More inclusive bipolar mixed depression definition by permitting overlapping and non-overlapping mood elevation symptoms.

OBJECTIVE: The objective of this study was to assess the strengths and limitations of a mixed bipolar depression definition made more inclusive than that of the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) by counting not only 'non-overlapping' mood elevation symptoms (NOMES) as in DSM-5, but also 'overlapping' mood elevation symptoms (OMES, psychomotor agitation, distractibility, and irritability). METHODS: Among bipolar disorder (BD) out-patients assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation, we assessed prevalence, demographics, and clinical correlates of mixed vs. pure depression, using more inclusive (≥3 NOMES/OMES) and less inclusive DSM-5 (≥3 NOMES) definitions. RESULTS: Among 153 depressed BD, counting not only NOMES but also OMES yielded a three-fold higher mixed depression rate (22.9% vs. 7.2%) and important statistically significant clinical correlates for mixed compared to pure depression (more lifetime anxiety disorder comorbidity, more current irritability, and less current antidepressant use), which were not significant using the DSM-5 threshold. CONCLUSION: To conclude, further studies with larger numbers of patients with DSM-5 bipolar mixed depression assessing strengths and limitations of more inclusive mixed depression definitions are warranted, including efforts to ascertain whether or not OMES should count toward mixed depression.

More inclusive bipolar mixed depression definitions by requiring fewer non-overlapping mood elevation symptoms.

OBJECTIVE: Assess strengths and limitations of mixed bipolar depression definitions made more inclusive than that of the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) by requiring fewer than three 'non-overlapping' mood elevation symptoms (NOMES). METHOD: Among bipolar disorder (BD) out-patients assessed with Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation, we assessed prevalence, demographics, and clinical correlates of mixed vs. pure depression, using less inclusive (≥3 NOMES, DSM-5), more inclusive (≥2 NOMES), and most inclusive (≥1 NOMES) definitions. RESULTS: Among 153 depressed BD, compared to less inclusive DSM-5 threshold, our more and most inclusive thresholds, yielded approximately two- and five-fold higher mixed depression rates (7.2%, 15.0%, and 34.6% respectively), and important statistically significant clinical correlates for mixed compared to pure depression (e.g. more lifetime anxiety disorder comorbidity, more current irritability), which were not significant using the DSM-5 threshold. CONCLUSION: Further studies assessing strengths and limitations of more inclusive mixed depression definitions are warranted, including assessing the extent to which enhanced statistical power vs. other factors contributes to more vs. less inclusive mixed bipolar depression thresholds having more statistically significant clinical correlates, and whether 'overlapping' mood elevation symptoms should be counted.

Optical diagnostics in the oral cavity: an overview.

As the emphasis shifts from damage mitigation to disease prevention or reversal of early disease in the oral cavity, the need for sensitive and accurate detection and diagnostic tools become more important. Many novel and emergent optical diagnostic modalities for the oral cavity are becoming available to clinicians with a variety of desirable attributes including: (i) non-invasiveness, (ii) absence of ionizing radiation, (iii) patient-friendliness, (iv) real-time information (v) repeatability, and (vi) high-resolution surface and subsurface images. In this article, the principles behind optical diagnostic approaches, their feasibility and applicability for imaging soft and hard tissues, and their potential usefulness as a tool in the diagnosis of oral mucosal lesions, dental pathologies, and other dental applications will be reviewed. The clinical applications of light-based imaging technologies in the oral cavity and of their derivative devices will be discussed to provide the reader with a comprehensive understanding of emergent diagnostic modalities.

Reliability and intraoperative validity of preoperative assessment of standardized plain radiographs in predicting bone loss at revision hip surgery.

