Evaluating fall event definitions relative to lower limb prosthesis users' lived experiences.

PURPOSE: Evaluate specific elements of previously proposed fall and near-fall definitions to determine whether they fully capture lower limb prosthesis (LLP) users' lived experiences. METHODS: Semi-structured interviews were conducted with 24 LLP users. Interview transcripts were reviewed, coded, and analyzed using deductive thematic analysis to identify shared experiences and inform revisions to previously reported definitions. RESULTS: Four major themes emerged: a fall can be initiated by more than just a loss of balance, loss of balance and losing balance are considered similar, falls are not limited to landing on the ground or floor, and catching yourself and recovering your balance are distinct responses to a loss of balance. CONCLUSIONS: Two revisions were made to previous definitions to better align with LLP users' experiences and historically overlooked fall circumstances. A fall is defined as a loss of balance or sudden loss of support where your body lands on the ground, floor, or another object. A near-fall was defined as a loss of balance where you caught yourself or recovered your balance without landing on the ground, floor, or another object. Implementation of these new definitions will aid the collection of accurate, consistent, and meaningful fall data, enhancing aggregation and comparison across studies.

Falls are a top health concern for lower limb prosthesis users.Understanding how lower limb prosthesis users experience falls helps build meaningful fall definitions.Standardized definitions allow clinicians to document fall events with greater consistency and justify fall prevention interventions.

Severe hurricanes increase recruitment and gene flow in the clonal sponge Aplysina cauliformis.

Upright branching sponges, such as Aplysina cauliformis, provide critical three-dimensional habitat for other organisms and assist in stabilizing coral reef substrata, but are highly susceptible to breakage during storms. Breakage can increase sponge fragmentation, contributing to population clonality and inbreeding. Conversely, storms could provide opportunities for new genotypes to enter populations via larval recruitment, resulting in greater genetic diversity in locations with frequent storms. The unprecedented occurrence of two Category 5 hurricanes in close succession during 2017 in the U.S. Virgin Islands (USVI) provided a unique opportunity to evaluate whether recolonization of newly available substrata on coral reefs was due to local (e.g. re-growth of remnants, fragmentation, larval recruitment) or remote (e.g. larval transport and immigration) sponge genotypes. We sampled A. cauliformis adults and juveniles from four reefs around St. Thomas and two in St. Croix (USVI). Using a 2bRAD protocol, all samples were genotyped for single-nucleotide polymorphisms (SNPs). Results showed that these major storm events favoured sponge larval recruitment but did not increase the genetic diversity of A. cauliformis populations. Recolonization of substratum post-storms via clonality was lower (15%) than expected and instead was mainly due to sexual reproduction (85%) via local larval recruitment. Storms did enhance gene flow among and within reef sites located south of St. Thomas and north of St. Croix. Therefore, populations of clonal marine species with low pelagic dispersion, such as A. cauliformis, may benefit from increased frequency and magnitude of hurricanes for the maintenance of genetic diversity and to combat inbreeding, enhancing the resilience of Caribbean sponge communities to extreme storm events.

CancerSupportSource-Spanish: Development of a Distress Screening Measure for Spanish-Speaking Hispanic and Latino Individuals with Cancer.

Introduction: CancerSupportSource (CSS), a distress screening and referral program, identifies unmet needs of people with cancer and links them to resources and support. We developed and validated a Spanish-language version (CSS-Spanish) to better serve Hispanic and Latino communities and promote health equity. Methods: The 25-item CSS-Spanish was created leveraging rigorous translation methods and cognitive interviews to ensure cultural relevance and topical breadth. A total of 210 Spanish-speaking Hispanic and Latino individuals completed CSS-Spanish and comparison measures. Psychometric analyses examined dimensionality and statistical validation, and determined scoring thresholds for depression and anxiety risk subscales. Results: CSS-Spanish represented key concerns across five factors and exhibited strong internal consistency and test-retest reliability, convergent validity, and known-groups validity. Risk subscales demonstrated adequate sensitivity. Conclusion: CSS-Spanish is a reliable, valid multidimensional distress screener that rapidly assesses needs of Hispanic and Latino individuals. Embedded depression and anxiety risk flags can support staff in identifying those with high-acuity needs.

