Variation in the clinical management of self-harm by area-level socio-economic deprivation: findings from the multicenter study of self-harm in England.

BACKGROUND: We investigated disparities in the clinical management of self-harm following hospital presentation with self-harm according to level of socio-economic deprivation (SED) in England. METHODS: 108 092 presentations to hospitals (by 57 306 individuals) after self-harm in the Multicenter Study of Self-harm spanning 17 years. Area-level SED was based on the English Index of Multiple Deprivation. Information about indicators of clinical care was obtained from each hospital's self-harm monitoring systems. We assessed the associations of SED with indicators of care using mixed effect models. RESULTS: Controlling for confounders, psychosocial assessment and admission to a general medical ward were less likely for presentations by patients living in more deprived areas relative to presentations by patients from the least deprived areas. Referral for outpatient mental health care was less likely for presentations by patients from the two most deprived localities (most deprived: adjusted odd ratio [aOR] 0.77, 95% CI 0.71-0.83, p < 0.0001; 2nd most deprived: aOR 0.80, 95% CI 0.74-0.87, p < 0.0001). Referral to substance use services and 'other' services increased with increased SED. Overall, referral for aftercare was less likely following presentations by patients living in the two most deprived areas (most deprived: aOR 0.85, 95% CI 0.78-0.92, p < 0.0001; 2nd most deprived: aOR 0.86, 95% CI 0.79-0.94, p = 0.001). CONCLUSIONS: SED is associated with differential care for patients who self-harm in England. Inequalities in care may exacerbate the risk of adverse outcomes in this disadvantaged population. Further work is needed to understand the reasons for these differences and ways of providing more equitable care.

The effect of financial incentives on top of behavioral support on quit rates in tobacco smoking employees: study protocol of a cluster-randomized trial.

BACKGROUND: Stimulating successful tobacco cessation among employees has multiple benefits. Employees who quit tobacco are healthier, more productive, less absent from work, and longer employable than employees who continue to use tobacco. Despite the evidence for these benefits of tobacco cessation, a successful method to stimulate employees to quit tobacco is lacking. The aim of this study is to evaluate whether adding a financial incentive to behavioral support (compared with no additional incentive) is effective and cost-effective in increasing abstinence rates in tobacco smoking employees participating in a smoking cessation group training. METHODS/DESIGN: In this cluster-randomized trial employees in the intervention and control group both participate in a smoking cessation group training consisting of seven weekly counseling sessions of ninety minutes each. In addition to the training, employees in the intervention group receive a voucher as an incentive for being abstinent from smoking at the end of the training (€50), after three months (€50), after six months (€50), and after one year (€200). The control group does not receive any incentive. The primary outcome is carbon monoxide validated 12-month continuous abstinence from smoking (Russel's standard). Additionally, an economic evaluation is performed from a societal and an employer perspective. DISCUSSION: The present paper describes the methods and design of this cluster-randomized trial in detail. We hypothesize that the financial incentive for abstinence in the form of vouchers increases abstinence rates over and above the group training. The results of this study can provide important recommendations for enhancement of employee tobacco cessation. TRIAL REGISTRATION: Dutch Trial Register: NTR5657 . First received 27-01-2016.

MAdCAM-1 does not play a central role in the early pathophysiology of autoimmune hepatitis.

