bluuebunny/crossref_metadata_2025 huggingface dataset:
Electroclinical features and phenotypic differences in adenylosuccinate lyase deficiency: Long‐term follow‐up of seven patients from four families and appraisal of the literature
Authors: Cutillo Gianni , Masnada Silvia , Lesca Gaetan , Ville Dorothée , Accorsi Patrizia , Giordano Lucio , Pichiecchio Anna , Valente Marialuisa , Borrelli Paola , Ferraro Ottavia Eleonora , Veggiotti Pierangelo
Published: October 2023

Objective

Adenylosuccinate lyase (ADSL) deficiency is a rare inherited metabolic disorder with a wide phenotypic presentation, classically grouped into three types (neonatal, type I, and type II). We aim to better delineate the pathological spectrum, focusing on the electroclinical characteristics and phenotypic differences of patients with ADSL deficiency.

Patients and Methods

Seven patients, from four different families, underwent serial electroencephalogram (EEG), clinical assessment, and neuroimaging. We also performed a systematic review of the cases published in the literature, summarizing the available clinical, neurophysiological, and genetic data.

Results

We report seven previously unreported ADSL deficiency patients with long‐term follow‐up (10–34 years). From the literature review, we collected 81 previously reported cases. Of the included patient population, 58 % (51/88) were classified as having ADSL deficiency type I, 28% (25/88) as having type II, and 14% (12/88) as having neonatal. The most frequently reported pathogenic variants are p.R426H homozygous (19 patients), p.Y114H in compound heterozygosity (13 patients), and p.D430N homozygous (6 patients). In the majority (89.2%), disease onset was within the first year of life. Epilepsy is present in 81.8% of the patients, with polymorphic and often intractable seizures. EEG features seem to display common patterns and developmental trajectories: (i) poor general background organization with theta‐delta activity; (ii) hypsarrhythmia with spasms, usually adrenocorticotropic hormone‐responsive; (iii) generalized epileptic discharges with frontal or frontal temporal predominance; and (iv) epileptic discharge activation in sleep with an altered sleep structure. Imaging features present consistent findings of cerebral atrophy with frontal predominance, cerebellar atrophy, and white matter abnormalities among the three types.

Significance

ADSL deficiency presents variable phenotypic expression, whose severity could be partially attributed to residual activity of the mutant protein. Although a precise phenotype‐genotype correlation was not yet feasible, we delineated a common pattern of clinical, neuroradiological, and neurophysiological features.
Value of ultralong‐term subcutaneous EEG monitoring for treatment decisions in temporal lobe epilepsy: A case report
Authors: Hirsch Martin , Novitskaya Yulia , Schulze‐Bonhage Andreas
Published: October 2023

Treatment decisions in epilepsy critically depend on information on the course of the disease, its severity and options for specific local interventions. We here report a patient with pharmaco‐resistant non‐lesional temporal lobe epilepsy with evidence for predominant right temporal epileptogenesis. While seizure frequency had been grossly underestimated for many years, ultralong‐term monitoring with a subcutaneous EEG device revealed actual seizure frequency (66 over 11 months vs four patient‐documented seizures), providing objective data on treatment efficacy and additional supportive lateralizing information that played a decisive role for the choice of surgical treatment, which had been rejected by the patient prior to this information.
Real‐world antiseizure medication treatment outcomes in drug‐resistant focal epilepsy patients
Authors: Hatoum Hind T. , Arcona Steve , Mao Jianbin , Walton Surrey
Published: October 2023

Objective

To gather real‐world evidence on antiseizure medications (ASMs) treatment patterns and related outcomes in patients with drug‐resistant focal epilepsy.

Methods

Medical insurance claims from the start of 2014 till the end of 2019 were used. Patient selection criteria included International Classification of Diseases (ICD) codes followed by documented ASM use. Baseline patient demographics along with ASM and rescue medication use patterns and related patient outcome were documented for first (index) ASM regimen. Patients who failed the first regimen and then failed the second regimen were considered drug resistant. Multivariate analyses were performed to identify risks and other characteristics for positive or negative treatment outcomes.

Results

Study cohort consisted of 46 474 patients with a mean age of 47.23 (SD: 16.94). Levetiracetam was the most first‐encountered ASM (37.94%). At baseline, 87.14% were treated with ASMs prior to having study‐confirmed diagnoses. Mental comorbidities were present in 37.86% of patients. After first‐year ASM treatment, 34.61% of patients persisted on their index regimen and 5.91% were seizure‐free. Patients failing first ASM regimen numbered 12 868 (27.69%). Drug‐resistant patients who failed first and then second ASM regimens numbered 6335 (49.23%). Percentages of patients who had successful second treatment and seizure‐free were 21.32 and 3.65, respectively.

Initiating patients on lamotrigine or carbamazepine (relative to levetiracetam), baseline use of index ASM, rescue medications, and older age or male gender all lowered the risk for treatment failure. Having higher comorbidity, comorbid mental illness, headache, or neoplasty increased such a risk. Baseline use of index ASM, depressive episode, or anxiety disorder all entailed higher risk of failing second ASM treatment.

