RELAY, ramucirumab plus erlotinib versus placebo plus erlotinib in patients with untreated, EGFR-mutated, metastatic non-small cell lung cancer: Europe/United States subset analysis.

BACKGROUND: In EGFR mutation-positive NSCLC, dual EGFR/VEGFR inhibition compared to EGFR alone increases anti-tumor efficacy. The Phase III RELAY trial demonstrated superior PFS for ramucirumab plus erlotinib (RAM + ERL) over placebo plus erlotinib (PBO + ERL) (HR 0.591 [95% CI 0.461-0.760], p<0.0001). EGFR mutated NSCLC is less prevalent in Western versus Asian patients. This prespecified analysis evaluates efficacy and safety of RAM + ERL in EU and US patients enrolled in RELAY. PATIENTS AND METHODS: Patients were randomized 1:1 to ERL + RAM (10 mg/kg IV) or PBO Q2W. Treatment continued until unacceptable toxicity or progressive disease. Patients were stratified by geographic region (East Asia vs "other" [EU/US and Canada (EU/US)]). Objectives included PFS, ORR, DoR, OS, PFS2, safety and biomarker analysis. RESULTS: EU/US subset included 113/449 (25.9%) patients (58 RAM + ERL, 55 PBO + ERL). RAM + ERL improved PFS (20.6 vs 10.9 months, HR 0.605 [95% CI: 0.362-1.010]). ORR and DCR were similar, but median DoR was longer with RAM + ERL (18.0 vs 10.1 months, HR 0.527 [95% CI: 0.296-0.939]). OS and PFS2 were immature at data cut-off (censoring rates 81.0-81.8% and 67.3-79.3%, respectively). Most commonly reported Grade ≥3 TEAE for RAM + ERL was hypertension (17 [29.8%]) and for PBO + ERL, dermatitis acneiform (5 [9.1%]). CONCLUSION: EU/US subset analysis showed improved efficacy outcomes for RAM + ERL and a safety profile consistent with the overall population. Ramucirumab is a safe and effective addition to standard-of-care EGFR-TKI for EGFR mutation-positive metastatic NSCLC.

Classification of accidents in the Arctic. A suggestion for adaptation of the Nordic classification for accident monitoring.

Since 1980 the Nordic Medico-Statistical Committee (NOMESCO) has supported the development of the Classification for Accident Monitoring. The objective of the Classification is to provide the foundation for accident prevention. In agreement with the purpose of NOMESCO to establish comparable medical statistics in the Nordic countries, it is considered how the Nordic Classification might be adapted to conditions in Arctic areas, in order also to facilitate accident prevention in these areas. The Classification is multiaxial and describes place of occurrence, injury mechanism, activity (of victim), products involved in accidents, and information of special relevance to traffic accidents and occupational accidents. The hierarchical build-up of the coding system allows subspecification of the variables mentioned above, thus enabling the system to contain such information which is suggested for Arctic areas, and at the same time preserving the comparability of data at an aggregated level. Further development is suggested in a plan of work.

[Diagnosis and treatment in general practice. 5. Attitudes of general practitioners--a review]. / Diagnostik og behandling i almen praksis. 5. Praktiserende laegers holdninger--en oversigt.

The word "attitude" means continuing orientation of the individual towards the world. Attitudes consist of cognitive beliefs and affective reactions, which predispose the individual towards certain action patterns and which have emotional (positive/negative) value. Doctors' attitudes are developed by the joint influences of selection and socialization. Doctors are predominantly recruited from the middle classes and are therefore characterized by middle class attitudes, valuing hard work, activity, self-discipline and rationality. The curriculum of medical school has a further and independent influence on the personalities of physicians-to-be, shaping their attitudes towards patients and medical work. This study gives a review of the official professional ideology of general practitioners (GP's) which, in some respects, differs from the ideology of other doctors. The basic issues, according to general practitioners' commission reports, textbooks, and research can be subdivided into four main principles: 1. A holistic model of disease, 2. The GP as a family doctor (a continuous and personal doctor-patient relationship), 3. The GP as a "gate-keeper" (the central referring role), 4. General practice as a "free enterprise". The two first principles deal with the substance of the GP's work and they stress holism, continuity and dialogue. The two last principles on the other hand deal with the structure of GP's work, stressing freedom and power. Thus general practitioners' ideology and attitudes serve to emphasize differences between hospital medicine and general practice. Differentiation between GP roles and roles of their psycho-social co-workers in the primary health care is not equally marked. Demarcation of general practice ideology in this respect is needed.

