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1.
Ter Arkh ; 96(3): 292-297, 2024 Apr 16.
Article in Russian | MEDLINE | ID: mdl-38713046

ABSTRACT

Chronic obstructive pulmonary disease is now one of the most common noncommunicable diseases and the main causes of morbidity, disability and mortality in the world. In recent years, new approaches to epidemiology, diagnosis, classification (categorization), evaluation of phenotypes, as well as characterization and assessment of the severity of сhronic obstructive pulmonary disease exacerbations have emerged. Modern approaches to starting and subsequent drug therapy have changed significantly. This is largely due to the results of recently conducted major clinical trials, demonstrated high efficacy of triple fixed combinations, including inhaled glucocorticosteroids, long-acting beta-agonists and long-acting anticholinergic drugs. The use of non-medication methods (smoking cessation, physical activity and respiratory rehabilitation) and modern approaches to the treatment of respiratory failure and antibiotic therapy remain important. In terms of their significance, all these updates have a significant impact on real clinical practice and can be considered as a novel paradigm of the approaches to the diagnosis and management of this disease.


Subject(s)
Practice Guidelines as Topic , Pulmonary Disease, Chronic Obstructive , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/therapy , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/physiopathology , Humans , Disease Management , Cholinergic Antagonists/therapeutic use , Bronchodilator Agents/therapeutic use
2.
BMC Womens Health ; 24(1): 290, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38755593

ABSTRACT

BACKGROUND: Overactive bladder (OAB) is a condition defined by urgency with or without incontinence which disproportionately affects female patients and has a negative impact on sexual enjoyment and avoidance behaviour. Pharmacotherapy can be considered one of the main options for treating OAB. This research set out to determine the impact of pharmacotherapy on sexual function in females with OAB. METHODS: This research used the robust methodology of a systematic review. The clinical question was formulated using the PICO (population, intervention, control, and outcomes) format to include females being treated with pharmacotherapy (anticholinergics or beta-3 adrenergic agonists) for idiopathic OAB with the use of a validated questionnaire assessing self-reported sexual function at baseline and post-treatment. The review incorporated the MEDLINE, PubMed and EMBASE databases. The AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews) appraisal tool was used to guide the review process. Two reviewers worked independently in screening abstracts, deciding on the inclusion of full-texts, data extraction and risk of bias assessment. RESULTS: In female patients with OAB, pharmacotherapy does seem to offer at least partial improvement in self-reported sexual function outcomes after 12 weeks of therapy. Still, the value of this finding is limited by an overall poor quality of evidence. Patients with a higher degree of bother at baseline stand to benefit the most from treatment when an improvement within this health-related quality of life domain is sought. CONCLUSION: This research should form the basis for a well-conducted randomized controlled study to accurately assess sexual function improvements in females being treated with pharmacotherapy for OAB.


Subject(s)
Urinary Bladder, Overactive , Humans , Urinary Bladder, Overactive/drug therapy , Female , Adrenergic beta-3 Receptor Agonists/therapeutic use , Sexual Dysfunction, Physiological/drug therapy , Cholinergic Antagonists/therapeutic use , Sexual Behavior/drug effects , Sexual Behavior/psychology , Quality of Life
3.
J Emerg Med ; 66(5): e589-e591, 2024 May.
Article in English | MEDLINE | ID: mdl-38658202

ABSTRACT

BACKGROUND: Anticholinergic toxicity is commonly encountered in the emergency department. However, the availability of physostigmine, a central acetylcholinesterase inhibitor used to reverse anticholinergic delirium, has been significantly limited due to national drug shortages in the United States. Several articles have explored the viability of rivastigmine as an alternative treatment in these patients. CASE REPORT: A 33-year-old man presented to the emergency department after a suspected suicide attempt. The patient was found with an empty bottle of diphenhydramine at the scene. On arrival, he was tachycardic and delirious, with dilated and nonreactive pupils and dry skin. As the clinical picture was highly suggestive of anticholinergic toxicity, the patient was treated with oral rivastigmine at a starting dose of 4.5 mg to reverse his anticholinergic delirium. Although a repeat dose was required, his delirium resolved without recurrence. Why Should an Emergency Physician Be Aware of This? Oral rivastigmine has been applied successfully here and in other case reports to reverse anticholinergic delirium with the benefit of prolonged agitation control. Emergency physicians may consider this medication in consultation with a specialist, with initial doses starting at 4.5-6 mg, if encountering anticholinergic delirium when physostigmine is not available.


