Principles and recommendations for incorporating estimands into clinical study protocol templates.

Clinical study protocols are the foundation of good clinical studies. Prospective and multidisciplinary collaboration that pays attention to the design of all components of the study protocol can ensure that a clinical study will answer the research questions posed in a reliable manner that is meaningful for decision-makers and patients. The ICH E9(R1) addendum on estimands and sensitivity analysis in clinical trials provides a framework for clinical study planning to ensure alignment between study objectives, design, conduct, and analysis. The estimand or clinical question posed can be regarded as the backbone of the study and the clinical study protocol should reflect estimands accordingly. In practice, stakeholders are still learning how to embrace the estimand framework and how it impacts studies and study documents. In this paper, we anticipate that a protocol structure centred around estimands, or objectives rather than endpoints alone will prevail for all types of studies. To assist sponsors during this paradigm shift, this paper provides discussion and guidance for implementing the estimand framework in protocol templates.

Prevalence of metabolic syndrome in female and male patients at risk of psychosis.

Metabolic Syndrome (MetS) is one of the most common factors underlying the high rate of mortality observed in patients with schizophrenia. Recent research on this topic revealed that many of the patients studied were, in fact, in a medicated state. As such, it is unclear whether MetS is causally associated with the disorder itself or the medication used to treat it. In this study, patients with a clinically high risk of expressing first episode psychosis (CHR) were examined regarding the prevalence of MetS. N=144 unmedicated and antipsychotic-naïve CHR patients, aged between 18 and 42years and suffering from unmanifested prodromal symptoms, were compared with a cohort of N=3995 individuals from the "German Metabolic and Cardiovascular Risk Study" (GEMCAS). A slightly higher prevalence of individual MetS criteria was observed in the CHR group compared to the GEMCAS sample; specifically, the following were noted: a higher blood pressure (35.0% vs. 28.0%), increased waist circumference (17.6% vs. 15.1%), and increased fasting blood glucose (9.4% vs. 4.0%) in CHR patients. Additionally, the rate of reduced HDL cholesterol concentrations was lower in the control group (20.2% vs. 13.3%).

Safety of levetiracetam among infants younger than 12 months--Results from a European multicenter observational study.

BACKGROUND: There are limited data on the use of the antiepileptic drug (AED) levetiracetam for the treatment of infants. AIM: To prospectively evaluate the safety of levetiracetam oral solution and its impact on epilepsy severity in infants with different seizure types. METHODS: This noninterventional post-authorization safety study included patients 1-11 months of age. Patients' treatment - levetiracetam dose, and addition, withdrawal or changes in the doses of concomitant medications and AEDs - was at the discretion of the physician. The primary variable was treatment-emergent adverse events (TEAEs). RESULTS: Of 101 infants, 75 completed and 26 discontinued the study. Mean age was 6.0 months, 50 were male, most (80%) took 1 ≥ concomitant AED and had cryptogenic or symptomatic epilepsy that was focal (38.6%) or generalized (20.8%), particularly frontal lobe epilepsy (20.0%) or West syndrome/infantile spasms (20.0%). Among known aetiologies, congenital factors (22.8%) such as dysplastic lesions or perinatal events (17.8%) were predominant. Overall, 54.5% of patients had ≥ 1 TEAE. Five patients experienced drug-related TEAEs - convulsion, irritability, somnolence and hypotonia, all listed in the product label, with the exception of hypotonia, which was reported for one patient and resolved without any change in study medication. Seven patients discontinued due to TEAEs, mainly due to infantile spasms and respiratory disorders. At study end, 71.8% of patients showed improvement in epilepsy severity, 18.8% remained stable and 9.4% showed worsening. Levetiracetam did not appear to have a negative effect on growth parameters. CONCLUSION: In this prospective study, which included the largest number of patients in this age range so far, levetiracetam was found to be well tolerated and efficacious for the treatment of infants with epilepsy.

Prevalence and control of high blood pressure in primary care: results from the German Metabolic and Cardiovascular Risk Study (GEMCAS).

