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Background: Elderly patients with multiple chronic conditions are closely linked to polymedication, a condition that is also highly associated with the presence of adverse effects, such as those observed by anticholinergic activity. Anticholinergic burden is defined in a very variable way and is described inconsistently using different scores and providing different interpretations of the risk of suffering from anticholinergic adverse effects. Objective: The objective is to analyse the anticholinergic risk exposure in elderly complex chronic patients. Methods: A observational multicentre study was performed for a cohort of complex chronic patients over 65 years who received treatment with at least one drug with anticholinergic activity. Anticholinergic exposure was assessed using ten scales included in the Anticholinergic Burden Calculator. Results: 473 patients were recruited, being 67.7% with excessive polypharmacy. 80 was the total number of anticholinergic drugs with any scale, with a median of 2 drugs with anticholinergic activity per patient (IQR=2). Three scales evaluated more than 70% of the patients (Chew: 79.1%; Drug Burden Index (DBI): 77.8%; Anticholinergic Cognitive Burden (ACB): 75.9%). The percentage of different drugs with anticholinergic properties evaluated ranged from 13.8% (Anticholinergic Burden Classification (ABC)) to 57.5% (DBI) and anticholinergic drugs prescriptions oscillated from 14% (Anticholinergic Risk Scale (ARS)) to 53.3% (DBI). 71.1% of patients were at risk (moderate and high risk) according to DBI vs. 9.7% by ARS at the opposite side. Important differences of anticholinergic risk in patients with excessive polypharmacy were in ACB, ABC and DBI scales. Conclusions: This study has highlighted clear differences between the scales used. DBI seems to be the scale that identifies a higher number of elderly chronic complex patients at risk of developing anticholinergic adverse effects.

Objective: The aim of the study was to evaluate the concordance among 10 anticholinergic scales for the measurement of anticholinergic drug ex posure in at-risk elderly complex chronic patients in primary care. Methods: An 8-month cross-sectional, multicenter study was carried out in a cohort of complex chronic patients older than 65 years in treatment with at least 1 drug with anticholinergic activity. Demographic, pharmaco logical, and clinical data were collected. Anticholinergic burden and risk were detected using the 10 scales included on the anticholinergic burden calculator (http://www.anticholinergicscales.es/). We used κ statistics to evaluated the concordance 2 to 2 (according to risk: high, medium, low or without risk) among the included scales. Results: Four hundred seventy-three patients were recruited (60.3% fe male, median age of 84 years [interquartile range = 10]). Eighty was the to tal number of anticholinergic drugs with any scale (1197 prescriptions), with a median of 2 drugs with anticholinergic activity per patient (inter quartile range = 2). The κ statistics comparing all the 10 scales ranged from −0.175 (Drug Burden Index versus Chew Scale) to 0.708 (Anticholinergic Activity Scale [AAS] versus Chew Scale). The best concordance was ob tained between AAS and Chew Scale (κ = 0.708), followed by Clinician Rated Anticholinergic Scale and Duran Scale (κ = 0.632) and AAS and Anticholinergic Cognitive Burden Scale (κ = 0.618), being considered sub stantial strengths of concordance. Conclusions: The agreement among the 10 scales in elderly patients with complex chronic conditions was highly variable. Great care should be taken when assessing anticholinergic drug exposure using existing scales because of the wide variability among them. The only scales that showed agreement were the AAS-Chew, Clinician-Rated Anticholinergic Scale– Duran, and AAS–Anticholinergic Cognitive Burden Scale pairs. In the rest of the cases, the scales are not interchangeable.

Oculopalatal tremor (OPT) is an acquired pathology characterized by continuous and rhythmical soft palatal movements combined with pendular nystagmus. Aside from vascular lesions, oncological masses affecting the dentatorubro-olivary pathway can impair brainstem and/or cerebellar pathways, manifesting as dyssynchronous movement. In this review, we delve into the neurophysiology of OPT along with oncological causes and treatment options based on the most recent clinical trial data. This literature review includes medication treatment data from clinical trials enrolling individuals with features of OPT, including acquired pendular nystagmus (APN). Trials were deemed eligible for inclusion in this review if one or more participants had symptoms determined by the trial authors to be caused by OPT. Trials investigating the treatment of APN secondary to a separate cause, such as multiple sclerosis, were excluded from this review. Several early treatments failed to demonstrate a benefit for patients with APN due to OPT. Trials of anticholinergic agents were largely ineffective and poorly tolerated. Botulinum toxin A demonstrated improvement in APN symptoms. Most recently, trials including memantine and gabapentin have demonstrated success with attenuation of APN. Surgical modalities such as DBS have yet to show improvement, though with only a single case report as evidence. Oculopalatal tremor is a unique manifestation of posterior fossa tumors disrupting the Guillain-Mollaret triangle. Symptom control through medication management has had limited success attributed to poor response and medication intolerance. Surgical modalities like DBS may have an emerging role in OPT treatment by targeting dyssynchronous activity in the dentatorubro-olivary pathway.

Objectives: This study aims to determine the current trends in evaluation and management of neurogenic bladder secondary to spinal cord injury (SCI) among Physical Medicine and Rehabilitation (PMR) specialists in Turkey. Materials and methods: Between September 2013 and November 2013, a total of 100 PMR specialists from 18 different provinces of Turkey were included in the study. A 23-item questionnaire was developed to evaluate the current practice on assessment and follow-up of upper and lower urinary tract dysfunction. The questionnaire was delivered via e-mail to the participants routinely providing care for patients with SCI and all responses were obtained electronically. Results: For surveillance of the upper urinary tract dysfunction, 93% of the participants preferred ultrasonography. A total of 59% of the participants favored an annual assessment and 36% preferred six-month intervals. Multichannel urodynamics, voiding cystourethrography combined with urodynamics, and video-urodynamics were preferred by 62%, 25%, and 10% of the participants, respectively for surveillance of the lower urinary tract. Urodynamic evaluation was performed annually by 51% of the participants. In patients with detrusor overactivity unresponsive to the combination of intermittent catheterization (IC) and anticholinergic agents, 66% preferred to increase the dose and 22% preferred to switch to another medication. For treatment of areflexic bladder, 78% preferred IC and 12% preferred the Credé' or Valsalva maneuvers. Treatment of asymptomatic bacteriuria was not favored in patients on IC and indwelling urethral catheter by 33% and 44% of the participants respectively. Totally, 84% participants preferred to administer antibiotics for 10 to 14 days for the treatment of symptomatic urinary tract infection. Conclusion: Our study results indicate that there are some differences in the current practice of PMR specialists for surveillance and management of SCI patients with neurogenic bladder. These results also emphasize the need for development of guidelines and implementation of continuous medical education activities in this field.

Objectives To evaluate whether the long-term usage of mirabegron, which was reported to have potential side effects on male reproductive organs in animal studies, was harmful to spermatogenesis in human testis. Methods Thirty consecutive patients with spinal cord injury (20-48 years old) who performed clean intermittent catheterization were involved in this study. Ten patients were treated with mirabegron (50 mg/d) for more than 2 years and refrained from using an antimuscarinic agent due to the side effects of constipation and dry mouth. Twenty patients were treated with neither anticholinergic agents nor mirabegron. All underwent conventional testicular sperm extraction. The sperm recovery rate and histopathologic findings of the retrieved testicular tissue were compared between both groups. Results We found no difference in the sperm recovery rate (P = .083) between both groups. Spinal cord injury patients treated with mirabegron had better spermatogenesis than those not treated with mirabegron (P Conclusions From these data, we conclude that the therapeutic dose of mirabegron had no harmful effect on spermatogenesis in spinal cord injury patients of reproductive age.

Anticholinergic burden (AB) is related to cognitive impairment (CI) and older complex chronic patients (OCCP) are more susceptible. Our objective was to evaluate the predictive value of ten anticholinergic scales to predict a potential CI due to anticholinergic pharmacotherapy in OCCP. An eight-month longitudinal multicentre study was carried out in a cohort of OCCP, in treatment with at least one anticholinergic drug and whose cognition status had been evaluated by Pfeiffer test twice for a period of 6–15 months. CI was considered when the Pfeiffer test increased 2 or more points. AB was detected using ten scales included on the Anticholinergic Burden Calculator. An ROC curve analysis was performed to assess the discriminative capacity of the scales to predict a potential CI and the cut-off point of AB that obtains better validity indicators. 415 patients were included (60.2% female, median age of 85 years (IQR = 11)). 190 patients (45.8%) manifested CI. Only the DBI (Drug Burden Index) showed statistically significant differences in the median AB between patients without CI and with CI (0.5 (1.00) vs. 0.67 (0.65), p = 0.006). At the ROC curve analysis, statistically significant values were obtained only with the DBI (AUC: 0.578 (0.523–0.633), p = 0.006). The cut-off point with the greatest validity selected for the DBI was an AB of 0.41 (moderate risk) (sensitivity = 81%, specificity = 36%, PPV = 51%). The DBI is the scale with the greatest discriminatory power to detect OCCP at risk of CI and the best cut-off point is a load value of 0.41.

