The impact of housing on birth outcomes in breeding macaque groups across multiple research centers.

Demand for nonhuman primates in research has increased over the past several years, while nonhuman primate supply remains a challenge in the United States. Global nonhuman primate supply issues make it increasingly important to maximize domestic colony production. To explore how housing conditions across primate breeding colonies impact infant survival and animal production more broadly, we collected medical records from 7959 rhesus macaques (Macaca mulatta) and 492 pigtail macaques (Macaca nemestrina) across seven breeding facilities and used generalized mixed-effect modeling to determine prenatal and infant survival odds by housing type and group size. Infant survival odds for each housing type and group size varied for prenatal, neonatal, early infant, and late infant age groups. Odds of prenatal survival were lowest in paired indoor housing and small and medium outdoor groups. No housing type performed better than large outdoor groups for neonatal survival. Odds of early infant survival was greatest in indoor and mixed indoor/outdoor housing compared to large outdoor enclosures. Large outdoor housing was associated with higher survival odds for late infant survival compared to small and medium outdoor housing. These results may influence housing choices at macaque breeding facilities hoping to maximize infant success, although there are relative care costs, the promotion of species-typical behaviors, and infrastructure factors to also consider. Our study used an interinstitutional collaboration that allowed for the analysis of more infant macaque medical records than ever before and used the broad variations across the seven national primate research centers to make the results applicable to many other facilities housing macaques.

Comparing Radiologist Performance in Diagnosing Clinically Significant Prostate Cancer with Multiparametric versus Hybrid Multidimensional MRI.

Background Variability of acquisition and interpretation of prostate multiparametric MRI (mpMRI) persists despite implementation of the Prostate Imaging Reporting and Data System (PI-RADS) version 2.1 due to the range of reader experience and subjectivity of lesion characterization. A quantitative method, hybrid multidimensional MRI (HM-MRI), may introduce objectivity. Purpose To compare performance, interobserver agreement, and interpretation time of radiologists using mpMRI versus HM-MRI to diagnose clinically significant prostate cancer. Materials and Methods In this retrospective analysis, men with prostatectomy or MRI-fused transrectal US biopsy-confirmed prostate cancer underwent mpMRI (triplanar T2-weighted, diffusion-weighted, and dynamic contrast-enhanced imaging) and HM-MRI (with multiple echo times and b value combinations) from August 2012 to February 2020. Four readers with 1-20 years of experience interpreted mpMRI and HM-MRI examinations independently, with a 4-week washout period between interpretations. PI-RADS score, lesion location, and interpretation time were recorded. mpMRI and HM-MRI interpretation time, interobserver agreement (Cronbach alpha), and performance of area under the receiver operating characteristic curve (AUC) analysis were compared for each radiologist with use of bootstrap analysis. Results Sixty-one men (mean age, 61 years ± 8 [SD]) were evaluated. Per-patient AUC was higher for HM-MRI for reader 4 compared with mpMRI (AUCs for readers 1-4: 0.61, 0.71, 0.59, and 0.64 vs 0.66, 0.60, 0.50, and 0.46; P = .57, .20, .32, and .04, respectively). Per-patient specificity was higher for HM-MRI for readers 2-4 compared with mpMRI (specificity for readers 1-4: 48%, 78%, 48%, and 46% vs 37%, 26%, 0%, and 7%; P = .34, P < .001, P < .001, and P < .001, respectively). Diagnostic performance improved for the reader least experienced with HM-MRI, reader 4 (AUC, 0.64 vs 0.46; P = .04). HM-MRI interobserver agreement (Cronbach alpha = 0.88 [95% CI: 0.82, 0.92]) was higher than that of mpMRI (Cronbach alpha = 0.26 [95% CI: 0.10, 0.52]; α > .60 indicates reliability; P = .03). HM-MRI mean interpretation time (73 seconds ± 43 [SD]) was shorter than that of mpMRI (254 seconds ± 133; P = .03). Conclusion Radiologists had similar or improved diagnostic performance, higher interobserver agreement, and lower interpretation time for clinically significant prostate cancer with hybrid multidimensional MRI than multiparametric MRI. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Turkbey in this issue.

Life Satisfaction and Incumbent Voting: Examining the Mediating Effect of Trust in Government.

