Sedimentation rate and suPAR in relation to disease activity and mortality in patients with tuberculosis.

OBJECTIVE: To investigate how levels of the soluble urokinase plasminogen activator receptor (suPAR) and erythrocyte sedimentation rate (ESR) correlate with disease activity and prognosis in pulmonary tuberculosis (PTB).DESIGN: This was a retrospective analysis of patients with active PTB (n = 500) in Gondar, Ethiopia, for whom the suPAR (n = 301) and ESR (n = 330) were analysed at the start of treatment. Both biomarkers were available for 176 patients. Human immunodeficiency virus (HIV) status, chest X-ray (CXR) findings, classification according to the clinical TBscore and treatment outcome were all recorded.RESULTS: In a multivariable logistic regression analysis adjusted for age, sex and HIV status, surrogate markers of disease activity such as advanced CXR patterns correlated with increased levels of suPAR (adjusted OR [aOR] 8.24, P < 0.001) and of ESR (aOR 1.63, P = 0.030), whereas ESR only correlated significantly with a TBscore >6 points. Increased levels of both suPAR and ESR were associated with unsuccessful treatment outcomes (aOR 2.93, P = 0.013; aOR 2.52, P = 0.025). The highest quartile of suPAR (aOR 13.3, P = 0.029) but not ESR levels correlated independently with increased mortality.CONCLUSION: SuPAR and ESR levels correlate with disease activity in PTB; however, the clinical role of these potentially prognostic biomarkers needs to be verified in prospective studies.

Safety and efficacy of denosumab in children with osteogenesis imperfect--a first prospective trial.

OBJECTIVES: Osteogenesis imperfecta (OI) is a rare hereditary disease leading to bone fragility. Denosumab as a RANK ligand antibody inhibiting osteoclast maturation has been approved for osteoporosis treatment in adults. Aim of this study was a 48-week, open-label, pilot study of the safety and efficacy of denosumab in 10 children with OI. METHODS: Ten patients (age range: 5.0-11.0 years; at least two years of prior bisphosphonate treatment) with genetically confirmed OI were studied. Denosumab was administered subcutaneously every 12 weeks with 1 mg/kg body weight. Primary endpoint was change of areal bone mineral density (aBMD) using dual energy x-ray absorptiometry of the lumbar spine after 48 weeks. Safety was assessed by bone metabolism markers and adverse event reporting. RESULTS: Mean relative change of lumbar aBMD was +19 % (95%-CI: 7-31%). Lumbar spine aBMD Z-Scores increased from -2.23±2.03 (mean±SD) to -1.27±2.37 (p=0.0006). Mobility did not change (GMFM-88 +2.72±4.62% (p=0.16); one-minute walking test +11.00±15.82 m (p=0.15). No severe side effects occurred. CONCLUSIONS: On average, there was a significant increase in lumbar spine aBMD percent change after 48 weeks of denosumab. There was no change in mobility parameters and no serious adverse events. Further trials are necessary to assess long-term side effects and efficacy.

[Patients with prostate cancer after radical prostatectomy: Stage migration and changes in tumor characteristics from 1998-2012]. / Patienten mit Prostatakrebs nach radikaler Prostatektomie : Stadienmigration und Veränderung von Tumoreigenschaften in den Jahren 1998-2012.

