A Study of Physical Resilience and Aging (SPRING): Conceptual framework, rationale, and study design.

Understanding the physiological basis of physical resilience to clinical stressors is crucial for the well-being of older adults. This article presents a novel framework to discover the biological underpinnings of physical resilience in older adults as part of the "Characterizing Resiliencies to Physical Stressors in Older Adults: A Dynamical Physiological Systems Approach" study, also known as The Study of Physical Resilience and Aging (SPRING). Physical resilience, defined as the capacity of a person to withstand clinical stressors and quickly recover or improve upon a baseline functional level, is examined in adults aged 55 years and older by studying the dynamics of stress response systems. The hypothesis is that well-regulated stress response systems promote physical resilience. The study employs dynamic stimulation tests to assess energy metabolism, the hypothalamic-pituitary-adrenal axis, the autonomic nervous system, and the innate immune system. Baseline characteristics influencing resilience outcomes are identified through deep phenotyping of physical and cognitive function, as well as of biological, environmental, and psychosocial characteristics. SPRING aims to study participants undergoing knee replacement surgery (n = 100), bone and marrow transplantation (n = 100), or anticipating dialysis initiation (n = 60). Phenotypic and functional measures are collected pre-stressor and at multiple times after stressor for up to 12 months to examine resilience trajectories. By improving our understanding of physical resilience in older adults, SPRING has the potential to enhance resilient outcomes to major clinical stressors. The article provides an overview of the study's background, rationale, design, pilot phase, implementation, and implications for improving the health and well-being of older adults.

Clinical trial participation predicts improved survival in older adults receiving allogeneic blood and marrow transplant.

BACKGROUND: Older adults represent a large oncologic demographic and are under-represented within oncology research despite constituting nearly two-thirds of the oncologic population in the United States. Because many social factors influence research participation, those who enroll in research do not reflect the oncology population at large, introducing bias and creating issue with external validity of studies. The same factors that influence study enrollment may also impact cancer outcomes, meaning that those who enroll in studies may already have an improved chance of cancer survival, further skewing results of these studies. This study evaluates characteristics that influence study enrollment in older adults and explore to what degree these factors may influence survival after allogeneic blood or marrow transplantation. METHODS: This retrospective comparison study evaluates 63 adults aged 60 and above undergoing allogenic transplantation at one institution. Patients who elected and declined enrollment in a non-therapeutic observational study were evaluated. Demographic and clinical characteristics between groups were compared and assessed as predictors of transplant survival, including decision to enroll in the study. RESULTS: Participants who chose to enroll in the parent study were not different with regard to gender, race/ethnicity, age, insurance type, donor age, and neighborhood income/poverty level compared to patients who were invited to participate but declined enrollment. The research participant group had higher proportion assessed as being fully active (23.8% vs. 12.7%, p = 0.034) and lower mean comorbidity scores (1.0 vs 2.47, p = 0.008). Enrollment in an observational study independently predicted transplant survival (HR = 0.316, 95% CI 0.12-0.82, p = 0.017). When controlling for relevant confounders of disease severity, comorbidities, and transplant age, enrolling in the parent study was associated with a lower hazards of death following transplant (HR = 0.302, 95% CI 0.10-0.87, p = 0.027). CONCLUSIONS: Despite being demographically comparable, persons who enrolled in one non-therapeutic transplant study had significantly improved survivorship than those who did not participate in observational research. These findings suggest that there are unidentified factors that influence study involvement that may also impact disease survivorship, over-estimating outcomes from these studies. Results from prospective observational studies should be interpreted with the consideration that study participants have an improved chance of survival at baseline.

Single-Agent Post-Transplantation Cyclophosphamide as Graft-versus-Host Disease Prophylaxis after Human Leukocyte Antigen-Matched Related Bone Marrow Transplantation for Pediatric and Young Adult Patients with Hematologic Malignancies.

High-dose cyclophosphamide given after HLA-matched related and unrelated allogeneic bone marrow transplantation (BMT) for patients with hematologic malignancies is effective single-agent graft-versus-host disease (GVHD) prophylaxis in adults. Data describing outcomes for pediatric and young adult patients have not been reported. Between the years 2007 and 2013, 29 pediatric and young adult patients ages ≤21 years of age treated at our institution for high-risk hematologic malignancies underwent myeloablative HLA-matched related T cell-replete BMT. Eleven patients received post-transplantation cyclophosphamide (PTCy) as single-agent GVHD prophylaxis and were followed prospectively. Eighteen patients received calcineurin inhibitor (CNI)-based standard GVHD prophylaxis and were studied retrospectively as a control group. No acute GVHD (aGVHD) developed in patients receiving PTCy, whereas patients receiving CNI-based GVHD prophylaxis had cumulative incidences of grades II to IV and grades III and IV aGVHD of 27% and 5%, respectively. No patients receiving PTCy developed chronic GHVD, compared to 1 in the control group. Two-year overall survival was similar between the 2 groups (54% PTCy versus 58% CNI-based prophylaxis), as was event-free survival (42% PTCy versus 47% CNI-based). The 5-year cumulative incidence of relapse was 58% for PTCy and 42% for CNI-based GVHD prophylaxis (P = .45). These results suggest that PTCy is a safe and efficacious method of GVHD prophylaxis after an HLA-matched related BMT in the pediatric and young adult population that affords patients to be off all post-transplantation immunosuppression on day +5.

