Heritability, determinants and reference values of renal length: a family-based population study

OBJECTIVES: In this population-based study, reference values were generated for renal length, and the heritability and factors associated with kidney length were assessed. METHODS: Anthropometric parameters and renal ultrasound measurements were assessed in randomly selected nuclear families of European ancestry (Switzerland). The adjusted narrow sense heritability of kidney size parameters was estimated by maximum likelihood assuming multivariate normality after power transformation. Gender-specific reference centiles were generated for renal length according to body height in the subset of non-diabetic non-obese participants with normal renal function. RESULTS: We included 374 men and 419 women (mean ± SD, age 47 ± 18 and 48 ± 17 years, BMI 26.2 ± 4 and 24.5 ± 5 kg/m(2), respectively) from 205 families. Renal length was 11.4 ± 0.8 cm in men and 10.7 ± 0.8 cm in women; there was no difference between right and left renal length. Body height, weight and estimated glomerular filtration rate (eGFR) were positively associated with renal length, kidney function negatively, age quadratically, whereas gender and hypertension were not. The adjusted heritability estimates of renal length and volume were 47.3 ± 8.5 % and 45.5 ± 8.8 %, respectively (P < 0.001). CONCLUSION: The significant heritability of renal length and volume highlights the familial aggregation of this trait, independently of age and body size. Population-based references for renal length provide a useful guide for clinicians. KEY POINTS: • Renal length and volume are heritable traits, independent of age and size. • Based on a European population, gender-specific reference values/percentiles are provided for renal length. • Renal length correlates positively with body length and weight. • There was no difference between right and left renal lengths in this study. • This negates general teaching that the left kidney is larger and longer.

Responsiveness and habituation of soluble icam-1 to acute psychosocial stress in men: determinants and efect of stress-hemoconcentration

We studied the psychophysiology of soluble intercellular adhesion molecule-1 (sICAM-1) in 25 apparently healthy middle-aged men who underwent an acute psychosocial stressor three times with one week apart. Measures of the biological stress response were obtained at week one and three. The magnitude of the sICAM-1 stress response showed no habituation between visits. At week one, cognitive stress appraisal independently predicted integrated sICAM-1 area under the curve (AUC) between rest, immediately post-stress, and 45 min and 105 min post-stress (beta=.67, p=.012, deltaR(2)=.41). Diastolic blood pressure AUC (beta=-.45, p=.048, deltaR(2)=.21) and heart rate (AUC) (beta=.44, p=.055, deltaR(2)=.21) were independent predictors of sICAM-1 (AUC) at week three. Adjustment for hemoconcentration yielded a decrease in sICAM-1 levels from rest to post-stress (p<.001). Stress responsiveness of plasma sICAM-1 was predicted by stress perception and hemodynamic reactivity and affected by stress-hemoconcentration but unrelated to cortisol reactivity and not readily adapting to stress repeats.

Socioeconomic determinants of health related quality of life in childhood and adolescence: results from a European study

STUDY OBJECTIVE: The objective of this study was to investigate the impact of two different socioeconomic status (SES) measures on child and adolescent self reported health related quality of life (HRQoL). The European KIDSCREEN project aims at simultaneous developing, testing, and implementing a generic HRQoL instrument. DESIGN AND SETTING: The pilot version of the questionnaire was applied in school surveys to students from 8 to 18 years of age, as well as to their parents, together with such determinants of health status as two SES indicators, the parental educational status and the number of material goods in the family (FAS, family affluence scale). PARTICIPANTS: Students from seven European countries: 754 children (39.8%; mean: 9.8 years), and 1142 adolescents (60.2 %; mean: 14.1 years), as well as their respective parents. MAIN RESULTS: In children, a higher parental educational status was found to have a significant positive impact on the KIDSCREEN dimensions: physical wellbeing, psychological wellbeing, moods and emotions, bullying and perceived financial resources. Increased risk of low HRQoL was detected for adolescents in connection with their physical wellbeing. Family wealth plays a part for children's physical wellbeing, parent relations and home life, and perceived financial resources. For adolescents, family wealth furthermore predicts HRQoL on all KIDSCREEN dimensions. CONCLUSIONS: There is evidence to suggest that exposure to low parental educational status may result in a decreased HRQoL in childhood, whereas reduced access to material (and thereby social) resources may lead to a lower HRQoL especially in adolescence.