Significance

Overall, reported findings indicated that patient history at baseline and the early selection of an ASM all influenced treatment outcomes. Findings pointed to the complex nature of ASM treatment in drug‐resistant focal epilepsy patients calling for additional research to identify the optimal treatment to achieve beneficial patient outcomes.
Nanofluids effect on the overall transfer coefficients change mechanism analysis
Authors: Zhu Hao , Fan Liwen
Published: October 2023

The understanding of the enhanced thermal conductivity mechanism in nanofluids remains elusive, underscoring the necessity for investigating their influence on heat conduction. A comparative analysis was carried out on the overall heat transfer coefficients of SiO2, TiO2, MgO, ZrO2, CeO2, Al2O3, and Fe3O4, yielding 346.5, 442.9, 569.2, 465.6, 663.2, 562.4, and 706.2 W/m2 K, respectively. Our investigation further extended to the differential impacts of various nanofluids on heat transfer conduction coefficients, with Fe3O4 nanofluids demonstrating the greatest, and SiO2 the least, heat transfer coefficients. Importantly, these nanofluids play a cooperative role in enhancing heat transfer coefficients. Previous studies have largely concentrated on the effects of individual and mixed nanofluids on overall heat transfer coefficients, neglecting the combined effects of different nanofluids. Moreover, the mechanisms underlying these effects remain vague, with insufficient corresponding characterizations. Our study seeks to address these limitations. We also studied the impact of nanofluid concentration, pH, and temperature on heat conduction. Our results suggest that the overall heat transfer coefficient escalates with increasing nanofluid concentration and temperature. For example, the overall heat transfer coefficients for SiO2 nanofluids surged from 346.5 W/m2 K at 25°C to 369.4 W/m2 K at 35°C, 411.4 W/m2 K at 45°C, and 427.6 W/m2 K at 55°C. A rise in pH also led to an increase in overall heat transfer coefficients up to a certain point, after which they started decreasing. The zeta potentials of the aforementioned nanofluids were −12.1, −24.8, −28.6, −23.2, −35.9, −31.3, and −40.4 mV, respectively, and these potentials dwindled with an increase in pH. The influence of nanofluids on overall heat transfer may have implications for the enhanced oil recovery effect.
Performance analysis of dual‐hop dual‐branch amplify‐and‐forward relaying cooperative diversity system using best‐path selection technique over Nakagami‐m fading channels
Authors: Aqel Arwa Sh. , Al‐Mistarihi Mamoun F.
Published: October 2023

One of the promising technologies for achieving virtual diversity gains is cooperative relaying. This study considers a dual‐hop dual‐branch cooperative diversity system with an amplify‐and‐forward mechanism where the hop count here means the total number of relays between source and destination which equals two. Utilizing the best‐path selection combining technique, a closed‐form formula for the average bit error rate and outage probability is obtained. Furthermore, between the nodes in the two branches, we consider independent non‐identical Nakagami‐m slow flat fading channels. The Monte Carlo simulation results are confirmed with the analytical ones.
Yellowstone Cutthroat Trout Recovery in Yellowstone Lake: Complex Interactions Among Invasive Species Suppression, Disease, and Climate Change
Authors: Glassic Hayley C , Chagaris David D , Guy Christopher S , Tronstad Lusha M , Lujan Dominique R , Briggs Michelle A , Albertson Lindsey K , Brenden Travis O , Walsworth Timothy E , Koel Todd M
Published: October 2023

In Yellowstone Lake, Wyoming, the largest inland population of nonhybridized Yellowstone Cutthroat Trout Oncorhynchus clarkii bouvieri, hereafter Cutthroat Trout, declined throughout the 2000s because of predation from invasive Lake Trout Salvelinus namaycush, drought, and whirling disease Myxobolus cerebralis. To maintain ecosystem function and conserve Cutthroat Trout, a Lake Trout gill netting suppression program was established in 1995, decreasing Lake Trout abundance and biomass. Yet, the response of Cutthroat Trout to varying Lake Trout suppression levels, collectively with the influence of disease and climate, is unknown. We developed an ecosystem model (calibrated to historical data) to forecast (2020–2050) whether Cutthroat Trout would achieve recovery benchmarks given disease, varying suppression effort, and climate change. Lake Trout suppression influenced Cutthroat Trout recovery; current suppression effort levels resulted in Cutthroat Trout recovering from historical lows in the early 2000s. However, Cutthroat Trout did not achieve conservation benchmarks when incorporating the influence of disease and climate. Therefore, the National Park Service intends to incorporate age-specific abundance, spawner biomass, or both in conservation benchmarks to provide better indication of how management actions and environmental conditions influence Cutthroat Trout. Our results illustrate how complex interactions within an ecosystem must be simultaneously considered to establish and achieve realistic benchmarks for species of conservation concern.
The effect of Chlorella supplementation in pregnant women with low‐grade inflammation
Authors: Uchiyama‐Tanaka Yoko , Shimabukuro Fumi , Okumura Eri , Fujishima Masaki
Published: October 2023