INTRODUCTION: CD4+ T cells are thought to have a central role in the pathogenesis of autoimmune hepatitis (AIH). Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) directs homing of CD4+ T cells in the alimentary tract and is a therapeutic target in inflammatory bowel diseases. Here we assessed MAdCAM-1 expression in AIH and viral hepatitis and related its expression with immune infiltrate analysis and histopathological key features. METHODS: Hepatic portal areas of pretreatment biopsies (n=10) and follow-up biopsies (n=9) of patients with a confirmed diagnosis of AIH were assessed for MAdCAM-1 expression and infiltrate composition using immunohistochemistry and multispectral imaging (Vectra® Polaris™). Controls consisted of biopsies of patients with untreated chronic viral hepatitis B or C (n=22). RESULTS: MAdCAM-1 expression on endothelium was sparsely present in portal fields of two treatment-naïve AIH patients. Three patients showed MAdCAM-1 expression within lymphoid aggregates. No expression of significance (including single-cell expression) was observed in the remaining 6 patients. In contrast, viral hepatitis C biopsies showed endothelial MAdCAM-1 expression in 8 of 13 untreated patients. Densities of both B-cells (CD20+) and CD4+ T-cells (CD3+ CD8-) were increased in AIH and viral hepatitis patients with MAdCAM-1 expression. CONCLUSION: MAdCAM-1 was detected in liver biopsies in a minority of patients with AIH at the time of diagnosis suggesting no central role in its pathophysiology. Lymphoid or reticular MAdCAM-1 pattern expression was associated with more dense infiltrates of both B-cells and CD4+ T-cells, and may be related to the formation of secondary lymphoid follicles.

Risk factors and treatment for recurrent vulvar squamous cell carcinoma.

Recurrent disease occurs in 12-37% of patients with vulvar squamous cell carcinoma (VSCC). Decisions about treatment of recurrent VSCC mainly depend on the location of the recurrence and previous treatment, resulting in individualized and consensus-based approaches. Most recurrences (40-80%) occur within 2 years after initial treatment. Currently, wide local excision is the treatment of choice for local recurrences. Isolated local recurrence of VSCC has a good prognosis, with reported 5-year survival rates of up to 60%. Groin recurrences and distant recurrences are less common and have an extremely poor prognosis. For groin recurrences, surgery with or without (chemo) radiotherapy is a treatment option, depending on prior treatment. For distant recurrences, there are only palliative treatment options. In this review, we give an overview of the available literature and discuss epidemiology, risk factors, and prognostic factors for the different types of recurrent VSCC and we describe treatment options and clinical outcome.

The uptake of R-type cobalamin-binding protein by isolated rat liver cells.

The uptake of R-type cobalamin-binding protein from human granulocytes and plasma by isolated parenchymal rat liver cells has been studied. When [57Co] cyanocobalamin-saturated granulocyte-binding protein or transcobalamin III was incubated with the liver cells in a concentration of 500 pM, more than 80% of the vitamin was taken up in 1 h. Vitamin B-12 bound to plasma transcobalamin I, however, was not taken up unless the protein was desialylated by neuraminidase from Vibrio cholerae. The uptake of iodinated pure granulocyte-binding protein, saturated with cobalamin, reached 100% and was accompanied by increasing intracellular proteolytic degradation of the binding protein. EGTA and asialo-orosomucoid completely inhibited this process of uptake and degradation, whereas partial inhibition was caused by chloroquine and colchicine. These observations provide evidence that these (asialo)-R-type cobalamin-binding proteins are taken up by the cell through the plasma membrane receptor for asialoglycoproteins by means of endocytosis followed by proteolysis of the binding protein in the lysosomes.

Diabetes, intermittent claudication, and risk of cardiovascular events. The Framingham Study.

The impact of diabetes on intermittent claudication was examined in 1813 men and 2504 women with 34-yr follow-up data in the Framingham study. For both sexes, diabetes was associated with a two- to threefold excess risk of intermittent claudication compared with its absence. A pronounced excess risk was also observed in subjects on oral hypoglycemic therapy and in women receiving insulin. Although diabetes was often associated with an atherogenic-risk profile, controlling for age and several concomitant risk factors failed to eliminate the association with intermittent claudication. Those who developed both intermittent claudication and diabetes were at an especially high risk of incident cardiovascular events. In women, the risk of coronary heart disease, stroke, and cardiac failure was increased 3-4 times when diabetes and intermittent claudication occurred together compared with when either condition existed alone. In diabetic men, the presence of intermittent claudication doubled the risk of stroke, and cardiac failure was approximately 3 times more likely in subjects with both conditions compared with either alone. We conclude that diabetes is an important risk factor for intermittent claudication, which in turn confers a serious prognosis for subsequent cardiovascular outcomes in the patient with diabetes.

