Trombólise em paciente jovem com tromboembolia pulmonar aguda de risco intermediário alto bem sucedida / Thrombolysis in a young patient with acute intermediate high-risk acute pulmonary embolism

INTRODUÇÃO: O Tromboembolismo pulmonar (TEP) agudo é uma condição bastante prevalente e potencialmente fatal, é a terceira maior causa de mortalidade cardiovascular mundial, sendo crucial suspeita e condução adequadas. Após diagnóstico do TEP agudo, deve-se avaliar sua repercussão clínica, sendo considerado de alto risco aquele com instabilidade hemodinâmica, devendo ser tratado com trombolítico para reperfusão. Esta conduta, nos casos de risco intermediário é controversa. Relato: Relato de caso de paciente sexo feminino, 33 anos, obesa e portadora de sd ovário policístico, que procurou pronto socorro (PS)por dispnéia progressiva e dor torácica opressiva há 10 dias. Diagnosticada com TEP após Angiotomografia Tórax e estratificada como risco intermediário alto. Paciente apresentava AngioCT Tórax com falha de enchimento importante em bifurcação das arterias pulmonares (oclusão > 50% luz). Observado em ECO TT da admissão (urgência) aumento moderado câmaras cardíacas direitas, hipocontratilidade de segmento basal e parede livre de VD, com presença hipercontratilidade em ápice de VD (sinal McCONNEL). Dosagem NT pro-BNP 2740,00 (Valor Normalidade < 125). Paciente apresentava-se sintomática porém mantendo estabilidade hemodinâmica. Fora então optado por terapia trombólise com alteplase 100mg em 02 horas. Houve resposta e evolução satisfatória. Em ECO TT (após 10 dias) houve melhora função sistolica VD e de Hipertensão Pulmonar em comparação ao exame prévio. Recebeu alta em uso de Anticoagulante Oral varfarina, com dispneia Classe Funcional II. Feito contato telefônico com paciente após 10 meses, referindo dispneia CF I, sem limitação para atividades diárias. CONCLUSÃO: O tratamento do TEP risco intermediário alto é controverso em protocolos mundiais; A conduta apresentada com trombólise foi de suma importância para o desfecho apresentado, evitando que uma paciente jovem evoluísse para insuficiência cardíaca com interferência importante em sua qualidade de vida.

Protecting my turf: The moderating role of generational differences on the relationships between self-direction and hedonism values and reactions to generational diversity.

Drawing from basic human values theory and generational identity theory, we hypothesize that two self-focused values, self-direction and hedonism, will be negatively associated with reactions to generational diversity initiatives, and that this relationship will differ between millennials and non-millennials. As expected, our findings illustrate that self-direction and hedonism are negatively related to reactions to generational diversity initiatives. Additionally, self-direction's influence on reactions to diversity initiatives is significantly higher for non-millennials than millennials. These findings suggest that generational differences affect cognitive processes surrounding reactions to generational diversity initiatives.

One-Year Effect of the Medicare Annual Wellness Visit on Detection of Cognitive Impairment: A Cohort Study.

OBJECTIVES: To examine the effect of the Medicare Annual Wellness Visit (AWV) on the detection of cognitive impairment and on follow-up cognitive care for older adults. DESIGN: Retrospective matched-cohort study. SETTING: United States. PARTICIPANTS: A 5% random sample of fee-for-service Medicare beneficiaries continuously enrolled for 12 months before and after an index ambulatory visit occurring from 2011 to 2013 with no claims evidence of cognitive impairment before index. MEASUREMENTS: Outcomes include 12-month post-index visit claims-based measurements of cognitive impairment, including new Alzheimer's disease and related dementia (ADRD) diagnoses; medications for ADRD; and cognitive care-related diagnostic examination such as neurobehavioral testing, brain imaging, and blood tests for thyroid-stimulating hormone (TSH), serum B12, folate, and syphilis. We also measured changes in burden of anticholinergic medication. RESULTS: There were no clinically relevant differences between the AWV and control groups in the rates of incident ADRD diagnoses (6.16% vs 6.86%, p<.001) and initiation of ADRD medications (1.00% vs 1.08%, p=.15), although there were differences favoring the AWV group in rates of TSH (39.80% vs 28.36%, p<.001), B12 (9.41% vs 6.97%, p<.001), folate (4.76% vs 3.72%, p<.001), and neurobehavioral (0.75% vs 0.55%, p<.001) testing. CONCLUSIONS: Although the AWV is correlated with an increase in some measures of cognitive care, such as laboratory testing for reversible causes of cognitive impairment, it does not appear to substantially increase recognition of undetected ADRD.

