Lack of health insurance among juvenile offenders: a predictor of inappropriate healthcare use and reincarceration?

OBJECTIVES: Relationships between the health insurance status and healthcare use among justice-involved youths transitioning into adulthood is an underexplored topic, even if transition to adulthood is a crucial time period for healthcare outcomes. To fill in these knowledge gaps, this study had two aims: (1) to examine trajectories of health insurance coverage and healthcare use among serious juvenile offenders transitioning into adulthood; and (2) to explore associations between the lack of health insurance, healthcare use and reincarceration. STUDY DESIGN: We conducted a secondary analysis on the data of the US longitudinal Pathways to Desistance study between ages 20 and 23 years (2000-2010). METHODS: Participant data on health insurance coverage, healthcare use, reincarceration and sociodemographic variables (n = 1215) were extracted and analysed using descriptive statistics, generalized linear regressions and cross-lagged panel models. RESULTS: About half of the young offenders had no health insurance coverage or intermittent coverage between the age of 20 and 23 years. Emergency services were used (≥17.4%), notably more by insured participants and were increasingly used over time. Being uninsured at the age of 20 years was associated with reincarceration at the age of 23 years (b = -0.052, p = 0.014, odd-ratio = 0.95), but incarceration at the age of 20 years did not predict the insurance status at the age of 23 years (b = 0.009, p = 0.792). CONCLUSIONS: Serious juvenile offenders, especially if uninsured, faced major barriers to accessing health care and often reported an inappropriate healthcare use. This likely led to reincarceration. The lack of continuity of care and of access to health care may, therefore, increase health disparities, and efforts are needed to mitigate detrimental outcomes, by effective in and out of detention coordination of health insurance coverage and among health services.

Anagrelide platelet-lowering effect is due to inhibition of both megakaryocyte maturation and proplatelet formation: insight into potential mechanisms.

BACKGROUND AND OBJECTIVES: Anagrelide represents a treatment option for essential thrombocythemia patients. It lowers platelet counts through inhibition of megakaryocyte maturation and polyploidization, although the basis for this effect remains unclear. Based on its rapid onset of action, we assessed whether, besides blocking megakaryopoiesis, anagrelide represses proplatelet formation (PPF) and aimed to clarify the underlying mechanisms. METHODS AND RESULTS: Exposure of cord blood-derived megakaryocytes to anagrelide during late stages of culture led to a dose- and time-dependent inhibition of PPF and reduced proplatelet complexity, which were independent of the anagrelide-induced effect on megakaryocyte maturation. Whereas anagrelide was shown to phosphorylate cAMP-substrate VASP, two pharmacologic inhibitors of the cAMP pathway were completely unable to revert anagrelide-induced repression in megakaryopoiesis and PPF, suggesting these effects are unrelated to its ability to inhibit phosphodiesterase (PDE) 3. The reduction in thrombopoiesis was not the result of down-regulation of transcription factors which coordinate PPF, while the myosin pathway was identified as a candidate target, as anagrelide was shown to phosphorylate the myosin light chain and the PPF phenotype was partially rescued after inhibition of myosin activity with blebbistatin. CONCLUSIONS: The platelet-lowering effect of anagrelide results from impaired megakaryocyte maturation and reduced PPF, both of which are deregulated in essential thrombocythemia. These effects seem unrelated to PDE3 inhibition, which is responsible for anagrelide's cardiovascular side-effects and antiplatelet activity. Further work in this field may lead to the potential development of drugs to treat thrombocytosis in myeloproliferative disorders with an improved pharmacologic profile.

Mechanisms underlying platelet function defect in a pedigree with familial platelet disorder with a predisposition to acute myelogenous leukemia: potential role for candidate RUNX1 targets.

