Pigeon Circovirus over Three Decades of Research: Bibliometrics, Scoping Review, and Perspectives.

The pigeon circovirus (PiCV), first described in the literature in the early 1990s, is considered one of the most important infectious agents affecting pigeon health. Thirty years after its discovery, the current review has employed bibliometric strategies to map the entire accessible PiCV-related research corpus with the aim of understanding its present research landscape, particularly in consideration of its historical context. Subsequently, developments, current knowledge, and important updates were provided. Additionally, this review also provides a textual analysis examining the relationship between PiCV and the young pigeon disease syndrome (YPDS), as described and propagated in the literature. Our examination revealed that usages of the term 'YPDS' in the literature are characterizations that are diverse in range, and neither standard nor equivalent. Guided by our understanding of the PiCV research corpus, a conceptualization of PiCV diseases was also presented in this review. Proposed definitions and diagnostic criteria for PiCV subclinical infection (PiCV-SI) and PiCV systemic disease (PiCV-SD) were also provided. Lastly, knowledge gaps and open research questions relevant to future PiCV-related studies were identified and discussed.

Myosteatosis evaluation using erector spinae and psoas muscles to predict adverse events during adjuvant chemotherapy for breast cancer.

BACKGROUND: Myosteatosis (intramuscular adiposity) is predictive of chemotherapy toxicity in women undergoing adjuvant chemotherapy for breast cancer (BC). We evaluated a novel, user-friendly and cost-effective technique utilizing a Picture Archiving and Communication Systems (PACS) tool that is readily available in the electronic medical record (EMR), using skeletal muscle density (SMD) to detect myosteatosis and then compared PACS results with those derived from widely used body composition software (SliceOMatic, QC, Canada). METHODS: Using retrospective data from a sample of women with early BC (Stage I-III) who had CT scan and received chemotherapy. Pearson correlation coefficients were used to compare SliceOMatic with PACS results. Associations of PACS results with chemotherapy-related adverse events were evaluated using multivariable (MV) log-binomial models adjusted for age, race, BMI, anthracycline-based therapy, and number of comorbidities. RESULTS: In 338 patients, mean age was 51, 32% were non-white, and 40% had obesity (BMI ≥ 30 kg/m2). Correlation of SMD using SliceOMatic whole muscle measurements with PACS psoas muscle was 0.76 (p < .0001) and with PACS erector spinae muscle 0.91 (p < .0001). Using PACS psoas muscle, myosteatosis was associated with any adverse event [RR 1.66, CI 1.22-2.26 (p < .0001)], dose reduction [RR 1.63, CI 1.01-2.65 (p = .05)], and early treatment discontinuation [RR 2.14, CI 1.10-4.14 (p = 0.03)]. Using PACS erector spinae muscle, myosteatosis was associated any adverse event [RR 1.59, CI 1.11-2.27 (p = 0.01)] and dose reduction [RR 1.91, CI 1.07-3.42 (p = .03)]. CONCLUSION AND RELEVANCE: Skeletal muscle density measures using PACS correlated strongly with SliceOMatic results and both are similarly predictive of chemotherapy-related adverse events.

A 2-stage distal femur reconstruction with expandable endoprosthesis in a pediatric patient presenting with a pathologic fracture through an osteosarcoma

@#<p style="text-align: justify;">Osteosarcoma in pediatric patients has traditionally been treated with amputation, especially if there is a pathologic fracture through the tumor.</p><p style="text-align: justify;">We report the case of a 12-year-old boy who sustained a pathologic fracture through distal femoral osteosarcoma. After neoadjuvant chemotherapy, he underwent limb saving surgery: wide excision of the osteosarcoma followed by a second-stage reconstruction with an expandable tumor endoprosthesis. He has a functional score of 93% and is free of disease 8 years since diagnosis and 2 years since the end of lengthening.</p><p style="text-align: justify;">This is the first reported case in Philippine medical literature of limb saving surgery in osteosarcoma reconstructed with an expandable endoprosthesis.</p>

Disrupting LXRα phosphorylation promotes FoxM1 expression and modulates atherosclerosis by inducing macrophage proliferation.

