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2.
BMC Psychiatry ; 24(1): 401, 2024 May 29.
Article En | MEDLINE | ID: mdl-38811916

BACKGROUND: Motor alterations and lowered physical activity are common in affective disorders. Previous research has indicated a link between depressive symptoms and declining muscle strength primarily focusing on the elderly but not younger individuals. Thus, we aimed to evaluate the relationship between mood and muscle strength in a sample of N = 73 young to middle-aged hospitalized patients (18-49 years, mean age 30.7 years) diagnosed with major depressive, bipolar and schizoaffective disorder, with a focus on moderating effects of psychopharmacotherapy. The study was carried out as a prospective observational study at a German psychiatric university hospital between September 2021 and March 2022. METHODS: Employing a standardized strength circuit consisting of computerized strength training devices, we measured the maximal muscle strength (Fmax) using three repetitions maximum across four muscle regions (abdomen, arm, back, leg) at three time points (t1-t3) over four weeks accompanied by psychometric testing (MADRS, BPRS, YRMS) and blood lipid profiling in a clinical setting. For analysis of psychopharmacotherapy, medication was split into activating (AM) and inhibiting (IM) medication and dosages were normalized by the respective WHO defined daily dose. RESULTS: While we observed a significant decrease of the MADRS score and increase of the relative total Fmax (rTFmax) in the first two weeks (t1-t2) but not later (both p < .001), we did not reveal a significant bivariate correlation between disease severity (MADRS) and muscle strength (rTFmax) at any of the timepoints. Individuals with longer disease history displayed reduced rTFmax (p = .048). IM was significantly associated with decreased rTFmax (p = .032). Regression models provide a more substantial effect of gender, age, and IM on muscle strength than the depressive episode itself (p < .001). CONCLUSIONS: The results of the study indicate that disease severity and muscle strength are not associated in young to middle-aged inpatients with affective disorders using a strength circuit as observational measurement. Future research will be needed to differentiate the effect of medication, gender, and age on muscle strength and to develop interventions for prevention of muscle weakness, especially in younger patients with chronic affective illnesses.


Muscle Strength , Humans , Muscle Strength/drug effects , Muscle Strength/physiology , Male , Pilot Projects , Adult , Female , Prospective Studies , Middle Aged , Young Adult , Adolescent , Inpatients , Bipolar Disorder/drug therapy , Bipolar Disorder/physiopathology , Depressive Disorder, Major/drug therapy , Depressive Disorder, Major/physiopathology , Psychotic Disorders/drug therapy , Psychotic Disorders/physiopathology , Severity of Illness Index
3.
Article En | MEDLINE | ID: mdl-38762161

OBJECTIVE: Increasing evidence suggests that the physiological changes of pregnancy may impact pharmacokinetics of antiseizure medications (ASM), and this may affect treatment outcomes. The aim of this study was to quantify the pregnancy impact on the ASM pharmacokinetics. METHODS: A systematic literature search was conducted in PubMed/EMBASE in November 2022 and updated in August 2023 for studies comparing levels of ASM in the same individuals during pregnancy and in the preconception/postpartum period. Alteration ratios between the 3rd trimester and baseline were estimated. We also performed a random-effects meta-analysis calculating between-timepoint differences in mean differences (MDs) and 95% confidence intervals (95%CIs) for dose-adjusted plasma concentrations (C/D ratios). Study quality was assessed using the ClinPK guidelines. RESULTS: A total of 65 studies investigating 15 ASMs in 674 pregnancies were included. The largest differences were reported for lamotrigine, oxcarbazepine and levetiracetam (alteration ratio 0.42, range 0.07-2.45, 0.42, range 0.08-0.82 and 0.52, range 0.04-2.77 respectively): accordingly, C/D levels were lower in the 3rd trimester for lamotrigine, levetiracetam and the main oxcarbazepine metabolite monohydroxycarbazepine (MD = -12.33 × 10-3, 95%CI = -16.08 to -8.58 × 10-3 (µg/mL)/(mg/day), p < 0.001, MD = -7.16 (µg/mL)/(mg/day), 95%CI = -9.96 to -4.36, p < 0.001, and MD = -4.87 (µg/mL)/(mg/day), 95%CI = -9.39 to -0.35, p = 0.035, respectively), but not for oxcarbazepine (MD = 1.16 × 10-3 (µg/mL)/(mg/day), 95%CI = -2.55 to 0.24 × 10-3, p = 0.10). The quality of studies was acceptable with an average rating score of 11.5. CONCLUSIONS: Data for lamotrigine, oxcarbazepine (and monohydroxycarbazepine) and levetiracetam demonstrate major changes in pharmacokinetics during pregnancy, suggesting the importance of therapeutic drug monitoring to assist clinicians in optimizing treatment outcomes.


