Traumatic spinal cord injury and its correlation to risk of autoimmune/-inflammatory disease.

STUDY DESIGN: Nationwide epidemiological open cohort study. OBJECTIVES: To evaluate whether individuals with traumatic spinal cord injury (TSCI) are more prone to develop autoimmune diseases compared to a general non-TSCI population. SETTING: Danish public national registries. METHODS: An open nationwide cohort, including individuals born in Denmark from or alive during 1945-2018 was collected and the study period was 1980-2018. Poissons Log-linear regression estimated the incidence rate ratio (IRR) for developing eight groups of autoimmune diseases. A dose-response relationship based on the cervical/thoracic level of injury was assessed by stratification. RESULTS: The cohort included 3,272 individuals with TSCI and 4.8 million background individuals, accounting for 50,865 and 140 million person-years respectively. The TSCI population had an overall IRR of 1.81 (95% CI, 1.59 to 2.05) of getting any autoimmune disease. Subgroup analysis found positive associations for; a) Other neurologic IRR 5.19 (95% CI, 2.79 to 9.65), b) multiple sclerosis IRR 3.70 (95% CI, 2.54 to 5.40), c) Dermatologic IRR 2.57 (95% CI, 1.86 to 3.55), d) Type 1 diabetes mellitus IRR 2.01 (95% CI, 1.54 to 2.61), e) Systemic 1.92 (95% CI, 1.44 to 2.55), and f) Gastroenterologic IRR 1.42 (95% CI, 1.05 to 1.92). Cervical levels of TSCI showed an IRR of 1.70 (95% CI, 1.43 to 2.02), while thoracic levels had an IRR 1.98 (95% CI, 1.63 to 2.39). CONCLUSIONS: TSCI may be an individual risk factor of developing an autoimmune disease. There does not appear to exist a dose-response relationship from the level of injury. SPONSORSHIP: None.

Maternal coffee consumption and biomarkers of reproductive health in young, adult sons: a cohort study.

It has been proposed that poor semen quality may have its origins from fetal programming due to environmental factors. We investigated whether maternal coffee consumption during early pregnancy was associated with biomarkers of reproductive health in adult sons in the Fetal Programming of Semen Quality (FEPOS) cohort. In 2017-2019, 1058 young men provided a semen and blood sample and self-measured their testis volume. Daily maternal coffee consumption was reported by the mothers around gestational week 17. We estimated relative percentage differences with 95 % confidence intervals (CI) for semen quality measures, testis volume, and reproductive hormone levels according to maternal coffee consumption during pregnancy. Maternal coffee consumption (yes/no (reference)) was associated with lower semen volume (-7.0 % (95 % CI:-12.9;-0.7)), lower proportion of morphologically normal spermatozoa (-8.3 % (95 % CI:-16.5;0.8)), higher proportion of non-progressive and immotile spermatozoa (4.3 % (95 % CI:-1.5;10.3)), and lower testis volume (-4.8 % (95 % CI:-9.0;-0.4)). No indication of a dose-response association or threshold effects was observed in the categorized and continuous analyses. No associations with reproductive hormone levels were observed in any of the analyses. Overall, the study does not provide obvious indications that maternal coffee consumption in early pregnancy deteriorates male offspring fecundity. While some minor changes were observed, most estimates were small with confidence intervals overlapping the null. Future studies, preferably with greater exposure contrast, are warranted before a conclusion can be drawn as to whether maternal coffee consumption during pregnancy constitutes a risk for reproductive health in adult sons.

Low-dose ketamine as an adjunct to morphine: A randomized controlled trial among patients with and without current opioid use.

