Use of Cotton Balls in Diapers for Collection of Urine Samples Impacts the Analysis of Routine Chemistry Tests: An Evaluation of Cotton Balls, Diapers, and Chemistry Analyzers.

OBJECTIVE: To evaluate the suitability of urine samples collected with cotton balls placed into diapers for routine laboratory chemistry analyses. STUDY DESIGN: Twenty pools of residual unpreserved urine samples were separated into control and treated aliquots. The treated samples were absorbed into 2 different brands of cotton balls, wrapped in 3 different brands of diapers, and incubated at 37°C for 1 hour. The urine-soaked cotton balls were placed into a syringe and expressed via plunger depression. Urine sodium, potassium, creatinine, urea, calcium, magnesium, inorganic phosphorus, albumin, and total protein were measured on all samples on 5 automated clinical chemistry platforms: Ortho Vitros 4600, Siemens Dimension Vista 500, Beckman Coulter AU5822, Roche Cobas 6000, and Abbott Architect c8000 at 5 separate hospital laboratories. Criteria used to exclude the presence of significant effects of urine from presoaked cotton balls in a diaper on the measurement of chemistry laboratory tests were R2 >0.95, slope of 0.9-1.1, and mean bias within ±10%. RESULTS: Albumin and total protein measurements demonstrated significant negative bias in urine from both brands of presoaked cotton balls with all brands of diapers on all 5 chemistry platforms compared with the control urine. We did not observe a significant effect of presoaking urine in cotton balls in a diaper on the measurement of sodium, inorganic phosphorus, and urea. The remaining tests demonstrated significant effects when measured in urine from presoaked cotton balls and/or diapers that were specific to the chemistry analyzer platform or diaper. CONCLUSIONS: Diaper and cotton ball-based urine collection significantly impacts the measurement of several common chemistry assays.

Characterization of biotin interference in 21 Vitros 5600 immunoassays and risk mitigation for patient safety at a large academic medical center.

BACKGROUND: Biotin and streptavidin are commonly used reagents in clinical immunoassays. Several cases of biotin interference with immunoassay testing for patients taking biotin supplements have been reported, yet, not all analytes and platforms susceptible to biotin interference have been characterized. The objectives of this study are to characterize biotin interference with 21 immunoassays using the Ortho Clinical Diagnostics Vitros 5600, evaluate a biotin-depletion method, and apply risk mitigation strategies for biotin interference during routine clinical testing at our institution. METHODS: Residual serum without and with increasing concentrations of exogenous biotin were used to evaluate biotin interference with 21 immunoassays using the Vitros 5600. Biotin-depletion was evaluated by comparing measured analyte concentrations in serum with and without exogenous biotin and streptavidin-microparticle pretreatment. Focused education for healthcare professionals about biotin interference was performed in February 2018. Samples with suspected biotin interference were investigated using this biotin-depletion method, and analyte testing by alternate methodology for select samples. RESULTS: Exogenous biotin in serum caused dose-dependent negative biases in 15 immunometric assays, and dose-dependent positive biases in 6 competitive immunoassays. Streptavidin-microparticle pretreatment of serum containing exogenous biotin demonstrated recoveries 100 ±â€¯15% of expected values for all 21 analytes. Physicians identified 21 samples suspicious for biotin interference over 11 months, and streptavidin-microparticle pretreatment verified 11 cases of biotin interference. CONCLUSIONS: Analytical bias caused by biotin interference is dependent on biotin concentration but independent of analyte concentration for immunometric methods using the Vitros 5600, and dependent on both biotin and analyte concentration for competitive immunoassays. Multi-disciplinary education and a lab streptavidin-microparticle pretreatment method help mitigate risk of erroneous results due to biotin interference for patient safety.

Suspected Testosterone-Producing Tumor in a Patient Taking Biotin Supplements.

