bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenges in the Diagnosis of the Antiphospholipid Syndrome
Authors: Devreese Katrien , Hoylaerts Marc F 
Published: April 2010

Abstract
Background: The antiphospholipid syndrome (APS) is an important cause of acquired thromboembolic complications and pregnancy morbidity. Its diagnosis is based on clinical and laboratory criteria, defined by strict guidelines. The original clinical and laboratory criteria for the identification of APS patients were published in 1999, in the so-called Sapporo criteria. In 2006 these criteria were revised, and recently more precise guidelines for analysis of the lupus anticoagulant have been provided. However, several questions related to the diagnosis of APS remain unanswered.
Content: In addition to providing a historical perspective, this review covers several challenges in the diagnosis of APS with respect to clinical and laboratory features, while highlighting pathogenic pathways of the syndrome. We discuss ongoing dilemmas in the diagnosis of this complex disease. Although antiphospholipid antibodies are found in association with various clinical manifestations, the older established clinical criteria were not substantively altered in the 2006 update. Several laboratory tests recommended in the latest criteria, including phospholipid-dependent coagulation tests for the detection of the lupus anticoagulant and ELISAs for measuring anticardiolipin and β2-glycoprotein I antibodies, still show methodological and diagnostic shortcomings. In addition, antiphospholipid antibodies have been described against other antigens, but their clinical role remains uncertain.
Conclusions: Despite updated APS criteria, diagnosis of this syndrome remains challenging. Further research on clinically relevant antibodies and standardization of their detection are needed to improve clinical risk assessment in APS.
GNRH analog therapy in girls with early puberty is associated with the achievement of predicted final height but also with increased risk of polycystic ovary syndrome
Authors: Chiavaroli Valentina , Liberati Marco , D'Antonio Francesco , Masuccio Fabio , Capanna Rita , Verrotti Alberto , Chiarelli Francesco , Mohn Angelika 
Published: April 2010

ObjectiveGNRH analog (GNRHa) therapy has not been supported by beneficial effects on adult stature in girls with early puberty. Furthermore, an increased prevalence of polycystic ovary syndrome (PCOS) has been described in girls treated for central precocious puberty. Women with PCOS are at increased risk of cardiometabolic dysfunctions and infertility. Our aim was to assess GNRHa effectiveness on reaching adult stature and the risk of PCOS in girls with early puberty.DesignLongitudinal study of GNRHa-treated and GNRHa-untreated girls at baseline and at final height.MethodsTwenty-five GNRHa-treated girls and 55 controls were compared. Insulin resistance (IR; homeostasis model assessment of IR (HOMA-IR) and glucose-to-insulin ratio (G/I)), the effect of GNRHa on final height, and the prevalence of PCOS were assessed.ResultsIn GNRHa-treated girls, no significant difference was found between predicted final height and final height, whereas a significant difference was detected in untreated girls (P=0.0001). At final height, GNRHa-treated girls showed higher HOMA-IR and lower G/I (P=0.03 for both) as well as higher DHEAS and androstenedione levels (P=0.02 andP=0.01 respectively) than untreated girls. The prevalence of PCOS and hyperandrogenemia was significantly higher in GNRHa-treated adolescents than in untreated adolescents (36 and 14.5% respectively,P=0.04; 56 and 23.6% respectively,P=0.01). Finally, gonadotropin-suppressive therapy was significantly related to PCOS during adolescence (P=0.03).ConclusionsIn girls with early puberty, GNRHa therapy is associated with the achievement of predicted final height; nevertheless, this treatment seems to act as an independent risk factor for the development of PCOS already during adolescence.
Neonatal Informatics—Dream of a Paperless NICU: Part Four: Integrating Caregiving, Automated Process Management, and Clinical Decision Support
Authors: Drummond Willa H. 
Published: April 2010

