Survival of patients with initially unresectable colorectal liver metastases treated with FOLFOX/cetuximab or FOLFIRI/cetuximab in a multidisciplinary concept (CELIM study).

BACKGROUND: Initially, unresectable colorectal liver metastases can be resected after response to chemotherapy. While cetuximab has been shown to increase response and resection rates, the survival outcome for this conversion strategy needs further evaluation. PATIENTS AND METHODS: Patients with technically unresectable and/or ≥5 liver metastases were treated with FOLFOX/cetuximab (arm A) or FOLFIRI/cetuximab (arm B) and evaluated with regard to resectability every 2 months. Tumour response and secondary resection data have been reported previously. A final analysis of overall survival (OS) and progression-free survival (PFS) was carried out in December 2012. RESULTS: Between December 2004 and March 2008, 56 patients were randomised to arm A, 55 to arm B. The median OS was 35.7 [95% confidence interval (CI) 27.2-44.2] months [arm A: 35.8 (95% CI 28.1-43.6), arm B: 29.0 (95% CI 16.0-41.9) months, HR 1.03 (95% CI 0.66-1.61), P = 0.9]. The median PFS was 10.8 (95% CI 9.3-12.2) months [arm A: 11.2 (95% CI 7.2-15.3), arm B: 10.5 (95% CI 8.9-12.2) months, HR 1.18 (95% CI 0.79-1.74), P = 0.4]. Patients who underwent R0 resection (n = 36) achieved a better median OS [53.9 (95% CI 35.9-71.9) months] than those who did not [21.9 (95% CI 17.1-26.7) months, P < 0.001]. The median disease-free survival for R0 resected patients was 9.9 (95% CI 5.8-14.0) months, and the 5-year OS rate was 46.2% (95% CI 29.5% to 62.9%). CONCLUSIONS: This study confirms a favourable long-term survival for patients with initially sub-optimal or unresectable colorectal liver metastases who respond to conversion therapy and undergo secondary resection. Both FOLFOX/FOLFIRI plus cetuximab, appear to be appropriate regimens for 'conversion' treatment in patients with K-RAS codon 12/13/61 wild-type tumours. Thus, liver surgery can be considered curative or alternatively as an additional 'line of therapy' in those patients who are not cured. CLINICAL TRIAL NUMBER: NCT00153998, www.clinicaltrials.gov.

Impact of the adaptor protein GIPC1/Synectin on radioresistance and survival after irradiation of prostate cancer.

PURPOSE: Studies have shown that GIPC1/Synectin is an essential adaptor protein of receptors that play an important role in cancer progression and therapy resistance. This is the first study to explore the role of GIPC1/Synectin in radioresistance of prostate cancer and as a possible predictive marker for outcome of primary radiation therapy. MATERIALS AND METHODS: The effect of RNA interference-mediated GIPC1/Synectin depletion on clonogenic cell survival after irradiation with 0, 2, 4, or 6 Gy was assayed in two different GIPC1/Synectin-expressing human prostate cancer cell lines. The clinical outcome data of 358 men who underwent radiotherapy of prostate cancer with a curative intention were analyzed retrospectively. Uni- and multivariate analysis was performed of prostate-specific antigen recurrence-free survival and overall survival in correlation with protein expression in pretreatment biopsy specimens. Protein expression was evaluated by standard immunohistochemistry methods. RESULTS: In cell culture experiments, no change was detected in radiosensitivity after depletion of GIPC1/Synectin in GIPC1/Synectin-expressing prostate cancer cell lines. Furthermore, there was no correlation between GIPC1/Synectin expression in human pretreatment biopsy samples and overall or biochemical recurrence-free survival after radiotherapy in a retrospective analysis of the study cohort. CONCLUSION: Our results do not show a predictive or prognostic function of GIPC1/Synectin expression for the outcome of radiotherapy in prostate cancer. Furthermore, our in vitro results do not support a role of GIPC1 in the cellular radiation response. However, the role of GIPC1 in the progression of prostate cancer and its precursors should be subject to further research.

Outpatient costs of osteoporosis in a national health insurance population.