[Diagnosis and treatment in general practice. I. The course of illness in primary health service]. / Diagnostik og behandling i almen praksis. 1. Forløbsundersøgelser i den primaere sundhedstjeneste.

The purpose of this review is to present an outline of the use of the unifying concepts of "episodes of medical care" and "episodes of illness" in recent research. The review focuses on theoretical and methodical problems connected with the use of these concepts in research related to general practice. The concept of "episodes of medical care" has been accepted as a valid and useful method of clustering discrete units of services into cohesive entities in previous literature. The concept of "episodes of illness" is, on the other hand, not yet fully defined and further development of this concept is suggested in the paper. The major methodical problem in connection with the use of these concepts is how to define when an episode starts and ends. Three typical examples on how research workers have dealt with this problem are presented and the consequences their choice of definitions have on the results from such studies are outlined. The concept of "episodes of medical care" has hitherto been used mostly in various utilization and morbidity studies in the primary health care sector and psychiatry. In the last decade the concept has also been used especially in American research in connection with studies focussing on the performance of medical care systems. The concept of "episodes of illness" has only been used in connection with relatively few population studies.

[Diagnosis and treatment in general practice. 2. Episodes of medical care of health problems during a period of 3 months]. / Diagnostik og behandling i almen praksis. 2. Kontaktforløb af helbredsproblemer over 3 måneder.

The object of this article is to describe the working process in general practice. One hundred general practices were selected at random in the County of Copenhagen. Fifty-five general practices participated and registered the contacts during the period 13.9.1982 and the next three months for a random sample of group I patients from the low income group of the Danish Health Insurance and born on the 13th of a month. Where each contact is concerned, the individual health problems were registered together with the form of contact, the reason for contact, the wishes of the patient and the doctor's actions and also the diagnosis. Thirty-six % of the low income insurance group men and 37% of the women had at least one contact with general practice in the course of the three-month period. Seventy-nine episodes of medical care per 100 persons were found in a period of investigation of three months and women had nearly twice as many episodes of medical care as the men. In 59% of the episodes of medical care, the patients had at least one symptom. In 22% of the episodes of medical care, the patients were referred to other persons or instances. In 73% of the episodes of medical care, the general practitioner established the final diagnosis.

[Diagnosis and treatment in general practice. 3. Reasons for contact and diagnoses in episodes of medical care]. / Diagnostik og behandling i almen praksis. 3. Kontaktårsager og diagnoser ved kontaktforløb i almen praksis.

The object of this article is to describe the reasons for contact and the diagnoses in general practice by following the course of health problems in a random sample of patients (group 1 in the National Health Insurance System) for three months. In 55 general practices in the County of Copenhagen, all contacts concerning a given health problem in the single individuals were registered. This totalled 1,974 episodes of medical care in approximately 1,200 persons who formed 47% of the random sample. This investigation assessed the various classifications of reasons for encounter with primary health care as regards employability for central coding, information value and agreement with the general medical disease model. Employing the Reason for Visit Classification (USA) supplemented by classifications elaborated by the authors, three dimensions of the concept of "reasons for encounter" could be described: symptoms, the patient's wishes for contact with the doctor and reasons for the current problem. Health problems are described as episodes of one or more contacts. In single-contact episodes, the symptoms and diagnoses are most frequently those of respiratory diseases whereas multi-contact episodes are most frequently found where musculo-skeletal diseases are concerned. It is concluded that a multi-dimensional description of the reasons for contact and a description of the disease pattern on the basis of episodes of medical care can provide more differentiated knowledge about health problems in general practice.

