Is shared decision-making vanishing at the end-of-life? A descriptive and qualitative study of advanced cancer patients’ involvement in specific therapies decision-making

Background

Little is known about what is at stake at a subjective level for the oncologists and the advanced cancer patients when they face the question whether to continue, limit or stop specific therapies. We studied (1) the frequency of such questioning, and (2) subjective determinants of the decision-making process from the physicians’ and the patients’ perspectives.

Methods

(1) All hospitalized patients were screened during 1 week in oncology and/or hematology units of five institutions. We included those with advanced cancer for whom a questioning about the pursuit, the limitation or the withholding of specific therapies (QST) was raised. (2) Qualitative design was based on in-depth interviews.

Results

In conventional units, 12.8 % of cancer patients (26 out of 202) were concerned by a QST during the study period. Interviews were conducted with all physicians and 21 advanced cancer patients. The timing of this questioning occurred most frequently as physicians estimated life expectancy between 15 days and 3 months. Faced with the most frequent dilemma (uncertain risk-benefit balance), physicians showed different ways of involving patients. The first two were called the “no choice” models: 1) trying to resolve the dilemma via a technical answer or a “wait-and-see” posture, instead of involving the patients in the questioning and the thinking; and 2), giving a “last minute” choice to the patients, leaving to them the responsibility of the decision. In a third model, they engaged early in shared reflections and dialogue about uncertainties and limits with patients, proxies and care teams. These schematic trends influenced patients’ attitudes towards uncertainty and limits, as they were influenced by these ones. Individual and systemic barriers to a shared questioning were pointed out by physicians and patients.

Conclusions

This study indicate to what extent these difficult decisions are related to physicians’ and patients’ respective and mutually influenced abilities to deal with and share about uncertainties and limits, throughout the disease trajectory. These insights may help physicians, patients and policy makers to enrich their understanding of underestimated and sensitive key issues of the decision-making process.

     

Living with AIDS in Uganda: a qualitative study of patients’ and families’ experiences following referral to hospice

Background

Globally, the majority of people with HIV/AIDS live in sub-Saharan Africa. While the increasing availability of antiretroviral therapy is improving the outlook for many, its effects are yet to reach all of those in need and patients still present with advanced disease. This paper reports findings from qualitative interviews with patients living with AIDS and their caregivers who were receiving palliative care from Hospice Africa Uganda (HAU). We aimed to understand what motivated patients and their families to seek formal healthcare, whether there were any barriers to help- seeking and how the help and support provided to them by HAU was perceived.

Methods

We invited patients with AIDS and their relatives who were newly referred to HAU to participate in qualitative interviews. Patients and carers were interviewed in their homes approximately four weeks after the patient’s enrolment at HAU. Interviews were translated, transcribed and analysed using narrative and thematic approaches.

Results

Interviews were completed with 22 patients (10 women and 12 men) and 20 family caregivers, nominated by patients. Interviews revealed the extent of suffering patients endured and the strain that family caregivers experienced before help was sought or accessed. Patients reported a wide range of severe physical symptoms. Patients and their relatives reported worries about the disclosure of the AIDS diagnosis and fear of stigma. Profound poverty framed all accounts. Poverty and stigma were, depending on the patient and family situation, both motivators and barriers to help seeking behaviour. Hospice services were perceived to provide essential relief of pain and symptoms, as well as providing rehabilitative support and a sense of caring. The hospice was perceived relieve utter destitution, although it was unable to meet all the expectations that patients had.

Conclusion

Hospice care was highly valued and perceived to effectively manage problems such as pain and other symptoms and to provide rehabilitation. Participants noted a strong sense of being “cared for”. However, poverty and a sense of stigma were widespread. Further research is needed to understand how poverty and stigma can be effectively managed in hospice care for patients for advanced AIDS and their families.

     

The relationship between pain management and psychospiritual distress in patients with advanced cancer following admission to a palliative care unit

Background

Although many cross-sectional studies have demonstrated the association between cancer pain and psychospiritual distress, the time-dependent relationship has not been fully explored. For that reason, this study aims to investigate the time-dependent relationship between psychospiritual distress and cancer pain management in advanced cancer patients.

