Sample records for target patient populations

  1. Targeted population screening of late onset Pompe disease in unspecified myopathy patients for Korean population.

    PubMed

    Lee, Jung Hwan; Shin, Jin-Hong; Park, Hyung Jun; Kim, Sook Za; Jeon, Young Mi; Kim, Hye Kyoung; Kim, Dae-Seong; Choi, Young-Chul

    2017-06-01

    We performed targeted population screening of late onset Pompe disease (LOPD) in unspecified myopathy patients, because early diagnosis is difficult due to its heterogeneous clinical features. We prospectively enrolled 90 unrelated myopathic patients who had one or more signs out of five LOPD-like clinical findings (proximal weakness, axial weakness, lingual weakness, respiratory difficulty, idiopathic hyperCKemia). Acid alpha glucosidase activity was evaluated with dried blood spot and mixed leukocyte simultaneously. For a final diagnosis of LOPD, 16 patients with decreased enzyme activity were genotyped by GAA molecular analysis. We found two patients with LOPD (2.2%), and the remaining 14 patients had at least one G576S or E689K mutation, known as the pseudodeficiency allele. Acid alpha glucosidase activity of LOPD patients was significantly lower than that of patients with at least one pseudodeficiency allele (p = 0.017). This study is the first LOPD screening study for targeted Korean population, and more generally, an Asian population. Our findings suggest that for diagnosis of LOPD in Asian population, modified cutoff value of acid alpha glucosidase activity with dry blood spot considering that of patients having heterozygote pathogenic variants or pseudodeficiency alleles may reduce time and cost requirements and increase the comfort of patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Transfer of genetic therapy across human populations: molecular targets for increasing patient coverage in repeat expansion diseases

    PubMed Central

    Varela, Miguel A; Curtis, Helen J; Douglas, Andrew GL; Hammond, Suzan M; O'Loughlin, Aisling J; Sobrido, Maria J; Scholefield, Janine; Wood, Matthew JA

    2016-01-01

    Allele-specific gene therapy aims to silence expression of mutant alleles through targeting of disease-linked single-nucleotide polymorphisms (SNPs). However, SNP linkage to disease varies between populations, making such molecular therapies applicable only to a subset of patients. Moreover, not all SNPs have the molecular features necessary for potent gene silencing. Here we provide knowledge to allow the maximisation of patient coverage by building a comprehensive understanding of SNPs ranked according to their predicted suitability toward allele-specific silencing in 14 repeat expansion diseases: amyotrophic lateral sclerosis and frontotemporal dementia, dentatorubral-pallidoluysian atrophy, myotonic dystrophy 1, myotonic dystrophy 2, Huntington's disease and several spinocerebellar ataxias. Our systematic analysis of DNA sequence variation shows that most annotated SNPs are not suitable for potent allele-specific silencing across populations because of suboptimal sequence features and low variability (>97% in HD). We suggest maximising patient coverage by selecting SNPs with high heterozygosity across populations, and preferentially targeting SNPs that lead to purine:purine mismatches in wild-type alleles to obtain potent allele-specific silencing. We therefore provide fundamental knowledge on strategies for optimising patient coverage of therapeutics for microsatellite expansion disorders by linking analysis of population genetic variation to the selection of molecular targets. PMID:25990798

  3. Transfer of genetic therapy across human populations: molecular targets for increasing patient coverage in repeat expansion diseases.

    PubMed

    Varela, Miguel A; Curtis, Helen J; Douglas, Andrew G L; Hammond, Suzan M; O'Loughlin, Aisling J; Sobrido, Maria J; Scholefield, Janine; Wood, Matthew J A

    2016-02-01

    Allele-specific gene therapy aims to silence expression of mutant alleles through targeting of disease-linked single-nucleotide polymorphisms (SNPs). However, SNP linkage to disease varies between populations, making such molecular therapies applicable only to a subset of patients. Moreover, not all SNPs have the molecular features necessary for potent gene silencing. Here we provide knowledge to allow the maximisation of patient coverage by building a comprehensive understanding of SNPs ranked according to their predicted suitability toward allele-specific silencing in 14 repeat expansion diseases: amyotrophic lateral sclerosis and frontotemporal dementia, dentatorubral-pallidoluysian atrophy, myotonic dystrophy 1, myotonic dystrophy 2, Huntington's disease and several spinocerebellar ataxias. Our systematic analysis of DNA sequence variation shows that most annotated SNPs are not suitable for potent allele-specific silencing across populations because of suboptimal sequence features and low variability (>97% in HD). We suggest maximising patient coverage by selecting SNPs with high heterozygosity across populations, and preferentially targeting SNPs that lead to purine:purine mismatches in wild-type alleles to obtain potent allele-specific silencing. We therefore provide fundamental knowledge on strategies for optimising patient coverage of therapeutics for microsatellite expansion disorders by linking analysis of population genetic variation to the selection of molecular targets.

  4. A Distribution-based Method for Assessing The Differences between Clinical Trial Target Populations and Patient Populations in Electronic Health Records

    PubMed Central

    Li, Y.; Ryan, P.; Zhang, Y.; Liu, F.; Gao, J.; Bigger, J.T.; Hripcsak, G.

    2014-01-01

    Summary Objective To improve the transparency of clinical trial generalizability and to illustrate the method using Type 2 diabetes as an example. Methods Our data included 1,761 diabetes clinical trials and the electronic health records (EHR) of 26,120 patients with Type 2 diabetes who visited Columbia University Medical Center of New-York Presbyterian Hospital. The two populations were compared using the Generalizability Index for Study Traits (GIST) on the earliest diagnosis age and the mean hemoglobin A1c (HbA1c) values. Results Greater than 70% of Type 2 diabetes studies allow patients with HbA1c measures between 7 and 10.5, but less than 40% of studies allow HbA1c<7 and fewer than 45% of studies allow HbA1c>10.5. In the real-world population, only 38% of patients had HbA1c between 7 and 10.5, with 12% having values above the range and 52% having HbA1c<7. The GIST for HbA1c was 0.51. Most studies adopted broad age value ranges, with the most common restrictions excluding patients >80 or <18 years. Most of the real-world population fell within this range, but 2% of patients were <18 at time of first diagnosis and 8% were >80. The GIST for age was 0.75. Conclusions We contribute a scalable method to profile and compare aggregated clinical trial target populations with EHR patient populations. We demonstrate that Type 2 diabetes studies are more generalizable with regard to age than they are with regard to HbA1c. We found that the generalizability of age increased from Phase 1 to Phase 3 while the generalizability of HbA1c decreased during those same phases. This method can generalize to other medical conditions and other continuous or binary variables. We envision the potential use of EHR data for examining the generalizability of clinical trials and for defining population-representative clinical trial eligibility criteria. PMID:25024761

  5. Epidemiology of hepatocellular carcinoma: target population for surveillance and diagnosis.

    PubMed

    Tang, An; Hallouch, Oussama; Chernyak, Victoria; Kamaya, Aya; Sirlin, Claude B

    2018-01-01

    Hepatocellular carcinoma (HCC) is the sixth most common cancer and the second leading cause of cancer mortality worldwide. Incidence rates of liver cancer vary widely between geographic regions and are highest in Eastern Asia and sub-Saharan Africa. In the United States, the incidence of HCC has increased since the 1980s. HCC detection at an early stage through surveillance and curative therapy has considerably improved the 5-year survival. Therefore, medical societies advocate systematic screening and surveillance of target populations at particularly high risk for developing HCC to facilitate early-stage detection. Risk factors for HCC include cirrhosis, chronic infection with hepatitis B virus (HBV), hepatitis C virus (HCV), excess alcohol consumption, non-alcoholic fatty liver disease, family history of HCC, obesity, type 2 diabetes mellitus, and smoking. Medical societies utilize risk estimates to define target patient populations in which imaging surveillance is recommended (risk above threshold) or in which the benefits of surveillance are uncertain (risk unknown or below threshold). All medical societies currently recommend screening and surveillance in patients with cirrhosis and subsets of patients with chronic HBV; some societies also include patients with stage 3 fibrosis due to HCV as well as additional groups. Thus, target population definitions vary between regions, reflecting cultural, demographic, economic, healthcare priority, and biological differences. The Liver Imaging Reporting and Data System (LI-RADS) defines different patient populations for surveillance and for diagnosis and staging. We also discuss general trends pertaining to geographic region, age, gender, ethnicity, impact of surveillance on survival, mortality, and future trends.

  6. Setting population targets for mammals using body mass as a predictor of population persistence.

    PubMed

    Hilbers, Jelle P; Santini, Luca; Visconti, Piero; Schipper, Aafke M; Pinto, Cecilia; Rondinini, Carlo; Huijbregts, Mark A J

    2017-04-01

    Conservation planning and biodiversity assessments need quantitative targets to optimize planning options and assess the adequacy of current species protection. However, targets aiming at persistence require population-specific data, which limit their use in favor of fixed and nonspecific targets, likely leading to unequal distribution of conservation efforts among species. We devised a method to derive equitable population targets; that is, quantitative targets of population size that ensure equal probabilities of persistence across a set of species and that can be easily inferred from species-specific traits. In our method, we used models of population dynamics across a range of life-history traits related to species' body mass to estimate minimum viable population targets. We applied our method to a range of body masses of mammals, from 2 g to 3825 kg. The minimum viable population targets decreased asymptotically with increasing body mass and were on the same order of magnitude as minimum viable population estimates from species- and context-specific studies. Our approach provides a compromise between pragmatic, nonspecific population targets and detailed context-specific estimates of population viability for which only limited data are available. It enables a first estimation of species-specific population targets based on a readily available trait and thus allows setting equitable targets for population persistence in large-scale and multispecies conservation assessments and planning. © 2016 The Authors. Conservation Biology published by Wiley Periodicals, Inc. on behalf of Society for Conservation Biology.

  7. Estimated Prevalence of the Target Population for Brain-Computer Interface Neurotechnology in the Netherlands.

    PubMed

    Pels, Elmar G M; Aarnoutse, Erik J; Ramsey, Nick F; Vansteensel, Mariska J

    2017-07-01

    People who suffer from paralysis have difficulties participating in society. Particularly burdensome is the locked-in syndrome (LIS). LIS patients are not able to move and speak but are cognitively healthy. They rely on assistive technology to interact with the world and may benefit from neurotechnological advances. Optimal research and design of such aids requires a well-defined target population. However, the LIS population is poorly characterized and the number of patients in this condition is unknown. Here we estimated and described the LIS patient population in the Netherlands to define the target population for assistive (neuro)technology. We asked physicians in the Netherlands if they had patients suffering from severe paralysis and communication problems in their files. Physicians responding affirmatively were asked to fill out a questionnaire on the patients' status. We sent out 9570 letters to general practitioners (GPs), who reported 83 patients. After first screening, the GPs of 46 patients received the questionnaire. Based on the responses, 26 patients were classified as having LIS. Extrapolation of these numbers resulted in a prevalence of 0.73 patients per 100 000 inhabitants. Notable results from the questionnaire were the percentage of patients with neuromuscular disease (>50%) and living at home (>70%). We revealed an etiologically diverse group of LIS patients. The functioning and needs of these patients were, however, similar and many relied on assistive technology. By characterizing the LIS population, our study may contribute to optimal development of assistive (neuro)technology.

  8. Observed-Score Equating with a Heterogeneous Target Population

    ERIC Educational Resources Information Center

    Duong, Minh Q.; von Davier, Alina A.

    2012-01-01

    Test equating is a statistical procedure for adjusting for test form differences in difficulty in a standardized assessment. Equating results are supposed to hold for a specified target population (Kolen & Brennan, 2004; von Davier, Holland, & Thayer, 2004) and to be (relatively) independent of the subpopulations from the target population (see…

  9. Rabies Vaccination Targets for Stray Dog Populations

    PubMed Central

    Leung, Tiffany; Davis, Stephen A.

    2017-01-01

    The role of stray dogs in the persistence of domestic dog rabies, and whether removal of such dogs is beneficial, remains contentious issues for control programs seeking to eliminate rabies. While a community might reach the WHO vaccination target of 70% for dogs that can be handled, the stray or neighborhood dogs that are too wary of humans to be held are a more problematic population to vaccinate. Here, we present a method to estimate vaccination targets for stray dogs when the dog population is made up of stray, free-roaming, and confined dogs, where the latter two types are considered to have an identifiable owner. The control effort required for stray dogs is determined by the type-reproduction number, T1, the number of stray dogs infected by one rabid stray dog either directly or via any chain of infection involving owned dogs. Like the basic reproduction number R0 for single host populations, T1 determines the vaccination effort required to control the spread of disease when control is targeted at one host type, and there is a mix of host types. The application of T1 to rabies in mixed populations of stray and owned dogs is novel. We show that the outcome is sensitive to the vaccination coverage in the owned dog population, such that if vaccination rates of owned dogs were too low then no control effort targeting stray dogs is able to control or eliminate rabies. The required vaccination level also depends on the composition of the dog population, where a high proportion of either stray or free-roaming dogs implies unrealistically high vaccination levels are required to prevent rabies. We find that the required control effort is less sensitive to continuous culling that increases the death rate of stray dogs than to changes in the carrying capacity of the stray dog population. PMID:28451589

  10. A geodemographic analysis of the Denplan patient population in the North West Region.

    PubMed

    Tickle, M; Blinkhorn, A S; Brown, P J; Matthews, R

    2000-11-11

    To provide a preliminary descriptive investigation of Denplan patients in the North West Region, by plotting the age/gender and payment banding distribution, and to identify the area types where Denplan patients live and the areas in the North West Region where Denplan practices are most likely to thrive. North West Region of England The study included Denplan patients resident in the North West Region. Age/gender and payment banding frequency distributions were constructed. A market penetration ranking report using the Target Market level of the Super Profiles geodemographic classification was produced by a spreadsheet analysis in Microsoft Excel. A Lorenz curve was plotted to graphically represent the output of the market penetration analysis. Following the market penetration analysis the enumeration districts (EDs) of the six top ranked Target Markets in the North West Region were identified and mapped out across the Region. Finally, the number and percentage of EDs in the six top ranked Target Markets were identified for each health authority in the Region. 47,106 patients were registered with Denplan. In all but one 5-year age band (16-20-year-olds) female patients were in the majority. Patients were concentrated (40.5%) into the 40-55 age group. Nearly 50% (22,329) of patients were allocated to the second lowest payment banding. Under 0.5% of patients (N = 199) were categorised into the highest payment band. The Target Markets at the top of the penetration ranking were more affluent in nature, with a strong rural element and an older demographic profile as part of their descriptive titles. At the bottom of the ranking deprived area types with young demographic profiles predominated. About one half (49.9%) of Denplan patients were present in just over a quarter (25.7%) of the total population of the North West Region. The Lorenz curve demonstrated that Super Profiles at Target Market level had an effectiveness of 37.9% in segmenting the population of the North

  11. Assessing the Generalizability of Randomized Trial Results to Target Populations

    PubMed Central

    Stuart, Elizabeth A.; Bradshaw, Catherine P.; Leaf, Philip J.

    2014-01-01

    Recent years have seen increasing interest in and attention to evidence-based practices, where the “evidence” generally comes from well-conducted randomized trials. However, while those trials yield accurate estimates of the effect of the intervention for the participants in the trial (known as “internal validity”), they do not always yield relevant information about the effects in a particular target population (known as “external validity”). This may be due to a lack of specification of a target population when designing the trial, difficulties recruiting a sample that is representative of a pre-specified target population, or to interest in considering a target population somewhat different from the population directly targeted by the trial. This paper first provides an overview of existing design and analysis methods for assessing and enhancing the ability of a randomized trial to estimate treatment effects in a target population. It then provides a case study using one particular method, which weights the subjects in a randomized trial to match the population on a set of observed characteristics. The case study uses data from a randomized trial of School-wide Positive Behavioral Interventions and Supports (PBIS); our interest is in generalizing the results to the state of Maryland. In the case of PBIS, after weighting, estimated effects in the target population were similar to those observed in the randomized trial. The paper illustrates that statistical methods can be used to assess and enhance the external validity of randomized trials, making the results more applicable to policy and clinical questions. However, there are also many open research questions; future research should focus on questions of treatment effect heterogeneity and further developing these methods for enhancing external validity. Researchers should think carefully about the external validity of randomized trials and be cautious about extrapolating results to specific

  12. Assessing the generalizability of randomized trial results to target populations.

    PubMed

    Stuart, Elizabeth A; Bradshaw, Catherine P; Leaf, Philip J

    2015-04-01

    Recent years have seen increasing interest in and attention to evidence-based practices, where the "evidence" generally comes from well-conducted randomized trials. However, while those trials yield accurate estimates of the effect of the intervention for the participants in the trial (known as "internal validity"), they do not always yield relevant information about the effects in a particular target population (known as "external validity"). This may be due to a lack of specification of a target population when designing the trial, difficulties recruiting a sample that is representative of a prespecified target population, or to interest in considering a target population somewhat different from the population directly targeted by the trial. This paper first provides an overview of existing design and analysis methods for assessing and enhancing the ability of a randomized trial to estimate treatment effects in a target population. It then provides a case study using one particular method, which weights the subjects in a randomized trial to match the population on a set of observed characteristics. The case study uses data from a randomized trial of school-wide positive behavioral interventions and supports (PBIS); our interest is in generalizing the results to the state of Maryland. In the case of PBIS, after weighting, estimated effects in the target population were similar to those observed in the randomized trial. The paper illustrates that statistical methods can be used to assess and enhance the external validity of randomized trials, making the results more applicable to policy and clinical questions. However, there are also many open research questions; future research should focus on questions of treatment effect heterogeneity and further developing these methods for enhancing external validity. Researchers should think carefully about the external validity of randomized trials and be cautious about extrapolating results to specific populations unless

  13. Population Pharmacokinetics of Enoxaparin in Pediatric Patients.

    PubMed

    Moffett, Brady S; Lee-Kim, YoungNa; Galati, Marianne; Mahoney, Donald; Shah, Mona D; Teruya, Jun; Yee, Donald

    2018-02-01

    There are no studies evaluating the pharmacokinetics of enoxaparin in the hospitalized pediatric patient population. To characterize the pharmacokinetics of enoxaparin in pediatric patients. A retrospective review of inpatients 1 to 18 years of age admitted to our institution who received enoxaparin with anti-factor Xa activity level monitoring was performed. Demographic variables, enoxaparin dosing, and anti-factor Xa activity levels were collected. Population pharmacokinetic analysis was performed with bootstrap analysis. Simulation (n = 10 000) was performed to determine the percentage who achieved targeted anti-Xa levels at various doses. A total of 853 patients (male 52.1%, median age = 12.2 years; interquartile range [IQR] = 4.6-15.8 years) received a mean enoxaparin dose of 0.86 ± 0.31 mg/kg/dose. A median of 3 (IQR = 1-5) anti-factor Xa levels were sampled at 4.4 ± 1.3 hours after a dose, with a mean anti-factor Xa level of 0.52 ± 0.23 U/mL. A 1-compartment model best fit the data, and significant covariates included allometrically scaled weight, serum creatinine, and hematocrit on clearance, and platelets on volume of distribution. Simulations were run for patients both without and with reduced kidney function (creatinine clearance of ≤30 mL/min/1.73 m 2 ). A dose of 1 mg/kg/dose every 12 hours had the highest probability (72.3%) of achieving an anti-Xa level within the target range (0.5-1 U/mL), whereas a dose reduction of ~30% achieved the same result in patients with reduced kidney function. Pediatric patients should initially be dosed at 1-mg/kg/dose subcutaneously every 12 hours for treatment of thromboembolism followed by anti-Xa activity monitoring. Dose reductions of ~30% for creatinine clearance ≤30 mL/min/1.73 m 2 are required.

  14. Generalizing Evidence From Randomized Clinical Trials to Target Populations

    PubMed Central

    Cole, Stephen R.; Stuart, Elizabeth A.

    2010-01-01

    Properly planned and conducted randomized clinical trials remain susceptible to a lack of external validity. The authors illustrate a model-based method to standardize observed trial results to a specified target population using a seminal human immunodeficiency virus (HIV) treatment trial, and they provide Monte Carlo simulation evidence supporting the method. The example trial enrolled 1,156 HIV-infected adult men and women in the United States in 1996, randomly assigned 577 to a highly active antiretroviral therapy and 579 to a largely ineffective combination therapy, and followed participants for 52 weeks. The target population was US people infected with HIV in 2006, as estimated by the Centers for Disease Control and Prevention. Results from the trial apply, albeit muted by 12%, to the target population, under the assumption that the authors have measured and correctly modeled the determinants of selection that reflect heterogeneity in the treatment effect. In simulations with a heterogeneous treatment effect, a conventional intent-to-treat estimate was biased with poor confidence limit coverage, but the proposed estimate was largely unbiased with appropriate confidence limit coverage. The proposed method standardizes observed trial results to a specified target population and thereby provides information regarding the generalizability of trial results. PMID:20547574

  15. Inclusion of populations at risk of advanced melanoma in an opportunistic targeted screening project involving general practitioners

    PubMed Central

    Rat, Cédric; Quereux, Gaelle; Grimault, Charlotte; Fernandez, Jérémy; Poiraud, Mickael; Gaultier, Aurélie; Chaslerie, Anicet; Pivette, Jacques; Khammari, Amir; Dreno, Brigitte; Nguyen, Jean-Michel

    2016-01-01

    Objective The study objective was to measure the rates of inclusion of populations at risk of advanced melanoma in a pilot targeted screening project involving general practitioners. Design This cross-sectional database study compared the inclusion rates of patients who signed inclusion in a targeted screening project with those of patients who did not, during a period in which both groups of patients consulted investigators. Setting Data were extracted from the national healthcare insurance records in western France from 11 April to 30 October 2011. Patients Patients, older than 18, considered for the data extraction had consulted one of the 78 participating GPs during the study period, and were affiliated with the national healthcare insurance. Main outcome measures Inclusion in the screening was the main outcome measure. Patients at risk of advanced melanoma were characterized by male gender, age over 50, low income, rural residence, farmer, and presence of chronic disease. Results A total of 57,279 patients consulted GPs during the inclusion period and 2711 (4.73%) were included in the targeted screening. Populations at risk of advanced melanoma were less included: men (OR = 0.67; 95%CI [0.61–0.73]; p < 0.001), older than 50 (OR = 0.67; 95%CI [0.60–0.74]; p < 0.001), low income (OR = 0.65; 95%CI [0.55–0.77]; p < 0.001), farmer (OR = 0.23; 95%CI [0.17–0.30]; p < 0.001) and presence of a chronic disease (OR = 0.87; 95%CI [0.77–0.98]; p < 0.028). Conclusion This study demonstrated inequalities in the inclusion of patients in a melanoma screening. Patients at risk of advanced cancer were screened less often. Further studies should focus on GPs ability to identify and screen these patients. Key Points Advanced melanoma is more frequently diagnosed in men, older patients and socioeconomically disadvantaged populations, which leads to survival inequalities.• Despite the involvement of general practitioners, the

  16. Too many targets, not enough patients: rethinking neuroblastoma clinical trials.

    PubMed

    Fletcher, Jamie I; Ziegler, David S; Trahair, Toby N; Marshall, Glenn M; Haber, Michelle; Norris, Murray D

    2018-06-01

    Neuroblastoma is a rare solid tumour of infancy and early childhood with a disproportionate contribution to paediatric cancer mortality and morbidity. Combination chemotherapy, radiation therapy and immunotherapy remains the standard approach to treat high-risk disease, with few recurrent, actionable genetic aberrations identified at diagnosis. However, recent studies indicate that actionable aberrations are far more common in relapsed neuroblastoma, possibly as a result of clonal expansion. In addition, although the major validated disease driver, MYCN, is not currently directly targetable, multiple promising approaches to target MYCN indirectly are in development. We propose that clinical trial design needs to be rethought in order to meet the challenge of providing rigorous, evidence-based assessment of these new approaches within a fairly small patient population and that experimental therapies need to be assessed at diagnosis in very-high-risk patients rather than in relapsed and refractory patients.

  17. A Method for Analyzing Commonalities in Clinical Trial Target Populations

    PubMed Central

    He, Zhe; Carini, Simona; Hao, Tianyong; Sim, Ida; Weng, Chunhua

    2014-01-01

    ClinicalTrials.gov presents great opportunities for analyzing commonalities in clinical trial target populations to facilitate knowledge reuse when designing eligibility criteria of future trials or to reveal potential systematic biases in selecting population subgroups for clinical research. Towards this goal, this paper presents a novel data resource for enabling such analyses. Our method includes two parts: (1) parsing and indexing eligibility criteria text; and (2) mining common eligibility features and attributes of common numeric features (e.g., A1c). We designed and built a database called “Commonalities in Target Populations of Clinical Trials” (COMPACT), which stores structured eligibility criteria and trial metadata in a readily computable format. We illustrate its use in an example analytic module called CONECT using COMPACT as the backend. Type 2 diabetes is used as an example to analyze commonalities in the target populations of 4,493 clinical trials on this disease. PMID:25954450

  18. Negotiating targets with patients: choice of target in relation to occupational state.

    PubMed

    Robinson, Sandra M; Walker, David J

    2012-02-01

    Following the recent National Institute for Health and Clinical Excellence guidance on the management of RA, we were interested to see if we could negotiate targets for treatment with patients in routine clinics, how they would express this and whether staying at work would be a target. One hundred RA patients were recruited. They were consecutive within clinics, but not all clinics were used. They were asked their understanding of the DAS score and a target for treatment negotiated. Any impact of the RA on their paid employment was then explored. Four participants were unable to specify a target for their RA. Negotiated targets were expressed as restricted activities and either as maintaining an activity (70) if the disease was stable, or regaining an activity (26) if the treatment was being increased. Targets were walking a distance for 50% of patients; leisure activities for 18%; domestic activities for 17%; work for 14% and personal care for 2%. For the 21 participants currently working, maintaining work was the target for 12, with 1 wishing to regain lost hours. No patient currently not working expressed returning to work as a target. There were some differences in targets between men and women. Patients are able to negotiate a target for their treatment, expressed as maintaining or regaining a physical activity. Work ceases to be a target once it is lost. Therefore, preventing loss of occupation is likely to be more effective than trying to regain it.

  19. Many Mobile Health Apps Target High-Need, High-Cost Populations, But Gaps Remain.

    PubMed

    Singh, Karandeep; Drouin, Kaitlin; Newmark, Lisa P; Lee, JaeHo; Faxvaag, Arild; Rozenblum, Ronen; Pabo, Erika A; Landman, Adam; Klinger, Elissa; Bates, David W

    2016-12-01

    With rising smartphone ownership, mobile health applications (mHealth apps) have the potential to support high-need, high-cost populations in managing their health. While the number of available mHealth apps has grown substantially, no clear strategy has emerged on how providers should evaluate and recommend such apps to patients. Key stakeholders, including medical professional societies, insurers, and policy makers, have largely avoided formally recommending apps, which forces patients to obtain recommendations from other sources. To help stakeholders overcome barriers to reviewing and recommending apps, we evaluated 137 patient-facing mHealth apps-those intended for use by patients to manage their health-that were highly rated by consumers and recommended by experts and that targeted high-need, high-cost populations. We found that there is a wide variety of apps in the marketplace but that few apps address the needs of the patients who could benefit the most. We also found that consumers' ratings were poor indications of apps' clinical utility or usability and that most apps did not respond appropriately when a user entered potentially dangerous health information. Going forward, data privacy and security will continue to be major concerns in the dissemination of mHealth apps. Project HOPE—The People-to-People Health Foundation, Inc.

  20. Culturally targeted patient navigation for increasing african americans' adherence to screening colonoscopy: a randomized clinical trial.

    PubMed

    Jandorf, Lina; Braschi, Caitlyn; Ernstoff, Elizabeth; Wong, Carrie R; Thelemaque, Linda; Winkel, Gary; Thompson, Hayley S; Redd, William H; Itzkowitz, Steven H

    2013-09-01

    Patient navigation has been an effective intervention to increase cancer screening rates. This study focuses on predicting outcomes of screening colonoscopy for colorectal cancer among African Americans using different patient navigation formats. In a randomized clinical trial, patients more than 50 years of age without significant comorbidities were randomized into three navigation groups: peer-patient navigation (n = 181), pro-patient navigation (n = 123), and standard (n = 46). Pro-patient navigations were health care professionals who conducted culturally targeted navigation, whereas peer-patient navigations were community members trained in patient navigation who also discussed their personal experiences with screening colonoscopy. Two assessments gathered sociodemographic, medical, and intrapersonal information. Screening colonoscopy completion rate was 75.7% across all groups with no significant differences in completion between the three study arms. Annual income more than $10,000 was an independent predictor of screening colonoscopy adherence. Unexpectedly, low social influence also predicted screening colonoscopy completion. In an urban African American population, patient navigation was effective in increasing screening colonoscopy rates to 15% above the national average, regardless of patient navigation type or content. Because patient navigation successfully increases colonoscopy adherence, cultural targeting may not be necessary in some populations.

  1. Patient safety is not enough: targeting quality improvements to optimize the health of the population.

    PubMed

    Woolf, Steven H

    2004-01-06

    Ensuring patient safety is essential for better health care, but preoccupation with niches of medicine, such as patient safety, can inadvertently compromise outcomes if it distracts from other problems that pose a greater threat to health. The greatest benefit for the population comes from a comprehensive view of population needs and making improvements in proportion with their potential effect on public health; anything less subjects an excess of people to morbidity and death. Patient safety, in context, is a subset of health problems affecting Americans. Safety is a subcategory of medical errors, which also includes mistakes in health promotion and chronic disease management that cost lives but do not affect "safety." These errors are a subset of lapses in quality, which result not only from errors but also from systemic problems, such as lack of access, inequity, and flawed system designs. Lapses in quality are a subset of deficient caring, which encompasses gaps in therapeutics, respect, and compassion that are undetected by normative quality indicators. These larger problems arguably cost hundreds of thousands more lives than do lapses in safety, and the system redesigns to correct them should receive proportionately greater emphasis. Ensuring such rational prioritization requires policy and medical leaders to eschew parochialism and take a global perspective in gauging health problems. The public's well-being requires policymakers to view the system as a whole and consider the potential effect on overall population health when prioritizing care improvements and system redesigns.

  2. Frequency of MELAS main mutation in a phenotype-targeted young ischemic stroke patient population.

    PubMed

    Tatlisumak, Turgut; Putaala, Jukka; Innilä, Markus; Enzinger, Christian; Metso, Tiina M; Curtze, Sami; von Sarnowski, Bettina; Amaral-Silva, Alexandre; Jungehulsing, Gerhard Jan; Tanislav, Christian; Thijs, Vincent; Rolfs, Arndt; Norrving, Bo; Fazekas, Franz; Suomalainen, Anu; Kolodny, Edwin H

    2016-02-01

    Mitochondrial diseases, predominantly mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), may occasionally underlie or coincide with ischemic stroke (IS) in young and middle-aged individuals. We searched for undiagnosed patients with MELAS in a target subpopulation of unselected young IS patients enrolled in the Stroke in Young Fabry Patients study (sifap1). Among the 3291 IS patients aged 18-55 years recruited to the sifap1 study at 47 centers across 14 European countries, we identified potential MELAS patients with the following phenotypic features: (a) diagnosed cardiomyopathy or (b) presence of two of the three following findings: migraine, short stature (≤165 cm for males; ≤155 cm for females), and diabetes. Identified patients' blood samples underwent analysis of the common MELAS mutation, m.3243A>G in the MTTL1 gene of mitochondrial DNA. Clinical and cerebral MRI features of the mutation carriers were reviewed. We analyzed blood samples of 238 patients (177 with cardiomyopathy) leading to identification of four previously unrecognized MELAS main mutation carrier-patients. Their clinical and MRI characteristics were within the expectation for common IS patients except for severe hearing loss in one patient and hyperintensity of the pulvinar thalami on T1-weighted MRI in another one. Genetic testing for the m.3243A>G MELAS mutation in young patients with IS based on phenotypes suggestive of mitochondrial disease identifies previously unrecognized carriers of MELAS main mutation, but does not prove MELAS as the putative cause.

  3. Creating targeted initial populations for genetic product searches in heterogeneous markets

    NASA Astrophysics Data System (ADS)

    Foster, Garrett; Turner, Callaway; Ferguson, Scott; Donndelinger, Joseph

    2014-12-01

    Genetic searches often use randomly generated initial populations to maximize diversity and enable a thorough sampling of the design space. While many of these initial configurations perform poorly, the trade-off between population diversity and solution quality is typically acceptable for small-scale problems. Navigating complex design spaces, however, often requires computationally intelligent approaches that improve solution quality. This article draws on research advances in market-based product design and heuristic optimization to strategically construct 'targeted' initial populations. Targeted initial designs are created using respondent-level part-worths estimated from discrete choice models. These designs are then integrated into a traditional genetic search. Two case study problems of differing complexity are presented to illustrate the benefits of this approach. In both problems, targeted populations lead to computational savings and product configurations with improved market share of preferences. Future research efforts to tailor this approach and extend it towards multiple objectives are also discussed.

  4. Target and Non-target Site Mechanisms Developed by Glyphosate-Resistant Hairy beggarticks (Bidens pilosa L.) Populations from Mexico

    PubMed Central

    Alcántara-de la Cruz, Ricardo; Fernández-Moreno, Pablo T.; Ozuna, Carmen V.; Rojano-Delgado, Antonia M.; Cruz-Hipolito, Hugo E.; Domínguez-Valenzuela, José A.; Barro, Francisco; De Prado, Rafael

    2016-01-01

    In 2014 hairy beggarticks (Bidens pilosa L.) has been identified as being glyphosate-resistant in citrus orchards from Mexico. The target and non-target site mechanisms involved in the response to glyphosate of two resistant populations (R1 and R2) and one susceptible (S) were studied. Experiments of dose-response, shikimic acid accumulation, uptake-translocation, enzyme activity and 5-enolpyruvyl shikimate-3-phosphate synthase (EPSPS) gene sequencing were carried out in each population. The R1 and R2 populations were 20.4 and 2.8-fold less glyphosate sensitive, respectively, than the S population. The resistant populations showed a lesser shikimic acid accumulation than the S population. In the latter one, 24.9% of 14C-glyphosate was translocated to the roots at 96 h after treatment; in the R1 and R2 populations only 12.9 and 15.5%, respectively, was translocated. Qualitative results confirmed the reduced 14C-glyphosate translocation in the resistant populations. The EPSPS enzyme activity of the S population was 128.4 and 8.5-fold higher than the R1 and R2 populations of glyphosate-treated plants, respectively. A single (Pro-106-Ser), and a double (Thr-102-Ile followed by Pro-106-Ser) mutations were identified in the EPSPS2 gene conferred high resistance in R1 population. Target-site mutations associated with a reduced translocation were responsible for the higher glyphosate resistance in the R1 population. The low-intermediate resistance of the R2 population was mediated by reduced translocation. This is the first glyphosate resistance case confirmed in hairy beggarticks in the world. PMID:27752259

  5. An Improved Compressive Sensing and Received Signal Strength-Based Target Localization Algorithm with Unknown Target Population for Wireless Local Area Networks.

    PubMed

    Yan, Jun; Yu, Kegen; Chen, Ruizhi; Chen, Liang

    2017-05-30

    In this paper a two-phase compressive sensing (CS) and received signal strength (RSS)-based target localization approach is proposed to improve position accuracy by dealing with the unknown target population and the effect of grid dimensions on position error. In the coarse localization phase, by formulating target localization as a sparse signal recovery problem, grids with recovery vector components greater than a threshold are chosen as the candidate target grids. In the fine localization phase, by partitioning each candidate grid, the target position in a grid is iteratively refined by using the minimum residual error rule and the least-squares technique. When all the candidate target grids are iteratively partitioned and the measurement matrix is updated, the recovery vector is re-estimated. Threshold-based detection is employed again to determine the target grids and hence the target population. As a consequence, both the target population and the position estimation accuracy can be significantly improved. Simulation results demonstrate that the proposed approach achieves the best accuracy among all the algorithms compared.

  6. Quasi-extinction risk and population targets for the Eastern, migratory population of monarch butterflies (Danaus plexippus)

    USGS Publications Warehouse

    Semmens, Brice X.; Semmens, Darius J.; Thogmartin, Wayne E.; Wiederholt, Ruscena; Lopez-Hoffman, Laura; Diffendorfer, James E.; Pleasants, John M.; Oberhauser, Karen S.; Taylor, Orley R.

    2016-01-01

    The Eastern, migratory population of monarch butterflies (Danaus plexippus), an iconic North American insect, has declined by ~80% over the last decade. The monarch’s multi-generational migration between overwintering grounds in central Mexico and the summer breeding grounds in the northern U.S. and southern Canada is celebrated in all three countries and creates shared management responsibilities across North America. Here we present a novel Bayesian multivariate auto-regressive state-space model to assess quasi-extinction risk and aid in the establishment of a target population size for monarch conservation planning. We find that, given a range of plausible quasi-extinction thresholds, the population has a substantial probability of quasi-extinction, from 11–57% over 20 years, although uncertainty in these estimates is large. Exceptionally high population stochasticity, declining numbers, and a small current population size act in concert to drive this risk. An approximately 5-fold increase of the monarch population size (relative to the winter of 2014–15) is necessary to halve the current risk of quasi-extinction across all thresholds considered. Conserving the monarch migration thus requires active management to reverse population declines, and the establishment of an ambitious target population size goal to buffer against future environmentally driven variability.

  7. Use of surveillance data to identify target populations for Staphylococcus aureus vaccines and prevent surgical site infections: A pilot study

    PubMed Central

    Gustin, Marie-Paule; Giard, Marine; Bénet, Thomas; Vanhems, Philippe

    2015-01-01

    The development of anti-staphylococcal vaccines is nowadays a priority to prevent surgical site infections (SSI). The objective of the present study was to identify a potential target population by assessing surveillance data on surgery patients for possible anti-staphylococcal vaccine administration. Individuals at high risk of SSI by Staphylococcus aureus (SA) were targeted by the French SSI Surveillance Network in south-eastern France between 2008 and 2011. Among 238,470 patients, those undergoing primary total hip replacement appeared to be an interesting and healthy enough population for anti-staphylococcal vaccine testing. These male patients, subjected to multiple procedures and with American Society of Anesthesiologists score >2, had a probability of SA SSI about 21 times higher than females with no severe systemic disease and no multiple procedures. Our study indicates that surveillance data on SSI might be an interesting epidemiological source for planning vaccine trials to prevent nosocomial infections. PMID:25668663

  8. Predicting Satisfaction for Unicompartmental Knee Arthroplasty Patients in an Asian Population.

    PubMed

    Lee, Merrill; Huang, Yilun; Chong, Hwei Chi; Ning, Yilin; Lo, Ngai Nung; Yeo, Seng Jin

    2016-08-01

    Despite renewed interest in unicompartmental knee arthroplasty (UKA), there is a paucity of published literature with regard to patient satisfaction after UKA within Asian populations. The purpose of this study is to identify characteristics and factors which may contribute to patient dissatisfaction after UKA in a multiracial Asian population. Seven hundred twenty-four UKAs were performed between January 2007 and April 2013. Preoperative and postoperative variables were prospectively captured, such as standardized knee scores, knee range of motion, and patient satisfaction scores. These variables were then analyzed with a multiple logistic regression model to determine statistically significant factors contributing to patients' satisfaction. Minimum duration of follow-up was 2 years, with an overall patient satisfaction rate of 92.2%. There was improvement in mean knee range of motion and across various standardized knee scores. Preoperative variables associated with patient dissatisfaction included a poorer preoperative Mental Component Summary, better preoperative knee extension, and better preoperative Oxford Knee Scores. Significant postoperative variables included better Oxford Knee Score at 6 months and Mental Component Summary at 2 years. Despite the impressive patient satisfaction rate of UKA in this Asian population, these findings suggest that there is a targeted group of patients with select preoperative factors who would benefit from preoperative counseling. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Neutrophil degranulation and immunosuppression in patients with GBM: restoration of cellular immune function by targeting arginase I.

    PubMed

    Sippel, Trisha R; White, Jason; Nag, Kamalika; Tsvankin, Vadim; Klaassen, Marci; Kleinschmidt-DeMasters, B K; Waziri, Allen

    2011-11-15

    The source of glioblastoma (GBM)-associated immunosuppression remains multifactorial. We sought to clarify and therapeutically target myeloid cell-derived peripheral immunosuppression in patients with GBM. Direct ex vivo T-cell function, serum Arginase I (ArgI) levels, and circulating myeloid lineage populations were compared between patients with GBM and normal donors or patients with other intracranial tumors. Immunofunctional assays were conducted using bulk and sorted cell populations to explore the potential transfer of myeloid cell-mediated immunosuppression and to identify a potential mechanism for these effects. ArgI-mediated immunosuppression was therapeutically targeted in vitro through pharmacologic inhibition or arginine supplementation. We identified a significantly expanded population of circulating, degranulated neutrophils associated with elevated levels of serum ArgI and decreased T-cell CD3ζ expression within peripheral blood from patients with GBM. Sorted CD11b(+) cells from patients with GBM were found to markedly suppress normal donor T-cell function in coculture, and media harvested from mitogen-stimulated GBM peripheral blood mononuclear cell (PBMC) or GBM-associated mixed lymphoid reactions showed ArgI levels that were significantly higher than controls. Critically, T-cell suppression in both settings could be completely reversed through pharmacologic ArgI inhibition or with arginine supplementation. These data indicate that peripheral cellular immunosuppression in patients with GBM is associated with neutrophil degranulation and elevated levels of circulating ArgI, and that T-cell function can be restored in these individuals by targeting ArgI. These data identify a novel pathway of GBM-mediated suppression of cellular immunity and offer a potential therapeutic window for improving antitumor immunity in affected patients.

  10. Influence of socioeconomic and demographic status on spirometry testing in patients initiating medication targeting obstructive lung disease: a population-based cohort study.

    PubMed

    Koefoed, Mette M; Søndergaard, Jens; Christensen, René dePont; Jarbøl, Dorte E

    2013-06-14

    Socioeconomic status is known to influence the prevalence, severity and mortality of obstructive lung diseases, but it is uncertain whether it affects the use of diagnostic spirometry in patients initiating treatment for these conditions. The objective of this paper was to examine a possible association between education, income, labour market affiliation, cohabitation status and having spirometry performed when initiating medication targeting obstructive pulmonary disease. We conducted a population-based cohort study. Danish national registers were linked, retrieving data on prescriptions, spirometry testing, socioeconomic and demographic variables in all first time users of medication targeting obstructive lung disease in 2008. A total of 37,734 persons were included and approximately half of the cohort had spirometry performed. Among medication users under 65 years of age, being unemployed was significantly associated with reduced odds of having spirometry performed, the strongest association was seen in men (OR = 0.82, CI = 0.73-0.91). Medium income was associated with increased odds of having spirometry performed in men (OR =1.18, CI = 1.06-1.30) and high educational level (>12 years) was associated with reduced odds of having spirometry performed in women (OR = 0.86, CI = 0.78-0.94). Cohabitation status was not associated with having spirometry performed. Among medication users over 65 years of age, living alone was associated with reduced odds of having spirometry performed among men (OR = 0.78, CI = 0.69-0.88). Social inequity in spirometry testing among patients initiating medication targeting obstructive lung disease was confirmed in this study. Increased focus on spirometry testing among elderly men living alone, among the unemployed and among women with higher education is required when initiating medication.

  11. Huntingtin Haplotypes Provide Prioritized Target Panels for Allele-specific Silencing in Huntington Disease Patients of European Ancestry

    PubMed Central

    Kay, Chris; Collins, Jennifer A; Skotte, Niels H; Southwell, Amber L; Warby, Simon C; Caron, Nicholas S; Doty, Crystal N; Nguyen, Betty; Griguoli, Annamaria; Ross, Colin J; Squitieri, Ferdinando; Hayden, Michael R

    2015-01-01

    Huntington disease (HD) is a dominant neurodegenerative disorder caused by a CAG repeat expansion in the Huntingtin gene (HTT). Heterozygous polymorphisms in cis with the mutation allow for allele-specific suppression of the pathogenic HTT transcript as a therapeutic strategy. To prioritize target selection, precise heterozygosity estimates are needed across diverse HD patient populations. Here we present the first comprehensive investigation of all common target alleles across the HTT gene, using 738 reference haplotypes from the 1000 Genomes Project and 2364 haplotypes from HD patients and relatives in Canada, Sweden, France, and Italy. The most common HD haplotypes (A1, A2, and A3a) define mutually exclusive sets of polymorphisms for allele-specific therapy in the greatest number of patients. Across all four populations, a maximum of 80% are treatable using these three target haplotypes. We identify a novel deletion found exclusively on the A1 haplotype, enabling potent and selective silencing of mutant HTT in approximately 40% of the patients. Antisense oligonucleotides complementary to the deletion reduce mutant A1 HTT mRNA by 78% in patient cells while sparing wild-type HTT expression. By suppressing specific haplotypes on which expanded CAG occurs, we demonstrate a rational approach to the development of allele-specific therapy for a monogenic disorder. PMID:26201449

  12. Targeted cardiopulmonary resuscitation training focused on the family members of high-risk patients at a regional medical center: A comparison between family members of high-risk and no-risk patients.