Bedside physicians, neonatal nurse practitioners (NNPs), clinical bedside nurses, respiratory therapists, and unit clerks in the neonatal intensive care unit (NICU) work as the team primarily responsible for integrating clinical data, updating diagnoses, judging infant stability, acting on treatment decisions, and placing orders in their individual areas of professional expertise. Current hospital computerization is fragmented, with poorly integrated, department-based computer systems communicating by local programming workarounds or by human-to-computer retyping. Existing clinical installations are unnecessarily time-consuming, create serious distractions, and disrupt real-time, “multisynchronicity” (N)ICU workflows. (1)(2)Critical results must be communicated to the proper caregiver in time to effect care changes. Situational communication delays occur because of the time of day (physician and nursing shift change), hospital information system (HIS) downtimes, patient admission surges in the larger hospital, and local unit emergencies (eg, stat delivery of preterm triplets).Automating and streamlining processes could help caregivers avoid problems that contribute to suboptimal patient care, such as relieving critical caregivers of time-consuming clerical work involving data gathering from multiple fragmented systems and aggregating all “electronically charted” information into cognitively meaningful clinical formats. Clinical decision support for complex clinical systems can help prevent system breakdowns that occur when nurses, doctors, and ancillary support staff are distracted by more acutely urgent situations. Time-pressured clinicians need systems that have been designed using human factors engineering principles, tested for usability, and monitored for ongoing system performance. (2)(3)(4)(5)(6)(7) Human factors-based failures occur when context-based reconciliation jobs are bypassed in laboratory and drug ordering loops by poorly designed and implemented computerized physician order entry, nurse charting, or other hospital systems, especially ones that slow caregivers’ workflow during emergencies. (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)Changes in complex systems reverberate, altering outcomes. Therefore, change responses must involve solutions that improve critical care computerization, patient care, and safety and lower costs of wasted resources (staff time, products, length of stay, and quality measures derived from administratively defined modeling methodologies). Effective systems change is important for overall integrity of the United States health-care system.
Simultaneous Detection of Circulating Autoreactive CD8+ T-Cells Specific for Different Islet Cell–Associated Epitopes Using Combinatorial MHC Multimers
Authors: Velthuis Jurjen H. , Unger Wendy W. , Abreu Joana R.F. , Duinkerken Gaby , Franken Kees , Peakman Mark , Bakker Arnold H. , Reker-Hadrup Sine , Keymeulen Bart , Drijfhout Jan Wouter , Schumacher Ton N. , Roep Bart O. 
Published: April 2010

OBJECTIVEType 1 diabetes results from selective T-cell–mediated destruction of the insulin-producing β-cells in the pancreas. In this process, islet epitope–specific CD8+ T-cells play a pivotal role. Thus, monitoring of multiple islet–specific CD8+ T-cells may prove to be valuable for measuring disease activity, progression, and intervention. Yet, conventional detection techniques (ELISPOT and HLA tetramers) require many cells and are relatively insensitive.RESEARCH DESIGN AND METHODSHere, we used a combinatorial quantum dot major histocompatibility complex multimer technique to simultaneously monitor the presence of HLA-A2 restricted insulin B10–18, prepro-insulin (PPI)15–24, islet antigen (IA)-2797–805, GAD65114–123, islet-specific glucose-6-phosphatase catalytic subunit–related protein (IGRP)265–273, and prepro islet amyloid polypeptide (ppIAPP)5–13–specific CD8+ T-cells in recent-onset diabetic patients, their siblings, healthy control subjects, and islet cell transplantation recipients.RESULTSUsing this kit, islet autoreactive CD8+ T-cells recognizing insulin B10–18, IA-2797–805, and IGRP265–273 were shown to be frequently detectable in recent-onset diabetic patients but rarely in healthy control subjects; PPI15–24 proved to be the most sensitive epitope. Applying the “Diab-Q-kit” to samples of islet cell transplantation recipients allowed detection of changes of autoreactive T-cell frequencies against multiple islet cell–derived epitopes that were associated with disease activity and correlated with clinical outcome.CONCLUSIONSA kit was developed that allows simultaneous detection of CD8+ T-cells reactive to multiple HLA-A2–restricted β-cell epitopes requiring limited amounts of blood, without a need for in vitro culture, that is applicable on stored blood samples.
PYY3–36 and Oxyntomodulin Can Be Additive in Their Effect on Food Intake in Overweight and Obese Humans
Authors: Field Benjamin C.T. , Wren Alison M. , Peters Veronique , Baynes Kevin C.R. , Martin Niamh M. , Patterson Michael , Alsaraf Sara , Amber Vian , Wynne Katie , Ghatei Mohammad A. , Bloom Stephen R. 
Published: April 2010