A perimenopausal woman presented with palpitations, hirsutism, and inability to lose weight. Laboratory tests revealed an unusual endocrine hormonal profile including pituitary hormones (TSH, ACTH, and prolactin) below reference intervals and gonadal (testosterone) and adrenal (cortisol) hormones above reference intervals. Ultimately, after a comprehensive workup including a scheduled surgical procedure, abnormal laboratories were determined due to biotin interference. Biotin (vitamin B7) is a water-soluble vitamin and essential cofactor for the metabolism of fatty acids, glucose, and amino acids. The recommended daily intake of biotin for adults is 30 µg/d. Many over-the-counter products, particularly those marketed for hair, skin, and nail growth, contain biotin 100-fold of recommended daily intake. This case is unique due to the abnormalities observed not only in the well-described TSH "sandwich" immunoassay, but also in tests for gonadal steroids, adrenal, and pituitary hormones. Falsely high as well as falsely low results can be ascribed to biotin. Competitive immunoassays (Fig. 1A)- in this case, tests used initially for serum cortisol and testosterone- can demonstrate falsely high results. Interference falsely lowers the immunometric "sandwich" immunoassay (Fig. 1B)-in this case, TSH. Biotin effect on our patient's endocrine testing led to decidedly abnormal findings, unnecessary medical referrals and diagnostic studies, and comprehensible psychological distress. Interference with one immunoassay, TSH, persisted a full 2 weeks after discontinuation of biotin; indeed, some tests demonstrate sensitivity to lesser quantities of biotin. Improved communication between patients, health care providers, and laboratory professionals is required concerning the likelihood of biotin interference with immunoassays.

Down-regulation of NOX2 activity in phagocytes mediated by ATM-kinase dependent phosphorylation.

NADPH oxidases (NOX) have many biological roles, but their regulation to control production of potentially toxic ROS molecules remains unclear. A previously identified insertion sequence of 21 residues (called NIS) influences NOX activity, and its predicted flexibility makes it a good candidate for providing a dynamic switch controlling the NOX active site. We constructed NOX2 chimeras in which NIS had been deleted or exchanged with those from other NOXs (NIS1, 3 and 4). All contained functional heme and were expressed normally at the plasma membrane of differentiated PLB-985 cells. However, NOX2-ΔNIS and NOX2-NIS1 had neither NADPH-oxidase nor reductase activity and exhibited abnormal translocation of p47phox and p67phox to the phagosomal membrane. This suggested a functional role of NIS. Interestingly after activation, NOX2-NIS3 cells exhibited superoxide overproduction compared with wild-type cells. Paradoxically, the Vmax of purified unstimulated NOX2-NIS3 was only one-third of that of WT-NOX2. We therefore hypothesized that post-translational events regulate NOX2 activity and differ between NOX2-NIS3 and WT-NOX2. We demonstrated that Ser486, a phosphorylation target of ataxia telangiectasia mutated kinase (ATM kinase) located in the NIS of NOX2 (NOX2-NIS), was phosphorylated in purified cytochrome b558 after stimulation with phorbol 12-myristate-13-acetate (PMA). Moreover, ATM kinase inhibition and a NOX2 Ser486Ala mutation enhanced NOX activity whereas a Ser486Glu mutation inhibited it. Thus, the absence of Ser486 in NIS3 could explain the superoxide overproduction in the NOX2-NIS3 mutant. These results suggest that PMA-stimulated NOX2-NIS phosphorylation by ATM kinase causes a dynamic switch that deactivates NOX2 activity. We hypothesize that this downregulation is defective in NOX2-NIS3 mutant because of the absence of Ser486.

Envisioning a social-health information exchange as a platform to support a patient-centered medical neighborhood: a feasibility study.

