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Rapid real-world data analysis of patients with cancer, with and without COVID-19, across distinct health systems.
Hwang, C, Izano, MA, Thompson, MA, Gadgeel, SM, Weese, JL, Mikkelsen, T, Schrag, A, Teka, M, Walters, S, Wolf, FM, et al
Cancer reports (Hoboken, N.J.). 2021;(5):e1388
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Abstract
BACKGROUND The understanding of the impact of COVID-19 in patients with cancer is evolving, with need for rapid analysis. AIMS This study aims to compare the clinical and demographic characteristics of patients with cancer (with and without COVID-19) and characterize the clinical outcomes of patients with COVID-19 and cancer. METHODS AND RESULTS Real-world data (RWD) from two health systems were used to identify 146 702 adults diagnosed with cancer between 2015 and 2020; 1267 COVID-19 cases were identified between February 1 and July 30, 2020. Demographic, clinical, and socioeconomic characteristics were extracted. Incidence of all-cause mortality, hospitalizations, and invasive respiratory support was assessed between February 1 and August 14, 2020. Among patients with cancer, patients with COVID-19 were more likely to be Non-Hispanic black (NHB), have active cancer, have comorbidities, and/or live in zip codes with median household income <$30 000. Patients with COVID-19 living in lower-income areas and NHB patients were at greatest risk for hospitalization from pneumonia, fluid and electrolyte disorders, cough, respiratory failure, and acute renal failure and were more likely to receive hydroxychloroquine. All-cause mortality, hospital admission, and invasive respiratory support were more frequent among patients with cancer and COVID-19. Male sex, increasing age, living in zip codes with median household income <$30 000, history of pulmonary circulation disorders, and recent treatment with immune checkpoint inhibitors or chemotherapy were associated with greater odds of all-cause mortality in multivariable logistic regression models. CONCLUSION RWD can be rapidly leveraged to understand urgent healthcare challenges. Patients with cancer are more vulnerable to COVID-19 effects, especially in the setting of active cancer and comorbidities, with additional risk observed in NHB patients and those living in zip codes with median household income <$30 000.
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[Effects of lifestyle interventions for arterial hypertension in primary care: A systematic review].
Sanftenberg, L, Badermann, M, Kohls, N, Weber, A, Schelling, J, Sirois, F, Toussaint, L, Hirsch, J, Offenbächer, M
Zeitschrift fur Evidenz, Fortbildung und Qualitat im Gesundheitswesen. 2020;:12-19
Abstract
BACKGROUND The proportion of adults suffering from hypertension worldwide was estimated at 31.1 % in 2010. The aim of this study was to evaluate the effects of lifestyle changes in patients with arterial hypertension (AH) in primary care. MATERIAL AND METHODS Systematic literature search in the online databases PubMed, Embase, Cochrane and Opengrey. Only randomized controlled trials of the years 2005 to 2017 in German or English were considered. RESULTS 11 studies out of 458 identified references were evaluated. The patient groups investigated were very heterogeneous and underwent different types of intervention. Educating patients about the clinical picture, regular self-measurements of blood pressure, or patient memories of maintaining a healthy lifestyle have been used most frequently. CONCLUSION There is a need for further studies focusing on primary care. However, many lifestyle interventions seem to show very good effects in patients with pre-existing AH (secondary prophylaxis), so these measures should form the basis of antihypertensive therapy in all patients with AH. In addition, it is important to maintain advice on a healthy lifestyle during drug therapy.
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[Potential cognitive alterations after treatment of benign prostate syndrome. Investigations on transurethral electroresection and 180 W GreenLight XPS laser therapy].
