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The Canadian Journal of Urology Aug 2021INTRODUCTION Urinary incontinence (UI) is a common condition in all demographics of women and consists of stress UI (SUI), Urgency UI (UUI), and mixed UI (MUI).... (Review)
Review
UNLABELLED
INTRODUCTION Urinary incontinence (UI) is a common condition in all demographics of women and consists of stress UI (SUI), Urgency UI (UUI), and mixed UI (MUI). Treatment includes lifestyle modifications, medical treatment, and surgery depending on the type of UI and severity of symptoms. This review is an update on the evaluation and management of UI in women.
MATERIALS AND METHODS
This review article covers the evaluation and management options for UI in women and includes the most recent guidelines from the American Urological Association (AUA) as well as recently published literature on the management of UI.
RESULTS
Any evaluation of UI should include a thorough targeted history and physical, and counseling for treatment should consider patient goals and desired outcomes. For both SUI and UUI, behavioral therapy and lifestyle modifications are effective first line treatments. Patients with UUI can benefit from medical therapy which includes anticholinergics and ß3-agonist medications, as well as neuromodulation in treatment refractory patients. SUI patients may further benefit from mechanical inserts which prevent leaks, urethral bulking agents, and surgical treatments such as the mid urethral sling and autologous fascial pubovaginal sling.
CONCLUSIONS
Treatment of UI in women requires a graded approach that considers patient goals and symptom severity, beginning with lifestyle and behavioral modifications before progressing to more aggressive interventions.
Topics: Cholinergic Antagonists; Female; Humans; Suburethral Slings; Urinary Incontinence; Urinary Incontinence, Stress; Urinary Incontinence, Urge
PubMed: 34453426
DOI: No ID Found -
American Family Physician Jun 2018Hyperhidrosis is excessive sweating that affects patients' quality of life, resulting in social and work impairment and emotional distress. Primary hyperhidrosis is... (Review)
Review
Hyperhidrosis is excessive sweating that affects patients' quality of life, resulting in social and work impairment and emotional distress. Primary hyperhidrosis is bilaterally symmetric, focal, excessive sweating of the axillae, palms, soles, or craniofacial region not caused by other underlying conditions. Secondary hyperhidrosis may be focal or generalized, and is caused by an underlying medical condition or medication use. The Hyperhidrosis Disease Severity Scale is a validated survey used to grade the tolerability of sweating and its impact on quality of life. The score can be used to guide treatment. Topical aluminum chloride solution is the initial treatment in most cases of primary focal hyperhidrosis. Topical glycopyrrolate is first-line treatment for craniofacial sweating. Botulinum toxin injection (onabotulinumtoxinA) is considered first- or second-line treatment for axillary, palmar, plantar, or craniofacial hyperhidrosis. Iontophoresis should be considered for treating hyperhidrosis of the palms and soles. Oral anticholinergics are useful adjuncts in severe cases of hyperhidrosis when other treatments fail. Local microwave therapy is a newer treatment option for axillary hyperhidrosis. Local surgery and endoscopic thoracic sympathectomy should be considered in severe cases of hyperhidrosis that have not responded to topical or medical therapies.
Topics: Botulinum Toxins, Type A; Cholinergic Antagonists; Humans; Hyperhidrosis; Patient Selection; Quality of Life; Sweating; Sympathectomy; Treatment Outcome
PubMed: 30215934
DOI: No ID Found -
Journal of Parkinson's Disease 2023The pathophysiology of Parkinson's disease (PD) tremor remains incompletely understood and there is a lack of clinical trials specifically addressing its pharmacological... (Review)
Review
The pathophysiology of Parkinson's disease (PD) tremor remains incompletely understood and there is a lack of clinical trials specifically addressing its pharmacological treatment. Levodopa is the most efficacious drug for most patients and should be used as primary approach to control troublesome tremor. While the efficacy of oral dopamine agonists on PD tremor has been demonstrated in controlled trials, there is no evidence of greater antitremor efficacy compared to levodopa. The magnitude of the antitremor effect of anticholinergics is generally lower than that of levodopa. Due to their adverse effects, anticholinergics have a limited role in selected young and cognitively intact patients. Propranolol may improve resting and action tremor and may be considered as an adjunct in patients with insufficient tremor response to levodopa and this also applies to clozapine, despite its unfavorable adverse effect profile. Treating motor fluctuations with MAO-B and COMT inhibitors, dopamine agonists, amantadine, or on-demand treatments such as subcutaneous or sublingual apomorphine and inhaled levodopa as well as with continuous infusions of levodopa or apomorphine will improve off period tremor episodes. For patients with drug-refractory PD tremor despite levodopa optimization deep brain stimulation and focused ultrasound are first-line considerations. Surgery can also be highly effective for the treatment medication-refractory tremor in selected patients without motor fluctuations. The present review highlights the clinical essentials of parkinsonian tremor, critically examines available trial data on the effects of medication and surgical approaches and provides guidance for the choice of treatments to control PD tremor in clinical practice.
