Managing Behavioral and Psychological Symptoms of Dementia (BPSD) in the Era of Boxed Warnings.

PURPOSE OF REVIEW: To provide a comprehensive overview on the evaluation and management of behavioral and psychological symptoms of dementia (BPSD) using evidence from literature. RECENT FINDINGS: Evidence indicates efficacy for some non-pharmacological techniques including education of caregivers and cognitive stimulation therapy and pharmacological agents like antidepressant and antipsychotics for the management of BPSD. The use of antipsychotics has generated controversy due to the recognition of their serious adverse effect profile including the risk of cerebrovascular adverse events and death. BPSD is associated with worsening of cognition and function among individuals with dementia, greater caregiver burden, more frequent institutionalization, overall poorer quality of life, and greater cost of caring for these individuals. Future management strategies for BPSD should include the use of technology for the provision of non-pharmacological interventions and the judicious use of cannabinoids and interventional procedures like ECT for the management of refractory symptoms.

Is there evidence for using anticonvulsants in the prevention and/or treatment of delirium among older adults?

OBJECTIVE: This systematic review aims to identify published randomized controlled trials (RCTs) that evaluated the use of anticonvulsants for the prevention and/or treatment of delirium among older adults. METHODS: A comprehensive search of databases: MEDLINE ALL (Ovid), Embase (Ovid), PsycINFO (Ovid), Web of Science Core Collection and Cochrane Central Register of Controlled was conducted. RESULTS: The search identified four RCTs that evaluated the use of anticonvulsants among older adults with delirium. One RCT evaluated the perioperative use of gabapentin among individuals undergoing spinal surgery and the development of postoperative delirium. One RCT evaluated the relationship between the use of perioperative gabapentin and the development of postoperative delirium among individuals undergoing spinal surgery and hip and knee arthroplasty. Two post-hoc analyses of RCTs evaluated the use of gabapentin and pregabalin among individuals undergoing total knee arthroplasty (TKA) and total hip arthroplasty (THA). The perioperative use of gabapentin reduced the incidence of postoperative delirium among older adults undergoing spinal surgery. The perioperative use of gabapentin did not reduce the rates, severity or duration of postoperative delirium among older adults who were undergoing spine and hip and knee arthroplasty. The perioperative use of gabapentin did not reduce the incidence or duration of postoperative delirium among older adults undergoing elective TKA. The perioperative use of pregabalin did not reduce the incidence of postoperative delirium among older adults undergoing elective THA. Gabapentin and pregabalin were well tolerated among the individuals enrolled in these trials. There were no RCTs identified that evaluated the use of other anticonvulsants for the prevention and/or treatment of delirium among older adults. CONCLUSIONS: Based on current evidence, the routine use of anticonvulsants for the prevention and/or treatment of delirium among older adults cannot be recommended.

Evaluation and treatment of older-age bipolar disorder: a narrative review.

OBJECTIVES: This narrative review aims to synthesize information from the literature regarding older-age bipolar disorder (OABD) in order to provide up-to-date information on this important illness. METHODS: We searched Ovid (Medline, Embase and PsychInfo) on October 1, 2020, using the keywords "bipolar disorder", "older adults" and "elderly" to identify relevant articles on OABD. Additionally, the bibliography of identified articles was reviewed for pertinent studies. DISCUSSIONS: OABD is a term that is used to describe bipolar disorder (BD) occurring amongst individuals ≥50 years of age. Evidence indicates that OABD accounts for a quarter of all cases of BD. When compared to individuals with early-onset BD, individuals with OABD have a greater association with cerebrovascular disease and other neurological disorders, less family history of mood disorders, and utilize almost four times the total amount of mental health services. In addition, they are four times more likely to have psychiatric hospitalizations when compared to age-matched controls. Despite a dearth of controlled studies on the use of pharmacotherapy amongst individuals with OABD, available evidence from mixed-age studies indicates the efficacy of commonly used medications in individuals with early-onset BD. Additionally, psychosocial treatments have been found to be effective as adjunctive management strategies amongst individuals with OABD. Furthermore, electroconvulsive therapy may be effective in the treatment of refractory cases of OABD. CONCLUSIONS: There is a great need for an improved understanding of the phenomenology and neurobiology of OABD. Additionally, research into effective treatments for this serious psychiatric disorder will mitigate the suffering of individuals with OABD.

A systematic review of ketamine for the treatment of depression among older adults.

OBJECTIVE: To review the currently available data on the use of ketamine in the treatment of depression among older adults from randomized controlled studies. DESIGN: Randomized controlled trials. SETTING: Variable. PARTICIPANTS: 60 years and older with depression. INTERVENTION: Ketamine. MEASUREMENTS: Change in Montgomery-Asberg Depression Rating Scale (MADRS) scores. RESULTS: Two studies met the inclusion criteria. The first study showed a significant reduction in depression symptoms with use of repeated subcutaneous ketamine administration among older adults with depression. The second study failed to achieve significance on its primary outcome measure but did show a decrease in MADRS scores with intranasal ketamine along with a higher response and remission rates in esketamine group compared with the placebo group. The adverse effects from ketamine generally lasted only a few hours and abated spontaneously. No cognitive adverse effects were noted in either trial from the use of ketamine. CONCLUSIONS: The current evidence for use of ketamine among older adults with depression indicates some benefits with one positive and one negative trial. Although one of the trials did not achieve significance on the primary outcome measure, it still showed benefit of ketamine in reducing depressive symptoms. Ketamine was well tolerated in both studies with adverse effects being mild and transient.