An emerging body of evidence suggests a causal relationship between wellbeing and incumbent voting. However, the evidence is primarily founded upon established democracies with regular turnovers of power. Moreover, the mechanism underlying this relationship is still relatively unknown. Using the intricacies of the Malaysian political context and Malaysian data from the seventh wave of the World Values Survey (WVS), this study examines the mediating role of trust in government to explain the relationship between life satisfaction and incumbent voting. Notably, the Malaysian WVS was concluded two weeks before Malaysia's fourteenth general election (GE14), which witnessed the end of the ruling coalition's six-decade hold on power since independence and subsequently ushered in the country's first-ever peaceful transfer of power. The empirical analysis indicated that the mediating role of trust in the relationship between life satisfaction and incumbent voting is supported. Further empirical analysis also showed that the mediating effect of trust was unique to the GE14 context compared to GE13, thus providing a better understanding of the role trust plays in the outcome of the election. The results provide valuable insights and implications in political science, especially for a nation emerging from its authoritarian state.

Oral fosfomycin use for pyelonephritis and complicated urinary tract infections: a 1 year review of outcomes and prescribing habits in a large municipal healthcare system.

BACKGROUND: The rising incidence of MDR uropathogens has driven increased use of oral fosfomycin for treatment of complicated urinary tract infections (cUTIs). However, there are limited data to support its use for cUTI, especially pyelonephritis. METHODS: We performed a retrospective review of all oral fosfomycin prescriptions between 1 January and 31 December 2017 in the Los Angeles County Department of Health Service system, the second largest US municipal health system. We examined demographics, clinical characteristics, adverse events and 30 day treatment success for patients with cUTI. Follow-up urine cultures till 31 December 2018 were examined for emergence of fosfomycin resistance. RESULTS: Of 154 patients prescribed fosfomycin, 99 (64%) had cUTI. Of these, 39 (39%) had lower tract, 37 (37%) pyelonephritis and 23 (23%) non-pyelonephritis upper tract cUTI. Escherichia coli ESBL producers were the predominant pathogens (73%). Of the 63 patients with 30 day follow-up, 49 (78%) had clinical success, including 16/20 (80%) treated for pyelonephritis. Treatment failure was associated with male sex (P < 0.01), urological abnormalities (P = 0.05), non-E. coli cUTI (P = 0.03) and receipt of <25% IV therapy prior to fosfomycin switch (P = 0.03). Of patients prescribed fosfomycin (n = 154), fosfomycin-resistant E. coli were found in 9/64 (14%) of the patients with follow-up urine cultures >30 days after initial treatment. CONCLUSIONS: Despite the lack of data supporting its use, we found that most patients receiving oral fosfomycin off-label for cUTI, including pyelonephritis, had clinical success. However, emergence of subsequent resistance warrants caution. Prospective comparative studies should be done to better evaluate oral fosfomycin use for cUTI.

Prior facility affects alopecia in adulthood for rhesus macaques.

Alopecia has proven to be a persistent problem for captive macaques; many cases continue to elude explanations and effective treatments. Although almost all captive populations exhibit alopecia rates higher than those seen in the wild, there also appear to be wide ranges in rates reported across primate facilities. In this study we looked at alopecia ratings for rhesus macaques (Macaca mulatta) obtained from five primary suppliers and currently housed at the Washington National Primate Research Center (WaNPRC). There were significant differences in alopecia ratings based on prior facility, despite the fact that animals had left their prior facilities at least 10 months previously and 60% had left more than 2 years previously. Possible explanations for the facility effect may include longer than anticipated time lines for alopecia amelioration, early experience effects, and genetic contributions. Our results should provide a cautionary note for those evaluating alopecia, treatments for alopecia, and the current environments of alopecic animals. It is possible that not all alopecia is caused, or can be ameliorated, by changes in the immediate environment. Am. J. Primatol. 79:e22551, 2017. © 2016 Wiley Periodicals, Inc.

Rhesus macaques (Macaca mulatta) with self-injurious behavior show less behavioral anxiety during the human intruder test.