Topics: Humans; Parkinson Disease; Levodopa; Tremor; Dopamine Agonists; Antiparkinson Agents; Apomorphine; Cholinergic Antagonists
PubMed: 36847017
DOI: 10.3233/JPD-225060 -
Journal of the American Medical... Jan 2021To investigate the association between anticholinergic drug burden (ADB), measured with anticholinergic drug scales, and delirium and delirium severity. (Review)
Review
OBJECTIVES
To investigate the association between anticholinergic drug burden (ADB), measured with anticholinergic drug scales, and delirium and delirium severity.
DESIGN
Systematic review.
SETTING AND PARTICIPANTS
All available studies.
METHODS
A systematic literature search was performed in Medline, Embase, PsycINFO, Web of Science, CINAHL, Cochrane library, and Google Scholar. Studies evaluating the association between ADB (measured as a total score) and delirium or delirium severity, published in English, were eligible for inclusion.
RESULTS
Sixteen studies, including 148,756 persons, were included. Fifteen studies investigated delirium. ADB was measured with the Anticholinergic Risk Scale (ARS, n = 5), the Anticholinergic Cognitive Burden Scale (ACB, n = 6), the list of Chew (n = 1), the Anticholinergic Drug Scale (ADS, n = 5), a modified version of the ARS (n = 1), and a modified version of the ACB (n = 1). A high ADB, measured with the ARS, was associated with delirium (5/5). Also with the modified version of the ARS and ACB, an association was found between a high ADB and delirium during 3-month (1/1) and 1-year follow-up (1/1), respectively. When ADB was assessed with other scales, the results were inconclusive, with only 1 positive association for the ACB (1/6) and ADS (1/5) each. The possible association between ADB and delirium severity has also been investigated (ADS n = 2, Summers Drug Risk Number n = 1). One study found an association between a high ADB, measured with the ADS, and an increase in severity of delirium.
CONCLUSIONS AND IMPLICATIONS
ADB assessed with the ARS is consistently associated with delirium. The association found between the modified versions of the ARS and ACB and delirium needs confirmation. When ADB was assessed with other scales, the findings were inconclusive. The current findings suggest that the ARS might be a useful tool to identify patients at increased risk for delirium.
Topics: Cholinergic Antagonists; Delirium; Humans; Pharmaceutical Preparations
PubMed: 32703688
DOI: 10.1016/j.jamda.2020.04.019 -
European Psychiatry : the Journal of... Sep 2022Although cognitive impairment is a core symptom of schizophrenia related to poorer outcomes in different functional domains, it still remains a major therapeutic... (Review)
Review
BACKGROUND
Although cognitive impairment is a core symptom of schizophrenia related to poorer outcomes in different functional domains, it still remains a major therapeutic challenge. To date, no comprehensive treatment guidelines for cognitive impairment in schizophrenia are implemented.
METHODS
The aim of the present guidance paper is to provide a comprehensive meta-review of the current available evidence-based treatments for cognitive impairment in schizophrenia. The guidance is structured into three sections: pharmacological treatment, psychosocial interventions, and somatic treatments.
RESULTS
Based on the reviewed evidence, this European Psychiatric Association guidance recommends an appropriate pharmacological management as a fundamental starting point in the treatment of cognitive impairment in schizophrenia. In particular, second-generation antipsychotics are recommended for their favorable cognitive profile compared to first-generation antipsychotics, although no clear superiority of a single second-generation antipsychotic has currently been found. Anticholinergic and benzodiazepine burdens should be kept to a minimum, considering the negative impact on cognitive functioning. Among psychosocial interventions, cognitive remediation and physical exercise are recommended for the treatment of cognitive impairment in schizophrenia. Noninvasive brain stimulation techniques could be taken into account as add-on therapy.
CONCLUSIONS
Overall, there is definitive progress in the field, but further research is needed to develop specific treatments for cognitive impairment in schizophrenia. The dissemination of this guidance paper may promote the development of shared guidelines concerning the treatment of cognitive functions in schizophrenia, with the purpose to improve the quality of care and to achieve recovery in this population.