    PubMed

    Han, Kap Su; Lee, Ji Sung; Kim, Su Jin; Lee, Sung Woo

    2018-05-01

    We developed a hospital-based cardiopulmonary resuscitation (CPR) training model focused on the target population (family members of patients with potential risks for cardiac arrest) and compared the outcome of CPR training between target and non-target populations for validity. Family members of patients in training were divided into three groups on the basis of patients' diseases, as follows: 1) the cardio-specific (CS) risk group, including family members of patients with cardiac disease at risk of cardiac arrest; 2) the cardiovascular (CV) risk group, including family members of patients with risk factors for cardiovascular disease; and 3) the no-risk group. Pre- and posttraining surveys and skill tests as well as a post-training 3-month telephone survey were conducted. Educational outcomes were analyzed. A total of 203 family members were enrolled into 21 CPR training classes. The CS group (n=88) included elderly persons and housewives with a lower level of education compared with the CV (n=79) and no-risk groups (n=36). The CS group was motivated by healthcare professionals and participated in the training course. The CS, CV, and no-risk groups showed improvements in knowledge, willingness to perform CPR, and skills. Despite the older age and lower level of education in the CS group, the effects of education were similar to those in the other groups. A high rate of response and secondary propagation of CPR training were observed in the CS group. Family members of patients with heart disease could be an appropriate target population for CPR training, particularly in terms of recruitment and secondary propagation. Targeted intervention may be an effective training strategy to improve bystander CPR rates.

  13. Discordance of somatic mutations between Asian and Caucasian patient populations with gastric cancer

    PubMed Central

    Jia, Feifei; Teer, Jamie K.; Knepper, Todd C.; Lee, Jae K.; Zhou, Hong-Hao; He, Yi-Jing; McLeod, Howard L.

    2017-01-01

    Background Differences in response to cancer treatments have been observed among racially and ethnically diverse gastric cancer patient populations. In the era of targeted therapy, mutation profiling of cancer is a crucial aspect of making therapeutic decisions. Mapping driver gene mutations for the gastric cancer patient population as a whole has significant potential to advance precision therapy. Methods Gastric cancer patient cases with sequencing data (total n=473) were obtained from The Cancer Genome Atlas (TCGA; n=295), Moffitt Cancer Center Total Cancer Care™ (TCC; n=33), and three published studies (n=145). Relevant somatic mutation frequency data were obtained from cBioPortal, TCC database and in-house analysis tool, and relevant publication Results We have found somatic mutation rates of several driver genes significantly vary between gastric cancer patients of Asian and Caucasian descent, with substantial variation across different geographic regions. Non-parametric statistical tests were performed to examine significant differences in protein-altering somatic mutations between Asian and Caucasian gastric cancer patient groups. Frequencies of somatic mutations of 5 genes were APC(Asian: Caucasian 6.06% vs. 14.40%, p=0.0076) ARIDIA(20.7% vs. 32.1%, p=0.01) KMT2A(4.04% vs. 12.35%, p=0.003) PIK3CA(9.6% vs. 18.52%, p=0.01) PTEN(2.52% vs. 9.05%, p=0.008), showing significant differences between Asian and Caucasian gastric cancer patients. Conclusions Our study has found significant differences in protein-altering somatic mutation frequencies in diverse geographic populations. In particular, we found that the somatic patterns may offer better insight and important opportunities for both targeted drug development and precision therapeutic strategies between Asian and Caucasian gastric cancer patients. PMID:28039579

  14. Discordance of Somatic Mutations Between Asian and Caucasian Patient Populations with Gastric Cancer.

    PubMed

    Jia, Feifei; Teer, Jamie K; Knepper, Todd C; Lee, Jae K; Zhou, Hong-Hao; He, Yi-Jing; McLeod, Howard L

    2017-04-01

    Differences in response to cancer treatments have been observed among racially and ethnically diverse gastric cancer (GC) patient populations. In the era of targeted therapy, mutation profiling of cancer is a crucial aspect of making therapeutic decisions. Mapping driver gene mutations for the GC patient population as a whole has significant potential to advance precision therapy. GC patients with sequencing data (N = 473) were obtained from The Cancer Genome Atlas (TCGA; n = 295), Moffitt Cancer Center Total Cancer Care™ (TCC; n = 33), and three published studies (n = 145). In addition, relevant somatic mutation frequency data were obtained from cBioPortal, the TCC database, and an in-house analysis tool, as well as relevant publications. We found that the somatic mutation rates of several driver genes vary significantly between GC patients of Asian and Caucasian descent, with substantial variation across different geographic regions. Non-parametric statistical tests were performed to examine the significant differences in protein-altering somatic mutations between Asian and Caucasian GC patient groups. The frequencies of somatic mutations of five genes were: APC (Asian: Caucasian 6.06 vs. 14.40%, p = 0.0076), ARIDIA (20.7 vs. 32.1%, p = 0.01), KMT2A (4.04 vs. 12.35%, p = 0.003), PIK3CA (9.6 vs. 18.52%, p = 0.01), and PTEN (2.52 vs. 9.05%, p = 0.008), showing significant differences between Asian and Caucasian GC patients. Our study found significant differences in protein-altering somatic mutation frequencies in diverse geographic populations. In particular, we found that the somatic patterns may offer better insight and important opportunities for both targeted drug development and precision therapeutic strategies between Asian and Caucasian GC patients.

  15. Controlling range expansion in habitat networks by adaptively targeting source populations.

    PubMed

    Hock, Karlo; Wolff, Nicholas H; Beeden, Roger; Hoey, Jessica; Condie, Scott A; Anthony, Kenneth R N; Possingham, Hugh P; Mumby, Peter J

    2016-08-01

    Controlling the spread of invasive species, pests, and pathogens is often logistically limited to interventions that target specific locations at specific periods. However, in complex, highly connected systems, such as marine environments connected by ocean currents, populations spread dynamically in both space and time via transient connectivity links. This results in nondeterministic future distributions of species in which local populations emerge dynamically and concurrently over a large area. The challenge, therefore, is to choose intervention locations that will maximize the effectiveness of the control efforts. We propose a novel method to manage dynamic species invasions and outbreaks that identifies the intervention locations most likely to curtail population expansion by selectively targeting local populations most likely to expand their future range. Critically, at any point during the development of the invasion or outbreak, the method identifies the local intervention that maximizes the long-term benefit across the ecosystem by restricting species' potential to spread. In so doing, the method adaptively selects the intervention targets under dynamically changing circumstances. To illustrate the effectiveness of the method we applied it to controlling the spread of crown-of-thorns starfish (Acanthaster sp.) outbreaks across Australia's Great Barrier Reef. Application of our method resulted in an 18-fold relative improvement in management outcomes compared with a random targeting of reefs in putative starfish control scenarios. Although we focused on applying the method to reducing the spread of an unwanted species, it can also be used to facilitate the spread of desirable species through connectivity networks. For example, the method could be used to select those fragments of habitat most likely to rebuild a population if they were sufficiently well protected. © 2016 Society for Conservation Biology.

  16. Social identity and support for counteracting tobacco company marketing that targets vulnerable populations

    PubMed Central

    Baig, Sabeeh A.; Pepper, Jessica K.; Morgan, Jennifer C.; Brewer, Noel T.

    2017-01-01

    Rationale Tobacco companies use advertising to target vulnerable populations, including youth, racial/ethnic minorities, and sexual minorities. Objective We sought to examine how personal identity affects support for population-specific anti-smoking advertisements that could serve as countermeasures to industry practices. Methods In 2014–2015, we surveyed probability phone samples of adults and adolescents (n = 6,139) and an online convenience sample of adults (n = 4,137) in the United States. We experimentally varied the description of tobacco industry marketing practices (no description, general, or specific to a target group). The four prevention target groups were teens; African Americans; Latinos; and gays, lesbians, and bisexuals (GLBs). Participants were either members or non-members of their prevention target group. Results Support was highest for anti-smoking advertisements targeting teens, moderate for Latinos and African Americans, and lowest for GLBs. In-group members expressed higher support than out-group members when anti-smoking advertisements targeted African Americans, Latinos, and GLBs (all p < .05). However, when teens were the target prevention group, in-group members expressed lower support than out-group members (p < .05). The description of industry marketing practices did not have an effect. Results were similar across the phone and online studies. Conclusions Our findings suggest that the public strongly supports advertisements to prevent smoking among teens, but support for similar efforts among other vulnerable populations is comparatively low. Anti-smoking campaigns for vulnerable populations may benefit from a greater understanding of the role of social identity in shaping public support for such campaigns. PMID:28427731

  17. Clinician-Patient Communication about Physical Activity in an Underserved Population

    PubMed Central

    Carroll, Jennifer K.; Fiscella, Kevin; Meldrum, Sean C.; Williams, Geoffrey C.; Sciamanna, Christopher N.; Jean-Pierre, Pascal; Morrow, Gary R.; Epstein, Ronald M.

    2010-01-01

    Introduction The 5A (Ask, Advise, Agree, Assist, Arrange) model, used to promote patient behavior changes in primary care, can also be applied to physical activity. Our goal was to assess primary care physicians’ use of the 5As in discussions about physical activity with underserved populations. Methods We analyzed 51 audiorecorded, transcribed office visits on randomly selected patient care days and post-visit patient surveys with adults in two community health centers in Rochester, New York. Results The patient sample was 51% African American, predominantly female (70%), with the majority having a high school level education or less (66%) and an annual household income less than $39,000 (57%). Physical activity was discussed during 19 of the 51 visits, which included 16 (84%) visits with "Ask", ten (53%) with “Advise”, four (21%) with "Agree", five (26%) with "Assist", and 0 with "Arrange" statements. Most discussions of physical activity contained several Ask or Advise statements, but few Agree, Assist, or Arrange statements. Conclusion Communication about physical activity that included Agree, Arrange, and Assist statements of the 5As was infrequent. Health promotion interventions in underserved populations should target these steps and prompt patients to initiate communication to improve physical activity. PMID:18343859

  18. [Patient first - The impact of characteristics of target populations on decisions about therapy effectiveness of complex interventions: Psychological variables to assess effectiveness in interdisciplinary multimodal pain therapy].

    PubMed

    Kaiser, Ulrike; Sabatowski, Rainer; Balck, Friedrich

    2017-08-01

    or large effects; changes in the subgroups were consistently caused by two subgroups, while the other four showed little or no change. In summary, only a small proportion of the target population (20 %) demonstrated clinically relevant scores in the psychological parameters applied. When selecting indicators for quality assurance, the heterogeneity of the target populations as well as conceptual and methodological aspects should be considered. The characteristics of the parameters intended, along with clinical and personal relevance of indicators for patients, should be investigated by specific procedures such as patient surveys and statistical analyses. Copyright © 2017. Published by Elsevier GmbH.

  19. What the patient wants: Addressing patients' treatment targets in an integrative group psychotherapy programme.

    PubMed

    Kealy, David; Joyce, Anthony S; Weber, Rainer; Ehrenthal, Johannes C; Ogrodniczuk, John S

    2018-02-13

    Limited empirical attention has been devoted to individualized treatment objectives in intensive group therapy for personality dysfunction. This study investigated patients' ratings of distress associated with individual therapy goals - referred to as target object severity - in an intensive Evening Treatment Programme for patients with personality dysfunction. Change in target objective severity was examined in a sample of 81 patients who completed treatment in an intensive, integrative group therapy programme. Correlation and regression analyses were used to examine associations between change in target object severity and patients' pre-treatment diagnosis, symptom distress, and treatment outcome expectancy, and between change in target objective severity and patients' ratings of group therapy process (group climate, therapeutic alliance, group cohesion). The relationship between change in target objective severity and longer-range life satisfaction was also examined in a subsample of patients who rated life satisfaction at follow-up. While change in target objective severity was not significantly related to pre-treatment variables, significant associations were found with several aspects of group therapy process. Patients' experience of a highly engaged group climate was uniquely associated with improvement in target object severity. Such improvement was significantly related to longer-term life satisfaction after controlling for general symptom change. The working atmosphere in group therapy contributes to patients' progress regarding individual treatment targets, and such progress is an important factor in later satisfaction. Attention to individualized treatment targets deserves further clinical and research attention in the context of integrative group therapy for personality dysfunction. This study found that patients attending an integrative group treatment programme for personality dysfunction experienced significant improvement in severity of distress

  20. Social identity and support for counteracting tobacco company marketing that targets vulnerable populations.

    PubMed

    Baig, Sabeeh A; Pepper, Jessica K; Morgan, Jennifer C; Brewer, Noel T

    2017-06-01

    Tobacco companies use advertising to target vulnerable populations, including youth, racial/ethnic minorities, and sexual minorities. We sought to examine how personal identity affects support for population-specific anti-smoking advertisements that could serve as countermeasures to industry marketing practices. In 2014-2015, we surveyed probability phone samples of adults and adolescents (n = 6,139) and an online convenience sample of adults (n = 4,137) in the United States. We experimentally varied the description of tobacco industry marketing practices (no description, general, or specific to a target group). The four prevention target groups were teens; African Americans; Latinos; and gays, lesbians, and bisexuals (GLBs). Participants were either members or non-members of their prevention target group. Support was highest for anti-smoking advertisements targeting teens, moderate for Latinos and African Americans, and lowest for GLBs. In-group members expressed higher support than out-group members when anti-smoking advertisements targeted African Americans, Latinos, and GLBs (all p < 0.05). However, when teens were the target prevention group, in-group members expressed lower support than out-group members (p < 0.05). The description of industry marketing practices did not have an effect. Results were similar across the phone and online studies. Our findings suggest that the public strongly supports advertisements to prevent smoking among teens, but support for similar efforts among other vulnerable populations is comparatively low. Anti-smoking campaigns for vulnerable populations may benefit from a greater understanding of the role of social identity in shaping public support for such campaigns. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Psychological well-being and social support in chronic myeloid leukemia patients receiving lifelong targeted therapies.

    PubMed

    Efficace, Fabio; Breccia, Massimo; Cottone, Francesco; Okumura, Iris; Doro, Maribel; Riccardi, Francesca; Rosti, Gianantonio; Baccarani, Michele

    2016-12-01

    The main objective of this study was to investigate whether social support is independently associated with psychological well-being in chronic myeloid leukemia (CML) patients. Secondary objectives were to compare the psychological well-being profile of CML patients with that of their peers in general population and to examine possible age- and sex-related differences. Analysis was performed on 417 patients in treatment with lifelong molecularly targeted therapies. Mean age of patients analyzed was 56 years (range 19-87 years) and 247 (59 %) were male and 170 (41 %) were female. Social support was assessed with the Multidimensional Scale of Perceived Social Support and psychological well-being was evaluated with the short version of the Psychological General Well-Being Index. Descriptive statistics and multivariate logistic regression analyses were used. Multivariate logistic regression analysis revealed that a greater social support was independently associated with lower anxiety and depression, as well as with higher positive well-being, self-control, and vitality (p < 0.001). Female patients reported statistically significant worse outcomes in all dimensions of psychological well-being. Age- and sex-adjusted comparisons with population norms revealed that depression (ES = -0.42, p < 0.001) and self-control (ES = -0.48, p < 0.001) were the two main impaired psychological dimensions. This study indicates that social support is a critical factor associated with psychological well-being of CML patients treated with modern lifelong targeted therapies.

  2. Widespread occurrence of both metabolic and target-site herbicide resistance mechanisms in Lolium rigidum populations.

    PubMed

    Han, Heping; Yu, Qin; Owen, Mechelle J; Cawthray, Gregory R; Powles, Stephen B

    2016-02-01

    Lolium rigidum populations in Australia and globally have demonstrated rapid and widespread evolution of resistance to acetyl coenzyme A carboxylase (ACCase)-inhibiting and acetolactate synthase (ALS)-inhibiting herbicides. Thirty-three resistant L. rigidum populations, randomly collected from crop fields in a most recent resistance survey, were analysed for non-target-site diclofop metabolism and all known target-site ACCase gene resistance-endowing mutations. The HPLC profile of [(14) C]-diclofop-methyl in vivo metabolism revealed that 79% of these resistant L. rigidum populations showed enhanced capacity for diclofop acid metabolism (metabolic resistance). ACCase gene sequencing identified that 91% of the populations contain plants with ACCase resistance mutation(s). Importantly, 70% of the populations exhibit both non-target-site metabolic resistance and target-site ACCase mutations. This work demonstrates that metabolic herbicide resistance is commonly occurring in L. rigidum, and coevolution of both metabolic resistance and target-site resistance is an evolutionary reality. Metabolic herbicide resistance can potentially endow resistance to many herbicides and poses a threat to herbicide sustainability and thus crop production, calling for major research and management efforts. © 2015 Society of Chemical Industry.

  3. Target organ damage in hypertensive patients of different ethnic groups.

    PubMed

    Wolak, Talya; Anfanger, Sharon; Wolak, Arik; Furman, Tsilla; Abuara'ar, Touphic; Biton, Amnon; Pilpel, Dina; Paran, Esther

    2007-03-20

    Hypertension is associated with involvement of target organs which varies among the different ethnic groups. The multiplicity of the population in Israel offers an opportunity for evaluating target organ damage in hypertensive patients of different ethnic origins. Data were collected from the computerized medical files of hypertensive patients in primary care clinics. The analysis was done on 576 hypertensive patients: 138 Bedouins (Arab residents), 141 Sephardic Jews (immigrants from North Africa and the Middle East), 152 Asian-Indian Jews (immigrants from India) and 145 Ashkenazi Jews (immigrants from Europe and North and South America). In multivariable logistic regressions adjusted for known risk factors and ethnicity, the prevalence of cerebrovascular disease was the highest among the Asian-Indian Jews (OR=3.09, p value=0.009). Renal damage was highest among the Bedouins (OR=4.54, p value<0.0001) and Asian-Indian Jews (OR=2.88, p value=0.005). The differences in the prevalence of renal damage among the various ethnic groups were even more pronounced among patients without diabetes (OR=8.31, p value<0.0001 in Bedouins and OR=7.46, p value=0.001 in Asian-Indian Jews). The prevalence of ischemic heart disease did not differ significantly among the four ethnic groups. The prevalence of cerebrovascular and renal diseases are both significantly associated with ethnic origin of Asian-Indian Jews and Bedouins. However, the multivariate analysis shows that the prevalence of ischemic heart disease is not associated with ethnicity.

  4. Prioritizing therapeutic targets using patient-derived xenograft models

    PubMed Central

    Lodhia, K.A; Hadley, A; Haluska, P; Scott, C.L

    2015-01-01

    Effective systemic treatment of cancer relies on the delivery of agents with optimal therapeutic potential. The molecular age of medicine has provided genomic tools that can identify a large number of potential therapeutic targets in individual patients, heralding the promise of personalized treatment. However, determining which potential targets actually drive tumor growth and should be prioritized for therapy is challenging. Indeed, reliable molecular matches of target and therapeutic agent have been stringently validated in the clinic for only a small number of targets. Patient-derived xenografts (PDX) are tumor models developed in immunocompromised mice using tumor procured directly from the patient. As patient surrogates, PDX models represent a powerful tool for addressing individualized therapy. Challenges include humanizing the immune system of PDX models and ensuring high quality molecular annotation, in order to maximise insights for the clinic. Importantly, PDX can be sampled repeatedly and in parallel, to reveal clonal evolution, which may predict mechanisms of drug resistance and inform therapeutic strategy design. PMID:25783201

  5. Intermittent targeted therapies and stochastic evolution in patients affected by chronic myeloid leukemia

    NASA Astrophysics Data System (ADS)

    Pizzolato, N.; Persano Adorno, D.; Valenti, D.; Spagnolo, B.

    2016-05-01

    Front line therapy for the treatment of patients affected by chronic myeloid leukemia (CML) is based on the administration of tyrosine kinase inhibitors, namely imatinib or, more recently, axitinib. Although imatinib is highly effective and represents an example of a successful molecular targeted therapy, the appearance of resistance is observed in a proportion of patients, especially those in advanced stages. In this work, we investigate the appearance of resistance in patients affected by CML, by modeling the evolutionary dynamics of cancerous cell populations in a simulated patient treated by an intermittent targeted therapy. We simulate, with the Monte Carlo method, the stochastic evolution of initially healthy cells to leukemic clones, due to genetic mutations and changes in their reproductive behavior. We first present the model and its validation with experimental data by considering a continuous therapy. Then, we investigate how fluctuations in the number of leukemic cells affect patient response to the therapy when the drug is administered with an intermittent time scheduling. Here we show that an intermittent therapy (IT) represents a valid choice in patients with high risk of toxicity, despite an associated delay to the complete restoration of healthy cells. Moreover, a suitably tuned IT can reduce the probability of developing resistance.

  6. Clinical research in small genomically stratified patient populations.

    PubMed

    Martin-Liberal, J; Rodon, J

    2017-07-01

    The paradigm of early drug development in cancer is shifting from 'histology-oriented' to 'molecularly oriented' clinical trials. This change can be attributed to the vast amount of tumour biology knowledge generated by large international research initiatives such as The Cancer Genome Atlas (TCGA) and the use of next generation sequencing (NGS) techniques developed in recent years. However, targeting infrequent molecular alterations entails a series of special challenges. The optimal molecular profiling method, the lack of standardised biological thresholds, inter- and intra-tumor heterogeneity, availability of enough tumour material, correct clinical trials design, attrition rate, logistics or costs are only some of the issues that need to be taken into consideration in clinical research in small genomically stratified patient populations. This article examines the most relevant challenges inherent to clinical research in these populations. Moreover, perspectives from the Academia point of view are reviewed as well as initiatives to be taken in forthcoming years. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Social network targeting to maximise population behaviour change: a cluster randomised controlled trial.

    PubMed

    Kim, David A; Hwong, Alison R; Stafford, Derek; Hughes, D Alex; O'Malley, A James; Fowler, James H; Christakis, Nicholas A

    2015-07-11

    Information and behaviour can spread through interpersonal ties. By targeting influential individuals, health interventions that harness the distributive properties of social networks could be made more effective and efficient than those that do not. Our aim was to assess which targeting methods produce the greatest cascades or spillover effects and hence maximise population-level behaviour change. In this cluster randomised trial, participants were recruited from villages of the Department of Lempira, Honduras. We blocked villages on the basis of network size, socioeconomic status, and baseline rates of water purification, for delivery of two public health interventions: chlorine for water purification and multivitamins for micronutrient deficiencies. We then randomised villages, separately for each intervention, to one of three targeting methods, introducing the interventions to 5% samples composed of either: randomly selected villagers (n=9 villages for each intervention); villagers with the most social ties (n=9); or nominated friends of random villagers (n=9; the last strategy exploiting the so-called friendship paradox of social networks). Participants and data collectors were not aware of the targeting methods. Primary endpoints were the proportions of available products redeemed by the entire population under each targeting method. This trial is registered with ClinicalTrials.gov, number NCT01672580. Between Aug 4, and Aug 14, 2012, 32 villages in rural Honduras (25-541 participants each; total study population of 5773) received public health interventions. For each intervention, nine villages (each with 1-20 initial target individuals) were randomised, using a blocked design, to each of the three targeting methods. In nomination-targeted villages, 951 (74·3%) of 1280 available multivitamin tickets were redeemed compared with 940 (66·2%) of 1420 in randomly targeted villages and 744 (61·0%) of 1220 in indegree-targeted villages. All pairwise differences

  8. Pharmacokinetics of Antibiotics in Sub-Saharan African Patient Populations: A Systematic Review.

    PubMed

    Bos, Jeannet C; van Hest, Reinier M; Prins, Jan M

    2017-08-01

    In sub-Saharan Africa (SSA), severe febrile illness accounts for a large majority of medical admissions. SSA patients may also suffer from cachexia and organ dysfunction resulting from tuberculosis, hepatitis B, and hypertension. It is hard to tell how these conditions influence the pharmacokinetics (PK) of antibiotics in this population. The aim of this systematic review was to summarize antibiotic PK data of SSA adult patient populations to clarify whether inappropriate drug concentrations that may also lead to antimicrobial resistance are likely to occur. An electronic search was conducted in Ovid MEDLINE, Embase, and the African Index Medicus collecting studies from 1946 to May 2016. Reviewers independently selected studies reporting outcome data on volume of distribution (V), clearance, and half-life. Relevant information was abstracted and quality assessed. Twelve studies were selected, addressing 6 antibiotic classes. There were 6 studies on fluoroquinolones and 1 on β-lactam antibiotics. Nine out of 12 originated from South Africa and 6 of those dealt with intensive care unit (ICU) populations. The quality of most studies was low. Studies on amikacin, teicoplanin, and ertapenem (n = 4) displayed a pattern of a large V with low drug concentrations. Fluoroquinolone PK changes were less prominent and more diverse whereas the probability of pharmacodynamic target attainment was low for the treatment of tuberculosis in South Africa. Interindividual variability of V was high for 10/12 studies. Antibiotic PK data of SSA adult patient populations are scarce, but disease-induced inappropriate drug concentrations do occur. Data from non-ICU, severely ill patients, and β-lactam data are particularly lacking, whereas β-lactam antibiotics are commonly used, and typically vulnerable to disease-induced PK changes. Studies investigating the PK and pharmacodynamics of β-lactam antibiotics in severely ill, adult SSA patient populations are needed to improve local

  9. Comparative Analysis of State Fish Consumption Advisories Targeting Sensitive Populations

    PubMed Central

    Scherer, Alison C.; Tsuchiya, Ami; Younglove, Lisa R.; Burbacher, Thomas M.; Faustman, Elaine M.

    2008-01-01

    Objective Fish consumption advisories are issued to warn the public of possible toxicological threats from consuming certain fish species. Although developing fetuses and children are particularly susceptible to toxicants in fish, fish also contain valuable nutrients. Hence, formulating advice for sensitive populations poses challenges. We conducted a comparative analysis of advisory Web sites issued by states to assess health messages that sensitive populations might access. Data sources We evaluated state advisories accessed via the National Listing of Fish Advisories issued by the U.S. Environmental Protection Agency. Data extraction We created criteria to evaluate advisory attributes such as risk and benefit message clarity. Data synthesis All 48 state advisories issued at the time of this analysis targeted children, 90% (43) targeted pregnant women, and 58% (28) targeted women of childbearing age. Only six advisories addressed single contaminants, while the remainder based advice on 2–12 contaminants. Results revealed that advisories associated a dozen contaminants with specific adverse health effects. Beneficial health effects of any kind were specifically associated only with omega-3 fatty acids found in fish. Conclusions These findings highlight the complexity of assessing and communicating information about multiple contaminant exposure from fish consumption. Communication regarding potential health benefits conferred by specific fish nutrients was minimal and focused primarily on omega-3 fatty acids. This overview suggests some lessons learned and highlights a lack of both clarity and consistency in providing the breadth of information that sensitive populations such as pregnant women need to make public health decisions about fish consumption during pregnancy. PMID:19079708

  10. Does targeting key-containers effectively reduce Aedes aegypti population density?

    PubMed

    Maciel-de-Freitas, Rafael; Lourenço-de-Oliveira, Ricardo

    2011-08-01

    The elimination of Aedes aegypti breeding sites has been broadly adopted worldwide to keep vector population density below a critical threshold. We observed the effectiveness of targeting the most productive containers on adult A. aegypti females density, which was evaluated weekly. Adult mosquitoes were collected weekly over 55 weeks and pupal surveys were done in intervals of 4 months to determine container productivity and guidelines for interventions. Pupal surveys indicated that water tanks (72% of pupae in first survey) and metal drums (30.7% of pupae in second survey) were the most productive container types. We observed a dramatic but short-term decrease in weekly adult female A. aegypti density after covering 733 water tanks with nylon net. A long-term decrease in female adult population density was achieved only when we covered both water tanks and metal drums. Overall, pupae abundance and pupae standing crop diminished after netting water tanks and metal drums. Pupae per person, per hectare and per house decreased gradually between the first and the third pupal surveys, suggesting that targeting the most productive container types (water tanks and metal drums) produced a reduction in adult population density and infestation levels. Overall, targeting the most productive container types caused the adult mosquito density to decrease over time, supporting the assumption that this intervention is an effective tool for dengue control. However, this effect was observed only when both water tanks and metal drums were covered, possibly due to the functional similarity between these container types, which are large, often shaded, perennial water storage containers. © 2011 Blackwell Publishing Ltd.

  11. Target weight achievement and ultrafiltration rate thresholds: potential patient implications.

    PubMed

    Flythe, Jennifer E; Assimon, Magdalene M; Overman, Robert A

    2017-06-02

    Higher ultrafiltration (UF) rates and extracellular hypo- and hypervolemia are associated with adverse outcomes among maintenance hemodialysis patients. The Centers for Medicare and Medicaid Services recently considered UF rate and target weight achievement measures for ESRD Quality Incentive Program inclusion. The dual measures were intended to promote balance between too aggressive and too conservative fluid removal. The National Quality Forum endorsed the UF rate measure but not the target weight measure. We examined the proposed target weight measure and quantified weight gains if UF rate thresholds were applied without treatment time (TT) extension or interdialytic weight gain (IDWG) reduction. Data were taken from the 2012 database of a large dialysis organization. Analyses considered 152,196 United States hemodialysis patients. We described monthly patient and dialysis facility target weight achievement patterns and examined differences in patient characteristics across target weight achievement status and differences in facilities across target weight measure scores. We computed the cumulative, theoretical 1-month fluid-related weight gain that would occur if UF rates were capped at 13 mL/h/kg without concurrent TT extension or IDWG reduction. Target weight achievement patterns were stable over the year. Patients who did not achieve target weight (post-dialysis weight ≥ 1 kg above or below target weight) tended to be younger, black and dialyze via catheter, and had shorter dialysis vintage, greater body weight, higher UF rate and more missed treatments compared with patients who achieved target weight. Facilities had, on average, 27.1 ± 9.7% of patients with average post-dialysis weight ≥ 1 kg above or below the prescribed target weight. In adjusted analyses, facilities located in the midwest and south and facilities with higher proportions of black and Hispanic patients and higher proportions of patients with shorter TTs were more likely to

  12. Can disease management target patients most likely to generate high costs? The impact of comorbidity.

    PubMed

    Charlson, Mary; Charlson, Robert E; Briggs, William; Hollenberg, James

    2007-04-01

    Disease management programs are increasingly used to manage costs of patients with chronic disease. We sought to examine the clinical characteristics and measure the health care expenditures of patients most likely to be targeted by disease management programs. Retrospective analysis of prospectively obtained data. A general medicine practice with both faculty and residents at an urban academic medical center. Five thousand eight hundred sixty-one patients enrolled in the practice for at least 1 year. Annual cost of diseases targeted by disease management. Patients' clinical and demographic information were collected from a computer system used to manage patients. Data included diagnostic information, medications, and resource usage over 1 year. We looked at 10 common diseases targeted by disease management programs. Unadjusted annual median costs for chronic diseases ranged between $1,100 and $1,500. Congestive heart failure ($1,500), stroke ($1,500), diabetes ($1,500), and cancer ($1,400) were the most expensive. As comorbidity increased, annual adjusted costs increased exponentially. Those with comorbidity scores of 2 or more accounted for 26% of the population but 50% of the overall costs. Costs for individual chronic conditions vary within a relatively narrow range. However, the costs for patients with multiple coexisting medical conditions increase rapidly. Reducing health care costs will require focusing on patients with multiple comorbid diseases, not just single diseases. The overwhelming impact of comorbidity on costs raises significant concerns about the potential ability of disease management programs to limit the costs of care.

  13. Culturally Targeted Strategies for Diabetes Prevention in Minority Population.

    PubMed

    Lagisetty, Pooja A; Priyadarshini, Shubadra; Terrell, Stephanie; Hamati, Mary; Landgraf, Jessica; Chopra, Vineet; Heisler, Michele

    2017-02-01

    Purpose The purpose of this study is to (a) assess the effectiveness of culturally tailored diabetes prevention interventions in minority populations and (b) develop a novel framework to characterize 4 key domains of culturally tailored interventions. Prevention strategies specifically tailored to the culture of ethnic minority patients may help reduce the incidence of diabetes. Methods We searched PubMed, EMBASE, and CINAHL for English-language, randomized controlled trials (RCTs) or quasi-experimental (QE) trials testing culturally tailored interventions to prevent diabetes in minority populations. Two reviewers independently extracted data and assessed risk of bias. Inductive thematic analysis was used to develop a framework with 4 domains (FiLLM: Facilitating [ie, delivering] Interventions Through Language, Location, and Message). The framework was used to assess the overall effectiveness of culturally tailored interventions. Results Thirty-four trials met eligibility criteria. Twelve studies were RCTs, and 22 were QE trials. Twenty-five out of 34 studies (74%) that used cultural tailoring demonstrated significantly improved A1C, fasting glucose, and/or weight loss. Of the 25 successful interventions, 21 (84%) incorporated at least 3 culturally targeted domains. Seven studies used all 4 domains and were all successful. The least utilized domain was delivery (4/34) of the intervention's key educational message. Conclusions Culturally tailoring interventions across the 4 domains of facilitators, language, location, and messaging can be effective in improving risk factors for progression to diabetes among ethnic minority groups. Future studies should evaluate how specific tailoring approaches work compared to usual care as well as comparative effectiveness of each tailoring domain.

  14. Assessing Methods for Generalizing Experimental Impact Estimates to Target Populations

    ERIC Educational Resources Information Center

    Kern, Holger L.; Stuart, Elizabeth A.; Hill, Jennifer; Green, Donald P.

    2016-01-01

    Randomized experiments are considered the gold standard for causal inference because they can provide unbiased estimates of treatment effects for the experimental participants. However, researchers and policymakers are often interested in using a specific experiment to inform decisions about other target populations. In education research,…

  15. Targeting Environmental Quality to Improve Population Health ...

    EPA Pesticide Factsheets

    Key goals of health care reform are to stimulate innovative approaches to improve healthcare quality and clinical outcomes while holding down costs. To achieve these goals value-based payment places the needs of the patient first and encourages multi-stakeholder cooperation. Yet, the stakeholders are typically all within the healthcare system, e.g. the Accountable Care Organization or Patient-Centered Medical Home, leaving important contributors to the health of the population such as the public health and environmental health systems absent. And rarely is the quality of the environment regarded as a modifiable factor capable of imparting a health benefit. Underscoring this point, a PubMed search of the search terms “environmental quality” with “value-based payment”, “value-based healthcare” or “value-based reimbursement” returned no relevant articles, providing further evidence that the healthcare industry largely disregards the quality of the environment as a significant determinant of wellbeing and an actionable risk factor for clinical disease management and population health intervention. Yet, the quality of the environment is unequivocally related to indicators of population health including all-cause mortality. The EPA’s Environmental Quality Index (EQI) composed of five different domains (air, land use, water, built environment and social) has provided new estimates of the associations between environmental quality and health stat

  16. Population pharmacokinetic-pharmacodynamic target attainment analysis of imipenem plasma and urine data in neonates and children.

    PubMed

    Yoshizawa, Kenichi; Ikawa, Kazuro; Ikeda, Kayo; Ohge, Hiroki; Morikawa, Norifumi

    2013-11-01

    Population pharmacokinetic (PK)-pharmacodynamic target attainment analysis of imipenem was performed to elucidate the PK properties in neonates and children and to rationalize and optimize dosing regimens. Population PK models were separately developed in neonates and children by simultaneously fitting plasma and urine data from 60 neonates and 39 children. The newly developed models were then used to estimate the probability of attaining the pharmacodynamic target (40% of the time above the minimum inhibitory concentration) against clinical isolates of common bacteria in pediatric patients. The data were best described by a 1-compartment model in neonates and a 2-compartment model in children, respectively. Renal clearance in children (0.187 L/h/kg) was double that of neonates (0.0783 L/h/kg), whereas the volume of distribution at steady-state was approximately 1.8-fold larger in neonates (0.466 L/kg) than in children (0.260 L/kg). Age was not a statistically significant covariate in the PK of both groups. Infusions (0.5 h) of 15 mg/kg every 8 h (45 mg/kg/day) and 25 mg/kg every 12 h (50 mg/kg/day) were shown to be sufficient against common bacterial isolates in both patient populations. However, 1.5-h infusions of 25 mg/kg every 8 h (75 mg/kg/day) in neonates and 25 mg/kg every 6 h (100 mg/kg/day) in children were required to be effective against Pseudomonas aeruginosa (minimum inhibitory concentration for 90% of the isolates=16 μg/mL). These results explain the changes in imipenem PK properties during the human growth process and provide guidance for tailoring dosing regimens in each pediatric age group.

  17. Improving patient outcomes to targeted therapies in melanoma.

    PubMed

    Eroglu, Zeynep; Smalley, Keiran S M; Sondak, Vernon K

    2016-06-01

    The arrival of targeted therapies has led to significant improvements in clinical outcomes for patients with BRAFV600 mutated advanced melanoma over the past five years. In several clinical trials, BRAF and MEK inhibitors have shown improvement in progression free and overall survival, along with much higher tumor response rates in comparison to chemotherapy, with the combination of these drugs superior to monotherapy. These agents are also being tested in earlier-stage patients, in addition to alternative dosing regimens and in combinations with other therapeutics. Efforts are also ongoing to expand the success found with targeted therapies to other subtypes of melanoma, including NRAS and c-kit mutated melanomas, uveal melanomas, and BRAF/NRAS wild type melanomas. Expert Commentary: We aim to provide an overview of clinical outcomes with targeted therapies in melanoma patients.

  18. Targeted mutation screening panels expose systematic population bias in detection of cystic fibrosis risk.

    PubMed

    Lim, Regine M; Silver, Ari J; Silver, Maxwell J; Borroto, Carlos; Spurrier, Brett; Petrossian, Tanya C; Larson, Jessica L; Silver, Lee M

    2016-02-01

    Carrier screening for mutations contributing to cystic fibrosis (CF) is typically accomplished with panels composed of variants that are clinically validated primarily in patients of European descent. This approach has created a static genetic and phenotypic profile for CF. An opportunity now exists to reevaluate the disease profile of CFTR at a global population level. CFTR allele and genotype frequencies were obtained from a nonpatient cohort with more than 60,000 unrelated personal genomes collected by the Exome Aggregation Consortium. Likely disease-contributing mutations were identified with the use of public database annotations and computational tools. We identified 131 previously described and likely pathogenic variants and another 210 untested variants with a high probability of causing protein damage. None of the current genetic screening panels or existing CFTR mutation databases covered a majority of deleterious variants in any geographical population outside of Europe. Both clinical annotation and mutation coverage by commercially available targeted screening panels for CF are strongly biased toward detection of reproductive risk in persons of European descent. South and East Asian populations are severely underrepresented, in part because of a definition of disease that preferences the phenotype associated with European-typical CFTR alleles.

  19. Use and outcomes of targeted therapies in early and metastatic HER2-positive breast cancer in Australia: protocol detailing observations in a whole of population cohort

    PubMed Central

    Daniels, Benjamin; Lord, Sarah J; Kiely, Belinda E; Houssami, Nehmat; Haywood, Philip; Lu, Christine Y; Ward, Robyn L; Pearson, Sallie-Anne

    2017-01-01

    Background The management of human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) has changed dramatically with the introduction and widespread use of HER2-targeted therapies. However, there is relatively limited real-world information on patterns of use, effectiveness and safety in whole of population cohorts. The research programme detailed in this protocol will generate evidence on the prescribing patterns, safety monitoring and outcomes of patients with BC treated with HER2-targeted therapies in Australia. Methods/design Our ongoing research programme will involve a series of retrospective cohort studies that include every patient accessing Commonwealth-funded HER2-targeted therapies for the treatment of early BC and advanced BC in Australia. At the time of writing, our cohorts consist of 11 406 patients with early BC and 5631 with advanced BC who accessed trastuzumab and lapatinib between 2001 and 2014. Pertuzumab and trastuzumab emtansine were publicly funded for metastatic BC in 2015, and future data updates will include patients accessing these medicines. We will use dispensing claims for cancer and other medicines, medical service claims and demographics data for each patient accessing HER2-targeted therapies to undertake this research. Ethics and dissemination Ethics approval has been granted by the Population Health Service Research Ethics Committee and data access approval has been granted by the Australian Department of Human Services (DHS) External Review Evaluation Committee. Our findings will be reported in peer-reviewed publications, conference presentations and policy forums. By providing detailed information on the use and outcomes associated with HER2-targeted therapies in a national cohort treated in routine clinical care, our research programme will better inform clinicians and patients about the real-world use of these treatments and will assist third-party payers to better understand the use and economic costs of these

  20. Impact of Targeted Tuberculosis Vaccination Among a Mining Population in South Africa: A Model-Based Study.

    PubMed

    Shrestha, Sourya; Chihota, Violet; White, Richard G; Grant, Alison D; Churchyard, Gavin J; Dowdy, David W

    2017-12-15

    Optimizing the use of new tools, such as vaccines, may play a crucial role in reaching global targets for tuberculosis (TB) control. Some of the most promising candidate vaccines target adults, although high-coverage mass vaccinations may be logistically more challenging among this population than among children. Vaccine-delivery strategies that target high-risk groups or settings might yield proportionally greater impact than do those that target the general population. We developed an individual-based TB transmission model representing a hypothetical population consisting of people who worked in South African gold mines or lived in associated labor-sending communities. We simulated the implementation of a postinfection adult vaccine with 60% efficacy and a mean effect duration of 10 years. We then compared the impact of a mine-targeted vaccination strategy, in which miners were vaccinated while in the mines, with that of a community-targeted strategy, in which random individuals within the labor-sending communities were vaccinated. Mine-targeted vaccination averted an estimated 0.37 TB cases per vaccine dose compared with 0.25 for community-targeted vaccination, for a relative efficacy of 1.46 (95% range, 1.13-1.91). The added benefit of mine-targeted vaccination primarily reflected the disproportionate demographic burden of TB among the population of adult males as a whole. As novel vaccines for TB are developed, venue-based vaccine delivery that targets high-risk demographic groups may improve both vaccine feasibility and the impact on transmission. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. The economic burden of patient safety targets in acute care: a systematic review

    PubMed Central

    Mittmann, Nicole; Koo, Marika; Daneman, Nick; McDonald, Andrew; Baker, Michael; Matlow, Anne; Krahn, Murray; Shojania, Kaveh G; Etchells, Edward

    2012-01-01

    Background Our objective was to determine the quality of literature in costing of the economic burden of patient safety. Methods We selected 15 types of patient safety targets for our systematic review. We searched the literature published between 2000 and 2010 using the following terms: “costs and cost analysis,” “cost-effectiveness,” “cost,” and “financial management, hospital.” We appraised the methodologic quality of potentially relevant studies using standard economic methods. We recorded results in the original currency, adjusted for inflation, and then converted to 2010 US dollars for comparative purposes (2010 US$1.00 = 2010 €0.76). The quality of each costing study per patient safety target was also evaluated. Results We screened 1948 abstracts, and identified 158 potentially eligible studies, of which only 61 (39%) reported any costing methodology. In these 61 studies, we found wide estimates of the attributable costs of patient safety events ranging from $2830 to $10,074. In general hospital populations, the cost per case of hospital-acquired infection ranged from $2132 to $15,018. Nosocomial bloodstream infection was associated with costs ranging from $2604 to $22,414. Conclusion There are wide variations in the estimates of economic burden due to differences in study methods and methodologic quality. Greater attention to methodologic standards for economic evaluations in patient safety is needed. PMID:23097615

  2. FOXP2 Targets Show Evidence of Positive Selection in European Populations

    PubMed Central

    Ayub, Qasim; Yngvadottir, Bryndis; Chen, Yuan; Xue, Yali; Hu, Min; Vernes, Sonja C.; Fisher, Simon E.; Tyler-Smith, Chris

    2013-01-01

    Forkhead box P2 (FOXP2) is a highly conserved transcription factor that has been implicated in human speech and language disorders and plays important roles in the plasticity of the developing brain. The pattern of nucleotide polymorphisms in FOXP2 in modern populations suggests that it has been the target of positive (Darwinian) selection during recent human evolution. In our study, we searched for evidence of selection that might have followed FOXP2 adaptations in modern humans. We examined whether or not putative FOXP2 targets identified by chromatin-immunoprecipitation genomic screening show evidence of positive selection. We developed an algorithm that, for any given gene list, systematically generates matched lists of control genes from the Ensembl database, collates summary statistics for three frequency-spectrum-based neutrality tests from the low-coverage resequencing data of the 1000 Genomes Project, and determines whether these statistics are significantly different between the given gene targets and the set of controls. Overall, there was strong evidence of selection of FOXP2 targets in Europeans, but not in the Han Chinese, Japanese, or Yoruba populations. Significant outliers included several genes linked to cellular movement, reproduction, development, and immune cell trafficking, and 13 of these constituted a significant network associated with cardiac arteriopathy. Strong signals of selection were observed for CNTNAP2 and RBFOX1, key neurally expressed genes that have been consistently identified as direct FOXP2 targets in multiple studies and that have themselves been associated with neurodevelopmental disorders involving language dysfunction. PMID:23602712

  3. Do We Need a Patient-Centered Target for Systolic Blood Pressure in Hypertensive Patients With Type 2 Diabetes Mellitus?

    PubMed

    Wan, Eric Yuk Fai; Yu, Esther Yee Tak; Fung, Colman Siu Cheung; Chin, Weng Yee; Fong, Daniel Yee Tak; Chan, Anca Ka Chun; Lam, Cindy Lo Kuen

    2017-12-01

    The current trend on diabetes mellitus management advocates replacing the paradigm from a uniform to an individualized patient-centered systolic blood pressure (SBP), but there is no consensus on the achieved treatment goals of SBP level. The study aimed at evaluating the association between SBP and the risk of cardiovascular diseases (CVD) and all-cause mortality for diabetic patients to identify patient-centered treatment targets. A retrospective study was conducted on 95 086 Chinese adult primary care patients with type 2 diabetes mellitus and hypertension. Using the average of the annual SBP records (updated SBP) over a median follow-up of 5.9 years, the risks of overall CVD, all-cause mortality, and their composite associated with SBP were evaluated using Cox proportional hazards regression. Subgroup analysis was performed on the incidence of CVD by stratifying patient's baseline characteristics. The SBP range for the lowest risk of CVD and all-cause mortality was 130 to 134 mm Hg among type 2 diabetes mellitus population. A J-shaped curvilinear relationship was identified between SBP and risk of CVD and all-cause mortality, irrespective of patients' characteristics. The findings showed that all patients with SBP <125 mm Hg or ≥140 mm Hg had an increased risk of CVD and mortality. This large territory-wide study showed the level of achieved SBP of 125 to 139 mm Hg in pharmacological therapy, irrespective of patients' characteristics, suggested that the SBP treatment goal of <140 mm Hg and individualized SBP target may not be necessary in diabetic management. © 2017 American Heart Association, Inc.

