Impact of Prosigna test on adjuvant treatment decision in lymph node-negative early breast cancer-a prospective national multicentre study (EMIT-1).

BACKGROUND: EMIT-1 is a national, observational, single-arm trial designed to assess the value of the Prosigna, Prediction Analysis of Microarray using the 50 gene classifier (PAM50)/Risk of Recurrence (ROR), test as a routine diagnostic tool, examining its impact on adjuvant treatment decisions, clinical outcomes, side-effects and cost-effectiveness. Here we present the impact on treatment decisions. PATIENTS AND METHODS: Patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative pT1-pT2 lymph node-negative early breast cancer (EBC) were included. The Prosigna test and standard histopathology assessments were carried out. Clinicians' treatment decisions were recorded before (pre-Prosigna) and after (post-Prosigna) the Prosigna test results were disclosed. RESULTS: Of 2217 patients included, 2178 had conclusive Prosigna results. The pre-Prosigna treatment decisions were: no systemic treatment (NT) in 27% of patients, endocrine treatment alone (ET) in 38% and chemotherapy (CT) followed by ET (CT + ET) in 35%. Post-Prosigna treatment decisions were 25% NT, 51% ET and 24% CT + ET, respectively. Adjuvant treatment changed in 28% of patients, including 21% change in CT use. Among patients assigned to CT + ET pre-Prosigna, 45% were de-escalated to ET post-Prosigna. Of patients assigned to ET, 12% were escalated to CT + ET and 8% were de-escalated to NT; of those assigned to NT, 18% were escalated to ET/CT + ET. CT was more frequently recommended for patients aged ≤50 years. In the subgroup with pT1c-pT2 G2 and intermediate Ki67 (0.5-1.5× local laboratory median Ki67 score), the pre-Prosigna CT treatment decision varied widely across hospitals (3%-51%). Post-Prosigna, the variability of CT use was markedly reduced (8%-24%). The correlation between Ki67 and ROR score within this subgroup was poor (r = 0.25-0.39). The median ROR score increased by increasing histological grade, but the ROR score ranges were wide (for G1 0-79, G2 0-90, G3 16-94). CONCLUSION: The Prosigna test result changed adjuvant treatment decisions in all EBC clinical risk groups, markedly decreased the CT use for patients categorized as higher clinical risk pre-Prosigna and reduced treatment decision discrepancies between hospitals.

CIN 2/3 and cervical cancer in an organised screening programme after an unsatisfactory or a normal Pap smear: a seven-year prospective study of the Norwegian population-based screening programme.

OBJECTIVES: To estimate the risk of cervical intraepithelial neoplasia (CIN) 2/3 and invasive cervical cancer (ICC) in an organised screening programme after an unsatisfactory or a normal Pap smear. SETTING: A seven-year prospective cohort study of the Norwegian population-based co-ordinated screening programme based on the actual diagnostic and screening procedures performed. Observations of 526,661 women with a normal index Pap smear and 21,405 women with an unsatisfactory index Pap smear were made during 3.26 million women-years. METHODS: The risk of being diagnosed with CIN 2/3 or ICC was calculated by logistic regression for the first two years of follow-up. The hazard of being diagnosed with CIN 2/3 or ICC for the women who were not diagnosed during the two first years was estimated by non-parametrical survival regression. RESULTS: After two years of follow-up, 0.2% of the women were diagnosed with CIN 2/3 and 0.01% with ICC after a normal Pap smear. An unsatisfactory Pap smear indicated a 1.6-4.0 times higher risk of harbouring a CIN 2/3 or ICC compared to women with a normal Pap smear. No increased risk of ICC was found during long-term follow-up for the 70% of the women with an unsatisfactory Pap smear who were returned to ordinary screening. Prior series of low-grade Pap smears followed by a normal Pap were associated with an increased risk of CIN 2/3 and ICC. CONCLUSIONS: An unsatisfactory Pap smear indicates a risk of harbouring CIN II/III or ICC. Repeated Pap smears are adequate as a follow-up of an unsatisfactory Pap smear. Women with repeated series of equivocal/LSIL Pap smears followed by a normal Pap should be considered at high risk.

The cervical cancer screening programme in Norway, 1992-2000: changes in Pap smear coverage and incidence of cervical cancer.

