A Review of the Association of Blue Food Coloring With Attention Deficit Hyperactivity Disorder Symptoms in Children.

Attention Deficit Hyperactivity Disorder, also known as ADHD, is a neurodevelopmental disorder diagnosed in children. The exact cause of ADHD is not known, but, along with genetic factors, it is possible that environmental factors including toxins and diet may affect symptom severity. Of these dietary components, artificial food coloring (AFC), while approved by the Food and Drug Administration (FDA), has been suspected to be associated with ADHD symptoms. Of the nine FDA-certified food colors, two are used for artificial blue coloring: Blue No. 1 and Blue No. 2. There is limited literature describing the possible role of blue AFC in causing symptoms of ADHD in children. This paper provides a review of the literature surrounding artificial food coloring and its ability to affect the neurodevelopment of children in a way that could increase the behavioral indicators of ADHD. To do this, search criteria were established using a combination of MeSH terms about blue AFCs and ADHD and were entered into PubMed, along with limits on article types and publication dates from January 2000 to June 2022. There was a total of 20 articles that met this search criterion. These articles were reviewed by authors, and the ones not relevant to the topic were excluded. In total, four studies were chosen to be included in this article. After reviewing the literature, it was found that restriction diets, specifically those excluding AFCs, may affect symptom severity. The source of these changes is not known, but possible mechanisms include AFCs causing nutritional deficiencies and allergic reactions or altering neurotransmitter levels. More research is necessary to describe the neurotoxicity of artificial blue dyes in humans.

The Influence of the Pretreatment Immune State on Response to Radiation Therapy in High-Risk Prostate Cancer: A Validation Study From NRG/RTOG 0521.

PURPOSE: The immunoinflammatory state has been shown to be associated with poor outcomes after radiation therapy (RT). We conducted an a priori designed validation study using serum specimens from Radiation Therapy Oncology Group (RTOG) 0521. It was hypothesized the pretreatment inflammatory state would correlate with clinical outcomes. METHODS AND MATERIALS: Patients on RTOG 0521 had serum banked for biomarker validation. This study was designed to validate previous findings showing an association between elevations in C-reactive protein (CRP) and shorter biochemical disease free survival (bDFS). CRP levels were measured in pretreatment samples. An exploratory panel of related cytokines was also measured including: monocyte chemotactic protein-1, granulocyte-macrophage colony-stimulating factor, interferon-γ, interleukin (IL)-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17A, IL-23, and tumor necrosis factor. The primary endpoint examined was bDFS. Additional exploratory endpoints included overall survival, distant metastases, and toxicity events attributed to RT. RESULTS: Two hundred and two patients in RTOG/NRG 0521 had serum samples available. Median age was 66 years (48-83), and 90% of patients were White. There was not an association between CRP and bDFS (adjusted hazard ratio [HR], 1.07 per 1 log increase in CRP; 95% confidence interval, 0.83-1.38; P = .60). In the exploratory, unplanned analysis, pretreatment IL-10 was significantly associated with worse bDFS (adjusted HR, 1.61 per log increase; P = .0027) and distant metastases (HR, 1.55 per log increase; P = .028). The association of IL-10 with bDFS was maintained on a multiplicity adjustment. The exploratory analyses of pretreatment levels of interferon-γ, IL-1b, IL-2, IL-13, IL-23 were negatively associated with grade 2 or higher pollakiuria (adjusted odds ratio, 0.64, 0.65, 0.71, 0.72, and 0.74, respectively, all P < .05), and IL-6 was negatively associated with grade 2 or higher erectile dysfunction (odds ratio, 0.62; P = .027). CONCLUSIONS: Pretreatment CRP was not associated with a poorer bDFS after RT. In a hypothesis- generating analysis, higher baseline levels of IL-10 were associated with lower rates of bDFS. These findings require additional prospective evaluation.

Intergenerational Consequences: Women's Experiences of Discrimination in Pregnancy Predict Infant Social-Emotional Development at 6 Months and 1 Year.

