Abstract Background Numerous treatment guidelines recommend that long-term use of benzodiazepines (BZD) should be avoided primarily due to development of tolerance and a risk for BZD dependence. ...Despite this, long-term BZD use remains a controversial subject in clinical patient care with “for and against” debates. However, there is no explicit understanding of what is meant by long-term BZD use in real world. The aim of this study was to assess different definitions, usage patterns, prevalence and other characteristics of long-term BZD use based on published register-based studies. Synthesis of these characteristics is essential to derive a meaningful definition of long-term BZD. Methods Systematic review of register-based studies on long-term BZD use published in 1994–2014. Results Fourty-one studies met our predetermined inclusion criteria. The length of BZD use defined as “long-term” varied in these studies ranging from one month to several years. The most common definition was six months or longer during a year. The prevalence of long-term BZD use in the general population was estimated to be about 3%. The relative proportion of long-term BZD users (all definitions) in adult BZD users ranged from 6% to 76% (mean 24%; 95% CL 13–36%). The estimates were higher in studies only on the elderly (47%; 95% CL 31–64%). Long-term use involved typically steady treatment with low BZD doses. However, in elderly patients long-term BZD use and exceeding recommended doses was relatively common. Several characteristics associated with long-term use were found. Conclusions Long-term BZD use is common and a clinical reality. Uniform definitions for “long-term”, which is in line with population-based evidence, is needed to have more comparable results between studies. Our systematic review suggests that duration of BZD treatment over six months, the most common definition for long-term BZD use in the included studies. As also recommended previously, it is a useful starting point for further analyses on disadvantages but also potential advantages associated with long-term BZD use.
Background
Repetitive transcranial magnetic stimulation (rTMS) at M1/S1 cortex has been shown to alleviate neuropathic pain.
Objectives
To investigate the possible neurobiological correlates of ...cortical neurostimulation for the pain relief.
Methods
We studied the effects of M1/S1 rTMS on nociception, brain dopamine D2 and μ‐opioid receptors using a randomized, sham‐controlled, double‐blinded crossover study design and 3D‐positron emission tomography (PET). Ten healthy subjects underwent active and sham rTMS treatments to the right M1/S1 cortex with E‐field navigated device. Dopamine D2 and μ‐receptor availabilities were assessed with PET radiotracers 11Craclopride and 11Ccarfentanil after each rTMS treatment. Thermal quantitative sensory testing (QST), contact heat evoked potential (CHEP) and blink reflex (BR) recordings were performed between the PET scans.
Results
μ‐Opioid receptor availability was lower after active than sham rTMS (P ≤ 0.0001) suggested release of endogenous opioids in the right ventral striatum, medial orbitofrontal, prefrontal and anterior cingulate cortices, and left insula, superior temporal gyrus, dorsolateral prefrontal cortex and precentral gyrus. There were no differences in striatal dopamine D2 receptor availability between active and sham rTMS, consistent with lack of long‐lasting measurable dopamine release. Active rTMS potentiated the dopamine‐regulated habituation of the BR compared to sham (P = 0.02). Thermal QST and CHEP remained unchanged after active rTMS.
Conclusions
rTMS given to M1/S1 activates the endogenous opioid system in a wide brain network associated with processing of pain and other salient stimuli. Direct enhancement of top‐down opioid‐mediated inhibition may partly explain the clinical analgesic effects of rTMS.
Significance
Neurobiological correlates of rTMS for the pain relief are unclear. rTMS on M1/S1 with 11C‐carfentanyl‐PET activates endogenous opioids. Thermal and heat pain thresholds remain unchanged. rTMS induces top‐down opioid‐mediated inhibition but not change the sensory discrimination of painful stimuli.
Childhood adverse experiences (CAE) are associated with clinical psychiatric disorders and symptoms, and with volumetric abnormalities in the amygdala-hippocampus complex (AmHiC) and frontal lobe ...(FroL) in adulthood.
To study whether CAE are associated with reduced AmHiC and FroL and whether these structures mediate the effect of CAE on social anxiety and depression.
In seven European centres, 374 patients with recent onset of psychosis (n = 127), clinical high-risk to psychosis (n = 119) or recent onset of depression (n = 128) were scanned with MRI and their FroL and AmHiC volumes were measured. They all completed self-report scales for assessment of CAE, social anxiety and depression.
Of the CAE domains, physical abuse was associated specifically with reduced grey and white matter volumes of FroL and AmHiC in psychotic and high-risk patients. After controlling intracranial volume, PhyAb associated significantly with FroL and its grey matter volume in high-risk patients only. In mediation analyses, the effect of physical abuse on social anxiety was mediated via reduced FroL grey mater volume in high-risk patients. In them, when the effects of AmHiC and depression were controlled, the effect of physical abuse on social anxiety was mediated via FroL grey matter volume reduction.
Childhood physical abuse is associated with reduced frontal lobe and amygdala-hippocampus complex volume in adult subjects with psychotic symptoms. Reduced frontal lobe and amygdala-hippocampus complex volume mediate the effect of physical abuse on social anxiety in high-risk patients. The effect of physical abuse on depression-independent social anxiety is mediated via reduced frontal lobe.