OBJECTIVES: Changes in the incidence of cervical cancer were studied to assess the impact of the Norwegian coordinated cervical cancer screening programme introduced in 1995. Attention was given as to whether recommendation letters sent to women without a screen in the previous 3 years could be an alternative to a conventional screening programme that invites women irrespectively of their spontaneous screening. SETTING: A population based, nationwide, screening programme in which women of 25 to 69 are recommended to have a conventional Pap smear every 3 years. METHODS: The impact of the screening programme was assessed indirectly by comparing trends in invasive cervical cancer, changes in coverage, and changes in interval between Pap smears in the 3 year period (1992-4) before screening with the two first screening rounds (1995-7 and 1998-2000). All Pap smears taken from women of all ages were included, a total of 4 744 967 Pap smears from more than 1.4 million women. Further, the impact was assessed directly by logistic regression by comparing the screening results of women recruited for the programme with women who had regularly had Pap smears. RESULTS: In the last 2 years studied, the incidence of invasive cancer was 22% lower than in the period before the programme. The proportion of women who had a Pap smear was higher after the implementation of the coordinated screening programme. The number of smears taken was less as the interval after a normal smear was greater. The newly recruited women had a threefold risk of having a high grade precursor and a 20-fold higher risk of cancer than the women who had had regular smears. CONCLUSIONS: The coordinated screening programme provides a low cost way of increasing the coverage of the female population, and consequently has reduced the rate of invasive cervical cancer.

Work ability and duration of certified sickness absence.

AIMS: The aim of this study was to examine the association between assessed work ability and the duration of certified sickness absence. METHODS: A total of 549 patients and 52 doctors provided questionnaire data about 549 episodes of absence. The episodes were classified as new, one month, or three months according to their duration at the time of questionnaire completion. Their duration after that was used as outcome. Uni-and multivariate Cox regression analyses were performed. RESULTS: In the multivariate analyses, a "very much reduced" work ability assessed by patients was associated with a longer duration than a "moderately reduced" work ability, in both one- and three-month episodes. Musculoskeletal and psychological disorders were associated with a longer duration, and respiratory disorders with a shorter duration than other disorders in new episodes. Patient age above 50 years was associated with a longer duration than lower age in new and three-month episodes. The doctors' use of referral and tests in the consultations, and the presence of non-medical factors as judged by the patients, were associated with a longer duration than the absence of those factors in new episodes. The patients' degree of job satisfaction, and non-medical factors as judged by doctors. were significantly associated with duration only in univariate Cox regression analyses in new episodes. Work demands were not significantly associated with duration in any of the analyses. CONCLUSIONS: Work ability assessed by patients may be a useful prognostic indicator of duration in prolonged episodes of certified sickness absence. Further studies using other outcomes, such as disability pensioning, would be of interest to enlighten the concepts of work ability.

Sickness absence with psychiatric disorders--an increased risk for marginalisation among men?

BACKGROUND: Sickness absence with psychiatric disorders is a major public health problem with serious consequences for the individual, the employer and society. The aim was to assess the occurrence of psychiatric sickness absence with special focus on sex differences. METHODS: A nationwide sickness insurance register was used. Population at risk was defined as all individuals entitled to sickness benefits in 1994 (N = 1,978,030). Those who were sick-listed for more than 14 consecutive days with a psychiatric diagnosis (n = 28,799) were selected as cases. RESULTS: Of the population under study, 1.46% had at least one psychiatric sickness absence episode. Women had twice the male cumulative incidence of sickness absence for a psychiatric diagnosis. Cumulative incidence was highest among those aged 45-59 years. Men had more sickness absence days. Depression was the most common diagnosis among both women and men. CONCLUSION: Increased efforts are needed to recognise, treat and rehabilitate individuals with a lowered work capacity due to sickness absence. The increased risk of long sick-leave spells among men needs further attention.

Work ability assessed by patients and their GPs in new episodes of sickness certification.

BACKGROUND: Sickness certification legislation demands that work ability is reduced due to disease or injury. Most sickness certificates are issued by GPs. Assessment of work ability might introduce conflict in the doctor-patient relationship. OBJECTIVES: The aim of this study was to compare the level of work ability assessments by patients and their GPs in new episodes of sickness certification, and to explore how medical conditions and work demands are associated with the assessments. METHODS: Forty nine GPs supplied data about 408 patients certified sick <8 days before questionnaires were filled in. A total of 268 (66%) patients completed corresponding questionnaires. Patients and GPs independently answered the following question using a five-point scale: "To what degree is your (the patient's) ability to perform your (his or her) ordinary, remunerative work reduced today?" RESULTS: Work ability was assessed by patients as very much or much reduced in 66%, moderately reduced in 23% and not much or hardly reduced at all in 11% of the cases. Corresponding assessments made by GPs were 71, 27 and 2%. Patients and GPs agreed well on their assessments (+/- 1 answer category) in 81% (216/266) of the cases. The patients assessed work ability as more reduced the more stressful or physically strenuous their jobs were, and the older their GPs were. The GPs assessed work ability as more reduced the more their assessments were based on clinical findings. CONCLUSIONS: The agreement between work ability assessments made by patients and GPs was high, despite patients' assessments being associated with work demands and GPs' with medical conditions.