[Diagnosis and treatment in general practice. 4. General practitioners' knowledge of their patients]. / Diagnostik og behandling i almen praksis. 4. Praktiserende laegers kendskab til deres patienter.

The object of this work is to describe aspects of general practitioners' knowledge of their patients and to analyse the connection between this knowledge and certain activities involving the patients in the practice (examination in the practice, prescription of medicine, information and referral). Fifty-five practices with a clientele of 81,600 patients in the lower income group of the Danish National Health Insurance over the age of 15 years participated. A random sample of 1/30 of the insured persons were characterized by the practice prior to a period of observation of three months on the basis of the doctors' knowledge of the persons. During the period of observation, all practice-patient contacts were registered. The characteristics of the patients included: curation of attachment to the practice, degree of knowledge, previous problems etc. Contact data included information about diagnoses, symptoms, patient's wishes, prescriptions, referrals, information given and examinations in the practice. During the three months, a total of 1,974 episodes of medical care occurred. We did not find any connection between the duration of knowledge (as a measure of knowledge) and the number of abovementioned activities in the practice. This investigation, however, cannot exclude such a connection. Information is still required to illustrate the significance of the knowledge of the patients for the solution of their problems and, in particular, for the course of their health problems.

[Diagnosis and treatment in general practice. 6. Attitudes of general practitioners--a study in Copenhagen County]. / Diagnostik og behandling i almen praksis. 6. Praktiserende laegers holdninger--en undersøgelse fra Københavns Amt.

We assume that general practitioners' (GPs) attitudes have considerable significance for their daily work, partly because the "free enterprise" structure permits GPs a fair degree of work autonomy, partly because several studies point to notable variations in GP behaviour which have not been explained by other variables. General practitioners seem to have developed an official professional ideology which differs in some respects from the ideology of other doctors. The core issues of Danish GP ideology, according to commission reports, textbooks and research can be summarized into four main principles: 1. A holistic (bio-psycho-social) model of disease, 2. The GP as a family doctor, 3. The GP as a "gate-keeper" (the central referral role) and 4. General practice as a "free enterprise". We mailed attitude questionnaires to a random sample of 100 practices in the county of Copenhagen. The purpose of the study was to establish the extent to which GPs would agree to the above ideology, and also to look for systematic differences between groups of doctors. The response rate was 76%. We found overall agreement to the family doctor principle among GPs which is in accordance with earlier studies. Attitudes to the "free enterprise" principle of practice organization were favorable in a similarly homogeneous way, and a significant minority favored even further liberalization. Disagreements were more pronounced concerning the holistic (bio-psychosocial) model of disease. Just over half of respondents adhered fully to the model, but doctors from high-income areas were significantly less enthusiastic than other doctors about the model. Similarly, most general practitioners favored the "gate-keeper" role.(ABSTRACT TRUNCATED AT 250 WORDS)

[Diagnosis and treatment in general practice. Referral courses over a period of 1 year]. / Diagnostik og behandling i almen praksis. Kontaktforløb af helbredsproblemer over 1 år.

This study examined episodes of medical care in five practices, representing a number of municipalities in The Copenhagen County. For comparison of results, data from a similar survey from a 55 practices' study by Hollnagel et al were also used. In these two surveys all encounters were recorded, over period of one year and three months, respectively, each time a health problem or condition was presented to the general practitioner following a personal, telephone or written contact between the patient, or other person representing the patient, and physician. The study population analyzed here consists of 189 and 2,293 adults respectively, who were all registered as group 1 members of the Danish National Health Care system. The date and nature of each contact were registered, including information of the date of any previous contact concerning the same health problem, so that the contacts could be chronicled into episodes of medical care. In addition, detailed data concerning encounter form, reason for encounter, patient's expressed whished to obtain specific services, general practitioners treatment including referrals, and diagnosis were recorded. Compared with the study covering a period of three months, the data covering a period of one year include episodes which represent a larger fraction of the study population in all age groups, 85-95% compared with 55-68%. Similarly a greater number of contacts in the episodes with a total of more than one contact are recorded over a period of one year especially concerning the episodes in the age group 45-64 years of age and the group over 65 years.