National consensus on biologic dose reduction in psoriasis: a modified eDelphi procedure.

BACKGROUND: Dose reduction of biologics for psoriasis is applied in daily practice, although guidelines are lacking. Striving for clear criteria is important, as it leads to a consistent application of dose reduction. OBJECTIVE: To achieve consensus on criteria for biologic dose reduction in psoriasis patients with stable and low disease activity. METHODS: An online Delphi procedure (eDelphi) was conducted. Dutch dermatologists were invited to participate in a maximum of 3 voting rounds. Proposed statements were selected based on literature review and included criteria for the application of dose reduction and dosing schedules. Biologic dose reduction was defined as 'application of injection interval prolongation'. Proposed statements were rated using a 9-point Likert scale; consensus was reached when ≥70% of all voters rated 'agree' (7-9) and <15% rated 'disagree' (1-3). RESULTS: A total of 27 dermatologists participated and reached a consensus on 15 recommendations over 2 voting rounds. Agreed statements included criteria for dose reduction eligibility, criteria for dose reduction (dis)continuation, and dosing schedules for adalimumab, etanercept, and ustekinumab. Based on the eDelphi outcomes, an algorithm fit for implementation in current practice was developed. CONCLUSIONS: Recommendations of this national consensus process can guide clinicians, and consequently their patients, toward consistent application of biologic dose reduction.

Chromosomal aberrations in lymphocytes predict human cancer independently of exposure to carcinogens. European Study Group on Cytogenetic Biomarkers and Health.

An increased risk of cancer in healthy individuals with high levels of chromosomal aberrations (CAs) in peripheral blood lymphocytes has been described in recent epidemiological studies. This association did not appear to be modified by sex, age, country, or time since CA test, whereas the role played by exposure to carcinogens is still uncertain because of the requisite information concerning occupation and lifestyle was lacking. We evaluated in the present study whether CAs predicted cancer because they were the result of past exposure to carcinogens or because they were an intermediate end point in the pathway leading to disease. A nested case-control study was performed on 93 incident cancer cases and 62 deceased cancer cases coming from two prospective cohort studies performed in Nordic countries (Denmark, Finland, Norway, and Sweden) and Italy. For each case, four controls matched by country, sex, year of birth, and year of CA test were randomly selected. Occupational exposure and smoking habit were assessed by a collaborative group of occupational hygienists. Logistic regression models indicated a statistically significant increase in risk for subjects with a high level of CAs compared to those with a low level in the Nordic cohort (odds ratio, 2.35; 95% confidence interval, 1.31-4.23) and in the Italian cohort (odds ratio, 2.66; 95% confidence interval, 1.26-5.62). These estimates were not affected by the inclusion of occupational exposure level and smoking habit in the regression model. The risk for high versus low levels of CAs was similar in subjects heavily exposed to carcinogens and in those who had never, to their knowledge, been exposed to any major carcinogenic agent during their lifetime, supporting the idea that chromosome damage itself is involved in the pathway to cancer. The results have important ramifications for the understanding of the role played by sporadic chromosome damage for the origin of neoplasia-associated CAs.

Single-dose radiotherapy (6 Gy): palliation in painful bone metastases.

Approximately 50% of patients with cancer develop bone metastases and these have an important influence on the quality of life. PURPOSE OF THE STUDY. To evaluate a lower dose than the one already proven to be effective (8 Gy) in the palliation of painful bone metastases. METHODS AND MATERIALS. In a prospective study we analyzed the pain relief, after a single dose of 6 Gy, in 170 patients with painful bone metastases. This was assessed by a questionnaire. RESULTS. A degree of pain relief, was achieved in 88% of the treatments and there was complete relief in 39%. When the treatment was given to the vertebrae, infield spinal cord compression developed in 9%, and when given to the pelvis or femur, infield fractures developed in 8%. CONCLUSION. We concluded that a single dose of 6 Gy was very effective in the palliation of painful bone metastases.

