[Correlation and mechanism between chronic kidney disease and periodontitis based on cross-sectional data].

Objective: To explore the correlation between periodontitis (PD) and chronic kidney disease (CKD) in adults, as well as the potential mechanisms involved. Methods: Data on PD and CKD from the National Health and Nutrition Examination Survey (NHANES) database between 1999 and 2014 were downloaded. Weighted univariate and multivariate logistic regression analyses were conducted to investigate the risk factors associated with PD and CKD, considering demographic and clinical indicators. Using publicly available genome-wide association study (GWAS) summary datasets for CKD and PD as outcome variables, as well as 731 immune cell phenotypes and 91 inflammatory proteins as exposure factors from the OPEN GWAS database, a two-sample Mendelian randomization (TSMR) analysis was performed using the inverse-variance weighted (IVW) method. Results: Seven demographic indicators including gender, age, race, education level, marital status, income, and health are related to the incidence of CKD and PD. Among them, the elderly (≥60 years old), poverty (poverty-income ratio <1.3), divorce or widowhood, and male ratio in the comorbidity group of CKD and PD [67.12% (833/1 241), 36.83% (457/1 241), 34.41% (427/1 241), and 57.78% (717/1 241) respectively] were significantly higher than those in the control group [23.71% (4 179/17 623), 29.17% (5 141/17 623), 18.16% (3 200/17 623), and 48.73% (8 587/17 623) respectively] (all P<0.001). Those with high educational level (university and above) and self-rated excellent health accounted for a relatively small proportion in the comorbidity group [14.10% (175/1 241) and 8.22% (102/1 241) respectively]. The prevalence of PD increased among individuals with abnormal renal function indices, including glomerular filtration rate, urine protein/creatinine ratio, serum creatinine, serum uric acid, and blood urea nitrogen. Univariate logistic regression analysis showed a positive correlation between the incidence of PD and CKD (OR=2.14, 95%CI: 1.90-2.42, P<0.001). Multivariate logistic regression analysis also indicated that PD and CKD were potential risk factors for each other (PD for CKD: OR=1.22, 95%CI: 1.07-1.40, P=0.004; CKD for PD: OR=1.19, 95%CI: 1.04-1.37, P=0.012). Furthermore, after adjusting the model based on demographic indicators, there was still a significant correlation between PD and CKD (P=0.010). Mechanistically, the results of the TSMR analysis support the existence of a common risk factor mediated by immune cells between CKD and PD, namely the expression of CD64 on multiple innate immune cells mediates the occurrence of CKD and PD. The absolute count of CD64+ monocytes is associated with an increased risk for both CKD (HR=1.11) and PD (HR=1.07), while same tendency showed in the absolute count of CD64+ neutrophils for CKD (HR=1.22) and PD (HR=1.23). Conclusions: There is a positive correlation between CKD and PD, particularly moderate to severe PD, and the shared pathogenesis involves CD64+ monocytes in the circulatory system. Targeted interventions focusing on CD64 molecules or monocyte subsets may be beneficial.

Association between body mass index and suicide, and suicide attempt among British adults: the health improvement network database.