Pregnancy dramatically changes maternal metabolism and the microbiome. Low‐grade inflammation can cause maternal complications and fetal abnormalities. The objective of this open‐label, randomized, controlled study was to evaluate the efficacy and safety of orally administered Chlorella, a green alga that is commercially available as a dietary supplement with rich nutrients and dietary fiber for pregnant women with low‐grade inflammation. Patients with C‐reactive protein levels >0.05 mg/dL (16 weeks gestation, n = 22) were enrolled and randomly allocated to the Chlorella group (n = 10) or control group (n = 12). We conducted blood biochemical tests at 25, 30, and 35 weeks gestation and evaluated the evacuation status (symptoms depending on the Rome IV C2 criteria and laxative usage), side effects, and complications throughout the investigation. We also monitored the status of the offspring. The Chlorella group (n = 0) showed a significantly lower rate of constipation than the control group (n = 8). This study demonstrated the beneficial effects and safety of Chlorella supplementation in pregnant women, which prevented constipation and unnecessary laxative administration.
Salinity and cultivar effects on alfalfa forage yield and nutritive value in a Mediterranean climate
Authors: Anderson Aaron W. , Gull Umair , Benes Sharon E. , Singh Simarjeet , Hutmacher Robert B. , Brummer Edward Charles , Putnam Daniel H.
Published: October 2023

Background

Soil and water salinity are increasing problems worldwide, causing significantly reduced crop yields. Alfalfa (Medicago sativa L.) is often listed as salt‐sensitive, but field testing of improved cultivars is limited. Forage systems and improved high‐quality alfalfa varieties are needed to enable crop production under high salinity (HS) conditions.

Methods

The objective of this study was to measure the yield and quality response of alfalfa to high saline conditions in the field and to document the relative saline tolerance of its varieties. HS irrigation water (electrical conductivity of water, or ECw 8.0–11.0 dS m−1) was applied to 33 nondormant alfalfa cultivars and were compared with low salinity (LS) treatments (ECw 0.5–1.2 dS m−1) over 4 years in a Mediterranean environment on a clay loam soil utilizing a split‐plot design. Crops were harvested seven to eight times per year, and the forage quality was measured on selected harvests utilizing near‐infrared spectroscopy.

Results

The average yield loss due to HS treatment was 23.9% compared with LS treatment, but yields averaged 23.4 Mg ha−1 under HS over the 3 full years of production. This level of production is considered to be economically viable in this region. Differences in salinity tolerance between lines were identified in the field; individual cultivars lost 5%–35% of their LS yield when grown under HS conditions. Forage quality was significantly improved under HS versus LS conditions, but improvements were negatively correlated with biomass yield (R2 > 0.81), similar to responses observed in drought‐stressed alfalfa.

Conclusions

These yield results confirm greenhouse studies, indicating that alfalfa is highly salt tolerant once established in the field, with potential for further improvement with tolerant cultivars. Salinity tolerance should be chosen based on total biomass yield as well as on the salinity tolerance index (HS yield relative to LS yield). Agronomic practices to mitigate salinity and sodicity are critical, along with improved cultivars.
Experience and views of healthcare professionals towards people who use new psychoactive substances: Evidence from statutory, non‐statutory, and private mental health and addiction healthcare services
Authors: Solomon David , Grierson Jeffrey , Godier‐McBard Lauren , Guirguis Amira
Published: October 2023

Objective

It is unclear how healthcare professionals (HCPs) experience and view the challenges of working with people who use New Psychoactive Substances (PWUNPS), in different healthcare services (HCS). The aim of the study was to explore HCPs' experiences of working with individuals who use NPS across statutory, non‐statutory, and private mental health and addiction HCSs.

Methods

HCPs completed in‐depth semi‐structured interviews. Audio recordings were transcribed verbatim with a mean duration of 30 min 55 s. Data were analysed through thematic analysis.

Results

A purposive sample of 14 HCPs (6 men, 8 women) with a mean age of 42.5 years were interviewed in 2019. Organisational issues, including funding, impacted the treatment for PWUNPS and HCPs perceived a lack of support dependent on their qualifications. They reported a lack of assessment, policy, harm reduction, and awareness of NPS‐related symptoms including mental health problems and stigma faced by PWUNPS.

Conclusion

HCPs need better training, education, and assessment processes to manage acute NPS intoxications and address the stigma associated with PWUNPS. There is a need for policy‐making opportunities across different HCSs to ensure better healthcare outcomes for PWUNPS.
Exploring the experiences of autistic pupils through creative research methods: Reflections on a participatory approach
Authors: Lewis Kathryn , Hamilton Lorna G. , Vincent Jonathan
Published: October 2023

The use of creative qualitative research methods in psychology and other disciplines has increased over recent decades to address power imbalances within research and to centre the voices of participants. These considerations are particularly salient when conducting research with historically marginalized groups, including neurodivergent people. However, research foregrounding the first‐person perspectives of neurodivergent children is still limited. In this paper, we discuss the application of creative qualitative research methods when conducting research with neurodivergent children with a range of communication and wider skill profiles. The benefits and challenges of each method are considered, drawing on examples from the first phase of an ongoing longitudinal study. Additional considerations for working ethically and respectfully with neurodivergent children are discussed. Readers are encouraged to consider how best to adapt their research protocols when working with neurodivergent children, in order to minimize research hierarchies, build positive relationships, and produce rich and meaningful data.
Prognostic and predictive impact of metastatic organ involvement on maintenance therapy in advanced metastatic colorectal cancer: Subgroup analysis of patients treated within the PanaMa trial (AIO KRK 0212)
Authors: Sommerhäuser Greta , Karthaus Meinolf , Kurreck Annika , Ballhausen Alexej , Meyer‐Knees Johanna W. , Fruehauf Stefan , Graeven Ullrich , Mueller Lothar , Koenig Alexander O. , Weikersthal Ludwig Fischer V. , Goekkurt Eray , Haas Siegfried , Stahler Arndt , Heinemann Volker , Held Swantje , Alig Annabel H. S. , Kasper‐Virchow Stefan , Stintzing Sebastian , Trarbach Tanja , Modest Dominik P.
Published: October 2023

