Minor tranquillizers for short-term treatment of newly onset symptoms of anxiety and distress: a systematic review with network meta-analysis of randomized trials.

Unspecific symptoms of anxiety and distress are frequently encountered in patients in both general practice and acute psychiatric services. Minor tranquillizers may be a treatment option when non-pharmacological interventions are insufficient or unavailable. We conducted a systematic review with network meta-analysis of the evidence for short-term (1-4 weeks) pharmacological treatment of newly onset symptoms of anxiety and distress. We searched the PsycInfo, MEDLINE, EMBASE and Cochrane Library databases and extracted data following a predefined hierarchy of outcomes. We assessed risk of bias using the Cochrane Risk of Bias tool and the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation framework (GRADE). We included 34 randomized trials comprising a total of 7044 patients with adjustment disorders or anxiety spectrum disorders. The network meta-analysis showed that regarding the critical outcome symptoms of anxiety within 1-4 weeks benzodiazepines (SMD - 0.58, 95% CI - 0.77 to - 0.40), quetiapine (SMD - 0.51, 95% CI - 0.90 to - 0.13) and pregabalin (SMD - 0.58, 95% CI - 0.87 to - 0.28) all performed better than placebo with no statistically significant difference between the drugs. Data on other important outcomes were inconsistently reported. Adverse effects varied, but overall, it was uncertain whether adverse effects differed between interventions. The evidence regarding the risk of dependence was uncertain, but dependence may be a concern in susceptible individuals even with short-term treatment. Overall, the certainty of the evidence according to GRADE was rated as low to very low across outcomes. Despite the limitations in the evidence, the results of this review can inform treatment guidelines, supporting clinicians in the choice of minor tranquillizer in this prevalent and help-seeking, clinically heterogeneous population.

Effects of DPP-4 inhibitors, GLP-1 receptor agonists, SGLT-2 inhibitors and sulphonylureas on mortality, cardiovascular and renal outcomes in type 2 diabetes: A network meta-analyses-driven approach.

AIMS: The aim of our meta-analyses was to compare the effects of glucose-lowering drugs on mortality, cardiovascular and renal endpoints for a range of type 2 diabetes (T2D) subgroups defined by their specific cardiovascular risk profile. METHODS: Meta-analyses comparing drugs within the classes of GLP-1RAs and SGLT-2 inhibitors were performed and compared to sulphonylureas and DPP-4 inhibitors with available cardiovascular outcome trials. The comparison between the different classes of glucose-lowering drugs included analyses of T2D populations with low risk and high risk for cardiovascular disease including populations with established cardiovascular disease and/or kidney disease. Outcomes included mortality, major cardiovascular adverse events (MACE), hospitalisation for heart failure (HHF) and a composite renal endpoint as applied in the underlying clinical trials. RESULTS: SGLT-2 inhibitors and GLP-1RAs showed beneficial effects on mortality and MACE compared to the classes of DPP-4 inhibitors and sulphonylureas. SGLT-2 inhibitors were shown to be the most effective treatment in terms of HHF and kidney disease. Metformin was used as background therapy for the vast majority of participants in all included studies. Overall, the absolute effects of SGLT-2 inhibitors and GLP-1RAs on these important outcomes were evident for patients with established or at high risk for cardiovascular disease but limited for the low-risk subgroup. CONCLUSIONS: The findings from our analyses substantiate the relevance of treatment with SGLT-2 inhibitors or GLP-1RAs as an add-on to metformin in patients with T2D and a high risk for cardiovascular disease, and furthermore, support the recommendation for SGLT-2 inhibitor treatment in patients with T2D and heart failure or established kidney disease.

Polypharmacy and cross-sectoral collaboration.

Medication review is a pillar in the new recommendations from the Danish Health Authorities regarding patients with multimorbidity and polypharmacy. This review finds that general practitioners should be primary in coordinating medication. Medication reviews can be conducted differently with various co-interventions to try to improve cross-sectoral collaboration. It seems imperative that the interventions involve improved communication for optimal sharing and implementation of changes to the medication with primary care in a key role.

Demographic and clinical characteristics in relation to patient and health system delays in a tuberculosis low-incidence country.