BACKGROUND: Pain is a common complaint among patients presenting to the emergency department (ED), yet pain treatment is frequently suboptimal. The aim of this study was to determine the effectiveness of low-dose ketamine (LDK) as an adjunct to morphine versus morphine alone for treatment of acute pain among ED patients with and without current opioid use. METHODS: Adult patients presenting with acute pain of ≥5 on a numeric rating scale (0-10) who were deemed by their treating ED physician to require intravenous opioids were randomized to receive either 0.1 mg/kg ketamine (treatment group) or isotonic saline (placebo) as an adjunct to morphine. Patients with and without current opioid use were randomized separately. Pain was measured at baseline (T0) and 10, 20, 30, 45, 60, and 120 min after randomization. The primary outcome was pain reduction from T0 to T10. Secondary outcomes included pain intensity over 120 min, need of rescue opioids, side effects, and patient and provider satisfaction. RESULTS: A total of 116 patients were included from May 2022 to August 2023. Median (IQR) age was 51 (36.5-67) years; 58% were male and 36% had current opioid use. Pain reduction from T0 to T10 was greater in the LDK group (4 [IQR 3-6]) compared to the placebo group (1 [IQR 0-2]; p = 0.001). Pain intensity was lower in the LDK group at T10, T20, and T30, compared to the placebo group. There was a higher risk of nausea, vomiting, and dissociation in the LDK group during the first 10 min. CONCLUSIONS: LDK may be effective as an adjunct analgesic to morphine for short-term pain relief in treatment of acute pain in the ED for both patients with and without current opioid use.

COVID-19 vaccination and involuntary movements: A longitudinal panel study.

OBJECTIVE: Despite high COVID-19 vaccination rates in many populations, concerns persist about potential adverse events, including concerns about involuntary movements. While case studies have shown occurrences of involuntary movements following COVID-19 vaccination, no systematic studies have explored this association. Our study aims to investigate the relationship between COVID-19 vaccination and involuntary movements. METHODS: This study employs a longitudinal panel design. The study population consists of 165,834 responses from a total of 97,537 unique individuals sourced from the BiCoVac cohort, which is a randomly sampled cohort of Danish individuals aged 16 to 65. Data were collected through a combination of questionnaires and national registers, and analyses were conducted using mixed effects logistic regression. RESULTS: Vaccinated individuals had lower odds of reporting involuntary movements compared to non-vaccinated individuals. Although adjustments attenuated the results, a consistent pattern of lower odds was observed among the vaccinated individuals. The strongest association for the first dose was observed in individuals who received the vaccine within the last 4 weeks before reporting symptoms (OR = 0.72 (0.60; 0.85)). For the second dose, the strongest association was found in individuals who received the second vaccine dose more than 4 weeks before reporting symptoms (OR = 0.77 (0.65; 0.91)). CONCLUSION: The results of the study do not indicate involuntary movements as an adverse reaction to the COVID-19 vaccine. These findings support the safety profile of the COVID-19 vaccine concerning involuntary movements and contribute to enhancing public trust in vaccination programs.

Ophthalmic quality of life in the adult Danish population: an epidemiological study.

BACKGROUND: Ophthalmic quality of life (OQoL) has been investigated in selected parts of general populations and in patients with ocular disease, but OQoL in unselected general populations has not been studied in detail. The present study reports OQoL obtained from a representative sample of the adult Danish population 2020-2022. METHODS: The FORSYN study invited 10 350 citizen representatives for the adult Danish population for a non-mydriatic eye examination and answer the National Eye Institute Visual Function Questionnaire with 39 items in the validated Danish translation. The results from the 3384 (32.7%) persons who participated in the study were weighted on the basis of relevant socio-economic factors, and data were projected to represent the total population. Binocular visual acuity was below 0.1 corresponding to legal blindness in 0.22% of this population. RESULTS: OQoL was positively correlated with binocular visual acuity up to better than 93 ETDRS letters, negatively correlated with age for persons younger than 60 years of age and again positively correlated with age for persons older than 60 years. OQoL was negatively correlated with increasing ametropia and refractive error above 1 dioptre and encompassed more OQoL parameters for hyperopic than for myopic persons. CONCLUSIONS: The study underlines the benefits of improving visual acuity even within the normal range and of adjusting uncorrected refraction errors in the general population. OQoL is positively correlated with age in older persons independently of visual acuity, sex, refractive power and previous cataract surgery.

Point-of-care testing and antibiotics prescribing in out-of-hours general practice: a register-based study in Denmark.