Macrophages are key immune cells for the initiation and development of atherosclerotic lesions. However, the macrophage regulatory nodes that determine how lesions progress in response to dietary challenges are not fully understood. Liver X receptors (LXRs) are sterol-regulated transcription factors that play a central role in atherosclerosis by integrating cholesterol homeostasis and immunity. LXR pharmacological activation elicits a robust antiatherosclerotic transcriptional program in macrophages that can be affected by LXRα S196 phosphorylation in vitro. To investigate the impact of these transcriptional changes in atherosclerosis development, we have generated mice carrying a Ser-to-Ala mutation in myeloid cells in the LDL receptor (LDLR)-deficient atherosclerotic background (M-S196ALdlr-KO). M-S196ALdlr-KO mice fed a high-fat diet exhibit increased atherosclerotic plaque burden and lesions with smaller necrotic cores and thinner fibrous caps. These diet-induced phenotypic changes are consistent with a reprogramed macrophage transcriptome promoted by LXRα-S196A during atherosclerosis development. Remarkably, expression of several proliferation-promoting factors, including the protooncogene FoxM1 and its targets, is induced by LXRα-S196A. This is consistent with increased proliferation of plaque-resident cells in M-S196ALdlr-KO mice. Moreover, disrupted LXRα phosphorylation increases expression of phagocytic molecules, resulting in increased apoptotic cell removal by macrophages, explaining the reduced necrotic cores. Finally, the macrophage transcriptome promoted by LXRα-S196A under dietary perturbation is markedly distinct from that revealed by LXR ligand activation, highlighting the singularity of this posttranslational modification. Overall, our findings demonstrate that LXRα phosphorylation at S196 is an important determinant of atherosclerotic plaque development through selective changes in gene transcription that affect multiple pathways.

The histone demethylase KDM4B regulates peritoneal seeding of ovarian cancer.

Epithelial ovarian cancer (EOC) has poor prognosis and rapid recurrence because of widespread dissemination of peritoneal metastases at diagnosis. Multiple pathways contribute to the aggressiveness of ovarian cancer, including hypoxic signaling mechanisms. In this study, we have determined that the hypoxia-inducible histone demethylase KDM4B is expressed in ∼60% of EOC tumors assayed, including primary and matched metastatic tumors. Expression of KDM4B in tumors is positively correlated with expression of the tumor hypoxia marker CA-IX, and is robustly induced in EOC cell lines exposed to hypoxia. KDM4B regulates expression of metastatic genes and pathways, and loss of KDM4B increases H3K9 trimethylation at the promoters of target genes like LOXL2, LCN2 and PDGFB. Suppressing KDM4B inhibits ovarian cancer cell invasion, migration and spheroid formation in vitro. KDM4B also regulates seeding and growth of peritoneal tumors in vivo, where its expression corresponds to hypoxic regions. This is the first demonstration that a Jumonji-domain histone demethylase regulates cellular processes required for peritoneal dissemination of cancer cells, one of the predominant factors affecting prognosis of EOC. The pathways regulated by KDM4B may present novel opportunities to develop combinatorial therapies to improve existing therapies for EOC patients.

Clinical pathways for the management of dyspepsia in family and community practice

