Nevin Manimala

Psychogeriatrics. 2023 May 29. doi: 10.1111/psyg.12976. Online ahead of print.

ABSTRACT

BACKGROUND: The noradrenergic systems in the brain maintain cognitive functions including attention/concentration and establishment of long-term memory. In addition, hypofunction of noradrenergic systems is supposed to be involved in the pathophysiology of Alzheimer’s disease. In this study, we tried to examine the possible associations of concentrations of basal salivary 3-methoxy-4-hydroxyphenylglycol (sMHPG), a major metabolite of noradrenaline, and brain volume changes during 4 years in elderly people living in a rural community.

METHODS: The survey was conducted twice in Kurokawa-cho, Imari, Saga Prefecture, Japan, among people aged 65 years and older. We collected data from 226 residents. Measurements of sMHPG and brain MRIs were collected at Time 1 (2005-2007). Follow-up brain MRIs were taken at Time 2 (2009-2011). A total of 70 participants (18 men, mean age 71.9 ± 4.8 years; 52 women, mean age 72.0 ± 4.3 years) completed this survey. Concentrations of sMHPG at baseline were divided into two groups using the mean value (12.83 ng/ml). We compared the brain volumes between groups with higher and lower sMHPG concentrations over time using voxel-based morphometry implemented with statistical parametric mapping.

RESULTS: In participants with higher sMHPG concentrations at baseline, brain volumes including right precuneus were significantly larger 4 years after baseline than those with lower sMHPG concentrations at baseline. No interaction between sMHPG concentration and MRI acquisition interval was found.

CONCLUSION: Our results suggest that higher sMHPG concentrations in elderly people might be associated with maintenance of brain volume, especially in brain regions closely related to cognitive function.

PMID:37248036 | DOI:10.1111/psyg.12976

Rev Infirm. 2023 May;72(291):39-41. doi: 10.1016/j.revinf.2023.04.011. Epub 2023 May 10.

ABSTRACT

Adapted physical activities (APA) in the workplace improve workers’ health. Paradoxically, APA remains marginal in the very places where improving health is the central objective of health care workers, namely clinics and hospitals. Promoting physical activity in the workplace is a twofold challenge. Not only does PA improve the health and well-being of caregivers, but it also allows them to be more effective in their daily work with patients.

PMID:37247988 | DOI:10.1016/j.revinf.2023.04.011

BMJ Open. 2023 May 29;13(5):e068130. doi: 10.1136/bmjopen-2022-068130.

ABSTRACT

OBJECTIVE: The aim is to integrate quantitative and qualitative evidence to understand the effectiveness and experience of advance care planning (ACP) for frail elderly.

DESIGN: A mixed-methods systematic review and meta-analysis was conducted. Quality evaluation was conducted using critical appraisal tools from the Joanna Briggs Institute. Data were synthesised and pooled for meta-analysis or meta-aggregation as needed.

DATA SOURCES: An electronic search of MEDLINE, CINAHL, Embase, PubMed, PsycINFO, and Cochrane Library databases from January 2003 to April 2022.

ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included experimental and mixed-methods studies. The quantitative component attempts to incorporate a broader study design. The qualitative component aids in comprehending the participant’s experience with ACP and its efficacy.

DATA EXTRACTION AND SYNTHESIS: Two independent reviewers undertook screening, data extraction and quality assessment. The quantitative and qualitative data were synthesised and integrated using a convergent segregated approach.

RESULTS: There were 12 158 articles found, and 17 matched the inclusion criteria. The quality of the quantitative component of most included studies (6/10) was rated as low, and the qualitative component of half included studies (4/8) was rated as moderate. The meta-analysis showed that the intervention of ACP for frail elderly effectively increases readiness, knowledge and process of ACP behaviours. The meta-aggregation showed that the participants hold a positive attitude towards ACP and think it facilitates expressing their preferences for the medical decision.

CONCLUSION: ACP is an effective and feasible strategy to facilitate frail elderly to express their healthcare wishes timely and improve their outcomes. This study could provide proof for a better understanding of the subject and help direct future clinical practice. More well-designed randomised controlled trials evaluating the most effective ACP interventions and tools are needed for the frail elderly population.

PROSPERO REGISTRATION NUMBER: CRD42022329615.

