Pharmacotherapy in the heart transplant recipient: A primer for nurse clinicians and pharmacists.

Heart transplantation (HT) is the definitive treatment for eligible patients with end-stage heart disease. A major complication of HT is allograft rejection which can lead to graft dysfunction and death. The guiding principle of chronic immunosuppression therapy is to prevent rejection of the transplanted organ while avoiding oversuppression of the immune system, which can cause opportunistic infections and malignancy. The purpose of this review is to describe immunosuppressive management of the HT recipient-including agent-specific pharmacology and pharmacokinetics, outcomes data, adverse effects, clinical considerations, and recent guideline updates. We will also provide recommendations for medical prophylaxis of immunosuppressed patients based on the most recent clinical guidelines. Additionally, we highlight the importance of medical therapy adherence and the effect of social determinants of health on the long-term management of HT. HT recipients are a complex and high-risk population. The objective of this review is to describe basic pharmacotherapy in HT and implications for nurses and pharmacists.

Prolonged travel time to transplantation center is associated with poor outcomes following heart transplantation.

BACKGROUND: This study aims to examine the impact of home-to-transplantation center travel time as a potential barrier to healthcare accessibility. METHODS: Observational study examined adult heart transplant recipients who received a graft between 2012 and 2022 in the United States. Travel time was calculated using the Google Distance Matrix API between the recipient's residence and transplantation center. A multivariable parametric survival model was fitted to minimize confounding bias. RESULTS: Among the 25,923 recipients that met the selection criteria, the median travel time was 51 â€‹min and 95 â€‹% of recipients lived within a 5-h radius of their center. White recipients experienced longer median travel times (62 â€‹min, p â€‹< â€‹0.001) compared to Black (36 â€‹min) or Hispanic (40 â€‹min) recipients. A travel time of 1-2 â€‹h (survival time ratio [STR] 0.867, p â€‹= â€‹0.035) or >2 â€‹h (STR 0.873, p â€‹= â€‹0.026) away from the transplantation center was independently associated with lower long-term survival rates. CONCLUSION: Extended travel times to transplantation centers may negatively impact long-term survival outcomes for heart transplant recipients, suggesting the need to address this potential barrier to healthcare accessibility.

Mental health services implementation in Colombia-A systematic review.

Colombia's mental health services have a complex history shaped by 60 years of armed conflict, a predominantly clinical approach to mental health, and social factors such as inequities and stigma. The 1990 Caracas declaration proposed a shift towards decentralised community mental health services and interventions based on the recovery approach and emphasis on social determinants of mental health in the Americas. Colombia has adopted these approaches in its legal and practical framework in recent years, but implementation has been uneven. This systematic review aims to contribute to mental health services understanding in Colombia by examining the barriers and facilitators to the implementation of mental health services in Colombia. A search was conducted to explore available peer-reviewed studies on Colombian mental health services across five databases (Medline, PubMed, Scopus, Scielo and BVS) on quantitative and qualitative research papers published in the last ten years and without language restrictions. The Consolidated Framework for Implementation Research (CFIR) was used to structure the analysis and identify barriers and facilitators during the implementation of mental health services. We adapted the CFIR to attend to gender, race and age informed by the Socio-Political Economy of Global Mental Health framework, given the importance of these factors to the Colombian health landscape. Finally, narrative synthesis was used to summarise the data. 1 530 records were identified, and 12 articles met all inclusion criteria and were included in the analysis. 8 papers described substance use disorders services, 11 involved multidisciplinary healthcare professionals, and 7 were implemented at a local scale. The primary barriers to implementation were the lack of coordination, high workloads, and low funding. Facilitators included the use of protocols, and the involvement of communities, stakeholders, users, and external champions. Findings suggest the continued importance of community and recovery approaches and efforts to improve coordination between multi-sector actors involved in the mental health spaces (e.g., public, and private organisations, users and their families).

Think global, act local: using a translocal approach to understand community-based organisations' responses to planetary health crises during COVID-19.