  4. Improving the quality of primary care by allocating performance-based targets, in a diverse insured population.

    PubMed

    Peled, Ronit; Porath, Avi; Wilf-Miron, Rachel

    2016-11-21

    Primary Care Health organizations, operating under universal coverage and a regulated package of benefits, compete mainly over quality of care. Monitoring, primary care clinical performance, has been repeatedly proven effective in improving the quality of care. In 2004, Maccabi Healthcare Services (MHS), the second largest Israeli HMO, launched its Performance Measurement System (PMS) based on clinical quality indicators. A unique module was built in the PMS to adjust for case mix while tailoring targets to the local units. This article presents the concept and formulas developed to adjust targets to the units' current performance, and analyze change in clinical indicators over a six year period, between sub-population groups. Six process and intermediate outcome indicators, representing screening for breast and colorectal cancer and care for patients with diabetes and cardiovascular disease, were selected and analyzed for change over time (2003-2009) in overall performance, as well as the difference between the lowest and the highest socio-economic ranks (SERs) and Arab and non-Arab members. MHS demonstrated a significant improvement in the selected indicators over the years. Performance of members from low SERs and Arabs improved to a greater extent, as compared to members from high ranks and non-Arabs, respectively. The performance measurement system, with its module for tailoring of units' targets, served as a managerial vehicle for bridging existing gaps by allocating more resources to lower performing units. This concept was proven effective in improving performance while reducing disparities between diverse population groups.

  5. Characteristics of Interventions Targeting Multiple Lifestyle Risk Behaviours in Adult Populations: A Systematic Scoping Review

    PubMed Central

    King, Kristel; Meader, Nick; Wright, Kath; Graham, Hilary; Power, Christine; Petticrew, Mark; White, Martin; Sowden, Amanda J.

    2015-01-01

    Background Modifiable lifestyle risk behaviours such as smoking, unhealthy diet, physical inactivity and alcohol misuse are the leading causes of major, non-communicable diseases worldwide. It is increasingly being recognised that interventions which target more than one risk behaviour may be an effective and efficient way of improving people’s lifestyles. To date, there has been no attempt to summarise the global evidence base for interventions targeting multiple risk behaviours. Objective To identify and map the characteristics of studies evaluating multiple risk behaviour change interventions targeted at adult populations in any country. Methods Seven bibliographic databases were searched between January, 1990, and January/ May, 2013. Authors of protocols, conference abstracts, and other relevant articles were contacted. Study characteristics were extracted and inputted into Eppi-Reviewer 4. Results In total, 220 studies were included in the scoping review. Most were randomised controlled trials (62%) conducted in the United States (49%), and targeted diet and physical activity (56%) in people from general populations (14%) or subgroups of general populations (45%). Very few studies had been conducted in the Middle East (2%), Africa (0.5%), or South America (0.5%). There was also a scarcity of studies conducted among young adults (1%), or racial and minority ethnic populations (4%) worldwide. Conclusions Research is required to investigate the interrelationships of lifestyle risk behaviours in varying cultural contexts around the world. Cross-cultural development and evaluation of multiple risk behaviour change interventions is also needed, particularly in populations of young adults and racial and minority ethnic populations. PMID:25617783

  6. Culture-Independent Identification of Periodontitis-Associated Porphyromonas and Tannerella Populations by Targeted Molecular Analysis

    PubMed Central

    de Lillo, A.; Booth, V.; Kyriacou, L.; Weightman, A. J.; Wade, W. G.

    2004-01-01

    Periodontitis is the commonest bacterial disease of humans and is the major cause of adult tooth loss. About half of the oral microflora is unculturable; and 16S rRNA PCR, cloning, and sequencing techniques have demonstrated the high level of species richness of the oral microflora. In the present study, a PCR primer set specific for the genera Porphyromonas and Tannerella was designed and used to analyze the bacterial populations in subgingival plaque samples from inflamed shallow and deep sites in subjects with periodontitis and shallow sites in age- and sex-matched controls. A total of 308 clones were sequenced and found to belong to one of six Porphyromonas or Tannerella species or phylotypes, one of which, Porphyromonas P3, was novel. Tannerella forsythensis was found in significantly higher proportions in patients than in controls. Porphyromonas catoniae and Tannerella phylotype BU063 appeared to be associated with shallow sites. Targeted culture-independent molecular ecology studies have a valuable role to play in the identification of bacterial targets for further investigations of the pathogenesis of bacterial infections. PMID:15583276

  7. Can Disease Management Target Patients Most Likely to Generate High Costs? The Impact of Comorbidity

    PubMed Central

    Charlson, Robert E.; Briggs, William; Hollenberg, James

    2007-01-01

    Context Disease management programs are increasingly used to manage costs of patients with chronic disease. Objective We sought to examine the clinical characteristics and measure the health care expenditures of patients most likely to be targeted by disease management programs. Design Retrospective analysis of prospectively obtained data. Setting A general medicine practice with both faculty and residents at an urban academic medical center. Participants Five thousand eight hundred sixty-one patients enrolled in the practice for at least 1 year. Main Outcomes Annual cost of diseases targeted by disease management. Measurements Patients’ clinical and demographic information were collected from a computer system used to manage patients. Data included diagnostic information, medications, and resource usage over 1 year. We looked at 10 common diseases targeted by disease management programs. Results Unadjusted annual median costs for chronic diseases ranged between $1,100 and $1,500. Congestive heart failure ($1,500), stroke ($1,500), diabetes ($1,500), and cancer ($1,400) were the most expensive. As comorbidity increased, annual adjusted costs increased exponentially. Those with comorbidity scores of 2 or more accounted for 26% of the population but 50% of the overall costs. Conclusions Costs for individual chronic conditions vary within a relatively narrow range. However, the costs for patients with multiple coexisting medical conditions increase rapidly. Reducing health care costs will require focusing on patients with multiple comorbid diseases, not just single diseases. The overwhelming impact of comorbidity on costs raises significant concerns about the potential ability of disease management programs to limit the costs of care. PMID:17372794

  8. FOXP2 targets show evidence of positive selection in European populations.

    PubMed

    Ayub, Qasim; Yngvadottir, Bryndis; Chen, Yuan; Xue, Yali; Hu, Min; Vernes, Sonja C; Fisher, Simon E; Tyler-Smith, Chris

    2013-05-02

    Forkhead box P2 (FOXP2) is a highly conserved transcription factor that has been implicated in human speech and language disorders and plays important roles in the plasticity of the developing brain. The pattern of nucleotide polymorphisms in FOXP2 in modern populations suggests that it has been the target of positive (Darwinian) selection during recent human evolution. In our study, we searched for evidence of selection that might have followed FOXP2 adaptations in modern humans. We examined whether or not putative FOXP2 targets identified by chromatin-immunoprecipitation genomic screening show evidence of positive selection. We developed an algorithm that, for any given gene list, systematically generates matched lists of control genes from the Ensembl database, collates summary statistics for three frequency-spectrum-based neutrality tests from the low-coverage resequencing data of the 1000 Genomes Project, and determines whether these statistics are significantly different between the given gene targets and the set of controls. Overall, there was strong evidence of selection of FOXP2 targets in Europeans, but not in the Han Chinese, Japanese, or Yoruba populations. Significant outliers included several genes linked to cellular movement, reproduction, development, and immune cell trafficking, and 13 of these constituted a significant network associated with cardiac arteriopathy. Strong signals of selection were observed for CNTNAP2 and RBFOX1, key neurally expressed genes that have been consistently identified as direct FOXP2 targets in multiple studies and that have themselves been associated with neurodevelopmental disorders involving language dysfunction. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  9. Cognition As a Therapeutic Target in the Suicidal Patient Approach

    PubMed Central

    da Silva, Antônio Geraldo; Malloy-Diniz, Leandro Fernandes; Garcia, Marina Saraiva; Figueiredo, Carlos Guilherme Silva; Figueiredo, Renata Nayara; Diaz, Alexandre Paim; Palha, António Pacheco

    2018-01-01

    The current considerations about completed suicides and suicide attempts in different cultures call the attention of professionals to this serious public health problem. Integrative approaches have shown that the confluence of multiple biological and social factors modulate various psychopathologies and dysfunctional behaviors, such as suicidal behavior. Considering the level of intermediate analysis, personality traits and cognitive functioning are also of great importance for understanding the suicide phenomenon. About cognitive factors, we can group them into cognitive schemas of reality interpretation and underlying cognitive processes. On the other hand, different types of primary cognitive alterations are related to suicidal behavior, especially those resulting from changes in frontostriatal circuits. Among such cognitive mechanisms can be highlighted the attentional bias for environmental cues related to suicide, impulsive behavior, verbal fluency deficits, non-adaptive decision-making, and reduced planning skills. Attentional bias consists in the effect of thoughts and emotions, frequently not conscious, about the perception of environmental stimuli. Suicidal ideation and hopelessness can make the patient unable to find alternative solutions to their problems other than suicide, biasing their attention to environmental cues related to such behavior. Recent research efforts are directed to assess the possible use of attention bias as a therapeutic target in patients presenting suicide behavior. The relationship between impulsivity and suicide has been largely investigated over the last decades, and there is still controversy about the theme. Although there is strong evidence linking impulsivity to suicide attempts. Effective interventions address to reduce impulsivity in clinical populations at higher risk for suicide could help in the prevention. Deficits in problem-solving ability also seem to be distorted in patients who attempt suicide. Understanding

  10. Clinical performance targets and quality of life in hemodialysis patients.

    PubMed

    Mazairac, Albert H A; de Wit, G Ardine; Grooteman, Muriel P C; Penne, E Lars; van der Weerd, Neelke C; den Hoedt, Claire H; Lévesque, Renée; van den Dorpel, Marinus A; Nubé, Menso J; Ter Wee, Piet M; Blankestijn, Peter J; Bots, Michiel L

    2012-01-01

    Patients value health-related quality of life (HRQOL) over survival. It was our aim to study the relation between attainment of widely accepted performance targets and HRQOL in hemodialysis patients. This study included baseline data from 715 hemodialysis patients from 29 dialysis centers. Six clinical performance targets, as recommended by the Kidney Disease Outcomes Quality Initiative (KDOQI), were evaluated: single-pool Kt/V (≥1.2), hemoglobin (11-13 g/dl), vascular access (fistula), phosphorus (2.3-4.5 mg/dl), parathyroid hormone (150-300 pg/ml), and blood pressure (predialysis <140/90 and postdialysis <130/ 80 mm Hg). After correction for case-mix and multiple comparisons, no association was found between the 6 KDOQI clinical performance targets and the 14 HRQOL domains, or between the number of performance targets reached and HRQOL. Attainment with widely accepted clinical performance targets was not related to the HRQOL of hemodialysis patients. Hence, in clinical guidelines, HRQOL should be adopted as an explicit treatment goal for these individuals. Copyright © 2011 S. Karger AG, Basel.

  11. Non-coding glucometers among pediatric patients with diabetes: looking for the target population and an accuracy evaluation of no-coding personal glucometer.

    PubMed

    Fendler, Wojciech; Hogendorf, Anna; Szadkowska, Agnieszka; Młynarski, Wojciech

    2011-01-01

    Self-monitoring of blood glucose (SMBG) is one of the cornerstones of diabetes management. To evaluate the potential for miscoding of a personal glucometer, to define a target population among pediatric patients with diabetes for a non-coding glucometer and the accuracy of the Contour TS non-coding system. Potential for miscoding during self-monitoring of blood glucose was evaluated by means of an anonymous questionnaire, with worst and best case scenarios evaluated depending on the responses pattern. Testing of the Contour TS system was performed according to guidelines set by the national committee for clinical laboratory standards. Estimated frequency of individuals prone to non-coding ranged from 68.21% (95% 60.70- 75.72%) to 7.95% (95%CI 3.86-12.31%) for the worse and best case scenarios respectively. Factors associated with increased likelihood of non-coding were: a smaller number of tests per day, a greater number of individuals involved in testing and self-testing by the patient with diabetes. The Contour TS device showed intra- and inter-assay accuracy -95%, linear association with laboratory measurements (R2=0.99, p <0.0001) and consistent, but small bias of -1.12% (95% Confidence Interval -3.27 to 1.02%). Clarke error grid analysis showed 4% of values within the benign error zone (B) with the other measurements yielding an acceptably accurate result (zone A). The Contour TS system showed sufficient accuracy to be safely used in monitoring of pediatric diabetic patients. Patients from families with a high throughput of test-strips or multiple individuals involved in SMBG using the same meter are candidates for clinical use of such devices due to an increased risk of calibration errors.

  12. Population pharmacokinetics and dosing simulations of imipenem in serious bacteraemia in immunocompromised patients with febrile neutropenia.

    PubMed

    Jaruratanasirikul, Sutep; Wongpoowarak, Wibul; Jullangkoon, Monchana; Samaeng, Maseetoh

    2015-02-01

    The aims of this study were to i) reveal the population pharmacokinetics; and ii) assess the probability of target attainment (PTA) and cumulative fraction of response (CFR) (defined as the expected population PTA for a specific drug dose and a specific population of microorganisms) of imipenem in febrile neutropenic patients with bacteraemia. Ten patients were randomised into two groups: Group I received a 0.5-h infusion of 0.5 g of imipenem every 6 h (q6h) for 8 doses; and Group II received a 4-h infusion of 0.5 g q6h for 8 doses. A Monte Carlo simulation was performed to determine the PTA. The volume of distribution and total clearance of imipenem were 20.78 ± 1.35 l and 23.19 ± 1.34 l/h, respectively. Only a 4-h infusion of 1 g q6h regimen achieved a PTA >93% for 80% T>MIC for a MIC of 2 μg/ml. A 4-h infusion of all simulated regimens and a 0.5-h infusion of 0.5 g q6h and 1 g q6h achieved targets (CFR ≥ 90%) against Escherichia coli and Klebsiella spp. However, against Pseudomonas aeruginosa and Acinetobacter spp., no regimens achieved their targets. In conclusion, the results indicate that a higher than manufacturer's dosage recommendation is required to maximize the activity of imipenem. Copyright © 2014 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.

  13. Individualised treatment targets in patients with type-2 diabetes and hypertension.

    PubMed

    Schmieder, Roland E; Tschöpe, Diethelm; Koch, Cornelia; Ouarrak, Taoufik; Gitt, Anselm K

    2018-01-22

    Patients with type-2 diabetes mellitus (T2DM) are at high risk of cardiovascular events, accentuated in the presence of hypertension. At present, it is unclear to what extent the guidelines for the management of T2DM, advocating reduction in HbA1c levels to below target levels, are being adhered to in clinical practice. DIALOGUE was a prospective, observational, non-interventional registry performed across multiple centres in Germany. Patients aged 18 years or older who had T2DM and hypertension for whom the treating physician considered blood glucose lowering medication as inadequate and/or not safe/tolerable and chose to add a further oral drug or switch drug treatment were included. Patients were assigned a treatment target HbA1c value (≤ 6.5% [strict]; > 6.5 to ≤ 7.0% [intermediate]; > 7.0 to ≤ 7.5% [lenient]). 8568 patients with T2DM and hypertension were enrolled. 6691 (78.1%) had 12-month follow-up. Patients who were assigned a strict HbA1c treatment target (n = 2644) were younger, had shorter diabetes duration, and less comorbidity in comparison to those with intermediate (n = 2912) or lenient targets (n = 1135). Only 53.1% of patients achieved their HbA1c treatment target (46.2% [strict], 56.8% [intermediate], 59.4% [lenient]). There was little sign of treatment intensification for patients that had not achieved their HbA1c target. Achievement of treatment targets was poor, leaving many patients with sub-optimal blood glucose levels. The apparent reluctance of physicians to intensify antidiabetic drug therapy is alarming, especially considering the evidence pointing to an association of hyperglycaemia and microvascular complications in patients with T2DM.

  14. Similar clinical benefits from below-target and target dose enalapril in patients with heart failure in the SOLVD Treatment trial.

    PubMed

    Lam, Phillip H; Dooley, Daniel J; Fonarow, Gregg C; Butler, Javed; Bhatt, Deepak L; Filippatos, Gerasimos S; Deedwania, Prakash; Forman, Daniel E; White, Michel; Fletcher, Ross D; Arundel, Cherinne; Blackman, Marc R; Adamopoulos, Chris; Kanonidis, Ioannis E; Aban, Inmaculada B; Patel, Kanan; Aronow, Wilbert S; Allman, Richard M; Anker, Stefan D; Pitt, Bertram; Ahmed, Ali

    2018-02-01

    To examine associations of below-target and target dose of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, with outcomes in patients with heart failure and reduced ejection fraction (HFrEF) in the Studies of Left Ventricular Dysfunction (SOLVD) Treatment trial. Two thousand five hundred and sixty-nine patients with HFrEF (ejection fraction ≤35%) were randomized to below-target (5-10 mg/day) dose placebo (n = 1284) or enalapril (n = 1285). One month post-randomization, blind up-titration to target (20 mg/day) dose was attempted for both study drugs in 2458 patients. Among the 1444 patients who achieved dose up-titration (placebo, n = 748; enalapril, n = 696; mean dose for both groups, 20.0 mg/day), target dose enalapril (vs. target dose placebo) was associated with a 9% absolute lower risk of the combined endpoint of heart failure hospitalization or all-cause mortality [adjusted hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.60-0.81; P < 0.001] during 4 years of follow-up. Among the 1014 patients who could not achieve target dose (placebo, n = 486; enalapril, n = 528; mean dose for both groups, 8.8 mg/day), below-target dose enalapril (vs. below-target dose placebo) was associated with a 12% absolute lower risk of the combined endpoint of heart failure hospitalization or all-cause mortality (adjusted HR 0.68; 95% CI 0.57-0.81; P < 0.001). Among the 1224 patients receiving enalapril, target (vs. below-target) dose had no association with the combined endpoint of heart failure hospitalization or all-cause mortality (adjusted HR 1.04; 95% CI 0.87-1.23; P = 0.695). In patients with HFrEF, the clinical benefits of ACE inhibitors appear to be similar at both below-target and target doses. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

  15. How are metabolic control targets of patients with Type 1 diabetes mellitus achieved in daily practice in the area with high diabetes prevalence?

    PubMed

    Kekäläinen, Päivi; Tirkkonen, Hilkka; Laatikainen, Tiina

    2016-05-01

    We assessed the prevalence of Type 1 diabetes mellitus and determined how the targets established in the guidelines for patients with Type 1 diabetes mellitus were achieved in clinical practice in North Karelia, Finland. All adult Type 1 diabetes mellitus patients (n=1075) were identified from the regional electronic patient database. The data for HbA1c and LDL cholesterol measurements during the years 2013 and 2014 were obtained from medical records. The prevalence of Type 1 diabetes mellitus in the adult population in North Karelia was 0.8%, which is among the highest worldwide. HbA1c and LDL cholesterol were measured in 93% and 90% of participants, respectively. Nineteen percent of patients reached the HbA1c target of <7.0% (53mmol/mol) and 45% attained LDL cholesterol <2.5mmol/l. Overall, 26% of patients over 60 years old with diabetes achieved glycaemic control targets compared with 13-16% of younger patients with diabetes. Glycaemic control was in line with the recommendations in only one-fifth of Type 1 diabetes mellitus patients and less than half of them had LDL cholesterol levels within the target range. Interestingly, older Type 1 diabetes mellitus patients met the glycaemic control target more often than younger patients with diabetes. The targets established for patients with Type 1 diabetes mellitus are not achieved satisfactorily in daily practice. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Interarm blood pressure difference and target organ damage in the general population.

    PubMed

    Johansson, Jouni K; Puukka, Pauli J; Jula, Antti M

    2014-02-01

    The objective of the study was to investigate interarm differences of blood pressure (BP) and its determinants, and to clarify whether both arms are equally good in assessing BP and target organ damage in the general population. We studied a representative sample of Finnish adult population with 484 study participants, ages 25-74 years. BP was measured twice by an oscillometric monitor simultaneously on both arms. Study participants underwent a clinical examination including measurements of serum lipids, glucose and indicators of target organ damage. BP was 2.3/0.2 mmHg higher on right than on left arm (P < 0.001/P = 0.15 for SBP/DBP differences). SBP and DBP measured on right and left arms correlated equally with left ventricular mass index (LVMI), interventricular septal thickness (IVST), posterior wall thickness (PWT), pulse wave velocity (PWV) and albuminuria. Higher SBP level was an independent determinant of both greater systolic and diastolic interarm BP difference. Exaggerated absolute diastolic interarm BP difference (>5 mmHg) was associated with higher BMI, arm circumference, LVMI, IVST and PWT, whereas exaggerated absolute systolic interarm BP difference (>10 mmHg) was not associated with any clinical variables. There was only a small difference in BP between arms in a healthy general population. Both arms are equally good determinants of target organ damage. BP should be measured at least once on both arms and prefer the arm with higher BP readings in the future BP measurements.

  17. Deprescribing Benzodiazepines in Older Patients: Impact of Interventions Targeting Physicians, Pharmacists, and Patients.

    PubMed

    Ng, Brendan J; Le Couteur, David G; Hilmer, Sarah N

    2018-04-28

    Benzodiazepines (BZDs; including the related Z-drugs) are frequently targets for deprescribing; long-term use in older people is harmful and often not beneficial. BZDs can result in significant harms, including falls, fractures, cognitive impairment, car crashes and a significant financial and legal burden to society. Deprescribing BZDs is problematic due to a complex interaction of drug, patient, physician and systematic barriers, including concern about a potentially distressing but rarely fatal withdrawal syndrome. Multiple studies have trialled interventions to deprescribe BZDs in older people and are discussed in this narrative review. Reported success rates of deprescribing BZD interventions range between 27 and 80%, and this variability can be attributed to heterogeneity of methodological approaches and limited generalisability to cognitively impaired patients. Interventions targeting the patient and/or carer include raising awareness (direct-to-consumer education, minimal interventions, and 'one-off' geriatrician counselling) and resourcing the patient (gradual dose reduction [GDR] with or without cognitive behavioural therapy, teaching relaxation techniques, and sleep hygiene). These are effective if the patient is motivated to cease and is not significantly cognitively impaired. Interventions targeted to physicians include prescribing interventions by audit, algorithm or medication review, and providing supervised GDR in combination with medication substitution. Pharmacists have less frequently been the targets for studies, but have key roles in several multifaceted interventions. Interventions are evaluated according to the Behaviour Change Wheel. Research supports trialling a stepwise approach in the cognitively intact older person, but having a low threshold to use less-consultative methods in patients with dementia. Several resources are available to support deprescribing of BZDs in clinical practice, including online protocols.

  18. CIP2A is a candidate therapeutic target in clinically challenging prostate cancer cell populations.

    PubMed

    Khanna, Anchit; Rane, Jayant K; Kivinummi, Kati K; Urbanucci, Alfonso; Helenius, Merja A; Tolonen, Teemu T; Saramäki, Outi R; Latonen, Leena; Manni, Visa; Pimanda, John E; Maitland, Norman J; Westermarck, Jukka; Visakorpi, Tapio

    2015-08-14

    Residual androgen receptor (AR)-signaling and presence of cancer stem-like cells (SCs) are the two emerging paradigms for clinically challenging castration-resistant prostate cancer (CRPC). Therefore, identification of AR-target proteins that are also overexpressed in the cancer SC population would be an attractive therapeutic approach.Our analysis of over three hundred clinical samples and patient-derived prostate epithelial cultures (PPECs), revealed Cancerous inhibitor of protein phosphatase 2A (CIP2A) as one such target. CIP2A is significantly overexpressed in both hormone-naïve prostate cancer (HN-PC) and CRPC patients . CIP2A is also overexpressed, by 3- and 30-fold, in HN-PC and CRPC SCs respectively. In vivo binding of the AR to the intronic region of CIP2A and its functionality in the AR-moderate and AR-high expressing LNCaP cell-model systems is also demonstrated. Further, we show that AR positively regulates CIP2A expression, both at the mRNA and protein level. Finally, CIP2A depletion reduced cell viability and colony forming efficiency of AR-independent PPECs as well as AR-responsive LNCaP cells, in which anchorage-independent growth is also impaired.These findings identify CIP2A as a common denominator for AR-signaling and cancer SC functionality, highlighting its potential therapeutic significance in the most clinically challenging prostate pathology: castration-resistant prostate cancer.

  19. Integrated Population Pharmacokinetic Analysis of Rivaroxaban Across Multiple Patient Populations

    PubMed Central

    Zhang, Liping; Frede, Matthias; Kubitza, Dagmar; Mueck, Wolfgang; Schmidt, Stephan; Solms, Alexander; Yan, Xiaoyu; Garmann, Dirk

    2018-01-01

    The population pharmacokinetics (PK) of rivaroxaban have been evaluated in several population‐specific models. We developed an integrated population PK model using pooled data from 4,918 patients in 7 clinical trials across all approved indications. Effects of gender, age, and weight on apparent clearance (CL/F) and apparent volume of distribution (V/F), renal function, and comedication on CL/F, and relative bioavailability as a function of dose (F) were analyzed. Virtual subpopulations for exposure simulations were defined by age, creatinine clearance (CrCL) and body mass index (BMI). Rivaroxaban PK were adequately described by a one‐compartment disposition model with a first‐order absorption rate constant. Significant effects of CrCL, use of comedications, and study population on CL/F, age, weight, and gender on V/F, and dose on F were identified. CrCL had a modest influence on exposure, whereas age and BMI had a minor influence. The model was suitable to predict rivaroxaban exposure in patient subgroups of special interest. PMID:29660785

  20. Blood pressure and antihypertensive medication profile in a multiethnic Asian population of stable chronic kidney disease patients.

    PubMed

    Teo, Boon Wee; Chua, Horng Ruey; Wong, Weng Kin; Haroon, Sabrina; Subramanian, Srinivas; Loh, Ping Tyug; Sethi, Sunil; Lau, Titus

    2016-05-01

    Clinical practice guidelines recommend different blood pressure (BP) goals for chronic kidney disease (CKD) patients. Usage of antihypertensive medication and attainment of BP targets in Asian CKD patients remain unclear. This study describes the profile of antihypertensive agents used and BP components in a multiethnic Asian population with stable CKD. Stable CKD outpatients with variability of serum creatinine levels < 20%, taken > 3 months apart, were recruited. Mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured using automated manometers, according to practice guidelines. Serum creatinine was assayed and the estimated glomerular filtration rate (GFR) calculated using the CKD Epidemiology Collaboration equation. BP and antihypertensive medication profile was examined using univariate analyses. 613 patients (55.1% male; 74.7% Chinese, 6.4% Indian, 11.4% Malay; 35.7% diabetes mellitus) with a mean age of 57.8 ± 14.5 years were recruited. Mean SBP was 139 ± 20 mmHg, DBP was 74 ± 11 mmHg, serum creatinine was 166 ± 115 µmol/L and GFR was 53 ± 32 mL/min/1.73 m(2). At a lower GFR, SBP increased (p < 0.001), whereas DBP decreased (p = 0.0052). Mean SBP increased in tandem with the number of antihypertensive agents used (p < 0.001), while mean DBP decreased when ≥ 3 antihypertensive agents were used (p = 0.0020). Different targets are recommended for each BP component in CKD patients. A majority of patients cannot attain SBP targets and/or exceed DBP targets. Research into monitoring and treatment methods is required to better define BP targets in CKD patients. Copyright: © Singapore Medical Association.

  1. Diet and Inflammatory Bowel Disease: Review of Patient-Targeted Recommendations

    PubMed Central

    Hou, Jason K.; Lee, Dale; Lewis, James

    2014-01-01

    Patients have strong beliefs about the role of diet in the cause of inflammatory bowel disease (IBD) and in exacerbating or alleviating ongoing symptoms from IBD. The rapid increase in the incidence and prevalence of IBD in the past several decades strongly suggests an environmental trigger for IBD, one of which may be dietary patterns. There are several pathways where diet may influence intestinal inflammation such as direct dietary antigens, altering the gut microbiome, and affecting gastrointestinal permeability. However, data that altering diet can change the natural history of IBD are scarce and evidence based dietary guidelines for patients with IBD are lacking. Patients therefore seek non-medical resources for dietary guidance such as patient support groups and unverified sources on the internet. The aim of this review is to identify patient-targeted dietary recommendations for IBD and to critically appraise the nutritional value of these recommendations. We review patient-targeted dietary information for IBD from structured internet searches and popular defined diets. Patient-targeted dietary recommendations focus on food restrictions and are highly conflicting. High quality dietary intervention studies are needed to facilitate creation of evidence-based dietary guidelines for patients with IBD. PMID:24107394

  2. Nonlinear dynamics support a linear population code in a retinal target-tracking circuit.

    PubMed

    Leonardo, Anthony; Meister, Markus

    2013-10-23

    A basic task faced by the visual system of many organisms is to accurately track the position of moving prey. The retina is the first stage in the processing of such stimuli; the nature of the transformation here, from photons to spike trains, constrains not only the ultimate fidelity of the tracking signal but also the ease with which it can be extracted by other brain regions. Here we demonstrate that a population of fast-OFF ganglion cells in the salamander retina, whose dynamics are governed by a nonlinear circuit, serve to compute the future position of the target over hundreds of milliseconds. The extrapolated position of the target is not found by stimulus reconstruction but is instead computed by a weighted sum of ganglion cell outputs, the population vector average (PVA). The magnitude of PVA extrapolation varies systematically with target size, speed, and acceleration, such that large targets are tracked most accurately at high speeds, and small targets at low speeds, just as is seen in the motion of real prey. Tracking precision reaches the resolution of single photoreceptors, and the PVA algorithm performs more robustly than several alternative algorithms. If the salamander brain uses the fast-OFF cell circuit for target extrapolation as we suggest, the circuit dynamics should leave a microstructure on the behavior that may be measured in future experiments. Our analysis highlights the utility of simple computations that, while not globally optimal, are efficiently implemented and have close to optimal performance over a limited but ethologically relevant range of stimuli.

  3. Unveiling changes in the landscape of patient populations in cancer early drug development

    PubMed Central

    Hierro, Cinta; Azaro, Analía; Argilés, Guillem; Elez, Elena; Gómez, Patricia; Carles, Joan; Rodon, Jordi

    2017-01-01

    The introduction of new Molecularly Targeted Agents (MTA) has changed the landscape in Early Drug Development (EDD) over the last two decades, leading to an improvement in clinical trial design. Previous Phase 1 (Ph1) studies with cytotoxics focused on safety objectives, only recruiting heavily pre-treated cancer patients, have been left behind. In this review, we will illustrate the slow although unstoppable change that has increasingly been observed in those populations candidate to participate in EDD trials with the advent of MTA. As more evidence regarding oncogene addiction becomes available, molecular-biomarker driven selection has been implemented among Molecularly-Selected Population (MSP) studies. New Window-Of-Opportunity (WOO) and Phase 0 (Ph0) studies have been developed in order to assess whether a MTA produces the hypothetical proposed biological effect. The rising need of getting early pharmacokinetics and pharmacodynamics data has led to the conduction of Healthy Volunteer (HV) studies, in part favoured for the particular and different toxicity profile of these MTA. However, several challenges will need to be addressed in order to boost the implementation of these new clinical trial designs in the forthcoming years. Among the problems to overcome, we would highlight a better coordination effort between centers for ensuring adequate patient accrual among small patient populations and a deepening into the ethics implied in enrolling patients in studies with no therapeutic intent. However, these tribulations will be certainly compensated by the possibility of opening a new horizon of treatment for diseases with dismal prognosis. PMID:27835915

  4. Relative prevalence of Aboriginal patients in a Canadian uveitic population.

    PubMed

    Roy, Mili

    2012-04-01

    To determine whether the prevalence of Aboriginal patients in a consecutive series of patients with uveitis differs significantly from the prevalence of Aboriginal persons in the general population. Retrospective chart review. 133 consecutive patients with uveitis. The proportion of Aboriginal patients in a series of 133 consecutive patients with uveitis was compared to the proportion of Aboriginal persons within the general population to determine whether Aboriginal patients were under- or overrepresented in the population with uveitis, relative to their numbers in the population in general. The main outcome measure was the self-reported race of patients. The mean age, sex, and prior disease duration were also compared between Aboriginal and non-Aboriginal patients in the consecutive series. There was no significant difference (p = 0.84) between the proportion of Aboriginal persons in the uveitis population studied (22 of 133; 16.5%) compared to general population census data (15.5% Aboriginal). Mean age at presentation was 36.8 years in the Aboriginal population versus 47.3 years in the control non-Aboriginal group (p = 0.01). Mean prior disease duration was 20.3 months in the Aboriginal population versus 21.1 months in the control group (p = 0.79). The gender proportion was 68.2% female in the Aboriginal group versus 53.2% female in the non-Aboriginal group (p = 0.02). This study finds no statistically significant difference between the prevalence of Aboriginal versus non-Aboriginal persons occurring within a consecutive series of uveitis patients as compared to the general population. Mean age at presentation was significantly younger, and female preponderance was significantly greater in the Aboriginal than in the non-Aboriginal group. Prior disease duration was comparable in the 2 groups. Copyright © 2012 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

  5. Diet and inflammatory bowel disease: review of patient-targeted recommendations.

    PubMed

    Hou, Jason K; Lee, Dale; Lewis, James

    2014-10-01

    Patients have strong beliefs about the role of diet in the cause of inflammatory bowel disease (IBD) and in exacerbating or alleviating ongoing symptoms from IBD. The rapid increase in the incidence and prevalence of IBD in recent decades strongly suggests an environmental trigger for IBD, one of which may be dietary patterns. There are several pathways where diet may influence intestinal inflammation, such as direct dietary antigens, altering the gut microbiome, and affecting gastrointestinal permeability. However, data that altering diet can change the natural history of IBD are scarce, and evidence-based dietary guidelines for patients with IBD are lacking. Patients, therefore, seek nonmedical resources for dietary guidance, such as patient support groups and unverified sources on the Internet. The aim of this review is to identify patient-targeted dietary recommendations for IBD and to critically appraise the nutritional value of these recommendations. We review patient-targeted dietary information for IBD from structured Internet searches and popular defined diets. Patient-targeted dietary recommendations focus on food restrictions and are highly conflicting. High-quality dietary intervention studies are needed to facilitate creation of evidence-based dietary guidelines for patients with IBD. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  6. Achievement of therapeutic targets in Mexican patients with diabetes mellitus.

    PubMed

    Lavalle-González, Fernando J; Chiquete, Erwin; de la Luz, Julieta; Ochoa-Guzmán, Ana; Sánchez-Orozco, Laura V; Godínez-Gutiérrez, Sergio A

    2012-12-01

    Complications of diabetes comprise the leading cause of death in Mexico. We aimed to describe the characteristics of management and achievement of therapeutic targets in Mexican patients with diabetes mellitus. We analyzed data from 2642 Mexican patients with type 1 (T1D, n=203, 7.7%) and type 2 diabetes (T2D, n=2439, 92.3%) included in the third wave of the International Diabetes Management Practices Study. Of T2D patients, 63% were on oral glucose-lowering drugs (OGLD) exclusively (mostly metformin), 11% on insulin, 22% on OGLD plus insulin, and 4% on diet and exercise exclusively. T2D patients on insulin were more likely to be trained on diabetes, but they were older, had worse control, longer disease duration and more chronic complications than patients on OGLD only. Glycated hemoglobin (HbA1c) <7% was achieved by 21% and 37% of T1D and T2D patients, respectively. Only 5% of T1D and 3% of T2D attained the composite target of HbA1c <7%, blood pressure <130/80 mmHg and low-density lipoprotein cholesterol <100 mg/dl. T1D patients had less macrovascular but more microvascular complications, compared with T2D patients. Late complications increased with disease duration, so that about 80% of patients after 20 years of diagnosis have at least one late complication. Reaching the target HbA1c <7% was associated with a reduced number of microvascular but not with less macrovascular complications. A great proportion of these Mexican patients with diabetes did not reach therapeutic targets. Insulin was used mostly in complicated cases with advanced disease. Copyright © 2011 SEEN. Published by Elsevier Espana. All rights reserved.

  7. RNAi screen for rapid therapeutic target identification in leukemia patients

    PubMed Central

    Tyner, Jeffrey W.; Deininger, Michael W.; Loriaux, Marc M.; Chang, Bill H.; Gotlib, Jason R.; Willis, Stephanie G.; Erickson, Heidi; Kovacsovics, Tibor; O'Hare, Thomas; Heinrich, Michael C.; Druker, Brian J.

    2009-01-01

    Targeted therapy has vastly improved outcomes in certain types of cancer. Extension of this paradigm across a broad spectrum of malignancies will require an efficient method to determine the molecular vulnerabilities of cancerous cells. Improvements in sequencing technology will soon enable high-throughput sequencing of entire genomes of cancer patients; however, determining the relevance of identified sequence variants will require complementary functional analyses. Here, we report an RNAi-assisted protein target identification (RAPID) technology that individually assesses targeting of each member of the tyrosine kinase gene family. We demonstrate that RAPID screening of primary leukemia cells from 30 patients identifies targets that are critical to survival of the malignant cells from 10 of these individuals. We identify known, activating mutations in JAK2 and K-RAS, as well as patient-specific sensitivity to down-regulation of FLT1, CSF1R, PDGFR, ROR1, EPHA4/5, JAK1/3, LMTK3, LYN, FYN, PTK2B, and N-RAS. We also describe a previously undescribed, somatic, activating mutation in the thrombopoietin receptor that is sensitive to down-stream pharmacologic inhibition. Hence, the RAPID technique can quickly identify molecular vulnerabilities in malignant cells. Combination of this technique with whole-genome sequencing will represent an ideal tool for oncogenic target identification such that specific therapies can be matched with individual patients. PMID:19433805

  8. Comprehensive target populations for current active safety systems using national crash databases.

    PubMed

    Kusano, Kristofer D; Gabler, Hampton C

    2014-01-01

    The objective of active safety systems is to prevent or mitigate collisions. A critical component in the design of active safety systems is the identification of the target population for a proposed system. The target population for an active safety system is that set of crashes that a proposed system could prevent or mitigate. Target crashes have scenarios in which the sensors and algorithms would likely activate. For example, the rear-end crash scenario, where the front of one vehicle contacts another vehicle traveling in the same direction and in the same lane as the striking vehicle, is one scenario for which forward collision warning (FCW) would be most effective in mitigating or preventing. This article presents a novel set of precrash scenarios based on coded variables from NHTSA's nationally representative crash databases in the United States. Using 4 databases (National Automotive Sampling System-General Estimates System [NASS-GES], NASS Crashworthiness Data System [NASS-CDS], Fatality Analysis Reporting System [FARS], and National Motor Vehicle Crash Causation Survey [NMVCCS]) the scenarios developed in this study can be used to quantify the number of police-reported crashes, seriously injured occupants, and fatalities that are applicable to proposed active safety systems. In this article, we use the precrash scenarios to identify the target populations for FCW, pedestrian crash avoidance systems (PCAS), lane departure warning (LDW), and vehicle-to-vehicle (V2V) or vehicle-to-infrastructure (V2I) systems. Crash scenarios were derived using precrash variables (critical event, accident type, precrash movement) present in all 4 data sources. This study found that these active safety systems could potentially mitigate approximately 1 in 5 of all severity and serious injury crashes in the United States and 26 percent of fatal crashes. Annually, this corresponds to 1.2 million all severity, 14,353 serious injury (MAIS 3+), and 7412 fatal crashes. In addition

  9. Attainment of Canadian Diabetes Association recommended targets in patients with type 2 diabetes

    PubMed Central

    McCrate, Farah; Godwin, Marshall; Murphy, Laura

    2010-01-01

    OBJECTIVE To examine the degree to which targets for diabetes (blood pressure [BP], glycated hemoglobin [HbA1c], and low-density lipoprotein cholesterol [LDL-C]) are achieved in family practices and how these results compare with family physicians’ perceptions of how well targets are being achieved. DESIGN Chart audit and physician survey. SETTING Newfoundland and Labrador. PARTICIPANTS Patients with type 2 diabetes and their family physicians. INTERVENTIONS The charts of 20 patients with type 2 diabetes were randomly chosen from each of 8 family physician practices in St John’s, Nfld, and data were abstracted. All family physicians in the province were surveyed using a modified Dillman method. MAIN OUTCOME MEASURES The most recent HbA1c, LDL-C, and BP measurements listed in each audited chart; surveyed family physicians’ knowledge of the recommended targets for HbA1c, LDL-C, and BP and their estimates of what percentage of their patients were at those recommended targets. RESULTS The chart audit revealed that 20.6% of patients were at the recommended target for BP, 48.1% were at the recommended target for HbA1c, and 17.5% were at the recommended target for LDL-C. When targets were examined collectively, only 2.5% of patients were achieving targets in all 3 areas. The survey found that most family physicians were aware of the recommended targets for BP, LDL-C, and HbA1c. However, their estimates of the percentages of patients in their practices achieving these targets appeared high (59.3% for BP, 58.2% for HbA1c, and 48.4% for LDL-C) compared with the results of the chart audit. CONCLUSION The findings of the chart audit are consistent with other published reports, which have illustrated that a large majority of patients with diabetes fall short of reaching recommended targets for BP, blood glucose, and lipid levels. Although family physicians are knowledgeable about recommended targets, there is a gap between knowledge and clinical outcomes. The reasons for

  10. "Community vital signs": incorporating geocoded social determinants into electronic records to promote patient and population health.

    PubMed

    Bazemore, Andrew W; Cottrell, Erika K; Gold, Rachel; Hughes, Lauren S; Phillips, Robert L; Angier, Heather; Burdick, Timothy E; Carrozza, Mark A; DeVoe, Jennifer E

    2016-03-01

    Social determinants of health significantly impact morbidity and mortality; however, physicians lack ready access to this information in patient care and population management. Just as traditional vital signs give providers a biometric assessment of any patient, "community vital signs" (Community VS) can provide an aggregated overview of the social and environmental factors impacting patient health. Knowing Community VS could inform clinical recommendations for individual patients, facilitate referrals to community services, and expand understanding of factors impacting treatment adherence and health outcomes. This information could also help care teams target disease prevention initiatives and other health improvement efforts for clinic panels and populations. Given the proliferation of big data, geospatial technologies, and democratization of data, the time has come to integrate Community VS into the electronic health record (EHR). Here, the authors describe (i) historical precedent for this concept, (ii) opportunities to expand upon these historical foundations, and (iii) a novel approach to EHR integration. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Mortality and cardiovascular diseases risk in patients with Barrett's oesophagus: a population-based nationwide cohort study.

    PubMed

    Erichsen, R; Horvath-Puho, E; Lund, J L; Dellon, E S; Shaheen, N J; Pedersen, L; Davey Smith, G; Sørensen, H T

    2017-04-01

    Patients with Barrett's oesophagus may be at increased risk of mortality overall, and cardiovascular disease has been suggested as the main underlying cause of death. To examine cause-specific mortality and risk of cardiovascular events among patients with Barrett's oesophagus. Utilising existing Danish data sources (1997-2011), we identified all patients with histologically verified Barrett's oesophagus (n = 13 435) and 123 526 members of the general population matched by age, sex and individual comorbidities. We calculated cause-specific mortality rates and incidence rates of cardiovascular diseases. We then compared rates between patients with Barrett's oesophagus and the general population comparison cohort, using stratified Cox proportional hazard regression. Patients with Barrett's oesophagus had a 71% increased risk of overall mortality. The cause-specific mortality rate per 1000 person-years for patients with Barrett's oesophagus was 8.5 for cardiovascular diseases, 14.7 for non-oesophageal cancers, and 5.4 for oesophageal cancer. Compared to the general population cohort, corresponding hazard ratios were 1.26 (95% confidence interval (CI): 1.15-1.38), 1.77 (95% CI: 1.65-1.90), and 19.4 (95% CI: 16.1-23.4), respectively. The incidence rates of cardiovascular diseases per 1000 person-years for Barrett's oesophagus patients and for persons from the general population cohort, respectively, varied from 0.4 and 0.2 for subarachnoid bleeding (hazard ratio 1.10, 95% CI: 0.87-1.39) to 8.1 and 5.9 for congestive heart failure (hazard ratio 1.33, 95% CI: 1.21-1.46). Prophylactic measures targeted at cardiovascular diseases and non-oesophageal cancers potentially could be more important than measures against oesophageal cancer, for improving prognosis among patients with Barrett's oesophagus. © 2017 John Wiley & Sons Ltd.

  12. Dosing algorithm to target a predefined AUC in patients with primary central nervous system lymphoma receiving high dose methotrexate.