Contemporary epidemiological data on blood pressure readings, hypertension prevalence and control in unselected patient populations covering a broad age range are scarce. The aim here is to report the prevalence of high blood pressure and to identify factors associated with blood pressure control in a large German primary care sample. We used data from the German Metabolic and Cardiovascular Risk Study including 35 869 patients aged 18-99 years. High blood pressure was defined as systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg or using antihypertensive therapy. Factors associated with blood pressure control among patients receiving antihypertensive therapy were examined using multiple logistic regressions to estimate odds ratios and 95% confidence intervals. The prevalence of high blood pressure, uncontrolled high blood pressure and untreated high blood pressure was 54.8%, 21.3% and 17.6%, respectively. Age >50 years (1.52; 1.40-1.65), male sex (1.30; 1.20-1.41), elevated waist circumference (1.55; 1.45-1.65), high cholesterol (1.24; 1.16-1.33), high triglycerides (1.11; 1.04-1.19) and concomitant diabetes (1.29; 1.20-1.40) were independently associated with uncontrolled high blood pressure. In a majority of patients we observed hypertension despite treatment for high blood pressures. Studies examining the reasons for treatment failure are highly warranted.

Prevalence of the metabolic syndrome in patients with borderline personality disorder: results from a cross-sectional study.

Metabolic syndrome (MetS) is an important risk factor for the development of type-2 diabetes and coronary artery disease. We aimed to compare the MetS prevalence in patients with borderline personality disorder (BPD) with comparison subjects followed in primary care from a similar region. One hundred and thirty-five BPD patients according to DSM-IV diagnostic criteria were compared to 1009 subjects from primary care. We used the American Heart Association/National Heart, Lung and Blood Institute criteria to determine the rate of MetS. The age-standardized prevalence of MetS was more than double in patients with BPD compared to comparison subjects (23.3 vs. 10.6 %, p < 0.05). Regarding individual MetS criteria, hyperglycemia was significantly more prevalent in both genders (p < 0.05). Abdominal obesity (p < 0.05) and hypertriglyceridemia (p < 0.05) were significantly higher only in women with BPD. Within BPD patients, an increased rate of MetS was associated with higher BMI (p = 0.004), age (p = 0.03), treatment with second-generation antipsychotics (quetiapine, olanzapine and clozapine; p = 0.032), dysthymia (p = 0.031), panic disorder (p = 0.032), benzodiazepine dependency (p = 0.015) and binge eating disorder p = 0.02). Our results demonstrate an increased MetS rate, dysregulated glucose and lipid metabolism in patients with BPD. Cardiometabolic monitoring and careful screening for physical health conditions among people with BPD is warranted.

Prevalence of the metabolic syndrome in unipolar major depression.

Previous studies on the association between affective disorders and the metabolic syndrome yielded inconclusive results. Therefore, we examined the prevalence of the metabolic syndrome in 230 men and women with unipolar major depressive disorder during inpatient treatment and compared it to 1,673 subjects from primary care from a similar region in northern Germany. We used the AHA/NHBLI criteria to determine the rate of metabolic syndrome (MetS) and each single criterion of MetS in both groups. The age-standardized prevalence of MetS was 2.4× as high in patients with major depressive disorder (MDD) compared with data from comparison subjects (41.0% vs. 17.0%). With respect to the single criteria, elevations were found in MDD patients for fasting glucose and triglycerides in both genders, and waist circumference in women. Men in the patient and the comparison groups were found to have higher rates of increased fasting glucose and triglycerides than women in the respective groups. Factors associated with the MetS in MDD patients comprise body mass index and the severity of depression. Our results demonstrate an increased prevalence of the MetS in men and women with MDD. Interventions for the frequently untreated metabolic abnormalities and careful screening for physical health conditions among people with MDD are warranted.

Efficacy and safety of regional citrate anticoagulation in liver transplant patients requiring post-operative renal replacement therapy.

