Interventions for behavioral health comorbidities in the hospice setting: a scoping review.

BACKGROUND: Behavioral health (BH) comorbidities in hospice patients are widespread and impact important outcomes, including symptom burden, quality of life, and caregiver wellbeing. However, evidencebased BH interventions tailored for the hospice setting remain understudied. METHODS: We conducted a scoping review with the objective of mapping studies of interventions for BH comorbidities in the hospice setting. We included empirical studies among hospice patients of interventions with BH outcomes. We abstracted data on study design, intervention type, and patient characteristics. RESULTS: Our search generated 7,672 unique results, of which 37 were ultimately included in our analysis. Studies represented 16 regions, with the United Kingdom (n=13) most represented. The most frequent intervention type was complementary and alternative interventions (n=13), followed by psychotherapeutic interventions (n=12). Most of the studies were either pilot or feasibility investigations. Fifteen studies employed a randomized controlled trial design. The most frequently utilized measurement tools for BH outcomes included the Hospital Anxiety and Depression Scale and the Edmonton Symptom Assessment Scale. Seventeen studies demonstrated statistically significant results in a BH outcome measure. BH conditions prevalent among hospice patients that were the focus of intervention efforts included depression symptoms, anxiety symptoms, and general psychological distress. No study focused on trauma-related disorders or substance use disorders. CONCLUSIONS: This scoping review reveals a concerning gap in research regarding evidence-based BH interventions in hospice settings, especially in the U.S. Despite extensive utilization of hospice care services and the high prevalence of BH conditions among hospice patients, randomized controlled trials focused on improving BH outcomes remain scant. The current BH practices, like the widespread use of benzodiazepines and antipsychotics, may not be rooted in robust evidence, underscoring an urgent need for investment in hospice research infrastructure and tailored clinical trials to test behavioral approaches to mitigate mental health outcomes at the end of life.

The QseB response regulator imparts tolerance to positively charged antibiotics by controlling metabolism and minor changes to LPS.

The modification of lipopolysaccharide (LPS) in Escherichia coli and Salmonella spp. is primarily controlled by the two-component system PmrAB. LPS modification allows bacteria to avoid killing by positively charged antibiotics like polymyxin B (PMB). We previously demonstrated that in uropathogenic E. coli (UPEC), the sensor histidine kinase PmrB also activates a non-cognate transcription factor, QseB, and this activation somehow augments PMB tolerance in UPEC. Here, we demonstrate-for the first time-that in the absence of the canonical LPS transcriptional regulator, PmrA, QseB can direct some modifications on the LPS. In agreement with this observation, transcriptional profiling analyses demonstrate regulatory overlaps between PmrA and QseB in terms of regulating LPS modification genes. However, both PmrA and QseB must be present for UPEC to mount robust tolerance to PMB. Transcriptional and metabolomic analyses also reveal that QseB transcriptionally regulates the metabolism of glutamate and 2-oxoglutarate, which are consumed and produced during the modification of lipid A. We show that deletion of qseB alters glutamate levels in the bacterial cells. The qseB deletion mutant, which is susceptible to positively charged antibiotics, is rescued by exogenous addition of 2-oxoglutarate. These findings uncover a previously unknown mechanism of metabolic control of antibiotic tolerance that may be contributing to antibiotic treatment failure in the clinic. IMPORTANCE Although antibiotic prescriptions are guided by well-established susceptibility testing methods, antibiotic treatments oftentimes fail. The presented work is significant because it uncovers a mechanism by which bacteria transiently avoid killing by antibiotics. This mechanism involves two closely related transcription factors, PmrA and QseB, which are conserved across Enterobacterales. We demonstrate that PmrA and QseB share regulatory targets in lipid A modification pathway and prove that QseB can orchestrate modifications of lipid A in Escherichia coli in the absence of PmrA. Finally, we show that QseB controls glutamate metabolism during the antibiotic response. These results suggest that rewiring of QseB-mediated metabolic genes could lead to stable antibiotic resistance in subpopulations within the host, thereby contributing to antibiotic treatment failure.

SARS-CoV-2 vaccination, booster, and infection in pregnant population enhances passive immunity in neonates.

The effects of heterogeneous infection, vaccination and boosting histories prior to and during pregnancy have not been extensively studied and are likely important for protection of neonates. We measure levels of spike binding antibodies in 4600 patients and their neonates with different vaccination statuses, with and without history of SARS-CoV-2 infection. We investigate neutralizing antibody activity against different SARS-CoV-2 variant pseudotypes in a subset of 259 patients and determined correlation between IgG levels and variant neutralizing activity. We further study the ability of maternal antibody and neutralizing measurements to predict neutralizing antibody activity in the umbilical cord blood of neonates. In this work, we show SARS-CoV-2 vaccination and boosting, especially in the setting of previous infection, leads to significant increases in antibody levels and neutralizing activity even against the recent omicron BA.1 and BA.5 variants in both pregnant patients and their neonates.

The QseB response regulator imparts tolerance to positively charged antibiotics by controlling metabolism and minor changes to LPS.

The modification of lipopolysaccharide (LPS) in Escherichia coli and Salmonella spp . is primarily controlled by the two-component system PmrAB. LPS modification allows bacteria to avoid killing by positively charged antibiotics like polymyxin B. We previously demonstrated that in uropathogenic E. coli (UPEC), the sensor histidine kinase PmrB also activates a non-cognate transcription factor, QseB, and this activation somehow augments polymyxin B tolerance in UPEC. Here, we demonstrate - for the first time - that in the absence of the canonical LPS transcriptional regulator, PmrA, QseB can direct some modifications on the LPS. In agreement with this observation, transcriptional profiling analyses demonstrate regulatory overlaps between PmrA and QseB in terms of regulating LPS modification genes. However, both PmrA and QseB must be present for UPEC to mount robust tolerance to polymyxin B. Transcriptional and metabolomic analyses also reveal that QseB transcriptionally regulates the metabolism of glutamate and 2-oxoglutarate, which are consumed and produced during the modification of lipid A. We show that deletion of qseB alters glutamate levels in the bacterial cells. The qseB deletion mutant, which is susceptible to positively charged antibiotics, is rescued by exogenous addition of 2-oxoglutarate. These findings uncover a previously unknown mechanism of metabolic control of antibiotic tolerance that may be contributing to antibiotic treatment failure in the clinic. IMPORTANCE: Although antibiotic prescriptions are guided by well-established susceptibility testing methods, antibiotic treatments oftentimes fail. The presented work is significant, because it uncovers a mechanism by which bacteria transiently avoid killing by antibiotics. This mechanism involves two closely related transcription factors, PmrA and QseB, which are conserved across Enterobacteriaceae. We demonstrate that PmrA and QseB share regulatory targets in lipid A modification pathway and prove that QseB can orchestrate modifications of lipid A in E. coli in the absence of PmrA. Finally, we show that QseB controls glutamate metabolism during the antibiotic response. These results suggest that rewiring of QseB-mediated metabolic genes can lead to stable antibiotic resistance in subpopulations within the host, thereby contributing to antibiotic treatment failure.