Relation between health problems and sickness absence: gender and age differences--a comparison of low-back pain, psychiatric disorders, and injuries.

Women have higher long-term sickness absence rates than men, and higher rates of most health problems. The rates vary with type of problem and diagnosis. The objectives were to examine whether equal proportions of women and men had sickness absence when they had a given health problem, and if disparities were diagnosis specific. Prevalence of low-back pain, psychiatric disorders, and injuries was assessed in random samples of two populations in Norway. Prevalence of long-term sickness absence for the same diagnostic categories was estimated for the same time period (1990). For injuries, the prevalence ratios between a health problem and a sickness absence were equal for women and men. For psychiatric health problems, there were 1.7 more women than men behind each sickness absence. Low-back pain showed an intermediate gender ratio of 1.3, indicating that also for this condition women tended to have less sickness absence. Musculoskeletal and psychiatric health problems (fluctuating, chronic) may result in more gender-biased, subjective, and random assessment of work ability than injuries (acute health problem).

Prevalence, incidence and age at onset of psychiatric disorders in Norway.

BACKGROUND: Increased demands for psychiatric services and increased rates of sickness absence for depression have raised the question of the occurrence of psychiatric disorders in Norway, and whether there is in fact a rising incidence rate. METHODS: Between 1989-1991, 2015 and 617 persons participated in a two-phase population study. Phase I comprised screening by the Hopkins Symptom Check List 25 items (HSCL-25), and phase II a diagnostic interview by the Composite International Diagnostic Interview (CIDI), including report of date (year) of the first occurrence of any symptoms, and any consequent diagnosis: RESULTS: A symptom score of 1.75 or more was found in 19.8% of the women and 9.3% of the men by the HSCL-25. Depression, anxiety or somatoform disorder by CIDI was found in 21.5% of the women and 11.5% of the men. The incidence rate increased significantly from 3.3 to 12.8 per 1000 person years from 1930 to 1991. The incidence rate in the year before the interview was 42.6 per 1000 person years. Age of onset became lower. More women became ill, but the illness seemed to last longer in men. A major problem in comparing results between studies is the different concepts and operationalisations of psychiatric illness, and the varying time periods given for estimates. CONCLUSION: The findings provide evidence of psychiatric illness being a rising and major health problem, but the role of recall bias must be further investigated.

The gender gap in musculoskeletal-related long-term sickness absence in Norway.

OBJECTIVE: To examine the gender differences in long-term (> 14 days) sickness absence due to musculoskeletal health problems. DESIGN: Analysis of data from the National Sickness Benefit Register, 1994. SETTING: The economically active population in Norway, except civil servants (n = 1,978,030). SUBJECTS: All persons, 16-66 years old, with long-term sickness absence episodes due to musculoskeletal health problems in 1994 (n = 141,839). MAIN OUTCOME MEASURES: Cumulative incidence, episode frequency, and episode duration of sickness absence. RESULTS: Women had higher cumulative incidence of sickness absence than men-80.6 pr 1,000 vs. 64.1 pr 1,000, and longer mean duration of episodes-94 calendar days vs. 86 days counted from the first day of absence. Episode frequency did not differ between the genders. After adjustment for age and income the gender ratio (men/women) in cumulative incidence changed from 0.80 to 1.08, and in mean duration from 0.91 to 0.96. CONCLUSION: Long-term sickness absence due to musculoskeletal health problems was strongly associated with gender, age, income, and diagnosis. Multivariate analysis indicated that the large gender differences in sickness absence might be overstated due to lack of adjustment for income and income-related factors.

[Occupational injuries and prolonged sick listings during the period 1989-93]. / Yrkesskader og langtidssykmeldinger i perioden 1989-93.

Norway lacks reliable data on the magnitude and development of occupational injuries. Each year about 25,000 occupational injuries and 2,000 occupational diseases are reported to the Labour Inspection. These constitute only one-third of all expected injuries and accidents related to the work environment. The aim of this study was to estimate the magnitude of occupational injuries in Norway causing long-term certification of illness. There was a 35% reduction in the incidence of occupational injuries in Norway from 1990 to 1993. The reduction applies to men and women combined, all age groups and most counties. The distribution of characteristics by age, sex, diagnosis and place of residence corresponds well with previous, limited studies. Injuries, especially fractures, account for approximately 70 per cent of the occupational injuries. Possible explanations for the decrease in incidence could be preventive efforts, a tighter labour market, a change from primary and secondary to tertiary industry, and the overall reduction in long-term certification of illness in Norway from 1990 to 1993.

