Nanoformulations of anticancer FGFR inhibitors with improved therapeutic index

Fibroblast growth factor receptor (FGFR) inhibitors like ponatinib and nintedanib are clinically approved for defined cancer patient cohorts but often exert dose-limiting adverse effects. Hence, we encapsulated the FGFR inhibitors ponatinib, PD173074, and nintedanib into polylactic acid nanoparticles and liposomes to enable increased tumor accumulation/specificity and reduce side effects. Different methods of drug loading were tested and the resulting formulations compared regarding average size distribution as well as encapsulation efficiency. Appropriate encapsulation levels were achieved for liposomal preparations only. Nanoencapsulation resulted in significantly decelerated uptake kinetics in vitro with clearly decreased short-term (up to 72?h) cytotoxicity at higher concentrations. However, in long-term clonogenic assays liposomal formations were equally or even more active as compared to the free drugs. Accordingly, in an FGFR inhibitor-sensitive murine osteosarcoma transplantation model (K7M2), only liposomal but not free ponatinib resulted in significant tumor growth inhibition (by 60.4%) at markedly reduced side effects.     

Lipid based nanocarriers: a translational perspective

Over the recent couple of decades, pharmaceutical field has embarked most phenomenal noteworthy achievements in the field of medications as well as drug delivery. The rise of Nanotechnology in this field has reformed the existing drug delivery for targeting, diagnostic, remedial applications and patient monitoring. The convincing usage of nanotechnology in the conveyance of medications that prompts an extension of novel lipid-based nanocarriers and non-liposomal systems has been discussed. Present review deals with the late advances and updates in lipidic nanocarriers, their formulation strategies, challenging aspects, stability profile, clinical applications alongside commercially available products and products under clinical trials. This exploration may give a complete idea viewing the lipid based nanocarriers as a promising choice for the formulation of pharmaceutical products, the challenges looked by the translational process of lipid-based nanocarriers and the combating methodologies to guarantee the headway of these nanocarriers from bench to bedside.     

The Role of Patient–Provider Communication in Engagement and Re-engagement in HIV Treatment in Bamako,Mali: A Qualitative Study

Mounting evidence in sub-Saharan Africa suggests poor patient-provider communication (PPC) negatively impacts patient engagement (retention in care and adherence to medication) in antiretroviral therapy (ART) programs. In Bamako, Mali, where 36% of ART patients are lost to follow-up within 12 months of initiating treatment, we aimed to define features of positive PPC according to patient values and explore the mechanisms by which these features may sustain engagement and re-engagement according to patient and provider experiences. We conducted 33 in-depth interviews and 7 focus groups with 69 patients and 17 providers in five ART clinics. Regarding sustaining engagement, participants highlighted “establishing rapport” as a foundational feature of effective PPC, but also described how “responding to emotional needs”, “eliciting patient conflicts and perspective” and “partnering to mitigate conflicts” functioned to address barriers to engagement and increase connectedness to care. Patients who had disengaged felt that “communicating reacceptance” may have prompted them re-engage sooner and that tailored “partnering to mitigate conflicts” would be more effective in sustaining re-engagement than the standard adherence education providers typically offer. Optimizing provider skills related to these key PPC features may help maximize ART patient engagement, ultimately improving health outcomes and decreasing HIV transmission in sub-Saharan Africa.     

Organizational configuration of hospitals succeeding in attracting and retaining nurses

AIM: This paper contrasts structural and managerial characteristics of low- and high-turnover hospitals, and describes the organizational configuration of attractive hospitals. BACKGROUND: In countries facing nurse shortages and turnover, some hospitals succeed in recruiting and retaining nurses. In Magnet Hospitals, managerial practices and environmental characteristics increase nurses' job satisfaction and their commitment to the organization, which in turn decreases nurse turnover. Such an approach suggests that organizations are best understood as clusters of interconnected structures and practices, i.e. organizational configurations rather than entities whose components can be understood in isolation. METHOD: From a sample of 12 hospitals whose nurse turnover was studied for 1 year, structural and organizational features of hospitals in the first and fourth quartiles, i.e. attractive (turnover <3.1%) vs. conventional (turnover >11.8%) were contrasted. A questionnaire, including perceptions of health-related factors, job demands, stressors, work schedules, organizational climate, and work adjustments antecedent to turnover, was received from 401 nurses working in attractive hospitals (response rate = 53.8%) and 774 nurses in conventional hospitals (response rate = 54.5%). FINDINGS: Structural characteristics did not differentiate attractive and conventional hospitals, but employee perceptions towards the organization differed strikingly. Differences were observed for risk exposure, emotional demands, role ambiguity and conflicts, work-family conflicts, effort-reward imbalance and the meaning of work, all in favour of attractive hospitals (P < 0.001). Relationships with nursing management, work ability and satisfaction with working time, handover shifts and schedules were also better in attractive hospitals (P < 0.001). Job satisfaction and commitment were higher in attractive hospitals, whereas burnout and intention to leave were lower (P < 0.001). CONCLUSION: Organizational characteristics are key factors in nurse attraction and retention. Nurses face difficulties in their work situations, but some hospitals are perceived as healthy organizations. The concept of attractive institutions could serve as a catalyst for improvement in nurses' work environments in Europe.     