BACKGROUND: The aim of this study was to verify the described inverse stage migration after radical prostatectomy by a tertiary care center in 2011 in a national collective. MATERIALS AND METHODS: Data from 10,323 patients with prostate cancer (PCa), who had radical prostatectomy between 1998 and 2012, were analyzed regarding prostate-specific antigen (PSA) and age at diagnosis, T stage, and Gleason score. A trend over time was determined by using the Jonckheere-Terpstra test. RESULTS: Median age at surgery was 65 years (1998: 63.7; 2012: 66.5). The proportion of low-risk tumors decreased from 39% in 2005 to 25% in 2012, while the intermediate-risk tumors showed a continuous increase since 1998 from 35 to 52% in 2012. The proportion of patients with a Gleason score ≤ 6 decreased from 60% in 1998 to 25 % in 2012. The Gleason score groups 7a and 7b, however, increased from 12 to 46, % and 12 to 19%, respectively. The proportion of tumors with a Gleason score of 8-10 decreased from 16 to 10%. The proportion of organ-confined prostate cancer increased from 1998 to 2007 continuously from 57 to 73%. Since 2007 the proportion dropped to 64%. CONCLUSIONS: In this national population a trend towards inverse stage migration can be noted. Both the increase in Gleason score ≥ 6 and intermediate-risk tumors can be explained by the modification of the Gleason score. The tendency towards higher age and nonorgan-confined cancers at surgery could be dependent of the growing recognition of radical prostatectomy as a treatment for locally advanced prostate cancer, on the one hand, and the increase of alternative treatments for low-risk cancers, on the other hand.

Ultraviolet exposure and risk of melanoma and basal cell carcinoma in Ulm and Dresden, Germany.

BACKGROUND: There is a perpetuating increase in melanoma and basal cell carcinoma (BCC) incidence in Europe. Few studies are evaluating various risk factors for both tumours. OBJECTIVES: This pre-planned additional analysis directly compared occupational and past-time ultraviolet exposure behaviour, and examined the effects of sun sensitivity between melanoma and sporadic BCC, and assessed its importance for the two entities. PATIENTS/METHODS: The study included 503 patients (melanoma, n = 291 and BCC, n = 212), and 329 controls from Germany. In all, 244 (49%) of the cases and 165 (50%) of the controls were male (median age melanoma, 55 years; BCC, 69 years; and controls, 57 years). Selection of important risk factors was performed by backward elimination in a polytomous logistic regression. RESULTS: When directly comparing melanoma and sporadic BCC, actinic elastosis (OR 48.83; 95% CI 17.87, 133.40) and site were associated with a higher risk of melanoma, whereas mountaineering in childhood, sunburn 20 years before diagnosis, farming full time, sunbed use in general, seborrheic keratosis, actinic cheilitis, actinic keratosis and age were associated with a higher risk of sporadic BCC. Gardening 20 years before melanoma, hair colour and solar lentigo were risk factors for both entities. A re-evaluation of the data excluding lentiginous melanoma entities (i.e. acro-lentiginous and lentigo-maligna melanoma) resulted in selection of the same factors. However, compared to controls, atopy evolved as a protective factor for melanoma (OR 0.29; 95% CI 0.15, 0.57) and BCC (OR 0.41; 95% CI 0.17, 0.99), respectively, but was associated with a higher risk of sporadic BCC compared to melanoma. CONCLUSION: The odds for having clinical actinic elastosis was lower in BCC compared to melanoma. In contrast, various factors associated with chronic UV exposure and age had higher odds for sporadic BCC, rather than melanoma. Further research is required to set the context for these findings, especially regarding, atopy in non-lentiginous vs. lentiginous forms of melanoma, and possible molecular pathways involved.

One-year maintenance outcomes among patients with moderately-to-severely active ulcerative colitis who responded to induction therapy with adalimumab: subgroup analyses from ULTRA 2.