Anticholinergic agents are widely used in clinical practice. However, they can cause various cumulative side effects (dry mouth, drowsiness, confusion, residual urine accumulation, etc.). The purpose of the study is to perform an analytical review of the literature dedicated to causes, complications and rehabilitation of patients with cumulative anticholinergic effect. The analytical review of the literature highlights the risks and benefits of using anticholinergic drugs. Anticholinergic agents make up to one third of all medicines for the aged people. Recent data have proved the relationship between the long-term use of anticholinergics and dementia. New results relating to the cholinergic system in the regulation of cerebral vascularisation and in neuritis indicate that anticholinergics may contribute to the absolute risk and progression of neurodegenerative diseases. It has been proven that more than 600 drugs taken by aged patients carry the so-called "anticholinergic load". The number of drugs with anticholinergic properties is constantly increasing, they include: antidepressants, antihistamines, antiparkinsonian, antipsychotic, antispasmodic, mydriatic drugs, drugs for the treatment of overactive bladder and many others. Conclusions. The number of drugs that have anticholinergic activity and can cause complications associated with anticholinergic load is increasing. To assess the anticholinergic action of drugs, several methods have been proposed, taking into account the amount of dose and the intensity of anticholinergic activity of drugs. The research of the general medical community about the anticholinergic load problem and high alertness when prescribing drugs with anticholinergic properties can prevent the cumulative anticholinergic effect development and severe complications, and, thus, save the life and health of patients.

Aim Overactive bladder (OAB) is a common and troublesome condition that can significantly impair quality of life. This review aims to educate providers of obstetrics and gynecology services about available therapies for OAB and what to expect following treatment. Methods Here, we review published data from studies that have evaluated available treatments for OAB. Relevant articles published over the past 2 decades, including large multicenter trials, were identified through a literature search using PubMed.gov, and the references in those articles were also manually searched to find additional articles. Treatment guidelines and product labels were also reviewed. Results Behavioral therapy is recommended as a first choice for OAB management; pharmacologic treatment (anticholinergics, β3 -adrenoceptor agonists) as second-line treatment; and onabotulinumtoxinA, peripheral tibial nerve stimulation, and sacral nerve stimulation as third-line therapy for patients refractory or intolerant to first- and second-line treatments. A stepwise approach to treatment through first-, second-, and third-line therapies is recommended, recognizing this may not be appropriate for all patients. Conclusions To optimize symptom control and set realistic expectations, patients should be carefully monitored and counseled appropriately on available treatment options.

Retrometabolic drug design approaches (RMDD) combine quantitative structure-activity and structure-metabolism relations (QSAR and QSMR) to improve the therapeutic index (ratio of toxic and effective dose, TI = TD50/ED50), of newly designed drugs. Soft drug (SD) design approaches, a subclass of RMDD, have been successfully employed in the development of safer drugs. The combination of “soft analog” and “inactive metabolite” techniques in drug development was first exemplified by the highly successful and safe soft corticosteroid, Loteprednol Etabonate. Similar techniques have been used to design safe topically active anticholinergic drugs with much reduced side effects. The “soft analog” and some of the “inactive metabolite” approaches have led to improved antimuscarinic drug candidates, which all (n = 76) can be fit with a bilinear exponential equation of activity vs molecular descriptors. The “remote inactive metabolite” approach was the most successful, having resulted in the new and very safe drug Sofpironium Bromide, which received regulatory approval to treat hyperhidrosis, a debilitating idiopathic disease and an unmet need.

Introduction Potentially inappropriate medications (PIMsare associated with falls, hospitalisation, and cognitive decline. Few studies have investigated the association between PIMsrelated to cognitive impairment (PIMCog) and mortality in dementia or mild cognitive impairment (MCI). Methods This was a retrospective observational study. Patients diagnosed with MCI or dementia (DSM-IV criteria) presenting to a tertiary-referral memory clinic from 2013–2019 were eligible. The primary outcome was all-cause death. Secondary outcomes were vascular death and non-vascular death defined according to formal certification. The primary exposure variable of interest was PIMCog, defined as any medication in the Beers 2015 or STOPP criteria, classified as potentially inappropriate for patients with cognitive impairment. Anticholinergic burden was measured using the anticholinergic cognitive burden (ACB) scale. Polypharmacy was defined as ≥5 medications. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). Results There were 418 patients included (n = 261 dementia, n = 157 MCI). The median age was 79 (interquartile range {IQR} 74–82) and median follow-up was 809 days (IQR 552–1,571). One or more PIMCog was prescribed in 141 patients (33.4%). PIMCog use was associated with all-cause mortality after adjustment for age, sex, dementia severity, Charlson Co-morbidity Index, chronic obstructive pulmonary disease, congestive cardiac failure, and peripheral vascular disease. (HR 1.96, 95% CI 1.24–3.09). PIMCog use was associated with vascular death (HR 3.28, 95% CI 1.51–7.11) but not with non-vascular death (HR 1.40 95% CI: 0.78–2.52). Neither an ACB ≥3 (HR 0.87, 95% CI: 0.46–1.64) or polypharmacy (HR 1.87, 95% CI: 0.67–5.24) were associated with death. Conclusion The burden of PIMCog use in patients with cognitive impairment is high. PIMCog use is independently associated with all-cause mortality and vascular death. This is a potential modifiable risk factor for death in patients with neurocognitive disorders. Further research is required to independently validate this finding.

Myricetin—a flavonoid capable of inhibiting the SNARE complex formation in neurons—reduces focal sweating after skin-application when delivers as encapsulated in lipid nanoparticles (M-LNPs). The stability of M-LNP enables efficient delivery of myricetin to sudomotor nerves located underneath sweat glands through transappendageal pathways while free myricetin just remained on the skin. Furthermore, release of myricetin from M-LNP is accelerated through lipase-/esterase-induced lipolysis in the skin-appendages, enabling uptake of myricetin by the surrounding cells. The amount of sweat is reduced by 55% after application of M-LNP (0.8 mg kg−1) on the mouse footpad. This is comparable to that of subcutaneously injected anticholinergic agents [0.25 mg kg−1 glycopyrrolate; 0.8 U kg−1 botulinum neurotoxin-A-type (BoNT/A)]. M-LNP neither shows a distal effect after skin-application nor induced cellular/ocular toxicity. In conclusion, M-LNP is an efficient skin-applicable antiperspirant. SNARE-inhibitory small molecules with suitable delivery systems have the potential to replace many BoNT/A interventions for which self-applications are preferred.

Background Multiple comorbidities are common in older adults, resulting in polypharmacy that often includes medications with anticholinergic properties. These medications have multiple side effects, which are more pronounced in the older population. This study examined the association between the use of anticholinergics and changes in the cognitive function of older adults. Methods The study population consisted of 2,222 individuals aged 65–69 years at baseline from the Personality and Total Health (PATH) Through Life Study in Australia. Medication data were obtained from the Pharmaceutical Benefits Scheme (PBS). Cognitive measures were obtained from neuropsychological battery assessment. Exposure to cumulative anticholinergic use was quantified to a total standardized daily dose (TSDD). The association between change in cognitive measures between baseline and 4-year follow-up, and cumulative use of anticholinergic was assessed through generalized linear models. Results During the study period, 18.6% (n = 413) of participants filled at least one prescription for anticholinergics. Compared to those not on anticholinergics, participants on anticholinergics were more likely to be woman (62.7% compared to 45.1%) and spent lesser time engaging in vigorous physical activity (0.4 h/week compared to 0.9 h/week). Cumulative use of anticholinergic resulting in a TSDD exceeding 1,095 was significantly associated with poorer performance in Trail Making Test Part B (Model 1: β = 5.77, Model 2: β = 5.33, Model 3: β = 8.32, p < .01), indicating impairment in processing speed. Conclusions In our study, except for speed of processing, other cognitive domains measured were not affected by cumulative anticholinergic use over a 4-year period.