Antibiotic use in the nursing home. Physician practice patterns.

Antibiotic usage patterns were studied in two nonproprietary nursing homes that included 720 intermediate care and skilled nursing home beds. Medical records of residents receiving antibiotics were reviewed every fourth month for 1 year. Of 181 antibiotic prescriptions written for indications other than prophylaxis, 41% were for presumed urinary tract infections, 35% for respiratory tract infections, and 14% for skin/soft-tissue infections. The majority of antibiotic prescriptions (54%) were made by telephone order. Cultures were obtained in 60% of suspected infections; two thirds of cultures were of the urine. Antibiotics were changed during the course of therapy in only 12% of cases. Eighty-one percent of residents treated with antibiotics improved or were cured, 9.5% were hospitalized or died, and an additional 9.5% failed to improve but remained in the nursing home. Fever was present in 48% of cases prior to treatment, but had no predictive value for patient outcome. We conclude that antibiotic treatment in the nursing home is often initiated in the absence of fever, culture information, or examination of the patient. Empiric prescription of antibiotics in this setting generally is associated with favorable clinical course.

Eggs, serum cholesterol, and coronary heart disease.

The Framingham Study has investigated the effect of host and environmental factors on the development of coronary heart disease since 1949. Serum cholesterol level was determined to the one of the risk factors for coronary heart disease. The nutrient intake, in a subsample of the study population, was determined in 1957. A review of this material has permitted an estimate of egg consumption on each of 912 subjects. The serum cholesterol distribution curves of the subjects according to tertile of egg intake were almost identical, and no relationship between egg intake and coronary heart disease incidence was found. It is concluded that within the range of egg intake of this population differences in egg consumption were unrelated to blood cholesterol level or to coronary heart disease incidence.

Epidemiology of some peripheral arterial findings in diabetic men and women: experiences from the Framingham Study.

PURPOSE AND PATIENTS AND METHODS: The purpose of this study was to determine the relationship between diabetes and the development of some peripheral arterial findings--carotid and femoral bruits and nonpalpable pedal pulse--and acute cardiovascular events in 1,196 men and 1,582 women based on 20-year follow-up data in the Framingham Study. RESULTS: For both men and women without diabetes, the incidence of carotid bruits and nonpalapble pedal pulses increased significantly with age (p less than 0.05) without any apparent male predominance. In contrast, diabetic men and women were at an elevated risk of each peripheral arterial condition that was not appreciably different across age groups. Compared with women without diabetes, those with diabetes experienced nearly a twofold excess of femoral bruits (p less than 0.05) and a 50% excess of nonpalpable pedal pulses (p less than 0.01). Among men, diabetes nearly doubled the risk of carotid bruits (p less than 0.05). Those who had both diabetes and symptoms of peripheral arterial disease were at especially high risk of incident cardiovascular events. In particular, nonpalpable pedal pulses were associated with more than a twofold excess of coronary heart disease (p less than 0.05) and stroke (p less than 0.01) in diabetic women and more than a twofold excess of coronary heart disease and cardiac failure in diabetic men (p less than 0.01). Femoral bruits doubled the risk of coronary heart disease in diabetic men (p less than 0.05). CONCLUSION: We conclude that while diabetes predisposes to various forms and locations of peripheral arterial disease, the enhanced risk of acute cardiovascular events experienced by diabetic patients is increased further when diabetes is accompanied by indications of a peripheral arterial condition. Since signs of peripheral arterial disease may suggest an impending or coexistent atherosclerotic process, careful examination of arterial circulation by evaluating peripheral pulses and assessing whether bruits are present is important.

Prevalence and correlates of posterior extra echocardiographic spaces in a free-living population based sample (the Framingham study).

