-
Multiple Sclerosis and Related Disorders Jul 2024The prevalence of depression in Multiple Sclerosis (MS) is often assessed by administering patient reported outcome measures (PROMs) examining depressive symptomatology...
BACKGROUND
The prevalence of depression in Multiple Sclerosis (MS) is often assessed by administering patient reported outcome measures (PROMs) examining depressive symptomatology to population cohorts; a recent review summarised 12 such studies, eight of which used the Hospital Anxiety and Depression Scale-Depression (HADS-D). In clinical practice, depression is diagnosed by an individual structured clinical interview; diagnosis often leads to treatment options including antidepressant medication. It follows that an MS population will include those whose current depressive symptoms meet threshold for depression diagnosis, plus those who previously met diagnostic criteria for depression and have been treated such that depressive symptoms have improved below that threshold. We examined a large MS population to establish a multi-attribute estimate of depression, taking into account probable depression on HADS-D, as well as anti-depressant medication use and co-morbidity data reporting current treatment for depression. We then studied associations with demographic and health status measures and the trajectories of depressive symptoms over time.
METHODS
Participants were recruited into the UK-wide Trajectories of Outcome in Neurological Conditions-MS (TONiC-MS) study, with demographic and disease data from clinical records, PROMs collected at intervals of at least 9 months, as well as co-morbidities and medication. Interval level conversions of PROM data followed Rasch analysis. Logistic regression examined associations of demographic characteristics and symptoms with depression. Finally, a group-based trajectory model was applied to those with depression.
RESULTS
Baseline data in 5633 participants showed the prevalence of depression to be 25.3 % (CI: 24.2-26.5). There were significant differences in prevalence by MS subtype: relapsing 23.2 % (CI: 21.8- 24.5), primary progressive 25.8 % (CI: 22.5-29.3), secondary progressive 31.5 % (CI: 29.0-34.0); disability: EDSS 0-4 19.2 % (CI: 17.8-20.6), EDSS ≥4.5 31.9 % (CI: 30.2-33.6); and age: 42-57 years 27.7 % (CI: 26.0-29.3), above or below this range 23.1 % (CI: 21.6-24.7). Fatigue, disability, self-efficacy and self esteem correlated with depression with a large effect size (>0.8) whereas sleep, spasticity pain, vision and bladder had an effect size >0.5. The logistic regression model (N = 4938) correctly classified 80 % with 93 % specificity: risk of depression was increased with disability, fatigue, anxiety, more comorbidities or current smoking. Higher self-efficacy or self esteem and marriage reduced depression. Trajectory analysis of depressive symptoms over 40 months in those with depression (N = 1096) showed three groups: 19.1 % with low symptoms, 49.2 % with greater symptoms between the threshold of possible and probable depression, and 31.7 % with high depressive symptoms. 29.9 % (CI: 27.6-32.3) of depressed subjects were untreated, conversely of those treated, 26.1 % still had a symptom level consistent with a probable case (CI: 23.5-28.9).
CONCLUSION
A multi-attribute estimate of depression in MS is essential because using only screening questionnaires, diagnoses or antidepressant medication all under-estimate the true prevalence. Depression affects 25.3 % of those with MS, almost half of those with depression were either untreated or still had symptoms indicating probable depression despite treatment. Services for depression in MS must be pro-active and flexible, recognising the heterogeneity of outcomes and reaching out to those with ongoing symptoms.
Topics: Humans; Female; Male; Prevalence; Middle Aged; Adult; Multiple Sclerosis; Depression; Antidepressive Agents; Comorbidity; Patient Reported Outcome Measures; United Kingdom
PubMed: 38713965
DOI: 10.1016/j.msard.2024.105648 -
Croatian Medical Journal Apr 2024To review the literature data on the prevalence of benzodiazepines abuse and poisoning in older adults; the prevalence of polypharmacy with benzodiazepines in this... (Review)
Review
AIM
To review the literature data on the prevalence of benzodiazepines abuse and poisoning in older adults; the prevalence of polypharmacy with benzodiazepines in this demographic; and determine whether benzodiazepine anxiolytics or hypnotics were more frequently implicated in the cases of abuse and poisoning.