Extended gamma-ray sources around pulsars constrain the origin of the positron flux at Earth.

The unexpectedly high flux of cosmic-ray positrons detected at Earth may originate from nearby astrophysical sources, dark matter, or unknown processes of cosmic-ray secondary production. We report the detection, using the High-Altitude Water Cherenkov Observatory (HAWC), of extended tera-electron volt gamma-ray emission coincident with the locations of two nearby middle-aged pulsars (Geminga and PSR B0656+14). The HAWC observations demonstrate that these pulsars are indeed local sources of accelerated leptons, but the measured tera-electron volt emission profile constrains the diffusion of particles away from these sources to be much slower than previously assumed. We demonstrate that the leptons emitted by these objects are therefore unlikely to be the origin of the excess positrons, which may have a more exotic origin.

Analysis of the psychological impact of cancer-related symptoms on patients with non-small cell lung cancer.

BACKGROUND: Patients with non-small cell lung cancer (NSCLC) experience adverse physical symptoms because of cancer, cancer treatment, and comorbidities. The relations among Cancer-Related Symptoms, Functional Impairment, and Psychological Symptoms in patients with NSCLC is not well understood. METHODS: Retrospective analysis of patient-reported symptoms with the 38-item Patient Care Monitor survey, collected in routine clinical care for 1138 patients with NSCLC at eight US community oncology practices. Study sample was randomly split, and structural equation models examined the direct and mediated effects of Cancer-Related Symptoms and Functional Impairment on symptoms of acute distress (Distress) and depression (Despair) in the training sample. The training model was cross validated in testing sample. Results are presented for the full model using the entire sample. RESULTS: Patients were 48.3% female, with mean age of 66.0 years. The most common comorbidities were anemia (60.8%) and respiratory disease (24.5%). Severity of Cancer-Related Symptoms was strongly and positively related to Functional Impairment and Psychological Symptoms in both training and testing models. The modeled effect of Functional Impairment on Distress and Despair was significant in the overall model using the total sample, and significant or near-significant in the training and testing models. The mediated effect of Cancer-Related Symptoms by Functional Impairment tended to be weaker than its direct modeled effect on Distress and Despair. CONCLUSIONS: Despite prior research suggesting that Functional Impairment plays a larger role than symptom burden in depression in NSCLC, the independent modeled effects of Functional Impairment were no greater than the direct modeled effects of Cancer-Related Symptoms. Copyright © 2016 John Wiley & Sons, Ltd.

Treatment patterns and cost-effectiveness of first line treatment of advanced non-squamous non-small cell lung cancer in Medicare patients.