BACKGROUND: Delays in the diagnosis and treatment of tuberculosis (TB) are commonly encountered. METHODS: A study was undertaken among pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) patients in a Danish university hospital to describe demographic and clinical characteristics in relation to delay. RESULTS: Of the 313 patients enrolled, 213 (68%) were diagnosed with PTB and 100 (32%) with EPTB only. Logistic regression analysis of EPTB showed an association with female sex and non-Danish ethnicity. Mean total delay from onset of symptoms until initiation of TB treatment was 123 (95% confidence interval (CI) 106-138) days. Mean patient delay was significantly longer than mean health system delay: 90 (95% CI 74-105) vs 33 (95% CI 23-44) days (p < 0.0001). Delay was independent of ethnicity and significantly shorter for PTB patients compared to EPTB patients. Fever was found to be strongly predictive of a short patient delay (<1 month), whereas weight loss was associated with a long patient delay (> 3 months). In contrast, weight loss was associated with a short health system delay (<1 week). Elevated inflammatory markers were also associated with a short delay in the diagnosis of TB. CONCLUSIONS: This study confirmed a typical delay of months in duration in the diagnosis and treatment of TB in the low endemic country of Denmark. Increased TB awareness is needed, in particular in communities with immigrants originating from high-endemic areas.

Exploration of Symptom Scale as an Outcome for Deprescribing: A Medication Review Study in Nursing Homes.

The use of inappropriate medication is an increasing problem among the elderly, leading to hospitalizations, mortality, adverse effects, and lower quality of life (QoL). Deprescribing interventions (e.g., medication reviews (MRs)) have been examined as a possible remedy for this problem. In order to be able to evaluate the potential benefits and harms of a deprescribing intervention, quality of life (QoL) has increasingly been used as an outcome. The sensitivity of QoL measurements may, however, not be sufficient to detect a change in specific disease symptoms, e.g., a flair-up in symptoms or relief of side effects after deprescribing. Using symptom assessments as an outcome, we might be able to identify and evaluate the adverse effects of overmedication and deprescribing alike. The objective of this study was to explore whether symptom assessment is a feasible and valuable method of evaluating outcomes of MRs among the elderly in nursing homes. To the best of our knowledge, this has not been investigated before. We performed a feasibility study based on an experimental design and conducted MRs for elderly patients in nursing homes. Their symptoms were registered at baseline and at a follow-up 3 months after performing the MR. In total, 86 patients, corresponding to 68% of the included patients, received the MR and completed the symptom questionnaires as well as the QoL measurements at baseline and follow-up, respectively. Forty-eight of these patients had at least one deprescribing recommendation implemented. Overall, a tendency towards the improvement of most symptoms was seen after deprescribing, which correlated with the tendencies observed for the QoL measurements. Remarkably, deprescribing did not cause a deterioration of symptoms or QoL, which might otherwise be expected for patients of this age group, of whom the health is often rapidly declining. In conclusion, it was found that symptom assessments were feasible among nursing home residents and resulted in additional relevant information about the potential benefits and harms of deprescribing. It is thus recommended to further explore the use of symptom assessment as an outcome of deprescribing interventions, e.g., in a controlled trial.

Prevalence of Swallowing and Eating Difficulties in an Elderly Postoperative Hip Fracture Population-A Multi-Center-Based Pilot Study.

Elderly patients operated for hip fracture are characterized by high age and high degree of comorbidity and need of care, factors previously found to be associated with swallowing and eating difficulties. The aim of this study was to investigate the prevalence of swallowing and eating difficulties in an elderly postoperative hip fracture population and to identify factors associated with swallowing and eating difficulties. A cross-sectional multi-center pilot study was performed, including patients ≥65 years, operated for hip fracture, and able to participate in a swallowing and eating assessment. A clinical assessment was conducted using Danish versions of the standardized tools Volume-Viscosity Swallow Test and Minimal Eating Observation Form-version II. Demographic data and clinical characteristics were examined. A total of 78 patients (mean age 81.4 years (SD 7.8), 30.8% male) were included. Swallowing and eating difficulties were present in 60 patients (77%). Swallowing and eating difficulties were significantly associated with living in a nursing home before hospital admission (p = 0.014), low habitual New Mobility Score (p = 0.018), and absence of cardiac comorbidity (p = 0.023). The results underline the importance of focusing on swallowing and eating difficulties in elderly patients operated for hip fracture to ensure effectivity and safety and optimize the prognosis for the patient.

Do cognitive deficits persist into adolescence in autism?

