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Objectives The aim of the study is to synthesize the evidence and evaluate the total cell-free deoxyribonucleic (cfDNA) associated with the prediction of preeclampsia (PE). Total cfDNA is constituted by both cell-free fetal DNA (cffDNA) originated mainly from the placenta, and maternal cfDNA derived from maternal leukocytes. Methods A systematic review was conducted by searching PubMed and Medline. Literature reporting levels of total cfDNA in the development of PE was included. Studies that only reported cffDNA, but no cfDNA concentrations were not included in this review. Results Eight studies were included. Seven reported values of cfDNA in PE patients, regardless of early or late onset PE, six of which demonstrated a significant increase of cfDNA in patients who subsequently developed PE. Seven studies evaluated cfDNA levels in the first trimester, six of which showed significant increase of cfDNA concentrations in women who later developed PE. Five studies investigated cfDNA levels in the second trimester, all presenting increased total cfDNA levels in the PE group compared with normal controls. Conclusion Total cfDNA may play a role as a biochemical marker of PE, compared with fetal cfDNA. Large prospective studies with homogeneous populations and standardized methodology are needed to further confirm its predictive value.

The progression of the human immunodeficiency virus (HIV) infection to acquired immunodeficiency syndrome (AIDS) can be efficiently interrupted by antiretroviral therapy (ART). However, even successfully treated HIV-infected individuals are prone to develop non-AIDS-related diseases that affect the metabolism and several organs and systems. Biomarkers that predict the occurrence of comorbidities may help develop preventive measures. Current research shows that CD4+ T cell counts and viral load do not predict the development of non-AIDS-related diseases. The CD4/CD8 ratio has been indicated as a suitable marker of persistent immune dysfunction and the occurrence of non-AIDS-related events in treated HIV-positive patients. In this study, we explored the relationship between CD4/CD8 ratios, comorbidities, and aging in ART-treated HIV patients on viral suppression. We collected and evaluated data from 352 HIV-positive adults who were virologically suppressed (

Background: We conducted a study to assess whether testosterone therapy (TT) alters prostate cancer risk using a large U.S. commercial insurance research database. Methods: From the HealthCore Integrated Research Database (HIRD), we selected men ages 30 years or greater who were new users of TT during 2007 to 2015. We selected two comparison groups: (i) unexposed (matched 10:1) and (ii) new users of phosphodiesterase type 5 inhibitor (PDE5i). Incident prostate cancer was defined as diagnosis of prostate cancer within 4 weeks following prostate biopsy. Propensity scores and inverse probability of treatment weights were used in Poisson regression models to estimate adjusted incidence rates, incidence rate ratios (IRR), and 95% confidence intervals (CI). Subgroup analyses included stratification by prostate cancer screening, hypogonadism, and follow-up time. Results: The adjusted prostate cancer IRR was 0.77 (95% CI, 0.68–0.86) when comparing TT with the unexposed group and 0.85 (95% CI, 0.79–0.91) in comparison with the PDE5i group. Inverse associations between TT and prostate cancer were observed in a majority of subgroup analyses, although in both comparisons estimates generally attenuated with increasing time following initial exposure. Among TT users, duration of exposure was not associated with prostate cancer. Conclusions: Men who received TT did not have a higher rate of prostate cancer compared with the unexposed or PDE5i comparison groups. The inverse association between TT and prostate cancer could be the result of residual confounding, contraindication bias, or undefined biological effect. Impact: This study suggests that limited TT exposure does not increase risk of prostate cancer in the short term.

Background and purpose Excessive adiposity is associated with cardiometabolic complications in Turner syndrome (TS) subjects. Reference data for predictive anthropometric indices of overweight/obesity and metabolic syndrome (MetS) are lacking for subjects with TS. The purpose of this study was to identify the best anthropometric predictor of cardiometabolic risk in a Latin-American cohort of TS subjects. Patients and methods This was a cross-sectional correlational study conducted in adult TS subjects (n=88) over the past seven years. Anthropometric parameters, body composition and biochemical variables were evaluated in a study and in a reference (n=57) group. Overweight/obesity and MetS were diagnosed using international consensus. The area under the ROC curve (AUC-ROC) was then used to determine the value of each anthropometric variable in predicting MetS or overweight/obesity. Results The prevalence of MetS and overweight/obesity in TS subjects was 40% and 48%, respectively. All anthropometric and cardiometabolic variables were significantly increased in TS subjects when compared to the reference group, except for body mass index (BMI) and HDL-c. To detect MetS and overweight/obesity, waist to height ratio (WHtR) was found to have a higher correlation with cardiometabolic variables (TC, LDL-c, HDL-c levels and the LDL-c/HDL-c ratio), and to have a higher AUC-ROC and odds ratio than BMI, waist circumference (WC) and the waist to hip ratio (WHR). Conclusion The prevalence of MetS and overweight/obesity is elevated in TS subjects. WHtR was the most useful variable in predicting the presence of MetS and overweight and obesity in this TS cohort. A combination of WHtR with BMI or with WC could have the best clinical utility in identifying adult TS subjects with overweight/obesity and MetS, respectively.

Objective: to assess salivary cortisol concentrations in hematology/oncology nurses on working days and days off. Methods: a cross-sectional study carried out with 28 nurses from a university hospital. A sociodemographic, employment and health profile questionnaire was applied. For saliva collection, Salivette® tubes were used. Descriptive and analytical analysis was used. Results: there was no significant difference in cortisol concentrations between working days and days off (p>0.05). The high cortisol concentration was associated with not having children (0.621±0.340; p=0.046), not using medication (0.623±0.133; p=0.017) and birth control pills (0.556 ± 0.228; p=0.047) and intention to leave work (0.951±0.154; p=0.001). A positive correlation was identified between cortisol and absence from work due to health issues (0.72; p=0.05) and weight gain (0.935; p=0.02). Conclusion: in general, cortisol concentration is within the reference parameters, with no significant difference in its secretion on working days and days off. RESUMEN Objetivo: evaluar la concentración de cortisol salival en enfermeras de Hemato-Oncología en días laborales y días libres. Métodos: estudio transversal realizado con 28 enfermeras de un hospital universitario. Se aplicó un cuestionario de perfil sociodemográfico, laboral y de salud. Para la recolección de saliva se utilizaron tubos Salivette ®. Se utilizó análisis descriptivo y analítico. Resultados: no hubo diferencia significativa en la concentración de cortisol entre los días laborables y los días libres (p> 0.05). La alta concentración de cortisol se asoció con no tener hijos (0.621±0.340; p=0.046), no usar medicación (0.623±0.133; p=0.017) y anticonceptivos orales (0.556±0.228; p=0.047) y tener la intención de dejar el trabajo (0.951±0,154; p=0.001). Se identificó una correlación positiva entre cortisol y absentismo laboral por problemas de salud (0.72; p=0.05) y aumento de peso (0.935; p=0.02). Conclusión: en general, la concentración de cortisol se encuentra dentro de los parámetros de referencia, sin diferencia significativa en su secreción el día de trabajo y tiempo libre. RESUMO Objetivo: avaliar a concentração de cortisol salivar em enfermeiros de Hemato-Oncologia nos dias de trabalho e de folga. Métodos: estudo transversal, realizado com 28 enfermeiros de um hospital universitário. Aplicou-se questionário sociodemográfico, laboral e perfil de saúde. Para coleta de saliva, foram utilizados tubos Salivette®. Empregou-se análise descritiva e analítica. Resultados: não houve diferença significativa na concentração de cortisol entre os dias de trabalho e de folga (p>0,05). A concentração de cortisol elevada esteve associada a não possuir filhos (0,621±0,340; p=0,046), não fazer uso de medicação (0,623±0,133; p=0,017) e de anticoncepcional oral (0,556±0,228; p=0,047) e ter a intenção de deixar o trabalho (0,951±0,154; p=0,001). Identificou-se correlação positiva entre cortisol e afastamento do trabalho por problemas de saúde (0,72; p=0,05) e aumento de peso (0,935; p=0,02). Conclusão: em geral, a concentração de cortisol está dentro dos parâmetros de referência, não apresentando diferença significativa na sua secreção no dia de trabalho e folga.

