The impact of premorbid adjustment, neurocognition, and depression on social and role functioning in patients in an early psychosis treatment program

Objective: Functional impairments are debilitating concomitants of psychotic disorders and are present early in the illness course and, commonly, prior to psychosis onset. The factors affecting social and role functioning in early psychosis (EP) following treatment are unclear. We evaluated whether six months of participation in the PREPR, Boston, EP treatment program, part of a public-academic community mental health center, was related to improvements in social and role functioning and whether premorbid adjustment in adolescence, baseline neurocognition, and depression symptoms predicted functional improvement. Method: The Global Functioning Social and Role scales, MATRICS neurocognitive battery, and Calgary Depression Scale were assessed at baseline and six months during naturalistic treatment, while premorbid adjustment was measured at baseline. All participants were psychotic disorder patients in PREPR (n = 46 with social functioning and 47 with role functioning measures at both time points). Results: Large improvements were observed in role functioning (d = 0.84) and medium to large improvements were observed in social functioning (d = 0.70). Models consisting of adolescent premorbid adjustment and change in depression symptoms predicted social and role functioning change, whereas neuropsychological functioning did not. Conclusions: Substantial improvements in social and role functioning were observed among this sample participating in a recovery-based EP program. The impact of clinical factors on social and role functioning was highlighted. Further studies of premorbid adjustment in adolescence and the treatment of depression in EP programs in controlled treatment trials are needed to confirm these findings

Role of Raltegravir in HIV-1 Management

OBJECTIVE: To review the literature concerning the role of raltegravir in the treatment of HIV-1 in antiretroviral (ARV)-experienced and ARV-naïve patients. DATA SOURCES: A PubMed search was conducted for published data through March 2012 using the search terms raltegravir, MK-0518, and integrase strand transfer inhibitor. An additional search of International Pharmaceutical Abstracts for unpublished data, including data from the Infectious Diseases Society of America, the Conference on Retroviruses and Opportunistic Infections, the International AIDS Society, and the Interscience Conference on Antimicrobial Agents and Chemotherapy, was conducted using similar search terms. STUDY SELECTION AND DATA EXTRACTION: In vitro and in vivo Phase 2, Phase 3, and postmarketing studies available in English, evaluating antiretroviral regimens that contain raltegravir for the treatment of HIV-1 infection in both ARV-naïve and ARV-experienced patients, were evaluated. Studies assessing raltegravir pharmacokinetics and pharmacodynamics were included for review. DATA SYNTHESIS: The nucleoside-based regimen of raltegravir with tenofovir/emtricitabine provides an effective first-line treatment option. However, nucleoside-sparing regimens appear unfavorable in ARV-naïve subjects and should be reserved for patients with limited treatment options. Raltegravir used with optimized background therapy provides an alternative regimen for ARV-experienced patients. This review describes the available in vitro and in vivo data on raltegravir potency, defined as the ability to achieve undetectable viral load, and safety profile, as well as comparison to standard HIV-1 therapies. CONCLUSIONS: Raltegravir has demonstrated potent antiretroviral activity against HIV-1 in both ARV-naïve and ARV-experienced subjects, with the benefits of a favorable adverse effect profile and minimal drug interactions. Raltegravir must be dosed twice daily, as once daily raltegravir displays decreased virologic efficacy compared to twice daily dosing. However, the ongoing development of new integrase strand transfer inhibitors may provide potent once daily regimens

Pangenome comparison of Bacteroides fragilis genomospecies unveils genetic diversity and ecological insights

Bacteroides fragilis is a Gram-negative commensal bacterium commonly found in the human colon, which differentiates into two genomospecies termed divisions I and II. Through a comprehensive collection of 694 B. fragilis whole genome sequences, we identify novel features distinguishing these divisions. Our study reveals a distinct geographic distribution with division I strains predominantly found in North America and division II strains in Asia. Additionally, division II strains are more frequently associated with bloodstream infections, suggesting a distinct pathogenic potential. We report differences between the two divisions in gene abundance related to metabolism, virulence, stress response, and colonization strategies. Notably, division II strains harbor more antimicrobial resistance (AMR) genes than division I strains. These findings offer new insights into the functional roles of division I and II strains, indicating specialized niches within the intestine and potential pathogenic roles in extraintestinal sites.ImportanceUnderstanding the distinct functions of microbial species in the gut microbiome is crucial for deciphering their impact on human health. Classifying division II strains as Bacteroides fragilis can lead to erroneous associations, as researchers may mistakenly attribute characteristics observed in division II strains to the more extensively studied division I B. fragilis. Our findings underscore the necessity of recognizing these divisions as separate species with distinct functions. We unveil new findings of differential gene prevalence between division I and II strains in genes associated with intestinal colonization and survival strategies, potentially influencing their role as gut commensals and their pathogenicity in extraintestinal sites. Despite the significant niche overlap and colonization patterns between these groups, our study highlights the complex dynamics that govern strain distribution and behavior, emphasizing the need for a nuanced understanding of these microorganisms

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes