Use Of Cholinesterase Inhibitors Research Articles

Pharmacotherapy of Alzheimer's disease: an overview of systematic reviews.

Alzheimer's disease (AD) is a neurodegenerative disease and the most common cause of dementia. In this umbrella systematic review (SR), we summarized the efficacy of different pharmacological interventions in improving cognitive function in patients with AD. A systematic search was performed through the PubMed, Scopus, Embase, and Cochrane databases for SRs of studies assessing the efficacy of pharmacological interventions versus placebo in improving cognitive function in AD or mild cognitive impairment due to AD. The risk of bias (RoB) was assessed using the Risk of Bias in SRs (ROBIS) tool. Out of 1748 articles found through the database survey, 33 SR articles were included. These studies assessed effects of immunotherapy, cholinesterase inhibitors (ChEIs), memantine, statins, lithium, nonsteroidal anti-inflammatory drugs (NSAIDs), antidiabetic agents, Cerebrolysin, RAS-targeting antihypertensive drugs (ARBs and ACEIs), psychostimulants, glycogen synthase kinase 3 (GSK-3) inhibitors, melatonin, and herbal medications on cognitive function in AD patients. There was no notable overall RoB in 18 studies (54.5%), the RoB in 14 studies (42.4%) was high, and in one study (3.0%) it was unclear. The use of ChEIs, including rivastigmine, galantamine, and donepezil, as well as memantine has demonstrated a positive impact on improving cognitive outcomes of AD patients, but no considerable effects were found for immunotherapies. Melatonin, statins, antihypertensive drugs, antidiabetic agents, Cerebrolysin, psychostimulants, and some herbal drugs such as Danggui-Shaoyao-San and Ginkgo biloba seem to be effective in improving cognitive function of AD patients, but the evidence in this regard is limited.

MSR65 Comparison of Machine Learning Approach with Traditional Method to Predict Risk of Serious Events Associated with Individual Cholinesterase Inhibitors Use in Older Adults with Dementia

Machine learning techniques have been recommended as promising alternatives to logistic regression for the estimation of propensity scores. This study compared the performance of the machine learning approach Inverse Probability Weighting- Gradient Boosted Modeling (IPTW-GBM) with traditional Propensity Scores (PS) method in predicting risk of serious events across individual Cholinesterase inhibitors (ChEIs) use in older adults with dementia.

P20 Risk of Antimuscarinic Initiation with Cholinesterase Inhibitor Use in Patients with Alzheimer's Disease

Antimuscarinic use in Alzheimer’s disease (AD) is a significant concern as it can worsen cognition due to its anticholinergic effects. This study evaluated the risk of antimuscarinic initiation with the use of individual Cholinesterase Inhibitors (CHEIs) in patients with AD.

RWD18 Sex-Based Differences in Risk of Serious Events with Individual Cholinesterase Inhibitors Use in Older Adults with Dementia: A Medicare Study

There is limited research evaluating the safety of Cholinesterase inhibitors (ChEIs) based on real-world data. Additionally, the moderating effect of sex on outcomes is not well-studied in dementia. This study evaluated the sex-based effects on the risk of serious events with individual ChEIs in older adults with dementia.

EPH163 Risk of Memantine Initiation with Use of Antimuscarinics and/or Cholinesterase Inhibitors in Older Adults with Alzheimer's Disease

Antimuscarinic use along with cholinesterase inhibitors (CHEIs) can nullify the modest treatment benefit of CHEIs and can worsen Alzheimer’s disease (AD) due to therapeutically opposing mechanisms of action. This worsening of cognition can precipitate prescribing of memantine for moderate-to-severe AD. Therefore, this study assessed the risk of memantine initiation in older adults with AD using antimuscarinics and CHEIs.

