Discharge Opioids are Unnecessary Following Radical Cystectomy.

OBJECTIVE: To show that zero-opioid discharges after both open and robotic cystectomy are feasible and to examine the impact of zero-opioid discharges on patient interaction with the physician's office. MATERIALS AND METHODS: One hundred seven patients who underwent either open or robotic radical cystectomy from March 1, 2020 to December 30, 2020 were identified. Patient demographics, perioperative data, and 30 day pain related outcomes including phone calls, office visits, requests for pain medication, emergency department visits, and readmissions were abstracted from the chart. We then examined variables associated with a zero-opioid discharge. RESULTS: Thirty-two patients were discharged with an opioid prescription (Median Oral Morphine Equivalents Prescribed = 90) and 75 were discharged without an opioid prescription. On regression analysis, age (OR 1.07, 95% CI [1.02-1.12]) and pathology (OR 0.36, 95% CI[0.14-0.9]) remained significantly associated with post-operative opioid prescriptions. There were no differences in the percent of patients presenting to the emergency department, being readmitted, calling the office, calling the office regarding pain, or requesting opioid prescriptions within 30 days of discharge, or the number of post-operative office visits (P >.05 for all). CONCLUSION: Patients can safely be discharged home without opioids following cystectomy, regardless of robotic or open approach. Age and pathology are predictors of the need for an opioid prescription on discharge. These patients did not have increased follow-up visits, phone calls, or requests for pain medication.

Chromosomal microarray impacts clinical management.

Chromosomal microarray analysis (CMA) is standard of care, first-tier clinical testing for detection of genomic copy number variation among patients with developmental disabilities. Although diagnostic yield is higher than traditional cytogenetic testing, management impact has not been well studied. We surveyed genetic services providers regarding CMA ordering practices and perceptions about reimbursement. Lack of insurance coverage because of perceived lack of clinical utility was cited among the most frequent reasons why CMA was not ordered when warranted. We compiled a list of genomic regions where haploinsufficiency or triplosensitivity cause genetic conditions with documented management recommendations, estimating that at least 146 conditions potentially diagnosable by CMA testing have published literature supporting specific clinical management implications. Comparison with an existing clinical CMA database to determine the proportion of cases involving these regions showed that CMA diagnoses associated with such recommendations are found in approximately 7% of all cases (n = 28,526). We conclude that CMA impacts clinical management at a rate similar to other genetic tests for which insurance coverage is more readily approved. The information presented here can be used to address barriers that continue to contribute to inequities in patient access and care in regard to CMA testing.

Adaptive optics and the eye (super resolution OCT).

The combination of adaptive optics (AO) and optical coherence tomography (OCT) was first reported 8 years ago and has undergone tremendous technological advances since then. The technical benefits of adding AO to OCT (increased lateral resolution, smaller speckle, and enhanced sensitivity) increase the imaging capability of OCT in ways that make it well suited for three-dimensional (3D) cellular imaging in the retina. Today, AO-OCT systems provide ultrahigh 3D resolution (3 × 3 × 3 µm³) and ultrahigh speed (up to an order of magnitude faster than commercial OCT). AO-OCT systems have been used to capture volume images of retinal structures, previously only visible with histology, and are being used for studying clinical conditions. Here, we present representative examples of cellular structures that can be visualized with AO-OCT. We overview three studies from our laboratory that used ultrahigh-resolution AO-OCT to measure the cross-sectional profiles of individual bundles in the retinal nerve fiber layer; the diameters of foveal capillaries that define the terminal rim of the foveal avascular zone; and the spacing and length of individual cone photoreceptor outer segments as close as 0.5° from the fovea center.

Microdeletion/duplication at 15q13.2q13.3 among individuals with features of autism and other neuropsychiatric disorders.