OBJECTIVE: Racial/ethnic and socioeconomic disparities in infant development in the United States have lifelong consequences. Discrimination predicts poorer health and academic outcomes. This study explored for the first time intergenerational consequences of women's experiences of discrimination reported during pregnancy for their infants' social-emotional development in the first year of life. METHODS: Data come from a longitudinal study with predominantly Black and Latina, socioeconomically disadvantaged, urban young women (N = 704, Mage = 18.53) across pregnancy through 1 year postpartum. Women were recruited from community hospitals and health centers in a Northeastern US city. Linear regression analyses examined whether women's experiences of everyday discrimination reported during pregnancy predicted social-emotional development outcomes among their infants at 6 months and 1 year of age, controlling for potentially confounding medical and sociodemographic factors. Path analyses tested if pregnancy distress, anxiety, or depressive symptoms mediated significant associations. RESULTS: Everyday discrimination reported during pregnancy prospectively predicted greater inhibition/separation problems and greater negative emotionality, but did not predict attention skills or positive emotionality, at 6 months and 1 year. Depressive symptoms mediated the association of discrimination with negative emotionality at 6 months, and pregnancy distress, anxiety, and depressive symptoms mediated the association of discrimination with negative emotionality at 1 year. CONCLUSION: Findings support that there are intergenerational consequences of discrimination, extending past findings to infant social-emotional development outcomes in the first year of life. It may be important to address discrimination before and during pregnancy and enhance support to mothers and infants exposed to discrimination to promote health equity across the life span.

Feasibility of Patient Reporting of Symptomatic Adverse Events via the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in a Chemoradiotherapy Cooperative Group Multicenter Clinical Trial.

PURPOSE: To assess the feasibility of measuring symptomatic adverse events (AEs) in a multicenter clinical trial using the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). METHODS AND MATERIALS: Patients enrolled in NRG Oncology's RTOG 1012 (Prophylactic Manuka Honey for Reduction of Chemoradiation Induced Esophagitis-Related Pain during Treatment of Lung Cancer) were asked to self-report 53 PRO-CTCAE items representing 30 symptomatic AEs at 6 time points (baseline; weekly ×4 during treatment; 12 weeks after treatment). Reporting was conducted via wireless tablet computers in clinic waiting areas. Compliance was defined as the proportion of visits when an expected PRO-CTCAE assessment was completed. RESULTS: Among 226 study sites participating in RTOG 1012, 100% completed 35-minute PRO-CTCAE training for clinical research associates (CRAs); 80 sites enrolled patients, of which 34 (43%) required tablet computers to be provided. All 152 patients in RTOG 1012 agreed to self-report using the PRO-CTCAE (median age 66 years; 47% female; 84% white). Median time for CRAs to learn the system was 60 minutes (range, 30-240 minutes), and median time for CRAs to teach a patient to self-report was 10 minutes (range, 2-60 minutes). Compliance was high, particularly during active treatment, when patients self-reported at 86% of expected time points, although compliance was lower after treatment (72%). Common reasons for noncompliance were institutional errors, such as forgetting to provide computers to participants; patients missing clinic visits; Internet connectivity; and patients feeling "too sick." CONCLUSIONS: Most patients enrolled in a multicenter chemoradiotherapy trial were willing and able to self-report symptomatic AEs at visits using tablet computers. Minimal effort was required by local site staff to support this system. The observed causes of missing data may be obviated by allowing patients to self-report electronically between visits, and by using central compliance monitoring. These approaches are being incorporated into ongoing studies.

Abnormal circumferential strain measured by echocardiography is present in patients with Shwachman-Diamond syndrome despite normal shortening fraction.