Despite molecular selection, patients (pts) with RAS wildtype mCRC represent a heterogeneous population including diversity in metastatic spread. We investigated metastatic patterns for their prognostic and predictive impact on maintenance therapy with 5‐fluorouracil/folinic acid ± panitumumab. The study population was stratified according to (1) number of involved metastatic sites (single vs multiple organ metastasis), liver‐limited disease vs (2) liver metastasis plus one additional site, and (3) vs liver metastasis plus ≥two additional sites. Kaplan‐Meier method and Cox regressions were used to correlate efficacy endpoints. Single organ metastasis was observed in 133 pts (53.6%) with 102 pts (41.1%) presenting with liver‐limited disease, while multiple organ metastases were reported in 114 pts (46.0). Multiple compared to single organ metastases were associated with less favorable PFS (HR 1.48, 95% CI 1.13‐1.93; P = .004) and OS (HR 1.37, 95% CI 0.98‐1.93; P = .068) of maintenance therapy. While metastatic spread involving one additional extrahepatic site was not associated with clearly impaired survival compared to liver‐limited disease, pts with liver metastasis plus ≥two additional sites demonstrated less favorable PFS (HR 1.92, 95% CI 1.30‐2.83; P < .001), and OS (HR 2.38, 95% CI 1.51‐3.76; P < .001) of maintenance therapy. Pmab‐containing maintenance therapy appeared active in both pts with multiple (HR 0.58; 95% CI, 0.39‐0.86; P = .006) as well as to a lesser numerical extent in pts with single organ metastasis (HR 0.83; 95% CI, 0.57‐1.21; P = .332; Interaction P = .183). These data may support clinical decisions when EGFR‐based maintenance therapy is considered.
Dynamic mechanisms of exercise to improve body satisfaction: Perceived or actual fat loss?
Authors: Wang Yu‐Bu , Bird Jonathan , Guo Lu
Published: October 2023

We examined the dynamic mechanisms of aerobic training (AT) and strength training (ST) to improve body satisfaction. Sixty‐six participants were randomised to either the AT or ST condition and completed an 8‐week intervention. Participants completed 3 weekly, 30‐minute sessions of moderate intensity AT (65–75% VO2max) or ST (65–75% 1‐RM). The energy consumption of each session was approximately equivalent under both conditions. Body satisfaction, body composition, perceived fitness and exercise self‐efficacy were measured at baseline and biweekly during the intervention. Exercise improved individuals' body satisfaction (p < .05). When the energy expenditures of AT and ST were equal, there was no difference in body satisfaction improvement. There were dynamic mechanisms underlying the effects of exercise on body satisfaction. Specifically, perceived fitness influenced body satisfaction improvements during the early stages of the exercise program, while changes in body composition influenced body satisfaction toward the end of the exercise program. There were sex differences in the mechanisms underlying body satisfaction. For women, perceived fat was more important in the early intervention period; for men, actual body fat was more valuable in the late intervention period. An effective strategy to improve body satisfaction is to initially target perceived fitness before focusing on changing body composition.
The Clinical Pharmacology and Use of Paroxetine, a New Selective Serotonin Reuptake Inhibitor
Authors: Nemeroff Charles B.
Published: October 2023

Major depression afflicts a significant percentage of the population, and optimum therapy is often limited by the poor tolerability and lethality in overdose of the tricyclic antidepressants. The selective serotonin reuptake inhibitors (SSRIs) fluoxetine, sertraline, and, more recently, paroxetine are viewed as welcome additions to existing therapy. The SSRIs are as effective as the tricyclic antidepressants, but are not associated with their adverse effect profile. Paroxetine in dosages of 20–50 mg/day is as effective as the older classic antidepressants, including amitriptyline, imipramine, and doxepin. It is effective in the elderly and in patients with recurrent, resistant, or severe depression.
Comparison of Ampicillin‐Sulbactam and Ticarcillin‐Clavulanic Acid in Patients With Chronic Renal Failure: Effects of Differential Pharmacokinetics on Serum Bactericidal Activity
Authors: Hardin Thomas C. , Butler Steven C. , Ross Sabine , Wakeford John H. , Jorgensen James H.
Published: October 2023

Study Objectives. To evaluate the pharmacodynamic antibacterial activity of ticarcillin‐clavulanic acid (T‐C) and ampicillin‐sulbactam (A‐S) combinations against reference bacterial strains in patients with end‐stage renal disease maintained on long‐term hemodialysis.

Design. Randomized, crossover, controlled study.

Setting. National Institutes of Health‐funded general clinical research unit in a Veterans Administration Medical Center.

Patients. Nine adult men with end‐stage renal disease maintained on long‐term hemodialysis. Two subjects did not complete the study due to problems of vascular access, and another withdrew for personal reasons.

Interventions. On a nondialysis day, each subject was randomly administered either T‐C 3.1 g or A‐S 3 g as a slow intravenous infusion over 30 minutes. Serial blood samples were collected for measurement of antibiotic serum concentrations and determination of serum bactericidal titers. Following a washout period, the study was repeated with the alternative antibiotic combination.

