Power Has Pitfalls: (In)accuracy of Administrative Data for Nonoperative Management of Appendicitis.

INTRODUCTION: Nonoperative management (NOM) of uncomplicated appendicitis is increasingly common. Effectiveness of NOM has been studied by identifying patients via International Classification of Diseases (ICD) 9/ICD-10 codes for uncomplicated appendicitis and no code for appendectomy. We sought to assess the accuracy of such administrative definitions. METHODS: We retrospectively identified patients with ICD-9/ICD-10 codes for appendicitis at five sites across the United States. Initial management plan and clinical severity were recorded by trained abstractors. We identified a gold standard cohort of patients with surgeon-diagnosed uncomplicated appendicitis and planned NOM. We defined two administrative cohorts with ICD-9/ICD-10 codes for uncomplicated appendicitis and either no surgery during initial admission (definition #1) or no surgery on day 0-1 of admission (definition #2). We compared each definition to the gold standard. RESULTS: Among 1224 patients with uncomplicated appendicitis, 72 (5.9%) underwent planned NOM. NOM patients were older (median [Q1-Q3] of 37 [27-56] versus 32 [25-44] y) and less frequently male (51.4% versus 54.9%), White (54.1% versus 67.6%), and privately insured (38.9% versus 50.2%) than patients managed operatively. Definition #1 had sensitivity of 0.81 and positive predictive value of 0.87 for NOM of uncomplicated appendicitis. Definition #2 had sensitivity of 0.83 and positive predictive value of 0.72. The gold standard cohort had a true failure/recurrence rate of 23.6%, compared with apparent rates of 25.4% and 39.8%, respectively. CONCLUSIONS: Administrative definitions are prone to misclassification in identifying planned NOM of uncomplicated appendicitis. This likely impacts outcomes in studies using administrative databases. Investigators should disclose how misclassification may affect results and select an administrative definition that optimally balances sensitivity and specificity for their research question.

"not one size fits all" The challenges of measuring paediatric health-related quality of life and the potential role of digital ecological momentary assessment: a qualitative study.

PURPOSE: To explore the views of clinicians and researchers about the challenges of measuring health-related quality of life (HRQoL) in children (5-11 years) and to explore whether digital ecological momentary assessment (EMA) could enhance HRQoL measurement. METHODS: Semi-structured qualitative interviews with 18 professionals (10 academics/researchers, four clinicians, four with both professional backgrounds) experienced in child HRQoL measurement. We analysed data thematically. RESULTS: Theme One describes the uncertainty around conceptualising HRQoL for children and which domains to include; the greater immediacy and sensitivity of children's reflections on their HRQoL, leading to high variability of the construct; and the wide individual differences across childhood, incongruent with fixed HRQoL measures. Theme Two describes the challenges of proxy reporting, questioning whether proxies can meaningfully report a child's HRQoL and reflecting on discrepancies between child and proxy reporting. Theme Three covers the challenge of interpreting change in HRQoL over time; does a change in HRQoL reflect a change in health, or does this reflect developmental changes in how children report HRQoL. Theme Four discusses digital EMA for HRQoL data capture. In-the-moment, repeated measurement could provide rich data and address challenges of recall, ecological validity and variability; passive data could provide objective markers to supplement subjective responses; and technology could enable personalisation and child-centred design. However, participants also raised methodological, practical and ethical challenges of digital approaches. CONCLUSION: Digital EMA may address some of the challenges of HRQoL data collection with children. We conclude by discussing potential future research to explore and develop this approach.

Sex differences in body composition and serum metabolome responses to sustained, physical training suggest enhanced fat oxidation in women compared with men.

