC expansion.

Practice Implications

This result suggests that FQHC managers and policymakers may closely monitor cost, access, and quality implications of competition and FQHC expansion.
ACUTE EXUDATIVE MACULOPATHY AND BACILLARY LAYER DETACHMENT IN PATIENTS WITH CENTRAL SEROUS CHORIORETINOPATHY AFTER PHOTODYNAMIC THERAPY
Authors: Fernández-Vigo José Ignacio , Moreno-Morillo Francisco Javier , Valverde-Megías Alicia , Burgos-Blasco Bárbara , López-Guajardo Lorenzo , Donate-López Juan
Published: January 2022

Purpose:

To describe the incidence and characteristics of photodynamic therapy–induced acute exudative maculopathy (PAEM) and bacillary layer detachment in patients with chronic central serous chorioretinopathy.

Methods:

This was a prospective observational case series including 92 eyes of 75 patients who underwent photodynamic therapy. Best-corrected visual acuity, optical coherence tomography, and optical coherence tomography angiography were performed before, 3 days, 1 month, and 3 months after half-fluence photodynamic therapy. Two groups were established depending on the presence or absence (N = 28 and N = 64, respectively) of PAEM. Choriocapillaris flow voids increase, subfoveal choroidal thickness, and the presence of choroidal neovascularization were collected.

Results:

The incidence of PAEM was 28/92 (30.4%). There was no difference in the age, sex, baseline subretinal fluid, subfoveal choroidal thickness, or the presence of choroidal neovascularization between groups (P ≥ 0.094). No differences emerged in the subretinal fluid at 1 and 3 months after photodynamic therapy between groups (P ≥ 0.524), nor in the mean best-corrected visual acuity gain at 3 months (4.1 ± 7.6 vs. 3.6 ± 6.4 letters; P = 0.773). A bacillary layer detachment was observed in 13 patients with PAEM (46.4%).

Conclusion:

Photodynamic therapy–induced acute exudative maculopathy is frequent in patients with chronic central serous chorioretinopathy but has a favorable prognosis. There was no association between PAEM and age, sex, subfoveal choroidal thickness, or choroidal neovascularization; however, it was related to choriocapillaris flow voids increase.
Comparative Efficacy and Tolerability of Antipsychotics for Juvenile Psychotic Disorders
Authors: Yee Caitlin S. , Bahji Anees , Lolich Maria , Vázquez Gustavo H. , Baldessarini Ross J.
Published: January 2022

Background

Psychotic disorders produce important morbidity and disability in children and adolescents. There have been few relevant treatment trials, encouraging assessment of research aimed at testing efficacy and safety of antipsychotics for juveniles. We aimed to compare the short- and long-term efficacy and safety of antipsychotics to treat psychotic disorders among children and adolescents.

Methods

Four major bibliographic databases (PubMed, MEDLINE, PsycINFO, and EMBASE) were searched for clinical trials of antipsychotics in children or adolescents, from database inception to May 2021. We searched for clinical trials comparing antipsychotics with control conditions for juvenile psychosis based on blinded review by 2 independent investigators (C.S.Y. and M.L.). We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses and applied the Cochrane risk-of-bias tool to appraise study quality. One reviewer (A.B.) performed data abstraction which was confirmed by 2 independent, blinded reviewers (C.S.Y. and M.L.). Primary outcomes were scores rating psychosis symptoms and dichotomized retention in treatment protocols versus dropouts because of adverse events. Effect sizes were pooled using frequentist random-effects network meta-analysis modeling to generate summary rate ratios (RRs) and Cohen d standardized mean differences.

Results

Systematic searching generated 1330 unique records. Of these, short-term (n = 15, for 6 [3–12] weeks) and long-term (n = 10, for 12 [6–60] months) treatment trials involved 2208 (39.2% females; median age, 15.3 years), and 1366 subjects (35.0% females; median age, 15.6 years), respectively. Short-term reduction of psychosis scores ranked clozapine (d = −1.35; 95% confidence interval [CI], −1.97 to −0.73]), molindone (−1.22; 95% CI, −1.68 to −0.75), olanzapine (−1.12; 95% CI, −1.44 to –0.81), and risperidone (−0.93; 95% CI, −1.22 to −0.63) as the most effective agents. In longer-term treatment, only lurasidone was effective. Clozapine (RR, 12.8) and haloperidol (RR, 5.15) led to more all-cause and adverse event-related dropouts. There were few trials/drug (1 each for aripiprazole, asenapine, lurasidone, molindone, paliperidone, and ziprasidone, short term; aripiprazole, clozapine, haloperidol, lurasidone, and molindone, long-term). Heterogeneity and inconsistency were high, especially in long-term trials, without evidence of publication bias.

