<Emphasis Type="Italic">V</Emphasis>O<Subscript>2</Subscript>max during successive maximal efforts

The concept of VO₂max has been a defining paradigm in exercise physiology for >75 years. Within the last decade, this concept has been both challenged and defended. The purpose of this study was to test the concept of VO₂max by comparing VO₂ during a second exercise bout following a preliminary maximal effort exercise bout. The study had two parts. In Study #1, physically active non-athletes performed incremental cycle exercise. After 1-min recovery, a second bout was performed at a higher power output. In Study #2, competitive runners performed incremental treadmill exercise and, after 3-min recovery, a second bout at a higher speed. In Study #1 the highest VO₂ (bout 1 vs. bout 2) was not significantly different (3.95 ± 0.75 vs. 4.06 ± 0.75 l min⁻¹). Maximal heart rate was not different (179 ± 14 vs. 180 ± 13 bpm) although maximal V _E was higher in the second bout (141 ± 36 vs. 151 ± 34 l min⁻¹). In Study #2 the highest VO₂ (bout 1 vs. bout 2) was not significantly different (4.09 ± 0.97 vs. 4.03 ± 1.16 l min⁻¹), nor was maximal heart rate (184 + 6 vs. 181 ± 10 bpm) or maximal V _E (126 ± 29 vs. 126 ± 34 l min⁻¹). The results support the concept that the highest VO₂ during a maximal incremental exercise bout is unlikely to change during a subsequent exercise bout, despite higher muscular power output. As such, the results support the “classical” view of VO₂max.     

Hypothalamic and hindbrain NPY, AGRP and NE increase consummatory feeding responses

Feeding behavior is comprised of both appetitive and consummatory responses to food. Appetitive responses include the motivated acquisition of food. Consummatory responses, including swallowing, are those that move the food from the mouth to the stomach. Intraoral delivery of liquid food bypasses the requirement for appetitive responses and has been used to examine consummatory responses directly in intact rats. In the present study, we administered neuropeptide Y (NPY), agouti-related protein (AGRP) and norepinephrine (NE), into the paraventricular nucleus of the hypothalamus (PVN) or into the fourth cerebral ventricle to examine their effects on the consummatory component of feeding behavior in the rat. To measure consummatory responses, milk (40% lactose free cow's milk diluted with water) was infused intraorally through a chronic cheek fistula (1 ml/min), using an alternating 5 min on − 1 min off schedule, until rejection occurred. We found that both hypothalamic and fourth ventricle injections of NPY, AGRP and NE significantly increased consumption of the intraorally-delivered milk. Our results indicate that the circuitry for modulation of consummatory ingestive responses includes NE, NPY and AGRP receptors operating in both hypothalamic and hindbrain sites.     

Effect of micronutrients and iron supplementation on hemoglobin, iron status, and plasma hepatitis C and HIV RNA levels in female injection drug users: a controlled clinical trial

BACKGROUND: Iron deficiency is common among female injection drug users, but it is unclear whether iron supplementation can reduce anemia and improve iron status without increasing plasma hepatitis C virus (HCV) or HIV RNA levels. METHODS: We conducted a phase 3, double-blind, randomized, controlled clinical trial of daily micronutrients with 18 mg of iron (iron group) versus micronutrients without iron (control group) for 12 months among hepatitis C-positive female injection drug users in Baltimore, Maryland. The main outcome measures were hemoglobin, markers of iron status, plasma HCV RNA, plasma HIV RNA, and liver enzymes at 6 and 12 months of follow-up. RESULTS: Four hundred fifty-eight women (320 HIV-negative and 138 HIV-positive) enrolled in the trial. There were no significant differences in the proportion of women with anemia, ferritin<30 ng/mL, log10 plasma HCV RNA, or log10 plasma HIV RNA between treatment groups at enrollment. The proportion with anemia in the iron and control groups, respectively, was 20.7% versus 31.3% (P=0.026) at 6 months and 26.2% versus 30.4% (P=0.5) at 12 months; with ferritin<30 ng/mL, the proportion was 29.2% versus 55.5% (P<0.0001) at 6 months and 26.2% versus 46.9% (P=0.0018) at 12 months. In the iron and control groups, respectively, mean log10 plasma HCV RNA (IU/mL) was 5.2 versus 5.2 (P=0.86) at 6 months and 5.4 versus 5.3 (P=0.6) at 12 months. Among HIV-positive subjects, mean log10 plasma RNA (copies/mL) in the iron and placebo groups, respectively, was 3.8 versus 3.7 (P=0.75) at 6 months and 3.7 versus 4.1 (P=0.19) at 12 months. There were no significant differences in liver enzyme levels between the treatment groups at enrollment, 6 months, and 12 months. CONCLUSIONS: A daily micronutrient supplement with iron can reduce anemia and improve iron status in female injection drug users without increasing plasma HCV or HIV RNA levels or altering liver enzymes.     

