The rising of global geriatric population has contributed to increased prevalence of dementia. Dementia is a neurodegenerative disease, which is characterized by progressive deterioration of cognitive functions, such as judgment, language, memory, attention and visuospatial ability. Dementia not only has profoundly devastating physical and psychological health outcomes, but it also poses a considerable healthcare expenditure and burdens. Acetylcholinesterase inhibitors (AChEIs), or so-called anti-dementia medications, have been developed to delay the progression of neurocognitive disorders and to decrease healthcare needs. AChEIs have been widely prescribed in clinical practice for the treatment of Alzheimer's disease, which account for 70% of dementia. The rising use of AChEIs results in increased adverse drug reactions (ADRs) such as cardiovascular and gastrointestinal adverse effects, resulting from overstimulation of peripheral cholinergic activity and muscarinic receptor activation. Changes in pharmacokinetics (PK), pharmacodynamics (PD) and pharmacogenetics (PGx), and occurrence of drug interactions are said to be major risk factors of ADRs of AChEIs in this population. To date, comprehensive reviews in ADRs of AChEIs have so far been scarcely studied. Therefore, we aimed to recapitulate and update the diverse aspects of AChEIs, including the mechanisms of action, characteristics and risk factors of ADRs, and preventive strategies of their ADRs. The collation of this knowledge is essential to facilitate efforts to reduce ADRs of AChEIs.

Background There is still a lack of consensus on the efficacy of convalescent plasma (CP) treatment in COVID‐19 patients. We performed a systematic review and meta‐analysis to investigate the efficacy of CP vs standard treatment/non‐CP on clinical outcomes in COVID‐19 patients. Methods Cochrane Library, PubMed, EMBASE and ClinicalTrials.gov were searched from December 2019 to 16 July 2021, for data from clinical trials and observational studies. The primary outcome was all‐cause mortality. Risk estimates were pooled using a random‐effect model. Risk of bias was assessed by Cochrane Risk of Bias tool for clinical trials and Newcastle‐Ottawa Scale for observational studies. Results In total, 18 peer‐reviewed clinical trials, 3 preprints and 26 observational studies met the inclusion criteria. In the meta‐analysis of 18 peer‐reviewed trials, CP use had a 31% reduced risk of all‐cause mortality compared with standard treatment use (pooled risk ratio [RR] = 0.69, 95% confidence interval [CI]: 0.56‐0.86, P = .001, I 2 = 50.1%). Based on severity and region, CP treatment significantly reduced risk of all‐cause mortality in patients with severe and critical disease and studies conducted in Asia, pooled RR = 0.61, 95% CI: 0.47‐0.81, P = .001, I 2 = 0.0%; pooled RR = 0.67, 95% CI: 0.49‐0.92, P = .013, I 2 = 0.0%; and pooled RR = 0.62, 95% CI: 0.48‐0.80, P < .001, I 2 = 20.3%, respectively. The meta‐analysis of observational studies showed the similar results to the clinical trials. Conclusions Convalescent plasma use was associated with reduced risk of all‐cause mortality in severe or critical COVID‐19 patients. However, the findings were limited with a moderate degree of heterogeneity. Further studies with well‐designed and larger sample size are needed.

A large-scale surveillance is an important measure to monitor the regional spread of antimicrobial resistance. We prospectively studied the prevalence and molecular characteristics of clinically important Gram-negative bacilli, including Escherichia coli (EC), Klebsiella pneumoniae (KP), Acinetobacter baumannii complex (ABC), and Pseudomonas aeruginosa (PA) from blood, respiratory tract, urine, and sterile sites at 47 hospitals across Thailand. Among 187,619 isolates, 93,810 isolates (50.0%) were critically drug-resistant. Of which, 12,915 isolates (13.8%) were randomly selected for molecular characterization. EC was most commonly isolated from all specimens, except the respiratory tract in which ABC was predominant. Prevalence of extended-spectrum cephalosporin resistance (ESCR) was higher in EC (42.5%) than KP (32.0%), but carbapenem-resistant (CR)-KP (17.2%) was 4.5-fold higher than CR-EC (3.8%). A majority of ESCR-/CR-EC and KP carried bla CTX-M (64.6%-82.1%). bla NDM and bla OXA-48-like were the most prevalent carbapenemase genes in CR-EC/CR-KP (74.9%/52.9% and 22.4%/54.1%, respectively). Besides, 12.9%/23.0% of CR-EC/CR-KP co-carried bla NDM and bla OXA-48-like. Among ABC, 41.9% were extensively drug-resistant (XDR), and 35.7% were multidrug-resistant (MDR), while PA showed XDR/MDR at 6.3%/16.5%. A. baumannii (AB) was the most common species among ABC isolates. The major carbapenemase gene in MDR-AB/XDR-AB was bla OXA-23-like (85.8%/93.0%), which had much higher rates than other ABC species. bla IMP , bla VIM , bla OXA-40-like, and bla OXA-58-like were also detected in ABC at lower rates. The most common carbapenemase gene in MDR-/XDR-PA was bla IMP (29.0%/30.6%), followed by bla VIM (9.5%/25.3%). The findings reiterate an alarming situation of drug resistance that requires serious control measures.