Causes of death and determinants of outcome in critically ill patients

INTRODUCTION: Whereas most studies focus on laboratory and clinical research, little is known about the causes of death and risk factors for death in critically ill patients. METHODS: Three thousand seven hundred patients admitted to an adult intensive care unit (ICU) were prospectively evaluated. Study endpoints were to evaluate causes of death and risk factors for death in the ICU, in the hospital after discharge from ICU, and within one year after ICU admission. Causes of death in the ICU were defined according to standard ICU practice, whereas deaths in the hospital and at one year were defined and grouped according to the ICD-10 (International Statistical Classification of Diseases and Related Health Problems) score. Stepwise logistic regression analyses were separately calculated to identify independent risk factors for death during the given time periods. RESULTS: Acute, refractory multiple organ dysfunction syndrome was the most frequent cause of death in the ICU (47%), and central nervous system failure (relative risk [RR] 16.07, 95% confidence interval [CI] 8.3 to 31.4, p < 0.001) and cardiovascular failure (RR 11.83, 95% CI 5.2 to 27.1, p < 0.001) were the two most important risk factors for death in the ICU. Malignant tumour disease and exacerbation of chronic cardiovascular disease were the most frequent causes of death in the hospital (31.3% and 19.4%, respectively) and at one year (33.2% and 16.1%, respectively). CONCLUSION: In this primarily surgical critically ill patient population, acute or chronic multiple organ dysfunction syndrome prevailed over single-organ failure or unexpected cardiac arrest as a cause of death in the ICU. Malignant tumour disease and chronic cardiovascular disease were the most important causes of death after ICU discharge.

Prospectively assessed incidence, severity, and determinants of respiratory symptoms in the first year of life

Respiratory symptoms are common in infancy. Nevertheless, few prospective birth cohort studies have studied the epidemiology of respiratory symptoms in normal infants. The aim of this study was to prospectively obtain reliable data on incidence, severity, and determinants of common respiratory symptoms (including cough and wheeze) in normal infants and to determine factors associated with these symptoms. In a prospective population-based birth cohort, we assessed respiratory symptoms during the first year of life by weekly phone calls to the mothers. Poisson regression was used to examine the association between symptoms and various risk factors. In the first year of life, respiratory symptoms occurred in 181/195 infants (93%), more severe symptoms in 89 (46%). The average infant had respiratory symptoms for 4 weeks and 90% had symptoms for less than 12 weeks (range 0 to 23). Male sex, higher birth weight, maternal asthma, having older siblings and nursery care were associated with more, maternal hay fever with fewer respiratory symptoms. The association with prenatal maternal smoking decreased with time since birth. This study provides reliable data on the frequency of cough and wheeze during the first year of life in healthy infants; this may help in the interpretation of published hospital and community-based studies. The apparently reduced risk in children of mothers with hayfever but no asthma, and the decreasing effect of prenatal smoke exposure over time illustrate the complexity of respiratory pathology in the first year of life.

Microarray based study on virulence-associated genes and resistance determinants of Staphylococcus aureus isolates from cattle

Staphylococcus aureus is a common pathogen which can colonise and infect not only man, but also domestic animals. Especially, infection of cattle is of high economic relevance as S. aureus is an important causal agent of bovine mastitis. In the present contribution, a DNA microarray was applied for the study of 144 different gene targets, including resistance genes and genes encoding exotoxins, in S. aureus isolated from cows. One hundred and twenty-eight isolates from Germany and Switzerland were tested. These isolates were assigned to 20 different strains and nine clonal complexes. The majority of isolates belonged either to apparently closely related clonal complexes 8, 25, and 97 (together 34.4%) or were related to the sequenced bovine strain RF122 (48.4%). Notable characteristics of S. aureus of bovine origin are the carriage of intact haemolysin beta (in 82% of isolates tested), the absence of staphylokinase (in 89.1%), the presence of allelic variants of several exotoxins such as toxic shock syndrome toxin and enterotoxin N, and the occurrence of the leukocidin lukF-P83/lukM (in 53.1%). Two isolates were methicillin-resistant S. aureus (MRSA). One of them was a clonal complex 8 MRSA related to the epidemic MRSA strain Irish 01. The other one belonged to ST398/spa-type 34 resembling a newly emerging MRSA strain which has been described to occur in humans as well as in domestic animals. The presence of these two strains highlights the possibility of transfers of S. aureus strains between different host species.

Determinants of reduced walking speed in people with musculoskeletal pain

OBJECTIVE: Maintenance of good walking speed is essential to independent living. People with musculoskeletal disease often have reduced walking speed. We investigated determinants of slower walking, other than musculoskeletal disease, that might provide valuable additional targets for therapy. METHODS: We analyzed data from the Somerset and Avon Survey of Health, a community based survey of people aged over 35 years. A total of 2703 participants who reported hip or knee pain at baseline (1994/1995) were studied, and reassessed in 2002-2003; 1696 were available for followup, and walking speed was tested in 1074. Walking speed (m/s) was used as outcome measure. Baseline characteristics, including comorbidities and socioeconomic factors, were tested for their ability to predict reduced walking speed using multiple linear regression analysis. RESULTS: Age, female sex, and immobility at baseline were predictive of slower walking speed. Other independent risk factors included the presence of cataract, low socioeconomic status, intermittent claudication, and other cardiovascular conditions. Having a cataract was associated with a decrease of 0.10 m/s (95% CI 0.03, 0.16). Those in social class V had a walking speed 0.22 m/s (95% CI 0.126, 0.31) slower than those in social class I. CONCLUSION: Comorbidities, age, female sex, and lower socioeconomic position determine walking speed in people with joint pain. Issues such as poor vision and social-economic disadvantage may add to the effect of musculoskeletal disease, suggesting the need for a holistic approach to management of these patients.