Self-injurious behavior (SIB) has been linked to anxiety in the human literature, but relatively few studies have explored this link in rhesus macaques. A widely used behavioral assessment of anxiety, the human intruder test (HIT), employs the mildly stressful stimulus of an unfamiliar experimenter to assess anxious behavior in macaques. The HIT was conducted on 59 (20 male) laboratory housed rhesus macaques, 30 with a record of SIB (10 male). If monkeys with SIB have a more anxious phenotype, they should show stronger reactions to the HIT. However, contrary to our predictions, monkeys with SIB did not show higher levels of anxious behavior compared to controls. They spent significantly less time showing anxious behavior and displayed little aggression in response to the stare of the intruder. SIB and control monkeys did not differ in a range score (number of unique behaviors expressed per phase); however, SIB monkeys had a lower change score (total number of behaviors expressed including repetitions) than controls. In general, monkeys that paced regardless of SIB status, showed a reduction in pacing when the intruder entered the room. Possible explanations for the failure of SIB monkeys to show increased anxiety in the HIT include greater exposure of SIB monkeys to unfamiliar humans because of their condition, evidence for a subtype of SIB which is not anxiety related, and/or the presence of comorbid depressive-like symptoms. Am. J. Primatol. 79:e22569, 2017. © 2016 Wiley Periodicals, Inc.

Socialization in pigtailed macaques (Macaca nemestrina).

In response to new emphasis by regulatory agencies regarding socialization, behavioral management programs are allocating greater resources to maximize socialization opportunities for laboratory primates. Information regarding predictors of compatibility and risk of injury for all laboratory-housed species of macaques are needed to make social introductions and pairings as efficient and safe as possible. This study presents data on 674 pairs of pigtailed macaques (Macaca nemestrina) at the Washington National Primate Research Center over a 7-year period. During pair introduction, behavior was monitored while the degree of tactile contact was gradually increased. Based on observed behavior, pairs were assigned a behavioral introduction score (BIS), rating the quality of their interactions for each day of introduction. Animals deemed compatible, based on the BIS and technologist judgment, were allowed to progress to continuous contact with no staff present. A small proportion of animals deemed compatible at introduction was later separated for subsequent incompatibility or aggression; these proportions were higher in full contact compared to protected contact pairings. Of 674 pairs, 75% were deemed compatible at introduction in protected contact; 86 of these pairs were later transitioned to full contact with 98% compatibility. Predictors of decreased compatibility assessed during protected contact introductions included age (adult pairs were less compatible), the BIS on the last day of introduction, and aggression or injury during the introductory period. Predictors of injuries during the protected contact introduction process included: aggression on the first day of introduction, a negative BIS on the first or last day of introduction, and, surprisingly, the presence of grooming on the first day of introduction. Injuries during both introduction and subsequent pairing in protected contact were rare; however, injury rates increased significantly during full-contact pairing. These findings underscore the necessity of species-specific data to guide decision-making during the social introduction process. Am. J. Primatol. 79:e22556, 2017. © 2016 Wiley Periodicals, Inc.

The correlation between alopecia and temperament in rhesus macaques (Macaca mulatta) at four primate facilities.

Alopecia is a ubiquitous, multifaceted problem at facilities caring for captive rhesus macaques. There is a wide range of potential etiologies for the hair loss, including compromised immune function, dermatological pathologies, and environmental factors. However, few studies have examined whether various temperamental traits affect vulnerability to develop alopecia. We examined the correlation between alopecia and temperament in 101 (51M) indoor-housed rhesus macaques at four national primate centers. We utilized a cage side version of the Human Intruder test (HIT) to assess response to four conditions: no human present (Alone), human intruder standing next to the cage without making eye contact (Profile), intruder making direct eye contact (Stare) and intruder with back turned (Back). Behavior from all videos was quantified at one facility. We used generalized linear modeling to examine the relationship between behavior on the HIT and alopecia, controlling for facility, age, and sex. There was a significant negative correlation between alopecia and various behaviors associated with an inhibited or anxious temperament, including self-directed behavior (ß = -0.15, P < 0.001) and freeze in the Profile period (ß = -0.0092, P < 0.001), and defensive behaviors (ß = -0.0094, P < 0.001) and time spent in the back of the cage in the Stare period (ß = -0.0023, P = 0.015). Individuals with an inhibited or anxious temperament had less alopecia than others. Further, there were facility differences with respect to several variables on the HIT, including defensive behavior in Stare and freeze in Profile. These results suggest that temperament can influence the development of alopecia in rhesus macaques. Our results also highlight the degree to which facility differences can affect outcomes on standardized behavioral tests. Am. J. Primatol. 79:e22504, 2017. © 2015 Wiley Periodicals, Inc.