@#<p style="text-align: justify;"><strong>BACKGROUND:</strong> Dyspepsia is any chronic or recurrent discomfort in the epigastric area described as bloatedness, fullness, gnawing or burning continuously or intermittently for at least 2 weeks. About 40% of the adult population may suffer from dyspeptic symptoms but most of them are un-investigated because only about 2% consult their physician.<br /><strong>OBJECTIVE:</strong> The general objective of this clinical pathway is to improve outcomes of patients with dyspepsia in family and community practice<br /><strong>METHOD:</strong> The PAFP Clinical Pathways Group reviewed the previous Clinical Practice Guideline for the Treatment of Dyspepsia in Family Practice, a local guideline developed by the Family Medicine Research Group and adopted as policy statement by the Philippine Health Insurance Corporation. The reviewers then developed a time-related representation of recommendations on patient care processes, in terms of history and physical examination, laboratory tests, pharmacologic and non-pharmacologic interventions as well as social and community strategies to treat hypertension and prevent complications.<br /><strong>RECOMMENDATION:</strong> All patients with gastrointestinal pain or discomfort should have a detailed history focusing on weight loss, hematemesis, hemetochezia, melena, dysphagia, odynophagia, vomiting, NSAID intake, alcohol intake, smoking, frequent medical complaints, depression, anxiety, personal or family history of gastrointestinal disease using family genogram. Physical examination findings provide minimal information but should be done to rule out an organic pathology and to look for alarm clinical features like anemia, abdominal tenderness or mass, jaundice, melena etc. If the patient is with history of previous dyspepsia treatment, more than 45 years old or long-term use of NSAID, the physician may request for non-invasive H. pylori test. Upper abdominal ultrasound, liver function test, pancreatic amylase may be done if organic problem is considered. Start therapeutic trial of prokinetic treatment for 1-2 weeks or proton-pump inhibitor depending on the symptoms. Fixed drug combination may be used if symptoms are undifferentiated. The patient should be educated about upper gastrointestinal disorders and dyspepsia, risk factors and complications. If medications were prescribed, explain the dose, frequency, intended effect, possible side effects and importance of medication adherence. Lifestyle modifications focusing on low fat meals, weight reduction, avoidance of alcohol intake and smoking cessation, eating way before bedtime, elevated head while sleeping, etc. may also be done. Recommendations were also made on subsequent visits.<br /><strong>IMPLEMENTATION:</strong> Quality improvement strategy is recommended for implementation of this pathway. This will involve pre- and post-intervention data collection using records review. Intervention strategies may be feedback, group consensus or incentive mechanisms.</p>

Clinical pathways for the management of dyspepsia in family and community practice

BACKGROUND: Dyspepsia is any chronic or recurrent discomfort in the epigastric area described as bloatedness, fullness, gnawing or burning continuously or intermittently for at least 2 weeks. About 40% of the adult population may suffer from dyspeptic symptoms but most of them are un-investigated because only about 2% consult their physician.OBJECTIVE: The general objective of this clinical pathway is to improve outcomes of patients with dyspepsia in family and community practiceMETHOD: The PAFP Clinical Pathways Group reviewed the previous Clinical Practice Guideline for the Treatment of Dyspepsia in Family Practice, a local guideline developed by the Family Medicine Research Group and adopted as policy statement by the Philippine Health Insurance Corporation. The reviewers then developed a time-related representation of recommendations on patient care processes, in terms of history and physical examination, laboratory tests, pharmacologic and non-pharmacologic interventions as well as social and community strategies to treat hypertension and prevent complications.RECOMMENDATION: All patients with gastrointestinal pain or discomfort should have a detailed history focusing on weight loss, hematemesis, hemetochezia, melena, dysphagia, odynophagia, vomiting, NSAID intake, alcohol intake, smoking, frequent medical complaints, depression, anxiety, personal or family history of gastrointestinal disease using family genogram. Physical examination findings provide minimal information but should be done to rule out an organic pathology and to look for alarm clinical features like anemia, abdominal tenderness or mass, jaundice, melena etc. If the patient is with history of previous dyspepsia treatment, more than 45 years old or long-term use of NSAID, the physician may request for non-invasive H. pylori test. Upper abdominal ultrasound, liver function test, pancreatic amylase may be done if organic problem is considered. Start therapeutic trial of prokinetic treatment for 1-2 weeks or proton-pump inhibitor depending on the symptoms. Fixed drug combination may be used if symptoms are undifferentiated. The patient should be educated about upper gastrointestinal disorders and dyspepsia, risk factors and complications. If medications were prescribed, explain the dose, frequency, intended effect, possible side effects and importance of medication adherence. Lifestyle modifications focusing on low fat meals, weight reduction, avoidance of alcohol intake and smoking cessation, eating way before bedtime, elevated head while sleeping, etc. may also be done. Recommendations were also made on subsequent visits.IMPLEMENTATION: Quality improvement strategy is recommended for implementation of this pathway. This will involve pre- and post-intervention data collection using records review. Intervention strategies may be feedback, group consensus or incentive mechanisms.

ErbB3 upregulation by the HNSCC 3D microenvironment modulates cell survival and growth.