    PubMed

    Joerger, Markus; Ferreri, Andrés J M; Krähenbühl, Stephan; Schellens, Jan H M; Cerny, Thomas; Zucca, Emanuele; Huitema, Alwin D R

    2012-02-01

    There is no consensus regarding optimal dosing of high dose methotrexate (HDMTX) in patients with primary CNS lymphoma. Our aim was to develop a convenient dosing algorithm to target AUC(MTX) in the range between 1000 and 1100 µmol l(-1) h. A population covariate model from a pooled dataset of 131 patients receiving HDMTX was used to simulate concentration-time curves of 10,000 patients and test the efficacy of a dosing algorithm based on 24 h MTX plasma concentrations to target the prespecified AUC(MTX) . These data simulations included interindividual, interoccasion and residual unidentified variability. Patients received a total of four simulated cycles of HDMTX and adjusted MTX dosages were given for cycles two to four. The dosing algorithm proposes MTX dose adaptations ranging from +75% in patients with MTX C(24) < 0.5 µmol l(-1) up to -35% in patients with MTX C(24) > 12 µmol l(-1). The proposed dosing algorithm resulted in a marked improvement of the proportion of patients within the AUC(MTX) target between 1000 and 1100 µmol l(-1) h (11% with standard MTX dose, 35% with the adjusted dose) and a marked reduction of the interindividual variability of MTX exposure. A simple and practical dosing algorithm for HDMTX has been developed based on MTX 24 h plasma concentrations, and its potential efficacy in improving the proportion of patients within a prespecified target AUC(MTX) and reducing the interindividual variability of MTX exposure has been shown by data simulations. The clinical benefit of this dosing algorithm should be assessed in patients with primary central nervous system lymphoma (PCNSL). © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

  13. Effect of Multifactorial Treatment Targets and Relative Importance of Hemoglobin A1c, Blood Pressure, and Low-Density Lipoprotein-Cholesterol on Cardiovascular Diseases in Chinese Primary Care Patients With Type 2 Diabetes Mellitus: A Population-Based Retrospective Cohort Study.

    PubMed

    Wan, Eric Yuk Fai; Fung, Colman Siu Cheung; Yu, Esther Yee Tak; Chin, Weng Yee; Fong, Daniel Yee Tak; Chan, Anca Ka Chun; Lam, Cindy Lo Kuen

    2017-08-17

    The relative effect of hemoglobin A1c, blood pressure, and low-density lipoprotein-cholesterol (LDL-C) ("ABC" factors) on the prevention of cardiovascular diseases (CVD) among patients with type 2 diabetes mellitus is poorly understood. This study aimed to evaluate the association of key clinical parameters on CVD risk using a multifactorial optimal control approach in Chinese primary care patients with type 2 diabetes mellitus. A population-based retrospective cohort study was conducted on 144 271 Chinese type 2 diabetes mellitus primary care patients, aged 18 to 79 and without prior clinical diagnosis of CVD in 2008-2011. Cox regressions were conducted to examine the association between the combinations of ABC targets (hemoglobin A1c <7%, blood pressure <130/90 mm Hg, and LDL-C <2.6 mmol/L) and risks of CVD (overall), coronary heart disease, stroke, and heart failure. Achieving more ABC targets incrementally reduced the incidence of total CVD and individual disease including coronary heart disease, stroke, and heart failure, irrespective of other patient characteristics. Compared with suboptimal control in all ABC levels, achieving any 1, 2, and all 3 ABC targets reduced the relative risk of CVD by 13% to 42%, 31% to 52%, and 55%, respectively. Among those achieving only 1 ABC target, LDL-C reduction was associated with the greatest CVD risk reduction (42%), followed by blood pressure reduction (18%), and hemoglobin A1c reduction (13%). To achieve the greatest risk reduction for the incidence of CVD, the ultimate goal of treatment should be to achieve target control of hemoglobin A1c, blood pressure, and LDL-C. If it is not possible to achieve all 3 targets, efforts should be prioritized on treating the LDL-C to minimize CVD risk. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  14. Adolescent women as a key target population for community nutrition education programs in Indonesia.

    PubMed

    Savage, Amy; Februhartanty, Judhiastuty; Worsley, Anthony

    2017-05-01

    Adolescence is a critical life-stage that sets the foundation for health in adulthood. Adolescent women are a unique population and should be targeted as such for nutrition promotion activities. Using Indonesia as a case study, this qualitative study aimed to identify existing nutrition promotion programs aimed at adolescent girls, how best to target this population and effective recommendations to inform nutrition education program design for this important group. Semi-structured interviews and questionnaires were conducted with ten key informants working in public health in Indonesia. Interview transcripts were analysed and coded to identify key themes. No existing nutrition education programs targeting adolescent women in Indonesia were identified. Several strategies apply to nutrition programs for adolescent girls: 1) nutrition promotion messages that are relevant to the lifestyles and interests of adolescent women; 2) technology-based interventions show promise, however, they need to be appropriately targeted to sub-groups; 3) school remains an important setting; and 4) early marriage is an important issue affecting nutritional status and engagement of adolescent girls. The informants recommended that: 1) more research is needed about the underlying motivations for behaviour change among adolescent women and ways to effectively implement the identified engagement strategies; 2) adolescent girls should be included in program design to improve its suitability and uptake; and 3) government budget and policy support is crucial to success. Adolescent women are an important population group and more research is required to identify the optimal forms of engagement to improve nutrition programs for them.

  15. Patients with advanced and metastatic renal cell carcinoma treated with targeted therapy in the Czech Republic: twenty cancer centres, six agents, one database.

    PubMed

    Poprach, Alexandr; Bortlíček, Zbyněk; Büchler, Tomáš; Melichar, Bohuslav; Lakomý, Radek; Vyzula, Rostislav; Brabec, Petr; Svoboda, Marek; Dušek, Ladislav; Gregor, Jakub

    2012-12-01

    The incidence and mortality of renal cell carcinoma (RCC) in the Czech Republic are among the highest in the world. Several targeted agents have been recently approved for the treatment of advanced/metastatic RCC. Presentation of a national clinical database for monitoring and assessment of patients with advanced/metastatic RCC treated with targeted therapy. The RenIS (RENal Information System, http://renis.registry.cz ) registry is a non-interventional post-registration database of epidemiological and clinical data of patients with RCC treated with targeted therapies in the Czech Republic. Twenty cancer centres eligible for targeted therapy administration participate in the project. As of November 2011, six agents were approved and reimbursed from public health insurance, including bevacizumab, everolimus, pazopanib, sorafenib, sunitinib, and temsirolimus. As of 10 October 2011, 1,541 patients with valid records were entered into the database. Comparison with population-based data from the Czech National Cancer Registry revealed that RCC patients treated with targeted therapy are significantly younger (median age at diagnosis 59 vs. 66 years). Most RenIS registry patients were treated with sorafenib and sunitinib, many patients sequentially with both agents. Over 10 % of patients were also treated with everolimus in the second or third line. Progression-free survival times achieved were comparable to phase III clinical trials. The RenIS registry has become an important tool and source of information for the management of cancer care and clinical practice, providing comprehensive data on monitoring and assessment of RCC targeted therapy on a national level.

  16. Population pharmacokinetics and pharmacodynamics of fosfomycin in non-critically ill patients with bacteremic urinary infection caused by multidrug-resistant Escherichia coli.

    PubMed

    Merino-Bohórquez, V; Docobo-Pérez, F; Sojo, J; Morales, I; Lupión, C; Martín, D; Cameán, M; Hope, W; Pascual, Á; Rodríguez-Baño, J

    2018-04-10

    To describe the population pharmacokinetics of fosfomycin for patients with bacteraemic urinary tract infection (BUTI). The analysis identified optimal regimens on the basis of pharmacodynamic targets and assessed the adequacy of Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) susceptibility breakpoints for Escherichia coli. Data of 16 patients with BUTI caused by multidrug-resistant E. coli (FOREST clinical trial) received intravenous fosfomycin (4 g every 6 hours) were analysed. A population pharmacokinetic analysis was performed, and Monte Carlo simulations were undertaken using 4 g every 6 hours and 8 g every 8 hours. The probability of pharmacodynamic target attainment was assessed using pharmacodynamic targets for E. coli for static effect, 1-log drop in bacterial burden and resistance suppression. Sixty-four plasma samples were collected over a single dosing interval (day 2 or 3 after starting fosfomycin treatment). Fosfomycin concentrations were highly variable. Pharmacodynamic target attainment analysis showed mild improvement by increasing fosfomycin dosing (4 g every 6 hours vs. every 8 hours). These dosages showed success for decreasing 1-log bacterial burden in 89% to 96% (EUCAST breakpoints) and 33% to 54% (CLSI breakpoints) of patients, but they were unable to reach bacterial resistance suppression targets. Fosfomycin concentrations are highly variable-a fact partially explained by renal impairment. The present work supports the use of 4 g every 6 hours as an effective regimen for the treatment of non-critically ill patients with BUTI caused by multidrug-resistant E. coli, as higher dosages might increase toxicity but may not significantly increase efficacy. The current information may suggest that fosfomycin susceptibility breakpoints need to be reappraised. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by

  17. Reaching a Moveable Visual Target: Dissociations in Brain Tumour Patients

    ERIC Educational Resources Information Center

    Buiatti, Tania; Skrap, Miran; Shallice, Tim

    2013-01-01

    Damage to the posterior parietal cortex (PPC) can lead to Optic Ataxia (OA), in which patients misreach to peripheral targets. Recent research suggested that the PPC might be involved not only in simple reaching tasks toward peripheral targets, but also in changing the hand movement trajectory in real time if the target moves. The present study…

  18. Multi-Targeted Antithrombotic Therapy for Total Artificial Heart Device Patients.

    PubMed

    Ramirez, Angeleah; Riley, Jeffrey B; Joyce, Lyle D

    2016-03-01

    To prevent thrombotic or bleeding events in patients receiving a total artificial heart (TAH), agents have been used to avoid adverse events. The purpose of this article is to outline the adoption and results of a multi-targeted antithrombotic clinical procedure guideline (CPG) for TAH patients. Based on literature review of TAH anticoagulation and multiple case series, a CPG was designed to prescribe the use of multiple pharmacological agents. Total blood loss, Thromboelastograph(®) (TEG), and platelet light-transmission aggregometry (LTA) measurements were conducted on 13 TAH patients during the first 2 weeks of support in our institution. Target values and actual medians for postimplant days 1, 3, 7, and 14 were calculated for kaolinheparinase TEG, kaolin TEG, LTA, and estimated blood loss. Protocol guidelines were followed and anticoagulation management reduced bleeding and prevented thrombus formation as well as thromboembolic events in TAH patients postimplantation. The patients in this study were susceptible to a variety of possible complications such as mechanical device issues, thrombotic events, infection, and bleeding. Among them all it was clear that patients were at most risk for bleeding, particularly on postoperative days 1 through 3. However, bleeding was reduced into postoperative days 3 and 7, indicating that acceptable hemostasis was achieved with the anticoagulation protocol. The multidisciplinary, multi-targeted anticoagulation clinical procedure guideline was successful to maintain adequate antithrombotic therapy for TAH patients.

  19. [Estimates of Target Population for Pneumococcal Vaccination in People over 50 years in Catalonia and Spain].

    PubMed

    Vila-Córcoles, Angel; Ochoa-Gondar, Olga; Satué, Eva; de Diego, Cinta; Vila-Rovira, Marc; Jariod, Manel

    2017-03-15

    Published data about prevalence of distinct risk condictions for pneumococcal disease is scarce. This study investigated the prevalence of distinct risk conditions for pneumococal disease in Catalonian adults and stimated the potential size of target population for pneumococcal vaccination in Catalonia and Spain. Cross-sectional population-based study that included 2,033,465 individuals older than 49 years-old assigned to the Catalonian Health Institute (Catalonia, Spain) at 01/01/2015. The Catalonian Health Institute Information System for the Development of Research in Primary Care (SIDIAP) was used to identify comorbidities and/or underlying conditions in each subject and establish potential target population for pneumococcal vaccination on the basis of their risk for suffering pneumococcal infections: 1) immunocompromised subjects; 2) immunocompetents subjects with any risk condition; 3) immunocompetents subjects without risk conditions. Of the 2,033,465 study subjects, 1,053,155 (51.8%) had no risk conditions, 649,014 (31.9%) had one risk condition and 331,296 (16.3%) had multiple risk conditions (11.4% in 50-64 years vs 21.2% in people older than 65 years, p smaller than 0.001; 21.8% in men vs 11.6% in women, p smaller than 0.001). Overall, 176,600 (8.7%) and 803,710 (39.5%) were classified in risk stratum 1 and 2, respectively. According to distinct risk strata considered, the target population for pneumococcal vaccination varied between 0.2-1.9 million in Catalonia and 1.5-2.3 million in Spain. In our setting, almost fifty percent of people ≥50 years have at least one risk condition to suffert pneumococcal disease. Adult population susceptible for pneumococal vaccination largely varies depending on the risk stratum considered as targeted people for pneumococcal vaccination.

  20. Beta blockers and chronic heart failure patients: prognostic impact of a dose targeted beta blocker therapy vs. heart rate targeted strategy.

    PubMed

    Corletto, Anna; Fröhlich, Hanna; Täger, Tobias; Hochadel, Matthias; Zahn, Ralf; Kilkowski, Caroline; Winkler, Ralph; Senges, Jochen; Katus, Hugo A; Frankenstein, Lutz

    2018-05-17

    Beta blockers improve survival in patients with chronic systolic heart failure (CHF). Whether physicians should aim for target dose, target heart rate (HR), or both is still under debate. We identified 1,669 patients with systolic CHF due to ischemic heart disease or idiopathic dilated cardiomyopathy from the University Hospital Heidelberg and the Clinic of Ludwigshafen, Germany. All patients were treated with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker and had a history of CHF known for at least 6 months. Target dose was defined as treatment with ≥ 95% of the respective published guideline-recommended dose. Target HR was defined as 51-69 bpm. All-cause mortality during the median follow-up of 42.8 months was analysed with respect to beta blocker dosing and resting HR. 201 (12%) patients met the dose target (group A), 285 (17.1%) met the HR target (group B), 627 (37.6%) met no target (group C), and 556 (33.3%) did not receive beta blockers (Group D). 5-year mortality was 23.7, 22.7, 37.6, and 55.6% for group A, B, C, and D, respectively (p <  0.001). Survival for group A patients with a HR ≥ 70 bpm was 28.8% but 14.8% if HR was 50-70 bpm (p = 0.054). Achieving guidelines recommended beta blocker dose or to HR control has a similar positive impact on survival. When on target dose, supplemental HR control additionally improves survival.

  1. Methicillin-resistant Staphylococcus aureus in surgical patients: identification of high-risk populations for the development of targeted screening programmes

    PubMed Central

    Fraser, Stephanie; Brady, Richard R; Graham, Catriona; Paterson-Brown, Simon; Gibb, Alan P

    2010-01-01

    INTRODUCTION Methicillin-resistant Staphylococcus aureus (MRSA)-related hospital-acquired infection (HAI) in surgical patients is associated with high morbidity, mortality and financial cost. The identification and characterisation of populations of patients who are at high risk of developing MRSA infection or colonisation could inform the design of more effective strategies to prevent HAIs and reduce transmission of MRSA. PATIENTS AND METHODS An analysis of historical discharge data for the whole of 2005 (7145 surgical in-patients) was performed, for all patients admitted to general surgery at the Royal Infirmary of Edinburgh. Analysis specifically focused on MRSA laboratory data and coding data for patient demographics, medical co-morbidities, and progress of in-patient stay. RESULTS A total of 134 (1.88%) individual patients with colonisation or infection by MRSA were identified from indicated laboratory testing. Univariate analysis identified a significant association of concurrent MRSA-positive status with patients aged over 60 years (P < 0.01), a duration of inpatient stay > 7 days (P < 0.01), presence of a malignant neoplasm (P < 0.01), circulatory disease (P < 0.01), respiratory disease (P < 0.01), central nervous system disease (P < 0.01), renal failure (P < 0.01), and concurrent admission to ITU/HDU (P < 0.01). Multivariate analysis suggested MRSA colonisation or infection was strongest in those with co-morbid malignancy (P < 0.0001) or admission to ITU/HDU (P < 0.0001). CONCLUSIONS This large observational study has identified cancer patients as a UK surgical patient subpopulation which is at significantly higher risk of colonisation by MRSA. These data could inform the development of focused hospital in-patient screening protocols and provide a means to stratify patient risk. PMID:20385046

  2. Targeting anxiety to improve quality of life in patients with schizophrenia.

    PubMed

    Buonocore, M; Bosia, M; Bechi, M; Spangaro, M; Cavedoni, S; Cocchi, F; Bianchi, L; Guglielmino, C; Mastromatteo, A R; Cavallaro, R

    2017-09-01

    Several studies suggested that anxiety can significantly affect the outcome of schizophrenia. Despite this evidence, non-pharmacological interventions targeting anxiety are still heterogenous. This study aims to test the efficacy of a novel training specifically designed to target anxiety in patients with schizophrenia. Innovatively, this training, beyond psychoeducation and problem solving, also targets Theory of Mind, as it provides coping strategies. Twenty-seven outpatients with schizophrenia received a novel rehabilitative training targeting anxiety (Anxiety Management Group [AMG]) combined with a Computer-Assisted Cognitive Remediation (CACR), and twenty received CACR plus a control intervention (Control Newspaper discussion Group [CNG]). All patients were assessed at baseline and after treatment for quality of life, neurocognition and anxiety. After training, patients treated with AMG+CACR showed significantly greater improvements on anxiety. A significant increase in quality of life was observed only for AMG+CACR group. Moreover, the participants' appraisal showed a significant difference between treatment groups with higher ratings among patients who received the AMG+CACR. This study thus suggests feasibility and efficacy of the proposed intervention, that could be implemented in rehabilitative programs for patients with schizophrenia with potential benefits also on disease course and outcome. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Clinician-targeted intervention and patient-reported counseling on physical activity.

    PubMed

    Carroll, Jennifer K; Winters, Paul C; Sanders, Mechelle R; Decker, Francesca; Ngo, Thanh; Sciamanna, Christopher N

    2014-05-29

    Limited time and lack of knowledge are barriers to physical activity counseling in primary care. The objective of this study was to examine the effectiveness of a clinician-targeted intervention that used the 5As (Ask, Advise, Agree, Assist, Arrange) approach to physical activity counseling in a medically underserved patient population. Family medicine clinicians at 2 community health centers were randomized to Group 1 or Group 2 intervention. Both clinician groups participated in 4 training sessions on the 5As for physical activity counseling; Group 2 training took place 8 months after Group 1 training. Both groups were trained to refer patients to a community exercise program. We used a pre-post analysis to evaluate the effectiveness of the intervention on clinician use of 5As. Eligible patients (n = 319) rated their clinicians' counseling skills by using a modified Physical Activity Exit Interview (PAEI) survey. Clinicians (n = 10) self-assessed their use of the 5As through a survey and interviews. Both patient and clinician groups had similar sociodemographic characteristics. The PAEI score for both groups combined increased from 6.9 to 8.6 (on a scale of 0-15) from baseline to immediately postintervention (P = .01) and was 8.2 (P = .09) at 6-month follow-up; most of the improvement in PAEI score was due to increased use of 5As skills by Group 2 clinicians. Group 1 reported difficulty with problem solving, whereas Group 2 reported ease of referral to the community exercise program. A clinician training intervention showed mixed results for 5As physical activity counseling.

  4. Mean arterial pressure target in patients with septic shock.

    PubMed

    Beloncle, Francois; Radermacher, Peter; Guerin, Claude; Asfar, Pierre

    2016-07-01

    In patients with septic shock, a mean arterial pressure higher than 65 mmHg is recommended by the Surviving Sepsis Campaign Guidelines. However, a precise mean arterial pressure target has not been delineated. The aim of this paper was to review the physiological rationale and clinical evidence for increasing mean arterial pressure in septic shock. A mean arterial pressure level lower than renal autoregulatory threshold may lead to renal dysfunction. However, adjusting macrocirculation objectives in particular after the early phase of septic shock may not correct established microcirculation impairments. Moreover, sympathetic over-stimulation due to high doses of vasopressor (needed to achieve high mean arterial pressure targets) may be associated with numerous harmful effects. Observational and small short term interventional studies did not provide a definitive answer to this question but suggested that a high mean arterial pressure (around 75-85 mmHg) may prevent acute kidney injury in some patients. The SEPSISPAM Trial, a large prospective, randomized, controlled study, compared the targets of High (i.e. 80 to 85 mm Hg) versus Low (i.e. 65 to 70 mm Hg) mean arterial pressure in patients with septic shock. The mortality was not different in the two groups. However in patients with chronic hypertension, there were significantly less renal failure in the high mean arterial pressure group than the low mean arterial pressure group.

  5. Qualitative methods to ensure acceptability of behavioral and social interventions to the target population

    PubMed Central

    Ayala, Guadalupe X.; Elder, John P.

    2013-01-01

    This paper introduces qualitative methods for assessing the acceptability of an intervention. Acceptability refers to determining how well an intervention will be received by the target population and the extent to which the new intervention or its components might meet the needs of the target population and organizational setting. In this paper, we focus on two common qualitative methods for conducting acceptability research and their advantages and disadvantages: focus groups and interviews. We provide examples from our own research and other studies to demonstrate the use of these methods for conducting acceptability research and how one might adapt this approach for oral health research. Finally, we present emerging methods for conducting acceptability research, including the use of community-based participatory research, as well as the utility of conducting acceptability research for assessing the appropriateness of measures in intervention research. PMID:21656958

  6. Decoding Target Distance and Saccade Amplitude from Population Activity in the Macaque Lateral Intraparietal Area (LIP)

    PubMed Central

    Bremmer, Frank; Kaminiarz, Andre; Klingenhoefer, Steffen; Churan, Jan

    2016-01-01

    Primates perform saccadic eye movements in order to bring the image of an interesting target onto the fovea. Compared to stationary targets, saccades toward moving targets are computationally more demanding since the oculomotor system must use speed and direction information about the target as well as knowledge about its own processing latency to program an adequate, predictive saccade vector. In monkeys, different brain regions have been implicated in the control of voluntary saccades, among them the lateral intraparietal area (LIP). Here we asked, if activity in area LIP reflects the distance between fovea and saccade target, or the amplitude of an upcoming saccade, or both. We recorded single unit activity in area LIP of two macaque monkeys. First, we determined for each neuron its preferred saccade direction. Then, monkeys performed visually guided saccades along the preferred direction toward either stationary or moving targets in pseudo-randomized order. LIP population activity allowed to decode both, the distance between fovea and saccade target as well as the size of an upcoming saccade. Previous work has shown comparable results for saccade direction (Graf and Andersen, 2014a,b). Hence, LIP population activity allows to predict any two-dimensional saccade vector. Functional equivalents of macaque area LIP have been identified in humans. Accordingly, our results provide further support for the concept of activity from area LIP as neural basis for the control of an oculomotor brain-machine interface. PMID:27630547

  7. A Population Pharmacokinetic and Pharmacodynamic Analysis of Abemaciclib in a Phase I Clinical Trial in Cancer Patients.

    PubMed

    Tate, Sonya C; Sykes, Amanda K; Kulanthaivel, Palaniappan; Chan, Edward M; Turner, P Kellie; Cronier, Damien M

    2018-03-01

    Abemaciclib, a dual inhibitor of cyclin-dependent kinases 4 and 6, has demonstrated clinical activity in a number of different cancer types. The objectives of this study were to characterize the pharmacokinetics of abemaciclib in cancer patients using population pharmacokinetic (popPK) modeling, and to evaluate target engagement at clinically relevant dose levels. A phase I study was conducted in cancer patients which incorporated intensive pharmacokinetic sampling after single and multiple oral doses of abemaciclib. Data were analyzed by popPK modeling, and patient demographics contributing to pharmacokinetic variability were explored. Target engagement was evaluated by combining the clinical popPK model with a previously developed pre-clinical pharmacokinetic/pharmacodynamic model. The pharmacokinetic analysis incorporated 4012 plasma concentrations from 224 patients treated with abemaciclib at doses ranging from 50 to 225 mg every 24 h and 75 to 275 mg every 12 h. A linear one-compartment model with time- and dose-dependent relative bioavailability (F rel ) adequately described the pharmacokinetics of abemaciclib. Serum albumin and alkaline phosphatase were the only significant covariates identified in the model, the inclusion of which reduced inter-individual variability in F rel by 10.3 percentage points. By combining the clinical popPK model with the previously developed pre-clinical pharmacokinetic/pharmacodynamic model, the extent of target engagement in skin in cancer patients was successfully predicted. The proportion of abemaciclib pharmacokinetic variability that can be attributed to patient demographics is negligible, and as such there are currently no dose adjustments recommended for adult patients of different sex, age, or body weight. NCT01394016 (ClinicalTrials.gov).

  8. General practice variation in spirometry testing among patients receiving first-time prescriptions for medication targeting obstructive lung disease in Denmark: a population-based observational study

    PubMed Central

    2013-01-01

    Background Spirometry testing is essential to confirm an obstructive lung disease, but studies have reported that a large proportion of patients diagnosed with COPD or asthma have no history of spirometry testing. Also, it has been shown that many patients are prescribed medication for obstructive lung disease without a relevant diagnosis or spirometry test registered. General practice characteristics have been reported to influence diagnosis and management of several chronic diseases. However, these findings are inconsistent, and it is uncertain whether practice characteristics influence spirometry testing among patients receiving medication for obstructive lung disease. The aim of this study was therefore to examine if practice characteristics are associated with spirometry testing among patients receiving first-time prescriptions for medication targeting obstructive lung disease. Methods A national register-based cohort study was performed. All patients over 18 years receiving first-time prescriptions for medication targeting obstructive lung disease in 2008 were identified and detailed patient-specific data on sociodemographic status and spirometry tests were extracted. Information on practice characteristics like number of doctors, number of patients per doctor, training practice status, as well as age and gender of the general practitioners was linked to each medication user. Results Partnership practices had a higher odds ratio (OR) of performing spirometry compared with single-handed practices (OR 1.24, CI 1.09-1.40). We found a significant association between increasing general practitioner age and decreasing spirometry testing. This tendency was most pronounced among partnership practices, where doctors over 65 years had the lowest odds of spirometry testing (OR 0.25, CI 0.10-0.61). Training practice status was significantly associated with spirometry testing among single-handed practices (OR 1.40, CI 1.10-1.79). Conclusion Some of the variation in

  9. A D-Optimal designed population pharmacokinetic study of oral itraconazole in adult cystic fibrosis patients

    PubMed Central

    Hennig, Stefanie; Waterhouse, Timothy H; Bell, Scott C; France, Megan; Wainwright, Claire E; Miller, Hugh; Charles, Bruce G; Duffull, Stephen B

    2007-01-01

    What is already known about this subject • Itraconazole is a triazole antifungal used in the treatment of allergic bronchopulmonary aspergillosis in patients with cystic fibrosis (CF). • The pharmacokinetic (PK) properties of this drug and its active metabolite have been described before, mostly in healthy volunteers. • However, only sparse information from case reports were available of the PK properties of this drug in CF patients at the start of our study. What this study adds • This study reports for the first time the population pharmacokinetic properties of itraconazole and a known active metabolite, hydroxy-itraconazole in adult patients with CF. • As a result, this study offers new dosing approaches and their pharmacoeconomic impact as well as a PK model for therapeutic drug monitoring of this drug in this patient group. • Furthermore, it is an example of a successful d-optimal design application in a clinical setting. Aim The primary objective of the study was to estimate the population pharmacokinetic parameters for itraconazole and hydroxy-itraconazole, in particular, the relative oral bioavailability of the capsule compared with solution in adult cystic fibrosis patients, in order to develop new dosing guidelines. A secondary objective was to evaluate the performance of a population optimal design. Methods The blood sampling times for the population study were optimized previously using POPT v.2.0. The design was based on the administration of solution and capsules to 30 patients in a cross-over study. Prior information suggested that itraconazole is generally well described by a two-compartment disposition model with either linear or saturable elimination. The pharmacokinetics of itraconazole and the metabolite were modelled simultaneously using NONMEM. Dosing schedules were simulated to assess their ability to achieve a trough target concentration of 0.5 mg ml−1. Results Out of 241 blood samples, 94% were taken within the defined optimal

  10. Patterns of Mortality in Patients Treated with Dental Implants: A Comparison of Patient Age Groups and Corresponding Reference Populations.

    PubMed

    Jemt, Torsten; Kowar, Jan; Nilsson, Mats; Stenport, Victoria

    2015-01-01

    Little is known about the relationship between implant patient mortality compared to reference populations. The aim of this study was to report the mortality pattern in patients treated with dental implants up to a 15-year period, and to compare this to mortality in reference populations with regard to age at surgery, sex, and degree of tooth loss. Patient cumulative survival rate (CSR) was calculated for a total of 4,231 treated implant patients from a single clinic. Information was based on surgical registers in the clinic and the National Population Register in Sweden. Patients were arranged into age groups of 10 years, and CSR was compared to that of the reference population of comparable age and reported in relation to age at surgery, sex, and type of jaw/dentition. A similar, consistent, general relationship between CSR of different age groups of implant patients and reference populations could be observed for all parameters studied. Completely edentulous patients presented higher mortality than partially edentulous patients (P < .05). Furthermore, implant patients in younger age groups showed mortality similar to or higher than reference populations, while older patient age groups showed increasingly lower mortality than comparable reference populations for edentulous and partially edentulous patients (P < .05). A consistent pattern of mortality in different age groups of patients compared to reference populations was observed, indicating higher patient mortality in younger age groups and lower in older groups. The reported pattern is not assumed to be related to implant treatment per se, but is assumed to reflect the variation in general health of a selected subgroup of treated implant patients compared to the reference population in different age groups.

  11. Translational Approaches Targeting Reconsolidation

    PubMed Central

    Kroes, Marijn C.W.; LeDoux, Joseph E.; Phelps, Elizabeth A.

    2017-01-01

    Maladaptive learned responses and memories contribute to psychiatric disorders that constitute a significant socio-economic burden. Primary treatment methods teach patients to inhibit maladaptive responses, but do not get rid of the memory itself, which explains why many patients experience a return of symptoms even after initially successful treatment. This highlights the need to discover more persistent and robust techniques to diminish maladaptive learned behaviours. One potentially promising approach is to alter the original memory, as opposed to inhibiting it, by targeting memory reconsolidation. Recent research shows that reactivating an old memory results in a period of memory flexibility and requires restorage, or reconsolidation, for the memory to persist. This reconsolidation period allows a window for modification of a specific old memory. Renewal of memory flexibility following reactivation holds great clinical potential as it enables targeting reconsolidation and changing of specific learned responses and memories that contribute to maladaptive mental states and behaviours. Here, we will review translational research on non-human animals, healthy human subjects, and clinical populations aimed at altering memories by targeting reconsolidation using biological treatments (electrical stimulation, noradrenergic antagonists) or behavioural interference (reactivation–extinction paradigm). Both approaches have been used successfully to modify aversive and appetitive memories, yet effectiveness in treating clinical populations has been limited. We will discuss that memory flexibility depends on the type of memory tested and the brain regions that underlie specific types of memory. Further, when and how we can most effectively reactivate a memory and induce flexibility is largely unclear. Finally, the development of drugs that can target reconsolidation and are safe for use in humans would optimize cross-species translations. Increasing the understanding of

  12. Identifying Human Papillomavirus Vaccination Practices Among Primary Care Providers of Minority, Low-Income and Immigrant Patient Populations

    PubMed Central

    Bruno, Denise M.; Wilson, Tracey E.; Gany, Francesca; Aragones, Abraham

    2014-01-01

    Objective Minority populations in the United States are disproportionally affected by Human Papillomavirus (HPV) infection and HPV-related cancer. We sought to understand physician practices, knowledge and beliefs that affect utilization of the HPV vaccine in primary care settings serving large minority populations in areas with increased rates of HPV-related cancer. Study Design Cross-sectional survey of randomly selected primary care providers, including pediatricians, family practice physicians and internists, serving large minority populations in Brooklyn, N.Y. and in areas with higher than average cervical cancer rates. Results Of 156 physicians randomly selected, 121 eligible providers responded to the survey; 64% were pediatricians, 19% were internists and 17% were family practitioners. Thirty-four percent of respondents reported that they routinely offered HPV vaccine to their eligible patients. Seventy percent of physicians reported that the lack of preventive care visits for patients in the eligible age group limited their ability to recommend the HPV vaccine and 70% of those who reported this barrier do not routinely recommend HPV vaccine. The lack of time to educate parents about the HPV vaccine and cost of the vaccine to their patients were two commonly reported barriers that affected whether providers offered the vaccine. Conclusions Our study found that the majority of providers serving the highest risk populations for HPV infection and HPV-related cancers are not routinely recommending the HPV vaccine to their patients. Reasons for providers' failure to recommend the HPV vaccine routinely are identified and possible areas for targeted interventions to increase HPV vaccination rates are discussed. PMID:24886959

  13. The Population Care Coordination Process.

    PubMed

    Rushton, Sharron

    2015-01-01

    The purpose of the article was to outline a population-based approach to providing care coordination. The Population Care Coordination Process provides a framework for each provider and/or organization to provide multilevel care based on population- and patient-centered principles. The Population Care Coordination Process is scalable. It can be utilized in a smaller scale such as single provider office or in a larger scale such as an accountable care organization. There are many issues within our current health care structure that must be addressed. Care coordination has been identified as a potential solution to address the needs of complex patients within the system. The expansion to consider populations allows for a more targeted and efficient approach. The population care process entails a data-driven approach to care coordination. The inclusion of populations in the care coordination process provides an opportunity to maximize efforts and improve outcomes.

  14. Profiles of the Adult Education Target Population: Information from the 2000 Census. Revised

    ERIC Educational Resources Information Center

    Lasater, Beth; Elliott, Barbara

    2005-01-01

    This report presents national, regional, and state profiles of the target population for adult education, that is, those individuals aged 16 years and over, who have not attained a high school diploma or equivalent and are not currently enrolled in school. The tables contained in this report describe the following characteristics of the target…

  15. Clinician-Targeted Intervention and Patient-Reported Counseling on Physical Activity

    PubMed Central

    Winters, Paul C.; Sanders, Mechelle R.; Decker, Francesca; Ngo, Thanh; Sciamanna, Christopher N.

    2014-01-01

    Introduction Limited time and lack of knowledge are barriers to physical activity counseling in primary care. The objective of this study was to examine the effectiveness of a clinician-targeted intervention that used the 5As (Ask, Advise, Agree, Assist, Arrange) approach to physical activity counseling in a medically underserved patient population. Methods Family medicine clinicians at 2 community health centers were randomized to Group 1 or Group 2 intervention. Both clinician groups participated in 4 training sessions on the 5As for physical activity counseling; Group 2 training took place 8 months after Group 1 training. Both groups were trained to refer patients to a community exercise program. We used a pre–post analysis to evaluate the effectiveness of the intervention on clinician use of 5As. Eligible patients (n = 319) rated their clinicians’ counseling skills by using a modified Physical Activity Exit Interview (PAEI) survey. Clinicians (n = 10) self-assessed their use of the 5As through a survey and interviews. Results Both patient and clinician groups had similar sociodemographic characteristics. The PAEI score for both groups combined increased from 6.9 to 8.6 (on a scale of 0–15) from baseline to immediately postintervention (P = .01) and was 8.2 (P = .09) at 6-month follow-up; most of the improvement in PAEI score was due to increased use of 5As skills by Group 2 clinicians. Group 1 reported difficulty with problem solving, whereas Group 2 reported ease of referral to the community exercise program. Conclusion A clinician training intervention showed mixed results for 5As physical activity counseling. PMID:24874781

  16. Patient-Facing Mobile Apps to Treat High-Need, High-Cost Populations: A Scoping Review

    PubMed Central

    Drouin, Kaitlin; Newmark, Lisa P; Filkins, Malina; Silvers, Elizabeth; Bain, Paul A; Zulman, Donna M; Lee, Jae-Ho; Rozenblum, Ronen; Pabo, Erika; Landman, Adam; Klinger, Elissa V; Bates, David W

    2016-01-01

    Background Self-management is essential to caring for high-need, high-cost (HNHC) populations. Advances in mobile phone technology coupled with increased availability and adoption of health-focused mobile apps have made self-management more achievable, but the extent and quality of the literature supporting their use is not well defined. Objective The purpose of this review was to assess the breadth, quality, bias, and types of outcomes measured in the literature supporting the use of apps targeting HNHC populations. Methods Data sources included articles in PubMed and MEDLINE (National Center for Biotechnology Information), EMBASE (Elsevier), the Cochrane Central Register of Controlled Trials (EBSCO), Web of Science (Thomson Reuters), and the NTIS (National Technical Information Service) Bibliographic Database (EBSCO) published since 2008. We selected studies involving use of patient-facing iOS or Android mobile health apps. Extraction was performed by 1 reviewer; 40 randomly selected articles were evaluated by 2 reviewers to assess agreement. Results Our final analysis included 175 studies. The populations most commonly targeted by apps included patients with obesity, physical handicaps, diabetes, older age, and dementia. Only 30.3% (53/175) of the apps studied in the reviewed literature were identifiable and available to the public through app stores. Many of the studies were cross-sectional analyses (42.9%, 75/175), small (median number of participants=31, interquartile range 11.0-207.2, maximum 11,690), or performed by an app’s developers (61.1%, 107/175). Of the 175 studies, only 36 (20.6%, 36/175) studies evaluated a clinical outcome. Conclusions Most apps described in the literature could not be located on the iOS or Android app stores, and existing research does not robustly evaluate the potential of mobile apps. Whereas apps may be useful in patients with chronic conditions, data do not support this yet. Although we had 2-3 reviewers to screen and

  17. Role of renal function in risk assessment of target non-attainment after standard dosing of meropenem in critically ill patients: a prospective observational study.

    PubMed

    Ehmann, Lisa; Zoller, Michael; Minichmayr, Iris K; Scharf, Christina; Maier, Barbara; Schmitt, Maximilian V; Hartung, Niklas; Huisinga, Wilhelm; Vogeser, Michael; Frey, Lorenz; Zander, Johannes; Kloft, Charlotte

    2017-10-21

    Severe bacterial infections remain a major challenge in intensive care units because of their high prevalence and mortality. Adequate antibiotic exposure has been associated with clinical success in critically ill patients. The objective of this study was to investigate the target attainment of standard meropenem dosing in a heterogeneous critically ill population, to quantify the impact of the full renal function spectrum on meropenem exposure and target attainment, and ultimately to translate the findings into a tool for practical application. A prospective observational single-centre study was performed with critically ill patients with severe infections receiving standard dosing of meropenem. Serial blood samples were drawn over 4 study days to determine meropenem serum concentrations. Renal function was assessed by creatinine clearance according to the Cockcroft and Gault equation (CLCR CG ). Variability in meropenem serum concentrations was quantified at the middle and end of each monitored dosing interval. The attainment of two pharmacokinetic/pharmacodynamic targets (100%T >MIC , 50%T >4×MIC ) was evaluated for minimum inhibitory concentration (MIC) values of 2 mg/L and 8 mg/L and standard meropenem dosing (1000 mg, 30-minute infusion, every 8 h). Furthermore, we assessed the impact of CLCR CG on meropenem concentrations and target attainment and developed a tool for risk assessment of target non-attainment. Large inter- and intra-patient variability in meropenem concentrations was observed in the critically ill population (n = 48). Attainment of the target 100%T >MIC was merely 48.4% and 20.6%, given MIC values of 2 mg/L and 8 mg/L, respectively, and similar for the target 50%T >4×MIC . A hyperbolic relationship between CLCR CG (25-255 ml/minute) and meropenem serum concentrations at the end of the dosing interval (C 8h ) was derived. For infections with pathogens of MIC 2 mg/L, mild renal impairment up to augmented renal function was

  18. Isavuconazole Population Pharmacokinetic Analysis Using Nonparametric Estimation in Patients with Invasive Fungal Disease (Results from the VITAL Study)

    PubMed Central

    Kovanda, Laura L.; Desai, Amit V.; Lu, Qiaoyang; Townsend, Robert W.; Akhtar, Shahzad; Bonate, Peter

    2016-01-01

    Isavuconazonium sulfate (Cresemba; Astellas Pharma Inc.), a water-soluble prodrug of the triazole antifungal agent isavuconazole, is available for the treatment of invasive aspergillosis (IA) and invasive mucormycosis. A population pharmacokinetic (PPK) model was constructed using nonparametric estimation to compare the pharmacokinetic (PK) behaviors of isavuconazole in patients treated in the phase 3 VITAL open-label clinical trial, which evaluated the efficacy and safety of the drug for treatment of renally impaired IA patients and patients with invasive fungal disease (IFD) caused by emerging molds, yeasts, and dimorphic fungi. Covariates examined were body mass index (BMI), weight, race, impact of estimated glomerular filtration rate (eGFR) on clearance (CL), and impact of weight on volume. PK parameters were compared based on IFD type and other patient characteristics. Simulations were performed to describe the MICs covered by the clinical dosing regimen. Concentrations (n = 458) from 136 patients were used to construct a 2-compartment model (first-order absorption compartment and central compartment). Weight-related covariates affected clearance, but eGFR did not. PK parameters and intersubject variability of CL were similar across different IFD groups and populations. Target attainment analyses demonstrated that the clinical dosing regimen would be sufficient for total drug area under the concentration-time curve (AUC)/MIC targets ranging from 50.5 for Aspergillus spp. (up to the CLSI MIC of 0.5 mg/liter) to 270 and 5,053 for Candida albicans (up to MICs of 0.125 and 0.004 mg/liter, respectively) and 312 for non-albicans Candida spp. (up to a MIC of 0.125 mg/liter). The estimations for Candida spp. were exploratory considering that no patients with Candida infections were included in the current analyses. (The VITAL trial is registered at ClinicalTrials.gov under number NCT00634049.) PMID:27185799

  19. Increased subjective experience of non-target emotions in patients with frontotemporal dementia and Alzheimer’s disease

    PubMed Central

    Chen, Kuan-Hua; Lwi, Sandy J.; Hua, Alice Y.; Haase, Claudia M.; Miller, Bruce L.; Levenson, Robert W.

    2017-01-01

    Although laboratory procedures are designed to produce specific emotions, participants often experience mixed emotions (i.e., target and non-target emotions). We examined non-target emotions in patients with frontotemporal dementia (FTD), Alzheimer’s disease (AD), other neurodegenerative diseases, and healthy controls. Participants watched film clips designed to produce three target emotions. Subjective experience of non-target emotions was assessed and emotional facial expressions were coded. Compared to patients with other neurodegenerative diseases and healthy controls, FTD patients reported more positive and negative non-target emotions, whereas AD patients reported more positive non-target emotions. There were no group differences in facial expressions of non-target emotions. We interpret these findings as reflecting deficits in processing interoceptive and contextual information resulting from neurodegeneration in brain regions critical for creating subjective emotional experience. PMID:29457053

  20. Population Pharmacokinetics of Atazanavir in Patients with Human Immunodeficiency Virus Infection▿

    PubMed Central

    Colombo, Sara ; Buclin, Thierry; Cavassini, Matthias; Décosterd, Laurent A.; Telenti, Amalio; Biollaz, Jérôme; Csajka, Chantal

    2006-01-01

    Atazanavir (ATV) is a new azapeptide protease inhibitor recently approved and currently used at a fixed dose of either 300 mg once per day (q.d.) in combination with 100 mg ritonavir (RTV) or 400 mg q.d. without boosting. ATV is highly bound to plasma proteins and extensively metabolized by CYP3A4. Since ATV plasma levels are highly variable and seem to be correlated with both viral response and toxicity, dosage individualization based on plasma concentration monitoring might be indicated. This study aimed to assess the ATV pharmacokinetic profile in a target population of HIV patients, to characterize interpatient and intrapatient variability, and to identify covariates that might influence ATV disposition. A population analysis was performed with NONMEM with 574 plasma samples from a cohort of 214 randomly selected patients receiving ATV. A total of 346 randomly collected ATV plasma levels and 19 full concentration-time profiles at steady state were available. The pharmacokinetic parameter estimates were an oral clearance (CL) of 12.9 liters/h (coefficient of variation [CV], 26%), a volume of distribution of 88.3 liters (CV, 29%), an absorption rate constant of 0.405 h−1 (CV, 122%), and a lag time of 0.88 h. A relative bioavailability value was introduced to account for undercompliance due to infrequent follow-ups (0.81; CV, 45%). Among the covariates tested, only RTV significantly reduced CL by 46%, thereby increasing the ATV elimination half-life from 4.6 h to 8.8 h. The pharmacokinetic parameters of ATV were adequately described by a one-compartment population model. The concomitant use of RTV improved the pharmacokinetic profile. However, the remaining high interpatient variability suggests the possibility of an impact of unmeasured covariates, such as genetic traits or environmental influences. This population pharmacokinetic model, together with therapeutic drug monitoring and Bayesian dosage adaptation, can be helpful in the selection and adaptation of

  1. An Evaluation of Six Brief Interventions that Target Drug-Related Problems in Correctional Populations

    ERIC Educational Resources Information Center

    Joe, George W.; Knight, Kevin; Simpson, D. Dwayne; Flynn, Patrick M.; Morey, Janis T.; Bartholomew, Norma G.; Tindall, Michele Staton; Burdon, William M.; Hall, Elizabeth A.; Martin, Steve S.; O'Connell, Daniel J.

    2012-01-01

    Finding brief effective treatments for criminal justice populations is a major public need. The CJ-DATS Targeted Intervention for Corrections (TIC), which consists of six brief interventions (communication, anger, motivation, criminal thinking, social networks, and HIV/sexual health), was tested in separate federally-funded randomized control…

  2. Uptake of atrial fibrillation screening aiming at stroke prevention: geo-mapping of target population and non-participation.