METHODS
We searched PubMed and Scopus for relevant studies published from January 1, 2013, to May 1, 2023. Twelve studies were included in the final selection.
RESULTS
The review highlights the diverse prevalence rates of benzodiazepine abuse and poisoning in the older adult population. Benzodiazepine anxiolytics were more frequently associated with negative outcomes than benzodiazepine hypnotics. Concurrent use of benzodiazepines, benzodiazepine-related medications, and opioids was reported, although these medications were not the only ones commonly used by the elderly.
CONCLUSION
It is essential to increase awareness about adhering to prescribed pharmacological therapies to mitigate issues related to drug abuse and poisoning among older adults.
Topics: Humans; Benzodiazepines; Sleep Initiation and Maintenance Disorders; Aged; Hypnotics and Sedatives; Substance-Related Disorders; Polypharmacy; Prevalence; Aged, 80 and over; Anti-Anxiety Agents
PubMed: 38706240
DOI: 10.3325/cmj.2024.65.146 -
Toxicology Letters Jun 2024Animal research continues to serve a critical role in the testing and development of medical countermeasures. The Göttingen minipig, developed for laboratory research,...
Animal research continues to serve a critical role in the testing and development of medical countermeasures. The Göttingen minipig, developed for laboratory research, may provide many benefits for addressing research questions within chemical defense. Targeted development of the Göttingen minipig model could reduce reliance upon non-human primates, and improve study design, statistical power, and throughput to advance medical countermeasures for regulatory approval and fielding. In this vein, we completed foundational pharmacokinetics and physiological safety studies of intramuscularly administered atropine sulfate, pralidoxime chloride (2-PAM), and diazepam across a broad range of doses (1-6 autoinjector equivalent) using adult male Göttingen minipigs (n=11; n=4-8/study) surgically implanted with vascular access ports and telemetric devices to monitor cardiovascular, respiratory, arterial pressure, and temperature signals. Pharmacokinetic data were orderly and the concentration maximum mirrored available human data at comparably scaled doses clearly for atropine, moderately for 2-PAM, and poorly for diazepam. Time to peak concentration approximated 2, 7, and 20 min for atropine, 2-PAM, and diazepam, respectively, and the elimination half-life of these drugs approximated 2 hr (atropine), 3 hr (2-PAM), and 8 hr (diazepam). Atropine sulfate dose-dependently increased the magnitude and duration of tachycardia and decreased the PR and ST intervals (consistent with findings obtained from other species). Mild hypothermia was observed at the highest diazepam dose. Göttingen minipigs appear to provide a ready and appropriate large animal alternative to non-human primates, and further development and evaluation of novel nerve agent medical countermeasures and treatment strategies in this model are justified.
Topics: Animals; Swine, Miniature; Swine; Male; Diazepam; Atropine; Nerve Agents; Dose-Response Relationship, Drug; Injections, Intramuscular; Half-Life; Heart Rate; Telemetry; Models, Animal; Pralidoxime Compounds
PubMed: 38703967
DOI: 10.1016/j.toxlet.2024.04.014 -
Poultry Science Jul 2024Honokiol is a multifunctional polyphenol present in Magnolia officinalis. The effects of honokiol as a supplement in broiler chicken diets, and the underlying...