Little is known on how community-based responses to planetary health crises, such as the COVID-19 pandemic, can integrate concerns about livelihoods, equity, health, wellbeing, and the environment. We used a translocal learning approach to co-develop insights on community-based responses to complex health and environmental and economic crises with leaders from five organisations working with communities at the front line of intersecting planetary health challenges in Finland, India, Kenya, Peru, and the USA. Translocal learning supports collective knowledge production across different localities in ways that value local perspectives but transcend national boundaries. There were three main findings from the translocal learning process. First, thanks to their proximity to the communities they served, community-based organisations (CBOs) can quickly identify the ways in which COVID-19 might worsen existing social and health inequities. Second, localised CBO actions are key to supporting communities with unique challenges in the face of systemic planetary health crises. Third, CBOs can develop rights-based, ecologically-minded actions responding to local priorities and mobilising available resources. Our findings show how solutions to planetary health might come from small-scale community initiatives that are well connected within and across contexts. Locally-focused globally-aware actions should be harnessed through greater recognition, funding, and networking opportunities. Globally, planetary health initiatives should be supported by applying the principles of subsidiarity and translocalism.

Calcitriol protects against reductions in striatal serotonin in rats treated with neurotoxic doses of methamphetamine.

The present experiments were designed to examine the ability of calcitriol to protect against methamphetamine (METH)-induced reductions in striatal serotonin (5-HT) release and content. Male Fischer-344 rats were administered vehicle or calcitriol (0.3, 1.0, or 3.0 µg/kg, s.c.) once a day for 8 consecutive days. After the seventh day of treatment the animals were given METH (5 mg/kg, s.c.) or saline 4 times in 1 day at 2 h intervals. Seven days after the METH or saline treatments in vivo microdialysis experiments were conducted to measure potassium and d-amphetamine evoked overflow of 5-HT from the striatum. In animals treated with vehicle and METH there were significant reductions in both potassium and d-amphetamine evoked overflow of 5-HT. The 1.0 and 3.0 µg/kg/day doses of calcitriol provided significant protection against the 5-HT depleting effects of METH. A similar pattern of neuroprotection was found for post-mortem tissue levels of 5-HT. The calcitriol treatments did not prevent hyperthermia during the multiple injections of METH, indicating that the protective effects of calcitriol are not due to prevention of METH-induced increases in body temperature. These results suggest that calcitriol can provide significant protection against the 5-HT depleting effects of neurotoxic doses of METH.

Association of COVID-19 Vaccination With Risk of COVID-19 Infection, Hospitalization, and Death in Heart Transplant Recipients.

Importance: Orthotopic heart transplant (OHT) recipients are at increased risk for morbidity and mortality after SARS-CoV-2 infection. Although antibody response to COVID-19 vaccination is lower in solid organ transplant recipients, there has been no study assessing the safety and effectiveness of COVID-19 vaccination in OHT recipients. Objective: To assess the safety and effectiveness of COVID-19 vaccination and associations with SARS-CoV-2 infection and clinical outcomes in a large population of adult OHT recipients. Design, Setting, and Participants: This case-control study examined data from a US heart transplant program at a single center for all adult recipients of OHT who were followed up from January 15, 2021, through January 31, 2022. Main Outcomes and Measures: The primary outcome was number of SARS-CoV-2 infections and related hospitalizations, intensive care unit (ICU) admissions, and deaths between vaccinated vs unvaccinated adult recipients of OHT. Results: A total of 436 patients who received OHT were included in the study, of which 106 patients were infected with COVID-19. The mean (SD) age was 54 (17) years; 303 (69.5%) were men and 133 (30.5%) were women. There were 366 patients in the vaccinated cohort with 72 COVID-19 infections (19.7%), 15 hospitalizations (4.1%), 4 ICU admissions (1.1%), and 3 deaths (0.8%). There were 70 patients in the unvaccinated cohort with 34 COVID-19 infections (48.6%), 10 hospitalizations (14.3%), 3 ICU admissions (4.3%), and 3 deaths (4.3%). COVID-19 vaccination was associated with a lower risk of COVID-19 infection (risk ratio [RR], 0.41; 95% CI, 0.30-0.56), hospitalization (RR, 0.29; 95% CI, 0.14-0.61), and death (RR, 0.19; 95% CI, 0.05-0.82). Among the 366 vaccinated OHT recipients, there was no echocardiographic evidence of graft dysfunction, clinically significant rejection, or allosensitization at 6 months after they received the COVID-19 vaccine. Conclusions and Relevance: Patients with OHT who are infected with SARS-CoV-2 are at greater risk of severe infection and death compared with immunocompetent individuals. COVID-19 vaccination was associated with fewer COVID-19 infections, hospitalizations, and deaths, with no heart transplant-specific adverse events. COVID-19 vaccination for all OHT recipients is of paramount importance.