OBJECTIVE: To examine the associations between body mass index (BMI) and incidence rate (IR) of suicide attempt and suicide. DESIGN AND METHODS: 849,434 British adults were identified from The Health Improvement Network (THIN) database between January 2000 and October 2007. BMI was categorized into six levels: <18.5 (underweight), 18.5-24.9 (normal weight), 25.0-29.9 (overweight), 30.0-34.9, 35.0-39.9, and ≥40 (obese levels I-III). RESULTS: We identified 3,111 suicide attempts by Read codes and 75 suicides with medical records. The overall IR of suicide attempt was 82.2 cases per 100,000 person-years. The IR decreased with BMI in men with depression (471.3-166.0 cases per 100,000 person-years, P for trend = 0.02) and in men without depression (241.5-58.0 cases per 100,000 person-years, P for trend < 0.0001). In women with depression, an L-shaped relationship was observed, that is, a higher rate in underweight group when compared with reference group (503.2 vs. 282.7 per 100,000 person-years) and no significant differences in others (231.8-195.5 cases per 100,000 person-years). In women without depression, the IR was U-shaped with BMI (125.2 in underweight, 68.6 in reference, and 48.5-79.9 cases in overweight and obese I-III groups per 100,000 person-years, P for trend < 0.0001). The above trends remained after adjustment for the covariates. Regarding suicide, the overall IR was 2.0 cases per 100,000 person-years, which tended to decrease with BMI (P = 0.14). CONCLUSIONS: We concluded an inverse linear association between BMI and suicide attempt among men, an L-shaped association in nondepressive women, and a U-shaped association in depressive women were observed. The study also suggested an inverse linear tendency between BMI and suicide.

Gel-impregnated pore membranes with mesh-size asymmetry for biohybrid artificial organs.

Membranes based on mechanically supported poly(vinyl alcohol) (PVA) hydrogels with mesh-size asymmetry were developed for potential application in biohybrid artificial organs. The pores of cellulose ester microfiltration membranes were impregnated with a PVA solution, which was lightly crosslinked with glutaraldehyde and then modified under a glutaraldehyde gradient to produce mesh-size asymmetry. Permeation experiments were performed with the resulting homogeneous and asymmetric gel-impregnated pore membranes (GIPMs). Creatinine (MW: 113), goat Fab (MW: 50 kD) and human IgG (MW: 150 kD) were used to simulate the molecular size of nutrients, therapeutic proteins, and immunological molecules, respectively. The transport properties of the GIPMs were compared to those of conventional ultrafiltration (UF) and dialysis membranes. Experimental results indicate that GIPMs with mesh-size asymmetry have thickness-normalized creatinine permeabilities that are slightly higher than those in cellulosic UF membranes but as much as 100% greater than those in polysulfone UF or cellulosic dialysis membranes. IgG permeabilities in the GIPMs are from 5 to 50 times lower than those in the UF membranes. Fab permeabilities are 6 to 40 times higher in the UF membranes than those in the GIPMs, but the required permeability for a therapeutic protein is application specific. GIPMs may also be suitable as an alternative for hemodialysis.

Epidemiologists and adverse event data--a challenge to the field.

Spontaneous adverse event reports, albeit biased and incomplete data, remain very important and, frequently, are the sole data source to rely on during the postmarketing phase for regulatory decision making. However, little progress has been made in the past decade to improve the utility of these essential data. Further research that helps to improve our understanding of the extent and characteristics of adverse event reporting should be done to ensure the maximum, appropriate utilization of this highly cost-efficient data source. In addition, the authors challenge that research can and should be done to advance our understanding of the behaviour and motivations of those who report adverse events so as to improve the quality and the quantity of meaningful spontaneous adverse event reports.

An investigation of the safety of midazolam use in hospital.

OBJECTIVE: To investigate whether an association exists between midazolam use and serious cardiorespiratory events or death. DESIGN: Retrospective analysis of data in an inpatient record linkage database, collected between March 1986 and October 1987 from 14 hospitals in the United States. PATIENTS: A cohort of 19,112 patients who received injectable midazolam or diazepam on the same day that a medical procedure was performed. MAIN OUTCOME MEASURES: An attempt was made to identify suspected serious cardiorespiratory adverse events and deaths that occurred within 24 h of study-drug administration. Death rates within 24 h following study-drug administration were compared between patients who received injectable midazolam and those who received injectable diazepam. RESULTS: Validation analysis of the information in the computerized record linkage database indicated that serious cardiac and respiratory adverse events that occurred within 24 h of study-drug administration could not be reliably identified. Therefore, a comparison of the serious cardiorespiratory adverse event rates following administration of midazolam versus diazepam could not be made. Death rates within 24 h of study-drug administration could be evaluated. For the cohort as a whole, the death rate was significantly lower among patients who received midazolam than among those who received diazepam (0.76% versus 1.93%, p<0.01). This difference remained statistically significant, after adjusting for age, sex, comorbidity diagnosis, concomitant drug use, type of medical procedure, and hospital size and teaching capability. CONCLUSIONS: The results suggest that there is no increased risk of death associated with midazolam administration when compared to diazepam administration for endoscopic, conscious sedative, and general anesthetic procedures in hospitals.