BACKGROUND: Liver transplant patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) early post-operatively are at high risk for bleeding. Using heparin for anticoagulation during CRRT may contribute to the increased bleeding risk. Regional anticoagulation with citrate may decrease the risk of bleeding. However, citrate anticoagulation may be associated with metabolic complications in patients with liver impairment. The aim of the study was to evaluate the safety and efficacy of citrate anticoagulation in liver transplant patients. METHODS: All liver transplant recipients transplanted between November 2004 and August 2007, requiring CRRT and using citrate as the anticoagulant were included in this retrospective study. Demographic data, CRRT specific and metabolic data were collected and analysed. RESULTS: Sixty-eight patients (40 male/28 female) with a mean age of 47.1±11.8 years and a Model of End-stage Liver Disease score of 23±9 developed post-operative AKI requiring CRRT using citrate as the anticoagulant. The median duration on CRRT was 8 days (range 1-39 days) with a mean circuit life of 22.7±14.6 h. There was no relevant time trend of serum sodium, potassium, calcium, bicarbonate and pH values during CRRT. Bleeding occurred in 8 of 68 (11.7%) patients during CRRT. CONCLUSION: Regional citrate anticoagulation for CRRT in the early post-operative period after liver transplantation is effective and safe. Therefore, the general exclusion of citrate anticoagulation during CRRT in patients after liver transplantation is not justified.

Impact of time since last caloric intake on blood glucose levels.

Blood glucose (BG) is usually measured after a caloric restriction of at least 8 h; however evidence-based recommendations for the duration of a fasting status are missing. Here we analyze the effect of fasting duration on levels of BG to determine the minimal fasting duration to achieve comparable BG levels to conventional fasting measurements. We used data of a cross-sectional study on primary care patients, performed in October 2005. We included 28,024 individuals (age-range 18-99 years; 63% women) without known diabetes mellitus and without missing data for BG and fasting status. We computed general linear models, adjusting for age, sex, time of blood withdrawal, systolic blood pressure, waist circumference, total- and HDL-cholesterol, physical activity, smoking, intake of beta-blocker and alcohol. We tested the intra-individual variability with respect to fasting status. Overall, the mean BG differed only slightly between individuals fasting ≥ 8 h and those fasting <8 h (men: 5.1 ± 0.8 mmol/L versus 5.2 ± 1.2 mmol/L; women: 4.9 ± 0.7 mmol/L, 5.0 ± 1.0 mmol/L). After 3 h of fasting differences of BG diminished in men to -0.08 mmol/L (95%-CI: -0.15; -0.01 mmol/L), in women to -0.07 mmol/L (-0.12; -0.03 mmol/L) compared to individuals fasting ≥ 8 h. Noteworthy, age, time of day of blood withdrawal, physical activity, and intake of hard liquor influenced BG levels considerably. Our data challenge the necessity for a fasting duration of ≥ 8 h when measuring blood glucose, suggesting a random sampling or a fasting duration of 3 h as sufficient. Rather, our study indicates that essentially more effort on the assessment of additional external/internal factors on BG levels is necessary.

Age- and sex-specific prevalence and ten-year risk for cardiovascular disease of all 16 risk factor combinations of the metabolic syndrome - A cross-sectional study.

