Knowledge, feelings, and willingness to use palliative care in cancer patients with hematologic malignancies and solid tumors: a prospective, cross-sectional study in a comprehensive cancer center in Germany.

PURPOSE: Patients with hematologic malignancies (HM) receive palliative care (PC) less often and later than patients with solid tumors (ST). Patients' lack of knowledge about PC and negative feelings about PC are barriers to their willingness to use PC. Is there a difference between patients with HM and ST in their knowledge and willingness to use PC? METHODS: Two hundred ten patients (85 HM, 125 ST) from an oncology day clinic at a university hospital participated in this cross-sectional, questionnaire-based survey. RESULTS: Patients with HM and ST had high knowledge and mainly positive feelings about PC. More than half of the patients answered that they would feel reassured by the use of PC, and one-third would feel anxious or hopeless. The majority of patients (58.3%) were willing to use PC. There are no significant differences between patients with HM and ST. In multiple regression analysis, perceived chance of cure and feelings of reassurance and anxiety are associated with willingness to use PC, but not with the HM/ST disease group. More than half (53.9%) of the participants would like the treating physician to choose the timing of a discussion about PC. CONCLUSION: Our study shows a high level of knowledge and relatively positive feelings of patients about PC, with no differences between patients with HM or ST. They expect their treating physician to initiate communication about PC. Communication should include the patient's feelings about PC and their chances of a cure.

Interactions in cancer treatment considering cancer therapy, concomitant medications, food, herbal medicine and other supplements.

PURPOSE: The aim of our study was to analyse the frequency and severity of different types of potential interactions in oncological outpatients' therapy. Therefore, medications, food and substances in terms of complementary and alternative medicine (CAM) like dietary supplements, herbs and other processed ingredients were considered. METHODS: We obtained data from questionnaires and from analysing the patient records of 115 cancer outpatients treated at a German university hospital. Drug-drug interactions were identified using a drug interaction checking software. Potential CAM-drug interactions and food-drug interactions were identified based on literature research. RESULTS: 92.2% of all patients were at risk of one or more interaction of any kind and 61.7% of at least one major drug-drug interaction. On average, physicians prescribed 10.4 drugs to each patient and 6.9 interactions were found, 2.5 of which were classified as major. The most prevalent types of drug-drug interactions were a combination of QT prolonging drugs (32.3%) and drugs with a potential for myelotoxicity (13.4%) or hepatotoxicity (10.1%). In 37.2% of all patients using CAM supplements the likelihood of interactions with medications was rated as likely. Food-drug interactions were likely in 28.7% of all patients. CONCLUSION: The high amount of interactions could not be found in literature so far. We recommend running interaction checks when prescribing any new drug and capturing CAM supplements in medication lists too. If not advised explicitly in another way drugs should be taken separately from meals and by using nonmineralized water to minimize the risk for food-drug interactions.

Complementary and alternative medicine (CAM) supplements in cancer outpatients: analyses of usage and of interaction risks with cancer treatment.

PURPOSE: The aim of our study was to analyze the use of complementary and alternative medicine (CAM) supplements, identify possible predictors, and analyze and compile potential interactions of CAM supplements with conventional cancer therapy. METHODS: We included outpatient cancer patients treated at a German university hospital in March or April 2020. Information was obtained from questionnaires and patient records. CAM-drug interactions were identified based on literature research for each active ingredient of the supplements consumed by the patients. RESULTS: 37.4% of a total of 115 patients consumed CAM supplements. Potential interactions with conventional cancer treatment were identified in 51.2% of these patients. All types of CAM supplements were revealed to be a potential source for interactions: vitamins, minerals, food and plant extracts, and other processed CAM substances. Younger age (< 62 years) (p = 0.020, φc = 0.229) and duration of individual cancer history of more than 1 year (p = 0.006, φc = 0.264) were associated with increased likelihood of CAM supplement use. A wide range of different CAM supplement interactions were reviewed: effects of antioxidants, cytochrome (CYP) interactions, and specific agonistic or antagonistic effects with cancer treatment. CONCLUSION: The interaction risks of conventional cancer therapy with over-the-counter CAM supplements seem to be underestimated. Supplements without medical indication, as well as overdoses, should be avoided, especially in cancer patients. To increase patient safety, physicians should address the risks of interactions in physician-patient communication, document the use of CAM supplements in patient records, and check for interactions.

Elevated thalamic glutamate levels and reduced water diffusivity in alcohol use disorder: Association with impulsivity.