Conclusions

Some antipsychotics were effective and tolerated short term, but longer-term evidence was very limited. The overall paucity of trials and of adequate controls indicates that more well-designed randomized controlled trials are required for adequate assessment of antipsychotic drug treatment for juveniles.

Systematic Review Registration

PROSPERO CRD42021232937.
A Retrospective Evaluation of the Effectiveness of Cranial Remolding Orthoses for the Treatment of Deformational Brachycephaly
Authors: Weigand Kellen , Millay Kelly , Wang Jijia , Graham Tiffany
Published: January 2022

Introduction

This retrospective chart review aims to analyze the effects of initial severity and age on cranial remolding orthosis (CRO) treatment of deformational brachycephaly. It is predicted that younger cases will show greater rates of correction and more severe cases will require longer treatment times. With the data collected, statistical analysis will aid in the development of a measurement scale for categorizing severity for brachycephaly.

Methods

Subjects were diagnosed with brachycephaly and started CRO treatment between 3 and 18 months of age. Subjects had a cranial vault asymmetry index lower than 3.5 and cranial index of 90% or higher. Subjects were excluded if they had comorbidities affecting growth, failed to complete treatment, or were noncompliant. In total, 2977 charts were retrospectively reviewed, and 253 subjects were included.

Results

Statistical analyses showed that age at treatment initiation is significantly correlated with final cranial index and treatment duration, and initiation at a younger age allows for more correction and shorter treatment durations. In addition, a receiver operating characteristic curve analysis showed a statistically significant, inverse relationship between initial severity and the likelihood of achieving correction (milder head shapes are more likely to achieve correction).

Conclusion

Together, these findings suggest that CRO treatment should be initiated as early as possible and the head shape deformation should not be allowed to progress without intervention.

Clinical Relevance

Clinical decisions and caregiver expectations during orthotic treatment should be guided by historical treatment outcomes. This study examines the influence of initial age and cephalic index severity on CRO treatment outcomes for deformational brachycephaly.
Intracochlear New Fibro-Ossification and Neuronal Degeneration Following Cochlear Implant Electrode Translocation: Long-Term Histopathological Findings in Humans
Authors: Knoll Renata M. , Trakimas Danielle R. , Wu Matthew J. , Lubner Rory J. , Nadol Joseph B. , Ishiyama Akira , Santos Felipe , Jung David H. , Remenschneider Aaron K. , Kozin Elliott D.
Published: January 2022

Objective:

We aim to assess the histopathology of human temporal bones (TBs) with evidence of cochlear implantation (CI) electrode scalar translocation.

Study Design:

Otopathology study.

Setting:

Otopathology laboratory.

Patients:

TBs from patients who had a history of CI and histopathological evidence of interscalar translocation. Specimens with electrode placed entirely within the ST served as controls.

Intervention:

Histopathological assessment of human TBs.

Main Outcome Measures:

TBs from each patient were harvested postmortem and histologically analyzed for intracochlear changes in the context of CI electrode translocation and compared to controls. Intracochlear new fibro-ossification, and spiral ganglion neuron (SGN) counts were assessed. Postoperative word recognition scores (WRS) were also compared.

Results:

Nineteen human TBs with electrode translocation and eight controls were identified. The most common site of translocation was the ascending limb of the basal turn (n = 14 TBs). The average angle of insertion at the point of translocation was 159° ± 79°. Eighteen translocated cases presented moderate fibroosseous changes in the basal region of the cochlea, extending to the translocation point and/or throughout the electrode track in 42%. Lower SGN counts were more pronounced in translocated cases compared to controls, with a significant difference for segment II (p = 0.019). Although final postoperative hearing outcomes were similar between groups, translocated cases had slower rate of improvement in WRS (p = 0.021).

Conclusions:

Cochlear implant electrode translocation was associated with greater fibroosseous formation and lower SGN population. Our findings suggest that scalar translocations may slow the rate of improvement in WRS overtime as compared to atraumatic electrode insertions.

Level of evidence: IV.
Impact of Noninvasive Respiratory Support in Patients With COVID-19 Requiring V-V ECMO
Authors: Ahmad Qamar , Green Adam , Chandel Abhimanyu , Lantry James , Desai Mehul , Simou Jikerkhoun , Osborn Erik , Singh Ramesh , Puri Nitin , Moran Patrick , Dalton Heidi , Speir Alan , King Christopher
Published: January 2022