Topics: Antipsychotic Agents; Benzodiazepines; Cholinergic Antagonists; Cognitive Dysfunction; Humans; Schizophrenia; Schizophrenic Psychology
PubMed: 36059103
DOI: 10.1192/j.eurpsy.2022.2315 -
BMJ (Clinical Research Ed.) Apr 2018To estimate the association between the duration and level of exposure to different classes of anticholinergic drugs and subsequent incident dementia.
OBJECTIVES
To estimate the association between the duration and level of exposure to different classes of anticholinergic drugs and subsequent incident dementia.
DESIGN
Case-control study.
SETTING
General practices in the UK contributing to the Clinical Practice Research Datalink.
PARTICIPANTS
40 770 patients aged 65-99 with a diagnosis of dementia between April 2006 and July 2015, and 283 933 controls without dementia.
INTERVENTIONS
Daily defined doses of anticholinergic drugs coded using the Anticholinergic Cognitive Burden (ACB) scale, in total and grouped by subclass, prescribed 4-20 years before a diagnosis of dementia.
MAIN OUTCOME MEASURES
Odds ratios for incident dementia, adjusted for a range of demographic and health related covariates.
RESULTS
14 453 (35%) cases and 86 403 (30%) controls were prescribed at least one anticholinergic drug with an ACB score of 3 (definite anticholinergic activity) during the exposure period. The adjusted odds ratio for any anticholinergic drug with an ACB score of 3 was 1.11 (95% confidence interval 1.08 to 1.14). Dementia was associated with an increasing average ACB score. When considered by drug class, gastrointestinal drugs with an ACB score of 3 were not distinctively linked to dementia. The risk of dementia increased with greater exposure for antidepressant, urological, and antiparkinson drugs with an ACB score of 3. This result was also observed for exposure 15-20 years before a diagnosis.
CONCLUSIONS
A robust association between some classes of anticholinergic drugs and future dementia incidence was observed. This could be caused by a class specific effect, or by drugs being used for very early symptoms of dementia. Future research should examine anticholinergic drug classes as opposed to anticholinergic effects intrinsically or summing scales for anticholinergic exposure.
TRIAL REGISTRATION
Registered to the European Union electronic Register of Post-Authorisation Studies EUPAS8705.
Topics: Aged; Aged, 80 and over; Antidepressive Agents, Tricyclic; Case-Control Studies; Cholinergic Antagonists; Dementia; Female; Health Services Research; Humans; Male; Odds Ratio; Risk Assessment; United Kingdom
PubMed: 29695481
DOI: 10.1136/bmj.k1315 -
The American Journal of Psychiatry Sep 2021Many psychotropic medications used to treat schizophrenia have significant anticholinergic properties, which are linked to cognitive impairment and dementia risk in...
OBJECTIVE
Many psychotropic medications used to treat schizophrenia have significant anticholinergic properties, which are linked to cognitive impairment and dementia risk in healthy subjects. Clarifying the impact of cognitive impairment attributable to anticholinergic medication burden may help optimize cognitive outcomes in schizophrenia. The aim of this study was to comprehensively characterize how this burden affects functioning across multiple cognitive domains in schizophrenia outpatients.
METHODS
Cross-sectional data were analyzed using inferential statistics and exploratory structural equation modeling to determine the relationship between anticholinergic medication burden and cognition. Patients with a diagnosis of schizophrenia or schizoaffective disorder (N=1,120) were recruited from the community at five U.S. universities as part of the Consortium on the Genetics of Schizophrenia-2. For each participant, prescribed medications were rated and summed according to a modified Anticholinergic Cognitive Burden (ACB) scale. Cognitive functioning was assessed by performance on domains of the Penn Computerized Neurocognitive Battery (PCNB).
RESULTS
ACB score was significantly associated with cognitive performance, with higher ACB groups scoring worse than lower ACB groups on all domains tested on the PCNB. Similar effects were seen on other cognitive tests. Effects remained significant after controlling for demographic characteristics and potential proxies of illness severity, including clinical symptoms and chlorpromazine-equivalent antipsychotic dosage.
CONCLUSIONS
Anticholinergic medication burden in schizophrenia is substantial, common, conferred by multiple medication classes, and associated with cognitive impairments across all cognitive domains. Anticholinergic medication burden from all medication classes-including psychotropics used in usual care-should be considered in treatment decisions and accounted for in studies of cognitive functioning in schizophrenia.