Alcohol induces neuroinflammation but its role in cognitive impairment and impulsivity in alcohol use disorder (AUD) has been poorly investigated. We used proton magnetic resonance spectroscopy to measure brain glutamate (Glu) levels and diffusion-weighted imaging to measure functional anisotropy (FA) in the thalamus and ventral anterior cingulate cortex (vACC) in 15 recently detoxified patients with AUD and 14 matched controls. Compared to controls, AUD patients showed higher Glu levels (p = 0.04) and lower FA in the thalamus (p = 0.04) but not in the vACC. In AUD, thalamic Glu levels (r = 0.62, p = 0.019) and FA (r=-0.55, p = 0.034) were associated with severity of drinking (drinks/week). Compared to controls, AUD patients showed higher scores on Conners' Adult ADHD Rating Scale for impulsivity (p = 0.03), which correlated with glutamate levels in the thalamus (r = 0.58, p = 0.03) and vACC (r = 0.55, p = 0.036). In a second cohort of AUD patients (n = 32), Glu in dorsal ACC (dACC) also correlated with Barrett Impulsiveness Scale total score (r = 0.43, p = 0.014). We interpret the elevated thalamic Glu levels and the parallel reduction in FA in AUD-which correlated with drinking severity-as possible evidence of neurotoxicity from neuroinflammation. The association of Glu with impulsivity suggests that neurotoxic effects of chronic alcohol exposure in the thalamus and dACC may contribute to impulsivity.

Neural correlates for perception of companion animal photographs.

Anthrozoological neuroscience, which we propose as the use of neuroscience techniques to study human-animal interaction, may help to elucidate mechanisms underlying the associated psychological, physiological, and other purported health effects. This preliminary study investigates the neural response to animal photographs in pet owners and non-pet owners, and both attraction and attachment to companion animals as modulators of human perception of companion animal photographs. Thirty male participants, 15 "Pet Owners" (PO) and 15 "Non-Pet Owners" (NPO), viewed photographs of companion animals during functional MRI (fMRI) scans at 3 T and provided ratings of attraction to the animal species represented in the photographs. Fourteen subjects additionally submitted and viewed personal pet photographs during fMRI scans, and completed the Lexington Attachment to Pets Scale (LAPS). PO exhibited greater activation than NPO during the viewing of animal photographs in areas of the insula, and frontal and occipital cortices. Moreover, ratings of attraction to animals correlated positively with neural activation in the cingulate gyrus, precentral gyrus, inferior parietal lobule, and superior temporal gyrus during the viewing of representative photographs. For subjects with household pets, scores on the LAPS correlated positively with neural activation during the viewing of owned pet photographs in the precuneus, cuneus, and superior parietal lobule. Our preliminary findings suggest that human perception of companion animals involve the visual attention network, which may be modulated at the neural level by subjective experiences of attraction or attachment to animals. Our understanding of human-animal interactions through anthrozoological neuroscience may better direct therapeutic applications, such as animal-assisted therapy.

Multi-Wire Tri-Gate Silicon Nanowires Reaching Milli-pH Unit Resolution in One Micron Square Footprint.

The signal-to-noise ratio of planar ISFET pH sensors deteriorates when reducing the area occupied by the device, thus hampering the scalability of on-chip analytical systems which detect the DNA polymerase through pH measurements. Top-down nano-sized tri-gate transistors, such as silicon nanowires, are designed for high performance solid-state circuits thanks to their superior properties of voltage-to-current transduction, which can be advantageously exploited for pH sensing. A systematic study is carried out on rectangular-shaped nanowires developed in a complementary metal-oxide-semiconductor (CMOS)-compatible technology, showing that reducing the width of the devices below a few hundreds of nanometers leads to higher charge sensitivity. Moreover, devices composed of several wires in parallel further increase the exposed surface per unit footprint area, thus maximizing the signal-to-noise ratio. This technology allows a sub milli-pH unit resolution with a sensor footprint of about 1 µm², exceeding the performance of previously reported studies on silicon nanowires by two orders of magnitude.

Structural growth trajectories and rates of change in the first 3 months of infant brain development.

