Mindfulness messages on napkins: The efficacy of dining hall napkins as a messaging channel.

OBJECTIVE: To assess the efficacy of utilizing dining hall napkins as a novel health messaging strategy to promote mindfulness. PARTICIPANTS: Undergraduate students at a large Midwestern university.Methods: Utilizing a place-based promotional strategy, mindfulness messages were printed on over 8-million napkins at dining halls. Surveys (N = 573) were used to measure message viewership, and attitudes toward mindfulness. RESULTS: While only a few small significant effects for students who read the messaging were found (e.g., increases in self-efficacy for keeping ones phone out of sight while speaking with someone), napkins appeared to be a successful channel for reaching students. About 97% of students who dined in-person indicated they saw the napkin messaging. Additionally, students were more likely to read the napkin messaging when dining in-person rather than when they took their food "to-go." CONCLUSION: Future research should continue to test napkins' efficacy as a messaging channel for health messaging for college students.

Fluoroquinolone prophylaxis does not increase risk of neuropathy in children with acute lymphoblastic leukemia.

BACKGROUND: Fluoroquinolone antibiotics are frequently utilized in pediatric oncology patients as prophylaxis or step-down therapy following broad spectrum beta-lactam therapy for febrile neutropenia. Concerns regarding neurotoxicity limit the use of these agents. No studies have evaluated the association between fluoroquinolone use and neurotoxicity in pediatric oncology patients receiving other neurotoxic agents such as vincristine. METHODS: An observational cohort study comprising patients aged 0-18 at diagnosis enrolled on a prospective study for treatment of acute lymphoblastic leukemia (ALL) at a pediatric comprehensive cancer center between October 2007 and November 2018. Data for neuropathic pain and sensory or motor neuropathy were collected prospectively, and a Cox proportional hazards regression model was used to evaluate associations between administration of fluoroquinolone antibiotics during induction therapy and subsequent development of vincristine-induced peripheral neurotoxicity (VIPN). RESULTS: A total of 598 participants were enrolled, including 338 (57%) who received fluoroquinolones during induction therapy; of these 470 (79%) were diagnosed with VIPN and 139 (23%) were diagnosed with high-grade (Grade 3+) VIPN. On unadjusted analyses, and analyses adjusted for age and race, there was no evidence of an association between fluoroquinolone exposure and subsequent VIPN (hazard ratio [HR] 0.8, 95% CI 0.5-1.04, P = .08) or high-grade VIPN (HR 1.1, 95% CI 0.4-2.2, P = .87). CONCLUSIONS: The results of this observational study do not show an association between exposure to fluoroquinolone antibiotics during induction therapy for ALL and subsequent development of vincristine-induced peripheral neuropathies, and suggest that a large increase in VIPN is unlikely.

Engaging African American Parents to Develop a Mobile Health Technology for Breastfeeding: KULEA-NET.

BACKGROUND: African Americans breastfeed less than other groups, which has implications for health throughout the life course. Little is known about mobile health technologies to support breastfeeding. RESEARCH AIMS: This study proceeded in two phases. The aim of Phase 1 was to identify ideal technological components and content of a mobile health intervention. The aim of Phase 2 was to determine the usability of a prototype, KULEA-NET, based on the Phase 1 findings. METHODS: For this mixed-methods study, we used community-based participatory research methods and user-centered technology design methods. We used open coding in NVivo 11 to organize data from focus groups and in-depth interviews, then we analyzed the data. We then developed a prototype and tested the prototype's usability with the System Usability Scale. Fifty pregnant and postpartum African Americans from the District of Columbia participated. RESULTS: Participants preferred an app with text messaging technology and identified areas for intervention: self-efficacy, parent-child attachment beliefs, social support, public breastfeeding and social desirability, and returning to work. Desired features included local resources, support person access, baby care logs, identification of public breastfeeding venues, and peer discussions. The System Usability Scale score was 73.8, which indicates above average usability. CONCLUSIONS: A mobile health technology like KULEA-NET can be used to meet the breastfeeding needs of African Americans, build social desirability, and complement traditional health care. The appeal of an African American-specific intervention is unclear. Responding to mixed feeding practices is challenging. KULEA-NET is a mobile breastfeeding intervention guided by the preferences of African American parents and offers promising usability metrics.

