Developing a best-practice agenda for music therapy research to support informal carers of terminally ill patients pre- and post-death bereavement: a world café approach.

BACKGROUND: Informal carers of terminally ill patients play a vital role in providing palliative care at home, which impacts on their pre- and post-death bereavement experience and presents an up to 50% greater risk for mental-health problems. However, developing and implementing effective bereavement support remains challenging. There is a need to build the evidence base for music therapy as a potentially promising bereavement support for this vulnerable population. This study aimed to co-design an international best practice agenda for research into music therapy for informal carers of patients pre- and post-death bereavement. METHODS: Online half day workshop using a World Café approach; an innovative method for harnessing group intelligence within a group of international expert stakeholders (music therapy clinicians and academics with experience of music therapy with informal carers at end-of-life). Demographics, experience, key priorities and methodological challenges were gathered during a pre-workshop survey to inform workshop discussions. The online workshop involved four rounds of rotating, 25-minute, small group parallel discussions using Padlet. One final large group discussion involved a consensus building activity. All data were analysed thematically to identify patterns to inform priorities and recommendations. RESULTS: Twenty-two consented and completed the pre-event survey (response rate 44%), from countries representing 10 different time zones. Sixteen participated in the workshop and developed the following best practice agenda. The effectiveness of music therapy in supporting informal carers across the bereavement continuum should be prioritised. This should be done using a mixed methods design to draw on the strengths of different methodological approaches to building the evidence base. It should involve service users throughout and should use a core outcome set to guide the choice of clinically important bereavement outcome measures in efficacy/effectiveness research. CONCLUSIONS: Findings should inform future pre- and post-death bereavement support research for informal caregivers of terminally ill patients. This is an important step in building the evidence base for commissioners and service providers on how to incorporate more innovative approaches in palliative care bereavement services.

Unveiling the Evidence for the Use of Pulses in Managing Type 2 Diabetes Mellitus: A Scoping Review.

Management of type 2 diabetes mellitus (T2DM) is a pressing global healthcare challenge. Innovative strategies that integrate superior medical and nutritional practices are essential for holistic care. As such, pulse consumption is encouraged for its potential benefit in reducing hypercholesterolaemia, dyslipidaemia, and triglyceride levels, as well as enhancing glycaemic control. This scoping review aims to assess the depth of evidence supporting the recommendation for pulse consumption in T2DM management and to identify gaps in the existing literature. We conducted a comprehensive search across the databases MEDLINE, Global Health, EMBASE, CINAHL, Web of Science, and the Cochrane Library (up to July 2023). We included population-based studies of any design, and excluded review-style articles. Articles published in languages other than English were also excluded. From the 2449 studies initially identified, 28 met our inclusion criteria. Acute postprandial trials demonstrated improved glucose responses and enhanced insulin responses to pulse-based intervention. Meanwhile, long-term trials reported meaningful improvements in T2DM indicators such as haemoglobin A1C (HbA1c), fasting glucose, fasting insulin, C-peptide, and markers of insulin resistance like homeostatic model assessment (HOMA). Integrating more pulses into the diets of diabetic individuals might offer an efficient and cost-effective strategy in the global initiative to combat T2DM.

Racial Disparities in Psychiatric Decisional Capacity Consultations.

OBJECTIVE: In this study, the authors examined potential disparities and biases in the placement and outcomes of decisional capacity evaluations across races, controlling for patient characteristics. METHODS: The authors reviewed 181 patient decisional capacity consultations requested for the consultation-liaison psychiatry service at a tertiary care medical center from 2018 to 2019. The racial distribution of patients in these consultations was compared with the racial distribution of hospital inpatient admissions from 2018 to 2019. The authors analyzed patient outcomes by using logistic regression that controlled for race, gender, age, education, primary insurance, type of capacity assessment, and psychiatric diagnosis. RESULTS: Decisional capacity consultations were placed disproportionately for Black (43% of consultations vs. 18% of total admissions) and Hispanic patients (26% of consultations vs. 21% of admissions) compared with White and Asian patients. Among 130 patients with a capacity determination, 95 (53% of total sample) were determined not to have capacity, an outcome that did not differ by race but was more likely to occur among patients diagnosed as having delirium. Sixty-seven patients with no capacity (37% of total sample) experienced a change in treatment, an outcome that was less likely to occur among Hispanic patients in the univariable analysis. CONCLUSIONS: Significant racial disparities were observed during the placement of a decisional capacity consultation. These findings reveal the potential biases introduced with both the initial challenge to a patient's capacity and the subsequent outcomes of the consultation. As such, the balance of risk versus benefit or utility of these consultations in certain populations must be carefully considered.