    PubMed

    Engdahl, Johan; Holmén, Anders; Rosenqvist, Mårten; Strömberg, Ulf

    2013-08-03

    In a screening study for silent atrial fibrillation (AF), which is a frequent source of cardiac emboli with ischemic stroke, the proportion of non-participants was considerable and their clinical profile differed from the participants' profile. We intended to geo-map the target population and non-participation in an attempt to understand factors related to screening uptake and, thereby, obtain useful information needed to intervene for improved uptake. In the municipality of Halmstad, Sweden, all residents born in 1934-1935 were invited to the screening study during April 2010 to February 2012. The total study group included 848 participants and 367 non-participants from 12 parishes. Geo-maps displaying participation, along with target-population-based geo-maps displaying proportion of immigrants and ischemic stroke incidence, were used. Smoothed non-participation ratios (SmNPR) varied from 0.81 to 1.24 across different parishes (SmNRP=1 corresponds to the expected participation based on the total study group). Among high risk individuals, the geographical variation was more pronounced (SmNPR range 0.75-1.51). Two parishes with higher share of immigrants and elevated population-based ischemic stroke incidence showed markedly lower participation, particularly among high-risk individuals. AF screening uptake varied evidently between parishes, particularly among high-risk individuals. Geo-mapping of target population and non-participation yielded useful information needed to intervene for improved screening uptake.

  3. Comparison of therapeutic lipid target achievements among high-risk patients in Oman.

    PubMed

    Al-Waili, Khalid; Al-Zakwani, Ibrahim; Al-Dughaishi, Tamima; Baneerje, Yajnavalka; Al-Sabti, Hilal; Al-Hashmi, Khamis; Farhan, Hatem; Habsi, Khadija Al; Al-Hinai, Ali T; Al-Rasadi, Khalid

    2014-05-01

    We compared therapeutic lipid target achievements among patients with diabetes or coronary heart disease (CHD) in Oman. A retrospective chart review of 94 patients was conducted at an outpatient clinic in Sultan Qaboos University Hospital, Muscat, Oman. The variables included low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B (apo B). The overall mean age of the cohort was 59 ± 12 years, 54% were male, 66% were diabetic, 48% hypertensive, 45% had CHD, 94% were on simvastatin, 4% were on fenofibrate, and 2% were on both simvastatin and fenofibrate. Lipid goal attainments of calculated LDL-C (<2.6 mmol/L), apo B (<0.9 g/L), and non-HDL-C (<3.36 mmol/L) were reached in 52%, 39%, and 53% of the patients, respectively. A significant proportion of high-risk patients treated with lipid-lowering agents reach LDL-C but not the apo B treatment targets, suggesting that the use of apo B target values should also be considered.

  4. New targeted therapies for indolent B-cell malignancies in older patients.

    PubMed

    Krem, Maxwell M; Gopal, Ajay K

    2015-01-01

    Molecularly targeted agents have become an established component of the treatment of indolent B-cell malignancies (iNHL). iNHL disproportionately affects older adults, so treatments that have excellent tolerability and efficacy across multiple lines of therapy are in demand. The numbers and classes of targeted therapies for iNHL have proliferated rapidly in recent years; classes of agents that show promise for older patients with iNHL include anti-CD20 antibodies, phosphatidyl-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway inhibitors, immunomodulators, proteasome inhibitors, epigenetic modulators, and immunotherapies. Here, we review the proposed mechanisms of action, efficacy, and tolerability of novel agents for iNHL, with an emphasis on their applicability to older patients.

  5. A systematic review of dosing frequency with bone-targeted agents for patients with bone metastases from breast cancer

    PubMed Central

    Hutton, Brian; Addison, Christina L.; Campbell, Kaitryn; Fergusson, Dean; Mazarello, Sasha; Clemons, Mark

    2013-01-01

    Background Bone-targeted agents are usually administered to breast cancer patients with bone metastases every 3–4 weeks. Less frequent (‘de-escalated’) treatment may provide similar benefits with improved safety and reduced cost. Methods To systematically review randomised trials comparing de-escalated treatment with bone-targeted agents (i.e. every 12–16 weeks) to standard treatment (i.e. every 3–4 weeks), a formal systematic review of the literature was performed. Two individuals independently screened citations and full text articles. Random effects meta-analyses of clinically important outcomes were planned provided homogeneous studies were identified. Results Five relevant studies (n=1287 patients) were identified. Sample size ranged from 38 to 425. Information on outcomes including occurrence of SREs, bone pain, urinary N-telopeptide concentrations, serum C-telopeptide concentrations, pain medication use and safety outcomes was not consistently available. Two trials were non-inferiority studies, two dose-response evaluations and one was a pilot study. Bone-targeted agents use varied between studies, as did duration of prior therapy. Patient populations were considered heterogeneous in several ways, and thus no meta-analyses were performed. Observations from the included studies suggest there is potential that 3 month de-escalated treatment may provide similar benefits compared to 3–4 weekly treatment and that lower doses of zoledronic acid and denosumab might be equally effective. Conclusions Studies comparing standard and de-escalated treatment with bone-targeted agents in breast cancer are rare. The benefits of standard treatment compared to de-escalated therapy on important clinical outcomes remain unclear. Future pragmatic studies must be conducted to determine the merits of this approach. PMID:26909282

  6. Target-site mutations conferring resistance to glyphosate in feathertop Rhodes grass (Chloris virgata) populations in Australia.

    PubMed

    Ngo, The D; Krishnan, Mahima; Boutsalis, Peter; Gill, Gurjeet; Preston, Christopher

    2018-05-01

    Chloris virgata is a warm-season, C 4 , annual grass weed affecting field crops in northern Australia that has become an emerging weed in southern Australia. Four populations with suspected resistance to glyphosate were collected in South Australia, Queensland and New South Wales, Australia, and compared with one susceptible (S) population to confirm glyphosate resistance and elucidate possible mechanisms of resistance. Based on the rate of glyphosate required to kill 50% of treated plants (LD 50 ), glyphosate resistance (GR) was confirmed in four populations of C. virgata (V12, V14.2, V14.16 and V15). GR plants were 2-9.7-fold more resistant and accumulated less shikimate after glyphosate treatment than S plants. GR and S plants did not differ in glyphosate absorption and translocation. Target-site EPSPS mutations corresponding to Pro-106-Leu (V14.2) and Pro-106-Ser (V15, V14.16 and V12) substitutions were found in GR populations. The population with Pro-106-Leu substitution was 2.9-4.9-fold more resistant than the three other populations with Pro-106-Ser substitution. This report confirms glyphosate resistance in C. virgata and shows that target-site EPSPS mutations confer resistance to glyphosate in this species. The evolution of glyphosate resistance in C. virgata highlights the need to identify alternative control tactics. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  7. Pneumococcal vaccine targeting strategy for older adults: customized risk profiling.

    PubMed

    Balicer, Ran D; Cohen, Chandra J; Leibowitz, Morton; Feldman, Becca S; Brufman, Ilan; Roberts, Craig; Hoshen, Moshe

    2014-02-12

    Current pneumococcal vaccine campaigns take a broad, primarily age-based approach to immunization targeting, overlooking many clinical and administrative considerations necessary in disease prevention and resource planning for specific patient populations. We aim to demonstrate the utility of a population-specific predictive model for hospital-treated pneumonia to direct effective vaccine targeting. Data was extracted for 1,053,435 members of an Israeli HMO, age 50 and older, during the study period 2008-2010. We developed and validated a logistic regression model to predict hospital-treated pneumonia using training and test samples, including a set of standard and population-specific risk factors. The model's predictive value was tested for prospectively identifying cases of pneumonia and invasive pneumococcal disease (IPD), and was compared to the existing international paradigm for patient immunization targeting. In a multivariate regression, age, co-morbidity burden and previous pneumonia events were most strongly positively associated with hospital-treated pneumonia. The model predicting hospital-treated pneumonia yielded a c-statistic of 0.80. Utilizing the predictive model, the top 17% highest-risk within the study validation population were targeted to detect 54% of those members who were subsequently treated for hospitalized pneumonia in the follow up period. The high-risk population identified through this model included 46% of the follow-up year's IPD cases, and 27% of community-treated pneumonia cases. These outcomes were compared with international guidelines for risk for pneumococcal diseases that accurately identified only 35% of hospitalized pneumonia, 41% of IPD cases and 21% of community-treated pneumonia. We demonstrate that a customized model for vaccine targeting performs better than international guidelines, and therefore, risk modeling may allow for more precise vaccine targeting and resource allocation than current national and international

  8. Protocol adherence and the ability to achieve target haemoglobin levels in haemodialysis patients.

    PubMed

    Chan, Kevin; Moran, John; Hlatky, Mark; Lafayette, Richard

    2009-06-01

    Anemia management remains complicated in patients with endstage renal disease on hemodialysis. We wished to evaluate the effect of protocol adherence to EPO and intravenous iron dosing on achieving the desired range of hemoglobin levels. A cohort of hemodialysis patients was studied to evaluate the rate of adherence to EPO and iron dosing protocols over a 5 month period. A database was completed to evaluate all known comorbidities, demographic factors, and facility issues that might affect hemoglobin levels. A logistic regression model was employed to evaluate the effect of adherence to the anemia protocols on the probability of achieving a hemoglobin level below, within or above the targeted range of 11-12.5 g/dl. Among 2114 patients, we found that adherence to both the EPO and iron dosing protocol resulted in the greatest probability of achieving the target hemoglobin range (56 +/- 5% in anemia protocol adherent patients versus 42 +/- 7% in non adherent patients). This was predominantly due to a lowered risk of having above target hemoglobin levels rather than below. The use of the anemia protocols was associated with lower rates of hospitalization (9 +/- 0.7 visits/100 months in adherent group vs 15 +/- 2 in non adherent group) and lower utilization of both EPO and intravenous iron. Furthermore, patients in the adherent groups had less variability of their hemoglobin levels month by month, at least as judged by standard deviation. Adherence to anemia protocols, as practiced in the dialysis units included in this cohort, may improve hemodialysis patients' ability to achieve target hemoglobin levels, and by avoiding above target hemoglobin values, lower drug utilization and reduce variability of hemoglobin levels.

  9. Individualized population care: linking personal care to population care in general practice.

    PubMed

    Buetow, Stephen; Getz, Linn; Adams, Peter

    2008-10-01

    General practice is increasingly expected to deliver population care to individual patients. The feasibility and ethics of this policy shift have been challenged. Our aim is to suggest how to deliver population care while protecting personal care. We outline and discuss concepts of these types of care, their relation to the prevailing discourse regarding intervention benefits, and arguments for individualized population care. Individualized population care can enable general practice to meet the health targets of individual patients in the light of population-based goals. It unifies the concepts of personal care and whole population care. Personal care focuses on the individual good in particular consultations. Whole population care focuses on the overall health good of a population without reference to the individuality of each population member. These types of care constitute elements of a continuum that varies in purpose and objects of focus. The limitations of a crude dichotomy of personal care and population care are made explicit in a series of five arguments that lend support to the concept of individualized population care. We advocate a constructive but critical attitude towards the idea of population-based interventions in everyday general practice. Traditional personal care and whole population care can theoretically be integrated into individualized population care. However, this presupposes clinical-epidemiological expertise and moral awareness in practising clinicians.

  10. Cytoreductive Nephrectomy in Elderly Patients with Metastatic Renal Cell Carcinoma in the Targeted Therapy Era.

    PubMed

    Uprety, Dipesh; Bista, Amir; Smith, Angela L; Vallatharasu, Yazhini; Marinier, David E

    2018-05-01

    The role of cytoreductive nephrectomy (CN) for metastatic renal cell cancer (mRCC) is not clearly understood after the approval of targeted therapies, particularly in the elderly population. The aim of this study was to compare survivals between patients who did and did not receive CN. The SEER-18 database was utilized in order to identify elderly patients with mRCC to compare overall survival (OS) and cancer-specific survival (CSS) between patients who did or did not receive CN between February 2006 and 2012. Kaplan-Meier curve and log rank test were used to compare OS and CSS between these two arms. Cox proportional hazard model was used for multivariate analysis and statistical significance was defined as p≤0.05. There was a significant survival benefit for those who received CN compared to those who did not receive CN (median OS: 18 months vs. 4 months, p<0.001; median CSS: 21 months vs. 5 months, p<0.001). CN offered significant survival benefit, even in elderly patients with metastatic renal cell cancer. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  11. Communication Strategies Must Be Tailored to a Medication's Targeted Population: Lessons from the Case of BiDil.

    PubMed

    Hawkins-Taylor, Chamika; Carlson, Angeline M

    2013-09-01

    The American population's diversity continues to grow, and its racial and ethnic mixes are changing. The US healthcare system must confront this changing reality. The introduction of isosorbide dinitrate/hydralazine hydrochloride (BiDil) to the US marketplace was a move toward recognizing these changing consumer needs. BiDil was approved specifically as a secondary treatment for heart failure in African-American patients. It remains the first and only drug approved by the US Food and Drug Administration for a race-based indication. To ensure commercial success, a drug must be made "visible" to healthcare providers and to consumers. To describe and analyze the case of BiDil and its potential implications for drugs developed for targeted populations to help them avoid a similar fate of market withdrawal because of commercial considerations. This analysis is based on 12 comprehensive interviews with 5 clinical investigators, 1 minority healthcare provider, and 5 pharmaceutical representatives, as well as a review of the literature. Overall, 12 one-hour semistructured interviews were conducted. Of the 11 interviewees, 10 were interviewed once and 1 was interviewed once early in the process and then had a second interview by the end of the study. When the 12 scheduled interviews were completed, the recordings were transcribed and subjected to analysis through the use of a readily available computer software package, using concepts and themes collected from the literature and the interviewees' responses. The interviewees lacked consensus regarding the unique nature of BiDil. The clinical researchers considered it innovative in identifying that taking the 2 drugs together produced the greatest clinical effect in African-American patients with heart failure. For them, BiDil represented an innovation in the emerging field of personalized medicine. However, they were dismayed to see that these beliefs were challenged by the medical community and their physician colleagues

  12. Design and rationale for a real-world observational cohort of patients with nonalcoholic fatty liver disease: The TARGET-NASH study.

    PubMed

    Barritt, A S; Gitlin, Norman; Klein, Samuel; Lok, Anna S; Loomba, Rohit; Malahias, Laura; Powell, Margaret; Vos, Miriam B; Weiss, L Michael; Cusi, Kenneth; Neuschwander-Tetri, Brent A; Sanyal, Arun

    2017-10-01

    Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and can lead to cirrhosis, hepatocellular carcinoma, and end-stage liver disease. NAFLD comprises the spectrum from simple steatosis (nonalcoholic fatty liver, NAFL), to steatosis with inflammation (nonalcoholic steatohepatitis, NASH). Current primary therapy recommended for NAFLD is weight loss induced by lifestyle modification. The difficulty in achieving this has led to robust pharmacological therapy development. While new drugs may show efficacy in selected phase II/III clinical trial populations, their real-world effectiveness is unknown. TARGET-NASH is a 5-year, longitudinal, observational study of patients with NAFLD designed to evaluate the effectiveness of clinical practice interventions and provide practical information unobtainable in registration trials. A biological specimen repository is included in TARGET-NASH for translational studies of genomics and biomarkers of disease activity. Patients are enrolling at adult and pediatric sites representing multiple specialties. All patients being managed for NAFLD are eligible, whereas those in other NASH registries or clinical trials will be excluded. Enrolled patients range in age from 6 and up and will have 3years of clinical data reviewed. Patient comorbidities, concomitant medications, disease progression and off-label interventions will be assessed, and adverse outcomes, monitored. Confirming the use, safety and effectiveness of NAFLD interventions in children and adults and establishing pragmatic methods of assessing disease progression under real-world conditions are key study outcomes. Ultimately, TARGET-NASH will establish a large, diverse registry of NAFLD patients at academic and community practices to be leveraged to improve health and reduce development of cirrhosis and hepatocellular carcinoma. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Combining population and patient-specific characteristics for prostate segmentation on 3D CT images

    NASA Astrophysics Data System (ADS)

    Ma, Ling; Guo, Rongrong; Tian, Zhiqiang; Venkataraman, Rajesh; Sarkar, Saradwata; Liu, Xiabi; Tade, Funmilayo; Schuster, David M.; Fei, Baowei

    2016-03-01

    Prostate segmentation on CT images is a challenging task. In this paper, we explore the population and patient-specific characteristics for the segmentation of the prostate on CT images. Because population learning does not consider the inter-patient variations and because patient-specific learning may not perform well for different patients, we are combining the population and patient-specific information to improve segmentation performance. Specifically, we train a population model based on the population data and train a patient-specific model based on the manual segmentation on three slice of the new patient. We compute the similarity between the two models to explore the influence of applicable population knowledge on the specific patient. By combining the patient-specific knowledge with the influence, we can capture the population and patient-specific characteristics to calculate the probability of a pixel belonging to the prostate. Finally, we smooth the prostate surface according to the prostate-density value of the pixels in the distance transform image. We conducted the leave-one-out validation experiments on a set of CT volumes from 15 patients. Manual segmentation results from a radiologist serve as the gold standard for the evaluation. Experimental results show that our method achieved an average DSC of 85.1% as compared to the manual segmentation gold standard. This method outperformed the population learning method and the patient-specific learning approach alone. The CT segmentation method can have various applications in prostate cancer diagnosis and therapy.

  14. Depression in Cardiovascular Patients in Middle Eastern Populations: A Literature Review.

    PubMed

    Donnelly, Tam Truong; Al Suwaidi, Jassim Mohd; Al-Qahtani, Awad; Asaad, Nidal; Qader, Najlaa Abdul; Singh, Rajvir; Fung, Tak Shing; Mueed, Irem; Sharara, Shima; El Banna, Noha; Omar, Sarah

    2015-08-01

    Cardiovascular disease (CVD) is increasing in Middle Eastern countries. Depression is associated with increased morbidity and mortality rates among cardiovascular (CV) patients. Early detection of and intervention for depression among CV patients can reduce morbidity and mortality and save health care costs. Public information on mental health care needs of Arab CV patients living in Middle East regions is scattered and limited. This literature review surveyed and summarized research studies to learn what is known about the relationship between depression and CVD in Middle Eastern populations. The information will raise awareness among health care professionals and policy makers regarding the clinical significance of depression in Arab CV patients. It might contribute to development of culturally appropriate and effective mental health care services. Multiple databases were searched and 60 articles were assessed, including studies that investigated depression in Arab CV patient populations, physiological mechanisms of depression-CVD comorbidity, and intervention strategies that affect CV risk in depressed Arab patients. We discuss the extent to which this issue has been explored in Arab populations living in Middle East regions and Arab populations living abroad. We recommend that more comprehensive and in-depth research studies be conducted with Arab cardiac patients to enable implementation of culturally appropriate and effective mental health care interventions.

  15. Should anti-tobacco media messages be culturally targeted for Indigenous populations? A systematic review and narrative synthesis.

    PubMed

    Gould, Gillian Sandra; McEwen, Andy; Watters, Tracey; Clough, Alan R; van der Zwan, Rick

    2013-07-01

    To summarise published empirical research on culturally targeted anti-tobacco media messages for Indigenous or First Nations people and examine the evidence for the effectiveness of targeted and non-targeted campaigns. Studies were sought describing mass media and new media interventions for tobacco control or smoking cessation in Indigenous or First Nations populations. Studies of any design were included reporting outcomes of media-based interventions including: cognitions, awareness, recall, intention to quit and quit rates. Then, 2 reviewers independently applied inclusion criteria, which were met by 21 (5.8%) of the studies found. One author extracted data with crosschecking by a second. Both independently assessed papers using Scottish Intercollegiate Guidelines Network (SIGN; quantitative studies) and Daly et al (qualitative studies). A total of 21 studies were found (4 level 1 randomised controlled trials (RCTs), 11 level 2 studies and 6 qualitative studies) and combined with narrative synthesis. Eight evaluated anti-tobacco TV or radio campaigns; two assessed US websites; three New Zealand studies examined mobile phone interventions; five evaluated print media; three evaluated a CD-ROM, a video and an edutainment intervention. Although Indigenous people had good recall of generic anti-tobacco messages, culturally targeted messages were preferred. New Zealand Maori may be less responsive to holistic targeted campaigns, despite their additional benefits, compared to generic fear campaigns. Culturally targeted internet or mobile phone messages appear to be as effective in American Indians and Maori as generic messages in the general population. There is little research comparing the effect of culturally targeted versus generic messages with similar message content in Indigenous people.

  16. Molybdenum target specifications for cyclotron production of 99mTc based on patient dose estimates.

    PubMed

    Hou, X; Tanguay, J; Buckley, K; Schaffer, P; Bénard, F; Ruth, T J; Celler, A

    2016-01-21

    In response to the recognized fragility of reactor-produced (99)Mo supply, direct production of (99m)Tc via (100)Mo(p,2n)(99m)Tc reaction using medical cyclotrons has been investigated. However, due to the existence of other Molybdenum (Mo) isotopes in the target, in parallel with (99m)Tc, other technetium (Tc) radioactive isotopes (impurities) will be produced. They will be incorporated into the labeled radiopharmaceuticals and result in increased patient dose. The isotopic composition of the target and beam energy are main factors that determine production of impurities, thus also dose increases. Therefore, they both must be considered when selecting targets for clinical (99m)Tc production. Although for any given Mo target, the patient dose can be predicted based on complicated calculations of production yields for each Tc radioisotope, it would be very difficult to reverse these calculations to specify target composition based on dosimetry considerations. In this article, a relationship between patient dosimetry and Mo target composition is studied. A simple and easy algorithm for dose estimation, based solely on the knowledge of target composition and beam energy, is described. Using this algorithm, the patient dose increase due to every Mo isotope that could be present in the target is estimated. Most importantly, a technique to determine Mo target composition thresholds that would meet any given dosimetry requirement is proposed.

  17. Molybdenum target specifications for cyclotron production of 99mTc based on patient dose estimates

    NASA Astrophysics Data System (ADS)

    Hou, X.; Tanguay, J.; Buckley, K.; Schaffer, P.; Bénard, F.; Ruth, T. J.; Celler, A.

    2016-01-01

    In response to the recognized fragility of reactor-produced 99Mo supply, direct production of 99mTc via 100Mo(p,2n)99mTc reaction using medical cyclotrons has been investigated. However, due to the existence of other Molybdenum (Mo) isotopes in the target, in parallel with 99mTc, other technetium (Tc) radioactive isotopes (impurities) will be produced. They will be incorporated into the labeled radiopharmaceuticals and result in increased patient dose. The isotopic composition of the target and beam energy are main factors that determine production of impurities, thus also dose increases. Therefore, they both must be considered when selecting targets for clinical 99mTc production. Although for any given Mo target, the patient dose can be predicted based on complicated calculations of production yields for each Tc radioisotope, it would be very difficult to reverse these calculations to specify target composition based on dosimetry considerations. In this article, a relationship between patient dosimetry and Mo target composition is studied. A simple and easy algorithm for dose estimation, based solely on the knowledge of target composition and beam energy, is described. Using this algorithm, the patient dose increase due to every Mo isotope that could be present in the target is estimated. Most importantly, a technique to determine Mo target composition thresholds that would meet any given dosimetry requirement is proposed.

  18. Are brief alcohol interventions targeting alcohol use efficacious in military and veteran populations? A meta-analysis.

    PubMed

    Doherty, A M; Mason, C; Fear, N T; Rona, R; Greenberg, N; Goodwin, L

    2017-09-01

    Rates of hazardous and harm-related drinking are higher in the military and veteran populations compared to the general population. Brief alcohol interventions (BAIs) targeting alcohol use appear to reduce harmful drinking in the general population. However, less is known about the efficacy of BAIs targeting alcohol in military and veteran populations. A systematic review and meta-analysis was conducted to assess the type and efficacy of BAIs used to reduce alcohol use in military and veteran populations conducted from 2000 onwards. The meta-analysis was conducted using a standardised outcome measure of change in average weekly drinks (AWDs) from baseline to follow-up. The search revealed 10 papers that met the search criteria, and that reported data on 11 interventions included in the systematic review. 8 papers (reporting on 9 different interventions) were included in the meta-analysis after 2 papers were excluded for which the relevant outcome data were not available. There was no overall effect of BAIs; a non-significant weekly drink reduction of 0.95 drinks was found (95% CI, -0.17 to 2.07). This lack of efficacy persisted regardless of military group (conscripts, serving or veterans) and method of delivery (i.e., face-to-face, web-based or written information). Furthermore, sensitivity analyses revealed this small drink reduction was driven mainly by a single study. Based on these findings, existing BAIs do not seem to be efficacious in reducing alcohol use in military populations, despite some encouraging results from one electronic intervention which was of extensive duration. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Potential of targeting TGF-β for organ transplant patients

    PubMed Central

    Iwashima, Makio; Love, Robert

    2015-01-01

    TGF-β was originally considered as an immunoregulatory cytokine, but accumulating data demonstrate that it also plays a critical role in development of effector immunity. Since TGF-β has a potent ability to alter immune responses, modulation of the TGF-β pathway for treatment of transplantation patients could be effective if carried out in a target selective manner. This review will focus on the role of TGF-β in T cell differentiation and discuss the prospect of TGF-β as the therapeutic target of lung transplantation acceptance. PMID:23464518

  20. Population pharmacokinetics of oxycodone in patients with cancer-related pain.

    PubMed

    Komatsu, Toshiaki; Kokubun, Hideya; Suzuki, Ai; Takayanagi, Risa; Yamada, Yasuhiko; Matoba, Motohiro; Yago, Kazuo

    2012-09-01

    Oxycodone is an opioid widely prescribed to cancer patients for pain relief. However, the pharmacokinetics of oxycodone has not been sufficiently examined. Therefore the aim of this work was to study population pharmacokinetics of oxycodone in patients with cancer pain. The authors analyzed 108 serum oxycodone samples of 33 individuals with nonlinear mixed-effects model (NONMEM). Population pharmacokinetics was calculated using the one-compartment model of clearance, volume of distribution, bioavailability, absorption constant rate, and lag time. An exponential error model was used to determine interindividual variability and a relative error model was applied to assess residual variability. Population pharmacokinetics of oxycodone at the end point were as follows: CL(L/h) = 10.7 × [1 + (2 - Child-Pugh Classification)] (Class: A = 0, B = 1, C = 2); V(d) (L) = 193; k(a) (h(-1)) = 0.336; T(lag) (h) = 0.859; F (%) = 63.9. Interindividual variability was CL: 30.5%, V(d): 44.6%, and F: 37.0%, and residual variability was 16.2%. As the total clearance in patients with liver dysfunction (Child-Pugh class B) was reduced to 33.3%, serum concentration of oxycodone increased by 1.5. Therefore, it became clear that dose adjustments are essential when treating patients with liver dysfunction. These findings suggest that population parameters are useful for evaluating pharmacokinetics of oxycodone in patients with cancer pain.

  1. Managing American Oystercatcher (Haematopus palliatus) population qrowth by targeting nesting season vital rates

    USGS Publications Warehouse

    Felton, Shilo K.; Hostetter, Nathan J.; Pollock, Kenneth H.; Simons, Theodore R.

    2017-01-01

    In populations of long-lived species, adult survival typically has a relatively high influence on population growth. From a management perspective, however, adult survival can be difficult to increase in some instances, so other component rates must be considered to reverse population declines. In North Carolina, USA, management to conserve the American Oystercatcher (Haematopus palliatus) targets component vital rates related to fecundity, specifically nest and chick survival. The effectiveness of such a management approach in North Carolina was assessed by creating a three-stage female-based deterministic matrix model. Isoclines were produced from the matrix model to evaluate minimum nest and chick survival rates necessary to reverse population decline, assuming all other vital rates remained stable at mean values. Assuming accurate vital rates, breeding populations within North Carolina appear to be declining. To reverse this decline, combined nest and chick survival would need to increase from 0.14 to ≤ 0.27, a rate that appears to be attainable based on historical estimates. Results are heavily dependent on assumptions of other vital rates, most notably adult survival, revealing the need for accurate estimates of all vital rates to inform management actions. This approach provides valuable insights for evaluating conservation goals for species of concern.

  2. The Prevalence of Type 2 Diabetes Mellitus in a Wisconsin Hmong Patient Population.

    PubMed

    Thao, Kevin K; Arndt, Brian; Tandias, Aman; Hanrahan, Lawrence

    2015-10-01

    Wisconsin's largest Asian population, the Hmong, may be at high risk for type 2 diabetes. However, there are few population-based studies investigating the prevalence of diabetes in this population. This study compared the prevalence of diabetes between Hmong and non-Hispanic white patients of the University of Wisconsin departments of family medicine, pediatrics, and internal medicine clinics. The study utilized data from the University of Wisconsin Electronic Health Record Public Health Information Exchange (UW eHealth--PHINEX). The proportion of Hmong patients diagnosed with diabetes was compared with the prevalence of diabetes in non-Hispanic white patients. Multivariate logistic regression was used to control for the differences in age, sex, body mass index (BMI), and health insurance between the two populations. The total prevalence of diabetes in the Hmong patient population was 11.3% compared to 6.0% in the non-Hispanic white patient population (P < 0.001). The prevalence of diabetes in Hmong adult patients was 19.1% compared to 7.8% in white adult patients (P =< 0.001). Compared with non-Hispanic whites, the odds ratio (95% CI) for diabetes, adjusted for age, sex, BMI, and insurance was 3.3 (2.6-4.1) for Hmong patients. Despite being one of Wisconsin's newest immigrant populations, who came from an area of the world with low rates of diabetes, the adjusted relative odds of diabetes in this clinic sample of Hmong patients is 3.3 times higher than its non-Hispanic white counterpart. The results support previous findings of significantly increased diabetes risk in the Hmong of Wisconsin.

  3. Polycystic kidney disease among 4,436 intracranial aneurysm patients from a defined population.

    PubMed

    Nurmonen, Heidi J; Huttunen, Terhi; Huttunen, Jukka; Kurki, Mitja I; Helin, Katariina; Koivisto, Timo; von Und Zu Fraunberg, Mikael; Jääskeläinen, Juha E; Lindgren, Antti E

    2017-10-31

    To define the association of autosomal dominant polycystic kidney disease (ADPKD) with the characteristics of aneurysmal subarachnoid hemorrhage (aSAH) and unruptured intracranial aneurysm (IA) disease. We fused data from the Kuopio Intracranial Aneurysm database (n = 4,436 IA patients) and Finnish nationwide registries into a population-based series of 53 IA patients with ADPKD to compare the aneurysm- and patient-specific characteristics of IA disease in ADPKD and in the general IA population, and to identify risks for de novo IA formation. In total, there were 33 patients with ADPKD with aSAH and 20 patients with ADPKD with unruptured IAs. The median size of ruptured IAs in ADPKD was significantly smaller than in the general population (6.00 vs 8.00 mm) and the proportion of small ruptured IAs was significantly higher (31% vs 18%). Median age at aSAH was 42.8 years, 10 years younger than in the general IA population. Multiple IAs were present in 45% of patients with ADPKD compared to 28% in the general IA population. Cumulative risk of de novo IA formation was 1.3% per patient-year (vs 0.2% in the general IA population). Hazard for de novo aneurysm formation was significantly elevated in patients with ADPKD (Cox regression hazard ratio 7.7, 95% confidence interval 2.8-20; p < 0.0005). Subarachnoid hemorrhage occurs at younger age and from smaller IAs in patients with ADPKD and risk for de novo IAs is higher than in the general Eastern Finnish population. ADPKD should be considered as an indicator for long-term angiographic follow-up in patients with diagnosed IAs. © 2017 American Academy of Neurology.

  4. Estimating the Public Health Impact of Setting Targets at the European Level for the Reduction of Zoonotic Salmonella in Certain Poultry Populations

    PubMed Central

    Messens, Winy; Vivas-Alegre, Luis; Bashir, Saghir; Amore, Giusi; Romero-Barrios, Pablo; Hugas, Marta

    2013-01-01

    In the European Union (EU), targets are being set for the reduction of certain zoonotic Salmonella serovars in different animal populations, including poultry populations, within the framework of Regulation (EC) No. 2160/2003 on the control of zoonoses. For a three-year transitional period, the EU targets were to cover only Salmonella Enteritidis and S. Typhimurium (and in addition S. Hadar, S. Infantis and S. Virchow for breeding flocks of Gallus gallus). Before the end of that transitional period, the revision of the EU targets was to be considered, including the potentially addition of other serovars with public health significance to the permanent EU targets. This review article aims at providing an overview of the assessments carried out by the Scientific Panel on Biological Hazards of the European Food Safety Authority in the field of setting targets for Salmonella in poultry populations (breeding flocks of Gallus gallus, laying flocks of Gallus gallus, broiler flocks of Gallus gallus and flocks of breeding and fattening turkeys) and their impact in subsequent changes in EU legislation. PMID:24157508

  5. Population pharmacokinetic and pharmacogenetic analysis of 6-mercaptopurine in paediatric patients with acute lymphoblastic leukaemia.

    PubMed

    Hawwa, Ahmed F; Collier, Paul S; Millership, Jeff S; McCarthy, Anthony; Dempsey, Sid; Cairns, Carole; McElnay, James C

    2008-12-01

    To investigate the population pharmacokinetics of 6-mercaptopurine (6-MP) active metabolites in paediatric patients with acute lymphoblastic leukaemia (ALL) and examine the effects of various genetic polymorphisms on the disposition of these metabolites. Data were collected prospectively from 19 paediatric patients with ALL (n = 75 samples, 150 concentrations) who received 6-MP maintenance chemotherapy (titrated to a target dose of 75 mg m(-2) day(-1)). All patients were genotyped for polymorphisms in three enzymes involved in 6-MP metabolism. Population pharmacokinetic analysis was performed with the nonlinear mixed effects modelling program (nonmem) to determine the population mean parameter estimate of clearance for the active metabolites. The developed model revealed considerable interindividual variability (IIV) in the clearance of 6-MP active metabolites [6-thioguanine nucleotides (6-TGNs) and 6-methylmercaptopurine nucleotides (6-mMPNs)]. Body surface area explained a significant part of 6-TGNs clearance IIV when incorporated in the model (IIV reduced from 69.9 to 29.3%). The most influential covariate examined, however, was thiopurine methyltransferase (TPMT) genotype, which resulted in the greatest reduction in the model's objective function (P < 0.005) when incorporated as a covariate affecting the fractional metabolic transformation of 6-MP into 6-TGNs. The other genetic covariates tested were not statistically significant and therefore were not included in the final model. The developed pharmacokinetic model (if successful at external validation) would offer a more rational dosing approach for 6-MP than the traditional empirical method since it combines the current practice of using body surface area in 6-MP dosing with a pharmacogenetically guided dosing based on TPMT genotype.

  6. Can a public health package on glaucoma reach its target population?

    PubMed

    Baker, H; Murdoch, I E

    2004-05-01

    A pilot study to assess how successful a newspaper advertisement and a radio interview about glaucoma are at reaching their target population. The health intervention comprised two components: an interview on local radio and an advertisement in the local paper. Our target population were residents aged 45 years and above in either Southall (West London) or the Isle of Wight (IOW). A questionnaire was developed to be carried out pre- and post-intervention. The data from both locations pre and post were coded and cleaned. Tests of significance were carried out to assess statistical significance for differences in proportion, with tests for trend used where appropriate. All statistical analyses were carried out using Stata7. Overall, the proportion who had heard of glaucoma increased from 54% before the intervention to 60% after (chi(2) = 3.7, P = 0.055). The proportion who had heard of the disease increased by 13% (chi(2) = 8.76, P = 0.003) in Southall and by 8% (chi(2) = 5.02, P = 0.025) on the IOW. The proportion reporting seeing the advert increased significantly in both areas with greater effect in Southall. Those reporting hearing the radio interview only increased in Southall. On the IOW, females were more knowledgeable and responded more positively to the intervention. This differed in Southall where males tended to be the positive responders. Conclusion In both areas a significant effect on those having heard of glaucoma was found. This could be attributed to both the advert and interview in Southall but would appear to be attributable to the newspaper advertisement alone on the IOW.

  7. Application of the pMHC Array to Characterise Tumour Antigen Specific T Cell Populations in Leukaemia Patients at Disease Diagnosis.

    PubMed

    Brooks, Suzanne E; Bonney, Stephanie A; Lee, Cindy; Publicover, Amy; Khan, Ghazala; Smits, Evelien L; Sigurdardottir, Dagmar; Arno, Matthew; Li, Demin; Mills, Ken I; Pulford, Karen; Banham, Alison H; van Tendeloo, Viggo; Mufti, Ghulam J; Rammensee, Hans-Georg; Elliott, Tim J; Orchard, Kim H; Guinn, Barbara-ann

    2015-01-01

    Immunotherapy treatments for cancer are becoming increasingly successful, however to further improve our understanding of the T-cell recognition involved in effective responses and to encourage moves towards the development of personalised treatments for leukaemia immunotherapy, precise antigenic targets in individual patients have been identified. Cellular arrays using peptide-MHC (pMHC) tetramers allow the simultaneous detection of different antigen specific T-cell populations naturally circulating in patients and normal donors. We have developed the pMHC array to detect CD8+ T-cell populations in leukaemia patients that recognise epitopes within viral antigens (cytomegalovirus (CMV) and influenza (Flu)) and leukaemia antigens (including Per Arnt Sim domain 1 (PASD1), MelanA, Wilms' Tumour (WT1) and tyrosinase). We show that the pMHC array is at least as sensitive as flow cytometry and has the potential to rapidly identify more than 40 specific T-cell populations in a small sample of T-cells (0.8-1.4 x 10(6)). Fourteen of the twenty-six acute myeloid leukaemia (AML) patients analysed had T cells that recognised tumour antigen epitopes, and eight of these recognised PASD1 epitopes. Other tumour epitopes recognised were MelanA (n = 3), tyrosinase (n = 3) and WT1(126-134) (n = 1). One of the seven acute lymphocytic leukaemia (ALL) patients analysed had T cells that recognised the MUC1(950-958) epitope. In the future the pMHC array may be used provide point of care T-cell analyses, predict patient response to conventional therapy and direct personalised immunotherapy for patients.

  8. High-Target Versus Low-Target Blood Pressure Management During Cardiopulmonary Bypass to Prevent Cerebral Injury in Cardiac Surgery Patients: A Randomized Controlled Trial.

    PubMed

    Vedel, Anne G; Holmgaard, Frederik; Rasmussen, Lars S; Langkilde, Annika; Paulson, Olaf B; Lange, Theis; Thomsen, Carsten; Olsen, Peter Skov; Ravn, Hanne Berg; Nilsson, Jens C

    2018-04-24

    Cerebral injury is an important complication after cardiac surgery with the use of cardiopulmonary bypass. The rate of overt stroke after cardiac surgery is 1% to 2%, whereas silent strokes, detected by diffusion-weighted magnetic resonance imaging, are found in up to 50% of patients. It is unclear whether a higher versus a lower blood pressure during cardiopulmonary bypass reduces cerebral infarction in these patients. In a patient- and assessor-blinded randomized trial, we allocated patients to a higher (70-80 mm Hg) or lower (40-50 mm Hg) target for mean arterial pressure by the titration of norepinephrine during cardiopulmonary bypass. Pump flow was fixed at 2.4 L·min -1 ·m -2 . The primary outcome was the total volume of new ischemic cerebral lesions (summed in millimeters cubed), expressed as the difference between diffusion-weighted imaging conducted preoperatively and again postoperatively between days 3 and 6. Secondary outcomes included diffusion-weighted imaging-evaluated total number of new ischemic lesions. Among the 197 enrolled patients, mean (SD) age was 65.0 (10.7) years in the low-target group (n=99) and 69.4 (8.9) years in the high-target group (n=98). Procedural risk scores were comparable between groups. Overall, diffusion-weighted imaging revealed new cerebral lesions in 52.8% of patients in the low-target group versus 55.7% in the high-target group ( P =0.76). The primary outcome of volume of new cerebral lesions was comparable between groups, 25 mm 3 (interquartile range, 0-118 mm 3 ; range, 0-25 261 mm 3 ) in the low-target group versus 29 mm 3 (interquartile range, 0-143 mm 3 ; range, 0-22 116 mm 3 ) in the high-target group (median difference estimate, 0; 95% confidence interval, -25 to 0.028; P =0.99), as was the secondary outcome of number of new lesions (1 [interquartile range, 0-2; range, 0-24] versus 1 [interquartile range, 0-2; range, 0-29] respectively; median difference estimate, 0; 95% confidence interval, 0-0; P =0

  9. Managing patient pathways to achieve lung cancer waiting time targets: mixed methods study

    PubMed Central

    Ip, Hugh; Amer, Tarik; Dangoor, Michael; Zamir, Affan; Gibbings-Isaac, Darryl; Kochhar, Ranjeev; Heymann, Timothy

    2012-01-01

    Objectives England's National Health Service (NHS) introduced a 62-day target, from referral to treatment, to make lung cancer patient pathways more efficient. This study aims to understand pathway delays that lead to breaches of the target when patients need care in both secondary and tertiary setting, so more than one institution is involved. Design Mixed methods cross case analysis. Setting Two tertiary referral hospitals in London. Participants Database records of 53 patients were analysed. Nineteen sets of patient notes were used for pathway mapping. Seventeen doctors, four nurses, eight managers and administrators were interviewed. Main outcome measures Qualitative methods include pathway mapping and semi-structured interviews. Quantitative analysis of patient pathway times from cancer services records. Results The majority of the patient pathway (68.4%) is spent in secondary centres. There is more variability in the processes of secondary centres but tertiary centres do not have perfect processes either. Three themes emerged from discussions: information flows, pathway performance and the role of the multidisciplinary approach. Conclusions The actions of secondary centres have a greater influence on whether a patient breaches the 62-day target, compared with tertiary centres. Nevertheless variability exists in both, with potential for improvement. PMID:23162682

  10. Moyamoya vasculopathy - Patient demographics and characteristics in the Finnish population.

    PubMed

    Saarela, Marika; Mustanoja, Satu; Pekkola, Johanna; Tyni, Tiina; Hernesniemi, Juha; Kivipelto, Leena; Tatlisumak, Turgut

    2017-01-01

    Background and purpose Moyamoya vasculopathy, a rare steno-occlusive progressive cerebrovascular disorder, has not been thoroughly studied in Caucasian populations. We established a registry of Finnish patients treated at the Helsinki University Hospital, to collect and report demographic and clinical data. Methods We collected data both retrospectively and prospectively from all the patients with a moyamoya vasculopathy referred to our hospital between January 1987 and December 2014. All patients underwent a neurological outpatient clinic visit. Results We diagnosed 61 patients (50 females, 10 children) with moyamoya vasculopathy. The mean age at the disease-onset was 31.5 ± 17.9 years. The two most common presenting symptoms were ischemic stroke (n = 31) and hemorrhage (n = 8). Forty-four percent underwent revascularization surgery, and 70% were prescribed antithrombotic treatment. Conclusions The results support in part the Western phenotype of the disease considering the later presentation and larger female predominance compared to the Asian moyamoya vasculopathy reports. However, the proportion of ischemic strokes and hemorrhagic strokes is closer to Japanese population than German population. The absence of familial cases points to a different genetic profile in the Finnish patients.

  11. Proteomic identification of aldolase A as an autoantibody target in patients with atypical movement disorders.

    PubMed

    Privitera, Daniela; Corti, Valeria; Alessio, Massimo; Volontè, Maria Antonietta; Volontè, Antonietta; Lampasona, Vito; Comi, Giancarlo; Martino, Gianvito; Franciotta, Diego; Furlan, Roberto; Fazio, Raffaella

    2013-03-01

    We tried to identify the target/s of autoantibodies to basal ganglia neurons found in a patient with hyperkinetic movement disorders (HMD) characterized by rapid, rhythmic involuntary movements or spasms in both face and neck. Patient and control sera were used in Western blot to probe mouse brain homogenates. Two-dimensional gel electrophoresis (2-DE) SDS-PAGE protein spots recognized by the patient's antibodies were excised and sequenced by mass spectrometry analysis, and the glycolytic enzyme aldolase A was identified as the antigen recognized by the patient's autoantibodies. To assess relevance and specificity of these antibodies to the identified targets as biomarkers of autoimmunity in movement disorders, autoantibody responses to the identified target were then measured by ELISA in various diseases of the central nervous system. Anti-aldolase A autoantibodies were associated mainly with HMD (7/17, 41%) and Parkinson's disease (4/30, 13%) patients, and undetectable in subjects with other inflammatory and non-inflammatory central nervous system diseases. We, thus, identified aldolase A as an autoantigen in a sub-group of patients with HMD, a clinically ill-defined syndrome. Anti-aldolase A antibodies may represent a useful biomarker of autoimmunity in HMD patients.

  12. Target lesion response predicts survival of patients with hepatocellular carcinoma retreated with transarterial chemoembolization.

