Treatment response of colorectal cancer liver metastases to neoadjuvant or conversion therapy: a prospective multicentre follow-up study using MRI, diffusion-weighted imaging and 1H-MR spectroscopy compared with histology (subgroup in the RAXO trial).

BACKGROUND: Colorectal cancer liver metastases respond to chemotherapy and targeted agents not only by shrinking, but also by morphologic and metabolic changes. The aim of this study was to evaluate the value of advanced magnetic resonance imaging (MRI) methods in predicting treatment response and survival. PATIENTS AND METHODS: We investigated contrast-enhanced MRI, apparent diffusion coefficient (ADC) in diffusion-weighted imaging and 1H-magnetic resonance spectroscopy (1H-MRS) in detecting early morphologic and metabolic changes in borderline or resectable liver metastases, as a response to first-line neoadjuvant or conversion therapy in a prospective substudy of the RAXO trial (NCT01531621, EudraCT2011-003158-24). MRI findings were compared with histology of resected liver metastases and Kaplan-Meier estimates of overall survival (OS). RESULTS: In 2012-2018, 52 patients at four Finnish university hospitals were recruited. Forty-seven patients received neoadjuvant or conversion chemotherapy and 40 liver resections were carried out. Low ADC values (below median) of the representative liver metastases, at baseline and after systemic therapy, were associated with partial response according to RECIST criteria, but not with morphologic MRI changes or histology. Decreasing ADC values following systemic therapy were associated with improved OS compared to unchanged or increasing ADC, both in the liver resected subgroup (5-year OS rate 100% and 34%, respectively, P = 0.022) and systemic therapy subgroup (5-year OS rate 62% and 23%, P = 0.049). 1H-MRS revealed steatohepatosis induced by systemic therapy. CONCLUSIONS: Low ADC values at baseline or during systemic therapy were associated with treatment response by RECIST but not with histology, morphologic or detectable metabolic changes. A decreasing ADC during systemic therapy is associated with improved OS both in all patients receiving systemic therapy and in the resected subgroup.

Centralized repeated resectability assessment of patients with colorectal liver metastases during first-line treatment: prospective study.

BACKGROUND: Metastasectomy is probably underused in metastatic colorectal cancer. The aim of this study was to investigate the effect of centralized repeated assessment on resectability rate of liver metastases. METHODS: The prospective RAXO study was a nationwide study in Finland. Patients with treatable metastatic colorectal cancer at any site were eligible. This planned substudy included patients with baseline liver metastases between 2012 and 2018. Resectability was reassessed by the multidisciplinary team at Helsinki tertiary referral centre upfront and twice during first-line systemic therapy. Outcomes were resectability rates, management changes, and survival. RESULTS: Of 812 patients included, 301 (37.1 per cent) had liver-only metastases. Of these, tumours were categorized as upfront resectable in 161 (53.5 per cent), and became amenable to surgery during systemic treatment in 63 (20.9 per cent). Some 207 patients (68.7 per cent) eventually underwent liver resection or ablation. At baseline, a discrepancy in resectability between central and local judgement was noted for 102 patients (33.9 per cent). Median disease-free survival (DFS) after first resection was 20 months and overall survival (OS) 79 months. Median OS after diagnosis of metastatic colorectal cancer was 80, 32, and 21 months in R0-1 resection, R2/ablation, and non-resected groups, and 5-year OS rates were 68, 37, and 9 per cent, respectively. Liver and extrahepatic metastases were present in 511 patients. Of these, tumours in 72 patients (14.1 per cent) were categorized as upfront resectable, and 53 patients (10.4 per cent) became eligible for surgery. Eventually 110 patients (21.5 per cent) underwent liver resection or ablation. At baseline, a discrepancy between local and central resectability was noted for 116 patients (22.7 per cent). Median DFS from first resection was 7 months and median OS 55 months. Median OS after diagnosis of metastatic colorectal cancer was 79, 42, and 17 months in R0-1 resection, R2/ablation, and non-resected groups, with 5-year OS rates of 65, 39, and 2 per cent, respectively. CONCLUSION: Repeated centralized resectability assessment in patients with colorectal liver metastases improved resection and survival rates.

Scheduled Emergency Trauma Operation: The Green Line Orthopedic Trauma Surgery Process Of Care.