Honokiol is a multifunctional polyphenol present in Magnolia officinalis. The effects of honokiol as a supplement in broiler chicken diets, and the underlying mechanisms, remain unclear. Therefore, the aim of the present study was to investigate the effects of honokiol on the growth performance, antioxidant capacity, and intestinal histomorphology of broiler chickens and to explore the underlying mechanisms. In total, 240 one-day-old broilers were randomly allocated to 5 dietary treatments, with 6 replicate pens and 8 birds per pen. Birds were fed a basal diet supplemented with 0 (blank control, BC), 100, 200, or 400 mg/kg honokiol (H100, H200, and H400), or 200 mg/kg bacitracin zinc (PC) for 42 d. The results showed that H200 and H400 increased body weight gain (BWG) and decreased feed conversion ratio (FCR) during the starter period (P < 0.05). H100 and H200 increased total superoxide dismutase (T-SOD) activity in the serum and decreased malondialdehyde (MDA) amount in the jejunum on d 42 (P < 0.05). Moreover, H100 increased villus height-to-crypt depth ratio in both the jejunum and ileum on d 21 (P < 0.05). PCR analysis showed that honokiol upregulated intestinal expression of glutathione peroxidase (GSH-Px) and downregulated intestinal expression of inducible nitric oxide synthase (iNOS) on d 42 (P < 0.05). The Shannon index, which represents the microbial alpha diversity, was reduced for the PC, H200, and H400 groups. Notably, honokiol treatment altered the cecal microbial community structure and promoted the enrichment of several bacteria, including Firmicutes and Lactobacillus. Higher production of short-chain fatty acids was observed in the cecal digesta of H100 birds, accompanied by an enriched glycolysis/gluconeogenesis pathway, according to the functional prediction of the cecal microbiota. This study provides evidence that honokiol improves growth performance, antioxidant capacity, and intestinal health of broiler chickens, possibly by manipulating the composition and function of the microbial community.
Topics: Animals; Chickens; Lignans; Animal Feed; Biphenyl Compounds; Antioxidants; Diet; Dietary Supplements; Gastrointestinal Microbiome; Cecum; Random Allocation; Male; Intestines; Dose-Response Relationship, Drug; Animal Nutritional Physiological Phenomena; Allyl Compounds; Phenols
PubMed: 38703759
DOI: 10.1016/j.psj.2024.103798 -
Comprehensive Psychiatry Aug 2024To examine the long-term safety and tolerability of off-label high-dose serotonin reuptake inhibitors (OLHD-SRIs) in the treatment of obsessive-compulsive disorder (OCD).
OBJECTIVE
To examine the long-term safety and tolerability of off-label high-dose serotonin reuptake inhibitors (OLHD-SRIs) in the treatment of obsessive-compulsive disorder (OCD).
METHODS
A retrospective longitudinal study was performed on 105 randomly selected outpatients diagnosed with OCD and were treated with OLHD-SRIs for at least 6 months. Patients received sertraline >200 mg/day, escitalopram >20 mg/day, fluvoxamine >300 mg/day, and fluoxetine >60 mg/day, combined with exposure and response prevention therapy. Patients were divided into three dosing groups: sertraline equivalent dose (SED) ≤ 200 mg/day (n = 26, 24.7%), 201-400 mg/day (n = 51, 48.5%) and 401-650 mg/day (n = 28, 26.6%). Safety and tolerability were assessed with an electrocardiogram, blood biochemistry, complete blood count, and side-effects monitoring.
RESULTS
SED ranged from 100 to 650 mg/day and the mean duration of OLHD-SRI treatment was 20.8 months. The most common side-effects reported were sexual dysfunction (n = 36, 34%), weight gain (n = 28, 27%), sedation (n = 27, 26%), hyperhidrosis (n = 20, 19%), and tremor (n = 11, 10%). Abnormal ECG was documented in one patient, and another patient experienced a first-time seizure, whereas elevated liver enzymes were seen in 4.8% of the sample (n = 5). None of the patients had serotonin syndrome or drug-induced liver injury. Side-effects did not differ among the three dosing groups.
CONCLUSION
OLHD-SRIs appear to be safe and well tolerated in OCD patients in SED ≤ 650 mg/day doses and the side-effects did not differ between the three dosing groups.