BACKGROUND: Based on the AHA/NHLBI-definition three out of five cardiometabolic traits must be present for the diagnosis of the metabolic syndrome (MetS), resulting in 16 different combination types. The associated cardiovascular risk may however be different and specific combination may be indicative of an increased risk, furthermore little is known to which extent these 16 combinations contribute to the overall prevalence of MetS. Here we assessed the prevalence of all 16 combination types of MetS, analyzed the impact of age and gender on prevalence rates, and estimated the 10-year risk of fatal and non-fatal myocardial infarction (MI) of each MetS combination type. METHODS: We used data of the German Metabolic and Cardiovascular Risk Project (GEMCAS), a cross-sectional study, performed during October 2005, including 35,869 participants (aged 18-99 years, 61% women). Age-standardized prevalence and 10-year PROCAM and ESC risk scores for MI were calculated. RESULTS: In both men and women the combination with elevated waist-circumference, blood pressure and glucose (WC-BP-GL) was the most frequent combination (28%), however a distinct unequal distribution was observed regarding age and sex. Any combination with GL was common in the elderly, whereas any combination with dyslipidemia and without GL was frequent in the younger. Men without MetS had an estimated mean 10-year risk of 4.7% (95%-CI: 4.5%-4.8%) for MI (PROCAM), whereas the mean 10-year risk of men with MetS was clearly higher (age-standardized 7.9%; 7.8-8.0%). In women without MetS the mean 10-year risk for MI was 1.1%, in those with MetS 2.3%. The highest impact on an estimated 10-year risk for MI (PROCAM) was observed with TG-HDL-GL-BP in both sexes (men 14.7%, women 3.9%). However, we could identify combinations with equal risks of non-fatal and fatal MI compared to participants without MetS. CONCLUSIONS: We observed large variations in the prevalence of all 16 combination types and their association to cardiovascular risk. The importance of different combinations of MetS changes with age and between genders putting emphasis on a tailored approach towards very young or very old subjects. This knowledge may guide clinicians to effectively screen individuals and prioritize diagnostic procedures depending on age and gender.

Prevalence of the metabolic syndrome in men and women with alcohol dependence: results from a cross-sectional study during behavioural treatment in a controlled environment.

AIMS: Prevalence of metabolic syndrome (MetS) in men and women who use alcohol has been inconsistent in the literature. The aim of this study is to compare the prevalence of MetS in patients with a diagnosis of alcohol dependence who are currently abstinent in a controlled environment, and in control subjects followed in primary care from a similar region in Northern Germany. DESIGN: Cross-sectional study. SETTING: In-patient cognitive behavioural therapy. PARTICIPANTS: One hundred and ninety-seven men and women with alcohol dependence during behavioural treatment in a controlled environment were compared to 1158 subjects from primary care from a similar region in northern Germany. MEASUREMENTS: We used the American Heart Association/National Heart, Lung and Blood Institute (AHA/NHBLI) criteria to determine the rate of MetS and each single criterion of MetS in both groups. FINDINGS: The prevalence of MetS was almost twice as high in men and women with alcohol dependence compared to control subjects (30.6% versus 17.0%). With respect to the single criteria, elevations were found for fasting glucose and blood pressure in both genders and for triglycerides in women only. High density lipoprotein (HDL)-cholesterol was higher in men and women with alcohol dependence. CONCLUSIONS: Our results demonstrate an increased rate of MetS, increased blood pressure and dysregulation of glucose and lipid metabolism in alcohol-dependent patients. Whether high HDL-cholesterol has cardioprotective effects in this context remain doubtful.

Dyslipidemia in primary care--prevalence, recognition, treatment and control: data from the German Metabolic and Cardiovascular Risk Project (GEMCAS).

BACKGROUND: Current guidelines from the European Society of Cardiology (ESC) define low thresholds for the diagnosis of dyslipidemia using total cholesterol (TC) and LDL-cholesterol (LDL-C) to guide treatment. Although being mainly a prevention tool, its thresholds are difficult to meet in clinical practice, especially primary care. METHODS: In a nationwide study with 1,511 primary care physicians and 35,869 patients we determined the prevalence of dyslipidemia, its recognition, treatment, and control rates. Diagnosis of dyslipidemia was based on TC and LDL-C. Basic descriptive statistics and prevalence rate ratios, as well as 95% confidence intervals were calculated. RESULTS: Dyslipidemia was highly frequent in primary care (76% overall). 48.6% of male and 39.9% of female patients with dyslipidemia was diagnosed by the physicians. Life style intervention did however control dyslipidemia in about 10% of patients only. A higher proportion (34.1% of male and 26.7% female) was controlled when receiving pharmacotherapy. The chance to be diagnosed and subsequently controlled using pharmacotherapy was higher in male (PRR 1.15; 95%CI 1.12-1.17), in patients with concomitant cardiovascular risk factors, in patients with hypertension (PRR 1.20; 95%CI 1.05-1.37) and cardiovascular disease (PRR 1.46; 95%CI 1.29-1.64), previous myocardial infarction (PRR 1.32; 95%CI 1.19-1.47), and if patients knew to be hypertensive (PRR 1.18; 95%CI 1.04-1.34) or knew about their prior myocardial infarction (PRR 1.17; 95%CI 1.23-1.53). CONCLUSION: Thresholds of the ESC seem to be difficult to meet. A simple call for more aggressive treatment or higher patient compliance is apparently not enough to enhance the proportion of controlled patients. A shift towards a multifactorial treatment considering lifestyle interventions and pharmacotherapy to reduce weight and lipids may be the only way in a population where just to be normal is certainly not ideal.