Assessing the quality and usability of smartphone apps for pain self-management.

OBJECTIVE: To evaluate smartphone apps intended for self-management of pain using quality assessment criteria and usability testing with prospective users. DESIGN: 1) Survey and content analysis of available apps; and 2) individual usability study of two apps. SETTING: University of Leeds, United Kingdom. PARTICIPANTS: Forty-one participants (aged 19-59 years) with experience of chronic or recurrent pain episodes. METHODS: We undertook a survey, content analysis, and quality appraisal of all currently available mobile phone apps for self-management of pain. Two apps were then selected and assessed with usability testing. RESULTS: Twelve apps met the inclusion criteria. The quality assessment revealed wide variation in their clinical content, interface design, and usability to support self-management of pain. Very little user or clinician involvement was identified in the development of the apps. From the usability testing, participants stated a preference for an interface design employing a lighter color scheme and particular text font. Although very few participants were aware of pain-reporting apps prior to participation, many would consider use in the future. CONCLUSIONS: Variation in app quality and a lack of user and clinician engagement in development were found across the pain apps in this research. Usability testing identified a range of user preferences. Although useful information was obtained, it would be beneficial to involve users earlier in the process of development, as well as establishing ways to merge end user requirements with evidence-based content, to provide high-quality and usable apps for self-management of pain.

The state of radiological protection; views of the radiation protection profession: IRPA13, Glasgow, May 2012.

The IRPA13 Congress took place from 14-18 May 2012 in Glasgow, Scotland, UK, and was attended by almost 1500 radiological protection professionals. The scientific programme of the Congress was designed to capture a snapshot of the profession's views of the current state of knowledge, and of the challenges seen for the coming years. This paper provides a summary of these results of the Congress in twelve key scientific areas that served as the structural backbone of IRPA13.

Predicting the result of additional second-trimester markers from a woman's first-trimester marker profile: a new concept in Down syndrome screening.

OBJECTIVE: To describe a method for deciding whether an individual's first-trimester Down syndrome screening test result justifies further testing in the second trimester. METHODS: Statistical modelling was used to estimate the distribution of second-trimester marker profiles for a given first-trimester profile and hence the probability of a final positive result, using a 1 in 250 term cut-off. A multi-variate log Gaussian model was used with published parameters. Markers were maternal serum pregnancy-associated plasma protein-A and free beta-human chorionic gonadotrophin (hCG) at 10 weeks, nuchal translucency at 11 weeks, and second-trimester maternal serum alpha-fetoprotein, total hCG, unconjugated estriol and inhibin-A. To illustrate the method, the model was applied to a published series of 24 Down syndrome and 367 unaffected pregnancies. RESULTS: Modelling predicts that for 63% Down syndrome and 0.4% unaffected pregnancies having first-trimester tests, there is a 50% or more probability of a final positive result. A step-wise sequential screening policy based on immediate prenatal diagnosis for those with high probability and second-trimester testing for the remainder would have a 90% detection rate and 1.7% false-positive rate. Modelling also predicts 8.0% Down syndrome and 89% unaffected pregnancies with probabilities below 3%. A contingent screening policy restricting second-trimester testing to those with 3-49% probabilities would have an 88% detection rate and 1.4% false-positive rate. CONCLUSION: Predicting the probability of a positive final result from the first-trimester marker profile has potential utility, either as a decision aide for individual women or as a formal part of screening policy in selecting a subset of women for second-trimester testing.

The L locus, one of complementary genes required for anthocyanin production in onions (Allium cepa), encodes anthocyanidin synthase.

Bulb color in onions (Allium cepa) is an important trait, but its complex, unclear mechanism of inheritance has been a limiting factor in onion cultivar improvement. The identity of the L locus, which is involved in the color difference between Brazilian yellow and red onions, is revealed in this study. A cross was made between a US-type yellow breeding line and a Brazilian yellow cultivar. The segregation ratio of nine red to seven yellow onions in the F(2) population supports the involvement of two complementary genes in anthocyanin production in the F(1) hybrids. The high-performance liquid chromatography (HPLC) and reverse-transcriptase (RT)-PCR analysis of the Brazilian yellow onions indicated that the genes are involved late in the anthocyanin synthesis pathway. The genomic sequence of the anthocyanidin synthase (ANS) gene in Brazilian yellow onions showed a point mutation, which results in an amino acid change of a glycine to an arginine at residue 229. Because this residue is located adjacent to a highly conserved iron-binding active site, this mutation is likely responsible for the inactivation of the ANS gene in Brazilian yellow onions. Following the isolation of the promoter sequence of the mutant allele, a PCR-based marker for allelic selection of the ANS gene was designed. This assay is based on an insertion (larger than 3 kb) mutation. The marker perfectly co-segregated with the color phenotypes in the F(2) populations, thereby indicating that the L locus encodes ANS.

