Evidence from Finland and Sweden on the relationship between early-life diseases and lifetime childlessness in men and women.

The percentage of people without children over their lifetime is approximately 25% in men and 20% in women. Individual diseases have been linked to childlessness, mostly in women, yet we lack a comprehensive picture of the effect of early-life diseases on lifetime childlessness. We examined all individuals born in 1956-1968 (men) and 1956-1973 (women) in Finland (n = 1,035,928) and Sweden (n = 1,509,092) to the completion of their reproductive lifespan in 2018. Leveraging nationwide registers, we associated sociodemographic and reproductive information with 414 diseases across 16 categories, using a population and matched-pair case-control design of siblings discordant for childlessness (71,524 full sisters and 77,622 full brothers). The strongest associations were mental-behavioural disorders (particularly among men), congenital anomalies and endocrine-nutritional-metabolic disorders (strongest among women). We identified new associations for inflammatory and autoimmune diseases. Associations were dependent on age at onset and mediated by singlehood and education. This evidence can be used to understand how disease contributes to involuntary childlessness.

Risk factors for severe respiratory syncytial virus infection during the first year of life: development and validation of a clinical prediction model.

BACKGROUND: Novel immunisation methods against respiratory syncytial virus (RSV) are emerging, but knowledge of risk factors for severe RSV disease is insufficient for optimal targeting of interventions against them. Our aims were to identify predictors for RSV hospital admission from registry-based data and to develop and validate a clinical prediction model to guide RSV immunoprophylaxis for infants younger than 1 year. METHODS: In this model development and validation study, we studied all infants born in Finland between June 1, 1997, and May 31, 2020, and in Sweden between June 1, 2006, and May 31, 2020, along with the data for their parents and siblings. Infants were excluded if they died or were admitted to hospital for RSV within the first 7 days of life. The outcome was hospital admission due to RSV bronchiolitis during the first year of life. The Finnish study population was divided into a development dataset (born between June 1, 1997, and May 31, 2017) and a temporal hold-out validation dataset (born between June 1, 2017, and May 31, 2020). The development dataset was used for predictor discovery and selection in which we screened 1511 candidate predictors from the infants', parents', and siblings' data, and developed a logistic regression model with the 16 most important predictors. This model was then validated using the Finnish hold-out validation dataset and the Swedish dataset. FINDINGS: In total, there were 1 124 561 infants in the Finnish development dataset, 130 352 infants in the Finnish hold-out validation dataset, and 1 459 472 infants in the Swedish dataset. In addition to known predictors such as severe congenital heart defects (adjusted odds ratio 2·89, 95% CI 2·28-3·65), we confirmed some less established predictors for RSV hospital admission, most notably oesophageal malformations (3·11, 1·86-5·19) and lower complexity congenital heart defects (1·43, 1·25-1·63). The prediction model's C-statistic was 0·766 (95% CI 0·742-0·789) in Finnish data and 0·737 (0·710-0·762) in Swedish validation data. The infants in the highest decile of predicted RSV hospital admission probability had 4·5 times higher observed risk compared with others. Calibration varied according to epidemic intensity. The model's performance was similar to a machine learning (XGboost) model using all 1511 candidate predictors (C-statistic in Finland 0·771, 95% CI 0·754-0·788). The prediction model showed clinical utility in decision curve analysis and in hypothetical number needed to treat calculations for immunisation, and its C-statistic was similar across different strata of parental income. INTERPRETATION: The identified predictors and the prediction model can be used in guiding RSV immunoprophylaxis in infants, or as a basis for further immunoprophylaxis targeting tools. FUNDING: Sigrid Jusélius Foundation, European Research Council, Pediatric Research Foundation, and Academy of Finland.

Nationwide health, socio-economic and genetic predictors of COVID-19 vaccination status in Finland.