    PubMed

    Zhang, Yong-Fa; Guo, Rong-Ping; OuYang, Han-Yue; Shen, Jing-Xian; Zhao, Jing; Tan, Guo-Sheng; Le, Yong; Wei, Wei; Shi, Ming

    2016-10-01

    The discontinuation rules of transarterial chemoembolization (TACE) for patients who were assessed as progressive disease (PD) but stage progression-free (SP-free: still belongs to Barcelona Clinic Liver Cancer B) after TACE are unclear. We aimed to evaluate the impact of the PD-pattern on the survival of these patients retreated with TACE. In total, 115 consecutive patients who were assessed as PD but SP-free after TACE and then underwent at least one subsequent TACE session were included. Sixty patients were assessed as PD with target lesion progression (TP), and 55 patients were assessed as PD with target lesion non-progression (TNP). Survival and treatment-related adverse events were compared between the two groups. Additional external validation was performed using a data set (n = 103) from another institution. Patients with TNP had significantly longer median post-progression survival (PPS) than those with TP (21.0 vs. 11.9 months, P = 0.004). After TACE retreatment, the incidence of liver dysfunction was significantly higher for patients with TP than for patients with TNP (45% vs. 20%, P = 0.031). In the multivariate analysis, the target lesion response was one of the most significant prognostic factors for PPS (HR = 2.01; 95% confidence interval: 1.23-3.27; P = 0.005). The findings were supported by an independent external cohort. Compared to patients with TNP, patients with TP might exhibit no improvement in survival and even present damaged liver function after retreatment with TACE. Target lesion response is useful as a clinical decision for repeated TACE in these patients. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Molecular mechanisms and therapeutic targets in neuroblastoma.

    PubMed

    Johnsen, John Inge; Dyberg, Cecilia; Fransson, Susanne; Wickström, Malin

    2018-05-01

    Neuroblastoma is the most common extracranical tumor of childhood and the most deadly tumor of infancy. It is characterized by early age onset and high frequencies of metastatic disease but also the capacity to spontaneously regress. Despite intensive therapy, the survival for patients with high-risk neuroblastoma and those with recurrent or relapsed disease is low. Hence, there is an urgent need to develop new therapies for these patient groups. The molecular pathogenesis based on high-throughput omics technologies of neuroblastoma is beginning to be resolved which have given the opportunity to develop personalized therapies for high-risk patients. Here we discuss the potential of developing targeted therapies against aberrantly expressed molecules detected in sub-populations of neuroblastoma patients and how these selected targets can be drugged in order to overcome treatment resistance, improve survival and quality of life for these patients and also the possibilities to transfer preclinical research into clinical testing. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. HLA-targeted flow cytometric sorting of blood cells allows separation of pure and viable microchimeric cell populations.

    PubMed

    Drabbels, Jos J M; van de Keur, Carin; Kemps, Berit M; Mulder, Arend; Scherjon, Sicco A; Claas, Frans H J; Eikmans, Michael

    2011-11-10

    Microchimerism is defined by the presence of low levels of nonhost cells in a person. We developed a reliable method for separating viable microchimeric cells from the host environment. For flow cytometric cell sorting, HLA antigens were targeted with human monoclonal HLA antibodies (mAbs). Optimal separation of microchimeric cells (present at a proportion as low as 0.01% in artificial mixtures) was obtained with 2 different HLA mAbs, one targeting the chimeric cells and the other the background cells. To verify purity of separated cell populations, flow-sorted fractions of 1000 cells were processed for DNA analysis by HLA-allele-specific and Y-chromosome-directed real-time quantitative PCR assays. After sorting, PCR signals of chimeric DNA markers in the positive fractions were significantly enhanced compared with those in the presort samples, and they were similar to those in 100% chimeric control samples. Next, we demonstrate applicability of HLA-targeted FACS sorting after pregnancy by separating chimeric maternal cells from child umbilical cord mononuclear cells. Targeting allelic differences with anti-HLA mAbs with FACS sorting allows maximal enrichment of viable microchimeric cells from a background cell population. The current methodology enables reliable microchimeric cell detection and separation in clinical specimens.

  15. Population Pharmacokinetics of Busulfan in Pediatric and Young Adult Patients Undergoing Hematopoietic Cell Transplant: A Model-Based Dosing Algorithm for Personalized Therapy and Implementation into Routine Clinical Use

    PubMed Central

    Long-Boyle, Janel; Savic, Rada; Yan, Shirley; Bartelink, Imke; Musick, Lisa; French, Deborah; Law, Jason; Horn, Biljana; Cowan, Morton J.; Dvorak, Christopher C.

    2014-01-01

    Background Population pharmacokinetic (PK) studies of busulfan in children have shown that individualized model-based algorithms provide improved targeted busulfan therapy when compared to conventional dosing. The adoption of population PK models into routine clinical practice has been hampered by the tendency of pharmacologists to develop complex models too impractical for clinicians to use. The authors aimed to develop a population PK model for busulfan in children that can reliably achieve therapeutic exposure (concentration-at-steady-state, Css) and implement a simple, model-based tool for the initial dosing of busulfan in children undergoing HCT. Patients and Methods Model development was conducted using retrospective data available in 90 pediatric and young adult patients who had undergone HCT with busulfan conditioning. Busulfan drug levels and potential covariates influencing drug exposure were analyzed using the non-linear mixed effects modeling software, NONMEM. The final population PK model was implemented into a clinician-friendly, Microsoft Excel-based tool and used to recommend initial doses of busulfan in a group of 21 pediatric patients prospectively dosed based on the population PK model. Results Modeling of busulfan time-concentration data indicates busulfan CL displays non-linearity in children, decreasing up to approximately 20% between the concentrations of 250–2000 ng/mL. Important patient-specific covariates found to significantly impact busulfan CL were actual body weight and age. The percentage of individuals achieving a therapeutic Css was significantly higher in subjects receiving initial doses based on the population PK model (81%) versus historical controls dosed on conventional guidelines (52%) (p = 0.02). Conclusion When compared to the conventional dosing guidelines, the model-based algorithm demonstrates significant improvement for providing targeted busulfan therapy in children and young adults. PMID:25162216

  16. Identifying water price and population criteria for meeting future urban water demand targets

    NASA Astrophysics Data System (ADS)

    Ashoori, Negin; Dzombak, David A.; Small, Mitchell J.

    2017-12-01

    Predictive models for urban water demand can help identify the set of factors that must be satisfied in order to meet future targets for water demand. Some of the explanatory variables used in such models, such as service area population and changing temperature and rainfall rates, are outside the immediate control of water planners and managers. Others, such as water pricing and the intensity of voluntary water conservation efforts, are subject to decisions and programs implemented by the water utility. In order to understand this relationship, a multiple regression model fit to 44 years of monthly demand data (1970-2014) for Los Angeles, California was applied to predict possible future demand through 2050 under alternative scenarios for the explanatory variables: population, price, voluntary conservation efforts, and temperature and precipitation outcomes predicted by four global climate models with two CO2 emission scenarios. Future residential water demand in Los Angeles is projected to be largely driven by price and population rather than climate change and conservation. A median projection for the year 2050 indicates that residential water demand in Los Angeles will increase by approximately 36 percent, to a level of 620 million m3 per year. The Monte Carlo simulations of the fitted model for water demand were then used to find the set of conditions in the future for which water demand is predicted to be above or below the Los Angeles Department of Water and Power 2035 goal to reduce residential water demand by 25%. Results indicate that increases in price can not ensure that the 2035 water demand target can be met when population increases. Los Angeles must rely on furthering their conservation initiatives and increasing their use of stormwater capture, recycled water, and expanding their groundwater storage. The forecasting approach developed in this study can be utilized by other cities to understand the future of water demand in water-stressed areas

  17. Smooth Pursuit Eye Movement Deficits in Patients With Whiplash and Neck Pain are Modulated by Target Predictability.

    PubMed

    Janssen, Malou; Ischebeck, Britta K; de Vries, Jurryt; Kleinrensink, Gert-Jan; Frens, Maarten A; van der Geest, Jos N

    2015-10-01

    This is a cross-sectional study. The purpose of this study is to support and extend previous observations on oculomotor disturbances in patients with neck pain and whiplash-associated disorders (WADs) by systematically investigating the effect of static neck torsion on smooth pursuit in response to both predictably and unpredictably moving targets using video-oculography. Previous studies showed that in patients with neck complaints, for instance due to WAD, extreme static neck torsion deteriorates smooth pursuit eye movements in response to predictably moving targets compared with healthy controls. Eye movements in response to a smoothly moving target were recorded with video-oculography in a heterogeneous group of 55 patients with neck pain (including 11 patients with WAD) and 20 healthy controls. Smooth pursuit performance was determined while the trunk was fixed in 7 static rotations relative to the head (from 45° to the left to 45° to right), using both predictably and unpredictably moving stimuli. Patients had reduced smooth pursuit gains and smooth pursuit gain decreased due to neck torsion. Healthy controls showed higher gains for predictably moving targets compared with unpredictably moving targets, whereas patients with neck pain had similar gains in response to both types of target movements. In 11 patients with WAD, increased neck torsion decreased smooth pursuit performance, but only for predictably moving targets. Smooth pursuit of patients with neck pain is affected. The previously reported WAD-specific decline in smooth pursuit due to increased neck torsion seems to be modulated by the predictability of the movement of the target. The observed oculomotor disturbances in patients with WAD are therefore unlikely to be induced by impaired neck proprioception alone. 3.

  18. Population Pharmacokinetic and Pharmacodynamic Analysis of Belimumab Administered Subcutaneously in Healthy Volunteers and Patients with Systemic Lupus Erythematosus.

    PubMed

    Struemper, Herbert; Thapar, Mita; Roth, David

    2017-09-08

    Intravenous belimumab 10 mg/kg every 4 weeks is indicated in patients with active, autoantibody-positive systemic lupus erythematosus receiving standard systemic lupus erythematosus care. Subcutaneous 200-mg weekly administration, which may prove more convenient for patients and improve adherence, is currently under investigation. The objective of this study was to characterize the population pharmacokinetics and exposure-efficacy response of subcutaneous belimumab in a pooled analysis of pharmacokinetic data [phase I: BEL114448 (NCT01583530) and BEL116119 (NCT01516450) in healthy subjects (n = 134); phase III: BEL112341 (NCT01484496) in adults with systemic lupus erythematosus (n = 554)] and pharmacodynamic data [BEL112341 in adults with systemic lupus erythematosus (n = 833)]. Non-linear mixed-effects modeling (NONMEM®) was used to develop a population pharmacokinetic model and perform a covariate analysis. Subsequently, exploratory exposure-response analysis and logistic regression modeling was performed based on the individual parameter estimates of the population pharmacokinetic model. Population-pharmacokinetic parameters for subcutaneous belimumab were consistent with those for intravenous belimumab and other immunoglobulin G1 monoclonal antibodies. Pharmacokinetic parameters and subcutaneous belimumab exposure were consistent between healthy subjects and patients with systemic lupus erythematosus, and no evidence for target-mediated disposition of belimumab was found. Subcutaneous belimumab steady-state exposure was achieved after ~11 weeks; subcutaneous belimumab steady-state minimum concentration exceeded that of intravenous belimumab after <4 weeks, and average steady-state concentration was similar to that achieved following intravenous administration. In patients with moderate-to-severe systemic lupus erythematosus, subcutaneous belimumab 200 mg once weekly plus standard of care significantly improved the systemic lupus erythematosus

  19. Communication Strategies Must Be Tailored to a Medication's Targeted Population: Lessons from the Case of BiDil

    PubMed Central

    Hawkins-Taylor, Chamika; Carlson, Angeline M

    2013-01-01

    Background The American population's diversity continues to grow, and its racial and ethnic mixes are changing. The US healthcare system must confront this changing reality. The introduction of isosorbide dinitrate/hydralazine hydrochloride (BiDil) to the US marketplace was a move toward recognizing these changing consumer needs. BiDil was approved specifically as a secondary treatment for heart failure in African-American patients. It remains the first and only drug approved by the US Food and Drug Administration for a race-based indication. To ensure commercial success, a drug must be made “visible” to healthcare providers and to consumers. Objectives To describe and analyze the case of BiDil and its potential implications for drugs developed for targeted populations to help them avoid a similar fate of market withdrawal because of commercial considerations. Method This analysis is based on 12 comprehensive interviews with 5 clinical investigators, 1 minority healthcare provider, and 5 pharmaceutical representatives, as well as a review of the literature. Overall, 12 one-hour semistructured interviews were conducted. Of the 11 interviewees, 10 were interviewed once and 1 was interviewed once early in the process and then had a second interview by the end of the study. When the 12 scheduled interviews were completed, the recordings were transcribed and subjected to analysis through the use of a readily available computer software package, using concepts and themes collected from the literature and the interviewees' responses. Results The interviewees lacked consensus regarding the unique nature of BiDil. The clinical researchers considered it innovative in identifying that taking the 2 drugs together produced the greatest clinical effect in African-American patients with heart failure. For them, BiDil represented an innovation in the emerging field of personalized medicine. However, they were dismayed to see that these beliefs were challenged by the medical

  20. Developing Culturally Targeted Diabetes Educational Materials for Older Russian-Speaking Immigrants.

    PubMed

    Van Son, Catherine R

    2014-07-01

    Older adults who immigrate late in life face many challenges adapting to a new country. Immigrants bring their cultural beliefs and behaviors with them, which can influence their ability to make dietary changes required when they have type 2 diabetes. Culturally targeted patient education materials are needed to improve immigrants' health literacy and abilities to self-manage diabetes. Currently, there is a scarcity of diabetes patient education materials to meet the educational needs of the Russian-speaking immigrant group. The purpose of this article is to describe a project in which culturally targeted diabetes education materials for older Russian-speaking immigrants were designed and developed. Culturally targeted patient education materials are essential if they are to be accepted and used by clients from different ethnic minority populations. The creation of culturally relevant materials requires a team effort and community stakeholder input. The availability of materials on the internet facilitates access and use by health care providers. Culturally targeted education materials are an important component in addressing health literacy in ethnic minority populations. Next steps require that these materials be evaluated to test their impact on diabetes self-management behaviors and clinical outcomes such as adherence, amount of physical activity, and blood glucose levels. © 2014 The Author(s).

  1. Using health information technology to manage a patient population in accountable care organizations.

    PubMed

    Wu, Frances M; Rundall, Thomas G; Shortell, Stephen M; Bloom, Joan R

    2016-06-20

    Purpose - The purpose of this paper is to describe the current landscape of health information technology (HIT) in early accountable care organizations (ACOs), the different strategies ACOs are using to develop HIT-based capabilities, and how ACOs are using these capabilities within their care management processes to advance health outcomes for their patient population. Design/methodology/approach - Mixed methods study pairing data from a cross-sectional National Survey of ACOs with in-depth, semi-structured interviews with leaders from 11 ACOs (both completed in 2013). Findings - Early ACOs vary widely in their electronic health record, data integration, and analytic capabilities. The most common HIT capability was drug-drug and drug-allergy interaction checks, with 53.2 percent of respondents reporting that the ACO possessed the capability to a high degree. Outpatient and inpatient data integration was the least common HIT capability (8.1 percent). In the interviews, ACO leaders commented on different HIT development strategies to gain a more comprehensive picture of patient needs and service utilization. ACOs realize the necessity for robust data analytics, and are exploring a variety of approaches to achieve it. Research limitations/implications - Data are self-reported. The qualitative portion was based on interviews with 11 ACOs, limiting generalizability to the universe of ACOs but allowing for a range of responses. Practical implications - ACOs are challenged with the development of sophisticated HIT infrastructure. They may benefit from targeted assistance and incentives to implement health information exchanges with other providers to promote more coordinated care management for their patient population. Originality/value - Using new empirical data, this study increases understanding of the extent of ACOs' current and developing HIT capabilities to support ongoing care management.

  2. Nationwide population-based study of cause-specific death rates in patients with psoriasis.

    PubMed

    Salahadeen, E; Torp-Pedersen, C; Gislason, G; Hansen, P R; Ahlehoff, O

    2015-05-01

    Psoriasis is a common chronic disease, mediated by type 1 and 17 helper T cell-driven inflammation. Epidemiological studies have demonstrated a wide range of comorbidities and increased mortality rates. However, the current evidence on psoriasis-related mortality is limited and nationwide data have not been presented previously. In a nationwide population-based cohort we evaluated all-cause and cause-specific death rates in patients with psoriasis as compared to the general population. The entire Danish population aged 18 and above, corresponding to a total of 5,458,627 individuals (50.7% female, 40.9 years ± 19.7), including 94,069 with mild psoriasis (53% female, 42.0 ± 17.0 years) and 28,253 with severe psoriasis (53.4% female, 43.0 ± 16.5 years), was included. A total of 884,661 deaths were recorded, including 10 916 in patients with mild psoriasis and 3699 in patients with severe psoriasis. The age at time of death varied by psoriasis status, i.e. 76.5 ± 14.0, 74.4 ± 12.8 and 72.0 ± 13.4 years, for the general population, mild psoriasis and severe psoriasis respectively. In general, the highest death rates were observed in patients with severe psoriasis. Overall death rates per 1000 patient years were 13.8 [confidence interval (CI) 13.8-13.8], 17.0 (CI 16.7-17.3) and 25.4 (CI 24.6-26.3) for the general population, patients with mild psoriasis and patients with severe psoriasis respectively. This nationwide population-based study of cause-specific death rates in patients with psoriasis demonstrated reduced lifespan and increased rates of all examined specific causes of death in patients with psoriasis compared to the general population. © 2014 European Academy of Dermatology and Venereology.

  3. Use of targeted transversus abdominus plane blocks in pediatric patients with anterior cutaneous nerve entrapment syndrome.

    PubMed

    Nizamuddin, Sarah L; Koury, Katharine M; Lau, Mary E; Watt, Lisa D; Gulur, Padma

    2014-01-01

    Anterior cutaneous nerve entrapment syndrome (ACNES) is a commonly overlooked source of chronic abdominal wall pain. A diagnosis of ACNES should be considered in cases of severe, localized abdominal pain that is accentuated by physical activity. Providers should consider diagnosing ACNES once a patient has both a positive result from a Carnett's test and precise localization of pain. We describe the use of transversus abdominus plane (TAP) blocks to treat ACNES in the pediatric patient population. TAP blocks are a treatment modality which have been described less frequently in the management of this syndrome, with rectus sheath blocks being used more commonly. TAP blocks can be used effectively for ACNES by targeting the site of maximal tenderness, which was identified using ultrasound guidance. Moreover, TAP blocks are an attractive procedure option for ACNES as they are less invasive than other commonly used techniques. We present 3 case series reports of pediatric patients evaluated at our institution for severe abdominal pain to describe the clinical manifestations, sequelae, and outcome of ACNES. Though the exact incidence of ACNES in the pediatric population is unknown, this condition has significant implications from chronic pain. Chronic pain can lead to significant emotional and social impacts on these pediatric patients, as well as their on their families. Further, the extensive utilization of health care resources is impacted when children with undiagnosed ACNES undergo invasive treatments when ACNES is not in the early differential. The purpose of this case series report is to prompt better recognition of the condition ACNES, and to highlight the efficacy of TAP blocks as a management strategy.

  4. Blood-pressure targets in patients with recent lacunar stroke: the SPS3 randomised trial.

    PubMed

    Benavente, O R; Coffey, C S; Conwit, R; Hart, R G; McClure, L A; Pearce, L A; Pergola, P E; Szychowski, J M

    2013-08-10

    Lowering of blood pressure prevents stroke but optimum target levels to prevent recurrent stroke are unknown. We investigated the effects of different blood-pressure targets on the rate of recurrent stroke in patients with recent lacunar stroke. In this randomised open-label trial, eligible patients lived in North America, Latin America, and Spain and had recent, MRI-defined symptomatic lacunar infarctions. Patients were recruited between March, 2003, and April, 2011, and randomly assigned, according to a two-by-two multifactorial design, to a systolic-blood-pressure target of 130-149 mm Hg or less than 130 mm Hg. The primary endpoint was reduction in all stroke (including ischaemic strokes and intracranial haemorrhages). Analysis was done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT 00059306. 3020 enrolled patients, 1519 in the higher-target group and 1501 in the lower-target group, were followed up for a mean of 3·7 (SD 2·0) years. Mean age was 63 (SD 11) years. After 1 year, mean systolic blood pressure was 138 mm Hg (95% CI 137-139) in the higher-target group and 127 mm Hg (95% CI 126-128) in the lower-target group. Non-significant rate reductions were seen for all stroke (hazard ratio 0·81, 95% CI 0·64-1·03, p=0·08), disabling or fatal stroke (0·81, 0·53-1·23, p=0·32), and the composite outcome of myocardial infarction or vascular death (0·84, 0·68-1·04, p=0·32) with the lower target. The rate of intracerebral haemorrhage was reduced significantly (0·37, 0·15-0·95, p=0·03). Treatment-related serious adverse events were infrequent. Although the reduction in stroke was not significant, our results support that in patients with recent lacunar stroke, the use of a systolic-blood-pressure target of less than 130 mm Hg is likely to be beneficial. National Institutes of Health-National Institute of Neurological Disorders and Stroke (NIH-NINDS). Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Evaluation of Aztreonam Dosing Regimens in Patients With Normal and Impaired Renal Function: A Population Pharmacokinetic Modeling and Monte Carlo Simulation Analysis.

    PubMed

    Xu, Hongmei; Zhou, Wangda; Zhou, Diansong; Li, Jianguo; Al-Huniti, Nidal

    2017-03-01

    Aztreonam is a monocyclic β-lactam antibiotic often used to treat infections caused by Enterobacteriaceae or Pseudomonas aeruginosa. Despite the long history of clinical use, population pharmacokinetic modeling of aztreonam in renally impaired patients is not yet available. The aims of this study were to assess the impact of renal impairment on aztreonam exposure and to evaluate dosing regimens for patients with renal impairment. A population model describing aztreonam pharmacokinetics following intravenous administration was developed using plasma concentrations from 42 healthy volunteers and renally impaired patients from 2 clinical studies. The final pharmacokinetic model was used to predict aztreonam plasma concentrations and evaluate the probability of pharmacodynamic target attainment (PTA) in patients with different levels of renal function. A 2-compartment model with first-order elimination adequately described aztreonam pharmacokinetics. The population mean estimates of aztreonam clearance, intercompartmental clearance, volume of distribution of the central compartment, and volume of distribution of the peripheral compartment were 4.93 L/h, 9.26 L/h, 7.43 L, and 6.44 L, respectively. Creatinine clearance and body weight were the most significant variables to explain patient variability in aztreonam clearance and volume of distribution, respectively. Simulations using the final pharmacokinetic model resulted in a clinical susceptibility break point of 4 and 8 mg/L, respectively, based on the clinical use of 1- and 2-g loading doses with the same or reduced maintenance dose every 8 hours for various renal deficiency patients. The population pharmacokinetic modeling and PTA estimation support adequate PTAs (>90% PTA) from the aztreonam label for dose adjustment of aztreonam in patients with moderate and severe renal impairment. © 2016, The American College of Clinical Pharmacology.

  6. Increased effect of target eccentricity on covert shifts of visual attention in patients with neglect.

    PubMed

    Hamilton, Roy H; Stark, Marianna; Coslett, H Branch

    2010-01-01

    Debate continues regarding the mechanisms underlying covert shifts of visual attention. We examined the relationship between target eccentricity and the speed of covert shifts of attention in normal subjects and patients with brain lesions using a cued-response task in which cues and targets were presented at 2 degrees or 8 degrees lateral to the fixation point. Normal subjects were slower on invalid trials in the 8 degrees as compared to 2 degrees condition. Patients with right-hemisphere stroke with neglect were slower in their responses to left-sided invalid targets compared to valid targets, and demonstrated a significant increase in the effect of target validity as a function of target eccentricity. Additional data from one neglect patient (JM) demonstrated an exaggerated validity x eccentricity x side interaction for contralesional targets on a cued reaction time task with a central (arrow) cue. We frame these results in the context of a continuous 'moving spotlight' model of attention, and also consider the potential role of spatial saliency maps. By either account, we argue that neglect is characterized by an eccentricity-dependent deficit in the allocation of attention.

  7. [Population pharmacokinetics applied to optimising cisplatin doses in cancer patients].

    PubMed

    Ramón-López, A; Escudero-Ortiz, V; Carbonell, V; Pérez-Ruixo, J J; Valenzuela, B

    2012-01-01

    To develop and internally validate a population pharmacokinetics model for cisplatin and assess its prediction capacity for personalising doses in cancer patients. Cisplatin plasma concentrations in forty-six cancer patients were used to determine the pharmacokinetic parameters of a two-compartment pharmacokinetic model implemented in NONMEN VI software. Pharmacokinetic parameter identification capacity was assessed using the parametric bootstrap method and the model was validated using the nonparametric bootstrap method and standardised visual and numerical predictive checks. The final model's prediction capacity was evaluated in terms of accuracy and precision during the first (a priori) and second (a posteriori) chemotherapy cycles. Mean population cisplatin clearance is 1.03 L/h with an interpatient variability of 78.0%. Estimated distribution volume at steady state was 48.3 L, with inter- and intrapatient variabilities of 31,3% and 11,7%, respectively. Internal validation confirmed that the population pharmacokinetics model is appropriate to describe changes over time in cisplatin plasma concentrations, as well as its variability in the study population. The accuracy and precision of a posteriori prediction of cisplatin concentrations improved by 21% and 54% compared to a priori prediction. The population pharmacokinetic model developed adequately described the changes in cisplatin plasma concentrations in cancer patients and can be used to optimise cisplatin dosing regimes accurately and precisely. Copyright © 2011 SEFH. Published by Elsevier Espana. All rights reserved.

  8. Targeting distinct myeloid cell populations in vivo using polymers, liposomes and microbubbles.

    PubMed

    Ergen, Can; Heymann, Felix; Al Rawashdeh, Wa'el; Gremse, Felix; Bartneck, Matthias; Panzer, Ulf; Pola, Robert; Pechar, Michal; Storm, Gert; Mohr, Nicole; Barz, Matthias; Zentel, Rudolf; Kiessling, Fabian; Trautwein, Christian; Lammers, Twan; Tacke, Frank

    2017-01-01

    Identifying intended or accidental cellular targets for drug delivery systems is highly relevant for evaluating therapeutic and toxic effects. However, limited knowledge exists on the distribution of nano- and micrometer-sized carrier systems at the cellular level in different organs. We hypothesized that clinically relevant carrier materials, differing in composition and size, are able to target distinct myeloid cell subsets that control inflammatory processes, such as macrophages, neutrophils, monocytes and dendritic cells. Therefore, we analyzed the biodistribution and in vivo cellular uptake of intravenously injected poly(N-(2-hydroxypropyl) methacrylamide) polymers, PEGylated liposomes and poly(butyl cyanoacrylate) microbubbles in mice, using whole-body imaging (computed tomography - fluorescence-mediated tomography), intra-organ imaging (intravital multi-photon microscopy) and cellular analysis (flow cytometry of blood, liver, spleen, lung and kidney). While the three carrier materials shared accumulation in tissue macrophages in liver and spleen, they notably differed in uptake by other myeloid subsets. Kupffer cells and splenic red pulp macrophages rapidly take up microbubbles. Liposomes efficiently reach dendritic cells in liver, lung and kidney. Polymers exhibit the longest circulation half-life and target endothelial cells in the liver, neutrophils and alveolar macrophages. The identification of such previously unrecognized target cell populations might open up new avenues for more efficient drug delivery. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Culturally Targeted Strategies for Diabetes Prevention in Minority Populations: A Systematic Review and Framework

    PubMed Central

    Lagisetty, Pooja A.; Priyadarshini, Shubadra; Terrell, Stephanie; Hamati, Mary; Landgraf, Jessica; Chopra, Vineet; Heisler, Michele

    2017-01-01

    Purpose The purpose of this study is to (a) assess the effectiveness of culturally tailored diabetes prevention interventions in minority populations and (b) develop a novel framework to characterize four key domains of culturally tailored interventions. Prevention strategies specifically tailored to the culture of ethnic minority patients may help reduce the incidence of diabetes. Methods We searched PubMed, EMBASE, and CINAHL for English-language, randomized controlled trials (RCTs) or quasi-experimental (QE) trials testing culturally tailored interventions to prevent diabetes in minority populations. Two reviewers independently extracted data and assessed risk of bias. Inductive thematic analysis was used to develop a framework with four domains (FiLLM: Facilitating [i.e., delivering] Interventions through Language, Location and Message). The framework was used to assess the overall effectiveness of culturally tailored interventions. Results Thirty-four trials met eligibility criteria. Twelve studies were randomized controlled trials, and 22 were quasi-experimental trials. Twenty-five out of 34 studies (74%) that used cultural tailoring demonstrated significantly improved Hemoglobin A1C, fasting glucose, and/or weight loss. Of the 25 successful interventions, 21 (84%) incorporated at least three culturally targeted domains. Seven studies used all four domains and were all successful. The least utilized domain was delivery (4/34) of the intervention’s key educational message. Conclusions Culturally tailoring interventions across the four domains of facilitators, language, location, and messaging can be effective in improving risk factors for progression to diabetes among ethnic minority groups. Future studies should evaluate how specific tailoring approaches work compared to usual care as well as comparative effectiveness of each tailoring domain. Registration (PROSPERO registration: CRD42015016914) PMID:28118127

  10. Current advances in targeted therapies for metastatic gastric cancer: improving patient care.

    PubMed

    Aguiar, Pedro Nazareth; Muniz, Thiago Pimentel; Miranda, Raelson Rodrigues; Tadokoro, Hakaru; Forones, Nora Manoukian; Monteiro, Ines-de-Paula; Castelo-Branco, Pedro; Janjigian, Yelena Y; De Mello, Ramon Andrade

    2016-03-01

    In this article, we review the literature on the current advances in targeted therapies for metastatic gastric cancer aimed at improving patient care. We conclude that the key to guiding targeted therapy is individual biomarkers, which are not completely elucidated. HER2 overexpression is the only predictive biomarker currently in use. Furthermore, it is necessary to understand that gastric tumors are heterogeneous; therefore, is impossible to evaluate a novel biological compound without evaluating personal biomarkers. The selection of patients who are able to receive each treatment is paramount for improving advanced gastric cancer survival and reducing unnecessary costs.

  11. Patient-Facing Mobile Apps to Treat High-Need, High-Cost Populations: A Scoping Review.

    PubMed

    Singh, Karandeep; Drouin, Kaitlin; Newmark, Lisa P; Filkins, Malina; Silvers, Elizabeth; Bain, Paul A; Zulman, Donna M; Lee, Jae-Ho; Rozenblum, Ronen; Pabo, Erika; Landman, Adam; Klinger, Elissa V; Bates, David W

    2016-12-19

    Self-management is essential to caring for high-need, high-cost (HNHC) populations. Advances in mobile phone technology coupled with increased availability and adoption of health-focused mobile apps have made self-management more achievable, but the extent and quality of the literature supporting their use is not well defined. The purpose of this review was to assess the breadth, quality, bias, and types of outcomes measured in the literature supporting the use of apps targeting HNHC populations. Data sources included articles in PubMed and MEDLINE (National Center for Biotechnology Information), EMBASE (Elsevier), the Cochrane Central Register of Controlled Trials (EBSCO), Web of Science (Thomson Reuters), and the NTIS (National Technical Information Service) Bibliographic Database (EBSCO) published since 2008. We selected studies involving use of patient-facing iOS or Android mobile health apps. Extraction was performed by 1 reviewer; 40 randomly selected articles were evaluated by 2 reviewers to assess agreement. Our final analysis included 175 studies. The populations most commonly targeted by apps included patients with obesity, physical handicaps, diabetes, older age, and dementia. Only 30.3% (53/175) of the apps studied in the reviewed literature were identifiable and available to the public through app stores. Many of the studies were cross-sectional analyses (42.9%, 75/175), small (median number of participants=31, interquartile range 11.0-207.2, maximum 11,690), or performed by an app's developers (61.1%, 107/175). Of the 175 studies, only 36 (20.6%, 36/175) studies evaluated a clinical outcome. Most apps described in the literature could not be located on the iOS or Android app stores, and existing research does not robustly evaluate the potential of mobile apps. Whereas apps may be useful in patients with chronic conditions, data do not support this yet. Although we had 2-3 reviewers to screen and assess abstract eligibility, only 1 reviewer abstracted

  12. Comparison of gatifloxacin and levofloxacin administered at various dosing regimens to hospitalised patients with community-acquired pneumonia: pharmacodynamic target attainment study using North American surveillance data for Streptococcus pneumoniae.

    PubMed

    Noreddin, Ayman M; Hoban, Daryl J; Zhanel, George G

    2005-08-01

    This work aimed at determining the target attainment potential of gatifloxacin and levofloxacin in specific age-related patient populations such as elderly (> or =65 years) versus younger (<65 years) hospitalised patients with community-acquired pneumonia (CAP). Previously described population pharmacokinetic models of gatifloxacin and levofloxacin administration in patients with serious CAP were utilised to simulate gatifloxacin and levofloxacin pharmacokinetics. Pharmacokinetic simulations and susceptibility data for Streptococcus pneumoniae from the ongoing national surveillance study, Canadian Respiratory Organism Susceptibility Study (CROSS), were then used to produce pharmacodynamic indices of free-drug area under the curve over 24h relative to the minimum inhibitory concentration (free-drug AUC(0-24)/MIC(all)). Monte Carlo simulations were then used to analyse target attainment both of gatifloxacin and levofloxacin to achieve free-drug AUC(0-24)/MIC(all)> or =30 against S. pneumoniae in patients with CAP. Dosing regimens for gatifloxacin were 400 mg once daily (qd) administered to younger patients (<65 years) and gatifloxacin 200 mg qd to elderly patients (> or =65 years). Dosing regimens for levofloxacin were simulated as 500 mg, 750 mg and 1000 mg qd administered to elderly patients as well as younger patients. Monte Carlo simulations using gatifloxacin 400mg against S. pneumoniae yielded probabilities of achieving free-drug AUC(0-24)/MIC(all) of 30 of 96.6% for all patients, 92.3% for younger patients and 97.7% for elderly patients. When administered to elderly patients, a reduced dose of gatifloxacin 200mg qd could achieve a target attainment potential of 91.4%. Monte Carlo simulation using levofloxacin 500 mg qd yielded probabilities of achieving free-drug AUC(0-24)/MIC(all) of 30 of 92.3% for all patients, 95.7% for elderly patients compared with 72.7% for younger patients. Using levofloxacin 750 mg and 1000 mg qd had probabilities of achieving free

  13. Target biomarker profile for the clinical management of paracetamol overdose

    PubMed Central

    Vliegenthart, A D Bastiaan; Antoine, Daniel J; Dear, James W

    2015-01-01

    Paracetamol (acetaminophen) overdose is one of the most common causes of acute liver injury in the Western world. To improve patient care and reduce pressure on already stretched health care providers new biomarkers are needed that identify or exclude liver injury soon after an overdose of paracetamol is ingested. This review highlights the current state of paracetamol poisoning management and how novel biomarkers could improve patient care and save healthcare providers money. Based on the widely used concept of defining a target product profile, a target biomarker profile is proposed that identifies desirable and acceptable key properties for a biomarker in development to enable the improved treatment of this patient population. The current biomarker candidates, with improved hepatic specificity and based on the fundamental mechanistic basis of paracetamol-induced liver injury, are reviewed and their performance compared with our target profile. PMID:26076366

  14. Translational research: precision medicine, personalized medicine, targeted therapies: marketing or science?

    PubMed

    Marquet, Pierre; Longeray, Pierre-Henry; Barlesi, Fabrice; Ameye, Véronique; Augé, Pascale; Cazeneuve, Béatrice; Chatelut, Etienne; Diaz, Isabelle; Diviné, Marine; Froguel, Philippe; Goni, Sylvia; Gueyffier, François; Hoog-Labouret, Natalie; Mourah, Samia; Morin-Surroca, Michèle; Perche, Olivier; Perin-Dureau, Florent; Pigeon, Martine; Tisseau, Anne; Verstuyft, Céline

    2015-01-01

    Personalized medicine is based on: 1) improved clinical or non-clinical methods (including biomarkers) for a more discriminating and precise diagnosis of diseases; 2) targeted therapies of the choice or the best drug for each patient among those available; 3) dose adjustment methods to optimize the benefit-risk ratio of the drugs chosen; 4) biomarkers of efficacy, toxicity, treatment discontinuation, relapse, etc. Unfortunately, it is still too often a theoretical concept because of the lack of convenient diagnostic methods or treatments, particularly of drugs corresponding to each subtype of pathology, hence to each patient. Stratified medicine is a component of personalized medicine employing biomarkers and companion diagnostics to target the patients likely to present the best benefit-risk balance for a given active compound. The concept of targeted therapy, mostly used in cancer treatment, relies on the existence of a defined molecular target, involved or not in the pathological process, and/or on the existence of a biomarker able to identify the target population, which should logically be small as compared to the population presenting the disease considered. Targeted therapies and biomarkers represent important stakes for the pharmaceutical industry, in terms of market access, of return on investment and of image among the prescribers. At the same time, they probably represent only the first generation of products resulting from the combination of clinical, pathophysiological and molecular research, i.e. of translational research. © 2015 Société Française de Pharmacologie et de Thérapeutique.

  15. The quest for population-level cancer recurrence data; current deficiencies and targets for improvement.

    PubMed

    In, Haejin; Simon, Cassie A; Phillips, Jerri Linn; Posner, Mitchell C; Ko, Clifford Y; Winchester, David P

    2015-05-01

    Cancer recurrence is a critical outcome in cancer care. However, population-level recurrence information is currently unavailable. Tumor registries provide an opportunity to generate this information, but require major reform. Our objectives were to (1) determine causes for variability in collection of recurrence, and (2) identify targets for intervention. On-site interviews and observations of tumor registry follow-up procedures were conducted at Commission on Cancer (CoC) accredited hospitals. Information regarding registry resources (caseload, staffing, chart availability), follow-up methods and perceived causes for difficulty in obtaining recurrence information was obtained. Seven NCI/academic, 5 comprehensive community and 2 community centers agreed to participate. Hospitals were inconsistent in their investigation of cancer recurrence, resulting in underreporting of rates of recurrence. Hospital characteristics, registry staffing, staff qualifications and medical chart access influenced follow-up practices. Coding standards and definitions for recurrence were suboptimal, resulting in hospital variability of recurrence reporting. Finally, inability to identify cases lost to follow-up in collected data prevents accurate analysis of recurrence rates. Tumor registries collect varying degrees of recurrence information and provide the underpinnings to capture population-level cancer recurrence data. Targets for intervention are listed, and provide a roadmap to obtain this critical information in cancer care. © 2015 Wiley Periodicals, Inc.

  16. [Blood pressure targets : The lower the better does not suit all].

    PubMed

    Hoffmann, U

    2018-04-01

    The systolic blood pressure intervention trial (SPRINT) published in 2015 has opened up new discussions on whether a lower blood pressure target as recommended by the current guidelines would be better for some patient groups. To review patient groups in which lower blood pressure targets would not be better. The results of SPRINT, its post-hoc and subgroup analyses, other studies and newer studies, as well as metaanalyses on the topic of blood pressure targets are reviewed and discussed. Studies with patients excluded from the SPRINT study were also analysed. The current international guidelines and recommendations of the Deutsche Hochdruckliga e. V. DHL® are included. Blood pressure monitoring methods differed considerably in the previously published studies. The low blood pressure value in SPRINT was mainly achieved due to the unusual method of blood pressure monitoring used and, as such, cannot be compared with blood pressure values in other studies. Based on current evidence, "the lower the better" should not be recommended in the following patient groups: older patients, in particular infirm older patients, patients with diabetes, patients without coronary heart disease or with low cardiovascular risk. When determining a blood pressure target, the method of blood pressure monitoring should be defined. A lower blood pressure target has been shown to be better in some well defined patient groups. However, adverse events due to antihypertensive medications should always be taken into account. Given the multiple exclusion criteria in trials and the results of many studies, "new" lower blood pressure targets could not be recommended in a large population of patients.

  17. Changes in Renal Function of Patients with Metastatic Renal Cell Carcinoma During Treatment with Molecular-Targeted Agents.

    PubMed

    Miyake, Hideaki; Muramaki, Mototsugu; Imai, Satoshi; Harada, Ken-Ichi; Fujisawa, Masato

    2016-06-01

    Impairment of renal function is a serious issue that should be considered in patients undergoing treatment with molecular-targeted agents for metastatic renal cell carcinoma (mRCC). The objective of this study was to assess the impact of molecular-targeted therapy on changes in renal function among patients with mRCC. The study included 408 mRCC patients treated with sunitinib, sorafenib, axitinib, everolimus and/or temsirolimus. Among these, 185, 128 and 95 received molecular-targeted agents as first-line (group 1), second-line (group 2) and third-line (group 3) therapy, respectively. No significant differences between the estimated glomerular filtration rate (eGFR) at baseline and that at the end of molecular-targeted therapy were noted among the three groups of patients. In addition, there were no significant differences between eGFR prior to the introduction of molecular-targeted therapy and that at the end of therapy across agents and lines of targeted therapy, with the exception of patients treated with axitinib and everolimus in second-line and third-line therapy, respectively. In group 1, a reduction in eGFR of >10 % from baseline was independently associated with performance status, hypertension and treatment duration, while in groups 2 and 3, only treatment duration was independently related to a reduction in eGFR of >10 %. It appears that renal function in patients with mRCC is not markedly impaired by molecular-targeted therapies, irrespective of the specific agents introduced; however, it may be necessary to pay special attention to deterioration in renal function when molecular-targeted therapy is continued for longer periods.

  18. Obesity and kidney disease: from population to basic science and the search for new therapeutic targets.

    PubMed

    Whaley-Connell, Adam; Sowers, James R

    2017-08-01

    The global burden of kidney disease is increasing strikingly in parallel with increases in obesity and diabetes. Indeed, chronic kidney disease (CKD) and end-stage renal disease (ESRD) coupled with comorbidities such as obesity, diabetes, and hypertension cost the health care system hundreds of billions of dollars in the US alone. The progression to ESRD in patients with obesity and diabetes continues despite widespread use of inhibitors of the renin-angiotensin-aldosterone system (RAAS) along with aggressive blood pressure and glycemic control in these high-risk populations. Thereby, it is increasingly important to better understand the underlying mechanisms involved in obesity-related CKD in order to develop new strategies that prevent or interrupt the progression of this costly disease. In this context, a key mechanism that drives development and progression of kidney disease in obesity is endothelial dysfunction and associated tubulointerstitial fibrosis. However, the precise interactive mechanisms in the development of aortic and kidney endothelial dysfunction and tubulointerstitial fibrosis remain unclear. Further, strategies specifically targeting kidney fibrosis have yielded inconclusive benefits in human studies. While clinical data support the benefits derived from inhibition of the RAAS, there is a tremendous amount of residual risk for the progression of kidney disease in individuals with obesity and diabetes. There is promising experimental data to suggest that exercise, targeting inflammation and oxidative stress, lowering uric acid, and targeting the mineralocorticoid receptor signaling and/or sodium channel inhibition could improve tubulointerstitial fibrosis and mitigate progression of kidney disease in persons with obesity and diabetes. Published by Elsevier Inc.

  19. [The management of asymptomatic bacteriuria in different patient population].

    PubMed

    Ivanov, M-L; Malinverni, R

    2008-11-12

    Who should be screened for asymptomatic bacteriuria (AB) and who should be treated? This review updates some aspects of the management of AB in different patient populations. A systematic screening for AB is recommended for pregnant women because of a significant risk of complications. In these cases as well as before any uro-gynecologic surgical procedure treatment of AB is strongly recommended. The management of AB in immunosuppressed or transplanted patients is more controversial. In other populations treating AB is not recommended and the outcome seems to be worse in case of treatment due to possible side effects and selection of resistant organisms. Recent studies have shown a considerable gap between clinical practice and recommendations.

  20. Impact of systemic targeted agents on the clinical outcomes of patients with brain metastases

    PubMed Central

    Johnson, Adam G.; Ruiz, Jimmy; Hughes, Ryan; Page, Brandi R.; Isom, Scott; Lucas, John T.; McTyre, Emory R.; Houseknecht, Kristin W.; Ayala-Peacock, Diandra N.; Bourland, Daniel J.; Hinson, William H.; Laxton, Adrian W.; Tatter, Stephen B.; Debinski, Waldemar; Watabe, Kounosuke; Chan, Michael D.