Personal resilience as a strategy for surviving and thriving in the face of workplace adversity: a literature review

AIM: This paper is a report of a literature review to explore the concept of personal resilience as a strategy for responding to workplace adversity and to identify strategies to enhance personal resilience in nurses. BACKGROUND: Workplace adversity in nursing is associated with excessive workloads, lack of autonomy, bullying and violence and organizational issues such as restructuring, and has been associated with problems retaining nurses in the workforce. However, despite these difficulties many nurses choose to remain in nursing, and survive and even thrive despite a climate of workplace adversity. DATA SOURCES: The literature CINAHL, EBSCO, Medline and Pubmed databases were searched from 1996 to 2006 using the keywords 'resilience', 'resilience in nursing', and 'workplace adversity' together with 'nursing'. Papers in English were included. FINDINGS: Resilience is the ability of an individual to positively adjust to adversity, and can be applied to building personal strengths in nurses through strategies such as: building positive and nurturing professional relationships; maintaining positivity; developing emotional insight; achieving life balance and spirituality; and, becoming more reflective. CONCLUSION: Our findings suggest that nurses can actively participate in the development and strengthening of their own personal resilience to reduce their vulnerability to workplace adversity and thus improve the overall healthcare setting. We recommend that resilience-building be incorporated into nursing education and that professional support should be encouraged through mentorship programmes outside nurses' immediate working environments.     

Is debridement really the best we can do for periprosthetic joint infections following total ankle replacements? A systematic review and meta-analysis

BackgroundAnkle periprosthetic joint infections are rising in number, but an evidence-based gold standard treatment has not been defined yet.MethodsWe made a systematic review about the operative treatment of infections following total ankle arthroplasty. Proportional meta-analysis was used to summarize effects of the surgical techniques included. Primary outcome of this study was infection eradication, followed by complications, re-interventions, amputation rates and functions.ResultsWe included six studies(113 patients) reporting 6 types of surgical interventions, mostly irrigation and debridement (35.4%) and two-stage revisions (24.8%). No differences among all analyzed techniques were found in the infection eradication outcome as well as in the secondary outcomes. Patients receiving a permanent spacer are most likely to end up with amputation.ConclusionsLiterature dealing with infections after total ankle replacement is currently composed by few low-quality articles. The overlapping of confidence intervals related to all analyzed interventions showed no superiority of either technique.Level of evidenceIII.     

情绪诱发在护理本科生心肺复苏技能教学中的应用

目的 探讨情绪诱发在护理本科生心肺复苏技能教学中的应用效果。 方法 将2018级35名和2019级31名护理本科生分别设为对照组和观察组。对照组在心肺复苏技能教学中采用教师演示、学生练习、教师指导的传统教学模式,观察组在传统教学模式的基础上融入不同主题的情绪诱发内容。 结果 课程结束后即刻、3个月和6个月观察组心肺复苏技能及心肺复苏施救自我效能得分显著优于对照组（均P＜0.05）,随着时间的推移心肺复苏技能得分无显著下降。 结论 情绪诱发融入式教学可有效提高护理本科生的学习投入度,从而提高学习效果,促进心肺复苏技能、心肺复苏施救自我效能的保留。     

胚胎移植术中胚胎滞留的发生及其对妊娠结局的影响

目的了解胚胎移植术中胚胎滞留的发生率并探讨其对妊娠结局的影响。方法回顾性分析2017年1月至2020年12月于我院生殖中心行IVF-ET助孕的1834个周期的临床资料,根据胚胎移植术中是否发生胚胎滞留分为两组,发生胚胎滞留的为胚胎滞留组(n=65),未发生胚胎滞留的为对照组(n=1769),比较两组患者的一般资料和妊娠结局;同时,根据移植管不同污染因素分为4个亚组,即血液污染组、粘液污染组、渣污染组和未见异常组,比较各亚组的妊娠结局。结果两组患者一般资料比较无显著差异(P>0.05);两组间临床妊娠率、种植率、异位妊娠率、流产率和活产率比较均无显著差异(P>0.05);胚胎滞留组移植管被血液、粘液污染的发生率(分别为24.62%、16.92%)均显著高于对照组(分别为14.09%、7.70%)(P<0.05),而未见异常的发生率显著低于对照组(50.77%vs.71.48%,P<0.05)。在发生胚胎滞留的情况下,移植管血液污染亚组的临床妊娠率显著低于粘液污染亚组和移植管未见异常组(12.5%vs.63.64%、54.55%,P<0.05);在未发生胚胎滞留的情况下,移植管血液污染亚组的临床妊娠率显著低于粘液污染亚组(44.58%vs.55.88%,P<0.05)。结论本研究提示胚胎移植中胚胎滞留未显著影响妊娠结局,但与移植管粘液污染相比,血液污染可能对妊娠结局带来更多的负面影响。