AIM: To assess the cost-effectiveness of first-line pemetrexed/platinum and other commonly administered regimens in a representative US elderly population with advanced non-squamous non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: This study utilized the Surveillance Epidemiology and End Results (SEER) cancer registry linked to Medicare claims records. The study population included all SEER-Medicare patients diagnosed in 2008-2009 with advanced non-squamous NSCLC (stages IIIB-IV) as their only primary cancer and who started chemotherapy within 90 days of diagnosis. The study evaluated the four most commonly observed first-line regimens: paclitaxel/carboplatin, platinum monotherapy, pemetrexed/platinum, and paclitaxel/carboplatin/bevacizumab. Overall survival and total healthcare cost comparisons as well as incremental cost-effectiveness ratios (ICERs) were calculated for pemetrexed/platinum vs each of the other three. Unstratified analyses and analyses stratified by initial disease stage were conducted. RESULTS: The final study population consisted of 2,461 patients. Greater administrative censorship of pemetrexed recipients at the end of the study period disproportionately reduced the observed mean survival for pemetrexed/platinum recipients. The disease stage-stratified ICER analysis found that the pemetrexed/platinum incurred total Medicare costs of $536,424 and $283,560 per observed additional year of life relative to platinum monotherapy and paclitaxel/carboplatin, respectively. The pemetrexed/platinum vs triplet comparator analysis indicated that pemetrexed/platinum was associated with considerably lower total Medicare costs, with no appreciable survival difference. LIMITATIONS: Limitations included differential censorship of the study regimen recipients and differential administration of radiotherapy. CONCLUSIONS: Pemetrexed/platinum yielded either improved survival at increased cost or similar survival at reduced cost relative to comparator regimens in the treatment of advanced non-squamous NSCLC. Limitations in the study methodology suggest that the observed pemetrexed survival benefit was likely conservative.

Comparison of demographics, treatment patterns, health care utilization, and costs among elderly patients with extensive-stage small cell and metastatic non-small cell lung cancers.

BACKGROUND: Limited data exist regarding real-world treatment patterns, resource utilization, and costs of extensive-stage small cell lung cancer (esSCLC) among elderly patients in the United States. While abundant data are available on treatment patterns in metastatic non-small cell lung cancer (mNSCLC), to our knowledge no data exist comparing costs and resource use between patients with esSCLC or mNSCLC. METHODS: We retrospectively analyzed administrative claims data (2000-2008) of patients aged ≥65 years from the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database. Patients were selected on the basis of having newly diagnosed esSCLC (n=5,855) or mNSCLC (n=24,090) during 1/1/2000-12/31/2005, and were required to have received cancer-directed therapy. Survival and other measures were compared between esSCLC and mNSCLC patients using Kaplan-Meier log-rank and univariate chi-square and t-tests. Study measures were followed from first diagnosis date of either esSCLC or mNSCLC until the earlier of death or end of the database. RESULTS: Survival between the cohorts did not differ significantly: mean of 10.4 months for esSCLC patients versus 11.1 months for mNSCLC; median survival was 7.4 months versus 5.9 months. A higher percentage of mNSCLC patients (vs. esSCLC) received radiation therapy (75.6% vs. 65.4%; P < 0.001) and surgery (13.6% vs. 7.8%; P < 0.001) during the metastatic disease period. Conversely, a higher percentage of esSCLC patients than mNSCLC patients received chemotherapy (85.5% vs. 60.3%; P < 0.001), red blood-cell transfusion (20.7% vs. 10.9%; P < 0.001), platelet transfusion (5.6% vs. 1.8%; P < 0.001), and growth-factor support (59.0% vs. 39.5%; P < 0.001). esSCLC patients incurred higher lifetime disease-related costs ($44,167 vs. $37,932; P < 0.001) and all-cause costs ($70,549 vs. $67,176; P < 0.001) than mNSCLC patients. CONCLUSIONS: Lifetime total and disease-related costs per patient were high. Increased use of chemotherapy, supportive care therapies (including growth factors), and disease-related hospitalizations were observed in esSCLC patients as compared with mNSCLC patients. Disease-related and all-cause costs for esSCLC also exceeded those of mNSCLC, except for hospice and skilled nursing services. Survival and per-patient costs for both groups underscore the unmet medical need for more effective therapies in patients with esSCLC or mNSCLC.

Blood pressure-lowering effect of simvastatin: a placebo-controlled randomized clinical trial with 24-h ambulatory blood pressure monitoring.