A simple alopecia scoring system for use in colony management of laboratory-housed primates.

BACKGROUND: Alopecia in captive primates continues to receive attention from animal care personnel and regulatory agencies. However, a method that enables personnel to reliably score alopecia over time and under various conditions has proven difficult to achieve. METHODS: The scoring system developed by the behavioral and veterinary staffs at the Washington National Primate Research Center (WaNPRC) uses the rule of 9s to estimate the percentage of the body affected with alopecia (severity) and how the alopecia presents itself (pattern). Training and scoring can conveniently be managed using photographic images, cage-side observations, and/or physical examinations. RESULTS: Personnel with varying degrees of experience were quickly trained with reliability scores ranging from 0.82 to 0.96 for severity and 0.82 to 0.89 for pattern using Cohen's κ. CONCLUSIONS: This system allows for reliable and consistent scoring across species, sex, age, housing condition, seasons, clinical or behavioral treatments, and level of personnel experience.

Effect of supplementary private health insurance on inpatient utilisation: Evidence from Malaysia.

Supplementary private health insurance (PHI) provides better access to healthcare, improves health outcomes, potentially lowers the costs for health systems and supports the social security system. Improperly regulated PHI, however, may aggravate inequity of access towards preferential care and encourage moral hazard among PHI purchasers, altering the health-seeking behaviour, which is often observed through the pattern of health care utilisation. We investigated the effect of PHI ownership on private inpatient care utilisation, its frequency of admission and length of stay by conducting secondary data analysis of the Malaysian National Health Morbidity Survey (NHMS) 2015 data, a nationally representative community health survey. Malaysian adults 18 years of age and above who utilised inpatient healthcare facilities were included. In this cross-sectional study, we addressed the endogeneity effect of health insurance by employing instrumental variable estimation and a two-stage residual inclusion analysis. We found a significant increase in private inpatient utilisation among those who owned PHI compared to those who did not (ß = 4.39, p < 0.001). There was no significant difference in the frequency of admission and length of stay. The increase in private inpatient utilisation among PHI owners may reflect the demand for timely care and hospitality provided by the private sector, potentially exacerbating the moral hazard behaviour among PHI owners. Further exploration of this issue could impact future healthcare systems financing designs and PHI regulation.

Comparing the relative benefits of grooming-contact and full-contact pairing for laboratory-housed adult female Macaca fascicularis.

Tactile social contact is the most effective form of environmental enrichment for promoting normal behavior in captive primates. For laboratory macaques housed indoors, pair housing is the most common method for socialization. Pairs can be housed either in full contact (FC), or in protected contact (PC). At Washington National Primate Research Center, PC is provided by grooming-contact (GC) cages whereby two partners are housed individually in adjacent cages with access to each other through widely spaced vertical bars. Grooming-contact has been used to accommodate research protocol restrictions and improve the likelihood of compatibility for various pairings, in part by enabling male-female pairs. This study compares the benefits between the two housing types by video recording 14 pairs of adult female Macaca fascicularis in four sequential housing phases following an ABBA design: baseline grooming-contact, full contact shortly after introduction, 1-month-later full contact, and after reversion to grooming-contact. Prior to this study, pairs had been housed compatibly in GC. Twelve of the 14 long-term pairs transitioned successfully to full contact and data presented exclude the two failed pairs. Allogrooming increased significantly when pairs first switched from GC to FC (P = 0.018), but the effect did not last through the on 1-month-later FC phase suggesting that the initial improvement in affiliative behavior was a transitory novelty response that did not persist. Self-grooming significantly decreased between the first GC and first FC phases (P = 0.016), likely due to redirected allogrooming. Non-contact affiliative behavior towards partner or other conspecifics in the room did not differ, nor did agonism towards partner or others in the room. Occurrence of abnormal, tension, manipulation, miscellaneous active, and inactive behaviors did not differ significantly across housing phases. Proximity measurements indicated that pairs were significantly out of arm's reach more often in protected contact than when in full contact (P ≤ 0.02). Proportion of time spent in physical contact significantly increased between the first GC and first FC phases (P = 0.002), but subsequently declined. For both FC phases, partners chose to spend about 50% of their time in the same cage. Few behavioral improvements were seen after pairs switched to full contact and no negative effects came of reversion to grooming contact. This study suggests that tactile contact provided through widely spaced bars (grooming-contact) is a viable alternative to full contact housing for adult female longtailed macaques. It provides a degree of social housing while allowing both partners choice and control, key concepts in contemporary animal welfare guidelines.