Topics: Humans; Obsessive-Compulsive Disorder; Selective Serotonin Reuptake Inhibitors; Female; Adult; Male; Retrospective Studies; Off-Label Use; Fluvoxamine; Sertraline; Middle Aged; Longitudinal Studies; Fluoxetine; Escitalopram; Young Adult; Treatment Outcome; Dose-Response Relationship, Drug
PubMed: 38703743
DOI: 10.1016/j.comppsych.2024.152486 -
Clinical and Translational Science May 2024This parallel-arm, phase I study investigated the potential cytochrome P450 (CYP)3A induction effect of NBI-1065845 (TAK-653), an investigational... (Randomized Controlled Trial)
Randomized Controlled Trial
This parallel-arm, phase I study investigated the potential cytochrome P450 (CYP)3A induction effect of NBI-1065845 (TAK-653), an investigational α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor potentiator in phase II development for major depressive disorder. The midazolam treatment arm received the sensitive CYP3A substrate midazolam on Day 1, followed by NBI-1065845 alone on Days 5-13; on Day 14, NBI-1065845 was administered with midazolam, then NBI-1065845 alone on Day 15. The oral contraceptive treatment arm received ethinyl estradiol-levonorgestrel on Day 1, then NBI-1065845 alone on Days 5-13; on Day 14, NBI-1065845 was administered with ethinyl estradiol-levonorgestrel, then NBI-1065845 alone on Days 15-17. Blood samples were collected for pharmacokinetic analyses. The midazolam treatment arm comprised 14 men and 4 women, of whom 16 completed the study. Sixteen of the 17 healthy women completed the oral contraceptive treatment arm. After multiple daily doses of NBI-1065845, the geometric mean ratios (GMRs) (90% confidence interval) for maximum observed concentration were: midazolam, 0.94 (0.79-1.13); ethinyl estradiol, 1.00 (0.87-1.15); and levonorgestrel, 0.99 (0.87-1.13). For area under the plasma concentration-time curve (AUC) from time 0 to infinity, the GMRs were as follows: midazolam, 0.88 (0.78-0.98); and ethinyl estradiol, 1.01 (0.88-1.15). For levonorgestrel, the GMR for AUC from time 0 to the last quantifiable concentration was 0.87 (0.78-0.96). These findings indicate that NBI-1065845 is not a CYP3A inducer and support its administration with CYP3A substrates. NBI-1065845 was generally well tolerated, with no new safety signals observed after coadministration of midazolam, ethinyl estradiol, or levonorgestrel.
Topics: Humans; Midazolam; Ethinyl Estradiol; Female; Adult; Male; Young Adult; Contraceptives, Oral, Combined; Levonorgestrel; Drug Interactions; Drug Combinations; Healthy Volunteers; Adolescent; Cytochrome P-450 CYP3A; Middle Aged; Area Under Curve; Cytochrome P-450 CYP3A Inducers
PubMed: 38700236
DOI: 10.1111/cts.13791 -
Psychiatry Research Jul 2024Positive leadership behaviours at work are associated with worker well-being and performance. However there is less knowledge about whether exposure to low levels of...
Positive leadership behaviours at work are associated with worker well-being and performance. However there is less knowledge about whether exposure to low levels of positive leadership behaviours increase workers' risk of clinical mental disorders. We investigated whether low levels of positive leadership behaviours are prospectively associated with risk of treatment for depressive and anxiety disorders. In a cohort study, we linked survey data from 59,743 respondents from the Work Environment and Health in Denmark survey with national health register data. Leadership behaviours were measured with an eight-item scale. Treatment was defined as redeemed prescription for antidepressants or anxiolytics or hospital treatment for depression or anxiety. Using Cox proportional hazard regression, adjusting for demographic variables, job type and sector, adverse life events and childhood adversities, we estimated the association between leadership behaviours at baseline and risk of treatment during follow-up. We identified 999 cases of depression and anxiety treatment during follow-up. Compared to high levels of leadership behaviours, exposure to medium low and low levels were associated with an increased risk of treatment after adjustment for covariates. The results suggest that low levels of positive leadership behaviours are associated with an increased risk of treatment for depressive or anxiety disorders.
Topics: Humans; Denmark; Male; Female; Anxiety Disorders; Adult; Leadership; Middle Aged; Registries; Prospective Studies; Depressive Disorder; Follow-Up Studies; Young Adult; Workplace
PubMed: 38696969
DOI: 10.1016/j.psychres.2024.115870 -
Journal of the International AIDS... May 2024Adherence counselling with point-of-care (POC) drug-level feedback using a novel tenofovir assay may support pre-exposure prophylaxis (PrEP) adherence; however,... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Adherence counselling with point-of-care (POC) drug-level feedback using a novel tenofovir assay may support pre-exposure prophylaxis (PrEP) adherence; however, perceptions of urine testing and its impact on adherence are not well studied. We qualitatively examined how POC tenofovir testing was experienced by transgender women (TGW) in Uganda.