Background: Neuromuscular blockers (NMBs) used during surgery have historically been reversed with acetylcholinesterase inhibitors and anticholinergic agents, which can slow gastrointestinal motility. Sugammadex (SUG) provides NMB reversal with minimal effects on gastrointestinal motility. Objective: The purpose of this study was to determine if SUG for reversal of NMB is associated with decreased time to first bowel movement (BM) following laparoscopic colorectal surgery. Methods: A retrospective cohort analysis divided 224 patients undergoing laparoscopic colorectal surgeries based on whether they received SUG or a combination of neostigmine and glycopyrrolate (NG) for NMB reversal. The primary outcome was time (in hours) from NMB reversal until first recorded BM. Secondary end points were postoperative ileus, postoperative nausea and vomiting, prevalence of residual NMB, and hospital length of stay. The relationship between NMB reversal agent and outcomes were analyzed using multivariable linear regression and Cox proportional hazards model. Results: There were 128 patients who received NG and 96 who received SUG. Time to first BM was faster in the SUG group by 11.7 hours ( P = 0.004). SUG maintained the effect in a multiple regression model ( P = 0.012). A Cox Proportional Hazards regression model found 50% increased odds of a BM across time for the SUG group ( P = 0.003). No adverse effects were noted. Conclusion and Relevance: This represents the first report demonstrating faster return of BM following colorectal surgery with SUG when compared with NG. Application of these data may add another tool to enhance recovery after colorectal surgery.

Akathisia is one of the most prevalent and distressing adverse effects associated with antipsychotic drug treatment. Propranolol, a non-selective beta-adrenergic receptor antagonist, is currently considered a first-line treatment for antipsychotic-induced akathisia (AIA). Surprisingly, the evidence for its anti-akathisia effect is modest. Propranolol’s side effects (e.g. orthostatic hypotension, bradycardia), contraindications (e.g. asthma) and increased complexity in titration schedules limit its use in some patients. Anticholinergic agents and benzodiazepines merely provide symptomatic relief in patients with AIA. Effective and well-tolerated treatment remains a major unmet need in akathisia and warrants a search for new anti-akathisia agents. Accumulating evidence during the last two decades indicates that agents with marked postsynaptic serotonin 5-HT2a receptor antagonism (ritanserin, cyproheptadine, trazodone, mianserin, mirtazapine) may represent a new class of potential anti-akathisia remedies. Among these agents, low-dose mirtazapine (7.5 mg or 15 mg once daily) has demonstrated the most compelling evidence for therapeutic efficacy. In this narrative review we highlight the clinical significance of AIA, outline major approaches for its management and propose a practical algorithm for its treatment.

Background Acetylcholinesterase inhibitors (e.g., pyridostigmine bromide) are used for neuromuscular blockade (NMB) reversal in patients undergoing surgery under general anesthesia (GA). Concurrent use of anticholinergic agents (e.g., glycopyrrolate) decreases cholinergic side effects but can impede bowel movements. Sugammadex has no cholinergic effects; its use modifies recovery of gastrointestinal (GI) motility following laparoscopic cholecystectomy compared to pyridostigmine/glycopyrrolate. This study evaluated the contribution of sugammadex to the recovery of GI motility compared with pyridostigmine and glycopyrrolate. Methods We conducted a prospective study of patients who underwent laparoscopic cholecystectomy. Patients were randomly allocated to the experimental group (sugammadex, Group S) or control group (pyridostigmine-glycopyrrolate, Group P). After anesthesia (propofol and rocuronium, and 2% sevoflurane), recovery was induced by injection of sugammadex or a pyridostigmine-glycopyrrolate mixture. As a primary outcome, patients recorded the time of their first passage of flatus (‘gas-out time’) and defecation. The secondary outcome was stool types. Results One-hundred and two patients participated (Group S [n = 49], Group P [n = 53]). Mean time from injection of NMB reversal agents to gas-out time was 15.03 (6.36–20.25) h in Group S and 20.85 (16.34–25.86) h in Group P (P = 0.001). Inter-group differences were significant. Time until the first defecation as well as types of stools was not significantly different. Conclusions Sugammadex after laparoscopic cholecystectomy under GA resulted in an earlier first postoperative passage of flatus compared with the use of a mixture of pyridostigmine and glycopyrrolate. These findings suggest that the use of sugammadex has positive effects on the recovery of GI motility.

Purpose Brain dysfunction related to areas regarding attention and arousal may occur not only in patients with attention-deficit/hyperactivity disorder (ADHD) but also in patients with enuresis and daytime symptoms. This study aimed to investigate changes in computerized comprehensive attention tests (CATs), a psychometric test for ADHD when patients with nonmonosymptomatic enuresis (NME) were treated with anticholinergic agents. Materials and methods Thirty patients with NME featuring overactive bladder were prospectively enrolled. They were treated with 5 mg of solifenacin to control daytime symptoms. Using CATs, patients were evaluated during 12 weeks of treatment. Four subtests of attention (visual and auditory selective attention, sustained attention, and flanker tests) were measured. For each subtest, four domains (omission error, commission error, response time [RT], and standard deviation of RT) were assessed. Results Only one domain of the flanker test was in the deficient range at baseline. The presence of urge incontinence affected follow-up results on the sustained attention tests. Treatment with anticholinergic agents did not significantly affect attention variables but changes in several variables were correlated with bladder symptoms and enuresis. Conclusions Minimal baseline defects in attention function were seen in patients with NME. Follow-up results for some attention variables were affected by daytime symptoms and enuresis. These results suggest that altered brain function in enuretic patients influences improvement in both attention and bladder function.

Background: Anticholinergic and sedative medications are frequently prescribed to older individuals. These medications are associated with short-term cognitive and physical impairment, but less is known about long-term associations. We therefore examined over twenty years whether cumulative exposure to these medications was related to poorer cognitive and physical functioning.Methods: Older adult participants of the Longitudinal Aging Study Amsterdam (LASA) were followed from 1992-2012. On 7 measurement occasions, cumulative exposure to anticholinergic and sedative medications was quantified with the Drug Burden Index (DBI), a linear additive pharmacological dose-response model. Cognitive functioning was assessed with the Mini Mental State Examination (MMSE), Alphabet Coding Task (ACT, 3 trials), Auditory Verbal Learning Test (AVLT, learning and retention condition), and Raven Colored Progressive Matrices (RCPM, 2 trials). Physical functioning was assessed with the Walking Test (WT), Cardigan Test (CT), Chair Stands Test (CST), Balance Test (BT), and self-reported Functional Independence (FI). Data were analyzed with linear mixed models adjusted for age, education, sex, living with a partner, BMI, depressive symptoms, co-morbidities (cardiovascular disease, diabetes, cancer, COPD, osteoarthritis, CNS diseases), and prescribed medications.Results: Longitudinal associations were found of the DBI with poorer cognitive functioning (less items correct on the 3 ACT trials, AVLT learning condition, and the 2 RCPM trials) and with poorer physical functioning (longer completion time on the CT, CST, and lower self-reported FI).Conclusions: This longitudinal analysis of data collected over 20 years, showed that higher long-term cumulative exposure to anticholinergic and sedative medications was associated with poorer cognitive and physical functioning.

Background: Motion sickness is a common phenomenon that affects almost everybody at some point in their lifetime. Clinicians should be familiar with the proper management of this condition. Objective: To provide an update on the current understanding of the pathophysiology and management of motion sickness. Methods: A PubMed search was performed with Clinical Queries using the key term ‘motion sickness.’ The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. The search was restricted to English literature. The information retrieved from the earlier search was used in the compilation of the present article. Results: Motion sickness is typically triggered by low-frequency vertical, lateral, angular, rotary motion, or virtual stimulator motion, to which an individual has not adapted. Sine qua non for developing motion sickness is when the brain receives conflicting information from different sensors about real body movements or virtual environment. The principal sensors are the eyes, the vestibular apparatus, and proprioceptive receptors. The conflicting information is judged in relation to a pattern of expected associations formed under normal or experienced conditions stored in the brain. Motion sickness typically presents with malaise, anorexia, nausea, yawning, sighing, increased salivation, burping, headache, blurred vision, non-vertiginous dizziness, drowsiness, spatial disorientation, difficulty concentrating, and sometimes vomiting. Simple behavioral and environmental modifications can be effective in the prevention of motion sickness. Medications that are effective in the prophylaxis and/or treatment of motion sickness include anticholinergics, antihistamines, and sympathomimetics. Conclusion: In most cases, motion sickness can be prevented by behavioral and environmental modifications (avoidance, habituation, and minimization of motion stimuli). Pharmacotherapy should be considered in the prevention and/ or treatment of more severe motion sickness and for patients who do not respond to conservative measures. Medications are most effective when combined with behavioral and environmental modifications. Drugs that are effective in the prophylaxis and/or treatment of motion sickness include anticholinergic agents and antihistamines.

