Age and co-morbidities as independent risk factors of infections leading to hospital admission in the last year of life among the elderly: A retrospective registry-based study.

Background: The immune system declines with age, but the impact of chronological age may be affected by sex, co-morbidities, and sociodemographic factors. Objective: The article aims to study infections associated with hospital admission in the elderly in their last year of life and the impact of age, sex, co-morbidities, and sociodemographic factors. Method: A retrospective study based on registry data covering all care visits in Stockholm Region, Sweden, for 7 years was conducted. All deceased subjects with at least one hospital admission with infection as the main diagnosis in the last year of life were compared with subjects with no such admission. Subjects were categorized into three different age-groups 65-79, 80-89, and 90 years and above. Co-morbidity was measured by the Charlson Comorbidity Index (CCI) and sociodemographic factors were assessed using the 'Mosaic-system'. Subjects living in nursing homes were analyzed separately. Uni- and multivariable logistic regressions were conducted. Results: Of the 55,238 subjects in the study population, 14,192 (26%) had at least one hospital admission due to infection in the last year of life. The risk of having a severe infection increased with age, adjusted odds ratio (OR): 1.30 (1.25-1.36), and 1.60 (1.52-1.69) for the age-groups 80-89 and ≥ 90 compared to the age-group 65-79. The most important factor for infection was a high co-morbidity score; adjusted OR: 1.75 (1.68-1.82). Male sex and living in a less affluent area were weaker risk factors for infections. Conclusion: Chronological age and co-morbidities are independent risk factors of infections associated with hospital admission in the last year in life while male sex and sociodemographic factors have less impact.

Patient experiences of randomised placebo-controlled trial participation during end-of-life palliative cancer care.

BACKGROUND: Performing clinical trials in palliative cancer care is known to be challenging. OBJECTIVE: This study aimed to explore how patients with advanced cancer experienced their participation in a randomised, placebo-controlled trial while receiving palliative cancer care at end of life. METHOD: A descriptive design with a qualitative approach was used. 14 patients who had participated in the 'Palliative-D' study were interviewed. Data were analysed using content analysis. RESULTS: Three categories were identified understanding the study design, willingness to participate and collaboration with the research team alongside standard care. Being randomised, with the risk of receiving placebo, was perceived as non-problematic since it was understood as being important for the quality of the research. Patients showed a willingness to participate for the sake of others and also for their own sake, hoping for a cure or at least to live as long as possible. Patients felt proud of being useful and contributing to research. Consent to participate was made autonomously without discussing with others. Patients considered the study design uncomplicated and well-integrated into the standard care. CONCLUSION: Study participation in a randomised, placebo-controlled trial can be a positive and meaningful experience for patients despite advanced cancer in end of life. Participation may support patients' autonomy and give hope, and therefore, might have a positive effect on quality of life. A carefully planned and simple study design, well integrated into standard care, can facilitate the feasibility of clinical studies in specialised palliative home care.

Five-Year Follow-Up of Health-Related Quality of Life in Differentiated Thyroid Cancer Patients Treated with Total Thyroidectomy and Radioiodine in Sweden: A Nationwide Prospective Cohort Study.