BACKGROUND: Shwachman-Diamond Syndrome (SDS) is an autosomal recessive disorder characterized by bone marrow failure and exocrine pancreatic dysfunction. Heart failure has been described in patients with SDS. Circumferential strain (ε(cc)) is a measure of cardiac performance that may identify dysfunction when standard measures are normal. PROCEDURES: Patients with SDS were identified and the echocardiographic database queried. Cardiac anatomy and function were recorded, and ε(cc) was measured retrospectively. RESULTS: From 1995-2013, 27 patients with biallelic SBDS mutations confirming the diagnosis of SDS were identified at our institution: 14 had at least one echocardiogram available; 10 underwent HSCT, with echocardiograms available in nine. Ejection fraction (EF) was normal in all 14 patients evaluated; however, ε(cc) was decreased in 4/12 studies prior to HSCT. In two patients, ε(cc) was abnormal both before and after HSCT, in one, ε(cc) changed from normal to abnormal after HSCT, and in one, ε(cc) was normal after HSCT despite being abnormal prior. Echocardiogram reports were also available for six patients in the North American SDS registry, all with normal EF. CONCLUSIONS: While EF was normal in all patients with SDS, ε(cc) was abnormal in 33% prior to HSCT and 33% of those who had undergone HSCT. This suggests that SDS is associated with systolic dysfunction. Further studies are needed to define the incidence of dysfunction in this group and the progression to heart failure.

Development of a policy and procedure for accidental chemotherapy overdose.

A policy regarding rapid response to chemotherapy overdoses was developed by the authors in an attempt to minimize morbidity and mortality. The parameters of a chemotherapy overdose were defined to promote early recognition of an overdose incident. Resources needed to guide potential therapeutic interventions and required monitoring were developed. The policy defines the immediate actions to be taken in the event of a chemotherapy overdose. The availability of a chemotherapy overdose policy provides an enhanced level of safety for patients by ensuring that appropriate treatment is initiated without delay. The development of the policy was in response to the reporting of a tragic error at another institution. Healthcare providers must recognize and address potential areas of vulnerability to maximize patient safety.

Can electronic web-based technology improve quality of life data collection? Analysis of Radiation Therapy Oncology Group 0828.

PURPOSE: Missing data are a significant problem in clinical trials, particularly for quality of life (QOL), which cannot be obtained retrospectively. The purpose of this study was to evaluate the feasibility of an electronic web-based strategy for QOL data collection in a cooperative group radiation oncology trial setting. METHODS AND MATERIALS: Radiation Therapy Oncology Group (RTOG) 0828 was a prospective National Cancer Institute cooperative group companion study of RTOG-0415, a randomized study of conventional versus hypofractionated radiation. Forty-nine English-speaking patients with favorable risk prostate cancer who enrolled on RTOG-0415 consented to using web-based technology for completing QOL. In RTOG-0415, using paper forms, the 6-month QOL compliance rate was 52%. The purpose of RTOG-0828 was to test the feasibility of a web-based strategy with the goal of increasing the 6-month QOL completion rate by 25% (from 52% to 77%) for a relative improvement of ~50%. The web-based tool used in this study was VisionTree Optimal Care (VTOC; VisionTree Software, Inc, San Diego, CA), a Health-Insurance-Portability-Accountability-Act secure, online technology that allows real-time tracking and e-mail reminders. The primary endpoint was the 6-month compliance rate for the validated QOL instrument, Expanded Prostate Index Composite. RESULTS: The QOL completion rate at baseline was 98%. Compared with the prior 52% QOL completion rate at 6 months using paper forms, the QOL web-based completion rate at 6 months was 90% (2-sided P value < .001). At 12 months, the EPIC completion rate was 82% (compared with 36% using paper forms). CONCLUSIONS: This RTOG study suggests that a web-based strategy to collect QOL appears to be feasible in the cooperative group radiation oncology trial setting and is associated with an increase in the 6-month QOL compliance rate compared with the prior method of using paper forms. The RTOG plans to further test this strategy in a head-and-neck cancer trial across all participating RTOG sites.