BACKGROUND AND AIMS: Traditionally, patients requiring an orthopedic emergency operation were admitted to an inpatient ward to await surgery. This often led to congestion of wards and operation rooms while, for less urgent traumas, the time spent waiting for the operation often became unacceptably long. The purpose of this study was to evaluate the flow of patients coded green in a traffic light-based coding process aimed at decreasing the burden on wards and enabling a scheduled emergency operation in Central Finland Hospital. MATERIALS AND METHODS: Operation urgency was divided into three categories: green (>48 h), yellow (8-48 h), and red (<8 h). Patients, who had sustained an orthopedic trauma requiring surgery, but not inpatient care (green), were assigned an operation via green line process. They were discharged until the operation, which was scheduled to take place during office hours. RESULTS: Between January 2010 and April 2015, 1830 green line process operations and 5838 inpatient emergency operations were performed. The most common green line process diagnoses were distal radial fracture (15.4% of green line process), (postoperative) complications (7.7%), and finger fractures (4.9%). The most common inpatient emergency operation diagnosis was hip fracture (24.3%). Green line process and inpatient emergency operation patients differed in age, physical status, diagnoses, and surgical procedures. CONCLUSION: The system was found to be a safe and effective method of implementing orthopedic trauma care. It has the potential to release operation room time for more urgent surgery, shorten the time spent in hospital, and reduce the need to operate outside normal office hours.

Sense of coherence and four-year caries incidence in Finnish adults.

This study assesses whether sense of coherence (SOC) predicts incidence of tooth decay over 4 years and the role of dental behaviours in explaining the effect of SOC on incidence of tooth decay. Data from 994 adults who participated in both the Health 2000 survey and the Follow-Up Study of Finnish Adults' Oral Health were analysed for this study. At baseline, participants provided information on demographic characteristics, education level, the SOC scale and dental behaviours (tooth brushing frequency, dental attendance and sugar intake frequency). The 4-year incidence of tooth decay was calculated using data from baseline and follow-up clinical oral examinations. Baseline SOC was significantly related to 4-year incidence of tooth decay after adjustment for demographic factors and education (relative risk: 0.79, 95% CI: 0.63-0.98). This effect was fully attenuated after further adjustment for the three dental behaviours. Tooth brushing frequency and dental attendance were the only dental behaviours significantly related to incidence of tooth decay. This prospective study suggests that SOC predicts incidence of tooth decay and that dental behaviours may help explaining why adults with strong SOC have lower risk of developing tooth decay than those with weak SOC.

Sense of coherence associates with oral and general health behaviours.

OBJECTIVE: Our aim was to investigate the mutual relationship between oral and general health behaviours and oral and general subjective health among adults, and to explore whether sense of coherence (SOC) could be a common health-promoting correlate for them. PARTICIPANTS: The present study included data for 4096 30- to 64-year-old dentate adults (2177 females and 1919 males). BASIC RESEARCH DESIGN: In the nationally representative, cross-sectional sample including 8028 persons aged 30, or more, 88% were surveyed. The questionnaire and home interview included information about socio-economic and demographic factors, behavioural and psycho-social variables. Chi-square test and logistic regression models were used in the data analysis. MAIN OUTCOME MEASURES: The main outcome measures were oral health behaviours (regular dental attendance, twice a day tooth-brushing frequency), general health behaviours (non-smoking habits, physical activity at least twice a week), subjective oral and general health and the SOC (12-item) scale. RESULTS: Among females, positive health behaviours tended to occur together significantly more often than among males. Thus, 83% of females with more than once a week physical exercise frequency, and 79% of the non-smoking females, brushed their teeth at least twice a day, while the corresponding figures for the males were merely 55% and 50%. A strong SOC was associated with uniformly positive health behaviours and subjective oral and general health. CONCLUSIONS: Our results suggest that a strong SOC has a universal positive association with several health behaviours and subjective health measures, also concerning oral health. Thus, the role of psycho-social factors should not be underestimated in health promotion.

Genetic testing for maturity onset diabetes of the young: uptake, attitudes and comparison with hereditary non-polyposis colorectal cancer.