Floating limb behaviors and self-biting are associated in laboratory monkeys.

Early descriptions of floating limb behaviors in monkeys were associated with isolation rearing, a practice that ended more than two decades ago. The present authors named various forms of behaviors in which a leg is elevated for no apparent reason: "Floating Limb Suite" (FLS). Floating limb behaviors, identified in laboratory monkeys at the Washington National Primate Research Center (WaNPRC), consist of two subcategories distinguished by whether monkeys seem to react to the elevated leg or ignore it. Given the past association of isolation rearing with both self-biting (SB) and floating limb, the investigators predicted that SB and FLS would be associated in monkeys not reared in isolation. The investigators tracked, over a period of 3 years, the presence of FLS and SB in macaques (Macaca nemestrina, M. fascicularis, M. mulatta) and Papio cynocephalus at WaNPRC. SB and both subcategories of FLS occurred in mother-reared and surrogate-peer-nursery-reared monkeys. We analyzed presence of FLS, the two subcategories of FLS, and SB in 1,117 macaques monitored for up to 3 years, and 781 macaques observed for 8 min of structured data collection. The Papio sample size was insufficient for statistical analysis. Both sampling methodologies found FLS and FLS subcategories to be associated with SB. Nearly half the monkeys only engaging in seemingly harmless nonreactive forms of FLS also performed the potentially injurious behavior of self-biting. The positive association between FLS and SB suggests that monkeys exhibiting one of these behaviors are at a heightened risk for developing the other. One impediment to studying floating limb behaviors is lack of consensus on definitions. This study defined seven forms of apparently functionless elevated limb behaviors. Continued research on factors associated with floating limb behaviors across demographic groups and settings may provide insights into the etiology and treatment of self-biting.

Predictors of hyporesponsiveness to erythropoiesis-stimulating agents in hemodialysis patients.

BACKGROUND: Identification of predictors of hyporesponsiveness to erythropoietin-stimulating agents (ESAs) in hemodialysis (HD) patients may help improve anemia management and reduce hemoglobin level variability. STUDY DESIGN: We conducted repeated-measure and logistic regression analyses in a retrospective cohort of long-term HD patients to examine the association of iron markers and measures of renal osteodystrophy with ESA responsiveness. The ESA response coefficient at the individual level, ie, the least confounded dose-response association, was separated from the population level, assumed to represent confounding by medical indication. SETTING/PARTICIPANTS: The national database of a large dialysis organization (DaVita Inc, El Segundo, CA) with 38,328 surviving prevalent HD patients during 12 months who received ESA for at least 3 consecutive calendar quarters was examined. PREDICTORS: Serum levels of ferritin, iron saturation ratio, intact parathyroid hormone, and alkaline phosphatase. OUTCOMES/OTHER MEASUREMENTS: The main outcome was case-mix-adjusted hemoglobin response to quarterly averaged ESA dose at the individual level. The odds ratio (OR) of the greatest versus poorest ESA-response quartile at the patient level was calculated. OR less than 1.0 indicated ESA hyporesponsiveness, and OR greater than 1.0, enhanced responsiveness. RESULTS: Mean ESA-response coefficients of the least to most responsive quartiles were 0.301 +/- 0.033 (SD), 0.344 +/- 0.004, 0.357 +/- 0.004, and 0.389 +/- 0.026 g/dL greater hemoglobin level per 1,000 U/wk greater ESA dose in each quarter, respectively. The ORs of greatest versus poorest ESA responsiveness at the patient level were serum ferritin level less than 200 ng/mL (0.77; 95% confidence interval [CI], 0.70 to 0.86; reference, 200 to 500 ng/mL), iron saturation ratio less than 20% (0.54; 95% CI, 0.49 to 0.59; reference, 20% to 30%), intact parathyroid hormone level of 600 pg/mL or greater (0.54; 95% CI, 0.49 to 0.60; reference, 150 to 300 pg/mL), and alkaline phosphatase level of 160 IU/L or greater (0.64; 95% CI, 0.58 to 0.70; reference, 80 to 120 IU/L). Lower estimated dietary protein intake and serum levels of nutritional markers were also associated with greater risk of ESA hyporesponsiveness. LIMITATIONS: Our results may incorporate uncontrolled confounding. Achieved hemoglobin level may have different associations than targeted hemoglobin level. CONCLUSIONS: In long-term HD patients, low iron stores, hyperparathyroidism, and high-turnover bone disease are associated with significant ESA hyporesponsiveness. Prospective studies are needed to verify these associations.