BACKGROUND: Point-of-care testing may reduce diagnostic uncertainty in case of suspicion of bacterial infection, thereby contributing to prudent antibiotic prescribing. We aimed to study variations in the use of point-of-care tests (C-reactive protein test, rapid streptococcal antigen detection test, and urine dipstick) among general practitioners (GPs) and the potential association between point-of-care testing and antibiotic prescribing in out-of-hours general practice. METHODS: We conducted a population-based observational register-based study, based on patient contacts with out-of-hours general practice in the Central Denmark Region in 2014-2017. The tendency of GPs to use point-of-care testing was calculated, and the association between the use of point-of-care testing and antibiotic prescribing was evaluated with the use of binomial regression. RESULTS: Out-of-hours general practice conducted 794,220 clinic consultations from 2014 to 2017, of which 16.1% resulted in an antibiotic prescription. The GP variation in the use of point-of-care testing was largest for C-reactive protein tests, with an observed variation (p90/p10 ratio) of 3.0; this means that the GPs in the 90th percentile used C-reactive protein tests three times as often as the GPs in the 10th percentile. The observed variation was 2.1 for rapid streptococcal antigen detection tests and 1.9 for urine dipsticks. The GPs who tended to use more point-of-care tests prescribed significantly more antibiotics than the GPs who tended to use fewer point-of-care tests. The GPs in the upper quintile of the tendency to use C-reactive protein test prescribed 22% more antibiotics than the GPs in the lowest quintile (21% for rapid streptococcal antigen detection tests and 8% for urine dipsticks). Up through the quintiles, this effect exhibited a positive linear dose-response correlation. CONCLUSION: The GPs varied in use of point-of-care testing. The GPs who tended to perform more point-of-care testing prescribed more antibiotics compared with the GPs who tended to perform fewer of these tests.

Psychiatric Morbidity Is Common Among Children With Juvenile Idiopathic Arthritis: A National Matched Cohort Study.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a chronic rheumatic disease that causes joint inflammation and pain. Previous studies have indicated affected mental health and increased risk of psychiatric conditions among patients with JIA. We aimed to explore differences in psychiatric morbidity between children with JIA and their peers. We further studied if parental socioeconomic status (SES) influences the association between JIA and the risk of psychiatric morbidity. METHODS: We used a matched cohort design to estimate the association between JIA and psychiatric disease. Children with JIA, born between 1995 and 2014, were identified in Danish national registers. Based on birth registers, we randomly selected 100 age- and sex-matched children per index child. Index date was the date of the fifth JIA diagnosis code or the date of matching for reference children. End of follow-up was the date of psychiatric diagnosis, death, emigration, or December 31, 2018, whatever came first. Data were analyzed using a Cox proportional hazard model. RESULTS: We identified 2086 children with JIA with a mean age at diagnosis of 8.1 years. Children with JIA had a 17% higher instantaneous risk of a psychiatric diagnosis when compared with the reference group, with an adjusted hazard ratio of 1.17 (95% CI 1.02-1.34). Relevant associations were found only for depression and adjustment disorders. Stratifying our analysis for SES showed no modifying effect of SES. CONCLUSION: Children with JIA had a higher risk of psychiatric diagnoses compared to their peers, especially diagnoses of depression and adjustment disorders. The association between JIA and psychiatric disease did not depend on parental SES.

Parental physical disease severity and severe documented physical child abuse: a prospective cohort study.

Successful prevention of physical child abuse is dependent on improvements in risk assessment. The risk of abuse is assumed to increase when family stressors overcome resources. Severe physical disease can increase stress, and parental physical disease has been studied as a risk factor for physical child abuse, but with heterogeneous definitions. This study evaluated the relation between parental physical disease severity and severe documented physical child abuse. Models were based on data on children aged 0-17 years in Denmark between 1997 and 2018, and their parents. Severe documented physical child abuse was modeled as violence against a child registered by either health authorities in treatment or mortality registries, or police authorities in cases confirmed by the courts. Parental physical disease severity was modeled as the sum of Charlson Comorbidity Index scores for the child's parents. The causal connection was examined in two model types: a survival model comparing exposed with non-exposed children, adjusted for covariates at baseline, and a G-model, taking time-varying covariates, including income and parental psychiatric disease into account. Neither model showed an association between parental physical disease severity and severe documented physical child abuse, with RR 0.99 and 95% CI (0.93-1.05) for the survival model and RR 1.08 for the G-model (CI not calculated).  Conclusion: In the model studied, parental physical disease severity was not a risk factor for severe documented physical child abuse. Individual categories of physical disease remain to be examined.  Trial registration: The study was pre-registered on Open Science Framework, https://osf.io/fh2sr . What is Known: • Parental physical disease severity has been studied previously as a risk indicator of physical child abuse, but based on heterogeneous definitions. • Previous studies have not studied parental physical disease severity preceding physical child abuse. What is New: • Parental severe physical disease was not prospectively associated with severe documented physical child abuse in a survival model, a G-model and a number of sensitivity analyses, respectively. • Results should be replicated in samples from populations without universal health care, and using different categories of disease.