OBJECTIVE
Peptide YY3–36 (PYY3–36), a Y2 receptor agonist, and oxyntomodulin, a glucagon-like peptide 1 (GLP-1) receptor agonist, are cosecreted by intestinal L-cells after each meal. Separately each hormone acts as an endogenous satiety signal and reduces appetite in humans when infused intravenously. The aim of the current study was to investigate whether the anorectic effects of PYY3–36 and oxyntomodulin can be additive.

RESEARCH DESIGN AND METHODS
Twelve overweight or obese human volunteers underwent a randomized, double-blinded, placebo-controlled study. An ad libitum test meal was used to measure energy intake during intravenous infusions of either PYY3–36 or oxyntomodulin or combined PYY3–36/oxyntomodulin.

RESULTS
Energy intake during coadministration of PYY3–36 and oxyntomodulin was reduced by 42.7% in comparison with the saline control and was significantly lower than that during infusions of either hormone alone.

CONCLUSIONS
The anorectic effects of PYY3–36 and oxyntomodulin can be additive in overweight and obese humans. Coadministration of Y2 receptor agonists and GLP-1 receptor agonists may be a useful treatment strategy for obesity.
Racial Disparities in Health Status
Authors: O'Connell Joan , Yi Rong , Wilson Charlton , Manson Spero M. , Acton Kelly J. 
Published: April 2010

OBJECTIVE
American Indians and Alaska Natives are 2.3 times more likely to have diabetes than are individuals in the U.S. general population. The objective of this study was to compare morbidity among American Indian and U.S. adults with diabetes.

RESEARCH DESIGN AND METHODS
We extracted demographic and health service utilization data for an adult American Indian population aged 18–64 years (n = 30,121) served by the Phoenix Service Unit from the Indian Health Service clinical reporting system. Similar data for a U.S. population (n = 1,500,002) with commercial health insurance, matched by age and sex to the American Indian population, were drawn from the MartketScan Research Database. We used Diagnostic Cost Groups to identify medical conditions for which each individual was treated and to assign a risk score to quantify his or her morbidity burden. We compared the prevalence of comorbidities and morbidity burden of American Indian and U.S. adults with diabetes.

RESULTS
American Indians with diabetes had significantly higher rates of hypertension, cerebrovascular disease, renal failure, lower-extremity amputations, and liver disease than commercially insured U.S. adults with diabetes (P &lt; 0.05). The American Indian prevalence rates were 61.2, 6.9, 3.9, 1.8, and 7.1%, respectively. The morbidity burden among the American Indian with diabetes exceeded that of the insured U.S. adults with diabetes by 50%.

CONCLUSIONS
The morbidity burden associated with diabetes among American Indians seen at the Phoenix Service Unit far exceeded that of commercially insured U.S. adults. These findings point to the urgency of enhancing diabetes prevention and treatment services for American Indians/Alaska Natives to reduce diabetes-related disparities.
A Single Nucleotide Polymorphism in STK11 Influences Insulin Sensitivity and Metformin Efficacy in Hyperinsulinemic Girls With Androgen Excess
Authors: López-Bermejo Abel , Díaz Marta , Morán Erica , de Zegher Francis , Ibáñez Lourdes 
Published: April 2010

OBJECTIVE
Serine-threonine kinase STK11 catalyzes the AMP-activated protein kinase complex. We tested the hypothesis that a gene variant in STK11 contributes to variation in insulin sensitivity and metformin efficacy.