Methods

This is a prospective observational study. Two hundred thirty-seven advanced cancer patients were recruited from a palliative care unit in Taiwan. Demographic and clinical data were retrieved at admission. Pain and psychospiritual distress (i.e.: anxiety, depression, anger, level of family and social support, fear of death) were assessed upon admission and one week later, by using a “Symptom Reporting Form”. Patients were divided into two groups according to the pain status one week post-admission (improved versus not improved groups).

Results

One hundred sixty-three (68.8 %) patients were assigned to the improved group, and 74 (31.2 %) patients were assigned to the not improved group. There were no differences in the psychospiritual variables between groups upon admission. In overall patients, all psychospiritual variables improved one week post-admission, but the improvement of depression and family/social support in the not improved group was not significant. Consistent with this, for depression scores, there was a statistically significant pain group x time interaction effect detected, meaning that the pain group effect on depression scores was dependent on time.

Conclusions

We demonstrated a time-dependent relationship between depression and pain management in advanced cancer patients. Our results suggest that poor pain management may be associated with intractable depression. The inclusion of interventions that effectively improve psychospiritual distress may contribute to pain management strategies for advanced cancer patients.

     

Exploring end of life priorities in Saudi males: usefulness of Q-methodology

Background

Quality end-of-life care depends on understanding patients’ end-of-life choices. Individuals and cultures may hold end-of-life priorities at different hierarchy. Forced ranking rather than independent rating, and by-person factor analysis rather than averaging may reveal otherwise masked typologies.

Methods

We explored Saudi males’ forced-ranked, end-of-life priorities and dis-priorities. Respondents (n?=?120) rank-ordered 47 opinion statements on end-of-life care following a 9-category symmetrical distribution. Statements’ scores were analyzed by averaging analysis and factor analysis (Q-methodology).

Results

Respondents’ mean age was 32.1 years (range, 18–65); 52 % reported average religiosity, 88 and 83 %?≥?very good health and life-quality, respectively, and 100 %?≥?high school education. Averaging analysis revealed that the extreme five end-of-life priorities were to, be at peace with God, be able to say the statement of faith, maintain dignity, resolve conflicts, and have religious death rituals respected, respectively. The extreme five dis-priorities were to, die in the hospital, not receive intensive care if in coma, die at peak of life, be informed about impending death by family/friends rather than doctor, and keep medical status confidential from family/friends, respectively. Q-methodology classified 67 % of respondents into five highly transcendent opinion types. Type-I (rituals-averse, family-caring, monitoring-coping, life-quality-concerned) and Type-V (rituals-apt, family-centered, neutral-coping, life-quantity-concerned) reported the lowest and highest religiosity, respectively. Type-II (rituals-apt, family-dependent, monitoring-coping, life-quantity-concerned) and Type-III (rituals-silent, self/family-neutral, avoidance-coping, life-quality & quantity-concerned) reported the best and worst life-quality, respectively. Type-I respondents were the oldest with the lowest general health, in contrast to Type-IV (rituals-apt, self-centered, monitoring-coping, life-quality/quantity-neutral). Of the extreme 14 priorities/dis-priorities for the five types, 29, 14, 14, 50, and 36 %, respectively, were not among the extreme 20 priorities/dis-priorities identified by averaging analysis for the entire cohort.

Conclusions

1) Transcendence was the extreme end-of-life priority, and dying in the hospital was the extreme dis-priority. 2) Quality of life was conceptualized differently with less emphasize on its physiological aspects. 3) Disclosure of terminal illness to family/close friends was preferred as long it is through the patient. 4) Q-methodology identified five types of constellations of end-of-life priorities and dis-priorities that may be related to respondents’ demographics and are partially masked by averaging analysis.