Objectives: Describe the results of the red reflex test in full-term newborns, as well as identify factors associated with red reflex test outcome and compare hospital length of stay between patients with inconclusive and normal red reflex test results. Methods: Descriptive cross-sectional study of the results of the red reflex test performed in a tertiary hospital maternity unit between 2014 and 2018. A nested case-control study was also performed to search for anthropometric, gestational, and neonatal variables associated with the outcome of the red reflex test. Results: There were121 identified cases of inconclusive red reflex test in 11,833 newborns. Sixteen alterations were confirmed, four considered severe: two cases of congenital glaucoma, one of cataract, and one of coloboma. Mean birth weight (p = 0.04), length (p = 0.03), and head circumference (p = 0.02) were lower in patients with inconclusive red reflex test; however without a relevant effect size (d = −0.21, −0.22, and −0.25, respectively).The proportion of white, mixed-race, and black patients was significantly different between the groups (p < 0.001), with a higher chance of inconclusive results in mixed-race (OR = 2.22) and black (OR = 3.37) patients when compared to whites. An inconclusive red reflex test led to an increase in hospital length of stay from 62 to 82 hours (p < 0.001). Conclusions: The red reflex test was able to identify four severe alterations in 11,833 newborns (0.03%). In the 121 newborns in which the red reflex test was classified as inconclusive, there was a 20-hour increase in the hospital length of stay, but a severe alteration was confirmed in only 3.3% of them. Differences in red reflex between white, mixed-race, and black patients should be considered. Resumo Objetivos: Descrever os resultados do teste do reflexo vermelho em recém-nascidos a termo. Identificar fatores associados ao resultado do teste do reflexo vermelho e comparar o tempo de internação entre pacientes com teste do reflexo vermelho duvidoso e normal. Métodos: Estudo transversal descritivo dos resultados do teste do reflexo vermelho feito em maternidade de hospital terciário entre 2014 e 2018. Foi ainda feito estudo de caso-controle aninhado para pesquisa de variáveis antropométricas, gestacionais e neonatais associadas ao resultado do teste do reflexo vermelho. Resultados: Foram identificados 121 casos de teste do reflexo vermelho duvidoso em 11.833 recém-nascidos. Foram confirmadas 16 alterações, 4 consideradas graves: 2 casos de glaucoma congênito, um de catarata e um de coloboma. As médias de peso de nascimento (p = 0,04), comprimento (p = 0,03) e perímetro cefálico (p = 0,02) foram menores nos pacientes com teste do reflexo vermelho duvidoso, entretanto sem um tamanho de efeito relevante (d = -0,21; -0,22 e -0,25; respectivamente). A proporção de pacientes brancos, pardos e negros foi estatisticamente diferente entre os grupos (p < 0,001), com maior chance de resultado duvidoso para pardos (OR = 2,22) e negros (OR = 3,37) em comparação a brancos. O teste do reflexo vermelho duvidoso levou a um aumento no tempo de internação de 62 para 82 horas (p < 0,001). Conclusões: O teste do reflexo vermelho foi capaz de identificar 4 alterações graves em 11.833 recém-nascidos (0,03%). Nos 121 recém-nascidos em que o teste do reflexo vermelho foi classificado como duvidoso, houve aumento de 20 horas no tempo de internação hospitalar, porém se confirmou alteração grave em apenas 3,3% deles. Diferenças no reflexo vermelho entre brancos, pardos e negros devem ser consideradas.

Background There is limited real-world safety information on palbociclib for treatment of advanced stage HR+/HER2- breast cancer. Methods We conducted a cohort study of breast cancer patients initiating palbociclib and fulvestrant from February 2015 to September 2017 using the HealthCore Integrated Research Database (HIRD), a longitudinal claims database of commercial health plan members in the United States. The historical comparator cohort comprised patients initiating fulvestrant monotherapy from January 2011 to January 2015. Propensity score matching and Cox regression were used to estimate hazard ratios for various safety events. For acute liver injury (ALI), additional analyses and medical record validation were conducted. Results There were 2445 patients who initiated palbociclib including 566 new users of palbociclib-fulvestrant, and 2316 historical new users of fulvestrant monotherapy. Compared to these historical new users of fulvestrant monotherapy, new users of palbociclib-fulvestrant had a greater than 2-fold elevated risk for neutropenia, leukopenia, thrombocytopenia, stomatitis and mucositis, and ALI. Incidence of anemia and QT prolongation were more weakly associated, and incidences of serious infections and pulmonary embolism were similar between groups after propensity score matching. After adjustment for additional ALI risk factors, the elevated risk of ALI in new users of palbociclib-fulvestrant persisted (e.g. primary ALI algorithm hazard ratio (HR) = 3.0, 95% confidence interval (CI) = 1.1–8.4). Conclusions This real-world study found increased risks of several adverse events identified in clinical trials, including neutropenia, leukopenia, and thrombocytopenia, but no increased risk of serious infections or pulmonary embolism when comparing new users of palbociclib-fulvestrant to fulvestrant monotherapy. We observed an increased risk of ALI, extending clinical trial findings of significant imbalances in grade 3/4 elevations of alanine aminotransferase (ALT).

Background Detailed epidemiologic descriptions of large populations of advanced stage ovarian cancer patients have been lacking to date. This study aimed to describe the patient characteristics, treatment patterns, survival, and incidence rates of health outcomes of interest (HOI) in a large cohort of advanced stage ovarian cancer patients in the United States (US). Methods This cohort study identified incident advanced stage (III/IV) ovarian cancer patients in the US diagnosed from 2010 to 2018 in the HealthCore Integrated Research Database (HIRD) using a validated predictive model algorithm. Descriptive characteristics were presented overall and by treatment line. The incidence rates and 95% confidence intervals for pre-specified HOIs were evaluated after advanced stage diagnosis. Overall survival, time to treatment discontinuation or death (TTD), and time to next treatment or death (TTNT) were defined using treatment information in claims and linkage with the National Death Index. Results We identified 12,659 patients with incident advanced stage ovarian cancer during the study period. Most patients undergoing treatment received platinum agents (75%) and/or taxanes (70%). The most common HOIs (> 24 per 100 person-years) included abdominal pain, nausea and vomiting, anemia, and serious infections. The median overall survival from diagnosis was 4.5 years, while approximately half of the treated cohort had a first-line time to treatment discontinuation or death (TTD) within the first 4 months, and a time to next treatment or death (TTNT) from first to second-line of about 6 months. Conclusions This study describes commercially insured US patients with advanced stage ovarian cancer from 2010 to 2018, and observed diverse treatment patterns, incidence of numerous HOIs, and limited survival in this population.

PURPOSE: Women with polycystic ovary syndrome (PCOS) have an increased ovarian responsiveness to exogenous recombinant follicle stimulating hormone (rFSH) but also have high rates of obesity, which is known to affect serum FSH concentrations following exogenous injection. The purpose of this study was to compare rFSH absorption and ovarian response between lean and overweight/obese PCOS subjects and normo-ovulatory controls. METHODS: Fourteen women with PCOS aged 18–42 years old with a BMI of 18.5–24.9 kg/m(2) (normal) or 25.0–40.0 kg/m(2) (overweight/obese) and eleven normo-ovulatory controls matched by age and BMI were included. After downregulation with oral contraceptives, participants were administered a single subcutaneous injection of 225 IU rFSH and underwent serial blood draws over 72 h. RESULTS: Lean PCOS subjects exhibited a significantly higher area under the curve (AUC) of baseline-corrected serum FSH over 72 h when compared with overweight/obese PCOS subjects (183.3 vs 139.8 IU*h/L, p = 0.0002), and lean, normo-ovulatory women had a significantly higher AUC FSH when compared with overweight/obese, normo-ovulatory women (193.3 vs 93.8 IU*h/L, p

Background: Immunological cross-reactivity between common cold coronaviruses (CCC) and SARS-CoV-2 might account for the reduced incidence of COVID-19 in children. Evidence to support speculation includes in vitro evidence for humoral and cellular cross-reactivity with SARS-CoV-2 in specimens obtained before the pandemic started. Method: We used retrospective health insurance enrollment records, claims, and laboratory results to assemble a cohort of 869,236 insured individuals who had a PCR test for SARS-CoV-2. We estimated the effects of having clinical encounters for various diagnostic categories in the year preceding the study period on the risk of a positive test result. Findings: After adjusting for age, gender and care seeking behavior, we identified that individuals with diagnoses for common cold symptoms, including acute sinusitis, bronchitis, or pharyngitis in the preceding year had a lower risk of testing positive for SARS-CoV-2 (OR=0.76, 95%CI=0.75, 0.77). No reduction in the odds of a positive test for SARS-CoV-2 was seen in individuals under 18 years. The reduction in odds in adults remained stable for four years but was strongest in those with recent common cold symptoms. Interpretation: While this study cannot attribute this association to cross-immunity resulting from a prior CCC infection, it is one potential explanation. Regardless of the cause, the reduction in the odds of being infected by SARS-CoV-2 among those with a recent diagnosis of common cold symptoms may have a role in shifting future COVD-19 infection patterns from endemic to episodic. Funding: All authors are employees or consultants for Anthem Inc. or HealthCore Inc. There was no funding for this study. Declaration of Interests: Drs. Beachler and Lanes are employees of HealthCore Inc., a subsidiary of Anthem Inc. Dr. Ovehage is a consultant for HealthCore. Dr. Aran is a consutlant for Anthem Innovation Israel. None of the authors have any competing interests. Ethics Approval Statement: This study was designed as an analysis based on medical claims data, and there was no active enrollment or active follow-up of study subjects, and no data were collected directly from individuals. The study was not required to obtain additional IRB approval, as the HIPAA Privacy Rule permits protected health information (PHI) in a limited data set to be used or disclosed for research, without individual authorization, if certain criteria are met.

