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1.
Rev. neurol. (Ed. impr.) ; 78(9)1-15 may 2024. ilus
Article in Spanish | IBECS | ID: ibc-CR-366

ABSTRACT

Introducción Presentamos un paciente diagnosticado de narcolepsia de tipo 1 que desarrolló una encefalitis autoinmune posvacunal y/o tras una infección por el SARS-CoV-2. Caso clínico Paciente de 23 años que es remitido a urgencias por trastorno del lenguaje y temblor, acompañados de cefalea, trastorno del comportamiento, disfunción autonómica, crisis focal motora derecha y letargo. El paciente había sido vacunado siete semanas antes con la primera dosis de la vacuna Moderna (ARN mensajero) y, cuatro semanas después de la vacunación, presentó una infección por el SARS-CoV-2 con test de antígenos positivo. Resultados La exploración neurológica mostró un nivel de conciencia normal y una afasia mixta de predominio motor (campimetría, pares craneales, reflejos y sensibilidad normales). El test de reacción en cadena de la polimerasa para la COVID-19 fue negativo. En el líquido cefalorraquídeo se apreció una linfocitosis y proteínas elevadas. Los cultivos para hongos y bacterias fueron negativos. Los anticuerpos onconeuronales fueron normales. La resonancia magnética cerebral mostró en la secuencia de difusión una restricción con afectación cortical y morfología giral en el hemisferio cerebral izquierdo, y distribución parcheada con afectación de lóbulo frontal y temporal izquierdos. Una tomografía axial computarizada de tórax-abdomen-pelvis fue normal, al igual que las ecografías pélvica y escrotal. Al paciente se le trató con plasmaféresis y corticoides, con buena evolución clínica y resolución casi completa de las anomalías en la neuroimagen. Conclusión Se trata de un paciente con narcolepsia de tipo 1 con criterios de encefalitis autoinmune de comienzo subagudo. La infección por el SARS-CoV-2 o la vacunación, o ambas, constituyen un riesgo para desarrollar una o más enfermedades autoinmunes con la edad –como sucede en este caso–, lo que permite comprender la implicación de procesos inmunomediados en la fisiopatología de estas enfermedades. (AU)


INTRODUCTION We present a narcolepsy type 1 patient that develop an autoimmune encephalitis post vaccine and/or a SARS-CoV-2 infection.CASE REPORTAt 23 years old, the patient was referred to the emergency room with difficult speaking, headache and tremor followed by changes in behavior, autonomic dysfunction, right focal motor seizure and lethargy. He has received seven weeks before mRNA-1273 (Moderna) vaccine followed by a SARS-CoV-2 infection four weeks after vaccination (positive antigen test).RESULTSThe neurological examination was normal (visual fields, cranial nerves, motor, sensory and reflexes). Nasopharyngeal swab polymerase chain reaction (PCR) testing for COVID-19 was negative. Cerebrospinalfluid (CSF) had highly elevated protein and lymphocytic pleocytosis. CSF bacterial and fungal cultures for viral infections were negative. Brain magnetic resonance imaging (MRI) showed no abnormality on the non-enhanced sequences but the diffusion weighted imaging showed restricted diffusion with high signal on the left hemisphere mainly in the cerebral cortex with a gyro morphology, patched distribution with involvement of the temporal and frontal lobes. Chest, abdomen and pelvis computed tomography; pelvic and scrotum ultrasound, showed no malignancy. Onconeural antibodies were negative. The patient was treated with plasmapheresis and corticosteroids with a good clinical outcome and near complete resolution of the MRI abnormalities. CONCLUSION. The patient fulfilled the diagnostic criteria for autoimmune encephalitis with subacute onset. COVID-19 infection and vaccination could constitute a risk in a patient with narcolepsy as in this case and, could help to provide better understanding of the implication of immune-mediated processes in the pathophysiology of the diseases. (AU)


Subject(s)
Humans , Young Adult , Comorbidity , Autoimmune Diseases of the Nervous System/diagnostic imaging , Vaccination/adverse effects , Narcolepsy
2.
BMC Med ; 22(1): 151, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38589864