Exploratory assessment of parental physical disease categories as predictors of documented physical child abuse.

Improved prediction of physical child abuse could aid in developing preventive measures. Parental physical disease has been tested previously as a predictor of documented physical child abuse but in broad categories and with differing results. No prior studies have tested clinically recognizable categories of parental disease in a high-powered dataset. Using Danish registries, data on children and their parents from the years 1997-2018 were used to explore several parental physical disease categories' associations with documented physical child abuse. For each disease category, survival analysis using pseudovalues was applied. When a parent of a child was diagnosed or received medication that qualified for a category, this family and five comparison families not in this disease category were included, creating separate cohorts for each category of disease. Multiple analyses used samples drawn from 2,705,770 children. Estimates were produced for 32 categories of physical diseases. Using Bonferroni-corrected confidence intervals (CIc), ischemic heart disease showed a relative risk (RR) of 1.44 (CIc 1.13-1.84); peripheral artery occlusive disease, RR 1.39 (CIc 1.01-1.90); stroke, RR 1.19 (1.01-1.41); chronic pulmonary disease, RR 1.33 (CIc 1.18-1.51); ulcer/chronic gastritis, RR 1.27 (CIc 1.08-1.49); painful condition, 1.17 (CIc 1.00-1.37); epilepsy, RR 1.24 (CIc 1.00-1.52); and unspecific somatic symptoms, RR 1.37 (CIc 1.21-1.55). Unspecific somatic symptoms were present in 71.87% of families at some point during the study period. CONCLUSION: Most parental physical disease categories did not show statistically significant associations, but some showed predictive ability. Further research is needed to explore preventive potential. WHAT IS KNOWN: • Few and broad categories of parental physical disease have been examined as risk factors for severe physical child abuse; no prior study has used several categories as predictors. WHAT IS NEW: • Unspecific symptoms, ischemic heart disease, peripheral artery occlusive disease, stroke, chronic pulmonary disease, stomach ulcer/chronic gastritis, painful condition, and epilepsy all showed to be potential predictors, with unspecific symptoms being the most prevalent.

As-needed opioid dosing for emergency patients with a daily use of opioids.

BACKGROUND: Patients with a daily use of opioids have a higher risk of insufficient pain treatment during hospitalization than other patients. This study aimed to examine whether as-needed opioid doses (PRN) were adequately adjusted when patients were admitted to the emergency department (ED) with pain. METHODS: Patients, with a daily use of opioids, who received PRN opioid within the first 3 h after admission at the ED at Aarhus University Hospital, Denmark, were prospectively included from February 2021 to June 2021. The primary outcome was the proportion of patients receiving an inadequate initial dose of PRN opioid, here defined as <15% of daily dose of opioids (DDO) based on sparse evidence, but aligning with the prevailing clinical practice. Secondary outcomes included risk of an inadequate PRN dose in relation to DDO (patients were dichotomized into two groups (DDO <60 or ≥60 mg/day). RESULTS: Among 252 patients admitted to the ED with a daily use of opioids, 149 were admitted with pain and 82 received a PRN opioid dose within 3 h. Twenty-seven out of 82 (33%) patients received a PRN dose of <15% of DDO (95% CI: 23.7-43). When dichotomised; 10 out of 50 (20%) patients with a DDO <60 mg/day (95% CI: 10.0-33.7) versus 17 out of 32 (53.1%) patients with a DDO ≥60 mg/day (95% CI: 34.7-70.9) received an inadequate PRN dose (relative risk, RR: 2.65 [95% CI: 1.4-5.1]). CONCLUSIONS: Patients with daily use of opioids presenting in the ED with acute pain had a high risk of inadequate PRN opioid dose, especially if the DDO was high. Awareness about and education focusing on sufficient PRN doses for patients with a daily use of opioids is (still) called for.