BACKGROUND: Familial platelet disorder with a predisposition to acute myelogenous leukemia (FPD/AML) is an inherited platelet disorder caused by a germline RUNX1 mutation and characterized by thrombocytopenia, a platelet function defect, and leukemia predisposition. The mechanisms underlying FPD/AML platelet dysfunction remain incompletely clarified. We aimed to determine the contribution of platelet structural abnormalities and defective activation pathways to the platelet phenotype. In addition, by using a candidate gene approach, we sought to identify potential RUNX1-regulated genes involved in these defects. METHODS: Lumiaggregometry, α-granule and dense granule content and release, platelet ultrastructure, αIIb ß3 integrin activation and outside-in signaling were assessed in members of one FPD/AML pedigree. Expression levels of candidate genes were measured and luciferase reporter assays and chromatin immunoprecipitation were performed to study NF-E2 regulation by RUNX1. RESULTS: A severe decrease in platelet aggregation, defective αIIb ß3 integrin activation and combined αδ storage pool deficiency were found. However, whereas the number of dense granules was markedly reduced, α-granule content was heterogeneous. A trend towards decreased platelet spreading was found, and ß3 integrin phosphorylation was impaired, reflecting altered outside-in signaling. A decrease in the level of transcription factor p45 NF-E2 was shown in platelet RNA and lysates, and other deregulated genes included RAB27B and MYL9. RUNX1 was shown to bind to the NF-E2 promoter in primary megakaryocytes, and wild-type RUNX1, but not FPD/AML mutants, was able to activate NF-E2 expression. CONCLUSIONS: The FPD/AML platelet function defect represents a complex trait, and RUNX1 orchestrates platelet function by regulating diverse aspects of this process. This study highlights the RUNX1 target NF-E2 as part of the molecular network by which RUNX1 regulates platelet biogenesis and function.

International collaboration as a tool for diagnosis of patients with inherited thrombocytopenia in the setting of a developing country.

BACKGROUND: Inherited thrombocytopenias (ITs) are heterogeneous genetic disorders that frequently represent a diagnostic challenge. The requirement of highly specialized tests for diagnosis represents a particular problem in resource-limited settings. To overcome this difficulty, we applied a diagnostic algorithm and developed a collaboration program with a specialized international center in order to increase the diagnostic yield in a cohort of patients in Argentina. METHODS: Based on the algorithm, initial evaluation included collection of clinical data, platelet size, blood smear examination and platelet aggregation tests. Confirmatory tests were performed according to diagnostic suspicion, which included platelet glycoprotein expression, immunofluorescence for myosin-9 in granulocytes and platelet thrombospondin-1 and molecular screening of candidate genes. RESULTS: Thirty-one patients from 14 pedigrees were included; their median age was 32 (4-72) years and platelet count 72 (4-147)×10(9) L(-1). Autosomal dominant inheritance was found in nine (64%) pedigrees; 10 (71%) had large platelets and nine (29%) patients presented with syndromic forms. A definitive diagnosis was made in 10 of 14 pedigrees and comprised MYH9-related disease in four, while classic and monoallelic Bernard-Soulier syndrome, gray platelet syndrome, X-linked thrombocytopenia, thrombocytopenia 2 (ANKRD26 mutation) and familial platelet disorder with predisposition to acute myelogenous leukemia were diagnosed in one pedigree each. CONCLUSIONS: Adoption of an established diagnostic algorithm and collaboration with an expert referral center proved useful for diagnosis of IT patients in the setting of a developing country. This initiative may serve as a model to develop international networks with the goal of improving diagnosis and care of patients with these rare diseases.

Production of functional platelet-like particles by the megakaryoblastic DAMI cell line provides a model for platelet biogenesis.

The aim of this study was to evaluate cell maturation and the platelet production capacity of the megakaryoblastic DAMI cell line, to characterize platelet-like particles produced and to investigate the mechanisms involved in their production. DAMI cell maturation was induced by phorbol myristate acetate (PMA) and thrombopoietin (TPO). Expression levels of GATA-1, Fli-1 and NF-E2 were evaluated using real-time PCR and western blot. Platelet-like particles were characterized by the presence of GPIb and GPIIb by flow cytometry, while the soluble fragment of GPIb, glycocalicin, was detected by enzyme immunoassay. Dense and alpha granules were evaluated by mepacrine staining and thrombospondin-1 detection, respectively, and by electron microscopy. Functional capacity of platelet-like particles was studied by measuring P-selectin membrane after thrombin stimulation by flow cytometry and actin polymerization using phalloidin-FITC by immunofluorescence. We found that stimulation of DAMI cells with high concentration of PMA and TPO induced the expression of transcription factors GATA-1 and Fli-1 followed by an increase in the isoform a of NF-E2. Mature DAMI cells give rise to extensions resembling proplatelets and later, produce platelet-like particles expressing GPIIb and GPIb on their surface and containing dense and alpha granules, which were confirmed by electron microscopy. Platelet functionality was demonstrated by the increase in P-selectin membrane expression after thrombin stimulation and by their ability to spread on fibrinogen matrices. DAMI cell line induced to differentiate into mature megakaryocytes is able to produce functional platelets providing a suitable model to study the mechanisms involved in platelet generation.