The effect of vitamin D3 in oral solution (VD3) and vitamin D3-loaded nanocapsules (NC-VD3) was analysed in animals with complete Freund's adjuvant (CFA) induced arthritis (AR). For this purpose, we evaluated scores for arthritis, thermal hyperalgesia and paw oedema, as well as histological analyses and measurements of the activity of the ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) and ecto-adenosine deaminase (E-ADA) enzymes in rat lymphocytes. Haematological and biochemical parameters were also determined. The doses administered were 120 UI/day of VD3 and 15.84 UI/day of NC-VD3. Fifteen days after the induction of AR, the groups were treated for 15 days with vitamin D3. The results demonstrated that VD3 was able to reduce arthritis scores, thermal hyperalgesia and paw oedema in rats with CFA-induced arthritis. However, treatment with NC-VD3 did not reduce arthritis scores. The histological analyses showed that both formulations were able to reduce the inflammatory changes induced by CFA. The activity of E-NTPDase in rat lymphocytes was higher in the AR compared with the control group, while the activity of E-ADA was lower. This effect was reversed after the 15-day treatment. Data from this study indicates that both forms of vitamin D3 seem to contribute to decreasing the inflammatory process induced by CFA, possibly altering the activities of ectoenzymes. Copyright © 2016 John Wiley & Sons, Ltd. Significance Paragraph The effects promoted by both formulations of vitamin D3, either in oral solution or nanoencapsulated form, strongly suggests the softening of the inflammatory process induced by complete Freund's adjuvant (CFA), possibly altering the E-NTPDase and E-ADA activities. However, it is known that vitamin D has a beneficial effect on the modulation of the immune system components responsible for the inflammatory process. Moreover, the establishment of responses to treatment with vitamin D3 may provide an alternative for inhibiting the proinflammatory response, assisting in our understanding of the immunopathology of this disease and possibly improving the signs and symptoms that hinder the quality of life of patients with rheumatoid arthritis. Highlights: Evaluation of the effects on the E-NTPDase and E-ADA activities in an animal model of induced arthritis. Two formulations of vitamin D3 were used: form oral solution and nanoencapsulated. Vitamin D3 seems to contribute to the inflammatory process induced by CFA. Vitamin D3 possibly alters the E-NTPDase and E-ADA activities. Vitamin D3 may be an alternative supplementary treatment for chronic arthritis.

Temozolomide (TMZ) is used to treat adult patients with glioblastoma multiforme (GBM). Cases of hepatotoxicity have been reported among patients using TMZ. The objective of the study was to assess the relation, if any, between exposure to TMZ and serious acute liver injury (SALI). We used the HealthCore Integrated Research Database to perform a case-control study nested within a retrospective cohort of adult patients aged 18-100 years with at least two diagnoses of brain cancer anytime between 2006 and 2014. Patients without continuous eligibility or with a SALI diagnosis within 6 months prior to the date of incident brain cancer diagnosis were excluded. Medical records were sought for potential SALI cases and reviewed by two hepatologists. Five controls were selected for each case using incidence density sampling, matched on age and calendar year of index date. The analysis included 61 confirmed SALI cases and 305 selected controls. Exposure to TMZ was classified according to dispensing date and days supply of medication dispensed. We estimated odds ratios using conditional logistic regression models. The odds ratio for any exposure to TMZ was 0.91 (95% CI 0.44-1.91), for recent exposure to TMZ was 0.62 (95% CI 0.21-1.85). There was no increased risk of SALI with increasing duration of exposure to TMZ. When patients with unconfirmed SALI were included in the analysis, results were similar (OR 1.04; 95% CI 0.70-1.54). In conclusion, this study did not find an association between TMZ and SALI risk among patients with brain cancer.

Background Preeclampsia remains a significant danger to both mother and child and current prevention and treatment management strategies are limited. The objective of this systematic review was to investigate the current literature on evidence for the use of the regenerative capacity of mesenchymal stem cell (MSC) therapy, the anticoagulant activity of antithrombin (AT), or the free radical scavenging activity of alpha-1-microglobulin (A1M) as potential novel treatments for severe preeclampsia and Hemolysis, Elevated Liver enzymes, Low Platelet count (HELLP). Method We conducted a systematic review of potential biological therapies for preeclampsia. We screened MEDLINE and Embase from inception through May 2017 for studies using AT, A1M or MSCs as potential treatments for preeclampsia and/or HELLP. A meta-analysis was performed to pool data from randomized control trials (RCTs) with homogenous outcomes using the inverse variance method. The Newcastle-Ottawa Scale, the Cochrane risk of bias tool for RCTs, and SYRCLE’s risk of bias tool for animal studies were used to investigate potential bias of studies. Results The literature search retrieved a total of 1015 articles, however, only 17 studies met the selection criteria: AT (n = 9, 8 human and 1 animal); A1M (n = 4, 3 animal and 1 ex-vivo); and, MSCs (n = 4, 3 animal and 1 ex-vivo). A meta-analysis of AT therapy versus placebo and a meta-analysis for AT therapy with heparin versus heparin alone did not show significant differences between study groups. Animal and ex-vivo studies demonstrated significant benefits in relevant outcomes for A1M and MSCs versus control treatments. Most RCT studies were rated as having a low risk of bias across categories with some studies showing an unclear risk of bias in some categories. The two cohort studies both received a total of four out of nine stars (a rating of “poor” quality). Most animal studies had an unclear risk of bias across most categories, with some studies having a low risk of bias in some categories. Conclusions The findings of this review are strengthened by rigorous systematic search and review of the literature. Results of our meta-analyses do not currently warrant further exploration of AT as a treatment of preeclampsia in human trials. Results of animal and ex-vivo studies of A1M and MSCs were encouraging and supportive of initiating human investigations. Electronic supplementary material The online version of this article (10.1186/s12884-019-2268-9) contains supplementary material, which is available to authorized users.

Background Hydralazine, labetalol, and nifedipine are the recommended first-line treatments for severe hypertension in pregnancy. While all three are effective, there is a lack of sufficient evidence regarding their comparative safety and efficacy. Objective To determine the comparative safety and efficacy of the first-line treatment options for severe hypertension in pregnancy. Methods A systematic search of Medline, Embase, and Cochrane Central Register of Controlled Trials up to May 31, 2018 was conducted. RCTs in pregnancy comparing a first-line antihypertensive agent to another first-line agent for the treatment of severe hypertension in pregnancy. Screening, data abstraction, and quality assessment were done by two independent reviewers. To estimate relative effects from all available evidence, a Bayesian network meta-analysis with vague priors was conducted. Main Results Of the 1330 publications identified, 17 RCTs comprised of a total of 1591 women met our selection criteria. For successful treatment of severe hypertension, nifedipine was found to be superior to hydralazine (OR 4.13 [95% CrI 1.01–20.75]) but not labetalol (OR 3.43 [95% CrI 0.94–19.95]). This was not associated with an increased risk for caesarean delivery or maternal side effects. There was no significant difference between labetalol and hydralazine. Conclusions Given the results of this systematic review and network meta-analysis, maternity care providers should feel comfortable initiating management of severe hypertension in pregnancy using oral nifedipine.

This study was conducted to investigate the occurrence of oxidative stress in the heart tissue of rats infected with Trypanosoma evansi. Rats were divided into 2 groups (A and B) with 12 animals each, and further subdivided into 4 subgroups (A1 and A2, 6 animals/each; and B1 and B2, 6 animals/each). Animals in the groups B1 and B2 were subcutaneously inoculated with T. evansi. Thiobarbituric acid reactive substances (TBARS), superoxide dismutase activity (SOD), glutathione S-transferase activity (GST), reduced glutathione activity (GSH), and non-protein thiols (NPSH) in the heart tissue were evaluated. At day 5 and 15 post-infection (PI), an increase in the TBARS levels and a decrease in the SOD activity (P

Growth hormone deficiency (GHD) in adulthood is associated with an increased risk of developing adverse cardiovascular events and with reduced life expectancy. Cardiovascular and metabolic abnormalities have so far been evaluated only in a small number of children with GHD and adolescents. In this article we review these abnormalities and their underlying mechanisms and discuss the beneficial effect of growth hormone treatment in subjects with GHD.