Subject(s)
Cholinesterase Inhibitors , Delirium , Rivastigmine , Humans , Rivastigmine/therapeutic use , Male , Delirium/drug therapy , Adult , Cholinesterase Inhibitors/therapeutic use , Cholinergic Antagonists/adverse effects , Cholinergic Antagonists/therapeutic use , Cholinergic Antagonists/administration & dosage , Administration, Oral , Suicide, Attempted , Emergency Service, Hospital/organization & administration
4.
Urogynecology (Phila) ; 30(3): 214-222, 2024 03 01.
Article in English | MEDLINE | ID: mdl-38484234

ABSTRACT

IMPORTANCE: There is strong evidence for long-term cognitive effects with anticholinergic use. Differences in insurance coverage of anticholinergics and beta-3 agonists hinder individualization of overactive bladder (OAB) treatment. OBJECTIVES: The aims of the study were to assess individual and family health insurance plan coverage for select OAB medications and to compare coverage of preferred medications to those with a greater risk of cognitive dysfunction. STUDY DESIGN: This cross-sectional study analyzed formularies for the top 7 U.S. medical insurers. Coverage tiers were assessed for the following 7 OAB medications: (1) oxybutynin instant-release 5 mg, (2) oxybutynin extended-release 5 mg, (3) solifenacin 5 mg, (4) trospium instant-release 20 mg, (5) trospium extended-release 60 mg, (6) mirabegron 25 mg, and (7) vibegron 75 mg. Coverage was compared between nonpreferred (oxybutynin, solifenacin) and preferred medications (trospium, mirabegron, vibegron). Coverage scores, representing a weighted average based on coverage tier frequency relative to the number of plans investigated for each state or insurer, were generated with a lower coverage score indicating better coverage (range, 0.2-1.0). RESULTS: A total of 2,780 insurance plans from 41 states representing a 47% market share for the individual and family marketplace were evaluated. Oxybutynin IR had the best coverage score across insurers (0.2) while vibegron had the worst (0.92). Preferred medications were more often designated to higher tiers with worse coverage compared with nonpreferred medications (P < 0.001). Less concordance in coverage between insurers was noted for anticholinergics with greater bladder specificity and for extended-release formulations. CONCLUSIONS: Despite risks with anticholinergics, beta-3 agonists were more expensive across all insurers highlighting the need for expanded coverage of preferred medications to avoid cognitive dysfunction when undergoing treatment for OAB.


Subject(s)
Acetanilides , Mandelic Acids , Thiazoles , Urinary Bladder, Overactive , Humans , Urinary Bladder, Overactive/drug therapy , Solifenacin Succinate/therapeutic use , Cross-Sectional Studies , Muscarinic Antagonists/therapeutic use , Cholinergic Antagonists/therapeutic use
5.
Clin Toxicol (Phila) ; 62(2): 82-87, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38465631

ABSTRACT

INTRODUCTION: Anticholinergic agents are commonly taken in overdose, often causing delirium. The spectrum of anticholinergic delirium ranges from mild agitation to severe behavioural disturbance. Physostigmine is an effective treatment for anticholinergic delirium, but its availability is limited. As rivastigmine is readily available, it has been used to manage anticholinergic delirium; however, there is limited research investigating its use. METHOD: This was a retrospective review of patients with anticholinergic delirium treated in two toxicology units with rivastigmine (oral capsule or transdermal patch) from January 2019 to June 2023. The primary outcome was the use of further parenteral treatment (sedation or physostigmine) for delirium post rivastigmine administration. RESULTS: Fifty patients were administered rivastigmine for the management of anticholinergic delirium. The median age was 36 years (interquartile range: 25-49 years) and 27 (54 per cent) were females. Features consistent with anticholinergic toxicity included tachycardia in 44 (88 per cent) and urinary retention requiring catheterisation in 40 (80 per cent). Forty-three patients (86 per cent) were treated with physostigmine before rivastigmine administration. Twenty-two were managed with transdermal rivastigmine (most commonly 9.5 mg/24 hour patch), and 28 with oral rivastigmine 6 mg. Further parenteral sedation and/or physostigmine treatment were required more often in patients given transdermal than oral rivastigmine [16/22 (73 per cent) versus 9/28 (32 per cent), P = 0.010)]. No patients had bradycardia or gastrointestinal symptoms following rivastigmine administration. One patient with a history of epilepsy had a seizure, 1.5 hours post physostigmine administration and 7 hours post transdermal rivastigmine. DISCUSSION: Rivastigmine has been increasingly used for the management of patients with anticholinergic delirium, due to the lack of availability of physostigmine. In this case series, rivastigmine transdermal patch appeared to be less effective than oral rivastigmine capsules, likely due to its slow onset of action and/or insufficient dose. CONCLUSION: Rivastigmine can be used to treat anticholinergic delirium. In our case series oral rivastigmine appeared more effective than transdermal rivastigmine.