Systematic review of benzodiazepines for anxiety disorders in late life.

BACKGROUND: Benzodiazepines are currently the most commonly prescribed medication for the treatment of anxiety in older adults, although there is a dearth of good-quality data on this subject. The aim of this review was to systematically review studies examining the efficacy and tolerability of benzodiazepines for the treatment of anxiety disorders among older adults. METHODS: The authors conducted a systematic review, searching PubMed, Ovid MEDLINE, Ovid Embase, Web of Science, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials. All searches were limited to English-language articles. The quality of each study was appraised using criteria developed by the Centre for Evidence-Based Medicine for randomized controlled trials. RESULTS: A total of 8,785 citations were retrieved and pooled in EndNote and de-duplicated to 3,753. This set was uploaded to Covidence for screening. Two separate screeners (AG and SAF) evaluated the titles, abstracts, and full text of the eligible articles. Five studies met the inclusion criteria. Across all studies, benzodiazepines were associated with decreased anxiety at the end of the study period. The limited tolerability data show mild adverse effects from the benzodiazepines studied. Limitations of the trials included limited data on the long-term use of benzodiazepines for anxiety and a preponderance of trials examining generalized anxiety disorder, with relatively less data on other anxiety disorders. CONCLUSIONS: Benzodiazepines are effective for treating anxiety disorders in late life, at least in the short term, but more data is needed to establish tolerability and their long-term benefits.

On the Safety of Human Body Communication.

Human Body Communication (HBC) utilizes the electrical conductivity properties of the human body to communicate between devices in and around the body. The increased energy-efficiency and security provided by HBC compared to traditional radio wave based communication makes it a promising alternative to communicate between energy constrained wearable and implantable devices around the body.However, HBC requires electrical signals to be transmitted through the body, which makes it essential to have a thorough analysis of the safety aspects of such transmission. This paper looks into the compliance of the current density and electric/magnetic fields generated in different modalities of HBC with the established safety standards. Circuit and Finite Element Method (FEM) based simulations are carried out to quantitatively find the compliance of current density and fields with the established safety limits. The results show the currents and fields in capacitive HBC are orders of magnitude smaller than the specified limits. However, certain excitation modalties in galvanic HBC can result in current densities and fields exceeding the safety limits around the excitation point on the body near the electrode. A study with 7 human subjects (4 male, 3 female) is carried out over a month, using capacitive HBC.The study monitors the change in 5 vital parameters (Heart Rate, Mean Arterial Pressure, Respiration Rate, Peripheral Capillary Oxygen Saturation, Temperature), while wearing a HBC enabled device. Analysis of the acquired data statistically shows no significant change in any of the vital parameters of the subjects, confirming the results of the simulation study.

Exposure to sub-inhibitory concentrations of gentamicin, ciprofloxacin and cefotaxime induces multidrug resistance and reactive oxygen species generation in meticillin-sensitive Staphylococcus aureus.

PURPOSE: The role of antibiotics below their MIC in the development of bacterial drug resistance is becoming increasingly important. We investigated the effect of sub-MICs of bactericidal antibiotics on the susceptibility pattern of Staphylococcus aureus and evaluated the role of free radicals. METHODOLOGY: A total of 12 S. aureus strains were recovered from pus samples and their antibiograms determined. The test isolates were treated with sub-MIC levels of tetracycline, gentamicin, ciprofloxacin and cefotaxime. Alterations in their respective breakpoints were observed along with measurements of free radical generation by nitro blue tetrazolium test.Results/Key findings. Gentamicin, ciprofloxacin and cefotaxime exposure significantly altered the breakpoints of exposed isolates against several tested antibiotics and higher levels of free radicals were generated after antibiotic exposure. CONCLUSIONS: Our study demonstrates that sub-MIC levels of antimicrobials can lead to resistance and cross-resistance across several classes of antibiotics in wild strains of S. aureus, possibly by free radical production. The molecular mechanisms behind the acquisition of drug resistance at low antibiotic concentrations and the specific target genes of reactive oxygen speciesneed to be explored further.

Perceptions of sexual harassment by evidence quality, perceiver gender, feminism, and right wing authoritarianism: Debunking popular myths.