Head and neck squamous carcinomas (HNSCC) present as dense epithelioid three-dimensional (3D) tumor nests that can mediate signals via the human epidermal growth factor receptor (ErbB) tyrosine kinase family to promote intratumoral survival and growth. We examined the role of the tumor microenvironment on ErbB receptor family expression and found that the status of intercellular organization altered the receptor profile. We showed that HNSCC cells forced into tumor island-like 3D aggregates strongly upregulated ErbB3 at the level of transcription. Not only was the elevated ErbB3 responsive to HRG-ß1-induced enhanced signaling mechanism, but also analysis by siRNA-knockdown and kinase inhibitor strategies revealed that the ErbB3/AKT signaling pathway was sufficient to enhance tumor cell survival and growth potential. Elevated ErbB3 expression in the high-density 3D culture system was strongly associated with hypoxia-induced HIF-1α. Hypoxia-regulated ErbB3 expression was mediated by the HIF-1α-binding consensus sequence in the ErbB3 proximal promoter. The findings show that the local 3D tumor microenvironment can trigger reprograming and switching of ErbB family members and thereby influence ErbB3-driven tumor growth.

Modeling the aneuploidy control of cancer.

BACKGROUND: Aneuploidy has long been recognized to be associated with cancer. A growing body of evidence suggests that tumorigenesis, the formation of new tumors, can be attributed to some extent to errors occurring at the mitotic checkpoint, a major cell cycle control mechanism that acts to prevent chromosome missegregation. However, so far no statistical model has been available quantify the role aneuploidy plays in determining cancer. METHODS: We develop a statistical model for testing the association between aneuploidy loci and cancer risk in a genome-wide association study. The model incorporates quantitative genetic principles into a mixture-model framework in which various genetic effects, including additive, dominant, imprinting, and their interactions, are estimated by implementing the EM algorithm. RESULTS: Under the new model, a series of hypotheses tests are formulated to explain the pattern of the genetic control of cancer through aneuploid loci. Simulation studies were performed to investigate the statistical behavior of the model. CONCLUSIONS: The model will provide a tool for estimating the effects of genetic loci on aneuploidy abnormality in genome-wide studies of cancer cells.

Effectiveness of blood pressure monitoring card on pharmacoadherence and hypertension control: A randomized controlled trial

Background: Blood pressure (BP) monitoring was identified to have a direct relationship with adherence and BP control. Measurement of blood pressure (BP) at home or out-of-clinic can accomplish several of the advantages of ambulatory BP monitoring. Furthermore, regular measurement of BP may increase awareness of the condition and may lead to behavioral changes needed in the management of hyepertension such as DASH diet, smoking cessation, limited alcohol intake and regular exercise. It may also increase compliance with antihypertensive therapy and reduce the number of visits required for the diagnosis and treatment of hypertension. Objective: To determine the effect of provision of BP monitoring card on improving patient's adherence to medication and control of BP among hypertensive patients of PGH-Family Medicine Clinic. Design, Setting, and Participants: An open, randomized controlled trial based on a Chronic Care Model. The trial was conducted at the Philippine General Hospital-Family Medicine Clinic enrolling 102 participants aged 30-70 years with uncontrolled essential hypertension based on JNC VII classification. Participants were recruited from December 2008 to March 2009 and were followed up for 6 months. Intervention participants were assigned and randomized to usual care (control group) and usual care plus BP card (intervention group). Patients were instructed to do BP measurements at least twice a week for the whole duration of study. Outcome Measures: The primary outcome measures were the percentage of patients with controlled BP ( 0.05). Comparison of clinical profile, associated risk factors in hypertension, behaviors related to hypertension, and presence of co-morbid conditions and target-organ damage, factors affecting blood pressure monitoring and pharmacoadherence exhibited similar results (P value> 0.05). Mean SBP and DBP for study population was also similar 158.3 (18.46) and 159.76 (16.51) mmHg; and 93.86 (8.27) and 94.15 (7.74) mmHg for control and intervention groups, respectively. Compared with patients receiving usual care, the proportion of patients adherent to the prescribed regimen was higher in the group with usual care plus BP card in all clinic visits [29(70.7%) 30(73.2%) 32(78.0%)]. The difference was statistically significant on the 6th month of follow-up (P value =: 0.02). A greater proportion of patients had controlled BP in the intervention group [24(54.5%) vs 32(78.0%)] after six months. The intervention group had a lower systolic and diastolic SP than the control group [SBP 135.68 (11.74), 129.15 (9.02) DBP 82.73 (5.55), 78.90 (5.914)] and this was statistically significant with a P value of 0.01 for both measurements. Conclusions: A new model of patient-centered care that uses BP card can improve BP monitoring, and this may lead to behavioral change particularly adherence to medication and improve SP control in patients with hypertension. This very simple and cost-effective model proved to be effective and the same intervention could be used to improve the care of large numbers of patients with uncontrolled hypertension and the provision of SP monitoring cards to all hypertensive patients could be included in the standard care.