Subject(s)
Delirium , Physostigmine , Female , Humans , Adult , Male , Rivastigmine/therapeutic use , Physostigmine/therapeutic use , Cholinergic Antagonists/therapeutic use , Cholinergic Antagonists/toxicity , Cholinesterase Inhibitors/therapeutic use , Delirium/chemically induced , Delirium/drug therapy
6.
Actas Dermosifiliogr ; 115(4): T356-T367, 2024 Apr.
Article in English, Spanish | MEDLINE | ID: mdl-38331172

ABSTRACT

Hyperhidrosis, or excessive sweating, is characterized by overactivity of the eccrine sweat glands, usually associated with dysfunction of the autonomic nervous system. Primary focal hyperhidrosis is the most common form and can affect the axillae, palms, soles, and/or face, often leading to significantly impaired quality of life and social functioning. Treatment is complex. Topical antiperspirants are normally recommended as the first-line treatment for mild hyperhidrosis. Multiple clinical trials and prospective studies support the efficacy and tolerability of oral and topical anticholinergics in the management of hyperhidrosis. Topical glycopyrronium, which has been investigated in at least 8 clinical trials enrolling more than 2000 patients, is probably the first-line pharmacological treatment for axillary hyperhidrosis in patients with moderate to severe disease poorly controlled with topical antiperspirants. Second-line treatments include botulinum toxin injections, microwave treatment, and oral anticholinergics. We review the use of topical anticholinergics in the management of focal hyperhidrosis in adults and children.


Subject(s)
Botulinum Toxins, Type A , Hyperhidrosis , Adult , Child , Humans , Antiperspirants/therapeutic use , Cholinergic Antagonists/therapeutic use , Quality of Life , Prospective Studies , Sympathectomy , Hyperhidrosis/drug therapy
7.
Arch Gerontol Geriatr ; 121: 105365, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38364710

ABSTRACT

OBJECTIVES: To describe the extent, characteristics, and knowledge gaps regarding explicit decision criteria for deprescribing drugs with anticholinergic or sedative properties (Ach/Sed) in older adults. DESIGN: Scoping review. SETTING AND PARTICIPANTS: Original studies, clinical trial protocols, grey literature, and Summaries of Product Characteristics. METHODS: Searches targeting explicit decision criteria for deprescribing Ach/Sed were performed across MEDLINE, EMBASE, CINAHL, and Web of Science, including trial registries (clinicaltrials.gov, ICTRP, EU-CTR, ANZCTR) for pertinent articles, study protocols. Additionally, to encompass non-traditional or 'grey literature' sources, Google searches and relevant agency websites were explored, alongside the summary of product characteristics for Ach/Sed. RESULTS: The initial literature search identified 8,192 unique data sources. After review, 188 original articles or books, 79 internet sources, and 127 SmPCs were included. Examining these sources for explicit criteria for 154 Ach/Sed, overall, 1,271 explicit criteria guidance for identifying clinical scenarios warranting deprescription of Ach/Sed across 145/154 Ach/Sed were identified. These criteria were identified mainly from qualitative research and Summaries of Product Characteristics. Additionally, 455 criteria-based recommendations suggesting approaches for tapering implementation across 76/154 Ach/Sed were identified, mostly from sources classified as expert opinions. Significant heterogeneity was found across the approaches for tapering Ach/Sed. CONCLUSIONS: This scoping review provides a comprehensive overview of the literature providing guidance for clinical scenarios where Ach/Sed should be deprescribed and highlights the existing knowledge gaps regarding comprehensive guidance on tapering these drugs which warranties future research and development.


