Patient-reported outcome (PRO) measurements in chronic and malignant diseases: ten years' experience with PRO-algorithm-based patient-clinician interaction (telePRO) in AmbuFlex.

BACKGROUND: Patient-reported Outcome (PRO) measures may be used as the basis for out-patient follow-up instead of fixed appointments. The patients attend follow-up from home by filling in questionnaires developed for that specific aim and patient group (telePRO). The questionnaires are handled in real time by a specific algorithm, which assigns an outcome color reflecting clinical need. The specific questionnaires and algorithms (named solutions) are constructed in a consensus process with clinicians. We aimed to describe AmbuFlex' telePRO solutions and the algorithm outcomes and variation between patient groups, and to discuss possible applications and challenges. METHODS: TelePRO solutions with more than 100 processed questionnaires were included in the analysis. Data were retrieved together with data from national registers. Characteristics of patients, questionnaires and outcomes were tabulated for each solution. Graphs were constructed depicting the overall and within-patient distribution of algorithm outcomes for each solution. RESULTS: From 2011 to 2021, 29 specific telePRO solutions were implemented within 24 different ICD-10 groups. A total of 42,015 patients were referred and answered 171,268 questionnaires. An existing applicable instrument with cut-off values was available for four solutions, whereas items were selected or developed ad hoc for the other solutions. Mean age ranged from 10.7 (Pain in children) to 73.3 years (chronic kidney disease). Mortality among referred patients varied between 0 (obesity, asthma, endometriosis and pain in children) and 528 per 1000 patient years (Lung cancer). There was substantial variation in algorithm outcome across patient groups while different solutions within the same patient group varied little. DISCUSSION: TelePRO can be applied in diseases where PRO can reflect clinical status and needs. Questionnaires and algorithms should be adapted for the specific patient groups and clinical aims. When PRO is used as replacement for clinical contact, special carefulness should be observed with respect to patient safety.

Fifteen Years' Use of Patient-Reported Outcome Measures at the Group and Patient Levels: Trend Analysis.

BACKGROUND: Since 2004, we have collected patient-reported outcome (PRO) data from several Danish patient populations for use at the group and patient levels. OBJECTIVE: The aim of this paper is to highlight trends during the last 15 years with respect to patient inclusion, the methods for collection of PRO data, the processing of the data, and the actual applications and use of the PRO measurements. METHODS: All PRO data have been collected using the AmbuFlex/WestChronic PRO system, which was developed by the author in 2004 and has been continuously updated since. The analysis of trends was based on a generic model applicable for any kind of clinical health data, according to which any application of clinical data may be divided into four processes: patient identification, data collection, data aggregation, and the actual data use. Data for analysis were generated by a specific application in the system and transferred for analysis to the R package. RESULTS: During the 15-year period, 78,980 patients within 28 different groups of chronic and malignant illnesses have answered 260,433 questionnaires containing a total of 13,538,760 responses. Several marked changes have taken place: (1) the creation of cohorts for clinical epidemiological research purposes has shifted towards cohorts defined by clinical use of PRO data at the patient level; (2) the development of AmbuFlex, where PRO data are used as the entire basis for outpatient follow-up instead of fixed appointments, has undergone exponential growth and the system is currently in use in 47 International Statistical Classification of Diseases and Related Health Problems groups, covering 16,000 patients and 94 departments throughout Denmark; (3) response rates (up to 92%) and low attrition rates have been reached in group level projects, and there are even higher response rates in AmbuFlex where the patients are individually referred; (4) The answering method has shifted, as while in 2005 a total of 66.5% of questionnaires were paper based, this is the case for only 4.3% in 2019; and (5) the approach methods for questionnaires and reminders have changed dramatically from letter, emails, and short message service text messaging to a national, secure electronic mail system through which 93.2% of the communication to patients took place in 2019. The combination of secure email and web-based answering has resulted in a low turnaround time in which half of responses are now received within 5 days. CONCLUSIONS: The demand for clinical use of PRO measurements has increased, driven by a wish among patients as well as clinicians to use PRO to promote better symptom assessment, more patient-centered care, and more efficient use of resources. Important technological changes have occurred, creating new opportunities, and making PRO collection and use cheaper and more feasible. Several legal changes may constitute a barrier for further development as well as a barrier for better utilization of patients' questionnaire data. The current legal restrictions on the joint use of health data imposed by the European Union's General Data Protection Regulation makes no distinction between use and misuse, and steps should be taken to alleviate these restrictions on the joint use of PRO data.

The relation between daily activities and scrotal temperature.

Normal sperm production depends on a testicular temperature below body temperature, but the thermogenic effects of daily life activities are not well known. We described the association between scrotal temperature and daily activities in 101 males using a non-invasive method for measuring scrotal temperature. A thermistor was attached to the underwear and the temperature of the scrotal skin was logged by a portable device every 5 min for 24h. Participants reported sedentary position and activities at work and during spare time in a questionnaire. Scrotal temperature was strongly correlated with sedentary work position with a dose-effect association (<1 h sedentary: 33.1 degrees C, >6 h sedentary: 34.7 degrees C, median values). The variation in sedentary work accounted for 31.5% of the variation in median temperature during the entire 24h. Sedentary position during spare time did not correlate with scrotal temperature. Median temperature at night was 1.2 degrees C higher than during the daytime. No effect was found for size or reported tightness of the underwear. In a model experiment, the deviance between testicular and scrotal temperature was estimated as maximally 0.1-0.6 degrees C, depending on the type of activity. Measuring scrotal temperature provides a valid estimate of testicular temperature and is feasible in large cohorts. We conclude that work position is an important determinant of testicular temperature.

