Introduction Nursing home residents often have a high number of comorbidities resulting in polypharmacy. Inappropriate prescribing is therefore likely to occur, which in turn is expected to worsen cognitive impairment, to increase the fall risk and to decrease residents’ quality of life. The objective of the ‘Discontinuing Inappropriate Medication in Nursing Home Residents’ (DIM-NHR) study is to examine the efficacy and cost-effectiveness of the Multidisciplinary Multistep Medication Review (3MR) that is aimed at optimising prescribing and discontinuing inappropriate medication. Methods A cluster randomised controlled trial will be conducted. Elderly care physicians and their wards (clusters) will be randomised. Data will be collected at baseline and 4 months after the 3MR has taken place. Six hundred nursing home residents will be recruited of whom more than half are expected to suffer from dementia. The 3MR will be based on consensus criteria and the relevant literature and will be performed by the patient’s elderly care physician in collaboration with a pharmacist. Analysis Primary outcomes—the difference in proportion of residents who successfully discontinued inappropriate medication between the intervention and control group at follow-up. Secondary outcomes—undertreatment, exposure to anticholinergic and sedative medicines, neuropsychiatric symptoms, cognitive function, falls, hospital admission, quality of life and cost-effectiveness. Ethics and dissemination Participant burden will be kept at a minimum. The elderly care physician will remain free to adjust medication when symptoms relapse or adverse events occur, rendering serious adverse events highly unlikely. Study findings will be published in peer-reviewed journals and a 3MR toolkit will be developed. Trial registration number This study has been registered at http://www.ClinicalTrials.gov (trial registration number: NCT01876095)

As a traditional medical therapy, stimulation at the Lianquan (CV23) acupoint, located at the depression superior to the hyoid bone, has been shown to be beneficial in dysphagia. However, little is known about the neurological mechanism by which this peripheral stimulation approach treats for dysphagia. Here, we first identified a cluster of excitatory neurons in layer 5 (L5) of the primary motor cortex (M1) that can regulate swallowing function in male mice by modulating mylohyoid activity. Moreover, we found that focal ischemia in the M1 mimicked the post-stroke dysphagia (PSD) pathology, as indicated by impaired water consumption and electromyographic responses in the mylohyoid. This dysfunction could be rescued by electroacupuncture (EA) stimulation at the CV23 acupoint (EA-CV23) in a manner dependent on the excitatory neurons in the contralateral M1 L5. Furthermore, neuronal activation in both the parabrachial nuclei (PBN) and nucleus tractus solitarii (NTS), which was modulated by the M1, was required for the ability of EA-CV23 treatment to improve swallowing function in male PSD model mice. Together, these results uncover the importance of the M1-PBN-NTS neural circuit in driving the protective effect of EA-CV23 against swallowing dysfunction and thus reveal a potential strategy for dysphagia intervention.

Objective To provide a route map regarding systematic reviews (SRs) of acupuncture therapies that will meet two goals: (1) to identify areas in which more or better evidence is required and (2) to identify acupuncture applications that, although proven effective, remain underused in practice, and thus warrant more effective knowledge dissemination. Eligibility criteria We included SRs that conducted meta-analyses (MAs) of randomised controlled trials (RCTs) for this overview. Information sources We searched for SRs without language restrictions from January 2015 to November 2020 in four Chinese electronic databases and Epistemonikos database. And we also searched for newly published RCTs that were eligible for selected best SRs in PubMed, Medline, Cochrane Central Register of Controlled Trials, Embase and four Chinese electronic databases from its lasted search dates to November 2020. Synthesis of results We reanalysed the selected MAs if new primary studies were added. We used random-effect model to calculate the overall effect. Results Our search identified 120 SRs published in the last 5 years addressing acupuncture therapies across 12 therapeutic areas and 77 diseases and conditions. The SRs included 205 outcomes and involved 138 995 participants from 1402 RCTs. We constructed 77 evidence matrices, including 120 SRs and their included RCTs in the Epistemonikos database. Seventy-seven SRs represented the effect estimate of acupuncture therapies. Finally, we system summarised the areas of possible underutilisation of acupuncture therapies (high or moderate certainty evidence of large or moderate effects), and the areas of warranting additional investigation of acupuncture therapies (low or very low certainty evidence of moderate or large effects). Conclusion The evidence maps and overview of SRs on acupuncture therapies identified both therapies with substantial benefits that may require more assertive evidence dissemination and promising acupuncture therapies that require further investigation.