Background: Despite a good prognosis, survivors of differentiated thyroid cancer (DTC) may have reduced health-related quality of life (HRQOL) many years after treatment, and it is unclear how suppression of thyroid-stimulating hormone (TSH) may contribute to HRQOL. This study investigated changes in HRQOL in the 5 years following DTC treatment, the association between HRQOL and TSH suppression, and how HRQOL compares to the general population. Methods: In this nationwide prospective cohort study, 487 patients with DTC were identified between 2012 and 2017 from all Swedish hospitals treating patients with DTC. Patients treated with total thyroidectomy and planned for radioiodine answered the Swedish version of the Short Form-36 Health Survey (SF-36) and a study specific questionnaire at treatment and after 1, 3, and 5 years. Summary measures for physical and mental QOL were derived from the SF-36, and TSH values were collected from patient records. To study changes in HRQOL over time, linear mixed models were fitted on multiply imputed data, with all patients and measurement points included in the model. Results: In total, 351 patients consented to participate in the study. In the 5 years following DTC treatment, physical QOL did not change significantly with time, while mental QOL improved by on average 0.61 (p < 0.001) per year. TSH levels were not predictive of either physical or mental QOL, or their change over time. At 5 years, there was a significant difference in physical and mental QOL compared with the Swedish general population, but effect sizes were small (Cohen's d = 0.29 and -0.21, respectively). The SF-36 domains general health, vitality, social functioning, and mental health were lower at 5 years compared with the general population (difference 8.7-13.3), and these differences were clinically significant. Conclusions: The mental component of HRQOL improves over time following DTC treatment. HRQOL in patients with DTC is not explained by TSH suppression. Although overall differences in physical and mental HRQOL compared with the general population were small 5 years after treatment, several specific psychosocial HRQOL domains were clinically meaningfully reduced. Psychosocial health issues should be screened for during DTC follow-up.

Methylphenidate for treating fatigue in palliative cancer care - effect and side effects in real-world data from a palliative care unit.

BACKGROUND: Methylphenidate can be used for the treatment of cancer-related fatigue (CRF), although randomized controlled trials have shown conflicting results. The aim of this study was to use 'real-world' data to evaluate the effect and side effects of using methylphenidate in palliative cancer care with a focus on the late palliative phase and dose-response. METHOD: A retrospective review of medical records from a palliative care unit in Sweden was performed to evaluate the effect and adverse events (AEs) of using methylphenidate to treat CRF. Univariable and multivariable regression was performed and odds ratio (OR) calculated. Adjustments were made for sex, age, cancer type, dose and starting treatment <4 weeks before death. RESULTS: Of the 2,419 screened patients, 112 had been treated with methylphenidate for CRF. The treatment was assessed as being effective in 51 patients (46%). Twenty-six patients (23%) experienced AEs that were generally mild, including anxiety, palpitations, and insomnia. Patients starting the treatment <4 weeks before death (n = 54) were less likely to have an effect from treatment compared to those starting earlier; adjusted OR 0.24 (95% CI 0.10-0.55). Doses of 20 mg and above were well-tolerated and had a higher frequency of effect in the crude data but not after adjustment for confounding factors. CONCLUSION: Methylphenidate is generally effective and well-tolerated for the treatment of CRF in palliative care. However, patients with a short life expectancy (<4 weeks) seem to benefit less from the treatment regardless of age, cancer type and dose.

Appetite and its association with mortality in patients with advanced cancer - a Post-hoc Analysis from the Palliative D-study.

BACKGROUND: Loss of appetite is a common nutrition symptom in patients with cancer. Understanding the trajectory of appetite could be of clinical use for prognostication in palliative cancer care. Our primary aim was to explore the association between self-assessed appetite and mortality in patients suffering from advanced cancer. Secondary aims included the relation between fatigue, albumin levels and CRP/albumin ratio and mortality. We also aimed to study potential sex-differences in the associations. METHODS: Post-hoc analyses were performed using data from the Palliative D-study comprising 530 patients with cancer admitted to palliative care. Appetite and fatigue were assessed with the Edmonton Symptom Assessment System (ESAS). Cox proportional hazards models were used to calculate Hazard ratios (HR) with 95% confidence intervals (CI) for exposures of appetite, fatigue, albumin and CRP/albumin ratio, and time from study inclusion to death or censoring. Analyses were also performed stratified by sex. RESULTS: The follow-up time ranged between 7 to 1420 days. Moderate and poor appetite were significantly associated with a higher mortality rate compared to reporting a good appetite; HR 1.44 (95%CI: 1.16-1.79) and HR 1.78 (95%CI: 1.39-2.29), respectively. A higher mortality rate was also seen among participants reporting severe fatigue compared to those reporting no fatigue; HR 1.84 (95%CI:1.43-2.36). Participants with low albumin levels (< 25 g/L) and those in the highest tertile of CRP/albumin ratio, had higher mortality rates, HR 5.35 (95%CI:3.75-7.63) and HR 2.66 (95%CI:212-3.35), compared to participants with high albumin levels (> 36 g/L) and those in lowest tertile of CRP/albumin ratio. These associations were more pronounced in men than in women. CONCLUSION: Poor appetite, severe fatigue, low albumin level and a high CRP/albumin ratio were associated with increased mortality rates among patients with advanced cancer. All these variables might be clinically useful for prognostication in palliative cancer care. TRIAL REGISTRATION: Clinicaltrial.gov. Identifier: NCT03038516;31, January 2017.