BACKGROUND: Patients with moderately-to-severely active ulcerative colitis (UC) are unlikely to continue anti-TNF therapy in the absence of early therapeutic response. AIM: To assess week 52 efficacy, safety and benefit/risk balance of adalimumab treatment in patients with moderately-to-severely active UC failing conventional therapy who achieved clinical response at week 8 in the 52-week ULTRA 2 trial. METHODS: Patients randomised to adalimumab (160/80 mg, week 0/2; 40 mg, every other week thereafter) in ULTRA 2 who achieved clinical response at week 8 per partial Mayo score (Mayo score without endoscopy subscore) were assessed for week 52 clinical remission, clinical response, mucosal healing, steroid-free remission and steroid discontinuation rates, overall and by prior anti-TNF use. Benefit/risk balance for the overall ITT population (regardless of week 8 responder status) was assessed using 'net efficacy adjusted for risk' (NEAR) odds ratios. Safety was assessed using adverse event rates. RESULTS: Of 248 adalimumab-treated patients, 123 (49.6%) achieved clinical response at week 8. Of these, 30.9%, 49.6%, and 43.1% achieved clinical remission, clinical response, and mucosal healing, respectively, at week 52. Of the week 8 responders using corticosteroids at baseline (N = 90), 21.1% achieved steroid-free remission and 37.8% were steroid-free at week 52. NEAR odds ratios indicated a positive benefit/risk balance for achievement of week 8 and week 52 response or remission without serious adverse events or serious infections. No safety concerns were identified. CONCLUSIONS: Adalimumab treatment was associated with a positive benefit/risk balance in the overall population of patients with moderately-to-severely active ulcerative colitis in ULTRA 2; early response was predictive of a positive outcome at 1 year (NCT00408629).

Adjuvant chemoradiotherapy of advanced resectable rectal cancer: results of a randomised trial comparing modulation of 5-fluorouracil with folinic acid or with interferon-α.

BACKGROUND: Standard adjuvant chemoradiotherapy of rectal cancer still consists of 5-fluorouracil (5-FU) only. Its cytotoxicity is enhanced by folinic acid (FA) and interferon-α (INFα). In this trial, the effects of FA and IFNα on adjuvant 5-FU chemoradiotherapy in locally advanced rectal cancer were investigated. METHODS: Patients with R(0)-resected rectal cancer (UICC stage II and III) were stratified and randomised to a 12-month adjuvant chemoradiotherapy with 5-FU, 5-FU+FA, or 5-FU+IFNα. All patients received levamisol and local irradiation with 50.4 Gy. RESULTS: Median follow-up was 4.9 years (n=796). Toxicities (WHO III+IV) were observed in 32, 28, and 58% of patients receiving 5-FU, 5-FU+FA, and 5-FU+IFNα, respectively. No differences between the groups were observed for local or distant recurrence. Five-year overall survival (OS) rates were 60.3% (95% confidence interval (CI): 54.3-65.8), 60.4% (54.4-65.8), and 59.9% (53.0-66.1) for 5-FU, 5-FU+FA, and 5-FU+IFNα, respectively. A subgroup analysis in stage II (pT3/4pN0) disease (n=271) revealed that the addition of FA tended to reduce the 5-year local recurrence (LR) rate by 55% and increase recurrence-free survival and OS rates by 12 and 13%, respectively, relative to 5-FU alone. CONCLUSIONS: Interferon-α cannot be recommended for adjuvant chemoradiotherapy of rectal cancer. In UICC stage II disease, the addition of FA tended to lower LR and increased survival. The addition of FA to 5-FU may be an effective option for adjuvant chemoradiotherapy of UICC stage II rectal cancer.

Impaired hippocampal Ca2+ homeostasis and concomitant K+ channel dysfunction in a mouse model of Rett syndrome during anoxia.