BACKGROUND: The most challenging aspect of revision hip surgery is the management of bone loss. A reliable and valid measure of bone loss is important since it will aid in future studies of hip revisions and in preoperative planning. We developed a measure of femoral and acetabular bone loss associated with failed total hip arthroplasty. The purpose of the present study was to measure the reliability and the intraoperative validity of this measure and to determine how it may be useful in preoperative planning. METHODS: From July 1997 to December 1998, forty-five consecutive patients with a failed hip prosthesis in need of revision surgery were prospectively followed. Three general orthopaedic surgeons were taught the radiographic classification system, and two of them classified standardized preoperative anteroposterior and lateral hip radiographs with use of the system. Interobserver testing was carried out in a blinded fashion. These results were then compared with the intraoperative findings of the third surgeon, who was blinded to the preoperative ratings. Kappa statistics (unweighted and weighted) were used to assess correlation. Interobserver reliability was assessed by examining the agreement between the two preoperative raters. Prognostic validity was assessed by examining the agreement between the assessment by either Rater 1 or Rater 2 and the intraoperative assessment (reference standard). RESULTS: With regard to the assessments of both the femur and the acetabulum, there was significant agreement (p < 0.0001) between the preoperative raters (reliability), with weighted kappa values of >0.75. There was also significant agreement (p < 0.0001) between each rater's assessment and the intraoperative assessment (validity) of both the femur and the acetabulum, with weighted kappa values of >0.75. CONCLUSIONS: With use of the newly developed classification system, preoperative radiographs are reliable and valid for assessment of the severity of bone loss that will be found intraoperatively.

Development, test reliability and validation of a classification for revision hip arthroplasty.

The objective of the study was to develop a valid and reliable classification system for failed hip arthroplasties. The study uses research principals derived from multi-attribute utility theory and consensus group techniques. The development of the severity measure was done in two phases. Phase I of the study included: (a) questionnaire development, (b) submission of the questionnaire to the respondents, (c) data synthesis of the responses and item reduction, and (d) classification development and inter-observer reliability testing. Phase II included: (a) resubmission of the instrument to the respondents for suggestions/feedback, (b) instrument revision by the co-investigators based on the respondents' second feedback, and (c) inter-observer reliability testing and intraoperative validity testing of the instrument. The questionnaires sought to capture expert opinion as to what clinical determinants obtained preoperatively (during patient interview, physical exam and review of plain radiographs - AP pelvis and hip lateral) that would in their clinical experience reveal intraoperative severity. There was an 80% (16/20) response rate from the outside experts invited to participate in the study. Based on item reduction and test retest analysis, a five-grade radiographic classification for the acetabulum as well as the femur was developed. This system was then reviewed by 13 of the initial outside experts (16, 80%) who participated in the first round. Inter-rater reliability testing of the final format of the classification revealed a weighted kappa statistic value of 0.88 between the two-blinded raters (inter-rater reliability) and 0.87 between the blinded raters and the reference standard (intraoperative validity). We conclude that the study developed a reliable and valid radiographic classification system for failed hip arthroplasty.

Epidemiological study of urinary 6beta-hydroxycortisol to cortisol ratios and breast cancer risk.

The ratio of urinary 6beta-hydroxycortisol:cortisol is a measure of the activity of cytochrome p450 3A4 (CYP3A4). CYP3A4 catalyzes the formation of the genotoxic estrogen, 16alpha-hydroxyestrone. It is also involved in the activation of many other mammary carcinogens, such as the polycyclic aromatic hydrocarbons and heterocyclic amines. We evaluated the association between urinary cortisol ratios and breast cancer risk in a subgroup of women who participated in a population-based case-control study in Shanghai. Overnight urine samples from 246 case-control pairs were assayed for 6beta-hydroxycortisol (6beta-OHC) to cortisol. The urine samples from all of the breast cancer patients were collected before any chemotherapy or radiotherapy. In-person interviews were conducted to obtain comprehensive information on dietary habits, reproductive history, and other lifestyle factors. The median levels of 6beta-OHC:cortisol ratios were 2.61 in cases and 2.16 in controls, a 20.8% difference (P < 0.001). The case-control difference was larger in women over 45 years of age (31.3% difference; P < 0.001) than younger women (6.0%; P = 0.45). After adjusting for confounding variables, the risks of breast cancer were increased from 1.0 (reference) to 1.6 [95% confidence interval (CI), 0.9-3.1], 2.2 (95% CI, 1.1-4.2), and 3.7 (95% CI, 1.9-7.4; P for trend, <0.001) with increasing levels of 6beta-OHC:cortisol ratios. The positive association was more pronounced among older women (>45 years) than among younger women (< or = 45 years). The adjusted odds ratios associated with the highest cortisol ratio were 6.0 (95%CI, 2.2-16.1) among older women and 2.2 (95%CI, 0.8-6.1) among younger women. The association of the 6beta-OHC:cortisol ratio was stronger among older women who had a high body mass index, late age at menopause, and early age at menarche (factors related to high endogenous estrogen exposure) than those who did not have these factors. These findings are consistent with the role of CYP3A4 in estrogen and carcinogen metabolism and suggest that high CYP3A4 activity may be a risk factor for breast cancer risk.