AIMS/HYPOTHESIS: Mutations in hepatic nuclear factor 1alpha cause a monogenic form of diabetes, maturity onset diabetes of the young type 3 (MODY3). Our aim was (1) to assess the uptake of genetic testing for MODY3 and to determine factors affecting it, and (2) to compare attitudes to predictive genetic testing between families with MODY3 and a previously studied group at risk of hereditary non-polyposis colorectal cancer (HNPCC). METHODS: Adult members of two extended MODY3 pedigrees, either with diabetes or a 50% risk of having inherited the mutation (n=144, age 18-60 years), were invited to an educational counselling session followed by a possibility to obtain the gene test result. Data were collected through questionnaires before counselling and 1 month after the test disclosure. RESULTS: Eighty-nine out of 144 (62%) participated in counselling, and all but one wanted the test result disclosed. No significant sociodemographic differences were observed between the participants and non-participants. The counselling uptake was similar among diabetic and non-diabetic subjects. Uncertainty about the future and the risk for the children were the most common reasons to take the gene test. At follow-up, most subjects in both MODY3 (100%) and HNPCC (99%) families were satisfied with their decision to take the test and trusted the result. The majority of both diabetic and non-diabetic subjects considered that the MODY3 gene test should be offered either in childhood (50 and 37%) or as a teenager (30 and 37%). CONCLUSIONS: Genetic testing for MODY3 was well accepted among both diabetic and non-diabetic participants. The subjects found the gene test reliable and they were satisfied with their decision regarding the predictive test.

Did Finland's Tobacco Control Act of 1976 have an impact on ever smoking? An examination based on male and female cohort trends.

OBJECTIVE: To examine patterns of ever smoking among Finnish adults by gender and birth cohort from 1978 to 2001, with special emphasis on the possible effects of the 1976 Tobacco Control Act (TCA). METHODS: The data were derived from independent, annual cross sectional postal surveys among 15-64 year olds (n = 91,342), average response rate 75%. For the analyses 13 five year birth cohorts from 1916 to 1980 were constructed. Birth cohort variations in ever regular smoking were first examined graphically, and then logistic models were used to test the impact of the TCA. RESULTS: Among men there was a decrease in smoking from older to younger cohorts. For women an increase in smoking was observed between successive cohorts. A clear decline in the prevalence of ever smokers concurrent with the TCA was found among both men and women. CONCLUSIONS: The smoking behaviour trends across successive birth cohorts suggest the impact of tobacco policy in decreasing smoking initiation in youth. These findings thus support the acceptability and effectiveness of antismoking and smoke free policy measures in society.

Income and health behaviours. Evidence from monitoring surveys among Finnish adults.

STUDY OBJECTIVE: To examine the associations of individual and household income with various health behaviours, before and after adjusting for educational attainment and occupational social class. DESIGN AND SETTING: Data from 19 982 respondents to nationwide health behaviour surveys from 1993 to 1999 (response rate 70%) were linked with socioeconomic information from population registers. MEASUREMENTS: The income measures were total individual income liable to taxation and household's monthly disposable income. Health behaviours included smoking, alcohol use, leisure time physical activity, use of vegetables, use of saturated fat on bread, and being overweight. MAIN RESULTS: In men, smoking and infrequent vegetable use were more common among those with lower individual and household income. However, adjusting for education and occupational class removed most of the differences. Use of saturated fat on bread increased with decreasing individual income, before and after the adjustments. In women, smoking, infrequent vegetable use and being overweight were more common among those with lower income, but the differences by both income measures were largely removed by the adjustments. Women with higher income more often also were high alcohol users and had less physical activity, in particular when income was measured by the respondents' individual income. CONCLUSIONS: Adjusting for education and occupation largely removed income differences in health behaviours, but for some behaviours some independent effect remained. The results suggest that income does not only reflect the available material resources, but works as a general socioeconomic indicator that is associated with health behaviours in much the same way as other socioeconomic indicators.

Associations between health-related behaviors: a 7-year follow-up of adults.