Sex differences in energy metabolism during acute, submaximal exercise are well documented. Whether these sex differences influence metabolic and physiological responses to sustained, physically demanding activities is not well characterized. This study aimed to identify sex differences within changes in the serum metabolome in relation to changes in body composition, physical performance, and circulating markers of endocrine and metabolic status during a 17-day military training exercise. Blood was collected, and body composition and lower body power were measured before and after the training on 72 cadets (18 women). Total daily energy expenditure (TDEE) was assessed using doubly labeled water in a subset throughout. TDEE was greater in men (4,085 ± 482 kcal/d) than in women (2,982 ± 472 kcal/d, P < 0.001), but not after adjustment for dry lean mass (DLM). Men tended to lose more DLM than women (mean change [95% CI]: -0.2[-0.3, -0.1] vs. -0.0[-0.0, 0.0] kg, P = 0.063, Cohen's d = 0.50) and have greater reductions in lower body power (-244[-314, -174] vs. -130[-209, -51] W, P = 0.085, d = 0.49). Reductions in DLM and lower body power were correlated (r = 0.325, P = 0.006). Women demonstrated greater fat oxidation than men (Δfat mass/DLM: -0.20[-0.24, -0.17] vs. -0.15[-0.17, -0.13] kg, P = 0.012, d = 0.64). Metabolites within pathways of fatty acid, endocannabinoid, lysophospholipid, phosphatidylcholine, phosphatidylethanolamine, and plasmalogen metabolism increased in women relative to men. Independent of sex, changes in metabolites related to lipid metabolism were inversely associated with changes in body mass and positively associated with changes in endocrine and metabolic status. These data suggest that during sustained military training, women preferentially mobilize fat stores compared with men, which may be beneficial for mitigating loss of lean mass and lower body power.NEW & NOTEWORTHY Women preferentially mobilize fat stores compared with men in response to sustained, physically demanding military training, as evidenced by increased lipid metabolites and enhanced fat oxidation, which may be beneficial for mitigating loss of lean mass and lower body power.

Biomarkers of oxidative stress, diet and exercise distinguish soldiers selected and non-selected for special forces training.

INTRODUCTION: The metabolomic profiles of Soldiers entering the U.S. Special Forces Assessment and Selection course (SFAS) have not been evaluated. OBJECTIVES: To compare pre-SFAS blood metabolomes of Soldiers selected during SFAS versus those not selected, and explore the relationships between the metabolome, physical performance, and diet quality. METHODS: Fasted blood samples and food frequency questionnaires were collected from 761 Soldiers prior to entering SFAS to assess metabolomic profiles and diet quality, respectively. Physical performance was assessed throughout SFAS. RESULTS: Between-group differences (False Discovery Rate < 0.05) in 108 metabolites were detected. Selected candidates had higher levels of compounds within xenobiotic, pentose phosphate, and corticosteroid metabolic pathways, while non-selected candidates had higher levels of compounds potentially indicative of oxidative stress (i.e., sphingomyelins, acylcarnitines, glutathione, amino acids). Multiple compounds higher in non-selected versus selected candidates included: 1-carboxyethylphenylalanine; 4-hydroxy-nonenal-glutathione; α-hydroxyisocaproate; hexanoylcarnitine; sphingomyelin and were associated with lower diet quality and worse physical performance.  CONCLUSION: Candidates selected during SFAS had higher pre-SFAS levels of circulating metabolites that were associated with resistance to oxidative stress, higher physical performance and higher diet quality. In contrast, non-selected candidates had higher levels of metabolites potentially indicating elevated oxidative stress. These findings indicate that Soldiers who were selected for continued Special Forces training enter the SFAS course with metabolites associated with healthier diets and better physical performance. Additionally, the non-selected candidates had higher levels of metabolites that may indicate elevated oxidative stress, which could result from poor nutrition, non-functional overreaching/overtraining, or incomplete recovery from previous physical activity.

Climate warming has direct and indirect effects on microbes associated with carbon cycling in northern lakes.

Northern lakes disproportionately influence the global carbon cycle, and may do so more in the future depending on how their microbial communities respond to climate warming. Microbial communities can change because of the direct effects of climate warming on their metabolism and the indirect effects of climate warming on groundwater connectivity from thawing of surrounding permafrost, especially at lower landscape positions. Here we used shotgun metagenomics to compare the taxonomic and functional gene composition of sediment microbes in 19 peatland lakes across a 1600-km permafrost transect in boreal western Canada. We found microbes responded differently to the loss of regional permafrost cover than to increases in local groundwater connectivity. These results suggest that both the direct and indirect effects of climate warming, which were respectively associated with loss of permafrost and subsequent changes in groundwater connectivity interact to change microbial composition and function. Archaeal methanogens and genes involved in all major methanogenesis pathways were more abundant in warmer regions with less permafrost, but higher groundwater connectivity partly offset these effects. Bacterial community composition and methanotrophy genes did not vary with regional permafrost cover, and the latter changed similarly to methanogenesis with groundwater connectivity. Finally, we found an increase in sugar utilization genes in regions with less permafrost, which may further fuel methanogenesis. These results provide the microbial mechanism for observed increases in methane emissions associated with loss of permafrost cover in this region and suggest that future emissions will primarily be controlled by archaeal methanogens over methanotrophic bacteria as northern lakes warm. Our study more generally suggests that future predictions of aquatic carbon cycling will be improved by considering how climate warming exerts both direct effects associated with regional-scale permafrost thaw and indirect effects associated with local hydrology.