Risk factors for hospital-acquired pneumonia among inpatients with mental disorders in a large mental health center within a tertiary general hospital

Few researchers have investigated the incidence of and risk factors for hospital-acquired pneumonia (HAP) among inpatients with mental disorders in a general hospital. This study included patients with mental disorders hospitalized in a large mental health center (situated in a general hospital) between January 1, 2017, and July 31, 2021 (excluding January 1, 2020- May 31, 2020). Risk factors for HAP were identified by logistic regression analysis after propensity score matching (PSM, 1:4) for gender, age, duration of observation, and hospital ward. The study included 16,864 patients. HAP incidence rate was 1.15% overall, 2.11% in closed wards, 0.75% in open wards, 4.45% in patients with organic mental disorders, 1.80% in patients with schizophrenia spectrum disorders, and 0.84% in patients with mood disorders. Risk factors for HAP after PSM were hypoproteinemia, chronic liver disease, use of clozapine, hospitalization during the previous 180 days, body mass index (BMI) ≤18.5 kg/m2, cholinesterase inhibitor use, and mood stabilizer use. HAP was common among inpatients with mental disorders. Risk factors for HAP in patients with mental disorders include hypoproteinemia, chronic liver disease, hospitalization during the past 180 days, BMI ≤18.5 kg/m2, and use of clozapine, cholinesterase inhibitors, or mood stabilizers.

Association of cognitive enhancers and incident seizure risk in dementia: a population-based study

BackgroundAlthough individuals with dementia have a high risk of developing seizures, whether seizures are associated with cholinesterase inhibitors, which are commonly prescribed to treat individuals with dementia, remains unknown. This study investigated the risk of incident seizure following cholinesterase inhibitor use in patients with dementia.MethodsA nationwide, nested case-control study was conducted using data from the Korean Health Insurance Review and Assessment Service (HIRA) from 2014 through 2018. A total of 13,767 participants aged 65–95 years who experienced incident seizure were propensity score-matched for medical comorbidities and drug exposure at a 1:3 ratio with a control group of 39,084 participants. The study examined the incidence of seizures in patients diagnosed with dementia within one year after receiving cognitive enhancers. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for seizure incidence according to cholinesterase inhibitor use were analyzed using a multivariable conditional logistic regression model.ResultsThere was no statistically significant association between duration of cholinesterase inhibitors use and seizure risk. Although there was slight increased seizure risk in patient after receiving donepezil for 1 year compared to memantine, subgroup analyses stratified age and sex did not reveal any significant association between cholinesterase inhibitors use and late-onset seizure.ConclusionsOur findings suggest no immediate increase in seizure risk is associated with cholinesterase inhibitor use, although the risk of seizure in patients with dementia did increase after one year of continued medication intake. Further study is required to obtain confirmatory results on the seizure-related safety of cognitive enhancers in patients with dementia.

Risk of Serious Adverse Events Associated With Individual Cholinesterase Inhibitors Use in Older Adults With Dementia: A Population-Based Cohort Study.

Cholinesterase inhibitors (ChEIs) are used as first-line pharmacotherapy to manage dementia. However, there are limited data regarding their relative safety. This study evaluated the risk of serious adverse events (SAEs) associated with individual ChEIs in older adults with dementia and also examined sex-based and dose-based effects on this risk. This was a retrospective cohort study using 2013-2015 US Medicare claims data involving Parts A, B, and D. Patients aged ≥ 65 years with a dementia diagnosis and incident use of the ChEIs, namely donepezil, galantamine, or rivastigmine, were included. The primary outcome of interest was SAEs defined as emergency department visits, inpatient hospitalizations, or death within 6 months of ChEI initiation. Multivariable Cox proportional hazards regression with propensity score (PS) as a covariate and inverse probability of treatment weighting generated using generalized boosted models was used to assess the risk of SAEs across individual ChEIs. The study included 767,684 older adults with dementia who were incident new users of ChEIs (donepezil 79.42%, rivastigmine 17.67%, galantamine 2.91%). SAEs were observed in 15.5% of the cohort within 6 months of ChEI prescription. Cox regression model with PS as covariate found that patients prescribed rivastigmine (adjusted hazard ratio [aHR] 1.12; 95% CI 1.03-1.33) and galantamine (aHR 1.51; 95% CI 1.24-1.84) were at increased risk of SAEs compared with patients on donepezil. Stratified analyses revealed that rivastigmine was associated with an 18% increased risk for SAEs in females (aHR 1.18; 95% CI 1.06-1.31), and galantamine was associated with a 71% increased risk in males (aHR 1.71; 95% CI 1.17-2.51) compared with donepezil. High and recommended index doses of rivastigmine and galantamine were associated with an increased risk of SAEs compared with donepezil. The findings were consistent in sensitivity analyses. The study found that the risk of SAEs varied across individual ChEIs, with sex and dose moderating these effects. Therefore, these moderating effects should be carefully considered in personalizing dementia care.

