Defining remission in childhood-onset lupus: PReS-endorsed consensus definitions by an international task force.

OBJECTIVE: To derive childhood-onset SLE (cSLE) specific remission definitions for future treat-to-target (T2T) trials, observational studies, and clinical practice. METHODS: The cSLE International T2T Task Force conducted Delphi surveys exploring paediatric perspectives on adult-onset SLE remission targets. A modified nominal group technique was used to discuss, refine, and agree on the cSLE remission target criteria. RESULTS: The Task Force proposed two definitions of remission: 'cSLE clinical remission on steroids (cCR)' and 'cSLE clinical remission off steroids (cCR-0)'. The common criteria are: (1) Clinical-SLEDAI-2 K = 0; (2) PGA score < 0.5 (0-3 scale); (4) stable antimalarials, immunosuppressive, and biologic therapy (changes due to side-effects, adherence, weight, or when building up to target dose allowed). Criterion (3) in cCR is the prednisolone dose ≤0.1 mg/kg/day (maximum 5 mg/day), whereas in cCR-0 it is zero. CONCLUSIONS: cSLE definitions of remission have been proposed, maintaining sufficient alignment with the adult-SLE definition to facilitate life-course research.

Mechanisms by which feeding synthetic zeolite A and dietary cation-anion difference diets affect mineral metabolism in multiparous Holstein cows: Part I.

The periparturient period is characterized by the increased demand for calcium (Ca) in dairy cows. This has resulted in the use of several different prepartal nutritional strategies to prevent hypocalcemia postpartum. The objective of our study was to determine the effects of feeding synthetic zeolite A (XZ), a diet with negative dietary cation-anion difference (-DCAD), or a positive-DCAD diet (CON) during the close-up period on peripartal mineral dynamics and hormones involved in calcium metabolism. To this end, 121 multiparous Holstein cows, blocked by lactation number and expected due date, were enrolled at 254 d of gestation and randomly assigned to 1 of 3 prepartum diets: CON (+190 mEq/kg; n = 40), -DCAD (-65 mEq/kg; n = 41), or a diet supplemented with sodium aluminum silicate (XZ; +278 mEq/kg, fed at 3.3% DM, targeting 500 g/d; n = 40; Protekta Inc.). Blood, urine, and saliva samples were collected from enrollment until parturition, with data analyzed and presented beginning 14 d before parturition (d -14) until parturition (d 0), and on d 1, 2, 3, 6, 9, 12, 15, 18, 21, 35, and 49 postpartum, to assess mineral and hormone dynamics. Total fecal collections were performed in a subset of 8 cows per treatment group to assess fecal mineral loss. Data were analyzed as a randomized complete block design in SAS. Cows fed XZ and -DCAD had higher blood Ca concentrations compared with CON-fed cows, with XZ-fed cows exhibiting the highest blood Ca concentrations pre- and postpartum. Cows fed XZ had decreased blood and salivary phosphorus (P), increased fecal water-extractable phosphate, and the highest blood calcium concentrations pre- and postpartum. Parathyroid hormone was unaffected by diet but was increased at parturition in all treatments. Serotonin concentrations were increased in -DCAD and XZ cows compared with CON during the prepartum period. Our data indicate that the XZ group's improvement in blood Ca concentrations pre- and postpartum is most likely regulated by a dietary P restriction. Taken together, these data suggest that XZ and -DCAD diets improve postpartum calcium metabolism; however, they appear to work through different mechanisms.

Mechanisms by which feeding synthetic zeolite A and dietary cation-anion difference diets affect feed intake, energy metabolism, and milk performance: Part II.