Monocyte IL-2Ralpha expression is associated with thrombosis and the JAK2V617F mutation in myeloproliferative neoplasms.

The development of bone marrow fibrosis and thrombosis are main causes of morbidity in essential thrombocythemia (ET). Monocyte activation has been associated to the production of fibrosis-related cytokines and pro-thrombotic factors. The aim of this study was to identify new markers of monocyte activation in Phi-negative myeloproliferative neoplasms and to search for their relationship with clinical features. Forty-five patients comprising 30 ET, eight myelofibrosis and seven polycythemia vera were included. We evaluated the alpha subunit of IL-2 receptor (CD25) on monocytes, basal and LPS-induced IL-1beta release from mononuclear cells, and monocyte TGF-beta mRNA content. Patients who had thrombotic events displayed higher monocyte CD25 levels (6.2%) than those without symptoms (1.3%) and controls (2.6%), p=0.0006. JAK2V617F-positive patients had higher monocyte CD25 expression levels (4.7%), than JAK2V617F-negative (2.6%), p=0.0213. Patients with myeloproliferative neoplasms had similar monocyte CD25 expression than controls, both, in basal conditions and after cell adhesion. IL-1beta release and TGF-beta mRNA levels were normal. In conclusion, increased monocyte CD25 expression is associated with history of thrombosis and is also up-regulated in patients harboring JAK2V617F mutation. The finding of increased CD25 levels together with normal IL-1beta and TGF-beta production reveals a selective monocyte activation profile in myeloproliferative neoplasms.

Immunization of sows in an integrated pig-breeding herd using a homologous inactivated Salmonella vaccine decreases the prevalence of Salmonella typhimurium infection in the offspring.

The efficacy of a homologous vaccination in preventing infection of suckling piglets with Salmonella (S.) Typhimurium was evaluated after an immunization of pregnant sows using an inactivated herd-specific S. Typhimurium vaccine. Twenty-five pregnant sows were vaccinated three times antepartum. The efficiency of this vaccine regime was assessed by comparison with a control group of 37 sows and their suckling piglets, which were daily treated with enrofloxacin from day 14 antepartum until the day of weaning. From the first day of life until day 142 post-partum, faecal samples of the piglets were collected and analysed for Salmonella shedding. In parallel, systemic antibody responses were monitored using a whole cell-based isotype-specific enzyme-linked immunosorbent assay (ELISA). The bacteriological investigation showed marked effects of vaccination. Salmonella Typhimurium could not be detected in any of the faecal samples of the piglets from the vaccinated sows. In contrast, the piglets of the group with long-time antibiotic treatment shed salmonellae rating to 47.4% of the animals. Furthermore, the offspring from vaccinated sows showed significantly decreased antibody activities of immunoglobulin (Ig)A and IgG. These bacteriological and serological results indicate a significantly lower Salmonella prevalence in piglets of the vaccinated group. As this study shows, the presented strategy of vaccination of pregnant sows with an inactivated Salmonella vaccine seems to be a suitable measure in decreasing Salmonella prevalence in offspring of infected sows.

Effects of fluorequinolone treatment acidified feed, and improved hygiene measures on the occurrence of Salmonella Typhimurium DT104 in an integrated pig breeding herd.