ABSTRACT

BACKGROUND: Clinical complexity, as the interaction between ageing, frailty, multimorbidity and polypharmacy, is an increasing concern in patients with AF. There remains uncertainty regarding how combinations of comorbidities influence management and prognosis of patients with atrial fibrillation (AF). We aimed to identify phenotypes of AF patients according to comorbidities and to assess associations between comorbidity patterns, drug use and risk of major outcomes. METHODS: From the prospective GLORIA-AF Registry, we performed a latent class analysis based on 18 diseases, encompassing cardiovascular, metabolic, respiratory and other conditions; we then analysed the association between phenotypes of patients and (i) treatments received and (ii) the risk of major outcomes. Primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACE). Secondary exploratory outcomes were also analysed. RESULTS: 32,560 AF patients (mean age 70.0 ± 10.5 years, 45.4% females) were included. We identified 6 phenotypes: (i) low complexity (39.2% of patients); (ii) cardiovascular (CV) risk factors (28.2%); (iii) atherosclerotic (10.2%); (iv) thromboembolic (8.1%); (v) cardiometabolic (7.6%) and (vi) high complexity (6.6%). Higher use of oral anticoagulants was found in more complex groups, with highest magnitude observed for the cardiometabolic and high complexity phenotypes (odds ratio and 95% confidence interval CI): 1.76 [1.49-2.09] and 1.57 [1.35-1.81], respectively); similar results were observed for beta-blockers and verapamil or diltiazem. We found higher risk of the primary outcome in all phenotypes, except the CV risk factor one, with highest risk observed for the cardiometabolic and high complexity groups (hazard ratio and 95%CI: 1.37 [1.13-1.67] and 1.47 [1.24-1.75], respectively). CONCLUSIONS: Comorbidities influence management and long-term prognosis of patients with AF. Patients with complex phenotypes may require comprehensive and holistic approaches to improve their prognosis.


Subject(s)
Atrial Fibrillation , Stroke , Female , Humans , Middle Aged , Aged , Aged, 80 and over , Male , Atrial Fibrillation/drug therapy , Atrial Fibrillation/epidemiology , Prospective Studies , Risk Factors , Treatment Outcome , Comorbidity , Anticoagulants , Registries , Stroke/epidemiology
3.
Sci Rep ; 14(1): 6007, 2024 03 12.
Article in English | MEDLINE | ID: mdl-38472388

ABSTRACT

Although coffee is one of the most consumed caffeinated beverages worldwide, the role of coffee consumption in migraine is controversial. This study examined the relationship between coffee consumption and clinical characteristics in participants with migraine compared to those with non-migraine headache. This cross-sectional study used data from a nationwide survey on headache and sleep. Coffee consumption was classified as no-to-low (< 1 cup/day), moderate (1-2 cups/day), or high (≥ 3 cups/day). Of the 3030 survey participants, 170 (5.6%) and 1,768 (58.3%) were identified as having migraine and non-migraine headache, respectively. Coffee consumption tended to increase in the order of non-headache, non-migraine headache, and migraine (linear-by-linear association, p = 0.011). Although psychiatric comorbidities (depression for migraine and anxiety for non-migraine headache) and stress significantly differed according to coffee consumption, most headache characteristics and accompanying symptoms did not differ among the three groups for participants with migraine and non-migraine headache. Response to acute headache treatment-adjusted for age, sex, depression, anxiety, stress, preventive medication use, and current smoking-was not significantly different by coffee consumption in participants with migraine and non-migraine headache. In conclusion, most headache-related characteristics and acute treatment response did not significantly differ by coffee consumption in migraine and non-migraine headache.


Subject(s)
Coffee , Migraine Disorders , Humans , Cross-Sectional Studies , Migraine Disorders/epidemiology , Headache/epidemiology , Comorbidity
4.
PLoS One ; 19(3): e0299904, 2024.
Article in English | MEDLINE | ID: mdl-38489252

ABSTRACT

BACKGROUND: Integrated health care is an approach characterized by a high degree of collaboration and communication among health professionals. Integration of HIV/NCD is recommended to enhance the quality of healthcare services being provided. Duplication of limited resources is minimized, and a holistic care approach is promoted by shifting from acute and reactive care to care that embraces patient-centredness that includes promotive health and disease surveillance. The high burden of HIV disease in sub-Saharan Africa (SSA) combined with the increasing prevalence of chronic non-communicable diseases (NCDs) necessitates a review of how health systems has been doing to deliver quality integrated care for people living with HIV (PLWH) and comorbid chronic NCDs. METHODS: A scoping review was conducted to identify and describe all publications on integrated chronic care management models at the primary care level in the SSA context, particularly those that addressed the care of PLHIV with co-morbid chronic NCDs. The inclusion and exclusion criteria were applied, and duplicates were removed. RESULTS: A total of twenty-one articles were included in the final review. Integrated healthcare systems were reported in only eight SSA countries-(South Africa, Uganda, Kenya, the United Republic of Tanzania, Zambia, Malawi, Zimbabwe and Swaziland). Integrated care systems adopted one of three health models. These included added-on NCD services to previously dedicated HIV care facilities, expansion of primary care facilities to include HIV care and establishment of integrated care services. Short-term benefits included staff capacitation, improved retention of patients and improved screening and detection of NCDs. However, the expansion of existing services resulted in an increased workload with no additional staff. A significant positive change noted by communities was that there was less or no stigmatisation of people living with HIV when attending dedicated HIV clinics. CONCLUSION: Evidence of integrated healthcare services for PLWH and co-morbid of NCDs in SSA is scanty. Data on some short-term benefits of integrated care was available, but evidence was absent on the long-term outcomes. Randomized clinical trials with clearly defined comparator groups and standardized measures of HIV and NCD outcomes are needed to demonstrate non-inferiority of integrated against non-integrated care.