To obtain epidemiologic information on extra echocardiographic spaces immediately posterior to the left ventricular free wall, 2,028 subjects in the original Framingham cohort study (mean age 70 +/- 7 years) and 3,624 of the offspring of the cohort (and their spouses) (mean age 44 +/- 10 years) with adequate echocardiograms were evaluated. Extra echocardiographic spaces were detected in 370 (6.5%) of the 5,652 subjects. The prevalence ranged from less than 1% in subjects in the 20- to 30-year age decade to greater than 15% for those in their 80s. Extra echocardiographic spaces tended to be more common in subjects who were older, female, obese, more hypertensive, and who had higher blood sugar levels and higher low density lipoprotein cholesterol levels (measured 8 years earlier). The high prevalence of extra echocardiographic spaces and the independent association with age (cohort and offspring), obesity (cohort and male offspring), and ventricular septal hypertrophy (cohort and male offspring) is compatible with at least 2 hypotheses among others that should be tested: (1) Subepicardial fat may often masquerade as pericardial fluid producing a posterior extra echocardiographic space, especially in obese elderly subjects. (2) Small posterior extra echocardiographic spaces may often be early markers of subclinical hypertensive heart disease.

Structural requirements of alloxan and ninhydrin for glucokinase inhibition and of glucose for protection against inhibition.

1. In order to elucidate the mechanism underlying the interactions between glucose and alloxan when competing for the sugar binding site of glucokinase from pancreatic B-cells or liver, the structural requirements of the enzyme for inhibition by alloxan and for protection by glucose were determined. 2. With a half-maximal inhibitory concentration of 5 microM, alloxan was the most potent pyrimidine derivative inhibitor of glucokinase. Uramil was a less potent enzyme inhibitor. A variety of other pyrimidine derivatives and related substances were ineffective. 3. Ninhydrin also inhibited glucokinase with a half-maximal inhibitory concentration of 5 microM. Isatin was a slightly less potent enzyme inhibitor. Several other indoline derivatives were ineffective. 4. Only glucose derivatives with a sufficiently bulky substituent in position C-2, such as the glucokinase substrates glucose and mannose and the inhibitors mannoheptulose, glucosamine, and N-acetylglucosamine, protected glucokinase against inhibition by alloxan by binding to the active site of the enzyme. Glucose epimers which differed in other positions did not protect the enzyme against alloxan inhibition. 5. DTT (dithiothreitol) protected glucokinase against inhibition by alloxan and reversed the inhibition of the enzyme induced by alloxan. Thus the mechanism of glucokinase inhibition by alloxan and other inhibitors, such as uramil and ninhydrin, is an oxidation of functionally essential SH groups of the enzyme, where the most reactive keto group of the inhibitor acts as the hydrogen acceptor. The protective action of glucose and several C-2 epimers demonstrates that these functionally essential SH groups are situated in the sugar binding site of the glucokinase. 6. The present results support our contention, that the pancreatic B-cell glucokinase is the major target mediating the inhibition of insulin secretion by alloxan.

Gout and coronary heart disease: the Framingham Study.

The relationship between gout, not associated with the use of diuretics, and the development of coronary heart disease was examined in 5209 subjects originally enrolled in the Framingham Study. Based on 32 years of follow-up, the two year incidence of gout was six times greater in men (3.2/1000) as compared to women (0.5/1000). For both sexes, the incidence of gout showed no clear relationship with age. Among men who never received diuretics, those afflicted by gout, as compared to those without gout, experienced a 60% excess of coronary heart disease (95% confidence limits, 1.1-2.2), primarily attributed to a two fold excess of angina pectoris (95% confidence limits, 1.2-3.1). Although gout was usually associated with other atherogenic risk factors, control of systolic blood pressure, total cholesterol, alcohol intake, body mass index, and diabetes failed to alter the effect of gout on the preceding coronary events in men. For women, there were no significant associations between gout and coronary heart disease. We conclude that gout, unrelated to the intake of diuretics, imparts an additional risk of coronary heart disease in men, unexplained by clinically measured risk factors.

Family patterns of coronary heart disease mortality: the Framingham Longevity Study.