Part of the efficacy of statins in the prevention of cardiovascular events can be attributed to their blood pressure-lowering effect, but clinical trials primarily designed to investigate this effect are scarce. In a double-blind parallel placebo-controlled clinical trial with ambulatory blood pressure (ABP) monitoring, 79 hypertensive patients were randomly assigned to 40 mg of simvastatin (n=40) or placebo (n=39) taken in the morning for 2 months. Between-group deltas of ABP change, adjusted for the corresponding baseline BP, were 2.8 mm Hg (95% CI: 0.4-5.1; P=0.02) for 24-h diastolic blood pressure (DBP), 4.2 mm Hg (95% CI: 0.1-8.4; P=0.04) for daytime systolic BP and 3.1 mm Hg (95% CI: 0.4-5.9; P=0.02) for daytime DBP. There was no effect on nighttime BP. There was an interaction between baseline cholesterol levels and treatment effect, which was restricted to patients with cholesterol above the median of the whole sample. There was no significant change in office BP. In conclusion, simvastatin lowers ABP in patients with hypertension, particularly in the presence of higher levels of cholesterol. This effect may contribute to the beneficial effects of statins in the prevention of cardiovascular disease.

Healthcare costs and workloss burden of patients with chemotherapy-associated peripheral neuropathy in breast, ovarian, head and neck, and nonsmall cell lung cancer.

Objective. Chemotherapy-associated peripheral neuropathy (CAPN) is a painful side-effect of chemotherapy. This study assesses healthcare and workloss costs of CAPN patients with breast, ovarian, head/neck, or non-small cell lung cancer (NSCLC) from a third-party payor/employer perspective. Research Design and Methods. Patients with qualifying tumors, and claims for chemotherapy and services indicative of peripheral neuropathy (PN) within 9-months of chemotherapy (cases) were identified in a administrative claims database. Cases were matched 1 : 1 to controls with no PN-related claims based on demographics, diabetes history and propensity for having a diagnosis of PN during the study period (based on resource use and comorbidities in a 3-month baseline period). Average all-cause healthcare costs, resource use and workloss burden were determined. Results. Average healthcare costs were $17,344 higher for CAPN cases than their non-CAPN controls, with outpatient costs being the highest component (with cases having excess costs of $8,092). On average, each CAPN case had 12 more outpatient visits than controls, and spent more days in the hospital. Workloss burden was higher for cases but not statistically different from controls. Conclusion. This study establishes that breast, ovarian, head/neck, or NSCLC patients with CAPN have significant excess healthcare costs and resource use.

Illness-associated productivity costs among women with employer-sponsored insurance and newly diagnosed breast cancer.

OBJECTIVE: Determine lost work time and job attrition for incident breast cancer (BC). METHODS: The cases were employed women, aged 18 to 64, with BC identified by a validated algorithm between 1999 and 2005, from claims (MarketScan) and attendance databases. Controls without cancer were matched 3:1 on age, comorbidity, and index year. RESULTS: First-year mean disability days were 60 (cases, N = 880) versus 5 (controls, N = 2640) (P < 0.001). The first-year disability costs were $4900 for cases versus $385 for controls (P < 0.001). In years 2 through 4, the disability days and associated costs were similar for the cases versus controls. After 4 years, 56.4% of cases were still enrolled in the employer-sponsored insurance programs compared to 6.5% of controls (P < 0.001). CONCLUSIONS: The lost work associated with BC is substantial in the first year after diagnosis. Employee retention is much higher for BC cases versus controls.

A retrospective claims analysis of combination therapy in the treatment of adult attention-deficit/hyperactivity disorder (ADHD).