A comparative study of the risk factors for lung cancer in Guangdong, China.

A case-control study involving 390 lung cancer cases, matched 1:1 with controls, was carried out in Guangdong Province to compare risk factors for different histopathologic types of lung cancer in both sexes. Female and male lung cancers appear to differ in epidemiological characteristics, pathologic types, and risk factors. The 291 lung cancer cases in males were predominantly squamous cell lung carcinoma (squamous cell carcinoma/adenocarcinoma = 1:0.5), whereas the 99 female lung cancer cases were predominantly adenocarcinoma (squamous cell carcinoma/adenocarcinoma = 1:2.7). The age at which lung cancer was first diagnosed was lower for females than for males (P < 0.0001). Single-factor conditional logistic regression analysis showed an association of lung cancer with family history of tumors, family history of lung cancer, history of chronic bronchitis/emphysema, history of tuberculosis, history of other lung disease, smoking, exposure to environmental tobacco smoke (ETS) in the home and in the workplace, being professional drivers, use of oral contraceptives, and consumption of pickled and salted fish (P < 0.05). Further multivariate logistic regression analysis showed that family history of tuberculosis, history of chronic bronchitis/emphysema, family history of tumors, smoking, exposure to ETS in the home and in the workplace, and consumption of pickled and salted fish were independent risk factors for lung cancer. Using log-linear model analysis, it was confirmed that lung cancer had significant interactions with chronic bronchitis/emphysema, exposure to ETS, history of tuberculosis and smoking. Smoking, however, could only explain 1/5 of the incidence of female lung cancers. Family history of lung cancer and the use of oral contraceptives were related to lung cancer in women. Except for a weak relationship with history of chronic bronchitis/emphysema, adenocarcinoma was found to have no association with the other risk factors.

Epidemiology of isotretinoin exposure during pregnancy.

BACKGROUND: Exposure to isotretinoin during pregnancy is associated with a high risk of major fetal malformations. OBJECTIVE: Our purpose was to determine the reasons for and outcomes of in utero isotretinoin exposure. METHODS: On the basis of 433 spontaneous reports, we describe the likely reasons these exposures occurred and the outcomes of these pregnancies. In our analysis of the outcomes of pregnancy, we separately consider the pregnancies known to us before their outcomes were determined as prospective cases. RESULTS: Timing of conception in relation to initiation of therapy with isotretinoin was known for 396 women. Of these, 130 patients (33%) were already pregnant when they started isotretinoin. An additional 65 patients (16%) became pregnant in the first 3 weeks of isotretinoin use. Pregnancy outcomes were known on 409 pregnancies. Among these, 222 (54%) ended in elective abortion and 29 (7%) in spontaneous or missed abortion. Of 151 births, 72 (48%) were normal, 71 (47%) had congenital malformations, and 8 (5%) had abnormalities other than malformations. Of 94 prospectively ascertained pregnancies that ended in births, 28% had congenital malformations (95% confidence interval 19% to 37%). Exposure to isotretinoin during any time and for as little as one capsule within the first trimester have been associated with congenital malformations. CONCLUSION: The high proportion of exposures in already or recently pregnant women illustrates the importance of obtaining a negative pregnancy test before the initiation of isotretinoin therapy and of delaying the commencement of isotretinoin therapy until the onset of the next menstrual period. Furthermore, the importance of reliable contraceptive methods should be emphasized to patients when isotretinoin is prescribed. Young women seem to be at an especially high risk of pregnancy exposure to isotretinoin. There is a substantial risk of congenital malformation at all therapeutic doses of isotretinoin, even when the duration of exposure is brief.

