This review provides an overview of the role of long-term treatment of severe asthma with oral corticosteroids (OCS) and its associated side-effects in adults. It is based on a systematic literature search conducted in MEDLINE, Embase and the Cochrane Library to identify relevant studies. After a short overview of severe asthma and its treatment we present studies showing a dose-response relationship in asthmatic patients treated with OCS and then consider by organ systems the undesired effects demonstrated in clinical and epidemiological studies in patients with OCS-dependent asthma. It was found that the risk of developing various OCS-related complications, including infections, diabetes and osteoporosis as well as psychiatric disorders, was higher for patients with long-term exposure to OCS compared with control groups. In addition, studies showed a significant increase in healthcare resource utilisation due to OCS treatment. Therefore, it is incumbent on every clinician to carefully weigh the potential benefit of preventing loss of asthma control against this risk before opting to prescribe long-term OCS therapy. Effective corticosteroid-sparing strategies must be used and should aim at short-term use with the lowest effective dose and start tapering as soon as possible until OCS therapy is terminated.

Context The effect of age on excess mortality from all causes associated with obesity is controversial. Few studies have investigated the association between body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters), age, and mortality, with sufficient numbers of subjects at all levels of obesity. Objective To assess the effect of age on the excess mortality associated with all degrees of obesity. Design Prospective cohort study. Setting and Participants A total of 6193 obese patients with mean (SD) BMI of 36.6 (6.1) kg/m 2 and mean (SD) age of 40.4 (12.9) years who had been referred to the obesity clinic of Heinrich-Heine University, Dü sseldorf, Germany, between 1961 and 1994. Median follow-up time was 14.8 years. Main Outcome Measure All-cause mortality through 1994 among 6053 patients for whom follow-up data were available (1028 deaths) analyzed as standardized mortality ratios (SMRs) using the male-female population of the geographic region (North Rhine Westphalia) as reference. Results The cohort was grouped into approximate quartiles according to age (18-29, 30-39, 40-49, and 50-74 years) and BMI (25 to Ͻ32, 32 to Ͻ36, 36 to Ͻ40, and Ն40 kg/m 2) at baseline. The SMRs showed a significant excess mortality with an SMR for

OBJECTIVE -A reduction of diabetes-related amputations by at least one-half within 5 years was declared a primary objective for Europe (St. Vincent Declaration, 1989). We collected data about incidence rates of amputations in one German city (Leverkusen, with a population of ϳ160,000 inhabitants) between 1990 and 1998 to ascertain a potential change in rates of incidence. RESEARCH DESIGN AND METHODS-From all three hospitals in Leverkusen, we obtained complete lists of lower-limb amputations. From each patient record, diabetic status was determined. Only the first observed amputation was counted for the analysis. We estimated incidence rates of amputations in the entire population, the diabetic population, and the nondiabetic population. To test for time trend, we fitted Poisson regression models, adjusting for age and sex.RESULTS -During the defined period (the years 1990, 1991, and 1994 -1998), 339 patients (all residents of Leverkusen) without previous amputations had nontraumatic lower-limb amputations. Of all subjects, 46% were female. Moreover, 76% of the subjects were known to have diabetes. Mean age was 71.3 years. Incidence rates in the diabetic population (standardized to the estimated German diabetic population, per 100,000 person-years) were as follows : 1990, 549; 1991, 356; 1994, 544; 1995, 386; 1996, 426; 1997, 433; and 1998, 463. The Poisson models showed no significant change of incident amputations over time in the diabetic population or in the nondiabetic population.CONCLUSIONS -Beyond random variation, no change of incidence rates could be observed over the past 9 years. More specific interventions are needed to achieve a substantial reduction of diabetes-related amputations. Diabetes Care 24:855-859, 2001

We found incidence rates similar to those in the non-Indian population of the U.S. Great relative and population-attributable risks indicate that improving foot care in diabetic individuals appears to be the main target for the reduction of amputations in the general population.