Risk of SAEs with cholinesterase inhibitor use in elderly

Risk of SAEs with cholinesterase inhibitor use in elderly

FC081: Cholinesterase Inhibitors and Kidney Function Decline in Patients with Alzheimer's Dementia

Abstract BACKGROUND AND AIMS Preclinical evidence shows that activation of the cholinergic anti-inflammatory pathway (CAP) may have direct and indirect beneficial effects on the kidney. Cholinesterase inhibitors (ChEIs) are specific Alzheimer's dementia (AD) therapies that block the action of cholinesterases and activate CAP. This study explores a plausible effect of ChEIs on slowing kidney function decline. METHOD Observational study with a landmark design of patients with incident AD from the Swedish Dementia Registry (SveDem) 2007–2018 with complete extraction of routine serum creatinine tests from the Stockholm CREAtinine Measurements (SCREAM) registry to evaluate estimated glomerular filtration rate (eGFR) over time. Patients starting on ChEI within 90 days of an AD diagnosis were compared to patients with AD not receiving ChEI. The primary study outcome was CKD progression, defined as the composite of a sustained eGFR decline of >30% from baseline, initiation of kidney replacement therapy or death attributed to kidney disease. Secondary outcome was death. Inverse probability of treatment weighting Cox models were used to estimate hazard ratios, balancing 45 confounders. RESULTS We included 11 898 incident patients, of whom 6803 started on ChEI and 5095 did not. Mean age was 80 years, 64% were women and mean baseline eGFR was 68 mL/min/1.73 m2. After weighting, and during median follow-up time of 3.0 (IQR 1.3–4.5) years, 1231 events of CKD progression occurred, along with 5691 deaths. Compared to noninitiators, ChEI use was associated with a 18% lower risk of CKD progression [adjusted hazards ratio (aHR) 0.82; 95% confidence interval (95% CI) 0.70–0.96] and a 21% lower risk of death (aHR 0.79; 0.72–0.86). Results were consistent across subgroups of age, sex, and across ChEI subclasses and after accounting for competing risks. CONCLUSION In routinely cared patients with incident AD diagnosis, use of ChEI (versus no-use) was associated with lower risk of CKD progression and death, lending support to the role of CAP activation on preservation of kidney function.

Neuroprotective Effects of Cholinesterase Inhibitors: Current Scenario in Therapies for Alzheimer's Disease and Future Perspectives.

Alzheimer’s disease (AD) is a slowly progressive neurodegenerative disease conceptualized as a continuous process, ranging from mild cognitive impairment (MCI), to the mild, moderate, and severe clinical stages of AD dementia. AD is considered a complex multifactorial disease. Currently, the use of cholinesterase inhibitors (ChEI), such as tacrine, donepezil, rivastigmine, and galantamine, has been the main treatment for AD patients. Interestingly, there is evidence that ChEI also promotes neuroprotective effects, bringing some benefits to AD patients. The mechanisms by which the ChEI act have been investigated in AD. ChEI can modulate the PI3K/AKT pathway, which is an important signaling cascade that is capable of causing a significant functional impact on neurons by activating cell survival pathways to promote neuroprotective effects. However, there is still a huge challenge in the field of neuroprotection, but in the context of unravelling the details of the PI3K/AKT pathway, a new scenario has emerged for the development of more efficient drugs that act on multiple protein targets. Thus, the mechanisms by which ChEI can promote neuroprotective effects and prospects for the development of new drug candidates for the treatment of AD are discussed in this review.