Measurements and Main Results. The mean observed apparent β‐half‐life of clavulanic acid was substantially shorter than that for the other three drugs. The bactericidal activity of both A‐S and T‐C against non‐β‐lactamase‐producing (Nβ‐LP) strains of S. aureus and E. coli was consistently high, as indicated by geometric mean SBTs of at least 1:5 at 24 hours. Against β‐lactamase‐producing (β‐LP) S. aureus, the geometric mean SBTs for A‐S were at least 1:25 throughout the study period, while the geometric mean SBTs for T‐C decreased over 24 hours from 1:29 to 1:6. Against β‐LP E. coli, the bactericidal activities for both A‐S and T‐C were poor, with geometric mean peak SBTs of only 1:6 and 1:3, respectively. The geometric mean SBT for T‐C against this E. coli strain had declined to 1:1 at 6 hrs.

Conclusion. Increasing the dosing interval for T‐C in patients with end‐stage renal disease may lead to periods of insufficient clavulanic acid to protect ticarcillin from β‐lactamase degradation.
Individualizing Vancomycin Dosing Regimens: An Evaluation of Two Pharmacokinetic Dosing Programs In Critically Ill Patients
Authors: Gatta Fernández de Ma del Mar , Fruns Ignacio , Domínguez‐Gil Alfonso
Published: October 2023

We evaluated the predictive performance of two commercial computer programs (Abbott and Simkin) for pharmacokinetic dosing of vancomycin in 50 critically ill patients, 40 with hematologic malignancies and 10 in intensive care. Predictive performance was assessed for both pharmacokinetics and forecasting vancomycin serum levels by using a set of peak and trough drug levels per patient. The effect of renal function and serum sampling (steady state, nonsteady state) on predictive performance of both programs was also analyzed. No statistically significant differences were found between the programs for predicting either pharmacokinetics or serum levels, regardless of a patient's renal function or serum sampling. The Abbott and Simkin programs were similar for individualizing vancomycin dosage regimens.
The Effect of Short‐Term Administration of Theophylline on Erythropoietin Levels in Healthy Adults
Authors: Sharma Renu , Blake Kathryn , Murphy Suzanne , Clancy Mary , Duckworth Laurie , Pitel Paul , Lawrence Stewart
Published: October 2023

A previous study demonstrated suppression of erythropoietin production in patients treated with long‐term theophylline. This effect could exacerbate anemia of prematurity in neonates receiving this drug for apnea of prematurity. In this pilot project we evaluated the effect of short‐term theophylline administration on serum erythropoietin in healthy adults. Six subjects were given a bolus followed by a continuous infusion of theophylline targeted to achieve a serum level of at least 10 μg/ml, followed by oral theophylline for 36 hours. Serum erythropoietin and theophylline levels were measured before, during, and after drug infusion. Complete hemograms were performed before and after completion of the infusion. No significant changes in serum erythropoietin levels were seen at any time (F=1.57, p=0.12). Hematologic values also remained unaltered. We conclude that short‐term administration of theophylline is unlikely to have any effect on serum erythropoietin levels in healthy adults.
Comparison of PT, aPTT, and Factor VII Values Obtained by Concurrent Sample Collection by Direct Venipuncture and Peripheral Venous Catheters
Authors: Lindley Celeste , Sawyer William , Haddon Teri , Meade James , Nolen Jacqueline , Johansen Lise , Roberts Harold
Published: October 2023

Study Objective. To compare prothrombin time (PT), activated partial thromboplastin time (aPTT), and factor VII values in concurrent blood samples obtained by direct venipuncture and from a peripheral venous catheter.

Design. Concurrent samples obtained from catheters and by direct venipuncture were studied. In a separate crossover bioequivalence assessment of DNA‐derived factor VIIa (rFVIIa) from two different batches, sample results of each technique were compared.

Setting. University hospital clinical research unit.

Patients. Six patients with hemophilia A under nonbleeding conditions.

Interventions. The patients received a single dose of rFVIIa 70 μg/kg administered by intravenous push over 2 minutes. Concurrent blood samples were collected at 2, 3, 4, 6, 8, 10, and 12 hours after rFVIIa administration. Catheter blood samples were drawn from a three‐way stopcock attached to an 18‐gauge peripheral venous catheter in the patient's forearm and connected to an intravenous solution of 5% dextrose with half normal saline maintained at a rate of 30 ml/hour. Venipuncture samples were drawn from the opposite arm.

Measurements and Main Results. The PT and aPTT values were determined by using a BBL Fibrometer (PT) and a Coagamate X‐2 with automated aPTT reagent. Blood samples were analyzed for factor VII concentration using the Novo Clot assay. The mean venipuncture‐obtained PT (8.9 ± 1.0 sec) and aPTT (48.7 ± 13.6 sec) values were numerically equivalent to mean catheter‐derived PT (9.0 ± 1.0 sec) and aPTT (48.3 ± 12.5 sec) results, as were mean venipuncture and catheter‐obtained FVII:C values.

Conclusions. The PT and aPTT values determined after venipuncture and through the peripheral catheter were not statistically different (p>0.05) when compared by paired or unpaired analysis. Similarly, values of FVII:C measured after venipuncture were statistically equivalent to those after sampling through the peripheral catheter. All six patients preferred the catheter method of blood collection over venipuncture.
Impact of Compliance and Side Effects on the Clinical Outcome of Patients Treated With Oral Erythromycin
Authors: Anastasio Geraldine D. , Little John M. , Robinson Mark D. , Pettice Yvonne L. , Leitch Beatrice B. , Norton H. James
Published: October 2023

Study Objective. To determine the relationship among compliance, side effects, and self‐reported outcome for patients in an erythromycin trial.