Moringa oleifera-derived coagulants for water treatment: Floc structure, residual organics, and performance trade-offs.

The study explored the suitability of unfractionated extracts from the seeds of the Moringa oleifera tree as a coagulant for water treatment. The coagulant was obtained by soaking crushed and sieved seeds in a low salinity aqueous solution: a simple and inexpensive alternative to conventional coagulants in settings where specialized expertise and equipment are lacking. The performance of M. oleifera-derived coagulants was quantified in terms of turbidity removal, bacteriophage clearance, concentration of residual organics, as well as meta-parameters such as floc size and fractal dimension. Treating high turbidity clay suspensions at the optimal coagulant dosage (14.7 mg(DOC)/L) and flocculation mixing conditions ([Formula: see text]= 22.4 s-1) removed > 94% of turbidity, similar to that recorded in reference tests with alum. Floc size distribution shifted to larger sizes during the first 10 min of flocculation with no change afterwards, while the floc fractal dimension, [Formula: see text], continued to increase, pointing to the gradual formation of denser ([Formula: see text]= 2.1 to 2.2), more settleable flocs. Preliminary tests with MS2 bacteriophage showed that coagulation with M. oleifera decreased the viable MS2 titre by ~ 1.3 log, which was significantly above the turbidity removal (~ 1 log). The extraction process, however, allowed a large amount of residual organics (> 78% of extracted DOC) into the treated water. Combining the coagulants with downstream filtration and adsorption, employing UV or solar disinfection, or limiting applications to non-potable reuse is suggested for mitigating the concerns related to residual DOC.

No evidence to support the impact of migration background on treatment response rates and cancer survival: a retrospective matched-pair analysis in Germany.

BACKGROUND: Immigration has taken the central stage in world politics, especially in the developed countries like Germany, where the continuous flow of immigrants has been well documented since 1960s. Strikingly, emerging data suggest that migrant patients have a poorer response to the treatment and lower survival rates in their new host country, raising concerns about health disparities. Herein, we present our investigation on the treatment response rate and cancer survival in German patients with and without an immigrant background that were treated at our comprehensive cancer center in Germany. METHODS: Initially, we considered 8162 cancer patients treated at the Center for Integrated Oncology (CIO), University Hospital Bonn, Germany (April 2002-December 2015) for matched-pair analysis. Subsequently, the German patients with a migration background and those from the native German population were manually identified and catalogued using a highly specific name-based algorithm. The clinical parameters such as demographic characteristics, tumor characteristics, defined staging criteria, and primary therapy were further adjusted. Using these stringent criteria, a total of 422 patients (n = 211, Germans with migration background; n = 211, native German population) were screened to compare for the treatment response and survival rates (i.e., 5-year overall survival, progression-free survival, and time to progression). RESULTS: Compared to the cohort with migration background, the cohort without migration background was slightly older (54.9 vs. 57.9 years) while having the same sex distribution (54.5% vs. 55.0% female) and longer follow-up time (36.9 vs. 42.6 months). We did not find significant differences in cancer survival (5-year overall survival, P = 0.771) and the response rates (Overall Remission Rate; McNemar's test, P = 0.346) between both collectives. CONCLUSION: Contrary to prior reports, we found no significant differences in cancer survival between German patients with immigrant background and native German patients. Nevertheless, the advanced treatment protocols implemented at our comprehensive cancer center may possibly account for the low variance in outcome. To conduct similar studies with a broader perspective, we propose that certain risk factors (country-of-origin-specific infections, dietary habits, epigenetics for chronic diseases etc.) should be considered, specially in the future studies that will recruit new arrivals from the 2015 German refugee crisis.

Fragment-Based Covalent Ligand Screening Enables Rapid Discovery of Inhibitors for the RBR E3 Ubiquitin Ligase HOIP.