BACKGROUND: The study examines pairwise associations between smoking, alcohol use, physical activity, dietary behavior and body mass index using long-term follow-up data of Finnish adults. METHODS: Respondents to large nationwide health behavior surveys conducted in 1989/1990 were recontacted in 1997. First, we examined whether each health behavior predicted other behaviors 7 years later. Second, we examined whether changes in each health behavior were accompanied by changes in other behaviors. RESULTS: Smoking at baseline predicted all other health behaviors except body mass index in men. On the other hand, other behaviors tended to predict smoking. Physical inactivity and unhealthy diet were predictive of each other in men. Those with an unhealthy diet at baseline were less likely to be high alcohol users in the follow-up. Baseline body mass index did not predict any of the other behaviors. Concurrent changes in health behaviors involved either smoking or body mass index. Changes in diet and alcohol use were differently related to changes in body mass index in men than in women. CONCLUSIONS: Overall, smoking seemed to play a central role in the associations between health behaviors. Smoking was predictive of most other health behaviors. Concurrent changes in health behaviors related either to smoking or to body weight. The associations between health behaviors were fairly similar for men and women, but the variation in the associations between body mass index and some other health behaviors suggests gender differences in the behavioral response to body weight.

Smokers who do not want to quit--is consonant smoking related to lifestyle and socioeconomic factors?

AIMS: To examine whether consonant smokers (who say they would not like to quit) differ from dissonant smokers (who would like to quit) in other forms of health-related behaviour and socioeconomic background. METHODS: The participants included 2,709 male and 1,774 female smokers (aged 25-64 years old) from six annual population-based samples, examined between 1989 and 1994 via a mailed questionnaire. RESULTS: Consonant male smokers were more likely to be heavy drinkers, use mostly butter on bread, and to not eat vegetables. Particularly in the middle educational and income groups, consonant male smokers were more likely to be heavy drinkers. Consonant female smokers were more often heavy drinkers and more sedentary than dissonant female smokers. If a male smoker belonged to the lower income group he was more likely to be a consonant smoker. CONCLUSIONS: Consonant male smokers had more adverse health behaviours compared to dissonant smokers, but nearly half of them did not have any other adverse health behaviours. However, a negative attitude towards smoking cessation was associated with other adverse health behaviours. There were no socioeconomic differences in willingness to quit smoking among female smokers and those differences between male smoker groups were small. Factors other than motivation to quit should be targeted to diminish socioeconomic differences in smoking cessation.

Gender-associated differences in the quality of life after allogeneic BMT.

The purpose of this study was to compare the quality of life (QOL) of male and female allogeneic BMT recipients. One hundred and nine BMT patients participated in this cross-sectional survey and completed the following instruments: Functional Assessment of Cancer Treatment (FACT-BMT version 3), shortened version of Profile of Mood States (POMS), MOS Survey of Social Support, and A Brief Measure of Social Support (SSQ6). Independent of the time post-BMT, perceived physical well-being, age at BMT, and education, females reported worse emotional well-being and more fatigue than males. Females also indicated more tiredness and less quality sleep. Males were found to experience less satisfaction with social support regardless of marital status. On the other hand, married males were more satisfied with their sexual life, more interested in sexual relationships, and more sexually active compared to married females. However, no significant differences between males and females were found in terms of overall physical, functional, and social well-being assessed by the FACT-BMT. The present results indicated that important gender differences exist among allogeneic BMT recipients which need to be addressed when designing post-treatment intervention programs for BMT recipients.

Psychological consequences of predictive genetic testing for hereditary non-polyposis colorectal cancer (HNPCC): a prospective follow-up study.

Predictive genetic testing for cancer allows identification of those with the mutation (mutation positive) who should undergo cancer surveillance aiming at early detection of cancer and those without the mutation (mutation negative), whose unnecessary worry can be alleviated and who need not undergo frequent surveillance. However, there is a risk that predictive testing might have a harmful emotional impact on an individual. In the course of a predictive genetic testing protocol, we assessed general anxiety (by the State-Trait Anxiety Inventory [STAI]), fear of cancer and death, satisfaction with life and attitude to the future using a questionnaire survey in 271 individuals tested for hereditary non-polyposis colorectal cancer (HNPCC). Measurements were made before the first counseling (baseline), at the test disclosure session (STAI only) and 1 and 12 months after disclosure. Although at every measurement, the mutation-positive individuals were more afraid of cancer than those who were mutation negative, in both groups fear of cancer decreased significantly from baseline after disclosure. The mutation-positive subjects were more anxious than their counterparts immediately after the test disclosure, but the differences had disappeared at the follow-ups. In other variables, neither differences between the groups defined by mutation status nor changes with time were detected. Our findings suggest that counseling and testing relieve fear of cancer; no harmful emotional impact was detectable at the 1-year follow-up. To confirm these findings, however, the impact of testing should be studied after a longer interval. Furthermore, to evaluate the ultimate interpretation of these results, studies are needed to investigate the impact of fear of cancer on surveillance behavior among the mutation-positive subjects.