SEVERAL THEORIES HAVE ATTEMPTED TO CHARACTERISE AUTISM SPECTRUM DISORDERS (ASDS) AT THE COGNITIVE LEVEL, MOST NOTABLY: THEORY OF MIND (TOM), EXECUTIVE FUNCTION (EF), AND A LOCAL PROCESSING BIAS (LB). THE AIM OF THIS STUDY WAS TO INVESTIGATE HOW THESE COGNITIVE FUNCTIONS DEVELOP OVER TIME: The three cognitive domains (ToM, EF, and LB) were examined in a group of high-functioning children (age: 8-12, mean 10.85; IQ: 78-139, mean 105.48) with ASD and a matched group of children with neurotypical development (NTD) (IQ: 75-145, mean: 109.47), and several tasks were used within each domain to ensure the validity of the cognitive measures. Approximately 3 years later (mean age: 14.34), all children and their families were invited to participate in the follow-up (ASD, N = 21; NTD, N = 30). While the understanding of other's minds does improve from childhood to adolescence, ToM impairment persists in adolescents with ASD relative to their peers. Likewise, a development in EF was observed in the ASD group, while no significant improvement was seen in the NTD group, leading the ASD group to catch up in this domain. We did not detect any group differences at any time point regarding local bias processing (LB). Individual patterns of development were seen, but remarkably, ToM deficits were present in every child with ASD in whom we could detect any cognitive impairment at baseline, and a similar pattern was found at follow-up. These findings indicate that ToM is a persistent cognitive deficit in ASD. Autism Res 2018, 11: 1229-1238. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This was the first study to investigate the development of three well-known cognitive functions into adolescence: While the understanding of other's minds improves from childhood to adolescence, adolescents with ASD are still impaired relative to their peers. The EFs, however, seem to improve to a neurotypical level in ASD as children enter adolescence, while local processing bias seems to differentiate the groups only in early childhood.

[Eosinophilia].

When the number of eosinophil granulocytes in blood increases, the cause is not always easy to disentangle. This review highlights the symptoms of rare clonal and common reactive diagnoses, how to approach the patient clinically, and how to implement the armamentarium of available tests in order to identify the correct diagnosis and offer the proper treatment. Two referral centres for eosinophilia have been established in Denmark to support this activity by a collaboration between all departments of haematology and the relevant specialities, meeting the manifestations of eosinophilia.

Auditory processing in autism spectrum disorder: Mismatch negativity deficits.

Children with autism spectrum disorders (ASD) often show changes in (automatic) auditory processing. Electrophysiology provides a method to study auditory processing, by investigating event-related potentials such as mismatch negativity (MMN) and P3a-amplitude. However, findings on MMN in autism are highly inconsistent, partly due to small sample sizes in the studies and differences in MMN paradigms. Therefore, in the current study, MMN and P3a amplitude were assessed in a relatively large sample of children with ASD, using a more extensive MMN paradigm and compared with that of typically developing children (TDC). Thirty-five children (aged 8-12 years) with ASD and 38 age and gender matched TDC were assessed with a MMN paradigm with three types of deviants, i.e., frequency, duration and a combination of these two. MMN elicited by duration and frequency-duration deviants was significantly reduced in the ASD group. P3a-amplitude elicited by duration deviants was significantly increased in the ASD group. Reduced MMN in children with ASD suggests that children with ASD may be less responsive to environmentally deviant stimuli at an early (sensory) level. P3a-amplitude was increased in ASD, implying a hyper-responsivity at the attentional level. In addition, as similar MMN deficits are found in schizophrenia, these MMN results may explain some of the frequently reported increased risk of children with ASD to develop schizophrenia later in life. Autism Res 2017, 10: 1857-1865. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Automatic detection of deviant sounds in the environment, such as upcoming traffic, is often affected in children with autism spectrum disorders (ASD). Mismatch negativity (MMN) is a way to quantify automatic deviancy detection, using electroencephalography. In this study, auditory MMN was assessed in 35 children with ASD and 38 matched control children, revealing significantly reduced MMN in the ASD group. This may indicate that children with ASD are less able to automatically detect environmentally deviant stimuli.

Exploring 'The autisms' at a cognitive level.