Anticonvulsants , Humans , Pregnancy , Anticonvulsants/pharmacokinetics , Anticonvulsants/blood , Female , Pregnancy Complications/drug therapy , Levetiracetam/pharmacokinetics , Lamotrigine/pharmacokinetics , Lamotrigine/blood , Epilepsy/drug therapy , Epilepsy/blood , Oxcarbazepine/pharmacokinetics
4.
Article En | MEDLINE | ID: mdl-38613195

OBJECTIVE: Ample literature shows voice and swallowing therapy, in-person or virtual, to be essential for Otolaryngology and Speech-Language Pathology care. In March 2023, Medicare announced discontinuing teletherapy reimbursement in hospital-based outpatient departments, effective May 2023. This decision was subsequently reversed; however, the uncertain interval period provided the opportunity to study the impact of eliminating teletherapy. STUDY DESIGN: Prospective cohort. SETTING: Tertiary laryngology center. METHODS: Affected Medicare patients were contacted via mailed letter, phone, and secure patient portal and offered to change appointments to in-person, teletherapy with cash self-payment ($165-282/session) or cancellation. Demographics and responses were collected. Statistical analyses conducted using Student's t test. RESULTS: Fifty-three patients (28 female; mean age 66.8 ± 14.2 years) were impacted. 64% (n = 34) changed to in-person appointment, 28% (n = 15) canceled, 8% (n = 4) did not respond. No patients opted to self-pay. 67% of patients that canceled telehealth care cited distance from in-person care location. The mean distance for canceled versus rescheduled patients was 92.3 ± 93.0 versus 32.8 ± 57.4 miles, P = .034. Mean age, gender, and number of sessions were not different between groups. Mean time to third next available therapy appointment was 96 ± 46 versus 46 ± 12 days before and after rule change, P = .007. Upon Medicare's reversal, this trend rebounded to nearly baseline (mean 77 ± 12 days, P = .12). CONCLUSION: Medicare's discontinuation of reimbursement for teletherapy services caused nearly 30% of patients to cancel voice and swallowing therapy, primarily due to distance. These cancellations led to decreased access to care for Medicare patients with voice/swallowing diagnoses, which affect function, quality of life, and potentially even mortality risk.