     

Antipyretic,anti-inflammatory and analgesic activity of <Emphasis Type="Italic">Acacia hydaspica</Emphasis> R. Parker and its phytochemical analysis

Background

Inflammation and pain underlies several pathological conditions. Synthetic drugs used for the management of these conditions carry severe toxic effects. Globally efforts are ongoing to introduce novel medicinal plants to develop effective, economic and innocuous drugs. The current study was aimed at investigating the antipyretic, anti-inflammatory and analgesic activity of methanol extract of A. hydaspica aerial parts (AHM) and its active fraction. Furthermore identification and isolation of polyphenolic compounds was carried out to identify the active principles.

Methods

Yeast induced pyrexia, Paw edema, acetic acid-induced writhing and hot plate test were carried out in vivo. HPLC-DAD analysis and combination of different chromatographic techniques, involving vacuum liquid chromatography (VLC) and flash chromatography (FC) were carried out for chemical characterization. The structural heterogeneity of flavanols was characterized by ESI- MS, ¹H NMR, ¹³C NMR and ²D NMR spectroscopic analyses, and also by comparison with reported literature.

Results

Oral administration of A. hydaspica methanol extract (AHM) and A. hydaspica ethyl acetate fraction (AHE), showed dose and time dependent decrease in body temperature in yeast induced pyrexia, comparable to standard, Paracetamol. AHM and AHE (150 mg/kg) significantly (p?<?0.001) inhibit pain sensation in various pain models, i.e. acetic acid induced writhing and hot plate test. Similarly AHM and AHE demonstrated an anti-inflammatory effect in carrageenan-induced paw edema in rats and 150 mg/kg dose being distinctly more effective (91.92% inhibition). When studied on prostaglandin E₂ (PGE₂) induced edema in rats, AHM and AHE showed maximum inhibition of edema at 150 mg/kg after 4 h. HPLC chromatogram of AHM revealed the presence of gallic acid, catechin, rutin and caffeic acid. Chromatographic separation and structure characterization of AHE, has led to the identification of three flavan-3-ol derivative including 7-O-galloyl catechin, +catechin and methyl gallate, which have been reported for the first time in A. hydaspica.

Conclusion

These results revealed that the presence of bioactive compounds in A. hydaspica might be responsible for the pharmacological activities, confirming the indigenous utility of A. hydaspica against inflammatory disorders.

     

Antidepressant-like effects of methanolic extract of <Emphasis Type="Italic">Bacopa monniera</Emphasis> in mice

Background

Bacopa monniera has been used as a cure for various ailments that include anxiety, epileptic disorders, dementia, blood purifier, cough and rheumatism, and some important local uses of the plant are in dermatitis, anemia, diabetes, promote fertility and prevent miscarriage for many years in Bangladesh. According to this background, the aim of the study was to evaluate the antidepressant-like effect of the methanolic extract of B. monniera (MEBM) in different behavioral models such as forced swimming test (FST), measurement of locomotor activity test (MLAT) and tail suspension test (TST) on mice after two weeks treatment.

Methods

Mice were divided into five groups (n?=?5/group): control group (deionized water), standard group where Imipramine hydrochloride (30 mg/kg) was used as standard drug and three test groups where three doses of the methanolic extract of B. monniera (MEBM) (50, 100, and 200 mg/kg) was used for two weeks treatment. All the drug and test samples were administered via gavage through oral route. To assess the antidepressant-like effect of MEBM forced swimming test (FST), tail suspension test (TST) and measurement of locomotor activity test (MLAT) have been done in mice.

Results

The results showed that a strong and dose-dependent antidepressant effects in different mice models. The main findings of the MEBM significantly reduced the duration of immobility times in the forced swimming test (p?<?0.001). Likewise, the extract significantly decreased the immobility time in the tail suspension test (p?<?0.001). Moreover, we employed an additional measurement of locomotor activity test to check the motor stimulating activity of the MEBM. The extract also significantly increased the locomotion, rearing and defecation effects in comparison to the control group (p?<?0.001).