Subject(s)
Cholinergic Antagonists , Hypnotics and Sedatives , Humans , Aged , Hypnotics and Sedatives/therapeutic use , Qualitative Research , Cholinergic Antagonists/therapeutic use
8.
J Pediatr Surg ; 59(6): 1177-1181, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38402132

ABSTRACT

BACKGROUND: Recent decades have seen changes in the urological treatment of myelomeningocele (MMC). We aimed to evaluate the urological outcomes in post-pubertal patients and to clarify associations with walking status, hydrocephalus, and sex. METHODS: A retrospective study of 103 MMC patients at their final pediatric urological control. Urological procedures, the necessity for Clean Intermittent Catheterization (CIC) and anticholinergic medication, the state of continence, renal ultrasound findings, and serum creatinine values were assessed. RESULTS: The median age of the patients was 18 years (IQR 16.7-19.6), with 51 (49.5%) being female. Renal function was preserved in all but of one, who presented with mild hydronephrosis. 38 patients walked without assistance, 46 used wheelchairs. Most patients (93%) utilized CIC, and 83% had interventions for overactive or poorly compliant bladder, including anticholinergic medication (47%), Botox treatments (35%), or bladder augmentation (36%). Nearly half (45%) had undergone bladder neck procedures. Continence status revealed 55% fully continent, 18% were rarely incontinent, and 26% were incontinent daily, with most episodes limited to droplet leakage. Incontinence was not associated with the ambulatory status, hydrocephalus, or sex (p = 0.08, >0.99, and 0.07 respectively). CONCLUSIONS: Renal function was effectively maintained with our treatment strategy; however, daily incontinence episodes occurred in one out of four patients, with an additional 18% experiencing occasional rare incontinence episodes. Incontinence, when present, was mostly mild. We found no association between patient characteristics, treatment approach, and continence. Emphasizing incontinence treatment becomes a mainstay in future studies. LEVEL OF EVIDENCE: IV.


Subject(s)
Meningomyelocele , Urinary Incontinence , Humans , Meningomyelocele/complications , Retrospective Studies , Female , Male , Adolescent , Urinary Incontinence/etiology , Young Adult , Treatment Outcome , Hydrocephalus/etiology , Hydrocephalus/surgery , Cholinergic Antagonists/therapeutic use , Urologic Surgical Procedures/methods , Walking , Sex Factors
9.
Urol Pract ; 11(2): 394-401, 2024 03.
Article in English | MEDLINE | ID: mdl-38226920

ABSTRACT

INTRODUCTION: Overactive bladder (OAB) patients who do not achieve satisfactory results with second-line OAB medications should be offered third-line therapies (percutaneous tibial nerve stimulation, sacral neuromodulation, onabotulinumtoxinA bladder injection [BTX-A]). We aimed to determine which clinical factors affect progression from second- to third-line OAB therapy. METHODS: Between 2014 and 2020, the AUA Quality Registry was queried for adult patients with idiopathic OAB. For the primary outcome, patient and provider factors associated with increased odds of progression from second- to third-line therapy were assessed. Secondary outcomes included median time for progression to third-line therapy and third-line therapy utilization across subgroups. RESULTS: A total of 641,122 patients met inclusion criteria and were included in analysis. Of these, only 7487 (1.2%) received third-line therapy after receiving second-line therapy. On multivariate analysis, patients aged 65 to 79, women, White race, history of dual anticholinergic and ß3 agonist therapy, metropolitan area, government insurance, and single specialty practice had the greatest odds of progressing to third-line therapy. Black and Asian race, male gender, and rural setting had lower odds of progressing to third-line therapy. BTX-A was the most common therapy overall (40% BTX-A, 32% sacral neuromodulation, 28% percutaneous tibial nerve stimulation). The median time of progression from second- to third-line therapy was 15.4 months (IQR 5.9, 32.4). Patients < 50 years old and women progressed fastest to third-line therapy. CONCLUSIONS: Very few patients received third-line therapies, and the time to progression from second- to third-line therapies is > 1 year. The study findings highlight a potential need to improve third-line therapy implementation.