ICPC as a standard classification in Norway.

BACKGROUND: The International Classification for Primary Care (ICPC) has been the standard classification for diagnoses on sickness certificates and bills for services to the National Insurance Administration in Norway since 1992. Coding according to ICPC is compulsory for all general practitioners. OBJECTIVE: The objective of the present study was to describe the introduction of ICPC in Norway, to comment on introduction problems, and to examine the compliance and validity of coding. METHODS: The study was based on statistics for episodes of sickness certification in the National Benefit Absence Register. RESULTS: In 1994, the underlying medical diagnosis was coded in 98% of the sickness absence episodes lasting more than 2 weeks. Component 1 codes (symptom codes) were used in 23% of episodes, compared with 26-31% in practice studies. CONCLUSIONS: ICPC-coded data in a large Norwegian register appear promising. Most doctors do accurate and careful work in coding, and data appear to be of acceptable quality for further analysis. It is a matter of concern, however, that as many as 23% of episodes had component 1 codes, since these certificates were issued during follow-up encounters. The introduction of ICPC coding has enabled researchers to use diagnoses in the analyses of sickness absence. The growing use of ICPC in general practice has made multi-practice studies possible. The introduction of criteria is mandatory for the improvement of validity in diagnostic coding.

[Unemployed patients in 60 family practices]. / Arbeidsløse pasienter i 60 allmennpraksiser.

In a one week registration of consultations by 60 general practitioners, 7% (95% confidence interval 6-8%) of all patients aged 16 to 66 were registered as unemployed. This was 145% of the mean unemployment rates in the municipalities where the doctors practiced. The age and gender composition of the unemployed patients was the same as for all registered unemployed. Psychiatric diagnoses were nearly twice as prevalent among the patients. A fifth of the unemployed patients attended for illnesses and conditions which seemed to relate to the unemployment. Most of them had somatic or mental disorders which probably were caused or worsened by lack of paid work. A few needed to discuss social insurance issues. The study did not support the idea that general practitioners medicalize unemployment problems, but provided no decisive evidence on this complicated question, which will be elaborated further during the next stage of the study.

[Patients who are in danger of being dropped from the labour-market. A study from family practice]. / Pasienter som står i fare for å falle ut av arbeidslivet. Undersøkelse fra allmennpraksis.

During one week, 60 general practitioners in different parts of Norway registered those of their patients whom they believed were in danger of falling out of the labour market. Patients who risked losing their job completely constituted 12% (95% confidence interval 10-14%) of all patients aged 16-66 years. The fear of possible permanent lack of employment arose in connection with plans for a disability pension in 39% of the patients, vocational rehabilitation in 18%, current unemployment in 18% and long-term sickness certification in 16%. The doctors considered a disability pension in the case of only a quarter of the patients, while more patients, one third, had plans to apply for one. The doctors did not seem to act as promoters of early retirement. On the contrary, they often recommended vocational rehabilitation, even though earlier studies have shown that doctors are generally pessimistic about the chances of success in present day Norway. If the Government wants the doctors' help in promoting its policy of employment rather than social security benefit it will have to take practical steps to support their efforts to encourage vocational rehabilitation.

[ICPC diagnoses in 60 offices of general practitioners]. / ICPC-diagnoser i 60 allmennpraksiser.

The new classification system ICPC was used by 60 general practitioners to record consulting room encounters during one week. The study focused on unemployed and marginalized patients, and provided experience in the use of ICPC shortly after the system was made mandatory by National Insurance Administration. One to five months afterwards, 85% of the GPs used ICPC fully and 10% to some extent. We had no problems in coding the remaining text diagnoses, nor in recoding to the chapters of the diagnostic system ICHPPC. A quarter of the main diagnoses concerned the component of symptoms. Within the problematic chapters of psychiatric and musculosceletal illnesses, the doctors applied diagnoses of symptoms and diseases to very varying degrees. ICPC makes it possible to exclude gender-related causes for the consultation. Consequently, the gender differences in the distribution of components and chapters virtually disappeared. The female surplus among the patients was reduced to 10%, of which 6.5% can be attributed to the larger share of women among the elderly. Thus, ICPC seems to be a useful tool in epidemiology.