Subject(s)
Delivery of Health Care, Integrated , HIV Infections , Noncommunicable Diseases , Humans , Noncommunicable Diseases/therapy , Noncommunicable Diseases/prevention & control , HIV Infections/complications , HIV Infections/epidemiology , HIV Infections/therapy , Comorbidity , Persistent Infection , South Africa
5.
Int Rev Neurobiol ; 175: 1-19, 2024.
Article in English | MEDLINE | ID: mdl-38555113

ABSTRACT

Alcohol is a major cause of pre-mature death and individual suffering worldwide, and the importance of diagnosing and treating AUD cannot be overstated. Given the global burden and the high attributable factor of alcohol in a vast number of diseases, the need for additional interventions and the development of new medicines is considered a priority by the World Health Organization (WHO). As of today, AUD is severely under-treated with a treatment gap nearing 90%, strikingly higher than that for other psychiatric disorders. Patients often seek treatment late in the progress of the disease and even among those who seek treatment only a minority receive medication, mirroring the still-prevailing stigma of the disease, and a lack of access to effective treatments, as well as a reluctance to total abstinence. To increase adherence, treatment goals should focus not only on maintaining abstinence, but also on harm reduction and psychosocial functioning. A personalised approach to AUD treatment, with a holistic view, and tailored therapy has the potential to improve AUD treatment outcomes by targeting the heterogeneity in genetics and pathophysiology, as well as reason for, and reaction to drinking. Also, the psychiatric co-morbidity rates are high in AUD and dual diagnosis can worsen symptoms and influence treatment response and should be considered in the treatment strategies.


Subject(s)
Alcoholism , Humans , Alcoholism/diagnosis , Alcoholism/epidemiology , Alcoholism/therapy , Treatment Outcome , Comorbidity
6.
J Neurosci ; 44(15)2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38453468

ABSTRACT

The comorbidity of chronic pain and depression poses tremendous challenges for the treatment of either one because they exacerbate each other with unknown mechanisms. As the posterior insular cortex (PIC) integrates multiple somatosensory and emotional information and is implicated in either chronic pain or depression, we hypothesize that the PIC and its projections may contribute to the pathophysiology of comorbid chronic pain and depression. We show that PIC neurons were readily activated by mechanical, thermal, aversive, and stressful and appetitive stimulation in naive and neuropathic pain male mice subjected to spared nerve injury (SNI). Optogenetic activation of PIC neurons induced hyperalgesia and conditioned place aversion in naive mice, whereas inhibition of these neurons led to analgesia, conditioned place preference (CPP), and antidepressant effect in both naive and SNI mice. Combining neuronal tracing, optogenetics, and electrophysiological techniques, we found that the monosynaptic glutamatergic projections from the PIC to the basolateral amygdala (BLA) and the ventromedial nucleus (VM) of the thalamus mimicked PIC neurons in pain modulation in naive mice; in SNI mice, both projections were enhanced accompanied by hyperactivity of PIC, BLA, and VM neurons and inhibition of these projections led to analgesia, CPP, and antidepressant-like effect. The present study suggests that potentiation of the PIC→BLA and PIC→VM projections may be important pathophysiological bases for hyperalgesia and depression-like behavior in neuropathic pain and reversing the potentiation may be a promising therapeutic strategy for comorbid chronic pain and depression.