Topics: Adolescent; Adult; Aged; Cholinergic Antagonists; Cognition; Cognitive Dysfunction; Cohort Studies; Cross-Sectional Studies; Humans; Middle Aged; Neuropsychological Tests; Schizophrenia; Young Adult
PubMed: 33985348
DOI: 10.1176/appi.ajp.2020.20081212 -
The New England Journal of Medicine Feb 2021The muscarinic receptor agonist xanomeline has antipsychotic properties and is devoid of dopamine receptor-blocking activity but causes cholinergic adverse events.... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The muscarinic receptor agonist xanomeline has antipsychotic properties and is devoid of dopamine receptor-blocking activity but causes cholinergic adverse events. Trospium is a peripherally restricted muscarinic receptor antagonist that reduces peripheral cholinergic effects of xanomeline. The efficacy and safety of combined xanomeline and trospium in patients with schizophrenia are unknown.
METHODS
In this double-blind, phase 2 trial, we randomly assigned patients with schizophrenia in a 1:1 ratio to receive twice-daily xanomeline-trospium (increased to a maximum of 125 mg of xanomeline and 30 mg of trospium per dose) or placebo for 5 weeks. The primary end point was the change from baseline to week 5 in the total score on the Positive and Negative Syndrome Scale (PANSS; range, 30 to 210, with higher scores indicating more severe symptoms of schizophrenia). Secondary end points were the change in the PANSS positive symptom subscore, the score on the Clinical Global Impression-Severity (CGI-S) scale (range, 1 to 7, with higher scores indicating greater severity of illness), the change in the PANSS negative symptom subscore, the change in the PANSS Marder negative symptom subscore, and the percentage of patients with a response according to a CGI-S score of 1 or 2.
RESULTS
A total of 182 patients were enrolled, with 90 assigned to receive xanomeline-trospium and 92 to receive placebo. The PANSS total score at baseline was 97.7 in the xanomeline-trospium group and 96.6 in the placebo group. The change from baseline to week 5 was -17.4 points with xanomeline-trospium and -5.9 points with placebo (least-squares mean difference, -11.6 points; 95% confidence interval, -16.1 to -7.1; P<0.001). The results for the secondary end points were significantly better in the xanomeline-trospium group than in the placebo group, with the exception of the percentage of patients with a CGI-S response. The most common adverse events in the xanomeline-trospium group were constipation, nausea, dry mouth, dyspepsia, and vomiting. The incidences of somnolence, weight gain, restlessness, and extrapyramidal symptoms were similar in the two groups.
CONCLUSIONS
In a 5-week trial, xanomeline-trospium resulted in a greater decrease in the PANSS total score than placebo but was associated with cholinergic and anticholinergic adverse events. Larger and longer trials are required to determine the efficacy and safety of xanomeline-trospium in patients with schizophrenia. (Funded by Karuna Therapeutics and the Wellcome Trust; ClinicalTrials.gov number, NCT03697252.).
Topics: Administration, Oral; Adult; Antipsychotic Agents; Benzilates; Cholinergic Antagonists; Double-Blind Method; Drug Combinations; Female; Humans; Least-Squares Analysis; Male; Middle Aged; Muscarinic Agonists; Nortropanes; Pyridines; Schizophrenia; Thiadiazoles
PubMed: 33626254
DOI: 10.1056/NEJMoa2017015 -
BMJ (Clinical Research Ed.) Sep 2023To evaluate the association between recently raised anticholinergic burden and risk of acute cardiovascular events in older adults.
OBJECTIVE
To evaluate the association between recently raised anticholinergic burden and risk of acute cardiovascular events in older adults.
DESIGN
Case-case-time-control study (ie, incorporating a case crossover design and a control crossover design consisting of future cases).
SETTING
Taiwan's National Health Insurance Research Database.
PARTICIPANTS
317 446 adults aged ≥65 who were admitted to hospital because of an incident acute cardiovascular event between 2011 and 2018. Acute cardiovascular events included myocardial infarction, strokes, arrhythmias, conduction disorders, and cardiovascular death.
MAIN OUTCOME MEASURES
The anticholinergic burden was measured for each participant by adding up the anticholinergic scores for individual drugs using the Anticholinergic Cognitive Burden Scale. Scores were classified into three levels (0 points, 1-2 points, and ≥3 points). For each participant, anticholinergic burden levels during hazard periods (day -1 to -30 before the cardiovascular event) were compared with randomly selected 30 day reference periods (ie, periods between days -61 and -180). Conditional logistic regression determined odds ratios with 95% confidence intervals to evaluate the association between acute cardiovascular events and recently raised anticholinergic burden.