BACKGROUND: Combination therapy in managing psychiatric disorders is not uncommon. While combination therapy has been documented for depression and schizophrenia, little is known about combination therapy practices in managing attention-deficit/hyperactivity disorder (ADHD). This study seeks to quantify the combination use of ADHD medications and to understand predictors of combination therapy. METHODS: Prescription dispensing events were drawn from a U.S. national claims database including over 80 managed-care plans. Patients studied were age 18 or over with at least 1 medical claim with a diagnosis of ADHD (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 314.0), a pharmacy claim for ADHD medication during the study period July 2003 to June 2004, and continuous enrollment 6 months prior to and throughout the study period. Dispensing events were grouped into 6 categories: atomoxetine (ATX), long-acting stimulants (LAS), intermediate-acting stimulants (IAS), short-acting stimulants (SAS), bupropion (BUP), and Alpha-2 Adrenergic Agonists (A2A). Events were assigned to calendar months, and months with combined use from multiple categories within patient were identified. Predictors of combination therapy for LAS and for ATX were modeled for patients covered by commercial plans using logistic regression in a generalized estimating equations framework to adjust for within-patient correlation between months of observation. Factors included age, gender, presence of the hyperactive component of ADHD, prior diagnoses for psychiatric disorders, claims history of recent psychiatric visit, insurance plan type, and geographic region. RESULTS: There were 18,609 patients identified representing a total of 11,886 months of therapy with ATX; 40,949 months with LAS; 13,622 months with IAS; 38,141 months with SAS; 22,087 months with BUP; and 1,916 months with A2A. Combination therapy was present in 19.7% of continuing months (months after the first month of therapy) for ATX, 21.0% for LAS, 27.4% for IAS, 23.1% for SAS, 36.9% for BUP, and 53.0% for A2A.For patients receiving LAS, being age 25-44 or age 45 and older versus being 18-24 years old, seeing a psychiatrist, having comorbid depression, or having point-of-service coverage versus a Health Maintenance Organization (HMO) resulted in odds ratios significantly greater than 1, representing increased likelihood for combination therapy in managing adult ADHD.For patients receiving ATX, being age 25-44 or age 45 and older versus being 18-24 years old, seeing a psychiatrist, having a hyperactive component to ADHD, or having comorbid depression resulted in odds ratios significantly greater than 1, representing increased likelihood for combination therapy in managing adult ADHD. CONCLUSION: ATX and LAS are the most likely drugs to be used as monotherapy. Factors predicting combination use were similar for months in which ATX was used and for months in which LAS was used except that a hyperactive component to ADHD predicted increased combination use for ATX but not for LAS.

Teaching the "hybrid approach": a novel swine model of muscular ventricular septal defect.

This report describes a reproducible swine model for creating muscular ventricular septal defects (VSDs). The model not only facilitates the development and modification of hybrid techniques for closing muscular VSDs, but also serves as a teaching tool that allows operators to become accustomed to the specific technical requirements necessary when using the hybrid approach to perform periventricular VSD device closure. The authors' institutional experience using this novel animal model is presented.

Characteristics of patients initiating raloxifene compared to those initiating bisphosphonates.