PMID:37247960 | DOI:10.1136/bmjopen-2022-068130

Anticancer Res. 2023 Jun;43(6):2593-2599. doi: 10.21873/anticanres.16426.

ABSTRACT

BACKGROUND/AIM: Cancer cachexia describes a multifactorial wasting syndrome marked by a metabolic imbalance leading to the loss of muscle and fat tissue. Extracellular vesicles (EV) provide unique insights into their parental cells’ metabolism. The value of these vesicles as diagnostic tools in cancer cachexia has not been investigated so far.

PATIENTS AND METHODS: A previously analyzed metabolomics dataset on large EV from breast cancer patients was used for analyzing the metabolomic changes in patients with malnutrition. Follow-up time was 6 months. The data were analyzed using fold change analysis, volcano plotting, receiver operator characteristic (ROC) analysis, pathway analysis, and survival analysis.

RESULTS: In patients with weight loss, statistical analysis revealed an increase in lysophosphatidylcholines (lysoPC a C16:0, lysoPC a C18:0, lysoPC a C18:1, lysoPC a C18:2, lysoPC a C20:4), sphingomyelins (SM (OH) C22:2 and SM C18:1), and phosphatidylcholines (PC aa C24:0, PC ae C34:3). When combined, these metabolites are a good predictor for cachexia in ROC curve analysis (AUC of 0.970; 95%CI=0.920-1.000; p<0.0001). Pathway analysis revealed an involvement of metabolites in “choline metabolism in cancer” and “glycerophospholipid metabolism”.

CONCLUSION: Large EV reflect metabolic changes in cancer patients suffering from cancer cachexia. Metabolic changes at the time of drawing blood were associated with the weight status (stable vs. weight loss) six months later and thereby could have a predictive impact.

PMID:37247938 | DOI:10.21873/anticanres.16426

Anticancer Res. 2023 Jun;43(6):2733-2739. doi: 10.21873/anticanres.16440.

ABSTRACT

BACKGROUND/AIM: The aim of this study was to investigate the relationship between radiation exposure to the spleen, dose-dependent organ changes, and their possible influence on clinical and oncological outcome. Furthermore, to provide evidence and sensitivity for considering the spleen as an relevant organ at risk.

PATIENTS AND METHODS: A total of 93 patients with carcinoma of the distal esophagus or gastroesophageal junction were selected for this retrospective study. Changes in spleen volume, infections, and oncological outcome were assessed during follow-up using linear and logistic regression models.

RESULTS: Spleen volume decreased significantly by a median of 27.5 ml to an absolute value of 178.1 ml (p<0.001) within twelve months. Statistical analyses revealed a significant association of infectious events with worse progression-free survival (PFS) (p=0.002) and overall survival (OS) (p=0.001). With a mean spleen dose <4 Gray, both OS and PFS were also significantly prolonged.

CONCLUSION: A decrease in spleen organ volume after neoadjuvant radiochemotherapy was demonstrated with a consecutive increased incidence of infectious events, significantly correlating with worse PFS and OS.

PMID:37247933 | DOI:10.21873/anticanres.16440

Anticancer Res. 2023 Jun;43(6):2645-2657. doi: 10.21873/anticanres.16431.

ABSTRACT

BACKGROUND/AIM: Interferon-alpha (IFN-alpha) has shown survival benefits in metastatic renal cell carcinoma (mRCC), but the knowledge about long-term outcome is sparse. Additional knowledge is beneficial because IFN-alpha usage in combination therapy such as immune checkpoint inhibitor for mRCC is an area of interest. This is the longest follow-up concerning IFN-alpha treatment.

PATIENTS AND METHODS: A total of 117 metastatic renal cell cancer (mRCC) patients without prior chemotherapy were enrolled between 1994-2002 and followed-up until January 2022. The median follow-up was 18 months. After progression to IFN-alpha, the patients were not treated with tyrosine kinase, mTOR inhibitors or bevacizumab as these were not standard therapies at that time or the patients’ performance status was too poor. Mean treatment duration was 11 months.