Effects of communication-debilitating illnesses and injuries on close relationships: a relational maintenance perspective

A communication-debilitating illness or injury (CDI) presents significant challenges for patients as well as for friends and family. In a qualitative study of the effects of a CDI on close relationships, 28 individuals with loved ones who had experienced a CDI were interviewed. Participants described adjustments in communication with the patient and explained what it is like to experience a relationship with a CDI patient. Themes that emerged transcended the type of illness and relationship. Recommendations are made for further research that focuses on patients' relationships with a variety of social network members, beyond primary caregivers.     

Perceptions of care coordination among older adult cancer survivors: A SEER-CAHPS study

ObjectiveCare coordination reflects deliberate efforts to harmonize patient care. This study examined variables associated with patient-reported care coordination scores among Medicare beneficiaries with a history of cancer.MethodsWe utilized Surveillance, Epidemiology, and End Results-Consumer Assessment of Healthcare Providers and Systems (SEER-CAHPS) linked data, which includes cancer registry data, patient experience surveys, and Medicare claims. We identified Medicare beneficiaries with a CAHPS survey ≤10 years after cancer diagnosis who reported seeing a personal doctor within six months. Multivariable regression models examined associations between cancer survivor characteristics and patient-reported care coordination, with higher scores indicating better coordination.ResultsCancer site distribution of the 14,646 survey respondents was 33.7% prostate, 22.1% breast, 11.1% colorectal, 7.2% lung, and 25.9% other. Rural residence at diagnosis (versus urban, 1.1-point difference; p = 0.04) and reporting >4 visits with a personal doctor (versus 1–2 visits, 3.0-point difference; p < 0.001) were significantly associated with higher care coordination. Older age (p < 0.001) and seeing more specialists (p = 0.006) were associated with significantly lower care coordination. Patients with melanoma (women: 5.2-point difference, p < 0.001; men: 2.7 points, p = 0.01) or breast cancer (women: 2.4 points; p < 0.001) reported significantly lower care coordination scores than did men with prostate cancer (reference group). Time from diagnosis to survey, cancer stage, number of cancers, and comorbidities were not significantly associated with care coordination scores.DiscussionCancer site, rural residence, and number of physician interactions are associated with patient-reported care coordination scores. Future research should address multilevel influences that lead to worse care coordination for older adult cancer survivors.     

The association between patient experience and healthcare outcomes using SEER-CAHPS patient experience and outcomes among cancer survivors

ObjectiveTo understand the relationship between patient experience, as measured by scores on the Consumer Assessment of Healthcare Providers and Systems (CAHPS®) survey, and clinical and financial outcomes among older cancer survivors.Materials and MethodsWe analyzed the records of all Fee-for-Service (FFS) Medicare beneficiaries 66 years and older who completed one CAHPS survey from 2001 to 2004 or 2007–2013 with one of the five following cancer types: breast, bladder, colorectal, lung, or prostate; and completed a CAHPS survey within 5 years of cancer diagnosis date. We conducted a multivariate analysis, controlling for clinical and demographic variables, to evaluate the association between excellent CAHPS scores and the following clinical and financial outcomes: mortality, emergency department visits, and total healthcare expenditures.ResultsA total of 7395 individuals were present in our cohort, with 57% being male and 85.7% non-Hispanic White. Breakdown of the cohort by cancer site is as follows: prostate (40.4%), breast (28.6%), colorectal (14.0%), lung (9.4%), and bladder (7.6%). When looking at the relationship between CAHPS scores and clinical outcomes, there was no significant difference between excellent and non-excellent CAHPS score respondents in all three of the clinical outcomes studied. Furthermore, there was no association between ED utilization and patient experience scores when stratifying by cancer site and race/ethnicity among this cohort.ConclusionIn this cohort, a highly rated patient experience, as measured by responses on the CAHPS survey, is not associated with improved clinical outcomes among older cancer survivors.     