Age-related changes in oral sensitivity, taste and smell.

Oropharyngeal sensitivity plays a vital role in the initiation of the swallowing reflex and is thought to decline as part of the aging-process. Taste and smell functions appear to decline with age as well. The aim of our study was to generate data of oral sensitivity in healthy participants for future studies and to analyse age-related changes and their interdependence by measuring oral sensitivity, taste, and smell function. The experiment involved 30 participants younger than and 30 participants older than 60. Sensitivity threshold as a surrogate of oral sensitivity was measured at the anterior faucial pillar by electrical stimulation using commercially available pudendal electrode mounted on a gloved finger. Smell and taste were evaluated using commercially available test kits. Mean sensitivity was lower in young participants compared to older participants (1.9 ± 0.59 mA vs. 2.42 ± 1.03 mA; p = 0.021). Young participants also performed better in smell (Score 11.13 ± 0.86 vs 9.3 ± 1.93; p < 0.001) and taste examinations (Score 11.83 ± 1.86 vs 8.53 ± 3.18; p < 0.001). ANCOVA revealed a statistical association between sensitivity and smell (p = 0.08) that was moderated by age (p = 0.044). Electrical threshold testing at the anterior faucial pillar is a simple, safe, and accurate diagnostic measure of oral sensitivity. We detected a decline of oral sensitivity, taste, and smell in older adults.Trial registration: Clinicaltrials.gov, NCT03240965. Registered 7th August 2017- https://clinicaltrials.gov/ct2/show/NCT03240965 .

Synthesising the shifting terminology of community health: A critiquing review of agent-based approaches.

The field of community health promotion encompasses a wide range of approaches, including bottom-up approaches that recognise and build on the agency and strengths of communities to define and pursue their health goals. Momentum towards agent-based approaches to community health promotion has grown in recent years, and several related but distinct conceptual and methodological bodies of work have developed largely in isolation from each other. The lack of a cohesive collection of research, practice, and policy has made it difficult to learn from the innovations, best practices, and shortcomings of these approaches, which is exacerbated by the imprecise and inconsistent use of related terms. This article provides a review of three agent-based approaches to promoting community health: asset-based approaches, capacity building, and capabilities approaches, noting the theoretical origins and fundamental concepts, applications and methodologies, and limitations and critiques of each. This article discusses their commonalities and differences in terms of how they conceptualise and approach the promotion of community health, including a critical consideration of their limitations and where they may prove to be counterproductive. This article argues that agent-based approaches to community health must be met with meaningful opportunities to disengage from the structures that constrain their health.

Toward resourcefulness: pathways for community positive health.

Communities are powerful and necessary agents for defining and pursuing their health, but outside organizations often adopt community health promotion approaches that are patronizing and top-down. Conversely, bottom-up approaches that build on and mobilize community health assets are often critiqued for tasking the most vulnerable and marginalized communities to use their own limited resources without real opportunities for change. Taking into consideration these community health promotion shortcomings, this article asks how communities may be most effectively and appropriately supported in pursuing their health. This article reviews how community health is understood, moving from negative to positive conceptualizations; how it is determined, moving from a risk-factor orientation to social determination; and how it is promoted, moving from top-down to bottom-up approaches. Building on these understandings, we offer the concept of 'resourcefulness' as an approach to strengthen positive health for communities, and we discuss how it engages with three interrelated tensions in community health promotion: resources and sustainability, interdependence and autonomy, and community diversity and inclusion. We make practical suggestions for outside organizations to apply resourcefulness as a process-based, place-based, and relational approach to community health promotion, arguing that resourcefulness can forge new pathways to sustainable and self-sustaining community positive health.