Airways in smooth muscle α-actin null mice experience a compensatory mechanism that modulates their contractile response.

We hypothesized that ablation of smooth muscle α-actin (SM α-A), a contractile-cytoskeletal protein expressed in airway smooth muscle (ASM) cells, abolishes ASM shortening capacity and decreases lung stiffness. In both SM α-A knockout and wild-type (WT) mice, airway resistance (Raw) determined by the forced oscillation technique rose in response to intravenous methacholine (Mch). However, the slope of Raw (cmH(2)O·ml(-1)·s) vs. log(2) Mch dose (µg·kg(-1)·min(-1)) was lower (P = 0.007) in mutant (0.54 ± 0.14) than in WT mice (1.23 ± 0.19). RT-PCR analysis performed on lung tissues confirmed that mutant mice lacked SM α-A mRNA and showed that these mice had robust expressions of both SM γ-A mRNA and skeletal muscle (SKM) α-A mRNA, which were not expressed in WT mice, and an enhanced SM22 mRNA expression relative to that in WT mice. Compared with corresponding spontaneously breathing mice, mechanical ventilation-induced lung mechanical strain increased the expression of SM α-A mRNA in WT lungs; in mutant mice, it augmented the expressions of SM γ-A mRNA and SM22 mRNA and did not alter that of SKM α-A mRNA. In mutant mice, the expression of SM γ-A mRNA in the lung during spontaneous breathing and its enhanced expression following mechanical ventilation are consistent with the likely possibility that in the absence of SM α-A, SM γ-A underwent polymerization and interacted with smooth muscle myosin to produce ASM shortening during cholinergic stimulation. Thus our data are consistent with ASM in mutant mice experiencing compensatory mechanisms that modulated its contractile muscle capacity.

Evaluation of screening risk and nonrisk patients for methicillin-resistant Staphylococcus aureus on admission in an acute care hospital.

BACKGROUND: Screening for methicillin-resistant Staphylocccus aureus (MRSA) is advocated as part of control measures, but screening all patients on admission to hospital may not be cost-effective. OBJECTIVE: Our objective was to evaluate the additional yield of screening all patients on admission compared with only patients with risk factors and to assess cost aspects. METHODS: A prospective, nonrandomized observational study of screening nonrisk patients ≤72 hours of admission compared with only screening patients with risk factors over 3 years in a tertiary referral hospital was conducted. We also assessed the costs of screening both groups. RESULTS: A total of 48 of 892 (5%) patients was MRSA positive; 28 of 314 (9%) during year 1, 12 of 257 (5%) during year 2, and 8 of 321 (2%) during year 3. There were significantly fewer MRSA-positive patients among nonrisk compared with MRSA-risk patients: 4 of 340 (1%) versus 44 of 552 (8%), P ≤ .0001, respectively. However, screening nonrisk patients increased the number of screening samples by 62% with a proportionate increase in the costs of screening. A backward stepwise logistic regression model identified age > 70 years, diagnosis of chronic pulmonary disease, previous MRSA infection, and admission to hospital during the previous 18 months as the most important independent predictors to discriminate between MRSA-positive and MRSA-negative patients on admission (94.3% accuracy, P < .001). CONCLUSION: Screening patients without risk factors increased the number of screenings and costs but resulted in few additional cases being detected. In a hospital where MRSA is endemic, targeted screening of at-risk patients on admission remains the most efficient strategy for the early identification of MRSA-positive patients.

The effect of rapid screening for methicillin-resistant Staphylococcus aureus (MRSA) on the identification and earlier isolation of MRSA-positive patients.