Prevalence of obesity in primary care using different anthropometric measures--results of the German Metabolic and Cardiovascular Risk Project (GEMCAS).

BACKGROUND: Obesity is one of the greatest challenges in primary health care. The BMI describes fat mass and waist circumference (WC) fat distribution and total metabolic and cardiovascular risk. It was aim of the present study to assess the prevalence of a) overweight and obesity and b) an increased and high WC in adults seeking primary care in Germany and to describe the associations of both measures with cardiovascular risk factors and prognosis. METHODS: This was a point prevalence study with 1,511 primary care physicians and 35,869 adult patients in 2005. Bodyweight, height and waist circumference was measured and blood samples taken to determine the presence of cardiovascular risk factors, including lipids, blood pressure, fasting glucose, low physical activity, smoking and family history of myocardial infarction. We calculated rate ratios stratified for age and gender. RESULTS: There was a high prevalence of overweight (45.7% male [95%CI 44.9-46.5]; 30.6% female [95%CI 30.0-31.2]) and obesity (24.7% male [95%CI 24.0-25.4]; 23.3% female [95%CI 22.8-23.9]). 36.4% of male [95%CI 35.6-37.2] and 41.5% of female [95%CI 40.8-42.1] had a high WC (male > 102, female > 88 cm). A high WC in addition to an overweight BMI identified patients with more risk factors (male: mean of 3.93 risk factors (RF) at a WC > 102 cm vs. 2.88 RF in patients < or = 94 cm; female 3.58 RF at a WC > 88 cm vs. 2.41 RF < or = 80 cm). CONCLUSION: There is a high prevalence of obesity (24.7% of male and 23.3% of female) and, in particular, abdominal obesity (36.4% of male and 41.5% of female) in adults attending a primary care physician in Germany. The determination of the BMI is sufficient to assess risk in normal weight and obese patients, while a high WC identifies high risk patients from within the overweight group.

Distribution and prevalence of reflux in the superficial and deep venous system in the general population--results from the Bonn Vein Study, Germany.

OBJECTIVE: Venous diseases are among the most frequent diseases in the general population of industrialized countries. The aim of this article is to investigate the population-based prevalence of pathologic reflux in superficial and deep leg veins, taking into account factors as gender, age, and clinical classification of venous disease. METHODS: In a population-based cross-sectional study, 3072 subjects aged 18 to 79 years (1350 male, 1722 female, response 59%) were enrolled from October 2000 through November 2001. A standardized interview was conducted to document phlebological history and clinical examinations including duplex sonography of selected superficial and deep leg veins. Pathological reflux was defined as being >500 ms. All participants where classified according to the CEAP classification. RESULTS: Using the highest clinical stage per participant, 9.6% where classified C0, 59.0% C1, 14.3% C2, 13.5% C3, 2.9% C4, and 0.7% C5-C6. A pathological reflux (>500 ms) was found in 35.3% (95% confidence interval [CI] 33.6-37.1) of subjects with 21.0% (95% CI 19.5-22.5) showing reflux in at least one superficial vein and 20.0% (95% CI 18.6-21.5) showing reflux in at least one deep vein. We observed significantly higher reflux prevalence for the superficial veins in women while for the deep veins reflux prevalence were significantly higher in men. Prevalence of reflux in the superficial veins markedly increases with age. In the deep venous system, no clear changes in reflux prevalence with age can be observed. For superficial veins, reflux prevalence is markedly higher with higher C-stages. For the deep veins, the proportion of refluxes is relatively constant in stages C0-C3 with a distinct increase of prevalence from stage C4 onward. CONCLUSION: Our results show a high prevalence of reflux both for the superficial and the deep venous system. Reflux prevalence is associated with gender, age, and the clinical stage as measured by the CEAP classification. Further longitudinal studies are needed to clarify the relevance of pathological reflux in subjects with otherwise healthy veins.

