Peripartum heart failure in Finland: A population-based record linkage study.

AIMS: Heart failure in late pregnancy and the postpartum period (HFPP) is a rare but potentially life-threatening condition, with peripartum cardiomyopathy (PPCM) being the most common subtype. This study aims to comprehensively investigate the prevalence of HFPP in the Finnish population and identify the underlying risk factors associated with its occurrence. METHODS: We conducted a retrospective analysis using data from the Finnish Medical Birth Register and the Finnish Care Register for Health Care, covering 1996 to 2021. The dataset comprised 1 387 457 deliveries. HFPP cases were identified based on specific ICD-10 codes. To ensure the accuracy of our findings, we excluded cases with pre-existing cardiomyopathies and other significant cardiac diseases diagnosed before pregnancy. We employed logistic regression models to evaluate the associations between maternal factors and the incidence of HFPP. RESULTS: We identified 159 cases of HFPP, resulting in an incidence rate of 11.5 per 100 000 deliveries. This incidence is comparable with rates reported in other Scandinavian countries and lower than those observed in Germany. Consistent with findings from European cohorts, our study confirmed that pregnancy-associated hypertensive disorders, particularly preeclampsia, as well as complications such as preterm delivery, twin pregnancy and elective caesarean section, are substantial risk factors for HFPP. These results support previous research linking angiogenic imbalance to the pathogenesis of PPCM. Significant risk factors for HFPP included maternal pre-pregnancy body mass index ≥35 [adjusted odds ratio (aOR) 2.04, 95% confidence interval (CI) 1.28-3.25, P = 0.003], history of maternal hypertensive disorder (aOR 2.44, 95% CI 1.22-4.88, P = 0.012), gestational hypertension without significant proteinuria (aOR 2.14, 95% CI 1.27-3.61, P = 0.004), preeclampsia (aOR 2.43, 95% CI 1.39-4.23, P = 0.002), type 1 or type 2 diabetes (aOR 3.27, 95% CI 1.66-6.45, P < 0.001) and twin pregnancy (aOR 2.74, 95% CI 1.37-5.49, P = 0.005). Additionally, extensive prepartum [odds ratio (OR) 2.86, 95% CI 1.18-6.98, P = 0.018] and postpartum blood loss (OR 2.50, 95% CI 1.44-5.02, P = 0.001) and maternal mental disorders (OR 7.39, 95% CI 4.10-13.31, P < 0.001) were significantly more common among HFPP patients. CONCLUSIONS: The incidence of HFPP among women in Finland from 1996 to 2021 was low. HFPP exhibited a strong association with several risk factors, including preeclampsia, obesity, preterm delivery, twin pregnancy, elective caesarean section, multifoetal births, type 1 and type 2 diabetes, significant prepartum and postpartum blood loss and maternal mental health disorders. These findings underscore the importance of targeted interventions and careful monitoring in high-risk groups to mitigate the impact of HFPP on maternal health.

X-linked pyruvate dehydrogenase complex deficiency due to a novel PDHA1 variant associated with structural brain abnormalities in a fetus.

We report a case of pyruvate dehydrogenase E1 alpha subunit deficiency associated with a novel hemizygous PDHA1 variant presenting prenatally as multiple structural brain abnormalities in a male fetus. A healthy Finnish couple was initially referred to the Fetomaternal Medical Center because of suspected fetal choroid plexus cyst at 11 + 2 weeks of pregnancy. At 20 + 0 weeks, multiple abnormalities were observed with ultrasound including narrow thorax, slightly enlarged heart, hypoplastic cerebellum, absent cerebellar vermis and ventriculomegaly. Autopsy and genetic analyses were performed after the termination of pregnancy. The findings of macroscopic examination included cleft palate, abnormally overlapping position of fingers and toes and dysmorphic facial features. Neuropathological examination confirmed the absence of corpus callosum, cerebellar hypoplasia and ventriculomegaly. Nodular neuronal heterotopia was also observed. Trio exome sequencing revealed a novel hemizygous de novo variant c.1144C>T p.(Gln382*) in the PDHA1 gene, classified as likely pathogenic. We suggest that inherited metabolic disorders should be kept in mind as differential diagnoses in fetuses with structural brain abnormalities.

Pharmacodynamic and pharmacokinetic profile of SM-1, a triple-drug combination to increase total sleep time.

