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Oral treatment (targeted or chemotherapy) for cancer is being increasingly used. While fatigue is a known side effect of intravenous chemotherapy, the rate of fatigue and the impact of fatigue on other patient-reported outcomes are not well described.
At Massachusetts General Hospital Cancer Center, 180 adult patients prescribed oral targeted or chemotherapy for various malignancies enrolled in a randomized controlled trial of adherence and symptom management. Patients completed baseline self-reported measures of fatigue (Brief Fatigue Inventory; BFI), anxiety and depressive symptoms (Hospital Anxiety and Depression Scale; HADS), and quality of life, including subscales for physical, social, emotional, and functional well-being ([QOL] Functional Assessment of Cancer Therapy — General; FACT-G). We examined clinically relevant fatigue using a validated cut-off score for moderate-severe fatigue (BFI global fatigue ≥4) and tested the associations with anxiety symptoms, depressive symptoms, and QOL with independent samples t-tests.
At baseline, 45 of 180 participants (25.0%) reported moderate-severe fatigue. Fatigued patients experienced more anxiety symptoms (mean diff. 3.73, P < 0.001), more depressive symptoms (mean diff. 4.14, P < 0.001), and worse QOL on the total FACT-G score (mean diff. −19.58, P < 0.001) and all subscales of the FACT-G compared to patients without moderate-severe fatigue.
Significance of results
One in four patients on oral treatment for cancer experienced clinically relevant fatigue that is associated with greater anxiety and depressive symptoms and worse QOL.
On many Australian commercial pig farms, groups of growing pigs are mass-medicated through their drinking water with selected antimicrobials for short periods to manage herd health. However, delivery of medication in drinking water cannot be assumed to deliver an equal dose to all animals in a group. There is substantial between-animal variability in systemic exposure to an antimicrobial (i.e. the antimicrobial concentration in plasma), resulting in under-dosing or over-dosing of many pigs. Three sources of this between-animal variability during a water medication dosing event are differences in: (1) concentration of the active constituent of the antimicrobial product in water available to pigs at drinking appliances in each pen over time, (2) medicated water consumption patterns of pigs in each pen over time, and (3) pharmacokinetics (i.e. oral bioavailability, volume of distribution and clearance between pigs and within pigs over time). It is essential that factors operating on each farm that influence the range of systemic exposures of pigs to an antimicrobial are factored into antimicrobial administration regimens to reduce under-dosing and over-dosing.
The role of aromatherapy in supportive symptom management for pediatric patients receiving palliative care has been underexplored. This pilot study aimed to measure the impact of aromatherapy using validated child-reported nausea, pain, and mood scales 5 minutes and 60 minutes after aromatherapy exposure.
The 3 intervention arms included use of a symptom-specific aromatherapy sachet scent involving deep breathing. The parallel default control arm (for those children with medical exclusion criteria to aromatherapy) included use of a visual imagery picture envelope and deep breathing. Symptom burden was sequentially assessed at 5 and 60 minutes using the Baxter Retching Faces scale for nausea, the Wong-Baker FACES scale for pain, and the Children's Anxiety and Pain Scale (CAPS) for anxious mood. Ninety children or adolescents (mean age 9.4 years) at a free-standing children's hospital in the United States were included in each arm (total n = 180).
At 5 minutes, there was a mean improvement of 3/10 (standard deviation [SD] 2.21) on the nausea scale; 2.6/10 (SD 1.83) on the pain scale; and 1.6/5 (SD 0.93) on the mood scale for the aromatherapy cohort (p < 0.0001). Symptom burden remained improved at 60 minutes post-intervention (<0.0001). Visual imagery with deep breathing improved self-reports of symptoms but was not as consistently sustained at 60 minutes.
Significance of results
Aromatherapy represents an implementable supportive care intervention for pediatric patients receiving palliative care consults for symptom burden. The high number of children disqualified from the aromatherapy arm because of pulmonary or allergy indications warrants further attention to outcomes for additional breathing-based integrative modalities.
Understanding perceptions of family caregivers’ roles and responsibilities regarding their child with complex cardiac needs has potential to help care teams better support parents. Paternal experience has been under-explored in pediatric cardiac cohorts.
