Campylobacter control measures in indoor broiler chicken: critical re-assessment of cost-utility and putative barriers to implementation.

As campylobacteriosis is one of the most important foodborne infections, a European Union (EU)-27 level cost-effectiveness model has been developed on the socio-economic costs and benefits of applying certain control measures for the reduction of Campylobacter in broiler meat. This is expected to be a gold standard for food safety policymakers in the EU; hence, the validity of its modelling assumptions is essential. The authors of the present paper conducted an independent review of model input parameters on health and economic burden and found that the model most probably overestimated the burden of human campylobacteriosis. A discounted, quality-adjusted life year (QALY)-based European estimate has been developed for human campylobacteriosis and resulted in 15.23 QALY loss per 1000 human gastroenteritis cases. Country-specific cost of illness estimates have been developed for various countries in the EU-27. Based on these model adaptations, a selected Campylobacter control strategy was re-assessed and its high cost-effectiveness was confirmed at the EU level, and also in all but three Member States. Bacteriocin treatment or vaccination of the animals, two alternative control measures were also re-evaluated, and these strategies seemed to be far less cost-effective than the investigated strategy. Putative barriers to the rapid implementation of the investigated Campylobacter control strategy are discussed, and potential solutions are proposed. Further research is required on stakeholder perspectives pertaining to the realistic barriers and implementation opportunities.

Comparison of efficacy and local tolerability of estradiol metered-dose transdermal spray to estradiol patch in a network meta-analysis.

OBJECTIVES: Transdermal hormone replacement therapy is preferred for menopausal vasomotor symptoms. Our purpose was to compare the efficacy and local tolerability of a patch and a metered-dose transdermal spray that have never been directly compared. METHOD: The relative change in the number of hot flushes between baseline and week 12 was selected as an efficacy indicator and the frequency of local skin reactions as a tolerability indicator. A network meta-analysis was performed to compare efficacy. Application site tolerability was compared descriptively. RESULTS: Overall 46 studies were identified. In the efficacy analysis, eight active treatment arms and a placebo arm were determined based on the estradiol daily dose (from 14 µg to 50 µg). All but one had a significantly higher effect on relative change in the number of hot flushes than did the placebo. We found no evidence for different efficacy of the patch and the metered-dose transdermal spray. The latter performed better in terms of local skin reactions. CONCLUSION: The patch and the metered-dose transdermal spray seem to have the same efficacy on vasomotor symptoms in estradiol hormone replacement. The local tolerability of the metered-dose transdermal spray is favorable.

Wintertime surgery increases the risk of conversion to hip arthroplasty after internal fixation of femoral neck fracture.

UNLABELLED: The study demonstrates that wintertime surgeries are associated with impaired fracture healing and increases the risk of conversion to hip arthroplasty after osteosynthesis of femoral neck fracture. Furthermore, the results raise the possibility of association between seasonal changes in vitamin D levels and impaired fracture healing of femoral neck fracture. INTRODUCTION: Although the changes of vitamin D level and calcitropic hormones influencing bone metabolism are seasonal, the effect of seasons on hip fracture healing is unknown. We assessed the effects of seasonal periodicity on conversion to hip arthroplasty after primary osteosynthesis of femoral neck fracture. METHODS: This nationwide retrospective observational cohort study involved 2779 patients aged ≥ 60 years who underwent internal screw fixation for primary femoral neck fracture and were discharged in 2000. Cases requiring conversion to arthroplasty during the 8-year follow-up derived from the Hungarian health insurance database were registered. Risk factors assessed included sex, age, fracture type, season of primary surgery and surgical delay. Competing-risks regression analysis was used for data analyses. RESULTS: During the observation period, 190 conversions to hip arthroplasty (6.8%) were identified, yielding an overall incidence of 19.5 per 1000 person-years. The crude incidence rates of conversions after osteosynthesis in winter, spring, summer and fall were 28.6, 17.8, 16.9 and 14.7 per 1000 person-years, respectively. Besides younger age, female sex and intracapsular fracture displacement, wintertime primary osteosynthesis significantly increased the risk of conversion (fall vs. winter, hazard ratio (HR): 0.50, 95% confidence interval [95% CI 0.33-0.76]; spring vs. winter, HR: 0.63, [95% CI 0.44-0.92]; summer vs. winter, HR: 0.62, [95% CI 0.42-0.91]). CONCLUSIONS: Our study demonstrate that wintertime primary osteosynthesis increases the risk of conversion surgeries. The results may help improving the outcome of primary fixation of femoral neck fractures.