RESULTS: Median overall survival was 19.0 months, 5-year survival rate 16.2%, and 10-year survival rate 9.0%. There were statistically significant differences in survival in response to treatment (log-rank test, p<0.001): median overall survival was 52.0 months for objective responses, 25.0 months for stable disease and 5.0 months for progressive disease. Proportion of 5-year survivors was 29% in low, 20% in intermediate, and 7% in high-risk groups, respectively (p=0.001).

CONCLUSION: With prolonged INF-alpha treatment stable and responding patients can obtain late objective responses, long-lasting complete responses, and long-term outcome with acceptable toxicity. IFN-alpha is an alternative therapy when multiple treatment lines are used for mRCC and an interesting option to study for combined therapies such as immune checkpoint inhibitor-based therapies.

PMID:37247917 | DOI:10.21873/anticanres.16431

Anticancer Res. 2023 Jun;43(6):2821-2829. doi: 10.21873/anticanres.16451.

ABSTRACT

BACKGROUND/AIM: Chronic inflammation and cytokine storm can cause uncontrolled events in cancer. Pro-inflammatory molecules released by malignant cells send signals to the brain, liver, and neuroendocrine cells, interfering with appetite and promoting anorexia. Malnutrition in cancer patients is associated with increased treatment toxicity, reduced physical efficiency, and decreased survival. Therefore, early recognition of malnutrition could improve quality of life, treatment compliance, and survival. The aim of the study was to explore the relationship between inflammatory parameters with disease stage and nutritional status in patients with solid cancers.

PATIENTS AND METHODS: We screened 77 consecutive patients from 3 clinical Institutions in Sicily, Italy, with solid tumors who were either in follow-up after curative treatment or being treated for metastatic disease using the Mini Nutritional Assessment (MNA) questionnaire. Inflammatory parameters, including interleukin 6 (IL6), C-reactive protein (CRP), β2-microglobulin, ferritin, and transferrin were evaluated.

RESULTS: A statistically significant difference was found in mean values of IL6, CRP, β2-microglobulin, ferritin, and transferrin between patients without evidence of disease and metastatic patients. Among the metastatic group, there was a significant difference in mean values of these inflammatory parameters between patients with malnutrition and those with normal nutritional status. The difference in average IL6, CRP, β2-microglobulin, and ferritin between patients at risk of malnutrition and those with normal nutritional status was also significant. However, the difference between patients at risk of malnutrition and those with malnutrition was not significant.

CONCLUSION: IL6, CRP, transferrin, ferritin, and β2-microglobulin are functional inflammatory parameters that indicate risk of malnutrition and support the MNA screening test to identify patients with solid tumors who require nutritional support.

PMID:37247899 | DOI:10.21873/anticanres.16451

Anticancer Res. 2023 Jun;43(6):2671-2681. doi: 10.21873/anticanres.16433.

ABSTRACT

BACKGROUND/AIM: The role of single nucleotide polymorphisms (SNPs) in the frequency and intensity of chemotherapy-induced nausea and vomiting (CINV) in women with breast cancer (BC) is unclear. The primary purpose of this study was to compare/evaluate the effect of SNP-guided antiemetic treatment versus standard CINV treatment.

PATIENTS AND METHODS: A randomised, factorial, phase II multicentre study design was used. Women planned for neoadjuvant or adjuvant chemotherapy with epirubicin, cyclophosphamide and fluorouracil (FEC /EC, with or without fluorouracil) for BC were randomised to SNP-guided antiemetic treatment (based on the results of SNP analyses) versus standard CINV treatment. Blood samples were taken before the treatment was initiated. Patient-reported data on CINV (during 10 days from onset of cancer treatment) and health-related quality of life (HRQoL), were collected before and after the first cancer treatment.

RESULTS: A total of 188 women were included. Overall, nausea was reported by 86% (n=129) of the patients during the ten-day period from the start of cancer treatment. The SNP genotype studied varied. In FAS-CD95, the genotypes AG and GG were overrepresented; in RB1-LPAR6, GG was overrepresented, and in CCL2, both AA and GG were overrepresented. We found no statistically significant difference in CINV between SNP-guided antiemetic treatment versus standard CINV treatment.

CONCLUSION: SNP-guided antiemetic treatment could be as effective as standard treatment. SNP-guided antiemetic treatment of CINV is possibly useful in detecting patients with a higher or lower risk for CINV and thus may help in avoiding over-treatment with toxic components. CINV negatively affects the HRQL.