Impact of diurnal scrotal temperature on semen quality.

A high scrotal temperature is a common finding in infertile patients and experimental studies indicate that specific types of heat exposure reduce semen quality. More and more men have a sedentary work position, which increases scrotal temperature. Semen and blood samples from 99 healthy men were analysed in relation to scrotal skin temperature obtained by a 24-h continuous monitoring protocol. Information on sedentary position at work and during spare time was collected by questionnaires. A negative correlation was found between high scrotal temperature and sperm output. Sperm concentration decreased 40% per 1 degrees C increment of median daytime scrotal temperature (95% CI: 8-71%). Similar results were found for total sperm count, FSH, and inhibin B. Motility, morphology, pH, and testosterone were not significantly associated with temperature. Only weak and inconsistent associations were found between sedentary position and semen quality. We conclude that scrotal temperature and semen quality are closely associated. Sedentary work position encountered in ordinary jobs, although a strong determinant of scrotal temperature, does not seem to have any effect on semen quality.

Semen quality and sedentary work position.

Increased scrotal temperature can, in experimental settings, markedly disturb the production of semen. Sedentary work position may increase the temperature of the scrotum, but previous studies have failed to determine whether changes in scrotal temperature caused by sedentary work actually do affect semen quality. This study was carried out to elucidate the possible harmful effects of sedentary work on sperm count and other semen characteristics. In 1981-1983 a semen sample was obtained from 3119 men who attended an infertility workup in one of four Danish fertility centres. A total of 2517 men returned a postal questionnaire with information on life style, leisure time activities, occupational history and job duties. Information on job specific work position was obtained from The Danish Work Environment Cohort study 1990 (DWECS). In this analysis DWECS data for a total of 1747 men was included from men aged 18-39 years with >30 h of work per week. For all job titles represented in the DWECS, the mean proportion of sedentary work was estimated. The sperm cell concentration was 30.6 million/mL among men in the quintile with lowest job specific sedentary work compared with 40.5 million/mL in the highest quintile. The difference was, however, not statistically significant. Stratification on infertility period, educational level of the man, fertility centre, and fertility-related disease of the spouse did not influence the results. The analyses do not suggest that sedentary work is a risk factor for abnormal semen characteristics.

Correlation of scrotal temperature in twins.

BACKGROUND: Scrotal temperature and semen quality have been found to be inversely correlated in several studies, and variation in scrotal temperature may contribute to the well known variation in semen quality. The reason for the variation in scrotal temperature is not well understood although determinants could be of a genetic nature. METHODS: We monitored scrotal skin temperature for 24 h in a group of monozygotic and dizygotic twins and single-born brothers (n = 48 males). A thermistor was attached to the underwear and the temperature of the scrotal skin was recorded every 5 min using a small portable data logger. RESULTS: A correlation in median scrotal temperature was found among monozygotic twins (r = 0.64, P = 0.01), but not in dizygotic twins and single-born brothers (r = 0.17, NS). Similar results were found for other percentiles of temperature. CONCLUSIONS: The results suggest a genetic component to the variation in scrotal temperature. An hereditary element in male fecundity may be expressed through scrotal temperature, which constitutes a mechanism independent of those responsible for the development of the sperm producing epithelium.

Reproductive effects of male psychologic stress.

OBJECTIVES: Male psychologic stress can affect semen quality and couple fecundability. METHODS: We conducted a prospective study of 430 Danish couples who were trying to become pregnant for the first time. In each menstrual cycle, both partners filled out a 12-item version of the General Health Questionnaire (GHQ-12), an assessment of psychologic stress. A blood sample was drawn from both partners. The men collected a semen sample at enrollment and each month during follow up. RESULTS: Semen quality was not related to the man's GHQ score in either within-subject analyses or between-subject analyses. There were no consistent associations between stress and serum concentration of luteinizing hormone, follicle-stimulating hormone, inhibin B, testosterone, or estradiol. The pregnancy rate was 14% in cycles with an absolute GHQ-12 score in the highest quartile, compared with 18% in low-stress cycles. Odds of pregnancy decreased moderately with increasing score. The effect was confined to 77 men with a sperm density below 20 million/mL (adjusted odds ratio = 0.06; 95% confidence interval = 1.01-0.58 for highest distressed quartile vs. lowest distressed quartile in this low sperm density group). In within-subject analyses, cycle-specific changes in male stress did not change the odds of pregnancy. High absolute score was associated with a lower frequency of sexual intercourse, but adjustment for frequency had little effect. CONCLUSION: The effect of a man's daily life psychologic stress on his semen quality is small or nonexistent. Our results indicate an effect of stress only on fecundability, and this only among men with low sperm concentration.

Job strain and male fertility.

BACKGROUND: Job strain, defined as high job demands and low job control, has not previously been explored as a possible determinant of male fertility. We collected prospective data on job strain among men, and describe the associations with semen quality and probability of conceiving a clinical pregnancy during a menstrual cycle. METHODS: Danish couples (N = 399) who were trying to become pregnant for the first time were followed for up to 6 menstrual periods. All men collected semen samples, and a blood sample was drawn from both partners. Job demand and job control were measured by a self-administered questionnaire at entry, and in each cycle the participants recorded changes in job control or job demand during the previous 30 days. RESULTS: In adjusted analyses, no associations were found between any semen characteristic or sexual hormones and any job strain variable. The odds for pregnancy were not associated with job strain. CONCLUSIONS: Psychologic job strain encountered in normal jobs in Denmark does not seem to affect male reproductive function.