5.
Alzheimers Res Ther ; 16(1): 66, 2024 Mar 28.
Article En | MEDLINE | ID: mdl-38539243

BACKGROUND: Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid concentrations of the progranulin protein (PGRN). This has led to a number of ongoing therapeutic trials aiming to treat this form of FTD by increasing PGRN levels in mutation carriers. However, we currently lack a complete understanding of factors that affect PGRN levels and potential variation in measurement methods. Here, we aimed to address this gap in knowledge by systematically reviewing published literature on biofluid PGRN concentrations. METHODS: Published data including biofluid PGRN concentration, age, sex, diagnosis and GRN mutation were collected for 7071 individuals from 75 publications. The majority of analyses (72%) had focused on plasma PGRN concentrations, with many of these (56%) measured with a single assay type (Adipogen) and so the influence of mutation type, age at onset, sex, and diagnosis were investigated in this subset of the data. RESULTS: We established a plasma PGRN concentration cut-off between pathogenic mutation carriers and non-carriers of 74.8 ng/mL using the Adipogen assay based on 3301 individuals, with a CSF concentration cut-off of 3.43 ng/mL. Plasma PGRN concentration varied by GRN mutation type as well as by clinical diagnosis in those without a GRN mutation. Plasma PGRN concentration was significantly higher in women than men in GRN mutation carriers (p = 0.007) with a trend in non-carriers (p = 0.062), and there was a significant but weak positive correlation with age in both GRN mutation carriers and non-carriers. No significant association was seen with weight or with TMEM106B rs1990622 genotype. However, higher plasma PGRN levels were seen in those with the GRN rs5848 CC genotype in both GRN mutation carriers and non-carriers. CONCLUSIONS: These results further support the usefulness of PGRN concentration for the identification of the large majority of pathogenic mutations in the GRN gene. Furthermore, these results highlight the importance of considering additional factors, such as mutation type, sex and age when interpreting PGRN concentrations. This will be particularly important as we enter the era of trials for progranulin-associated FTD.


Frontotemporal Dementia , Male , Humans , Female , Progranulins/genetics , Frontotemporal Dementia/genetics , Frontotemporal Dementia/pathology , Intercellular Signaling Peptides and Proteins/genetics , Virulence , Mutation/genetics , Membrane Proteins/genetics , Nerve Tissue Proteins/genetics
6.
J Pharmacol Exp Ther ; 389(2): 174-185, 2024 Apr 18.
Article En | MEDLINE | ID: mdl-38531640

There is a debate on whether H1-histamine receptors can alter contractility in the mammalian heart. We studied here a new transgenic mouse model where we increased genetically the cardiac level of the H1-histamine receptor. We wanted to know if histamine could augment or decrease contractile parameters in mice with cardiac-specific overexpression of human H1-histamine receptors (H1-TG) and compared these findings with those in littermate wild-type mice (WT). In H1-TG mice, we studied the presence of H1-histamine receptors by autoradiography of the atrium and ventricle using [3H]mepyramine. The messenger RNA for human H1-histamine receptors was present in the heart from H1-TG and absent from WT. Using in situ hybridization, we noted mRNA for the human H1-histamine receptor in cardiac cells from H1-TG. We noted that histamine (1 nM-10 µM) in paced (1 Hz) left atrial preparations from H1-TG, exerted at each concentration of histamine initially reduced force of contraction and then raised contractile force. Likewise, in spontaneously beating left atrial preparations from H1-TG, we noted that histamine led to a transient reduction in the spontaneous beating rate followed by an augmentation in the beating rate. The negative inotropic and chronotropic and the positive inotropic effects on histamine in isolated atrial muscle strips from H1-TG were attenuated by the H1-histamine receptor antagonist mepyramine. Histamine failed to exert an increased force or reduce the heartbeat in atrial preparations from WT. We concluded that stimulation of H1-histamine-receptors can decrease and then augment contractile force in the mammalian heart and stimulation of H1-histamine receptors exerts a negative chronotropic effect. SIGNIFICANCE STATEMENT: We made novel transgenic mice with cardiomyocyte-specific high expressional levels of the human H1-histamine receptor to contribute to the clarification of the controversy on whether H1-histamine receptors increase or decrease contractility and beating rate in the mammalian heart. From our data, we conclude that stimulation of H1-histamine receptors first decrease and then raise contractile force in the mammalian heart but exert solely negative chronotropic effects.