Congenital diaphragmatic hernia in siblings with PIGA-related congenital disorder of glycosylation.

There are over 150 proteins involved in glycosylphosphatidylinositol (GPI)-anchored protein biosynthesis, a class within the larger category of congenital disorders of glycosylation (CDG). Pathogenic variants identified in phosphatidylinositol glycan class A protein (PIGA) are associated with X-linked PIGA-CDG, a GPI-anchor defect. The disease has primarily been characterized by hypotonia, epilepsy, and global developmental delay; however, only 89 known cases are reported, so the phenotypic spectrum has likely not yet been fully delineated. Congenital diaphragmatic hernia (CDH) has been reported in patients with various GPI-anchor related defects but has only been described in one prior individual with PIGA-CDG. Here, we describe the second and third reported cases of CDH in two brothers with PIGA-CDG caused by a pathogenic missense variant in PIGA: c.355C > T, p.R119W. Chromosomal microarray and whole exome sequencing did not reveal another plausible explanation for the CDH. We relate our patients' clinical features to the single previously reported individual with CDH and PIGA-CDG. We then compare this case series with the subset of individuals with CDH and other GPI-anchor defects. These findings suggest that CDH should be considered in the phenotypic disease spectrum of PIGA-CDG.

Unexpected High Rates of Persistent Trichomonas vaginalis Infection in a Retrospective Cohort of Treated Pregnant Women.

BACKGROUND: Our primary objective was to determine the rate of persistent Trichomonas infection among pregnant women posttreatment. The secondary objective was to determine if oral multidose metronidazole was associated with fewer cases of persistent Trichomonas compared with single-dose treatment. METHODS: This is a retrospective cohort study of women diagnosed with genital Trichomonas vaginalis from 2008 to 2017. We calculated the rate of persistent Trichomonas by dividing the number of positive Trichomonas tests collected 21 days or longer posttreatment by the total number of women treated and retested. Bivariate analysis was performed to compare the rates of positive tests after single and multidose metronidazole. Multivariate logistic regression was used to evaluate factors associated with persistent infection. RESULTS: Five hundred forty-two women with 565 pregnancies were diagnosed with Trichomonas infection. The majority of subjects were prescribed either single-dose (n = 352) or multidose metronidazole (n = 74). Posttreatment Trichomonas tests were collected 21 days or longer in 326 subjects and 44% (143) were positive. Rates of positive Trichomonas tests among women receiving single-dose and multidose regimens were similar (45% vs. 40%, P = 0.50). Women who had ≥1 pregnancy affected by Trichomonas infection were more likely to have a positive test posttreatment (adjusted odds ratio, 20.1; 95% confidence interval, 1.9-215.3). Obese women were less likely to have a positive test posttreatment (adjusted odds ratio, 0.3; 95% confidence interval, 0.1-0.9). CONCLUSIONS: Given high rates of positive Trichomonas tests and increased detection with nucleic acid amplification tests (NAATs), all pregnant women should be retested with NAATs approximately 3 weeks posttreatment. Further studies are needed to determine the most effective treatment of Trichomonas infection in pregnant women.

The politics of female pain: women's citizenship, twilight sleep and the early birth control movement.

The medical intervention of 'twilight sleep', or the use of a scopolamine-morphine mixture to anaesthetise labouring women, caused a furore among doctors and early 20th-century feminists. Suffragists and women's rights advocates led the Twilight Sleep Association in a quest to encourage doctors and their female patients to widely embrace the practice. Activists felt the method revolutionised the notoriously dangerous and painful childbirth process for women, touting its benefits as the key to allowing women to control their birth experience at a time when the maternal mortality rate remained high despite medical advances in obstetrics. Yet many physicians attacked the practice as dangerous for patients and their babies and antithetical to the expectations for proper womanhood and motherly duty. Historians of women's health have rightly cited Twilight Sleep as the beginning of the medicalisation and depersonalisation of the childbirth process in the 20th century. This article instead repositions the feminist political arguments for the method as an important precursor for the rhetoric of the early birth control movement, led by Mary Ware Dennett (a former leader in the Twilight Sleep Association) and Margaret Sanger. Both Twilight Sleep and the birth control movement represent a distinct moment in the early 20th century wherein pain was deeply connected to politics and the rhetoric of equal rights. The two reformers emphasised in their publications and appeals to the public the vast social significance of reproductive pain-both physical and psychological. They contended that women's lack of control over both pregnancy and birth represented the greatest hindrance to women's fulfilment of their political rights and a danger to the healthy development of larger society. In their arguments for legal contraception, Dennett and Sanger placed women's pain front and centre as the primary reason for changing a law that hindered women's full participation in the public order.