The objectives of this study were to assess the effects of feeding 2 different diets, a diet with low dietary cation-anion difference (DCAD) or a diet with synthetic zeolite A, to multiparous Holstein cows during the close-up period on dry matter intake (DMI) and energy metabolism, as well as to evaluate colostrum and milk production. A total of 121 multiparous Holstein cows, blocked by lactation number and expected parturition date were enrolled at 254 d of gestation and randomly assigned to 1 of 3 dietary treatments: control (CON; +190 mEq/kg; n = 40), negative DCAD (-DCAD, -65 mEq/kg; n = 41; Ultra Chlor; Vita Plus, Lake Mills, WI), or a diet containing sodium aluminum silicate zeolite (XZ; +278 mEq/kg, fed at 3.3% dry matter, targeting 500 g/d; n = 40; X-Zelit, Protekta Inc., Lucknow, ON, Canada/Vilofoss, Graasten, Denmark). Prepartum DMI was measured daily using Insentec roughage intake control (RIC) gates (RIC System, Holofarm Group, the Netherlands). All cows received the same postpartum diet. Blood and urine samples were collected daily beginning 14 d before parturition (d -14) until parturition (d 0), and on 1, 2, 3, 6, 9, 12, 15, 18, 21, 35, and 49 d postpartum. Colostrum collected within 6 h of parturition, weighed, and based on samples' Brix value, IgG concentrations, and nutrient composition were analyzed. Prepartum, cows fed the XZ diet had decreased DMI (11.70 ± 0.26, 13.88 ± 0.26, and 13.45 ± 0.25 kg/d for XZ, CON, and -DCAD, respectively) and lower rumination (487 ± 8.1, 531 ± 8.3, and 527 ± 8.5 min for XZ, CON, and -DCAD, respectively) compared with CON and -DCAD. However, rumination was not different postpartum due to treatment. No prepartum or postpartum differences were observed for glucose or BHB concentrations in blood between dietary treatments. Colostrum collected from cows fed XZ had the highest IgG concentrations (91.10 ± 2.63, 78.00 ± 2.63, and 78.90 ± 2.63 mg/mL for XZ, CON, and -DCAD, respectively), but yield did not differ between dietary treatments. Additionally, cows in their third lactation or greater fed XZ had the highest milk production (51.0 ± 1.1 kg) during the first 49 d in milk. This study demonstrates that despite a decrease in DMI and rumination in cows fed XZ prepartum, blood BHB concentrations were not altered. Additionally, cows fed XZ had higher colostral IgG concentrations and cows in their third lactation or greater fed XZ produced the most milk. These data suggest that feeding XZ prepartum may improve colostrum quality and milk yield in mature cows, and does not affect energy metabolism.

PReS-endorsed international childhood lupus T2T task force definition of childhood lupus low disease activity state (cLLDAS).

OBJECTIVE: To achieve a consensus-based definition of Low Disease Activity (LDA) for use in cSLE trials. METHODS: The International cSLE T2T Task Force, comprising of paediatric rheumatologists/nephrologists, and adult rheumatologists undertook a series of Delphi surveys/consensus meetings to discuss, refine, and vote upon cSLE LDA criteria. RESULTS: The Task Force agreed that LDA should be based upon the adult-SLE Lupus Low Disease Activity State definition (LLDAS), with modifications to make it applicable to cSLE (cLLDAS). They agreed upon five cLLDAS criteria: (1) SLE Disease Activity Index (SLEDAI)-2 K ≤4, with no activity in major organ systems; (2) no new features of lupus disease activity compared with the last assessment; (3) Physician Global Assessment score of ≤1 (0-3 scale); (4) prednisolone dose of ≤0.15 mg/kg/day, 7.5 mg/day/maximum; while on (5) stable antimalarials, immunosuppressives, and biologics. CONCLUSIONS: A cSLE-appropriate definition of cLLDAS has been generated, maintaining alignment with the adult-SLE definition to promote life-course research.

A Markov Multi-State model of lupus nephritis urine biomarker panel dynamics in children: Predicting changes in disease activity.

