Dietary Caffeine and Brain Dopaminergic Function in Parkinson Disease.

OBJECTIVE: This study was undertaken to investigate the effects of dietary caffeine intake on striatal dopamine function and clinical symptoms in Parkinson disease in a cross-sectional and longitudinal setting. METHODS: One hundred sixty-three early Parkinson disease patients and 40 healthy controls were investigated with [123I]FP-CIT single photon emission computed tomography, and striatal dopamine transporter binding was evaluated in association with the level of daily coffee consumption and clinical measures. After a median interval of 6.1 years, 44 patients with various caffeine consumption levels underwent clinical and imaging reexamination including blood caffeine metabolite profiling. RESULTS: Unmedicated early Parkinson disease patients with high coffee consumption had 8.3 to 15.4% lower dopamine transporter binding in all studied striatal regions than low consumers, after accounting for age, sex, and motor symptom severity. Higher caffeine consumption was further associated with a progressive decline in striatal binding over time. No significant effects of caffeine on motor function were observed. Blood analyses demonstrated a positive correlation between caffeine metabolites after recent caffeine intake and dopamine transporter binding in the ipsilateral putamen. INTERPRETATION: Chronic caffeine intake prompts compensatory and cumulative dopamine transporter downregulation, consistent with caffeine's reported risk reduction in Parkinson disease. However, this decline does not manifest in symptom changes. Transiently increased dopamine transporter binding after recent caffeine intake has implications for dopaminergic imaging guidelines. ANN NEUROL 2024;96:262-275.

Predicting successful ageing among older adults seems possible even as far as two decades ahead.

BACKGROUND: Successful ageing is the term often used for depicting exceptional ageing and can be measured with multidimensional models including physical, psychological and social wellbeing. The aim of this study was to test multidimensional successful ageing models to investigate whether these models can predict successful ageing, and which individual subcomponents included in the models are most significantly associated with successful ageing. METHODS: Successful ageing was defined as the ability to live at home without daily care at the age of 84 years or over. Data on the participants' physical, psychological and social wellbeing were gathered at baseline and the follow-up period was 20 years. Four successful ageing models were constructed. Backward stepwise logistic regression analysis was used to identify the individual subcomponents of the models which best predicted successful ageing. RESULTS: All successful ageing models were able to predict ageing successfully after the 20-year follow-up period. After the backward stepwise logistic regression analysis, three individual subcomponents of four models remained statistically significant and were included in the new model: having no heart disease, having good self-rated health and feeling useful. As a model, using only these three subcomponents, the association with successful ageing was similar to using the full models. CONCLUSIONS: Multidimensional successful ageing models were able to predict successful ageing after a 20-year follow-up period. However, according to the backward stepwise logistic regression analysis, the three subcomponents (absence of heart disease, good self-rated health and feeling useful) significantly associated with successful ageing performed as well as the multidimensional successful ageing models in predicting ageing successfully.

Neuroprotective Effects of Inhaled Xenon Gas on Brain Structural Gray Matter Changes After Out-of-Hospital Cardiac Arrest Evaluated by Morphometric Analysis: A Substudy of the Randomized Xe-Hypotheca Trial.