BACKGROUND: Segmental duplications at breakpoints (BP4-BP5) of chromosome 15q13.2q13.3 mediate a recurrent genomic imbalance syndrome associated with mental retardation, epilepsy, and/or electroencephalogram (EEG) abnormalities. PATIENTS: DNA samples from 1445 unrelated patients submitted consecutively for clinical array comparative genomic hybridisation (CGH) testing at Children's Hospital Boston and DNA samples from 1441 individuals with autism from 751 families in the Autism Genetic Resource Exchange (AGRE) repository. RESULTS: We report the clinical features of five patients with a BP4-BP5 deletion, three with a BP4-BP5 duplication, and two with an overlapping but smaller duplication identified by whole genome high resolution oligonucleotide array CGH. These BP4-BP5 deletion cases exhibit minor dysmorphic features, significant expressive language deficits, and a spectrum of neuropsychiatric impairments that include autism spectrum disorder, attention deficit hyperactivity disorder, anxiety disorder, and mood disorder. Cognitive impairment varied from moderate mental retardation to normal IQ with learning disability. BP4-BP5 covers approximately 1.5 Mb (chr15:28.719-30.298 Mb) and includes six reference genes and 1 miRNA gene, while the smaller duplications cover approximately 500 kb (chr15:28.902-29.404 Mb) and contain three reference genes and one miRNA gene. The BP4-BP5 deletion and duplication events span CHRNA7, a candidate gene for seizures. However, none of these individuals reported here have epilepsy, although two have an abnormal EEG. CONCLUSIONS: The phenotype of chromosome 15q13.2q13.3 BP4-BP5 microdeletion/duplication syndrome may include features of autism spectrum disorder, a variety of neuropsychiatric disorders, and cognitive impairment. Recognition of this broader phenotype has implications for clinical diagnostic testing and efforts to understand the underlying aetiology of this syndrome.

Influence of genetic variation in the C-reactive protein gene on the inflammatory response during and after acute coronary ischemia.

The aim of this research was to assess whether common genetic variants within the C-reactive protein gene (CRP) are related to the degree of acute rise in plasma C-reactive protein (CRP) levels following an acute coronary syndrome (ACS). While polymorphisms within CRP are associated with basal CRP levels in healthy men and women, less is known about the relationship of such genetic variants and the degree of CRP rise during and after acute ischemia. Plasma CRP is associated with increased rates of recurrent coronary events. We evaluated seven common genetic variants within CRP and assessed their relationship to the degree of rise in CRP levels immediately following an acute coronary syndrome in 1827 European American patients. Variants in the putative promoter region, -757T > C and -286C > T > A, were associated with the highest CRP elevations after ACS. Patients with two copies of the A allele of SNP -286C > T > A had median CRP values of 76.6 mg/L, compared to 11.1 mg/L in patients with no copies of the rare variant (p-value <0.0001), post ACS. The lowest CRP values were found for patients with minor alleles of the exonic 1059G > C and the 3'untranslated region 1846G > A SNPs. For example, patients homozygous for the minor allele of 1059G > C had 71% lower median CRP values than those homozygous for the major allele [3.5 vs 12.0 mg/L, p < 0.0001]. These trends persisted in the chronic stable phase after ischemia had resolved, and after adjustment for infarct size by peak creatinine kinase levels and clinical status by Killip class. Assessment of CRP genetic variants identified patients with higher and lower CRP elevation after acute coronary syndrome.

Genetic determinants of C-reactive protein in COPD.

Chronic obstructive pulmonary disease (COPD) is associated with a systemic inflammatory state, marked by elevations in serum inflammatory markers including C-reactive protein (CRP). The present study sought to determine epidemiological predictors of CRP levels, to estimate the genetic influence on CRP levels, and to identify genetic variants that affect CRP in a family-based study of COPD. CRP was measured by a high-sensitivity assay in participants from the Boston Early-Onset COPD Study. Predictors of CRP level were determined using multilevel linear models. Variance component analysis was used to estimate heritability and to perform genome-wide linkage analysis for CRP levels. Two variants in the surfactant protein B (SFTPB) gene were tested for association with CRP levels. Increased age, female sex, higher body mass index, greater smoking pack-yrs and reduced forced expiratory volume in one second were all associated with increased CRP levels. There was a significant genetic influence on CRP (heritability = 0.25). Genome-wide linkage analysis revealed several potentially interesting chromosomal regions, though no significant evidence for linkage was found. A short tandem repeat marker near SFTPB was significantly associated with CRP levels. There is a genetic influence on C-reactive protein levels in chronic obstructive pulmonary disease patients. Preliminary evidence suggests an association of the surfactant protein B gene with systemic inflammation in chronic obstructive pulmonary disease.

