Objective
To develop a Childhood Lupus Improvement Index (CHILI) as a tool to measure response to therapy in childhood‐onset systemic lupus erythematosus (cSLE), with a focus on clinically relevant ...improvement (CRIcSLE).
Methods
Pediatric nephrology and rheumatology subspecialists (n = 213) experienced in cSLE management were invited to define CRIcSLE and rate a total of 433 unique patient profiles for the presence/absence of CRIcSLE. Patient profiles included the following cSLE core response variables (CRVs): global assessment of patient well‐being (patient‐global), physician assessment of cSLE activity (MD‐global), disease activity index score (here, we used the Systemic Lupus Erythematosus Disease Activity Index), urine protein‐to‐creatinine ratio, and Child Health Questionnaire physical summary score. Percentage and absolute changes in these cSLE‐CRVs (baseline versus follow‐up) were considered in order to develop candidate algorithms and validate their performance (sensitivity, specificity, area under the receiver operating characteristic curve AUC; range 0–1).
Results
During an international consensus conference, unanimous agreement on a definition of CRIcSLE was achieved; cSLE experts (n = 13) concurred (100%) that the preferred CHILI algorithm considers absolute changes in the cSLE‐CRVs. After transformation to a range of 0–100, a CHILI score of ≥54 had outstanding accuracy for identifying CRIcSLE (AUC 0.93, sensitivity 81.1%, and specificity 84.2%). CHILI scores also reflect minor, moderate, and major improvement for values exceeding 15, 68, and 92, respectively (all AUC ≥0.92, sensitivity ≥93.1%, and specificity ≥73.4%).
Conclusion
The CHILI is a new, seemingly highly accurate index for measuring CRI in cSLE over time. This index is useful to categorize the degree of response to therapy in children and adolescents with cSLE.
Human chromosome 16 features one of the highest levels of segmentally duplicated sequence among the human autosomes. We report here the 78,884,754 base pairs of finished chromosome 16 sequence, ...representing over 99.9% of its euchromatin. Manual annotation revealed 880 protein-coding genes confirmed by 1,670 aligned transcripts, 19 transfer RNA genes, 341 pseudogenes and three RNA pseudogenes. These genes include metallothionein, cadherin and iroquois gene families, as well as the disease genes for polycystic kidney disease and acute myelomonocytic leukaemia. Several large-scale structural polymorphisms spanning hundreds of kilobase pairs were identified and result in gene content differences among humans. Whereas the segmental duplications of chromosome 16 are enriched in the relatively gene-poor pericentromere of the p arm, some are involved in recent gene duplication and conversion events that are likely to have had an impact on the evolution of primates and human disease susceptibility.
Abstract Background: In the past decade, health insurers have increased their reliance on cost control policies such as prior authorization and 3-tier formularies. Little is known about how these ...policies are being applied to psychotropic medications, many of which have low rates of patient adherence. Objective: This study reports on plans' cost-sharing tier placement and authorization policies for 12 brandonly psychotropic medications in 3 classes: antidepressants, antitipsychotics, and medications for attentiondeficit/hyperactivity disorder (ADFID). Methods: Data were from a nationally representativesurvey of private health plans regarding mental health and substance-abuse services in 2003; 368 plans responded (83% response rate). Results were weighted and represent national estimates of health-plan characteristics. Results: The majority of insurance products provided unrestricted placement on Tier 2 (medium copayment) for at least 2 brand-only antidepressants and at least 2 brand-only antipsychotics. This approach allows clinicians some limited leeway in initial medication selection. However, most patients who did not respond to the Tier-2 options typically faced a substantial escalation in copaynnent (Tier 3), possibly leading to premature medication discontinuation. For ADHI)5 the options were considerably more limited, with 22.1% of products applying some restriction to all 3 medications and only 15.9% of products leaving all 3 medications unrestricted. Plans with specialty contracts for mental health were considerably more likely to use Tier 3 (highest copayinerit) as their only restriction approach. Conclusions: Based on the results of this analysis,private plans were managing psychotropic costs using copayment incentives rather than administrative controls. This approach was less intrusive for clinicians, but resulting higher copayments could worsen already high rates of nonadherence; future research should examine this issue.
Shoulder arthroscopy is very commonly associated with postoperative leakage of irrigation fluid. This causes apprehension to patients and their relatives and leads to frequent change of dressings. We ...describe a simple and effective diaper dressing for patients undergoing arthroscopic shoulder surgery. It is highly absorbent, cost-effective, and easy to apply. We have used this dressing successfully in more than 1,500 shoulder arthroscopies over the last 3 years with no adverse reaction.