METHODS
Within a cluster randomized trial of peer-delivered HIV self-testing, self-sampling for sexually transmitted infections and PrEP among HIV-negative TGW showing overall low PrEP prevention-effective adherence (NCT04328025), we conducted a nested qualitative sub-study of the urine POC assay among a random sample of 30 TGW (August 2021-February 2022). TGW interviews explored: (1) experiences with POC urine tenofovir testing and (2) perceptions of PrEP adherence counselling with drug-level feedback. We used an inductive content analytic approach for analysis.
RESULTS
Median age was 21 years (interquartile range 20-24), and 70% engaged in sex work. Four content categories describe how TGW experienced POC urine tenofovir testing: (1) Urine tenofovir testing was initially met with scepticism: Testing urine to detect PrEP initially induced anxiety, with some perceptions of being intrusive and unwarranted. With counselling, however, participants found POC testing acceptable and beneficial. (2) Alignment of urine test results and adherence behaviours: Drug-level feedback aligned with what TGW knew about their adherence. Concurrence between pill taking and tenofovir detection in urine reinforced confidence in test accuracy. (3) Interpretation of urine tenofovir results: TGW familiar with the interpretation of oral-fluid HIV self-tests knew that two lines on the test device signified positivity (presence of HIV). However, two lines on the urine test strip indicated a positive result for non-adherence (absence of tenofovir), causing confusion. Research nurses explained the difference in test interpretation to participants' satisfaction. (4) White coat dosing: Some TGW deliberately chose not to attend scheduled clinic appointments to avoid detecting their PrEP non-adherence during urine testing. They restarted PrEP before returning to clinic, a behaviour called "white coat dosing."
CONCLUSIONS
Incorporating POC urine testing into routine PrEP adherence counselling was acceptable and potentially beneficial for TGW but required attention to context. Additional research is needed to identify effective strategies for optimizing adherence monitoring and counselling for this population.
Topics: Humans; Tenofovir; Uganda; Pre-Exposure Prophylaxis; Female; HIV Infections; Transgender Persons; Young Adult; Medication Adherence; Anti-HIV Agents; Male; Qualitative Research; Adult; Counseling
PubMed: 38695107
DOI: 10.1002/jia2.26255 -
Journal of Ethnopharmacology Sep 2024The use of medicinal plants for central nervous system (CNS)-related ailments, such as epilepsy and anxiety, is prevalent in South Africa. Plants from the Lamiaceae...
ETHNOPHARMACOLOGICAL RELEVANCE
The use of medicinal plants for central nervous system (CNS)-related ailments, such as epilepsy and anxiety, is prevalent in South Africa. Plants from the Lamiaceae family are commonly used for their therapeutic benefits. Leonotis leonurus (L.) R.Br. has been reported in ethnobotanical literature to have anticonvulsant and anxiolytic effects through the inhalation of pyrolysis products obtained by combustion of the aerial parts.
AIM AND OBJECTIVES
To explore the chemical profiles and CNS activity of the smoke extract and isolated constituents of L. leonurus in zebrafish larvae, through anticonvulsive and anxiolytic activity assays.
MATERIALS AND METHODS
The smoke extract of L. leonurus was obtained through the combustion of the aerial parts of the plant using a custom-built smoke recovery apparatus. The chemical profile of the smoke constituents was determined using Ultra-Performance Liquid Chromatography coupled with Mass Spectrometry (UPLC-MS). Targeted compounds were subjected to preparative High-Performance Liquid Chromatography for separation before structure elucidation using Nuclear Magnetic Resonance (NMR). The maximum tolerated concentrations, as well as the anxiolytic activity of the smoke extract were determined in five days post fertilisation zebrafish larvae. Reverse-thigmotaxis and locomotor activity of larvae in the light/dark transition assay were used to determine anxiolytic activity. Zebrafish larvae at six days post fertilisation (dpf) were subjected to several concentrations of the smoke constituents of L. leonurus. The baseline locomotor activity of the larvae was tracked for 30 min, prior to addition of pentylenetetrazole (PTZ) to induce seizure-like behaviour in the larvae, after which the locomotor activity of the larvae was once again tracked for an additional 30 min.