BACKGROUND: Both raloxifene and bisphosphonates are indicated for the prevention and treatment of postmenopausal osteoporosis, however these medications have different efficacy and safety profiles. It is plausible that physicians would prescribe these agents to optimize the benefit/risk profile for individual patients. The objective of this study was to compare demographic and clinical characteristics of patients initiating raloxifene with those of patients initiating bisphosphonates for the prevention and treatment of osteoporosis. METHODS: This study was conducted using a retrospective cohort design. Female beneficiaries (45 years and older) with at least one claim for raloxifene or a bisphosphonate in 2003 through 2005 and continuous enrollment in the previous 12 months and subsequent 6 months were identified using a collection of large national commercial, Medicare supplemental, and Medicaid administrative claims databases (MarketScan). Patients were divided into two cohorts, a combined commercial/Medicare cohort and a Medicaid cohort. Within each cohort, characteristics (demographic, clinical, and resource utilization) of patients initiating raloxifene were compared to those of patients initiating bisphosphonate therapy. Group comparisons were made using chi-square tests for proportions of categorical measures and Wilcoxon rank-sum tests for continuous variables. Logistic regression was used to simultaneously examine factors independently associated with initiation of raloxifene versus a bisphosphonate. RESULTS: Within both the commercial/Medicare and Medicaid cohorts, raloxifene patients were younger, had fewer comorbid conditions, and fewer pre-existing fractures than bisphosphonate patients. Raloxifene patients in both cohorts were less likely to have had a bone mineral density (BMD) screening in the previous year than were bisphosphonate patients, and were also more likely to have used estrogen or estrogen/progestin therapy in the previous 12 months. These differences remained statistically significant in the multivariate model. CONCLUSION: In this sample of patients enrolled in commercial, Medicare, and Medicaid plans, patients who initiated raloxifene treatment differed from those initiating bisphosphonates. Raloxifene patients were younger, had better overall health status and appeared to be less likely to have risk factors for new osteoporotic fractures than bisphosphonate patients. Differences in the clinical profiles of these agents may impact prescribing decisions. Investigators using observational data to make comparisons of treatment outcomes associated with these medications should take these important differences in patient characteristics into consideration.

Factors associated with initiation with atomoxetine versus stimulants in the treatment of adults with ADHD: retrospective analysis of administrative claims data.

OBJECTIVE: To determine which factors are associated with use of atomoxetine (ATX) relative to stimulant medications (STIMs) for treatment initiation in adults with attention-deficit/hyperactivity disorder (ADHD). A similar exploratory analysis of the use of ATX versus STIMs in children has been published previously. METHODS: This was an exploratory analysis using a retrospective observational cohort design applied to administrative pharmacy and medical claims from an integrated managed care database. Patients were identified if they had at least 1 administrative claim with a diagnosis for ADHD. Treatment .initiation. was defined as a new prescription for an ADHD medication preceded by 3 months without similar therapy. Two separate analyses were done, one comparing medication starts for ATX with those of any STIM, the other comparing starts of ATX with long-acting stimulants (LA-STIMs). Logistic regression analyses of prior-year administrative claims were used to compare the frequencies of differential predictors of the use of medication. RESULTS: There were 10,359 patients aged >18 years who initiated ATX or a STIM between April and December of 2003 and had at least 1 claim with a diagnosis for ADHD (International Classification of Diseases, Ninth Revision, Clinical Modification codes 314.0x). Approximately one third (28 of 82) of the comparisons related to patient demographics, diagnostic history, and previous treatment history was found to be related to the use of ATX versus STIMs and/or LA-STIMs. Patients were more likely to have received ATX than a STIM if they had prior diagnoses of bipolar disorder (odds ratio [OR] 1.47; 95% confidence interval [CI], 1.16-1.87), alcohol dependence (OR 1.80; 95% CI, 1.26-2.58), anxiety (OR 1.21; 95% CI, 1.05-1.40), previous use of antipsychotic medication (OR 1.55; 95% CI, 1.22-1.96), or previous antidepressant use (OR 1.14; 95% CI, 1.01-1.28). Prior use of behavioral services greater than 12 visits was associated with the use of ATX relative to STIMs (OR 1.46; 95% CI, 1.20-1.77) but not for ATX relative to LA-STIMs. Conversely, ATX was used less often than STIMs for initiation in younger adults aged 18 to 24 years (OR 0.66; 95% CI, 0.58-0.74), female patients (OR 0.89, 95% CI, 0.80-0.99), patients with personality disorders (OR 0.53; 95% CI, 0.34-0.82), and those with prior use of STIMs (OR 0.62; 95% CI, 0.56-0.69). The majority of comparisons (54 of 82) related to demographics, diagnostic history, and previous treatment history did not show statistically significant associations. CONCLUSIONS: During the first year of ATX.s market introduction, some differences in the frequency of various clinical factors were found in adults treated with ATX compared with those patients who received STIMs. This association may suggest that STIMs and ATX are used to address different treatment needs in adults with ADHD. Future studies will need to determine the significance of the practice pattern differences inferred here and if they persist after ATX has been on the market longer.

