[Can the antibiotic prescription practice in a hospital be influenced by in-house guidelines? An interventional study at the University Hospital Halle (Saale), Germany]. / Lässt sich die Antibiotikaverordnungspraxis im Krankenhaus durch hausinterne Richtlinien beeinflussen? Interventionsstudie am Universitätsklinikum Halle (Saale).

BACKGROUND: In-house guidelines are an essential tool of antibiotic stewardship (ABS) programs to guide antimicrobial therapy. We studied the effect of in-house guidelines adapted to the local pathogen and resistance epidemiology on prescribing behavior. METHODS: At the University Hospital Halle (Saale) guidelines for the antimicrobial therapy and essential microbiological diagnostics were introduced. Main objectives were reducing the use of third generation cephalosporines and fluoroquinolones, decreasing selection pressure for enterococci and multidrug-resistant Gram-negative bacteria, minimizing Clostridium difficile infections (CDI), and improving microbiological diagnostics to enhance de-escalation strategies. 12 months thereafter a comparison of antibiotic consumption, pathogen and resistance statistics and use of blood cultures was performed. RESULTS: There was a decrease of third-generation cephalosporines (-18.6%) and fluoroquinolones (-9.8%), while consumption of broad- and intermediate-spectrum penicillins (+23.8% and +37%) as well as carbapenems (+11.9%) increased. The total volume of prescribed anti-infectives remained unchanged. The number of enterococcal isolates (-18.3%) and CDI (-26.3%) decreased considerably. Gram-negatives, particulary ESBL-producing Enterobacteriaceae, were detected more frequently due to an expanded screening program. The rate of blood cultures/1000 patient-days was unaffected. CONCLUSION: In-house guidelines for the empiric antiinfective therapy appear to be suitable to influence the prescribing behavior and the selection pressure on individual pathogen groups. The total volume of antibiotic prescriptions was not affected in this study.

Trends in skin cancer incidence in Vaud: an update, 1976-1998.

Trends of skin cancer incidence by histotype in the Swiss Canton of Vaud (608,000 inhabitants) between 1976 and 1992 were updated on the basis of 6720 further skin cancers registered over the period 1993-1998. Trends in the last period were downwards for squamous cell carcinoma in both sexes, still on the rise for basal cell carcinoma, and levelled off for malignant melanoma in females.

Trends in skin cancer incidence in Neuchâtel, 1976-98.

AIMS AND BACKGROUND: Limited data are available on trends in skin cancer incidence. This paper examines trends of the three major histotypes of skin cancer in an environment favorable for skin cancer registration. METHODS: Trends of skin cancer incidence by histotype in the Swiss Canton of Neuchâtel (165,000 inhabitants) were analyzed on the basis of 4,455 incident cases of basal cell, squamous cell carcinoma, and malignant melanoma registered over the period 1976-1998. RESULTS: Trends over the last decade considered tended to be downwards for squamous cell carcinoma in both sexes, were still on the rise for basal cell carcinoma, and leveled off for malignant melanoma in both sexes. CONCLUSIONS: Different trends were confirmed in this population between skin cancer histotypes related to cumulative intense sun exposure (squamous cell carcinoma) and those mainly related to more complex patterns of exposure to sunlight (basal cell carcinoma and malignant melanoma).

Interaction patterns between dentin and adhesive on prepared class V cavities in vitro and in vivo.

The interface between dentin and an acetone-based single-component adhesive system (Prime&Bond 2.1, DeTrey Dentsply, Germany) was morphologically investigated by scanning electron microscopy (SEM). Interaction patterns of human teeth were correlated in vivo and in vitro. The SEM examination proved that the formation of a hybrid and an adhesive layer, the peri- and intratubular adhesive penetration, as well as hiatus and nanoleakage formation were no different on vital and nonvital dentin within the limitation of the experimental arrangement of this study.

Second primary tumors after prostate carcinoma.

BACKGROUND: Several large datasets have shown a reduced risk of all neoplasms after a diagnosis of prostate carcinoma but an increased incidence rate of urologic carcinoma has been suggested. METHODS: Data collected by the Cancer Registries of the Swiss Cantons of Vaud and Neuchâtel (approximately 760,000 inhabitants) were used to estimate the incidence rate of a second primary tumor after a diagnosis of prostate carcinoma. A total of 4503 cases registered between 1974 and 1994 were followed until the end of 1996 (17,065 person-years). RESULTS: A total of 380 second primary neoplasms were observed versus 534.1 expected primary neoplasms (standardized incidence ratio [SIR] = 0.7; 95% confidence interval, 0.6-0.8). SIRs were significantly below unity for lung carcinoma (SIR = 0.7) and other major tobacco-related neoplasms, including those of the mouth or pharynx (SIR = 0.5), esophagus (SIR = 0.4), pancreas (SIR = 0.5), and larynx (SIR = 0.8). There was no excess rate of subsequent urologic carcinoma (SIR = 1.0) or colorectal carcinoma (SIR = 0.9). The reduced SIRs for lung carcinoma were stronger in elderly men (age >/= 75 years) and in patients with a shorter period since diagnosis (< 5 years). CONCLUSIONS: The incidence of all neoplasms was reduced significantly in men diagnosed with prostate carcinoma. Selection of the population, under-registration of second primary tumors, and reduced surveillance in elderly men with prostate carcinoma may, at least in part, explain this reduction in risk. No excess risk was observed for the complex of urologic neoplasms nor for tobacco-related neoplasms. This finding would not support an association between cigarette smoking and prostate carcinoma.