HIV Support Source: Development of a Distress Screening Measure for Adults with HIV.

To provide an effective, multidimensional, and psychometrically valid measure to screen for distress among people with HIV, we developed and assessed the psychometric properties of HIV Support Source, a distress screening, referral, and support program designed to identify the unmet needs of adults with HIV and link them to desired resources and support. Development and testing were completed in three phases: (1) item generation and initial item pool testing (N = 375), (2) scale refinement via exploratory factor analysis (N = 220); external/internal item quality, and judging theoretical and practical implications of items, and (3) confirmatory validation (N = 150) including confirmatory factor analysis along with reliability and validity analyses to corroborate dimensionality and psychometric properties of the final measure. Nonparametric receiver operating characteristic (ROC) curve analyses determined scoring thresholds for depression and anxiety risk subscales. The final measure comprises 17-items representing four domains of concern: emotional well-being, financial and practical needs, physical well-being, and HIV treatment and sexual health, plus one screening item assessing tobacco and substance use. Our analyses showed strong internal consistency reliability, a replicable factor structure, and adequate convergent, discriminant, and known groups validity. Sensitivity of 2-item depression and 2-item anxiety risk subscales was 0.90 and 0.79, respectively. HIV Support Source is a reliable and valid multidimensional measure of distress that also screens for risk for clinically significant depression and anxiety. It can be implemented within a distress screening, referral, and follow-up program to rapidly assess and support the unmet needs of adults with HIV.

The interplay of financial toxicity, health care team communication, and psychosocial well-being among rural cancer patients and survivors.

BACKGROUND: Financial toxicity contributes to psychosocial distress among cancer patients and survivors. Yet, contextual factors unique to rural settings affect patient experiences, and a deeper understanding is needed of the interplay between financial toxicity and health care team communication and its association with psychosocial well-being among rural oncology patients. PURPOSE: We examined associations between financial toxicity and psychosocial well-being among rural cancer patients, exploring variability in these linkages by health care team communication. METHODS: Using data from 273 rural cancer patients who participated in Cancer Support Community's Cancer Experience Registry, we estimated multivariable regression models predicting depression, anxiety, and social function by financial toxicity, health care team communication, and the interplay between them. RESULTS: We demonstrate robust associations between financial toxicity and psychosocial outcomes among our sample of rural cancer patients and survivors. As financial toxicity increased, symptoms of depression and anxiety increased. Further, financial toxicity was linked with decreasing social function. Having health care team conversations about treatment costs and distress-related care reduced the negative impact of financial toxicity on depressive symptoms and social function, respectively, in rural cancer patients at greatest risk for financial burden. CONCLUSIONS: Financial toxicity and psychosocial well-being are strongly linked, and these associations were confirmed in a rural sample. A theorized buffer to the detrimental impacts of financial toxicity-health care team communication-played a role in moderating these associations. Our findings suggest that health care providers in rural oncology settings may benefit from tools and resources to bolster communication with patients about costs, financial distress, and coordination of care.

Investigating the interactive effects of temperature, pH, and salinity on Naegleria fowleri persistence.