A population-based study of Stevens-Johnson syndrome. Incidence and antecedent drug exposures.

To determine the incidence of Stevens-Johnson syndrome, a descriptive epidemiology study was performed using computerized Medicaid billing data from 1980 to 1984 from the states of Michigan, Minnesota, and Florida. The ratio of persons hospitalized with a discharge diagnosis of erythema multiforme (ICD-9-CM code 695.1) to persons with any claim for medical service was first used as an estimate of the incidence rate of the disease. Then, since the ICD-9-CM code for erythema multiforme includes other illnesses in addition to Stevens-Johnson syndrome and because these illnesses are frequently misdiagnosed, the information provided by a review of medical records for a subset of cases of erythema multiforme was used to determine the proportion of patients with true Stevens-Johnson syndrome. The incidence rates of Stevens-Johnson syndrome were 7.1 (6.1 to 8.2), 2.6 (1.6 to 4.0), and 6.8 (4.3 to 10.3) per million per year in each state, respectively. Penicillins, especially aminopenicillins, were frequently used in the 19 patients judged to be true cases of Stevens-Johnson syndrome. In conclusion, Stevens-Johnson syndrome is a uncommon condition. The excess risk of Stevens-Johnson syndrome due to any drug must, therefore, be very low.

Using a claims database to investigate drug-induced Stevens-Johnson syndrome.

In order to explore a priori hypotheses about drug-induced Stevens-Johnson Syndrome (SJS), a case-control study was initiated using data from COMPASS, a computerized data base consisting of Medicaid claims data. The records of 3.8 million patients in five U.S. states were searched to identify patients with an inpatient diagnosis of ICD-9-CM code 695.1 (erythema multiforme-EM). Out of the total of 367 cases that were identified, primary medical records for 249 were sought and 128 (51.4 per cent) of these were obtained. The remainder could not be obtained because: in 36 (29.8 per cent) the hospital refused to provide medical records; in 33 (27.3 per cent) there were transcription errors; in 20 (16.5 per cent) the state could not translate the identification number, primarily because the patients lost Medicaid eligibility too long before our request; in 27 (22.3 per cent) the hospital could not locate the patient's record; and in 5 (4.1 per cent) there were other reasons. Of those with a medical record, 121 (94.5 per cent) had a skin diagnosis and 109 (85.2 per cent) had a diagnosis compatible with ICD-9-CM code 695.1 specified on their discharge summary. However, in 35 (27.3 per cent) an expert reviewer felt that the discharge diagnosis was incorrect. In 50 (39 per cent) the computer diagnosis was incorrect. Only 19 (14.8 per cent) were judged by the expert reviewer to truly have Stevens-Johnson Syndrome, and an additional 37 (28.9 per cent) were judged to have erythema multiforme minor. Thus, the computerized diagnosis agreed very well with the diagnoses specified on the discharge summary. However, EM is frequently misdiagnosed, ICD-9-CM code 695.1 contains multiple other diagnoses which are not EM, and much of hospitalized EM is EM minor. Thus, studies of SJS cannot be performed except in patients whose medical records are available.

Safety of pregnancy after discontinuation of isotretinoin.

Isotretinoin (13-cis-retinoic acid, Accutane) increases the risk of major congenital malformations in infants exposed to isotretinoin during pregnancy. However, there have been no epidemiologic reports to date on the effect of a subsequent pregnancy after discontinuation of isotretinoin. This article describes our analysis of pregnancy case reports from patients in whom conception occurred after isotretinoin treatment had been discontinued. Based on the 88 prospectively ascertained cases, the incidence rate of both spontaneous and missed abortions from all pregnancies was 9.1% (eight patients), and the incidence rate of congenital malformation among the live births was 5.0% (four patients). The incidence rates for both these outcomes were not significantly different from the rates reported for women of reproductive age in the general population. In addition, the malformations reported were not characteristic of retinoic acid-induced congenital anomalies.