Physiologic concentrations of homocysteine inhibit the human plasma GSH peroxidase that reduces organic hydroperoxides.

The plasma reduced glutathione (GSH) selenoperoxidase is a highly conserved enzyme. Furthermore, a small clinical study reported that patients with severe atherosclerosis had low peroxidase activities. Together these observations suggest that the peroxidase is important in preventing atherosclerosis. Yet others have reported that when the assay was run in Tris buffer, it was inactive with the concentrations of GSH found in the plasma. Second, it is known that hyperhomocysteinemia increases the rate of atherogenesis. Because there is some homology between homocysteine and the cysteine in GSH, the question is whether the hyperhomocysteinemia effect may be due to inhibition of the peroxidase. We purified the peroxidase from human plasma and determined its activity by a coupled spectrophotometric assay and a substrate disappearance chemiluminescence assay. When the peroxidase activity was determined in phosphate-buffered saline solution (PBS), there was significant activity with the reported plasma GSH concentrations (5 to 20 micromol/L). The peroxidase was exclusively in the HDL fraction. There was no correlation between the peroxidase activity and the HDL or LDL cholesterol concentrations. Finally, at physiologic concentrations of GSH (9 micromol/L), the peroxidase was inhibited by physiologic, free homocysteine concentrations (1 to 5 micromol/L). These data suggest that the peroxidase is active in vivo and may be important in protecting the endothelium from atherosclerosis by preventing oxidant injury. The homocysteine inhibition of the peroxidase suggests a possible biochemical basis for the observed association between hyperhomocysteinemia and cardiovascular disease. Our studies imply that low concentrations of this peroxidase may be an independent risk factor for atherosclerosis.

Effect of methoxychlor administration to male rats on hepatic, microsomal iodothyronine 5'-deiodinase, form I.

We previously reported that methoxychlor administration inhibits the activity of the hepatic, microsomal iodothyronine 5'-deiodinase, form I (ID-I; ). Our data further suggested that the inhibition was due to the covalent binding of a methoxychlor metabolite to a 56-kDa protein identified as ID-I (; ). This protein is 98% homologous to the thiol:protein disulfide oxidoreductase, form Q5 (ERp55;; ). Although at the time there was some controversy, most studies now suggest that ID-I is actually catalyzed by a 27-kDa selenoprotein that does not form adducts with methoxychlor (;; ). Because the 27-kDa protein is considered to be ID-I instead of ERp55, we have further examined the basis for the decreased ID-I activity observed after methoxychlor administration. Male, 150- to 200-g Sprague-Dawley rats were given methoxychlor (0-100 mg/kg/day) in corn oil by gavage for 14 days. ID-I was determined by a thyronine-specific immunoassay. Treated rats showed a significant 15% decline in total hepatic, microsomal protein at all doses. The ID-I-specific activity showed a linear decrease with increasing log doses of methoxychlor. The maximum decrease was 42% at 100 mg/kg/day. The 27-kDa protein specific content declined 37%. In rats given methoxychlor the ratios of the 27-kDa protein mRNA to the 18S ribosomal RNA declined from 2.2 +/- 0.27 x 10(-3) (controls) to 0.99 +/- 0.09 x 10(-3) (100 mg/kg/day). These data suggest that the decreased ID-I observed with chronic methoxychlor administration was due to decreased transcription or stability of the mRNA encoding the 27-kDa protein.

Within-person variability of the ratios of urinary 2-hydroxyestrone to 16alpha-hydroxyestrone in Caucasian women.

The ratio of urinary 2-hydroxyestrone (2-OHE1) to 16alpha-hydroxyestrone (16alpha-OHE1) has been suggested as a potential biomarker for breast cancer risk. We evaluated within-person variability of this biomarker in ten healthy Caucasian women aged 23-58 years. Each study participant was asked to provide an overnight fasting morning urine sample once a week for an average of 8 weeks. These urine samples were assayed for 2-OHE1 and 16alpha-OHE1 by using competitive enzyme immunoassay kits purchased from the ImmunaCare Corporation. The coefficients of variation for urinary 2-OHE1/16alpha-OHE1 over the study period ranged from 13.7 to 59.6% (mean, 33.3%) in our study participants. There was a good correlation between the level of the urinary 2-OHE1/16alpha-OHE1 ratio in any single urine sample and the average ratio over the 8-week study period from the same woman, with the mean correlation coefficient of 0.85. These results indicated that the within-person variation of the 2-OHE1 to 16alpha-OHE1 ratio for most women was moderate and the level of this ratio in a single urine sample, in general, reflects reasonably well the level of this biomarker over a 2-month period.

