Multicenter external validation of two malignancy risk prediction models in patients undergoing 18F-FDG-PET for solitary pulmonary nodule evaluation.

OBJECTIVES: To achieve multicentre external validation of the Herder and Bayesian Inference Malignancy Calculator (BIMC) models. METHODS: Two hundred and fifty-nine solitary pulmonary nodules (SPNs) collected from four major hospitals which underwent 18-FDG-PET characterization were included in this multicentre retrospective study. The Herder model was tested on all available lesions (group A). A subgroup of 180 SPNs (group B) was used to provide unbiased comparison between the Herder and BIMC models. Receiver operating characteristic (ROC) area under the curve (AUC) analysis was performed to assess diagnostic accuracy. Decision analysis was performed by adopting the risk threshold stated in British Thoracic Society (BTS) guidelines. RESULTS: Unbiased comparison performed In Group B showed a ROC AUC for the Herder model of 0.807 (95 % CI 0.742-0.862) and for the BIMC model of 0.822 (95 % CI 0.758-0.875). CONCLUSIONS: Both the Herder and the BIMC models were proven to accurately predict the risk of malignancy when tested on a large multicentre external case series. The BIMC model seems advantageous on the basis of a more favourable decision analysis. KEY POINTS: • The Herder model showed a ROC AUC of 0.807 on 180 SPNs. • The BIMC model showed a ROC AUC of 0.822 on 180 SPNs. • Decision analysis is more favourable to the BIMC model.

Moisture effect on the storage, handling and flow properties of poultry litter.

Poultry litter, a combination of accumulated chicken manure, feathers and bedding materials, is a potential feedstock for bioenergy and other value-added applications. The effect of moisture on the physical properties, equilibrium moisture relations, flow properties and wall friction characteristics of poultry litter were measured. Poultry litter densities (bulk, particle and tap) reduced and compressibility increased with increase in moisture content. The fit of the GAB equation to poultry litter equilibrium moisture isotherm at 25 degrees C indicated that the monolayer moisture content for poultry litter is 5.5% (wb). Increasing the moisture content of the poultry litter reduced its flowability from easy flowing (flow index of 6.4) at moisture content of 10.3% (wb) to very cohesive (non-flowing) (flow index of 1.9) at moisture content of 30.9% (wb). Flow on a stainless steel surface was improved when the surface was mirror-finished or galvanized coated.

Interferon-alpha for the treatment of elderly patients with chronic myeloid leukaemia.

The present retrospective analysis is based on data of 213 patients with chronic myeloid leukaemia (CML). They were treated with interferon (IFN)alpha-2C (Berofor) at daily doses of 3.5 MU subcutaneously (s.c.), alone or in combination with low-dose ara-C or hydroxyurea, according to four consecutive studies of the Austrian CML Study Group. Comparisons were made between 41 patients aged > or = 60 years and 172 younger patients. The elderly patients (median: 64 years; range: 60-73) showed similar pretreatment characteristics compared with the younger group, but included a higher percentage of Sokal Stage three (51 vs 20%). Median observation periods were similar (38 vs 39 months), whereas the duration of IFNalpha treatment was shorter in the elderly group (median 57 vs 42 weeks). The rate of overall haematological responses (73 vs 78%) and complete haematological response (44 vs 54%), was similar in both cohorts. Differences seen in partial (5 vs 12%) and complete cytogenetic response (10 vs 13%), were not statistically significant, but a tendency in favour of the younger cohort had to be noted. Summing up, in elderly patients acceptable rates of haematological and cytogentic response can be expected after treatment with IFNalpha alone or in combination with LD ara-C or HU.

Interferon-alpha-2C and LD ara-C for the treatment of patients with CML: results of the Austrian multi-center phase II study.