Methyl-CpG-binding protein 2 (MeCP2) deficiency causes Rett syndrome (RTT), a neurodevelopmental disorder characterized by severe cognitive impairment, synaptic dysfunction, and hyperexcitability. Previously we reported that the hippocampus of MeCP2-deficient mice (Mecp2(-/y)), a mouse model for RTT, is more susceptible to hypoxia. To identify the underlying mechanisms we now focused on the anoxic responses of wildtype (WT) and Mecp2(-/y) CA1 neurons in acute hippocampal slices. Intracellular recordings revealed that Mecp2(-/y) neurons show only reduced or no hyperpolarizations early during cyanide-induced anoxia, suggesting potassium channel (K(+) channel) dysfunction. Blocking adenosine-5'-triphosphate-sensitive K(+) channels (K(ATP-)) and big-conductance Ca(2+)-activated K(+) channels (BK-channels) did not affect the early anoxic hyperpolarization in either genotype. However, blocking Ca(2+) release from the endoplasmic reticulum almost abolished the anoxic hyperpolarizations in Mecp2(-/y) neurons. Single-channel recordings confirmed that neither K(ATP)- nor BK-channels are the sole mediators of the early anoxic hyperpolarization. Instead, anoxia Ca(2+)-dependently activated various small/intermediate-conductance K(+) channels in WT neurons, which was less evident in Mecp2(-/y) neurons. Yet, pharmacologically increasing the Ca(2+) sensitivity of small/intermediate-conductance K(Ca) channels fully restored the anoxic hyperpolarization in Mecp2(-/y) neurons. Furthermore, Ca(2+) imaging unveiled lower intracellular Ca(2+) levels in resting Mecp2(-/y) neurons and reduced anoxic Ca(2+) transients with diminished Ca(2+) release from intracellular stores. In conclusion, the enhanced hypoxia susceptibility of Mecp2(-/y) hippocampus is primarily associated with disturbed Ca(2+) homeostasis and diminished Ca(2+) rises during anoxia. This secondarily attenuates the activation of K(Ca) channels and thereby increases the hypoxia susceptibility of Mecp2(-/y) neuronal networks. Since cytosolic Ca(2+) levels also determine neuronal excitability and synaptic plasticity, Ca(2+) homeostasis may constitute a promising target for pharmacotherapy in RTT.

Comparison of haematology, coagulation and clinical chemistry parameters in blood samples from the sublingual vein and vena cava in Sprague-Dawley rats.

The investigation of clinical pathology parameters (haematology, clinical chemistry and coagulation) is an important part of the preclinical evaluation of drug safety. However, the blood sampling method employed should avoid or minimize stress and injury in laboratory animals. In the present study, we compared the clinical pathology results from blood samples collected terminally from the vena cava (VC) immediately before necropsy with samples taken from the sublingual vein (VS) also prior to necropsy in order to determine whether the sampling method has an influence on clinical pathology parameters. Forty-six 12-week-old male Sprague-Dawley rats were assigned to two groups (VC or VS; n = 23 each). All rats were anaesthetized with isoflurane prior to sampling. In the VC group, blood was withdrawn from the inferior VC. For VS sampling, the tongue was gently pulled out and the VS was punctured. The haematology, coagulation and clinical chemistry parameters were compared. Equivalence was established for 13 parameters, such as mean corpuscular volume, white blood cells and calcium. No equivalence was found for the remaining 26 parameters, although they were considered to be similar when compared with the historical data and normal ranges. The most conspicuous finding was that activated prothrombin time was 30.3% less in blood taken from the VC (16.6 ± 0.89 s) than that in the VS samples (23.8 ± 1.58 s). Summing up, blood sampling from the inferior VC prior to necropsy appears to be a suitable and reliable method for terminal blood sampling that reduces stress and injury to laboratory rats in preclinical drug safety studies.

Effectiveness of adalimumab in treating patients with active psoriatic arthritis and predictors of good clinical responses for arthritis, skin and nail lesions.

OBJECTIVES: To evaluate the effectiveness of adalimumab in patients with psoriatic arthritis (PsA) and identify predictors of good clinical response for joint and skin lesions. METHODS: Patients received adalimumab 40 mg every other week in addition to standard therapy in this prospective, 12-week, open-label, uncontrolled study. Four definitions of good clinical response were used: > or =50% improvement in American College of Rheumatology response criteria (ACR50), good response according to European League Against Rheumatism (EULAR) guidelines, a > or =3-grade improvement in Physician Global Assessment of psoriasis (PGA) and a > or =50% improvement in the Nail Psoriasis Severity Index (NAPSI). Response predictors were determined by logistic regression with backward elimination (selection level was 5%). RESULTS: Of 442 patients, 94% completed 12 weeks of treatment. At week 12, 74%, 51% and 32% of the patients had achieved ACR20, 50 and 70, respectively; 87% and 61% experienced moderate and good responses according to EULAR criteria, respectively. The percentage of patients with PGA results of "clear/almost clear" increased from 34% (baseline) to 68%. The mean NAPSI score was reduced by 44%. No new safety signals were detected. A lower Health Assessment Questionnaire Disability Index (HAQ-DI) score, greater pain assessment, male sex and absence of systemic glucocorticoid therapy were strongly associated with achievement of ACR50 and good response according to EULAR criteria. In addition, greater C-reactive protein concentration and polyarthritis predicted ACR50, and non-involvement of large joints predicted a good response according to EULAR criteria. CONCLUSIONS: Adalimumab was effective in patients with PsA. Lower impairment of physical function, greater pain, male sex and no systemic treatment with glucocorticoids were factors that increased the chance of achieving a good clinical response.