Conclusion

The present results clearly demonstrate that the methanolic extract of B. monniera possesses antidepressant-like activity in the animal behavioral models. The current study warrants further investigation into identification of the active compounds in herbal medicines, in particular extract of B. monniera with antidepressant-like effects.

     

The antioxidative effects of acidic-, alkalic-, and enzymatic-extractable mycelium zinc polysaccharides by <Emphasis Type="Italic">Pleurotus djamor</Emphasis> on liver and kidney of streptozocin-induced diabetic mice

Background

Edible mushrooms, especially the genus of Pleurotus, have been well studied for their nutrition as well as non-toxic medicinal properties. Recently, much attention has been paid to the therapeutic values of mushrooms in genus of Pleurotus with diabetes mellitus (DM), which was a complex metabolic disorder that induced by increased oxidative stress and characterized by hyperglycemia. However, scare attention has been paid to polysaccharides from P. djamor. Meanwhile, zinc is an essential trace element in the human body and it participates in various pathways of metabolism. Therefore, the objective of present study was aimed to evaluate the protective effects of the three extractable mycelium zinc polysaccharides (MZPS), including acidic-MZPS (Ac-MZPS), alkalic-MZPS (Al-MZPS) and enzymatic-MZPS (En-MZPS), on the liver and kidneys in diabetic mice induced by streptozocin (STZ) aiming to better understand the possible hypoglycemic mechanisms and their health benefits.

Methods

The Ac-, Al-, and En-MZPS were extracted with hydrochloric acid (1 M), sodium hydroxide (1 M) and snailase (4 %) from P. djamor zinc-enriched mycelium, respectively. The diabetic mice were induced by injection of STZ. Besides the histopathological analyses of liver and kidney, the following biochemical analysis were processed to investigate the antioxidative effects, including activities of superoxide dismutase (SOD), GSH peroxide (GSH-Px) and catalase (CAT), and contents of malondialdehyde (MDA) in liver and kidney homogenate; activities of alamine aminotransferase (ALT) and aspertate aminotransferase (AST), and levels of urea nitrogen (BUN), creatinine (CRE), total cholesterol (TC), albumin (ALB), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein choles-terol (LDL-C) and very low-density lipoprotein cholesterol (VLDL-C) in serum.

Results

Results showed that the activities of SOD, GSH-Px and CAT were significantly increased, the MDA contents remarkably reduced, and the values of ALT, AST, BUN, CRE, TC, LDL-C and HDL-C observably mitigated in the liver, kidneys and serum of diabetic mice by these three polysaccharides treatment. Biochemical and histopathological analyses also showed that MZPS could alleviate liver and kidneys injury.

Conclusion

These results demonstrated that Ac-, Al-, and En-MZPS possessed potent antioxidant activities, and could be used as a potentially functional food for the prevention of diabetes and its complications induced by STZ.

     

Electroacupuncture prevents white adipose tissue inflammation through modulation of hypoxia-inducible factors-1α-dependent pathway in obese mice

Background

Electroacupuncture (EA) shows anti-inflammation and several pleiotropic effects that interact with metabolic pathways. In the present study we tested the hypothesis that EA prevents inflammatory response and weight gain in obese mice through modulation of hypoxia-inducible factors-1α (HIF1-α)-dependent pathways in white adipose tissues.

Methods

Mice were divided in 4 groups: Non-obese, ob/ob, ob/ob submitted to 3 treatments, ob/ob submitted to 7 treatments. Low-frequency EA (2 Hz) was applied at the Zusanli (ST36) acupoint 10 min three times weekly for one or two consecutive weeks in male ob/ob mice. At 22 weeks of age, plasma lipid, glucose, other metabolites and relevant markers were measured by standard assays. Adipose tissue was assessed with immunohistochemical staining. Adipose tissue extracts were also analyzed with quantitative real-time polymerase chain reaction (Q-PCR) and Western blotting.