Small pilot studies of patients with CML have reported on encouraging response rates after treatment with interferon-alpha (IFNalpha) in combination with low-dose cytosine arabinoside (LD ara-C). We therefore initiated a multi-center phase II trial in order to investigate the efficacy and tolerability of this combination in newly diagnosed patients with Ph-positive chronic myelogenous leukemia (CML). Eighty-four patients were treated with IFN-alpha-2c at daily subcutaneous doses of 3.5 MU and LD ara-C added subcutaneously for 10 days every month at a dose of 10 mg/m2, following an initial reduction of WBC to less than 20 x 10(9)/l with hydroxyurea (HU). Within a median observation period of 28 (5-59) months the patients received a median of 7 (1-35) IFNalpha and LD ara-C cycles. Treatment was stopped due to side effects in 16 cases (19%) and to primary or secondary treatment failure in 38 cases (45%). In 45 patients (54%) complete hematological response (CHR) was achieved; in 39 patients (46%) cytogenetic responses including 15 (18%) complete cytogenetic responses (CHR) were observed. Median duration of cytogenetic responses was 15 months. Relapses were seen in 8/15 patients (53%) with complete cytogenetic remission (CCR), in 3/6 patients (50%) with partial cytogenetic response and in 9/18 patients (50%) with minor cytogenetic response. In conclusion, the combination of IFNalpha and LD ara-C resulted in encouraging rates of hematological and cytogenetic responses in patients with CML with low to moderate toxicity.

Dose escalation of ara-c may improve response rates in a subgroup of chronic myeloid leukemia patients with poor response to interferon-alpha and low-dose ara-C.

The present analysis was performed to evaluate the impact of cytosine arabinoside (ara-C) dose escalation on hematological and cytogenetic responses in patients with chronic myelogenous leukemia (CML) who failed to respond to low-dose ara-C (LD ara-C) at a dose of 10 mg/m2/d over 10 days per month and interferon-alpha (IFNalpha, 3.5 MU/d). Following the same administration schedule, dose escalation of ara-C to 15 and 20 mg/m2/d 1-10 was performed in 36 of 119 patients (30%) due to inadequate hematological response and/or disease progression. As a result, improvement of hematological and cytogenetic responses was achieved in 22 (61%) and nine (25%) patients, respectively. Escalated ara-C dose levels were usually well tolerated, although some patients experienced deterioration of preexisting side effects. Our results support the critical role of ara-C dose towards a better disease control in CML.

Patient satisfaction in developing countries.

Efforts to obtain useful information on patient satisfaction in Indonesia have been frustrated by a tendency of respondents to withhold critical comment. A survey of 75 patients in eleven health centers on three islands attempted to obtain credible information on satisfaction by asking for information on events, not opinions, and on the relative importance of the factors surveyed. Unlike previous research where 95% of respondents typically answered they were 'fully satisfied', 28% of the respondents replied that their consultation had not been conducted in private (ranked first in importance among the nonmedical factors), 65% said the facility could be cleaner (ranked second in importance) and 19-48% reported not receiving various kinds of information (ranked third). Lending credence to these results, the respondents were able to support their positive answers with corroborative information in a high percentage of instances. The ranking of relative importance of satisfaction factors was unexpected. At the bottom of the list were continuity of provider, waiting time, availability of amenities, cost and social interaction with the provider. Despite the diversity among cultures that is characteristic of Indonesia, there was a high degree of similarity in the importance rankings among respondents on the three islands which were chosen to represent cultural divisions in the nation. The only notable differences in the rankings of relative importance appeared to be a function of the purpose of the visit to the facility.

[A questionnaire suitable for general practice for detection of the health status and quality of life of patients with hemato-oncologic diseases: psychometric properties. The Study G "Quality of Life" of the International Society for Chemo- and Immunotherapy (I.G.C.I.)]. / Ein praxisgerechter Fragebogen zur Erfassung von Gesundheitsqualität und Lebensqualität bei Patienten mit hämato-onkologischen Erkrankungen: psychometrische Eigenschaften. The Study Group "Quatify of Life" of the International Society for Chemo- and Immunotherapy (I.G.C.I.).