Time to do more: addressing clinical inertia in the management of type 2 diabetes mellitus.

AIMS: Clinical inertia, the tendency to maintain current treatment strategies despite results demanding escalation, is thought to substantially contribute to the disconnect between clinical aspirations for patients with diabetes and targets achieved. We wished to explore potential causes of clinical inertia among physicians and people with diabetes. METHODS: A 20-min online survey of 652 adults with diabetes and 337 treating physicians in six countries explored opinions relating to clinical inertia from both perspectives, in order to correlate perceptions and expectations relating to diagnosis, treatment, diabetes complications and therapeutic escalation. RESULTS: Physicians had low expectations for their patients, despite the belief that the importance of good glycaemic control through lifestyle and pharmacological interventions had been adequately conveyed. Conversely, people with diabetes had, at best, a rudimentary understanding of the risks of complications and the importance of good control; indeed, only a small proportion believed lifestyle changes were important and the majority did not intend to comply. CONCLUSIONS: The principal findings of this survey suggest that impairments in communication are at the heart of clinical inertia. This manuscript lays out four key principles that we believe are achievable in all environments and can improve the lives of people with diabetes.

Transferability of National Institute for Health and Clinical Excellence recommendations for pharmaceutical therapies in oncology to Central-Eastern European countries.

The health burden of malignancies is greater in Central-Eastern Europe than in Western Europe. Furthermore, these countries have more limited healthcare resources, and therefore transparent decision criteria for innovative cancer therapies, including the assessment of cost-effectiveness, are an absolute necessity. Transferability of good-quality technology assessment reports, especially those prepared by National Institute for Health and Clinical Excellence (NICE) in the UK, could be highly beneficial to prevent duplication of efforts and save resources for local technology assessment. Our objective was to summarise key factors influencing the transferability of NICE recommendations in oncology for policy makers and oncologists in Central-Eastern Europe without personal experience in health technology assessment. In general, NICE recommendations are not transferable without adjustment of the analyses to local data. Even if the recommendation is positive, the conclusion can still be negative in lower-income countries, mainly due to relative price differences and the significance of the local budget impact. Technologies with negative NICE recommendations can still be cost-effective in Central-Eastern Europe due to the worse health status and therefore the greater potential health gain of the targeted population. The appropriateness of reimbursement decisions must be improved in Central-Eastern Europe, but copying NICE recommendations without local adjustment may do more harm than good.

Epidemiology of the metabolic syndrome in Hungary.

OBJECTIVES: Hungary has high cardiovascular mortality. Recent studies have revealed a high prevalence of several cardiovascular risk factors, including obesity, diabetes and hypertension. The objective of this study was to assess the prevalence of the metabolic syndrome in Hungary. STUDY DESIGN: Cross-sectional study. METHODS: Within the framework of the Hungarian General Practitioners' Morbidity Sentinel Stations Programme, a random sample of 2006 individuals aged 20-69 years was selected in 2006. Physical examinations, blood sampling and data collection were performed by general practitioners. Information on environmental factors was gathered using a questionnaire. The population prevalence was estimated based on the sample frequencies. RESULTS: The overall response rate was 91%. The age-adjusted prevalence of the metabolic syndrome using the 2009 Harmonized definition was 38% [95% confidence interval (CI) 35-42%] in males and 30% (95% CI 28-33%) in females aged 20-69 years. There were no significant regional differences in the frequency figures. CONCLUSIONS: The high prevalence of the metabolic syndrome is a serious public health problem in Hungary, and remains a major determinant of the high burden of cardiovascular disease.

Does socioeconomic status fully mediate the effect of ethnicity on the health of Roma people in Hungary?