Association of common CRP gene variants with CRP levels and cardiovascular events.

C-reactive protein (CRP) is a well-documented marker of atherosclerotic cardiovascular disease risk. We resequenced CRP to identify a comprehensive set of common SNP variants, then studied and replicated their association with baseline CRP level among apparently healthy subjects in the Women's Health Study (WHS; n = 717), Pravastatin Inflammation/CRP Evaluation trial (PRINCE; n = 1,110) and Physicians' Health Study (PHS; n = 509) cohorts. The minor alleles of four SNPs were consistently associated in all three cohorts with higher CRP, while the minor alleles of two SNPs were associated with lower CRP (p < 0.05 for each). Single marker and haplotype analysis in all three cohorts were consistent with functional roles for the 5'-flanking triallelic SNP -286C>T>A and the 3'-UTR SNP 1846G>A. None of the SNPs associated with higher CRP were associated with risk of incident myocardial infarction (MI) or ischemic stroke in a prospective, nested case-control study design from the PHS cohort (610 case-control pairs). One SNP, -717A>G, was unrelated to CRP levels but associated with decreased risk of MI (p = 0.001). Taken together, these data imply significant interactions between both genetic and environmental contributions to the increased CRP levels that predict a greater risk of future atherothrombotic events in epidemiological studies.

Moral credentials and the expression of prejudice.

Three experiments supported the hypothesis that people are more willing to express attitudes that could be viewed as prejudiced when their past behavior has established their credentials as nonprejudiced persons. In Study 1, participants given the opportunity to disagree with blatantly sexist statements were later more willing to favor a man for a stereotypically male job. In Study 2, participants who first had the opportunity to select a member of a stereotyped group (a woman or an African American) for a category-neutral job were more likely to reject a member of that group for a job stereotypically suited for majority members. In Study 3, participants who had established credentials as nonprejudiced persons revealed a greater willingness to express a politically incorrect opinion even when the audience was unaware of their credentials. The general conditions under which people feel licensed to act on illicit motives are discussed.

The norm of self-interest and its effects on social action.

Four studies investigated whether people feel inhibited from engaging in social action incongruent with their apparent self-interest. Participants in Study 1 predicted that they would be evaluated negatively were they to take action on behalf of a cause in which they had no stake or in which they had a stake but held stake-incongruent attitudes. Participants in Study 2 reported both surprise and anger when a target person took action on behalf of a cause in which he or she had no stake or in which he or she held stake-incongruent attitudes. In Study 3, individuals felt more comfortable engaging in social action and expected others to respond more favorably toward their actions if the issue was described as more relevant to their own sex than to the opposite sex. In Study 4, the authors found that providing nonvested individuals with psychological standing rendered them as likely as vested individuals to undertake social action. The authors discuss the implications of these results for the relationship between vested interest, social action, and attitude-behavior consistency.

Disrespect and the experience of injustice.

This review analyzes research and theory pertaining to the psychology of injustice, using as its organizing theme the role that the perception of disrespect plays in the experience of injustice. The analysis focuses primarily on the links between disrespect and anger, disrespect and injustice, and anger and injustice. Determinants of the intensity of people's reactions to injustices are also reviewed. In addition, the review examines the goals of retaliation as well as the forms that retaliation can take. Parallels between justice reactions to those acts of disrespect directed toward the self and those directed toward others are noted. Finally, the review discusses the implications of justice research for understanding the specific and general entitlements that people believe are their due.

Contributions of flow cytometry to the analysis of the myelodysplastic syndrome.

As the population of North America ages, the incidence of MDS is likely to rise. Epidemiologic survey instruments need to be put in place to document changes in the incidence. The basic mechanism of disease in MDS is largely unknown. No unifying, testable hypothesis is yet available, but apoptosis, with mitochondria playing a key role, are central to any discussion of MDS. Cytogenetic abnormalities have not provided an explanation of MDS but are of diagnostic and prognostic significance. The emergence of immunologic factors is of major importance and emphasizes the need for early detection. Flow cytometry can be used diagnostically to exclude other causes of cytopenias, document the phenotypic manifestations of myeloid dysmaturation, and provide blast enumeration. The distinctions between MDS and acute leukemia are arbitrary, and the process should be conceptualized as a continuum. There is a need for continued work to establish minimal diagnostic criteria for MDS. The current prognostic scoring systems do not incorporate findings from the newer technologies.

