Physician antipsychotic overprescribing letters and cognitive, behavioral, and physical health outcomes among people with dementia: a secondary analysis of a randomized clinical trial

Importance Antipsychotics, such as quetiapine, are frequently prescribed to people with dementia to address behavioral symptoms but can also cause harm in this population. Objective To determine whether warning letters to high prescribers of quetiapine can successfully reduce its use among patients with dementia and to investigate the impacts on patients’ health outcomes. Design, Setting, and Participants This is a secondary analysis of a randomized clinical trial of overprescribing letters that began in April 2015 and included the highest-volume primary care physician (PCP) prescribers of quetiapine in original Medicare. Outcomes of patients with dementia were analyzed in repeated 90-day cross-sections through December 2018. Analyses were conducted from September 2021 to February 2024. Interventions PCPs were randomized to a placebo letter or 3 overprescribing warning letters stating that their prescribing of quetiapine was high and under review by Medicare. Main Outcomes and Measures The primary outcome of this analysis was patients’ total quetiapine use in days per 90-day period (the original trial primary outcome was total quetiapine prescribing by study PCPs). Prespecified secondary outcomes included measures of cognitive function and behavioral symptoms from nursing home assessments, indicators of depression from screening questionnaires in assessments and diagnoses in claims, metabolic diagnoses derived from assessments and claims, indicators of use of the hospital and other health care services, and death. Outcomes were analyzed separately for patients living in nursing homes and in the community. Results Of the 5055 study PCPs, 2528 were randomized to the placebo letter, and 2527 were randomized to the 3 warning letters. A total of 84 881 patients with dementia living in nursing homes and 261 288 community-dwelling patients with dementia were attributed to these PCPs. There were 92 874 baseline patients (mean [SD] age, 81.5 [10.5] years; 64 242 female [69.2%]). The intervention reduced quetiapine use among both nursing home patients (adjusted difference, –0.7 days; 95% CI, −1.3 to −0.1 days; P = .02) and community-dwelling patients (adjusted difference, −1.5 days; 95% CI, −1.8 to −1.1 days; P < .001). There were no detected adverse effects on cognitive function (cognitive function scale adjusted difference, 0.01; 95% CI, −0.01 to 0.03; P = .19), behavioral symptoms (agitated or reactive behavior adjusted difference, −0.2%; 95% CI −1.2% to 0.8% percentage points; P = .72), depression, metabolic diagnoses, or more severe outcomes, including hospitalization and death. Conclusions and Relevance This study found that overprescribing warning letters to PCPs safely reduced quetiapine prescribing to their patients with dementia. This intervention and others like it may be useful for future efforts to promote guideline-concordant care

Bifidobacterium breve reduces apoptotic epithelial cell shedding in an exopolysaccharide and MyD88-dependent manner

Certain members of the microbiota genus Bifidobacterium are known to positively influence host well-being. Importantly, reduced bifidobacterial levels are associated with inflammatory bowel disease (IBD) patients, who also have impaired epithelial barrier function, including elevated rates of apoptotic extrusion of small intestinal epithelial cells (IECs) from villi—a process termed ‘cell shedding’. Using a mouse model of pathological cell shedding, we show that mice receiving Bifidobacterium breve UCC2003 exhibit significantly reduced rates of small IEC shedding. Bifidobacterial-induced protection appears to be mediated by a specific bifidobacterial surface exopolysaccharide and interactions with host MyD88 resulting in downregulation of intrinsic and extrinsic apoptotic responses to protect epithelial cells under highly inflammatory conditions. Our results reveal an important and previously undescribed role for B. breve, in positively modulating epithelial cell shedding outcomes via bacterial- and host-dependent factors, supporting the notion that manipulation of the microbiota affects intestinal disease outcomes

Syntrophy drives the microbial electrochemical oxidation of toluene in a continuous-flow "bioelectric well"

Microbial electrochemical technologies (MET) are promising for the remediation of groundwater pollutants such as petroleum hydrocarbons (PH). Indeed, MET can provide virtually inexhaustible electron donors or acceptors directly in the subsurface environment. However, the degradation mechanisms linking contaminants removal to electric current flow are still largely unknown, hindering the development of robust design criteria. Here, we analysed the degradation of toluene, a model PH, in a bioelectrochemical reactor known as "bioelectric well"operated in continuous-flow mode at various influent toluene concentrations. With increasing concentration of toluene, the removal rate increased while the current tended to a plateau, hence the columbic efficiency decreased. Operation at open circuit confirmed that the bioelectrochemical degradation of toluene proceeded via a syntrophic pathway involving cooperation between different microbial populations. First of all, hydrocarbon degraders quickly converted toluene into metabolic intermediates probably by breaking the aromatic ring upon fumarate addition. Subsequently, fermentative bacteria converted these intermediates into volatile fatty acids (VFA) and likely also H2, which were then used as substrates by electroactive microorganisms forming the anodic biofilm. As toluene degradation is faster than subsequent conversion steps, the increase in intermediate concentration could not result in a current increase. This work provides valuable insights on the syntrophic degradation of BTEX, which are essential for the application of microbial electrochemical system to groundwater remediation of petroleum hydrocarbons