Mechanisms of imipridones in targeting mitochondrial metabolism in cancer cells

ONC201 is the first member of the imipridone family of anticancer drugs to enter the clinic for the treatment of diverse solid and hematologic cancers. A subset of pediatric and adult patients with highly aggressive brain tumors has shown remarkable clinical responses to ONC201, and recently, the more potent derivative ONC206 entered clinical trials as a single agent for the treatment of central nervous system (CNS) cancers. Despite the emerging clinical interest in the utility of imipridones, their exact molecular mechanisms are not fully described. In fact, the existing literature points to multiple pathways (e.g. tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) signaling, dopamine receptor antagonism, and mitochondrial metabolism) as putative drug targets. We have performed a comprehensive literature review and highlighted mitochondrial metabolism as the major target of imipridones. In support of this, we performed a meta-analysis of an ONC201 screen across 539 human cancer cell lines and showed that the mitochondrial caseinolytic protease proteolytic subunit (ClpP) is the most significant predictive biomarker of response to treatment. Herein, we summarize the main findings on the anticancer mechanisms of this potent class of drugs, provide clarity on their role, and identify clinically relevant predictive biomarkers of response.     

Human papilloma virus circulating tumor DNA assay predicts treatment response in recurrent/metastatic head and neck squamous cell carcinoma

Despite the rising incidence of human papillomavirus related (HPV+) oropharyngeal squamous cell carcinoma (OPSCC), treatment of metastatic disease remains palliative. Even with new treatments such as immunotherapy, response rates are low and can be delayed, while even mild tumor progression in the face of an ineffective therapy can lead to rapid death. Real-time biomarkers of response to therapy could improve outcomes by guiding early change of therapy in the metastatic setting. Herein, we developed and analytically validated a new droplet digital PCR (ddPCR)-based assay for HPV16 circulating tumor DNA (ctDNA) and evaluated plasma HPV16 ctDNA for predicting treatment response in metastatic HPV+ OPSCC. We found that longitudinal changes HPV16 ctDNA correlate with treatment response and that ctDNA responses are observed earlier than conventional imaging (average 70 days, range: 35–166). With additional validation in multi-site studies, this assay may enable early identification of treatment failure, allowing patients to be directed promptly toward clinical trials or alternative therapies.     

Low plasma vitamin B-12 in Kenyan school children is highly prevalent and improved by supplemental animal source foods

The high prevalence of vitamin B-12 deficiency in many regions of the world is becoming recognized as a widespread public health problem, but it is not known to what extent this deficiency results from a low intake of the vitamin or from its malabsorption from food. In rural Kenya, where a previous study identified a high prevalence of inadequate vitamin B-12 intakes, this study examined whether plasma vitamin B-12 concentrations were associated with dietary sources of the vitamin at baseline and could be increased by supplementation with animal source foods (ASF). The 4 experimental groups in 503 school children were: 1) control (no food provided); 2) githeri (a maize and bean staple with added oil); 3) githeri + meat (githeri + minced beef); or 4) githeri + milk (githeri + milk). Feedings were isocaloric. Dietary data were collected at baseline, and biochemical data at baseline and after 1 and 2 y of feeding. Baseline plasma vitamin B-12 concentration was 193.6 +/- 105.3 pmol/L and correlated with % energy from ASF (r = 0.308, P < 0.001). The odds ratio for low plasma vitamin B-12 (<148 pmol/L), which occurred in 40% of children, was 6.28 [95% CI: 3.07-12.82] for the lowest vs. highest ASF intake tertile (P < 0.001). Feeding ASF (meat or milk) greatly reduced the prevalence of low plasma vitamin B-12 (P < 0.001). The high prevalence of low plasma vitamin B-12 concentrations in these children is predicted by a low intake of ASF, and supplemental ASF improves vitamin B-12 status.