Histamine , Myocardial Contraction , Humans , Mice , Animals , Mice, Transgenic , Histamine/pharmacology , Pyrilamine/pharmacology , Heart , Receptors, Histamine , Heart Atria , Heart Rate , Receptors, Histamine H1/genetics , Mammals
7.
Leukemia ; 38(5): 1143-1155, 2024 May.
Article En | MEDLINE | ID: mdl-38467768

Hematopoietic stem and progenitor cells (HSPCs) maintain blood-forming and immune activity, yet intrinsic regulators of HSPCs remain elusive. STAT3 function in HSPCs has been difficult to dissect as Stat3-deficiency in the hematopoietic compartment induces systemic inflammation, which can impact HSPC activity. Here, we developed mixed bone marrow (BM) chimeric mice with inducible Stat3 deletion in 20% of the hematopoietic compartment to avoid systemic inflammation. Stat3-deficient HSPCs were significantly impaired in reconstitution ability following primary or secondary bone marrow transplantation, indicating hematopoietic stem cell (HSC) defects. Single-cell RNA sequencing of Lin-ckit+Sca1+ BM cells (LSKs) revealed aberrant activation of cell cycle, p53, and interferon (IFN) pathways in Stat3-deficient HSPCs. Stat3-deficient LSKs accumulated γH2AX and showed increased expression of DNA sensors and type-I IFN (IFN-I), while treatment with A151-ODN inhibited expression of IFN-I and IFN-responsive genes. Further, the blockade of IFN-I receptor signaling suppressed aberrant cell cycling, STAT1 activation, and nuclear p53 accumulation. Collectively, our results show that STAT3 inhibits a deleterious autocrine IFN response in HSCs to maintain long-term HSC function. These data signify the importance of ensuring therapeutic STAT3 inhibitors are targeted specifically to diseased cells to avoid off-target loss of healthy HSPCs.


Autocrine Communication , Hematopoietic Stem Cells , Interferon Type I , STAT3 Transcription Factor , Animals , STAT3 Transcription Factor/metabolism , Mice , Hematopoietic Stem Cells/metabolism , Interferon Type I/metabolism , Signal Transduction , Mice, Inbred C57BL , Mice, Knockout
8.
Nat Struct Mol Biol ; 31(5): 752-756, 2024 May.
Article En | MEDLINE | ID: mdl-38467877

The 20S U5 small nuclear ribonucleoprotein particle (snRNP) is a 17-subunit RNA-protein complex and a precursor of the U4/U6.U5 tri-snRNP, the major building block of the precatalytic spliceosome. CD2BP2 is a hallmark protein of the 20S U5 snRNP, absent from the mature tri-snRNP. Here we report a high-resolution cryogenic electron microscopy structure of the 20S U5 snRNP, shedding light on the mutually exclusive interfaces utilized during tri-snRNP assembly and the role of the CD2BP2 in facilitating this process.


Cryoelectron Microscopy , Models, Molecular , Ribonucleoprotein, U5 Small Nuclear , Humans , Ribonucleoprotein, U5 Small Nuclear/chemistry , Ribonucleoprotein, U5 Small Nuclear/metabolism , Spliceosomes/metabolism , Spliceosomes/chemistry , Spliceosomes/ultrastructure , Protein Conformation , Molecular Chaperones/metabolism , Molecular Chaperones/chemistry
9.
Article En | MEDLINE | ID: mdl-38305896

PURPOSE: To examine the association between partner support for women's antidepressant treatment and depressive symptoms in pregnant women, those planning pregnancy, and mothers who ever used antidepressants. METHODS: We included 334 women (n=44 planners, n=182 pregnant, n=108 mothers) ever treated with antidepressants within the HEALTHx2 study, a web-based cross-sectional study conducted across Norway in June 2020 to June 2021. The Edinburgh Postnatal Depression Scale and two questions of the Patient Health Questionnaire measured depressive symptoms, by degree of severity and for depressed mood, anxiety, and anhedonia sub-dimensions. Partner support was measured using one item from the Antidepressant Compliance Questionnaire. Association was estimated via unadjusted and adjusted linear and logistic regression models. RESULTS: Being unsupported by the partner was associated with increased odds of reporting moderate-to-very-severe depressive symptoms in mothers (adjusted odds ratio (aOR), 3.57; 95% confidence interval (CI), 1.04-12.19) and pregnant women (aOR, 3.26; 95% CI, 0.95-11.14), relative to being supported. Pregnant women (adjusted mean difference (ß), 0.76; 95% CI, 0.14-1.38) and mothers (ß, 0.93; 95% CI, 0.23-1.64) with no support for their antidepressant treatment presented greater symptoms of anhedonia; for women planning pregnancy, this association emerged in relation to anxiety symptoms (ß among non-users of antidepressant, 2.58; 95% CI, 1.04-4.13). CONCLUSIONS: Partner support for women's antidepressant treatment may play a key role in depressive symptoms severity and the subtypes of anhedonia and anxiety, among women planning pregnancy, pregnant women, and mothers. This highlights the importance of partner inclusion in the complex decision-making process for antidepressant treatment around the time of pregnancy.