Modification of proteins with polyubiquitin chains is a key regulatory mechanism to control cellular behavior and alterations in the ubiquitin system are linked to many diseases. Linear (M1-linked) polyubiquitin chains play pivotal roles in several cellular signaling pathways mediating immune and inflammatory responses and apoptotic cell death. These chains are formed by the linear ubiquitin chain assembly complex (LUBAC), a multiprotein E3 ligase that consists of 3 subunits, HOIP, HOIL-1L, and SHARPIN. Herein, we describe the discovery of inhibitors targeting the active site cysteine of the catalytic subunit HOIP using fragment-based covalent ligand screening. We report the synthesis of a diverse library of electrophilic fragments and demonstrate an integrated use of protein LC-MS, biochemical ubiquitination assays, chemical synthesis, and protein crystallography to enable the first structure-based development of covalent inhibitors for an RBR E3 ligase. Furthermore, using cell-based assays and chemoproteomics, we demonstrate that these compounds effectively penetrate mammalian cells to label and inhibit HOIP and NF-κB activation, making them suitable hits for the development of selective probes to study LUBAC biology. Our results illustrate the power of fragment-based covalent ligand screening to discover lead compounds for challenging targets, which holds promise to be a general approach for the development of cell-permeable inhibitors of thioester-forming E3 ubiquitin ligases.

Early experience of implementing a national HIV pre-exposure prophylaxis service in Wales, United Kingdom 2017.

Background Pre-exposure prophylaxis (PrEP) was introduced in Sexual Health Services of the Welsh National Health Service (NHS Wales) in July 2017 as a 3-year pilot service. METHODS: Data were collected through the pre-existing Sexual Health in Wales Surveillance System, to which codes were added to capture PrEP eligibility, outcome of offer of PrEP, reasons for declining and adherence. Eligibility categories were defined based on nationally agreed criteria: men who have sex with men (MSM) and transgender people at high risk of HIV acquisition; partners of HIV-positive individuals not known to be virally suppressed; and heterosexuals reporting condomless intercourse with a HIV-positive individual not known to be virally suppressed. RESULTS: During the first 6 months, 516 people were eligible, 96% of which were MSM. Overall, 57% of those eligible (296/516) started PrEP. Reasons for declining PrEP were given by 88 (56%) of 157 people; 50 (57%) of whom did not believe themselves to be at risk. Of the available adherence assessments, 89% considered that all risk episodes had been covered. Persistence at 3 months was assessed for 141 people, of which 93 (66%) were still using PrEP. There were no HIV diagnoses in people taking PrEP during the first 6 months. Twenty-nine people were diagnosed with 37 episodes of sexually transmissible infections (STIs) while on PrEP. STI incidence was 105.7 per 100 person-years. CONCLUSIONS: The early trend indicates that implementation of PrEP is progressing as planned, and the service has been utilised by clients. This analysis can help refine implementation, inform planning and research around uptake, use and effect in Wales and internationally.

Cost effectiveness of full coverage of the medical management of smoking cessation in France.

OBJECTIVE: To estimate the incremental cost effectiveness of full coverage of the medical management of smoking cessation from the perspective of statutory health insurance (SHI) in France. DESIGN AND POPULATION: Cost-effectiveness analysis based on a Markov state-transition decision analytic model was used to compare full SHI coverage of smoking cessation and actual coverage based on an annual €50 lump sum per insured person among current French smokers aged 15-75 years. We used a scenario approach to take into account the many different behaviours of smokers and the likely variability of SHI policy choices in terms of participation rate and number and frequency of attempts covered. INTERVENTIONS: Drug treatments for smoking cessation combined with six medical consultations including individual counselling. MAIN OUTCOMES MEASURES: The cost effectiveness of full coverage was expressed by the incremental cost-effectiveness ratio (ICER) in 2009 euros per life-year gained (LYG) at the lifetime horizon. RESULTS: The cost effectiveness per LYG for smokers ranged from €1786 to €2012, with an average value of €1911. The minimum value was very close to the maximum value with a difference of only €226. The cost-effectiveness ratio was only minimally sensitive to the participation rate, the number of attempts covered and the cessation rate. CONCLUSIONS: Compared to other health measures in primary and secondary prevention of cardiovascular disease already covered by SHI, full coverage of smoking cessation is the most cost-effective approach.