Family patterns for age at death were examined in a 40 year follow-up of 5209 men and women (2900 deceased, 2309 living) in the Framingham Study and their parents. Age at death of both mothers and fathers was significantly older for surviving offspring when compared to decreased offspring (p less than 0.0001). When longevity was assessed according to cause of death in the offspring, parental age at death was a significant predictor of death by coronary heart disease (CHD), but not for stroke or cancer. Multiple regression analysis for offspring with sudden CHD death revealed that mother's age at death was a significant predictor of age at sudden CHD death (p less than 0.0003) whereas father's age at death was a significant predictor of age at death in non-sudden CHD death (p less than 0.004). Life table analysis showed longest survival rates associated with both parents surviving to age 75 or older followed by mother only surviving to age 75 or older, then father only, and shortest survival with neither parent surviving to age 75. Longevity appears to be more strongly associated with maternal death age than parental death age. Proportional hazards analysis of risk factors associated with CHD revealed that systolic blood pressure, sex of the individual, and cigarette smoking were the most significant predictors of death age. These findings suggest that familial similarities for death age may be mediated primarily through shared CHD risk factors within families, either genetic or non-genetic.

The epidemiology of varicose veins: the Framingham Study.

The epidemiology of varicose veins was examined in 3,822 adults in the Framingham Study. Findings indicate that the incidence of varicose veins is higher among women than men, with no clear age differences. Compared to women without varicose veins, women with varicose veins were more often obese (p less than .01), had lower levels of physical activity (p less than .001) and higher systolic blood pressure (p less than .001), and were older at menopause (p less than .001). Women who reported spending eight or more hours in an average day in sedentary activities (sitting or standing) also had a significantly higher incidence of varicose veins than those who spent four or fewer hours a day in such activities (p less than .05). For men, varicose veins coexisted with lower levels of physical activity (p less than .05) and higher smoking rates (p less than .05). While men and women with varicose veins had a higher incidence of atherosclerotic cardiovascular disease than those without varicose veins, only the excess risk of coronary heart disease in women was statistically significant (p less than .05). However, this finding was not significant after controlling for body mass and systolic blood pressure. These results suggest that increased physical activity and weight control may help prevent varicose veins among adults at high risk, and reduce the overall risk of atherosclerotic cardiovascular disease as well.

Mechanism of antinociceptive action of clonidine in nonmyelinated nerve fibres.

Despite a large body of clinical evidence in favour of a local anesthetic effect of clonidine, the underlying mechanism has not yet been elucidated. In this study we have used the sucrose-gap method to measure the effects of clonidine on the electrophysiological properties of nonmyelinated nerve fibers in the rabbit vagus nerve. The results showed that clonidine enhanced the hyperpolarizing and reduced the depolarizing afterpotential that follow compound action potentials during electrical activity. We showed that summation of these afterpotentials shifts the membrane potential toward more negative values, thus creating a region of low safety conduction, where the local circuit currents might fail to depolarize the axonal membrane to the threshold value needed to open voltage-dependent Na(+) channels. Yohimbine did not reverse the inhibitory effects of clonidine on impulse propagation, indicating that the observed effects of clonidine relies on mechanisms not mediated by alpha(2)-adrenoceptors.

Effect of economic barriers to medical care on patients' noncompliance.

The post-hospital care of 290 patients with selected chronic conditions of a specific severity who were discharged over a 3-month period from a general hospital in Halifax, Canada, was studied. The majority of the patients were married. The average age of the men was 59.2 years and of the women 58.1. More than half of the patients belonged to the low socioeconomic group earning between $1,000 and $6,999 a year. Their average period of education was 8.4 years. Interviews with the patients about their compliance with physicians' orders revealed that 40.4 percent had not complied with one or more of their physician's recommendations. Lack of compliance was related to age, marital status, education, income, and severity of disease. It was also associated with high dosages of medicine and multiple prescriptions. Cost barriers constituted a significant factor in noncompliance.