Results

EA treatment is associated with decreased adipose tissue inflammation, and markedly decreased fat mass and adipocyte size in ob/ob mice. In obese mice, The protein levels of HIF-α were increased, EA shown a marked trend in inhibiting the hypoxic response in adipose tissue. The expression level of hypoxia-related genes (vascular endothelial growth factor A, VEGFA; glucose transporter type 1, Slc2al; glutathione peroxidase 1, GPX1) and inflammation-related genes (TNF-α, IL-6, MCP-1) expression were also reduced in adipose tissue after EA treatment. EA treatment decreased the macrophage recruitment and infiltration (F4/80), and in addition we found that decrease in NF-κB and increase in IkBα were both correlated to reduction in inflammatory processes in adipose tissue. This phenomenon was paralleled by the decrease in the levels of inflammatory cytokines, such as TNF-α, IL-6 and IL-1β in obese mice.

Conclusions

We conclude that EA prevents weight gain through modulation of HIF-1α-dependent pathways and inflammatory response in obese adipose tissues.

     

Comparison of targeted next-generation sequencing and Sanger sequencing for the detection of <Emphasis Type="Italic">PIK3CA</Emphasis> mutations in breast cancer

Background

Phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha, PIK3CA, is one of the most frequently mutated genes in breast cancer, and the mutation status of PIK3CA has clinical relevance related to response to therapy.The aim of our study was to investigate the mutation status of PIK3CA gene and to evaluate the concordance between NGS and SGS for the most important hotspot regions in exon 9 and 20, to investigate additional hotspots outside of these exons using NGS, and to correlate the PIK3CA mutation status with the clinicopathological characteristics of the cohort.

Methods

In the current study, next-generation sequencing (NGS) and Sanger Sequencing (SGS) was used for the mutational analysis of PIK3CA in 186 breast carcinomas.

Results

Altogether, 64 tumors had PIK3CA mutations, 55 of these mutations occurred in exons 9 and 20. Out of these 55 mutations, 52 could also be detected by Sanger sequencing resulting in a concordance of 98.4 % between the two sequencing methods. The three mutations missed by SGS had low variant frequencies below 10 %. Additionally, 4.8 % of the tumors had mutations in exons 1, 4, 7, and 13 of PIK3CA that were not detected by SGS. PIK3CA mutation status was significantly associated with hormone receptor-positivity, HER2-negativity, tumor grade, and lymph node involvement. However, there was no statistically significant association between the PIK3CA mutation status and overall survival.

Conclusions

Based on our study, NGS is recommended as follows: 1) for correctly assessing the mutation status of PIK3CA in breast cancer, especially for cases with low tumor content, 2) for the detection of subclonal mutations, and 3) for simultaneous mutation detection in multiple exons.

     

Does attendance at anatomy practical classes correlate with assessment outcome? A retrospective study of a large cohort of undergraduate anatomy students

Background

Anatomy in medical curricula is typically taught via pedagogy consisting of didactic lectures combined with a practical component. The practical component often includes traditional cadaveric dissection classes and/or workshops utilizing anatomical models, carefully prosected cadaveric material and radiology. The primary aim of this study was to determine if there is an association between attendance at practical classes in anatomy and student assessment outcomes. A secondary aim was to determine if student assessment outcomes were better when students preferentially attended workshops or prosection style practical classes.

Method

We retrospectively examined practical attendance records and assessment outcomes from a single large anatomy subject (approx. 450 students) to identify how attendance at anatomy practical classes correlates with assessment outcome.

Results

Students who scored above the median mark for each assessment attended significantly more practical classes than students who scored below the median assessment mark (Mann Whitney; p?<?0.001), and students who attended more than half the practical classes had significantly higher scores on assessments than students that attended less than half the practical classes (Mann Whitney; P?<?0.01). There was a statistically significant positive correlation between attendance at practical classes and outcomes for each assessment (Spearman’s correlation; p?<?0.01). There was no difference in assessment outcomes for students who preferentially attended more dissection compared to prosection style classes and vice versa (Mann Whitney; p?>?0.05).

Conclusions

Our findings show there is an association between student attendance at practical classes and performance on anatomy assessment.