There are few valid data on the outpatient diagnosis and treatment of osteoporosis in Germany, despite the high prevalence of this disease and the high costs associated with its complications. We therefore conducted a retrospective cohort study to investigate the prevalence of documented osteoporosis and the use of health care resources in its outpatient treatment in a representative random sample of 7490 patients from the Dresden area who were insured under the national health insurance program for a 1-year period from the 3rd quarter of 1993 to the 2nd quarter of 1994. Documented cases of osteoporosis were identified by International Statistical Classification of Diseases, 10th Revision diagnostic codes M80 to M82, and the costs of diagnostic services for osteoporosis were calculated using a uniform fee schedule. Specific and nonspecific osteoporosis medications were classified using a published anatomic-therapeutic-chemical code, and their costs were calculated on the basis of pharmacy sales prices. Three age- and sex-matched controls without documented osteoporosis (n = 705) were assigned for each case patient in estimating the net use of resources. Data for the region, as well as age-standardized information for the overall German national health insurance system, were calculated. The 1-year prevalence of documented osteoporosis in the region was 3.14% (5.20% in women, 0.89% in men), and the age-standardized prevalence in the German national health insurance system was 2.25%. During the study period, 51.1% of the cases and 2.1% of the controls were examined by osteodensitometry. Patients received 106 defined daily doses of osteoporosis medications during the year; 37.0% of the prescribed daily doses were for sodium fluorophosphate/calcium combinations, 4.3% were for sodium fluoride, and 7.7% were for calcium alone. Sex hormones and calcitonin each accounted for 7.7% of the prescribed daily doses. Only a fraction of epidemiologically expected cases of osteoporosis have been identified and documented in the outpatient sector. Only approximately 50% of these receive osteoporosis-specific therapy, and compliance with therapy is low. To reduce osteoporosis-associated fracture rates, which are extremely cost intensive and greatly impair patients' quality of life, more consistent treatment is needed.

The prescribing of lipid lowering drugs during a 1-year period: analysis of 7490 health insurance files.

A study of prescription patterns by office-based physicians was conducted to analyse the use of lipid lowering drugs (LLD) in a Germany area of 1,768,874 inhabitants during a 1-year period. The prescription database consisted of health insurance files from a random sampling of persons (n=7490) belonging to a large statutory health insurance organization during 1993-1994. During the study period LLD were prescribed to about 2.8% of the study population. Fibrates (43.7%) were the most frequently prescribed drugs followed by HMG-CoA reductase inhibitors (29.5%) and nicotinic acid with derivatives (21.7%). The prevalence of treatment rose with increasing age peaking among 60- to 69-year-olds (7.5%). More than two-thirds of the patients were not treated continuously, receiving LLD for less than 6 months. Thus, in patients being treated with LLD, the therapy seems to be ineffective due to the short episodes of drug administration. The presence of hyperlipidaemia plus additional risk factors such as hypertension led to a higher rate of LLD prescriptions than that for hyperlipidaemia alone. Only half of the patients with a history of previous myocardial infarction and hyperlipidaemia received LLD. Furthermore, patients with hyperlipidaemia and additional risk factors such as arterial hypertension, diabetes mellitus and coronary heart disease (CHD), in whom administration of LLD has often been shown to be effective, were by far too infrequently treated with these drugs. Copyright (c) 2000 John Wiley & Sons, Ltd.

Effects of an oral health program on the occurrence of oral candidosis in a long-term care facility.

OBJECTIVES: The aim was to evaluate the effectiveness of a preventive oral health program on the prevalence of oral candidosis in 237 frail or dependent residents in a long-term care facility. Half of the residents were included in an experimental group which benefited from a preventive oral hygiene program including instruction of the carers and implementation of a recall program for professional oral hygiene care. METHODS: Intraoral examinations and yeast cultures from the oral mucosa and the fitting denture surface were carried out at baseline and 18 months later. The outgrowth of yeast was estimated on Oricult-N dip slides using the scale: no growth; 1-20 colonies; 21-100 colonies; >100 colonies. RESULTS: At baseline (n = 237) and at 18 months (n = 159) the experimental and the control groups were similar with regard to the residents' distribution by age, sex, dental and prosthetic status and prevalence of denture stomatitis. The 78 residents lost had the same baseline characteristics as the survivors, except for being older. In the experimental group the severity of the inflammation of the palate decreased (P = 0.005) as well as the prevalence of glossitis (P = 0.005). At baseline high yeast scores from the mucosa (>20) were observed in about 50% of the residents in the experimental as well as the control group. At 18 months this figure was 23.4% for the experimental and 48.7% for the control group (P = 0.001). There was also a reduction of the number of residents with positive cultures and the denture yeast scores at 18 months in the experimental group (P = 0.05). CONCLUSIONS: This study has shown that the preventive program was effective in reducing the colonization of the oral mucosa and dentures by Candida and thereby improving the health of the oral mucosa.

