Addressing the needs of terminally-ill patients in Bosnia-Herzegovina: patients’ perceptions and expectations

Background

Many terminally ill patients in Bosnia-Herzegovina (BiH) fail to receive needed medical attention and social support. In 2016 a primary healthcare centreer (PHCC) in Doboj (BiH) requested the methodological and technical support of a local partner (Fondacija fami) and the Geneva University Hospitals to address the needs of terminally ill patients living at home. In order to design acceptable, affordable and sustainable solutions, we involved patients and their families in exploring needs, barriers and available resources.

Methods

We conducted interviews with 62 purposely selected patients using a semi-structured interview guide designed to elicit patients’ experiences, needs and expectations. Both qualitative and quantitative analyses were conducted, using an inductive thematic approach.

Results

While patients were aware that their illnesses were incurable, they were poorly informed about medical and social support resources available to them. Family members appeared to be patients’ main source of support, and often suffered from exhaustion and financial strain. Patients expressed feelings of helplessness and lack of control over their health. They wanted more support from health professionals for pain and other symptom management, as well as for anxiety and depression. Patients who were bedridden or with reduced mobility expressed strong feelings of loneliness, social exclusion, and stigma from community members and – occasionally - from health workers.

Conclusions

Our findings suggest a wide gap between patients’ end-of-life care needs and existing services. In order to address the medical, psychological and social needs of terminally ill patients, a multi-pronged approach is called for, including not only better symptom management through training of health professionals and improved access to medication and equipment, but also a coordinated inter-professional, inter-institutional and multi-stakeholder effort aimed at offering comprehensive medical, psycho-social, educational and spiritual support.

     

Region-Specific Sex-Dependent Pattern of Age-Related Changes of Proximal Femoral Cancellous Bone and Its Implications on Differential Bone Fragility

Despite evident interest in age-related bone changes, data on regional differences within the proximal femur are scarce. To date, there has been no comprehensive study on site-specific age-related changes in the trabecular architecture of three biomechanically important femoral subregions (medial neck, lateral neck, and intertrochanteric region) for both genders. In this study we investigated age-related deterioration in the trabecular architecture of those three subregions of the femoral neck for both genders. The research sample included 52 proximal femora (26 males, 26 females; age range, 26–96 years) from Forensic Department at University of Belgrade. Bone sections from the three regions of interest were scanned by micro-CT at University of Hamburg. The study revealed that proximal femoral microarchitecture cannot be perceived as homogeneous and, more importantly, that the aging process is not uniform. Besides the initial intersite differences, microarchitecture changed differently with increasing age, maintaining significant differences between the regions. In addition, we observed a different aging pattern between genders: deterioration was most significant in the intertrochanteric region in women, while the lateral neck was most affected in men. This finding supports epidemiological data about the differential occurrence of cervical vs. trochanteric fractures in aging males and females. In conclusion, the aging process in the proximal femur cannot be regarded as a simple function of quantitative bone loss but, rather, as an alteration of specific architecture that may degrade bone strength.     

Systemic rapamycin without loading dose for restenosis prevention after coronary bare metal stent implantation

Objectives : The aim of this study was to assess the role of short oral administration of rapamycin, without loading dose, in the reduction of restenosis rate after bare metal stent implantation. Background : Previous studies suggest that the administration of oral rapamycin reduces angiographic restenosis after bare metal stent implantation. Methods : This was prospective, open‐label study of 80 patients randomized to either oral rapamycin (2 mg/day for 30 days, starting within 24 hr of stent implantation) or no therapy after implantation of a coronary bare metal stent. The primary study end point was incidence of angiographic binary restenosis and late loss at six months. The secondary end points were target lesion revascularization (TLR), target vessel revascularization (TVR), and incidence of major adverse cardiovascular events (MACE) at 6 months. Results : Angiographic follow up was completed in 72/80 (90%) of patients. In the rapamycin group, the drug was well tolerated (22.5% minor side effects) and was maintained in 100% of patients. At six months, the in‐segment binary restenosis was 10.5% in rapamycin group vs. 51.4% in no‐therapy group, P < 0.001) and the in‐stent binary restenosis was 7.9% in rapamycin group vs. 48.7% in no‐therapy group, P < 0.001. The in‐segment late loss was also significantly reduced with oral therapy (0.29 ± 0.39 vs. 0.86 ± 0.64 mm, respectively, P < 0.001). Similarly, after six months, patients in the oral rapamycin group also showed a significantly lower incidence of TLR and TVR (7% vs. 22.7%, respectively, P = 0.039) and MACE (7% vs. 22.7%, respectively, P = 0.039). Conclusions : This study showed that the administration of oral rapamycin (2 mg/day, without loading dose) during 30 days after stent implantation significantly reduces angiographic and clinical parameters of restenosis. © 2009 Wiley‐Liss, Inc.     