BACKGROUND: We have earlier reported that inhaled xenon combined with hypothermia attenuates brain white matter injury in comatose survivors of out-of-hospital cardiac arrest (OHCA). A predefined secondary objective was to assess the effect of inhaled xenon on the structural changes in gray matter in comatose survivors after OHCA. METHODS: Patients were randomly assigned to receive either inhaled xenon combined with target temperature management (33 °C) for 24 h (n = 55, xenon group) or target temperature management alone (n = 55, control group). A change of brain gray matter volume was assessed with a voxel-based morphometry evaluation of high-resolution structural brain magnetic resonance imaging (MRI) data with Statistical Parametric Mapping. Patients were scheduled to undergo the first MRI between 36 and 52 h and a second MRI 10 days after OHCA. RESULTS: Of the 110 randomly assigned patients in the Xe-Hypotheca trial, 66 patients completed both MRI scans. After all imaging-based exclusions, 21 patients in the control group and 24 patients in the xenon group had both scan 1 and scan 2 available for analyses with scans that fulfilled the quality criteria. Compared with the xenon group, the control group had a significant decrease in brain gray matter volume in several clusters in the second scan compared with the first. In a between-group analysis, significant reductions were found in the right amygdala/entorhinal cortex (p = 0.025), left amygdala (p = 0.043), left middle temporal gyrus (p = 0.042), left inferior temporal gyrus (p = 0.008), left parahippocampal gyrus (p = 0.042), left temporal pole (p = 0.042), and left cerebellar cortex (p = 0.005). In the remaining gray matter areas, there were no significant changes between the groups. CONCLUSIONS: In comatose survivors of OHCA, inhaled xenon combined with targeted temperature management preserved gray matter better than hypothermia alone. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT00879892.

Close Collaboration with Parents Affects the Length of Stay and Growth in Preterm Infants: A Register-Based Study in Finland.

INTRODUCTION: This study aimed to evaluate how Close Collaboration with Parents (CC), a neonatal intensive care unit (NICU)-wide educational model for healthcare staff to improve their family-centred care practices, affects the length of stay (LOS), growth, and later hospital visits and rehospitalizations of preterm infants. METHODS: This register-based study included all preterm infants born below 35 weeks of gestation in Finland from 2006 to 2020. Eligible infants were classified into the Full Close Collaboration (Full-CC) group (n = 2,104) if the NICUs of both the delivery and discharge hospitals had implemented the intervention; into the Partial-CC group (n = 515) if only one of the NICUs had implemented the intervention; and into the control group (n = 11,621) if neither had implemented the intervention. RESULTS: The adjusted LOS, the primary outcome, was 1.8 days or 6% shorter in the Full-CC group than in the control group (geometric mean ratio 0.94, 95% confidence interval [95% CI] 0.89-1.00). Growth was better in the Full-CC group compared to the control group: adjusted group difference 11.7 g/week (95% CI, 1.4-22.0) for weight, 1.3 mm/week (95% CI, 0.6-2.0) for length. The Full-CC group infants had lower odds of having any unscheduled outpatient visits compared to the control group (adjusted odds ratio 0.81; 95% CI, 0.67-0.98). No significant differences were found in any other comparisons. DISCUSSION/CONCLUSION: The unit-wide intervention improving family-centred care practices in NICUs may lead to more efficient use of hospital resources by shortening the LOS, improving growth, and decreasing hospital visits of preterm infants.

The knowledge of and educational interest in sexual medicine among Finnish medical and midwifery students: A web-based study.

INTRODUCTION: Many elements of life can affect sexual health; thus, healthcare professionals require good knowledge of sexual medicine to encounter patients with these issues. We aimed to study final-year medical and midwifery students' self-reported knowledge of factors associated with sexuality and their knowledge of how to evaluate and treat/counsel patients with sexual problems. In addition, educational interests regarding sexual medicine were assessed. METHODS: In a cross-sectional study, a web-based questionnaire was distributed to final-year medical (n=233) and midwifery (n=131) students graduating between December 2018 and May 2019 in Finland. RESULTS: Both student groups self-reported insufficient knowledge of how to consider sexuality in mentally ill patients, how to encounter victims of domestic violence/sexual abuse, and how multiculturalism affects sexuality. In addition, compared to the midwifery students, the medical students were more likely to self-report insufficient knowledge of the basics of sexual pleasure and treating the lack of it (p<0.001), including how to treat sexual problems due to relationship problems (p<0.001) or chronic diseases (p=0.015). Although several educational areas of interest arose, both student groups had two mutual most desirable educational interests: 1) reasons for dyspareunia and its treatment, n=117/233 (50.2%) for medical students, and n=60/131 (45.8%) for midwifery students; and 2) lack of sexual desire and its treatment, n=100/233 (42.9%) for medical students, and n=55/131 (42.0%) for midwifery students. CONCLUSIONS: In both student groups, the self-reported knowledge of sexual medicine was insufficient. Thus, more education on sexual medicine should be included in the curricula of medical and midwifery education.