    2015-01-01

    Background To determine the clinical benefits of systemic targeted agents across multiple histologies after stereotactic radiosurgery (SRS) for brain metastases. Methods Between 2000 and 2013, 737 patients underwent upfront SRS for brain metastases. Patients were stratified by whether or not they received targeted agents with SRS. 167 (23%) received targeted agents compared to 570 (77%) that received other available treatment options. Time to event data were summarized using Kaplan-Meier plots, and the log rank test was used to determine statistical differences between groups. Results Patients who received SRS with targeted agents vs those that did not had improved overall survival (65% vs. 30% at 12 months, p < 0.0001), improved freedom from local failure (94% vs 90% at 12 months, p = 0.06), improved distant failure-free survival (32% vs. 18% at 12 months, p = 0.0001) and improved freedom from whole brain radiation (88% vs. 77% at 12 months, p = 0.03). Improvement in freedom from local failure was driven by improvements seen in breast cancer (100% vs 92% at 12 months, p < 0.01), and renal cell cancer (100% vs 88%, p = 0.04). Multivariate analysis revealed that use of targeted agents improved all cause mortality (HR = 0.6, p < 0.0001). Conclusions Targeted agent use with SRS appears to improve survival and intracranial outcomes. PMID:26087184

  1. Targeted presurgical decompensation in patients with yaw-dependent facial asymmetry

    PubMed Central

    Kim, Kyung-A; Lee, Ji-Won; Park, Jeong-Ho; Kim, Byoung-Ho; Ahn, Hyo-Won

    2017-01-01

    Facial asymmetry can be classified into the rolling-dominant type (R-type), translation-dominant type (T-type), yawing-dominant type (Y-type), and atypical type (A-type) based on the distorted skeletal components that cause canting, translation, and yawing of the maxilla and/or mandible. Each facial asymmetry type represents dentoalveolar compensations in three dimensions that correspond to the main skeletal discrepancies. To obtain sufficient surgical correction, it is necessary to analyze the main skeletal discrepancies contributing to the facial asymmetry and then the skeletal-dental relationships in the maxilla and mandible separately. Particularly in cases of facial asymmetry accompanied by mandibular yawing, it is not simple to establish pre-surgical goals of tooth movement since chin deviation and posterior gonial prominence can be either aggravated or compromised according to the direction of mandibular yawing. Thus, strategic dentoalveolar decompensations targeting the real basal skeletal discrepancies should be performed during presurgical orthodontic treatment to allow for sufficient skeletal correction with stability. In this report, we document targeted decompensation of two asymmetry patients focusing on more complicated yaw-dependent types than others: Y-type and A-type. This may suggest a clinical guideline on the targeted decompensation in patient with different types of facial asymmetries. PMID:28523246

  2. Targeted presurgical decompensation in patients with yaw-dependent facial asymmetry.

    PubMed

    Kim, Kyung-A; Lee, Ji-Won; Park, Jeong-Ho; Kim, Byoung-Ho; Ahn, Hyo-Won; Kim, Su-Jung

    2017-05-01

    Facial asymmetry can be classified into the rolling-dominant type (R-type), translation-dominant type (T-type), yawing-dominant type (Y-type), and atypical type (A-type) based on the distorted skeletal components that cause canting, translation, and yawing of the maxilla and/or mandible. Each facial asymmetry type represents dentoalveolar compensations in three dimensions that correspond to the main skeletal discrepancies. To obtain sufficient surgical correction, it is necessary to analyze the main skeletal discrepancies contributing to the facial asymmetry and then the skeletal-dental relationships in the maxilla and mandible separately. Particularly in cases of facial asymmetry accompanied by mandibular yawing, it is not simple to establish pre-surgical goals of tooth movement since chin deviation and posterior gonial prominence can be either aggravated or compromised according to the direction of mandibular yawing. Thus, strategic dentoalveolar decompensations targeting the real basal skeletal discrepancies should be performed during presurgical orthodontic treatment to allow for sufficient skeletal correction with stability. In this report, we document targeted decompensation of two asymmetry patients focusing on more complicated yaw-dependent types than others: Y-type and A-type. This may suggest a clinical guideline on the targeted decompensation in patient with different types of facial asymmetries.

  3. Why Do Patients With Cancer Visit Emergency Departments? Results of a 2008 Population Study in North Carolina

    PubMed Central

    Mayer, Deborah K.; Travers, Debbie; Wyss, Annah; Leak, Ashley; Waller, Anna

    2011-01-01

    Purpose Emergency departments (EDs) in the United States are used by patients with cancer for disease or treatment-related problems and unrelated issues. The North Carolina Disease Event Tracking and Epidemiologic Collection Tool (NC DETECT) collects information about ED visits through a statewide database. Patients and Methods After approval by the institutional review board, 2008 NC DETECT ED visit data were acquired and cancer-related visits were identified. Descriptive statistics and logistic regressions were performed. Of 4,190,911 ED visits in 2008, there were 37,760 ED visits by 27,644 patients with cancer. Results Among patients, 77.2% had only one ED visit in 2008, the mean age was 64 years, and there were slightly more men than women. Among visits, the payor was Medicare for 52.4% and Medicaid for 12.1%. More than half the visits by patients with cancer occurred on weekends or evenings, and 44.9% occurred during normal hours. The top three chief complaints were related to pain, respiratory distress, and GI issues. Lung, breast, prostate, and colorectal cancers were identified in 26.9%, 6.3%, 6%, and 7.7% of visits, respectively, with diagnosis. A total of 63.2% of visits resulted in hospital admittance. When controlling for sex, age, time of day, day of week, insurance, and diagnosis position, patients with lung cancer were more likely to be admitted than patients with other types of cancer. Conclusion To the best of our knowledge, this is the first study to provide a population-based snapshot of ED visits by patients with cancer in North Carolina. Efforts that target clinical problems and specific populations may improve delivery of quality cancer care and avoid ED visits. PMID:21606431

  4. Which population groups should be targeted for cardiovascular prevention? A modelling study based on the Norwegian Hordaland Health Study (HUSK).

    PubMed

    Brekke, Mette; Rekdal, Magne; Straand, Jørund

    2007-06-01

    To assess level of cardiovascular risk factors in a non-selected, middle-aged population. To estimate the proportion target for risk intervention according to present guidelines and according to different cut-off levels for two risk algorithms. Population survey, modelling study. The Norwegian Hordaland Health Study (HUSK) 1997-99. A total of 22 289 persons born in 1950-57. Own and relatives' cardiovascular morbidity, antihypertensive and lipid-lowering treatment, smoking, blood pressure, cholesterol. Framingham and Systematic Coronary Risk Evaluation (SCORE) algorithms. The European guidelines on CVD prevention in clinical practice were applied to estimate size of risk groups. Some 9.7% of men and 7.6% of women had CVD, diabetes mellitus, a high level of one specific risk factor, or received lipid-lowering or antihypertensive treatment. Applying a SCORE (60 years) cut-off level at 5% to the rest of the population selected 52.4% of men and 0.8% of women into a primary prevention group, while a cut-off level at 8% included 22.0% and 0.06% respectively. A cut-off level for the Framingham score (60 years) of 20% selected 43.6% of men and 4.7% of women, while a cut-off level of 25% selected 25.6% of men and 1.8% of women. The findings illustrate how choices regarding risk estimation highly affect the size of the target population. Modelling studies are important when preparing guidelines, to address implications for resource allocation and risk of medicalization. The population share to be targeted for primary prevention ought to be estimated, including the impact of various cut-off points for risk algorithms on the size of the risk population.

  5. A Targeted Swallow Screen for the Detection of Postoperative Dysphagia.

    PubMed

    Gee, Erica; Lancaster, Elizabeth; Meltzer, Jospeh; Mendelsohn, Abie H; Benharash, Peyman

    2015-10-01

    Postoperative dysphagia leads to aspiration pneumonia, prolonged hospital stay, and is associated with increased mortality. A simple and sensitive screening test to identify patients requiring objective dysphagia evaluation is presently lacking. In this study, we evaluated the efficacy of a novel targeted swallow screen evaluation. This was a prospective trial involving all adult patients who underwent elective cardiac surgery with cardiopulmonary bypass at our institution over an 8-week period. Within 24 hours of extubation and before the initiation of oral intake, all postsurgical patients were evaluated using the targeted swallow screen. A fiberoptic endoscopic evaluation of swallowing was requested for failed screenings. During the study, 50 postcardiac surgery patients were screened. Fifteen (30%) failed the targeted swallow screen, and ten of the fifteen (66%) failed the subsequent fiberoptic endoscopic evaluation of swallowing exam and were confirmed to have dysphagia. The screening test had 100 per cent sensitivity for detecting dysphagia in our patient population, and a specificity of 87.5 per cent. The overall incidence of dysphagia was 20 per cent. We have shown that a targeted swallow evaluation can efficiently screen patients during the postcardiac surgery period. Furthermore, we have shown that the true incidence of dysphagia after cardiac surgery is significantly higher than previously recognized in literature.

  6. Depression screening with patient-targeted feedback in cardiology: DEPSCREEN-INFO randomised clinical trial.

    PubMed

    Löwe, Bernd; Blankenberg, Stefan; Wegscheider, Karl; König, Hans-Helmut; Walter, Dirk; Murray, Alexandra M; Gierk, Benjamin; Kohlmann, Sebastian

    2017-02-01

    International guidelines advocate depression screening in patients with coronary heart disease (CHD) and other chronic illnesses, but evidence is lacking. To test the differential efficacy of written patient-targeted feedback v. no written patient feedback after depression screening. Patients with CHD or hypertension from three cardiology settings were randomised and screened for depression (ClinicalTrials.gov Identifier: NCT01879111). Compared with the control group, where only cardiologists received written feedback, in the intervention group both cardiologists and patients received written feedback regarding depression status. Depression severity was measured 1 month (primary outcome) and 6 months after screening. The control group (n = 220) and the patient-feedback group (n = 155) did not differ in depression severity 1 month after screening. Six months after screening, the patient-feedback group showed significantly greater improvements in depression severity and was twice as likely to seek information about depression compared with the control group. Patient-targeted feedback in addition to screening has a significant but small effect on depression severity after 6 months and may encourage patients to take an active role in the self-management of depression. © The Royal College of Psychiatrists 2017.

  7. Anxiety and depression in cardiac patients: age differences and comparisons with the general population.

    PubMed

    Hinz, Andreas; Kittel, Jörg; Karoff, Marthin; Daig, Isolde

    2011-01-01

    Anxiety and depression are often found in cardiac patients, but also in the general population. Therefore, evaluation of these symptoms in patients requires a comparison with norm values. The purpose of this study was to explore differences between cardiac patients and the general population in age dependency of anxiety and depression, and to discuss possible reasons for these differences. A sample of German cardiac patients (n = 2,696) and a sample of the German general population (n = 2,037) were tested using the Hospital Anxiety and Depression Scale (HADS). While we confirmed a linear age trend of anxiety and depression in the general population, we observed an inverted U-shaped age dependency in the patient sample. Young patients are especially affected by anxiety and depression. Five items of the HADS that mainly contributed to the age differences were identified. Formal characteristics of these 5 items could not explain the age differences. Concerning the meaning of the items, however, most of the items refer to worrying about the future. The relatively low rates of anxiety and depression in older patients (compared with the general population) indicate that adaptation processes took place, which should be taken into account in studies concerning the psychological status of patients. Young patients need special attention when dealing with mental distress. Copyright © 2011 S. Karger AG, Basel.

  8. Interferon-targeted therapy in systemic lupus erythematosus: Is this an alternative to targeting B and T cells?

    PubMed

    Kalunian, K C

    2016-09-01

    Clinical trials of investigational agents in systemic lupus erythematosus (SLE) have focused on targeting dysregulated B and T cells; however, recent translational research findings of the importance of the dysregulation of the innate immune system in SLE have led to clinical trials that target interferon. Three biologics that target type I interferons have been tested for their efficacy and safety in active SLE patients; these phase II trials have tested the hypothesis that down-regulation of interferon-regulated gene expression (the interferon signature) lessen the clinical burden of SLE. Rontalizumab, an anti-interferon-α monoclonal antibody, was studied in patients who had discontinued immunosuppressants. This study failed to show efficacy as assessed by both two outcome assessments; however, in low interferon signature patients, response was higher and corticosteroid usage was less in rontalizumab-treated patients. Sifalimumab, another anti-interferon-α monoclonal antibody, was studied in patients who remained on standard of care therapy. This study showed significantly better efficacy in patients treated with two sifalimumab dosages; significant differences were seen in the high interferon signature group. In a similar design and in a similar population as the sifalimumab study, anifrolumab, a monoclonal antibody that binds to a type I interferon receptor, was studied in patients who remained on standard of care therapy. In this study, one dosage group demonstrated efficacy and statistically significant effects were achieved in both tested dosage groups with secondary end points. Oral corticosteroid reduction to ≤7.5 mg daily was achieved in one of the tested dosage groups and organ-specific outcomes were significantly improved in that same group. For all studies, no significant differences in serious adverse effects were seen; although, herpes zoster infections were increased in sifalimumab- and anifrolumab-treated patients and influenza rates were

  9. Evaluation of kidney motion and target localization in abdominal SBRT patients

    PubMed Central

    Sonier, Marcus; Chu, William; Lalani, Nafisha; Erler, Darby; Cheung, Patrick

    2016-01-01

    The purpose of this study was to evaluate bilateral kidney and target translational/rotational intrafraction motion during stereotactic body radiation therapy treatment delivery of primary renal cell carcinoma and oligometastatic adrenal lesions for patients immobilized in the Elekta BodyFIX system. Bilateral kidney motion was assessed at midplane for 30 patients immobilized in a full‐body dual‐vacuum‐cushion system with two patients immobilized via abdominal compression. Intrafraction motion was assessed for 15 patients using kilovoltage cone‐beam computed tomography (kV‐CBCT) datasets (n=151) correlated to the planning CT. Patient positioning was corrected for translational and rotational misalignments using a robotic couch in six degrees of freedom if setup errors exceeded 1 mm and 1°. Absolute bilateral kidney motion between inhale and exhale 4D CT imaging phases for left–right (LR), superior–inferior (SI), and anterior–posterior (AP) directions was 1.51±1.00mm,8.10±4.33mm, and 3.08±2.11mm, respectively. Residual setup error determined across CBCT type (pretreatment, intrafraction, and post‐treatment) for x (LR), y (SI), and z (AP) translations was 0.63±0.74mm,1.08±1.38mm, and 0.70±1.00mm; while for x (pitch), y (roll), and z (yaw) rotations was 0.24±0.39°,0.19±0.34°, and 0.26±0.43°, respectively. Targets were localized to within 2.1 mm and 0.8° 95% of the time. The frequency of misalignments in the y direction was significant (p<0.05) when compared to the x and z directions with no significant difference in translations between IMRT and VMAT. This technique is robust using BodyFIX for patient immobilization and reproducible localization of kidney and adrenal targets and daily CBCT image guidance for correction of positional errors to maintain treatment accuracy. PACS number(s): 87.55.‐x, 87.56.‐v, 87.56.Da PMID:27929514

  10. A Data-Driven Evaluation of the Stop TB Global Partnership Strategy of Targeting Key Populations at Greater Risk for Tuberculosis

    PubMed Central

    Schnippel, Kathryn; Sharp, Alana

    2016-01-01

    Objective Identifying those infected with tuberculosis (TB) is an important component of any strategy for reducing TB transmission and population prevalence. The Stop TB Global Partnership recently launched an initiative with a focus on key populations at greater risk for TB infection or poor clinical outcomes, due to housing and working conditions, incarceration, low household income, malnutrition, co-morbidities, exposure to tobacco and silica dust, or barriers to accessing medical care. To achieve operational targets, the global health community needs effective, low cost, and large-scale strategies for identifying key populations. Using South Africa as a test case, we assess the feasibility and effectiveness of targeting active case finding to populations with TB risk factors identified from regularly collected sources of data. Our approach is applicable to all countries with TB testing and census data. It allows countries to tailor their outreach activities to the particular risk factors of greatest significance in their national context. Methods We use a national database of TB test results to estimate municipality-level TB infection prevalence, and link it to Census data to measure population risk factors for TB including rates of urban households, informal settlements, household income, unemployment, and mobile phone ownership. To examine the relationship between TB prevalence and risk factors, we perform linear regression analysis and plot the set of population characteristics against TB prevalence and TB testing rate by municipality. We overlay lines of best fit and smoothed curves of best fit from locally weighted scatter plot smoothing. Findings Higher TB prevalence is statistically significantly associated with more urban municipalities (slope coefficient β1 = 0.129, p < 0.0001, R2 = 0.133), lower mobile phone access (β1 = -0.053, p < 0.001, R2 = 0.089), lower unemployment rates (β1 = -0.020, p = 0.003, R2 = 0.048), and a lower proportion of low

  11. A Data-Driven Evaluation of the Stop TB Global Partnership Strategy of Targeting Key Populations at Greater Risk for Tuberculosis.

    PubMed

    McLaren, Zoë M; Schnippel, Kathryn; Sharp, Alana

    2016-01-01

    Identifying those infected with tuberculosis (TB) is an important component of any strategy for reducing TB transmission and population prevalence. The Stop TB Global Partnership recently launched an initiative with a focus on key populations at greater risk for TB infection or poor clinical outcomes, due to housing and working conditions, incarceration, low household income, malnutrition, co-morbidities, exposure to tobacco and silica dust, or barriers to accessing medical care. To achieve operational targets, the global health community needs effective, low cost, and large-scale strategies for identifying key populations. Using South Africa as a test case, we assess the feasibility and effectiveness of targeting active case finding to populations with TB risk factors identified from regularly collected sources of data. Our approach is applicable to all countries with TB testing and census data. It allows countries to tailor their outreach activities to the particular risk factors of greatest significance in their national context. We use a national database of TB test results to estimate municipality-level TB infection prevalence, and link it to Census data to measure population risk factors for TB including rates of urban households, informal settlements, household income, unemployment, and mobile phone ownership. To examine the relationship between TB prevalence and risk factors, we perform linear regression analysis and plot the set of population characteristics against TB prevalence and TB testing rate by municipality. We overlay lines of best fit and smoothed curves of best fit from locally weighted scatter plot smoothing. Higher TB prevalence is statistically significantly associated with more urban municipalities (slope coefficient β1 = 0.129, p < 0.0001, R2 = 0.133), lower mobile phone access (β1 = -0.053, p < 0.001, R2 = 0.089), lower unemployment rates (β1 = -0.020, p = 0.003, R2 = 0.048), and a lower proportion of low-income households (β1 = -0

  12. Population pharmacokinetics of busulfan in pediatric and young adult patients undergoing hematopoietic cell transplant: a model-based dosing algorithm for personalized therapy and implementation into routine clinical use.

    PubMed

    Long-Boyle, Janel R; Savic, Rada; Yan, Shirley; Bartelink, Imke; Musick, Lisa; French, Deborah; Law, Jason; Horn, Biljana; Cowan, Morton J; Dvorak, Christopher C

    2015-04-01

    Population pharmacokinetic (PK) studies of busulfan in children have shown that individualized model-based algorithms provide improved targeted busulfan therapy when compared with conventional dose guidelines. The adoption of population PK models into routine clinical practice has been hampered by the tendency of pharmacologists to develop complex models too impractical for clinicians to use. The authors aimed to develop a population PK model for busulfan in children that can reliably achieve therapeutic exposure (concentration at steady state) and implement a simple model-based tool for the initial dosing of busulfan in children undergoing hematopoietic cell transplantation. Model development was conducted using retrospective data available in 90 pediatric and young adult patients who had undergone hematopoietic cell transplantation with busulfan conditioning. Busulfan drug levels and potential covariates influencing drug exposure were analyzed using the nonlinear mixed effects modeling software, NONMEM. The final population PK model was implemented into a clinician-friendly Microsoft Excel-based tool and used to recommend initial doses of busulfan in a group of 21 pediatric patients prospectively dosed based on the population PK model. Modeling of busulfan time-concentration data indicates that busulfan clearance displays nonlinearity in children, decreasing up to approximately 20% between the concentrations of 250-2000 ng/mL. Important patient-specific covariates found to significantly impact busulfan clearance were actual body weight and age. The percentage of individuals achieving a therapeutic concentration at steady state was significantly higher in subjects receiving initial doses based on the population PK model (81%) than in historical controls dosed on conventional guidelines (52%) (P = 0.02). When compared with the conventional dosing guidelines, the model-based algorithm demonstrates significant improvement for providing targeted busulfan therapy in

  13. Design of ligand-targeted nanoparticles for enhanced cancer targeting

    NASA Astrophysics Data System (ADS)

    Stefanick, Jared F.

    nanoparticles, a dual-receptor targeted approach was evaluated by targeting multiple cell surface receptors simultaneously. Liposomes functionalized with two distinct peptide antagonists to target VLA-4 and Leukocyte Peyer's Patch Adhesion Molecule-1 (LPAM-1) demonstrated synergistically enhanced cellular uptake by cells overexpressing both target receptors and negligible uptake by cells that do not simultaneously express both receptors, providing a strategy to improve selectivity over conventional single receptor-targeted designs. Taken together, this process of systematic optimization of well-defined nanoparticle drug delivery systems has the potential to improve cancer therapy for a broader patient population.

  14. GM biofortified crops: potential effects on targeting the micronutrient intake gap in human populations.

    PubMed

    De Steur, Hans; Mehta, Saurabh; Gellynck, Xavier; Finkelstein, Julia L

    2017-04-01

    Genetic engineering has been successfully applied to increase micronutrient content in staple crops. Nutrition evidence is key to ensure scale-up and successful implementation. Unlike conventional plant breeding efforts, research on the efficacy or effectiveness of GM biofortified crops on nutritional status in human populations is lacking. This review reports on the potential role of GM biofortified crops in closing the micronutrient gap - increasing the dietary intake of micronutrients in human populations. To date, one clinical trial in the United States reported a high bio-conversion rate of β-carotene in Golden Rice, and potential effects of GM biofortified crop consumption on dietary intake and nutritional outcomes are promising. However, further research needs to confirm the ex ante assessments in target regions. Copyright © 2017. Published by Elsevier Ltd.

  15. The mitochondria-targeted antioxidant MitoQ modulates oxidative stress, inflammation and leukocyte-endothelium interactions in leukocytes isolated from type 2 diabetic patients.

    PubMed

    Escribano-Lopez, Irene; Diaz-Morales, Noelia; Rovira-Llopis, Susana; de Marañon, Arantxa Martinez; Orden, Samuel; Alvarez, Angeles; Bañuls, Celia; Rocha, Milagros; Murphy, Michael P; Hernandez-Mijares, Antonio; Victor, Victor M

    2016-12-01

    It is not known if the mitochondria-targeted antioxidants such as mitoquinone (MitoQ) can modulate oxidative stress and leukocyte-endothelium interactions in T2D patients. We aimed to evaluate the beneficial effect of MitoQ on oxidative stress parameters and leukocyte-endothelium interactions in leukocytes of T2D patients. The study population consisted of 98 T2D patients and 71 control subjects. We assessed metabolic and anthropometric parameters, mitochondrial reactive oxygen species (ROS) production, glutathione peroxidase 1 (GPX-1), NFκB-p65, TNFα and leukocyte-endothelium interactions. Diabetic patients exhibited higher weight, BMI, waist circumference, SBP, DBP, glucose, insulin, HOMA-IR, HbA1c, triglycerides, hs-CRP and lower HDL-c with respect to controls. Mitochondrial ROS production was enhanced in T2D patients and decreased by MitoQ. The antioxidant also increased GPX-1 levels and PMN rolling velocity and decreased PMN rolling flux and PMN adhesion in T2D patients. NFκB-p65 and TNFα were augmented in T2D and were both reduced by MitoQ treatment. Our findings support that the antioxidant MitoQ has an anti-inflammatory and antioxidant action in the leukocytes of T2D patients by decreasing ROS production, leukocyte-endothelium interactions and TNFα through the action of NFκB. These data suggest that mitochondria-targeted antioxidants such as MitoQ should be investigated as a novel means of preventing cardiovascular events in T2D patients. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Targeting populations at higher risk for malaria: a survey of national malaria elimination programmes in the Asia Pacific.

    PubMed

    Wen, Shawn; Harvard, Kelly E; Gueye, Cara Smith; Canavati, Sara E; Chancellor, Arna; Ahmed, Be-Nazir; Leaburi, John; Lek, Dysoley; Namgay, Rinzin; Surya, Asik; Thakur, Garib D; Whittaker, Maxine Anne; Gosling, Roly D

    2016-05-10

    Significant progress has been made in reducing the malaria burden in the Asia Pacific region, which is aggressively pursuing a 2030 regional elimination goal. Moving from malaria control to elimination requires National Malaria Control Programmes (NMCPs) to target interventions at populations at higher risk, who are often not reached by health services, highly mobile and difficult to test, treat, and track with routine measures, and if undiagnosed, can maintain parasite reservoirs and contribute to ongoing transmission. A qualitative, free-text questionnaire was developed and disseminated among 17 of the 18 partner countries of the Asia Pacific Malaria Elimination Network (APMEN). All 14 countries that responded to the survey identified key populations at higher risk of malaria in their respective countries. Thirteen countries engage in the dissemination of malaria-related Information, Education, and Communication (IEC) materials. Eight countries engage in diagnostic screening, including of mobile and migrant workers, military staff, and/or overseas workers. Ten countries reported distributing or recommending the use of long-lasting insecticide-treated nets (LLINs) among populations at higher risk with fewer countries engaging in other prevention measures such as indoor residual spraying (IRS) (two countries), spatial repellents (four countries), chemoprophylaxis (five countries), and mass drug administration (MDA) (three countries). Though not specifically tailored to populations at higher risk, 11 countries reported using mass blood surveys as a surveillance tool and ten countries map case data. Most NMCPs lack a monitoring and evaluation structure. Countries in the Asia Pacific have identified populations at higher risk and targeted interventions to these groups but there is limited information on the effectiveness of these interventions. Platforms like APMEN offer the opportunity for the sharing of protocols and lessons learned related to finding, targeting and

  17. Is health literacy related to health behaviors and cell phone usage patterns among the text4baby target population?

    PubMed

    Poorman, Elisabeth; Gazmararian, Julie; Elon, Lisa; Parker, Ruth

    2014-01-01

    Text4baby provides educational text messages to pregnant and postpartum women and targets underserved women. The primary purpose of this study is to examine the health behaviors and cell phone usage patterns of a text4baby target population and the associations with health literacy. Pregnant and postpartum women were recruited from two Women, Infant and Children clinics in Atlanta. Women were asked about their demographics, selected pregnancy or postpartum health behaviors, and cell phone usage patterns. Health literacy skills were measured with the English version of the Newest Vital Sign. Multivariable logistic regression was used to examine health behaviors and cell usage patterns by health literacy classification, controlling for commonly accepted confounders. Four hundred sixty-eight women were recruited, and 445 completed the Newest Vital Sign. Of these, 22% had inadequate health literacy, 50% had intermediate health literacy, and 28% had adequate health literacy skills. Compared to adequate health literacy, limited literacy was independently associated with not taking a daily vitamin during pregnancy (OR 3.6, 95% CI: 1.6, 8.5) and never breastfeeding their infant (OR 1.4, 95% CI: 1.1, 1.8). The majority (69.4%) of respondents received nine or more text messages a day prior to enrollment, one in four participants (24.6%) had changed their number within the last six months, and 7.0% of study participants shared a cell phone. Controlling for potentially confounding factors, those with limited health literacy were more likely to share a cell phone than those with adequate health literacy (OR 2.57, 95% CI: 1.79, 3.69). Text4baby messages should be appropriate for low health literacy levels, especially as this population may have higher prevalence of targeted unhealthy behaviors. Text4baby and other mhealth programs targetting low health literacy populations should also be aware of the different ways that these populations use their cell phones, including: sharing

  18. Depression screening with patient-targeted feedback in cardiology: The cost-effectiveness of DEPSCREEN-INFO

    PubMed Central

    Kohlmann, Sebastian; Gierk, Benjamin

    2017-01-01

    Background Although depression is common in patients with heart disease, screening for depression is much debated. DEPSCREEN-INFO showed that a patient-targeted feedback in addition to screening results in lower depression level six months after screening. The purpose of this analysis was to perform a cost-effectiveness analysis of DEPSCREEN-INFO. Methods Patients with coronary heart disease or arterial hypertension were included. Participants in both groups were screened for depression. Participants in the intervention group additionally received a patient-targeted feedback of their result and recommended treatment options. A cost-utility analysis using quality-adjusted life years (QALY) based on the EQ-5D was performed. The time horizon was 6 months. Resource utilization was assessed by a telephone interview. Multiple imputation using chained equations was used. Net-benefit regressions controlled for prognostic variables at baseline were performed to construct cost-effectiveness acceptability curves. Different sensitivity analyses were performed. Results 375 participants (intervention group: 155; control group: 220) were included at baseline. After 6 months, in the intervention group adjusted total costs were lower (-€2,098; SE: €1,717) and more QALY were gained (0.0067; SD: 0.0133); yet differences were not statistically significant. The probability of cost-effectiveness was around 80% independent of the willingness-to-pay (range: €0/QALY–€130,000/QALY). The results were robust. Conclusions A patient-targeted feedback in addition to depression screening in cardiology is cost-effective with a high probability. This underpins the use of the patient-targeted feedbacks and the PHQ-9 that are both freely available and easy to implement in routine care. PMID:28806775

  19. Depression screening with patient-targeted feedback in cardiology: The cost-effectiveness of DEPSCREEN-INFO.

    PubMed

    Brettschneider, Christian; Kohlmann, Sebastian; Gierk, Benjamin; Löwe, Bernd; König, Hans-Helmut

    2017-01-01

    Although depression is common in patients with heart disease, screening for depression is much debated. DEPSCREEN-INFO showed that a patient-targeted feedback in addition to screening results in lower depression level six months after screening. The purpose of this analysis was to perform a cost-effectiveness analysis of DEPSCREEN-INFO. Patients with coronary heart disease or arterial hypertension were included. Participants in both groups were screened for depression. Participants in the intervention group additionally received a patient-targeted feedback of their result and recommended treatment options. A cost-utility analysis using quality-adjusted life years (QALY) based on the EQ-5D was performed. The time horizon was 6 months. Resource utilization was assessed by a telephone interview. Multiple imputation using chained equations was used. Net-benefit regressions controlled for prognostic variables at baseline were performed to construct cost-effectiveness acceptability curves. Different sensitivity analyses were performed. 375 participants (intervention group: 155; control group: 220) were included at baseline. After 6 months, in the intervention group adjusted total costs were lower (-€2,098; SE: €1,717) and more QALY were gained (0.0067; SD: 0.0133); yet differences were not statistically significant. The probability of cost-effectiveness was around 80% independent of the willingness-to-pay (range: €0/QALY-€130,000/QALY). The results were robust. A patient-targeted feedback in addition to depression screening in cardiology is cost-effective with a high probability. This underpins the use of the patient-targeted feedbacks and the PHQ-9 that are both freely available and easy to implement in routine care.

  20. Clinical impact of targeted therapies in patients with metastatic clear-cell renal cell carcinoma

    PubMed Central

    Nerich, Virginie; Hugues, Marion; Paillard, Marie Justine; Borowski, Laëtitia; Nai, Thierry; Stein, Ulrich; Nguyen Tan Hon, Thierry; Montcuquet, Philippe; Maurina, Tristan; Mouillet, Guillaume; Kleinclauss, François; Pivot, Xavier; Limat, Samuel; Thiery-Vuillemin, Antoine

    2014-01-01

    Introduction The aim of this retrospective clinical study was to assess, in the context of the recent evolution of systemic therapies, the potential effect of targeted therapies on overall survival (OS) of patients with metastatic clear-cell renal cell carcinoma (mccRCC) in daily practice. Patients and methods All consecutive patients with histologically confirmed mccRCC who received systemic therapy between January 2000 and December 2010 in two oncology treatment centers in our Franche-Comté region in eastern France were included in the analysis. The primary end point was OS. The analysis of prognostic factors was performed using a two-step approach: univariate then multivariate analysis with a stepwise Cox proportional hazards regression model. Results For the entire cohort of 111 patients, the median OS was 17 months (95% confidence interval [CI]; 13–22 months) and the two-year OS was 39%. Three prognostic factors were independent predictors of long survival: prior nephrectomy (hazard ratio =0.38 [0.22–0.64], P<0.0001); systemic therapy by targeted therapy (hazard ratio =0.50 [0.31–0.80], P=0.005); and lack of liver metastasis (hazard ratio =0.43 [0.22–0.82], P=0.002). Median OS was 21 months [14–29 months] for patients who received at least one targeted therapy compared with 12 months [7–15 months] for patients who were treated only by immunotherapy agents (P=0.003). Conclusion Our results suggest that targeted therapies are associated with improved OS in comparison with cytokines, which is in line with other publications. PMID:24600236

  1. Exclusion of patients from pay-for-performance targets by English physicians.

    PubMed

    Doran, Tim; Fullwood, Catherine; Reeves, David; Gravelle, Hugh; Roland, Martin

    2008-07-17

    In the English pay-for-performance program, physicians use a range of criteria to exclude individual patients from the quality calculations that determine their pay. This process, which is called exception reporting, is intended to safeguard patients against inappropriate treatment by physicians seeking to maximize their income. However, exception reporting may allow physicians to inappropriately exclude patients for whom targets have been missed (a practice known as gaming). We analyzed data extracted automatically from clinical computing systems for 8105 family practices in England (96% of all practices), data from the U.K. Census, and data on practice characteristics from the U.K. Department of Health. We determined the rate of exception reporting for 65 clinical activities and the association between this rate and the characteristics of patients and medical practices. From April 2005 through March 2006, physicians excluded a median of 5.3% of patients (interquartile range, 4.0 to 6.9) from the quality calculations. Physicians were most likely to exclude patients from indicators that were related to providing treatments and achieving target levels of intermediate outcomes; they were least likely to exclude patients from indicators that were related to routine checks and measurements and to offers of treatment. The characteristics of patients and practices explained only 2.7% of the variance in exception reporting. We estimate that exception reporting accounted for approximately 1.5% of the cost of the pay-for-performance program. Exception reporting brings substantial benefits to pay-for-performance programs, providing that the process is used appropriately. In England, rates of exception reporting have generally been low, with little evidence of widespread gaming. 2008 Massachusetts Medical Society

  2. Pharmacokinetics and Tolerability of Lorcaserin in Special Populations: Elderly Patients and Patients with Renal or Hepatic Impairment.

    PubMed

    Christopher, Ronald J; Morgan, Michael E; Tang, Yong; Anderson, Christen; Sanchez, Matilde; Shanahan, William

    2017-04-01

    To determine whether dosage adjustment is likely to be necessary for effective and well-tolerated use of a pharmaceutical agent, guidance documents from the US Food and Drug Administration recommend pharmacokinetics studies in patients with impaired renal or impaired hepatic function and in the elderly population. Three studies were conducted to evaluate the pharmacokinetic properties and tolerability of lorcaserin in these populations. Lorcaserin was evaluated in single-dose pharmacokinetics studies of 3 overweight/obese populations: (1) elderly (aged >65 years) patients; (2) patients with impaired renal function; and (3) those with impaired hepatic function. In elderly patients, C max was lower (geometric mean ratio [GMR], 0.83; 90% CI, 0.71-0.97), but AUC was unchanged versus adult patients. In patients with renal impairment, C max was reduced versus that in patients with normal renal function (GMR: mild impairment, 0.99 [90% CI, 0.76-1.29]; moderate, 0.70 [90% CI, 0.54-0.90]; and severe, 0.69 [90% CI, 0.53-0.89]); no trend in AUC was observed in this group versus renal impairment. In patients with hepatic impairment, C max was decreased (GMR: mild impairment, 0.92 [90% CI, 0.76-1.11]; moderate, 0.86 [90% CI, 0.71-1.04]), and AUC was increased versus patients with normal hepatic function. Based on these findings, no lorcaserin dose adjustments are necessary in elderly patients with normal renal function or in patients with mild/moderate renal or hepatic impairment. ClinicalTrials.gov identifiers: NCT00828581, NCT00828438, and NCT00828932. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  3. Suicidal ideation and attempts in patients with stroke: a population-based study.

    PubMed

    Chung, Jae Ho; Kim, Jung Bin; Kim, Ji Hyun

    2016-10-01

    Stroke is known to be associated with an increase in the risk for suicide. However, there are very few population-based studies investigating the risk of suicidal ideation and attempts in patients with stroke. The purpose of this study was to compare the risk of suicidal ideation and attempts between patients with stroke and population without stroke using nationwide survey data. Individual-level data were obtained from 228,735 participants (4560 with stroke and 224,175 without stroke) of the 2013 Korean Community Health Survey. Demographic characteristics, socioeconomic status, physical health status, and mental health status were compared between patients with stroke and population without stroke. Multivariable logistic regression was performed to investigate the independent effects of the stroke on suicidal ideation and attempts. Stroke patients had more depressive mood (12.6 %) than population without stroke (5.7 %, p < 0.001). Stroke patients experienced more suicidal ideation (24.4 %) and attempts (1.3 %) than population without stroke (9.8 and 0.4 %, respectively; both p < 0.001). Stroke was found to increase the risk for suicidal ideation (OR 1.65, 95 % CI 1.52-1.79) and suicidal attempts (OR 1.64, 95 % CI 1.21-2.22), adjusting for demographics, socioeconomic factors, and physical health and mental health factors. We found that stroke increased the risk for suicidal ideation and attempts, independent of other factors that are known to be associated with suicidality, suggesting that stroke per se may be an independent risk factor for suicidality.

  4. The predictive value of multi-targeted fluorescent in-situ hybridization in patients with history of bladder cancer.

    PubMed

    Gofrit, Ofer N; Zorn, Kevin C; Silvestre, Josephine; Shalhav, Arieh L; Zagaja, Gregory P; Msezane, Lambda P; Steinberg, Gary D

    2008-01-01

    UroVysion (Abbott Molecular Inc., Des Plaines, IL) is a multi-target fluorescent in-situ hybridization (FISH) assay that detects aneuploidy of chromosomes 3, 7, and 17, and loss of the 9p21 locus in exfoliated cells in urine. In this study, we evaluated if UroVysion can predict tumor recurrence in patients with negative cystoscopy and urinary cytology at the time of (FISH) assay. The study population included patients with history of non-muscle invasive bladder cancer treated by transurethral resection. Follow-up included cystoscopy, barbotage, urinary cytology, and UroVysion testing. Patients were followed for at least 6 months after their initial UroVysion testing. A total of 64 patients (37 males) were enrolled into the study. Mean patient age was 62 years (S.D. 13.2 years). Initial highest tumor stage was Ta in 42 patients (65.6%), T1 in 21 patients (33%), and isolated Tis in a single patient. Abnormal UroVysion results were observed in 40 patients (62.5%). After a median follow-up of 13.5 months, 21 patients (33%) developed tumor recurrence (Ta in 13 patients, T1 in 5, and Tis in 3). Recurrent tumors developed in 45% of the patients with abnormal UroVysion test compared with 12.5% of the patients with normal assay (P = 0.01). An abnormal UroVysion result preceded the diagnosis of tumor recurrence in 18/21 cases (86%), including all high-grade recurrences. This data suggest that UroVysion may be a useful tool for predicting tumor recurrence. Cystoscopy may be spared and surveillance intervals widened in patients with history of low grade tumors and a normal UroVysion test.

  5. A comparison of the EQ-5D-3L and ICECAP-O in an older post-acute patient population relative to the general population.

    PubMed

    Couzner, Leah; Crotty, Maria; Norman, Richard; Ratcliffe, Julie

    2013-08-01

    The measurement and valuation of quality of life forms a major component of economic evaluation in health care and is a major issue in health services research. However, differing approaches exist in the measurement and valuation of quality of life from a health economics perspective. While some instruments such as the EQ-5D-3L focus on health-related quality of life alone, others assess quality of life in broader terms, for example, the newly developed ICECAP-O. The aim of this study was to utilize two generic preference-based instruments, the EQ-5D-3L and the ICECAP-O, to measure and value the quality of life of older adult patients receiving post-acute care. An additional objective was to compare the values obtained by each instrument with those generated from two community-based general population samples. Data were collected from a clinical patient population of older adults receiving post-acute outpatient rehabilitation or residential transition care and two Australian general population samples of individuals residing in the general community. The individual responses to the ICECAP-O and EQ-5D-3L instruments were scored using recently developed Australian general population algorithms. Empirical comparisons were made of the resulting patient and general population sample values for the total population and dis-aggregated according to age (65-79 and 80+ years) and gender. A total of 1,260 participants aged 65-99 years (n = 86 clinical patient sample, n = 385 EQ-5D-3L general population sample, n = 789 ICECAP-O general population sample) completed one or both of the EQ-5D-3L and ICECAP-O instruments. As expected, the patient group demonstrated lower quality of life than the general population sample as measured by both quality-of-life instruments. The difference in values between the patient and general population groups was found to be far more pronounced for the EQ-5D-3L than for the ICECAP-O. The ICECAP-O was associated with a mean difference in values of 0

  6. Population Pharmacokinetics and Dosing Regimen Optimization of Meropenem in Cerebrospinal Fluid and Plasma in Patients with Meningitis after Neurosurgery

    PubMed Central

    Lu, Cheng; Zhang, Yuyi; Chen, Mingyu; Zhong, Ping; Chen, Yuancheng; Yu, Jicheng; Wu, Xiaojie; Wu, Jufang

    2016-01-01

    Meropenem is used to manage postneurosurgical meningitis, but its population pharmacokinetics (PPK) in plasma and cerebrospinal fluid (CSF) in this patient group are not well-known. Our aims were to (i) characterize meropenem PPK in plasma and CSF and (ii) recommend favorable dosing regimens in postneurosurgical meningitis patients. Eighty-two patients were enrolled to receive meropenem infusions of 2 g every 8 h (q8h), 1 g q8h, or 1 g q6h for at least 3 days. Serial blood and CSF samples were collected, and concentrations were determined and analyzed via population modeling. Probabilities of target attainment (PTA) were predicted via Monte Carlo simulations, using the target of unbound meropenem concentrations above the MICs for at least 40% of dosing intervals in plasma and at least of 50% or 100% of dosing intervals in CSF. A two-compartment model plus another CSF compartment best described the data. The central, intercentral/peripheral, and intercentral/CSF compartment clearances were 22.2 liters/h, 1.79 liters/h, and 0.01 liter/h, respectively. Distribution volumes of the central and peripheral compartments were 17.9 liters and 3.84 liters, respectively. The CSF compartment volume was fixed at 0.13 liter, with its clearance calculated by the observed drainage amount. The multiplier for the transfer from the central to the CSF compartment was 0.172. Simulation results show that the PTAs increase as infusion is prolonged and as the daily CSF drainage volume decreases. A 4-hour infusion of 2 g q8h with CSF drainage of less than 150 ml/day, which provides a PTA of >90% for MICs of ≤8 mg/liter in blood and of ≤0.5 mg/liter or 0.25 mg/liter in CSF, is recommended. (This study has been registered at ClinicalTrials.gov under identifier NCT02506686.) PMID:27572392

  7. Choice of Target Population Weights in Rater Comparability Scoring and Equating. Research Report. ETS RR-13-03

    ERIC Educational Resources Information Center

    Puhan, Gautam

    2013-01-01

    The purpose of this study was to demonstrate that the choice of sample weights when defining the target population under poststratification equating can be a critical factor in determining the accuracy of the equating results under a unique equating scenario, known as "rater comparability scoring and equating." The nature of data…

  8. Adaptive radiation therapy for postprostatectomy patients using real-time electromagnetic target motion tracking during external beam radiation therapy.

    PubMed

    Zhu, Mingyao; Bharat, Shyam; Michalski, Jeff M; Gay, Hiram A; Hou, Wei-Hsien; Parikh, Parag J

    2013-03-15

    Using real-time electromagnetic (EM) transponder tracking data recorded by the Calypso 4D Localization System, we report inter- and intrafractional target motion of the prostate bed, describe a strategy to evaluate treatment adequacy in postprostatectomy patients receiving intensity modulated radiation therapy (IMRT), and propose an adaptive workflow. Tracking data recorded by Calypso EM transponders was analyzed for postprostatectomy patients that underwent step-and-shoot IMRT. Rigid target motion parameters during beam delivery were calculated from recorded transponder positions in 16 patients with rigid transponder geometry. The delivered doses to the clinical target volume (CTV) were estimated from the planned dose matrix and the target motion for the first 3, 5, 10, and all fractions. Treatment adequacy was determined by comparing the delivered minimum dose (Dmin) with the planned Dmin to the CTV. Treatments were considered adequate if the delivered CTV Dmin is at least 95% of the planned CTV Dmin. Translational target motion was minimal for all 16 patients (mean: 0.02 cm; range: -0.12 cm to 0.07 cm). Rotational motion was patient-specific, and maximum pitch, yaw, and roll were 12.2, 4.1, and 10.5°, respectively. We observed inadequate treatments in 5 patients. In these treatments, we observed greater target rotations along with large distances between the CTV centroid and transponder centroid. The treatment adequacy from the initial 10 fractions successfully predicted the overall adequacy in 4 of 5 inadequate treatments and 10 of 11 adequate treatments. Target rotational motion could cause underdosage to partial volume of the postprostatectomy targets. Our adaptive treatment strategy is applicable to post-prostatectomy patients receiving IMRT to evaluate and improve radiation therapy delivery. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Semi-mechanistic autoinduction model of midazolam in critically ill patients: population pharmacokinetic analysis.

    PubMed

    Aoyama, T; Hirata, K; Yamamoto, Y; Yokota, H; Hayashi, H; Aoyama, Y; Matsumoto, Y

    2016-08-01

    Midazolam (MDZ) is commonly used for sedating critically ill patients. The daily dose required for adequate sedation increases in increments over 100 h after administration. The objectives of this study were to characterize the MDZ pharmacokinetics in critically ill patients and to describe the phenomenon of increasing daily dose by means of population pharmacokinetic analysis. Data were obtained from 30 patients treated in an intensive care unit. The patients received MDZ intravenously as a combination of bolus and continuous infusion. Serum MDZ concentration was assayed by high-performance liquid chromatography. Population pharmacokinetic analysis was performed using the NONMEM software package. The alteration of clearance unexplained by demographic factors and clinical laboratory data was described as an autoinduction of MDZ clearance using a semi-mechanistic pharmacokinetic-enzyme turnover model. The final population pharmacokinetic model was a one-compartment model estimated by incorporating a semi-mechanistic pharmacokinetic-enzyme turnover model for clearance, taking autoinduction into account. A significant covariate for MDZ clearance was total bilirubin. An increase in total bilirubin indicated a reduction in MDZ clearance. From simulation using the population pharmacokinetic parameters obtained in this study, MDZ clearance increased 2·3 times compared with pre-induced clearance 100 h after the start of 12·5 mg/h continuous infusion. Autoinduction and total bilirubin were significant predictors of the clearance of MDZ in this population. Step-by-step dosage adjustment using this population pharmacokinetic model may be useful for establishing a MDZ dosage regimen in critically ill patients. © 2016 John Wiley & Sons Ltd.