Association Between Cholinesterase Inhibitors and New-Onset Heart Failure in Patients With Alzheimer's Disease: A Nationwide Propensity Score Matching Study

BackgroundAutonomic nervous dysfunction is a shared clinical feature in Alzheimer's disease (AD) and heart failure (HF). Cholinesterase inhibitors (ChEIs) are widely used autonomic modulators in patients with AD, but their primary preventive benefit on new-onset HF is still uncertain.ObjectiveThis study examined whether ChEIs have a primary preventive effect on new-onset HF in patients with AD.MethodsThis propensity score matching (PSM) study was conducted using data from the National Health Insurance Research Database of Taiwan for 1995 to 2017. Certificated patients with AD and without a history of HF were divided into ChEI (donepezil, rivastigmine, or galantamine) users or nonusers. The primary endpoint was new-onset HF, and the secondary endpoints were myocardial infarction and cardiovascular death after 10-year follow-up.ResultsAfter screening 16,042 patients, 7,411 patients were enrolled, of whom 668 were ChEI users and 1,336 were nonusers after 1:2 PSM. Compared with nonusers, ChEI users exhibited a significantly lower incidence of new-onset HF (HR 0.48; 95% CI 0.34–0.68, p < 0.001) and cardiovascular death (HR 0.55; 95% CI 0.37–0.82, p = 0.003) but not of myocardial infarction (HR 1.09; 95% CI 0.52–1.62, p = 0.821) after 10-year follow-up. The preventive benefit of ChEI use compared with Non-use (controls) was consistent across all exploratory subgroups without statistically significant treatment-by-subgroup interactions.ConclusionsPrescription of ChEIs may provide a preventive benefit associated with lower incidence of new-onset HF in patients with AD after 10-year follow-up.

Профилактика и лечение пареза кишечника у детей

Dynamic intestinal obstruction (DIO) is one of the disorders reported after gastrointestinal (GI) surgical procedures. DIO raises special concerns, as it affects patients’ condition in the postoperative period and increases the duration of hospital treatment. The review section of the article is focused on DIO pathogenetic mechanisms, clinical manifestations, diagnostic criteria, and treatment strategies. In addition to diet therapy and the use of cholinesterase inhibitors, the conservative therapy in children includes various physiotherapy treatment techniques, facilitating intestinal motility The comparative analysis shows that their ultimate efficiency is not the same and that there are significant limitations and differences associated with the access to the optimal areas for electrode placement The article presents the results of introducing an original technique of dynamic electrical stimulation of the intestine with point paravertebral massage which was used in the early postoperative period for 117 children. The children had undergone either emergency surgeries in cases of acute surgical conditions or planned (stage-by- stage) intestinal reconstruction surgeries for preventing DIO.The data have demonstrated the efficacy of electrical stimulation used both as monotherapy and in combination with proserine (the number of required injections was decreased to 1 or 2). Restoration of the intestinal passage was achieved in 95% of cases within the first 24–36 hours after surgery (spontaneous defecation occurred in 70% of patients by the end of the first day). A later response to electrical stimulation with the restoration of peristalsis was determined after small intestine surgeries: spontaneous emptying of the intestine on the first day occurred only in 43% of children versus 52% after surgery of the lower portion of the abdominal cavity KEYWORDS: postoperative intestinal paresis; children; clinical course; diagnostics; electrical stimulation; original technique; acupressure device FOR CITATION: Pen’tkovskaya O.S., Bardenikova S.I. Prevention and treatment of enteroparesis in children. Russian Journal of Woman and Child Health. 2022;5(4):373–381 (in Russ.). DOI: 10.32364/2618-8430-2022-5-4-373-381.

Associations of hippocampal cholinergic receptor binding and subcortical cerebrovascular disease with whole brain volume in cognitive aging and AD