Adalimumab effectively reduces the rate of anterior uveitis flares in patients with active ankylosing spondylitis: results of a prospective open-label study.

OBJECTIVE: To evaluate the effect of adalimumab on the frequency of anterior uveitis (AU) flares in patients with active ankylosing spondylitis (AS). METHODS: We determined the history of ophthalmologist-diagnosed AU in 1250 patients with active AS who were enrolled in a multinational, open-label, uncontrolled clinical study of treatment with adalimumab, 40 mg every other week for up to 20 weeks. All AU flares were documented throughout the adalimumab treatment period plus 70 days. We compared the rates of AU flares per 100 patient years (PYs) reported during the year before adalimumab treatment with rates during adalimumab treatment, in total and by patient subgroups. RESULTS: The AU flare rates before adalimumab treatment were 15/100 PYs in all patients (n = 1250), 68.4/100 PYs in 274 patients with a history of AU flares, 176.9/100 PYs in 106 patients with a recent history of AU flares, 192.9/100 PYs in 28 patients with symptomatic AU at baseline and 129.1/100 PYs in 43 patients with a history of chronic uveitis. During adalimumab treatment, the rate of AU flares was reduced by 51% in all patients, by 58% in 274 patients with a history of AU, by 68% in 106 patients with a recent history of AU, by 50% in 28 patients with symptomatic AU at baseline and by 45% in 43 patients with chronic uveitis. AU flares during adalimumab treatment were predominantly mild. Two patients with periods of high AS disease activity had new-onset AU during the treatment period. CONCLUSIONS: Results of this prospective open-label study suggest that adalimumab had a substantial preventive effect on AU flares in patients with active AS, including patients with a recent history of AU flares. Clinical trials: ClinicalTrials.gov Identifier: NCT00478660.

Prognostic factors influencing the survival of patients with colon cancer receiving adjuvant 5-FU treatment.

AIM: Adjuvant chemotherapy is recommended for stage III colon cancer. The aim of this study was to identify important prognostic factors among patients with colon cancer receiving adjuvant 5-FU-based treatment. METHODS: Data sets of 855 colon cancer patients treated between 1992 and 1999 within a multicenter adjuvant trial comparing 5-FU modulation with folinic acid or interfereron-alpha were examined. Backward elimination in a proportional hazards model was used to identify prognostically relevant clinical and pathological factors. RESULTS: Tumor recurrence (p<0.001), duration of adjuvant treatment (p<0.001), tumor substage (p=0.004), age (p=0.005), grading (p=0.016), treatment-related toxicity (p=0.021), and treatment (p=0.031) were identified in descending order of importance as prognostic factors for overall survival. CONCLUSIONS: Adjuvant 5-FU-based treatment should be performed for at least 6months with a stepwise adjustment of 5-FU doses until toxicity >WHO II. Substages should be reported separately and used for stratification in future trials due to their broad variation in outcome. In the future, this may result in adjuvant treatment of stage III colon cancer adjusted for the risk of substages.