Effects of Pregnancy, Outdoor Access, and Antifungal Medication on Hair Loss in Breeding-age Female Pigtailed Macaques (Macaca nemestrina).

Over 18 mo, adult female pigtailed macaques (Macaca nemestrina) housed at a breeding facility in Arizona were monitored every 6 mo for alopecia. The study period coincided with the movement of a majority of animals from primarily outdoor housing to continuous indoor housing and a corresponding decrease in available space. These changes were made due to the newly recognized prevalence of coccidioidomycosis at this site. The effects of pregnancy status, changes in outdoor access or space, and administration of fluconazole for the treatment of coccidioidomycosis on alopecia were explored. In this group of pigtailed macaques pregnancy did not appear to affect alopecia, in contrast to findings from a closely related species, rhesus macaques. Fluconazole administration increased alopecia in older animals but not in the youngest age group. Conversely, the effects of limited outdoor access or decreased space on increasing alopecia were greatest in the youngest group of animals.

An A2A adenosine receptor agonist, ATL313, reduces inflammation and improves survival in murine sepsis models.

BACKGROUND: The pathophysiology of sepsis is due in part to early systemic inflammation. Here we describe molecular and cellular responses, as well as survival, in A 2A adenosine receptor (AR) agonist treated and untreated animals during experimental sepsis. METHODS: Sepsis was induced in mice by intraperitoneal inoculation of live bacteria (Escherichia coli or Staphylococcus aureus) or lipopolysaccharide (LPS). Mice inoculated with live bacteria were treated with an A 2A AR agonist (ATL313) or phosphate buffered saline (PBS), with or without the addition of a dose of ceftriaxone. LPS inoculated mice were treated with ATL313 or PBS. Serum cytokines and chemokines were measured sequentially at 1, 2, 4, 8, and 24 hours after LPS was administered. In survival studies, mice were followed until death or for 7 days. RESULTS: There was a significant survival benefit in mice infected with live E. coli (100% vs. 20%, p = 0.013) or S. aureus (60% vs. 20%, p = 0.02) when treated with ATL313 in conjunction with an antibiotic versus antibiotic alone. ATL313 also improved survival from endotoxic shock when compared to PBS treatment (90% vs. 40%, p = 0.005). The serum concentrations of TNF-alpha, MIP-1 alpha, MCP-1, IFN-gamma, and IL-17 were decreased by ATL313 after LPS injection (p < 0.05). Additionally, ATL313 increased the concentration of IL-10 under the same conditions (p < 0.05). Circulating white blood cell concentrations were higher in ATL313 treated animals (p < 0.01). CONCLUSION: Further studies are warranted to determine the clinical utility of ATL313 as a novel treatment for sepsis.

A Case of Musical Hallucinations Related to Mirtazapine.

Musical hallucinations (MHs) are relatively uncommon phenomena sometimes encountered in older patients, especially older women. They usually involve popular, overlearned music, either entire songs or repetitive snippets. While MHs are most commonly associated with hearing loss, they may occur in a variety of psychiatric, neurologic, and iatrogenic conditions. We report a 91-year-old man whose MHs were causally related to the antidepressant mirtazapine. Although mirtazapine is generally well tolerated, it may rarely cause MHs or other psychotic symptoms.

Impact of kidney bone disease and its management on survival of patients on dialysis.