BACKGROUND: A urine 'biomarker panel' comprising alpha-1-acid-glycoprotein, ceruloplasmin, transferrin and lipocalin-like-prostaglandin-D synthase performs to an 'excellent' level for lupus nephritis identification in children cross-sectionally. The aim of this study was to assess if this biomarker panel predicts lupus nephritis flare/remission longitudinally. METHODS: The novel urinary biomarker panel was quantified by enzyme linked immunoabsorbant assay in participants of the United Kingdom Juvenile Systemic Lupus Erythematosus (UK JSLE) Cohort Study, the Einstein Lupus Cohort, and the South African Paediatric Lupus Cohort. Monocyte chemoattractant protein-1 and vascular cell adhesion molecule-1 were also quantified in view of evidence from other longitudinal studies. Serial urine samples were collected during routine care with detailed clinical and demographic data. A Markov Multi-State model of state transitions was fitted, with predictive clinical/biomarker factors assessed by a corrected Akaike Information Criterion (AICc) score (the better the model, the lower the AICc score). RESULTS: The study included 184 longitudinal observations from 80 patients. The homogeneous multi-state Markov model of lupus nephritis activity AICc score was 147.85. Alpha-1-acid-glycoprotein and ceruloplasmin were identified to be the best predictive factors, reducing the AICc score to 139.81 and 141.40 respectively. Ceruloplasmin was associated with the active-to-inactive transition (hazard ratio 0.60 (95% confidence interval [0.39, 0.93])), and alpha-1-acid-glycoprotein with the inactive-to-active transition (hazard ratio 1.49 (95% confidence interval [1.10, 2.02])). Inputting individual alpha-1-acid-glycoprotein/ceruloplasmin values provides 3, 6 and 12 months probabilities of state transition. CONCLUSIONS: Alpha-1-acid-glycoprotein was predictive of active lupus nephritis flare, whereas ceruloplasmin was predictive of remission. The Markov state-space model warrants testing in a prospective clinical trial of lupus nephritis biomarker led monitoring.

Growing international evidence for urinary biomarker panels identifying lupus nephritis in children - verification within the South African Paediatric Lupus Cohort.

BACKGROUND: A urinary biomarker panel including alpha-1-acid-glycoprotein (AGP), lipocalin-like-prostaglandin-D-synthase (LPGDS), transferrin and ceruloplasmin demonstrates an 'excellent' ability for identifying active lupus nephritis in UK/US children. This study aimed to assess whether this panel identifies active lupus nephritis within the South African Paediatric Lupus Cohort. METHODS: Juvenile-onset-systemic lupus erythematosus (JSLE) patients aged < 19 years at diagnosis and healthy controls were recruited. Patients were categorized as having active lupus nephritis (renal BILAG score; A/B and previous histological confirmation) or inactive lupus nephritis (renal BILAG score: D/E). Urinary biomarkers were quantified by ELISA. Mann-Whitney U-test compared biomarker levels between groups. Binary logistic regression and receiver operating curve analysis assessed biomarker combinations. RESULTS: Twenty-three juvenile-onset-systemic lupus erythematosus patients were recruited with a median age of 13.5 years (interquartile range (IQR) 12.7-14.9) and disease duration of 2.6 years (IQR 1.8-4.0). Eighteen healthy controls had a median age of 11.0 years (IQR 10.0-12.0). AGP, LPGDS, transferrin, ceruloplasmin and VCAM-1 were significantly higher in active than in inactive lupus nephritis patients (corrected p-values, all pc < 0.05), with no difference between inactive lupus nephritis patients and healthy controls (all pc = 1.0). The optimal biomarker combination included AGP, ceruloplasmin, LPGDS and transferrin (area under the curve = 1.0). CONCLUSIONS: A urinary biomarker panel comprising AGP, ceruloplasmin, LPGDS and transferrin previously validated within UK/US cohorts also performed excellently within a racially distinct South African cohort which displayed more severe lupus nephritis.

Severe disease presentation and poor outcomes among pediatric systemic lupus erythematosus patients in South Africa.