Down's syndrome risk estimates demonstrate considerable heterogeneity despite homogeneity of input.

BACKGROUND: Due to concerns about screening quality, Down's syndrome screening laboratories were surveyed to identify the range of variation in risk-calculation software. METHODS: All UK Down's syndrome screening laboratories were sent the confidential survey via the National External Quality Assessment Scheme. This covered the software used, its origin, the risk calculation methodology and the Gaussian population parameters. Laboratories were also given multiples of the median (MoM) data from five representative cases and asked to calculate Down's syndrome risks on their systems. RESULTS: Most parameter sets could be traced to published literature. The range of risk results for identical patient data was wide; the largest differences between lowest and highest risk for a test MoM set were: alpha-fetoprotein (AFP)+human chorionic gonadotrophin (hCG), 1:95 to 1:388 = 408%; AFP+hCG+urine estriol (UE(3)), 1:2011 to 1:7000 = 348%; AFP+free-beta-hCG, 1:280 to 1:1681 = 600%; AFP+free-beta-hCG+UE(3), 1:340 to 1:13000 = 3823%. Two explanations for this variation - the prior age risk result (half-year correction) and the population parameters - are described. CONCLUSIONS: (a) All laboratories should apply half-year correction for maternal age risk calculation. (b) Triple-test parameter variations result in huge variation of risk estimates, and a single national risk threshold of 1 in 250 will be unlikely to improve screening equity unless attention is also paid to standardizing population parameters. Down's syndrome screening has been controversial since it was introduced, and the possibility that more central control (including listing acceptable population parameters) may be necessary to ensure comparability of results is certain to ensure that this controversy continues.

Information management and informatics: need for a modern pathology service.

Requirements for information technology in pathology now extend well beyond the provision of purely analytical data. With the aim of achieving seamless integration of laboratory data into the total clinical pathway, "informatics"--the art and science of turning data into useful information--is becoming increasingly important in laboratory medicine. Informatics is a powerful tool in pathology--whether in implementing processes for pathology modernization, introducing new diagnostic modalities (e.g. proteomics, genomics), providing timely and evidence-based disease management, or enabling best use of limited and often costly resources. Providing appropriate information to empowered and interested patients--which requires critical assessment of the ever-increasing volume of information available--can also benefit greatly from appropriate use of informatics. General trends in medical informatics are reflected in current priorities for laboratory medicine, including the need for unified electronic records, computerized order entry, data security and recovery, and audit. The increasing demands placed on pathology information systems in the context of wider developmental change in healthcare delivery are explored in this paper.

Wrong biochemistry results: two case reports and observational study in 5310 patients on potentially misleading thyroid-stimulating hormone and gonadotropin immunoassay results.

BACKGROUND: Immunoassays are used in almost all medical and surgical specialties, but they suffer from interference from proteins such as antibodies in some patients' sera. Such interferences are usually reported in the literature only as case reports after the introduction of a new assay. METHODS: We undertook a prospective observational study on 5310 patients for whom the common immunoassay tests for thyroid-stimulating hormone (TSH) and/or gonadotropins were requested. All TSH and gonadotropin results were critically assessed for a mismatch between the clinical details and analytical results to identify samples suspected of analytical unreliability. These were tested further by three approaches to screen for interference. RESULTS: From the 5310 sets of results, 59 patients' samples were identified as suspect and were tested further. Analytically incorrect results were found in 28 (0.53% of the total studied). The magnitude of interference varied, but in 23 of 28 patients (82%), it was considered large enough to have a potentially adverse effect on cost and/or the clinical care of these patients. Two cases, described in detail, illustrate the adverse effect of error on patient care and cost, and the second highlights the difficulties and limitations of current approaches for identifying interference and inaccuracy in immunoassays. CONCLUSIONS: Because millions of TSH/gonadotropin tests are carried out in UK hospital laboratories alone, our data suggest that thousands of patients could be adversely affected by errors from interferences. Early identification of interference in cases with unusual results could be valuable.

Readmission rates for adjustment disorders: comparison with other mood disorders.

BACKGROUND: The diagnostic category of adjustment disorders continues to receive little attention in the research literature despite its estimated incidence of 5-21% in psychiatric consultation services for adults and 7.1% in inpatient admissions. METHODS: Ten years of readmission data were reviewed for six diagnostic categories: adjustment disorders, major depressive disorder (single episode and recurrent), dysthymia, any anxiety disorder and depression NOS. Cox regression analysis was used. RESULTS: Admission diagnosis was a significant predictor of readmission, with adjustment disorders resulting in significantly fewer readmissions than the group as a whole, and major depression recurrent resulting in significantly more readmissions. LIMITATIONS: Structured interviews were not used for the establishment of admission diagnoses. CONCLUSIONS: Readmission rates in this sample support the construct validity of the adjustment disorders category. The category includes a significant minority of patients admitted to psychiatric hospitalization.