OBJECTIVES: (1) To determine whether rapid screening with polymerase chain reaction (PCR) assays leads to the earlier isolation of patients at risk for methicillin-resistant Staphylococcus aureus (MRSA) colonization, (2) to assess compliance with routine MRSA screening protocols, (3) to confirm the diagnostic accuracy of the Xpert MRSA real-time PCR assay (Cepheid) by comparison with culture, and (4) to compare turnaround times for PCR assay results with those for culture results. DESIGN: Before-and-after study conducted in a 700-bed acute tertiary care referral hospital. Study periods were (1) a 5-week period before PCR testing began, (2) a 10-week period when the PCR assay was used, and (3) a 5-week period after PCR testing was discontinued. RESULTS: Among 489 at-risk patients, MRSA was isolated from 20 (33%) of 60 patients during period 1, 77 (22%) of 349 patients during period 2, and 18 (23%) of 80 patients during period 3. Twenty-two (27%) of 82 at-risk patients were not screened during period 1, compared with 40 (10%) of 389 at-risk patients not screened during period 2 (P < .001). More MRSA-positive patients were preemptively isolated during periods 1 and 3 compared with period 2 (34 [24%] of 140 vs 28 [8%] of 389; P < .001); however, more MRSA-positive patients were isolated after notification of MRSA-positive results during period 2 (47 [13%] of 349) compared with periods 1 and 3 (2 [1%] of 140; P < .001). The sensitivity, specificity, positive predictive value, and negative predictive value of the PCR assay were 95%, 97%, 82%, and 99%, respectively. The mean turnaround time from receipt of specimens in the laboratory to PCR assay result was 2.6 hours. CONCLUSIONS: Rapid screening with the Xpert MRSA PCR assay facilitated compliance with screening policies and the earlier isolation of MRSA-positive patients. Discrepant results confirm that PCR testing should be used as a screening tool rather than as a diagnostic tool.

Promoting skill building and confidence in freshman nursing students with a "Skills-a-Thon".

Freshman nursing students returning for their second semester after summer break benefited by reviewing previously learned clinical skills presented in a Skills-a-Thon. Skills stations were established and facilitated by faculty and senior students. Senior students were first trained in mentoring and specific steps in skills competencies. Freshman students demonstrated skills in various mock clinical situations including catheter insertion, sterile dressings, medications, and physical assessment. The strategy reinforced learning and provided an opportunity for students to experience risk-free skills performance among peers. Freshman students gained proficiency and appreciated guidance by senior students without the pressures of testing. Seniors benefited from a condensed version of the program to review their own skills prior to the event. Responses were positive, with students reporting improved performance and confidence with hands-on application in a non-threatening environment. Nursing faculty observed improvement in skill performance and competence, and plan to offer future events.

Ruby laser for the treatment of trichiasis.

Trichiasis, the misdirection of eyelashes arising from their normal sites of origin, may cause discomfort, corneal abrasions, ulceration and scarring. The therapies currently used for this condition have a variety of success rates and complications. In this report we describe epilation using a ruby laser to treat ten patients (11 lids). In six patients laser treatment was completely successful in achieving alopecia, in three patients the treatment was partly successful, and one patient was lost to follow up. In all cases ruby laser treatment was well tolerated, and there were no reported complications; thus, ruby laser treatment can be a viable and well-tolerated option for the relief of the symptoms of trichiasis.

Meeting the challenge of assessing clinical competence of occupational therapists within a program management environment.

BACKGROUND: Program management models have raised concerns among occupational therapists about professional standards related to clinical competence, performance review procedures, and quality improvement initiatives. PURPOSE: This paper describes how a chart-stimulated recall (CSR) peer-review process and interview tool was revised, implemented, and evaluated as a pilot project to assess the clinical competence of occupational therapy staff at a large urban health centre in southern Ontario. METHODS: Fourteen pairs (n=28) of occupational therapists representing various practice areas participated in this project. Half served as peer assessors and half as interviewees. Peer assessors conducted an independent chart review followed by a one-hour personal interview with a peer partner to discuss clinical management issues related to the client cases. Each interviewer rated his or her partner's clinical competence in eight areas of performance using a 7-point Likert scale. FINDINGS: Results indicated that the CSR tool could discriminate among occupational therapists in terms of overall levels of clinical competence and also identify specific areas of concern that could be targeted for professional development. Feedback from participants was positive. CONCLUSIONS: The CSR tool was found to be useful for assessing clinical competence of occupational therapists in this large health centre as a quality improvement initiative within that discipline group. Further research is needed to establish the reliability and validity of the CSR tool.