AbstractBackgroundAlzheimer’s Disease (AD) is associated with compromise to the cholinergic system. Using PET ligand imaging, our group has reported reduced nicotinic cholinergic receptors (nAchR) in the hippocampus in AD relative to cognitively unimpaired older adults. Studies have increasingly identified that chronic ischemic cerebrovascular disease (CVD) serves as a risk factor for neurodegeneration, and also directly correlates with B‐amyloid and tau accumulation (Flaherty et al., 2020; Wei et al., 2019). We sought to determine the unique contributions of cholinergic dysfunction and CVD to brain health in cognitive aging. We therefore tested differential contributions of T1 white matter hypointensities and hippocampal nAchR binding in predicting whole brain volume among individuals with varying levels of cognitive impairment.Method84 individuals (clinical Alzheimer’s Disease (AD), n=27; Mild Cognitive Impairment (MCI), n=25; and Cognitively Unimpaired (CU), n=32) completed MRI and 2‐18F‐fluoro‐3(2(S)azetidinylmethoxy) pyridine (2FA) ‐PET imaging sessions. Total Brain Volume, excluding cerebellum, brain stem, and ventricles, was calculated using FreeSurfer. SPM was used to generate nAchR binding estimates using anatomical ROI of bilateral hippocampus.ResultWhen covarying for diagnostic group, age, and use of cholinesterase inhibitors, hierarchical linear regressions identified a significant association between hippocampal nAchR binding and total brain volume (B(SE)=.013(.003); p&lt;.001), while the association between white matter hypointensities and total brain volume was not significant (B(SE)=‐.99(.84); p=.24). Stratified by group, the same pattern emerged in a combined sample of clinical AD and MCI (nAchR binding B(SE)=.013(.005); p&lt;.01, hypointensities B(SE)=‐.18(.91); p=.84). In CU, however, white matter hypointensities were negatively associated with total brain volume (B(SE)=‐10.60(3.53); p&lt;.01), while the relationship between hippocampal nAchR binding and total brain volume was not significant (B(SE)=.006(.005); p=.26).ConclusionWhite matter hypointensities are associated with a measure of brain health among CU; such vascular risk factors may be important to track in preventative treatment. Hippocampal cholinergic function, relative to hypointensities, may be more closely aligned with brain health among those with cognitive decline. Longitudinal study of vascular and cholinergic systems and their interactions are warranted; corroboration of these findings in longitudinal studies may elucidate different treatment targets across stages of AD.

Alzheimer’s disease medication utilization patterns: Disparities in treatment initiation, non‐adherence, and discontinuation

AbstractBackgroundAlthough currently there is no disease‐modifying treatment for Alzheimer’s disease (AD), several FDA‐approved prescription drugs may ameliorate AD symptoms. This study analyzed AD‐targeted medication utilization patterns in a representative US population overall and by race and ethnicity.MethodWe analyzed use of cholinesterase inhibitors and memantine for AD, using data from the 2000‐2014 Health and Retirement Study (HRS), linked with Medicare and Medicaid claims. We examined medication initiation among newly‐diagnosed AD patients: 1) the proportion filling an AD prescription ≤90 and ≤365 days after diagnosis; 2) mean/median time from diagnosis to first AD prescription fill; and 3) AD symptom severity at treatment initiation, measured by cognitive and functional limitations. We measured AD medication non‐adherence and discontinuation rates in the year following treatment initiation. We used logistic regression to examine whether AD medication initiation, non‐adherence and discontinuation rates differed by race and ethnicity. We used HRS survey reports to compare the proportion of subjects not filling any prescription due to cost, by race and ethnicity.ResultAmong individuals with newly‐diagnosed AD (n=1,299), 26% filled an AD prescription ≤90 days and 36% ≤365 days of diagnosis. These proportions and the median time from an incident AD diagnosis to first AD prescription fill did not vary by race/ethnicity. For 3 of 4 measures, AD severity at treatment initiation did not differ across racial/ethnic groups. Of all individuals who initiated AD‐targeted treatment, 44% were non‐adherent and 24% discontinued the medication during the year following treatment initiation. Non‐Hispanic Blacks were more likely than non‐Hispanic whites to not adhere to AD medication therapy (OR: 1.50 [95% CI: 1.07‐2.09] or discontinue treatment (OR: 1.83 [95% CI: 1.27‐2.63]). More non‐Hispanic Blacks and Hispanics with AD reported ever not filling a prescription due to cost, compared to non‐Hispanic whites (42% and 40% vs. 22%, p&lt;0.01).ConclusionInitiation of AD‐targeted medications among newly‐diagnosed patients was suboptimal in all ethnoracial groups, with nearly two‐thirds having no prescription for cholinesterase inhibitors or memantine during the first year post‐diagnosis. Rates of AD medication non‐adherence and discontinuation were substantial and may relate to cost and access to care.