Subject(s)
Chronic Pain , Neuralgia , Mice , Male , Animals , Hyperalgesia , Chronic Pain/complications , Depression , Insular Cortex , Amygdala/metabolism , Neuralgia/metabolism , Comorbidity , Thalamus , Antidepressive Agents/therapeutic use
7.
Haemophilia ; 30 Suppl 3: 5-11, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38539058

ABSTRACT

As treatments for individuals with inherited bleeding disorders improve, life expectancy increases and is approaching that of the normal population. Concomitant with this we are now seeing the problems of ageing in the bleeding disorder population. Although the clear-cut association between low clotting factor levels and risk of bleeding is well recognised, a relationship between high levels, some non-factor therapies and thrombotic risk also exists. The management of thrombosis in persons with inherited bleeding disorders is complex but manageable with modern treatments and collaboration in decision making between health care professionals and patients. Despite the improvements in treatment and reduction in bleeding, mostly musculoskeletal pain continues to be a major issue with advancing age. The management of pain amongst older people with haemophilia who may have multiple comorbidities should involve a person-centred, holistic, multi-disciplinary approach to support and optimise long-term physical functioning and overall quality of life.


Subject(s)
Hemophilia A , Humans , Aged , Hemophilia A/complications , Hemophilia A/therapy , Hemophilia A/epidemiology , Quality of Life , Blood Coagulation Factors , Aging , Comorbidity
8.
Basic Clin Pharmacol Toxicol ; 134(5): 574-601, 2024 May.
Article in English | MEDLINE | ID: mdl-38477419

ABSTRACT

Studies have demonstrated the neuroprotective effect of cannabidiol (CBD) and other Cannabis sativa L. derivatives on diseases of the central nervous system caused by their direct or indirect interaction with endocannabinoid system-related receptors and other molecular targets, such as the 5-HT1A receptor, which is a potential pharmacological target of CBD. Interestingly, CBD binding with the 5-HT1A receptor may be suitable for the treatment of epilepsies, parkinsonian syndromes and amyotrophic lateral sclerosis, in which the 5-HT1A serotonergic receptor plays a key role. The aim of this review was to provide an overview of cannabinoid effects on neurological disorders, such as epilepsy, multiple sclerosis and Parkinson's diseases, and discuss their possible mechanism of action, highlighting interactions with molecular targets and the potential neuroprotective effects of phytocannabinoids. CBD has been shown to have significant therapeutic effects on epilepsy and Parkinson's disease, while nabiximols contribute to a reduction in spasticity and are a frequent option for the treatment of multiple sclerosis. Although there are multiple theories on the therapeutic potential of cannabinoids for neurological disorders, substantially greater progress in the search for strong scientific evidence of their pharmacological effectiveness is needed.


Subject(s)
Cannabidiol , Cannabinoids , Epilepsy , Mental Disorders , Multiple Sclerosis , Parkinson Disease , Humans , Cannabidiol/pharmacology , Cannabidiol/therapeutic use , Parkinson Disease/drug therapy , Multiple Sclerosis/drug therapy , Receptor, Serotonin, 5-HT1A/therapeutic use , Cannabinoids/pharmacology , Cannabinoids/therapeutic use , Epilepsy/drug therapy , Mental Disorders/drug therapy , Comorbidity
9.
Article in English | MEDLINE | ID: mdl-38505581

ABSTRACT

Preserved Ratio Impaired Spirometry (PRISm) manifests notable epidemiological disparities across the globe, with its prevalence and influential factors showcasing pronounced diversities among various geographical territories and demographics. The prevalence of PRISm fluctuates considerably among regions such as Latin America, the United States, and Asian nations, potentially correlating with a myriad of determinants, including socioeconomic status, environmental factors, and lifestyle modalities. Concurrently, the link between PRISm and health risks and other disorders, especially its distinction and interrelation with chronic obstructive pulmonary disease (COPD), has become a pivotal subject of scientific enquiry. Radiographic anomalies, such as perturbations in the pulmonary parenchyma and structural alterations, are posited as salient characteristics of PRISm. Furthermore, PRISm unveils intricate associations with multiple comorbidities, inclusive of hypertension and type 2 diabetes, thereby amplifying the intricacy in comprehending and managing this condition. In this review, we aim to holistically elucidate the epidemiological peculiarities of PRISm, its potential aetiological contributors, its nexus with COPD, and its association with radiographic aberrations and other comorbidities. An integrative understanding of these dimensions will provide pivotal insights for the formulation of more precise and personalised preventative and therapeutic strategies.