Functional SARS-CoV-2 cross-reactive CD4+ T cells established in early childhood decline with age.

Pre-existing SARS-CoV-2-reactive T cells have been identified in SARS-CoV-2-unexposed individuals, potentially modulating COVID-19 and vaccination outcomes. Here, we provide evidence that functional cross-reactive memory CD4+ T cell immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is established in early childhood, mirroring early seroconversion with seasonal human coronavirus OC43. Humoral and cellular immune responses against OC43 and SARS-CoV-2 were assessed in SARS-CoV-2-unexposed children (paired samples at age two and six) and adults (age 26 to 83). Pre-existing SARS-CoV-2-reactive CD4+ T cell responses targeting spike, nucleocapsid, and membrane were closely linked to the frequency of OC43-specific memory CD4+ T cells in childhood. The functional quality of the cross-reactive memory CD4+ T cell responses targeting SARS-CoV-2 spike, but not nucleocapsid, paralleled OC43-specific T cell responses. OC43-specific antibodies were prevalent already at age two. However, they did not increase further with age, contrasting with the antibody magnitudes against HKU1 (ß-coronavirus), 229E and NL63 (α-coronaviruses), rhinovirus, Epstein-Barr virus (EBV), and influenza virus, which increased after age two. The quality of the memory CD4+ T cell responses peaked at age six and subsequently declined with age, with diminished expression of interferon (IFN)-γ, interleukin (IL)-2, tumor necrosis factor (TNF), and CD38 in late adulthood. Age-dependent qualitative differences in the pre-existing SARS-CoV-2-reactive T cell responses may reflect the ability of the host to control coronavirus infections and respond to vaccination.

Comparison of Creatinine and Cystatin C to Estimate Renal Function in Geriatric and Frail Patients.

The aim of this study was to compare estimated glomerular filtration rate (eGFR) with creatinine (eGFRcrea) and cystatin C (eGFRcys) in geriatric and frail patients. A retrospective, cross-sectional study was performed at a geriatric clinic in Stockholm (n = 95). The revised Lund−Malmö equation was used to calculate eGFRcrea and the Caucasian-Asian-Pediatric-Adult (CAPA) equation was used for eGFRcys. The absolute mean percentage difference between eGFRcrea and eGFRcys was used as a surrogate measure for accuracy in eGFR. Other outcome measures were consistency expressed in Lin's concordance correlation coefficient and the proportion of consistent staging of renal failure. Subgroup analyses were performed with regard to frailty (according to Clinical Frailty Scale) and age. eGFRcys estimated lower GFR than eGFRcrea across the entire study population as well as in all subgroups (p < 0.05). Difference between the estimates increased with increasing frailty (r2 = 0.15, p < 0.01), but was not significantly affected by age (r2 = 0.004, p = 0.55). In conclusion, eGFRcys was significantly lower compared to eGFRcrea in geriatric and frail patients. Moreover, frailty had greater impact than age on the accuracy of eGFR. However, this study cannot determine if any of the estimates are preferable over the other in this patient group.

Deprescribing in Palliative Cancer Care.