BACKGROUND: Social determinants directly contribute to poorer health, and coordination between healthcare and community-based resources is pivotal to addressing these needs. However, our healthcare system remains poorly equipped to address social determinants of health. The potential of health information technology to bridge this gap across the delivery of healthcare and social services remains unrealized. OBJECTIVE, DESIGN, AND PARTICIPANTS: We conducted in-depth, in-person interviews with 50 healthcare and social service providers to determine the feasibility of a social-health information exchange (S-HIE) in an urban safety-net setting in Dallas County, Texas. After completion of interviews, we conducted a town hall meeting to identify desired functionalities for a S-HIE. APPROACH: We conducted thematic analysis of interview responses using the constant comparative method to explore perceptions about current communication and coordination across sectors, and barriers and enablers to S-HIE implementation. We sought participant confirmation of findings and conducted a forced-rank vote during the town hall to prioritize potential S-HIE functionalities. KEY RESULTS: We found that healthcare and social service providers perceived a need for improved information sharing, communication, and care coordination across sectors and were enthusiastic about the potential of a S-HIE, but shared many technical, legal, and ethical concerns around cross-sector information sharing. Desired technical S-HIE functionalities encompassed fairly simple transactional operations such as the ability to view basic demographic information, visit and referral data, and medical history from both healthcare and social service settings. CONCLUSIONS: A S-HIE is an innovative and feasible approach to enabling better linkages between healthcare and social service providers. However, to develop S-HIEs in communities across the country, policy interventions are needed to standardize regulatory requirements, to foster increased IT capability and uptake among social service agencies, and to align healthcare and social service priorities to enable dissemination and broader adoption of this and similar IT initiatives.

An examination of end-of-life care in a safety net hospital system: a decade in review.

OBJECTIVES: To examine patterns of use of end-of-life care in patients receiving treatment at a large, urban safety-net hospital from 2000 to 2010. METHODS: Data from the Parkland Hospital palliative care database, which tracked all consults for this period, were analyzed. Logistic regression was used to identify predictors of hospice use, and Cox proportional hazards modeling to examine survival. RESULTS: There were 5,083 palliative care consults over the study period. More patients were Black (41%) or White (31%), and younger than 65 years old (75%). Cancer patients or those who received palliative care services longer were more likely to receive hospice; those who had no form of health care assistance were less likely. There were no racial/ethnic differences in hospice use. CONCLUSION: In this cohort, there were no racial/ethnic disparities in hospice use. Those who had no form of health care assistance were less likely to receive hospice.

Predictors of intensive end-of-life and hospice care in Latino and white advanced cancer patients.

BACKGROUND: The role of end-of-life (EOL) care preferences and conversations in receipt of care near death for Latinos is unclear. OBJECTIVE: This study examines rates and predictors of intensive EOL and hospice care among Latino and white advanced cancer patients. DESIGN: Two-hundred-and-ninety-two self-reported Latino (n=58) and white (n=234) Stage IV cancer patients participated in a U.S. multisite, prospective, cohort study from September 2002 to August 2008. The Latino and white, non-Hispanic participants were interviewed and followed until death, a median of 118.5 days from baseline. MEASUREMENTS: Patient-reported, baseline predictors of EOL care included EOL care preference; terminal illness acknowledgement; EOL discussion; completion of a DNR order; and religious coping. Caregiver postmortem interviews provided information regarding EOL care received. Intensive EOL care was defined as resuscitation and/or ventilation followed by death in an intensive care unit. Hospice was either in- or outpatient. RESULTS: Latino and white patients received intensive EOL and hospice care at similar rates (5.2% and 3.4% for intensive care, p=0.88; 70.7% versus 73.4% for hospice, p=0.33). No white or Latino patient who reported a DNR order or EOL discussion at baseline received intensive EOL care. Religious coping and a preference for life-extending care predicted intensive EOL care for white patients (adjusted odds ratio [aOR] 6.69 [p=0.02] and aOR 6.63 [p=0.01], respectively), but not for Latinos. No predictors were associated with Latino hospice care. CONCLUSIONS: EOL discussions and DNR orders may prevent intensive EOL care among Latino cancer patients. Efforts should continue to engage Latino patients and caregivers in these activities.

United states acculturation and cancer patients' end-of-life care.