A Survey Instrument to Assess Intake of Dietary Supplements, Related Products, and Caffeine in High-Use Populations.

Substantial data on the use of dietary supplements by the general adult population are available, but many population subgroups have not been extensively studied. Because military service members and young people consume large amounts of dietary supplements, including for enhancement of physical performance, weight control, and bodybuilding, which can be dangerous, we developed a comprehensive questionnaire to characterize patterns of supplement use in these and other populations. The questionnaire has been used to study >7000 military service members and 1000 college students. This supplement article presents a detailed description of the questionnaire, which contains comprehensive questions on demographic characteristics, exercise habits, attitudes with regard to dietary supplements, and amount of money spent on supplements. Intakes of specific dietary supplements and caffeine, frequency of use, and reasons for use are assessed. The questionnaire was designed for studying dietary supplement and caffeine intake patterns with the use of paper-and-pencil administration to military populations and was modified for use with college students and for computer and Web administration. It is available online at https://go.usa.gov/xn9FP and in the Supplemental File for this publication. It can be used to study other populations if minor modifications are made. The online version of the questionnairewill be updated periodically as newversions become available. In conclusion, a validated, detailed, noncopyrighted questionnaire designed to assess the use of dietary supplements, energy drinks (and related products), and caffeine is available for use in diverse populations. The format of the questionnaire is adaptable to computer administration and scoring, and it can be customized for specific subpopulations, locations, and product categories including updates that reflect changes in the availability of supplements or availability of new products.

Ruptured Abdominal Aortic Aneurysm: Prediction of Mortality From Clinical Presentation and Glasgow Aneurysm Score.

OBJECTIVE: To examine association of presenting clinical acuity and Glasgow Aneurysm Score (GAS) with perioperative and 1-year mortality. DESIGN: Retrospective chart review. SETTING: Major tertiary care facility. PARTICIPANTS: Patients with ruptured abdominal aortic aneurysm (rAAA) from 2003 through 2013. INTERVENTIONS: Emergency repair of rAAA. MEASUREMENTS AND MAIN RESULTS: The authors reviewed outcomes after stable versus unstable presentation and by GAS. Unstable presentation included hypotension, cardiac arrest, loss of consciousness, and preoperative tracheal intubation. In total, 125 patients (40 stable) underwent repair. Perioperative mortality rates were 41% and 12% in unstable and stable patients, respectively (p<0.001). Unstable status had 88% sensitivity and 41% specificity for predicting perioperative mortality. Using logistic regression, higher GAS was associated with perioperative mortality (p<0.001). Using receiver operating characteristic analysis, the area under the curve was 0.72 (95% CI, 0.62-0.82) and cutoff GAS≥96 had 63% and 72% sensitivity and specificity, respectively. Perioperative mortality for GAS≥96 was 51% (25/49), whereas it was 20% (15/76) for GAS≤95. The estimated 1-year survival (95% CI) was 75% (62%-91%) for stable patients and 48% (38%-60%) for unstable patients. Estimated 1-year survival (95% CI) was 23% (13%-40%) for GAS≥96 and 77% (67%-87%) for GAS≤95. CONCLUSIONS: Clinical presentation and GAS identified patients with rAAA who were likely to have a poor surgical outcome. GAS≥96 was associated with poor long-term survival, but>20% of these patients survived 1 year. Thus, neither clinical presentation nor GAS provided reliable guidance for decisions regarding futility of surgery.

ERK regulation of phosphodiesterase 4 enhances dopamine-stimulated AMPA receptor membrane insertion.