Objective To understand whether spontaneous vs induced puberty and the type and route of estrogen influence the height of girls with Turner syndrome on growth hormone (GH). Study design Search of an international database of children treated with GH revealed 772 girls with Turner syndrome followed from GH initiation to near adult height. Data from girls with sustained spontaneous puberty (n = 145) were compared with those requiring estrogens for induction or maintenance of puberty (n = 627). Results At GH start, mean age (7.5 vs 7.9 years), weight (−1.7 vs −1.7 SDS), and body mass index (0.2 SDS vs 0.1 SDS) were similar for girls with spontaneous puberty and with induced puberty. Although those girls with spontaneous puberty were shorter than those with induced puberty, when midparental height was taken into consideration, starting heights in both groups averaged −2.8 SDS. Both groups received approximately 0.3 mg/kg/week of GH. Girls with spontaneous puberty initiated puberty and reached near adult height earlier than girls with induced puberty (12.6 ± 1.8 years vs 13.4 ± 1.4 years and 16.0 ± 1.3 years vs 16.9 ± 1.4 years, respectively). Although girls with spontaneous puberty grew more in the first year of GH therapy and between the onset of puberty and near adult height (11.0 cm vs 9.3 cm), height SDS at near adult height and the length of time in puberty before reaching near adult height were comparable. A 45,X karyotype was detected in 22.1% of girls with spontaneous puberty and in 58.4% of girls with induced puberty. Patients receiving transdermal estrogens did not grow better than those on oral estrogens. Adverse event reporting was comparable between groups. Conclusions Girls with Turner syndrome with spontaneous puberty tended to grow better in response to GH than girls with induced puberty, but not enough to produce a difference in height SDS at near adult height.

Background Although healthcare databases are a valuable source for real-world oncology data, cancer stage is often lacking. We developed predictive models using claims data to identify metastatic/advanced-stage patients with ovarian cancer, urothelial carcinoma, gastric adenocarcinoma, Merkel cell carcinoma (MCC), and non-small cell lung cancer (NSCLC). Methods Patients with ≥1 diagnosis of a cancer of interest were identified in the HealthCore Integrated Research Database (HIRD), a United States (US) healthcare database (2010–2016). Data were linked to three US state cancer registries and the HealthCore Integrated Research Environment Oncology database to identify cancer stage. Predictive models were constructed to estimate the probability of metastatic/advanced stage. Predictors available in the HIRD were identified and coefficients estimated by Least Absolute Shrinkage and Selection Operator (LASSO) regression with cross-validation to control overfitting. Classification error rates and receiver operating characteristic curves were used to select probability thresholds for classifying patients as cases of metastatic/advanced cancer. Results We used 2723 ovarian cancer, 6522 urothelial carcinoma, 1441 gastric adenocarcinoma, 109 MCC, and 12,373 NSCLC cases of early and metastatic/advanced cancer to develop predictive models. All models had high discrimination (C > 0.85). At thresholds selected for each model, PPVs were all >0.75: ovarian cancer = 0.95 (95% confidence interval [95% CI]: 0.94–0.96), urothelial carcinoma = 0.78 (95% CI: 0.70–0.86), gastric adenocarcinoma = 0.86 (95% CI: 0.83–0.88), MCC = 0.77 (95% CI 0.68–0.89), and NSCLC = 0.91 (95% CI 0.90 – 0.92). Conclusion Predictive modeling was used to identify five types of metastatic/advanced cancer in a healthcare claims database with greater accuracy than previous methods.

Inflammatory bowel disease (IBD) is a chronic condition commonly requiring lifelong care. Both IBD and IBD-related treatments can cause significant morbidity, and it is often difficult to differentiate their relative etiologic contribution to adverse events (AEs). The objectives of this study were to assess the rates of select AEs among patients with IBD as a function of disease severity and of the use of anti-tumor necrosis factor alpha (anti-TNFα) medications.We conducted a retrospective cohort study of IBD patients in the HealthCore Integrated Research Database (HIRD(TM)) between January 2004 and January 2011 to determine rates of AEs in patients with mild and moderate to severe IBD. Key study endpoints were select prespecified malignant neoplasms, infections, and other AEs of interest.A total of 33,386 IBD patients (52.7% ulcerative colitis; 47.3% Crohn's disease) met the inclusion criteria, and 60% had been followed for ≥1 year. Patients with moderate to severe IBD had increased rates of infections, lymphatic and digestive tract cancers, gastrointestinal (GI) perforations, and myocardial infarctions versus patients with mild IBD. Patients with IBD who used anti-TNFα therapies during the study had increased incidence of many types of infections, certain GI cancers (including rectal and anal cancer), intestinal perforations, and kidney stones compared with patients who had never used anti-TNFα therapies.Results from this large US cohort provide descriptive information on AE rates in a population of IBD patients undergoing routine care, estimating background incidence rates of AEs that are not readily available in the published literature. Our study findings may be limited owing to a lack of generalizability and potential for misclassification due to reliance on medical diagnosis and treatment and procedure codes to identify disease, comorbidities, and treatments. Further research and validation of our findings in other populations and databases are needed.

Insulin resistance (IR) increases with advancing age, yet the underlying mechanism is not well established. Anthropometric and body composition indicators are alternative tools for assessing insulin resistance in a fast, non-invasive and inexpensive way. This study aimed to evaluate the association between anthropometric indicators and insulin resistance in older men. This cross-sectional study included 62 men aged between 60 and 92 years. We evaluated waist circumference (WC), sagit-tal abdominal diameter (SAD), body mass index (BMI), sagittal index (SI), conicity index (CI), body fat percentage (BF%), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and waist-to-thigh ratio (WTR). IR was determined by homeostasis model assessment (HOMA-IR). Statistical analysis consisted of correlation coefficient. All anthropometric indicators cor-related with HOMA-IR, highlighting the SAD (r = 0.680), BF% (r = 0.651) and WC (r = 0.591), which showed the highest correlations with the index. All measurements showed significant differences and progressive increase with increasing HOMA-IR. The differences between quartiles of HOMA-IR were even more pronounced for WC, SAD and BF%. BF% was a significant predictor for insulin resistance. Thus, obesity indicators correlated with the HOMA-IR index. We emphasize the stronger relationship between measures of central adiposity and insulin resistance, suggesting the usefulness of SAD in evaluating elderly subjects.

Purpose Claims databases offer large populations for research, but lack clinical details. We aimed to develop predictive models to identify estrogen receptor positive (ER+) and human epidermal growth factor negative (HER2-) early breast cancer (ESBC) and advanced stage breast cancer (ASBC) in a claims database. Methods Female breast cancer cases in Anthem's Cancer Care Quality Program served as the gold standard validation sample. Predictive models were developed from clinical knowledge and empirically from claims data using logistic and lasso regression. Model performance was assessed by classification rates and c-statistics. Models were applied to the HealthCore Integrated Research Database (claims) to identify cohorts of women with ER+/HER2- ESBC and ASBC. Results The validation sample included 3184 women with ER+/HER2- ESBC and 1436 with ER+/HER2- ASBC. Predictive models for ER+/HER2- ESBC and ASBC included 25 and 20 factors, respectively. Models had robust discrimination in identifying cases (c-stat = 0.92 for ESBC and 0.95 for ASBC). Compared with a traditional a priori algorithm developed with clinical insight alone, the ER+/HER2- ASBC-predictive model had better positive predictive value (PPV) (0.91, 95% CI, 0.90-0.93, vs 0.69, 95% CI, 0.66-0.73) and sensitivity (0.54 vs 0.35). Models were applied to the claims database to identify cohorts of 33 001 and 3198 women with ER+/HER2- ESBC and ASBC. Conclusion We conducted a validation study and developed predictive models to identify in a claims database cohorts of women with ER+/HER2- ESBC and ASBC. The models identified large cohorts in the claims data that can be used to characterize indications in the evaluation of targeted therapies.

To describe patient and provider characteristics for patients with type 2 diabetes (T2DM) initiating basal insulin and describe basal insulin's impact on sulfonylurea (SU) discontinuation.A retrospective cohort study was conducted using the HealthCore Integrated Research Database. Patients had ≥12 months of continuous coverage prior to initiating insulin, and were utilizing at least one anti-hyperglycemic drug at the time of insulin initiation. Predictors for SU discontinuation were evaluated utilizing Cox proportional hazards models.Among the 74,334 individuals aged ≥18 years with T2DM who initiated basal insulin from 2006-2015, 30% were taking metformin (MET) and SU when initiating insulin. Among the 22,418 MET/SU patients, 31% discontinued SU within 3 months of insulin initiation and, by 12 months, 55% had discontinued SU. Sulfonylurea discontinuation was similar among many patient and provider characteristics, while being modestly positively associated (p .05; HRs1.5) with female gender, more co-morbidities, cardiac revascularization, chronic liver disease, hospitalizations with a T2DM diagnosis, and hypoglycemia prior to insulin initiation. SU discontinuation was modestly inversely associated with receiving an insulin prescription from an endocrinologist (HR = 0.90, 95% CI = 0.85-0.95).Roughly half of commercially-insured T2DM patients discontinued SU within 1 year after insulin initiation, and SU discontinuation was not strongly associated with a range of patient and provider characteristics.

