Early Post-treatment Prostate-specific Antigen at 4 Weeks and Abiraterone and Enzalutamide Treatment for Advanced Prostate Cancer: An International Collaborative Analysis.

BACKGROUND: Declines in prostate-specific antigen (PSA) levels at 12wk are used to evaluate treatment response in metastatic castration-resistant prostate cancer (mCRPC). PSA fall by ≥30% at 4wk (PSA4w30) has been reported to be associated with better outcome in a single-centre cohort study. OBJECTIVE: To evaluate clinical relevance of early PSA decline in mCRPC patients treated with next-generation hormonal treatments (NGHTs) such as abiraterone and enzalutamide. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective multicentre analysis. Eligible patients received NGHT for mCRPC between 6 January 2006 and 31 December 2017 in 13 cancer centres worldwide, and had PSA levels assessed at baseline and at 4 and/or 12wk after treatment. PSA response was defined as a ≥30% decline (progression as a ≥25% increase) from baseline. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Association with overall survival (OS) was analysed using landmark multivariable Cox regression adjusting for previous chemotherapy, including cancer centre as a shared frailty term. RESULTS AND LIMITATIONS: We identified 1358 mCRPC patients treated with first-line NGHT (1133 had PSA available at 4wk, and 948 at both 4 and 12wk). Overall, 583 (52%) had a PSA4w30; it was associated with longer OS (median: 23; 95% confidence interval [CI]: 21-25) compared with no change (median: 17; 95% CI: 15-18) and progression (median: 13; 95% CI: 10-15). A PSA12w30 was associated with lower mortality (median OS 22 vs 14; hazard ratio=0.57; 95% CI=0.48-0.67; p<0.001). PSA4w30 strongly correlated with PSA12w30 (ρ=0.91; 95% CI=0.90-0.92; p<0.001). In total, 432/494 (87%) with a PSA4w30 achieved a PSA12w30. Overall, 11/152 (7%) patients progressing at 4wk had a PSA12w30 (1% of the overall population). CONCLUSIONS: PSA changes in the first 4wk of NGHT therapies are strongly associated with clinical outcome from mCRPC and can help guide early treatment switch decisions. PATIENT SUMMARY: Prostate-specific antigen changes at 4wk after abiraterone/enzalutamide treatment are important to determine patients' outcome and should be taken into consideration in clinical practice.

Activity of cabazitaxel in castration-resistant prostate cancer progressing after docetaxel and next-generation endocrine agents.

BACKGROUND: Cabazitaxel, abiraterone, and enzalutamide are survival-prolonging treatments in men with castration-resistant prostate cancer (CRPC) progressing following docetaxel chemotherapy. The sequential activity of these agents has not been studied and treatment sequencing remains a key dilemma for clinicians. OBJECTIVE: To describe the antitumour activity of cabazitaxel after docetaxel and next-generation endocrine agents. DESIGN, SETTING, AND PARTICIPANTS: We report on a cohort of 59 men with progressing CRPC treated with cabazitaxel, 37 of whom had received prior abiraterone and 9 of whom had received prior enzalutamide. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Changes in prostate-specific antigen (PSA) level were used to determine activity on abiraterone, enzalutamide, and cabazitaxel treatment. Radiologic tumour regressions according to Response Evaluation Criteria in Solid Tumors (RECIST) and symptomatic benefit were evaluated for cabazitaxel therapy. RESULTS AND LIMITATIONS: The post-endocrine-therapy patients received abiraterone (n=32), sequential abiraterone and enzalutamide (n=5) or enzalutamide (n=4). These patients received a median of 7 mo of abiraterone and 11 mo of enzalutamide. A median of six cabazitaxel cycles (range: 1-10 cycles) were delivered, with ≥ 50% PSA declines in 16 of 41 (39%) patients, soft tissue radiologic responses in 3 of 22 (14%) evaluable patients, and symptomatic benefit in 9 of 37 evaluable patients (24%). Median overall survival and progression-free survival were 15.8 and 4.6 mo, respectively. Antitumor activity on cabazitaxel was less favourable in the abiraterone- and enzalutamide-naïve cohort (n=18), likely reflecting biologic differences in this cohort. These data were obtained from a retrospective analysis. CONCLUSIONS: This is the first report of cabazitaxel activity in CRPC progressing after treatment with docetaxel and abiraterone or enzalutamide. We demonstrate significant cabazitaxel activity in this setting. PATIENT SUMMARY: We looked at the antitumour activity of the chemotherapy drug cabazitaxel in men previously treated with docetaxel chemotherapy and the hormonal drugs abiraterone and enzalutamide. Cabazitaxel appeared active when given after abiraterone and enzalutamide. We can reassure men that cabazitaxel can be used after these novel endocrine treatments.