Incidence, mortality and survival from prostate cancer in Vaud and Neuchâtel, Switzerland, 1974-1994.

BACKGROUND: Prostate cancer incidence has been increasing in most developed countries in the absence of similar trends in mortality, and with variable patterns in different areas of the world. MATERIALS AND METHODS: Trends in incidence and mortality from prostate cancer for the period 1974-1994 were analysed using data from the Cancer Registries of the Swiss Cantons of Vaud and Neuchâtel. Of 5,010 cases registered, 80% were histologically or cytologically confirmed. RESULTS: Age-standardized incidence rates increased from 33.1 to 48.6 per 100,000 (+47%). The upward trends were greater in the most recent calendar periods, and in the younger age groups (+77% at age 45 to 54; +57% at age 55 to 64). In contrast, mortality was stable, with an overall increase of only 3% in age-standardized rates (from 20.4 to 21.0 per 100,000), due to some increase in men aged 65 or above. Consequently, the incidence/mortality rate ratios increased from 1.6 in 1974-1979 to 2.3 in 1990-1994. Five-year observed and relative survivals increased from 26% to 41% and from 46% to 58%, respectively. Ten-year observed and relative survival for cases diagnosed in 1985-1989 were 19% and 42%, respectively. Survival improvements were greater below age 75. CONCLUSION: The pattern of trends in incidence, mortality and survival confirms the influence of improved diagnosis of prostate cancer over the last few years in this European population. Still, while Swiss prostatic cancer mortality rates are the highest in the world (20.3 per 100,000, world standard), i.e., about 30% higher than in the United States, all races combined, incidence rates are still half as much. On account of the steady increase of prostate-specific antigen testing in Switzerland, further incidence increases are likely.

Incidence of invasive cancers following basal cell skin cancer.

To obtain quantitative information on the risk of invasive cancers following a diagnosis of basal cell carcinoma (BCC) of the skin, patients with incident BCC cases listed in the cancer registries of the Swiss cantons of Vaud and Neuchâtel between 1974 and 1994 were actively followed up through December 31, 1994, for the occurrence of subsequent invasive neoplasms. Among 11,878 persons with incident BCC who were followed for a total of 76,510 person-years at risk, 1,543 metachronous cancers were observed versus 1,397.9 expected, corresponding to a standardized incidence ratio (SIR) of 1.1 (95% confidence interval (CI) 1.0-1.2). However, after exclusion of skin cancers (mostly squamous cell carcinoma and melanoma), 975 second primary cancers were observed versus 1,059 expected (SIR = 0.9, 95% CI 0.8-1.0). Significant excesses were registered for cancer of the lip (SIR = 2.2), for squamous cell skin cancer (SIR = 4.5) and melanoma of the skin (SIR = 2.5), and for non-Hodgkin's lymphoma (SIR = 1.9). The SIRs were also above unity, though not significantly, for cancers of the salivary glands (SIR = 2.8) and the small intestine (SIR = 2.1) and for soft-tissue sarcomas (SIR = 1.7). The SIR for lung cancer was 0.9. The SIRs for salivary gland and skin cancer were appreciably greater below age 70 years. For most sites, particularly for squamous cell cancer and melanoma of the skin, the SIRs remained elevated 5 or more years after BCC diagnosis. The cumulative incidence of squamous cell skin cancer was 13% at 19 years; this stresses the importance of carefully monitoring skin lesions among persons previously diagnosed with BCC.

Incidence of invasive cancers following squamous cell skin cancer.

The authors describe the incidence of new primary cancers among 4,639 cases of squamous cell skin cancer (SCC) diagnosed between 1974 and 1994 in the cancer registries of the Swiss cantons of Vaud and Neuchâtel (total person-years at risk = 23,152). Overall, 729 metachronous cancers were observed versus 527.6 expected, corresponding to a standardized incidence ratio (SIR) of 1.4 (95% confidence interval (CI) 1.3-1.5). After exclusion of skin cancers, however, 384 second primary neoplasms were observed versus 397.2 expected (SIR = 1.0). Excesses were observed for cancers of the lip (SIR = 3.1) and lung (SIR = 1.3), for basal cell (SIR = 4.3) and melanomatous skin cancers (SIR = 3.3), and non-Hodgkin's lymphomas (SIR = 1.7). Rates were elevated for cancers of the salivary glands (SIR = 4.3) and for Hodgkin's disease (SIR = 2.7), and, below age 65 years, for cancers of the lung (SIR = 1.6), breast (SIR = 1.5), and prostate (SIR = 1.8), for Hodgkin's disease (SIR = 15.8), as well as for all neoplasms except skin (SIR = 1.2; 95% CI 1.0-1.5). The cumulative risk of basal cell skin cancer reached 17% after 15 years. The authors believe that the excesses for basal cell carcinomas and melanomas of the skin following SCC, and possibly of lymphomas, were likely attributable to common phenotypic characteristics and exposure to UV radiation. The elevated rates of lung cancer are suggestive for a role of tobacco as a cause of squamous cell skin cancer.