Design. A retrospective analysis of data from a multicenter, prospective, single‐blind, randomized trial.

Setting. Five metropolitan ambulatory care offices.

Patients. The 252 adults (> 18 yrs) were prescribed oral erythromycin 1.0 g/day (base equivalent) for infectious disorders.

Intervention. Subjects received erythromycin for 10 days and reported compliance, drug efficacy, and side effects in a daily diary Compliance was measured by tablet count.

Results. A negative correlation was found between gastrointestinal symptom severity score and percentage of tablets taken (p<0.001). A significant positive correlation was seen between compliance and outcome (p<0.001). Subjects who took greater than 80% of the drug achieved the treatment goal more frequently than those taking 80% or less (94% vs 59%, p<0.001).

Conclusions. Side effects of erythromycin adversely affected compliance. Compliance had a positive effect on self‐reported outcome.
A Large Population‐Based Follow‐Up Study of Trimethoprim‐Sulfamethoxazole, Trimethoprim, and Cephalexin for Uncommon Serious Drug Toxicity
Authors: Jick Hershel , Derby Laura E.
Published: October 2023

We conducted a population‐based 45‐day follow‐up study of 232,390 people who were prescribed trimethoprim‐sulfamethoxazole (TMP‐SMZ), 266,951 prescribed trimethoprim alone, and 196,397 prescribed cephalexin, to estimate the risk of serious liver, blood, skin, and renal disorders resulting in referral or hospitalization associated with these drugs. The results were based on information recorded on office computers by selected general practitioners in the United Kingdom, together with a review of clinical records. The risk of clinically important idiopathic liver disease was similar for persons prescribed TMP‐SMZ (5.2/100,000) and those prescribed trimethoprim alone (3.8/100,000). The risk for those prescribed cephalexin was somewhat lower (2.0/100,000). Only five patients experienced blood disorders, one of whom was exposed to TMP‐SMZ; of seven with erythema multiforme and Stevens‐Johnson syndrome, four were exposed to TMP‐SMZ. The one case of toxic epidermal necrolysis occurred in a patient who took cephalexin. Finally, only five cases of acute parenchymal renal disease occurred, none likely to be caused by a study drug. We conclude that the risk of the serious diseases studied is small for the three agents, and compares reasonably with the risk for many other antibiotics.
Comparison of the Pharmacodynamic Activity of Cefotaxime plus Metronidazole With Cefoxitin and Ampicillin plus Sulbactam
Authors: Sullivan Maureen C. , Nightingale Charles H. , Quintiliani Richard , Sweeney Kevin R.
Published: October 2023

Study Objective. To compare the pharmacokinetic and pharmacodynamic activity of three drug regimens: cefotaxime plus metronidazole, cefoxitin, and ampicillin‐sulbactam against two organisms frequently isolated in intraabdominal infection, Escherichia coli and Bacteroides fragilis.

Design. Open‐label, three‐way crossover study.

Setting. Hartford Hospital Clinical Research Center.

Participants. Nine healthy volunteers.

Interventions. Subjects received the following regimens: (1) a single 1‐g intravenous dose of cefotaxime plus a single 500‐mg oral dose of metronidazole; (2) two intravenous doses of cefoxitin, 2 g each dose given every 6 hours; and (3) two intravenous doses of ampicillin‐sulbactam, 3 g each dose given every 6 hours.

Measurements and Main Results. Serum bactericidal titers and drug concentrations were measured over a 12‐hour period. The cefotaxime‐metronidazole regimen showed superior activity against E. coli compared with ampicillin‐sulbactam and cefoxitin. The mean areas under the bactericidal activity curve (AUBC) for the three regimens were 550.2, 68.7, and 48.9, respectively (p=0.0001). There was no significant difference in AUBC among the three regimens for B. fragilis. Serum concentrations of cefotaxime remained above the minimum inhibitory concentration (MIC) for E. coli significantly longer than did concentrations of ampicillin‐sulbactam and cefoxitin (p=0.0002 and p=0.0023, respectively). Serum concentrations of metronidazole were still at 9 times the MIC for B. fragilis at the end of the 12‐hour dosing interval; for ampicillin‐sulbactam and cefoxitin concentrations remained above the MIC for one‐half and less than one‐fourth, respectively, of the dosing interval (p<0.0001). The ratio of AUC:MIC was also favorable for metronidazole (212.2) compared with 63.4 for ampicillin‐sulbactam and 9.2 for cefoxitin.