Naegleria fowleri causes primary amoebic meningoencephalitis, a deadly infection that occurs when free-living amoebae enter the nose via freshwater and travel to the brain. N. fowleri naturally thrives in freshwater and soil and is thought to be associated with elevated water temperatures. While environmental and laboratory studies have sought to identify what environmental factors influence its presence, many questions remain. This study investigated the interactive effects of temperature, pH, and salinity on N. fowleri in deionized and environmental waters. Three temperatures (15, 25, 35°C), pH values (6.5, 7.5, 8.5), and salinity concentrations (0.5%, 1.5%, 2.5% NaCl) were used to evaluate the growth of N. fowleri via ATP luminescent assays. Results indicated N. fowleri grew best at 25°C, and multiple interactive effects occurred between abiotic factors. Interactions varied slightly by water type but were largely driven by temperature and salinity. Lower temperature increased N. fowleri persistence at higher salinity levels, while low salinity (0.5% NaCl) supported N. fowleri growth at all temperatures. This research provided an experimental approach to assess interactive effects influencing the persistence of N. fowleri. As climate change impacts water temperatures and conditions, understanding the microbial ecology of N. fowleri will be needed minimize pathogen exposure.

CancerSupportSourceTM -Caregiver: Development of a distress screening measure for cancer caregivers.

OBJECTIVE: Given the substantial demands of cancer caregiving, practical and psychometrically sound tools to evaluate distress among cancer caregivers are needed. CancerSupportSourceTM -Caregiver is a distress screening, referral, and support program designed to identify the unmet needs of cancer caregivers and link caregivers to desired resources and support. This study refined and finalized the CancerSupportSource-Caregiver screening measure and examined its psychometric properties. METHODS: Using an analytic sample of 400 caregivers to people with cancer, we first performed item reduction by assessing exploratory factor analysis, external/internal item quality, and judging theoretical and practical implications of items. Confirmatory factor analysis along with reliability and validity analyses were then conducted to corroborate dimensionality and psychometric properties of the final measure. Nonparametric receiver operating characteristic curve analyses determined scoring thresholds for depression and anxiety risk subscales. RESULTS: Scale refinement resulted in an 18-item measure plus one screening item assessing tobacco and substance use. Items represented five domains of caregiver concerns: emotional well-being, patient well-being, caregiving tasks, finances, and healthy lifestyle. Our analyses showed strong internal consistency and test-retest reliability, a replicable factor structure, and adequate convergent, discriminant, and known groups validity. Sensitivity of 2-item depression and 2-item anxiety risk subscales were 0.95 and 0.87, respectively. CONCLUSIONS: CancerSupportSource-Caregiver is a reliable and valid multidimensional measure of caregiver distress that also screens for risk for clinically significant depression and anxiety. It can be implemented within a distress screening, referral, and follow-up program to rapidly assess caregivers' unmet needs and enhance caregiver well-being across the care continuum.

Pain and Nausea Intensity, Social Function, and Psychological Well-Being among Women with Metastatic Breast Cancer.

Advances in diagnostics and therapeutics have improved prognosis for metastatic breast cancer (MBC). Yet, treatment and disease burden-including experiences of pain and nausea-present practical and emotional challenges. To better support patients and enhance quality of life, deeper understanding of the pathways linking physical and psychological health is needed. To this end, we examined associations of pain and nausea with depression and anxiety among women with MBC. In doing so, we highlighted social function as a potentially important mechanism in this relationship. This observational, cross-sectional study included 148 predominantly non-Hispanic White, highly educated women living with MBC. Multivariate regression models demonstrated that more intense pain and nausea were significantly associated with higher levels of depression and anxiety (p < .001). Causal mediation analyses confirmed significant indirect effects whereby decreases in social function associated with pain and nausea contributed to depression and anxiety. Thus, our findings illustrate decreased social function as one pathway through which pain and nausea contribute to escalation of depression and anxiety. Our results, therefore, underscore the importance of supporting social function among women with MBC to potentially reduce psychological sequelae of pain and nausea.

Title: P2x7 Receptor Activation and Estrogen Status Drive Neuroinflammatory Mechanisms in a Rat Model for Dry Eye.