Pneumococcal vaccination in splenectomised cancer patients.

Although pneumococcal vaccination has been recommended in splenectomised patients for more than 30 years, its use remains unsatisfactory. We conducted two consecutive retrospective assessments to determine the rate of pneumococcal vaccination among splenectomised cancer patients at a single institution. We found that 75% (82 of 115) of splenectomised cancer patients had received at least one documented pneumococcal vaccination as compared to only 59.7% of patients identified in a previous assessment conducted 1997. 20% (22 of 115) of the patients had not been vaccinated at all. Splenectomy was performed in 54% because of Hodgkin lymphoma. The pneumococcal vaccination coverage in this subgroup has risen from 40% in the previous assessment (1997) to 93% in the current survey. In conclusion, patients splenectomised at a young age because of Hodgkin lymphoma are the key group at risk for insufficient pneumococcal vaccination. Repeated assessments of the pneumococcal vaccination status increased the rate of vaccination.

Home visiting the newborn baby as a basis for developmental surveillance at child welfare centres.

Home visiting is a part of the Swedish child health surveillance programme. In the present study, part of a longitudinal prospective project, the predictive power of observations at home visits to 338 newborn babies was evaluated. The regular home visit was made by the nurse at a Child Welfare Centre also using a check-list developed for this project. Her check-list assessments seemed valid in identifying families with stressful psychosocial conditions. When the general home situation was judged as "poor" or "dubious", the boys showed signs of a delayed mental development at 4-5 years of age. Assessments of "feeding problems" among boys were associated with behavioural problems at 4-5 years of age. The results underline the importance of an early home visit as a base for the developmental surveillance at Child Welfare Centres. However, the results of the home visit observations were not followed by any extra interventions at CWC. It seems the nurse should feel confident in her check-list judgement and initiate interventions where appropriate.

Accidents in childhood: relation to psychosocial conditions and mental development.

In a longitudinal cohort study we investigated if children experiencing psychosocial stress and exhibiting certain psychopathological symptoms run a higher risk of having accidents than other children. In 366 children the number of hospital-treated casualties during the first 10 years of their lives was related to the physical and mental characteristics of the children and to the social conditions in their families. Boys had a higher number of accidents when one or both of the parents were known to have alcohol problems. Girls exhibiting symptoms of depression, anxiety and problems in social relationships at 4-5 years of age had more accidents than girls without such symptoms. However, the differences in accident rates were small, perhaps due to the physical environment in the housing areas and the general attitude, both aiming towards reducing childhood accidents.

Height, weight, and body mass index (BMI) of Vietnamese (Hanoi) schoolchildren aged 7-11 years related to parents' occupation and education.

In the spring of 1992 schoolchildren (679 boys and 661 girls) aged 6-12 years in a school in central Hanoi, Vietnam were enrolled for a medical examination including measurements of height and weight. Most of them were measured a second time almost exactly 1 year after the first measurement. Thus, values for height, weight, and body mass index (BMI), and their yearly increments were obtained for the ages 7-11 years. When these heights and weights were compared with those for children from Bangkok, Tokyo and Sweden, the Hanoi values were very close to the Bangkok ones. There were overall no significant differences in height, weight, and BMI between children whose parents were of different occupational and educational groups, except for girls whose mothers were workers/farmers, who were shorter (P <0.05), lighter (P <0.01), and had a lower BMI (P <0.05) than girls whose mothers were from upper occupational status (government staff). The overall incidence of low birthweight (<2500 g) was 11 per cent, but this was not associated with either parents' occupation or education. At the time of measurements 31.6% of the children were rated by the doctors as being in 'general bad condition'; there was a higher proportion of girls than boys (P <0.01) and a higher proportion of girls whose mothers were workers/farmers (P <0.001).