Worldwide, the use of antimicrobials in food production has been associated with drug resistance in foodborne pathogens such as Salmonella. However, little is known about the efficaciousness of fluorequinolone treatment on Salmonella Typhimurium T104 infections in pig breeding herds. A combined eradication procedure with enrofloxacin application on sows and piglets, feeding of encapsulated organic acids to sows, disinfection with peracetic acid, separation of the growers from the sows and serological discrimination using a new whole-cell-based enzyme-linked immnosorbent assay (ELISA) was evaluated for the suitability to eradicate and to control endemic S. Typhimurium DT104 infections in a closed herd. Thirty-seven sows and their piglets were treated everyday from day 14 ante partum until the day of weaning. Eighteen sows and their piglets served as controls. From the first day of life until day 168 after birth, faecal samples (n = 1671) of all piglets were analysed for Salmonella shedding. In parallel, systemic antibody responses were monitored by whole-cell-based isotype-specific ELISA systems. From birth to weaning the prevalence in both groups was between 2% and 9%. After weaning, intermittent shedding could be observed in both groups, and salmonellae could be found in up to 7.7% of the faecal samples. As a result, a dramatic increase in Salmonella-infected growers was observed, as of day 115 after birth, 47.4% of the animals of the treated group were tested positive for S. Typhimurium. Our results indicate that despite long-term antibiosis treatment and optimized hygiene measures, shedding of S. Typhimurium by the sows and the subsequent infection of their offspring could not be effectively prevented. Although it could be not shown that elimination of S. Typhimurium DT104 infection was achieved, the disinfection procedures described and the diagnostic test used are effective instruments to decrease the Salmonella load and to identify individual infected animals. Both of these are important factors for an improved consumer protection.

[Psychological stress in patients with environmentally-induced disorders. A comparison between self concept and expert assessment]. / Seelische Belastung bei Menschen mit umweltbezogenen Störungen Ein Vergleich zwischen Selbstbild und Fremdeinschätzung.

Environmental illnesses raise diagnostic and therapeutic conflicts in scientific discussions and clinical practice. When a patient's health-belief model, based on environmental origins, does not match that of the expert, the therapeutic relationship can be endangered. Our study investigates this discrepancy, which has not been empirically evaluated so far. Patient (n=61) and expert disease concepts were systematically investigated. Our results indicate that in cases in which both concepts are favourable, the patient suffered minor psychiatric disorders with stable psychic structures and the symptoms were associated with medical or environmental causes. If both concepts were unfavourable, a higher proportion of psychiatric disorders with unstable psychic structures were present. In the case of incongruent concepts, the expert evaluations allow a more accurate assessment of the psychiatric diagnoses, psychic states and the psychic attribution of somatic and psychic burden.

Evaluation of a cervical cytology device (cell-sweep) based on comparison to colposcopic findings.

A new cytology sampling device, the CellSweep, identifies squamous intraepithelial lesions with a sensitivity of 75%. The purpose of this study was to evaluate the accuracy of cervical cytology using a new sampling device combining an endocervical brush and ectocervical spatula into one unit (CellSweep, patented by R. Mohajer, Troy, Michigan). From April 1995 to July 1995, 71 patients referred to the Allegheny University Hospitals Colposcopy Clinic had cervical cytology obtained with the CellSweep and underwent colposcopic evaluation of the cervix. The ability of the CellSweep to detect an abnormality confirmed by colposcopic evaluation was studied. Colposcopically directed ectocervical biopsies were obtained only in patients with identifiable lesions (n = 32). No random biopsies were obtained. The cytology smear was unsatisfactory for interpretation in one case. The remaining 70 Papanicolaou smears were read as normal in 17 (24%) cases and atypical squamous cells in 19 (27%). A squamous intraepithelial lesion (SIL) was detected in 34 (48%) smears. The colposcopic evaluation was normal in 50 patients who had satisfactory Papanicolaou smears, whereas SIL was detected in 20 cases. In 31 patients, SIL was not present in either colposcopy or cytology. In this preliminary study, the CellSweep identified SIL with a sensitivity of 75% and a specificity of 62%. The CellSweep, which combines an endocervical brush and an ectocervical spatula into a single unit, seems to be an acceptable device for obtaining cervical cells for cytologic screening.

Pathological analysis of local delivery of paclitaxel via a polymer-coated stent.