Sepsis is a potentially lethal condition, and it is associated with platelet alterations. The present study sought to investigate the activity of ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase), E-5'-nucleotidase, and ecto-adenosine deaminase (E-ADA) in the platelets of rats that were induced with sepsis. Male Wistar rats were divided into three groups of ten animals each: a negative control group (normal; NC); a group that underwent surgical procedures (sham); and a group that underwent cecal ligation and perforation (CLP). The induction of sepsis was confirmed by bacteremia, and the causative pathogen identified was Escherichia coli. Hematological parameters showed leukocytosis and thrombocytopenia in animals in the septic group. The results also revealed that there were significant (p

e13082 Background: Our main objective was to identify, in healthcare claims data, patients with advanced or metastatic: urothelial carcinoma (amUC), gastric cancer (amGC) and non-small cell lung cancer (amNSCLC) and to report on their characteristics, treatments, and survival rates using contemporaneous real-world data. Methods: This cohort study was conducted in the HealthCore Integrated Research Database (HIRD), from January 2010 to January 2018, which contains healthcare claims data from commercial health plans across the US (60 million lives). We applied algorithms, previously validated on registry data, to the HIRD to define 3 cohorts of advanced stage cancer. Cohort characteristics and treatment patterns were described. Patient vital status was captured through probabilistic linkage with the National Death Index (NDI) and survival was assessed using the Kaplan-Meier method. Results: Algorithms to predict advanced stage cancer resulted in the following cohorts: 1,501 amUC, 6,253 amGC and 38,451 amNSCLC cases. Most patients in each cohort were de novo advanced or metastatic, but subsets were diagnosed at early stage and progressed to advanced stage (ranging from 15.1% for amNSCLC to 23.1% for amUC). Patient characteristics, treatments and survival outcomes are described in Table. Not all received systemic treatment; Immune Checkpoint inhibitors (ICI) were used in 5.3%, 2.2% and 10.8% of treated amUC, amGC and amNSCLC patients, respectively. Conclusions: In these cohorts of advanced or metastatic cancer patients, median survival time was limited despite most receiving treatment: radiation, systemic therapy or surgery. Treatment with ICI was low despite recent data in amUC and amNSCLC. Characteristics, treatments, and survival from estimated advanced stage date. [Table: see text]

Aims. To examine incidence and trends of Type 1 diabetes worldwide for the period 1990–1999. Methods. The incidence of Type 1 diabetes (per 100000/year) was analysed in children aged ≤ 14 years from 114 populations in 112 centres in 57 countries. Trends in the incidence of Type 1 diabetes were analysed by fitting Poisson regression models to the dataset. Results. A total of 43013 cases were diagnosed in the study populations of 84 million children. The age-adjusted incidence of Type 1 diabetes among 112 centres (114 populations) varied from 0.1 per 100000/year in China and Venezuela to 40.9 per 100000/year in Finland. The average annual increase in incidence calculated from 103 centres was 2.8% (95% CI 2.4–3.2%). During the years 1990–1994, this increase was 2.4% (95% CI 1.3–3.4%) and during the second study period of 1995–1999 it was slightly higher at 3.4% (95% CI 2.7– 4.3%). The trends estimated for continents showed statistically significant increases all over the world (4.0% in Asia, 3.2% in Europe and 5.3% in North America), except in Central America and the West Indies where the trend was a decrease of 3.6%. Only among the European populations did the trend in incidence diminish with age. Conclusions. The rising incidence of Type 1 diabetes globally suggests the need for continuous monitoring of incidence by using standardized methods in order to plan or assess prevention strategies.

Purpose The impact of i.v. drug delivery via point-of-care (POC)-activated and closed systems versus traditional manual admixture systems on the risk of hospital-acquired bloodstream infection (BSI) is examined. Methods Using data from a proprietary hospital database, a retrospective observational cohort study of patients receiving one or more i.v. drug administrations via POC-activated or closed systems during a three-year period (2007–09) was conducted. Cases of hospital-acquired BSI were identified using diagnosis codes and billing charges for blood cultures and antibiotic use. The risk of BSI in patients with exposure to POC-activated systems, closed systems, or both relative to that of patients exposed to open systems was estimated by odds ratios (ORs) calculated by multivariate logistic regression analysis. Results The evaluated data indicated that of the 4,073,864 patients included in the study cohort, 0.5% ( n = 20,251) experienced hospital-acquired BSI. After adjusting for selected confounding variables, the use of POC-activated systems was associated with a 16% reduction in BSI risk relative to the use of open systems (OR, 0.84; 95% confidence interval [CI], 0.76–0.93), and the use of closed systems correlated with a 12% risk reduction (OR, 0.88; 95% CI, 0.82–0.96). Patients who received i.v. drugs via both POC-activated and closed systems appeared to derive the greatest relative risk reduction benefit (OR, 0.12; 95% CI, 0.06–0.23). Conclusion Use of POC-activated and closed systems for i.v. drug delivery was associated with a significantly reduced risk of hospital-acquired BSI compared with exclusive use of open systems in a large population of hospitalized patients.

GHD subjects may present with an abnormal body composition, with elevated fasting cholesterol levels and with increased fasting and postprandial triglyceride concentrations. In addition, concentrations of peripheral inflammatory and fibrinolytic markers have been found to be increased in GHD. Increased carotid artery intima-media thickness and vascular rigidity, as well as abnormalities in cardiac mass and function, have also been noted in GHD. Many of these abnormalities seem to be already detectable early on in life, so that children and adolescents with severe GHD need to be followed carefully as they enter into adulthood. GH treatment seems to have a beneficial impact on body fat distribution, on lipid abnormalities, on cardiac mass and function and on vascular rigidity and may lead to a reduction of the risk of cardiac events in adult GHD subjects.

How to cite this article de Almeida Paula H.A., de Cassia Lanes Ribeiro R., de Lima Rosado L.E.F.P., Abranches M.V. & do Carmo Castro Franceschini S. (2012) Relationship between waist circumference and supine abdominal height measured at different anatomical sites and cardiometabolic risk factors in older women. J Hum Nutr Diet. Abstract Objectives: To measure waist circumference (WC) and supine abdominal height (SAH) at different anatomic sites and to assess the relationship with cardiometabolic risk factors in women aged >60 years. Methods: The present study included 113 women from Vicosa, Minas Gerais, Brazil. The evaluations comprised anthropometric, biochemical and haemodynamic measurements. Different anatomical sites were used to measure WC: (i) the midpoint between the last rib and iliac crest; (ii) umbilical level; (iii) immediately above the iliac crests; and (iv) the narrowest point between the last rib and the iliac crest. Measurements were also taken at different anatomic sites for SAH: (i) the midpoint between the iliac crests; (ii) umbilical level; (iii) higher abdominal diameter; and (iv) the narrowest point between the last rib and the iliac crest. Results: It was found that 35.4% of women were overweight, and the area (SE) body mass index was 25.8 (4.2) kg/m2. WC at the umbilical level [area (SE) area under the curve (AUC) = 0.694 (0.079)] and SAH at the midpoint between the iliac crests [AUC = 0.747 (0.076)] showed the largest areas under the receiver operating characteristic curve (P

We investigated the effect of the -278A>C polymorphism in the CYP7A1 gene on the response of plasma lipids to a reduced-fat diet for 6 to 8 weeks in a group of 82 dyslipidemic males with a mean age of 46.0 ± 11.7 years. Individuals who presented at least one high alteration in total cholesterol, low-density lipoprotein cholesterol or triglyceride values were considered to be dyslipidemic. Exclusion criteria were secondary dyslipidemia due to diabetes mellitus, renal, liver, or thyroid disease. None of the subjects were using lipid-lowering medication. Baseline and follow-up lipid concentrations were measured. The genotypes were determined by the digestion of PCR products with the BsaI restriction endonuclease. There were statistically significant reductions in plasma total cholesterol, low-density lipoprotein cholesterol and triglyceride concentrations after dietary intervention. The minor allele C has a frequency of 43%. Carriers of the C allele had significantly lower triglyceride concentrations (P = 0.02) than AA homozygotes. After adjustment of covariates, subjects with the AC and CC genotypes showed a greater reduction in triglyceride concentrations compared to subjects with the AA genotype. Multiple linear regression analyses showed that the AC and CC CYP7A1 genotypes accounted for 5.2 and 6.2% of triglyceride concentration during follow-up and adjusted percent of change of triglyceride concentration, respectively. The present study provides evidence that -278A>C polymorphism in the CYP7A1 gene can modify triglyceride concentrations in response to a reduced fat diet in a dyslipidemic male population. This gene represents a potential locus for a nutrigenetic directed approach.