Attitudes and practice patterns of Finnish obstetrician-gynecologists regarding patients' sexual problems.

OBJECTIVE: Female sexual problems are common but are not routinely assessed in obstetrician-gynecologist appointments. Therefore, we evaluated obstetrician-gynecologists' attitudes and practice patterns regarding their patients' sexual problems. STUDY DESIGN: A web-based questionnaire was used to collect information from each respondent on gender, age, education, occupational status, and the total number of patients treated per day and sexual issues dealt with per day. MAIN OUTCOME MEASURES: This study covered three fields of interest: 1) attitudes toward sexual problems, 2) practice patterns in sexual history-taking, and 3) practice patterns in the treatment of sexual problems. RESULTS: Of the 328 respondents, 299 provided eligible responses (specialists, 83 %, n = 249; residents, 17 %, n = 50). Almost all obstetrician-gynecologists (95 %) considered treating sexual problems as an important health care practice, but only 45 % and 53 % asked about sexual problems and sexual life satisfaction during general medical history-taking, respectively. Most obstetrician-gynecologists (86 %) used open conversation to assess sexual history. Half (52 %) of them reported that diagnosing female sexual problems is difficult, with the female obstetrician-gynecologists (54 %) more likely to report difficulty than the male obstetrician-gynecologists (29 %). Of the obstetrician-gynecologists, 15 % prescribed medications, whereas 58 % prescribed other treatments. A third (34 %) received distinct instructions from their organization for referring patients to continued care. CONCLUSIONS: Although almost all obstetrician-gynecologists reported that treating sexual problems is an important health care issue, fewer than half routinely inquired about sexual problems. The practice patterns regarding sexual problems were disorganized. Our results show a need for additional clinical practice guidelines and education in sexual medicine.

Temporal trends in mortality and associated factors among persons with mental disorders: A register-based cohort study.

This study aims to examine 20-year temporal trends in all-cause mortality among psychiatric patients and investigating impacts of risk factors on the time trends based on 218,703 Finnish adults with mental disorders who were discharged from 87 psychiatric hospitals between 1 Jan 1995 and 31 Dec 2014. The age-period-cohort analysis of Poisson model with random hospital effects estimated temporal trends in death rate and associated factors at individual, healthcare system, and society levels, following the WHO multilevel intervention framework model for six major psychiatric diagnosis. The adjusted annual mortality declined by 2.2 % annually (RR: 0.978 [95 % CI 0.976-0.980]) for all individuals, and by 2.8 % after adjusting for all risk factors, with varied decreasing rate between 2.0 % and 3.6 % by diagnosis. Individual level factors accounted for the declining rate by 54.5 % for all patients, with the highest impact on patients with personality disorders, followed by patients with affective disorders and patients with schizophrenia. Identified declining trends and associated factors which are preventable and modifiable for individuals with specific psychiatric diagnosis may lead to develop targeted service and intervention strategies in bringing down mortality further for the population.

Maternal Diabetes and Overweight and Congenital Heart Defects in Offspring.