AMPA-type glutamate receptor (AMPAR) trafficking is essential for modulating synaptic transmission strength. Prior studies that have characterized signaling pathways underlying AMPAR trafficking have identified the cAMP/PKA-mediated phosphorylation of GluA1, an AMPAR subunit, as a key step in the membrane insertion of AMPAR. Inhibition of ERK impairs AMPAR membrane insertion, but the mechanism by which ERK exerts its effect is unknown. Dopamine, an activator of both PKA and ERK, induces AMPAR insertion, but the relationship between the two protein kinases in the process is not understood. We used a combination of computational modeling and live cell imaging to determine the relationship between ERK and PKA in AMPAR insertion. We developed a dynamical model to study the effects of phosphodiesterase 4 (PDE4), a cAMP phosphodiesterase that is phosphorylated and inhibited by ERK, on the membrane insertion of AMPAR. The model predicted that PKA could be a downstream effector of ERK in regulating AMPAR insertion. We experimentally tested the model predictions and found that dopamine-induced ERK phosphorylates and inhibits PDE4. This regulation results in increased cAMP levels and PKA-mediated phosphorylation of DARPP-32 and GluA1, leading to increased GluA1 trafficking to the membrane. These findings provide unique insight into an unanticipated network topology in which ERK uses PDE4 to regulate PKA output during dopamine signaling. The combination of dynamical models and experiments has helped us unravel the complex interactions between two protein kinase pathways in regulating a fundamental molecular process underlying synaptic plasticity.

Patient-reported outcomes in heart failure: existing measures and future uses.

Patient-reported outcomes (PROs) are any report obtained directly from a patient about how they feel or function in relation to their health condition and its therapies. Strong support for PROs exists at multiple levels of the health-care community from regulatory boards to clinical researchers. PROs are particularly important in heart failure because it is a common chronic illness marked with acute exacerbations, often requiring hospitalization, and significant symptom burden. Use of PROs to understand patient perspectives will help providers deliver more patient-centered care, and thus improve the quality of care. This review provides a contemporary overview of the current state of PROs in heart failure and suggests future directions and opportunities to advance PRO use to provide more comprehensive care. Advancing PRO measurement along with incorporating longitudinal measures in national databases and local electronic health records will serve to improve patient-centered care for patients with heart failure.

Erythematous nodule of the ear.

An elderly may with eccrine porocarcinoma of the ear is presented. This rare tumor in an unusual location has the potential for metastasis and local recurrence.

A Potentially Versatile Enzyme Sensor Platform: Enzyme-Loaded, Tagged, Porous Polymeric Nanocapsules.

Enzymes are essential to life and indispensable in a wide range of industries (food, pharmaceutical, medical, biosensing, etc.); however, a significant shortcoming of these fragile biological catalysts is their poor stability. To address this challenge, a variety of immobilization methods have been described to enhance the enzyme's stability. These immobilization methods generally are specific to an individual enzyme or optimal for a particular application. The aim of this study is to explore the utility of porous, indicator moiety-tagged, polymeric nanocapsules (NCs) for the encapsulation of enzymes and measurement of the enzyme's substrate. As a model enzyme, glucose oxidase (GOx) is used. The GOx enzyme-loaded, fluorophore-tagged NCs were synthesized by using self-assembled surfactant vesicle templates. To show that the biological activity of GOx is preserved during entrapment, the rate of the GOx enzyme catalyzed reaction was measured. To evaluate the protective features of the porous NCs, the encapsulated GOx enzyme activity was followed in the presence of hydrolytic enzymes. During the encapsulation of GOx and the purification of the GOx-loaded NCs, the GOx activity decayed less than 10%, and up to 30% of the encapsulated GOx activity could be retained for 3-5 days in the presence of hydrolytic enzymes. In support of the potentially unique advantages of the enzyme-loaded NCs, as a proof-of-concept example, the fluorophore-tagged, GOx-loaded NCs were used for the determination of glucose in the concentration range between 18 and 162 mg/dL and for imaging the distribution of glucose concentration in imaging experiments.

Differences in Sleep EEG Coherence and Spindle Metrics in Toddlers With and Without Language Delay: A Prospective Observational Study.