In the evaluation of therapeutic measures it is important to consider the consequences of the proposed treatment on the subjective quality of health and the subjective quality of life. Since no adequate instrument existed to provide such assessments, a short, theoretically based questionnaire was developed and psychometrically tested. The construction phase was based on data of 104 adults with haemato-oncological diseases, leading to the design of a questionnaire which was tested using data of a further 292 patients. The validity of the "questionnaire for attitudes towards quality of health and quality of life" was assessed by comparing it with physicians' ratings and by correlation with the results of an extensive questionnaire. The reliability was satisfactory; the questionnaire met with high acceptance by patients, physicians and health care personnel. It complies with the requirements of clinical trials where the objective is to measure quality of health and quality of life.

[Prognostic factors in myelodysplastic syndromes: analysis of 72 cases]. / Prognostische Faktoren bei myelodysplastischen syndromen (MDS): eine Analyse von 72 Fällen.

72 patients were diagnosed as suffering from myelodysplastic syndromes (MDS) according to the FAB classification: 16 patients with refractory anaemia (RA), 11 patients with acquired idiopathic sideroblastic anaemia (AISA), 14 patients with refractory anaemia with an excess of blast cells (RAEB), 7 patients with RAEB in transformation (RAEB/t) and 24 patients with chronic myelomonocytic leukaemia (CMML). The duration of the preleukaemic phase was between 2 and 189 months (median: 15 months); RAEB in transformation and CMML showed a median phase of less than 12 months. Transformation into acute leukaemia (AL) occurred in 46 patients (64%). Of the clinical signs only thrombocytopenia was a significant poor prognostic factor (p less than 0.01). Cytogenetic studies were made in 31 patients. 14 had clonal aneuploidy: these patients had a higher risk of AL, but not a significantly shorter preleukaemic phase (p greater than 0.1). Stem cell cultures (CFUc) were carried out in 31 patients. Patients without colony growth or only cluster growth showed a high incidence (10/11 and 8/8) of transformation into AL; preleukaemic phases were significantly shorter than in patients with normal colony growth or cluster + colony growth in all FAB subgroups (p less than 0.001). The bone marrow blast cell count was indirectly proportional to the duration of the preleukaemic phase: thrombocytopenia, cytogenic aberrations and failure of in vitro colony growth are additional poor prognostic factors in MDS.

Compaction of poultry litter.

Poultry litter, a combination of accumulated chicken manure, feathers and bedding materials, is a potential feedstock for bioenergy and other value-added applications. The use of this waste product has been historically limited to within few miles of the place of generation because of its inherent low density. Compaction is one possible way to enhance the storage and transportation of the litter. This study therefore investigates the effect of moisture content (19.8-70.7%, d.b.) and pressure (0.8-8.4 MPa) on the compaction characteristics of poultry litter. Results obtained showed that the initial density of densified poultry litter, energy required for compaction and the strength of the densified material after 2 months of storage were significantly (P<0.05) affected by moisture content and pressure applied during compaction. The density of the compacted material was only affected by pressure applied during compaction after 2 months of storage. The specific energy required to produce the densified material varied from 0.25 to 2.00 kJ/kg and was significantly less than the energy required to produce pellets from biological materials. The results obtained from the study can be used for the economical design of on-farm compaction equipment for poultry litter.

Management of community distribution programs in Bangladesh.

In Bangladesh, five high- and five low-performing nongovernmental organization-supported community distribution projects were studied to determine which management, supervisory, and field activities differed between the better and poorer performers. A total of 37 variables were studied, and differences between the higher- and lower-performing projects were noted for nearly all of the variables. In general, project effectiveness was associated with higher service quality, more proactive field supervision, and greater organizational clarity. No project performed all of the 37 activities well. No one or two variables predicted project success, and none of them was found to be a necessary condition for project success. Higher performance was associated with doing well on many of these variables.

