Stakeholder collaboration in long-term care of older people in Lithuania

Demographic situation, changes in the role of women in society and growing demand for long-term care (LTC) of older people have challenged the ability to meet the growing LTC needs in most developed countries. In countries where responsibility for LTC is still largely laid on families, it is, however, even more critical and calls for improvements in formal LTC systems. More intensive stakeholder collaboration in LTC policy development, organising and delivery are of primary importance in improving LTC systems. Such collaboration, however, is not always successful; thus, it is critical to understand what makes it effective and efficient. In this paper, we specifically look into multistakeholder collaboration in LTC in Lithuania, one of the fastest ageing countries in the EU, with the demand for LTC services growing fast and exceeding the supply despite rising business and NGO engagement. To determine facilitators of such collaboration, we build on the data obtained through eight focus group discussions with all key stakeholder representatives (LTC policymakers, organisers and service providers [public, private and NGOs], 54 participants in total). Our findings indicate that in addition to national and organisational level facilitators studied in prior research, there are important individual level factors, such as meaningfulness at work, concern and care for others, possibility for personal growth and development, satisfaction with supervision, a sense of belonging and role clarity. On the other hand, our results show that collaboration is constrained by a shortage of human resources, increased workload caused by growing LTC demand, bureaucratic requirements, legal restrictions, lack of awareness of LTC service availability among elder persons, and prevailing social norms and attitudes to institutionalised care. Interestingly, a lack of financial resources is not perceived as a major constraint.     

The role of extra-hepatic bile duct resection in the surgical management of gallbladder carcinoma. A first meta-analysis

ObjectiveTo systematically evaluate the clinicopathological and prognostic value of extra-hepatic bile duct resection (EHBDR) in the surgical management of patients with gallbladder carcinoma (GBC), especially in non-jaundiced patients.MethodsPubMed, EMBASE and the Cochrane Library were searched up to March 1^st 2021 for comparative studies between bile duct resected and non-resected groups. RevMan5.3 and Stata 13.0 software were used for the statistical analyses.ResultsEHBDR did not correlate with a better overall survival (OS) (P = 0.17) or disease-free survival (P = 0.27). No survival benefit was also observed in patients with T2N1 (P = 0.4), T3N0 (P = 0.14) disease and node-positive patients (P = 0.75), rather, EHBDR was even harmful for patients with T2N0 (P = 0.01) and node-negative disease (P = 0.02). Significantly higher incidences of recurrent disease (P = 0.0007), postoperative complications (P < 0.00001) and positive margins (P = 0.02) were detected in the bile duct-resected group. The duration of postoperative hospital stay between the two groups was comparable (P = 0.58). Selection bias was also detected in our analysis that a significantly higher proportion of advanced lesions with T3-4 or III-IV disease was observed in the bile duct-resected group (P < 0.00001). EHBDR only contributed to a greater lymph yield (P = 0.01).ConclusionEHBDR has no survival advantage for patients with GBC, especially for those with non-jaundiced disease. Considering the unfairness of comparing OS between jaundiced patients receiving EHBDR with non-jaundiced patients without EHBDR, we could only conclude that routine EHBDR in non-jaundiced patients is not recommended and future well-designed studies with more specific subgroup analyses are required for further validation.     

Marmoset cytochrome P450 2B6, a propofol hydroxylase expressed in liver

1. The common marmoset (Callithrix jacchus) is a useful experimental animal to evaluate the pharmacokinetics of drug candidates. Cytochrome P450 (P450) 2B enzyme in marmoset livers has been identified; however, only limited information on the enzymatic properties and distribution has been available.

2. Marmoset P450 2B6 amino acids showed high sequence identities (>86%) with those of primates including humans and cynomolgus monkeys. Phylogenetic analysis using amino acid sequences indicated that marmoset P450 2B6 was closer to human and cynomolgus monkey P450 2B6 than to P450 2B orthologs of other species, including pigs, dogs, rabbits and rodents.

3. Quantitative polymerase chain reaction analysis using specific primers showed P450 2B6 mRNA predominantly expressed in livers among the five marmoset tissues, similar to those of humans and cynomolgus monkeys.

4. Marmoset P450 2B6 heterologously expressed in Escherichia coli membranes oxidized 7-ethoxycoumarin, pentoxyresorufin, propofol and testosterone, at roughly similar rates to those of humans and/or cynomolgus monkeys. A high capacity of marmoset P450 2B6 with propofol 4-hydroxylation (at low ionic strength conditions) with a low K_m value was relatively comparable to that for marmoset livers.

5. These results collectively indicated a high propofol 4-hydroxylation activity of P450 2B6 expressed in marmoset livers.

     

Trends in HIV sexual prevention: Attitudinal beliefs and behavioral intention in Spanish young people over the past two decades (1999–2020)

Despite preventive efforts, HIV exposure is still a concern for public health. The current prevalence is related to unsafe sex, which is based on socio-cognitive variables. Therefore, information about these variables is required to verify whether the past preventive strategies have been effective and improve the future ones. However, there is not updated information to adjust future preventive interventions. For this reason, this study analyzes trends by gender in Spanish young people over the past two decades in perceived susceptibility to HIV, severity perceived to HIV, condom confidence and the intention of condom use, from 1999 to 2020. For this purpose, 11,665 Spanish young people (from 17 to 40 years old) completed the AIDS Prevention Questionnaire in each year. Following our results, in general, the socio-cognitive variables have revealed an unsatisfactory trend: a low perceived susceptibility to HIV and a behavioral intention that have remained stable or even declined slightly over the past years. Particularly, men are more likely to report a riskier level in socio-cognitive variables although, in the latest evaluations, women would decrease condom use intention largely than men. In general, regarding age, young adult would report better levels of condom confidence, but early youth would get higher results in perceived severity, as well as better scores in the latest evaluations of condom use intention. Considering these results, policies should make an effort in HIV prevention programs, and emphasize the attention to attitudinal beliefs and behavioral intention to improve their effectiveness.     

Immunisation with the BCG and DTPw vaccines induces different programs of trained immunity in mice

In addition to providing pathogen-specific immunity, vaccines can also confer nonspecific effects (NSEs) on mortality and morbidity unrelated to the targeted disease. Immunisation with live vaccines, such as the BCG vaccine, has generally been associated with significantly reduced all-cause infant mortality. In contrast, some inactivated vaccines, such as the diphtheria, tetanus, whole-cell pertussis (DTPw) vaccine, have been controversially associated with increased all-cause mortality especially in female infants in high-mortality settings. The NSEs associated with BCG have been attributed, in part, to the induction of trained immunity, an epigenetic and metabolic reprograming of innate immune cells, increasing their responsiveness to subsequent microbial encounters. Whether non-live vaccines such as DTPw induce trained immunity is currently poorly understood. Here, we report that immunisation of mice with DTPw induced a unique program of trained immunity in comparison to BCG immunised mice. Altered monocyte and DC cytokine responses were evident in DTPw immunised mice even months after vaccination. Furthermore, splenic cDCs from DTPw immunised mice had altered chromatin accessibility at loci involved in immunity and metabolism, suggesting that these changes were epigenetically mediated. Interestingly, changing the order in which the BCG and DTPw vaccines were co-administered to mice altered subsequent trained immune responses. Given these differences in trained immunity, we also assessed whether administration of these vaccines altered susceptibility to sepsis in two different mouse models. Immunisation with either BCG or a DTPw-containing vaccine prior to the induction of sepsis did not significantly alter survival. Further studies are now needed to more fully investigate the potential consequences of DTPw induced trained immunity in different contexts and to assess whether other non-live vaccines also induce similar changes.