Cigarette smoking and serum sex hormones in men.

The relation between cigarette smoking and serum sex hormone concentrations was examined in two samples of the Multiple Risk Factor Intervention Trial (MRFIT) population. One sample consisted of 121 men at the Pittsburgh, Pennsylvania MRFIT center who were followed longitudinally for four years. The other sample was drawn from the entire MRFIT cohort and consisted of 163 MRFIT participants who subsequently developed coronary heart disease and 163 matched controls. The results indicated a positive correlation between cigarette smoking and serum total androstenedione concentration. The association was independent of age, relative weight, alcohol drinking, blood pressure, and high density lipoprotein (HDL) cholesterol. Serum total and free testosterone concentrations were positively correlated with cigarette smoking among the longitudinal sample and the controls, but not for the baseline sera from the coronary heart disease cases. This positive correlation was also independent of age, relative weight, alcohol drinking, blood pressure, and HDL cholesterol. There was no association between either serum estradiol or estrone concentrations and cigarette smoking in this population. These observations may have important implications for epidemiologic studies of diseases with significant smoking relations.

Usefulness of sex steroid hormone levels in predicting coronary artery disease in men.

The relation between sex hormone levels and subsequent risk of a major coronary event was studied in a nested case-control study among 163 men in the Multiple Risk Factor Intervention Trial who later had a major coronary event and in 163 controls. Cases and controls were matched for age, serum cholesterol level, randomization group, randomization date and clinic. Blood samples were collected at baseline before randomization and frozen at -70 degrees C. Follow-up extended over 6 to 8 years. Sixty-one patients had a nonfatal acute myocardial infarction and 102 fatal infarction. Total and free testosterone, total and free estradiol, androstenedione and estrone concentrations were measured. There were no significant differences between cases and controls for any sex hormone level. There was also no difference in the ratio of testosterone to estradiol. Controlling for other cardiovascular risk factors did not change these results. These results do not support previous case-control studies of a relation between sex hormone levels and risk of heart attack among men.

Studies on the association between alcohol and high density lipoprotein cholesterol: possible benefits and risks.

The weight of the evidence suggests a positive relationship between alcohol consumption and HDLc. The relationship showed a linear dose response relationship with HDLc over the range of alcohol consumption from non-drinkers to alcoholics. The effect appears to be reversible since changes in alcohol intake result in changes in HDLc. Preliminary evidence has suggested that in alcoholics, the effect may primarily be on the HDL-2 subfraction, while in the general population, it may primarily raise the HDL-3 subfraction. Limited research has shown a positive relationship between alcohol consumption and apo A-I levels. The exact underlying mechanisms for this relationship is not known. It remains to be determined if alcohol also exerts an effect on Coronary Heart Disease that is independent of its effect on HDLc. It is important to further evaluate these important leads both because it may provide a better understanding of the relationship between HDL, lipoprotein metabolism and coronary artery disease and the role of alcohol in the genesis of heart disease. A public health recommendation to increase alcohol consumption to reduce risk of heart attack is not indicated. Cessation of moderate alcohol consumption, however, should also not be part of the current recommendation to improve lipoprotein profiles.

Lipoprotein cholesterol, vitamin A, and vitamin E in an alcoholic population.