CATS II Long-term Anthropometric and Metabolic Effects of Maternal Sub-optimal Thyroid Function in Offspring and Mothers.

CONTEXT AND OBJECTIVES: The Controlled Antenatal Thyroid Screening Study I (CATS-I) was a randomized controlled trial investigating the effects of levothyroxine therapy for suboptimal gestational thyroid function (SGTF), comparing outcomes in children of treated (SGTF-T) with untreated (SGTF-U) women during pregnancy. This follow-up study, CATS-II, reports the long-term effects on anthropometric, bone, and cardiometabolic outcomes in mothers and offspring and includes a group with normal gestational thyroid function (NGTF). DESIGN & PARTICIPANTS: 332 mothers (197 NGTF, 56 SGTF-U, 79 SGTF-T) aged 41.2±5.3 years (mean±SD) and 326 paired children assessed 9.3±1.0 years after birth for (i) body mass index (BMI); (ii) lean, fat, and bone mass by dual-energy X-ray absorptiometry; (iii) blood pressure, augmentation index, and aortic pulse-wave-velocity; and (iv) thyroid function, lipids, insulin, and adiponectin. The difference between group means was compared using linear regression. RESULTS: Offspring's measurements were similar between groups. Although maternal BMI was similar between groups at CATS-I, after 9 years (at CATS-II) SGTF-U mothers showed higher BMI (median [interquartile ratio] 28.3 [24.6-32.6] kg/m2) compared with NGTF (25.8 [22.9-30.0] kg/m2; P = 0.029), driven by fat mass increase. At CATS-II SGTF-U mothers also had higher thyroid-stimulating hormone (TSH) values (2.45 [1.43-3.50] mU/L) than NGTF (1.54 [1.12-2.07] mU/L; P = 0.015), since 64% had never received levothyroxine. At CATS-II, SGTF-T mothers had BMI (25.8 [23.1-29.8] kg/m2, P = 0.672) and TSH (1.68 [0.89-2.96] mU/L; P = 0.474) values similar to NGTF mothers. CONCLUSIONS: Levothyroxine supplementation of women with SGTF did not affect long-term offspring anthropometric, bone, and cardiometabolic measurements. However, absence of treatment was associated with sustained long-term increase in BMI and fat mass in women with SGTF.

Effects of testosterone supplementation on body composition and lower-body muscle function during severe exercise- and diet-induced energy deficit: A proof-of-concept, single centre, randomised, double-blind, controlled trial.

BACKGROUND: Severe energy deficits during military operations, produced by significant increases in exercise and limited dietary intake, result in conditions that degrade lean body mass and lower-body muscle function, which may be mediated by concomitant reductions in circulating testosterone. METHODS: We conducted a three-phase, proof-of-concept, single centre, randomised, double-blind, placebo-controlled trial (CinicalTrials.gov, NCT02734238) of non-obese men: 14-d run-in, free-living, eucaloric diet phase; 28-d live-in, 55% exercise- and diet-induced energy deficit phase with (200 mg testosterone enanthate per week, Testosterone, n = 24) or without (Placebo, n = 26) exogenous testosterone; and 14-d recovery, free-living, ad libitum diet phase. Body composition was the primary end point; secondary endpoints included lower-body muscle function and health-related biomarkers. FINDINGS: Following energy deficit, lean body mass increased in Testosterone and remained stable in Placebo, such that lean body mass significantly differed between groups [mean difference between groups (95% CI), 2.5 kg (3.3, 1.6); P < .0001]. Fat mass decreased similarly in both treatment groups [0.2 (-0.4, 0.7), P = 1]. Change in lean body mass was associated with change in total testosterone (r = 0.71, P < .0001). Supplemental testosterone had no effect on lower-body muscle function or health-related biomarkers. INTERPRETATION: Findings suggest that supplemental testosterone may increase lean body mass during short-term severe energy deficit in non-obese, young men, but it does not appear to attenuate lower-body functional decline. FUNDING: Collaborative Research to Optimize Warfighter Nutrition projects I and II, Joint Program Committee-5, funded by the US Department of Defence.

Asparaginase combined with discontinuous dexamethasone improves antileukemic efficacy without increasing osteonecrosis in preclinical models.