Antidepressant effects of augmentative transcranial magnetic stimulation: randomised multicentre trial.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a new treatment option for depression. Previous studies were performed with low sample sizes in single centres and reported heterogeneous results. AIMS: To investigate the efficacy of rTMS as augmentative treatment in depression. METHOD: In a randomised, double-blind, sham-controlled multicentre trial 127 patients with moderate to severe depressive episodes were randomly assigned to real or sham stimulation for 3 weeks in addition to simultaneously initiated antidepressant medication. RESULTS: We found no difference in the responder rates of the real and the sham treatment groups (31% in each) or in the decrease of the scores on the depression rating scales. CONCLUSIONS: The data do not support previous reports from smaller samples indicating an augmenting or accelerating antidepressant effect of rTMS. Further exploration of the possible efficacy of other stimulation protocols or within selected sub-populations of patients is necessary.

Effect of oestradiol and progesterone replacement on bronchopulmonary dysplasia in extremely preterm infants.

OBJECTIVE: To study whether postnatal replacement of oestradiol and progesterone may help to prevent bronchopulmonary dysplasia (BPD). METHODS: This randomised placebo-controlled double-blind study enrolled 83 infants of <29 weeks gestational age and 1000 g birth weight requiring mechanical ventilation within 12 h after birth. Oestradiol (2.5 mg/kg/day) and progesterone (22.5 mg/kg/day) were given by continuous intravenous infusion of a standard lipid emulsion (15 ml/kg/day) in the replacement group (ESTRA-PRO). The placebo group received the same lipid emulsion without oestradiol or progesterone. A replacement period of at least 2 weeks but not >4 weeks was strived for and defined as "according to protocol". The primary outcome variable was the incidence of BPD or death. RESULTS: The median birth weight was 670 g (min-max 400-990 g) and the gestational age 25 weeks (23.1-28.1 weeks). The incidence of BPD or death was 48% in the placebo group and 44% in the ESTRA-PRO group (p = 0.38, one-sided testing, intention to treat analysis). In infants treated according to protocol, 32% (9 of 28) in the placebo group and 14% (3 of 21) in the ESTRA-PRO group developed BPD (p = 0.08). CONCLUSION: Replacement of oestradiol and progesterone was not effective for prevention of BPD or death in extremely preterm born infants. Better-powered trials are needed to evaluate this new approach.

[Association of a positive family history with histopathology and clinical course in early-onset prostate cancer]. / Assoziation von familiärem Status mit Histologie und klinischem Verlauf beim frühen Prostatakarzinom.

BACKGROUND: In a large number of studies a positive family history is documented as one of the main risk factors for the development of prostate cancer. In a US population an association between early-onset prostate cancer among familial patients and a more differentiated tumour was shown. The aim of this study was to compare clinical parameters between sporadic and familial or hereditary patients with an age at diagnosis < or =55 years. MATERIAL AND METHODS: The clinical data of prostate cancer patients with an age at diagnosis < or =55 years and who were recruited between July 1999 and the end of June 2004 to the database "familial prostate cancer in Germany" were analysed. The following data were documented for all patients: PSA at diagnosis, histopathological stage, grading, Gleason score and progression-free survival. RESULTS: The clinical data of 685 patients could be completed: 222 (32.4%) had one first-degree relative with prostate cancer, 48 of whom (7.0%) were hereditary; 463 (67.6%) were sporadic. The median age at diagnosis in the hereditary patients was 51.6 (41-55) years, in the familial patients 51.1 (35-55) years and in the sporadic patients 52.0 (38-55) years. The median follow-up was 24 months in hereditary, 36 months in familial and 35 months in sporadic patients. An initial curative therapy with radical prostatectomy or radiotherapy/brachytherapy was planned in 657/685 (95.9%) of the patients. There were no clear differences regarding PSA at diagnosis, the postoperative parameters (organ-confined disease, lymph node involvement, Gleason score, grading) and the progression-free survival in sporadic and familial or hereditary patients. CONCLUSIONS: Patients with an age at diagnosis < or =55 years have a positive family history more often than all prostate cancer patients in Germany. No association could be shown between pathohistological stage or clinical course and a positive family history in patients with an age at diagnosis < or =55 years.