Hypoxic Processes Induce Complement Activation via Classical Pathway in Porcine Neuroretinas.

Considering the fact that many retinal diseases are yet to be cured, the pathomechanisms of these multifactorial diseases need to be investigated in more detail. Among others, oxidative stress and hypoxia are pathomechanisms that take place in retinal diseases, such as glaucoma, age-related macular degeneration, or diabetic retinopathy. In consideration of these diseases, it is also evidenced that the immune system, including the complement system and its activation, plays an important role. Suitable models to investigate neuroretinal diseases are organ cultures of porcine retina. Based on an established model, the role of the complement system was studied after the induction of oxidative stress or hypoxia. Both stressors led to a loss of retinal ganglion cells (RGCs) accompanied by apoptosis. Hypoxia activated the complement system as noted by higher C3+ and MAC+ cell numbers. In this model, activation of the complement cascade occurred via the classical pathway and the number of C1q+ microglia was increased. In oxidative stressed retinas, the complement system had no consideration, but strong inflammation took place, with elevated TNF, IL6, and IL8 mRNA expression levels. Together, this study shows that hypoxia and oxidative stress induce different mechanisms in the porcine retina inducing either the immune response or an inflammation. Our findings support the thesis that the immune system is involved in the development of retinal diseases. Furthermore, this study is evidence that both approaches seem suitable models to investigate undergoing pathomechanisms of several neuroretinal diseases.

Delivering the Promise of Sendai Framework for Disaster Risk Reduction in Fragile and Conflict-Affected Contexts (FCAC): A Case Study of the NGO GOAL's Response to the Syria Conflict.

The Sendai Framework for Disaster Risk Reduction (SFDRR) has helped to reduce global disaster risk, but there has been a lack of progress in disaster risk reduction (DRR) for people living in fragile and conflict affected contexts (FCAC). Given the mounting evidence that DRR cannot be implemented through conventional approaches in FCAC, serious efforts must be made to understand how to meet SFDRR's goals. This paper offers a case study of international non-governmental organization GOAL's programming that responds to the protracted crisis in Syria, with critical discussion on SFDRR and how to adapt humanitarian relief and disaster resilience.

Facilitation of oral sensitivity by electrical stimulation of the faucial pillars.

Dysphagia is common in neurological disease. However, our understanding of swallowing and its central nervous control is limited. Sensory information plays a vital role in the initiation of the swallowing reflex and is often reduced in stroke patients. We hypothesized that the sensitivity threshold of the anterior faucial pillar could be facilitated by either electrical stimulation (ES) or taste and smell information. The sensitivity threshold was measured by ES in the anterior faucial pillar region. The measurement was repeated 5 min after baseline. Thirty minutes after baseline, the participants underwent a test for taste and smell. Immediately after the test, the ES was repeated. Thirty healthy volunteers with a mean age of 27 ± 5.1 participated in the trial. Mean sensitivity threshold at baseline was 1.9 ± 0.59 mA. The values 5 min after baseline (1.74 ± 0.56 mA, p = 0.027) and 30 min after baseline (1.67 ± 0.58 mA, p = 0.011) were significantly lower compared to the baseline, but there was no difference between the latter (p = 0.321). After 5 min, a potentially facilitating effect was found on oral sensitivity by ES of the faucial pillar area. Thirty minutes later, this effect was still present.Trial registration Clinicaltrials.gov, NCT03240965. Registered 7th August 2017- https://clinicaltrials.gov/ct2/show/NCT03240965 .

Terra incognita: the contribution of disaster risk reduction in unpacking the sustainability-peace nexus.

The pursuit of sustainable development in the context of global environmental change requires enhanced capability to deal with changing hazard profiles, across scales and geographies. Humans attempt to manage human and natural systems interactions in ways that minimize disaster risks, and the political expression of this ambition is the Sendai Framework for Disaster Risk Reduction 2015-2030 ('Sendai Framework'). These efforts lay the foundation for sustainable development, as since the onset of the Sendai Framework, the policy objective of disaster risk reduction has been explicitly linked to global progress on the Sustainable Development Goals. Separately, peace is a focal point of SDG 16, and widely regarded as foundational to attainment of all SDGs. Meanwhile in academic and policy arenas throughout the 2000s, evidence attests of the amplifying negative impact of climate-related disaster events on increasing violent conflict. What remains underexplored are questions of whether and how effective management of human and natural systems interaction, through disaster risk reduction, can contribute towards conditions of peace through peacebuilding. This paper explores how delivery of the Sendai Framework is necessary for sustainability, and potentially also for peace. In the context of the sustainability-peace nexus, the contribution of disaster risk reduction is terra incognita. This paper aims to deepen understanding of those under-researched tripartite links.