[N-6 fatty acids and cardiovascular health: dietary intake recommendations]. / Acides gras oméga-6 et maladies cardiovasculaires: recommandations en matière d'apport alimentaire.

Omega-6 polyunsaturated fatty acids (n-6 PUFA) are well known for their critical role in many physiological functions and reduce risks of cardiovascular disease (CVD). However, some argue that excessive consumption of n-6 PUFA may lead to adverse effects on health and therefore recommend reducing dietary n-6 PUFA intake or fixing an upper limit. Epidemiological studies show that n-6 PUFA dietary intake significantly lowers blood LDL-cholesterol levels. In addition, n-6 PUFA intake lower several cardiovascular risk factors such as blood pressure, inflammatory markers, haemostatic parameters and obesity. Data from prospective cohort and interventional studies converge towards a specific protective role of dietary n-6 PUFA intake, in particular linoleic acid, against CVD. In regards to studies examined in this narrative review, recommendation for n-6 PUFA intake above 5%, and ideally about 10% of total energy appears justified for the prevention of ischemic heart disease.

Short-term and medium-term clinical outcomes of quinolone-resistant Campylobacter infection.

BACKGROUND: Campylobacter species is a leading cause of bacterial gastroenteritis worldwide. Quinolone resistance has emerged as an increasing problem among persons with Campylobacter infection over the past decade, but the clinical consequences are unclear. METHODS: A case-comparison study of patients infected with ciprofloxacin-resistant or ciprofloxacin-susceptible Campylobacter species was conducted in Wales during the period 2003-2004. Campylobacter isolates were classified as resistant or susceptible to ciprofloxacin on the basis of standardized disk diffusion methods. Participants were interviewed by telephone at the time of illness, 3 months later, and 6 months later to compare disease severity, duration of illness, and medium-term clinical outcomes. RESULTS: There was no difference between 145 persons with ciprofloxacin-resistant infection and 411 with ciprofloxacin-susceptible infection with regard to the severity or duration of acute illness. Mean duration of diarrhea was similar in patients with ciprofloxacin-resistant versus ciprofloxacin-susceptible infection (8.2 vs. 8.6 days; P = .57) and did not alter significantly after adjustment for potential covariates, including age, underlying disease, foreign travel, use of antidiarrheal medication, and use of antimicrobials in a multiple linear regression model. There was no difference between case patients and comparison patients in the frequency of reported symptoms or in general practitioner consultation rates at either the 3-month or the 6-month follow-up interview. CONCLUSIONS: In this study, there was no evidence of more-severe or prolonged illness in participants with quinolone-resistant Campylobacter infection, nor was there evidence of any adverse medium-term consequences. This suggests that the clinical significance of quinolone resistance in Campylobacter infection may have been overestimated.

Reactive oxygen species-mediated beta-cleavage of the prion protein in the cellular response to oxidative stress.

The cellular prion protein (PrP(C)) is critical for the development of prion diseases. However, the physiological role of PrP(C) is less clear, although a role in the cellular resistance to oxidative stress has been proposed. PrP(C) is cleaved at the end of the copper-binding octapeptide repeats through the action of reactive oxygen species (ROS), a process termed beta-cleavage. Here we show that ROS-mediated beta-cleavage of cell surface PrP(C) occurs within minutes and was inhibited by the hydroxyl radical quencher dimethyl sulfoxide and by an antibody against the octapeptide repeats. A construct of PrP lacking the octapeptide repeats, PrPDeltaoct, failed to undergo ROS-mediated beta-cleavage, as did two mutant forms of PrP, PG14 and A116V, associated with human prion diseases. As compared with cells expressing wild type PrP, when challenged with H2O2 and Cu2+, cells expressing PrPdeltaoct, PG14, or A116V had reduced viability and glutathione peroxidase activity and increased intracellular free radicals. Thus, lack of ROS-mediated beta-cleavage of PrP correlated with the sensitivity of the cells to oxidative stress. These data indicate that the beta-cleavage of PrP(C) is an early and critical event in the mechanism by which PrP protects cells against oxidative stress.