PURPOSE: To analyze bone repair process in Wistar rats' calvaria, with the use of two different biomaterials. METHODS: Forty two male Wistar rats were used, and four bicortical cranial cavities were created in each animal. The cavities were filled with: bioactive glass (BG); calcium sulfate barrier (CSB); bioactive glass covered with calcium sulfate barrier (BG/CSB); and autogenous blood clot (control). The animals were euthanized 7, 14, 21, 30, 60, 90, e 120 days after surgery. The scalps were removed and submitted to a routine process for histological preparation: staining with Haematoxylin and Eosin (HE). RESULTS: The BG was not completely resorbed; however, after 60 days, a decrease in size as well as a change in the morphological granule were observed. CSB was not observed in the last group (after 120 days). CONCLUSIONS: In Wistar rat calvaria bioactive glass, in an isolated form, negatively interfered in the bone repair process; the calcium sulfate barrier, in an isolated form, presented the capacity to maintain space, allowing the flow of osteogenic cells; the bioactive glass covered with calcium sulfate barrier association presented a better osteoconductive capacity when compared to isolated materials; calcium sulfate barrier was completely resorbed after 90 days; control cavities did not completely heal until 120 days after surgery.

A patient with clinical features of Turner syndrome and a 45,X karyotype in repeated blood cultures was re-evaluated when she spontaneously entered puberty. A ring X cell line was found in a small proportion of fibroblasts. A review of 35 previously published ring X cases is presented. All are mosaic, the major cell line in most cases being 45,X. There is wide variation in the frequency with which the abnormalities associated with Turner syndrome are found in these patients. All have short stature. Some are sexually developed and fertile. Cardiovascular anomalies are uncommon. This phenotypic variation may have at least two causes: the size of the deleted portion at each end of the X chromosome, and the relative frequency and distribution of 45,X and 46,X,r(X) cell lines in various body tissues.

Toxocara canis, Toxocara cati, are roundworms that live in the intestines of dogs and cats, respectively, and are predominantly agents of human toxocariasis. Studies have suggested that Toxocara spp. seroprevalence increases levels of total and aeroallergen-specific IgE (sIgE), asthma prevalence and asthma morbidity. Nevertheless, other work reported a negative association between Toxocara spp. seropositivity with skin hypersensititity and a positive association with sIgE. The objective of the present study was to evaluate risk factors for acquiring Toxocara spp. infection and to investigate possible significant association between its seroprevalence with atopy and asthma. Students from elementary schools, residents in a small town and its surroundings of Northeast Brazil, underwent blood sampling to measure levels of anti-Toxocara spp. IgG, peripheral blood eosinophils, and specific IgE to aeroallergens. We used univariable and multivariable logistic regression analyses to assess possible risk factors for Toxocara spp. seropositivity and its association with atopy, wheeze/asthma with asthma phenotypes, in a sample of 791 elementary school children aged 6-13 years. Toxocara spp. seroprevalence reached 63.6%; 49.9% had sIgE; 7.2% and 3.3% had atopic wheeze/asthma and non-atopic wheeze/asthma respectively. Risk factors associated with Toxocara spp. seropositivity were: contact with dogs (adj. OR 2.33; 95% CI=1.70-3.19) and cats (adj. OR 3.09; 95% CI=2.10-4.55), and male sex (adj. OR 2.21; 95% CI=1.62-3.02). The presence of anti-Toxocara IgG was statistically associated with blood eosinophils >4% and >10% (adj. OR 1.84; 95% CI=1.33-2.55 and adj. OR 2.07; 95% CI=1.45-2.97, respectively), and atopy (adj. OR 2.00; 95% CI=1.49-2.68), but it was not associated with wheeze/asthma. Concluding, the results obtained in this study showing the association of Toxocara spp. seroprevalence with sIgE may suggest a possible immunological cross-reactivity between IgE epitopes from Toxocara spp. and aeroallergens.

The method usually employed to stimulate gonadal maturation and spawning of captive shrimp involves unilateral eyestalk ablation, which results in the removal of the endocrine complex responsible for gonad-inhibiting hormone (GIH) synthesis and release. In the present study, RNAi technology was used to inhibit transcripts of GIH in Litopenaeus vannamei females. The effect of gene silencing on gonad development was assessed by analyzing the expression of GIH and vitellogenin, respectively, in the eyestalk and ovaries of L. vannamei females, following ablation or injection with dsRNA-GIH, dsRNA-IGSF4D (non-related dsRNA), or saline solution. Histological analyses were performed to determine the stage of gonadal development and to assess the diameter of oocytes throughout the experimental procedure. Only oocytes at pre-vitellogenesis and primary vitellogenesis stages were identified in females injected with dsRNA-GIH, dsRNA-IGSF4D, or saline solution. Oocytes at all developmental stages were observed in eyestalk-ablated females, with predominance of later stages, such as secondary vitellogenesis and mature oocytes. Despite achieving 64, 73, and 71% knockdown of eyestalk GIH mRNA levels by 15, 30, and 37 days post-injection (dpi), respectively, in dsRNA-GIH-injected females, the expected increase in ovary vitellogenin mRNA expression was only observed on the 37th dpi. This is the first report of the use of RNAi technology to develop an alternative method to eyestalk ablation in captive L. vannamei shrimps.

To identify predictors of chronic obstructive pulmonary disease (COPD) severity and assess the relation between COPD severity and risk of cardiovascular outcomes. A␣cohort of patients with diagnosed and treated COPD was compiled from the Saskatchewan Health longitudinal databases. We used multivariate modeling to identify predictors of hospitalization for COPD as an indicator of COPD severity, and we used the model to characterize patients according to quintiles of COPD severity. These severity levels were used as independent variables in multivariate models of cardiovascular outcomes. Determinants of COPD severity included emphysema, recent nebulizer use, home oxygen services, corticosteroid use, frequent bronchodilator use, pneumonia and prior COPD exacerbation. The 20% of patients with the highest COPD severity were 1.27 (CI: 1.07–1.50) times more likely to have arrhythmia, 1.25 (CI: 1.07–1.46) times more likely to have ischemic heart disease, 1.38 (CI: 1.11–1.71) times more likely to have angina, 2.28 (CI: 1.95–2.66) times more likely to have congestive heart failure, and 1.63 (CI: 1.22–2.16) times more likely to die of cardiovascular causes than the least severe 20% of patients. Patients with more severe COPD, as defined by our model, had higher cardiovascular morbidity and mortality than patients with less severe COPD.

Objective To determine whether coronary artery calcification (CAC), elevated fasting lipids, and lipoproteins and peripheral inflammatory markers are present in insulin-dependent diabetic adolescents and young adults several years after diagnosis. Study design Hispanic insulin-dependent diabetics (n = 32) diagnosed a mean of 7.8 ± 4.5 years ago (range, 3 to 16 years), with a mean glycosylated hemoglobin concentration at the time of the study of 8.8% ± 2.3% and a mean chronological age of 16.1 ± 4.4 years, were evaluated. Healthy patients (n = 15) with a chronological age (CA) of 15.2 ± 2.2 years served as control subjects. CAC was assessed by multiple slice computed tomography, and total CAC score in Agatston units was calculated. Fasting lipids, C-reactive protein, apolipoprotein (Apo) A, Apo B, and metalloproteinase-9 (MMP-9) concentrations were measured in all subjects. Results Neither adolescents with type 1 diabetes nor healthy control subjects presented with evidence of CAC. Fasting lipids, Apo A, Apo B, CRP, and MMP-9 concentrations were similar between diabetic subjects and control subjects. However, 34.4% and 25.0% of our type 1 diabetic subjects had elevated total and LDL cholesterol levels (>200 and >130 mg/dL, respectively), whereas 15.6% and 28.1% had elevated triglyceride and Apo B concentrations (>150 mg/dL and >100 mg/dL, respectively). In addition, 28.1% and 34.4% presented with elevated CRP and MMP-9 levels (>2 mg/L and >80 ng/mL, respectively). Total, LDL and HDL cholesterol, triglycerides, Apo B, CRP, and MMP-9 concentrations correlated positively with duration of the disease and with glycosylated hemoglobin levels. Conclusions Although the study adolescents with type 1 diabetes did not present any radiologic evidence of CAC at this stage of the disease, they remain a high-risk group for the development of microvascular and macrovascular artery disease, as risk factors such as elevated lipoproteins and proinflammatory markers are already present in a significant percentage of patients studied.