The aim of palliative care is to maintain as high a quality of life (QoL) as possible despite a life-threatening illness. Thus, the prescribed medications need to be evaluated and the benefit of each treatment must be weighed against potential side effects. Medications that contribute to symptom relief and maintained QoL should be prioritized. However, studies have shown that treatment with preventive drugs that may not benefit the patient in end-of-life is generally deprescribed very late in the disease trajectory of cancer patients. Yet, knowing how and when to deprescribe drugs can be difficult. In addition, some drugs, such as beta-blockers, proton pump inhibitors, anti-depressants and cortisone need to be scaled down slowly to avoid troublesome withdrawal symptoms. In contrast, other medicines, such as statins, antihypertensives and vitamins, can be discontinued directly. The aim of this review is to give some advice according to when and how to deprescribe medications in palliative cancer care according to current evidence and clinical praxis. The review includes antihypertensive drugs, statins, anti-coagulants, aspirin, anti-diabetics, proton pump inhibitors, histamin-2-blockers, bisphosphonates denosumab, urologicals, anti-depressants, cortisone, thyroxin and vitamins.

Appetite in Palliative Cancer Patients and Its Association with Albumin, CRP and Quality of Life in Men and Women-Cross-Sectional Data from the Palliative D-Study.

Albumin is an important biochemical marker in palliative cancer care, used for assessment of nutritional status, disease severity and prognosis. Our primary aim was to investigate sex differences in the association between appetite and albumin levels in palliative cancer patients. We also aimed to study associations between appetite and C-reactive protein (CRP), Quality of Life (QoL), pain and fatigue. In the Palliative D-cohort, consisting of 266 men and 264 women, we found a correlation between appetite and albumin; low appetite, measured with the Edmonton Symptom Assessment System, correlated significantly with low albumin in men: (r = -0.33, p < 0.001), but not in women (r = -0.03, p = 0.65). In a regression analysis adjusted for confounding factors, results were similar. Lower appetite was correlated with higher CRP in men (r = 0.27, p < 0.001), but not in women (r = 0.12, p = 0.05). Appetite was correlated with QoL, fatigue and pain in both men and women; those with a low appetite had a low QoL and high fatigue- and pain-scores (p < 0.001). In conclusion, our results indicated possible sex differences in the associations between appetite and albumin, and between appetite and CRP, in palliative care patients. Understanding these associations could provide additional value for clinical practice.

Evaluation of Whole Brain Radiotherapy among Lung Cancer Patients with Brain Metastases in Relation to Health Care Level and Survival.

Whole-brain radiotherapy (WBRT) as a treatment for brain metastases has been questioned over the last years. This study aimed to evaluate health care levels and survival after WBRT in a cohort of lung cancer patients with brain metastases receiving WBRT in Stockholm, Sweden, from 2008 to 2019 (n = 384). If the patients were able to come home again was estimated using logistic regression and odds ratios (OR) and survival by using Cox regression. The median age in the cohort was 65.6 years, the median survival following WBRT was 2.4 months (interquartile range (IQR) 1.2-6.2 months), and 84 (22%) patients were not able to come home after treatment. Significantly more males could come home again after WBRT compared to women (OR = 0.37, 95%CI 0.20-0.68). Patients with performance status scores WHO 3-4 had a median survival of 1.0 months, hazard ratio (HR) = 4.69 (95%CI 3.31-6.64) versus WHO score 0-1. Patients admitted to a palliative ward before WBRT had a median survival of 0.85 months, HR = 2.26 (95%CI 1.53-3.34) versus being at home. In conclusion, patients treated with WBRT had a short median survival and 20% could not be discharged from the hospital following treatment. Significantly more women did not come home again.

25-Hydroxyvitamin D in Cancer Patients Admitted to Palliative Care: A Post-Hoc Analysis of the Swedish Trial 'Palliative-D'.