The statistical analysis of a clinical trial when a protocol amendment changed the inclusion criteria.

BACKGROUND: Sometimes, protocol amendments that change the inclusion and exclusion criteria are required in clinical trials. Then, the patient populations before and after the amendment may differ. METHODS: We propose to perform separate statistical tests for the different phases, i.e. for the patients recruited before and after the amendment, and to combine the tests using Fisher's combination test. After a significant combination test a multiple testing procedure can be applied to identify the phase(s) to which a proof of efficacy refers. We assume that the amendment(s) are not based on any type of unblinded data. The proposed method is investigated within a simulation study. RESULTS: The proposed combination approach is superior to the 'naïve' strategy to ignore the differences between the phases and pooling the data to perform just one statistical test. This superiority disappears when there are hardly any differences between the two phases. CONCLUSION: When one or more protocol amendments change the inclusion and exclusion criteria, one should realize that the populations may differ. In this case, separate tests for the different phases together with a combination test are a powerful method that can be applied in a variety of settings. The (first) amendment should specify the combination test to be applied in order to combine the different phases.

Cognitive outcomes three years after coronary artery bypass surgery: relation to diffusion-weighted magnetic resonance imaging.

BACKGROUND: Cognitive decline is well recognized early after coronary artery bypass graft surgery (CABG), but controversy exists regarding the degree and duration of these changes. We investigated the course of cognitive performance during 3 years after surgery and determined whether ischemic brain injury detected by diffusion-weighted magnetic resonance imaging was related to cognitive decline. METHODS: Thirty-nine patients undergoing on-pump CABG completed preoperative neuropsychologic examination and were followed up prospectively at discharge, 3 months, and 3 years after surgery. Cognitive performance was assessed with a battery of 11 standardized psychometric tests assessing 7 cognitive domains. Cognitive outcome was analyzed by determining (1) mean changes in within-patient scores over time (identifying cognitive functions with decline), and (2) the incidence of cognitive deficit for each individual (identifying patients with decline). Objective evidence of acute cerebral ischemia was obtained by diffusion-weighted magnetic resonance imaging. Prospectively collected data were used to identify predictors of cognitive deficits. RESULTS: From baseline to discharge, cognitive test scores significantly declined in 7 measures. Most tests improved by 3 months. Between 3 months and 3 years, late decline was observed in 2 measures with persistent deterioration in 1 measure (verbal memory) relative to baseline. Postoperative cognitive deficits (drop of > or = 1 SD in scores on > or = 3 tests) were observed in 56% of patients at discharge, 23% at 3 months and 31% at 3 years. On postoperative diffusion-weighted magnetic resonance imaging, there were new ischemic cerebral lesions in 51% of patients. The presence of cognitive deficit at discharge was a significant univariate predictor of late cognitive decline (p = 0.025). A relation between the presence of new diffusion-weighted magnetic resonance imaging detected lesions and cognitive decline, however, was not found. CONCLUSIONS: Longitudinal cognitive performance of patients with CABG showed a two-stage course with early improvement followed by later decline. Long-term cognitive deficit was predicted by early cognitive decline, but not by ischemic brain lesions on magnetic resonance imaging.