BACKGROUND: Paclitaxel can inhibit vascular smooth muscle proliferation in vitro, and early studies suggest that paclitaxel may be useful in preventing restenosis. Early and late intimal growth and local vascular pathological changes associated with paclitaxel delivered via stents have not been fully explored. METHODS AND RESULTS: Localized drug delivery was accomplished with balloon-expandable stainless steel stents coated with a cross-linked biodegradable polymer, chondroitin sulfate and gelatin (CSG), containing various doses of paclitaxel. CSG-coated stents with paclitaxel (42.0, 20.2, 8.6, or 1.5 microgram of paclitaxel per stent), CSG-coated stents without paclitaxel, and uncoated stents (without paclitaxel or CSG) were deployed in the iliac arteries of New Zealand White rabbits, which were killed 28 days after implant. Mean neointimal thickness at stent strut sites was reduced 49% (P<0.0003) and 36% (P<0.007) with stents containing 42.0 and 20.2 microgram of paclitaxel per stent, respectively, versus CSG-coated stents without paclitaxel. However, histological findings suggested incomplete healing in the higher-dose (42.0 and 20.2 microgram) paclitaxel-containing stents consisting of persistent intimal fibrin deposition, intraintimal hemorrhage, and increased intimal and adventitial inflammation. Stents coated with CSG alone (without paclitaxel) had similar neointimal growth as uncoated stents. In a separate group of rabbits killed at 90 days, neointimal growth was no longer suppressed by CSG-coated stents containing 42.0 or 21.0 microgram of paclitaxel CONCLUSIONS: CSG coating appears to be a promising medium for localized drug delivery. Paclitaxel polymer-coated stents reduce neointima formation but are associated with evidence of incomplete healing at 28 days. However, neointimal suppression was not maintained at 90 days.

Paclitaxel stent coating inhibits neointimal hyperplasia at 4 weeks in a porcine model of coronary restenosis.

BACKGROUND: Despite limiting elastic recoil and late vascular remodeling after angioplasty, coronary stents remain vulnerable to restenosis, caused primarily by neointimal hyperplasia. Paclitaxel, a microtubule-stabilizing drug, has been shown to inhibit vascular smooth muscle cell migration and proliferation contributing to neointimal hyperplasia. We tested whether paclitaxel-coated coronary stents are effective at preventing neointimal proliferation in a porcine model of restenosis. METHODS AND RESULTS: Palmaz-Schatz stents were dip-coated with paclitaxel (0, 0.2, 15, or 187 microgram/stent) by immersion in ethanolic paclitaxel and evaporation of the solvent. Stents were deployed with mild oversizing in the left anterior descending coronary artery (LAD) of 41 minipigs. The treatment effect was assessed 4 weeks after stent implantation. The angiographic late loss index (mean luminal diameter) decreased with increasing paclitaxel dose (P<0.0028 by ANOVA), declining by 84.3% (from 0.352 to 0.055, P<0.05) at the highest level tested (187 microgram/stent versus control). Accompanying this change, the neointimal area decreased (by 39.5%, high-dose versus control; P<0.05) with increasing dose (P<0.040 by ANOVA), whereas the luminal area increased (by 90.4%, high-dose versus control; P<0.05) with escalating dose (P<0.0004 by ANOVA). Inflammatory cells were seen infrequently, and there were no cases of aneurysm or thrombosis. CONCLUSIONS: Paclitaxel-coated coronary stents produced a significant dose-dependent inhibition of neointimal hyperplasia and luminal encroachment in the pig LAD 28 days after implantation; later effects require further study. These results demonstrate the potential therapeutic benefit of paclitaxel-coated coronary stents in the prevention and treatment of human coronary restenosis.

The significance of thrombocytosis in patients with locally advanced cervical carcinoma: a Gynecologic Oncology Group study.