Conclusions. The combination of cefotaxime‐metronidazole, even at the relatively low doses used in this study, provides coverage against gram‐negative and anaerobic pathogens that is at least as effective as that of cefoxitin and ampicillin‐sulbactam. In addition, its cost is considerably less expensive than that of the other regimens.
Publication Rates in U.S. Schools and Colleges of Pharmacy, 1976–1992
Authors: Thompson Dennis F. , Segars Larry W.
Published: October 2023

To establish publication rates of U.S. schools and colleges of pharmacy (SCOP) for 1976–1992, we obtained data from the Science Citation Index (SCI) Corporate Index. The SCI data base covers the top 4500 journals in the technical and scientific fields. Citations were counted without regard to publication type (letter, abstract, review, etc.). Duplicative publications were eliminated. Faculty counts were obtained from the American Association of Colleges of Pharmacy Roster of Faculty and Staff for the inclusive years. Total publications for all schools increased over 100% from 1976 to 1992, and the number of faculty members increased by 40% during that time. However, only 12 (16%) of the SCOP averaged 50 or more publications/year, whereas 43 (59%) averaged fewer than 20. Data were also normalized by full‐time faculty members. Only 13 (18%) SCOP averaged 1.0 or more publication/faculty/year, and 38 (52%) averaged fewer than 0.5. Publication rates were greater for medical center‐based than for nonmedical center‐based SCOP (p<0.05), and for public than for private SCOP (p<0.05). These data suggest that over half of the existing SCOP are minimally productive, generating less than 20 publications/year or 0.5 publication/faculty/year.
Evaluation of Biotechnology Products
Authors: Tami Joseph , Evens Ronald P.
Published: October 2023

Biotechnology products have had a substantial impact on the health care system, including cost and patient care. In some hospitals, agents produced by biotechnology account for 10% or more of the pharmacy budget. As of May 1996, 29 biological products had been approved for use in the United States, including, in many instances, agents for diseases or conditions for which no drugs were previously available. These compounds are different molecules, often with very different types of properties from synthetic chemicals. They are relatively expensive compared with traditionally manufactured synthetic drugs. The increasing availability, individual characteristics, and relative expense of these products mandate a systematic method of evaluating them for use in various health care systems. Thirteen essential points must be considered when evaluating them for clinical use: availability of alternative agents; indications (both labeled and unlabeled); glycosylation; adverse events; administration and pharmacokinetics; monitoring needs; shipping, handling, and storage; stability; pharmacoeconomic studies; concomitant drug costs; special pharmacy procedures; reimbursement; and manufacturer's support.
Cryptococcal Meningitis in Patients with the Acquired Immunodeficiency Syndrome
Authors: Zeind Caroline S. , Cleveland Kerry O. , Menon Madhavi , Brown James R. , Solomon David K.
Published: October 2023

The optimum therapy for cryptococcal meningitis in patients with the acquired immunodeficiency syndrome (AIDS) remains unresolved. Traditional therapy consists of amphotericin B with or without flucytosine. Obstacles exist in administering these agents to patients with AIDS. Mortality rates during initial therapy are relatively high. Given the lack of proved benefit, we do not recommend adding flucytosine to amphotericin B routinely. The search for more efficacious and less toxic agents continues. The oral triazoles, especially fluconazole, have increased the options for treatment of this disease. New strategies and novel approaches in managing cryptococcal meningitis in patients with AIDS continue to be developed.
Immunopharmacologic Therapy in Renal Transplantation
Authors: Shoker Ahmed S.
Published: October 2023

The long‐term kidney allograft survival rate is still far from optimum. Conventional immunosuppressive drugs used to prevent allograft rejection are associated with significant side effects. Moreover, withdrawal of these agents is often associated with graft loss due to rejection. No treatment is available for chronic rejection. Graft tolerance is difficult to achieve in humans, and therefore a continued goal in organ transplantation is to develop immunosuppressive regimens that are associated with fewer side effects and decreased rates of rejection, and that promote graft tolerance. The advent of newer pharmacologic agents and bioreagents is expected to improve patient and graft survival rates.
The Comparative Safety and Diagnostic Accuracy of Adenosine Myocardial Perfusion Imaging in Women versus Men
Authors: Mohiuddin Syed M. , Ravage Christopher K. , Esterbrooks Dennis J. , Lucas B. Daniel , Hilleman Daniel E.
Published: October 2023

Study Objective. To determine if the diagnostic accuracy and safety of intravenous adenosine myocardial perfusion imaging is significantly different in men compared with women.

Design. Prospective, comparative, open‐label clinical trial.

Setting. Nuclear medicine laboratory in a university‐affiliated hospital.

Patients. Consecutive patients who were referred for evaluation of known or suspected coronary artery disease. Patients were judged not to be able to exercise adequately.

Interventions. Coronary angiography was conducted within 6 weeks of an adenosine thallium‐201 myocardial perfusion imaging study.

Measurements and Main Results. Diagnostic accuracy is shown in the table.

Overall, side effects from adenosine were not different between men and women. The frequencies of ST depression and chest pain were significantly greater in women than men, although their etiologies are unknown. The frequency of severe side effects such as heart block and hypotension was not different between men and women.

Conclusions. The diagnostic accuracy and safety of adenosine thallium‐201 myocardial perfusion imaging are generally similar in women and men.
Drug‐Related Hospital Admissions
Authors: Nelson Kent M. , Talbert Robert L.
Published: October 2023

To describe the frequency and pattern of drug‐related morbidity that results in hospital admission and the extent to which these admissions are avoidable, we prospectively reviewed the charts of 452 consecutive patients admitted to the intensive care unit or internal medicine service of a university‐affiliated, county hospital. Of these, 73 (16.2%) were admitted due to drug‐related morbidity Forty patients (54.8%) experienced drug therapy failure, 24 (32.9%) had an adverse reaction, and 9 (12.3%) had overdoses. Thirty‐six (49.3%) of these admissions were definitely avoidable. Compared with patients admitted for other reasons, these patients were more likely to report noncompliance with drug therapy (65.8% vs 15.7%, p<0.0001) and were taking more drugs (p=0.0037). We conclude that approximately half of drug‐related hospital admissions are avoidable. Targeting patients taking several drugs and with a history of noncompliance may reduce this problem.
Urate‐Lowering Drugs and Muscle Injury: A Systematic Review and Network Meta‐Analysis
Authors: Mitsuboshi Satoru , Morizumi Makoto , Kotake Kazumasa , Kaseda Ryohei , Narita Ichiei
Published: October 2023