Analysis of factors influencing the comparison of homocysteine values between the Third National Health and Nutrition Examination Survey (NHANES) and NHANES 1999+.

Two important changes occurred in the time between the Third National Health and Nutrition Examination Survey (NHANES III) (1991-1994) and the later survey (NHANES 1999+) regarding total homocysteine (tHcy), i.e., a change in matrix from serum to plasma and a change in analytical methods. The goals of this study were to determine the magnitude of potential differences between plasma and serum with regard to tHcy concentrations, and between the two analytical methods used in these surveys. Optimally prepared plasma, serum allowed to clot for 30 and 60 min at room temperature and serum allowed to clot for 30 and 60 min and subjected to four freeze-thaw cycles, prepared from blood samples collected from 30 healthy people, were analyzed by both methods. Serum samples had significantly higher tHcy concentrations than plasma samples, and the difference increased with longer clotting time. Freeze-thaw cycles had little or no effect on the variability or bias in the serum sample results. The tHcy results produced by the two analytical methods were significantly different, but consistent across sample types. On average, the results of the method used in NHANES III were lower by 0.64 micromol/L; however, the relative bias varied with tHcy concentration. The tHcy results determined in surplus serum from NHANES III overestimated tHcy concentrations by approximately 10% compared with optimally prepared plasma. The average method bias was 6% between the two analytical methods. On the basis of changes in matrix and methodology, direct comparison of tHcy results between the two surveys is inappropriate.

The Drosophila primo locus encodes two low-molecular-weight tyrosine phosphatases.

The fine modulation of tyrosine phosphorylation by protein tyrosine phosphatases and protein tyrosine kinases is a key regulatory mechanism for many cell signaling pathways active during development. In a screen for genes with interesting expression patterns in the developing Drosophila pupal retina, we identified a novel pair of protein tyrosine phosphatases that exhibit an expression pattern suggesting a role in multiple steps of Drosophila neurogenesis. Together, these phosphatases define the primo locus. Their sequence is approx. 50% identical to each other and to low-molecular-weight protein tyrosine phosphatases (LMW-PTPs) identified in other species. Little is understood of the biological role of LMW-PTPs, and the powerful tools available in Drosophila should provide important insight into their role in signaling and development.

Exposure of the U.S. population aged 6 years and older to cadmium: 1988-1994.

Cadmium was measured in urine specimens from 22,162 participants in the Third National Health and Nutrition Examination Survey (NHANES III 1988-1994). Urine cadmium, expressed either as uncorrected (microg/L) or creatinine corrected (microg/g creatinine) increased with age and with smoking. The arithmetic mean value for urine cadmium in the U.S. population was 0.57 microg/L or 0.48 microg/g creatinine. Based on our estimates, about 2.3% of the U.S. population have urine cadmium concentrations greater than 2 microg/g creatinine, and 0.2% have concentrations greater than 5 microg/g creatinine, the current World Health Organization health-based exposure limit.

Comparison of serum and plasma methylmalonic acid measurements in 13 laboratories: An international study.

BACKGROUND: Detection of cobalamin deficiency is increasingly important, and methylmalonic acid (MMA) appears to be a useful marker. Information on interlaboratory variation and on methodological differences for MMA in serum and plasma is limited. METHODS: Using gas chromatography/mass spectrometry, 13 laboratories participated in a 2-day analysis of 8 serum and 11 EDTA-plasma specimens. Results were analyzed for imprecision, recovery, and differences among laboratories and methods. RESULTS: The mean among-laboratory imprecision (CV) was 19% and 21% for serum and plasma samples, respectively, and 9.3% and 7.8% for serum and plasma samples with added MMA, respectively. The mean within-laboratory (among-run) CV was 13% for both serum and plasma samples and 5.2% and 4.9% for serum and plasma samples with added MMA. Within-method imprecision was the same or higher than among-method imprecision. The mean among-laboratory recovery of MMA was 105% and 95% in serum and plasma, respectively. Most laboratories showed a proportional bias relative to the consensus mean of up to 15%. Two laboratories reported results that on average were almost 30% higher than the consensus mean. CONCLUSIONS: No method differences were found, but significant among-laboratory imprecision was found in the present study. Improvements are needed to reduce the analytical imprecision of most laboratories, and attention must be focused on calibration issues. Differences among laboratories can be improved by introducing high-quality reference materials and by instituting external quality assessment programs.