Elevated alcohol consumption is associated with an increased risk of cancer. Reasons for this association are not well established but may relate to alterations in cholesterol, vitamin A (carotene and retinol), and vitamin E metabolism, since low levels of these factors have been linked to risk of cancer. Blood levels of cholesterol, carotene, retinol, and vitamin E were determined in 192 male alcoholics entering into an alcohol detoxification program. Compared to nonalcoholic populations, their cholesterol (187 mg/dl) and carotene (94 micrograms/dl) concentrations were markedly reduced at entrance; however, abstinence of 33 days returned both to normal levels. In contrast, the retinol and vitamin E levels were within the normal range at baseline and remained relatively stable throughout rehabilitation. Of particular interest was that the low density lipoprotein cholesterol was highly correlated with carotene (r = +0.40, whites, r = +0.54, blacks). The results suggest that alterations in the metabolism of cholesterol and carotene, due to alcohol intake, may partially account for the relationship of alcohol to increased cancer risk.

Alcohol consumption and high density lipoprotein cholesterol concentration among alcoholics.

Alcohol consumption is one of the major determinants of serum high density lipoprotein (HDL) cholesterol. Very few studies have examined the correlation between alcohol consumption and high density lipoprotein subclasses. It has been suggested that HDL2 is probably the fraction that is associated with reduced coronary heart disease. The current research investigated the relationship between alcohol consumption and HDL2 and HDL3 cholesterol among 234 alcoholics who were admitted for abstinence. The results indicated that the elevated serum HDL cholesterol concentrations among alcoholics were a combination of an increase in both HDL2 and HDL3 cholesterol. HDL cholesterol and HDL2 cholesterol increased with more alcohol consumption until about 450 ml of ethanol consumption per day when serum HDL cholesterol and HDL2 cholesterol decreased. HDL3 cholesterol showed a similar trend but was not statistically significant. In addition, the serum concentrations of HDL cholesterol and subclasses were positively correlated with liver enzymes. Those with alcohol-related liver disease had significantly higher HDL and HDL2 cholesterol levels than those without. Both HDL cholesterol and subclasses decreased concomitantly with the decline in liver enzymes within one month of abstinence. The possible biologic mechanisms linking alcohol drinking with HDL cholesterol through liver induction and sex hormone changes are discussed.

Asymptomatic carotid artery bruits in a population of elderly adults with isolated systolic hypertension.

A sample of 99 elderly (over age sixty) adults with isolated systolic hypertension were examined for cervical arterial bruits and systolic blood pressure measurements were taken in upper and lower extremities. The ratio of ankle to arm blood pressure (ankle/arm index) was used as a measure of the degree of obstruction in peripheral arterial circulation. The prevalence of bruit (asymptomatic in all cases) was high, with 24 bruits detected in 19 (19%) participants. This high prevelance of bruits is thought to be due to the blood pressure characteristics of this population. Those with bruit were found to have a 3.9 times greater chance of having an abnormal ankle/arm index. The relationship remained statistically significant even after controlling for the effects of age and smoking. These findings add further evidence to the hypothesis that asymptomatic cervical bruits are an indication of systemic vascular disease.

Relation between plasma high-density lipoprotein cholesterol and sex hormone concentrations in men.

High-density lipoprotein (HDL) cholesterol is inversely associated with risk of heart attack. Sex hormones have been suggested as possible factors contributing to the gender difference of coronary heart disease risk. Little is known about how endogenous sex hormone concentration might be related to HDL cholesterol. The relation was examined in 225 men participating in the Multiple Risk Factor Intervention Trial. Plasma testosterone concentration was positively correlated with HDL cholesterol and the change in testosterone concentration was also positively correlated with change in HDL cholesterol. The relation between testosterone and HDL cholesterol could not be fully explained by age, relative weight, alcohol consumption and cigarette smoking in the cross-sectional study. However, when this relation was examined longitudinally, the partial correlation between changes in testosterone and HDL cholesterol did not quite achieve statistical significance (0.05 less than p less than 0.10). The biologic process that relates HDL cholesterol to testosterone is not known. The results suggest an inverse relation between plasma estradiol concentration and low-density lipoprotein cholesterol, but no statistical significant correlation with HDL cholesterol. In addition, there was no association noted in the current research between estradiol concentrations and the known determinants of HDL cholesterol.