Dry eye disease (DED) is recognized as a chronic inflammatory condition with an increase in tear osmolarity and loss of tear film integrity. DED is often accompanied by adverse ocular symptoms which are more prevalent in females than males. The basis for ocular hyperalgesia in DED remains uncertain; however, both peripheral and central neural mechanisms are implicated. A model for aqueous deficient DED, exorbital gland excision, was used to determine if activation of the purinergic receptor subtype 7, P2X7R, expressed by non-neural cells in peripheral and central trigeminal nerve pathways, contributed to persistent ocular hyperalgesia. Densitometry of trigeminal brainstem sections revealed increases in P2X7R, the myeloid cell marker Iba1, and the inflammasome, NLRP3, of estradiol-treated DED females compared to estradiol-treated sham females, while expression in DED males and DED females not given estradiol displayed minor changes. No evidence of immune cell infiltration into the trigeminal brainstem was seen in DED rats; however, markers for microglia activation (Iba1) were increased in all groups. Isolated microglia expressed increased levels of P2X7R and P2X4R, IL-1ß (Ιnterleukin-1ß), NLRP3, and iNOS (nitric oxide synthase). Further, estradiol-treated DED females displayed greater increases in P2X7R, IL-1ß and NLRP3 expression compared to untreated DED females. Orbicularis oculi muscle activity (OOemg) evoked by ocular instillation of hypertonic saline (HS) was recorded as a surrogate measure of ocular hyperalgesia and was markedly enhanced in all DED groups compared to sham rats. Systemic minocycline reduced HS-evoked OOemg in all DED groups compared to sham rats. Local microinjection in the caudal trigeminal brainstem of an antagonist for P2X7R (A804598) greatly reduced HS-evoked OOemg activity in all DE groups, while responses in sham groups were not affected. Intra-trigeminal ganglion injection of siRNA for P2X7R significantly reduced HS-evoked OOemg activity in all DED groups, while evoked responses in sham animals were not affected. These results indicated that activation of P2X7R at central and peripheral sites in trigeminal pain pathways contributed to an increase in ocular hyperalgesia and microglia activation in DED males and females. Estrogen treatment in females further amplified ocular hyperalgesia and neuroimmune responses in this model for aqueous deficient DED.

Analysis of a panel-based pharmacogenomics testing program among members of a commercial and Medicare client of a pharmacy benefits manager.

BACKGROUND: Although the field of pharmacogenomics (PGx) has existed for decades, use of pharmacogenomic information by providers to optimize medication therapy for patients has had relatively slow adoption. There are many factors that have contributed to the slow adoption of PGx testing, but it is partially due to a lack of coverage by payers. If PGx testing is covered by payers, frequently only testing of a specific gene is covered, rather than a panel of many genes. As a result, little is known about how coverage of a panel-based PGx test will affect a member's medication therapy. OBJECTIVES: To determine how giving providers specific medication optimization recommendations, based on results of a panel-based PGx test, impacted members' medication regimens. METHODS: Pharmacy claims data were retrospectively reviewed for this exploratory study. Members who participated in PGx testing were in the intervention group and members who chose not to participate in the PGx testing, but who were eligible to participate, were in the control group. PGx test results, including suggested medication changes, were mailed to providers. To determine if providers adopted the suggested medication changes, pharmacy claims data were analyzed retrospectively for the 4-month period preceding and following the date from which recommendations were provided to prescribers. RESULTS: Of the 101 members included in the analysis, 50 were in the intervention group and 51 were in the control group. In the intervention group, members were taking in a total of 352 medications; 165 of the medications had PGx guidance. Based on the PGx test results, 62 of these medications (37.6%) had recommendations. Of members who received PGx testing, 76% had at least 1 recommended change. When pharmacist recommendations were made, a change was made to the medication 27% of the time. There was a statistically significant difference between the number of medication changes in the PGx group and the control group (P = 0.024). CONCLUSIONS: Recommendations based on PGx testing can lead to changes in medications and an optimized medication regimen for members. DISCLOSURES: The authors have no conflicts to disclose that may present a potential conflict of interest.