10.
Ther Drug Monit ; 46(2): 195-202, 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38321601

BACKGROUND: The escalating prescription of psychopharmacological medications to women of reproductive age underscores the growing significance of sex-specific variations in pharmacotherapy. Despite this, clinical trials have largely overlooked these differences. Preliminary data indicate sex-specific variations in the neurobiology of affective disorders and in the metabolism, pharmacodynamics, and kinetics of therapeutic drugs. This underscores the imperative for a more nuanced exploration of menstrual cycle-dependent fluctuations in psychotropic drugs. This pilot study aimed to investigate drug and hormone fluctuations in female patients with affective disorders, aiming to enhance comprehension of the interplay between cycle-related hormone fluctuations and pharmacokinetics. The ultimate goal is to facilitate more effective and safer pharmacological therapy in the future. METHODS: Blood samples were collected from 27 patients and 27 age-matched control participants at 3 distinct time points (early follicular phase, ovulation, and late luteal phase) during each menstrual cycle. Depressive and manic symptoms were assessed, and hormone concentrations were measured in the entire sample, while drug concentrations were assessed solely in the affective disorder sample using mass spectrometry. RESULTS: Significant variations in drug concentration were observed throughout the menstrual cycle for bupropion, with a trend toward altered concentration for venlafaxine. Moreover, notable differences in hormone concentrations were identified between patients and controls, even after accounting for the impact of contraceptive use, diagnoses, and medication. CONCLUSIONS: This pilot study reinforces previously reported data, underscoring the significance of sex-specific pharmacological therapy approaches. It provides further evidence supporting the interaction among sex hormones, drugs, and symptoms of affective disorders.


Menstrual Cycle , Progesterone , Male , Female , Humans , Pilot Projects , Luteal Phase , Psychotropic Drugs/therapeutic use
11.
J Public Health Manag Pract ; 30(2): 231-239, 2024.
Article En | MEDLINE | ID: mdl-38271105

CONTEXT: The Centers for Disease Control and Prevention (CDC) and the US Postal Service (USPS) consider anthrax to be a potential threat to USPS workers. A county health department-owned pharmacy supports local USPS response in the event of an exposure. The pharmacy team identified the need to review and update the local anthrax response plan. PROGRAM/POLICY: A Pharmacy Point-of-Dispensing Toolkit and response plan for initial 10-day post-exposure antibiotic prophylaxis was developed for use by a local health department in the event of a mass anthrax exposure at a US Post Office sorting facility. The pharmacist's role in medical countermeasures planning for anthrax exposure is also discussed to illustrate how pharmacists' medication expertise can be utilized. EVALUATION: The CDC's Public Health Preparedness Capabilities: National Standards for State and Local Planning framework and inputs from an interprofessional stakeholder team were used to develop a Medical Countermeasures Response Plan and Implementation Toolkit for mass point-of-dispensing (POD) in the event of an anthrax exposure. IMPLEMENTATION AND DISSEMINATION: Stakeholders attended a USPS Community Partner Training event where additional revisions to the toolkit were made. The toolkit and standing order are now implemented at the local health department to be reviewed and updated on a yearly basis by health department leadership. DISCUSSION: Pharmacists can use their medication expertise and experience with patient education to design emergency response plans focused on increasing patient safety and medication adherence. Pharmacists should be involved in emergency response and medical countermeasures planning that involve medications.