At present, prevention is particularly important when there is no effective treatment for cognitive decline. Since the adverse events of pharmacological interventions counterbalance the benefits, nonpharmacological approaches seem desirable to prevent cognitive decline. To our knowledge, no meta-analyses have been published on nonpharmacological interventions preventing cognitive decline. To investigate whether nonpharmacological interventions play a role in preventing cognitive decline among older people, we searched related trials up to March 31, 2019, in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials and the Cochrane library databases. Randomized controlled trials (RCTs) were included if they enrolled participants older than 60 years of age who had a risk of cognitive decline, and the interventions were nonpharmacological. Two reviewers independently extracted data and assessed study quality. The Grading of Recommendations Assessment Development and Evaluation (GRADE) approach was used to rate the quality of evidence. Heterogeneity was quantified with I². Subgroup analysis and meta-regression were used to research the sources of heterogeneity. Influence analyses were used to detect and remove extreme effect sizes (outliers) in our meta-analysis. Publication bias was assessed with funnel plots and Egger test. Primary outcomes were the incidence of mild cognitive impairment (MCI) or dementia and Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog) scores. Second outcomes were activities of daily living (ADL) and Mini-Mental State Examination (MMSE) scores. A total of 22 studies with 13,264 participants were identified for analysis. In terms of prevention, nonpharmacological interventions appeared to be more effective than control conditions, as assessed by the incidence of MCI or dementia (RR, 0.73; CI, 0.55–0.96; moderate-certainty evidence), while the results of ADAS-Cog suggested no significant differences between two groups (MD, −0.69; CI, −1.52–0.14; very low-certainty evidence). Second outcomes revealed a significant improvement from nonpharmacological interventions versus control in terms of the change in ADL (MD, 0.73; CI, 0.65–0.80) and MMSE scores (posttreatment scores: MD, 0.25; CI, 0.02–0.47; difference scores: MD, 0.59, CI, 0.29–0.88). Univariable meta-regression showed association between lower case of MCI or dementia and two subgroup factors (P = 0.013 for sample size; P = 0.037 for area). Multiple meta-regression suggested that these four subgroup factors were not associated with decreased incidence of MCI (P > 0.05 for interaction). The Naive RR estimate was calculated as 0.73. When the three studies that detected by outlier and influence analysis were left out, the Robust RR was 0.66. In conclusion, nonpharmacological therapy could have an indicative role in reducing the case of MCI or dementia. However, given the heterogeneity of the included RCTs, more preregistered trials are needed that explicitly examine the association between nonpharmacological therapy and cognitive decline prevention, and consider relevant moderators.

Maternal separation (MS), a stressful event in early life, has been linked to neuropsychiatric disorders later in life, especially depression. In this study we investigated whether treatment with electroacupuncture (EA) could ameliorate depression-related manifestations in adult animals that had adverse early life experiences. We demonstrated depression-like behavior deficiencies in a sucrose preference test and a forced swimming test in a rat model with neonatal MS. Repeated EA treatment at the acupoints Baihui (GV20) and Yintang (GV29) during adulthood was shown to be remarkably attenuated above behavioral deficits. Using unbiased genome-wide RNA sequencing to investigate alterations in the transcriptome of the prefrontal cortex (PFC), we explored the altered gene sets involved in circadian rhythm and neurotransmitter transporter activity in MS rats, and their expression tended to be reversed after EA treatment. In addition, we analyzed the interaction network of differentiated lncRNA– or circRNA–miRNA–mRNA by using the principle of competitive endogenous RNA (ceRNA). These results suggest that EA at GV20 and GV29 ameliorates depression-related manifestations by regulating the expression of multiple genes.