Ten fathers of children undergoing cardiac surgery completed quantitative surveys on their knowledge needs and preferred format of communication. In face-to-face recorded interviews, they responded to open-ended questions about the definition of being a good father to a child with a complex cardiac condition, perceived paternal responsibilities, personal growth as a parent to a child with a complex heart condition, support needs, and recommendations to medical staff for paternal inclusion. Semantic content analysis was utilised. The study reports strictly followed COnsolidated criteria for REporting Qualitative research guidelines.
The fathers reported high preference for knowledge about the child’s heart condition, communication about the treatment plan, and desire for inclusion in the care of their child. Paternal role was defined thematically as: providing a supportive presence, being there, offering bonded insight, serving as strong provider, and acting as an informed advocate. The fathers revealed that their responsibilities sometimes conflicted as they strove to serve as an emotional and economic stabiliser for their family, while also wanting to be foundationally present for their child perioperatively.
This study provides insight into paternal experience and strategies for paternal inclusion. This summary of the self-defined experience of the fathers of pediatric cardiac patients offers constructive and specific advice for medical teams.
Recent years have seen an exponential increase in the variety of healthcare data captured across numerous sources. However, mechanisms to leverage these data sources to support scientific investigation have remained limited. In 2013 the Pediatric Heart Network (PHN), funded by the National Heart, Lung, and Blood Institute, developed the Integrated CARdiac Data and Outcomes (iCARD) Collaborative with the goals of leveraging available data sources to aid in efficiently planning and conducting PHN studies; supporting integration of PHN data with other sources to foster novel research otherwise not possible; and mentoring young investigators in these areas. This review describes lessons learned through the development of iCARD, initial efforts and scientific output, challenges, and future directions. This information can aid in the use and optimisation of data integration methodologies across other research networks and organisations.
We examined the functions of mothers’ speech to infants during two tasks – book-sharing and bead-stringing – in low-income, ethnically diverse families. Mexican, Dominican, and African American mothers and their infants were video-recorded sharing wordless books and toy beads in the home when infants were aged 1;2 and 2;0. Mothers’ utterances were classified into seven categories (labels/descriptions, emotion/state language, attention directives, action directives, prohibitions, questions, and vocal elicitations) which were grouped into three broad language functions: referential language, regulatory language, and vocalization prompts. Mothers’ ethnicity, years of education, years living in the United States, and infant sex and age related to mothers’ language functions. Dominican and Mexican mothers were more likely to use regulatory language than were African American mothers, and African American mothers were more likely to use vocalization prompts than were Latina mothers. Vocalization prompts and referential language increased with mothers’ education and Latina mothers’ years living in the United States. Finally, mothers of boys used more regulatory language than did mothers of girls. Socio-cultural and developmental contexts shape the pragmatics of mothers’ language to infants.
Major transitions in trilobite ontogeny have historically been defined based on the number and distribution of trunk segments, and articulation between the trunk and cephalon. This study documents additional morphological change across the meraspid-holaspid transition on the Ordovician phacopid trilobite Calyptaulax strasburgensis. An extensive dataset of silicified cranidia and pygidia collected from the mid-Ordovician Edinburg Formation of Virginia was subjected to a series of multivariate analyses, with a primary focus on the intersections and termini of furrows. Multivariate regression of partial warp scores demonstrates statistically significant change in allometric growth patterns over the course of development. These changes are concentrated in earlier instars, but are coincident in cranidia and pygidia. This sharp decrease in the rate of allometry, present in both tagmata, is expressed as significant breakpoints derived from a segmented regression, with the largest portion of allometric change found in the pre-breakpoint individuals. The term holeidos is proposed to describe the completion of form during trilobite development, independent of the completion of the thorax. The most dramatic change in shape during this period of ontogeny includes lateral glabellar expansion through deflection of the axial and palpebral furrows, possibly reflecting a change in the feeding habit during later development. Other morphological changes include the development of a more angular appearance to the anterior portion of the glabella, and anterior migration of the pygidial anterior margin. The appearance of these growth patterns in Calyptaulax extends the temporal range of these changes, some of which have only been documented in Devonian phacopids.