BACKGROUND: Several models have been proposed to explain the association between ethnicity and health. It was investigated whether the association between Roma ethnicity and health is fully mediated by socioeconomic status in Hungary. METHODS: Comparative health interview surveys were performed in 2003-04 on representative samples of the Hungarian population and inhabitants of Roma settlements. Logistic regression models were applied to study whether the relationship between Roma ethnicity and health is fully mediated by socioeconomic status, and whether Roma ethnicity modifies the association between socioeconomic status and health. RESULTS: The health status of people living in Roma settlements was poorer than that of the general population (odds ratio of severe functional limitation after adjustment for age and gender 1.8 (95% confidence interval 1.4 to 2.3)). The difference in self-reported health and in functionality was fully explained by the socioeconomic status. The less healthy behaviours of people living in Roma settlements was also related very strongly to their socioeconomic status, but remained significantly different from the general population when differences in the socioeconomic status were taken into account, (eg odds ratio of daily smoking 1.6 (95% confidence interval 1.3 to 2.0) after adjustment for age, gender, education, income and employment). CONCLUSION: Socioeconomic status is a strong determinant of health of people living in Roma settlements in Hungary. It fully explains their worse health status but only partially determines their less healthy behaviours. Efforts to improve the health of Roma people should include a focus on socioeconomic status, but it is important to note that cultural differences must be taken into account in developing public health interventions.

Dietary antioxidants and the risk of ischemic stroke: the Rotterdam Study.

In the Rotterdam Study, the authors investigated whether high intake of antioxidants from food is associated with the risk of stroke. Among 5,197 participants who were followed on average for 6.4 years, 227 ischemic strokes occurred. Higher intake of antioxidants was associated with a lower risk of stroke. The relationship was dose-dependent, significant for vitamin C, and most pronounced in smokers. These results agree with the view that high dietary intake of antioxidants, in particular vitamin C and--in smokers--vitamin E, reduces the risk of stroke.

Aspirin use and risk of stroke in the elderly: the Rotterdam Study.

The objective of the study was to assess the association between aspirin use and the risk of stroke in a population-based study in the elderly. The study was carried out within the framework of the Rotterdam Study, a prospective population-based cohort study. In the total study population there was a weak, nonsignificant association between aspirin use and the risk of stroke (adjusted relative risk 1.29, 95% CI 0.91-1.83). Stratification by history of vascular diseases revealed that aspirin considerably increased the risk of first-ever stroke in subjects free from vascular disease (adjusted relative risk 1.80; 95% CI 1.03-3.13). In persons with vascular disease, no association was observed between aspirin use and risk of stroke (adjusted relative risk 0.99, 95% CI 0.56-1.73). Our findings suggest that aspirin use may increase the risk of stroke in elderly subjects free from vascular disease.

J-shaped relation between blood pressure and stroke in treated hypertensives.

The objective of this study was to investigate the relationship between hypertension and risk of stroke in the elderly. The study was performed within the framework of the Rotterdam Study, a prospective population-based cohort study. The risk of first-ever stroke was associated with hypertension (relative risk, 1.6; 95% CI, 1.2 to 2.0) and with isolated systolic hypertension (relative risk, 1.7; 95% CI, 1.1 to 2.6). We found a continuous increase in stroke incidence with increasing blood pressure in nontreated subjects. In treated subjects, we found a J-shaped relation between blood pressure and the risk of stroke. In the lowest category of diastolic blood pressure, the increase of stroke risk was statistically significant compared with the reference category. Hypertension and isolated systolic hypertension are strong risk factors for stroke in the elderly. The increased stroke risk in the lowest stratum of blood pressure in treated hypertensive patients may indicate that the therapeutic goal of "the lower the better" is not the optimal strategy in the elderly.

Excess stroke among hypertensive men and women attributable to undertreatment of hypertension.

BACKGROUND AND PURPOSE: Most population-based studies indicate that a considerable proportion of hypertensive subjects are undertreated and that undertreatment is more prevalent among hypertensive men than among hypertensive women. The aim of our study was to investigate the consequences of undertreatment of hypertension for women and men in terms of stroke occurrence. METHODS: Approximately 45 000 men and women aged >/=20 years were examined in 2 population-based studies in the Netherlands. A cohort of 2616 hypertensive subjects (pharmacologically treated hypertensives and untreated hypertensives who needed pharmacological treatment according to the severity of their hypertension and the coexistence of additional cardiovascular risk factors) was selected for a follow-up study. Follow-up (mean duration, 4.6 years) was complete for 2369 (91%) of the enrolled hypertensive subjects. RESULTS: Compared with treated and controlled hypertensives, the relative risks of stroke for treated and uncontrolled hypertensives and for untreated hypertensives who needed treatment were 1.30 (95% CI, 0.70 to 2.44) and 1.76 (95% CI, 1.05 to 2.94), respectively. These relative risks and the prevalence of (undertreated) hypertension in the total population of 45 000 subjects were used to estimate the number of strokes in the Netherlands attributable to undertreatment. Among hypertensive men and women aged >/=20 years in the Netherlands, the proportions of strokes attributable to treated but uncontrolled blood pressure were 3.1% (95% CI, -5.2% to 18.7%) and 4.1% (95% CI, -7.2% to 20.7%), respectively. For untreated hypertensive men and women who should have been treated, these proportions were 22.8% (95% CI, 0.8% to 38.4%) and 25.4% (95% CI, 0. 5% to 42.5%), respectively. CONCLUSIONS: Increasing the detection of hypertension and improving adherence to current guidelines might prevent a considerable proportion of the incident strokes among hypertensives. The potential impact of achieving control of blood pressure in patients already being treated on the reduction of strokes requires further investigation.