Reduced Retinal Degeneration in an Oxidative Stress Organ Culture Model through an iNOS-Inhibitor.

In retinal organ cultures, H2O2 can be used to simulate oxidative stress, which plays a role in the development of several retinal diseases including glaucoma. We investigated whether processes underlying oxidative stress can be prevented in retinal organ cultures by an inducible nitric oxide synthase (iNOS)-inhibitor. To this end, porcine retinal explants were cultivated for four and eight days. Oxidative stress was induced via 300 µM H2O2 on day one for three hours. Treatment with the iNOS-inhibitor 1400 W was applied simultaneously, remaining for 72 h. Retinal ganglion cells (RGC), bipolar and amacrine cells, apoptosis, autophagy, and hypoxia were evaluated immunohistologically and by RT-qPCR. Additionally, RGC morphology was analyzed via transmission electron microscopy. H2O2-induced RGCs loss after four days was prevented by the iNOS-inhibitor. Additionally, electron microscopy revealed a preservation from oxidative stress in iNOS-inhibitor treated retinas at four and eight days. A late rescue of bipolar cells was seen in iNOS-inhibitor treated retinas after eight days. Hypoxic stress and apoptosis almost reached the control situation after iNOS-inhibitor treatment, especially after four days. In sum, the iNOS-inhibitor was able to prevent strong H2O-induced degeneration in porcine retinas. Hence, this inhibitor seems to be a promising treatment option for retinal diseases.

Hennepin County Adult Detention Center's Response to a 2019 Hepatitis A Outbreak in Minnesota.

Hennepin County Adult Detention Center (Jail) is Minnesota's largest jail. In August 2019, the Minnesota Department of Health declared a statewide hepatitis A outbreak. Within three days, Hennepin County Jail Health Services made significant changes to vaccination protocols that increased vaccination rates from 0.6% to 7.1% among detainees, who have a greater risk of contracting hepatitis A. We highlight the opportunity for jails to develop sustainable public health interventions in the setting of community outbreaks.

Bariatric Surgery Is Associated With Decreased Calcineurin Inhibitor Time in Therapeutic Range After Heart Transplantation.

Bariatric surgery (BSg) is an effective treatment for morbid obesity, but little is known about the outcomes of BSg patients who undergo orthotopic heart transplantation (OHT). The aim of this study was to determine if BSg alters calcineurin inhibitor (CNI) level variability after OHT. Data were collected from 58 consecutive patients who underwent OHT at a single center from 1/2018 to 4/2019: 4 with BSg prior to OHT (BSg + OHT) and 54 without prior BSg (OHT). CNI level, cardiac biopsy, and left ventricular ejection fraction (LVEF) data were collected during the first 6 months post-OHT. Comparisons were made for 3 measures of CNI variability: coefficient of variation, time in therapeutic range (TTR), and TTR by the Rosendaal method. A Pearson's correlation coefficient was calculated to assess the relationship between CNI TTR, episodes of rejection, and LVEF. The results show TTR was lower in BSg + OHT compared to OHT (12.5% vs 31.3%, P < .05). For the entire cohort, greater TTR correlated with fewer episodes of rejection (r = 0.31, P < .05). In conclusion, these findings suggest BSg + OHT patients may warrant closer monitoring of CNI levels post-OHT. Furthermore, episodes of rejection and LVEF were similar for BSg + OHT patients, indicating that BSg should not be a contraindication to transplant.

Assessing the Impact on Health of Pharmacovigilance Activities: Example of Four Safety Signals.