Comparison of plasma total homocysteine measurements in 14 laboratories: an international study.

BACKGROUND: Information on interlaboratory variation and especially on methodological differences for plasma total homocysteine is lacking. METHODS: We studied 14 laboratories that used eight different method types: HPLC with electrochemical detection (HPLC-ED); HPLC with fluorescence detection (HPLC-FD) further subdivided by type of reducing/derivatizing agent; gas chromatography/mass spectrometry (GC/MS); enzyme immunoassay (EIA); and fluorescence polarization immunoassay (FPIA). Three of these laboratories used two methods. The laboratories participated in a 2-day analysis of 46 plasma samples, 4 additional plasma samples with added homocystine, and 3 plasma quality-control (QC) pools. Results were analyzed for imprecision, recovery, and methodological differences. RESULTS: The mean among-laboratory and among-run within-laboratory imprecision (CV) was 9.3% and 5.6% for plasma samples, 8.8% and 4.9% for samples with added homocystine, and 7.6% and 4.2% for the QC pools, respectively. Difference plots showed values systematically higher than GC/MS for HPLC-ED, HPLC-FD using sodium borohydride/monobromobimane (however, for only one laboratory), and EIA, and lower values for HPLC-FD using trialkylphosphine/4-(aminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole. The two HPLC-FD methods using tris(2-carboxyethyl) phosphine/ammonium 7-fluoro-2,1,3-benzoxadiazole-4-sulfonate (SBD-F) or tributyl phosphine/SBD-F, and the FPIA method showed no detectable systematic difference from GC/MS. CONCLUSIONS: Among-laboratory variations within one method can exceed among-method variations. Some of the methods tested could be used interchangeably, but there is an urgent need to improve analytical imprecision and to decrease differences among methods.

Uranium and thorium in urine of United States residents: reference range concentrations.

We measured uranium and thorium in urine of 500 U. S. residents to establish reference range concentrations using a magnetic-sector inductively coupled argon plasma mass spectrometer (ICP-MS). We found uranium at detectable concentrations in 96.6% of the urine specimens and thorium in 39.6% of the specimens. The 95th percentile concenetration for uranium was 34.5 ng/L (parts per trillion); concentrations ranged up to 4080 ng/L. Thorium had a 95th percentile concentration of 3.09 ng/L; concentrations ranged up to 7.7 ng/L.

Blood lead concentration and children's anthropometric dimensions in the Third National Health and Nutrition Examination Survey (NHANES III), 1988-1994.

OBJECTIVE: To assess the association between lead exposure and children's physical growth. DESIGN: Cross-sectional analysis of data from the Third National Health and Nutrition Examination Survey, 1988-1994. PARTICIPANTS: A total of 4391 non-Hispanic white, non-Hispanic black, and Mexican-American children age 1 to 7 years. MEASUREMENTS AND RESULTS: We investigated the association between blood lead concentration and stature, head circumference, weight, and body mass index with multiple regression analysis adjusting for sex, ethnic group, iron status, dietary intake, medical history, sociodemographic factors, and household characteristics. Blood lead concentration was significantly negatively associated with stature and head circumference. Regression models predicted reductions of 1. 57 cm in stature and 0.52 cm in head circumference for each 0.48 micromol/L (10 micrograms/dL) increase in blood lead concentration. We did not find significant associations between blood lead concentration and weight or body mass index. CONCLUSIONS: The significant negative associations between blood lead concentration and stature and head circumference among children age 1 through 7 years, similar in magnitude to those reported for the Second National Health and Nutrition Examination Survey, 1976-1980, suggest that although mean blood lead concentrations of children have been declining in the United States for 2 decades, lead exposure may continue to affect the growth of some children.