Background Systemic lupus erythematosus (SLE) is a life-threatening multisystem autoimmune disease that is more severe in patients of African ancestry and children, yet pediatric SLE on the African continent has been understudied. This study describes a cohort of pediatric SLE (PULSE) patients in South Africa. Methods Patients with a diagnosis of SLE (1997 American College of Rheumatology criteria) diagnosed prior to age 19 years in Cape Town, South Africa, were enrolled in this cross-sectional study from September 2013 to December 2014. Information on clinical and serological characteristics was extracted from medical records. Results were compared to a well-described North American pediatric SLE cohort. Results Seventy-two South African patients were enrolled in the study; mean age 11.5 years; 82% were girls. The racial distribution was 68% Coloured, 24% Black, 5% White and 3% Asian/Indian. Most patients presented with severe lupus nephritis documented by renal biopsy (61%). Of patients with lupus nephritis, 63% presented with International Society of Nephrology/Renal Pathology Society class III or IV. Patients in the PULSE cohort were more likely to be treated with cyclophosphamide, methotrexate and azathioprine. The PULSE cohort had high disease activity at diagnosis (mean Systemic Lupus Erythematosus Disease Activity Index-2K (SLEDAI-2K) 20.6). The SLEDAI-2K at enrolment in the PULSE cohort (5.0) did not differ from the North American pediatric SLE cohort (4.8). Sixty-three per cent of the PULSE cohort had end organ damage with Systemic Lupus International Collaborating Clinics Damage Index (SLICC-DI) score >0 (mean SLICC-DI 1.9), compared to 23% in a previously reported US cohort. Within the PULSE cohort, nine (13%) developed end-stage renal disease with six (8%) requiring transplant, strikingly higher than North American peers (transplant rate <1%). Conclusions The PULSE cohort had highly active multiorgan disease at diagnosis and significant disease damage at enrolment in the South African registry. South African patients have severe lupus nephritis and poor renal outcomes compared to North American peers. Our study revealed a severe disease phenotype in the PULSE cohort resulting in poor outcomes in this high-risk population.

CANDLE Syndrome: orodfacial manifestations and dental implications.

A South African girl with CANDLE Syndrome is reported with emphasis on the orodental features and dental management. Clinical manifestations included short stature, wasting of the soft tissue of the arms and legs, erythematous skin eruptions and a prominent abdomen due to hepatosplenomegaly. Generalized microdontia, confirmed by tooth measurement and osteopenia of her jaws, confirmed by digitalized radiography, were previously undescribed syndromic components. Intellectual impairment posed problems during dental intervention. The carious dental lesions and poor oral hygiene were treated conservatively under local anaesthetic. Prophylactic antibiotics were administered an hour before all procedures.Due to the nature of her general condition, invasive dental procedures were minimal. Regular follow-ups were scheduled at six monthly intervals. During this period, her overall oral health status had improved markedly.The CANDLE syndrome is a rare condition with grave complications including immunosuppression and diabetes mellitus. As with many genetic disorders, the dental manifestations are often overshadowed by other more conspicuous and complex syndromic features. Recognition of both the clinical and oral changes that occur in the CANDLE syndrome facilitates accurate diagnosis and appropriate dental management of this potentially lethal condition.

A clinical update on paediatric lupus.

Systemic lupus erythematosus in children is a life-threatening chronic disease that is being increasingly recognised. More black African children are being diagnosed and the proportion of males affected is much higher than in adult-onset lupus. The presenting manifestations of childhood-onset lupus are variable and many systems are involved. Children with lupus often present late with severe disease, and in South African (SA) children severe lupus nephritis occurs commonly at presentation. The investigations for lupus should be performed in a three-step process ­ initial essential investigations, antibody and serological tests, and supplementary investigations. The most important factor in the management is to involve a multidisciplinary team as soon as possible. All cases of lupus in SA should be discussed with a paediatric specialist so that a tailored management plan can be made, depending on the presenting features and course of the disease.

Hydrogen peroxide and superoxide anion production by polymorphonuclear neutrophils in patients with chronic periapical granuloma, before and after surgical treatment.

Chronic periapical granuloma represents a localized tissue injury with well established signs of systemic immunological reactions. The aim of the study was to investigate changes in superoxide anion and hydrogen peroxide production by polymorphonuclear neutrophils (PMN) in patients with chronic periapical granuloma before and after surgical treatment. The affected teeth were extracted from 20 patients with chronic periapical lesions. Blood samples were obtained at admission, before extraction and on day 14. PMNs were isolated from blood samples and superoxide anion (O2-) and hydrogen peroxide (H2O2) production were estimated without stimulation and after stimulation of the cells with opsonized zymosan. Similar procedures were performed with blood samples obtained from 20 healthy controls. Superoxide anions as well as hydrogen peroxide production by unstimulated cells obtained from patients before treatment were significantly higher in comparison with controls. Fourteen days after extraction O2- production by unstimulated cells was higher than the controls and significantly lower in comparison to PMNs obtained before treatment, while H2O2 production was not significantly higher when compared to controls and significantly lower in comparison with PMNs obtained before extraction. The results obtained strongly imply the termination of a generalized inflammatory response after elimination of local inflammation by tooth extraction.