The purpose of this study is to explore 25-hydroxyvitamin D (25-OHD) levels in patients with cancer in the palliative phase in relation to season, sex, age, tumor type, colectomy, and survival. To this end, we performed a post-hoc analysis of 'Palliative-D', a randomized placebo-controlled, double-blind trial investigating the effect of daily supplementation with 4000 IU of vitamin D for 12 weeks on pain in patients in palliative cancer care. In the screening cohort (n = 530), 10% of patients had 25-OHD levels < 25 nmol/L, 50% < 50, and 84% < 75 nmol/L. Baseline 25-OHD did not differ between seasons or tumor type and was not correlated with survival time. In vitamin D deficient patients supplemented with vitamin D (n = 67), 86% reached sufficient levels, i.e., >50 nmol/L, after 12 weeks. An increase in 25-OHD was larger in supplemented women than in men (53 vs. 37 nmol/L, p = 0.02) and was not affected by season. In the placebo-group (n = 83), decreased levels of 25-OHD levels were noted during the study period for patients recruited during the last quarter of the year. In conclusion, cancer patients in palliative phase have adequate increase in 25-OHD after vitamin D supplementation regardless of season, age, tumor type, or colectomy.

Sex Differences in the Effect of Vitamin D on Fatigue in Palliative Cancer Care-A Post Hoc Analysis of the Randomized, Controlled Trial 'Palliative-D'.

In the randomized, placebo-controlled, double-blind trial 'Palliative-D', vitamin D treatment of 4000 IE/day for 12 weeks reduced opioid use and fatigue in vitamin-D-deficient cancer patients. In screening data from this trial, lower levels of vitamin D were associated with more fatigue in men but not in women. The aim of the present study was to investigate possible sex differences in the effect of vitamin D in patients with advanced cancer, with a specific focus on fatigue. A post hoc analysis of sex differences in patients completing the Palliative-D study (n = 150) was performed. Fatigue assessed with the Edmonton Symptom Assessment Scale (ESAS) was reduced in vitamin-D-treated men; -1.50 ESAS points (95%CI -2.57 to -0.43; p = 0.007) but not in women; -0.75 (95%CI -1.85 to 0.36; p = 0.18). Fatigue measured with EORTC QLQ-C15-PAL had a borderline significant effect in men (-0.33 (95%CI -0.67 to 0.03; p = 0.05)) but not in women (p = 0.55). The effect on fatigue measured with ESAS in men remained the same after adjustment for opioid doses (p = 0.01). In conclusion, the positive effect of the correction of vitamin D deficiency on fatigue may be more pronounced in men than in women. However, studies focused on analyzing sex differences in this context must be performed before firm conclusions can be drawn.

Palliative Sedation-The Last Resort in Case of Difficult Symptom Control: A Narrative Review and Experiences from Palliative Care in Switzerland.

Palliative sedation can be considered as "the last resort" in order to treat unbearable, refractory symptoms or suffering in end-of-life patients. The aim is symptom relief and not to induce death as in the case of euthanasia. The treatment might be one of the most challenging therapeutic options in the field of palliative care, involving both ethical and practical issues. Still, studies have shown that it is a safe and valuable treatment and in general does not shorten the life of the patient. Since patients in Switzerland have the legal option of assisted suicide, palliative sedation is an alternative that has become increasingly important. The use of palliative sedation was reported in 17.5% of all patients admitted to palliative care in Switzerland, making the country of those with the highest use of this treatment. The aim of this narrative review is to discuss ethical and practical issues in palliative sedation, with specific focus on experiences from Switzerland. Indications, ethical considerations, drugs of choice and duration are discussed. Decision making should be based on solid guidelines. When used correctly, palliative sedation is an important and useful tool in palliative care in order to provide good symptom relief.

Weight Loss in Advanced Cancer: Sex Differences in Health-Related Quality of Life and Body Image.