INTRODUCTION: Combination therapy for acute lymphoblastic leukemia (ALL) is highly effective but results in significant toxicity including osteonecrosis. Asparaginase is known to potentiate both the antileukemic and osteonecrosis-inducing effects of dexamethasone. The schedule of dexamethasone alters osteonecrosis risk. However, the effects of the interaction with asparaginase are unknown when dexamethasone is given on a discontinuous schedule. METHODS: Using the murine model of osteonecrosis, we compared the frequency of osteonecrosis in mice receiving discontinuous dexamethasone (3.5 days/ week) with mice receiving asparaginase and discontinuous dexamethasone. We then tested the effect on antileukemic efficacy using six pediatric ALL xenografts. RESULTS: The addition of asparaginase to discontinuous dexamethasone did not alter the rate of osteonecrosis compared to dexamethasone alone (7/35 in dexamethasone with asparaginase combination vs. 10/36 in dexamethasone alone, p = 0.62) despite increasing steady-state plasma dexamethasone levels (103.9 nM vs. 33.4 nM, p = 9.2x10-7). Combination therapy with asparaginase and dexamethasone demonstrated synergistic antileukemic effects across all six xenografts studied. CONCLUSIONS: When discontinuous dexamethasone was given, its anti-leukemic activity synergized with asparaginase but the osteonecrosis-worsening effects of asparaginase (above dexamethasone alone) were not observed. Thus, there is a favorable drug interaction (unchanged toxicity, synergistic efficacy) between discontinuous dexamethasone and asparaginase.

Towards Integrating Primary Care with Cancer Care: A Regional Study of Current Gaps and Opportunities in Canada.

BACKGROUND AND OBJECTIVES: Better integration between cancer care systems and primary care physicians (PCPs) is a goal of most healthcare systems, but little direction exists on how this can be achieved. This study systematically examined the extent of integration between PCPs and a regional cancer program (RCP) to identify opportunities for improvement. METHOD: Cross-sectional survey of all practising PCPs in the region of interest using a study-specific instrument based on a three-tier conceptualization of integration. RESULTS: Among the 473 PCPs who responded (63% response rate), perceived role clarity and the desire for greater involvement in patient care varied across the care trajectory. Specific gaps were identified in PCPs' understanding of the referral process and patient follow-up after treatment. CONCLUSION: Our novel survey of PCPs explicated the strategies that could improve their integration in cancer care, including mechanisms to support PCPs in the initial diagnosis of their patients and standardized post-treatment transition plans outlining care roles and responsibilities.

Evidence-based evaluation of potential benefits and safety of beta-alanine supplementation for military personnel.

This Department of Defense-sponsored evidence-based review evaluates the safety and putative outcomes of enhancement of athletic performance or improved recovery from exhaustion in studies involving beta-alanine alone or in combination with other ingredients. Beta-alanine intervention studies and review articles were collected from 13 databases, and safety information was collected from adverse event reporting portals. Due to the lack of systematic studies involving military populations, all the available literature was assessed with a subgroup analysis of studies on athletes to determine if beta-alanine would be suitable for the military. Available literature provided only limited evidence concerning the benefits of beta-alanine use, and a majority of the studies were not designed to address safety. Overall, the strength of evidence in terms of the potential for risk of bias in the quality of the available literature, consistency, directness, and precision did not support the use of beta-alanine by military personnel. The strength of evidence for a causal relation between beta-alanine and paresthesia was moderate.

Methotrexate-induced neurotoxicity and leukoencephalopathy in childhood acute lymphoblastic leukemia.