Spinal dysraphism, which includes conditions such as myelomeningocele and sacral agenesis, is one of the most common causes of congenital lower urinary tract dysfunction. Early evaluation of the neurogenic bladder serves to minimize renal damage, and the main goals of management include preserving renal function, achieving acceptable continence, and optimizing quality of life. The survival of patients with such conditions has improved to greater than 80% reaching adulthood, owing to advances in diagnostic and therapeutic modalities. The result is a real, and unfortunately often unmet, need for successful transitional care in this complex patient population. Clinicians must be able to identify the unique challenges encountered by patients with neurogenic bladder as they shift through different stages of their life.

Background It is recommended that anticholinergic medication is avoided in older people, especially those with cognitive impairment. Objective To investigate anticholinergic load (ACL) over time in older primary care patients with and without cognitive impairment. Methods Community-dwelling general practice patients at baseline (n = 1768), at year one (n = 1373) and a restricted cohort (with possible or definite cognitive impairment) at year two (n = 370) had medication regimens documented by a research nurse during a home visit. Anticholinergic medicines were categorized as levels 1–3 (low-high potency) and summed for each participant as a measure of their ACL. Results Most participants had no change in ACL over time, but there was some turnover in the anticholinergic medications used. The mean change in ACL was 0.012 ± 0.99 from baseline to 12 months and −0.04 ± 1.3 from baseline to 24 months. Cardiovascular drugs were the most commonly used level 1 anticholinergics, followed by antidepressants and opioids. Antidepressants and urologicals were the most commonly used level 3 anticholinergics. The rate of anticholinergic deprescribing was equivalent to the rate of anticholinergic initiation, and commonly involved the level 1 drugs warfarin, furosemide and temazepam, and the level 3 drugs amitriptyline and oxybutynin. People with dementia had a higher ACL at baseline and year one compared with other participants. Conclusion ACL of community-dwelling older people was very stable over time. This may represent lost opportunities for deprescribing as well as potentially inappropriate prescribing, particularly in those with cognitive impairment.

Bradycardia and cardiac arrest are recognised complications of laparoscopic gynaecological surgery. Anticholinergic agents are indicated in the treatment of perioperative bradyarrhythmia; however, their role in the prevention of bradycardia as a result of insufflation of the peritoneum is less well defined. This article systematically reviewed the literature with respect to the role of anticholinergic agents in the prevention of clinically significant bradyarrhythmia during laparoscopic gynaecological surgery. Eight studies were included for review following an extensive database search. This review highlights the paucity of evidence supporting the prophylactic use of anticholinergic agents in preventing clinically significant bradycardia in women undergoing laparoscopic gynaecological surgery.

Background Stenting has been primarily used to treat urinary obstruction and the frequency of this use is increasing with the increase in ureteroscopic management. In cases of acute obstruction, a stent is used temporarily to stabilize the patient until definitive therapy. The stent is generally placed if there is accompanying ureteric injury or in those with a residual stone after ureteroscopic lithotripsy. Placing a ureteric stent after ureteroscopy with stone extraction is done by some urologists routinely to prevent possible stenosis or to decrease secondary pain caused by mucosal oedema. However, routinely placing a stent to prevent late complications or to relieve flank pain from a ureteric stricture or mucosal oedema after surgery is questionable. Stent-related symptoms are quite problem in nearly 80% of patients that has been implicated in short-term morbidities in terms of negative impact on the patients’ quality of life, body pains and hematuria. Various attempts had been made to minimize these symptoms but pharmacological treatment is the simplest and a noninvasive option. Numerous drugs had been tried to relieve these symptoms like alpha blockers, anticholinergics and analgesics. Objective To compare the efficacy of tamsulosin alone, tamsulosin in combination with solifenacin and tamsulosin in combination with trospium chloride in in the relief of Double-J stentrelated symptoms following uncomplicated ureteroscopic lithotripsy (URSL). Patients and Methods The present study was a prospective randomized comparative study conducted on 60 patients whith double-J stent inserted following uncomplicated ureteroscopic lithotripsy (URSL) in Ain Shams University Hospital and Karmouz Hospital over a period of 1 year. The patient were randomized into 3 equal groups (1:1:1 randomization): Group A:20 patients were treated by Tamsulosin (0.4 mg) alone once daily. Group B:20 patients were treated by Tamsulosin (0.4 mg) once daily in combination with Solifenacin (5 mg) once daily. Group C: 20 patients were treated by Tamsulosin (0.4 mg) once daily in combination with Trospium chloride (20 mg) twice daily. All patients were assessed 1 week postoperatively after Double-J stent insertion. Then, the patients were start the medical treatment and were assessed 3 weeks after starting the medical treatment. Results The study shows that the combination of the tamsulosin 0.4 mg/day and trospium chloride 20 mg twice/day are significantly superior to the tamsulosin 0.4 mg once alone / day and the combination of the tamsulosin 0.4 mg /day and the solifenacine 5 mg /day for the treatment of the LUTS in d.j stent cases except in the frecuncy the combination of tamsulosin 0.4 mg/day and the solifenacine 5 mg/day are signicantly superior. Also, the drugs are safe with mild few side effects. There were no significant differences regarding headache, dizziness, backache, myalgia and orthostatic hypotension. Conclusion The study show that the combination of the tamsulosin 0.4 mg/day and the trospium chloride 20 mg twice /day are significantly superior to the tamsulosin 0.4 mg once alone / day and the combination of the tamsulosin 0.4 mg /day and the solifenacine 5 mg /day for the treatment of the LUTS in d.j stent cases except in the frecuncy the combination of tamsulosin 0.4 mg/day and the solifenacine 5 mg/day are signicantly superior.

Ogilvie's syndrome is a clinical entity that occurs with signs of excessive dilatation of the colon and obstruction, despite the absence of a mechanical obstruction. Although its etiology remains uncertain, anticholinergic drugs, metabolic disorders, diabetes mellitus, hyperparathyroidism, Parkinson's disease, major orthopedic interventions, or blunt abdominal trauma are considered to be possible causes. Imbalance in sympathetic innervation plays a role in the pathogenesis. The characteristic feature of the syndrome is the presence of a major trauma or surgical history. Although this is an uncommon complication, especially after hip and knee arthroplasty, it is an important cause of mortality and morbidity. Conservative or surgical colonic decompression and anticholinergic agents play a role in the treatment of Ogilvie's syndrome, which is defined as acute colonic pseudo-obstruction (ACPO). In this case report, we present the postoperative process of an elderly patient with comorbid diseases who underwent hemiarthroplasty due to a hip fracture as a result of a domestic fall. We will discuss the diagnosis of ACPO and the approach to multidisciplinary management of the treatment in a case that is frequently encountered in daily practice and starts as a normal report. We aim to remind surgeons that they may encounter ACPO in the postoperative period and to emphasize that mortality and morbidity can be reduced with early diagnosis and a multidisciplinary approach. We would like to emphasize that Ogilvie's syndrome should be included in the differential diagnosis portfolio of all orthopedic surgeons.Das Ogilvie-Syndrom ist eine klinische Entität, die trotz fehlender mechanischer Obstruktion mit Anzeichen einer übermäßigen Erweiterung des Dickdarms und einer Obstruktion auftritt. Obwohl seine Ätiologie ungewiss bleibt; Anticholinergika, Stoffwechselstörungen, Diabetes mellitus, Hyperparathyreoidismus, Parkinson, größere orthopädische Eingriffe und stumpfe Abdominaltraumata werden als mögliche Ursachen angesehen. Das Ungleichgewicht der sympathischen Innervation spielt eine Rolle bei der Pathogenese. Das charakteristische Merkmal des Syndroms ist das Vorhandensein eines schweren Traumas oder einer Operationsanamnese. Obwohl es eine ungewöhnliche Komplikation ist, insbesondere nach einer Hüft- und Knieendoprothese, ist es eine wichtige Ursache für Mortalität und Morbidität. Konservative oder chirurgische Dekompression des Dickdarms und Anticholinergika spielen eine Rolle bei der Behandlung des Ogilvie-Syndroms, das als akute Pseudoobstruktion des Dickdarms (ACPO) definiert ist. In diesem Fallbericht stellen wir den postoperativen Prozess eines älteren Patienten mit komorbiden Erkrankungen vor, der sich aufgrund einer Hüftfraktur infolge eines Sturzes im Inland einer Hemiarthroplastik unterzogen hatte. Wir werden die Diagnose von ACPO und den Ansatz des multidisziplinären Managements der Behandlung in einem Fall diskutieren, der in der täglichen Praxis häufig vorkommt und als gewöhnliche Geschichte beginnt. Wir möchten die Chirurgen daran erinnern, dass sie in der postoperativen Phase möglicherweise auf ACPO stoßen, und betonen, dass Mortalität und Morbidität durch frühzeitige Diagnose und einen multidisziplinären Ansatz verringert werden können. Wir möchten betonen, dass das Ogilvie-Syndrom in das Differenzialdiagnose-Portfolio aller orthopädischen Chirurgen aufgenommen werden sollte.