RESULTS
The crossover analyses included 248 579 current cases. Participants' average age on the index date was 78.4 years (standard deviation 0.01), and 53.4% were men. The most frequently prescribed drugs with anticholinergic activity were antihistamines (68.9%), gastrointestinal antispasmodics (40.9%), and diuretics (33.8%). Among patients with varying levels of anticholinergic burden in different periods, more patients carried higher levels of anticholinergic burden during hazard periods than during reference periods. For example, 17 603 current cases had 1-2 points of anticholinergic burden in the hazard period with 0 points in the reference period, while 8507 current cases had 0 points in the hazard period and 1-2 points in the reference period. In the comparison of 1-2 points versus 0 points of anticholinergic burden, the odds ratio was 1.86 (95% confidence interval 1.83 to 1.90) in the case crossover analysis and 1.35 (1.33 to 1.38) in the control crossover analysis, which yielded a case-case-time-control odds ratio of 1.38 (1.34 to 1.42). Similar results were found in the comparison of ≥3 versus 0 points (2.03, 1.98 to 2.09) and ≥3 versus 1-2 points (1.48, 1.44 to 1.52). The findings remained consistent throughout a series of sensitivity analyses (eg, cut-off points for anticholinergic burden categories were redefined and different scales were used to measure anticholinergic burden).
CONCLUSIONS
An association was found between recently raised anticholinergic burden and increased risk of acute cardiovascular events. Furthermore, a greater increase in anticholinergic burden was associated with a higher risk of acute cardiovascular events.
Topics: Male; Humans; Aged; Female; Cholinergic Antagonists; Case-Control Studies; Hospitalization; Hospitals; Myocardial Infarction
PubMed: 37758279
DOI: 10.1136/bmj-2023-076045 -
JAMA Internal Medicine Mar 2015Many medications have anticholinergic effects. In general, anticholinergic-induced cognitive impairment is considered reversible on discontinuation of anticholinergic...
IMPORTANCE
Many medications have anticholinergic effects. In general, anticholinergic-induced cognitive impairment is considered reversible on discontinuation of anticholinergic therapy. However, a few studies suggest that anticholinergics may be associated with an increased risk for dementia.
OBJECTIVE
To examine whether cumulative anticholinergic use is associated with a higher risk for incident dementia.
DESIGN, SETTING, AND PARTICIPANTS
Prospective population-based cohort study using data from the Adult Changes in Thought study in Group Health, an integrated health care delivery system in Seattle, Washington. We included 3434 participants 65 years or older with no dementia at study entry. Initial recruitment occurred from 1994 through 1996 and from 2000 through 2003. Beginning in 2004, continuous replacement for deaths occurred. All participants were followed up every 2 years. Data through September 30, 2012, were included in these analyses.
EXPOSURES
Computerized pharmacy dispensing data were used to ascertain cumulative anticholinergic exposure, which was defined as the total standardized daily doses (TSDDs) dispensed in the past 10 years. The most recent 12 months of use was excluded to avoid use related to prodromal symptoms. Cumulative exposure was updated as participants were followed up over time.
MAIN OUTCOMES AND MEASURES
Incident dementia and Alzheimer disease using standard diagnostic criteria. Statistical analysis used Cox proportional hazards regression models adjusted for demographic characteristics, health behaviors, and health status, including comorbidities.
RESULTS
The most common anticholinergic classes used were tricyclic antidepressants, first-generation antihistamines, and bladder antimuscarinics. During a mean follow-up of 7.3 years, 797 participants (23.2%) developed dementia (637 of these [79.9%] developed Alzheimer disease). A 10-year cumulative dose-response relationship was observed for dementia and Alzheimer disease (test for trend, P < .001). For dementia, adjusted hazard ratios for cumulative anticholinergic use compared with nonuse were 0.92 (95% CI, 0.74-1.16) for TSDDs of 1 to 90; 1.19 (95% CI, 0.94-1.51) for TSDDs of 91 to 365; 1.23 (95% CI, 0.94-1.62) for TSDDs of 366 to 1095; and 1.54 (95% CI, 1.21-1.96) for TSDDs greater than 1095. A similar pattern of results was noted for Alzheimer disease. Results were robust in secondary, sensitivity, and post hoc analyses.
CONCLUSIONS AND RELEVANCE
Higher cumulative anticholinergic use is associated with an increased risk for dementia. Efforts to increase awareness among health care professionals and older adults about this potential medication-related risk are important to minimize anticholinergic use over time.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antidepressive Agents, Tricyclic; Cholinergic Antagonists; Cohort Studies; Dementia; Female; Histamine H1 Antagonists; Humans; Male; Muscarinic Antagonists; Prospective Studies
PubMed: 25621434
DOI: 10.1001/jamainternmed.2014.7663