Understanding factors associated with COVID-19 vaccination can highlight issues in public health systems. Using machine learning, we considered the effects of 2,890 health, socio-economic and demographic factors in the entire Finnish population aged 30-80 and genome-wide information from 273,765 individuals. The strongest predictors of vaccination status were labour income and medication purchase history. Mental health conditions and having unvaccinated first-degree relatives were associated with reduced vaccination. A prediction model combining all predictors achieved good discrimination (area under the receiver operating characteristic curve, 0.801; 95% confidence interval, 0.799-0.803). The 1% of individuals with the highest predicted risk of not vaccinating had an observed vaccination rate of 18.8%, compared with 90.3% in the study population. We identified eight genetic loci associated with vaccination uptake and derived a polygenic score, which was a weak predictor in an independent subset. Our results suggest that individuals at higher risk of suffering the worst consequences of COVID-19 are also less likely to vaccinate.

Determinants of responsiveness to multidisciplinary chronic pain management interventions: protocol for a systematic review and meta-analysis.

INTRODUCTION: The current manuscript presents a protocol for a systematic review and meta-analysis of the evidence regarding the determinants of responsiveness to multidisciplinary management of chronic pain, with pain intensity, pain-related interference, physical functioning and health-related quality of life as the main outcomes, with consideration to multiple secondary outcomes. METHODS AND ANALYSIS: To identify relevant studies, the Ovid MEDLINE, PubMed, Ovid PsycINFO, EBSCO CINAHL and Scopus databases will be searched for all studies exploring factors associated with responsiveness to multidisciplinary pain management from study inception to the present. Cohorts, case-control studies and randomised controlled trials will be included. Independent screening for eligible studies will be completed by a total of four researchers using defined criteria. Data extraction will be executed by two researchers. Study heterogeneity will be estimated using the I2 index. A meta-analysis will be performed using random effects models. Publication bias will be evaluated by means of funnel plots and Egger's test. ETHICS AND DISSEMINATION: The proposed study does not involve collection of primary data. Therefore, no ethical approval is required. The results of the systematic review and meta-analysis will be presented in a peer-reviewed journal and at conferences. PROSPERO REGISTRATION NUMBER: CRD42021236424.

Worse health-related quality of life, impaired functioning and psychiatric comorbidities are associated with excess mortality in patients with severe chronic pain.

BACKGROUND: Severe chronic pain that interferes with daily activities is associated with an increased risk of mortality. We assessed the overall mortality of tertiary chronic pain patients in comparison with the general population, with a special aim to analyse the association of health-related quality of life (HRQoL) and its dimensions with the risk of death. METHODS: In this prospective observational follow-up study, patients with non-cancer chronic pain attended an outpatient multidisciplinary pain management (MPM) episode in a tertiary pain clinic in 2004-2012 and were followed until May 2019. Mortality between the patients and the general population was compared with standardized mortality ratios (SMR) in different age groups. Causes of death and comorbidities were compared among the deceased. Association of mortality and HRQoL and its dimensions, measured with the 15D instrument, was studied with Cox proportional hazards model. RESULTS: During a mean of 10.4-year follow-up of 1498 patients, 296 died. The SMR in the youngest age group (18-49 years) was significantly higher than that of the general population: 2.6 for males and 2.9 for females. Even elderly females (60-69 years) had elevated mortality (SMR 2.3). Low baseline HRQoL at the time of MPM, as well as poor ratings in the psychosocial dimensions of HRQoL, was associated with an increased risk of death. CONCLUSIONS: Our results support the role of HRQoL measurement by a validated instrument such as the 15D in capturing both the physical and the psychological symptom burden, and consequently, an elevated risk of death, in patients with chronic pain. SIGNIFICANCE: Severe chronic pain is associated with elevated mortality. In patients in chronic pain under 50 years old, the mortality was 2.5-3 times higher than in the general population. Psychological distress appears to contribute to the increased mortality. Regular follow-up by health-related quality of life (HRQoL) measurement could be useful in identifying patients in chronic pain who are in need of intensive symptom management and to prevent early death.

Health-related quality of life in patients with chronic orofacial pain compared with other chronic pain patients.