INTRODUCTION: The impact of pharmacovigilance activities on public health remains under-investigated, and measuring the impact on health of pharmacovigilance activities for a specific safety signal is challenging. OBJECTIVE: To gain more insight into the methodological challenges and the data required, we assessed the impact of pharmacovigilance on public health for four identified product-specific safety signals using publicly available data in the Netherlands. The assessment was on the impact of the intertwined and complementary steps of the pharmacovigilance pathways. METHODS: The impact of pharmacovigilance on public health was assessed using the assessment support tool and 'open data' from the Netherlands for four different types of pharmacovigilance safety signals: (1) off-label use of cyproterone acetate/ethinyloestradiol (CPA/EE) and thrombotic risk after pharmacovigilance measures after 2014; (2) pergolide and the risk of cardiac valvulopathy after pharmacovigilance activities in 2003; (3) proton pump inhibitors and the risk of hypomagnesaemia after pharmacovigilance activities in 2011; (4) rosiglitazone withdrawal from the market because of cardiovascular effects in 2010. RESULTS: For the signals on CPA/EE and pergolide, a crude estimation of the impact could be made with varying degrees of assumptions based on the risk described in the literature and utilisation data. CONCLUSION: This article highlights the methodological challenges and the data required to assess the impact of product-specific safety signals. A structured assessment support tool can be used as a guide for the necessary data elements and steps needed for the measurement or estimation of impact of pharmacovigilance activities on public health, provided that the appropriate data are available.

Universal Depression Screen of Ambulatory Heart Transplant Recipients With Referral for Mental Health Intervention: A Quality Improvement Project.

BACKGROUND: Patients with a heart transplant and depression have higher rates of graft failure and noncompliance. LOCAL PROBLEM: The heart transplant clinic had no standardized approach to assess for depression. METHODS: The heart transplant clinic implemented routine use of the Patient Health Questionnaire (PHQ). INTERVENTIONS: Team members were educated via an online module about depression. A process for depression screening and follow-up was developed and implemented. RESULTS: From July 2018 to February 2019, there were 834 visits; PHQ2 screens were completed during 779 (93%) of those visits with 40 (5%) positive screens. All 40 patients had PHQ9 assessment, with 33 patients (4%) exhibiting moderate or severe depressive symptoms. All 33 patients were provided with mental health resources and received follow-up. Median time to administer PHQ2 was 2 minutes (range 1-3 minutes). CONCLUSIONS: Implementation of universal depression screening in a heart transplant clinic is feasible, identifies patients with depression, and does not add significant clinical burden.

Oxidative stress-induced retinal damage is prevented by mild hypothermia in an ex vivo model of cultivated porcine retinas.

BACKGROUND: Hydrogen peroxide (H2 O2 ) can be used in vitro to simulate oxidative stress. In retinal organ cultures, H2 O2 induces strong neurodegeneration of the retina. It is known that oxidative stress plays a role in the development of several retinal diseases including glaucoma and ischemia. Thus, we investigated whether processes underlying oxidative stress can be prevented by hypothermia using an ex vivo organ culture model of porcine retinas. METHODS: Porcine retinal explants were cultivated for 5 and 8 days. Oxidative stress was induced via 300 µM H2 O2 on day 1 for 3 hours. Hypothermia treatment at 30°C was applied simultaneously with H2 O2 , for 3 hours. Retinal ganglion cells (RGCs), apoptosis, bipolar and cholinergic amacrine cells, microglia and macroglia were evaluated immunohistologically. Apoptosis rate was additionally analysed via western blot. RESULTS: Reduced apoptosis rates through hypothermia led to a preservation of RGCs (P < .001). Amacrine cells were rescued after hypothermia treatment (P = .17), whereas bipolar cells were only protected partly. Additionally, at 8 days, microglial response due to oxidative stress was completely counteracted via hypothermia (P < .001). CONCLUSIONS: H2 O2 induced strong degenerative processes in porcine retinas. The role of oxidative stress in the progression of retinal diseases makes this ex vivo organ culture model suitable to investigate new therapeutic approaches. In the present study, the damaging effect of H2 O2 to several retinal cell types was counteracted or strongly alleviated through hypothermia treatment. Especially RGCs, which are affected in glaucoma disease, were protected due to a reduced apoptosis rate through hypothermia.