Wiedemann, A, Maykan, R, Pennekamp, J, Hirsch, J, Heppner, H
Zeitschrift fur Gerontologie und Geriatrie. 2015;(5):446-51
Abstract
OBJECTIVE The study was carried out to detect possible changes in cognition after transurethral resection of the prostate (TURP) and 180 W GreenLight-XPS laser treatment of the prostate. METHODS Cognitive capacity was assessed by the mini-mental state examination (MMSE) and the clock test preoperatively and on postoperative day 2 in addition to documentation of clinical parameters, such as patient age, prostate size, duration of surgery, comorbidities, co-medications and alterations in hemoglobin (Hb) and sodium concentrations. RESULTS Patients treated with TURP (n = 88) and 180 W GreenLight-XPS laser treatment of the prostate (n = 114) were comparable regarding age, prostate size and duration of surgery. Baseline characteristics of the patients treated by laser showed an increased potential for postoperative cognitive changes with an average of 3.8 comorbidities (TURP 3.11, p = 0.005) and were using an average of 6.79 multiple medications (TURP 5.24, p < 0.001); however, neither the MMSE nor the clock test demonstrated a decrease in the average postoperative score (difference between postoperative and preoperative MMSE + 0.6 ± 1.6 for 180 W GreenLight-XPS laser treatment and + 0.6 ± 1.6 for TURP, p = 0.944; difference postoperative and preoperative clock test + 0.43 ± 1.44 for 180 W GreenLight-XPS laser treatment and 0.13 ± 1.17 for TURP, p = 0.097). Neither postoperative hemoglobin nor sodium concentrations, as safety relevant parameters, demonstrated clinically relevant changes. The differences between the surgical procedures were not statistically significant. DISCUSSION Neither 180 W GreenLight-XPS laser treatment of the prostate nor TURP demonstrated changes in cognition by comparing the preoperative MMSE and the clock test scores. In this study, the baseline characteristics of laser-treated patients showed a higher number of comorbidities and a higher use of medications, particular those with anticholinergic potency; therefore, 180 W GreenLight-XPS laser treatment of the prostate appears particularly safe for elderly patients.
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Sleep restriction increases the neuronal response to unhealthy food in normal-weight individuals.
St-Onge, MP, Wolfe, S, Sy, M, Shechter, A, Hirsch, J
International journal of obesity (2005). 2014;38(3):411-6
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Plain language summary
Sleep patterns influence eating behaviour and the body’s response to food. Previous studies suggest that short sleep duration leads to increased caloric intake and a desire for high-fat foods, however the specific neural mechanisms explaining how sleep restriction modulates this response is unknown. The aim of this study was to determine whether a specific area of the brain is activated in response to unhealthy compared with healthy foods. 25 participants were included, all of which were normal weight and had normal sleeping patterns. Each participant was tested after five nights of either 4 or 9 hours in bed by functional magnetic resonance imaging (fMRI). The test was performed while the participant was shown healthy and unhealthy food photos in the fasted state. This study found that after a period of restricted sleep compared with habitual sleep, unhealthy foods led to greater activation in brain regions associated with reward compared with healthy foods. This finding provides a model of neuronal mechanisms relating short sleep duration to obesity and cardio-metabolic risk factors and warrants further investigation.
Abstract
CONTEXT Sleep restriction alters responses to food. However, the underlying neural mechanisms for this effect are not well understood. OBJECTIVE The purpose of this study was to determine whether there is a neural system that is preferentially activated in response to unhealthy compared with healthy foods. PARTICIPANTS Twenty-five normal-weight individuals, who normally slept 7-9 h per night, completed both phases of this randomized controlled study. INTERVENTION Each participant was tested after a period of five nights of either 4 or 9 h in bed. Functional magnetic resonance imaging (fMRI) was performed in the fasted state, presenting healthy and unhealthy food stimuli and objects in a block design. Neuronal responses to unhealthy, relative to healthy food stimuli after each sleep period were assessed and compared. RESULTS After a period of restricted sleep, viewing unhealthy foods led to greater activation in the superior and middle temporal gyri, middle and superior frontal gyri, left inferior parietal lobule, orbitofrontal cortex, and right insula compared with healthy foods. These same stimuli presented after a period of habitual sleep did not produce marked activity patterns specific to unhealthy foods. Further, food intake during restricted sleep increased in association with a relative decrease in brain oxygenation level-dependent (BOLD) activity observed in the right insula. CONCLUSION This inverse relationship between insula activity and food intake and enhanced activation in brain reward and food-sensitive centers in response to unhealthy foods provides a model of neuronal mechanisms relating short sleep duration to obesity.
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Amodal brain activation and functional connectivity in response to high-energy-density food cues in obesity.