Impaired vasoreactivity of the basilar artery system in patients with brainstem lacunar infarcts.

BACKGROUND AND PURPOSE: Diminished vasoreactivity (VR) has been evidenced in patients with hemispheric small vessel disease, however, there is no data regarding vertebrobasilar (VB) territory VR changes in patients with subcortical vascular encephalopathy located in the brainstem. Therefore, we compared the cerebral blood flow velocity (CBFV) responses of the VB system during different vasoregulatory challenges in healthy volunteers to those in patients with brainstem lacunar infarcts. METHODS: In 20 patients with brainstem lacunar infarcts and in 10 healthy volunteers the VR of the VB system was measured by analyzing the CBFV changes during different stimulation paradigms (ventilation, tilting and acetazolamide tests). During transcranial Doppler registration the systemic blood pressure and the expiratory partial CO2 pressure were monitored. RESULTS: During hypercapnia the VR was significantly higher in the control group than in the patient group (10.1 +/- 4.9 vs. 3.4 +/- 5.0 cm/s/kPa, p = 0.0025). In a subgroup of patients with mean baseline CBFV <25 cm/s the VR was 1.5 +/- 2.4 cm/ s/kPa, while patients with mean baseline CBFV >25 cm/s showed a significantly higher value (7.8 +/- 6.9 cm/s/kPa). Furthermore, in patients with mean baseline CBFV <25 cm/s the pulsatility index was significantly higher than in patients with mean baseline CBFV >25 cm/s (1.11 +/- 0.26 vs. 0.86 +/- 0.19, p = 0.0325), reflecting significantly higher vascular resistance in the former group. Although CBFV measurements during tilting and acetazolamide tests tended to support these findings, they showed no significant differences between patients and controls. CONCLUSION: Patients with cerebral microangiopathy involving the brainstem showed impaired VR in the VB flow territory in association with baseline CBFV.

Expression of membrane-bound and soluble cell adhesion molecules by human brain microvessel endothelial cells.

Expression of membrane-bound (mb) and soluble (s) forms of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) induced by tumor necrosis factor-alpha (TNF-alpha) has been measured by enzyme-linked immunosorbent assay in cultured human brain microvessel endothelial cells. Both the mb and the s forms of VCAM-1 and ICAM-1 were upregulated by TNF-alpha; however, the stimulation of the s forms was delayed in time. When piracetam, a neuroprotective drug, was added to the tissue culture medium simultaneously with TNF-alpha, the expression of mbVCAM-1 and ICAM-1 was lowered. Differential upregulation of mb and s forms of adhesion molecules and a novel effect of piracetam have been demonstrated in human brain microvessel endothelial cell cultures.

Endothelial cells cultured from human brain microvessels produce complement proteins factor H, factor B, C1 inhibitor, and C4.

The inflammatory mediators, cytokines and complement proteins are believed to regulate the sequential events during the development of lesions secondary to ischaemia and reperfusion. The endothelial cell monolayer of the brain microvasculature is the critical interface between the blood-borne mediators and brain tissue. The involvement of these cells in complement production and regulation has not been well documented. In the present study, expression of complement proteins (C1 inhibitor, factor H, factor B, C4) by cultured endothelial cells obtained from human brain microvessels has been characterized. Interferon gamma upregulates the production of all the complement factors studied. Serine proteases, plasmin and miniplasmin induce the expression of C4, decrease the level of ELISA detectable C1 inhibitor, and do not affect the production of factors H and B. These data indicate that complement proteins are expressed locally by the brain microvessels, and may modulate the inflammatory responses of brain tissue.