This study examined the critique in public discourse that sexual harassment (SH) victim advocates, particularly women and feminists, ignore the quality of evidence in a SH claim and are reluctant to find evidence of a false accusation. To balance the inquiry, the study also examined whether right wing authoritarians (RWAs) also ignore evidence quality and presume such claims are false accusations. Participants were 961 U.S. adults (51% female) who completed an online experiment in which they read either a gender harassment (GH) or unwanted sexual attention (USA) scenario of hostile work environment SH and rated the scenario on severity, perceived guilt of the accused, belief that the accused should receive negative job consequences, and likelihood that the claimant was making a false accusation. Scenarios varied by the strength of the evidence in support of the SH claim. Participants completed measures of identification with and support for feminism, RWA, and demographic variables. Results found that contrary to expectations, evidence had a stronger effect on women's, feminists', and feminism supporters' perceptions and to a lesser extent RWAs' perceptions of the scenarios. When evidence was weak, women and feminists, compared to others, were less supportive of the prosecution, but when evidence was strong they were more supportive of the prosecution than were others. These findings address criticisms that advocates for gender equity and victim's rights, particularly women and feminists, are unable to reach fair judgments of SH complaints. (PsycINFO Database Record

Influence of BCL11A, HBS1L-MYB, HBBP1 single nucleotide polymorphisms and the HBG2 XmnI polymorphism On Hb F levels.

In search of genetic alterations responsible for high fetal hemoglobin (Hb F) phenotypes in the population of eastern India, 91 probands were screened for four polymorphisms by sequencing and/or restriction fragment length polymorphism (RFLP) analysis. These are the A>G allele on the rs4895441 locus in the intergenic region between HBS1L and MYB on chromosome 6, the G>A allele on the rs4671393 locus on chromosome 2 (BCL11A gene), the A>C allele on the rs2071348 (HBBP1 gene) and the XmnI polymorphism (rs7482144, -158 position of HBG2) on chromosome 11. We found a significant association (p = 0.002 and 0.0013) of Hb F levels with rs2071348 and rs4895441, respectively. However, the polymorphism rs4671393 gene did not show significant association with Hb F levels (p = 0.0655). As is well known, the XmnI polymorphism (p <0.0001) showed the strongest association.

Hb Sallanches [alpha104(G11)Cys-->Tyr, TGC>TAC] occurs frequently on the Indian subcontinent.

Point mutations of alpha-globin genes in homozygous or in compound heterozygous states cause severe alpha-thalassemia (alpha-thal). Here we describe a polymerase chain reaction-restriction fragment length polymorphism-based method for easy detection of the point mutation Hb Sallanches [alpha104(G11)Cys-->Tyr, TGC>TAC], earlier detected by a sequencing technique. In a cohort of 104 unrelated putative alpha-thal patients, nine carried the mutation and two were homozygotes. The mutation occurred on both the alpha2- or alpha1-globin genes. The phenotypes, in conjunction with other point mutations or deletions, are presented. Earlier detected in Pakistan and Punjab of India, it is probably present all over the Indian subcontinent.

A user study to compare four uncertainty visualization methods for 1D and 2D datasets.

Many techniques have been proposed to show uncertainty in data visualizations. However, very little is known about their effectiveness in conveying meaningful information. In this paper, we present a user study that evaluates the perception of uncertainty amongst four of the most commonly used techniques for visualizing uncertainty in one-dimensional and two-dimensional data. The techniques evaluated are traditional errorbars, scaled size of glyphs, color-mapping on glyphs, and color-mapping of uncertainty on the data surface. The study uses generated data that was designed to represent the systematic and random uncertainty components. Twenty-seven users performed two types of search tasks and two types of counting tasks on 1D and 2D datasets. The search tasks involved finding data points that were least or most uncertain. The counting tasks involved counting data features or uncertainty features. A 4x4 full-factorial ANOVA indicated a significant interaction between the techniques used and the type of tasks assigned for both datasets indicating that differences in performance between the four techniques depended on the type of task performed. Several one-way ANOVAs were computed to explore the simple main effects. Bonferronni's correction was used to control for the family-wise error rate for alpha-inflation. Although we did not find a consistent order among the four techniques for all the tasks, there are several findings from the study that we think are useful for uncertainty visualization design. We found a significant difference in user performance between searching for locations of high and searching for locations of low uncertainty. Errorbars consistently underperformed throughout the experiment. Scaling the size of glyphs and color-mapping of the surface performed reasonably well. The efficiency of most of these techniques were highly dependent on the tasks performed. We believe that these findings can be used in future uncertainty visualization design. In addition, the framework developed in this user study presents a structured approach to evaluate uncertainty visualization techniques, as well as provides a basis for future research in uncertainty visualization.

Polymerase chain reaction-based search for two alpha-globin gene mutations in India.

We have used restriction site-dependent polymerase chain reaction (PCR)-based methodology for detection of the alpha-globin polyadenylation (poly A) signal mutation, AATAAA>AATA- - and Hb Sun Prairie [alpha 130(H13)Ala-->Pro, GCT>CCT (alpha2)] mutation. The former mutation produces Hb H disease in the homozygous state and occurs frequently in the Indian population. It was detected in nine of 77 putative alpha-thalassemia (alpha-thal) patients and in three of 13 beta-thal intermedia patients tested. Four of the nine alpha-thal patients were homozygotes for the mutation. The Hb Sun Prairie mutation was confirmed in two alpha-thal patients, one of whom was a homozygote and the other a heterozygote.