Cell cycle and apoptosis in tumours of oral cavity estimated by image cytometry.

The aim of investigations was to examine whether diploid and aneuploid tumours of oral cavity differ in frequencies of occurrence of individual phases of cell cycle and of apoptosis. Investigations were carried out on 53 tumours using techniques of image cytometry. The studies were performed on properly isolated cells of tumours, which were stained using Feulgen method and analysed by image cytometry. Using a suitable computer programme, the percentages of cells present in individual phases of cell cycle and in apoptosis were estimated. No respective differences could be disclosed between diploid and aneuploid tumours. In addition, the ratios of the fraction of cells in S phase of the cell cycle and those in apoptosis were calculated and were found to carry certain prognostic significance in patients with squamous cell carcinomas of oral cavity.

Sleep alterations in cancer patients.

This multi-institutional sleep study involved two phases aimed at investigating sleep alterations in patients with any stage of breast and lung cancer. The first phase of this study used an 82-item, 20-minute telephone survey to elicit information regarding the impact of sleep disturbances on a convenience sample of 150 patients. Of these patients, 44% reported a sleep problem during the month before the interview. Significant relations included these: report of sleep problems prediagnosis over the past month (x = 5.82; p = 0.02), duration of sleep medication use and frequency of sleep problem (r = 0.58; p = 0.05), age and severity of sleep problems (r = 0.38; p = 0.05), and frequency and severity of the sleep problem over the past month (r = 0.21; p < 0.10). Communication with health care providers occurred in 16.6% of patients reporting a sleep disturbance. The second phase of this study explored the type, frequency, and severity of sleep problems and perceptions of causation, support, and methods of coping with the sleep problem. A qualitative approach to the problem was used in this phase. A one-time telephone interview of 42 patients, derived from a convenience sample, revealed a 45% prevalence of sleep problems a month before the interview. A qualitative analysis of the responses suggested that sleep problems are related to experiences of other symptoms and perceptions of cancer and treatment. Content analysis of the responses identified the following categories: figuring out the reason, seeking help, seeking support and relation to the overall cancer experience.

Relationships among assisted suicide and religiousness, resources available, denial of dying, and autonomy.

A nonrandom sample of eligible voters in Michigan (N = 218; mean age 35.7 yr.) anonymously completed a questionnaire during the two weeks prior to voting on a ballot proposal endorsing physician-assisted suicide. Favoring assisted suicide correlated negatively with scores on religiousness, believing that only a troubled mind would favor assisted suicide and that vulnerable individuals would suffer were assisted suicide legal, with denial of dying, and with resources available during one's final years. Favoring assisted suicide correlated positively with indicating this to be a medical rather than moral issue, making one's own decisions on moral issues, and believing that people may have different opinions on assisted suicide. The role of experience with dying needs further study.

The LD label for relatively well-functioning students: a critical analysis.

The number of students identified since the mid-1970s as having learning disabilities has produced a corresponding increase in the population of such individuals in postsecondary programs. The Americans with Disabilities Act, along with Section 504 of the Vocational Rehabilitation Act of 1973, provide the basis for civil rights for students in higher education. These laws protect individuals who have a substantial limitation in a major life activity when compared with the general population. A disparity between the legal definition and the clinical definition of learning disabilities, which can encompass those identified on the basis of academic underachievement relative to intellectual potential, has stimulated debate about the fairest, most appropriate standard for declaring a student functionally impaired. Extending services to individuals without significant academic impairment may tax or even deplete scarce resources for others in greater needs, distort the normal processes by which individuals select careers, and diminish the credibility of the diagnosis itself.

International adoption: a primer for pediatric nurses.

Immigrant visas issued to orphans entering the United States (a proxy measure for international adoptions) totaled 13,620 in 1997, more than double the amount in 1992. As international adoption numbers rise, pediatric nurses encounter more adopted children and adoptive families. Among the many adoption-related issues confronting pediatric health care providers, the one most frequently voiced is: "Should we do or look for anything differently in adopted children? And, if so, what?" To address this issue, a three-fold approach is suggested: (a) recognize the physical conditions and medical problems prevalent in the international countries with high adoption rates; (b) identify the unique adoption-related tasks encountered by children according to their current developmental stage; and (c) determine recommendations for providers, parents, and children to successfully address or cope with these adoption-related tasks and conditions.