Subject(s)
Botulinum Toxins, Type A , Electric Stimulation Therapy , Urinary Bladder, Overactive , Adult , Humans , Male , Female , Middle Aged , Urinary Bladder, Overactive/drug therapy , Electric Stimulation Therapy/methods , Botulinum Toxins, Type A/therapeutic use , Cholinergic Antagonists/therapeutic use , Tibial Nerve
10.
Value Health Reg Issues ; 41: 72-79, 2024 May.
Article in English | MEDLINE | ID: mdl-38245933

ABSTRACT

OBJECTIVES: Frailty is common in older people and is associated with increased use of healthcare services and ongoing use of multiple medications. This study provides insights into the healthcare cost structure of a frail group of older adults in Aotearoa, New Zealand. Furthermore, we investigated the relationship between participants' anticholinergic and sedative medication burden and their total healthcare costs to explore the viability of deprescribing interventions within this cohort. METHODS: Healthcare cost analysis was conducted using data collected during a randomized controlled trial within a frail, older cohort. The collected information included participant demographics, medications used, frailty, cost of service use of aged residential care and outpatient hospital services, hospital admissions, and dispensed medications. RESULTS: Data from 338 study participants recruited between 25 September 2018 and 30 October 2020 with a mean age of 80 years were analyzed. The total cost of healthcare per participant ranged from New Zealand $15 (US dollar $10) to New Zealand $270 681 (US dollar $175 943) over 6 months postrecruitment into the study. Four individuals accounted for 26% of this cohort's total healthcare cost. We found frailty to be associated with increased healthcare costs, whereas the drug burden was only associated with increased pharmaceutical costs, not overall healthcare costs. CONCLUSIONS: With no relationship found between a patient's anticholinergic and sedative medication burden and their total healthcare costs, more research is required to understand how and where to unlock healthcare cost savings within frail, older populations.


Subject(s)
Frail Elderly , Health Care Costs , Humans , New Zealand , Female , Male , Aged, 80 and over , Health Care Costs/statistics & numerical data , Frail Elderly/statistics & numerical data , Aged , Cohort Studies , Frailty/economics , Frailty/epidemiology , Polypharmacy , Cholinergic Antagonists/economics , Cholinergic Antagonists/therapeutic use
11.
J Parkinsons Dis ; 14(1): 53-63, 2024.
Article in English | MEDLINE | ID: mdl-38217610

ABSTRACT

In the UK, guidance exists to aid clinicians and patients deciding when treatment for Parkinson's disease (PD) should be initiated and which therapies to consider. National Institute for Health and Care Excellence (NICE) guidance recommends that before starting PD treatment clinicians should discuss the following: the patient's individual clinical circumstances; lifestyle; preferences; needs and goals; as well as the potential benefits and harms of the different drug classes. Individualization of medicines and management in PD significantly improves patients' outcomes and quality of life. This article aims to provide simple and practical guidance to help clinicians address common, but often overlooked, co-morbidities. A multi-disciplinary group of PD experts discussed areas where clinical care can be improved by addressing commonly found co-morbidities in people with Parkinson's (PwP) based on clinical experience and existing literature, in a roundtable meeting organized and funded by Bial Pharma UK Ltd. The experts identified four core areas (bone health, cardiovascular risk, anticholinergic burden, and sleep quality) that, if further standardized may improve treatment outcomes for PwP patients. Focusing on anticholinergic burden, cardiac risk, sleep, and bone health could offer a significant contribution to personalizing regimes for PwP and improving overall patient outcomes. Within this opinion-based paper, the experts offer a list of guiding factors to help practitioners in the management of PwP.


Subject(s)
Parkinson Disease , Humans , Parkinson Disease/complications , Parkinson Disease/drug therapy , Parkinson Disease/epidemiology , Quality of Life , Life Style , Cholinergic Antagonists/therapeutic use , Sleep
12.
Dig Dis Sci ; 69(3): 766-774, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38273076