Smoking and passive smoking in Estonia, Lithuania and Finland. Identifying target groups of tobacco policy.

BACKGROUND: The aim of this study was to identify population groups which are the most crucial as targets for anti-tobacco action. METHODS: A comparison was made of the prevalence and patterns of smoking and passive smoking in Estonia, Finland and Lithuania. RESULTS: Total exposure to smoking, both one's own and passive smoking, was more common in two Baltic countries than in Finland. In these Baltic countries passive smoking was notably common among women. In all countries the exposure was more prevalent among the younger and less educated, but no difference emerged between urban and rural areas. CONCLUSIONS: The following target groups were identified as priorities for anti-tobacco actions: i) men of all ages in Estonia and Lithuania to stop their already established tobacco use, ii) young women in all three countries to prevent their starting a career of tobacco use and iii) young and less educated women in Estonia and Lithuania to prevent passive smoking, i.e. their exposure to environmental tobacco smoke.

Quality of life and factors related to perceived satisfaction with quality of life after allogeneic bone marrow transplantation.

The quality of life after bone marrow transplantation (BMT) was studied in 109 adult allogeneic BMT recipients transplanted on at the Helsinki University Central hospital for a haematological malignancy. Physical, functional, emotional and social well-being was measured on the Functional Assessment of Cancer Therapy Scale (FACT-BMT) and a shortened version of the Profile of Mood States Scale (POMS) and by the MOS social support survey and a Brief Measure of Social Support (SSQ6). The results of the present study replicate those of previous investigations by finding that physical well-being, educational level, age at BMT and social support have an impact on the perceived quality of life of BMT patients. Our results indicate that these factors have a varying impact at different time points during the post-BMT recovery process. During the first three years after BMT, physical well-being proved to be a highly significant (P < 0.001) factor for perceived life satisfaction. Moreover, physical well-being showed an average significant improvement after the first post-BMT year. The percentage of the recipients experiencing the highest levels of satisfaction with life increased from 51% during the first year after BMT to 81% for those patients five years post-BMT. One year after BMT, 75.6% of the BMT recipients were able to work, 67.8% of the patients were actively participating in work/school and 7.8% were unemployed.

Occasional smoking increases total and cardiovascular mortality among men.

The aim was to study whether occasional smoking increases mortality risk. The mortality of random samples of the Finnish Adult Health Behavior surveys from 1978 to 1991 were followed for 18 years from 1978 to 1995. Poisson models were used to determine the risk of total and cardiovascular mortality. It was found that occasional smokers were less often sedentary and had less often unhealthy diet than other smoking status groups. Occasional smoking among men was significantly related to the risk of both total (age-adjusted relative risk, RR, 1.6, 95% confidence interval, CI, 1.3-2.1) and cardiovascular mortality (age-adjusted RR 1.5, 95% CI 1.0-2.3). Controlling for education, period and chronic morbidity did not change results. Among women no significant associations could be established; when adjusted for age, period, education and morbidity the RR for cardiovascular mortality was 1.4 (95% CI 0.6-3.4) and total mortality 1.0 (95% CI 0.6-1.6). Occasional smoking is associated with increased risk of premature death, at least among men. Although occasional smoking is a less dangerous practice than regular smoking, it is not a safe alternative for daily smoking.

International Quit and Win 1996: comparative evaluation study in China and Finland.

OBJECTIVES: To compare background and process variables, as well as follow up status, of the participants in the International Quit and Win '96 contests of China and Finland, and analyse factors contributing to sustained maintenance. DESIGN: A standardised 12 month follow up was conducted in both countries with random samples of participants. The sample sizes were 3119 in China and 1448 in Finland, with response rates of 91.2% and 65.2%, respectively. INTERVENTIONS: The International Quit and Win '96 contest was the second coordinated, multinational smoking cessation campaign targeted at adult daily smokers. Altogether 25 countries participated, including China with 15 000 and Finland with 6000 smokers registered. MAIN OUTCOME MEASURES: Conservative (considering all non-respondents relapsed) and non-conservative (based on respondents only) estimates were calculated for one month abstinence, 12 month continuous abstinence, and point abstinence at the time point of follow up. RESULTS: Great differences were found in the background and process variables, as well as in the outcome measures. At one year follow up, the conservative continuous abstinence rates show that the Chinese participants maintained their abstinence better (38%) compared to the Finnish ones (12%). In China women reached higher abstinence rate (50%) than men (36%), whereas in Finland men achieved a better result (14%) than women (9%). CONCLUSIONS: The Quit and Win contest is a mass smoking cessation method feasible in countries showing great variance in smoking habits and rates. However, in countries with different stages of anti-smoking development, such as China and Finland, different practical implementation strategies may be needed.