BACKGROUND: Culture shapes how people understand illness and death, but few studies examine whether acculturation influences patients' end-of-life treatment preferences and medical care. METHODS AND FINDINGS: In this multi-site, prospective, longitudinal cohort study of terminally-ill cancer patients and their caregivers (n = 171 dyads), trained interviewers administered the United States Acculturation Scale (USAS). The USAS is a 19-item scale developed to assess the degree of "Americanization" in first generation or non-US born caregivers of terminally-ill cancer patients. We evaluated the internal consistency, concurrent, criterion, and content validity of the USAS. We also examined whether caregivers' USAS scores predicted patients' communication, treatment preferences, and end-of-life medical care in multivariable models that corrected for significant confounding influences (e.g. education, country of origin, English proficiency). The USAS measure was internally consistent (Cronbach α = 0.98); and significantly associated with US birthplace (r = 0.66, P<0.0001). USAS scores were predictive of patients' preferences for prognostic information (AOR = 1.31, 95% CI:1.00-1.72), but not comfort asking physicians' questions about care (AOR 1.23, 95% CI:0.87-1.73). They predicted patients' preferences for feeding tubes (AOR = 0.68, 95% CI:0.49-0.99) and wish to avoid dying in an intensive care unit (AOR = 1.36, 95% CI:1.05-1.76). Scores indicating greater acculturation were also associated with increased odds of patient participation in clinical trials (AOR = 2.20, 95% CI:1.28-3.78), compared with lower USAS scores, and greater odds of patients receiving chemotherapy (AOR = 1.59, 95% CI:1.20-2.12). CONCLUSION: The USAS is a reliable and valid measure of "Americanization" associated with advanced cancer patients' end-of-life preferences and care. USAS scores indicating greater caregiver acculturation were associated with increased odds of patient participation in cancer treatment (chemotherapy, clinical trials) compared with lower scores. Future studies should examine the effects of acculturation on end-of-life care to identify patient and provider factors that explain these effects and targets for future interventions to improve care (e.g., by designing more culturally-competent health education materials).

Benjamin Franklin, Philadelphia's favorite son, was a membrane biophysicist.

Benjamin Franklin, mostly known for his participation in writing The Declaration of Independence and work on electricity, was also one of the first scientists to seek to understand the properties of oil monolayers on water surfaces. During one of his many voyages across the Atlantic Ocean, Franklin observed that oil had a calming effect on waves when poured into rough ocean waters. Though at first taking a backseat to many of his other scientific and political endeavors, Franklin went on to experiment with oil, spreading monomolecular films on various bodies of water, and ultimately devised a concept of particle repulsion that is indirectly related to the hydrophobic effect. His early observations inspired others to measure the dimensions of oil monolayers, which eventually led to the formulation of the contemporary lipid bilayer model of the cell membrane.

Impact of social factors on risk of readmission or mortality in pneumonia and heart failure: systematic review.

BACKGROUND: Readmission and mortality after hospitalization for community-acquired pneumonia (CAP) and heart failure (HF) are publically reported. This systematic review assessed the impact of social factors on risk of readmission or mortality after hospitalization for CAP and HF-variables outside a hospital's control. METHODS: We searched OVID, PubMed and PSYCHINFO for studies from 1980 to 2012. Eligible articles examined the association between social factors and readmission or mortality in patients hospitalized with CAP or HF. We abstracted data on study characteristics, domains of social factors examined, and presence and magnitude of associations. RESULTS: Seventy-two articles met inclusion criteria (20 CAP, 52 HF). Most CAP studies evaluated age, gender, and race and found older age and non-White race were associated with worse outcomes. The results for gender were mixed. Few studies assessed higher level social factors, but those examined were often, but inconsistently, significantly associated with readmissions after CAP, including lower education, low income, and unemployment, and with mortality after CAP, including low income. For HF, older age was associated with worse outcomes and results for gender were mixed. Non-Whites had more readmissions after HF but decreased mortality. Again, higher level social factors were less frequently studied, but those examined were often, but inconsistently, significantly associated with readmissions, including low socioeconomic status (Medicaid insurance, low income), living situation (home stability rural address), lack of social support, being unmarried and risk behaviors (smoking, cocaine use and medical/visit non-adherence). Similar findings were observed for factors associated with mortality after HF, along with psychiatric comorbidities, lack of home resources and greater distance to hospital. CONCLUSIONS: A broad range of social factors affect the risk of post-discharge readmission and mortality in CAP and HF. Future research on adverse events after discharge should study social determinants of health.

Associations between United States acculturation and the end-of-life experience of caregivers of patients with advanced cancer.