A follow-up study on fall and fracture incidence in long-term care including the role of formal caregiver time on fall incidence rates.

OBJECTIVE: To examine the impact of a fall prevention programme over a 12 month follow-up period after the introduction of a RCT and to describe possible differences between incidence density rate of falls associated with caregiver time during weekends and ordinary working days. DESIGN: Prospective observational study, duration 12 months. SETTING: Six community nursing homes, Germany. PARTICIPANTS: Long-stay residents (n=881); 771 resident years; median age 85.0 years (min 60; max 101); 79.1% female. MEASUREMENTS: Incidence density rate of falls and fractures, staff time per resident. RESULTS: The incidence density rate over all days was 1367/1000 resident years (RY) for falls [95% confidence interval 1041;1693]. The incidence density rate of hip fractures was 29/1000 RY [95% confidence interval 12;45] and 29/1000 RY [95% confidence interval 12;45] for non-hip fractures. The incidence density rate showed similar results comparing weekends/ public holidays vs normal working days; falls 1193 vs 1447/ 1000 RY; hip fractures 25 vs 30/ 1000 RY and other fractures 16 vs 34/1000 RY. CONCLUSION: During the period, we observed a marked decline of the fracture rate compared with the controlled phase of the intervention trial. A lower number of nursing care hours on weekends was not associated with a higher incidence density rate for falls, fallers, or any type of fracture.

[Effectiveness of a multifactorial intervention to reduce physical restraints in nursing home residents with dementia]. / Effektivität einer multifaktoriellen Intervention zur Reduktion von körpernaher Fixierung bei demenzerkrankten Heimbewohnern Ziele und Studiendesign einer prospektiven clusterrandomisierten Interventionsstudie.

At present, observational studies and expert opinion are the best evidence for the use of physical restraints. Large regional and national disparities are described in acute and long-term care. Epidemiological data demonstrate a prevalence of 3-5% body-fixed or near body restraint devices. The hip fracture rate in Germany are approximately 50 per 1000 resident years. Between 40-50% of the residents in nursing homes are treated with psycho-tropic medication potentially limiting their physical mobility. The presented study protocol was designed to test the effectiveness of a multifactorial intervention to reduce physical restraints in long-term care (LTC) residents particularly with cognitive impairment. The intervention consists of an educational and an organizational part to empower staff members to improve their skills and practice in using restraints. Technical devices to reduce fall related injuries are additionally offered to the LTC facilities. The study population includes 200 LTC residents in 54 facilities in three states in Germany. The sample size calculation was based upon a 5% prevalence rate in the control group and an expected reduction of 50% in the intervention group. The protocol is a waiting-list control design. All waiting facilities will be offered to participate after their waiting period. Primary endpoints are the number of restrained residents and resident time (hours) of being restrained. The use of psychotropics, falls, fall-related injuries and the incidence of residents newly being restrained is being monitored. The study starts with a baseline documentation of all facilities followed by randomization and a three month intervention. Change agents will be responsible for the intervention. Technical devices will include a newly developed soft hip protector and sensor mats which notice the intent of leaving the bed. The aim of the study is to develop an evidence-based model for a knowledge transfer project to implement minimum restraint environments in LTC.

Risk and protective factors for sporadic basal cell carcinoma: results of a two-centre case-control study in southern Germany. Clinical actinic elastosis may be a protective factor.