Changes in activity of non-specific esterases in cadmium treated Lymantria dispar larvae

Many biochemical, physiological and histological criteria have been used as indicators of exposures and effects of the contaminants. These changes can indicate the response of an organism to a specific environmental stressor. In the present paper, the effect of the acute and chronic exposure to cadmium as well as recovery from two cadmium concentrations (10 and 30 μgCd/g dry food) on gypsy moth (Lymantria dispar) midgut esterases was investigated. The influence of cadmium on trait plasticity was also examined. Esterases showed great sensitivity to low metal concentrations during acute and chronic treatments. Their activities during short-term exposure and after recovery significantly depended on cadmium concentrations. The esterases had greater index of plasticity during chronic treatments with 10 and 30 μgCd/dry food. Five esterase isoforms between 64 and 250 kDa were detected. Isoforms of esterases exposed to any of the two cadmium effects differed among several egg-masses. Isozymes were distinguished in one egg-mass during different cadmium treatments. We conclude that these enzymes could be considered potential and sensitive non-selective biomarkers for the presence of cadmium in food.     

A Chronic Iron-Deficient/High-Manganese Diet in Rodents Results in Increased Brain Oxidative Stress and Behavioral Deficits in the Morris Water Maze

Iron deficiency (ID) is especially common in pregnant women and may even persist following childbirth. This is of concern in light of reports demonstrating that ID may be sufficient to produce homeostatic dysregulation of other metals, including manganese (Mn). These results are particularly important considering the potential introduction of the Mn-containing gas additive, methyl cyclopentadienyl manganese tricarbonyl (MMT), in various countries around the world. In order to model this potentially vulnerable population, we fed female rats fed either control (35 mg Fe/kg chow; 10 mg Mn/kg chow) or low iron/high-manganese (IDMn; 3.5 mg Fe/kg chow; 100 mg Mn/kg chow) diet, and examined whether these changes had any long-term behavioral effects on the animals’ spatial abilities, as tested by the Morris water maze (MWM). We also analyzed behavioral performance on auditory sensorimotor gating utilizing prepulse inhibition (PPI), which may be related to overall cognitive performance. Furthermore, brain and blood metal levels were assessed, as well as regional brain isoprostane production. We found that treated animals were slightly ID, with statistically significant increases in both iron (Fe) and Mn in the hippocampus, but statistically significantly less Fe in the cerebellum. Additionally, isoprostane levels, markers of oxidative stress, were increased in the brain stem of IDMn animals. Although treated animals were indistinguishable from controls in the PPI experiments, they performed less well than controls in the MWM. Taken together, our data suggest that vulnerable ID populations exposed to high levels of Mn may indeed be at risk of potentially dangerous alterations in brain metal levels which could also lead to behavioral deficits.     

Novel trends in high-throughput screening

Lead discovery by high-throughput screening (HTS) has evolved into a mature scientific discipline in modern drug discovery since its beginning about 10–15 years ago. Owing to the strong efforts in automation and miniaturization, even relatively large compound collections of over one million compounds or more can be screened against a large number of biological targets in relatively short time and at relatively low cost compared to the efforts of just 5 or 10 years ago. This was only possible with the concomitant development of high-quality readout technologies for highly miniaturized screening. Whereas most of the conventional drug targets can be approached via current HTS-readout technologies, the challenge goes toward the hitherto non-tractable families of drug targets. Future trends will focus strongly toward these novel target classes such as ion channels, transporters, protein–protein interactions, among many others. It will be essential to make proper readout technologies and adequate chemical libraries available for these target classes. Chemical libraries derived from natural products, but also derived from combinatorial chemistry and automated synthesis will be a key prerequisite for success in the field, as long as enough diversity and drug-like properties are included in these chemical libraries [25]. The proper readout technologies for screening of large chemical libraries have seen strong advances in recent years [^{[2], [7] and [22••]}], nevertheless none of these technologies is void of artifacts, in particular artifacts derived from the inherent physical nature of chemical compounds in aqueous buffer [11^••]. We therefore propose that future lead discovery should pay more attention toward unambiguous identification of these compound related artifacts and toward efficient removal of these false-positive compounds from the HTS hit-lists. We strongly recommend the use of biophysical and enzymological studies in the HTS hit-list follow-up phase (‘hit validation’) in order to deliver information of the highest possible quality for subsequent hit-to-lead studies. Finally, the science and art of HTS has evolved in various phases from its beginning in the early 1990s toward today's state-of-the-art operation in lead discovery. During these 15 years, one can distinguish three phases (‘generations’) of HTS operations: during the first phase, HTS has been just the same as laboratory screening, albeit at much larger capacity; in the second phase (‘second generation HTS’), HTS has evolved toward more sophisticated assay development/adaptation, more toward dedicated tool production, but also more toward counter-screening and hit-list follow-up; in the current phase (‘third generation HTS’) we see much more flexibility with regards to the applied processes for lead discovery, a stronger focus on quality and validation of the obtained results and a better awareness for choosing a proper lead finding strategy in a target-by-target specific manner.Taken together, we can conclude that better flexibility and creativity, more quality and the use of project-related, tailor-made lead finding strategies in the discovery process will become the key drivers for the successful application of high-throughput screening in the Pharmaceutical, Biotech, and Academic drug discovery programs of the future.

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

• of special interest

•• of outstanding interest