Waterhemp [Amaranthus tuberculatus (Moq.) J. D. Sauer] and Palmer amaranth (Amaranthus palmeri S. Watson) are troublesome weeds of row-crop production in the United States. Their dioecious reproductive systems ensure outcrossing, facilitating rapid evolution and distribution of resistances to multiple herbicides. Little is known, however, about the genetic basis of dioecy in Amaranthus species. In this work, we use restriction site–associated DNA sequencing (RAD-Seq) to investigate the genetic basis of sex determination in A. tuberculatus and A. palmeri. For each species, approximately 200 plants of each sex were sampled and used to create RAD-Seq libraries. The resulting libraries were separately bar-coded and then pooled for sequencing with the Illumina platform, yielding millions of 64-bp reads. These reads were analyzed to identify sex-specific and sex-biased sequences. We identified 345 male-specific sequences from the A. palmeri data set and 2,754 male-specific sequences in A. tuberculatus. An unexpected 723 female-specific sequences were identified in a subset of the A. tuberculatus females; subsequent research, however, indicated female specificity of these markers was limited to the population from which they were identified. Primer sets designed to specifically amplify male-specific sequences were tested for accuracy on multiple, geographically distinct populations of A. tuberculatus and A. palmeri, as well as other Amaranthus species. Two primer sets for A. palmeri and four primer sets for A. tuberculatus were each able to distinguish between male and female plants with at least 95% accuracy. In the near term, sex-specific markers will be useful to the A. tuberculatus and A. palmeri research communities (e.g., to predict sex for crossing experiments). In the long-term, this research will provide the foundational tools for detailed investigations into the molecular biology and evolution of dioecy in weedy Amaranthus species.
Using existing data from clinical registries to support clinical trials and other prospective studies has the potential to improve research efficiency. However, little has been reported about staff experiences and lessons learned from implementation of this method in pediatric cardiology.
We describe the process of using existing registry data in the Pediatric Heart Network Residual Lesion Score Study, report stakeholders’ perspectives, and provide recommendations to guide future studies using this methodology.
The Residual Lesion Score Study, a 17-site prospective, observational study, piloted the use of existing local surgical registry data (collected for submission to the Society of Thoracic Surgeons-Congenital Heart Surgery Database) to supplement manual data collection. A survey regarding processes and perceptions was administered to study site and data coordinating center staff.
Survey response rate was 98% (54/55). Overall, 57% perceived that using registry data saved research staff time in the current study, and 74% perceived that it would save time in future studies; 55% noted significant upfront time in developing a methodology for extracting registry data. Survey recommendations included simplifying data extraction processes and tailoring to the needs of the study, understanding registry characteristics to maximise data quality and security, and involving all stakeholders in design and implementation processes.
Use of existing registry data was perceived to save time and promote efficiency. Consideration must be given to the upfront investment of time and resources needed. Ongoing efforts focussed on automating and centralising data management may aid in further optimising this methodology for future studies.
Background: Cervical sponylotic myelopathy (CSM) may present with neck and arm pain. This study investiagtes the change in neck/arm pain post-operatively in CSM. Methods: This ambispective study llocated 402 patients through the Canadian Spine Outcomes and Research Network. Outcome measures were the visual analogue scales for neck and arm pain (VAS-NP and VAS-AP) and the neck disability index (NDI). The thresholds for minimum clinically important differences (MCIDs) for VAS-NP and VAS-AP were determined to be 2.6 and 4.1. Results: VAS-NP improved from mean of 5.6±2.9 to 3.8±2.7 at 12 months (P<0.001). VAS-AP improved from 5.8±2.9 to 3.5±3.0 at 12 months (P<0.001). The MCIDs for VAS-NP and VAS-AP were also reached at 12 months. Based on the NDI, patients were grouped into those with mild pain/no pain (33%) versus moderate/severe pain (67%). At 3 months, a significantly high proportion of patients with moderate/severe pain (45.8%) demonstrated an improvement into mild/no pain, whereas 27.2% with mild/no pain demonstrated worsening into moderate/severe pain (P <0.001). At 12 months, 17.4% with mild/no pain experienced worsening of their NDI (P<0.001). Conclusions: This study suggests that neck and arm pain responds to surgical decompression in patients with CSM and reaches the MCIDs for VAS-AP and VAS-NP at 12 months.