RESEARCH DESIGN AND METHODS
We studied the effects of a single nucleotide polymorphism (SNP) (rs8111699) in STK11 on endocrine-metabolic and body composition indexes before and after 1 year of metformin in 85 hyperinsulinemic girls with androgen excess, representing a continuum from prepuberal girls with a combined history of low birth weight and precocious pubarche over to postmenarchial girls with hyperinsulinemic ovarian hyperandrogenism. Metformin was dosed at 425 mg/day in younger girls and 850 mg/day in older girls. STK11 rs8111699 was genotyped. Endocrine-metabolic features were assessed in the fasting state; body composition was estimated by absorptiometry.

RESULTS
Genotype effects were similar in younger and older girls. At baseline, the mutated G allele in STK11 rs8111699 was associated with higher insulin and IGF-I levels (both P &lt; 0.005). The response to metformin differed by STK11 genotype: GG homozygotes (n = 24) had robust metabolic improvements, GC heterozygotes (n = 38) had intermediate responses, and CC homozygotes (n = 23) had almost no response. Such differences were found for 1-year changes in body composition, circulating insulin, IGF-I, free androgen index, and lipids (all P &lt; 0.005).

CONCLUSIONS
In hyperinsulinemic girls with androgen excess, the STK11 rs8111699 SNP influences insulin sensitivity and metformin efficacy, so that the girls with the least favorable endocrine-metabolic profile improve most with metformin therapy.
Glycemic Control, Coping, and Internalizing and Externalizing Symptoms in Adolescents With Type 1 Diabetes
Authors: Luyckx Koen , Seiffge-Krenke Inge , Hampson Sarah E. 
Published: April 2010

OBJECTIVE
This study examines how active coping and withdrawal, psychological (internalizing and externalizing) symptoms, and glycemic control (A1C values) influence each other across time in adolescents with type 1 diabetes.

RESEARCH DESIGN AND METHODS
One hundred and nine adolescents participated in a four-wave longitudinal study spanning four years (mean age at Time 1 was 13.77). Patients were visited at home and completed questionnaires measuring coping and psychological symptoms. The treating physicians were contacted to obtain A1C values. Cross-lagged path analysis from a structural equation modeling approach was used for data analysis.

RESULTS
Clinically meaningful pathways between coping and glycemic control were found across time. Active coping prospectively predicted lower A1C levels, which, in turn, predicted active coping. Higher A1C levels and higher psychological symptoms consistently predicted avoidance coping across time. Finally, psychological symptomatology constituted an important link in the observed longitudinal chain of effects. More specifically, higher A1C values and symptomatology at Time 1 positively predicted withdrawal at Time 2, which, in turn, positively predicted symptomatology at Time 3. Next, symptomatology at Time 3 positively predicted higher A1C values at Time 4, thus coming full circle.

CONCLUSIONS
Coping with everyday stress, psychological symptoms, and glycemic control were interrelated across time. Evidence was obtained for reciprocal pathways and mutually reinforcing mechanisms, indicating the need to monitor coping strategies and psychological symptoms along with glycemic control in optimizing clinical care in adolescents with type 1 diabetes.
Plasma Growth Differentiation Factor-15 Independently Predicts All-Cause and Cardiovascular Mortality As Well As Deterioration of Kidney Function in Type 1 Diabetic Patients With Nephropathy
Authors: Lajer Maria , Jorsal Anders , Tarnow Lise , Parving Hans-Henrik , Rossing Peter 
Published: April 2010

OBJECTIVE
Growth deferentiation factor-15 (GDF-15) is involved in inflammation and apoptosis. Expression is induced in the heart in response to ischemia and in atherosclerotic plaques. The aim of this study was to investigate GDF-15 levels in relation to all-cause mortality, cardiovascular mortality and morbidity, decline in glomerular filtration rate (GFR), and progression toward end-stage renal disease (ESRD).