Editors' Note: Long-term Effects of Cholinesterase Inhibitors on Cognitive Decline and Mortality

Dr. Xu et al. compared cognitive trajectories and the occurrence of severe dementia or death in 11,652 patients started on cholinesterase inhibitors (ChEIs) vs 5,826 untreated patients with Alzheimer dementia (AD) in the Swedish Dementia Registry. During an average of 5 years of follow-up, they found that ChEIs were associated with modest but persistent cognitive benefits with lower mortality. Galantamine was the only ChEI that was associated with a significantly lower risk of developing severe dementia. In response, Dr. Kuschpel noted that there were important baseline differences between patients who were and were not treated with ChEIs, with associated difficulties matching the 2 groups for analyses. Dr. Kuschpel also highlighted the importance of considering the stage and severity of comorbidities about survival estimates and is skeptical of the sizeable mortality reduction with ChEIs seen in the study, given the lack of precedence, the absence of a plausible molecular mechanism, and potential confounding by prescription bias. Concerns are raised about potential discrepancies in numbers between the abstract and the results section about observed differences in Mini-Mental State Examination (MMSE) scores. Responding to these comments, the authors argue that although there were significant baseline differences between the 2 groups, they were able to achieve a well-matched cohort, although they acknowledge the possibility of residual and unknown confounders, especially in the absence of data on comorbidity severity. They cite the previous work by their group observing reductions in myocardial infarction, stroke, and mortality with ChEI use, as well as a lower 2-year mortality with galantamine seen in a prior randomized-controlled trial. They note that previous trials of ChEIs have had considerably shorter follow-up durations. In summary, this exchange highlights the uncertain causal association between ChEI use and lower mortality in patients with AD, and the challenges of convincingly demonstrating such an association with observational data. Robust validation of this association would have important implications for the care of patients with AD. Dr. Xu et al. compared cognitive trajectories and the occurrence of severe dementia or death in 11,652 patients started on cholinesterase inhibitors (ChEIs) vs 5,826 untreated patients with Alzheimer dementia (AD) in the Swedish Dementia Registry. During an average of 5 years of follow-up, they found that ChEIs were associated with modest but persistent cognitive benefits with lower mortality. Galantamine was the only ChEI that was associated with a significantly lower risk of developing severe dementia. In response, Dr. Kuschpel noted that there were important baseline differences between patients who were and were not treated with ChEIs, with associated difficulties matching the 2 groups for analyses. Dr. Kuschpel also highlighted the importance of considering the stage and severity of comorbidities about survival estimates and is skeptical of the sizeable mortality reduction with ChEIs seen in the study, given the lack of precedence, the absence of a plausible molecular mechanism, and potential confounding by prescription bias. Concerns are raised about potential discrepancies in numbers between the abstract and the results section about observed differences in Mini-Mental State Examination (MMSE) scores. Responding to these comments, the authors argue that although there were significant baseline differences between the 2 groups, they were able to achieve a well-matched cohort, although they acknowledge the possibility of residual and unknown confounders, especially in the absence of data on comorbidity severity. They cite the previous work by their group observing reductions in myocardial infarction, stroke, and mortality with ChEI use, as well as a lower 2-year mortality with galantamine seen in a prior randomized-controlled trial. They note that previous trials of ChEIs have had considerably shorter follow-up durations. In summary, this exchange highlights the uncertain causal association between ChEI use and lower mortality in patients with AD, and the challenges of convincingly demonstrating such an association with observational data. Robust validation of this association would have important implications for the care of patients with AD.

Cholinesterase inhibitors for the treatment of dementia: real-life data in Hungary

Dementia is one of the leading causes of death and disability in older population. Previous reports have shown that antidementia medications are associated with longer survival; nonetheless, the prevalence of their use and the compliance with them are quite different worldwide. There is hardly any available information about the pharmacoepidemiology of these drugs in the Eastern-European region; we aimed to analyze the use of cholinesterase inhibitors (ChEis) for the treatment of dementia to provide real-life information from the Eastern European region. All medical and medication prescription reports of the in- and outpatient specialist services collected in the NEUROHUN database in Hungary were analyzed between 2013 and 2016. Survival, adherence, and persistence values were calculated. 8803 patients were treated with ChEis during the study period, which was only 14.5% of the diagnosed demented patients. The survival of treated patients (more than 4 years) was significantly longer than patients without ChEi treatment (2.50 years). The best compliance was observed with rivastigmine patch. Choosing the appropriate medication as soon as possible after the dementia diagnosis may lead to increased life expectancy.