[The orodental situation of aged patients hospitalized at the Hôpital de Gériatrie of Geneva]. / Situation bucco-dentaire chez les patients âgés hospitalisés à l'Hôpital de Gériatrie de Genève.

The purpose of the present study was to identify the major oral and dental problems and treatment needs among 216 patients who had been consecutively hospitalized at Hôpital de Gériatrie de Genéve. The patients were interviewed and examined during the week following their hospitalization. There were 150 women (73.6%) and 57 men with a mean age of 84 years. Of these 44.4% were completely edentulous. The patients with remaining teeth had on average 11 teeth, of which 24.1% showed active caries. Active root caries was observed in 54.2% of the patients with natural teeth. Of the remaining teeth 27.4% were crowned and three quarters of these had poorly adapted margins. Removable dentures were observed in 81% of the patients. Of the complete dentures 18.5% were poorly adapted and 30.3% of the removable partial dentures were unstable. Denture stomatitis was observed among 20.5% of the denture wearers. It appears from this study that elderly patients have many oral, dental and prosthetic problems and that their treatment needs are generally important. In order to improve the situation it seems necessary to introduce dental care programs for homebound and institutionalized elderly patients.

Relationship between prosthodontic status, caries, and periodontal disease in a geriatric population.

This study evaluated the influence of prosthodontic status on caries a and periodontal disease in a hospitalized population of elderly people. Among the data gathered was information on caries, gingival condition, oral hygiene, plaque accumulation, and factors related to the prevalence, type and quality of the prostheses present. There was no significant association between the type of rehabilitation and the economic, social, or educational variables, but it appeared that removable partial denture wearers had less concern for oral health. Root caries and periodontal diseases were more frequent when the restoration, either fixed or removable, was defective. Th results of this study indicate the importance of oral hygiene instruction and regular recalls among removable partial denture wearers.

[Psychopharmaceutical prescriptions to older people. A comparison between patients in aged- and nursing homes, outpatient treatment with nursing care and outpatients without nursing care]. / Psychopharmakaverordnungen an älteren Menschen. Ein Vergleich zwischen Patienten aus Alten- und Pflegeheimen, ambulant behandelten Pflegefällen und ambulanten Patienten ohne Pflegebedarf.

To determine, whether age, sex, grade of need of care and living in nursing homes can influence prescribing behavior in elderly. In a retrospective and longitudinal study, the pattern of psychoactive drug prescriptions of nursing home residents was compared with non-institutionalized people with and without need of care. During 1999, the computerized files of 3592 people (> 60 years), insured by a health insurance fund (BKK) in Berlin, Germany, were obtained. Nursing home residents received significantly more prescriptions of psychoactive drugs than the others, especially more neuroleptics (40.1% versus 12.4% and 7.4%). Quality of prescriptions seemed to be higher in nursing homes (use of drugs with fewer side effects and less possible interactions), psychoactive drug prescriptions were given more frequently by psychiatrists and neurologists (37%). Non-institutionalized patients received them most from general practitioners (45%). Women received more prescriptions of psychoactive drugs than male patients. With rising grade of need of care, proportionately more patients received psychoactive drugs. The results of this study show some evidence of the lacking quality in the prescriptions of psychopharmaceuticals to the elderly.

Effects of an oral health program on selected clinical parameters and salivary bacteria in a long-term care facility.

The aim of this study was to evaluate clinically and microbiologically the effects of a preventive oral health program in a long-term care facility. A total of 116 dentate elderly residents agreed to participate, and half of them were included in an experimental group. Almost all of the residents were mentally or physically handicapped, and many were dependent on care-givers for daily living activities. Oral examination and microbiological sampling were performed at baseline and 18 months later. The experimental group benefited from a preventive program, including an oral hygiene course for the health care providers and regular recalls by dental hygienists of the residents. After 18 months, the plaque indices were statistically similar to those at baseline in both groups. Mutans streptococci counts and active root caries at 18 months were lower compared to baseline in the experimental group but did not change significantly in the control group. Thus, it seems that, while the preventive program failed to decrease plaque indices, it was effective in reducing mutans streptococci colonisation and caries prevalence.