Screening for minimal brain dysfunction (MBD/DAMP) at six years of age: results of motor test in relation to perinatal conditions, development and family situation.

The aim of this study was to investigate if children aged 6 years of age, classified as having minimal brain dysfunction (MBD) or deficit in attention, motor control and perception (DAMP), exhibit special medical problems, specific developmental features or if special psychosocial conditions exist in the family. The screening program, using the psychoneurological part of the method developed by Gillberg et al., included 234 children who were followed-up prospectively from pregnancy and birth. The results were related to the physical and mental development of the children, to the psychosocial and socioeconomic conditions of the families, to pre- and postnatal conditions and to "reduced optimality score", as defined by Prechtl. Mental development was assessed by the use of Griffiths' test at 10-14 months and at 4-5 years of age. At the second Griffiths' test, the mother was also interviewed about the presence of aggressiveness and other symptoms of childhood psychopathology in her child, as defined by the DSM-III criteria, and a psychological observation was also made. In addition to screening for MBD/DAMP, at 6 years of age the parents were asked to complete a questionnaire aimed at identifying attention deficit disorder (ADD). No medical or psychological intervention was made before this stage. Fourteen children (9M, 5F) (6%) were identified as having a positive MBD/DAMP screening result. The results of the screening procedure showed a weak correlation with those obtained using the questionnaire based on the DSM-III criteria for ADD.(ABSTRACT TRUNCATED AT 250 WORDS)

Home visiting to families with a newborn child.

OBJECTIVE: To validate child health clinic nurses' observations at the first visit to families having a newborn baby. DESIGN: The nurses' observations were compared with results from a prenatal assessment of the home conditions and with observations made by a psychologist at a home visit about one year later. SETTING: A newbuilt suburb of Stockholm. PARTICIPANTS: 373 families with a newborn. OUTCOME MEASURES: Distribution of observations in subgroups, maximum likelihood, positive predictive value. RESULTS: A significant relationship between the nurses' observations, the prenatal assessment, and the psychologist's evaluation of the home situation was found. Children from homes assessed as "at risk" by the nurses also had lower quotients at Griffiths' test one year later. CONCLUSION: Already during the child's neonatal period, the nurses make valid observations that are useful in selecting children at risk of subsequent developmental problems.

Standards for height, weight and head circumference from one month to six years based on Stockholm children born in 1980.

Growth data on height, weight and head circumference were collected from Stockholm children from one month to six years of age, born in 1980, and representing all socio-economic groups. The sample consisted of 2471 children (1264 boys and 1207 girls), most of whom were measured on 10-15 occasions. From these measurements centile standards were constructed using a statistical technique which separates between-individual and within-individual variation, since only the former is appropriate to distance standards. Compared to former Swedish standards the present heights and weights were similar up to 2.0 years of age but thereafter considerably greater. Head circumference was larger throughout, perhaps due to a difference in measurement technique.

Developmental screening at four years of age. Relation to home situation, perinatal stress, development and behaviour.

A developmental screening programme constructed for the use of Swedish child welfare centres on four-year-old children has been tested on a cohort of 471 children who have been followed up from the stage of early pregnancy. The results of the screening test were compared with data in the project using a multidisciplinary, longitudinal and prospective design. The test, which can be performed by a child welfare centre nurse and which is not time-consuming, includes four items summed up in a four-years-of-age score: the child is asked to name three easily recognizable objects, to draw a cross (according to a model), and to draw a man; in addition, an evaluation is made of speech development. On average, boys were found to have a lower score than girls. The results of the screening test were related to data available in the ongoing project; to the psychosocial conditions of the families, to foetal and perinatal factors (reduced optimality score according to Prechtl), to the presence of psychopathology, and to the results of Griffiths' developmental scales. The developmental screening score, which in most instances was associated with the Griffiths' scales, was found to be related to psychosocial problems in the family and to abnormal behaviour and psychiatric symptoms in the child, but not to reduced optimality scores. The results indicate that a relatively simple screening method is of value for the identification of children who are at risk of abnormal mental and behavioural development, and who may thus be in need of special care and attention.