Anthrax , Pharmacy , Humans , Anthrax/drug therapy , Anthrax/prevention & control , Post-Exposure Prophylaxis , Pharmacists , Public Health
12.
Sci Rep ; 14(1): 2613, 2024 Jan 31.
Article En | MEDLINE | ID: mdl-38297060

Nonmarine rocks in sea cliffs of southern California store a detailed record of weathering under tropical conditions millions of years ago, where today the climate is much drier and cooler. This work examines early Eocene (~ 50-55 million-year-old) deeply weathered paleosols (ancient, buried soils) exposed in marine terraces of northern San Diego County, California, and uses their geochemistry and mineralogy to reconstruct climate and weathering intensity during early Eocene greenhouse climates. These Eocene warm spikes have been modeled as prequels for ongoing anthropogenic global warming driven by a spike in atmospheric CO2. Paleocene-Eocene thermal maximum (PETM, ~ 55 Ma) kaolinitic paleosols developed in volcaniclastic conglomerates are evidence of intense weathering (CIA > 98) under warm and wet conditions (mean annual temperature [MAT] of ~ 17 °C ± 4.4 °C and mean annual precipitation [MAP] of ~ 1500 ± 299 mm). Geologically younger Early Eocene climatic optimum (EECO, 50 Ma) high shrink-swell (Vertisol) paleosols developed in coarse sandstones are also intensely weathered (CIA > 80) with MAT estimates of ~ 20 °C ± 4.4 °C but have lower estimated MAP (~ 1100 ± 299 mm), suggesting a less humid climate for the EECO greenhouse spike than for the earlier PETM greenhouse spike.

13.
Article En | MEDLINE | ID: mdl-38177456

Dopamine can exert effects in the mammalian heart via five different dopamine receptors. There is controversy whether dopamine receptors increase contractility in the human heart. Therefore, we have generated mice that overexpress the human D1-dopamine receptor in the heart (D1-TG) and hypothesized that dopamine increases force of contraction and beating rate compared to wild-type mice (WT). In D1-TG hearts, we ascertained the presence of D1-dopamine receptors by autoradiography using [3H]SKF 38393. The mRNA for human D1-dopamine receptors was present in D1-TG hearts and absent in WT. We detected by in-situ-hybridization mRNA for D1-dopamine receptors in atrial and ventricular D1-TG cardiomyocytes compared to WT but also in human atrial preparations. We noted that in the presence of 10 µM propranolol (to antagonize ß-adrenoceptors), dopamine alone and the D1- and D5-dopamine receptor agonist SKF 38393 (0.1-10 µM cumulatively applied) exerted concentration- and time-dependent positive inotropic effects and positive chronotropic effects in left or right atrial preparations from D1-TG. The positive inotropic effects of SKF 38393 in left atrial preparations from D1-TG led to an increased rate of relaxation and accompanied by and probably caused by an augmented phosphorylation state of the inhibitory subunit of troponin. In the presence of 0.4 µM propranolol, 1 µM dopamine could increase left ventricular force of contraction in isolated perfused hearts from D1-TG. In this model, we have demonstrated a positive inotropic and chronotropic effect of dopamine. Thus, in principle, the human D1-dopamine receptor can couple to contractility in the mammalian heart.