Depression and smoking cessation: the role of motivation and self-efficacy.

The aim of this paper is to examine whether depression, assessed using the Beck Depression Inventory, is related to smoking cessation motivation and self-efficacy. In a population sample of 1,547 Finnish men and 1,856 Finnish women, aged between 25-64 years, there were 34% male and 21% female current smokers. The current smokers had higher mean depression scores than former or never smokers. The higher depression scores were related to greater motivation to quit smoking among female smokers [OR = 1.51 (1.15-1.97)]. In addition, higher depression scores were related to lower smoking cessation self-efficacy, especially among male smokers [OR = .63 (.45-.90)]. Depression scores were not related to whether a smoker had had previous cessation attempts. Our results suggest that depression is related to lower smoking cessation self-efficacy while smokers with higher depression scores seem to be more motivated to quit smoking.

Predictive genetic testing for hereditary non-polyposis colorectal cancer: uptake and long-term satisfaction.

The aim of this prospective study was to assess the uptake of predictive genetic testing for hereditary non-polyposis colorectal cancer (HNPCC) and its associations with sociodemographic and other factors, and long-term satisfaction with taking the test. The test was offered to all high-risk members (n = 446) of 36 Finnish HNPCC families in which the mutation was known. The procedure comprised an educational counselling session, a period for reflection, and a test disclosure session. Data were collected by questionnaires sent before the educational counselling and 1 month and 1 year after the test disclosure. Of those eligible, 85% (n = 381) completed the first questionnaire study. Non-participation was more common among men living alone who had not participated in the clinical cancer surveillance programme. Of the 347 subjects who attended counselling, 334 (75% of all subjects) were actually tested. After logistic-regression analysis, the only significant factor predicting test acceptance proved to be employment status: those employed were more likely than others to accept the test (odds ratio = 2.25; 95% confidence intervals, 1.09 to 4.6 1). At follow-up, over 90% of the subjects were fully satisfied with the decision to take the test. In conclusion, acceptance of the test was considerably higher than in previously reported studies. We attribute this to our careful face-to-face individualized counselling, our health care system, and to attitudes of the Finnish population, which are generally favourable towards health care and disease prevention.

Evaluation of a counselling protocol for predictive genetic testing for hereditary non-polyposis colorectal cancer.

OBJECTIVES: To evaluate the feasibility of a reduced counselling programme for predictive genetic testing for hereditary non-polyposis colorectal cancer (HNPCC) in terms of counsellees' opinions on the extent and significance of genetic counselling and need for psychological support at different phases of the testing procedure. DESIGN: Prospective follow up study with pre-test questionnaire assessment of background sociodemographic variables. The protocol comprised a pre-test counselling session, a period for reflection, and a test disclosure session. The outcome variables were studied by post-test questionnaires at one month and one year follow up. SUBJECTS: Two hundred and seventy one high risk members of 36 families with HNPCC who attended both counselling sessions and completed the questionnaires. RESULTS: The pre-test counselling was considered fairly or very useful by 89% of respondents and one post-test session was considered sufficient by over 80% of respondents at follow up. Fifty three percent would have used extra psychological support had it been offered with the counselling. On enquiry one year after receiving the test result, only 2% stated that the need for support was at its greatest at that time, while the majority (46%) reported that the need for support had been greatest at the moment of test disclosure. CONCLUSIONS: A protocol that includes one comprehensive pre-test counselling session and a test disclosure session, supplemented with the option of professional psychological support, seems to be sufficient for both the educational and supportive needs of counsellees. Only a minority expressed a need for post-test follow up sessions, which suggests that, in this disorder, resources can be directed to the beneficial surveillance programmes rather than to extensive psychological support.