Background: Sleep plays a crucial role in early language development, and sleep disturbances are common in children with neurodevelopmental disorders. Examining sleep microarchitecture in toddlers with and without language delays can offer key insights into neurophysiological abnormalities associated with atypical neurodevelopmental trajectories and potentially aid in early detection and intervention. Methods: Here, we investigated electroencephalogram (EEG) coherence and sleep spindles in 16 toddlers with language delay (LD) compared with a group of 39 typically developing (TD) toddlers. The sample was majority male (n = 34, 62%). Participants were aged 12-to-22 months at baseline, and 34 (LD, n=11; TD, n=23) participants were evaluated again at 36 months of age. Results: LD toddlers demonstrated increased EEG coherence compared to TD toddlers, with differences most prominent during slow-wave sleep. Within the LD group, lower expressive language skills were associated with higher coherence in REM sleep. Within the TD group, lower expressive language skills were associated with higher coherence in slow-wave sleep. Sleep spindle density, duration, and frequency changed between baseline and follow-up for both groups, with the LD group demonstrating a smaller magnitude of change than the TD group. The direction of change was frequency-dependent for both groups. Conclusions: These findings indicate that atypical sleep EEG connectivity and sleep spindle development can be detected in toddlers between 12 and 36 months and offers insights into neurophysiological mechanisms underlying the etiology of neurodevelopmental disorders. Trial registration: https://clinicaltrials.gov/study/NCT01339767; Registration date: 4/20/2011.

The minor allele of the serotonin transporter gene variant rs4251417 is associated with increased resilience in soldiers experiencing acute stress during survival training: preliminary findings.

BACKGROUND: Variation in cognitive, emotional and physical performance in response to stress is attributable to environmental and genetic factors. Ability to adapt to stress is resilience. OBJECTIVES: This study investigated genetic factors associated with resilience in soldiers exposed to severe stress due to intense physical and mental demands at Survive, Evade, Resist and Escape school, a unique environment to study acute stress and resiliency in real-world circumstances. DESIGN: A preliminary correlational study was conducted to identify genetic markers for resilience to stress. METHODS: Mood state, resiliency and dissociative state of 73 soldiers were assessed using: Connor-Davidson Resilience Scale (CD-RISC); Profile of Mood States (POMS); and Clinician-Administered Dissociative States Scale (CADSS). Change scores for resilience-related stress markers were computed; 116 single nucleotide polymorphisms (SNPs) associated with stress, depression, anxiety, sleep, or psychiatric disorders were assessed. RESULTS: A significant association between change in CD-RISC score and SNP rs4251417, present in an intron of SLC6A4, the serotonin transporter gene, was observed. CONCLUSIONS: Individuals with the minor allele of SNP rs4251417 had a greater positive change in CD-RISC, indicating increased self-assessed resilience. This study suggests the minor allele of SNP rs4251417 of SLC6A4 is associated with resilience when individuals are exposed to high stress.

Determination of unbound platinum concentrations in human plasma using ultrafiltration and precipitation methods.

Quantification of the unbound portion of platinum (Pt) in human plasma is important for assessing the pharmacokinetics of the chemotherapeutic drug cisplatin. In this study, we sought to compare the recovery of unbound Pt using Nanosep® filters to 1) traditional filters (Centrifree®, Centrisart®, Amicon®) or trichloroacetic acid (TCA) protein precipitation, and 2) unbound, bound, and total Pt concentrations in clinical specimens. For the tested filters, the impact of 1) molecular weight cut-offs, 2) centrifugation force, and 3) total Pt concentration on Pt binding in human plasma was evaluated. Pt was quantified using inductively coupled-plasma mass spectrometry. In human plasma spiked with 0.9 µg/mL Pt, the percent of unbound Pt increased at higher centrifugation speeds. By comparison, the percent of unbound Pt was highest (42.1%) following TCA protein precipitation. When total Pt was ≤0.9 µg/mL, unbound Pt (∼20-30%) was consistent across filters. Conversely, when plasma was spiked with Pt exceeding 0.9 µg/mL, the percent of unbound Pt increased from 36.5 to 48% using ultrafiltration, compared to 63.4% to 79% with TCA precipitation. In patients receiving cisplatin-containing chemotherapy, the fraction of unbound Pt at concentrations exceeding 0.9 µg/mL ranged between 35 and 90%. Moreover, the unbound fraction of Pt in plasma correlated with the concentration of unbound (R2 = 0.738) and total Pt (R2 = 0.335). In summary, this study demonstrates that 1) the percent of unbound Pt is influenced by total and unbound Pt levels in vitro and in clinical specimens, and 2) ultrafiltration with Nanosep® filters is a feasible method for quantifying unbound Pt concentrations in human plasma.