Subject(s)
Diabetes Mellitus, Type 2 , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/diagnostic imaging , Pulmonary Disease, Chronic Obstructive/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Comorbidity , Lung/diagnostic imaging , Spirometry/methods , Forced Expiratory Volume
10.
J Am Acad Orthop Surg ; 32(10): 464-471, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38484091

ABSTRACT

INTRODUCTION: Vitamin D plays a critical role in bone health, affecting bone mineral density and fracture healing. Insufficient serum vitamin D levels are associated with increased fracture rates. Despite guidelines advocating vitamin D supplementation, little is known about the prescription rates after fragility fractures. This study aims to characterize vitamin D prescription rates after three common fragility fractures in patients older than 50 years and explore potential factors influencing prescription rates. METHODS: The study used the PearlDiver Database, identifying patients older than 50 years with hip fractures, spinal compression fractures, or distal radius fractures between 2010 and 2020. Patient demographics, comorbidities, and vitamin D prescription rates were analyzed. Statistical methods included chi-square analysis and univariate and multivariable analyses. RESULTS: A total of 3,214,294 patients with fragility fractures were included. Vitamin D prescriptions increased from 2.50% to nearly 6% for all fracture types from 2010 to 2020. Regional variations existed, with the Midwest having the highest prescription rate (4.25%) and the West the lowest (3.31%). Patients with comorbidities such as diabetes, tobacco use, obesity, female sex, age older than 60 years, and osteoporosis were more likely to receive vitamin D prescriptions. DISCUSSION: Despite a notable increase in vitamin D prescriptions after fragility fractures, the absolute rates remain low. Patient comorbidities influenced prescription rates, perhaps indicating growing awareness of the link between vitamin D deficiency and these conditions. However, individuals older than 60 years, a high-risk group, were markedly less likely to receive prescriptions, possibly because of practice variations and concerns about polypharmacy. Educational initiatives and revised guidelines may have improved vitamin D prescription rates after fragility fractures. However, there is a need to raise awareness about the importance of vitamin D for bone health, particularly in older adults, and additional study variations in prescription practices. These findings emphasize the importance of enhancing post-fracture care to reduce morbidity and mortality associated with fragility fractures. LEVEL OF EVIDENCE: III.


Subject(s)
Databases, Factual , Vitamin D , Humans , Female , Male , Aged , Middle Aged , Vitamin D/therapeutic use , Vitamin D/blood , Aged, 80 and over , Osteoporotic Fractures/prevention & control , Osteoporotic Fractures/epidemiology , United States/epidemiology , Spinal Fractures/epidemiology , Hip Fractures , Radius Fractures , Practice Patterns, Physicians'/statistics & numerical data , Drug Prescriptions/statistics & numerical data , Osteoporosis/drug therapy , Comorbidity
11.
Psychiatr Clin North Am ; 47(1): 163-178, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38302205

ABSTRACT

Individuals with delayed sleep phase disorder (DSPD) are unable to naturally fall asleep and awake at conventional times; for this reason, DSPD is often mistaken for insomnia. However, unlike many patients with insomnia, those with DSPD struggle to get up at appropriate times. DSPD is associated with school refusal, academic difficulties, and lower employment rate. DSPD in youth has prevalence as high as 16%, and is often comorbid with other psychiatric disorders. Treatments include appropriate light exposure during the day, melatonin use, developing an evening routine that minimizes arousal-increasing activities, and gradually shifting sleep-wake times toward more functional ones.


Subject(s)
Melatonin , Sleep Disorders, Circadian Rhythm , Sleep Initiation and Maintenance Disorders , Humans , Adolescent , Sleep Initiation and Maintenance Disorders/diagnosis , Sleep Initiation and Maintenance Disorders/therapy , Sleep Initiation and Maintenance Disorders/epidemiology , Sleep Disorders, Circadian Rhythm/diagnosis , Sleep Disorders, Circadian Rhythm/therapy , Sleep Disorders, Circadian Rhythm/epidemiology , Sleep , Comorbidity , Melatonin/therapeutic use , Circadian Rhythm
12.
Prague Med Rep ; 125(1): 87-91, 2024.
Article in English | MEDLINE | ID: mdl-38380457

ABSTRACT

Chronic abdominal pain is a challenging problem in clinical practice, with several pathophysiological mechanisms underlying its aetiologies. This case report presents a geriatric patient with multiple comorbidities who had experienced intermittent abdominal pain for over 10 years. Alarming symptoms were ruled out, and a functional gastrointestinal disorder was determined as the most likely cause. The patient's medical history and previous treatments were thoroughly reviewed, revealing that long-term use of metformin and an oral iron supplement was the iatrogenic symptom triggers. The abdominal pain resolved upon discontinuation of these two medications. This case report highlights the significance of reviewing iatrogenic causes and periodically assessing chronic medical conditions to identify potential contributing factors of chronic abdominal pain.