Death rattle commonly occurs at the end of life and is typically managed with anticholinergic agents. Myasthenia gravis is an autoimmune disorder characterized by fatigability of skeletal muscle, resulting from autoimmune destruction of acetylcholine receptors at the motor endplate. The condition is treated with acetylcholinesterase inhibitors, which potentiate the action of acetylcholine. Agents that antagonize acetylcholine activity (e.g., anticholinergic agents, such as glycopyrrolate) can, therefore, exacerbate myasthenia gravis. We discuss the case of a patient dying with myasthenia gravis that developed problematic "death rattle," and the successful use of glycopyrrolate in treating this symptom.

Objectives To investigate the associations between central anticholinergic burden and mortality, hospitalization, and cognitive impairment in people with dementia prescribed anticholinergic drugs for urinary symptoms. Design Retrospective cohort study. Setting and Participants Patients diagnosed with dementia receiving anticholinergic medication for bladder conditions (N = 540), assembled from a large healthcare database. Methods Central anticholinergic burden related to bladder drugs was estimated using the anticholinergic effect on cognition scale. Data were linked to national mortality and hospitalization data sources, and serially recorded Mini-Mental State Examination scores were used to investigate cognitive decline. Results Patients had a median survival of 4.1 years. Urinary drugs with a high anticholinergic effect on cognition score (tolterodine, oxybutynin) were associated with a 55% increased mortality risk (hazard ratio 1.55; 95% confidence interval 1.19‒2.01; P = .001) compared with drugs with low or no central anticholinergic burden (darifenacin, fesoterodine, trospium, mirabegron, solifenacin). Cognitive decline over a 24-month period around diagnosis was only detectable in the high central anticholinergic group, but there was no significant difference in cognitive trajectories between the high and low/no anticholinergic bladder drug groups. No increase of emergency hospitalization risk was seen in relation to central anticholinergic burden. Conclusions and Implications Urinary drugs with high central anticholinergic burden cause more harm than those acting peripherally and should be avoided in people with dementia. Further research is needed to test whether centrally acting anticholinergic agents in general cause worse outcomes in dementia.

Many critically ill patients suffer from delirium which is associated with significant morbidity and mortality. There is a paucity of data about the incidence, symptoms, or treatment of delirium in the pediatric intensive care unit (PICU). Risk factors for delirium are common in the PICU including central nervous system immaturity, developmental delay, mechanical ventilation, and use of anticholinergic agents, corticosteroids, vasopressors, opioids, or benzodiazepines. Hypoactive delirium is the most common subtype in pediatric patients; however, hyperactive delirium has also been reported. Various screening tools are validated in the pediatric population, with the Cornell Assessment of Pediatric Delirium (CAPD) applicable to the largest age range and able to detect signs and symptoms consistent with both hypo- and hyperactive delirium. Treatment of delirium should always include identification and reversal of the underlying etiology, reserving pharmacologic management for those patients without symptom resolution, or with significant impact to medical care. Atypical antipsychotics (olanzapine, quetiapine, and risperidone) should be used first-line in patients requiring pharmacologic treatment owing to their apparent efficacy and low incidence of reported adverse effects. The choice of atypical antipsychotic should be based on adverse effect profile, available dosage forms, and consideration of medication interactions. Intravenous haloperidol may be a potential treatment option in patients unable to tolerate oral medications and with significant symptoms. However, given the high incidence of serious adverse effects with intravenous haloperidol, routine use should be avoided. Dexmedetomidine should be used when sedation is needed and when clinically appropriate, given the positive impact on delirium. Additional well-designed trials assessing screening and treatment of PICU delirium are needed.

Background A pre-existing neurocognitive disorder (NCD) is a relevant factor for the outcome of surgical patients. To improve understanding of these conditions, we investigated the association between parameters of the cholinergic system and NCD. Method This investigation is part of the BioCog project (www.biocog.eu), which is a prospective multicenter observational study including patients aged 65 years and older scheduled for elective surgery. Patients with a Mini-Mental State Examination (MMSE) score ≤23 points were excluded. Neurocognitive disorder was assessed according to the fifth Diagnostic and Statistical Manual of Mental Disorders criteria. The basal forebrain cholinergic system volume (BFCSV) was assessed with magnetic resonance imaging, the peripheral cholinesterase (ChE) activities with point-of-care measurements, and anticholinergic load by analyzing the long-term medication with anticholinergic scales (Anticholinergic Drug Scale [ADS], Anticholinergic Risk Scale [ARS], Anticholinergic Cognitive Burden Scale [ACBS]). The associations of BFCSV, ChE activities, and anticholinergic scales with NCD were studied with logistic regression analysis, adjusting for confounding factors. Results A total of 797 participants (mean age 72 years, 42% females) were included. One hundred and eleven patients (13.9%) fulfilled criteria for mild NCD and 82 patients (10.3%) for major NCD criteria. We found that AcetylChE activity was associated with major NCD (odds ratio [95% confidence interval]: [U/gHB] 1.061 [1.010, 1.115]), as well as ADS score ([points] 1.353 [1.063, 1.723]) or ARS score, respectively ([points] 1.623 [1.100, 2.397]) with major NCD. However, we found no association between BFCSV or ButyrylChE activity with mild or major NCD. Conclusions AcetylChE activity and anticholinergic load were associated with major NCD. Future research should focus on the association of the cholinergic system and the development of postoperative delirium and postoperative NCD.

Introduction Following a case study on scopolamine butyl bromide, an anticholinergic drug, we studied the effect of a central anticholinergic drug on post‐traumatic stress disorder (PTSD)‐related flashbacks and nightmares. Methods We administered trihexyphenidyl (TP) to 34 patients with refractory PTSD‐related nightmares and flashbacks (open‐label trial [n = 22]; single‐blind trial [n = 12]), who had previously received psychiatric treatment for approximately 2–15 years, without therapeutic benefits. The effect of TP was determined using the Clinician‐Administered PTSD Scale (CAPS) and the Impact of Event Scale‐Revised (IES‐R). Results Overall, most patients reported an improvement to none or mild on the CAPS for nightmares (88%) and flashbacks (79%). Conclusion This study is the first to demonstrate the potential efficacy of TP in the treatment of refractory PTSD‐related nightmares and flashbacks. Further double‐blind, randomized control trials are needed to explore the potential clinical benefits of TP in PTSD., Central anticholinergic agent (trihexyphenidyl) is very effective and fast‐acting against hallmark symptoms: nightmares and flashbacks of PTSD and its mechanism of action.

Impaired thermoregulation and heat intolerance may be intrinsic to autonomic dysfunction in Parkinson’s disease due to disturbances in perspiration regulation. Thermoregulatory impairment leading to hyperthermia/heatstroke can be accentuated with the usage of anticholinergics, which block the ability to sweat. Oxybutynin chloride is one of the most used anticholinergic agents in clinical practice for the management of detrusor hyperreflexia secondary to neurogenic bladder dysfunction and is often used in the setting of Parkinson’s disease. We present a rare instance of oxybutynin-induced heatstroke in an elderly patient with Parkinson’s disease.

Posterior urethral valves are the most common cause of bladder outlet obstruction in male newborns. Initial catheter drainage alleviates the urethral obstruction before definitive management by valve ablation. Newborns with posterior urethral valves often present with hypercontractile bladders that may inhibit upper tract drainage despite bladder catheterization. Anticholinergic agents are commonly used to treat detrusor hyperactivity, with oxybutynin being the most commonly used. We report the first case of a newborn with posterior urethral valves and ureterovesical junction obstruction caused by detrusor hypertrophy who underwent urgent intravesical instillation of oxybutynin at high doses in an attempt to avoid a diversion procedure.