PIP: In Bangladesh during 1987-1989, interviews and observations were conducted of current, prior, and never users (240 in each group); 40 field workers; and 4 focus groups with field workers who did not take part in field observation, to examine the characteristics and activities that distinguished from others the higher performing nongovernmental organizations providing community-based distribution of family planning services. The higher performance subprojects (HPS) had a higher contraceptive prevalence rate than did the lower performance subprojects (LPS) (31.7% vs. 14%; p .001). They also had a higher average new acceptor per field worker rate over the past 6 months than did the LPS (99 vs. 67; p .001) and a lower drop out rate (11% vs. 27%; p .001). HPS field workers were more likely to be the source of supplies and motivation than were LPS field workers (80% vs. 64% and 64% vs. 51%, respectively; p .001). HPS clients were more likely to recommend family planning to others than LPS clients (53% vs. 32%; p .001). HPS had a higher composite unweighted score than did LPS (76 vs. 54). Despite the better performance, HPS did not uniformly perform well all 37 activities. HPS performed better, and LPS performed worse, in general and not on just 1 or 2 activities. For nearly every variable, at least 1 HPS did not do well. Discord occurred at the top of 2 HPS. Dynamic leadership was not a condition of success. Failure to follow the chain of command at a HPS did not destroy the subproject but did have a likely cost. Field workers of 1 HPS received little training. No one variable was a prerequisite for success. Higher performance depended on performing well on many of the 37 variables.

Islam and family planning acceptance in Bangladesh.

One frequently cited barrier to more widespread adoption of family planning in Moslem countries is religious opposition. To examine the depth and extent of such opposition in Bangladesh, 106 men who had been identified by their wives as religiously opposed to family planning were interviewed. Unexpectedly, 26 percent of the "opposing" husbands reported that they were current users of a contraceptive and an additional 50 percent, although not practicing, said they were in favor of family planning. Of the alleged "opposers," only 23 percent said they opposed family planning on religious grounds. One-fourth of this last group were able to cite specific islamic injunctions against family planning. It appears on the basis of these data, which were collected in the religiously conservative area of Lakshimipur, that the perception of widespread Islamic-based resistance to contraception in Bangladesh is not founded in fact.

PIP: One frequently cited barrier to more widespread adoption of family planning (FP) in Moslem countries is religious opposition. To examine the depth and extent of such opposition in Bangladesh, 106 men who had been identified by their wives as religiously opposed to FP were interviewed. Unexpectedly, 26% of the "opposing" husbands reported that they were current users of a contraceptive and an additional 50%, although not practicing, said they were in favor of FP. Of the alleged "opposers," only 23% said they opposed FP on religious grounds. 1/4 of this last group were able to cite specific Islamic injunctions against FP. It appears on the basis of this data, which were collected in the religiously conservative area of Lakhimpur, that the perception of widespread Islamic-based resistance to contraception in Bangladesh is not founded in fact. This research was part of a larger study, done in 1988. Data come from 3 surveys and 1 set of indepth interviews. A survey of 1241 married women of reproductive age was done in January and February of 1988, using a 2-stage sampling approach. Sites were selected at random; 23 married women of reproductive age were polled from each site. In the 2nd survey, 40 "high-" and 40 "low-performing" field workers of a nongovernmental organization providing FP services in the area were interviewed. Their performance rankings were computed on the 2 indicators of dropouts and recruitment. There was a near perfect inverse correspondence between dropouts and recruitment. Field workers who were successful recruiters had the lowest numbers of dropouts and vice versa (R=83). There was an association between field worker's performance and reported religious opposition. Indepth interviews were conducted with 6 of the husbands. A questionnaire was given in 1989 by male interviewers to 106 husbands whose wives indicated were opposed to FP or religious grounds. Research found that contraceptive use by survey respondents was underreported. The man feel that a yes answer is not socially acceptable.

Remission may continue after termination of rIFN alpha-2b treatment for essential thrombocythemia.

Essential thrombocythemia, a myeloproliferative disorder of clonal origin, is often associated with various clinical manifestations resulting from thromboembolic or hemorrhagic complications. The long-established successful method of treatment with cytotoxic agents or radioactive phosphorus has recently been superseded by interferon alpha. We treated 14 symptomatic patients with 5 x 10(6) IU recombinant interferon alpha-2b s.c. daily. 12/14 pts responded within 14-75 days. When platelet counts decreased to below 450 g/l the frequency of administration was reduced stepwise. 7 patients remained in CR during this reduction phase and treatment was stopped in 5 pts after 12-32 months. Until now, 3 of them are still in continuous good PR without any drug therapy and free of symptoms for 3+, 19+ and 36+ months. Continuous response during maintenance was associated with age, initial platelet count and time required to reduce platelet counts to less than 450 g/l.