14.
Eur Arch Psychiatry Clin Neurosci ; 274(1): 71-82, 2024 Feb.
Article En | MEDLINE | ID: mdl-37479914

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation treatment used as an alternative or complementary treatment for various neuropsychiatric disorders, and could be an alternative or add-on therapy to psychostimulants in attention-deficit hyperactivity disorder (ADHD). Previous studies provided some evidence for improvements in cognition and clinical symptoms in pediatric and adult ADHD patients. However, data from multi-center randomized controlled trials (RCTs) for this condition are lacking. Thus, our aim is to evaluate short- and mid-term effects of tDCS in this multi-center, randomized, double blind, and sham-controlled, parallel group clinical trial with a 1:1 randomization ratio. Primary endpoint is the total score of DSM-IV scale of the internationally established Conners' Adult ADHD Rating Scales (German self-report screening version, CAARS-S-SR), at day 14 post-intervention (p.i.) to detect short-term lasting effects analyzed via analyses of covariance (ANCOVAs). In case of significant between-groups differences at day 14 p.i., hierarchically ordered hypotheses on mid-term lasting effects will be investigated by linear mixed models with visit (5 time points), treatment, treatment by visit interaction, and covariates as fixed categorical effects plus a patient-specific visit random effect, using an unstructured covariance structure to model the residual within-patient errors. Positive results of this clinical trial will expand the treatment options for adult ADHD patients with tDCS and provide an alternative or add-on therapy to psychostimulants with a low risk for side effects.Trial Registration The trial was registered on July 29, 2022 in the German Clinical Trials Register (DRKS00028148).


Attention Deficit Disorder with Hyperactivity , Central Nervous System Stimulants , Transcranial Direct Current Stimulation , Adult , Humans , Attention Deficit Disorder with Hyperactivity/diagnosis , Central Nervous System Stimulants/therapeutic use , Cognition , Double-Blind Method , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Transcranial Direct Current Stimulation/methods , Treatment Outcome
15.
Eur Neuropsychopharmacol ; 78: 43-53, 2024 Jan.
Article En | MEDLINE | ID: mdl-37913697

Early identification and intervention of individuals with an increased risk for bipolar disorder (BD) may improve the course of illness and prevent long­term consequences. Early-BipoLife, a multicenter, prospective, naturalistic study, examined risk factors of BD beyond family history in participants aged 15-35 years. At baseline, positively screened help-seeking participants (screenBD at-risk) were recruited at Early Detection Centers and in- and outpatient depression and attention-deficit/hyperactivity disorder (ADHD) settings, references (Ref) drawn from a representative cohort. Participants reported sociodemographics and medical history and were repeatedly examined regarding psychopathology and the course of risk factors. N = 1,083 screenBD at-risk and n = 172 Ref were eligible for baseline assessment. Within the first two years, n = 31 screenBD at-risk (2.9 %) and none of Ref developed a manifest BD. The cumulative transition risk was 0.0028 at the end of multistep assessment, 0.0169 at 12 and 0.0317 at 24 months (p = 0.021). The transition rate with a BD family history was 6.0 %, 4.7 % in the Early Phase Inventory for bipolar disorders (EPIbipolar), 6.6 % in the Bipolar Prodrome Interview and Symptom Scale-Prospective (BPSS-FP) and 3.2 % with extended Bipolar At-Risk - BARS criteria). In comparison to help-seeking young patients from psychosis detection services, transition rates in screenBD at-risk participants were lower. The findings of Early-BipoLife underscore the importance of considering risk factors beyond family history in order to improved early detection and interventions to prevent/ameliorate related impairment in the course of BD. Large long-term cohort studies are crucial to understand the developmental pathways and long-term course of BD, especially in people at- risk.