PMID:37247895 | DOI:10.21873/anticanres.16433

Med J Aust. 2023 May 29. doi: 10.5694/mja2.51978. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess the impact of the 2009 National Reform Program for organ donation in Australia on the number and characteristics of organ donors under 16 years of age.

DESIGN, SETTING, PARTICIPANTS: Retrospective observational time series study; analysis of Australia and New Zealand Organ Donation (ANZOD) registry data for all consented potential deceased organ donors under 16 years of age during 2000-2019, and of numbers of donors aged 16 years or more reported in ANZOD annual reports.

MAIN OUTCOME MEASURES: Difference between 2000-2008 (pre-reform) and 2009-2019 (reform period) in annual organ donor rates (donors per million population), by age group (under 16 years, 16 years or more), reported as incidence rate ratio (IRR).

SECONDARY OUTCOMES: Differences in child donor characteristics during 2000-2008 and 2009-2019.

RESULTS: During 2000-2019, 400 children under 16 years of age were consented potential deceased organ donors, of whom 374 were actual deceased donors (94%): 146 during 2000-2008, 228 during 2009-2019. The median annual rate was 3.3 (interquartile range [IQR], 3.0-4.3) actual donors per million population during 2000-2008 and 4.2 (IQR, 3.6-5.2) donors per million population during 2009-2019 (IRR, 1.15; 95% confidence interval [CI], 0.93-1.42). In contrast, the difference between the two periods was statistically significant for donors aged 16 years or more, rising from 11.7 (IQR, 11.2-11.8) to 19.9 (IQR, 18.3-24.4) actual donors per million population (IRR, 1.75; 95% CI, 1.66-1.85). The median age of actual organ donors under 16 was similar during 2000-2008 (11 years; IQR, 7-14 years) and 2009-2019 (10 years; IQR, 4-14 years), as was the proportion of donors in this age group under 10 kg (2000-2008: four of 146, 3%; 2009-2019: 14 of 228, 6%).

CONCLUSIONS: Despite its overall effect on organ donation rates, the National Reform Program was not effective in increasing the numbers of donors under 16 years of age. Relying on broad initiatives for adult donors may not be appropriate for achieving this aim.

PMID:37247848 | DOI:10.5694/mja2.51978

J Am Coll Radiol. 2023 May 27:S1546-1440(23)00390-3. doi: 10.1016/j.jacr.2023.02.033. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the efficacy of a multi-modal intervention in reducing CT pulmonary angiography (CTPA) overutilization in the evaluation of suspected pulmonary embolism (PE) in the emergency department (ED).

METHODS: Previous mixed methods analysis of barriers to guideline-concordant CTPA ordering results was used to develop a provider focused behavioral intervention consisting of a clinical decision support tool and an audit and feedback system at a multi-site, tertiary academic network. The primary outcome (guideline concordance), and secondary outcomes (yield, and CTPA and D-dimer order rates), were compared using a pre-intervention/post intervention design. ED encounters for adult patients from 7/5/2017 to 1/3/2019 were included. Fisher’s exact tests and statistical process control (SPC) charts were used to compare the pre-/post-intervention groups for each outcome.

RESULTS: Of the 201,912 ED patient visits evaluated, 3,587 included CTPA. Guideline concordance increased significantly after the intervention, from 66.9% to 77.5% (p<0.001). CTPA order rate and D-dimer order rate also increased significantly, from 17.1 to 18.4 per 1000 patients, p=0.035, and 30.6 to 37.3 per 1000 patients, p<0.001, respectively. Percent yield showed no significant change (12.3% pre- vs.10.8% post-intervention; p=0.173). SPC analysis showed sustained special-cause variation in the post-intervention period for guideline concordance and D-dimer order rates, temporary special-cause variation for CTPA order rates, and no special-cause variation for percent yield.

CONCLUSION: Our success in increasing guideline concordance demonstrates the efficacy of a mixed methods, human-centered approach to behavior change. Given that neither of the secondary outcomes improved, our results may demonstrate potential limitations to the guidelines directing the ordering of CTPA studies and/or D-dimer ordering.

PMID:37247831 | DOI:10.1016/j.jacr.2023.02.033