PURPOSE: Methotrexate (MTX) can cause significant clinical neurotoxicity and asymptomatic leukoencephalopathy. We sought to identify clinical, pharmacokinetic, and genetic risk factors for these MTX-related toxicities during childhood acute lymphoblastic leukemia (ALL) therapy and provide data on safety of intrathecal and high-dose MTX rechallenge in patients with neurotoxicity. PATIENTS AND METHODS: Prospective brain magnetic resonance imaging was performed at four time points for 369 children with ALL treated in a contemporary study that included five courses of high-dose MTX and 13 to 25 doses of triple intrathecal therapy. Logistic regression modeling was used to evaluate clinical and pharmacokinetic factors, and a genome-wide association study (GWAS) was performed to identify germline polymorphisms for their association with neurotoxicities. RESULTS: Fourteen patients (3.8%) developed MTX-related clinical neurotoxicity. Of 13 patients rechallenged with intrathecal and/or high-dose MTX, 12 did not experience recurrence of neurotoxicity. Leukoencephalopathy was found in 73 (20.6%) of 355 asymptomatic patients and in all symptomatic patients and persisted in 74% of asymptomatic and 58% of symptomatic patients at the end of therapy. A high 42-hour plasma MTX to leucovorin ratio (measure of MTX exposure) was associated with increased risk of leukoencephalopathy in multivariable analysis (P = .038). GWAS revealed polymorphisms in genes enriched for neurodevelopmental pathways with plausible mechanistic roles in neurotoxicity. CONCLUSION: MTX-related clinical neurotoxicity is transient, and most patients can receive subsequent MTX without recurrence of acute or subacute symptoms. All symptomatic patients and one in five asymptomatic patients develop leukoencephalopathy that can persist until the end of therapy. Polymorphisms in genes related to neurogenesis may contribute to susceptibility to MTX-related neurotoxicity.

Between-course targeting of methotrexate exposure using pharmacokinetically guided dosage adjustments.

PURPOSE: It is advantageous to individualize high-dose methotrexate (HDMTX) to maintain adequate exposure while minimizing toxicities. Previously, we accomplished this through within-course dose adjustments. METHODS: In this study, we evaluated a strategy to individualize HDMTX based on clearance of each individual's previous course of HDMTX in 485 patients with newly diagnosed acute lymphoblastic leukemia. Doses were individualized to achieve a steady-state plasma concentration (Cpss) of 33 or 65 µM (approximately 2.5 or 5 g/m(2)/day) for low- and standard-/high-risk patients, respectively. RESULTS: Individualized doses resulted in 70 and 63 % of courses being within 20 % of the targeted Cpss in the low- and standard-/high-risk arms, respectively, compared to 60 % (p < 0.001) and 61 % (p = 0.43) with conventionally dosed therapy. Only 1.3 % of the individualized courses in the standard-/high-risk arm had a Cpss greater than 50 % above the target compared to 7.3 % (p < 0.001) in conventionally dosed therapy. We observed a low rate (8.5 % of courses) of grade 3-4 toxicities. The odds of gastrointestinal toxicity were related to methotrexate plasma concentrations in both the low (p = 0.021)- and standard-/high-risk groups (p = 0.003). CONCLUSIONS: Individualizing HDMTX based on the clearance from the prior course resulted in fewer extreme Cpss values and less delayed excretion compared to conventional dosing.

Genome-wide study of methotrexate clearance replicates SLCO1B1.

Methotrexate clearance can influence the cure of and toxicity in children with acute lymphoblastic leukemia (ALL). We estimated methotrexate plasma clearance for 1279 patients with ALL treated with methotrexate (24-hour infusion of a 1 g/m2 dose or 4-hour infusion of a 2 g/m2 dose) on the Children's Oncology Group P9904 and P9905 protocols. Methotrexate clearance was lower in older children (P = 7 x 10(-7)), girls (P = 2.7 x 10(-4)), and those who received a delayed-intensification phase (P = .0022). A genome-wide analysis showed that methotrexate clearance was associated with polymorphisms in the organic anion transporter gene SLCO1B1 (P = 2.1 x 10(-11)). This replicates findings using different schedules of high-dose methotrexate in St Jude ALL treatment protocols; a combined meta-analysis yields a P value of 5.7 x 10(-19) for the association of methotrexate clearance with SLCO1B1 SNP rs4149056. Validation of this variant with 5 different treatment regimens of methotrexate solidifies the robustness of this pharmacogenomic determinant of methotrexate clearance. This study is registered at http://www.clinicaltrials.gov as NCT00005585 and NCT00005596.

Nutritional recommendations for the management of sarcopenia.

The Society for Sarcopenia, Cachexia, and Wasting Disease convened an expert panel to develop nutritional recommendations for prevention and management of sarcopenia. Exercise (both resistance and aerobic) in combination with adequate protein and energy intake is the key component of the prevention and management of sarcopenia. Adequate protein supplementation alone only slows loss of muscle mass. Adequate protein intake (leucine-enriched balanced amino acids and possibly creatine) may enhance muscle strength. Low 25(OH) vitamin D levels require vitamin D replacement.