Predictors of selecting atomoxetine therapy for children with attention-deficit-hyperactivity disorder.

STUDY OBJECTIVE: To investigate predictors of beginning treatment with atomoxetine, a new attention-deficit-hyperactivity disorder (ADHD) drug, shortly after it was introduced into the marketplace compared with well-established stimulants for children in a managed care setting. DESIGN: Retrospective cohort analysis. DATA SOURCE: Managed care claims database. PATIENTS: A total of 45,144 patients aged 18 years or younger who filled a prescription for an ADHD-specific drug. MEASUREMENTS AND MAIN RESULTS: For each patient, the most recent start of therapy between April 1 and December 31, 2003, was categorized by drug: atomoxetine; any stimulant; or short-, intermediate-, or long-acting stimulant. The categories were based on the first use of the drug without use of a drug in that same category in the previous 3 months. Logistic regression analysis of past-year administrative claims was applied to determine predictors of the start of specific pharmacotherapy. Patients with a claim of ADHD with hyperactivity were 1.50 times more likely to begin therapy with atomoxetine than with any stimulant (95% confidence interval [CI] 1.42-1.58). Patients with a history of tics (odds ratio [OR] 3.11, 95% CI 2.54-3.82), anxiety (OR 1.35, 95% CI 1.24-1.48), pervasive developmental disorders (OR 2.00, 95% CI 1.69-2.37), or frequent use of behavioral care services (OR 1.34, 95% CI 1.21-1.48) were predisposed to starting treatment with atomoxetine relative to any stimulant, but patients with obesity were not (OR 0.68, 95% CI 0.53-0.87). A short-acting stimulant was specifically preferred for patients with narcolepsy or hypersomnolence (OR 0.33, 95% CI 0.20-0.56). Alcohol dependence, but not drug dependence or drug abuse, was predictive of the selection of atomoxetine over a short-acting stimulant (OR 2.98, 95% CI 1.25-7.09). CONCLUSION: Atomoxetine therapy was systematically preferred for patients with psychiatric comorbidities, contraindications to stimulants, or relatively heavy use of behavioral health care.

In-depth, longitudinal analysis of viral quasispecies from an individual triply infected with late-stage human immunodeficiency virus type 1, using a multiple PCR primer approach.

Co-infections with more than one human immunodeficiency virus type 1 (HIV-1) subtype appear to be the source of new recombinant strains and may be commonplace in high-risk cohorts exposed to multiple subtypes. Many potential dual infections have been identified during the HIV Superinfection Study in Mbeya, Tanzania, where 600 female bar workers who are highly exposed to subtypes A, C, and D have been evaluated every 3 months for over 3 years by use of the MHAacd HIV-1 genotyping assay. Here we describe an in-depth, longitudinal analysis of the viral quasispecies in a woman who was triply infected with HIV-1 and who developed AIDS and passed away 15 months after enrollment. The MHA results obtained at 0, 3, 6, 9, and 12 months revealed dual-probe reactivities and shifts in subtype over time, indicating a potential dual infection and prompting further investigation. The multiple infection was confirmed by PCR amplification of three genome regions by a multiple primer approach, followed by molecular cloning and sequencing. A highly complex viral quasispecies was found, including several recombinant forms, with vpu/gp120 being the most diverse region. A significant fluctuation in molecular forms over time was observed, showing that the serial sample format is highly desirable, if not essential, for the identification of multiple infections. In a separate experiment, we confirmed that the detection of co-infections is more efficient with the use of multiple amplification primers to overcome the primer bias that results from the enormous diversity in the HIV-1 genome.