Background: Chronic intravenous immunoglobulin (IVIg) is used to treat refractory myasthenia gravis (MG). This subgroup analysis evaluated response to eculizumab in patients receiving chronic IVIg before entry to REGAIN, a phase 3, randomized, double-blind, placebo-controlled study of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalized MG. Methods: IVIg was only permitted during REGAIN as rescue therapy; previously treated patients underwent a 4-week washout before randomization. Patients included in this analysis had received chronic IVIg ≥4 times in 1 year, with ≥1 dose within 6 months before REGAIN entry. Exacerbations and MG status changes were assessed. Results: Eighteen patients were evaluated; four experienced exacerbations (eculizumab-treated, 1/9; placebo-treated, 3/9). Clinically relevant improvements were larger with eculizumab than placebo, respectively (mean change, standard deviation [SD]: MG Activities of Daily Living score [MG-ADL], -5.3 [4.0] vs -2.1 [2.8]; Quantitative MG score [QMG], -4.1 [6.1] vs -1.3 [3.5]). More patients receiving eculizumab (7/9) had clinically meaningful responses (MG-ADL ≥3 and/or QMG ≥5 points) than those receiving placebo (3/9). Eculizumab safety was consistent with previous reports. Interim data from the open-label extension of REGAIN will be presented. Conclusions: In patients previously receiving chronic IVIg, eculizumab showed a trend toward meaningful clinical improvements and fewer exacerbations compared with placebo. (NCT01997229, NCT02301624).
Background: Patients with anti-acetylcholine receptor antibody-positive (AChR+) generalized myasthenia gravis (MG) unresponsive to conventional treatment experience greater disease burden than responsive patients. This is partly due to exacerbations, which may result in significant healthcare resource utilization. Eculizumab is well tolerated and gives clinically meaningful benefits in these patients. We evaluated the effect of long-term eculizumab treatment on exacerbations, hospitalizations and rescue therapy in the REGAIN study and its open-label extension. Methods: Exacerbations were defined as clinical worsening/deterioration, MG crises or rescue therapy usage; pre-study exacerbations/hospitalizations were defined from patient records. Event rates adjusted for patient-years were calculated for all patients in the pre-study year, patients receiving placebo during REGAIN, and patients receiving eculizumab during REGAIN and its open-label extension (median exposure, 27.5 months [range, 22 days–42.8 months]); rates were compared using a Poisson regression model. Results: Eculizumab treatment reduced exacerbations by 65% (p=0.0057), hospitalizations by 71% (p=0.0316) and rescue therapy use by 66% (p=0.0072) versus placebo. Eculizumab treatment reduced exacerbations by 74% and hospitalizations by 83% (both p<0.0001) versus the pre-study year. Conclusions: Long-term eculizumab treatment reduces disease burden and healthcare resource utilization, demonstrating continuing improvements in clinical endpoints that lead to additional meaningful outcomes for patients with AChR+ generalized MG. (NCT01997229, NCT02301624).
Background: Cervical spondylotic myelopathy (CSM) is the leading cause of spinal cord impairment. In a public healthcare system, wait times to see spine specialists and eventually access surgical treatment for CSM can be substantial. The goals of this study were to determine consultation wait times (CWT) and surgical wait times (SWT), and identify predictors of wait time length. Methods: Consecutive patients enrolled in the Canadian Spine Outcomes and Research Network (CSORN) prospective and observational CSM study from March 2015 to July 2017 were included. A data-splitting technique was used to develop and internally validate multivariable models of potential predictors. Results: A CSORN query returned 264 CSM patients for CWT. The median was 46 days. There were 31% mild, 35% moderate, and 33% severe CSM. There was a statistically significant difference in median CWT between moderate and severe groups; 207 patients underwent surgical treatment. Median SWT was 42 days. There was a statistically significant difference in SWT between mild/moderate and severe groups. Short symptom duration, less pain, lower BMI, and lower physical component score of SF-12 were predictive of shorter CWT. Only baseline pain and medication duration were predictive of SWT. Both CWT and SWT were shorter compared to a concurrent cohort of lumbar stenosis patients (p <0.001). Conclusions: Patients with shorter duration (either symptoms or medication) and less neck pain waited less to see a spine specialist in Canada and to undergo surgical treatment. This study highlights some of the obstacles to overcome in expedited care for this patient population.