OBJECTIVE: The primary objective was to characterize the pharmacokinetics and pharmacodynamics of SM-1 after administration of a single oral dose to healthy volunteers in a placebo-controlled double-blind trial of daytime sedation. Secondary objectives were to determine the onset, duration, and offset of the sedative effects using subjective and objective measures of sedation. Safety and tolerability of SM-1 were also investigated. METHODS: Males and females 18-45 years of age received SM-1, a combination drug product comprised of diphenhydramine, zolpidem (delayed release), and lorazepam (delayed release). The pharmacokinetic profile of each drug was determined from blood samples. Sedative effects were assessed by visual analog scale, digit symbol substitution test, memory test, and quantitative electroencephalography. RESULTS: Similar number and severity of adverse events were observed following administration of SM-1 and placebo. Onset of sedation, as determined by subjective, performance, and electroencephalography measures, occurred 0.5-1 hr postdose, lasting about 7-7.5 hr. Plasma concentration curves for the two delayed-release components were altered compared with published data for unmodified drugs. Exposure values obtained with the combination product were in good agreement with published values of the drugs given individually. CONCLUSIONS: SM-1 was well tolerated and has pharmacologic activity starting within an hour of ingestion, lasting approximately 7-8 hr. Sedative activity was seen with subjective, psychomotor, and electroencephalography assays.

Neurophysiology and genetics of burning mouth syndrome.

BACKGROUND AND AIMS: Neuropathic mechanisms are involved in burning mouth syndrome (BMS), and variation of the dopamine D2 receptor (DRD2) gene contributes to experimental pain perception. We investigated whether neurophysiologic findings differ in BMS patients compared to healthy controls, and whether 957C>T polymorphism of the DRD2 gene influences thermal sensitivity or pain experience in BMS. METHODS: Forty-five BMS patients (43 women), mean age 62.5 years, and 32 healthy controls (30 women), mean age 64.8 years, participated. Patients estimated pain intensity, interference, suffering and sleep with Numeric Rating Scale. Blink reflex tests of the supraorbital (SON), mental (MN) and lingual (LN) nerves, and thermal quantitative sensory testing were done. The results were analysed with ANOVA. DRD2 gene 957C>T polymorphism was determined in 31 patients, and its effects on neurophysiologic and clinical variables were analysed. RESULTS: Cool (p = 0.0090) and warm detection thresholds (p = 0.0229) of the tongue were higher in BMS patients than controls. The stimulation threshold for SON BR was higher in patients than in controls (p = 0.0056). The latencies of R2 component were longer in BMS patients than in controls (p = 0.0005) at the SON distribution. Habituation of SON BR did not differ between the groups. The heat pain thresholds were highest (p = 0.0312) in homozygous patients with 957TT, who also reported most interference (p = 0.0352) and greatest suffering (p = 0.0341). Genotype 957CC associated with sleep disturbances (p = 0.0254). CONCLUSIONS: Burning mouth syndrome patients showed thermal hypoesthesia within LN distribution compatible with small fibre neuropathy. The DRD2 957C>T genotype influences perception and experience of BMS pain. SIGNIFICANCE: The results confirm earlier findings of neuropathic pain in BMS. The DRD2 957 C>T genotype influences perception and experience of clinical pain in BMS.

Preoperative pregabalin has no effect on intraoperative neurophysiological monitoring in adolescents undergoing posterior spinal fusion for spinal deformities: a double-blind, randomized, placebo-controlled clinical trial.

PURPOSE: This study was designed to evaluate the effect of preoperative pregabalin on intraoperative neurophysiological monitoring in adolescents undergoing surgery for spinal deformities. METHODS: Thirty-one adolescents undergoing posterior spinal fusion were randomized to receive preoperatively either pregabalin 2 mg/kg twice daily or placebo. The ability to make reliable intraoperative neurophysiological measurements, transcranial motor (MEPs) and sensory evoked potentials (SSEP) was evaluated. RESULTS: Two patients (pregabalin group) did not fulfil the inclusion criteria and one patient's (placebo group) spinal monitoring was technically incomplete and these were excluded from the final data. In the rest, spinal cord monitoring was successful. Anaesthesia prolonged the latency of MEPs and increased the threshold current of MEP. The current required to elicit MEPs did not differ between the study groups. There were no statistically significant differences between the study groups regarding the latency of bilateral SSEP (N32 and P37) and MEP latencies at any time point. CONCLUSIONS: Preoperative pregabalin does not interfere spinal cord monitoring in adolescents undergoing posterior spinal fusion. LEVEL OF EVIDENCE: I.