Weight maintenance is a priority in cancer care, but weight loss is common and a serious concern. This study explores if there are sex differences in the perception of weight loss and its association to health-related quality of life (HRQoL) and body image. Cancer patients admitted to Advanced Medical Home Care were recruited to answer a questionnaire, including characteristics, the HRQoL-questionnaire RAND-36, and a short form of the Body Image Scale. Linear regression analyses stratified by sex and adjusted for age were performed to examine associations between percent weight loss and separate domains of HRQoL and body image score in men and women separately. In total, 99 participants were enrolled, of which 80 had lost weight since diagnosis. In men, an inverse association between weight loss and the HRQoL-domain physical functioning, ß = -1.34 (95%CI: -2.44, -0.24), and a positive association with body image distress, ß = 0.22 (95%CI: 0.07, 0.37), were found. In women, weight loss was associated with improvement in the HRQoL-domain role limitations due to physical health, ß = 2.02 (95%CI: 0.63, 3.41). Following a cancer diagnosis, men appear to experience weight loss more negatively than women do. Recognizing different perceptions of weight loss may be of importance in clinical practice.

High-protein compared with standard parenteral nutrition in palliative cancer care.

OBJECTIVES: High-protein parenteral nutrition (PN) has been developed to counteract muscle loss in patients with cancer treated with PN. Nevertheless, it is not clear if high-protein PN is as safe as standard PN in patients with palliative cancer. Our primary aim was to compare the proportion of patients with elevated liver enzymes between high-protein and standard PN in patients with palliative cancer enrolled to Medical Home Care. Our secondary aim was to compare the two treatments with regard to weight and albumin levels during treatment. METHODS: Medical records from 2016 to 2018 were retrospectively reviewed to identify palliative cancer patients that had received PN for more than 3 weeks. Data on weight, height, albumin, liver enzymes, socioeconomic factors and dietitian consultations were collected at baseline and after 3-8 weeks of PN treatment. The odds of having elevated liver enzymes or having a maintained weight and/or stable albumin levels were calculated using logistic regression. RESULTS: 20 patients treated with high-protein PN were compared with 104 patients treated with standard PN. Patients treated with high-protein PN had a significantly higher weight at follow-up compared with patients treated with standard PN (p<0.05). There was no significant difference in the proportion of patients with elevated liver enzymes (OR 0.20; 95% CI 0.02 to 1.86), or maintained weight and/or albumin levels (OR 1.62; 95% CI 0.46 to 5.76) between high-protein and standard PN. CONCLUSION: High-protein PN was as safe, and at least as effective, as standard PN to patients with palliative cancer.

Successful Strategies and Areas of Improvement-Lessons Learned from Design and Conduction of a Randomized Placebo-Controlled Trial in Palliative Care, 'Palliative-D'.

Clinical trials in palliative care are challenging to design and conduct. Burden on patients should be minimized, while gatekeeping by professionals and next-of kin needs to be avoided. Clinical deterioration due to disease progression affects attrition unrelated to intervention, and different care settings complicate comparisons and reduce the generalizability of the results. The aim of this review is to provide advice for colleagues planning to perform clinical trials in palliative care based on our own experiences from performing the Palliative-D study and by a thorough literature review on this topic. The Palliative-D study was a double-blind trial with 244 randomized patients comparing the effect of vitamin D3 to placebo in patients with advanced or metastatic cancer in the palliative phase of their disease trajectory who were enrolled in specialized palliative home care teams. Endpoints were opioid and antibiotic use, fatigue, and QoL. Recruitment was successful, but attrition rates were higher than expected, and we did not reach targeted power. For the 150 patients who completed the study, the completeness of the data was exceptionally high. Rather than patient reported pain, we choose the difference in the mean change in opioid dose between groups after twelve weeks compared to baseline as the primary endpoint. In this paper we discuss challenges in palliative care research based on lessons learned from the "Palliative-D" trial regarding successful strategies as well as areas for improvement.

Studies on CYP3A activity during the menstrual cycle as measured by urinary 6ß-hydroxycortisol/cortisol.