IMPORTANCE: The very early postnatal period witnesses extraordinary rates of growth, but structural brain development in this period has largely not been explored longitudinally. Such assessment may be key in detecting and treating the earliest signs of neurodevelopmental disorders. OBJECTIVE: To assess structural growth trajectories and rates of change in the whole brain and regions of interest in infants during the first 3 months after birth. DESIGN, SETTING, AND PARTICIPANTS: Serial structural T1-weighted and/or T2-weighted magnetic resonance images were obtained for 211 time points from 87 healthy term-born or term-equivalent preterm-born infants, aged 2 to 90 days, between October 5, 2007, and June 12, 2013. MAIN OUTCOMES AND MEASURES: We segmented whole-brain and multiple subcortical regions of interest using a novel application of Bayesian-based methods. We modeled growth and rate of growth trajectories nonparametrically and assessed left-right asymmetries and sexual dimorphisms. RESULTS: Whole-brain volume at birth was approximately one-third of healthy elderly brain volume, and did not differ significantly between male and female infants (347 388 mm3 and 335 509 mm3, respectively, P = .12). The growth rate was approximately 1%/d, slowing to 0.4%/d by the end of the first 3 months, when the brain reached just more than half of elderly adult brain volume. Overall growth in the first 90 days was 64%. There was a significant age-by-sex effect leading to widening separation in brain sizes with age between male and female infants (with male infants growing faster than females by 200.4 mm3/d, SE = 67.2, P = .003). Longer gestation was associated with larger brain size (2215 mm3/d, SE = 284, P = 4×10-13). The expected brain size of an infant born one week earlier than average was 5% smaller than average; at 90 days it will not have caught up, being 2% smaller than average. The cerebellum grew at the highest rate, more than doubling in 90 days, and the hippocampus grew at the slowest rate, increasing by 47% in 90 days. There was left-right asymmetry in multiple regions of interest, particularly the lateral ventricles where the left was larger than the right by 462 mm3 on average (approximately 5% of lateral ventricular volume at 2 months). We calculated volume-by-age percentile plots for assessing individual development. CONCLUSIONS AND RELEVANCE: Normative trajectories for early postnatal brain structural development can be determined from magnetic resonance imaging and could be used to improve the detection of deviant maturational patterns indicative of neurodevelopmental disorders.

Effects of APOE ε4, age, and HIV on glial metabolites and cognitive deficits.

OBJECTIVE: We aimed to evaluate the combined effects of HIV and APOE ε4 allele(s) on glial metabolite levels, and on known cognitive deficits associated with either condition, across the ages. METHODS: One hundred seventy-seven participants, primarily of white and mixed race (97 seronegative subjects: aged 44.7 ± 1.3 years, 85 [87.6%] men, 28 [28.9%] APOE ε4+; 80 HIV+ subjects: aged 47.3 ± 1.1 years, 73 [91.3%] men, 23 [28.8%] APOE ε4+), were assessed cross-sectionally for metabolite concentrations using proton magnetic resonance spectroscopy in 4 brain regions and for neuropsychological performance. RESULTS: Frontal white matter myo-inositol was elevated in subjects with HIV across the age span but showed age-dependent increase in seronegative subjects, especially in APOE ε4+ carriers. In contrast, only seronegative APOE ε4+ subjects showed elevated myo-inositol in parietal cortex. All APOE ε4+ subjects had lower total creatine in basal ganglia. While all HIV subjects showed greater cognitive deficits, HIV+ APOE ε4+ subjects had the poorest executive function, fluency memory, and attention/working memory. Higher myo-inositol levels were associated with poorer fine motor function across all subjects, slower speed of information processing in APOE ε4+ subjects, and worse fluency in HIV+ APOE ε4+ subjects. CONCLUSIONS: In frontal white matter of subjects with HIV, the persistent elevation and lack of normal age-dependent increase in myo-inositol suggest that persistent glial activation attenuated the typical antagonistic pleiotropic effects of APOE ε4 on neuroinflammation. APOE ε4 negatively affects energy metabolism in brain regions rich in dopaminergic synapses. The combined effects of HIV infection and APOE ε4 may lead to greater cognitive deficits, especially in those with greater neuroinflammation. APOE ε4 allele(s) may be a useful genetic marker to identify white and mixed-race HIV subjects at risk for cognitive decline.

The human immunodeficiency virus reduces network capacity: acoustic noise effect.

OBJECTIVE: Increased acoustic noise (AN) during working memory leads to increased brain activation in healthy individuals and may have greater impact in human immunodeficiency virus (HIV) patients. RESULTS: Compared with control subjects, HIV patients showed reduced AN activation and lower neuronal marker N-acetylaspartate in prefrontal and parietal cortices. Competing use of the working memory network between AN and cognitive load showed lower dynamic range of the hemodynamic responses in prefrontal and parietal cortices in HIV patients. INTERPRETATION: These findings suggest that reduced reserve capacity of the working memory network in HIV patients and additional stress (eg, AN) might exhaust the impaired network for more demanding tasks.

A multicenter study of two magnetic resonance spectroscopy techniques in individuals with HIV dementia.