Influence of age, comorbidity and performance status on the choice of treatment for patients with non-small cell lung cancer; results of a population-based study.

BACKGROUND: In the Netherlands in 1997, 43% of patients with newly diagnosed lung cancer were over 70. Large age-specific differences in treatment exist. We examined whether age, comorbidity, performance status and pulmonary function influenced treatment. PATIENTS AND METHODS: Data on patients with newly diagnosed non-small cell lung cancer (N = 803) were obtained: comorbidity, performance status, pulmonary function (FEV1) and initial treatment. Age-specific differences in treatment according to the guidelines were examined. Odds ratios were calculated by means of logistic regression analyses. RESULTS: 82% with stage I or II disease received treatment according to the guidelines; this applied to 48% with stage IIIA disease and to 54% with stage IIIB disease. For all stages, this proportion decreased with increasing age. In stage IV disease, 36% did not receive any treatment; this applied to 52% of the elderly patients (75+ years). Multivariate analyses showed associations between comorbidity and treatment choice, but none with performance status. Age of 75+ years appeared to be the most important factor for not receiving treatment according to guidelines. CONCLUSION: A substantial proportion of elderly patients with non-small cell lung cancer did not receive standard treatment. Performance status and comorbidity seldom formed the underlying reason. Calendar rather than biological age seemed to play the most important role in choice of treatment for patients with non-small cell lung cancer.

A prospective longitudinal study on radiation-induced hearing loss.

Recent clinical reports indicate that patients receiving radiotherapy that includes the auditory system in the treatment volume are likely to develop an irradiation-induced hearing loss. Although the early, presumed reversible, conductive hearing impairment due to secretory otitis media following radiotherapy is a sequela well known by radiation oncologists, permanent hearing loss, both conductive and sensorineural, is believed to be rare. A prospective study was performed enrolling patients receiving postoperative radiotherapy for unilateral parotid tumors. Audiometric results prior to irradiation were compared with those obtained 2 years later. Up to 50% of the patients (9 of 18) developed a clinically relevant hearing loss in the irradiated ear, both conductive and/or sensorineural. The contralateral ear remained unaltered. The hearing loss was permanent in 6 patients (33%) and affected their quality of life. The data suggest that changes occur in the inner ear as well as in the auditory nerve and auditory brain stem with conventional irradiation schemes with daily fractions of 2 to 2.5 Gy with a total dose of 50 Gy.

[Sarcoma of the thoracic wall following mastitis radiotherapy 38 years previously]. / Sarcoom van de thoraxwand na radiotherapie voor mastitis 38 jaar eerder.

A 62-year-old woman presented with a feeling of pressure between her shoulder blades. Physical examination and laboratory test showed no abnormalities. Conventional X-ray of the thorax showed, by chance, a condensation of the second rib. CT scan showed a solitary lesion at the same location. Patient's history mentioned post-partum mastitis 38 years earlier, for which she was treated with X-ray therapy of about 4 to 5 Gray in 1 fraction. A partial rib resection was performed prior to diagnosis. The histopathological diagnosis was stage IA chondrosarcoma. It was excised in toto and an uneventful disease course ensued. In the past, X-ray therapy was used for many different benign diseases. Many doctors nowadays are not aware of this. This case illustrates that radiotherapy for benign disease can give rise to post irradiation sarcomas. Long-term follow-up of an irradiated region is essential for early diagnosis and may lead to higher cure rates.

Medical wastage in shipyard welders: a forty-year historical cohort study.

A 40-year historical cohort study of medical wastage among about 550 shipyard welders and 1100 controls (shipwrights and engine fitters), all employed at the same shipyard, was carried out. The welders left their job 20% more often than the controls; the excess considerably increased with duration of employment. Wastage was particularly due to respiratory, cardiovascular, locomotor and mental disorders. Both welders and controls contributed considerably (about 20%) to permanent work disability. Medical wastage among welders because of respiratory diseases was more than four times higher than among controls, which could not be explained by differential smoking habits alone. The study raises concern about locomotor health hazards for shipyard workers. Moreover, it underscores the need to reduce the large excess risk of respiratory diseases among shipyard welders. The same may be true for welders in other large metal construction plants, e.g. in boiler production.