BACKGROUND: Health-related quality of life (HRQoL) of orofacial pain patients is lower than that of the general population and impaired in multiple dimensions. The aim of the present study was to investigate HRQoL of orofacial pain patients in comparison with patients suffering from other chronic pain disorders. MATERIALS AND METHODS: One hundred and fifty-one tertiary care facial pain patients (mean age, 50 years; standard deviation [SD], 15; 119 females), were compared with 312 other non-cancer chronic pain patients (mean age, 46 years; SD, 13; 204 women), recruited from three multidisciplinary pain clinics in Finland. The groups were compared using the 15D, and pain-related measures such as pain interference, pain acceptance, anxiety, depression, and sleep. Statistical comparisons between groups were done using t test, χ2 test, or analysis of covariance. Multivariate linear regression analysis was used to study whether pain-related aspects influencing HRQoL are similar between the patient groups. RESULTS: The 15D score was significantly higher in facial pain patients (0.823; SD, 0.114) indicating better HRQoL in comparison with other chronic pain patients (0.732; SD, 0.107) (p < .001). The 15D profiles of studied populations resembled each other but orofacial pain patients showed significantly higher scores for most individual 15D dimensions. Dimensions regarding discomfort and symptoms and sleep were most affected in both groups. Orofacial pain patients showed less psychosocial disability and better acceptance of their pain. Pain acceptance was a weaker explanatory factor of HRQoL in orofacial pain patients. CONCLUSION: Compared to other non-cancer chronic pain, chronic pain in the orofacial area causes less impairment in HRQoL. Orofacial pain patients showed less psychosocial disability and better pain acceptance.

The impact of chronic orofacial pain on health-related quality of life.

Background and aims Health-related quality of life (HRQoL) assessments have been widely used in pain medicine as they are able to reflect the subjective and multidimensional nature of chronic pain. Studies have shown a consistent impairment in HRQoL in different chronic pain conditions. However, it is not known whether HRQoL is impaired in chronic orofacial pain (OFP). The generic 15D HRQoL instrument has been shown to fare as well as or better than other generic HRQoL instruments in the study of chronic pain. The aim was to investigate HRQoL in patients with chronic OFP using the generic 15D HRQoL instrument. The validity of the instrument was tested by studying the association of the 15D data with pain interference. Methods One hundred fifty-one patients (mean age 50 years, SD 15 years, 119 females) were recruited from three tertiary facial pain clinics. HRQoL data of the participants were contrasted with that of an age- and gender- standardized sample of general population by comparing the mean 15D scores and profiles. The data for the general population came from the National Health 2011 Survey representing Finnish population aged 18 years and older. Pain interference was assessed using Brief Pain Inventory. Based on pain interference distribution the participants were divided into tertiles. Statistical comparison between patient and population HRQoL values were performed using Monte-Carlo-type simulations. Statistical significance for the hypothesis of linearity was evaluated by using generalized linear models. Results The mean 15D score of OFP patients (0.824, SD 0.113) was statistically significantly lower than that of the age- and gender-standardized general population (0.929, SD 0.019) (p < 0.001). The difference between the patients and the general population was also clinically important, i.e. over the minimum clinically important difference in the 15D score. All mean 15D dimension values were significantly lower compared with the general population values (p < 0.001 for all dimensions). The largest differences were seen in the dimensions of discomfort and symptoms (0.418, SD 0.222 vs. 0.816, SD 0.027), sleeping (0.693, SD 0.258 vs. 0.838, SD 0.029), and vitality (0.702, SD 0.221 vs. 0.884 SD 0.026). There was a statistically significant linear decrease in the 15D dimension values (p < 0.001) with increasing pain interference. The greatest differences were found on the dimensions of discomfort and symptoms, sleeping and vitality. Conclusions HRQoL is significantly impaired in patients with chronic OFP. A decrease in the 15D dimension values with increasing pain interference indicated convergent validity between 15D and pain interference. Implications The findings suggest that 15D is an appropriate instrument for use in the assessment of HRQoL in OFP patients. By showing the usefulness of the 15D, the present study may encourage further use of generic HRQoL assessments in the study of chronic OFP, and contribute e.g. to the implementation of HRQoL as one of the core outcome measures in future treatment studies on chronic OFP.

Health-related quality of life change in patients treated at a multidisciplinary pain clinic.