Bipolar Disorder , Psychotic Disorders , Humans , Adolescent , Bipolar Disorder/diagnosis , Bipolar Disorder/epidemiology , Prospective Studies , Risk Factors , Risk Assessment
16.
J Voice ; 2023 Dec 02.
Article En | MEDLINE | ID: mdl-38044170

OBJECTIVES/HYPOTHESIS: The purpose of this study is to elucidate factors associated with voice therapy attendance within the interdisciplinary care model. STUDY DESIGN: This was a retrospective review. METHODS: Patients referred for voice therapy following interdisciplinary evaluation involving speech language pathology and laryngology were included. Independent variables were (1) duration between interdisciplinary voice evaluation and first voice therapy session, (2) plan of care determined at the time of evaluation, (3) mode of voice therapy delivery, and (4) stimulability for improvement during evaluation. Voice therapy attendance was measured as (1) attendance to the first voice therapy session and (2) overall voice therapy attendance. RESULTS: Of 272 patients referred for voice therapy, 69.12% attended the first session, 17.28% canceled/no-showed (C/NS), and 13.6% did not schedule the first session. Of 235 patients who scheduled voice therapy, 48.94% attended all their scheduled sessions, and 51.06% C/NS at least one session. Patients with a plan of care including voice therapy + surgery were 86% less likely (risk ratio [RR] = 0.14, P = 0.0014) to C/NS any of their voice therapy sessions. In contrast, patients with plan of care including voice therapy + medication were more likely to C/NS at least one voice therapy session (RR = 1.27, P = 0.1419), although this finding was not significant. No other covariates had a significant impact on voice therapy initiation or overall attendance. CONCLUSIONS: This study provides further support for the positive impact of interdisciplinary evaluation on voice therapy initiation. However, once voice therapy is initiated, overall C/NS rates are persistently high, consistent with previous investigations of voice therapy dropout. Our findings suggest that plan of care determined at the time of evaluation may have an impact on voice therapy attendance.

17.
Int J Mol Sci ; 24(24)2023 Dec 05.
Article En | MEDLINE | ID: mdl-38138957

Anxious depression represents a subtype of major depressive disorder and is associated with increased suicidality, severity, chronicity and lower treatment response. Only a few studies have investigated the differences between anxious depressed (aMDD) and non-anxious depressed (naMDD) patients regarding treatment dosage, serum-concentration and drug-specific treatment response. In our naturalistic and prospective study, we investigated whether the effectiveness of therapy including antidepressants (SSRI, SNRI, NaSSA, tricyclics and combinations) in aMDD patients differs significantly from that in naMDD patients. In a sample of 346 patients, we calculated the anxiety somatization factor (ASF) and defined treatment response as a reduction (≥50%) in the Hamilton Depression Rating Scale (HDRS)-21 score after 7 weeks of pharmacological treatment. We did not observe an association between therapy response and the baseline ASF-scores, or differences in therapy outcomes between aMDD and naMDD patients. However, non-responders had higher ASF-scores, and at week 7 aMDD patients displayed a worse therapy outcome than naMDD patients. In subgroup analyses for different antidepressant drugs, venlafaxine-treated aMDD patients showed a significantly worse outcome at week 7. Future prospective, randomized-controlled studies should address the question of a worse therapy outcome in aMDD patients for different psychopharmaceuticals individually.


Depression , Depressive Disorder, Major , Humans , Depressive Disorder, Major/drug therapy , Prospective Studies , Treatment Outcome , Antidepressive Agents/therapeutic use
18.
Front Psychiatry ; 14: 1130610, 2023.
Article En | MEDLINE | ID: mdl-37937233

Non-suicidal self-injury (NSSI) during adolescence is a high-risk marker for the development and persistence of mental health problems and has been recognized as a significant public health problem. Whereas targeted prevention has indeed shown to be effective in reducing NSSI and improve mental health problems, access to such programs is limited. By face validity, universal prevention of NSSI seems an ideal starting point for a stepped-care model to circumvent a lack of resources in the medical care system. However, it is yet unclear how effective such approaches are. Here, we provide a summary of existing work on universal prevention of NSSI in adolescents younger than 21 years based on a systematic literature search. We found that only seven studies are available. None of the programs evaluated was found to be effective in reducing the incidence or frequency of NSSI. After providing a comprehensive summary of the existing work, we evaluate the fact that existing work primarily focusses on selected/targeted prevention and on psychoeducational methods. We derive implications for future directions in the field of universal prevention of NSSI.

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