Clinical characterization of primary hyperoxaluria type 3 in comparison with types 1 and 2.

BACKGROUND: Primary hyperoxaluria (PH) type 3 (PH3) is caused by mutations in the hydroxy-oxo-glutarate aldolase 1 gene. PH3 patients often present with recurrent urinary stone disease in the first decade of life, but prior reports suggested PH3 may have a milder phenotype in adults. This study characterized clinical manifestations of PH3 across the decades of life in comparison with PH1 and PH2. METHODS: Clinical information was obtained from the Rare Kidney Stone Consortium PH Registry (PH1, n = 384; PH2, n = 51; PH3, n = 62). RESULTS: PH3 patients presented with symptoms at a median of 2.7 years old compared with PH1 (4.9 years) and PH2 (5.7 years) (P = 0.14). Nephrocalcinosis was present at diagnosis in 4 (7%) PH3 patients, while 55 (89%) had stones. Median urine oxalate excretion was lowest in PH3 patients compared with PH1 and PH2 (1.1 versus 1.6 and 1.5 mmol/day/1.73 m2, respectively, P < 0.001) while urine calcium was highest in PH3 (112 versus 51 and 98 mg/day/1.73 m2 in PH1 and PH2, respectively, P < 0.001). Stone events per decade of life were similar across the age span and the three PH types. At 40 years of age, 97% of PH3 patients had not progressed to end-stage kidney disease compared with 36% PH1 and 66% PH2 patients. CONCLUSIONS: Patients with all forms of PH experience lifelong stone events, often beginning in childhood. Kidney failure is common in PH1 but rare in PH3. Longer-term follow-up of larger cohorts will be important for a more complete understanding of the PH3 phenotype.

Transmission studies and the composition of prokaryotic communities associated with healthy and diseased Aplysina cauliformis sponges suggest that Aplysina Red Band Syndrome is a prokaryotic polymicrobial disease.

Aplysina cauliformis, the Caribbean purple rope sponge, is commonly affected by Aplysina Red Band Syndrome (ARBS). This transmissible disease manifests as circular lesions with red margins and results in bare spongin fibers. Leptolyngbya spp. appear to be responsible for the characteristic red coloration but transmission studies with a sponge-derived isolate failed to establish disease, leaving the etiology of ARBS unknown. To investigate the cause of ARBS, contact transmission experiments were performed between healthy and diseased sponges separated by filters with varying pore sizes. Transmission occurred when sponges were separated by filters with pore sizes ≥ 2.5 µm, suggesting a prokaryotic pathogen(s) but not completely eliminating eukaryotic pathogen(s). Using 16S rRNA gene sequencing methods, 38 prokaryotic taxa were significantly enriched in diseased sponges, including Leptolyngbya, whereas seven taxa were only found in some, but not all, of the ARBS-affected sponges. These results do not implicate a single taxon, but rather a suite of taxa that changed in relative abundance with disease, suggesting a polymicrobial etiology as well as dysbiosis. As a better understanding of dysbiosis is gained, changes in the composition of associated prokaryotic communities may have increasing importance for evaluating and maintaining the health of individuals and imperiled coral reef ecosystems.

hsa-MiR-19a-3p and hsa-MiR-19b-3p Are Associated with Spinal Cord Injury-Induced Neuropathic Pain: Findings from a Genome-Wide MicroRNA Expression Profiling Screen.