Despite the enormous cardiovascular disease epidemic and poor survival among individuals with chronic kidney disease (CKD), traditional risk factors such as hypercholesterolemia, hypertension, and obesity appear not as relevant as was previously thought, nor would their management improve survival in patients with CKD who are undergoing dialysis. On the contrary, kidney disease wasting (KDW) (also known as the malnutrition-inflammation complex), renal anemia, and kidney bone disease (KBD) appear to be the 3 most important nontraditional risk factors associated with cardiovascular disease in CKD. KBD-associated hyperparathyroidism may contribute to worsening refractory anemia and KDW/inflammation. The main cause of secondary hyperparathyroidism is active vitamin D deficiency. Hence, treatment of patients with KBD with vitamin D analogs, especially those with lesser effects on calcium and phosphorus such as paricalcitol, may be the most promising option for improving CKD outcomes. By conducting survival analyses in a 2-year (7/2001 to 6/2003) cohort of 58,058 patients on hemodialysis, we recently found that associations between high serum parathyroid hormone and increased death risk were masked by the demographic and clinical characteristics of patients, and that alkaline phosphatase had an incremental association with mortality. Administration of paricalcitol was associated with improved survival in time-varying models. We now present additional subgroup analyses that show that administration of any dose of paricalcitol, when compared with no paricalcitol, is associated with better likelihood of survival in virtually all subgroups of patients on hemodialysis. Because these associations may be secondary to bias by indication, randomized clinical trials are necessary to verify the findings of this and similar observational studies.

Effect of malnutrition-inflammation complex syndrome on EPO hyporesponsiveness in maintenance hemodialysis patients.

BACKGROUND: Elements of malnutrition-inflammation complex syndrome (MICS) may blunt the responsiveness of anemia of end-stage renal disease (ESRD) to recombinant human erythropoietin (EPO). METHODS: The authors examined cross-sectional associations between the required dose of EPO within a 13-week interval as prescribed by practicing nephrologists who were blind to the study and several laboratory values known to be related to nutrition and/or inflammation, as well as the malnutrition-inflammation score (MIS), which is a fully quantitative assessment tool based on the subjective global assessment of nutrition. RESULTS: A total of 339 maintenance hemodialysis (MHD) outpatients, including 181 men, who were aged 54.7 +/- 14.5 years (mean +/- SD), who had undergone dialysis for 36.3 +/- 33.2 months, were selected randomly from 7 DaVita dialysis units in Los Angeles South/East Bay area. The average weekly dose of administered recombinant human EPO within a 13-week interval was 217 +/- 187 U/kg. Patients were receiving intravenous iron supplementation (iron gluconate or dextran) averaging 39.5 +/- 47.5 mg/wk. The MIS and serum concentrations of high-sensitivity C-reactive protein, interleukin 6 (IL-6), tumor necrosis factor-alpha, and lactate dehydrogenase had positive correlation with required EPO dose and EPO responsiveness index (EPO divided by hemoglobin), whereas serum total iron binding capacity (TIBC), prealbumin and total cholesterol, as well as blood lymphocyte count had statistically significant but negative correlations with indices of refractory anemia. Most correlations remained significant even after multivariate adjustment for case-mix and anemia factors and other relevant covariates. Similar associations were noticed across EPO per body weight tertiles via analysis of variance and after estimating odds ratio for higher versus lower tertile via logistic regression after same case-mix adjustment. CONCLUSION: The existence of elements of MICS as indicated by a high MIS and increased levels of proinflammatory cytokines such as IL-6 as well as decreased nutritional values such as low serum concentrations of total cholesterol, prealbumin, and TIBC correlates with EPO hyporesponsiveness in MHD patients.

Relationship between dietary antioxidants and childhood asthma: more epidemiological studies are needed.

Approximately 15 million Americans including over 5 million children suffer from asthma, the most common chronic disease in childhood. The prevalence of pediatric asthma has risen sharply over the past four decades, with the sharpest increases occurring in children younger than 6 years and in urban, predominantly minority, populations. The reasons for this dramatic increase are not yet clear. Recent epidemiological studies indicate a higher prevalence of dietary antioxidant deficiency among asthmatics patients. However, the results of these studies are inconsistent or even contradictory. Epidemiological studies with robust design and use of novel epidemiological tools are urgently needed to examine the impact of dietary antioxidants on the incidence of asthma in preschool children. An incidence density case-control study which includes non-atopic controls, who are matched for age, gender, race, study center and sampling time to each asthmatic case will offer a robust study design. A validated food frequency questionnaire and an asthma and atopy severity score can be used to interview the parents of the recruited children. Risk set sampling may enable us to explore possible associations between the type and quantity of dietary antioxidants and the development and severity of asthma in such an epidemiological study.