The autism spectrum is characterized by genetic and behavioral heterogeneity. However, it is still unknown whether there is a universal pattern of cognitive impairment in autism spectrum disorder (ASD) and whether multiple cognitive impairments are needed to explain the full range of behavioral symptoms. This study aimed to determine whether three widely acknowledged cognitive abnormalities (Theory of Mind (ToM) impairment, Executive Function (EF) impairment, and the presence of a Local Processing Bias (LB)) are universal and fractionable in autism, and whether the relationship between cognition and behavior is dependent on the method of behavioral assessment. Thirty-one high-functioning children with ASD and thirty-seven children with neurotypical development (NTD), comparable in age, gender and Intelligence Quotient (IQ), completed several tasks tapping into ToM, EF, and LB, and autistic symptomatology was assessed through parental and teacher questionnaires, parental interview and direct observation. We found that ToM and EF deficits differentiated the groups and some ToM and EF tasks were related to each other. ToM and EF were together able to correctly classify more than three-quarters of the children into cases and controls, despite relating to none of the specific behavioral measures. Only a small subgroup of individuals displayed a LB, which was unrelated to ToM and EF, and did not aid diagnostic classification, most likely contributing to non-diagnostic symptoms in a subgroup. Despite the characteristic heterogeneity of the autism spectrum, it remains a possibility therefore that a single cognitive cause may underlie the range of diagnostic symptoms in all individuals with autism. Autism Res 2016, 9: 1328-1339. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Normal P50 Gating in Children with Autism, Yet Attenuated P50 Amplitude in the Asperger Subcategory.

Autism spectrum disorders (ASD) and schizophrenia are separate disorders, but there is evidence of conversion or comorbid overlap. The objective of this paper was to explore whether deficits in sensory gating, as seen in some schizophrenia patients, can also be found in a group of ASD children compared to neurotypically developed children. An additional aim was to investigate the possibility of subdividing our ASD sample based on these gating deficits. In a case-control design, we assessed gating of the P50 and N100 amplitude in 31 ASD children and 39 healthy matched controls (8-12 years) and screened for differences between groups and within the ASD group. We did not find disturbances in auditory P50 and N100 filtering in the group of ASD children as a whole, nor did we find abnormal P50 and N100 amplitudes. However, the P50 amplitude to the conditioning stimulus was significantly reduced in the Asperger subgroup compared to healthy controls. In contrast to what is usually reported for patients with schizophrenia, we found no evidence for sensory gating deficits in our group of ASD children taken as a whole. However, reduced P50 amplitude to conditioning stimuli was found in the Asperger group, which is similar to what has been described in some studies in schizophrenia patients. There was a positive correlation between the P50 amplitude of the conditioning stimuli and anxiety score in the pervasive developmental disorder not otherwise specified group, which indicates a relation between anxiety and sensory registration in this group.

Increased prepulse inhibition and sensitization of the startle reflex in autistic children.

The relation between autism spectrum disorders (ASD) and schizophrenia is a subject of intense debate and research due to evidence of common neurobiological pathways in the two disorders. The objective of this study was to explore whether deficits in prepulse inhibition (PPI) of the startle reflex, as usually seen in schizophrenic patients, can be replicated in a group of children with ASD in comparison with a group of matched neuro-typically developed (NTD) controls. An additional aim was to explore possible psychophysiological subgroups within our ASD sample. In a case-control design, 35 ASD patients and 40 matched NTD controls were tested in a psychophysiological test battery. The PPI of the acoustic startle reflex was analyzed in 18 ASD subjects and 34 NTD controls. Habituation and sensitization were analyzed in 23 ASD subjects and 39 NTD controls. In trials with less intense prestimuli (76 dB), patients with ASD did not display the drop in percentage PPI normally found in healthy controls. In addition, ASD patients showed significantly increased sensitization compared with NTD controls. Combined, our results may reflect the hypersensitivity to sensory information in children with ASD. The relation to PPI deficits observed in schizophrenia is not apparent. Future research should study the developmental course of PPI deficits in ASD patients in a longitudinal design.

[Cancer stem cells in the haematopoietic system]. / Kraeftstamceller i det hæmopoietiske system.

Cancer is dependent on so-called cancer stem cells that initiate and maintain the cancer cell population. Stem cells are described in normal tissue as low-frequent, self-renewing cells with a multi- or pluripotent differentiation potential. The true characteristics of the cancer-initiating cells are still not entirely known, but it is obvious that identifying these cells will enable us to better understand the biology of cancer. In this article, we focus on normal haematopoietic stem cells and cancer stem cells in leukaemia and multiple myeloma.

[Psychosis in childhood and adolescence. Psychopathology and differential diagnoses]. / Psykose i barne- og ungdomsalderen. Psykopatologi og differentialdiagnostik.

Psychosis in childhood and adolescence is rare. Psychotic manifestations in childhood are associated with diagnostic diversities. The diagnostic group pervasive developmental disorder, not otherwise specified (PDD-NOS) are often used in childhood and may be a precursor of schizophrenia or affective psychosis. In this short review, expressions of psychosis in childhood and adolescence are listed and discussed. The authors speak in favour of a closer collaboration between child- and adolescent psychiatry and adult psychiatry clinically as well as in research contexts to expand the knowledge about the genesis and aetiology of psychoses.