Skeletal muscle loss: cachexia, sarcopenia, and inactivity.

Loss of skeletal muscle mass occurs during aging (sarcopenia), disease (cachexia), or inactivity (atrophy). This article contrasts and compares the metabolic causes of loss of muscle resulting from these conditions. An understanding of the underlying causes of muscle loss is critical for the development of strategies and therapies to preserve muscle mass and function. Loss of skeletal muscle protein results from an imbalance between the rate of muscle protein synthesis and degradation. Cachexia, sarcopenia, and atrophy due to inactivity are characterized by a loss of muscle mass. Each of these conditions results in a metabolic adaptation of increased protein degradation (cachexia), decreased rate of muscle protein synthesis (inactivity), or an alteration in both (sarcopenia). The clinical consequences of bedrest may mimic those of cachexia, including rapid loss of muscle, insulin resistance, and weakness. Prophylaxis against bedrest-induced atrophy includes nutrition support with an emphasis on high-quality protein. Nutritional supplementation alone may not prevent muscle loss secondary to cachexia, but, in combination with the use of an anabolic agent, it may slow or prevent muscle loss.

Successful transcatheter cryoablation in infants with drug-resistant supraventricular tachycardia: a case series.

PURPOSE: Drug-resistant supraventricular tachycardia can cause hemodynamic instability, especially in infants. There are no case-series reports of transcatheter cryoablation treatment for infants with drug-resistant supraventricular tachycardia. Our purpose is to report our experience with transcatheter cryoablation in three infants with drug-resistant supraventricular tachycardia. METHODS: We reviewed clinical and electrophysiologic data from infants who underwent cryothermal ablation for drug-resistant supraventricular tachycardia (SVT) at our institution. RESULTS: Three patients (age 10-42 days) underwent transcatheter cryothermal ablation over a 1-year period. None had arrhythmia suppression on medical management, and all had hemodynamic instability from persistent SVT episodes. Cryothermal mapping (-30 C) localized the suspected foci. All foci were adjacent to the AV node. Cryoablation lesions were delivered at and around mapped foci. In one patient, cryothermal energy application eliminated the SVT but resulted in transient right bundle branch block that resolved later. Two patients had hemodynamically insignificant episodes of SVT in the immediate post-ablation period that resolved with standard antiarrhythmic treatment. One died of sepsis but remained SVT free for 10 days after the procedure without antiarrhythmic medications. Neither of the two surviving patients had SVT recurrence at 6-month follow-up off medications. CONCLUSIONS: In our series, transcatheter cryoablation was an effective treatment for drug-resistant SVT in infants. We encountered some early nonsustained post-procedure SVT; however, such episodes did not predict procedural failure.

EAA supplementation to increase nitrogen intake improves muscle function during bed rest in the elderly.

BACKGROUND & AIMS: Older individuals are more likely to experience extended hospitalization and become protein malnourished during hospitalization. The concomitant compulsory inactivity results in functional decline. Increasing protein intake in hospitalized patients improves nitrogen balance, but effects on function are unknown. In the present study, we examined the effects of increasing protein intake by essential amino acid (EAA) supplementation in older individuals subjected to 10 d bed rest on LBM and muscle function. METHODS: Subjects were given a placebo (n=12, 68+/-5 (SD) yrs, 83+/-19 kg) or 15 g of EAA (n=10, 71+/-6, 72+/-8 kg) 3 times per day throughout 10d of bed rest. LBM, muscle protein synthesis, and muscle function were determined before and after bed rest. Due to an imbalance in randomized gender distribution between groups, gender and beginning functional and LBM measures were utilized for analyses by repeated measures analysis of covariance (RMANCOVA). RESULTS: Analyses revealed the potential for the preservation of functional outcomes with EAA supplementation. CONCLUSIONS: Increasing protein intake above the RDA may preserve muscle function in the elderly during compulsory inactivity. EAA supplementation is potentially an efficient method of increasing protein intake without affecting satiety.

Evidence-based approach to the introduction of positron emission tomography in ontario, Canada.