Depth of penetration of an 850nm wavelength low level laser in human skin.

Low Level Laser Therapy is used for a wide variety of conditions including superficial skin sores, musculoskeletal and joint problems, and dentistry. Knowledge of the penetration depth of laser radiation in human skin is an essential prerequisite to identifying its method of action. Mathematical simulations and estimates from the literature suggest that the depth of penetration of laser radiation using wavelengths from 630nm up to 1100nm may be up to 50mm. The aim of this study is to directly measure the penetration depth of a Low Level Laser in human tissue. Human abdominal skin samples up to 0.784mm thickness were harvested by dermatome following abdominoplasty procedures. These samples were irradiated by a Gallium Aluminium Arsenide Laser (Wavelength 850nm near infra-red invisible light, 100mW, 24kHz, 0.28mm diameter probe) and the transmitted radiation measured with an Ophir Optronics 'Nova' external energy meter. The intensity of laser radiation reduced by 66% after being transmitted through a 0.784mm sample of human abdominal tissue. In this study most laser radiation was absorbed within the first 1mm of skin.

Monitoring the ups and downs of pulsed dye laser energy output.

The internal energy meter reading of a Chromos pulsed dye laser (PDL) set at 50% of maximum pumping energy was recorded at the start of every clinical session over an 898 day period and compared with the measurement from an Ophir Optronics 'Nova' external energy meter. This quick and inexpensive process improved quality control procedures for the use of the PDL and enabled the performance of laser components such as the dye, pumping mechanism and optics to be monitored. The stability of the laser output energy was also monitored during three simulated clinics on days 665, 870 and 898. External energy meter readings were recorded every 100 pulses during each simulated clinic comprising six series of 500 pulses. As the energy output was shown to be stable during each clinic (SD<4.7%) recalibration during treatments of up to 500 pulses with this laser was deemed to be unnecessary. However, it was noted that this output energy stability was maintained by varying the pumping energy from 42 to 88% of maximum. Subsequent measurements of pulse width conducted with an ET-2000 Silicon Photodetector demonstrated that although the nominal pulse width was 450 mus, this varied from 240 to 390 mus as the pumping energy increased from 20 to 50%.

Mechanical stretch activates nuclear factor-kappaB, activator protein-1, and mitogen-activated protein kinases in lung parenchyma: implications in asthma.

We investigated the effects of mechanical stretch and induced stimulation of lung parenchyma on the activation of proinflammatory transcription factors in normal mice and in a mouse model of asthma. Mechanical stretching of lung parenchyma led to increased activation of NF-kappaB and AP-1 transcription factors. Incubation of lung parenchyma with methacholine increased the activation of NF-kappaB, which was further augmented by stretch. Activation of NF-kappaB in response to mechanical stretch was associated with the phosphorylation and degradation of IkappaBalpha and the activation of IkappaB kinase. Stretch-induced activation of NF-kappaB involves activation of stretch-activated (SA) channels and the production of free radicals. Mechanical stretch and/or treatment with methacholine resulted in an increased activation of ERK1/2 and p38 MAP kinase, and the inhibition of the activity of these kinases partially blocked the stretch-induced NF-kappaB and AP-1 activation. A greater level of NF-kappaB and ERK1/2 activity was observed in the asthmatic mice, which was further increased by mechanical stretching. The level of cyclooxygenase-2, an NF-kappaB-regulated enzyme, was also higher in lung parenchyma from asthmatic mice than in normal mice. Our data suggest that mechanical stretching of lung parenchyma activates NF-kappaB and AP-1, at least in part, through the activation of MAP kinase signaling pathways.