Objective To examine the impact of adolescent growth hormone deficiency (GHD) on circulating adiponectin levels and the relation between adiponectin, fasting insulin, plasma lipid, and lipoprotein levels. Study design Twelve children with GHD on GH treatment with a chronological age (CA) of 14.4 2.0 years and 12 untreated adolescents with GHD with a CA of 14.9 2.3 years were studied. Adiponectin concentrations were measured in all patients, and the association of adiponectin with fasting insulin, total, LDL, and HDL cholesterol, triglycerides, apolipoprotein A-1, and apolipoprotein B was evaluated. Twelve healthy adolescents served as control subjects. Results Adiponectin levels were significantly lower in untreated GHD adolescents than in treated GHD subjects or in control subjects (P < .008). Total and LDL cholesterol, triglycerides, and Apo B concentrations were increased in untreated GHD adolescents, whereas HDL cholesterol levels were similar in all three groups. Insulin levels were significantly increased in treated GHD adolescents when compared with control subjects (P < .05) but similar to those with untreated GHD. Adiponectin was found to be negatively associated with body mass index, waist-to-hip ratio, and with Apo B, total cholesterol, triglycerides, and LDL cholesterol concentrations in untreated GHD adolescents, whereas a positive correlation between adiponectin and HDL cholesterol was noted in both untreated and treated GHD subjects. Adiponectin correlated inversely with fasting insulin levels in untreated and treated GHD adolescents. Conclusions GHD in adolescence is associated with low levels of adiponectin and with an unfavorable plasma lipid and lipoprotein profile. Our data suggest that treatment with GH may improve the abnormalities seen. (J Pediatr 2006;149:324-9)

Growth hormone (GH) has been available for more than 4 decades for the treatment of GH deficiency. Initially, GH was extracted from the pituitary glands of human cadavers, but its use was discontinued following the transmission of the Creutzfeldt-Jakob virus. After the development of recombinant GH (somatropin) in 1985, an 'unlimited' commercial source of GH has been available, allowing for the treatment of a large number of short GH-deficient and -sufficient children. Refinements in both the dosage and the frequency of administration of GH have allowed GH-deficient children to reach nearly normal final heights, although mostly they are still below their target heights. Decreased bone mineral densities and increased concentrations of fasting and postprandial lipids, coagulation factors, and several independent cardiovascular risk factors have been reported in GH-deficient children and adolescents and appear to improve with GH administration. The short-term administration of GH to mostly non-GH-deficient short children with Turner syndrome, chronic renal insufficiency (CRI), intrauterine growth retardation (IUGR), and idiopathic short stature (ISS) has resulted in increased growth velocities. In addition, the final height of patients with Turner syndrome and CRI appears to improve with the long-term administration of GH. Final height data are still lacking in adolescents with IUGR, but height standard deviation score and final height predictions appear to improve with therapy. Based on the incomplete and inconclusive available data, one must conclude that GH treatment of children with ISS cannot be advised. The use of GH at replacement doses in children with GH deficiency has resulted in rare and generally reversible adverse effects. The long-term administration of pharmacologic GH doses to short, mostly non-GH-deficient children must, however, still be viewed with caution, as long-term complications cannot as yet be fully evaluated. GH therapy must be individualized and should be limited only to children with severe short stature or a significantly decreased growth velocity, to children under considerable stress due to their short stature, and to patients in whom low GH or low insulin-like growth factor-1 secretion might be the rate-limiting factors for growth. The cost of the medication and the inconvenience of daily GH injections to otherwise mostly healthy short children must also be taken into account.

Objective: To determine whether postprandial lipids, coagulation factors and homocysteine levels are abnormal in young growth hormone (GH)-deficient (GHD) adolescents. Methods: Fifteen GHD adolescents on GH replacement were studied. Ten untreated GHD adolescents and 15 healthy subjects served as controls. Fasting lipids, lipoprotein(a), fibrinogen, plasminogen activator inhibitor-1, homocysteine, folate and vitamin B12 levels were measured. Cholesterol and triglycerides were measured 4 h after a high fat meal. Results: Fasting and postprandial triglycerides and homocysteine levels of untreated GHD patients were increased compared to those of GH-treated GHD subjects and healthy controls; fibrinogen concentrations were elevated in both treated and untreated adolescents. Conclusions: GHD adolescents present an abnormal fasting and postprandial lipid profile. In addition, the increased fibrinogen and homocysteine levels are suggestive of the accumulation of cardiovascular risk factors early on in life.

Summary Objective We recently reported that children with idiopathic short stature (ISS) have decreased lumbar spine bone mineral density (BMD) that increases after 1 year of GH therapy. The aim of this study was to confirm these short-term results and to evaluate the effect of long-term GH therapy on the BMD of children with ISS. Patients and Design We treated a group of 16 short, slow-growing but otherwise healthy non-GH-deficient prepubertal children (8 girls and 8 boys) with a chronological age of 9·5 ± 0·9 years, a bone age of 8·1 ± 1·2 years and a height of 124·3 ± 6·3 cm (height-SDS of −2·1 ± 0·6) with GH at a dose of 0·1 IU/kg/day for 3 consecutive years. Measurements Height was determined at 3-month intervals and annual growth velocities were calculated. Bone ages and BMD were measured every 12 months by dual-energy X-ray absorptiometry, as were serum concentrations of the carboxy-terminal propeptide of type 1 collagen (PICP) and the carboxy-terminal cross-linked telopeptide of type 1 collagen (ICPT). Results Growth velocity increased from 4·0 ± 0·8 cm/year to 8·7 ± 1·5 and 8·0 ± 1·7 cm/year at 12 and 36 months of GH therapy, respectively, while height-SDS improved from −2·1 ± 0·6 to −1·6 ± 0·4 after 36 months of GH (P

The objective of our study was to evaluate whether cardiac mass and function, carotid artery intima-media thickness, and serum lipid and lipoprotein(a) levels are abnormal in adolescents with GH deficiency. Young adults with childhood-onset and adulthood-onset GH deficiency have been found to have a higher cardiovascular risk, as manifested among other factors by reduced left ventricular mass, impaired systolic function, significant increase in arterial intima-media thickness, and dyslipidemia. Twelve adolescents (seven males and five females) with GH deficiency (10 idiopathic and 2 organic), with an age of 14.2 +/- 2.8 yr and a height of 140.6 +/- 17.9 cm (height SD score, -2.6 +/- 0.3), were studied. Six children had received GH in the past but were off therapy for several years, whereas six patients had never been treated with GH. Fasting blood samples were obtained for serum lipids and lipoprotein(a) analysis. Patients underwent transthoracic M-mode and two-dimensional echocardiographic evaluation for measurement of interventricular septal thickness, left ventricular posterior wall thickness, and left ventricular mass, as well as left ventricular ejection fraction at rest and pulmonary venous flow velocities; carotid artery intima-media thickness was measured using high-resolution mode B ultrasound. Seven GH-deficient (GHD) adolescents on GH at the time of the study and 19 healthy adolescents, all comparable for age, pubertal status, height, weight, blood pressure, and pulse, participated in this study as controls. Interventricular septal thickness (6.5 +/- 1.3 vs. 7.0 +/- 1.5 mm), left ventricular posterior wall thickness (7.0 +/- 1.8 vs. 7.5 +/- 2.0 mm), and left ventricular mass after correction for body surface area (71.2 +/- 21.8 vs. 70.7 +/- 18.0 g/m(2)) were similar in untreated GHD patients and healthy controls. Similarly, the left ventricular ejection fraction at rest was similar in untreated GHD subjects and controls (70.0 +/- 0.7 vs. 70.0 +/- 0.6%), as were the pulmonary venous flow velocities (0.54 +/- 0.16 vs. 0.55 +/- 0.10 m/s for diastolic peak velocity; 0.51 +/- 0.16 vs. 0.50 +/- 0.09 m/s for systolic peak velocity; and 0.19 +/- 0.06 vs. 0.19 +/- 0.05 m/s for atrial reversal filling). Carotid artery intima-media thickness (0.60 +/- 0.02 mm and 0.59 +/- 0.02 mm for the right and left carotid arteries, respectively) was also normal in our untreated GHD patients when compared with healthy controls. In addition, all echocardiographic measurements were similar in GHD subjects on or off GH at the time of the study. Low-density lipoprotein cholesterol levels were increased in untreated GHD patients when compared with healthy controls (3.17 +/- 0.70 vs. 2.33 +/- 0.36 mmol/L; P < 0.01), whereas total cholesterol, high-density lipoprotein cholesterol, and triglyceride concentrations were similar to that of controls. Total cholesterol levels were increased in our untreated GHD adolescents when compared with GHD subjects receiving GH therapy at the time of the study, while low-density lipoprotein cholesterol and triglyceride levels were also elevated, although not significantly. Lipoprotein(a) levels were elevated in untreated GHD adolescents when compared with healthy controls, and untreated GHD subjects had higher lipoprotein(a) concentrations than GH-treated patients. GHD adolescents, regardless of whether or not they received GH therapy, do not seem to show alterations in cardiac mass and function or early atherosclerotic changes. They must, however, be followed carefully because they already present cardiovascular risk factors such as dyslipidemia, which may increase their cardiovascular morbidity over time.