PURPOSE: The uptake of new health care technologies is usually driven by industry promotion, physician interest, patient demand, and institutional ability to acquire the technology. The introduction of positron emission tomography (PET) scanning in the province of Ontario, Canada, followed a different path. METHODS: The Ontario provincial government, through its Ministry of Health and Long-Term Care, commissioned a systematic review of the literature. When this found only weak evidence that PET has a positive impact on clinical outcomes, the Ministry introduced a provincial PET evaluation program to close the evidence gap. RESULTS: This article describes the challenges encountered establishing the PET evaluation program. These included the design and conduct of the initial clinical trials, the establishment of a PET cancer registry, standardizing how PET scans were performed and reported, and gaining acceptance by health professionals for the evaluative program. CONCLUSION: The proliferation of health technologies is a key driver of increasing health care costs. The Ontario approach to the introduction of PET is a model worth consideration by health systems seeking to ensure that they receive value for money based on a strong evidentiary base when introducing new health technologies.

Blood pressure surges during office-based transurethral microwave therapy for the prostate.

OBJECTIVE: To investigate the occurrence of adverse blood pressure (BP) events during transurethral microwave therapy (TUMT) for benign prostatic hyperplasia. PATIENTS AND METHODS: We conducted a retrospective study of the vital signs of 185 consecutive patients who received TUMT (via 6 devices) at 4 institutions from March 1, 2003, to September 18, 2005. Maximum change, percent change in systolic BP, diastolic BP, mean arterial pressures, heart rate, and oxygen saturation were evaluated. RESULTS: Of the 185 patients, 77 patients (42%; 95% confidence interval [CI], 35%-49%) experienced an increase in systolic BP of more than 30 mm Hg during TUMT; 30 patients (16%; 95% CI, 12%-22%), an increase of more than 50 mm Hg; and 10 patients (5%; 95% CI, 3%-10%), an increase of more than 70 mm Hg. A greater than 20% change in systolic BP from baseline was observed in 95 patients (51%; 95% CI, 44%-58%). Many men experienced multiple events, with an average time of onset of 15.9 minutes into treatment. Significant differences were noted among the devices. CONCLUSION: This retrospective study demonstrates a significant number of BP surges during TUMT for benign prostatic hyperplasia. These BP changes represent a potential risk of cardiovascular events in patients with known or occult cardiovascular disease. Our study is the first to recognize the incidence of this BP response. Until further studies identify the mechanisms responsible for these surges in BP, the results of this study suggest that BP should be monitored, treatment adjusted, and antihypertensive medications continued during all TUMT.

Interictal and postictal circadian and ultradian luteinizing hormone secretion in men with temporal lobe epilepsy.

PURPOSE: Hypothalamic regulation of the reproductive axis in temporal lobe epilepsy (TLE), represented by the ultradian pulsatile secretion of luteinizing hormone (LH), has been shown to be altered interictally and postictally. Our objective is to determine if epilepsy or seizures disrupt normal circadian fluctuations of LH as well as circadian organization of ultradian bursts of LH. METHODS: We characterized LH secretion in 10 men with TLE during two 24-h blocks: an interictal epoch and a postictal epoch initiated by a seizure. Serum LH was measured every 10 min and characterized by circadian and ultradian patterns with cosinor and deconvolution analysis. RESULTS: Mean peak serum concentrations of LH occurred at approximately 0400 in controls, were significantly delayed approximately 5 h interictally, and were randomly distributed postictally. Burst amplitudes differed significantly by phase among controls, with the largest amplitudes between 0101 and 0700 and the smallest between 1301 and 1900. No phase differences were present in interictal or postictal epochs. Burst frequency weakly but significantly was slowest between 0101 and 0700 in controls, but did not differ significantly by phase in either interictal or postictal epochs. Postictal LH burst frequencies, but not amplitudes, were significantly decreased immediately postictally. CONCLUSION: The pulsatile secretion of LH in TLE is abnormal both in the circadian as well as the ultradian domain. Interictal effects consist mainly in loss of circadian fluctuations in LH burst amplitude, whereas postictal effects consist of altered burst timing. Altered daily patterns of neuroendocrine signals may underlie other disorders of homeostasis in TLE.