Carnell, S, Benson, L, Pantazatos, SP, Hirsch, J, Geliebter, A
Obesity (Silver Spring, Md.). 2014;(11):2370-8
Abstract
OBJECTIVE The obesogenic environment is pervasive, yet only some people become obese. The aim was to investigate whether obese individuals show differential neural responses to visual and auditory food cues, independent of cue modality. METHODS Obese (BMI 29-41, n = 10) and lean (BMI 20-24, n = 10) females underwent fMRI scanning during presentation of auditory (spoken word) and visual (photograph) cues representing high-energy-density (ED) and low-ED foods. The effect of obesity on whole-brain activation, and on functional connectivity with the midbrain/VTA, was examined. RESULTS Obese compared with lean women showed greater modality-independent activation of the midbrain/VTA and putamen in response to high-ED (vs. low-ED) cues, as well as relatively greater functional connectivity between the midbrain/VTA and cerebellum (P < 0.05 corrected). CONCLUSIONS Heightened modality-independent responses to food cues within the midbrain/VTA and putamen, and altered functional connectivity between the midbrain/VTA and cerebellum, could contribute to excessive food intake in obese individuals.
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Sleep restriction leads to increased activation of brain regions sensitive to food stimuli.
St-Onge, MP, McReynolds, A, Trivedi, ZB, Roberts, AL, Sy, M, Hirsch, J
The American journal of clinical nutrition. 2012;(4):818-24
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Abstract
BACKGROUND Epidemiologic evidence shows an increase in obesity concurrent with a reduction in average sleep duration among Americans. Although clinical studies propose that restricted sleep affects hormones related to appetite, neuronal activity in response to food stimuli after restricted and habitual sleep has not been investigated. OBJECTIVE The objective of this study was to determine the effects of partial sleep restriction on neuronal activation in response to food stimuli. DESIGN Thirty healthy, normal-weight [BMI (in kg/m²): 22-26] men and women were recruited (26 completed) to participate in a 2-phase inpatient crossover study in which they spent either 4 h/night (restricted sleep) or 9 h/night (habitual sleep) in bed. Each phase lasted 6 d, and functional magnetic resonance imaging was performed in the fasted state on day 6. RESULTS Overall neuronal activity in response to food stimuli was greater after restricted sleep than after habitual sleep. In addition, a relative increase in brain activity in areas associated with reward, including the putamen, nucleus accumbens, thalamus, insula, and prefrontal cortex in response to food stimuli, was observed. CONCLUSION The findings of this study link restricted sleep and susceptibility to food stimuli and are consistent with the notion that reduced sleep may lead to greater propensity to overeat.
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Energy intake in weight-reduced humans.
Rosenbaum, M, Kissileff, HR, Mayer, LE, Hirsch, J, Leibel, RL
Brain research. 2010;:95-102
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Abstract
Almost anyone who has ever lost weight can attest that it is harder to sustain weight loss than to lose weight. Maintenance of a 10% or greater reduced body weight is accompanied by decreases in energy expenditure to levels significantly below what is predicted solely on the basis of weight and body composition changes. This disproportionate decline in energy expenditure would not be sufficient to account for the over 80% recidivism rate to pre-weight loss levels of body fatness after otherwise successful weight reduction if there were a corresponding reduction in energy intake. In fact, reduced body weight maintenance is accompanied by increased energy intake above that required to maintain reduced weight. The failure to reduce energy intake in response to decreased energy output reflects decreased satiation and perception of how much food is eaten and multiple changes in neuronal signaling in response to food which conspire with the decline in energy output to keep body energy stores (fat) above a CNS-defined minimum (threshold). Much of this biological opposition to sustained weight loss is mediated by the adipocyte-derived hormone "leptin."
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Leptin reverses weight loss-induced changes in regional neural activity responses to visual food stimuli.