The impact of the duration of noninvasive respiratory support (RS) including high-flow nasal cannula and noninvasive ventilation before the initiation of extracorporeal membrane oxygenation (ECMO) is unknown. We reviewed data of patients with coronavirus disease 2019 (COVID-19) treated with V-V ECMO at two high-volume tertiary care centers. Survival analysis was used to compare the effect of duration of RS on liberation from ECMO. A total of 78 patients required ECMO and the median duration of RS and invasive mechanical ventilation (IMV) before ECMO was 2 days (interquartile range [IQR]: 0, 6) and 2.5 days (IQR: 1, 5), respectively. The median duration of ECMO support was 24 days (IQR: 11, 73) and 59.0% (N = 46) remained alive at the time of censure. Patients that received RS for ≥3 days were significantly less likely to be liberated from ECMO (HR: 0.46; 95% CI: 0.26–0.83), IMV (HR: 0.42; 95% CI: 0.20–0.89) or be discharged from the hospital (HR: 0.52; 95% CI: 0.27–0.99) compared to patients that received RS for <3 days. There was no difference in hospital mortality between the groups (HR: 1.12; 95% CI: 0.56–2.26). These relationships persisted after adjustment for age, gender, and duration of IMV. Prolonged duration of RS before ECMO may result in lung injury and worse subsequent outcomes.
Construction and validation of sham insoles used in clinical trials: A systematic review
Authors: Morrow Eileen Mairi , Theologis Tim , Kothari Alpesh
Published: January 2022

Background:

Insoles are commonly prescribed to treat pathologies in a variety of patient groups; however, there is limited evidence to guide clinical decision-making. A well-validated sham insole is critical to conducting a double-blind placebo-controlled trial.

Objectives:

The aims were to establish: (1) How are sham insoles constructed? (2) What measures are undertaken to ensure adequate blinding? (3) What methods are used to validate the biomechanical effects?

Study Design:

A systematic search of the methodology of level I–II therapeutic evidence.

Methods:

Searches were conducted in MEDLINE, Embase, Cumulative Index of Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Trials. Inclusion criteria were placebo-controlled clinical trials, sham insoles used, treatment insoles alter biomechanics, treatment insoles meet the ISO definition of foot orthotics, sham and treatment insoles tested in normal walking, and article available in English.

Results:

The search generated 270 results. Twenty-four trials were included. 19% of sham insoles were described sufficiently to be replicated. The most common sham construction characteristics were full length, ethylene-vinyl acetate material, and flat insoles. 58% of studies were double-blinded; however, many did not describe any blinding methods. There is evidence that blinding the intervention details and a similar insole appearance is effective to blind participants. 13% of studies included a shoe-only condition to allow assessment of the biomechanical effects of sham insoles.

Conclusions:

There is inconsistent construction, blinding, and biomechanical validation of sham insoles. This casts a substantial doubt on the quality and reliability of the evidence base to support the prescription of insoles.
Basic and Advanced Metal-Artifact Reduction Techniques at Ultra-High Field 7-T Magnetic Resonance Imaging—Phantom Study Investigating Feasibility and Efficacy
Authors: Germann Christoph , Falkowski Anna L. , von Deuster Constantin , Nanz Daniel , Sutter Reto
Published: January 2022

Objectives

The aim of this study was to demonstrate the feasibility and efficacy of basic (increased receive bandwidth) and advanced (view-angle tilting [VAT] and slice-encoding for metal artifact correction [SEMAC]) techniques for metal-artifact reduction in ultra-high field 7-T magnetic resonance imaging (MRI).

Materials and Methods

In this experimental study, we performed 7-T MRI of titanium alloy phantom models composed of a spinal pedicle screw (phantom 1) and an intervertebral cage (phantom 2) centered in a rectangular LEGO frame, embedded in deionized-water-gadolinium (0.1 mmol/L) solution. The following turbo spin-echo sequences were acquired: (1) nonoptimized standard sequence; (2) optimized, that is, increased receive bandwidth sequence (oBW); (3) VAT; (4) combination of oBW and VAT (oBW-VAT); and (5) SEMAC. Two fellowship-trained musculoskeletal radiologists independently evaluated images regarding peri-implant signal void and geometric distortion (a, angle measurement and b, presence of circular shape loss). Statistics included Friedman test and Cochran Q test with Bonferroni correction for multiple comparisons. P values <0.05 were considered to represent statistical significance.

Results

All metal-artifact reduction techniques reduced peri-implant signal voids and diminished geometric distortions, with oBW-VAT and SEMAC being most efficient. Compared with nonoptimized sequences, oBW-VAT and SEMAC produced significantly smaller peri-implant signal voids (all P ≤ 0.008) and significantly smaller distortion angles (P ≤ 0.001). Only SEMAC could significantly reduce distortions of circular shapes in the peri-implant frame (P ≤ 0.006). Notably, increasing the number of slice-encoding steps in SEMAC sequences did not lead to a significantly better metal-artifact reduction (all P ≥ 0.257).