OBJECTIVE -We evaluated whether the incidence of amputations in one German city (Leverkusen, population ϳ160,000) had decreased between 1990 and 2005. RESEARCH DESIGN AND METHODS-From all three hospitals in the city, we obtained complete lists of nontraumatic lower-limb amputations in 1990 -1991 and 1994 -2005. Only the first observed amputation in residents of Leverkusen was counted. A total of 692 patients met the inclusion criteria. Data about the population stucture, separately for each year of the observation period, were received from the city administration and the Federal Office of Statistics. To test for time trend, we fitted Poisson regression models.RESULTS -Of all subjects, 72% had known diabetes and 58% were male. Mean age was 71.7 years. Incidence rates in the diabetic population (standardized to the estimated German diabetic population per 100,000 person-years) varied considerably between years (maximum 549 in 1990, minimum 281 in 2004). In the diabetic population, the estimated relative risk (RR) per year was 0.976 (95% CI 0.958 -0.996, P ϭ 0.0164). The same trend was observed when only amputations above the ankle (n ϭ 352) , P ϭ 0.0318) were considered. Over 15 years, an estimated reduction of amputations above the toe level by 37.1% (95% CI 12.3-54.8) results. There was no significant change of incident amputations in the nondiabetic population (RR 1.022 [0.989 -1.056], P ϭ 0.1981).CONCLUSIONS -This finding is likely to be due to improved management of the diabetic foot syndrome after a network of specialized physicians and defined clinical pathways for wound treatment and metabolic control were introduced. Diabetes Care 30:2633-2637, 2007I n 1989, a reduction of the number of amputations in the diabetic population by at least one-half within 5 years was declared a primary objective for Europe (St. Vincent Declaration) (1). We published baseline data about the incidence rates of amputations in the city of Leverkusen, Germany, in 1990 and 1991, as well as follow-up data through 1998 (2,3). We found that the risk of having an amputation was 26-fold (95% CI 17-39) in the diabetic population compared with that in the nondiabetic population. Moreover, 96% (94 -97) of the amputation risk in diabetic individuals and 70% (61-77) of the amputation risk in the entire population were due to diabetes (2,3). We estimated that ϳ31,000 patients in Germany underwent first amputations per year, that 23,000 of these patients had diabetes, and that 21,000 had their amputations due to their diabetes (4). No change in incidence rates over time could be detected between 1990 and 1998 (3). In the present study, we continued the collection of these data from 1999 through 2005 and combined them with the existing dataset to ascertain a potential change in incidence rates.The incidence of amputations in diabetic individuals dropped significantly in several areas in various countries and populations, such as Alaska Natives, American Indians, Denmark, and Sweden, after various specific programs for foot care and prevention...

In our first German nationwide study, we found the relative risk of lower limb amputation in the diabetic compared to the non-diabetic to be lower than in earlier regional studies in Germany, supporting results of regional reductions of the excess amputation risk due to diabetes. A repetition of the study is warranted to further evaluate trends according to the St. Vincent goals.

Quantification of the excess mortality from all causes associated with obesity remains controversial. In this paper, 6,193 obese patients, those with a body mass index (weight (kg)/height (m)2 (BMI)) range of 25-74 kg/m2, recruited from 1961 to 1994 in Düsseldorf, Germany, were followed for a mean time of 14 (standard deviation, 8.2) years, yielding 87,179 observed patient-years. During the study period, 1,028 patients (16.6%) died. The entire cohort was grouped into approximate quartiles according to BMI: group 1, BMI from 25 to < 32; group 2, BMI from 32 to < 36; group 3, BMI from 36 to < 40; group 4, BMI > or = 40 kg/m2. The following risk ratios were estimated by means of Cox proportional hazards models using the lowest BMI group as reference category: group 2 for men, 1.02 (95% confidence interval 0.76-1.37); for women, 1.23 (95% confidence interval 0.96-1.58); group 3 for men, 1.50 (95% confidence interval 1.09-2.06); for women, 1.33 (95% confidence interval 1.03-1.73); and group 4 for men, 2.10 (95% confidence interval 1.53-2.88); for women, 2.25 (95% confidence interval 1.78-2.84). The following standardized mortality ratios were calculated by using the respective geographic area (the Federal State of North Rhine Westphalia) as reference population: group 1 for men, 1.26 (95% confidence interval 0.98-1.61); for women, 1.00 (95% confidence interval 0.81-1.23); group 2 for men, 1.31 (95% confidence interval 1.09-1.57); for women, 1.20 (95% confidence interval 1.02-1.40); group 3 for men, 1.92 (95% confidence interval 1.53-2.38); for women, 1.27 (95% confidence interval 1.07-1.50); and group 4 for men, 3.05 (95% confidence interval 2.47-3.73); for women, 2.31 (95% confidence interval 2.04-2.60). In addition to age, sex, and BMI, Cox proportional hazards models revealed systolic blood pressure, glucose intolerance, diabetes, and smoking as significant independent mortality risk factors, whereas cholesterol was not significant. In this prospective study of a large cohort of obese persons, morbid obesity (BMI of > or = 40 kg/m2) was a strong predictor of premature death. Excess mortality risks associated with gross obesity (BMI from 32 to < 40 kg/m2) were considerably lower than hitherto assumed; moderate degrees of obesity (BMI from 25 to < 32 kg/m2) were not significantly associated with excess mortality.

Great relative and attributable risks, especially in younger age-groups, indicate the need for increased attention to preventive measures for microvascular complications.