The Mdm1 Locus and Maize Resistance to Maize dwarf mosaic virus.

Previously, Mdm1, a gene controlling resistance to Maize dwarf mosaic virus (MDMV), was identified in the inbred line Pa405. The gene was tightly linked to the restriction fragment length polymorphism marker umc85 on the short arm of chromosome 6. This chromosomal region is also the location of resistance genes to two other viruses in the family Potyviridae, Sugarcane mosaic virus (SCMV) and Wheat streak mosaic virus (WSMV). A diverse collection of 115 maize inbred lines was evaluated for resistance to MDMV and SCMV, and for MDMV resistance loci on chromosome 6S. Forty-six resistant inbred lines were crossed to three MDMVsusceptible inbred lines to develop F2 populations. The F2 populations were inoculated with MDMV and scored for infection and symptom type. Environmental factors influenced both the rate and type of symptom development. Bulked segregant analysis of each F2 population indicated that, in 42 of 43 MDMV-resistant lines, chromosome 6S markers found in the resistant parent also were present in the bulked resistant but not the susceptible tissue. Markers previously associated with resistance to both SCMV and WSMV on chromosome 3 and to WSMV on chromosome 10 were associated with resistance in nine and seven of the F2 populations, respectively. These data suggest that Mdm1 or closely linked genes on chromosome 6S are associated with MDMV resistance in most germplasm, but that other loci also may affect resistance.

Identification of quantitative trait loci controlling resistance to maize chlorotic dwarf virus.

Ineffective screening methods and low levels of disease resistance have hampered genetic analysis of maize (Zea mays L.) resistance to disease caused by maize chlorotic dwarf virus (MCDV). Progeny from a cross between the highly resistant maize inbred line Oh1VI and the susceptible inbred line Va35 were evaluated for MCDV symptoms after multiple virus inoculations, using the viral vector Graminella nigrifrons. Symptom severity scores from three rating dates were used to calculate area under the disease progress curve (AUDPC) scores for vein banding, leaf twist and tear, and whorl chlorosis. AUDPC scores for the F(2) population indicated that MCDV resistance was quantitatively inherited. Genotypic and phenotypic analyses of 314 F(2) individuals were compared using composite interval mapping (CIM) and analysis of variance. CIM identified two major quantitative trait loci (QTL) on chromosomes 3 and 10 and two minor QTL on chromosomes 4 and 6. Resistance was additive, with alleles from Oh1VI at the loci on chromosomes 3 and 10 contributing equally to resistance.

The use of continuous infusion topotecan in persistent and recurrent ovarian cancer.

We retrospectively review our experience with continuous infusion topotecan for the treatment of persistent or recurrent ovarian cancer in this paper. Nine patients were identified who were treated at the University of California Los Angeles Medical Center between January 1997 and December 1999 using a 14-21 day continuous infusion schedule (0.3-0.7 mg/m2/d). Dose adjustments were performed for grade 3-4 toxicities and treatment was discontinued for persistent severe toxicity or progressive disease. Response to treatment was analyzed and stratified by platinum refractory, resistant, and sensitive disease. A total of 41 treatment cycles were given to nine patients with a median of five per patient (range 1-11). Median follow-up was 8 months. There were two partial responses (22%) and four patients had stable disease (44%), which included two patients with platinum-refractory tumors. No grade 3 or 4 hematologic toxicities were observed. However, two patients suffered grade 3 gastrointestinal toxicity during the first cycle leading to discontinuation of topotecan administration. There was no cumulative toxicity. Topotecan administered by continuous infusion demonstrated response rates comparable to other dosing schedules with minimal hematologic toxicity. Treatment of patients with persistent or recurrent ovarian cancer with continuous infusion topotecan warrants further investigation.