BACKGROUND: Multidisciplinary pain management (MPM) is a generally accepted method for treating chronic pain, but heterogeneous outcome measures provide only limited conclusions concerning its effectiveness. Therefore, further studies on the effectiveness of MPM are needed to identify subgroups of patients who benefit, or do not benefit, from these interventions. Our aim was to analyse health-related quality of life (HRQoL) changes after MPM and to identify factors associated with treatment outcomes. METHODS: We carried out a real world observational follow-up study of chronic pain patients referred to a tertiary multidisciplinary outpatient pain clinic to describe, using the validated HRQoL instrument 15D, the HRQoL change after MPM and to identify factors associated with this change. 1,043 patients responded to the 15D HRQoL questionnaire at baseline and 12 months after the start of treatment. Background data were collected from the pre-admission questionnaire of the pain clinic. RESULTS: Fifty-three percent of the patients reported a clinically important improvement and, of these, 81% had a major improvement. Thirty-five percent reported a clinically important deterioration, and 12% had no change in HRQoL. Binary logistic regression analysis revealed that major improvement was positively associated with shorter duration of pain (<3 years), worse baseline HRQoL, higher education levels and being employed. CONCLUSIONS: The majority of the patients reported significant HRQoL improvement after multidisciplinary pain management. Better understanding of the factors associated with treatment outcomes is needed to meet the needs of those who had unfavourable outcomes. SIGNIFICANCE: Multidisciplinary pain management (MPM) increases the health-related quality of life (HRQoL) in most patients. More research into factors associated with HRQoL change is needed to understand why not all patients benefit from MPM and how MPM approaches could be improved to meet the needs of these patients.

Validation of EQ-5D and 15D in the assessment of health-related quality of life in chronic pain.

Chronic pain has a significant impact on quality of life. Measurement of health-related quality of life (HRQoL) is essential in the assessment of pain management outcomes, but different instruments have produced varying results. We assessed the validity of 2 HRQoL instruments, EuroQol 5 dimensions questionnaire (EQ-5D) and 15-dimensional health-related quality of life measure (15D), in patients with challenging chronic pain. Three hundred ninety-one chronic noncancer pain patients referred to tertiary pain clinics completed EQ-5D, 15D, and a broad set of questionnaires mapping socioeconomic factors, self-rated health, pain intensity and interference, depression, pain acceptance, pain-related anxiety, and sleep. The 2 HRQoL instruments were compared with each other, and head-to-head comparisons were made with self-rated health and the symptom-specific questionnaires. 15D and EQ-5D showed moderate agreement (ρ = 0.66), but there were also considerable differences between the instruments. 15D correlated better with self-rated health than EQ-5D (ρ = -0.62 vs -0.45, P < 0.001). The EQ-5D appeared less sensitive than 15D especially in those patients with chronic pain who had a better health status. The principal component constructed from measures of pain intensity and interference, anxiety, pain acceptance, depression, and sleep had higher standardized beta coefficients with 15D than with EQ-5D (P = 0.038). The principal component explained more variance in the 15D (R = 0.65) than in the EQ-5D (R = 0.43). The study identified differences in the pain-related variables between the EQ-5D and the 15D. In patients with chronic pain, both instruments are valid, but 15D appears somewhat more sensitive than EQ-5D.

Health-related quality of life and burden of disease in chronic pain measured with the 15D instrument.

Health-related quality of life (HRQoL) measurement aims to capture the complete, subjective health state of the patients and to comprehensively evaluate treatment outcomes. The aim of this study was to assess, using the 15D HRQoL instrument, HRQoL in a sample of 1528 chronic pain patients, referred to the multidisciplinary pain clinic of the Helsinki University Hospital during 2004 to 2012. The 15D results of the chronic pain patients were compared with those of a matched general population. To analyse the properties of the 15D, the results were compared with the preadmission questionnaire of the pain clinic, containing questions about background factors, aspects of the pain, and its impact on life. The mean 15D score of the chronic pain patients was one of the lowest reported using 15D; 0.710 vs 0.922 in the general population. It equalled the score of advanced cancer patients in palliative care. The 15D scores were normally distributed, and 15D showed both statistically and clinically significant discriminative power in pain-related background factors. Visual analogue scale on pain intensity, visual analogue scale on pain-related distress, and the impact of pain on daily life correlated well with the 15D score. Pain intensity did not have independent predictive value on the score. The results indicate heavy perceived burden of illness in chronic pain patients. In light of the questions analysed, 15D appears sensitive and discriminative in chronic pain patients in tertiary care. Instead of pain intensity, the impaired HRQoL in chronic pain was mainly because of the psychosocial aspects of pain.