Involvement of a direct neural mechanism in the control of gonadal functions.

Much time has been devoted to study of the hypothalamo-hypophyseal-gonadal axis. However, there is now evidence of a complementary control mechanism for the gonads, namely a pituitary-independent, direct neural link that exists between the central nervous system and the gonads. We investigated whether mediobasal temporal lobe structures could control gonadal functions by a purely neural mechanism or whether they acted through the classical hypothalamo-hypophyseal system. Right- or left-sided deafferentiation of the temporal lobe was combined with right- or left-sided hemicastration in adult and prepubertal male and female rats. In adult females right-sided deafferentiation, regardless of the side of hemiovariectomy significantly reduced the extent of compensatory ovarian hypertrophy. Similar lesions on the left side did not interfere with the usual compensatory ovarian growth. This difference in compensatory hypertrophy between right- and left-sided lesioned rats was observed even in the face of a significant drop in serum LH concentrations in both groups. In pre- and postpubertal females temporal lobe lesion in either side was unable to alter compensatory hypertrophy or serum LH or progesterone concentrations. In adult male rats only left-sided deafferentiation combined with left orchidectomy resulted in decreased T production, while in prepubertal male rats, only right-sided brain surgery plus left orchidectomy resulted in a significant decrease in basal testosterone secretion of the remaining testis. These findings indicate that mediobasal temporolimbic structures are involved in the neural control of gonadal functions. It appears that this lateralized mechanism is age- and sex-dependent.

Neuropeptide-E-I antagonizes the action of melanin-concentrating hormone on stress-induced release of adrenocorticotropin in the rat.

The physiological role of melanin-concentrating hormone (MCH) in mammals is still very elusive, but this peptide might participate in the central control of the hypothalamopituitary adrenal (HPA) axis during adaptation to stress. Cloning and sequencing of the rat MCH (rMCH) cDNA revealed the existence of additional peptides encoded into the MCH precursor. Among these peptides, neuropeptide (N) glutamic acid (E) isoleucine (I) amide (NEI) is co-processed and secreted with MCH in rat hypothalamus. In the present work we examined: (1) The pattern of rMCH mRNA expression during the light and dark conditions in the rat hypothalamus and (2) The effect of intracerebroventricular (ICV) injections of rMCH and NEI in the control of basal or ether stress-modified release of corticotropin (ACTH), prolactin (PRL) and growth hormone (GH) secretion in vivo in light-on and light-off conditions. Our data indicate that rMCH mRNA levels do not change during the light-on period, but increase after the onset of darkness. Either alone or co-administered, rMCH and NEI do not modify basal secretion of GH and PRL at any time tested nor do they alter ether stress-induced changes in these two hormonal secretions. At the end of the light on period corresponding to the peak of the circadian rhythm in ACTH, administration of rMCH but not NEI leads to a decrease in ACTH levels while MCH is not effective during the light off period of the cycle (i.e. when basal ACTH levels are already low). Using a moderate ether induced stress, ACTH levels are only stimulated during the dark phase of the cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of unilateral deafferentiation in the medial basal portion of the temporal lobe on the hypophyseo-ovarian axis in rats: an age-dependent lateralized control mechanism.

The possible physiological role of the medial basal portion of the temporal lobe (including the corticomedial amygdaloid nucleus) in the neural control of the hypophyseo-ovarian axis was studied in pre- and postpubertal as well as in adult rats. Unilateral deafferentiation of a small medio-basal portion of the temporal lobe was performed in unilaterally ovariectomized animals, and the rate of compensatory hypertrophy of the remaining ovary was recorded. In adults compensatory ovarian hypertrophy was significantly reduced following right- but not left-sided deafferentiation. Temporal lobe surgery did not significantly influence the usual compensatory ovarian growth in pre- and postpubertal rats. Serum luteinizing hormone levels decreased significantly in adults regardless of the side of brain interventions, while no obvious change in the hormone concentration could be observed in prepubertals. Serum follicle-stimulating hormone concentrations showed no alterations in any experimental group. In postpubertal rats the serum progesterone level was unchanged following brain surgery. The present observations indicate that unilateral deafferentation in the temporal lobe could modify compensatory ovarian hypertrophy by a direct neural mechanism and data further suggest functional laterality of these structures in the control of ovarian functions.