OBJECTIVE: The aim of this study was to determine the incidence of thrombocytosis and its possible impact on survival probability among women with locally advanced cervical carcinoma. METHODS: The database of 294 patients with Stages IIB-IVA cervical carcinoma without periaortic node metastasis who were treated with standardized radiation therapy and concurrent hydroxyurea or misonidazole was analyzed. Pretreatment platelet counts were available for 291 patients who are the subject of this study. RESULTS: Thrombocytosis (platelet count >400 x 10(9)/liter) was present in 86 (29.6%) of the 291 patients. A multivariate Cox proportional hazards model showed that patients without extrapelvic disease and with thrombocytosis had a 55% greater chance of dying than those without thrombocytosis (relative risk = 1.55, 95% confidence interval 1.08-2.21). Patients with thrombocytosis had larger tumors and more frequently had bilateral parametrial involvement, tumor fixation to the sidewall, and positive pelvic lymph nodes than patients without thrombocytosis. Thrombocytosis was not found to be a prognostic factor in patients with positive pelvic nodes. However, in patients with negative pelvic nodes, the presence or absence of thrombocytosis was related to survival. CONCLUSION: Thrombocytosis is a frequent finding among patients with advanced cervical carcinoma and seems to be related to tumor burden. Among patients with locally advanced cervical carcinoma who had negative pelvic nodes, those with thrombocytosis had a poorer survival.

The influence of religious and ethnic differences on marital intimacy: intermarriage versus intramarriage.

The influence of religious and ethnic differences on marital intimacy was examined by administering the Personal Assessment of Intimacy in Relationships and a demographic/attitudinal questionnaire to 25 Jewish couples (intramarried) and 25 couples with one Jewish partner (intermarried). All couples were childless and in the first 5 years of their first marriage. Results indicated that the groups did not differ regarding couple level of intimacy, similarity of intimate experience, or mutual understanding. However, in-depth interviews revealed differences in the pathways by which these two groups arrived at a similar level of intimacy. Intramarried couples appear to experience greater personal similarity and mutual understanding rooted in their ethnic bond, which aids the development of intimacy. Intermarried couples appear to find that the very process of negotiating ethnic differences leads to greater mutual understanding and intimacy. These findings indicate that clinicians and religious leaders should not assume that intermarriage constrains levels of intimacy. Nor should it be assumed that intramarriage assures high intimacy.

Clinical significance of a cytologic diagnosis of atypical glandular cells of undetermined significance.

OBJECTIVE: To assess the clinical significance of a cytologic diagnosis of atypical glandular cells of undetermined significance (AGUS) and determine the most appropriate evaluation of these patients. STUDY DESIGN: Between 1993 and 1995, 44,217 Papanicolaou smears were evaluated at Allegheny University Hospitals, Medical College of Pennsylvania Campus. There were 108 (0.24%) cases of AGUS smears during that time. No clinical information was available for 14 patients, and 19 were lost to follow-up. The charts of the remaining 75 cases were retrospectively reviewed. RESULTS: Tissue specimens were available for 62 of the 75 patients. There were 26 (42%) with no significant histopathologic findings, 13 (21%) with polyps, 5 (8%) cases of endometrial hyperplasia, 2 (3%) with endometrial adenocarcinoma, 12 (19%) with cervical intraepithelial neoplasia (CIN), 1 (2%) with adenosquamous carcinoma of the cervix, 2 (3%) with cervical adenocarcinoma in situ and 1 (2%) case of metastatic breast cancer. The total number of patients with significant histopathology other than polyps was 23 (37%). The median age of the patients was 49 years. There were more cases of endometrial hyperplasia and endometrial cancer (19%) in women 49 years or older than in younger women; only one (3%) case of endometrial hyperplasia was detected in the younger age group (P = .057). Patients who underwent more-aggressive evaluation (colposcopy and biopsies plus endometrial sampling, cone biopsy or hysterectomy) had greater numbers of abnormal histopathologic findings (55%) than patients who underwent endometrial sampling only (21%) or those who underwent colposcopy and biopsy only (33%). This difference approaches statistical significance (P = .057). A significant proportion of patients with a history of CIN and a cytologic diagnosis of AGUS were found to have CIN (47%), while 8% of those with no history of CIN were found to have CIN (P = .002). Fifty percent of patients with a history of cancer (all had breast cancer) and AGUS had abnormal histopathology. Patients with a subclassification of AGUS "favor neoplasia" had a greater proportion of significant histopathology (72%) as compared to AGUS "unspecified" (26%) and AGUS "favor reactive" (20%) (P = .003). CONCLUSION: A significant proportion of women with a cytologic diagnosis of AGUS have abnormal histopathology. Heightened awareness should be raised in patients with AGUS and a history of CIN or cancer and in those with the AGUS subclassification "favor neoplasia."