Subject(s)
Abdominal Pain , Gastrointestinal Diseases , Humans , Aged , Abdominal Pain/diagnosis , Abdominal Pain/etiology , Abdominal Pain/therapy , Gastrointestinal Diseases/complications , Chronic Disease , Comorbidity , Iatrogenic Disease
13.
Br J Oral Maxillofac Surg ; 62(3): 318-323, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38355385

ABSTRACT

Patients with chronic pain have a higher prevalence of mood disorders with depression and anxiety contributing to higher pain intensity, emotional allodynia, and neuro-anatomical changes. We sought to quantify the prevalence of psychiatric comorbidities (PCs) in a tertiary referral clinic for temporomandibular disorders (TMDs). Medical records of all patients attending clinics run by three tertiary temporomandibular joint (TMJ) surgeons for the period January to April 2022 inclusive were audited for the prevalence of concomitant psychiatric conditions. A total of 166 patients were identified with a female to male ratio of 5:1 and mean (SD) age of 45.1 (15.2) years. A total of 124 (89.9%) patients were tertiary referrals and 72 (43.4%) patients had concomitant psychiatric diagnoses, with 58 (34.9%) being on some form of psychotropic medication (PM) (patients on anticonvulsants for neuropathic pain were not included). A majority of 136 (81.9%) patients had some form of intervention (including Dysport® and minimally invasive surgery) which appeared more common in patients with co-existing psychiatric issues (p < 0.05). A higher proportion of mental health issues exist among TMD patients in a tertiary referral clinic than would be expected in the general population. We suggest a holistic approach to patients with multidisciplinary care taking into account this prevalence to ensure decision-making that contextualises the patient and not simply the pathology.


Subject(s)
Comorbidity , Mental Disorders , Temporomandibular Joint Disorders , Tertiary Care Centers , Humans , Temporomandibular Joint Disorders/epidemiology , Temporomandibular Joint Disorders/complications , Male , Female , Middle Aged , Mental Disorders/epidemiology , Mental Disorders/complications , Adult , Prevalence , Chronic Pain/epidemiology , Retrospective Studies
14.
J Neurosci ; 44(13)2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38378273

ABSTRACT

Patients with chronic pain often develop comorbid depressive symptoms, which makes the pain symptoms more complicated and refractory. However, the underlying mechanisms are poorly known. Here, in a repeated complete Freund's adjuvant (CFA) male mouse model, we reported a specific regulatory role of the paraventricular thalamic nucleus (PVT) glutamatergic neurons, particularly the anterior PVT (PVA) neurons, in mediating chronic pain and depression comorbidity (CDC). Our c-Fos protein staining observed increased PVA neuronal activity in CFA-CDC mice. In wild-type mice, chemogenetic activation of PVA glutamatergic neurons was sufficient to decrease the 50% paw withdrawal thresholds (50% PWTs), while depressive-like behaviors evaluated with immobile time in tail suspension test (TST) and forced swim test (FST) could only be achieved by repeated chemogenetic activation. Chemogenetic inhibition of PVA glutamatergic neurons reversed the decreased 50% PWTs in CFA mice without depressive-like symptoms and the increased TST and FST immobility in CFA-CDC mice. Surprisingly, in CFA-CDC mice, chemogenetically inhibiting PVA glutamatergic neurons failed to reverse the decrease of 50% PWTs, which could be restored by rapid-onset antidepressant S-ketamine. Further behavioral tests in chronic restraint stress mice and CFA pain mice indicated that PVA glutamatergic neuron inhibition and S-ketamine independently alleviate sensory and affective pain. Molecular profiling and pharmacological studies revealed the 5-hydroxytryptamine receptor 1D (Htr1d) in CFA pain-related PVT engram neurons as a potential target for treating CDC. These findings identified novel CDC neuronal and molecular mechanisms in the PVT and provided insight into the complicated pain neuropathology under a comorbid state with depression and related drug development.


Subject(s)
Chronic Pain , Ketamine , Humans , Mice , Male , Animals , Chronic Pain/metabolism , Depression/drug therapy , Thalamus , Neurons/metabolism , Comorbidity
15.
Curr Med Res Opin ; 40(4): 665-676, 2024 04.
Article in English | MEDLINE | ID: mdl-38363353