Major trauma with multiple injuries in German children: a retrospective review.

BACKGROUND: The aim of this study was to evaluate the demographics, mechanisms, pattern, injury severity, and the outcome (ie, length of intensive care unit [ICU] stay, length of mechanical ventilation, total length of stay, mortality) in multiple-injured children based on a review from the German trauma registry study ("Traumaregister") of the German Society of Trauma Surgery (Deutsche Gesellschaft für Unfallchirurgie e.V.). METHODS: One hundred three German trauma centers took part in the German trauma registry study from January 1997 to December 2003. Five hundred seventeen children (aged 0-15 years) with multiple injuries and an Injury Severity Score of more than 15 in comparison to 11,025 adults were included. Sex, age, and mechanisms and pattern of injury were assessed. The mechanisms of trauma and the anatomical distribution of severe injury (Abbreviated Injury Scale of 3 or more) were analyzed. The Injury Severity Score, the Revised Trauma Score, and the Trauma Score Injury Severity Score were calculated to estimate the severity of injury and mortality. RESULTS: The predominant sex was male. Most cases were caused by traffic-related accidents. Head injuries were most common in children, and severe thoracic injuries increased with age. Mean length of ICU treatment, mechanical ventilation, and total length of stay were shorter in children than in adults. A total of 22.6% of the children aged 0 to 5 years died in the hospital in comparison with in-hospital mortality rate of 13.7% in the 6- to 10-, 20.3% in the 11- to 15-, and 17.0% in the 16- to 55-year-old patients. CONCLUSIONS: There were differences between multiple-injured children and adults concerning injury mechanisms and pattern of injuries. Adults needed a longer mechanical ventilation and a longer ICU therapy. Most deaths could be seen in the youngest patients aged 0 to 5 years.

Regional differences in the prevalence of the metabolic syndrome in primary care practices in Germany.

INTRODUCTION: Data on the prevalence and regional distribution of the metabolic syndrome in Germany are lacking, in particular for primary care. METHODS: In October 2005 anthropometric measurements were taken from 35 869 consecutive patients aged 18 to 99 years, in 1511 primary care practices. Waist circumference, blood pressure, lifestyle, and past medical history were assessed and blood tests taken (HDL-, LDL- and total cholesterol, triglycerides, glucose). Crude and age-standardized prevalence were calculated. RESULTS: Women in the eastern part of Germany showed a higher age-standardized prevalence of the metabolic syndrome than women in the western part (21.1%; 95% CI: 19.9 to 22.4 respectively 17.7%; 95% CI: 17.2 to 18.3). In men the prevalences were 22.7% (95% CI: 20.9 to 24.4) and 21.4% (95% CI: 20.6 to 22.1) respectively. Patients from Saxony-Anhalt, Brandenburg, and Mecklenburg-Western Pomerania showed the highest prevalence, while women in Hamburg, Berlin, and Hesse and men in Schleswig-Holstein, Saarland, and Hamburg showed the lowest prevalence. Cardiovascular disease prevalence was comparable, while diabetes prevalence was higher in patients from eastern Germany (17% vs.13% in men; 12% vs. 9% in women). DISCUSSION: The prevalence of the metabolic syndrome in German primary care is high. Prevention efforts should focus in particular on differences in gender, socioeconomic status, and region.

Overweight, obesity and high waist circumference: regional differences in prevalence in primary medical care.