Does ex vivo labelling of proliferating cells in colonic and vaginal mucosa reflect the S-phase fraction in vivo?

The ex vivo labelling of DNA-synthesizing epithelial cells in colonic and vaginal mucosa was compared with in vivo labelling. For this purpose, in vivo S-phase cells were labelled with [3H]thymidine (Tdr) and ex vivo labelling was continued by culturing tissue specimens in bromodeoxyuridine (BrdU). Various methods of tissue culture were employed in order to improve diffusion of medium (and BrdU) in the tissue. BrdU and 3H-TdR labelling were evaluated by immunohistochemistry and autoradiography respectively. Ex vivo labelling resulted in a patchy distribution of labelled cells, which did not correspond with the 3H-TdR labelling pattern obtained in vivo. Under the described conditions ex vivo labelling does not appear to be a reliable for estimation of the proliferative activities in vivo.

Docetaxel (Taxotere), a novel taxoid, in the treatment of advanced colorectal carcinoma: an EORTC Early Clinical Trials Group Study.

Docetaxel (Taxotere), a new semisynthetic taxoid, is a potentially important chemotherapeutic agent for the treatment of cancer. Forty patients with bidimensionally measurable advanced adenocarcinoma of the colon were treated with docetaxel 100 mg m-2 every 3 weeks as a 1 h infusion without routine premedication. Thirty-nine patients were eligible: 23 males and 16 females. Median age was 60 years (range 41-75) and WHO performance status 1 (0-2). Prior adjuvant chemotherapy was performed in four patients and prior radiotherapy in nine patients. Bidimensionally measurable disease sites included: liver in 26 patients, lymph nodes and abdominal/peritoneal masses in 13, lung/mediastinal masses in ten and subcutaneous nodes in four. The median number of cycles given was 2 (range 1-15). Thirty-three patients were evaluable for response. One patient (3%) achieved a complete response and two (6%) (95% confidence limits 0-14%) a partial response. Side-effects were similar to those observed in other studies. Docetaxel, given at this dosage and schedule, has minimal activity in the treatment of colorectal carcinoma.

Retrospective exposure assessment and quality control in an international multi-centre case-control study.

The paper presents the exposure assessment method and quality control procedure used in an international, multi-centre case-control study within a joint Nordic and Italian cohort. This study was conducted to evaluate whether occupational exposure to carcinogens influenced the predictivity of high frequency of chromosomal aberrations (CA) in peripheral lymphocytes for increased cancer risk. Occupational hygienists assessed exposures in each participating country: Denmark, Finland, Italy, Norway and Sweden. The exposure status to a carcinogen or a clastogen was coded in the cohort according to the original CA studies at the time of CA testing, but not for the whole work life. An independent occupational hygienist coordinated harmonization of the assessment criteria and the quality control procedure. The reliability of the exposure assessments was calculated as deviation from the majority of the assessors, as Cohen's kappa and as overall proportion of the agreements. The reassessment of the exposures changed the exposure statuses significantly, when compared with the original cohort. Harmonization of the exposure criteria increased the conformity of the assessments. The prevalence of exposure was higher among the original assessors (the assessor from the same country as the subject) than the average prevalence assessed by the other four in the quality control round. The original assessors classified more job situations as exposed than the others. Several reasons for this are plausible: real country-specific differences, differences in information available to the home assessor and the others and misunderstandings or difficulties in translation of information. To ensure the consistency of exposure assessments in international retrospective case-control studies it is important to have a well-planned study protocol. Due to country-specific environments a hygienist from each participating country is necessary. A quality control study is recommended, to be performed as described, combined with round-table meetings to minimize information bias between the assessors.