Psychomotor and mental development during infancy. Relation to psychosocial conditions and health. Part IV of a longitudinal study of children in a new Stockholm suburb.

This article presents the fourth substudy in a Swedish research project of a birth cohort of children in a newly-built Stockholm suburb. The aims are to follow and to describe their mental development by prospective methods. Here we present the results of the one-year follow-up. The children's mental development, measured with the Griffiths' Development Scales, and their behaviour in the test situation and during the home visit are described. These results are related to various psychosocial background factors (such as the parents' ages, number of siblings, form of custody), home environment factors (the parents' mental disease, addictions and criminality) and the children's physical health and development. Children with deviant behaviour during the home visits are described separately. Of 640 women who paid their first visit to the maternal welfare centers in a new Stockholm suburb during one prospective year, 532 (85%) were interviewed with regard to 41 stress factors forming a "Life stress score" (LSS). The interviews were supplemented with data from hospital, social welfare and police records concerning the expectant mother and the father. The 532 mothers were divided into three groups according to the degree of psychosocial stress (194 without psychosocial stress, 171 with severe psychosocial stress and 167 in an intermediate group). The pregnancies and deliveries of all mothers were evaluated. The physical health and development (using information from the child welfare clinics) and the mental health and development (using information from home visits and testings) were studied during infancy in 452 children (226 boys and 226 girls)--i.e. 77% of all children born in the suburb during the year. The children were tested with the Griffiths' Development Scales and their behaviour during the test was observed on home visits by the same psychologist (L.N.) at the age of 10 months (79 boys, 73 girls) or 14 months (92 boys, 107 girls), or about the age of 18 months (55 boys, 46 girls). The test results are mainly reported by descriptive methods. In summary, the results of the evaluation of the children's mental health during the first year of life, generally showed average developmental quotients. However, 20% of the children had values below the average. Thirty-two per cent of the children with low test results (less than -1 standard deviation on the total test) came from homes with serious psychosocial stress and 29% from homes with a mild degree of psychosocial stress. Of the nine children who had generally very low scores in the Griffiths' evaluation, seven came from homes with psychosocial stress.(ABSTRACT TRUNCATED AT 400 WORDS)

Psychosocial factors and physical health during the first year of life. Children in a new Stockholm suburb. A prospective longitudinal study. III.

The study is part of a longitudinal research project of a cohort of 501 children in a Stockholm suburb. The aim of the project is to clarify the relation between the children's health and development and their home environment. The present work deals with the children's physical health during their first year of life and comparisons were made between infants in families suffering or not suffering from psychosocial stress. Indications of psychosocial stress in the homes include reports of alcohol abuse, mental disease or criminality in one or both of the parents. Judging by reports from child welfare centres and hospital records, children from homes with psychosocial stress do not have a higher rate of somatic illnesses, retarded psychomotor development and psychosomatic problems than the control children.

Psychosocial factors and pregnancy outcome. Part two of a prospective longitudinal study of children in a new Stockholm suburb.

In a current prospective sociomedical study of families in a Stockholm suburb, their home environments were investigated through interviews with the mothers on their first visit to a maternity health centre when pregnant, and through data obtained from various records. In a sample of 498 mothers, 109 women with psychosocial difficulties were compared with 255 women of the same age but who were not psychosocially deprived. While taking into account biomedical risk factors and parity, it appeared that there was little difference between the groups with regard to frequency of complications in pregnancy, delivery or in the newborn infant. The existence of supportive medical and social factors could be one explanation as to why anticipated differences between the groups were not observed.