Pattern of prescriptions issued by nursing home-based physicians versus office-based physicians for frail elderly patients in German nursing homes.

PURPOSE: The purpose of this study was to describe the physician prescription pattern for frail elderly patients in German nursing homes and to identify differences, if any, between that of physicians based in the nursing homes (A) and those with office-based practices (B). METHODS: Retrospective, longitudinal study of medication prescriptions on the basis of the database of a health insurance (Betriebskrankenkasse) in Berlin, Germany. We assessed the medication prescriptions for all 996 unselected insured individuals aged > or = 60 years who were insured throughout 1999 and lived in nursing homes. We analyzed selected patient characteristics and prescription data. Drugs were classified according to the WHO ATC code and were assigned a mean daily defined dose (DDD). RESULTS: 816 individuals were women and 180 were men. A total of 78% of women and 43% of men were aged 80 years or older. Two hundred sixty three patients were seen by nursing home-based physicians (A) and 733 by office-based physicians (B). The median of prescriptions per patient and year was 31 (A) and 37 (B) (p between groups < 0.001). Patients in Group A also received a lower number of DDDs in comparison to Group B (1109 vs 1250; p < 0.01). Costs were substantially higher in group B, and in both groups higher in the 60-69 years old in comparison to the more senior patients. The prescription pattern suggested a considerable frequency of inappropriate drug use in both groups in the following classes: psychopharmacological agents (neuroleptics, antidepressants, hypnotics), pain medication, digitalis glycosides, laxants and loop diuretics. On an average, office-based physicians (B) prescribed relatively more medications in all major classes with the exception of non-opiate analgesics, laxants and anxiolytics. CONCLUSIONS: These data are indicative of a considerable use of inappropriate medication for frail geriatric patients. Differences between the prescribing pattern among nursing home-based and office-based physicians were not substantial, however, the latter group prescribed relatively more drugs.

Caries prevalence and associated predisposing conditions in recently hospitalized elderly persons.

The prevalence of caries and caries risk factors was studied among 120 consecutively hospitalized elderly persons. Coronal caries was recorded using the WHO criteria, and active and inactive root caries in accordance with Fejerskov et al. The CPITN was used to evaluate the periodontal state and plaque accumulation in accordance with Löe & Silness. Of the 1212 teeth examined 5% had active coronal caries (2% inactive), 14% active root caries (2% inactive), and 10% fillings with recurrent caries. No relationship was found between caries prevalence, degree of dependence, number of medicaments, age, and gender. Patients with psychiatric diseases had increased caries prevalence (P < 0.01), and lower caries prevalence was associated with frequent tooth brushing (P < 0.05). At the tooth level root caries was associated with high plaque scores (P < 0.001), degree of gingival recession (P < 0.001), presence of coronal caries (P < 0.001), and increased pocket depth (P < 0.01). The results strongly indicate that oral hygiene measures should be introduced immediately after hospitalization of these patients.

[Validity of diagnoses of mental disorders by primary care physicians]. / Validität von Krankenscheindiagnosen psychischer Störungen.

BACKGROUND AND OBJECTIVE: Even in young adult age, psychological disorders are highly prevalent. Family doctors and gynaecologists are the physicians most often consulted by young women. Hence, they have a special responsibility to diagnose psychiatric disorders and--if necessary--to refer to a specialist. PATIENTS AND METHODS: In a prospective epidemiological study, 342 young women (between 18 and 25 years of age) were questioned two times with a structured interview (F-DIPS) designed for mental disorders. In the time period (1997 and 1998), we also investigated, by analysing personal health insurance data, primary-care physicians' diagnoses and payments for services rendered. The diagnoses were compared. RESULTS: There was only a small accordance between F-DIPS and claimcards. Ambulant treating doctors diagnosed somatoform disorders in 28 % of the young women (F-DIPS: 3, 8 %). The F- DIPS found mostly phobic disorders (29 %) (claimcards: 6,1 %). A disorder-specific therapy was only rarely initiated. The treatment (psychotherapy and/or drug therapy) of women with psychiatric disorders appeared to be insufficient. CONCLUSION: The study indicates that primary-care physicians should be urgently trained in psychiatric diagnostics und therapy.