Neuropathic pain in spinal cord injury (SCI) is associated with inflammation in both the peripheral and central nervous system (CNS), which may contribute to the initiation and maintenance of persistent pain. An understanding of factors contributing to neuroinflammation may lead to new therapeutic targets for neuropathic pain. Moreover, novel circulating biomarkers of neuropathic pain may facilitate earlier and more effective treatment. MicroRNAs (miRNAs) are short, non-coding single-stranded RNA that have emerged as important biomarkers and molecular mediators in physiological and pathological conditions. Using a genome-wide miRNA screening approach, we studied differential miRNA expression in plasma from 68 healthy, community-dwelling adults with and without SCI enrolled in ongoing clinical studies. We detected 2367 distinct miRNAs. Of these, 383 miRNAs were differentially expressed in acute SCI or chronic SCI versus no SCI and 71 were differentially expressed in chronic neuropathic pain versus no neuropathic pain. We selected homo sapiens (hsa)-miR-19a-3p and hsa-miR-19b-3p for additional analysis based on p-value, fold change, and their known role as regulators of neuropathic pain and neuroinflammation. Both hsa-miR-19a-3p and hsa-miR-19b-3p levels were significantly higher in those with chronic SCI and severe neuropathic pain versus those with chronic SCI and no neuropathic pain. In confirmatory studies, both hsa-miR-19a-3p and hsa-miR-19b-3p have moderate to strong discriminative ability to distinguish between those with and without pain. After adjusting for opioid use, hsa-miR-19b-3p levels were positively associated with pain interference with mood. Because hsa-miR-19 levels have been shown to change in response to exercise, folic acid, and resveratrol, these studies suggest that miRNAs are potential targets of therapeutic interventions.

Exosomes Secreted by Microglia During Virus Infection in the Central Nervous System Activate an Inflammatory Response in Bystander Cells.

Microglia become persistently infected during Theiler's murine encephalomyelitis virus (TMEV) infection in the central nervous system (CNS) of susceptible mice. We have previously shown that microglia infected with TMEV become activated through the innate immune receptors to express type I interferons, cytokines, and chemokines. Persistent TMEV infection in the CNS promotes chronic neuroinflammation and development of demyelinating disease similar to multiple sclerosis. In the current studies, we wanted to determine whether TMEV-infected microglia secrete exosomes which contribute to neuroinflammation in the CNS thus promoting the development of demyelinating disease. Exosomes are vesicles containing RNA, DNA, and proteins that are released from one cell and taken up by another cell to facilitate communication between cells. These studies isolated exosomes secreted by microglia during TMEV infection in vitro as well as exosomes secreted by microglia during early TMEV infection in mice. These studies show that microglia secrete exosomes during TMEV infection which contain the viral RNA coding region. The exosomes secreted by microglia during TMEV infection can be taken up by uninfected bystander cells, including CNS resident microglia, astrocytes, and neurons. The viral RNA in the exosomes can be transferred to the bystander cells. In addition, the bystander cells that took up these exosomes were activated through the innate immune response to express type I interferons, IFNα and IFNß, pro-inflammatory cytokines, IL-6, IL-12, and TNFα, and chemokines, CCL2. Most interestingly, exosomes secreted by microglia during early TMEV infection in mice activated an inflammatory response when transferred to the brains of naïve mice. These results show that exosomes secreted by microglia during early TMEV infection contain viral RNA and can activate uninfected bystander CNS cells to promote an inflammatory immune response. Thus, exosomes secreted by microglia during virus infection may promote viral persistence and neuroinflammation which contributes to the development of demyelinating disease.

Patient-Reported Communication With Their Health Care Team About New Treatment Options for Chronic Lymphocytic Leukemia.

Chronic lymphocytic leukemia (CLL) often requires consideration of multiple treatment options. Shared decision-making (SDM) is important, given the availability of increasingly novel therapies; however, patient-provider treatment conversations vary. We examined relationships between patient-provider discussions of new CLL treatment options and sociodemographic, clinical, and patient-provider communication variables among 187 CLL patients enrolled in Cancer Support Community's Cancer Experience Registry. Factors significantly associated with self-reports of whether patients' providers discussed new CLL treatment options with them were examined using χ2 tests, t tests, and hierarchical logistic regression. Fifty-eight percent of patients reported discussing new treatment options with their doctor. Patients with higher education were 3 times more likely to discuss new treatment options relative to those with lower education (OR = 3.06, P < .05). Patients who experienced a cancer recurrence were 7 times more likely to discuss new treatment options compared to those who had not (OR = 7.01, P < .05). Findings offer insights into the correlates of patient-provider discussions of new CLL treatment options. As novel therapies are incorporated into standards of care, opportunities exist for providers to improve patient care through enhanced SDM.