Long-term functional status and quality of life after lower extremity revascularization.

OBJECTIVE: The objective of this study was to assess the longer term (up to 7 years) functional status and quality of life outcomes from lower extremity revascularization. METHODS: This study was designed as a cross-sectional telephone survey and chart review at the University of Minnesota Hospital. The subjects were patients who underwent their first lower extremity revascularization procedure or a primary amputation for vascular disease between January 1, 1989, and January 31, 1995, who had granted consent or had died. The main outcome measures were ability to walk, SF-36 physical function, SF-12, subsequent amputation, and death. RESULTS: The medical records for all 329 subjects were reviewed after the qualifying procedures for details of the primary procedure (62.6% arterial bypass graft, 36.8% angioplasty, 0.6% atherectomy), comorbidities (64% diabetics), severity of disease, and other vascular risk factors. All 166 patients who were living were surveyed by telephone between June and August 1996. At 7 years after the qualifying procedure, 73% of the patients who were alive still had the qualifying limb, although 63% of the patients had died. Overall, at the time of the follow-up examination (1 to 7.5 years after the qualifying procedure), 65% of the patients who were living were able to walk independently and 43% had little or no limitation in walking several blocks. In a multiple regression model, patients with diabetes and patients who were older were less likely to be able to walk at follow-up examination and had a worse functional status on the SF-36 and a lower physical health on the SF-12. Number of years since the procedure was not a predictor in any of the analyses. CONCLUSION: Although the long-term mortality rate is high in the population that undergoes lower limb revascularization, the survivors are likely to retain their limb over time and have good functional status.

Facial attractiveness and the aged.

This study examined the relationship between dentofacial appearance and judgments of facial attractiveness in a sample of 60 subjects between ages 65 and 75. Subjects completed questionnaires regarding their current dental appearance and level of satisfaction with their facial attractiveness. Subjects then viewed and ranked four sets of five photographs that had been digitally manipulated to simulate common dental defects. Regardless of background facial attractiveness or gender of stimulus photographs, a specific ranking order for dental defects emerged with rank-order correlations in the 90% range. Findings suggest that dental appearance affects judgments of facial attractiveness regardless of gender or background facial attractiveness.

The effects of clinical pathways for renal transplant on patient outcomes and length of stay.

OBJECTIVES: Clinical pathways have been implemented nationwide but little is understood about their effects on efficiency of care and patient outcomes. The present study examined the effects of both development and implementation of two renal transplant pathways. METHODS: Cohorts of patients at a university hospital were compared before, during, and after the development and implementation of two renal transplant clinical pathways: isolated renal transplant from cadaveric donors (n = 170) or from living donors (n = 178). Clinical pathways for cadaveric and living related donor renal transplants were developed and implemented. Hospital length of stay and complications and infections after renal transplant were determined. RESULTS: Mean length of hospital stay decreased after development and implementation of the cadaveric donor pathway (11.8 days after implementation versus 17.5 days before development). Cadaveric kidney recipients also had statistically fewer complications and infections after both guideline development and guideline implementation (57.1% before, 24.5% during, 18.5% after), but the greatest effect occurred during development. All of these findings persisted after control for demographic and comorbid factors. There were no changes in hospital stay, complications, or infections in the patients who received kidneys from living donors. CONCLUSIONS: The development and use of a clinical pathway for cadaveric donor renal transplant patients was associated with a significant decline in length of stay, complications, and infections, but much of the effect was seen during development rather than during implementation, and a closely related pathway for living related donor patients had no effect. Further understanding of what factors predict an effective pathway and what elements (ie, development or implementation) have an effect should be undertaken.

The effect of HMO status on the outcomes of home-care after hospitalization in a Medicare population.

