Efficacy of non-invasive brain stimulation on global cognition and neuropsychiatric symptoms in Alzheimer's disease and mild cognitive impairment: A meta-analysis and systematic review.

BACKGROUND: Non-invasive brain stimulation (NIBS) techniques have shown some promise in improving cognitive and neuropsychiatric symptoms (NPS) in people with Alzheimer's disease (AD) and its prodromal stage, mild cognitive impairment (MCI). However, data from clinical trials involving NIBS have shown inconsistent results. This meta-analysis investigated the efficacy of NIBS, specifically repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS) compared to sham stimulation on global cognition and NPS in people with AD and MCI. METHOD: Multi-session randomized sham-controlled clinical trials were identified through MEDLINE, PsycINFO, and Embase until June 2021. Standardized mean difference (SMD) and 95% confidence interval (CI) between the active and sham treatments were calculated using random-effects meta-analyses. Included studies reported outcome measures for global cognition and/or NPS. Heterogeneity, from different NIBS techniques, disease populations, or tests used to assess global cognition or NPS, was measured using chi-square and I2, and investigated using subgroup analyses. Possible effects of covariates were also investigated using meta-regressions. RESULT: The pooled meta-analyses included 19 studies measuring global cognition (Nactive=288, Nsham=264), and 9 studies investigating NPS (Nactive=165, Nsham=140). NIBS significantly improved global cognition (SMD=1.14; 95% CI=0.49,1.78; p = 0.001; I2 = 90.2%) and NPS (SMD=0.82; 95% CI=0.13, 1.50; p = 0.019; I2 = 86.1%) relative to sham stimulation in patients with AD and MCI. Subgroup analyses found these effects were restricted to rTMS but not tDCS, and to patients with AD but not MCI. Meta-regression showed that age was significantly associated with global cognition response (Nstudies=16, p = 0.020, I2 = 89.51%, R2 = 28.96%), with larger effects sizes in younger populations. All significant meta-analyses had large effect sizes (SMD ≥0.8), suggesting clinical utility of NIBS in the short term. There remained substantial heterogeneity across all subgroup analyses and meta-regressions (all I2 > 50%). Egger's tests showed no evidence of publication biases. CONCLUSION: rTMS improved global cognition and NPS in those with AD. Further studies in MCI and using tDCS will help to fully evaluate the specific NIBS techniques and populations most likely to benefit on global cognition and NPS measures. Additional research should investigate the long term clinical utility of NIBS in these populations.

Bilateral sequential theta burst stimulation for multiple-therapy-resistant depression: A naturalistic observation study.

Depression is a significant health issue with treatment resistance reported in about one third of patients. Treatment resistance results in significant disability, impaired quality of life, and increased healthcare costs. Repetitive transcranial magnetic stimulation (rTMS) is a treatment option for treatment resistant depression (TRD) with response and remission rates in open-label studies being as high as 58% and 37% respectively. Theta-burst is a faster and novel rTMS paradigm that has shown promise as a treatment for TRD in some preliminary studies. In a naturalistic design, we evaluated the response, remission and tolerability of bilateral sequential (right then left) prefrontal theta-burst rTMS (bsTBS) in 50 patients with TRD (600 pulses/session, 20 sessions, 100% of resting motor threshold (80% if intolerant to 100%, n = 2), F4/F3 of 10-20-20 EEG localization). Data was collected over 36 months from a specialized academic TMS clinic. Patients had multiple-treatment resistance with at least two failed trials of different antidepressants with 20% also having failed electroconvulsive therapy and 66% having received professional therapy. We found a 28% remission rate (HAMD-17 score of ≤7) and a 52% response rate (≥50% reduction in HAMD-17) with a 42% reduction in average HAMD-17 score. The treatment was well tolerated, with muscle contractions, mild pain or discomfort, headache, scalp irritation, and changes to vitals being captured as occasional adverse events with two instances of syncope (0.22% of treatments). This naturalistic study shows that bsTBS is a promising paradigm for a multiple-TRD patient population with approximately one-third of treatments achieving remission and over half achieving significant response.

Cost-analysis of Withdrawing Immunoprophylaxis for Respiratory Syncytial Virus in Infants Born at 33-35 Weeks Gestational Age in Quebec: A Multicenter Retrospective Study.

BACKGROUND: In 2015, the Quebec Ministry of Health limited palivizumab prophylaxis for respiratory syncytial virus (RSV) in premature infants to those born at <33 weeks gestational age (wGA), unless other indications were present. We compared RSV-related costs for 2 seasons before the change (2013-2014, 2014-2015) and 2 seasons after (2015-2016, 2016-2017) in premature infants 33-35 wGA. METHODS: Using payer and societal perspectives, costs associated with hospitalizations for RSV and lower respiratory tract infection (LRTI) in infants born at 33-35 wGA were estimated. Inputs were from a 2013-2017 retrospective cohort study in 25 Quebec hospitals of RSV/LRTI hospitalizations among infants <6 months old at the start of, or born during, the RSV season. Resource utilization data (hospital stay, procedures, visits, transportation, out-of-pocket expenses and work productivity) were collected from charts and parent interviews allowing estimation of direct and indirect costs. Costs, including palivizumab administration, were derived from provincial sources and adjusted to 2018 Canadian dollars. Costs were modeled for preterm infants hospitalized for RSV/LRTI pre- and postrevision of guidelines and with matched term infants hospitalized for RSV/LRTI during 2015-2017 (comparator). RESULTS: Average total direct and indirect costs for 33-35 wGA infants were higher postrevision of guidelines ($29,208/patient, 2015-2017; n = 130) compared with prerevision ($16,976/patient, 2013-2015; n = 105). Total costs were higher in preterm infants compared with term infants (n = 234) postrevision of guidelines ($29,208/patient vs. $10,291/patient). CONCLUSIONS: Immunoprophylaxis for RSV in infants born at 33-35 wGA held a cost advantage for hospitalizations due to RSV/LRTI.

Current Agents in Development for Treating Behavioral and Psychological Symptoms Associated with Dementia.

Behavioral and psychological symptoms associated with dementia are highly prevalent and are associated with an increased risk of institutionalization and mortality. Current pharmacological treatments for these symptoms include cholinesterase inhibitors, antipsychotics, and selective serotonin reuptake inhibitors. When used for treating behavioral and psychological symptoms associated with dementia, they are associated with limited efficacy and/or serious adverse events. As such, there has been extensive research into novel agents with varying mechanisms of action targeting behavioral and psychological symptoms associated with dementia. In this article, we present the results of a comprehensive literature search and review that evaluates current agents that have completed or are currently in clinical trials for treating behavioral and psychological symptoms associated with dementia as a primary outcome. We highlight novel agents from miscellaneous drug classes, such as dextromethorphan/quinidine, bupropion/dextromethorphan, lumateperone, deudextromethorphan/quinidine, methylphenidate and scyllo-inositol, and drugs from various therapeutic classes (including atypical antipsychotics, selective serotonin reuptake inhibitors, and cannabinoids) that have demonstrated promising results and were generally well tolerated. Future research with large appropriately powered studies using validated outcome measures for behavioral and psychological symptoms associated with dementia should be conducted to further establish the clinical utility of these agents.