RESEARCH DESIGN AND METHODS
The study was a prospective observational follow-up study including 451 type 1 diabetic patients with diabetic nephropathy (274 men, aged 42.1 ± 0.5 years [means ± SD], diabetes duration 28.3 ± 8.9 years, GFR 76 ± 33 ml/min/1.73 m2) and a control group of 440 patients with longstanding type 1 diabetes and persistent normoalbuminuria (232 men, aged 45.4 ± 11.5 years, duration of diabetes 27.7 ± 10.1 years). The patients were followed for 8.1 (0.0–12.9) years (median [range]).

RESULTS
Among normoalbuminuric patients, GDF-15 above the median predicted an adjusted (age, systolic blood pressure [sBP], and estimated GFR) increased risk of all-cause mortality (hazard ratio [HR] 3.6 [95% CI 1.3–10.3]; P = 0.014). Among patients with diabetic nephropathy, higher (fourth quartile) versus lower (first quartile) GDF-15 levels predict all-cause mortality (covariate-adjusted [sex, age, smoking, blood pressure, A1C, cholesterol, GFR, N-terminal prohormone B-type natriuretic peptide, antihypertensive treatment, and previous cardiovascular events]; HR 4.86 [95% CI 1.37–17.30]) as well as fatal and nonfatal cardiovascular events (adjusted HR 5.59 [1.23–25.43] and 3.55 [1.08–11.64], respectively). In addition, higher GDF-15 levels predict faster decline in GFR (P &lt; 0.001) but not development of ESRD.

CONCLUSIONS
Higher levels of GDF-15 are a predictor of all-cause and cardiovascular mortality and morbidity in patients with diabetic nephropathy. Furthermore, higher levels of GDF-15 are associated with faster deterioration of kidney function.
Further Improvement in Postprandial Glucose Control With Addition of Exenatide or Sitagliptin to Combination Therapy With Insulin Glargine and Metformin
Authors: Arnolds Sabine , Dellweg Sibylle , Clair Janina , Dain Marie-Paule , Nauck Michael A. , Rave Klaus , Kapitza Christoph 
Published: April 2010

OBJECTIVE
To assess the effect of a 4-week adjunctive therapy of exenatide (EXE) (5–10 μg b.i.d.) or sitagliptin (SITA) (100 mg once daily) in response to a standardized breakfast meal challenge in 48 men or women with type 2 diabetes receiving insulin glargine (GLAR) + metformin (MET).

RESEARCH DESIGN AND METHODS
This was a single-center, randomized, open-label, active comparator–controlled study with a three-arm parallel group design, consisting of: screening, 4- to 8-week run-in period, 4-week treatment period, and follow-up. In all three groups, the GLAR dose was titrated according to an algorithm (fasting blood glucose ≤100 mg/dl).

RESULTS
The unadjusted 6-h postprandial blood glucose excursion of both GLAR + MET + EXE and GLAR + MET + SITA was statistically significantly smaller than that of GLAR + MET (606 ± 104 vs. 612 ± 133 vs. 728 ± 132 mg/dl/h; P = 0.0036 and 0.0008). A1C significantly decreased in all three groups (P &lt; 0.0001), with the greatest reduction of −1.9 ± 0.7 under GLAR + MET + EXE (GLAR + MET + SITA −1.5 ± 0.7; GLAR + MET −1.2 ± 0.5%-points; GLAR + MET + EXE vs. GLAR + MET P = 0.0154). The American Diabetes Association A1C target of &lt;7.0% was reached by 80.0, 87.5, and 62.5% of subjects, respectively. GLAR + MET + EXE had the highest number (47) of adverse events, mostly gastrointestinal (56%) with one dropout. GLAR + MET or GLAR + MET + SITA only had 10 and 12 adverse events, respectively, and no dropouts. Hypoglycemia (blood glucose &lt;50 mg/dl) rates were low and comparable among groups. Weight decreased with GLAR + MET + EXE (−0.9 ± 1.7 kg; P = 0.0396) and increased slightly with GLAR + MET (0.4 ± 1.5 kg; NS; GLAR + MET + EXE vs. GLAR + MET P = 0.0377).