RESULTS
The UPLC-MS profiles of the smoke extract revealed the presence of two main compounds, leoleorin A and leoleorin B, which were targeted and isolated. Upon subjection to NMR spectroscopy for structure elucidation, the compounds were confirmed to be labdane diterpenoids. Both leoleorin A and leoleorin B, and the smoke extract displayed suppression of the PTZ induced seizure-like behaviour in zebrafish larvae. Under light and dark conditions, the smoke extract and compounds displayed potential anxiolytic activity at different concentrations.
CONCLUSION
Our results suggest that the smoke constituents of L. leonurus may exert anticonvulsant and anxiolytic effects which align with the traditional indications and the mode of administration.
Topics: Animals; Zebrafish; Anti-Anxiety Agents; Smoke; Plant Extracts; Anticonvulsants; Seizures; Larva; Lamiaceae; Pentylenetetrazole; Plant Components, Aerial; South Africa; Behavior, Animal
PubMed: 38688356
DOI: 10.1016/j.jep.2024.118271 -
BMC Medicine Apr 2024The exact mechanisms linking the gut microbiota and social behavior are still under investigation. We aimed to explore the role of the gut microbiota in shaping social...
BACKGROUND
The exact mechanisms linking the gut microbiota and social behavior are still under investigation. We aimed to explore the role of the gut microbiota in shaping social behavior deficits using selectively bred mice possessing dominant (Dom) or submissive (Sub) behavior features. Sub mice exhibit asocial, depressive- and anxiety-like behaviors, as well as systemic inflammation, all of which are shaped by their impaired gut microbiota composition.
METHODS
An age-dependent comparative analysis of the gut microbiota composition of Dom and Sub mice was performed using 16S rRNA sequencing, from early infancy to adulthood. Dom and Sub gastrointestinal (GI) tract anatomy, function, and immune profiling analyses were performed using histology, RT-PCR, flow cytometry, cytokine array, and dextran-FITC permeability assays. Short chain fatty acids (SCFA) levels in the colons of Dom and Sub mice were quantified using targeted metabolomics. To support our findings, adult Sub mice were orally treated with hyaluronic acid (HA) (30 mg/kg) or with the non-steroidal anti-inflammatory agent celecoxib (16 mg/kg).
RESULTS
We demonstrate that from early infancy the Sub mouse gut microbiota lacks essential bacteria for immune maturation, including Lactobacillus and Bifidobacterium genera. Furthermore, from birth, Sub mice possess a thicker colon mucin layer, and from early adulthood, they exhibit shorter colonic length, altered colon integrity with increased gut permeability, reduced SCFA levels and decreased regulatory T-cells, compared to Dom mice. Therapeutic intervention in adult Sub mice treated with HA, celecoxib, or both agents, rescued Sub mice phenotypes. HA treatment reduced Sub mouse gut permeability, increased colon length, and improved mouse social behavior deficits. Treatment with celecoxib increased sociability, reduced depressive- and anxiety-like behaviors, and increased colon length, and a combined treatment resulted in similar effects as celecoxib administered as a single agent.
CONCLUSIONS
Overall, our data suggest that treating colon inflammation and decreasing gut permeability can restore gut physiology and prevent social deficits later in life. These findings provide critical insights into the importance of early life gut microbiota in shaping gut immunity, functionality, and social behavior, and may be beneficial for the development of future therapeutic strategies.
Topics: Animals; Gastrointestinal Microbiome; Celecoxib; Mice; Hyaluronic Acid; Social Behavior; Colon; Inflammation; Male; Behavior, Animal; RNA, Ribosomal, 16S
PubMed: 38685001
DOI: 10.1186/s12916-024-03323-0