ABSTRACT

OBJECTIVE: Limited real-world evidence exists to better understand the patient experience of living with symptoms and impacts of non-alcoholic steatohepatitis (NASH). This study aimed to (1) describe patient-reported perspectives of NASH symptoms and impacts on patients' daily lives and (2) develop a patient-centered conceptual NASH model. METHODS: A cross-sectional study using semi-structured qualitative interviews was conducted among adults (≥18 years) in the United States living with NASH. Eligible participants were diagnosed with NASH, had mild to advanced fibrosis (F1-F3), and no other causes of liver disease. The interview guide was informed by a targeted literature review (TLR) to identify clinical signs, symptoms, impacts, and unmet treatment needs of NASH. Participants described their experiences and perspectives around NASH and the symptoms, symptom severity/bother, and impact of NASH on their daily activities. Interviews were audio-recorded and transcribed verbatim for coding and thematic analysis. RESULTS: Twenty participants (age: 42.4 years; female: 50.0%) were interviewed. Participants discussed their experience with NASH symptoms (most frequent: fatigue [75.0%]; weakness/lethargy [70.0%]) and impacts (most frequent: physical and psychological/emotional [70.0% each]; dietary [68.4%]). Participants considered most symptoms to be moderately severe or severe and moderately or highly bothersome. Findings from the TLR and qualitative interviews were incorporated into a conceptual model that describes patient-reported symptoms and impacts of NASH, clinical signs, risk factors, and unmet treatment needs. CONCLUSION: Our study provides insights into patients' perspectives of NASH symptoms and their impact on their daily lives. These findings may guide patient-physician conversations, supporting patient-centered treatment decisions and disease management.


Study findings help to address the gap in current literature about patients' perspectives on NASH and its symptoms as well as its impact on daily life.The study proposes a holistic conceptual model that describes patients' perspectives of living with NASH, including symptoms and their impact, the clinical signs and risk factors of NASH, and the unmet treatment needs of the disease.Healthcare providers can use study findings to inform patient-focused decisions around treatment strategies for NASH.


Subject(s)
Non-alcoholic Fatty Liver Disease , Adult , Humans , Female , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/epidemiology , Cross-Sectional Studies , Comorbidity , Risk Factors
16.
J Appl Res Intellect Disabil ; 37(3): e13214, 2024 May.
Article in English | MEDLINE | ID: mdl-38383947

ABSTRACT

BACKGROUND: The Fragile X community has expressed a desire for centralised, national guidelines in the form of integrated guidance for Fragile X Syndrome (FXS). METHODS: This article draws on existing literature reviews, primary research and clinical trials on FXS, a Fragile X Society conference workshop and first-hand experience of clinicians who have worked with those living with FXS over many years. RESULTS: The article scopes proposed integrated guidance over the life course, including appendices of symptoms, comorbidities and referral options for FXS and Fragile X Premutation Associated Conditions. CONCLUSION: Integrated guidance would provide an authoritative source for doctors, health professionals, therapists, care workers, social workers, educators, employers, families and those living with FXS, so that a holistic, person-centred approach can be taken across the United Kingdom to garner the best outcomes for those with FXS.


Subject(s)
Fragile X Syndrome , Intellectual Disability , Humans , Fragile X Syndrome/therapy , Intellectual Disability/complications , Comorbidity , Health Personnel , Patient-Centered Care
17.
Curr Probl Cardiol ; 49(4): 102430, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38309544

ABSTRACT

The global epidemiological transition of atherosclerotic vascular diseases is witnessing a rapid redistribution of its burden, shifting from high-income to low- and middle-income countries. With a wide clinical spectrum, spanning from intermittent claudication to more complex critical limb threatening ischemia, nonhealing ulcers, gangrene as well as acute limb ischemia, peripheral artery disease is often faced with the challenges of under-diagnosis and under-treatment despite its high prevalence. The management of peripheral arterial disease in patients with multiple comorbidities presents a formidable challenge and remains a pressing global health concern. In this review, we aim to provide an in-depth overview of the pathophysiology of peripheral artery disease and explore evidence-based management strategies encompassing pharmacological, lifestyle, interventional, and surgical approaches. By addressing these challenges, the review contributes to a better understanding of the evolving landscape of peripheral artery disease, offering insights into effective and holistic management strategies.


Subject(s)
Atherosclerosis , Peripheral Arterial Disease , Humans , Peripheral Arterial Disease/therapy , Intermittent Claudication/therapy , Ischemia/therapy , Ischemia/diagnosis , Comorbidity
18.
AIDS ; 38(6): 835-846, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38265411