CONCLUSIONS
EXE or SITA added to GLAR + MET further substantially reduced postprandial blood glucose excursions. Longer-term studies in a larger population are warranted to confirm these findings.
Psychosocial Well-Being and Functional Outcomes in Youth With Type 1 Diabetes 12 years After Disease Onset
Authors: Northam Elisabeth A. , Lin Ashleigh , Finch Sue , Werther George A. , Cameron Fergus J. 
Published: April 2010

OBJECTIVE
Type 1 diabetes in youth and community controls were compared on functional outcomes. Relationships were examined between psychosocial variables at diagnosis and functional outcome 12 years later.

RESEARCH DESIGN AND METHODS
Participants were subjects with type 1 diabetes (n = 110, mean age 20.7 years, SD 4.3) and control subjects (n = 76, mean age 20.8 years, SD 4.0). The measures used included the Youth Self-Report and Young Adult Self-Report and a semi-structured interview of functional outcomes. Type 1 diabetes participants also provided information about current diabetes care and metabolic control from diagnosis.

RESULTS
Type 1 diabetes participants and control subjects reported similar levels of current well-being but for the youth with type 1 diabetes, the mental health referral rates over the previous 12 years were higher by 19% and school completion rates were lower by 17%. Over one-third of clinical participants were not currently receiving specialist care and this group had higher mental health service usage in the past (61 vs. 33%) and lower current psychosocial well- being. Within the type 1 diabetes group, behavior problems, high activity, and low family cohesion at diagnosis predicted lower current well-being, but were not associated with metabolic control history. Poorer metabolic control was associated with higher mental health service usage.

CONCLUSIONS
Type 1 diabetes participants report similar levels of current psychosocial well-being compared with control subjects, but higher levels of psychiatric morbidity since diagnosis and lower school completion rates. Psychiatric morbidity was associated with poor metabolic control and failure to transition to tertiary adult diabetes care.
No Effect of the 1α,25-Dihydroxyvitamin D3 on β-Cell Residual Function and Insulin Requirement in Adults With New-Onset Type 1 Diabetes
Authors: Walter Markus , Kaupper Thomas , Adler Kerstin , Foersch Johannes , Bonifacio Ezio , Ziegler Anette-G. 
Published: April 2010

OBJECTIVE
To determine whether daily intake of 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] is safe and improves β-cell function in patients with recently diagnosed type 1 diabetes.

RESEARCH DESIGN AND METHODS
Safety was assessed in an open study of 25 patients aged 18–39 years with recent-onset type 1 diabetes who received 0.25 μg 1,25(OH)2D3 daily for 9 months. An additional 40 patients were randomly assigned to 0.25 μg 1,25(OH)2D3 or placebo daily for 9 months and followed for a total of 18 months for safety, β-cell function, insulin requirement, and glycemic control.

RESULTS
Safety assessment showed values in the normal range in nearly all patients, regardless of whether they received 1,25(OH)2D3 or placebo. No differences in AUC C-peptide, peak C-peptide, and fasting C-peptide after a mixed-meal tolerance test between the treatment and placebo groups were observed at 9 and 18 months after study entry, with ∼40% loss for each parameter over the 18-month period. A1C and daily insulin requirement were similar between treatment and placebo groups throughout the study follow-up period.

CONCLUSIONS
Treatment with 1,25(OH)2D3 at a daily dose of 0.25 μg was safe but did not reduce loss of β-cell function.