Background Prolonged exposure to anticholinergic medication, particularly in midlife, is associated with increased risk of cognitive impairment/dementia. Less well explored is the ongoing use of drugs with anticholinergic properties in patients with Alzheimer’s Disease (AD), where the potential to accelerate cognitive decline may be greatest. Methods We analysed medication data from the NILVAD trial, a clinical trial examining the efficacy of Nilvadapine in mild-moderate Alzheimer’s Disease (AD). Drgs were coded based on their Anatomical Therapeutic Chemical (ATC) classification and Anticholinergic Burden Scale (ABS) applied to each participant’s medication list. Logistic and linear regression were used to model predictors of potential anticholinergic medication use/total ABS score. Results Of 510 participants with AD (mean age 72.8 +/-8.3 years; 62% female), just over one-quarter (N = 134, 26.27%) were prescribed a drug with potential/definite anticholinergic properties. Half of these had an anticholinergic burden score of 3 or greater (N = 67, 13.4%). The most frequent definite anticholinergics prescribed included quetiapine (N=27) oxybutynin (N = 22), paroxetine (N=14) and amitriptyline (N=8). Usage did not significantly differ by country or study arm. Overall, 88.43% of patients were prescribed a cholinesterase inhibitor. On multivariate analysis of potential/definite anticholinergic usage, age (p=0.044; OR 1.03, 1.01-1.06), total number of medications (p=0.001, OR 1.3, 1.18-1.41) as well as a greater dementia severity rated using the Alzheimer’s Disease Assessment Scale (ADAS-Cog) (p=0.008; 1.04 1.01-1.07) were associated with likelihood of anticholinergic use. Conclusion Over one-quarter of community-dwelling older patients with AD are prescribed a drug with potential or definite anticholinergic properties. Use of drugs with potential/definite anticholinergic properties were associated with total medication burden in addition to greater dementia severity at baseline. This is particularly pertinent given the deleterious cognitive effects of anticholinergic medication. Further attention to reducing total anticholinergic burden in patients with dementia is warranted.

Background and Purpose The bronchodilator tiotropium binds not only to its main binding site on the M-3 muscarinic receptor but also to an allosteric site. Here, we have investigated the functional relevance of this allosteric binding and the potential contribution of this behaviour to interactions with long-acting beta-adrenoceptor agonists, as combination therapy with anticholinergic agents and beta-adrenoceptor agonists improves lung function in chronic obstructive pulmonary disease. Experimental Approach ACh, tiotropium, and atropine binding to M-3 receptors were modelled using molecular dynamics simulations. Contractions of bovine and human tracheal smooth muscle strips were studied. Key Results Molecular dynamics simulation revealed extracellular vestibule binding of tiotropium, and not atropine, to M-3 receptors as a secondary low affinity binding site, preventing ACh entry into the orthosteric binding pocket. This resulted in a low (allosteric binding) and high (orthosteric binding) functional affinity of tiotropium in protecting against methacholine-induced contractions of airway smooth muscle, which was not observed for atropine and glycopyrrolate. Moreover, antagonism by tiotropium was insurmountable in nature. This behaviour facilitated functional interactions of tiotropium with the beta-agonist olodaterol, which synergistically enhanced bronchoprotective effects of tiotropium. This was not seen for glycopyrrolate and olodaterol or indacaterol but was mimicked by the interaction of tiotropium and forskolin, indicating no direct beta-adrenoceptor-M-3 receptor crosstalk in this effect. Conclusions and Implications We propose that tiotropium has two binding sites at the M-3 receptor that prevent ACh action, which, together with slow dissociation kinetics, may contribute to insurmountable antagonism and enhanced functional interactions with beta-adrenoceptor agonists.

Background: More than 1.3 million emergency department visits have been associated with adverse drug events (ADEs) in older adults. Increasing Alzheimer’s disease (AD) prevalence in the geriatric population poses an additive risk of ADEs because of the array of psychotropic medications prescribed for AD patients. Scant research has been conducted at a nationwide level on psychotropic-related ADEs in this population. Objective: This study aimed to determine the incidence and economic burden of psychotropic ADEs in the geriatric AD population compared with the non-AD geriatric population. Methods: A retrospective analysis was conducted of geriatric AD patients who visited the ED in 2013 with a psychotropic-related ADE to determine the incidence and resource utilization of these events. The relationship between presence of AD and an ADE was analyzed using multiple logistic regression. Results: There were 427 969 Alzheimer’s ED visits compared with 20 492 554 ED visits without. Of the AD cases, 1.04% were associated with at least 1 adverse event. AD cases more frequently were admitted as inpatients (64.90% vs 34.92%, P < 0.01). Common drug classes associated with AD-related ADEs were benzodiazepines, antipsychotics, and autonomic nervous system–affecting agents (adrenergic agonists, antimuscarinic agents, anticholinergic agents). There was a significantly higher likelihood for Alzheimer’s cases to experience any psychotropic-related adverse event (OR = 1.66; 95% CI = 1.20, 1.82). Conclusion and Relevance: Alzheimer’s patients more frequently experienced psychotropic-related adverse events and related adverse outcomes than older adults without Alzheimer’s. Application of these findings should be implemented in protocol development to reduce future psychotropic-related adverse outcomes for this population.

Tropenol ester is a highly toxic anticholinergic substance and an intermediate used in industrial production of the bronchodilator tiotropium bromide. The aim of this study was to systematically test workers involved in its production for tropenol ester in urine to identify any exposure pathways and define additional preventive measures. Twelve workers performing tasks involving potential exposure to tropenol ester were repeatedly monitored at the end of each production cycle. Medical exams revealed no symptoms of acute poisoning with tropenol ester, but biological monitoring of urine showed 36 positive findings in 79 samples, with tropenol ester concentrations ranging between the detection limit of 54 pg/mL and 2160 pg/mL. We managed to establish the cause of only one positive finding, which was a hole in a protective glove, whereas the rest most likely occurred due to human error. Because of this, the plant decided to modify the production process by replacing tropenol ester with a safer intermediate. While it is the safest course of action, there where it cannot be taken, biological monitoring can be very helpful in raising awareness about exposure to toxic substances, including the new ones that have not been studied for their adverse potential., Tropenol ester je iznimno toksičan antikolinergik, koji se rabi za sintezu bronhodilatatora tiotropijeva bromida. Cilj je ovog ispitivanja bio sustavno testirati radnike koji njime barataju u proizvodnji na tropenol ester u mokraći ne bi li se ustanovili putevi izloženosti i poboljšale preventivne mjere. Ispitivanje je obuhvatilo 12 radnika kroz 12 proizvodnih ciklusa, a uzorkovanje se provodilo na kraju svakog ciklusa. Liječničkim se pregledom nisu otkrili nikakvi simptomi akutnog otrovanja tropenol esterom, ali se biomonitoringom otkrilo 36 pozitivnih uzoraka od njih 79. Razine tropenol estera u pozitivnim uzorcima kretale su se od granice detekcije (54 pg/mL) do 2160 pg/mL. Međutim, samo smo za jedan pozitivan nalaz uspjeli utvrditi uzrok. Radilo se o rupi u zaštitnoj rukavici. Za ostale pozitivne uzorke pretpostavljamo da upućuju na ljudsku pogrešku prilikom skidanja ili čišćenja opreme. Zbog nemogućnosti da utvrdimo uzroke izloženosti, tvornica je promijenila proizvodni proces i tropenol ester zamijenila sigurnijim međuproizvodom. Iako je to najsigurniji način za sprječavanje izloženosti opasnim tvarima u proizvodnji, tamo gdje to nije moguće, biomonitoring može biti itekako koristan za podizanje svijesti o izloženosti, osobito kod novih tvari čije štetno djelovanje za zdravlje još nije istraženo.

Asthma is one of the most common pediatric emergencies among children throughout the world, where an estimated 300 million individuals are affected [1]. The prevalence of asthma in Saudi Arabia is 23% according to Alfrayeh [2]. Most asthma is uncontrolled and Jahdali estimated that up to 64% of patients have uncontrolled asthma [3]. Morbidity related to asthma has also increased in recent years. In addition, hospitalization for asthma has increased [4]. However, mortality due to asthma is decreasing worldwide [5]. Asthma is one of the main causes of health care utilization and the costs related to asthma are increasing [6]. Approximately 50% of pediatric asthma cases are still uncontrolled in Saudi Arabia, even in tertiary centers [7]. Numerous guidelines are available online and the guidelines of the Saudi Initiative for Asthma (SINA), which were updated in 2016, are very useful for the pediatric age group [8]. The availability of asthma guidelines can improve the outcomes of asthma in children [9]. In general, asthma treatments that involve the administration of oxygen, inhaled bronchodilators, systemic steroids, and anticholinergic agents are common, and these agents are the main forms of therapy. Frequent assessments and monitoring the response to these therapies are crucial for tailoring medications to needs. In this study, we aimed to minimize the controversy regarding asthma exacerbation management by providing the best evidence for patient care according to the resources available at a specific institute [10]. 1.1. Definition of exacerbation Asthma exacerbation is recognized clinically based on the following features: progressive increase in shortness of breath, coughing, wheezing, or chest tightness, and a progressive reduction in lung function that requires medical intervention [5,11]. An exacerbation may include an increase in coughing, especially when the child is asleep, a decrease in exercise tolerance, impairment of daily activities, and acute or sub-acute increases in wheezing or shortness of breath [12,13].