S1794 Refractory Hypokalemia in the Setting of Ogilvie Syndrome

Introduction: Ogilvie Syndrome often results from a disruption of the parasympathetic nervous system due to electrolyte abnormalities. This case study examines a unique presentation of Ogilvie Syndrome involving secretory diarrhea with increased fecal potassium losses resulting in refractory hypokalemia. This case explores the use of cholinesterase inhibitors, aldosterone antagonists and potassium sparing diuretics in the management of such cases of colonic pseudo-obstruction. Case Description/Methods: An 83 year-old male presented with encephalopathy and abdominal pain. Physical examination was notable for significant abdominal distention. Labs demonstrated severe hypokalemia. CT abdomen revealed massive colonic distention with cecal diameter at 10 cm. Neither CT nor contrast enema study showed signs of mechanical obstruction. Initial management was focused on replacing potassium prior to considering other pharmacologic therapy. Despite aggressive replacement, the hypokalemia persisted. Further workup of the hypokalemia was consistent with non-renal losses. Stool studies were consistent with fecal potassium losses. A potassium-sparing diuretic and aldosterone antagonist were used to increase potassium levels, but with ongoing diarrhea, hypokalemia continued to recur. The patient was subsequently treated with neostigmine with swift resolution of the pseudo-obstruction. Once the diarrhea resolved, the patient was able to maintain his response to hypokalemia therapy. Discussion: Ogilvie syndrome is a functional obstruction thought to be due to disturbance in the parasympathetic system that has been associated with electrolyte abnormalities and is usually treated with conservative management including electrolyte replacement and physical therapy. Colonic pseudo-obstruction is often associated with secretory diarrhea and hypokalemia. In some patients, most commonly, end stage renal patients, an overexpression of potassium cotransporters helps eliminate potassium when kidneys are unable. This has been thought to contribute to hypersecretion of potassium with diarrhea. Our patient had severe hypokalemia despite aggressive electrolyte replacement with high fecal potassium losses. As aldosterone increases urinary excretion of potassium in the urine, antagonists are used to treat hypokalemia. While it is not yet the standard of care, it is important to recognize that potassium-sparing aldosterone antagonists can improve and aid in the management of this type of Ogilvie Syndrome.

European Stroke Organisation and European Academy of Neurology joint guidelines on post-stroke cognitive impairment.

The optimal management of post-stroke cognitive impairment (PSCI) remains controversial. These joint European Stroke Organisation (ESO) and European Academy of Neurology (EAN) guidelines provide evidence-based recommendations to assist clinicians in decision making regarding prevention, diagnosis, treatment and prognosis. Guidelines were developed according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. The working group identified relevant clinical questions, performed systematic reviews, assessed the quality of the available evidence, and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available to provide recommendations. There was limited randomized controlled trial (RCT) evidence regarding single or multicomponent interventions to prevent post-stroke cognitive decline. Lifestyle interventions and treating vascular risk factors have many health benefits, but a cognitive effect is not proven. We found no evidence regarding routine cognitive screening following stroke, but recognize the importance of targeted cognitive assessment. We describe the accuracy of various cognitive screening tests, but found no clearly superior approach to testing. There was insufficient evidence to make a recommendation for use of cholinesterase inhibitors, memantine nootropics or cognitive rehabilitation. There was limited evidence on the use of prediction tools for post-stroke cognition. The association between PSCI and acute structural brain imaging features was unclear, although the presence of substantial white matter hyperintensities of presumed vascular origin on brain magnetic resonance imaging may help predict cognitive outcomes. These guidelines highlight fundamental areas where robust evidence is lacking. Further definitive RCTs are needed, and we suggest priority areas for future research.

Use of antipsychotic drugs and cholinesterase inhibitors and risk of falls and fractures: self-controlled case series

ObjectiveTo evaluate the association between the use of antipsychotic drugs and cholinesterase inhibitors and the risk of falls and fractures in elderly patients with major neurocognitive disorders.DesignSelf-controlled case series.SettingTaiwan’s National...