BACKGROUND: There are very few data regarding sun exposure behaviour of patients with basal cell carcinoma (BCC) in central Europe. OBJECTIVES: A case-control study of patients with sporadic BCC was conducted to assess the risk of occupational and leisure-time sun exposure behaviour, precursor lesions for skin cancer and phenotypic factors on the development of sporadic BCC in Ulm and Dresden, Germany. METHODS: A comparison was made of 213 patients with BCC (128 from Ulm, 85 from Dresden; 103 men and 110 women; median age at diagnosis 69 years) and 411 controls (237 from Ulm, 174 from Dresden; 197 men and 214 women; median age 58 years). Crude odds ratios (ORs) and corresponding 95% confidence intervals for all of 64 possible risk factors revealed strong associations in 33 items. Selection of important risk factors was performed in a multiple logistic regression. RESULTS: For sporadic BCC, an increased risk was shown for persons with actinic cheilitis (OR 7.1), actinic keratosis (OR 2.7) and solar lentigo (OR 2.5). The only phenotypic factor indicating risk of sporadic BCC was hair colour, with a higher risk for red/fair than brown/black hair (OR 4.3). There was an increased risk for persons with BCC in first-degree relatives (OR 5.1) and those with sunburn 20 years before sporadic BCC was diagnosed (OR 3.6). Additionally, occupational ultraviolet (UV) exposure appeared to be a risk factor (OR 2.4). In contrast, clinical actinic elastosis showed a protective effect (OR 0.1). CONCLUSIONS: In contrast to earlier reports, clinical actinic elastosis turned out to be the only protective factor for sporadic BCC. A special relationship between wrinkling and BCC risk could not be shown. For basic research, future work should be aimed at elucidating further the different forms of collagen repair processes after intermittent and/or chronic UV exposure. The data strongly support the recommendation that a change in recreational UV exposure habits in individuals, and sunburn avoidance in particular, are necessary not only because of the increased long-term risk of melanoma, but also because of the risk of other skin cancers such as sporadic BCC.

Whole blood interleukin 8 and plasma interleukin 8 levels in newborn infants with suspected bacterial infection.

AIM: To evaluate a new micro-method technique for measurement of interleukin 8 in detergent-lysed whole blood (whole blood IL-8) applicable to capillary blood sampling as a test for bacterial infections in neonates. METHODS: Whole blood IL-8 was measured at the first suspicion of infection along with IL-8 determined in plasma (plasma IL-8), C-reactive protein and blood cultures in 154 consecutive newborn infants with clinical signs of bacterial infection. Only 20 microl of whole blood were required for the new assay. RESULTS: Blood culture-proven infections were diagnosed in six infants and clinical infection (defined as a combination of clinical and laboratory signs) in 20 infants. 1000 pg/ml was determined as the suitable threshold for whole blood IL-8 by ROC-curve analysis. At that threshold, whole blood IL-8 detected blood culture-proven infections with a sensitivity of 83% and a specificity of 67%. The areas under the ROC curves were similar for whole blood IL-8 and plasma IL-8. CONCLUSIONS: Compared with plasma IL-8, whole blood IL-8 offers the advantages that measurements of whole blood IL-8 require a smaller blood sample volume and are not altered by haemolysis. The diagnostic accuracy of whole blood IL-8 remains to be studied in more detail in the future.

Risk indicators for falls in institutionalized frail elderly.

The aim of this study was to identify individual predisposing risk indicators for falls in a sample of institutionalized frail elderly in southern Germany. The design was a prospective observational study with a 1-year follow-up (October 1998-September 1999). The study population included 472 long-term-care residents whose mean age was 84 years; 77% were female. Risk indicators for accidental falls were analyzed by using logistic regression. Residents were found to have an incidence density rate of falls of 2,558 per 1,000 resident-years. Multiple logistic regression analysis revealed short-term memory loss, transfer assistance, urinary incontinence, positive fall history, and use of trunk restraints as predictors of falls. In a further logistic regression analysis, depressive symptoms, transfer assistance, urinary incontinence, and positive fall history were associated with frequent falls. Using these risk indicators as a screening procedure to identify fallers would be easy to administer and could be accomplished by nursing staff. Study results encourage specifically addressing urinary incontinence, cognitive impairment, use of restraints, depression, and transfer difficulties as modifiable predisposing risk factors for falls. Fall history represents an important nonmodifiable marker to identify residents at high risk.