The cholecystocolic bypass with jejunal interposition graft for bile acid depletion in bile and portal blood in guinea pigs.

Ileal bypass and cholecystostomy are used in children with selected cholestatic diseases to lower the bile acid (BA) levels in bile and blood and improve outcome. The efficacy of a cholecystocolic bypass in achieving the same goals was investigated in guinea pigs. In the study group (n=7), a cholecystocolic bypass was performed using a jejunal graft interposed between the gallbladder and the cecum. In the control group (n=5), a cholecystojejunal bypass was performed with a similar graft implanted in the proximal jejunum. Total BA concentration was measured in bile and portal blood at surgery (D0) and 30 days later (D30) by pooling the concentrations of 7 individual BA. D30/D0 BA ratios were compared. All animals developed normally without clinical symptoms. A 76% reduction in the bile T-BA levels was observed in both groups (p<0.05). A 80% decrease of T-BA levels was observed in portal vein in study group (p<0.05), suggesting that ileal bile flow and BA ileal reabsorption were highly impaired. No change in portal vein BA levels was observed in control group. Cholecystocolic bypass led to a significant loss of bile acids in guinea pigs and might be considered for bile diversion in pediatric patients with selected cholestatic diseases.

[Comparison of plasma total homocysteine determinations in 9 French hospital laboratories by using 6 different methods]. / Comparaison du dosage de l'homocystéine plasmatique totale dans neuf laboratoires par six techniques différentes.

A lot of methods are now available for total plasma homocysteine (tHcy) determination. Commercial kits using immunoassay, easier to use, begin to supplant in-house laboratory methods. Our aim is to evaluate the interchangeability of tHcy measurements in 9 French hospital laboratories. Six different method types were used: 2 gas chromatography-mass spectrometry (GC-MS), 2 HPLC with fluorescence detection subdivided in one in-house method and one commercial kit (Bio-Rad ), 3 fluorescence polarization immunoassays (FPIA), 1 enzyme immunoassay, 1 amino acid analyser, 1 capillary electrophoresis coupled with laser-induced fluorescence detection (EC-LIF). Each laboratory analysed 41 patient's plasma samples in which 8 samples contained added homocystine. Results were analysed for imprecision, recovery, and methodological differences. The mean among-laboratory imprecision (CV) ranged from 12.5 to 18% in function of plasma sample type and was identical to the mean among-method variation. In terms of recovery, we obtained underestimated results with immunoassays. The bias relative to the GC-MS method was less than 12.5% except for two laboratories, one using FPIA assay and the other EC-LIF. In conclusion, the interchangeability of tHcy results between laboratories is not satisfactory and does not allow us to evaluate cardiovascular risk linked to moderate increases of tHcy.

Bifidobacterium animalis strain DN-173 010 shortens the colonic transit time in healthy women: a double-blind, randomized, controlled study.

BACKGROUND: A previous study has suggested that Bifidobacterium animalis DN-173 010 shortens the colonic transit time in women. AIM: To confirm this effect and to determine whether modifications of the faecal bacterial mass and/or faecal secondary bile salts may be the explanation. METHODS: A double-blind, cross-over study was performed. Thirty-six healthy women were studied in four consecutive 10-day periods. During periods 2 and 4, they ingested three 125 g cups per day of a fermented milk which was either a product containing B. animalis DN-173 010 or a control without bifidobacteria. Periods 1 and 3 were run-in and washout periods, respectively. The total and segmental colonic transit times were assessed using a pellet method. In 12 subjects, all stools were collected and analysed for pH, faecal weight, bacterial mass and bile acids. RESULTS: The total and sigmoid transit times were significantly shorter during dosing with B. animalis compared to the control period. The other transit times, faecal weight, pH, bacterial mass and bile acids were not significantly affected. CONCLUSIONS: B. animalis DN-173 010 shortens the colonic transit time in healthy women. This effect is not explained by modifications of the faecal bacterial mass or secondary bile acids.