Drugs with strong anticholinergic properties are used under a variety of conditions; however, they can cause various adverse effects including a negative impact on cognitive functions, with older adults being more susceptible to these effects. We explored whether the use of anticholinergic agents (ACs) affects the risk of Alzheimer’s disease (AD) in terms of incidence by using National Health Insurance Service elderly cohort database (2002–2013). As a result, AD risk was higher in subjects with an increased amount of prescriptions for strong ACs over a long period of time (9–12 years) than that in the least-exposed reference group (0–9 dose/year) [hazard ratio (HR) (95% confidence interval (95% CI)) 0.99 (0.95–1.03), 1.19 (1.12–1.26), 1.39 (1.30–1.50); in the 10–49 doses/year, 50–119 doses/year, and ≥120 doses/year groups]. Hazard ratios were particularly high in the young-old subgroup (60–64 years old in 2002) [HR (95% CI) 1.11 (1.04–1.22), 1.43 (1.25–1.65), 1.83 (1.56–2.14); in the 10–49 doses/year, 50–119 doses/year, and ≥120 doses/year groups]. Use of strong ACs dose-dependently increased the risk of AD in terms of incidence when exposure was followed up for 9 years or more, and the association was greater in the young-old subgroup.

Background: Structural similarity in Chalcone and Pyrazoline brought our intention for the analysis of such compounds. This study involved the synthesis of chalcones and their pyrazoline derivatives and their screening as cholinesterase inhibitors. The newly synthesized compounds were also investigated for their antioxidant potential. Methods: Chalcones were synthesized by well-established methods of synthesis and their structural elucidation was carried out by H-NMR, 13C-NMR, Mass spectrometry and FTIR. For the determination of inhibition potency of synthesized compounds, spectrophotometric method was applied whereas, DPPH free radical scavenging method was used to check the antioxidant ability. Results: Chalcones and their pyrazoline derivatives were synthesized and characterised by 1HNMR, 13C-NMR, Mass spectrometry and FTIR. The compounds were screened for their anti- Alzheimer activity, which exhibited that compounds 1g, 1c and 1h, 1g showed strong inhibitory potency against acetylcholinesterase and butyrylcholinesterase, respectively. DPPH radical scavenging method was applied to check anti-oxidant potential of synthesized compounds and results explored that among all the synthesized compounds only compounds 1c and 1b showed strong scavenging potential. Conclusion: Chalcone and their pyrazoline derivatives were synthesized and screened for their anti-Alzheimer and antioxidant potential. The experimental results of anti-Alzheimer activity were compared with molecular docking studies, which showed that compounds 1g, 1c and 1h, 1g were active against AChE and BChE, respectively. Among the synthesized compounds 1c and 1b were found to be most potent antioxidants. These results suggest that compound 1b, 1c, 1g and 1h may further be explored for further developments.

Background The aims of this study were to evaluate the relationship between anticholinergic drug burden (ACB) cognitive impairment, physical frailty, and cognitive frailty, and to determine if ACB is predictive of these phenotypes when modeled with biological and genomic biomarkers. Methods In a retrospective cohort study, a total of 1,453 adults aged 20–102 years were used to examine ACB as a predictor for cognitive impairment, physical frailty, and cognitive frailty. Anticholinergic burden is examined as a predictor for all phenotypes in a cross-sectional analysis using logistic, ordinal regression models, and Extreme Gradient Boosting for population predictive modeling. Results A significant association was found between ACB and cognitive decline (p = .02), frailty (p < .001), and cognitive frailty (p < .001). The odds of cognitive impairment increased by 1.21 (95% confidence interval [CI] = 1.06–1.37, p < .001), odds of being frail increased by 1.33 (95% CI = 1.18–1.50, p < .001), and odds of having cognitive frailty increased by 1.36 (95% CI = 1.21–1.54, p < .001). Population modeling results indicated ACB score as one of the stronger predictors for cognitive impairment, physical frailty, and cognitive frailty with area under the curves ranging from 0.81 to 0.88. Conclusions Anticholinergic medications are a potentially modifiable risk factor for the prevention of cognitive and physical decline. Identification of reversible causes for cognitive and physical impairment is critical for the aging population. These findings encourage new research that may lead to effective interventions for deprescribing programs for the prevention of cognitive and physical decline in older adults.

To investigate whether scopolamine, an anticholinergic agent which induces hyposalivation, represents a risk factor for the occurrence of dental caries. A retrospective cohort study was carried out among sailors treated with scopolamine for seasickness. The study population included 370 young healthy male adults (18–30 years old) who served in the Israel Navy between 2012 and 2016. Of these, 66 subjects who were chronically treated with intermittent administration of scopolamine, either by the oral or transdermal route, were assigned to the study group. Documented subject characteristics included age, socioeconomic status, level of education, body mass index, smoking history, and dental hygiene. Follow-up lasted 1 to 3.5 years. Two- to 3.5-year follow-up revealed a higher risk of dental caries in 15 of 16 subjects (93.8%) treated with an average of 50.9 mg scopolamine, in contrast to only 71 of 108 control subjects (65.7%) (RR = 1.43, p = 0.02 [95% CI = 1.18–1.72]). Follow-up for 1–1.5 years revealed a lower occurrence of dental caries in both the study group (11/22, 50.0%) and the control group (46/104, 44.2%). Follow-up of 1.5–2 years also revealed less dental caries, in 16/28 subjects (57.1%) in the study group and 51/92 subjects (55.4%) in the control group. The differences were not statistically significant. In healthy young adults, prolonged intermittent use of scopolamine was found to be a risk factor for the development of dental caries. Dental care and hygiene should be intensified when administering hyposalivatory anticholinergic agents.

Anticholinergic toxicity is a relatively uncommon occurrence. When it does occur, it is usually attributed to an overdose of anticholinergic agents, especially in the elderly population. In younger patients, anticholingeric toxicity is usually due to an intentional overdose in a suicide attempt, accidental exposure to jimson weed or deadly nightshade plant, or the combination of anticholinergic drugs with recreational drugs (psilocybin mushroom). Over-the-counter cold medicines are well known to contain a variety of anticholinergic substances, the most well-known being diphenhydramine. Uncommonly, these readily available substances can produce anticholinergic toxicity in elderly patients, even when appropriate dosages are consumed. Younger patients are less likely to develop this clinical picture, due to higher renal clearance and lower drug volume of distribution. Nonetheless, clinical suspicion should remain high in the younger population. Patients can present with fever, tachycardia, diplopia, urinary retention, dry mucous membranes, and altered mental status. This case provides awareness to the unlikely complication of over-the-counter cold medicines in a young 19-year-old patient, while highlighting the need for diligent history taking and deliberate use of physostigmine in patients with altered mental status.

Background: The use of drugs with anticholinergic effects among elderly patients is associated with adverse clinical outcomes. There is paucity of information about anticholinergic drug burden among Nigerian elderly population.Objectives: To determine the anticholinergic drug burden among elderly Nigerian patients.Methods: This was a retrospective cross-sectional study conducted among elderly patients (aged 65 and above) who visited the Family Medicine outpatients’ clinics of the Ekiti State University Teaching Hospital, Ado-Ekiti, Nigeria between July 1 and October 31, 2018. Information extracted from the case files included patient’s age, sex, diagnoses, and list of prescribed medications. Medicines with anticholinergic effects were identified and scored using the anticholinergic drug burden calculator (http://www.acbcalc.com).Results: The medical records of 400 patients were analyzed with females accounting for 60.5% of the study population. The mean age of participants was 73 ± 7.4 years with only 28 (7%) of patients having more than two co-morbid conditions. Polypharmacy was identified in 152 (38%) of the patients while 147 (36.7%) had drugs with anticholinergic effects prescribed. The anticholinergic burden was high in 60 (15%) patients. Polypharmacy was significantly associated with having more than two diagnosed conditions and high anticholinergic burden (p value of < 0 .001 and 0.013 respectively). There was significant correlation between total number of prescribed drugs and count of diagnoses (r = 0.598; p < 0 .000) and between total number of prescribed drugs and number of drugs with anticholinergic effects (r = 0 .196; p < 0 .000).Conclusion: The anticholinergic burden in this group of elderly Nigerian patients was low; majority (67%) had no exposure to drugs with anticholinergic effects with only 15% having high anticholinergic burden. Polypharmacy and multiple diagnosed conditions were positively associated with high anticholinergic burden. Based on the positive and significant correlations found in this study, a reduction in the number of prescribed medicines especially those with significant anticholinergic effects used for secondary indications may lessen the anticholinergic burden among the elderly.

Beyond the most common etiologies of gastroparesis, there are several rarer causes that merit consideration in the appropriate clinical context. These include medications with deleterious effects on gastric motility (e.g. opiates, cannabinoids, anticholinergic agents), distal obstruction, connective tissue disorders, autoimmune autonomic neuropathy, malignancy and paraneoplastic syndromes, systemic neurologic disorders, pancreatitis, ischemia, non-diabetic endocrinopathy, and renal failure. Some of these associations are tenuous and/or governed by speculative mechanistic explanations that may be clarified through future investigation. Recognizing a rare or unusual cause of gastroparesis can offer up unique pathways toward effective symptom management.