Transmission of viral RNA and DNA to maize kernels by vascular puncture inoculation.

Vascular puncture inoculation (VPI) is an effective technique for transmission of maize viruses without using arthropods or other biological vectors. It involves using a jeweler's engraving tool to push minuten pins through a droplet of virus inoculum toward the major vascular bundle in the scutellum of germinating kernels. Here, VPI is shown to be useful for introducing RNA and DNA viral genomes into maize. Maize dwarf mosaic potyvirus (MDMV) virions, MDMV genomic RNA, foxtail mosaic potexvirus (FoMV) genomic RNA and maize streak geminivirus (MSV) DNA were introduced into kernels by VPI, and infection rates determined. At high concentrations, both MDMV virion and genomic RNA preparations produced 100% infection of susceptible maize. However, MDMV genomic RNA was transmitted with about 100-fold lower efficiency than virions. FoMV genomic RNA and MSV DNA were transmitted at lower efficiency than the MDMV RNA, and the highest transmission rates were about 50%. Ribonuclease A pretreatment prevented genomic MDMV and FoMV RNA transmission, but not MDMV virion transmission indicating the viral RNA was the infectious entity. Proteinase K (ProK) pretreatment reduced transmission of MDMV RNA suggesting that integrity of the viral genomic protein bound covalently to the viral RNA may be important for efficient transmission.

Oxygen effects on glucose meter measurements with glucose dehydrogenase- and oxidase-based test strips for point-of-care testing.

OBJECTIVES: To determine the effects of different oxygen tensions (Po2) on glucose measurements with glucose dehydrogenase (GD)-based and glucose oxidase (GO)-based test strips, to quantitate changes in glucose measurements observed with different Po2 levels, and to discuss the potential risks of oxygen-derived glucose errors in critical care. DESIGN: Venous blood from healthy volunteers was tonometered to create different oxygen tensions simulating patient arterial Po2 levels. Venous blood from diabetic patients was exposed to air to alter oxygen tensions simulating changes in Po2 during sample handling. Whole-blood glucose measurements obtained from these samples with six glucose meters were compared with reference analyzer plasma glucose measurements. Glucose differences were plotted vs. different Po2 levels to identify error trends. Error tolerances were as follows: a) within +/-15 mg/dL of the reference measurement for glucose levels 100 mg/dL. SETTING AND SUBJECTS: Five healthy volunteers in the bench study and 11 diabetic patients in the clinical study. RESULTS: In the bench study, increases in Po2 levels decreased glucose measured with GO-based amperometric test strips, mainly at Po2 levels >100 torr. At nearly constant glucose concentrations, glucose meter systems showed large variations at low (39 torr) vs. high (396 torr) Po2 levels. Glucose measured with GD-based amperometric and GO-based photometric test strips generally were within error tolerances. In the clinical study, 31.6% (Precision PCx), 20.2% (Precision QID), and 23.0% (Glucometer Elite) of glucose measurements with GO-based amperometric test strips, 14.3% (SureStep) of glucose measurements with GO-based photometric test strips, and 4.6% (Accu-Chek Advantage H) and 5.9% (Accu-Chek Comfort Curve) of glucose measurements with GD-based amperometric test strips were out of the error tolerances. CONCLUSIONS: Different oxygen tensions do not significantly affect glucose measured with the GD-based amperometric test strips, and have minimal effect on GO-based photometric test strips. Increases in oxygen tension lowered glucose measured with GO-based amperometric test strips. We recommend that the effects of different oxygen tensions in blood samples on glucose measurements be minimized by using oxygen-independent test strips for point-of-care glucose testing in critically ill and other patients with high or unpredictable blood Po2 levels.