OBJECTIVE: The literature suggests that Medicare health maintenance organization (HMO) patients may have poorer outcomes with formal home-health care than do fee-for-service (FFS) patients, but it is unclear whether this is related to case-mix or quality. Our objective was to compare the home-health care outcomes for HMO and FFS Medicare patients after hospitalization for stroke, COPD, CHF, hip replacement, or hip fracture with fixation or replacement while controlling for site of discharge and other patient characteristics. DESIGN: Patients were identified before hospital discharge with data collected at that time and then prospectively for 1 year. SETTING: Nineteen acute general hospitals in Minneapolis/St. Paul, Minnesota. PATIENTS: All Medicare patients in the above hospitals identified predischarge with stroke, COPD, CHF, hip replacement, or hip fracture with fixation or replacement. OUTCOME: weighted ADL scale and hospital readmission. Independent factors: site of discharge, HMO status, comorbidity, severity, and demographic factors. RESULTS: A total of 970 subjects were studied, 211 of whom were discharged to home-care. HMO patients were more likely to be discharged to a nursing home than to home-care after controlling for other factors (OR = 1.7; P = .015). After controlling for site of discharge and patient characteristics through either propensity scores or regression analysis, there was no statistically significant difference in ADL function at 6 weeks or at 6 months between HMO and FFS patients. Nor was there was a statistically significant difference in hospital readmission rates at 6 weeks and 6 months between HMO and FFS home-care patients. CONCLUSIONS: The outcomes of Medicare HMO patients discharged to home-care are not worse than those of FFS patients.

Development and testing of a process measure of nursing home quality of care.

OBJECTIVE: To develop and test quality of care process measures for three medical conditions of nursing home patients: fever, shortness of breath, and chest pain. DESIGN: Flowsheets designed to capture the critical elements of care for the above conditions were developed by an expert panel. Nursing home residents charts were reviewed retrospectively using the flow sheets. The reviews were translated into clinical scenarios, and the quality of care the scenarios represented was rated by an expert panel. SETTING: All nursing homes in Hennepin County, MN, that care for Medicaid patients. PATIENTS: A random sample of 1405 Medicaid nursing home residents from 1984 and 1988. MEASURES: Measures of quality of physician assessment and intervention, quality of nurse assessment and intervention, and global quality were developed and the intra- and interrater reliability were tested. The measures' validity was assessed by their ability to predict resident death. RESULTS: Intrarater reliability was measured as the correlation of the ratings of blinded duplicates. The correlation for the global scale and the four subscales ranged from .74 to .88 (P < .001 for all). Interrater reliability was tested by examining what percentage of the quality ratings were within one unit (1-5 scale) for all three raters. All three raters were within one unit for more than 72% scenarios for all scales. The subscale of quality of physician assessment was able to predict resident death when the worst episode of care (OR = .47, 95% CI(.31-.74)) or the mean episode of care (OR .54, 95% CI(.30-.99)) was used. None of the other subscales or the global measure predicted death. CONCLUSIONS: Through the use of an expert panel, measures of nursing home quality of care were developed for shortness of breath, fever, and chest pain. These measures have reasonable reliability and significant face validity. Their validity is supported further by the ability of one of the measures to predict resident death.

Catalysis of the cysteine conjugation and protein binding of acetaminophen by microsomes from a human lymphoblast line transfected with the cDNAs of various forms of human cytochrome P450.

We have previously found that for acetaminophen kinetic differences exist between the hepatic microsomal catalyzed protein binding and cysteine conjugation. We have also observed that the protein binding of acetaminophen is only to intralumenal proteins. Together these data suggested that two pools of the reactive metabolite, N-acetyl-p-benzoquinone imine (NABQI), are formed during the oxidative metabolism of acetaminophen: one on the cytosolic surface and the other within the lumen of the microsomes. This would indicate that some of forms of cytochrome P450 (CYP) catalyzing NABQI formation have their active site on the cytosolic surface and others on the lumenal surface. We have examined this question by comparing the rates of cysteine conjugation and protein binding of acetaminophen by microsomes from lymphoblasts transfected with the cDNAs for human CYPs. We found that CYP2D6 catalyzed only cysteine conjugation; CYP1A2 and 3A4 catalyzed only protein binding; CYP2E1 catalyzed both; and CYP1A1, CYP2A6 and CYP2B6 catalyzed neither. These data suggest that CYP2D6 has its active site only on the cytosolic surface; CYP1A2 and CYP3A4 only on the lumenal surface; and CYP2E1 has catalytic sites on both the lumenal and cytosolic surfaces of the membrane. In mouse studies we have found that ethanol administration increased acetaminophen protein binding by 265% but cysteine conjugation by only 61%. CYP2E1 and CYP2B increased, whereas CYP3A decreased and the others did not change. These data suggest that in control mice CYP2E1 catalyzes the bulk of protein binding, whereas CYP2D catalyzes slightly more cysteine conjugation than does CYP2E1.