Rosenbaum, M, Sy, M, Pavlovich, K, Leibel, RL, Hirsch, J
The Journal of clinical investigation. 2008;(7):2583-91
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Abstract
Increased hunger and food intake during attempts to maintain weight loss are a critical problem in clinical management of obesity. To determine whether reduced body weight maintenance is accompanied by leptin-sensitive changes in neural activity in brain regions affecting regulatory and hedonic aspects of energy homeostasis, we examined brain region-specific neural activity elicited by food-related visual cues using functional MRI in 6 inpatient obese subjects. Subjects were assessed at their usual weight and, following stabilization at a 10% reduced body weight, while receiving either twice daily subcutaneous injections of leptin or placebo. Following weight loss, there were predictable changes in neural activity, many of which were reversed by leptin, in brain areas known to be involved in the regulatory, emotional, and cognitive control of food intake. Specifically, following weight loss there were leptin-reversible increases in neural activity in response to visual food cues in the brainstem, culmen, parahippocampal gyrus, inferior and middle frontal gyri, middle temporal gyrus, and lingual gyrus. There were also leptin-reversible decreases in activity in response to food cues in the hypothalamus, cingulate gyrus, and middle frontal gyrus. These data are consistent with a model of the weight-reduced state as one of relative leptin deficiency.
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Reproducibility of single- and multi-voxel 1H MRS measurements of intramyocellular lipid in overweight and lean subjects under conditions of controlled dietary calorie and fat intake.
Shen, W, Mao, X, Wolper, C, Heshka, S, Dashnaw, S, Hirsch, J, Heymsfield, SB, Shungu, DC
NMR in biomedicine. 2008;(5):498-506
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Abstract
The reproducibility of repeated single-voxel 1H MRS (SV-MRS) and spectroscopic imaging (MRSI) measurements of intramyocellular lipid (IMCL) in the tibialis anterior muscle of five lean and five overweight female Caucasians, during 7 days of controlled dietary fat and calorie intake, was assessed at 1.5 T. Duplicate measures of IMCL relative to total muscle creatine (IMCL/tCr) obtained 3 days apart by both SV-MRS and MRSI correlated well (r = 0.65 and r = 0.95, respectively, P < 0.05). The coefficients of variation for repeated measures of IMCL/tCr by SV-MRS and MRSI were 24.4% and 10.7%, respectively. IMCL/tCr measured by MRSI was higher in overweight subjects than in lean subjects (8.3 +/- 3.8 vs 4.3 +/- 2.4, P < 0.05). Although both methods achieved good reproducibility in measuring IMCL in vivo, MRSI was found to offer greater flexibility and reliability, and higher sensitivity to IMCL differences, whereas SV-MRS was advantageous with respect to shorter scan time and ease of implementation.
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Relationship between carbohydrate-induced hypertriglyceridemia and fatty acid synthesis in lean and obese subjects.
Hudgins, LC, Hellerstein, MK, Seidman, CE, Neese, RA, Tremaroli, JD, Hirsch, J
Journal of lipid research. 2000;(4):595-604
Abstract
We previously reported that a eucaloric, low fat, liquid formula diet enriched in simple carbohydrate markedly increased the synthesis of fatty acids in lean volunteers. To examine the diet sensitivity of obese subjects, 7 obese and 12 lean volunteers were given two eucaloric low fat solid food diets enriched in simple sugars for 2 weeks each in a random-order, cross-over design (10% fat, 75% carbohydrate vs. 30% fat, 55% carbohydrate, ratio of sugar to starch 60:40). The fatty acid compositions of both diets were matched to the composition of each subject's adipose tissue and fatty acid synthesis measured by the method of linoleate dilution in plasma VLDL triglyceride. In all subjects, the maximum % de novo synthesized fatty acids in VLDL triglyceride 3;-9 h after the last meal was higher on the 10% versus the 30% fat diet. There was no significant difference between the dietary effects on lean (43+/-13 vs. 12+/-13%) and obese (37+/-15 vs. 6+/-6%) subjects, despite 2-fold elevated levels of insulin and reduced glucagon levels in the obese. Similar results were obtained for de novo palmitate synthesis in VLDL triglyceride measured by mass isotopomer distribution analysis after infusion of [(13)C]acetate. On the 10% fat diet, plasma triglycerides (fasting and 24 h) were increased and correlated with fatty acid synthesis. Triglycerides were higher when fatty acid synthesis was constantly elevated rather than having diurnal variation.Thus, eucaloric, solid food diets which are very low in fat and high in simple sugars markedly stimulate fatty acid synthesis from carbohydrate, and plasma triglycerides increase in proportion to the amount of fatty acid synthesis. However, this dietary effect is not related to body mass index, insulin, or glucagon levels.