PURPOSE: To evaluate single-voxel proton magnetic resonance spectroscopy (SV-MRS) and magnetic resonance spectroscopic imaging (MRSI) metabolite results in individuals with HIV dementia. MATERIALS AND METHODS: Twenty HIV-positive (HIV+) individuals underwent SV-MRS (TE 35 msec) and MRSI (TE 280 msec). Results were stratified according to serostatus, dementia severity, psychomotor speed performance, and functional impairment. RESULTS: HIV+ individuals with psychomotor slowing had an increased myoinositol/creatine (mI/Cr) ratio (0.63 vs. 0.45) in the frontal white matter using SV-MRS and an increased choline (Cho)/Cr ratio (1.88 vs. 1.41) in the mesial frontal gray matter using MRSI compared to HIV+ individuals without psychomotor slowing. Using MRSI, subjects with HIV dementia also had a decreased N-acetyl aspartate (NAA)/Cho ratio (1.55 vs. 2.53) compared to HIV+ individuals without cognitive impairment in the mesial frontal gray matter. Both techniques detected metabolite ratio abnormalities associated with abnormal functional performance. CONCLUSION: SV-MRS and MRSI offer complementary roles in evaluating individuals with HIV dementia. Short TE SV-MRS measures mI, which may be elevated in early HIV dementia, whereas MRSI provides wider spatial coverage to examine specific regional changes.

Additive effects of HIV and chronic methamphetamine use on brain metabolite abnormalities.

OBJECTIVE: Proton magnetic resonance spectroscopy (1H-MRS) showed decreased neuronal marker N-acetylaspartate and increased glial marker myo-inositol in subjects with chronic methamphetamine use and in subjects infected with HIV. The authors sought to determine whether HIV and a history of chronic methamphetamine use might have additive or interactive effects on brain metabolite abnormalities. METHOD: 1H-MRS was performed in 68 HIV-positive subjects (24 with a history of chronic methamphetamine use with a lifetime exposure of a mean of 2,167 g [SD=2,788] and last use a mean of 4.9 months earlier [SD=6.0]; 44 with no history of drug abuse) and 75 HIV-negative subjects (36 with a history of chronic methamphetamine use with a lifetime exposure of a mean of 8,241 g [SD=16,850] and last use a mean of 6.3 months earlier [SD=7.8]; 39 with no history of drug abuse). Concentrations of N-acetylaspartate, creatine, choline, and myo-inositol were measured in the frontal cortex, frontal white matter, and basal ganglia. RESULTS: HIV-negative subjects with a history of chronic methamphetamine use showed lower concentrations of the neuronal marker N-acetylaspartate in the frontal white matter and basal ganglia and higher concentrations of choline compounds and the glial marker myo-inositol in the frontal cortex, relative to subjects with no history of drug abuse. HIV-positive status was associated with lower concentrations of N-acetylaspartate and creatine in the frontal cortex and higher concentrations of myo-inositol in the white matter, compared with HIV-negative status. Compared to the mean concentrations of metabolites in HIV-negative subjects with no history of drug abuse, the mean concentrations in subjects with HIV and chronic methamphetamine use showed additive effects on N-acetylaspartate in all three regions (-9% in the basal ganglia, -7% in the frontal white matter, and -6% in the frontal gray matter), on creatine in the basal ganglia (-7%), and on myo-inositol in the frontal white matter (+11%). CONCLUSIONS: The combined effects of HIV and chronic methamphetamine use were consistent with an additive model, suggesting additional neuronal injury and glial activation due to the comorbid conditions.

Effect of aging on brain metabolism in antiretroviral-naive HIV patients.

OBJECTIVE: Normal aging as well as HIV infection may lead to inflammatory changes and injury to the brain; however, it is unclear if and how these processes interact. The goal of this pilot study was to evaluate the interaction between aging and HIV infection in the brain using proton magnetic resonance spectroscopy (H-MRS). DESIGN: Analyses of covariance (ANCOVA) were performed to determine the effects of HIV and age, and their interaction, on MRS variables. METHODS: Forty-six HIV patients naive to antiretroviral medications and 58 seronegative control subjects were examined using localized H-MRS in the frontal gray matter, frontal white matter and basal ganglia, and metabolite concentrations were determined. RESULTS: Compared with seronegative controls, HIV-positive subjects showed additional and marked increases in the concentration of glial markers, choline-containing compounds (seronegative controls +2%/decade; HIV-positive subjects +10%/decade) and myoinositol (seronegative controls +3%/decade; HIV-positive subjects +12%/decade), with aging in the frontal white matter. In the basal ganglia, N-acetyl compounds and total creatine decreased with age only in HIV patients (N-acetyl compounds -3.7%/decade; creatine -4%/decade). ANCOVA showed significant interaction effects between HIV and aging on the metabolites in the basal ganglia (N-acetyl peak P = 0.03; creatine P = 0.04) and in the frontal white matter (interaction: choline-containing compounds P = 0.002; myoinositol P = 0.007). CONCLUSION: In the basal ganglia, HIV infection appeared to induce neuronal damage or loss beyond that observed in normal aging. In the frontal white matter, HIV infection seemed to exacerbate glial activation beyond that observed in normal aging.