Maturation of mammalian H/ACA box snoRNAs: PAPD5-dependent adenylation and PARN-dependent trimming

Small nucleolar and small Cajal body RNAs (snoRNAs and scaRNAs) of the H/ACA box and C/D box type are generated by exonucleolytic shortening of longer precursors. Removal of the last few nucleotides at the 3' end is known to be a distinct step. We report that, in human cells, knock-down of the poly(A) specific ribonuclease (PARN), previously implicated only in mRNA metabolism, causes the accumulation of oligoadenylated processing intermediates of H/ACA box but not C/D box RNAs. In agreement with a role of PARN in snoRNA and scaRNA processing, the enzyme is concentrated in nucleoli and Cajal bodies. Oligo(A) tails are attached to a short stub of intron sequence remaining beyond the mature 3' end of the snoRNAs. The noncanonical poly(A) polymerase PAPD5 is responsible for addition of the oligo(A) tails. We suggest that deadenylation is coupled to clean 3' end trimming, which might serve to enhance snoRNA stability

Chapter 16 - Cross-cutting investment and finance issues

This is the first time an assessment report by the Intergovernmental Panel on Climate Change (IPCC) contains a chapter dedicated to investment and finance to address climate change. This reflects the growing awareness of the relevance of these issues for the design of efficient and effective climate policies

Casting for a sovereign role:Socialising an aspirant state in the Scottish independence referendum

This article examines international reactions to Scotland’s 2014 bid for independence as an instance of socialisation of an aspirant state, what we term ‘pre-socialisation’. Building on and contributing to research on state socialisation and role theory, this study proposes a nexus between roles and sovereignty. This nexus has three components: sovereignty itself is a role casted for by an actor; the sovereign role is entangled with the substantive foreign policy roles the actor might play; and the sovereign role implicates the substantive foreign policy roles of other actors. The Scottish debate on independence provides an effective laboratory to develop and explore these theoretical dimensions of pre-socialisation, revealing the contested value and meaning of sovereignty, the possible roles that an independent Scotland could play, and the projected implications for the role of the UK and other international actors. Our analysis of the Scottish case can provide insights for other cases of pre-socialisation and is more empirically significant following the UK’s 2016 referendum to leave the European Union.PostprintPeer reviewe

Summary for policymakers

The Working Group III contribution to the IPCC Fifth Assessment Report (WGIII AR5) provides a comprehensive assessment of all relevant options for mitigating climate change through limiting or preventing greenhouse gas emissions, as well as activities that remove them from the atmosphere. It draws on scientific literature accepted for publication prior to 4 October 2013. The WGIII Summary for Policymakers was approved at the Twelfth Session of Working Group III, held in Berlin, Germany, from 7 to 11 April, 2014. During the session, the IPCC plenary also accepted the underlying scientific and technical assessment, which stands at 2000 pages, including more than 700 pages of references

Quality of life after sleeve gastrectomy and adjustable gastric banding

Abstract Background: With the addition of laparoscopic vertical sleeve gastrectomy (SG) to the bariatric surgery procedural toolkit, patients desiring a restrictive bariatric procedure often choose between adjustable gastric banding (LAGB) and SG. One study compared quality of life after these 2 procedures and found no difference. The purpose of our study was to re-evaluate the postoperative quality of life in LAGB and SG patients at a military teaching hospital in the United States. Methods: A retrospective review of 108 consecutive laparoscopic restrictive bariatric procedures performed within 15 months at a Department of Defense hospital was conducted. Of these 108 patients, 69 had undergone laparoscopic vertical SG and 39 LAGB. A validated quality of life questionnaire (Bariatric Quality of Life) was conducted a mean of 9.3 Ϯ 3.2 months (range 5-16) postoperatively. The weight loss and standard laboratory parameters were measured at 0, 1, 3, 6, and 12 months. Results: The quality of life assessment revealed significantly better scores after SG than after LAGB (66.5 versus 57.9, P ϭ .0002). The excess weight loss and excess body mass index loss at 3, 6, and 12 months postoperatively were significantly greater in the laparoscopic SG group. The patients demonstrated a clear preference over time for SG once it was offered. Conclusion: Early postoperative quality of life was superior after SG than after LAGB. SG also resulted in superior early excess weight loss. In a practice not constrained by reimbursement, these findings were associated with increased patient choice of SG after it began to be offered. (Surg Obes Relat Dis 2012;8:31-40.