Several urate‐lowering drugs have been linked to muscle injury. This study investigated the association of oral urate‐lowering drugs with the risk of muscle injury by performing a network meta‐analysis of randomized and non‐randomized controlled trials. A systematic search of MEDLINE, via PubMed, the ClinicalTrials.gov website, and the Cochrane Central Register of Controlled Trials was conducted to identify relevant studies with a primary outcome of “all muscle injuries.” A random‐effects model was used to perform a frequentist network meta‐analysis to estimate whether there was significant heterogeneity among the studies. In total, 32 studies including 28,327 participants with 2694 (9.5%) “all muscle injuries” were assessed, and the overall risk of bias was judged to be low to moderate. No statistically significant differences were found between placebo and 6 urate‐lowering therapies: allopurinol (risk ratio, RR, 1.05; 95% confidence interval, 95%CI, 0.63‐1.73), febuxostat (RR 1.10, 95%CI 0.71‐1.70), lesinurad (RR 7.00, 95%CI 0.31‐160.36), lesinurad concomitant with allopurinol (RR 0.85, 95%CI 0.34‐2.11), lesinurad concomitant with febuxostat (RR 1.97, 95%CI 0.55‐7.03), and topiroxostat (RR 0.99, 95%CI 0.37‐2.65). The findings suggest that there is little need to consider the risk of muscle injury when using urate‐lowering drugs in the clinical setting.
Presenting time‐series data as absolute versus relative changes impacts judgments and choices
Authors: Tomaino Geoff , Walters Daniel J.
Published: October 2023

We examined how different ways of presenting time‐series data affect consumer judgments and behaviors. Specifically, we compared the use of absolute terms (e.g., actual dollar change) versus relative terms (e.g., annual percentage change) in charts. Our findings revealed that absolute charts tend to have a more positive visual slope than relative charts, leading consumers to extrapolate these trends and expect faster growth in quantities. In Study 1, participants who viewed COVID‐19 data in absolute charts, as opposed to relative charts, donated more money to a COVID‐19‐related charity and were less inclined to challenge quarantine advisories throughout the day. In Study 2, we observed that participants preferred investing in a country when its GDP was presented in an absolute chart, and visual trends were found to drive this effect. Study 3 demonstrated that individuals placed greater emphasis on absolute charts depicting population growth, particularly when the unit of measurement was more meaningful. Overall, the choice to represent data in absolute versus relative terms has a far reaching impact on judgments and choices.
ROS produced by NOX promote the neurite growth in a PI3K/Akt independent manner
Authors: Mora‐Zenil Janeth , Morán Julio
Published: October 2023

Reactive oxygen species (ROS) function as signaling molecules in several physiologic and pathologic processes. In central nervous system, ROS are critical for differentiation, migration, polarization, and neurite growth. These actions are mediated by reversible oxidation of target proteins. On the other hand, PI3K/Akt signaling pathway is susceptible to be modulated by ROS and it has been implicated in neurite growth. In this study, we evaluated the participation of ROS in the neurite growth of cultured rat cerebellar granule neurons (CGN), as well as the possible regulation of the PI3K/Akt pathway by ROS during neurite outgrowth. For this purpose, CGN were treated with cellular or mitochondrial antioxidants, or an NOX inhibitor and neurite growth was evaluated. Moreover, to assess the participation Akt in this process, the p‐Akt levels were measured in CGN treated with antioxidants or a NOX inhibitor. The effect of antioxidants on the neurite growth in the presence of a PI3K inhibitor was also measured. We found that cellular antioxidants and the NOX inhibitor decreased the neurite growth, but not the mitochondrial antioxidant. Interestingly, the antioxidants increased the p‐Akt levels; however, the effect of antioxidants on neurite growth was no dependent on the Akt activity since the inhibitor of PI3K did not modify the antioxidant action on neurite growth. Our results show that the PI3K/Akt pathway participates in neurite growth and that ROS produced by NOX could function as signals in this process; however, this action is not mediated by a redox regulation of Akt activity.
Internet Use and Creative Thinking in the Alternative Uses Task
Authors: Oliva Mercedes T. , Storm Benjamin C.
Published: October 2023

Research has shown that using the Internet to access information can influence memory, metacognition, and how people choose to access information in the future. The current experiment sought to expand this line of work by investigating the impact of using the Internet on creative thinking. A total of 378 participants completed a version of the Alternative Uses Test in which they were asked to list five uncommon uses for each of four objects (e.g., a brick). Half of the participants did this on their own, without help from the Internet. The other half of the participants used the Internet to generate uses for the first two objects, and then generated uses for the last two objects without the Internet. Responses were considered on a number of measures (e.g., creativity, effectiveness, fluency, flexibility). Although creative performance was similar between the two conditions, some differences were observed, particularly with regard to the distributions of uses generated. For example, a subset of object uses generated by participants in the Internet condition were rarely generated by participants in the No Internet condition.