Meloxicam is a nonsteroidal anti-inflammatory drug (NSAID) introduced in the UK and othercountries in 1996. Clinical trials have suggested that meloxicam could have better gastrointestinal(GI) tolerability than other NSAIDs, possibly due to its preferential inhibition of COX-2isoenzyme as compared with COX-1.(1,2) Despite being the largest NSAID trials conducted todate, these studies were not sufficiently large to conclude that the apparently improved GItolerability also extends to reduced risk of upper GI perforations, ulcers and bleeds.(1,2) Thus, itwas noted in the UK Drug and Therapeutics Bulletin(3) that “there is no convincing evidence thatthe risk of the severest adverse gastrointestinal events, namely peptic ulceration, perforation andbleeding, is lower with meloxicam than with other NSAIDs.” Post-marketing experience in theUK has been consistent with clinical trials in showing that the most common kinds of adverseevents most frequently reported with meloxicam are GI events.(4) For this reason, the labelingfor meloxicam was strengthened to alert health practitioners to the possible risk of GI events.It has been stated meloxicam “shares the common unwanted effects of other NSAIDs and thesame precautions apply to its use, especially in patients at high risk for peptic ulceration.”(3)Merely because meloxicam is associated with the same kinds of GI events as other NSAIDs,however, does not mean that meloxicam carries the same risk of these events as other NSAIDs.To make matters more complicated, in the post-marketing experience where conditions are notas well-controlled as they are in clinical trials, comparisons of disease frequency typically do notallow for valid inference. Indeed, even if meloxicam were safer than other NSAIDs in the generalpopulation, rates of GI events among patients receiving meloxicam could be greater than ratesof GI events among patients receiving other NSAIDs. For example, if meloxicam wasprescribed preferentially to patients who, at the time of receiving meloxicam, were already atincreased baseline risk of GI events, one would expect to observe high rates of GI eventsassociated with meloxicam but unrelated to any adverse drug effect.This study was conducted to evaluate whether or not patients receiving meloxicam soon after itsintroduction in the UK were at inherently greater baseline risk of GI events than patients receiving

Objective: To determine whether young women with Turner's syndrome who had normal bone mineral density (BMD) before the induction of puberty maintain normal BMD in young adulthood. Design: Controlled clinical study. Setting: A private hospital clinical research setting. Patients: Young women with Turner's syndrome in Tanner stage V of puberty with previously normal BMD. Interventions: Oral conjugated estrogens and progesterone acetate were administered continuously for a mean (±SD) of 4.1 ± 1.0 years. Bone mineral densities and blood samples were evaluated. Main Outcome Measure(s): The BMD of the lumbar spine and the femoral neck was determined during young adulthood. The change in BMD over the previous 6 years also was evaluated. Serum concentrations of the carboxy-terminal propeptide of type 1 collagen and of the carboxy-terminal cross-linked telopeptide of type 1 collagen were measured. Result(s): The BMD of the lumbar spine was reduced significantly in our patients. There was no change in the BMD of the femoral neck or lumbar spine over a period of 6.1 years. Concentrations of the carboxy-terminal propeptide of type 1 collagen were decreased, whereas concentrations of the carboxy-terminal cross-linked telopeptide of type 1 collagen were increased. Conclusion(s): Young women with Turner's syndrome do not attain normal peak bone mass even when estrogen replacement therapy is begun in adolescence. Their low BMD seems to be due to decreased bone formation and increased bone resorption.

OBJECTIVE Combined gonadotrophin-releasing hormone analogue and recombinant human growth hormone therapy has been used in an attempt to improve the final height of short non-GH deficient adolescents with normally timed puberty; its use, however, is still controversial as only short-term studies in a very limited number of patients have been undertaken, with either improvement in height prognosis or no beneficial effect on predicted growth. We have treated a group of extremely short healthy children with very low predicted adult heights entering into normally timed puberty with combined therapy, in order to determine whether we could improve their final height above their pretreatment predicted adult height. PATIENTS We treated 10 healthy adolescent short children (7 girls and 3 boys) simultaneously for 30.0 +/- 5.2 months with the GnRH analogue leuprolide acetate (0.3 mg/kg im every 28 days) and with rhGH (0.1 U/kg/day, sc, 6 days a week). The mean chronological age of our patients was 11.8 +/- 1.3 years, with a mean bone age of 11.2 +/- 0.9 years, height of 128.9 +/- 7.5 cm (-2.4 +/- 0.4 SD below the mean) and a predicted adult height of 150.7 +/- 9.8 cm; they were all in Tanner stage II-III of puberty. Ten healthy short children (7 girls and 3 boys) in the early stages of puberty with a mean chronological age of 11.4 +/- 1.0 years, a mean bone age of 11.0 +/- 0.8 years, height of 128.9 +/- 7.8 cm (-2.3 +/- 0.4 SD below the mean) and a mean adult predicted height of 151.8 +/- 10.1 cm served as controls and were simultaneously followed without therapy for the same study period. MEASUREMENTS Height and pubertal status were followed every 3 months during combined therapy and until final height of our patients was reached; bone ages were obtained every 6 months. Growth hormone deficiency was ruled out in all our subjects prior to beginning of the study by a normal response to oral clonidine and normal IGF-1 levels. Basal serum testosterone and/or oestradiol levels, as well as LH and FSH following administration of LH-releasing hormone were obtained before treatment and after 6 weeks and 4 months of combined therapy and every 6 months thereafter. Routine biochemistry as well as thyroid function tests were obtained at each visit. RESULTS Combined treatment resulted in an interruption of pubertal development with a suppression of gonadal steroids and of the LH response to LH-releasing hormone. Growth velocity decreased from 6.5 +/- 1.6 cm/year before treatment to 5.5 +/- 1.5 cm/year and 3.9 +/- 1.3 cm/year during the first and second year of treatment (P < 0.02 and P < 0.05, respectively) resulting in a height Z score reduction, declining from -2.4 +/- 04 to -2.6 +/- 0.7 SD. Bone age maturation declined averaging 0.75 bone age year/year of treatment but height SDS for bone age declined from -1.7 +/- 0.7 to -2.2 +/- 0.5 at the end of the second year of therapy with no improvement in predicted adult height (150.7 +/- 9.8 cm before and 150.0 +/- 8.0 after 2 years of therapy). After discontinuing treatment growth velocity did not improve and bone maturation advanced more rapidly (averaging 2.0 +/- 0.4 year/year of follow up) and the mean final height of our patients was 151 +/- 2.4 cm (-2.6 +/- 0.6 SD below the mean) which was not greater than the mean pretreatment predicted adult height and well below their target height; these results were also similar to those of the control population in whom the predicted adult height at the beginning of the study and after 2 years of follow up, was not different from their final height and well below their target height. CONCLUSIONS We conclude that combined rhGH and GnRH analogue therapy in short adolescents with normally timed puberty does not contribute to increase their final height above their pretreatment predicted adult height; we can therefore not recommend this form of therapy for this group of patients given the poor results obtained, as well as the cost of these medications and the

Background It is possible that genes on the X chromosome are expressed differently depending of its parental origin. The objective of this study was to determine the influence of the parental origin of the X-chromosome on phenotypic variability, response to rhGH and on the biochemical profile of TS patients. Methods This was a cross-sectional multicenter correlational study carried out over three years in six Latin-American university hospitals. Unrelated 45,X TS patients (n = 93; 18.3 ± 8.5 years )) were evaluated. A subgroup (n = 34) of the patients were prospectively treated with rhGH over two years. DNA profiles of patients and their mothers were compared to determine the parental origin of the retained X-chromosome through 10 polymorphic X-chromosome-STRs. The association with clinical features, biochemical profiles and anthropometric data at the beginning and after two years of rhGH treatment was determined. Results Seventy two percent of patients retained the maternal X chromosome (Xm). A trend towards significance between maternal height and patients final height (p ≤ 0.07) in 45,Xm subjects was observed. There was no correlation between paternal height and patient height. No differences were detected between both groups in regard to dysmorphic features, classical malformations or increase in the height-SDS after rhGH. There were higher levels of triglycerides, total and LDL cholesterol in patients >20 years who retained the Xm. Conclusions The parental origin of the retained X chromosome may influence lipid metabolism in TS patients, but its effect on growth seems to be minimal. No parental-origin-effect on the phenotypic features, associated anomalies and on the growth response to rhGH was found in 45,X TS individuals.