Tropane alkaloids (TAs) are a special class of alkaloids found naturally in a diverse group of flowering plant families. To date, about 200 TAs are known, the most prominent being hyoscyamine, scopolamine, calystegine, and cocaine. These compounds possess pharmacological properties and are used in medicine as anticholinergic agents and stimulants. Because of their medicinal value, tropane alkaloids have been the subject of study for several years now. Over the years, research has been directed at elucidating the biosynthetic pathways leading to the production of pharmacologically active TAs. The present chapter discusses recent developments in the understanding of TA biosynthesis with emphasis on the genes involved in the TA biosynthetic pathways and the role transcriptome profiling played in their identification. In recent years, mining of the transcriptome data of TA-producing plants, such as Atropa belladonna, has led to a near-complete elucidation of the biosynthesis of hyoscyamine and scopolamine. Advances in gene elucidation made through such studies can be potentially used for metabolic engineering in transgenic plant systems or microbial platforms to sustainably meet the global demand of pharmaceutically important TAs.

Various plant species are widely distributed across the world; commonly exploited for their nutritive, recreational, and medicinal functions. However, many plants are known to contain toxins, a group of chemical agents capable of causing deleterious effects in humans and animals. With their high proximity to plants of different kinds, service personnel can be exposed to these toxins through ingestion, inhalation, and dermal or eye contact. This chapter presents and discusses some of the plants that service personnel must get aware of and, systematically, plant to manage them and their potential effects. These plants include those that have anticholinergic agents (Brugmansia species), calcium oxalate crystals (Dieffenbachia species), toxalbumins (Ricinus communis, Abrus precatorius), cardioactive glycosides (Nerium oleander, Digitalis purpurea, Cerberin odollam), convulsants (Conium maculatum), sodium channel activators (Rhododendron species), and irritants (Hippomane mancinella). To minimize intoxication with phytotoxins, service personnel need to be aware of such poisonous plants and how the toxins interact with the human body. Formally including phytochemistry in the military, police, prison, and immigration personnel’s training curriculum could be one of the best ways to best fit its knowledge for the safety of the personnel in operations.

Nasal obstruction is a frequent disorder that interferes with the daily patient’s quality of life. The key element in the pathophysiology of the disorder is the inferior turbinate hypertrophy related to multiple conditions such as allergic rhinitis (AR). Many patients are managed using conventional drug therapies such as antihistamines, decongestants, and intranasal steroid sprays, anticholinergic agents, mast cell stabilizers, and desensitizing vaccines. When traditional therapy failed to relieve AR symptoms, surgical inferior turbinate reduction (ITR) is indicated. A vast variety of surgical techniques have been reported in the literature for AR such as resectioning, coagulating, and laser procedures. We aimed to revise all surgical options in AR management. We confirm that no ideal standard technique for turbinate reduction has been developed so far regarding the multitude of different surgical procedures. Furthermore, no prospective and comparable long-term studies are present in the literature; it is challenging to recommend evidence-based surgical techniques.

The basic mechanisms by which brain insults, such as trauma, stroke or status epilepticus produce epilepsy are not completely understood, and effective preventive measures and treatment are still not available in the clinical setting. Over the last 2 decades we have conducted several studies with animal models of epilepsy (rodents and non-human primates) and demonstrated that drugs that modify neuronal plastic processes, such as anticholinergic agents (e.g., antimuscarinic compounds), if administered soon after brain injury and over a period of 10-20 days, have the potential to modify the natural course of post-traumatic epilepsy. To that end treatment with scopolamine showed promising results as a candidate agent in both the pilocarpine and kainate models. We then showed that biperiden, yet another cholinergic antagonist acting in the muscarinic receptor, that is widely used to treat Parkinson's disease, also decreased the incidence and intensity of spontaneous epileptic seizures, delaying their appearance in the pilocarpine model of epilepsy. In other words, biperiden showed to be a potential candidate to be further investigated as an antiepileptogenic agent. Accordingly, we tested the safety of biperiden in a small group of patients (as a small phase II safety assessment) and confirmed its safety in the context of traumatic brain injury (TBI). Now, we provide information on our ongoing project to evaluate the efficacy of biperiden in preventing the development of epilepsy in patients that suffered TBI, in a double blind, randomized, placebo-controlled trial.

Background the long-term effect of the use of drugs with anticholinergic activity on cognitive function remains unclear. Methods we conducted a systematic review and meta-analysis of the relationship between anticholinergic drugs and risk of dementia, mild cognitive impairment (MCI) and cognitive decline in the older population. We identified studies published between January 2002 and April 2018 with ≥12 weeks follow-up between strongly anticholinergic drug exposure and the study outcome measurement. We pooled adjusted odds ratios (OR) for studies reporting any, and at least short-term (90+ days) or long-term (365+ days) anticholinergic use for dementia and MCI outcomes, and standardised mean differences (SMD) in global cognition test scores for cognitive decline outcomes. Statistical heterogeneity was measured using the I2 statistic and risk of bias using ROBINS-I. Results twenty-six studies (including 621,548 participants) met our inclusion criteria. ‘Any’ anticholinergic use was associated with incident dementia (OR 1.20, 95% confidence interval [CI] 1.09–1.32, I2 = 86%). Short-term and long-term use were also associated with incident dementia (OR 1.23, 95% CI 1.17–1.29, I2 = 2%; and OR 1.50, 95% CI 1.22–1.85, I2 = 90%). ‘Any’ anticholinergic use was associated with cognitive decline (SMD 0.15; 95% CI 0.09–0.21, I2 = 3%) but showed no statistically significant difference for MCI (OR 1.24, 95% CI 0.97–1.59, I2 = 0%). Conclusions anticholinergic drug use is associated with increased dementia incidence and cognitive decline in observational studies. However, a causal link cannot yet be inferred, as studies were observational with considerable risk of bias. Stronger evidence from high-quality studies is needed to guide the management of long-term use.

Holothurians are marine invertebrates also known as sea cucumbers. They are used in fresh or dried forms in various cuisines around the world and have alleged medicinal properties. Consequently, sea cucumbers, notably the orange-footed sea cucumber (Cucumaria frondosa)are increasingly harvested from the environment or farmed via aquaculture. We report three cases of unusual occupational exposure to C. frondosa resulting in cutaneous, respiratory and ocular irritating symptoms. These symptoms occurred as sea cucumbers were cut on half and eviscerated manually, following a machine breakdown in a sea cucumber processing factory. Given the composition of holothurians, these symptoms probably resulted from the aerosolization of various holothurins, saponins secreted by sea cucumbers as mean of defense. Treatment was solely symptomatic and included decontamination of the skin and the eyes, inhaled glucocorticoids, anticholinergic agents and oral glucocorticoids. As the exposure resulted from a machine breakdown, no specific protective equipment was put in place. Employees were advised not to handle manuallythe sea cucumbers in case such a breakdown was to happen again.

An impairment of long-term synaptic plasticity is considered as a peculiar endophenotype of distinct forms of dystonia, a common, disabling movement disorder. Among the few therapeutic options, broad-spectrum antimuscarinic drugs are utilized, aimed at counteracting abnormal striatal acetylcholine-mediated transmission, which plays a crucial role in dystonia pathophysiology. We previously demonstrated a complete loss of long-term synaptic depression (LTD) at corticostriatal synapses in rodent models of two distinct forms of isolated dystonia, resulting from mutations in the TOR1A (DYT1), and GNAL (DYT25) genes. In addition to anticholinergic agents, the aberrant excitability of striatal cholinergic cells can be modulated by group I metabotropic glutamate receptor subtypes (mGlu1 and 5). Here, we tested the efficacy of the negative allosteric modulator (NAM) of metabotropic glutamate 5 (mGlu) receptor, dipraglurant (ADX48621) on striatal LTD. We show that, whereas acute treatment failed to rescue LTD, chronic dipraglurant rescued this form of synaptic plasticity both in DYT1 mice and GNAL rats. Our analysis of the pharmacokinetic profile of dipraglurant revealed a relatively short half-life, which led us to uncover a peculiar time-course of recovery based on the timing from last dipraglurant injection. Indeed, striatal spiny projection neurons (SPNs) recorded within 2 h from last administration showed full expression of synaptic plasticity, whilst the extent of recovery progressively diminished when SPNs were recorded 4–6 h after treatment. Our findings suggest that distinct dystonia genes may share common signaling pathway dysfunction. More importantly, they indicate that dipraglurant might be a potential novel therapeutic agent for this disabling disorder.