Conclusions

The use of basic and advanced methods for metal-artifact reduction at 7-T MRI is feasible and effective. Both a combination of increased receive bandwidth and VAT as well as SEMAC significantly reduce the peri-implant signal void and geometric distortion around metal implants.
Differentiation of Reactive Lymph Nodes and Tumor Metastatic Lymph Nodes With 68Ga-FAPI PET/CT in a Patient With Squamous Cell Lung Cancer
Authors: Shang Qihang , Zhao Long , Pang Yizhen , Meng Tinghua , Chen Haojun
Published: January 2022

False-positive findings of mediastinal lymph node often confound the image interpretation of the preoperative PET/CT in non–small cell lung cancer. In this case, we reported 18F-FDG and 68Ga-FAPI PET/CT findings in a patient with squamous cell lung cancer. 18F-FDG–based TNM stage was stage IIIA (T1bN2M0) due to increased uptake in the enlarged right lower paratracheal lymph node. However, no abnormal 68Ga-FAPI uptake was observed in this lymph node. Subsequent histopathological examination revealed no evidence of malignancy in the mediastinal lymph nodes. Therefore, the tumor stage was downstaged to stage IA (T1bN0M0), which was in accordance with 68Ga-FAPI–based TNM stage.
FDG PET/CT in a Case of Diffuse Esophageal Adenocarcinoma
Authors: Zhang Jian , Yu Zhongfei , Li Zhi , Dong Aisheng , Zhu Yuzhao
Published: January 2022

Esophageal cancer usually shows focal intense FDG uptake on FDG PET. Diffuse FDG uptake pattern of the esophageal cancer has been rarely reported. We describe FDG PET/CT findings in a case of esophageal adenocarcinoma showing diffusely intense FDG uptake mimicking esophagitis.
18F-FDG PET/CT Findings in a Woman With Kaposiform Hemangioendothelioma in the Sacrum
Authors: Xu Haiqing , Song Liejing , Duan Jun
Published: January 2022

Kaposiform hemangioendothelioma is a rare vascular tumor with borderline malignancy and is typically diagnosed in infancy or early childhood. It most commonly affects cutaneous tissues, whereas the subtype with only primary bone involvement is extremely rare. Herein, we report a case of Kaposiform hemangioendothelioma involving the sacrum in a 37-year-old woman, with intense 18F-FDG accumulation in the lytic lesion on PET/CT. This case indicates that Kaposiform hemangioendothelioma with the primary bone involvement should be taken into consideration as a rare differential diagnosis for lytic lesions with increased 18F-FDG uptake on PET/CT.
Malignant External Otitis in a Patient With Diabetes Mellitus
Authors: Noroozbeigi Nasim , Dabbagh Vahid Reza , Pakdin Parizi Zahra , Soltani Samira , Sadeghi Ramin
Published: January 2022

We reported a 66-year-old woman with malignant external otitis who was referred to our department for evaluation of disease extension. Both 99mTc-MDP bone SPECT/CT and 68Ga-citrate PET/CT were done for the patient. Both studies showed concordant areas of increased uptake in the petrous bone. In addition, 68Ga-citrate PET/CT showed soft tissue infection in the nasopharyngeal wall. Our case showed the potential of 68Ga-citrate PET/CT for evaluation of malignant external otitis.
Rare Presentation of Inflammatory Lung Disease and Subcutaneous Nodules on FDG PET/CT Scan
Authors: Doroudinia Abtin , Karam Mehrdad Bakhshayesh , Yousefi Farhad , Ghadimi Niloufar
Published: January 2022

We present a 37-year-old man with cough and progressive dyspnea for the past 3 years. According to inconclusive chest CT scan and lung biopsy histopathology findings, the patient referred for 18F-FDG PET/CT scan for further evaluation. Classic pulmonary manifestations of Langerhans cell histiocytosis were seen on CT images with intense FDG uptake on PET scan. Moreover, PET/CT revealed multiple hypermetabolic subcutaneous foci throughout his body. Finally, the patient was treated with corticosteroids. Follow-up chest CT images demonstrated improvement of lung lesions in accordance with improvement in the patient's symptoms. We are briefly discussing differential diagnoses in this patient.
Sunitinib-Induced Myositis Detected on 18F-FDG PET/CT
Authors: Suthar Ritesh R. , Purandare Nilendu , Shah Sneha , Agrawal Archi , Puranik Ameya , Rangarajan Venkatesh
Published: January 2022

Sunitinib is one of the most commonly used multikinase inhibitors for metastatic renal cell carcinoma. Myositis is one of the rarest known adverse effects of sunitinib. Presenting herewith one such case with its relevant imaging findings on FDG PET/CT and ultrasound.