The Nordic countries have comprehensive, population-based health and medical registries linkable on individually unique personal identity codes, enabling complete long-term follow-up. The aims of this study were to describe the NorTwinCan cohort established in 2010 and assess whether the cancer mortality and incidence rates among Nordic twins are similar to those in the general population. We analyzed approximately 260,000 same-sexed twins in the nationwide twin registers in Denmark, Finland, Norway and Sweden. Cancer incidence was determined using follow-up through the national cancer registries. We estimated standardized incidence (SIR) and mortality (SMR) ratios with 95% confidence intervals (CI) across country, age, period, follow-up time, sex and zygosity. More than 30,000 malignant neoplasms have occurred among the twins through 2010. Mortality rates among twins were slightly lower than in the general population (SMR 0.96; CI 95% [0.95, 0.97]), but this depends on information about zygosity. Twins have slightly lower cancer incidence rates than the general population, with SIRs of 0.97 (95% CI [0.96, 0.99]) in men and 0.96 (95% CI [0.94, 0.97]) in women. Testicular cancer occurs more often among male twins than singletons (SIR 1.15; 95% CI [1.02, 1.30]), while cancers of the kidney (SIR 0.82; 95% CI [0.76, 0.89]), lung (SIR 0.89; 95% CI [0.85, 0.92]) and colon (SIR 0.90; 95% CI [0.87, 0.94]) occur less often in twins than in the background population. Our findings indicate that the risk of cancer among twins is so similar to the general population that cancer risk factors and estimates of heritability derived from the Nordic twin registers are generalizable to the background populations.
Although deficits in cognitive empathy are well established in individuals with autism spectrum disorder (ASD), the literature on emotional empathy, or emotional contagion, in individuals with ASD is sparse and contradictory. The authors tested susceptibility to contagious yawning and laughter in children with ASD (n = 60) and typically developing (TD) children (n = 60), ages 5–17 years, under various conditions, to elucidate factors that may affect emotional contagion in these populations. Although TD children showed equal amounts of emotional contagion across conditions, children with ASD were highly influenced by the familiarity of the target stimulus, as well as task instructions that encourage eye gaze to target. More specifically, children with ASD exhibited less contagious yawning and laughter than their TD peers except when their attention was explicitly directed to the eyes or (and even more so) when their parents served as the stimulus targets. The authors explore the implications of these findings for theories about the mechanisms underlying empathic deficits in ASD as well as the clinical implications of having parents involved in treatment.
A series of nanostructured Fe/Ag metal films were produced at various substrate temperatures to determine their magnetic characteristics. The magnetic coercivity was found to increase with the diffracting-particle size which is process controlled. The films produced at low substrate temperature (<200°C) consisted of small metallic clusters of Ag (<100 Å). As the substrate temperature was increased, the films exhibited increased crystallinity and larger diffracting-particle size. The position of the maximum in the particlesize distribution function and the width of the function increased with substrate temperature.
Wearable devices such as a wrist actigraph may have a potential to objectively estimate patients’ functioning and may supplement performance status (PS). This proof-of-concept study aimed to evaluate whether actigraphy data are significantly associated with patients’ functioning and are predictive of their survival in patients with metastatic non-small cell lung cancer.
We collected actigraphy data for a three-day period in ambulatory patients with stage IV non-small cell lung cancer. We computed correlations between actigraphy data (specifically, proportion of time spent immobile while awake) and clinician-rated PS, subjective report of physical activities, quality of life (the Functional Assessment of Cancer Therapy – Trial Outcome Index), and survival.
Actigraphy data (the proportion of time awake spent immobile) were significantly correlated with Functional Assessment of Cancer Therapy – Trial Outcome Index (r = −0.53, p < 0.001) and with the Eastern Cooperative Oncology Group PS (ECOG PS) (r = 0.37, p < 0.001). The proportion of time awake spent immobile was significantly associated with worse survival. For each 10% increase in this measure, the hazard ratio (HR) was 1.48 (95% confidence interval [CI95%] = 1.06, 2.06) for overall mortality, and odds ratio was 2.99 (CI95% = 1.27, 7.05) for six-month mortality. ECOG PS was also associated with worse survival (HR = 2.80, CI95% = 1.34, 5.86). Among patients with ECOG PS 0-1, the percentage of time awake spent immobile was significantly associated with worse survival, HR = 1.93 (CI95% = 1.10, 3.42), whereas ECOG PS did not predict survival.
Significance of Results
Actigraphy may have potential to predict important clinical outcomes, such as quality of life and survival, and may serve to supplement PS. Further validation study is warranted.