Importance: Maternal diabetes and overweight or obesity are known to be associated with increased risk of congenital heart defects (CHDs) in offspring, but there are no large studies analyzing outcomes associated with these factors in 1 model. Objective: To investigate the association of maternal diabetes and overweight or obesity with CHDs among offspring in 1 model. Design, Setting, and Participants: This nationwide, population-based register study was conducted in a birth cohort from Finland consisting of all children born between 2006 and 2016 (620 751 individuals) and their mothers. Data were analyzed from January 2022 until November 2023. Exposures: Maternal prepregnancy body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), categorized as underweight (<18.5), normal (18.5-24.9), overweight (25.0-29.9), and obesity (≥30), was assessed. Maternal diabetes status, classified as no diabetes, type 1 diabetes (T1D), type 2 or other diabetes, and gestational diabetes, was assessed. Main Outcomes and Measures: Odds ratios (ORs) of isolated CHDs in children were found. In addition, 9 anatomical CHD subgroups were studied. Results: Of 620 751 children (316 802 males [51.0%]; 573 259 mothers aged 20-40 years [92.3%]) born in Finland during the study period, 10 254 children (1.7%) had an isolated CHD. Maternal T1D was associated with increased odds of having a child with any CHD (OR, 3.77 [95% CI, 3.26-4.36]) and 6 of 9 CHD subgroups (OR range, 3.28 [95% CI, 1.55-6.95] for other septal defects to 7.39 [95% CI, 3.00-18.21] for transposition of great arteries) compared with no maternal diabetes. Maternal overweight was associated with left ventricular outflow tract obstruction (OR, 1.28 [95% CI, 1.10-1.49]) and ventricular septal defects (OR, 0.92 [95% CI, 0.86-0.98]), and obesity was associated with complex defects (OR, 2.70 [95% CI, 1.14-6.43]) and right outflow tract obstruction (OR, 1.31 [95% CI, 1.09-1.58]) compared with normal maternal BMI. Conclusions and Relevance: This study found that maternal T1D was associated with increased risk for most types of CHD in offspring, while obesity and overweight were associated with increased risk for complex defects and outflow tract obstruction and decreased risk for ventricular septal defects. These different risk profiles of T1D and overweight and obesity may suggest distinct underlying teratogenic mechanisms.

National treatment guidelines poorly achieved among older subjects with type 2 diabetes - call to action!

OBJECTIVE: To assess risk factors and factors associated with nonachievement of the treatment target levels among 75-year-old Finns with type 2 diabetes (T2D). DESIGN: Cross-sectional study. SETTING: Outpatient. SUBJECTS: Seventy-five-year-old participants of the Turku Senior Health Clinic Study (N = 1296) with T2D (n = 247). MAIN OUTCOME MEASURES: Nonachievement of fasting blood glucose (FBG), low-density lipoprotein (LDL-C), and blood pressure (BP) levels set by the national treatment guidelines. RESULTS: Nonachievement rates of FBG, BP and LDL-C were 47%, 85%, and 47%, respectively. Non-usage of T2D medication was negatively (adjusted OR 0.38, 95% CI 0.16-0.88) and central obesity positively (1.88, 1.09-3.24) related to nonachievement of FBG target level; alcohol use was positively (3.71, 1.04-13.16) and decreased self-rated health negatively (0.34, 0.12-0.97) related to the nonachievement of BP target level. Nonachievement of LDL-C target level was positively related to poor financial status (3.50, 1.19-10.28) and non-use of lipid-lowering medication (7.70, 4.07-14.56). CONCLUSIONS: Nonachievement rates of the national treatment goals were high among older T2D patients, and nonachievement was related to use of medication, obesity, alcohol use, poor health, and poor financial status. We emphasize the importance of customized target setting by risk factor levels and active treatment.

Disease Severity and Cytokine Expression in the Rhinovirus-Induced First Wheezing Episode.

Wheezing children infected with rhinovirus (RV) have a markedly increased risk of subsequently developing recurrencies and asthma. No previous studies have assessed the association between cytokine response and the severity of acute illness in the first wheezing episode in children infected with RV. Forty-seven children treated both as inpatients and as outpatients infected with RV only, aged 3-23 months, with severe first wheezing episodes were recruited. During acute illness, peripheral blood mononuclear cells (PBMCs) were isolated and stimulated with anti-CD3/anti-CD28 in vitro. A multiplex ELISA was used to quantitatively identify 56 different cytokines. The mean age of the children was 17 months, 74% were males, 79% were hospitalized, and 33% were sensitized. In adjusted analyses, the inpatient group was characterized by decreased expressions of interferon gamma (IFN-γ), interleukin 10 (IL-10), macrophage inflammatory protein 1 alpha (MIP-1α), RANTES (CCL5), and tumor necrosis factor-alpha (TNF-α) and an increased expression of ENA-78 (CXCL5) compared to the outpatient group. The cytokine response profiles from the PBMCs were different between the inpatient and outpatient groups. Our results support that firmly controlled interplay between pro-inflammatory and anti-inflammatory responses are required during acute viral infection to absolve the initial infection leading, to less severe illness.