INTRODUCTION: The prevalence of obesity and elevated waist circumference in Germany is high. However, there are insufficient data on the situation in primary care and on regional distribution to support medical preventive measures. METHODS: The German Metabolic and Cardiovascular Risk Project (GEMCAS) is a national cross-sectional study including 1511 primary care practices and 35 869 patients. Height, weight, waist circumference, laboratory values, and type 2 diabetes were documented. RESULTS: The crude prevalence of obesity was 23.9% (95% CI 23.4 to 24.3) (standardized 22.8% [95% CI 22.3 to 23.2]), with a minimum in Bremen (19.8% [95% CI 15.1 to 24.5]) and a maximum in Saxony-Anhalt (28.3% [95% CI 25.4 to 31.1]). The crude prevalence of high waist circumference (> 102/88 cm) was 39.5% (95% CI 39.0 to 40.0) (standardized 36.5% [95% CI 36.0 to 36.9]), with a minimum in Hamburg (30.5% [95% CI 26.2 to 34.8]) and a maximum in Saxony-Anhalt (42.1% [95% CI 39.2 to 45.1]). The prevalence of obesity as assessed by BMI was higher in men than in women, but greater in women as assessed by waist circumference. Nationwide, 50 out of every 100 patients with obesity had type 2 diabetes, and 32 of 100 patients with a high waist circumference had type 2 diabetes. CONCLUSIONS: The prevalence of obesity is higher in northeastern Germany than in the southwest. Overall, abdominal obesity is considerably more frequent than obesity based on BMI. Surprisingly, a high prevalence of obesity in some federal states does not automatically mean a higher number of people with type 2 diabetes.

Patients with severe Graves' ophthalmopathy have a higher risk of relapsing hyperthyroidism and are unlikely to remain in remission.

OBJECTIVE: To evaluate the relationship between severity of Graves' ophthalmopathy (GO) and relapse/remission rate of associated thyroid disease. PATIENTS AND METHODS: One hundred and fifty-eight patients with Graves' disease (GD) were seen within the first 6-12 months after the onset of GO and were followed for at least 18 months. During treatment, GO was classified as mild (n = 65) or severe course (n = 93) by severity and activity scores. All patients received standard anti-thyroid drug (ATD) treatment for 1 year, and in cases of relapse another cycle of ATD, thyroidectomy or radioiodine therapy. RESULTS: Following ATD treatment, 27 patients (42%) with a mild course of GO went into thyroid disease remission, while only seven (8%) patients with a severe course of GO achieved remission (P < 0.0001). Eventually, 32 patients (49%) with a mild course needed definitive thyroid therapy and the remaining 9% preferred another cycle of ATD. However, among patients with a severe GO course, 84% needed definitive therapy (P < 0.0001) and 8% opted for another course of ATD treatment. The probability of relapse could also be predicted by TBII levels 12 months after initiation of ATD therapy, as 96.8% of patients with TBII levels above 7.5 IU/l relapsed (odds ratio 24.3). CONCLUSION: Patients with severe GO and high TBII are unlikely to go into remission. This allows early decision-making regarding definitive treatment of the thyroid in GD patients with severe GO or very high TBII levels.

Hilar lymph nodes sampling at the time of liver transplantation for hepatocellular carcinoma: to do or not to do? Meta-analysis to determine the impact of hilar lymph nodes metastases on tumor recurrence and survival in patients with hepatocellular carcinoma undergoing liver transplantation.

The purpose of this study was to evaluate the impact of tumor-positive hilar lymph nodes (LN) on tumor recurrence and survival in patients with hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). A computer search of the Medline database was carried out. The outcome of patients with positive hilar LN (study group) was compared with that of patients with negative LN (reference group). Five clinical studies evaluating tumor recurrence after LT for HCC according to hilar LN status were identified. Five further clinical studies evaluated patients' survival in reference to LN metastases. The test of heterogeneity for each comparison revealed no significant differences (exact P=0.4638). A significant correlation between tumor-positive LN and tumor recurrence was shown (exact estimation of common odds ratio by 10.44, 95% confidence interval of 3.431-38.59). Furthermore, data analyses using the Fisher-combination test regarding patient survival in the two groups showed a statistical difference (P<0.0001). The negative prognostic value of hilar LN metastasis for both tumor recurrence and survival was confirmed by this analysis. Given the ever-present diagnostic dilemma associated with enlarged hilar LN, especially in hepatitis C-positive patients, hilar LN sampling during LT for HCC could better define patients at risk.