Purpose
Organ transplantation is an effective treatment for children with severe heart, liver, and kidney diseases. These patient groups may have more oral and dental diseases than healthy controls. ...It is important to eliminate oral infection foci before transplantation and to maintain good oral health to avoid potential post-transplant complications. The aim of this study was to describe and compare oral health in Finnish paediatric heart, liver, and kidney transplant recipients prior to organ transplantation.
Methods
Eighty-six children who received a heart (
n
= 21), liver (
n
= 19), or kidney (
n
= 46) transplant in Finland during the years 2014–2018 were included in this study. The inclusion criterion was a pre-transplantation oral examination. Oral hygiene, enamel anomalies, and the number of decayed, missing, and filled teeth (dmft/DMFT) were analyzed retrospectively from medical and dental records and compared between the three patient groups.
Results
Children with liver (
p
= 0.043) or heart (
p
= 0.047) disease had higher combined primary and permanent dentition dmft/DMFT scores compared to children with kidney disease. A higher combined dmft/DMFT score was associated with poor oral hygiene (
p
= 0.005). No significant differences in oral hygiene between the patient groups were found. Furthermore, all patient groups had a high prevalence of developmental dental defects.
Conclusion
Children with liver or heart disease seem to have a higher combined dmft/DMFT score, indicating a higher prevalence of caries compared to children with kidney disease. Prevention of dental caries, along with promoting a good oral hygiene routine and regular check-ups, is suggested in these patient groups.
The psychobiological model of personality by Cloninger and colleagues originally hypothesized that interindividual variability in the temperament dimension 'harm avoidance' (HA) is explained by ...differences in the activity of the brain serotonin system. We assessed brain serotonin transporter (5-HTT) density in vivo with positron emission tomography (PET) in healthy individuals with high or low HA scores using an 'oversampling' study design. Method Subjects consistently in either upper or lower quartiles for the HA trait were selected from a population-based cohort in Finland (n = 2075) with pre-existing Temperament and Character Inventory (TCI) scores. A total of 22 subjects free of psychiatric and somatic disorders were included in the matched high- and low-HA groups. The main outcome measure was regional 5-HTT binding potential (BPND) in high- and low-HA groups estimated with PET and 11CN,N-dimethyl-2-(2-amino-4-methylphenylthio)benzylamine (11CMADAM). In secondary analyses, 5-HTT BPND was correlated with other TCI dimensions.
5-HTT BPND did not differ between high- and low-HA groups in the midbrain or any other brain region. This result remained the same even after adjusting for other relevant TCI dimensions. Higher 5-HTT BPND in the raphe nucleus predicted higher scores in 'self-directedness'.
This study does not support an association between the temperament dimension HA and serotonin transporter density in healthy subjects. However, we found a link between high serotonin transporter density and high 'self-directedness' (ability to adapt and control one's behaviour to fit situations in accord with chosen goals and values). We suggest that biological factors are more important in explaining variability in character than previously thought.
Objective
Infections cause considerable morbidity after liver transplantation (LT). Acute liver failure is a rapidly progressing life‐threatening condition where pretransplant dental evaluation is ...not always possible. We investigated how missing pretransplant dental treatment in acute or subacute liver failure correlates with post‐transplant infectious complications.
Subjects and methods
Medical and dental data came from hospital records and infection data from the Finnish LT registry. The follow‐up was until February 2011. Of 51 patients (LT during 2000–2006), 16 had and 35 did not have dental treatment pretransplant.
Results
Univariate Cox regression analysis demonstrated a 2.46‐fold (95% CI 1.06–5.69) infection risk among the patients omitted from dental treatment. After adjustment for either pretransplant factors alone or both pre‐ and post‐transplant factors, the corresponding infection risk increased, respectively, to 8.17‐fold (95% CI 2.19–30.6) and 8.54‐fold (95% CI 1.82–40.1). This increased risk involved a variety of bacterial, viral, and fungal infections of various sources both < 6 and > 6 months after transplantation.
Conclusion
High risk of infections was noticed in acute liver failure patients without pretransplant dental treatment, but a more severe medical condition might have influenced the results. We encourage eradication of dental infection foci whenever clinical condition allows.
Positron emission tomography (PET) studies have revealed significant interindividual variation in dopamine D2 receptor density in vivo in human striatum. Low D2 receptor binding in vivo has been ...found to associate with alcohol/substance dependence. It has been suggested that the A1 allele of human D2 receptor gene might be associated to a specific type of alcoholism and possibly to a reduced D2 receptor density in vitro. We have determined D2 dopamine receptor-binding density (Bmax), affinity (Kd) and availability (Bmax/Kd) in 54 healthy Finnish volunteers using PET and 11Craclopride in order to determine whether the A1 allele is associated with a 'baseline' difference in D2 receptor characteristics in vivo. A statistically significant reduction in D2 receptor availability reflecting an alteration in receptor density was observed in the A1/A2 genotype group compared to the A2/A2 group. There was no difference in apparent Kd between the two groups. In conclusion, the association between the A1 allele and low D2 receptor availability in healthy subjects indicates that the A1 allele of the TaqIA polymorphism might be in linkage disequilibrium with a mutation in the promoter/regulatory gene element that affects dopamine D2 receptor expression. This study provides an in vivo neurobiological correlate to the A1 allele in healthy volunteers.
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