A metabolic profile of xenon and metabolite associations with 6-month mortality after out-of-hospital cardiac arrest: A post-hoc study of the randomised Xe-Hypotheca trial.

PURPOSE: Out-of-hospital cardiac arrest (OHCA) carries a relatively poor prognosis and requires multimodal prognostication to guide clinical decisions. Identification of previously unrecognized metabolic routes associated with patient outcome may contribute to future biomarker discovery. In OHCA, inhaled xenon elicits neuro- and cardioprotection. However, the metabolic effects remain unknown. MATERIALS AND METHODS: In this post-hoc study of the randomised, 2-group, single-blind, phase 2 Xe-Hypotheca trial, 110 OHCA survivors were randomised 1:1 to receive targeted temperature management (TTM) at 33°C with or without inhaled xenon during 24 h. Blood samples for nuclear magnetic resonance spectroscopy metabolic profiling were drawn upon admission, at 24 and 72 h. RESULTS: At 24 h, increased lactate, adjusted hazard-ratio 2.25, 95% CI [1.53; 3.30], p<0.001, and decreased branched-chain amino acids (BCAA) leucine 0.64 [0.5; 0.82], p = 0.007, and valine 0.37 [0.22; 0.63], p = 0.003, associated with 6-month mortality. At 72 h, increased lactate 2.77 [1.76; 4.36], p<0.001, and alanine 2.43 [1.56; 3.78], p = 0.001, and decreased small HDL cholesterol ester content (S-HDL-CE) 0.36 [0.19; 0.68], p = 0.021, associated with mortality. No difference was observed between xenon and control groups. CONCLUSIONS: In OHCA patients receiving TTM with or without xenon, high lactate and alanine and decreased BCAAs and S-HDL-CE associated with increased mortality. It remains to be established whether current observations on BCAAs, and possibly alanine and lactate, could reflect neural damage via their roles in the metabolism of the neurotransmitter glutamate. Xenon did not significantly alter the measured metabolic profile, a potentially beneficial attribute in the context of compromised ICU patients. TRIAL REGISTRATION: Trial Registry number: ClinicalTrials.gov Identifier: NCT00879892.

New reference limits for cardiac troponin T and N-terminal b-type natriuretic propeptide in elders.

BACKGROUND AND AIMS: Our aim was to define reference limits for cardiac troponin T (cTnT) and N-terminal pro B-type natriuretic peptide (proBNP) that would better reflect their concentrations in older people. In addition, the incidence of acute myocardial infarctions (AMIs) was studied using these reference limits in an older population with and without previous heart diseases. MATERIALS AND METHODS: A population-based study with a ten-year follow-up. The reference population was formed by 763 individuals aged over 64 years, with no diagnoses of heart or kidney diseases. RESULTS: There was a significant increase in cTnT and proBNP concentrations with age. The 99 % reference limits for cTnT were 25 ng/L, 28 ng/l, 38 ng/l, and 71 ng/l for men in five-year-intervals starting from 64 to 69 years to 80 years and older, and 18 ng/L, 22 ng/l, 26 ng/l, and 52 ng/L for women, respectively. The 97.5 % reference limits for proBNP were 272 ng/L, 287 ng/l, 373 ng/l and 686 ng/L for men, and 341 ng/L, 377 ng/l, 471 ng/l, and 794 ng/L for women, respectively. Elevated proBNP was statistically significantly associated with future AMIs in subjects with and without a previous heart disease. CONCLUSIONS: Age-specific reference limits for cTnT and proBNP are needed to better evaluate cardiac symptoms.