Effects of different hematocrit levels on glucose measurements with handheld meters for point-of-care testing.

OBJECTIVES: To determine the effects of low, normal, and high hematocrit levels on glucose meter measurements and to assess the clinical risks of hematocrit errors. DESIGN: Changes in glucose measurements between low and high hematocrit levels were calculated to determine hematocrit effects. The differences between glucose measured with meters and with a plasma glucose method (YSI 2300) also were compared. SETTING: Six hand-held glucose meters were assessed in vitro at low (19.1%), normal (38.5%), and high (58.3%) hematocrit levels, and at 6 glucose concentrations ranging from 2.06 mmol/L (37.1 mg/dL) to 30.24 mmol/L (544.7 mg/dL). RESULTS: Most systems, regardless of the reference to which they were calibrated, demonstrated positive bias at lower hematocrit levels and negative bias at higher hematocrit levels. Low, normal, and high hematocrit levels progressively lowered Precision G and Precision QID glucose measurements. Hematocrit effects on the other systems were more dependent on the glucose concentration. Overall, Accu-Chek Comfort Curve showed the least sensitivity to hematocrit changes, except at the lowest glucose concentration. CONCLUSIONS: We strongly recommend that clinical professionals choose glucose systems carefully and interpret glucose measurements with extreme caution when the patient's hematocrit value changes, particularly if there is a simultaneous change in glucose level.

Quality of care for patients with rheumatoid arthritis.

CONTEXT: Patients with rheumatoid arthritis are at risk for substantial morbidity because of their arthritis and premature mortality due to comorbid diseases. However, little is known about the quality of the health care that these patients receive. OBJECTIVE: To assess the quality of the health care that rheumatoid arthritis patients receive for their arthritis, comorbid diseases, and health care maintenance and to determine the effect of patterns of specialty care on quality. DESIGN, SETTING, AND PARTICIPANTS: Historical cohort study of 1355 adult rheumatoid arthritis patients enrolled in the fee-for-service or discounted fee-for-service plans of a nationwide US insurance company. Patients were identified and followed up through administrative data between 1991 and 1995. MAIN OUTCOME MEASURES: Quality scores for arthritis, comorbid disease, and health care maintenance were developed from performance on explicit process measures that related to each of these domains and described the percentage of indicated health care processes performed within each domain during each person-year of the study. RESULTS: During 4598 person-years of follow-up, quality scores were 62% (95% confidence interval [CI], 61%-64%) for arthritis care, 52% (95% CI, 49%-55%) for comorbid disease care, and 42% (95% CI, 40%-43%) for health care maintenance. Across domains, care patterns including relevant specialists yielded performance scores 30% to 187% higher than those that did not (P<.001) and 45% to 67% of person-years were associated with patterns of care that did not include a relevant specialist. Presence of primary care without specialty care yielded health care maintenance scores that were 43% higher than those for patterns that included neither primary nor relevant specialty care (P<.001). CONCLUSIONS: In this population, health care quality appears to be suboptimal for arthritis, comorbid disease, and health care maintenance. Patterns of care that included relevant specialists were associated with substantially higher quality across all domains. Patterns that included generalists were associated with substantially higher quality health care maintenance than patterns that included neither a generalist nor a relevant specialist. The optimal roles of primary care physicians and specialists in the care of patients with complex conditions should be reassessed. JAMA. 2000;284:984-992

Effects of pH on glucose measurements with handheld glucose meters and a portable glucose analyzer for point-of-care testing.

OBJECTIVES: To determine pH effects on glucose measurements obtained with the latest generation of glucose devices, to quantitate changes in glucose measurements obtained over a wide pH range, and to assess the potential clinical risks of pH effects with use of point-of-care glucose testing. DESIGN: Paired differences of glucose measurements between pH-altered and parallel control samples with target pH 7.40 were calculated. SETTING: A pH range of 6.94 to 7.84 was used to evaluate pH effects on glucose measurements in vitro with 6 handheld glucose meters and a portable glucose analyzer at both normal, 4.81 mmol/L (86.6 mg/dL), and high, 11.16 mmol/L (201 mg/dL), glucose levels. MAIN OUTCOME MEASURES: Glucose measurements obtained from test samples and control samples were compared by calculating paired differences, which were plotted against pH to show pH effects on glucose meter measurements. RESULTS: At the normal glucose level, different pH levels did not interfere significantly with glucose measurements. At the high glucose level, a trend whereby low pH decreased and high pH increased glucose measurements was observed on the Precision G and the Precision QID glucose meters. CONCLUSION: Because of potential risk in diabetic patients with ketoacidosis and in other patients with acid-base disorders, we recommend that clinicians choose glucose devices carefully and interpret the measurements cautiously when point-of-care glucose testing is performed in critically ill patients with acidemia, alkalemia, or changing acid-base status.