Incidence of invasive cancers following cutaneous malignant melanoma.

It has long been suggested that subjects diagnosed with cutaneous malignant melanoma (CMM) have an excess rate of subsequent neoplasms. To provide further quantitative information on the issue, we have considered 1,780 histologically confirmed CMM diagnosed between 1974 and 1994 by the Cancer Registries of the French-speaking Swiss Cantons of Vaud and Neuchatel (760,000 inhabitants) and followed up to the end of 1994 for the occurrence of a second primary. A total of 194 neoplasms was observed vs. 111.7 expected, corresponding to a standardized incidence ratio (SIR) of 1.7 [95% confidence interval (CI) 1.5-2.0]. When skin cancers were excluded, 87 subsequent neoplasms were observed vs. 84.9 expected (SIR 1.0). Significant excess rates were observed for basal cell (SIR 4.4), squamous cell (SIR 3.1) and melanoma (SIR 4.7) of the skin, as well as for prostatic cancer (SIR 2.1). The increased rates of subsequent skin cancer were somewhat larger in males, whereas all the SIRs were systematically greater below age 60. The SIRs of subsequent skin cancer remained above unity for 5 years or longer since diagnosis of CMM, in the absence of a clear pattern in trend with time since diagnosis. The cumulative incidence following CMM was 3% for CMM, 4% for squamous cell and 14% for basal cell carcinoma 20 years after diagnosis of CMM. Our results confirm that patients diagnosed with CMM have excess risks of subsequent melanoma and non-melanomatous skin neoplasms which justify focused prevention and surveillance of skin lesions in these patients. Subjects with CMM do not have any appreciable overall excess of non-skin neoplasms, even after long-term follow-up.

Reduction of mechanical sensitivity in an insect mechanoreceptor correlated with destruction of its tubular body.

The modified cilium (dendrite) of epithelial mechanoreceptors of insects contains microtubules in different arrangements: (1) microtubules distributed over the entire receptor and not fixed in a special configuration, therefore called free microtubules, (2) densely packed, interconnected microtubules called the tubular body, and (3) 9 doublet microtubules. These groups of microtubules have been discussed in relation to mechanotransduction. In a preceding paper the free microtubules were proved to be not involved in mechanotransduction. In this paper the hypothesis is examined that the tubular body may be essential to mechanotransduction. For this purpose the effect of the microtubule-disassembling drug vinblastine on both the tubular body and the sensitivity is examined in a femoral mechanoreceptor of the cricket Acheta domesticus. After 6- to 26-h exposure to vinblastine the tubular body is partially or totally destroyed. Simultaneously, mechanical sensitivity decays to zero. In contrast, the pacemaker property for nerve impulses of the apical dendritic segment is only slightly altered. We conclude from these results that the tubular body is essential to mechanotransduction. Three experiments in which a (small) response persisted, despite a totally destroyed tubular body, suggest that receptor potentials can in principle be evoked without an intact tubular body. In addition to the irreversible reduction of receptor sensitivity, vinblastine causes a reversible reduction during repetitive stimulation. This adaptation is supposed to be the consequence of altered properties of the tubular body.

Sensitivity of an insect mechanoreceptor after destruction of dendritic microtubules by means of vinblastine.

Microtubules (Mt) are present in the modified cilium of epithelial mechanoreceptors of insects in three different arrangements: (1) 9 doublet Mt in the proximal region of the outer segment, (2) densely packed, interconnected Mt of the tubular body in the dendritic tip receiving the adequate stimuli, and (3) Mt between ciliary neck and tubular body, which are not fixed in a special configuration and therefore called free Mt. The free Mt are considered by some authors to be elements of intracellular signal transmission. This hypothesis was examined by electrophysiological and morphological studies on a tibial hair-mechanoreceptor of a cricket (Acheta domesticus). Exposure of the receptor from the apical side to vinblastine disassembled the free Mt within 2 to 4 h, while Mt of the tubular body were only little affected during this time interval. In this state of Mt disassembly (up to 7 h of application) mechanosensitivity of the receptor is only slightly reduced or not at all. The pacemaker property of the dendrite for nerve impulse is also preserved. It is concluded that the free Mt are not elements of intracellular signal transmission and are not directly involved in mechanotransduction.