BACKGROUND: Cultural beliefs and values influence treatment preferences for and experiences with end-of-life (EOL) care among racial and ethnic groups. Within-group variations, however, may exist based on level of acculturation. OBJECTIVES: To examine the extent to which EOL treatment factors (EOL treatment preferences and physician-caregiver communication) and select psychosocial factors (mental health, complementary therapies, and internal and external social support) differ based on the level of acculturation of caregivers of patients with advanced cancer. METHODS: One hundred sixty-seven primary caregivers of patients with advanced cancer were interviewed as part of the multisite, prospective Coping with Cancer Study. RESULTS: Caregivers who were less acculturated were more positively predisposed to use of a feeding tube at EOL (odds ratio [OR] 0.99 [p = 0.05]), were more likely to perceive that they received too much information from their doctors (OR 0.95 [p = 0.05]), were less likely to use mental health services (OR 1.03 [p = 0.003] and OR 1.02 [p = 0.02]), and desire additional services (OR 1.03 [p = 0.10] to 1.05 [p = 0.009]) than their more acculturated counterparts. Additionally, caregivers who were less acculturated cared for patients who were less likely to report having a living will (OR 1.03 [p = 0.0003]) or durable power of attorney for health care (OR 1.02 [p = 0.007]) than more acculturated caregivers. Caregivers who were less acculturated felt their religious and spiritual needs were supported by both the community (beta -0.28 [p = 0.0003]) and medical system (beta -0.38 [p < 0.0001]), had higher degrees of self-efficacy (beta -0.22 [p = 0.005]), and had stronger family relationships and support (beta -0.27 [p = 0.0004]). CONCLUSIONS: The level of acculturation of caregivers of patients with advanced cancer does contribute to differences in EOL preferences and EOL medical decision-making.

Racial differences in predictors of intensive end-of-life care in patients with advanced cancer.

PURPOSE: Black patients are more likely than white patients to receive life-prolonging care near death. This study examined predictors of intensive end-of-life (EOL) care for black and white advanced cancer patients. PATIENTS AND METHODS: Three hundred two self-reported black (n = 68) and white (n = 234) patients with stage IV cancer and caregivers participated in a US multisite, prospective, interview-based cohort study from September 2002 to August 2008. Participants were observed until death, a median of 116 days from baseline. Patient-reported baseline predictors included EOL care preference, physician trust, EOL discussion, completion of a Do Not Resuscitate (DNR) order, and religious coping. Caregiver postmortem interviews provided information regarding EOL care received. Intensive EOL care was defined as resuscitation and/or ventilation followed by death in an intensive care unit. RESULTS: Although black patients were three times more likely than white patients to receive intensive EOL care (adjusted odds ratio [aOR] = 3.04, P = .037), white patients with a preference for this care were approximately three times more likely to receive it (aOR = 13.20, P = .008) than black patients with the same preference (aOR = 4.46, P = .058). White patients who reported an EOL discussion or DNR order did not receive intensive EOL care; similar reports were not protective for black patients (aOR = 0.53, P = .460; and aOR = 0.65, P = .618, respectively). CONCLUSION: White patients with advanced cancer are more likely than black patients with advanced cancer to receive the EOL care they initially prefer. EOL discussions and DNR orders are not associated with care for black patients, highlighting a need to improve communication between black patients and their clinicians.

Development of geriatrics-oriented faculty in general internal medicine.

The need for adequate geriatrics training for the physician workforce has been recognized for decades. However, there are not enough academic geriatricians to provide for the educational needs of trainees, and this situation is not expected to change in the future. General internists are often responsible for teaching medical students and internal medicine residents to care for elderly patients in inpatient and ambulatory settings. These academic general internists could play a pivotal role in providing geriatrics instruction. To characterize what is being done to develop geriatrics-oriented general internal medicine faculty, we identified current practices, "best practices," goals and targets, and barriers to achieving those goals and targets. We reviewed the literature on faculty-development programs for general internal medicine faculty, and we held focus groups and structured interviews with general internal medicine unit chiefs and directors of Geriatric Centers of Excellence at 46 medical schools throughout the United States. We found a need for programs to develop geriatrics-oriented academic general internists. Although general internal medicine faculties seem receptive to further geriatrics training, important obstacles exist. These include inadequate time and resources as well as motivational and attitudinal challenges. We discuss potential solutions for overcoming these barriers and the implications of these solutions for stakeholders.