Timentin in combination with tobramycin as empirical therapy in febrile neutropenic patients with haematological malignancies.

Timentin (5.2 g tds) and tobramycin (40 mg tds) were administered to 51 patients (22 male, 29 female, age range 17-72, mean age 40.4) with acute leukaemia, chronic myeloid leukaemia in blastic crisis, severe aplastic anaemia and acute agranulocytopenia. All patients had neutropenia (PMN less than 1000/mm3) and fever (greater than 38 degrees C). Febrile episodes consisted of 22 proved septicaemias due to Gram-positive organisms (Staphylococcus aureus, S. epidermidis, enterococcus) in 11 cases and to Gram-negative organisms (Escherichia coli, Pseudomonas aeruginosa, Alkaligenes faecalis, Serratia marcescens, Klebsiella pneumoniae) in 10 cases. One patient had a polymicrobial infection (P. aeruginosa, S. aureus, non-haemolytic streptococcus). Twenty-nine infections were diagnosed only clinically. The mean duration of treatment was 11.1 days (range 4-20 days). Eighty-seven per cent of evaluable febrile episodes improved. Among 11 infections due to Gram-positive cocci, eight (72%) resolved, and in nine (90%) of ten cases due to Gram-negative bacilli success was obtained. The polymicrobial infection also resolved. In only four patients were mild side effects seen, e.g. exanthema, pruritus, phlebitis: renal toxicity was not observed. These data suggest that the combination of Timentin and tobramycin is an effective and safe empirical antibiotic regimen in febrile neutropenic patients.

[Recombinant (IFN-alpha 2b) therapy in hairy cell leukemia]. / Rekombinante (IFN-alpha 2b)-Therapie der Haarzell-Leukämie.

Eighty-five patients with hairy-cell leukemia were treated in a multicentric "open label" study with IFN-alpha 2b and evaluated. Induction therapy was 2 X 10(6) U IFN-alpha 2b/m2, 3 times a week, s.c. The results show this regimen to be highly effective with only a few tolerable and transient side effects consisting mainly of flu-like symptoms. After 6 months of therapy 4% CR, 69% PR, and 16% MR, were noted. In a small group of four patients who had achieved CR or PR, we tested the effect of varying doses for maintenance therapy. Our preliminary results indicate that a relapse caused by interruption of IFN therapy or dose reduction to 3 X 10(6) U given once a week, o.c. could be successfully treated by readministration, or escalating the dosage of IFN. It seems that remission maintenance requires long-term treatment with IFN. In a short-term in vitro test we studied the effect of IFN-alpha 2 on the incorporation of 3H-thymidine and 3H-uridine into hairy cells of five patients. Fort both precursors no appreciable effect was detected. However, after prolonged incubation for 48 h, a significant enhancement of 3H-uridine incorporation was observed, while 3H-thymidine incorporation remained unaffected. Cell marker analysis performed with monoclonal antibodies before and after incubation of hairy cells with IFN-alpha 2 for up to 7 days did not reveal any change of the phenotype of hairy cells.

A short multilingual quality of life questionnaire--practicability, reliability and interlingual homogeneity.

International cooperative clinical trials require a multilingual quality of life questionnaire. The 'International Society for Chemo- and Immunotherapy' therefore designed a study to develop and test a 'health accentuated' quality of life questionnaire in the eight languages spoken in this society. The objective was to examine practicability, reliability and interlingual homogeneity. Versions of the questionnaire in Czech, German, Hungarian, Italian, Kroatian, Polish, Romanian and Slovakian have been prepared. The results are based on data of 1,104 adult patients. They demonstrate that the developed questionnaire is practicable. Patients need 10-15 min to answer it, usually without assistance. The proportion of missing values is for all but two questions less than 3%. The questionnaire also found high acceptance reflected by only 2.7% refusals. It is reasonably reliable in each language. Interlingual homogeneity could be shown by demonstration of strong structural similarities between the different versions using multidimensional scaling, factor analysis and comparison of mean profiles.