Extracellular Vesicles Secreted by Tumor Cells Promote the Generation of Suppressive Monocytes.

Monocytes are among the first cells to infiltrate the tumor microenvironment. The conversion of monocytes to suppressor cells in the tumor microenvironment is crucial in evasion of the immune response and tumor maintenance. Tumor cells may secrete products that promote the conversion of monocytes to suppressor cells. Cells secrete extracellular vesicles (EVs) containing cargos of genetic materials and proteins as a way to communicate with neighboring cells. During pathologic conditions like cancers, tumor cells increase their EVs production containing microRNA, RNA, and proteins that may affect the immune cell response, contributing to the immunosuppressive microenvironment. Our studies show that EVs secreted by a wide range of murine tumor cells, including osteosarcoma, glioma, colon carcinoma, sarcoma, and melanoma, can be taken up by bone marrow-derived monocytes. The monocytes that took up the EVs secreted by tumor cells matured toward an immune-suppressive phenotype by upregulating the expression of suppressive cytokines and effector molecules. The monocytes also downregulated MHC class II and costimulatory molecules while increasing the expression of PD-L1 on their surface after taking up EVs from tumor cells. Most importantly, monocytes exposed to EVs secreted by tumor cells suppressed activated Ag-specific CD4+ T cells. These results show that tumor cells from several different tumor types secrete EVs which promote the conversion of monocytes into suppressor cells, thus promoting immune evasion. These studies suggest that EVs secreted by tumors are potentially a new target for future cancer therapy.

Natural History of Clinical, Laboratory, and Echocardiographic Parameters of a Primary Hyperoxaluria Cohort on Long Term Hemodialysis.

Background: Primary hyperoxaluria type 1 (PH1) is a rare monogenic disorder characterized by excessive hepatic production of oxalate leading to recurrent nephrolithiasis, nephrocalcinosis, and progressive kidney damage, often requiring renal replacement therapy (RRT). Though systemic oxalate deposition is well-known, the natural history of PH1 during RRT has not been systematically described. In this study, we describe the clinical, laboratory, and echocardiographic features of a cohort of PH1 patients on RRT. Methods: Patients with PH1 enrolled in the Rare Kidney Stone Consortium PH Registry who progressed to require RRT, had ≥2 plasma oxalate (pOx) measurements 3-36 months after start of RRT, and at least one pair of pOx measurements between 6 and 18 months apart were retrospectively analyzed. Clinical, echocardiographic, and laboratory results were obtained from the Registry. Results: The 17 PH1 patients in our cohort had a mean total HD hours/week of 17.4 (SD 7.9; range 7.5-36) and a range of age of RRT start of 0.2-75.9 years. The average change in plasma oxalate (pOx) over time on RRT was -0.74 [-2.9, 1.4] µmol/L/month with the mean pOx never declining below 50 µmol/L. Over time on RRT, oxalosis progressively developed in multiple organ systems. Echocardiography performed on 13 subjects showed worsening of left ventricular global longitudinal strain correlated with pOx (p < 0.05). Conclusions: Even when a cohort of PH1 patients were treated with intensified RRT, their predialysis pOx remained above target and they developed increasing evidence of oxalosis. Echocardiographic data suggest that cardiac dysfunction could be related to elevated pOx and may worsen over time.

CancerSupportSource®-15+: development and evaluation of a short form of a distress screening program for cancer patients and survivors.