Tumor necrosis factor-alpha inhibits leptin production in subcutaneous and omental adipocytes from morbidly obese humans.

This study was undertaken to examine the regulation of leptin production from human adipocytes by tumor necrosis factor-alpha (TNFalpha). Adipocytes were isolated from adipose tissue obtained during bariatric surgical procedures (17 women and 3 men; body mass index, 52.5 +/- 2.4 kg/m2; age, 40 +/- 3 yr) and cultured in suspension. Leptin release from sc adipocytes was inhibited 17.7 +/- 5.2% (P < 0.01), 21.6 +/- 4.3% (P < 0.005), and 37.1 +/- 7.2% (P < 0.05) by 1, 10, and 100 ng/mL TNFalpha, respectively, after 48 h in culture. At 100 ng/mL, significant inhibition of leptin release (25.8 +/- 9.7%; P < 0.05) was detected by 24 h. TNFalpha (10 ng/mL) had no effect on dexamethasone (0.1 micromol/L)-stimulated leptin production in sc adipocytes. In omental adipocytes TNFalpha inhibited leptin release 21.0 +/- 9.6% and 40.8 +/- 6.3% at 10 and 100 ng/mL by 48 h (P < 0.05). Significant inhibition ofleptin release from omental adipocytes was observed at 24 h with 100 ng/mL TNFalpha (P < 0.05). Anti-TNFalpha antibody completely blocked TNFalpha inhibition of leptin release. The ob messenger ribonucleic acid was significantly reduced (23.6 +/- 5.9%) after 48 h of TNFalpha (100 ng/mL) treatment (P < 0.025). TNFalpha had no effect on glucose uptake or lactate production in sc and omental adipocytes. The data suggest that the direct paracrine effect of adipose-derived TNFalpha is inhibition of leptin production.

Point-of-care glucose testing: effects of critical care variables, influence of reference instruments, and a modular glucose meter design.

OBJECTIVE: To assess the clinical performance of glucose meter systems when used with critically ill patients. DESIGN: Two glucose meter systems (SureStepPro and Precision G) and a modular adaptation (Immediate Response Mobile Analysis-SureStepPro) were assessed clinically using arterial samples from critically ill patients. A biosensor-based analyzer (YSI 2700) and a hospital chemistry analyzer (Synchron CX-7) were the primary and secondary reference instruments, respectively. PATIENTS AND SETTING: Two hundred forty-seven critical care patients at the University of California, Davis, Medical Center participated in this study. OUTCOME MEASURES: Error tolerances of +/-15 mg/dL for glucose levels 100 mg/dL were used to evaluate glucose meter performance; 95% of glucose meter measurements should fall within these tolerances. RESULTS: Compared to the primary reference method, 98% to 100% of SureStepPro and 91% to 95% of Precision G measurements fell within the error tolerances. Paired differences of glucose measurements versus critical care variables (Po(2), pH, Pco(2), and hematocrit) were analyzed to determine the effects of these variables on meter measurements. Po(2) and Pco(2) decreased Precision G and SureStepPro measurements, respectively, but not enough to be clinically significant based on the error tolerance criteria. Hematocrit levels affected glucose measurements on both meter systems. Modular adaptation did not affect test strip performance. CONCLUSIONS: Glucose meter measurements correlated best with primary reference instrument measurements. Overall, both glucose meter systems showed acceptable performance for point-of-care testing. However, the effects of some critical care variables, especially low and high hematocrit values, could cause overestimated or underestimated glucose measurements.