Characteristics, determinants, and clinical relevance of CD4 T cell recovery to <500 cells/microL in HIV type 1-infected individuals receiving potent antiretroviral therapy

BACKGROUND: The CD4 T cell count recovery in human immunodeficiency virus type 1 (HIV-1)-infected individuals receiving potent antiretroviral therapy (ART) shows high variability. We studied the determinants and the clinical relevance of incomplete CD4 T cell restoration. METHODS: Longitudinal CD4 T cell count was analyzed in 293 participants of the Swiss HIV Cohort Study who had had a plasma HIV-1 RNA load <1000 copies/mL for > or =5 years. CD4 T cell recovery was stratified by CD4 T cell count 5 years after initiation of ART (> or =500 cells/microL was defined as a complete response, and <500 cells/microL was defined as an incomplete response). Determinants of incomplete responses and clinical events were evaluated using logistic regression and survival analyses. RESULTS: The median CD4 T cell count increased from 180 cells/microL at baseline to 576 cells/microL 5 years after ART initiation. A total of 35.8% of patients were incomplete responders, of whom 47.6% reached a CD4 T cell plateau <500 cells/microL. Centers for Disease Control and Prevention HIV-1 disease category B and/or C events occurred in 21% of incomplete responders and in 14.4% of complete responders (P>.05). Older age (adjusted odds ratio [aOR], 1.71 per 10-year increase; 95% confidence interval [CI], 1.21-2.43), lower baseline CD4 T cell count (aOR, 0.37 per 100-cell increase; 95% CI, 0.28-0.49), and longer duration of HIV infection (aOR, 2.39 per 10-year increase; 95% CI, 1.19-4.81) were significantly associated with a CD4 T cell count <500 cells/microL at 5 years. The median increases in CD4 T cell count after 3-6 months of ART were smaller in incomplete responders (P<.001) and predicted, in conjunction with baseline CD4 T cell count and age, incomplete response with 80% sensitivity and 72% specificity. CONCLUSION: Individuals with incomplete CD4 T cell recovery to <500 cells/microL had more advanced HIV-1 infection at baseline. CD4 T cell changes during the first 3-6 months of ART already reflect the capacity of the immune system to replenish depleted CD4 T lymphocytes.

Primary care physician supply and other key determinants of health care utilisation: The case of Switzerland

Background The Swiss government decided to freeze new accreditations for physicians in private practice in Switzerland based on the assumption that demand-induced health care spending may be cut by limiting care offers. This legislation initiated an ongoing controversial public debate in Switzerland. The aim of this study is therefore the determination of socio-demographic and health system-related factors of per capita consultation rates with primary care physicians in the multicultural population of Switzerland. Methods The data were derived from the complete claims data of Swiss health insurers for 2004 and included 21.4 million consultations provided by 6564 Swiss primary care physicians on a fee-for-service basis. Socio-demographic data were obtained from the Swiss Federal Statistical Office. Utilisation-based health service areas were created and were used as observational units for statistical procedures. Multivariate and hierarchical models were applied to analyze the data. Results Models within the study allowed the definition of 1018 primary care service areas with a median population of 3754 and an average per capita consultation rate of 2.95 per year. Statistical models yielded significant effects for various geographical, socio-demographic and cultural factors. The regional density of physicians in independent practice was also significantly associated with annual consultation rates and indicated an associated increase 0.10 for each additional primary care physician in a population of 10,000 inhabitants. Considerable differences across Swiss language regions were observed with reference to the supply of ambulatory health resources provided either by primary care physicians, specialists, or hospital-based ambulatory care. Conclusion The study documents a large small-area variation in utilisation and provision of health care resources in Switzerland. Effects of physician density appeared to be strongly related to Swiss language regions and may be rooted in the different cultural backgrounds of the served populations.

Determinants of cerebral extracellular potassium after severe human head injury

The key role players of brain swelling seen after severe human head injury have only been partly determined. We used our human head injury data base to determine relationships between potassium, glutamate, lactate and cerebral blood flow (CBF). A total of 70 severely head injured patients (GCS < or = 8) were studied using intracerebral microdialysis to measure extracellular glutamate, potassium and lactate. Xenon CT was used to determine regional cerebral blood flow (rCBF). The mean +/- SEM of the r value of all patients, between potassium and glutamate, and potassium and lactate was 0.25 +/- 0.04 (p < 0.0001) and 0.17 +/- 0.06 (p = 0.006), respectively, demonstrating in both cases a positive relationship. rCBF was negatively correlated with potassium with marginal significance (r = -0.35, p = 0.08). When separated into two groups, patients with contusion had higher potassium levels than patients without contusion (1.55 +/- 0.03 mmol/l versus 1.26 +/- 0.02 mmol/l, respectively). These results in severely head injured patients confirm previous in vitro and animal studies in which relationships between potassium, glutamate, lactate and CBF were found. Potassium efflux is a major determinant of cell swelling leading to clinically significant cytotoxic edema due to increased glutamate release during reduced cerebral blood flow.