Considerable debate exists over the accuracy of self-reported media use measures. This report compares two methodologies for studying Internet and traditional media use: online surveys and diaries. A ...study was conducted with undergraduate students from two universities. Participants were asked to (a) complete a survey and (b) keep a diary over the course of one day. Both instruments assessed how frequently they engaged in various media use activities, including television viewing, radio listening, Web surfing, email sending and receiving, music listening, and video game playing. Results indicate that survey estimates of media use are consistently higher than diary use, but both methods are significantly correlated with each other, within a given medium. Given uncertainty about which method is more accurate, a third method of data collection, electronic tracking, is described.
Salmonids, a group of tetraploid fish including salmon and trout, produce the vertebrate neuropeptide melanin-concentrating hormone (MCH) in a group of hypothalamic magnocellular neurons in the ...nucleus lateralis tuberis (NLT). NLT neurons project both to the brain and to the neural lobe of the pituitary gland from where MCH is released into the circulation to play a central role in camouflage (+/- stress). We have cloned and sequenced the MCH1 and MCH2 genes from the rainbow trout, Oncorhynchus mykiss, and used the data firstly to examine the position of O. mykiss in salmonid phylogeny, and secondly to enable central nervous system MCH1 and MCH2 gene expression to be mapped. In the immature adult female trout brain, only MCH2 was detectable at the hybridization stringency used. In addition to the known location of MCH-positive neurons, immunocytochemistry and in situ hybridization histochemistry revealed a previously undescribed nucleus of MCH-positive neurons located more dorsal and posterior to those of the NLT, over the paraventricular organ of the lateral ventricular recess. Axons from this second group of MCH neurons project dorsally into the brain, while a few extend down toward the lateral ventricle near the paraventricular organ. They make little, if any, direct contact with the neurohypophysis, and thus may subserve a central function, unrelated to hormonal colour regulation.
OBJECTIVE Various GH secretory responses to long‐acting somatostatin (SRIH) analogues have been observed during the treatment of acromegalic patients. The effects of SRIH on intracellular Ca2+ ...homeostasis in human somatotroph adenoma cells has not been examined in detail, and the underlying mechanisms therefore remain to be determined. Using isolated cells from human somatotroph adenomas, we have investigated the SRIH‐induced intracellular Ca2+ responses at a single‐cell level with computerized real time intracellular calcium ion (Ca2+i) imaging.
PATIENTS Adenoma specimens were obtained from 4 male and 11 female acromegalic patients (mean age 56, range 26–72 years) undergoing transsphenoidal hypophysectomy.
METHODS The identity of the biopsy material obtained was confirmed by immunocytochemistry for hGH and in situ hybridization histochemistry using a 35S end‐labelled hGH oligodeoxynucleotide probe and probes complementary to proopiomelanocortin and prolactin. Genomic DNA coding for somatostatin receptor (SSTR2) from each adenoma was PCR amplified and sequenced. Cells cultured from these adenoma were subject to computerized real time intracellular Ca2+i imaging at a single cell level.
RESULTS In cells from 11 of the 15 adenomas, SRIH produced a reversible, dose‐independent reduction in Ca2+i from the mean of 167±11 to 43±3 nM within 51±1.8s, and blocked the growth hormone releasing hormone (GRH)‐induced increase in Ca2+i as expected. In the same adenomas, withdrawal of SRIH after a 30 second exposure produced a small but significant increase in resting Ca2+i. Pretreatment with pertussis toxin abolished the SRIH‐induced inhibition of Ca2+i and prevented the SRIH‐induced inhibition of the effect of GRH on Ca2+i. One of the remaining 4 adenomas was completely unresponsive to SRIH despite responding vigorously to other ligands and immunostaining strongly for GH. Surprisingly, cells from 3 adenomas showed a paradoxical increase in Ca2+i in response to SRIH in some or, in one case, all of the cells examined. In all adenomas the sequence of SSTR2 corresponded to wild‐type.
CONCLUSIONS In the majority of cells derived from human somatotrophic adenomas, SRIH caused a reduction in baseline Ca2+i and inhibition of GRH‐induced Ca2+i increase, as observed in somatotrophs of other species. In addition, SRIH was found either to induce a paradoxical increase in Ca2+i or to have no effect on Ca2+i in a small proportion of somatotroph adenomas examined. This finding corroborates the clinical observation that the response to SRIH analogues varies markedly between somatotroph adenoma patients. There was no evidence of SSTR2 mutations in any of the adenomas examined.
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