Meta-analysis of cognitive-behavioral treatment studies for bulimia.

A meta-analysis was performed to systematically assess the effect of cognitive-behavioral treatments for bulimia. To protect against past criticisms of meta-analyses, this study focused on well-defined hypotheses with clearly articulated conceptual foundations. Twenty-six studies of the cognitive-behavioral treatment of bulimia were selected through computer searches. Effect sizes were calculated for changes in behavioral outcome measures (25 independent hypothesis tests) and cognitive-attitudinal outcome measures (17 independent hypothesis tests). Additionally, two effect sizes were generated for within and between group comparisons. The analysis revealed an effect size of average r = 0.69 for behavioral outcome measures (average r = 0.64 for between group and average r = 0.74 for within group) and average r = 0.67 for cognitive-attitudinal outcome measures (average r = 0.64 for between group and average r = 0.69 for within group). Follow-up effect sizes were less favorable; however, the diversity of time spans and outcome measures used to calculate follow-up effect sizes limit their utility. Overall, results suggest that the use of a cognitive-behavioral therapy will result in favorable treatment outcomes and implications for future research are discussed.

Mental and physical health effects of intimate partner violence on women and children.

The battering of female partners and the concomitant emotional abuse that is almost always part of the coercive control have significant mental and physical health consequences for the women who experience this type of violence. Children who live in households fraught with the conflict, violence, and unpredictable danger of domestic violence often witness the battering of their mothers and may also be victims of child abuse themselves. This article highlights current knowledge regarding the mental and physical health effects of intimate partner violence on women and their children, and discusses needed directions for screening, intervention, research, and changes in the health care system.

PIP: This article reviews the literature on the effects of domestic violence on women and children. The introduction notes that domestic violence affects millions of women in the US each year, significantly increasing their health problems and their use of the health care system. The next sections review the incidence of mortality related to such abuse and women's physical health sequelae from battering. Consideration of women's mental health consequences focuses on the traumatic response framework that has been developed to conceptualize the psychological effects of domestic violence. The article then considers studies of abuse during pregnancy. Next, the article turns to the children of battered women, noting how they often fit the description of traumatized children but that there have been no studies to date of the existence among them of post-traumatic stress disorder. After looking at studies that marked children's responses to traumatic events and the effects of domestic violence on the children, the review examines work that revealed developmental differences in children from violent homes. The article then points to several limitations in prior research in the area of domestic violence and highlights the lack of experimental evaluation of treatments or interventions. Next, research into possible opportunities for routine screening and intervention is considered. The article concludes by documenting the need for a change in the health care system so that it can respond appropriately to the needs of battered women.

Neurodevelopmental precursors to learning disabilities: a preliminary report from a parent survey.

This study documented the number and type of neurodevelopmental problems reported by parents of children with and without learning disabilities (LD), and examined whether a pattern of problems could be identified. One hundred parents, 50 for each group, responded to a retrospective developmental survey. Their children were between 9 and 13 years of age and had a history of either typical academic achievement or classification of a learning disability. Results indicated that the children with learning disabilities were reported to have significantly more neurodevelopmental problems or delays across domains (e.g., language, motor, attention, social behavior) than normal achievers. The study showed that a sizeable portion, although not all, of the children with LD had a history of neurodevelopmental problems. Despite findings that suggest that some difficulties more commonly co-occurred than others, a pattern of neurodevelopmental difficulties was not observed in these children. However, some specific difficulties, such as with following multistep directions, printing letters of the alphabet, and understanding directions (e.g., up, down, right, left), seemed to most typify the students with learning disabilities.

A parent has cancer: needs and responses of children.

Children who have a parent with cancer experience many changes, threats, and challenges that may engender many different thoughts, feelings, and responses. Sometimes the needs and reactions of these children may go unrecognized by their overstressed family members and they may feel alone and unsupported. Pediatric nurses in primary care settings are often in key positions to identify and assist well children in dealing with the stresses of having a seriously ill parent and to assist the parents in helping their children. Primary and secondary prevention and intervention strategies may be used by the nurse in working with families prior to and during major life events such as a parent's diagnosis of and treatment for cancer.