The 6ß-OH-cortisol/cortisol ratio (6ß-OHC/C) in urine is an endogenous marker of drug-metabolizing enzyme cytochrome P450 3A (CYP3A). The primary aim of this single center, prospective, non-interventional cohort study, was to investigate the variability of 6ß-OHC/C during the menstrual cycle. In addition, possible associations between the CYP3A activity and sex hormones, gut microbiota metabolite trimethylamine-N-Oxide (TMAO) and microRNA-27b, respectively, were investigated. Serum and urinary samples from healthy, regularly menstruating women followed for two menstrual cycles were analyzed. Twenty-six complete menstrual cycles including follicular, ovulatory, and luteal phase were defined based on hormone analyses in serum. 6ß-OHC/C were analyzed in urine and sex hormones, TMAO and miRNA-27b were analyzed in serum at the same time points. 6ß-OHC/C did not vary between the follicular, ovulatory, or luteal phases. There was a difference in the relative miRNA-27b expression between the follicular and ovulatory phase (p = .03). A significant association was found between 6ß-OHC/C and progesterone during the follicular (p = .005) and ovulatory (p = .01) phases (n = 26 for each phase). In addition, a significant association was found between the ratio and TMAO during the ovulatory (p = .02) and luteal (p = .002) phases. 6ß-OHC/C and gut microbiota TMAO were significantly associated (p = .003) when evaluating all values, for all phases (n = 78). Interestingly, the finding of an association between 6ß-OHC/C in urine and levels of TMAO in serum suggest that gut microbiota may affect CYP3A activity.

CYP3A Activity in End-of-Life Cancer Patients Measured by 4ß-Hydroxycholesterol/cholesterol Ratio, in Men and Women.

More than 50% of all drugs are metabolized by the cytochrome P450 3A enzyme (CYP3A). The aim of this study was to investigate if the CYP3A activity, measured by the endogenous marker 4ß-hydroxycholesterol/cholesterol ratio (4ß-OHC/C), is changed during the last weeks and days of life in men and women. To this end, serum samples from 137 deceased patients (median age 70 years) collected at a single time point 1-60 days before death, were analyzed and compared to 280 young (median 27 years), and 30 elderly (median age 70 years) non-cancer controls. There were no significant differences in the 4ß-OHC/C ratio between men and women in end-of-life patients (p < 0.25). The median 4ß-OHC/C was significantly higher in end-of-life male patients compared to both young (p < 0.0001) and elderly (p < 0.05) male controls. In a similar manner, 4ß-OHC/C in end-of-life female patients was significantly higher compared to young and elderly female controls, p < 0.0001 and p < 0.001, respectively. There was no significant correlation between 4ß-OHC/C and survival time. The results from this study suggest maintained CYP3A activity to the very last days of life and even a capacity of induction of the enzyme in end-of-life cancer patients.

'Palliative-D'-Vitamin D Supplementation to Palliative Cancer Patients: A Double Blind, Randomized Placebo-Controlled Multicenter Trial.

The aim of the 'Palliative-D' study was to test the hypothesis that correction of vitamin D deficiency reduces opioid use in cancer patients admitted to palliative care. A multicenter randomized, placebo-controlled, double-blind trial in three home-based palliative care facilities in Sweden was performed. Patients with advanced cancer and 25-hydroxyvitamin D < 50 nmol/L were randomized to vitamin D3 4000 IU/day or placebo for 12 weeks. The primary endpoint was the difference of long-acting opioid use (fentanyl ug/h) between the groups during 12 weeks, based on four time points. Secondary outcomes included changes in antibiotic use, fatigue and Quality of Life (QoL). A total of 244 patients were randomized, and 150 patients completed the 12 weeks. The major reason for drop-out was death due to cancer. The vitamin D-group had a significantly smaller increase of opioid doses compared to the placebo-group; beta coefficient -0.56 (p = 0.03), i.e., 0.56 µg less fentanyl/h per week with vitamin D treatment. Vitamin D-reduced fatigue assessed with ESAS was -1.1 points after 12 weeks (p < 0.01). Antibiotic use or QoL did not differ significantly between the groups. The treatment was safe and well-tolerated. In conclusion, correction of vitamin D deficiency may have positive effects on opioid use and fatigue in palliative cancer patients, but only in those with a survival time more than 12 weeks.