ABSTRACT

BACKGROUND: Despite the growing prevalence of older adults with inflammatory bowel diseases (IBD), polypharmacy, an important geriatric construct, is poorly understood. We described polypharmacy and its implications in older adults with IBD. METHODS: In a cross sectional study of adults ≥ 60 years with IBD, we obtained medication lists from the medical record and patients. We assessed medications by the Beer's criteria, anti-cholinergic burden and drug-drug interactions. We constructed multi-variate logistic regression models to assess association between polypharmacy with low quality-of-life, controlling for age, sex, IBD-type, number of comorbidities and depression. RESULTS: In 100 adults ≥ 60 years with IBD, with a median age of 68 years, 56% met criteria for remission by a validated disease activity index. Polypharmacy, defined as ≥ 5 concomitant medications, was noted in 86% of the cohort and 45% had severe polypharmacy, defined as ≥ 10 concomitant medications. In this cohort, 48% were on ≥ 1 medication that met Beer's criteria for potentially inappropriate in older adults and 24% had a cumulative anti-cholinergic drug burden score of ≥ 3, the threshold for serious adverse events attributed to anti-cholinergic burden. Serious drug-drug interactions were found in 26% with 7% involving an IBD medication. Controlling for potential confounders, polypharmacy, defined both numerically (OR 22.79, p < 0.01) and by medication appropriateness (OR 1.95, p < 0.01), was significantly associated with low quality of life. CONCLUSION: Polypharmacy is prevalent in older adults with IBD and independently associated with low quality of life. Describing polypharmacy can guide de-prescription strategies tailored to GI clinic for older adults with IBD.


Subject(s)
Inflammatory Bowel Diseases , Polypharmacy , Humans , Aged , Potentially Inappropriate Medication List , Cross-Sectional Studies , Prevalence , Quality of Life , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/epidemiology , Cholinergic Antagonists/therapeutic use , Inappropriate Prescribing
13.
IEEE J Biomed Health Inform ; 28(2): 1122-1133, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37963002

ABSTRACT

Anticholinergic (AC) drugs are commonly prescribed to older adults for treating diseases and chronic conditions, such as chronic obstructive pulmonary disease, urinary incontinence, gastrointestinal disorder, or simply pain and allergy. The high prevalence of AC drug use can have a detrimental effect on the mental health of older adults. We aim to improve the prediction of future trends of AC drug use at the individual level, with pharmacy refill data. The individual drug use data presents challenges in the modeling, such as data being discrete-valued with excess zeros and having significant unobserved heterogeneity in the trend pattern. To address these challenges, we propose a statistical model of hierarchical structure and an EM scheme for the model parameter estimation. We evaluate the proposed modeling approach through a numerical study with synthetic data and a case study with real-world pharmacy refill data. The simulation study show that our analysis method outperforms the existing ones (e.g., reducing MSE significantly), particularly in terms of accurately predicting the trend pattern. The real-world case study further verifies the out-performance and demonstrate the advantageous features of our method. We expect the prediction tool developed based on our study can assist pharmacists' decision on initiating or strengthening behavioral interventions with the hope of discontinuing AC drug misuse.


Subject(s)
Pharmaceutical Services , Urinary Incontinence , Humans , Aged , Cholinergic Antagonists/therapeutic use , Models, Statistical , Computer Simulation
14.
Actas Dermosifiliogr ; 115(4): 356-367, 2024 Apr.
Article in English, Spanish | MEDLINE | ID: mdl-37714301

ABSTRACT

Hyperhidrosis, or excessive sweating, is characterized by overactivity of the eccrine sweat glands, usually associated with dysfunction of the autonomic nervous system. Primary focal hyperhidrosis is the most common form and can affect the axillae, palms, soles, and/or face, often leading to significantly impaired quality of life and social functioning. Treatment is complex. Topical antiperspirants are normally recommended as the first-line treatment for mild hyperhidrosis. Multiple clinical trials and prospective studies support the efficacy and tolerability of oral and topical anticholinergics in the management of hyperhidrosis. Topical glycopyrronium, which has been investigated in at least 8 clinical trials enrolling more than 2000 patients, is probably the first-line pharmacological treatment for axillary hyperhidrosis in patients with moderate to severe disease poorly controlled with topical antiperspirants. Second-line treatments include botulinum toxin injections, microwave treatment, and oral anticholinergics. We review the use of topical anticholinergics in the management of focal hyperhidrosis in adults and children.