ABSTRACT

OBJECTIVE: Social determinants of health (SDH) are important determinants of long-term conditions and multimorbidity in the general population. The intersecting relationship between SDH and multimorbidity in people with HIV remains poorly studied. DESIGN: A cross-sectional study investigating the relationships between eight socio-economic parameters and prevalent comorbidities of clinical significance and multimorbidity in adults of African ancestry with HIV aged 18-65 years in South London, UK. METHODS: Multivariable logistic regression analysis was used to evaluate associations between SDH and comorbidities and multimorbidity. RESULTS: Between September 2020 and January 2022, 398 participants (median age 52 years, 55% women) were enrolled; 85% reported at least one SDH and 72% had at least one comorbidity. There were no associations between SDH and diabetes mellitus or kidney disease, few associations between SDH (job and food insecurity) and cardiovascular or lung disease, and multiple associations between SDH (financial, food, housing and job insecurity, low educational level, social isolation, and discrimination) and poor mental health or chronic pain. Associations between SDH and multimorbidity mirrored those for constituent comorbidities. CONCLUSION: We demonstrate strong associations between SDH and poor mental health, chronic pain and multimorbidity in people of black ethnicities living with HIV in the UK. These findings highlight the likely impact of enduring socioeconomic hardship in these communities and underlines the importance of holistic health and social care for people with HIV to address these adverse psychosocial conditions.


Subject(s)
Chronic Pain , HIV Infections , Adult , Humans , Female , Middle Aged , Male , Multimorbidity , Social Determinants of Health , Cross-Sectional Studies , HIV Infections/complications , HIV Infections/epidemiology , Comorbidity
19.
J Clin Psychol ; 80(4): 824-835, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37058521

ABSTRACT

OBJECTIVE: Complex post-traumatic stress disorder (CPTSD) is a classification within the International Classification of Diseases, 11th Revision (ICD-11) that, besides the DSM-5 symptom clusters of post-post-traumatic stress disorder (PTSD), includes the presence of negative self-concept, difficulties in regulating emotions and relationship skills. The purpose of the present study was to provide guidance on how to deliver Eye Movement Desensitization and Reprocessing (EMDR) therapy in the context of CPTSD, based on current clinical knowledge and the latest scientific research findings. METHOD: This paper describes the treatment of a 52-year-old woman with CPTSD and borderline personality disorder for which immediate trauma-focused EMDR therapy was used. RESULTS: First, a description of what EMDR therapy entails and some important treatment strategies that the therapist may employ to assist in trauma-focused treatment of clients with CPTSD using EMDR therapy are outlined. CONCLUSION: The treatment results are in line with mounting evidence supporting the notion that EMDR therapy is a safe and potentially effective treatment alternative for individuals with CPTSD or personality problems.


Subject(s)
Eye Movement Desensitization Reprocessing , Stress Disorders, Post-Traumatic , Female , Humans , Middle Aged , Stress Disorders, Post-Traumatic/psychology , Eye Movement Desensitization Reprocessing/methods , Treatment Outcome , Comorbidity , Emotions
20.
J Trauma Stress ; 37(2): 257-266, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38085564

ABSTRACT

This study examined the impact of ongoing substance use during posttraumatic stress disorder (PTSD) and substance use disorder (SUD) treatment on PTSD symptoms and treatment discontinuation. The study represents a secondary analysis of U.S. military veterans (N = 183) who participated in a randomized clinical trial for the treatment of both PTSD and SUD. Veterans mostly identified as Black (53.8%) or White (41.9%) and male (92.4%). Substance use, PTSD symptoms, and treatment discontinuation were measured at 4-week intervals throughout treatment. Predictors were the percentage of days with alcohol, cannabis, and other substance use (primarily cocaine and opioids) and the average number of alcoholic drinks per drinking day. Outcomes were PTSD symptoms and treatment discontinuation at concurrent and prospective assessments. Multilevel models accounted for the nested structure of the longitudinal data. Alcohol, cannabis, and other substance use did not predict PTSD symptoms or treatment discontinuation prospectively. Concurrently, we observed that as a participant's percentage of drinking days increased by 34.7% (i.e., 1 standard deviation), PTSD symptoms during the same period were 0.07 standard deviations higher (i.e., 1 point on the PCL), B = 0.03, p = .033. No other substances were related to PTSD symptoms concurrently. The findings demonstrate that PTSD symptoms improved regardless of substance use during exposure-based PTSD and SUD treatment, and treatment discontinuation was not associated with substance use. This study suggests that substance use during treatment cannot directly explain the poorer treatment outcomes observed in the literature on comorbid PTSD/SUD compared to PTSD-only populations.


Subject(s)
Stress Disorders, Post-Traumatic , Substance-Related Disorders , Veterans , Humans , Male , Stress Disorders, Post-Traumatic/epidemiology , Prospective Studies , Comorbidity , Treatment Outcome , Substance-Related Disorders/complications , Substance-Related Disorders/epidemiology , Substance-Related Disorders/therapy
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