PURPOSE: CancerSupportSource® (CSS) is a distress screening program implemented at community-based organizations and hospitals nationwide. The 25-item CSS assesses distress across five domains, with capacity to screen for clinically significant depression and anxiety. This study examined psychometric properties of a shortened form to enhance screening opportunities when staff or patient burden considerations are significant. METHODS: Development and validation were completed in multiple phases. Item reduction decisions were made with 1436 cancer patients by assessing external/internal item quality and judging theoretical and practical implications of items. Pearson correlations and confirmatory factor analysis were conducted on a separate sample of 957 patients to corroborate psychometric properties and dimensionality of the shortened scale. Nonparametric receiver operating characteristic (ROC) curve analyses determined scoring thresholds for depression and anxiety risk scales. RESULTS: Scale refinement resulted in a 15-item short form plus one screening item assessing tobacco and substance use (CSS-15+). At least two items from each CSS domain were retained to preserve multidimensionality. In confirmatory analysis, the model explained 59% of the variance and demonstrated good fit. Correlation between CSS-15+ and 25-item CSS was 0.99, p < 0.001. Sensitivity of 2-item depression and 2-item anxiety risk scales in the confirmatory sample were 0.82 and 0.83, respectively. CONCLUSIONS: CSS-15+ is a brief, reliable, and valid multidimensional measure of distress. The measure retained excellent internal consistency (α = 0.94) and a stable factor structure. CSS-15+ is a practical and efficient screening tool for distress and risk for depression and anxiety among cancer patients and survivors, particularly in community-based settings.

Recovery From Dialysis in Patients With Primary Hyperoxaluria Type 1 Treated With Pyridoxine: A Report of 3 Cases.

Primary hyperoxaluria type 1 (PH1) is a genetic disorder characterized by overproduction of oxalate and eventual kidney failure. Kidney failure is usually irreversible in PH1. However, in patients with PH1 homozygous for the G170R mutation (in which the glycine at amino acid 170 is replaced by an arginine), pyridoxine is an enzyme cofactor and decreases urinary oxalate excretion by reducing hepatic oxalate production. We report recovery from dialysis in 3 patients with PH1 homozygous for the G170R mutation in response to pharmacologic-dose pyridoxine treatment. Median age at initiation or resumption of pyridoxine treatment was 37 (range, 20-53) years, and median daily pyridoxine dose was 8.8 (range, 6.8-14.0) mg per kilogram of body weight. Duration of hemodialysis before recovery of kidney function was 10 (range, 5-19) months. Plasma oxalate concentration improved after recovery of kidney function. At a median of 3 (range, 2-46) months following discontinuation of hemodialysis, estimated glomerular filtration rate was 34 (range, 23-52) mL/min/1.73m2, plasma oxalate concentration was 8.8 (range, 4.6-11.3) µmol/L, and urinary oxalate excretion was 0.93 (range, 0.47-1.03) mmol/d. Kidney function was maintained during a median of 3.2 (range, 1.3-3.8) years of follow-up. These observations suggest that kidney failure may be reversible in a subset of patients with PH1 homozygous for the G170R mutation treated with pharmacologic-dose pyridoxine.

Concentrated Poverty in U.S. Schools and Adolescents' Risk of Being Overweight.

The economic segregation of U.S. schools undermines the academic performance of students, particularly students from low-income families who are often concentrated in high-poverty schools. Yet it also fuels the reproduction of inequality by harming their physical health. Integrating research on school effects with social psychological and ecological theories on how local contexts shape life course outcomes, we examined a conceptual model linking school poverty and adolescent students' weight. Applying multilevel modeling techniques to the first wave of data (1994-1995) from the National Longitudinal Study of Adolescent to Adult Health (Add Health; n = 18,924), the results revealed that individual students' likelihood of being overweight increased as the concentration of students from low-income families in their schools increased, net of their own background characteristics. This linkage was connected to a key contextual factor: the exposure of students in high-poverty schools to other overweight students. This exposure may partly matter because of the lower prevalence of dieting norms in such schools, although future research should continue to examine potential mechanisms.