Subject(s)
Botulinum Toxins, Type A , Hyperhidrosis , Adult , Child , Humans , Antiperspirants/therapeutic use , Cholinergic Antagonists/therapeutic use , Quality of Life , Prospective Studies , Sympathectomy , Hyperhidrosis/drug therapy
15.
J Intellect Disabil Res ; 68(3): 277-284, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38031737

ABSTRACT

BACKGROUND: People with intellectual disabilities (ID) die on an average 20 years earlier to the general population. They have higher rates of multimorbidity and polypharmacy. Around 25% of people with ID report chronic constipation. The England Learning Disabilities Mortality Review found that nearly 25% of deaths identified constipation as a long-term health problem. However, the likely risk factors for constipation related harm are poorly enumerated. We sought to identify possible specific high-risk factors by examining the clinical characteristics of people with ID admitted to hospital with constipation. METHODS: Data of people with ID admitted with constipation in two general hospitals covering a population of 1.3 million from 2017 to 2022 were reported using the STROBE guideline for cohort studies. Collected data included age, gender, intellectual disability severity, recorded medication, presenting complaint and co-morbidities. The medication anticholinergic burden was calculated using the anticholinergic burden scale. Continuous variables were summarised by mean and standard deviation if normally distributed, with categorical variables summarised by the number and percentage in each category. RESULTS: Of 46 admissions (males 52%), 57% had moderate to profound ID, 37% had epilepsy, 41% prescribed antiseizure medication (ASM) and 45% were on laxatives. Average age was 46 years. The anticholinergic burden score mean was 2.3 and median, one. CONCLUSIONS: We can hypothesise that people with more severe ID, suffering from epilepsy and on ASM may be more at risk of developing severe constipation. Some admissions may be avoided with earlier use of laxatives in the community.


Subject(s)
Epilepsy , Intellectual Disability , Male , Humans , Middle Aged , Intellectual Disability/epidemiology , Laxatives , Constipation/epidemiology , Hospitals , Risk Factors , Cholinergic Antagonists/therapeutic use
16.
Spectrochim Acta A Mol Biomol Spectrosc ; 308: 123669, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38006865

ABSTRACT

Derivatives of thiazole-pyrazole fused benzo-coumarin compounds were successfully synthesized and characterized, followed by a comprehensive spectroscopic investigation on various photophysical properties in different media. The multipronged approach using steady state and time resolved fluorescence spectroscopy pointed out the impact of substitution in the estimated spectroscopic and other physicochemical properties of the systems. Further, the evaluation of anti-acetylcholinesterase (anti-AChE) activity yielded significant insight into the therapeutic potential of the synthesized coumarinyl compounds for the treatment of Alzheimer's disease (AD). The findings revealed a non-competitive mode of inhibition mechanism, with an estimated IC50 value of 67.72 ± 2.00 nM observed for one of the investigated systems as AChE inhibitor. Notably, this value is even lower than that of an FDA-approved AD drug Donepezil (DON), indicating the enhanced potency of the coumarin derivatives in inhibiting AChE. Interestingly, significant diminution in inhibition was observed in presence of human serum albumin (HSA) as evidenced by the relative increase in IC50 value by 8 âˆ¼ 39 % in different cases, which emphasized the role of albumin proteins to control therapeutic efficacies of potential medications. In-depth spectroscopic and in-silico analysis quantified the nature of interactions of the investigated systems with HSA and AChE. Overall, the outcomes of this study provide significant understanding into the biophysical characteristics of novel thiazole-pyrazole fused benzo-coumarin systems, which could aid in the development of new cholinergic agents for the treatment of AD and materials based on coumarin motifs.


Subject(s)
Alzheimer Disease , Serum Albumin, Human , Humans , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/chemistry , Molecular Docking Simulation , Cholinergic Antagonists/pharmacology , Cholinergic Antagonists/therapeutic use , Thiazoles/pharmacology , Thiazoles/chemistry , Coumarins/pharmacology , Coumarins/chemistry , Spectrometry, Fluorescence , Pyrazoles/pharmacology , Alzheimer Disease/drug therapy , Structure-Activity Relationship
17.
Neurourol Urodyn ; 43(2): 396-406, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38149719

ABSTRACT

PURPOSE: Utilization patterns of third-line onabotulinumtoxinA for overactive bladder (OAB) symptoms-including discontinuation and use of other therapeutic options during or after treatment-are not well understood. This retrospective analysis of administrative claims was designed to characterize the unmet need for OAB treatment. MATERIALS AND METHODS: A retrospective claims analysis of Optum's deidentified Clinformatics® Data Mart Database (2009-2021) was performed among patients with diagnosis of OAB newly starting onabotulinumtoxinA injection (2015-2017). Study measures were evaluated during an 18-month pretreatment baseline and over a minimum of 36 months of follow-up. These included number of injections, days between injections, other measures of onabotulinumtoxinA utilization, use of second-line pharmacologic treatments, use of device and surgical treatment options, and complications. RESULTS: Of 2505 eligible patients, 535 (21.4%; 66.8 ± 13.3 y, 87.3% females) continued onabotulinumtoxinA throughout the study. The remaining 1970 (78.6%; 71.4 ± 11.6 y, 79.1% females) were considered discontinuers. Of continuers, 57% received ≥5 treatments. Of discontinuers, 84% received ≤2 treatments. Anticholinergics and ß3-adrenoceptor agonist medication use declined in all patients from baseline to follow-up; however, the absolute reduction in the proportion with any medication fill was similar across continuers versus discontinuers (21% vs. 18%, p < 0.0001). Sacral neuromodulation was initiated by 15/535 (3%) of continuers and 137/1970 (7%) of discontinuers (p < 0.0001). No patients initiated percutaneous tibial neuromodulation. CONCLUSIONS: Early discontinuation of onabotulinumtoxinA therapy for OAB is common and most discontinuers do not receive alternative treatments. Providers have the opportunity to educate OAB patients with un- or undertreated symptoms regarding alternative options.


Subject(s)
Botulinum Toxins, Type A , Urinary Bladder, Overactive , Female , Humans , Male , Urinary Bladder, Overactive/diagnosis , Retrospective Studies , Injections, Intramuscular , Cholinergic Antagonists/therapeutic use , Treatment Outcome
19.
Article in Chinese | MEDLINE | ID: mdl-37805434

ABSTRACT

This paper reported 1 case of poisoning caused by stramonium. Cases of Datura poisoning have been reported nationwide, Its effect on the central nervous system of patients is characterized by first excitation and then inhibition, clinical manifestations include decreased gland secretion, dilated pupils, and tachycardia, etc. Its poisoning mechanism is anticholinergic effect, the effect on Peripheral nervous system is to inhibit Parasympathetic nervous system. Hemoperfusion combined with neostigmine anticholinergic therapy at the early stage of poisoning can effectively improve the clinical symptoms of patients in a short time.


Subject(s)
Datura stramonium , Plant Poisoning , Poisoning , Humans , Plant Poisoning/diagnosis , Plant Poisoning/therapy , Cholinergic Antagonists/therapeutic use , Poisoning/drug therapy
20.
Int Urogynecol J ; 34(12): 3041-3050, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37837459

ABSTRACT

INTRODUCTION AND HYPOTHESIS: Studies within the past decade have suggested associations among composition of the urinary microbiota, local immune responses, and urinary incontinence symptoms. To investigate these relationships, we evaluated the structure of the urinary microbiome, local inflammatory markers, and patient responses prior to and at 6-weeks after treatment with anticholinergic medication for urgency urinary incontinence (UUI). METHODS: Using a prospective pilot study, we enrolled women who presented with UUI symptoms and were prescribed treatment with anticholinergics. Catheterized urine samples were collected from participants at their baseline and 6-week follow-up visits for microbiological (standard and 16S rRNA gene phylotyping analyses) and cytokine analysis along with the UDI-6 questionnaire and 2-day bladder diary. RESULTS: Patients were Caucasian, post- menopausal, with a median age of 64 and median BMI of 30.1 kg/m2. Among the patients, 75% had UUI symptoms for less than 2 years, but with a frequency of at least a few times a week or every day. Most women were prescribed 10 mg oxybutynin ER daily at enrollment. Patients had varied urinary microbiota by culture and 16S phylotyping, with species of Lactobacillus being the most common, in six samples, in addition to taxa associated with Enterococcus, Staphylococcus, and mixed flora. Cytokine levels showed no differences before and after treatment with anticholinergics, nor correlation with urinary bacteria or microbiome composition. CONCLUSIONS: Our pilot study suggests factors in addition to the urinary microbiome and local immune responses may be involved in patients' response to anticholinergics for UUI.


Subject(s)
Cholinergic Antagonists , Microbiota , Urinary Incontinence, Urge , Urinary Incontinence , Female , Humans , Cholinergic Antagonists/therapeutic use , Cytokines/therapeutic use , Microbiota/genetics , Pilot Projects , Prospective Studies , RNA, Ribosomal, 16S/genetics , Treatment Outcome , Urinary Incontinence/drug therapy , Urinary Incontinence/microbiology , Urinary Incontinence, Urge/drug therapy , Urinary Incontinence, Urge/microbiology
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