  10. Targeting survival pathways in chronic myeloid leukaemia stem cells

    PubMed Central

    Sinclair, A; Latif, A L; Holyoake, T L

    2013-01-01

    Chronic myeloid leukaemia (CML) is a clonal myeloproliferative disorder characterized by the presence of a fusion oncogene BCR-ABL, which encodes a protein with constitutive TK activity. The implementation of tyrosine kinase inhibitors (TKIs) marked a major advance in CML therapy; however, there are problems with current treatment. For example, relapse occurs when these drugs are discontinued in the majority of patients who have achieved a complete molecular response on TKI and these agents are less effective in patients with mutations in the BCR-ABL kinase domain. Importantly, TKI can effectively target proliferating mature cells, but do not eradicate quiescent leukaemic stem cells (LSCs), therefore allowing disease persistence despite treatment. It is essential that alternative strategies are used to target the LSC population. BCR-ABL activation is responsible for the modulation of different signalling pathways, which allows the LSC fraction to evade cell death. Several pathways have been shown to be modulated by BCR-ABL, including PI3K/AKT/mTOR, JAK-STAT and autophagy signalling pathways. Targeting components of these survival pathways, alone or in combination with TKI, therefore represents an attractive potential therapeutic approach for targeting the LSC. However, many pathways are also active in normal stem cells. Therefore, potential targets must be validated to effectively eradicate CML stem cells while sparing normal counterparts. This review summarizes the main pathways modulated in CML stem cells, the recent developments and the use of novel drugs to target components in these pathways which may be used to target the LSC population. Linked Articles This article is part of a themed section on Emerging Therapeutic Aspects in Oncology. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-8 PMID:23517124

  11. Liver toxicity of chemotherapy and targeted therapy for breast cancer patients with hepatitis virus infection.

    PubMed

    Liu, Yu; Li, Zhan-Yi; Li, Xi; Wang, Jia-Ni; Huang, Qun-Ai; Huang, Yong

    2017-10-01

    Chemotherapy has greatly improved the prognosis of breast cancer patients. However, it may also result in undesirable side effects such as hepatitis virus reactivation. Little information is available on the liver toxicity of chemotherapy and targeted therapy for breast cancer patients with hepatitis virus (HBV/HCV) infection. We performed a retrospective survey of 835 patients diagnosed with breast cancer between January 2010 and December 2015 at our institution. All patients had been screened for HBV/HCV infection at the time of breast cancer diagnosis. We retrospectively investigated the toxicity of chemotherapy and the changes in HBV/HCV load based on a medical record review. 52 patients with positive anti-HBV antibody test and 21 patients with positive anti-HCV antibody tests received chemotherapy. 762 patients without HBV and HCV infection served as the control group. The morbidity of liver toxicity and disruptions in chemotherapy attributable to liver toxicity were not significantly different among control group, HBV group and HCV groups (27.7% vs 34.6% vs 42.9%, P = 0.189 and 5.0% vs 9.6% vs 9.5%, P = 0.173, respectively). No patients presented with HBV/HCV reactivation. Breast cancer patients with HCV can be treated with chemotherapy and targeted therapy with trastuzumab. Breast cancer patients with HBV who accept antiviral therapy can be treated with chemotherapy and targeted therapy with trastuzumab and patients can benefit from prophylactic antiviral therapy before chemotherapy. However, a multidisciplinary cooperation and closely monitoring liver function during the course of chemotherapy may benefit patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Patient-Reported Barriers to the Prekidney Transplant Evaluation in an At-Risk Population in the United States.

    PubMed

    Lockwood, Mark B; Saunders, Milda R; Nass, Rachel; McGivern, Claire L; Cunningham, Patrick N; Chon, W James; Josephson, Michelle A; Becker, Yolanda T; Lee, Christopher S

    2017-06-01

    Despite our knowledge of barriers to the early stages of the transplant process, we have limited insight into patient-reported barriers to the prekidney transplant medical evaluation in populations largely at-risk for evaluation failure. One-hundred consecutive adults were enrolled at an urban, Midwestern transplant center. Demographic, clinical, and quality of life data were collected prior to patients visit with a transplant surgeon/nephrologist (evaluation begins). Patient-reported barriers to evaluation completion were collected using the Subjective Barriers Questionnaire 90-days after the initial medical evaluation appointment (evaluation ends), our center targeted goal for transplant work-up completion. At 90 days, 40% of participants had not completed the transplant evaluation. Five barrier categories were created from the 85 responses to the Subjective Barriers Questionnaire. Patient-reported barriers included poor communication, physical health, socioeconomics, psychosocial influences, and access to care. In addition, determinants for successful evaluation completion included being of white race, higher income, free of dialysis, a lower comorbid burden, and reporting higher scores on the Kidney Disease Quality of Life subscale role-emotional. Poor communication between patients and providers, and among providers, was the most prominent patient-reported barrier identified. Barriers were more prominent in marginalized groups such as ethnic minorities and people with low income. Understanding the prevalence of patient-reported barriers may aid in the development of patient-centered interventions to improve completion rates.

  13. Tumor-targeting Salmonella typhimurium A1-R regresses an osteosarcoma in a patient-derived xenograft model resistant to a molecular-targeting drug.

    PubMed

    Murakami, Takashi; Igarashi, Kentaro; Kawaguchi, Kei; Kiyuna, Tasuku; Zhang, Yong; Zhao, Ming; Hiroshima, Yukihiko; Nelson, Scott D; Dry, Sarah M; Li, Yunfeng; Yanagawa, Jane; Russell, Tara; Federman, Noah; Singh, Arun; Elliott, Irmina; Matsuyama, Ryusei; Chishima, Takashi; Tanaka, Kuniya; Endo, Itaru; Eilber, Fritz C; Hoffman, Robert M

    2017-01-31

    Osteosarcoma occurs mostly in children and young adults, who are treated with multiple agents in combination with limb-salvage surgery. However, the overall 5-year survival rate for patients with recurrent or metastatic osteosarcoma is 20-30% which has not improved significantly over 30 years. Refractory patients would benefit from precise individualized therapy. We report here that a patient-derived osteosarcoma growing in a subcutaneous nude-mouse model was regressed by tumor-targeting Salmonella typhimurium A1-R (S. typhimurium A1-R, p<0.001 compared to untreated control). The osteosarcoma was only partially sensitive to the molecular-targeting drug sorafenib, which did not arrest its growth. S. typhimurium A1-R was significantly more effective than sorafenib (P <0.001). S. typhimurium grew in the treated tumors and caused extensive necrosis of the tumor tissue. These data show that S. typhimurium A1-R is powerful therapy for an osteosarcoma patient-derived xenograft model.

  14. Tumor-targeting Salmonella typhimurium A1-R regresses an osteosarcoma in a patient-derived xenograft model resistant to a molecular-targeting drug

    PubMed Central

    Murakami, Takashi; Igarashi, Kentaro; Kawaguchi, Kei; Kiyuna, Tasuku; Zhang, Yong; Zhao, Ming; Hiroshima, Yukihiko; Nelson, Scott D.; Dry, Sarah M.; Li, Yunfeng; Yanagawa, Jane; Russell, Tara; Federman, Noah; Singh, Arun; Elliott, Irmina; Matsuyama, Ryusei; Chishima, Takashi; Tanaka, Kuniya; Endo, Itaru; Eilber, Fritz C.; Hoffman, Robert M.

    2017-01-01

    Osteosarcoma occurs mostly in children and young adults, who are treated with multiple agents in combination with limb-salvage surgery. However, the overall 5-year survival rate for patients with recurrent or metastatic osteosarcoma is 20-30% which has not improved significantly over 30 years. Refractory patients would benefit from precise individualized therapy. We report here that a patient-derived osteosarcoma growing in a subcutaneous nude-mouse model was regressed by tumor-targeting Salmonella typhimurium A1-R (S. typhimurium A1-R, p<0.001 compared to untreated control). The osteosarcoma was only partially sensitive to the molecular-targeting drug sorafenib, which did not arrest its growth. S. typhimurium A1-R was significantly more effective than sorafenib (P <0.001). S. typhimurium grew in the treated tumors and caused extensive necrosis of the tumor tissue. These data show that S. typhimurium A1-R is powerful therapy for an osteosarcoma patient-derived xenograft model. PMID:28030831

  15. Increased risk of chronic liver disease in patients with bipolar disorder: A population-based study.

    PubMed

    Hsu, Jer-Hwa; Chien, I-Chia; Lin, Ching-Heng

    2016-01-01

    This study aimed to investigate the prevalence and incidence of chronic liver disease in patients with bipolar disorder. We used a random sample of 766,427 subjects aged ≥18 years from the National Health Research Institute database in the year 2005. Subjects with at least one primary diagnosis of bipolar disorder in 2005 were identified. Patients with a primary or secondary diagnosis of chronic liver disease were also defined. We compared the prevalence and associated factors of chronic liver disease between patients with bipolar disorder and the general population in 2005. We also compared the incidence of chronic liver disease in patients with bipolar disorder and the general population from 2006 to 2010. The prevalence of chronic liver disease in patients with bipolar disorder (13.9%) was 2.68 times higher than that of the general population (5.8%) in 2005. The average annual incidence of chronic liver disease in patients with bipolar disorder from 2006 to 2010 was also higher than that of the general population (2.95% vs. 1.73%; risk ratio: 1.71; 95% confidence interval: 1.46-2.01). Patients with bipolar disorder had a significantly higher prevalence and incidence of chronic liver disease than those in the general population, and younger patients with bipolar disorder have a much higher prevalence and incidence than those in the general population. Male sex, second-generation antipsychotic or antidepressant use, and hyperlipidemia were associated factors for chronic liver disease in patients with bipolar disorder. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Targeted therapy with apatinib in a patient with relapsed small cell lung cancer

    PubMed Central

    Zhao, Jun; Zhang, Xiaoling; Gong, Chaojie; Zhang, Jialei

    2017-01-01

    Abstract Rationale: Small cell lung cancer (SCLC) is a lethal malignancy. Once relapsed, the disease is irreversible and most of the patients will die of cancer aggravation in 1 to 2 months. In the past several decades, little progress has been made in the systemic treatment of SCLC. Apatinib, as a novel small-molecule tyrosine kinase inhibitor specifically targeting the vascular endothelial growth factor receptor 2 (VEGFR2), has achieved progress in treatment of a variety of cancers. However, there has been no report of the targeted therapy with apatinib in SCLC yet. Patient concerns: A 63-year-old man, an ex-smoker, presented with a slight hoarseness and cough. The patient was admitted to our department with a primary diagnosis of SCLC at an extensive stage (ES-SCLC). After 17 months of successful first-, second-, and third-line chemotherapy, the disease eventually became relapsed. Then, apatinib treatment started promptly on demand by the patient and his family. Intervention: After presenting an informed consent, the patient received apatinib treatment immediately at a dose of 250 mg/day orally. Outcomes: (1) On the 28th day of apatinib therapy, the symptoms of dyspnea and poor appetite of the patient were notably improved. (2) The CT scan taken on the 70th day showed that the pleural effusion in the left lung almost disappeared. (3) The elevated serum neuron-specific enolase (NSE) level was decreased. The patient died of acute respiratory failure on the 172nd day of apatinib treatment. Importantly, the tumor mass did not enlarge obviously during apatinib treatment. Lessons: Here, we presented a case with relapsed SCLC who unexpectedly responded to single-agent apatinib treatment. Therefore, this report will shed light on future studies of targeted therapy with apatinib in SCLC at different stages. PMID:29390367

  17. Strategic targeting of advance care planning interventions: the Goldilocks phenomenon.

    PubMed

    Billings, J Andrew; Bernacki, Rachelle

    2014-04-01

    Strategically selecting patients for discussions and documentation about limiting life-sustaining treatments-choosing the right time along the end-of-life trajectory for such an intervention and identifying patients at high risk of facing end-of-life decisions-can have a profound impact on the value of advance care planning (ACP) efforts. Timing is important because the completion of an advance directive (AD) too far from or too close to the time of death can lead to end-of-life decisions that do not optimally reflect the patient's values, goals, and preferences: a poorly chosen target patient population that is unlikely to need an AD in the near future may lead to patients making unrealistic, hypothetical choices, while assessing preferences in the emergency department or hospital in the face of a calamity is notoriously inadequate. Because much of the currently studied ACP efforts have led to a disappointingly small proportion of patients eventually benefitting from an AD, careful targeting of the intervention should also improve the efficacy of such projects. A key to optimal timing and strategic selection of target patients for an ACP program is prognostication, and we briefly highlight prognostication tools and studies that may point us toward high-value AD interventions.

  18. Alcohol Drinking Pattern: A Comparison between HIV-Infected Patients and Individuals from the General Population.

    PubMed

    Ikeda, Maria Leticia R; Barcellos, Nemora T; Alencastro, Paulo R; Wolff, Fernando H; Moreira, Leila B; Gus, Miguel; Brandão, Ajacio B M; Fuchs, Flavio D; Fuchs, Sandra C

    2016-01-01

    Alcohol consumption is highly prevalent in the general population and among HIV-infected population. This study aimed to compare the pattern of alcohol consumption and to describe characteristics associated with heavy alcohol consumption in individuals from the general population with patients infected with HIV. Participants for this analysis came from a population-based cross-sectional study and from a consecutive sampling of patients infected with HIV. Participants aged 18 years or older were interviewed using similar questionnaires with questions pertaining to socio-demographic characteristics, alcohol consumption, smoking, physical activity, and HIV-related characteristics, among others. Blood pressure and anthropometric measures were measured using standardized procedures. Weekly alcohol consumption was more prevalent among individuals from the general population than HIV-infected patients: 57.0 vs. 31.1%, P<0.001. The prevalence of heavy episodic drinking was higher in the population sample as well: 46.1 vs. 17.0%, P<0.001. In the general population, heavy alcohol consumption was more prevalent in men. Cigarette smoking was independently associated with heavy alcohol consumption among HIV infected (Prevalence Ratio; PR = 5.9; 95%CI 2.6-13.9; P<0,001) and general population (PR = 2.6; 95%CI 1.9-3.0; P<0.001). Years at school were inversely associated with heavy alcohol consumption among HIV-infected patients and directly associated among participants from the general population, even after controlling for sex, age, skin color, and smoking. Heavy alcohol consumption is more prevalent in the general population than among HIV-infected patients. Individuals aware about their disease may reduce the amount of alcoholic beverages consumption comparatively to healthy individuals from the general population.

  19. Fillers in the skin of color population.

    PubMed

    Heath, Candrice R; Taylor, Susan C

    2011-05-01

    The skin of color population in the United States is rapidly growing and the cosmetic industry is responding to the demand for skin of color targeted treatments. The aging face in skin of color patients has a unique pattern that can be successfully augmented by dermal fillers. Though many subjects with skin of color were not included in the pre-market dermal filler clinical trials, some post-market studies have examined the safety and risks of adverse events in this population. The safety data from a selection of these studies was examined. Though pigmentary changes occurred, there have been no reports of keloid development. Developing a patient-specific care plan and instituting close follow up is emphasized.

  20. Modeling Patient-Specific Magnetic Drug Targeting Within the Intracranial Vasculature

    PubMed Central

    Patronis, Alexander; Richardson, Robin A.; Schmieschek, Sebastian; Wylie, Brian J. N.; Nash, Rupert W.; Coveney, Peter V.

    2018-01-01

    Drug targeting promises to substantially enhance future therapies, for example through the focussing of chemotherapeutic drugs at the site of a tumor, thus reducing the exposure of healthy tissue to unwanted damage. Promising work on the steering of medication in the human body employs magnetic fields acting on nanoparticles made of paramagnetic materials. We develop a computational tool to aid in the optimization of the physical parameters of these particles and the magnetic configuration, estimating the fraction of particles reaching a given target site in a large patient-specific vascular system for different physiological states (heart rate, cardiac output, etc.). We demonstrate the excellent computational performance of our model by its application to the simulation of paramagnetic-nanoparticle-laden flows in a circle of Willis geometry obtained from an MRI scan. The results suggest a strong dependence of the particle density at the target site on the strength of the magnetic forcing and the velocity of the background fluid flow. PMID:29725303

  1. Modeling Patient-Specific Magnetic Drug Targeting Within the Intracranial Vasculature.

    PubMed

    Patronis, Alexander; Richardson, Robin A; Schmieschek, Sebastian; Wylie, Brian J N; Nash, Rupert W; Coveney, Peter V

    2018-01-01

    Drug targeting promises to substantially enhance future therapies, for example through the focussing of chemotherapeutic drugs at the site of a tumor, thus reducing the exposure of healthy tissue to unwanted damage. Promising work on the steering of medication in the human body employs magnetic fields acting on nanoparticles made of paramagnetic materials. We develop a computational tool to aid in the optimization of the physical parameters of these particles and the magnetic configuration, estimating the fraction of particles reaching a given target site in a large patient-specific vascular system for different physiological states (heart rate, cardiac output, etc.). We demonstrate the excellent computational performance of our model by its application to the simulation of paramagnetic-nanoparticle-laden flows in a circle of Willis geometry obtained from an MRI scan. The results suggest a strong dependence of the particle density at the target site on the strength of the magnetic forcing and the velocity of the background fluid flow.

  2. Empirical and targeted therapy of candidemia with fluconazole versus echinocandins: a propensity score-derived analysis of a population-based, multicentre prospective cohort.

    PubMed

    López-Cortés, L E; Almirante, B; Cuenca-Estrella, M; Garnacho-Montero, J; Padilla, B; Puig-Asensio, M; Ruiz-Camps, I; Rodríguez-Baño, J

    2016-08-01

    We compared the clinical efficacy of fluconazole and echinocandins in the treatment of candidemia in real practice. The CANDIPOP study is a prospective, population-based cohort study on candidemia carried out between May 2010 and April 2011 in 29 Spanish hospitals. Using strict inclusion criteria, we separately compared the impact of empirical and targeted therapy with fluconazole or echinocandins on 30-day mortality. Cox regression, including a propensity score (PS) for receiving echinocandins, stratified analysis on the PS quartiles and PS-based matched analyses, were performed. The empirical and targeted therapy cohorts comprised 316 and 421 cases, respectively; 30-day mortality was 18.7% with fluconazole and 33.9% with echinocandins (p 0.02) in the empirical therapy group and 19.8% with fluconazole and 27.7% with echinocandins (p 0.06) in the targeted therapy group. Multivariate Cox regression analysis including PS showed that empirical therapy with fluconazole was associated with better prognosis (adjusted hazard ratio 0.38; 95% confidence interval 0.17-0.81; p 0.01); no differences were found within each PS quartile or in cases matched according to PS. Targeted therapy with fluconazole did not show a significant association with mortality in the Cox regression analysis (adjusted hazard ratio 0.77; 95% confidence interval 0.41-1.46; p 0.63), in the PS quartiles or in PS-matched cases. The results were similar among patients with severe sepsis and septic shock. Empirical or targeted treatment with fluconazole was not associated with increased 30-day mortality compared to echinocandins among adults with candidemia. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  3. Population Pharmacokinetics and Therapeutic Efficacy of Febuxostat in Patients with Severe Renal Impairment.

    PubMed

    Hira, Daiki; Chisaki, Yugo; Noda, Satoshi; Araki, Hisazumi; Uzu, Takashi; Maegawa, Hiroshi; Yano, Yoshitaka; Morita, Shin-Ya; Terada, Tomohiro

    2015-01-01

    The aim of the present study was to determine the influence of severe renal dysfunction (estimated glomerular filtration rate <30 ml/min/1.73 m(2), including hemodialysis) on the pharmacokinetics and therapeutic effects of febuxostat using a population pharmacokinetic analysis. This study recruited patients with hyperuricemia who were initially treated with allopurinol, but were switched to febuxostat, and it consists of 2 sub-studies: a pharmacokinetic study (26 patients) and retrospective efficacy evaluation study (51 patients). The demographic and clinical data of patients were collected from electronic medical records. Plasma febuxostat concentrations were obtained at each hospital visit. Population pharmacokinetic modeling was performed with NONMEM version 7.2. A total of 128 plasma febuxostat concentrations from 26 patients were used in the population pharmacokinetic analysis. The data were best described by a 1-compartment model with first order absorption. Covariate analysis revealed that renal function did not influence the pharmacokinetics of febuxostat, whereas actual body weight significantly influenced apparent clearance and apparent volume of distribution. The retrospective efficacy analysis showed the favorable therapeutic response of febuxostat switched from allopurinol in patients with moderate to severe renal impairment. No serious adverse event associated with febuxostat was observed irrespective of renal function. The population pharmacokinetic analysis and therapeutic analysis of febuxostat revealed that severe renal dysfunction had no influence on the pharmacokinetic parameters of febuxostat. These results suggest that febuxostat is tolerated well by patients with severe renal impairment. © 2015 S. Karger AG, Basel.

  4. Enhanced Recovery After Surgery Program Implementation in 2 Surgical Populations in an Integrated Health Care Delivery System.

    PubMed

    Liu, Vincent X; Rosas, Efren; Hwang, Judith; Cain, Eric; Foss-Durant, Anne; Clopp, Molly; Huang, Mengfei; Lee, Derrick C; Mustille, Alex; Kipnis, Patricia; Parodi, Stephen

    2017-07-19

    Novel approaches to perioperative surgical care focus on optimizing nutrition, mobility, and pain management to minimize adverse events after surgical procedures. To evaluate the outcomes of an enhanced recovery after surgery (ERAS) program among 2 target populations: patients undergoing elective colorectal resection and patients undergoing emergency hip fracture repair. A pre-post difference-in-differences study before and after ERAS implementation in the target populations compared with contemporaneous surgical comparator groups (patients undergoing elective gastrointestinal surgery and emergency orthopedic surgery). Implementation began in February and March 2014 and concluded by the end of 2014 at 20 medical centers within the Kaiser Permanente Northern California integrated health care delivery system. A multifaceted ERAS program designed with a particular focus on perioperative pain management, mobility, nutrition, and patient engagement. The primary outcome was hospital length of stay. Secondary outcomes included hospital mortality, home discharge, 30-day readmission rates, and complication rates. The study included a total of 3768 patients undergoing elective colorectal resection (mean [SD] age, 62.7 [14.1] years; 1812 [48.1%] male) and 5002 patients undergoing emergency hip fracture repair (mean [SD] age, 79.5 [11.8] years; 1586 [31.7%] male). Comparator surgical patients included 5556 patients undergoing elective gastrointestinal surgery and 1523 patients undergoing emergency orthopedic surgery. Most process metrics had significantly greater changes in the ERAS target populations after implementation compared with comparator surgical populations, including those for ambulation, nutrition, and opioid use. Hospital length of stay and postoperative complication rates were also significantly lower among ERAS target populations after implementation. The rate ratios for postoperative complications were 0.68 (95% CI, 0.46-0.99; P = .04) for patients

  5. Greater Experience of Negative Non-Target Emotions by Patients with Neurodegenerative Diseases Is Related to Lower Emotional Well-Being in Caregivers.

    PubMed

    Chen, Kuan-Hua; Wells, Jenna L; Otero, Marcela C; Lwi, Sandy J; Haase, Claudia M; Levenson, Robert W

    2017-01-01

    Behavioral symptoms in patients with neurodegenerative diseases can be particularly challenging for caregivers. Previously, we reported that patients with frontotemporal dementia (FTD) and Alzheimer's disease (AD) experienced emotions that were atypical or incongruent with a given situation (i.e., non-target emotions). We tested the hypothesis that greater experience of non-target emotions by patients is associated with lower caregiver emotional well-being. 178 patients with FTD, AD, or other neurodegenerative diseases and 35 healthy individuals watched 3 films designed to induce amusement, sadness, and disgust, and then reported their emotions during the films. Caregivers of the patients reported their own emotional well-being on the Medical Outcomes Study 36-item Short-Form Health Survey. In response to the amusement and sadness (but not disgust) films, greater experience of non-target emotions by patients was related to lower caregiver emotional well-being. These effects were specific to patients' experience of negative non-target emotions (i.e., not found for positive non-target emotions or for negative or positive target emotions). The findings reveal a previously unstudied patient behavior that is related to worse caregiver emotional well-being. Future research and clinical assessment may benefit from evaluating non-target emotions in patients. © 2017 S. Karger AG, Basel.

  6. Fiscal Shenanigans, Targeted Federal Health Care Funds, and Patient Mortality

    PubMed Central

    Baicker, Katherine; Staiger, Douglas

    2007-01-01

    We explore the effectiveness of matching grants when lower levels of government can expropriate some of the funds for other uses. Using data on the Medicaid Disproportionate Share program, we identify states that were most able to expropriate funds. Payments to public hospitals in these states were systematically diverted and had no significant impact on patient mortality. Payments that were not expropriated were associated with significant declines in patient mortality. Overall, subsidies were an effective mechanism for improving outcomes for the poor, but the impact was limited by the ability of state and local governments to divert the targeted funds. PMID:18084627

  7. Targeted Next Generation Sequencing in Patients with Inborn Errors of Metabolism

    PubMed Central

    Yubero, Dèlia; Brandi, Núria; Ormazabal, Aida; Garcia-Cazorla, Àngels; Pérez-Dueñas, Belén; Campistol, Jaime; Ribes, Antonia; Palau, Francesc

    2016-01-01

    Background Next-generation sequencing (NGS) technology has allowed the promotion of genetic diagnosis and are becoming increasingly inexpensive and faster. To evaluate the utility of NGS in the clinical field, a targeted genetic panel approach was designed for the diagnosis of a set of inborn errors of metabolism (IEM). The final aim of the study was to compare the findings for the diagnostic yield of NGS in patients who presented with consistent clinical and biochemical suspicion of IEM with those obtained for patients who did not have specific biomarkers. Methods The subjects studied (n = 146) were classified into two categories: Group 1 (n = 81), which consisted of patients with clinical and biochemical suspicion of IEM, and Group 2 (n = 65), which consisted of IEM cases with clinical suspicion and unspecific biomarkers. A total of 171 genes were analyzed using a custom targeted panel of genes followed by Sanger validation. Results Genetic diagnosis was achieved in 50% of patients (73/146). In addition, the diagnostic yield obtained for Group 1 was 78% (63/81), and this rate decreased to 15.4% (10/65) in Group 2 (X2 = 76.171; p < 0.0001). Conclusions A rapid and effective genetic diagnosis was achieved in our cohort, particularly the group that had both clinical and biochemical indications for the diagnosis. PMID:27243974

  8. Cognition in patients with burn injury in the inpatient rehabilitation population.

    PubMed

    Purohit, Maulik; Goldstein, Richard; Nadler, Deborah; Mathews, Katie; Slocum, Chloe; Gerrard, Paul; DiVita, Margaret A; Ryan, Colleen M; Zafonte, Ross; Kowalske, Karen; Schneider, Jeffrey C

    2014-07-01

    To analyze potential cognitive impairment in patients with burn injury in the inpatient rehabilitation population. Rehabilitation patients with burn injury were compared with the following impairment groups: spinal cord injury, amputation, polytrauma and multiple fractures, and hip replacement. Differences between the groups were calculated for each cognitive subscale item and total cognitive FIM. Patients with burn injury were compared with the other groups using a bivariate linear regression model. A multivariable linear regression model was used to determine whether differences in cognition existed after adjusting for covariates (eg, sociodemographic factors, facility factors, medical complications) based on previous studies. Inpatient rehabilitation facilities. Data from Uniform Data System for Medical Rehabilitation from 2002 to 2011 for adults with burn injury (N=5347) were compared with other rehabilitation populations (N=668,816). Not applicable. Comparison of total cognitive FIM scores and subscales (memory, verbal comprehension, verbal expression, social interaction, problem solving) for patients with burn injury versus other rehabilitation populations. Adults with burn injuries had an average total cognitive FIM score ± SD of 26.8±7.0 compared with an average FIM score ± SD of 28.7±6.0 for the other groups combined (P<.001). The subscale with the greatest difference between those with burn injury and the other groups was memory (5.1±1.7 compared with 5.6±1.5, P<.001). These differences persisted after adjustment for covariates. Adults with burn injury have worse cognitive FIM scores than other rehabilitation populations. Future research is needed to determine the impact of this comorbidity on patient outcomes and potential interventions for these deficits. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  9. The case for expanding the definition of 'key populations' to include high-risk groups in the general population to improve targeted HIV prevention efforts.

    PubMed

    Shisana, Olive; Zungu, N; Evans, M; Risher, K; Rehle, T; Clementano, D

    2015-09-22

    Two additional key populations within the general population in South Africa (SA) that are at risk of HIV infection are black African women aged 20 - 34 years and black African men aged 25 - 49 years. To investigate the social determinants of HIV serostatus for these two high-risk populations. Data from the 2012 South African National HIV Prevalence, Incidence, and Behaviour Survey were analysed for black African women aged 20 - 34 years and black African men aged 25 - 49 years. Of the 6.4 million people living with HIV in SA in 2012, 1.8 million (28%) were black women aged 20 - 34 years and 1.9 million (30%) black men aged 25 - 49 years. In 2012, they constituted 58% of the total HIV-positive population and 48% of the newly infected population. Low socioeconomic status (SES) was strongly associated (p<0.001) with being HIV-positive among black women aged 20 - 34 years, and was marginally significant among black men aged 25 - 49 years (p<0.1). Low SES is a critical social determinant for HIV infection among the high-risk groups of black African women aged 20 - 34 years and black African men aged 25 - 49 years. Targeted interventions for these key populations should prioritise socioeconomic empowerment, access to formal housing and services, access to higher education, and broad economic transformation.

  10. Medical resource use and expenditure in patients with chronic heart failure: a population-based analysis of 88 195 patients.

    PubMed

    Farré, Nuria; Vela, Emili; Clèries, Montse; Bustins, Montse; Cainzos-Achirica, Miguel; Enjuanes, Cristina; Moliner, Pedro; Ruiz, Sonia; Verdú-Rotellar, Jose Maria; Comín-Colet, Josep

    2016-09-01

    Heart failure (HF) is one of the diseases with greater healthcare expenditure. However, little is known about the cost of HF at a population level. Hence, our aim was to study the population-level distribution and predictors of healthcare expenditure in patients with HF. This was a population-based longitudinal study including all prevalent HF cases in Catalonia (Spain) on 31 December 2012 (n = 88 195). We evaluated 1-year healthcare resource use and expenditure using the Health Department (CatSalut) surveillance system that collects detailed information on healthcare usage for the entire population. Mean age was 77.4 (12) years; 55% were women. One-year mortality rate was 14%. All-cause emergency department visits and unplanned hospitalizations were required at least once in 53.4% and 30.8% of patients, respectively. During 2013, a total of €536.2 million were spent in the care of HF patients (7.1% of the total healthcare budget). The main source of expenditure was hospitalization (39% of the total) whereas outpatient care represented 20% of the total expenditure. In the general population, outpatient care and hospitalization were the main expenses. In multivariate analysis, younger age, higher presence of co-morbidities, and a recent HF or all-cause hospitalization were independently associated with higher healthcare expenditure. In Catalonia, a large portion of the annual healthcare budget is devoted to HF patients. Unplanned hospitalization represents the main source of healthcare-related expenditure. The knowledge of how expenditure is distributed in a non-selected HF population might allow health providers to plan the distribution of resources in patients with HF. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

  11. The representation of vulnerable populations in quality improvement studies.

    PubMed

    Rolnitsky, Asaph; Kirtsman, Maksim; Goldberg, Hanna R; Dunn, Michael; Bell, Chaim M

    2018-05-01

    A mapping review to quantify representation of vulnerable populations, who suffer from disparity and often inequitable healthcare, in quality improvement (QI) research. Studies published in 2004-2014 inclusive from Medline, Embase and Cochrane databases for English language research with the terms 'quality improvement' or 'quality control' or 'QI' and 'plan-do-study-act' or 'PDSA' in the years 2004-2014 inclusively. Published clinical research that was a QI-themed, as identified by its declared search terms, MESH terms, abstract or title. Three reviewers identified the eligible studies independently. Excluded were publications that were not trials, evaluations or analyses. Of 2039 results, 1660 were eligible for inclusion. There were 586 (33.5%) publications that targeted a specific vulnerable population: children (184, 10.54%), mental health patients (125, 7.16%), the elderly (100, 5.73%), women (57, 3.27%), the poor (30, 1.72%), rural residents (29, 1.66%), visible minorities (27, 1.55%), the terminally ill (17, 0.97%), adolescents (16, 0.92%) and prisoners (1 study). Seventy-four articles targeted two or more vulnerable populations, and 11 targeted three population categories. On average, there were 158 QI research studies published per year, increasing from 69 in 2004 to 396 in 2014 (R2 = 0.7, P < 0.001). The relative representation of vulnerable populations had a mean of 33.58% and was stable over the time period (standard deviation (SD) = 5.9%, R2 = 0.001). Seven countries contributed to over 85% of the publications targeting vulnerable populations, with the USA contributing 62% of the studies. Over 11 years, there has been a marked increase in QI publications. Roughly one-third of all published QI research is on vulnerable populations, a stable proportion over time. Nevertheless, some vulnerable populations are under-represented. Increased education, resources and attention are encouraged to improve the health of vulnerable populations through focused QI

  12. Population pharmacokinetic and pharmacogenetic analysis of 6-mercaptopurine in paediatric patients with acute lymphoblastic leukaemia

    PubMed Central

    Hawwa, Ahmed F; Collier, Paul S; Millership, Jeff S; McCarthy, Anthony; Dempsey, Sid; Cairns, Carole; McElnay, James C

    2008-01-01

    WHAT IS ALREADY KNOWN ABOUT THIS SUBJECTThe cytotoxic effects of 6-mercaptopurine (6-MP) were found to be due to drug-derived intracellular metabolites (mainly 6-thioguanine nucleotides and to some extent 6-methylmercaptopurine nucleotides) rather than the drug itself.Current empirical dosing methods for oral 6-MP result in highly variable drug and metabolite concentrations and hence variability in treatment outcome. WHAT THIS STUDY ADDSThe first population pharmacokinetic model has been developed for 6-MP active metabolites in paediatric patients with acute lymphoblastic leukaemia and the potential demographic and genetically controlled factors that could lead to interpatient pharmacokinetic variability among this population have been assessed.The model shows a large reduction in interindividual variability of pharmacokinetic parameters when body surface area and thiopurine methyltransferase polymorphism are incorporated into the model as covariates.The developed model offers a more rational dosing approach for 6-MP than the traditional empirical method (based on body surface area) through combining it with pharmacogenetically guided dosing based on thiopurine methyltransferase genotype. AIMS To investigate the population pharmacokinetics of 6-mercaptopurine (6-MP) active metabolites in paediatric patients with acute lymphoblastic leukaemia (ALL) and examine the effects of various genetic polymorphisms on the disposition of these metabolites. METHODS Data were collected prospectively from 19 paediatric patients with ALL (n = 75 samples, 150 concentrations) who received 6-MP maintenance chemotherapy (titrated to a target dose of 75 mg m−2 day−1). All patients were genotyped for polymorphisms in three enzymes involved in 6-MP metabolism. Population pharmacokinetic analysis was performed with the nonlinear mixed effects modelling program (nonmem) to determine the population mean parameter estimate of clearance for the active metabolites. RESULTS The developed

  13. [Gene Expression and Clinical Characteristics of Molecular Targeted Therapy 
in Non-small Cell Lung Cancer Patients in Shandong].

    PubMed

    Qiao, Xiuli; Ai, Dan; Liang, Honglu; Mu, Dianbin; Guo, Qisen

    2017-01-20

    Molecular targeted therapy has gradually become an important treatment for lung cancer, the aim of this research is to analyze the clinicopathologic features associated with the gene mutation status of epidermal growth factor receptor (EGFR), echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK), ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) and Kirsten rat sarcoma viral oncogene (KRAS) in non-small cell lung cancer (NSCLC) patients and determine the most likely populations to benefit from molecular target therapy treatment. The mutation status of EGFR, EML4-ALK fusion gene, ROS1 and KARS gene were determined by Real-time PCR, the relationship between clinical pathologic features and concomitant gene were analyzed with χ2 test by SPSS software 19.0. A total of 514 specimens from Shandong tumor hospital were collected from NSCLC patients between January 2014 and May 2016. The total mutation rate of EGFR gene was 36.70%, major occurred in exon 19 (36.61%) and exon 21 (51.36%), respectively, and EGFR mutations usually occurred in female, non-smoking and adenocarcinoma patients (P<0.05). The total rearrangements rate of EML4-ALK fusion gene was 9.37%, EML4-ALK fusion gene usually occurred in younger age (≤60 yr) and non-smoking patients (P<0.05). Mutations were not related to gender and pathological type (P>0.05). ROS1 fusion gene was detected in 136 cases, the positive rate was 3.67%, all patients were 60 years old, and the difference was statistically significant (P<0.05). Only 23 samples were tested KARS gene mutations, two of them were positive and the positive rate was 8.70%. They all occurred in non-smoker and adenocarcinoma patients. No mutation was detected to coexist in EGFR, EML4-ALK and KARS gene mutation. EGFR, EML4-ALK, ROS1 and KRAS defines different molecular subset of NSCLC with distinct characteristic, which provides a new option for the clinical treatment of patients with NSCLC.

  14. Using eHealth to improve health literacy among the patient population.

    PubMed

    Landry, Kathryn E

    2015-01-01

    There is no denying the global influence of eHealth, in its various forms, on the health care system in the 21st Century. Health care professionals are often familiar with technological tools used to enhance health outcomes by assisting clinicians in meeting the needs of the patient population. In an age of social media, web-based information, and material available literally in an instant, it is crucial for nurses to use and proactively share their knowledge regarding accessing and finding credible sources of online health information with the patient population. By improving health literacy among consumers, self-sufficiency and competence can be developed and promoted to improve health outcomes, placing the patient in a participatory starring role of managing and improving his or her overall well-being.

  15. Targeting Hispanic populations: future research and prevention strategies.

    PubMed Central

    Ramirez, A G; McAlister, A; Gallion, K J; Villarreal, R

    1995-01-01

    Minority populations face a wide variety of economic, institutional, and cultural barriers to health care. These barriers and low levels of education and income pose significant challenges for health professionals in developing cancer research and prevention-control strategies. It is suggested that specific segments of Hispanic populations fit the model of an underdeveloped country in the intermediate stage of epidemiological transition. Since noncommunicable diseases have not yet fully emerged in some of these Hispanic population segments, the opportunity exists to apply primordial prevention strategies. Such campaigns would focus on dissuading members of these populations from adopting negative health behaviors while promoting positive lifestyle choices. Optimal programs would increase cancer screening participation and discourage risk behaviors through community-oriented, population-based interventions. Future directions in prevention and control efforts for minority populations should include expanded health insurance coverage, improved access to health care, greater emphasis on minority recruitment in health care fields, focused epidemiologic and clinical research, and identification and replication of effective components within existing prevention-control programs. PMID:8741800

  16. The Case for Diabetes Population Health Improvement: Evidence-Based Programming for Population Outcomes in Diabetes.

    PubMed

    Golden, Sherita Hill; Maruthur, Nisa; Mathioudakis, Nestoras; Spanakis, Elias; Rubin, Daniel; Zilbermint, Mihail; Hill-Briggs, Felicia

    2017-07-01

    The goal of this review is to describe diabetes within a population health improvement framework and to review the evidence for a diabetes population health continuum of intervention approaches, including diabetes prevention and chronic and acute diabetes management, to improve clinical and economic outcomes. Recent studies have shown that compared to usual care, lifestyle interventions in prediabetes lower diabetes risk at the population-level and that group-based programs have low incremental medial cost effectiveness ratio for health systems. Effective outpatient interventions that improve diabetes control and process outcomes are multi-level, targeting the patient, provider, and healthcare system simultaneously and integrate community health workers as a liaison between the patient and community-based healthcare resources. A multi-faceted approach to diabetes management is also effective in the inpatient setting. Interventions shown to promote safe and effective glycemic control and use of evidence-based glucose management practices include provider reminder and clinical decision support systems, automated computer order entry, provider education, and organizational change. Future studies should examine the cost-effectiveness of multi-faceted outpatient and inpatient diabetes management programs to determine the best financial models for incorporating them into diabetes population health strategies.

  17. Bacterial meningitis in patients with HIV: A population-based prospective study.

    PubMed

    van Veen, Kiril E B; Brouwer, Matthijs C; van der Ende, Arie; van de Beek, Diederik

    2016-03-01

    We studied occurrence, disease course, and prognosis of community-acquired bacterial meningitis in HIV-infected adults in the Netherlands. We performed a nationwide, prospective cohort study. Patients over 16 years old with bacterial meningitis were included. Data on patient history, symptoms and signs on admission, laboratory findings, radiologic examination, treatment, and outcome were collected prospectively. For HIV-positive patients additional information was collected retrospectively. From March 2006 to December 2013, 1354 episodes of community-acquired meningitis were included in the cohort. Thirteen patients were HIV-infected (1.0%). The annual incidence of bacterial meningitis was 8.3-fold higher (95%CI 4.6-15.1, P < 0.001) among HIV-infected patients as compared to the general population (10.79 [95%CI 5.97-19.48] vs 1.29 [95%CI 1.22-1.37] per 100.000 patients per year). Predisposing factors (other than HIV), clinical symptoms and signs, ancillary investigations, causative organisms and outcome were comparable between HIV-infected and patients without HIV infection. HIV-infected patients in the Netherlands have a 8.3-fold higher risk for bacterial meningitis as compared to the general population despite cART therapy. Clinical presentation and outcome of patients with acute bacterial meningitis with and without HIV are similar. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  18. Do selective immunisation against tuberculosis and hepatitis B reach the targeted populations? A nationwide register-based study evaluating the recommendations in the Norwegian Childhood Immunisation Programme.

    PubMed

    Feiring, Berit; Laake, Ida; Molden, Tor; Håberg, Siri E; Nøkleby, Hanne; Seterelv, Siri Schøyen; Magnus, Per; Trogstad, Lill

    2016-04-12

    Selective immunisation is an alternative to universal vaccination if children at increased risk of disease can be identified. Within the Norwegian Childhood Immunisation Programme, BCG vaccine against tuberculosis and vaccine against hepatitis B virus (HBV) are offered only to children with parents from countries with high burden of the respective disease. We wanted to study whether this selective immunisation policy reaches the targeted groups. The study population was identified through the Norwegian Central Population Registry and consisted of all children born in Norway 2007-2010 and residing in Norway until their second birthday, in total 240,484 children. Information on vaccinations from the Norwegian Immunisation Registry, and on parental country of birth from Statistics Norway, was linked to the population registry by personal identifiers. The coverage of BCG and HBV vaccine was compared with the coverage of vaccines in the universal programme. Among the study population, 16.1% and 15.9% belonged to the target groups for BCG and HBV vaccine, respectively. Among children in the BCG target group the BCG vaccine coverage was lower than the coverage of pertussis and measles vaccine (83.6% vs. 98.6% and 92.3%, respectively). Likewise, the HBV vaccine coverage was lower than the coverage of pertussis and measles vaccine in the HBV target group (90.0% vs. 98.6% and 92.3%, respectively). The coverage of the targeted vaccines was highest among children with parents from South Asia and Sub-Saharan Africa. The coverage of vaccines in the universal programme was similar in targeted and non-targeted groups. Children targeted by selective vaccination had lower coverage of the target vaccines than of vaccines in the universal programme, indicating that selective vaccination is challenging. Improved routines for identifying eligible children and delivering the target vaccines are needed. Universal vaccination of all children with these vaccines could be considered

  19. Evaluation of a 12-week targeted vitamin D supplementation regimen in patients with active inflammatory bowel disease.

    PubMed

    Garg, Mayur; Rosella, Ourania; Rosella, Gennaro; Wu, Yunqiu; Lubel, John S; Gibson, Peter R

    2017-06-15

    Vitamin D at serum 25(OH)D concentrations above 100 nmol/L is associated with disease remission in patients with IBD, suggesting targeted dosing might be anti-inflammatory. This study aimed to assess the effectiveness, safety and predictors of a 12-week regimen of vitamin D supplementation to achieve such a target in patients with active disease. In a pilot study, patients with active colitis and a serum 25(OH)D concentration <75 nmol/L were prescribed oral liquid vitamin D supplementation over 12 weeks using a specific protocol with dose adjusted 4-weekly to aim for a target level of 100-125 nmol/L. Five patients each with Crohn's colitis or ulcerative colitis (UC) had mean 25(OH)D concentration 52 (range 27-73 nmol/L). Five reached the targeted level and four 89-95 nmol/L. One withdrew after 4 weeks (88 nmol/L). Target dose was met only in those with BMI <30 kg/m 2 and total dose inversely correlated with initial serum 25(OH)D. One patient had developed a high level at 8 weeks (146 nmol/L) and another new hypercalciuria. There were no serious adverse events attributable to the therapy. Clinical disease activity consistently declined, but faecal calprotectin and circulating markers of inflammation did not. A specified oral vitamin D regimen successfully and safely achieved target or near-target levels, improved symptom-based activity scores, but did not alter objective measures of intestinal or systemic inflammation. A modified version of this dose-escalating regimen would be suitable for a randomised placebo-controlled trial, but does require regular safety monitoring. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  20. Survival-related Selection Bias in Studies of Racial Health Disparities: The Importance of the Target Population and Study Design.

    PubMed

    Howe, Chanelle J; Robinson, Whitney R

    2018-07-01

    The impact of survival-related selection bias has not always been discussed in relevant studies of racial health disparities. Moreover, the analytic approaches most frequently employed in the epidemiologic literature to minimize selection bias are difficult to implement appropriately in racial disparities research. This difficulty stems from the fact that frequently employed analytic techniques require that common causes of survival and the outcome are accurately measured. Unfortunately, such common causes are often unmeasured or poorly measured in racial health disparities studies. In the absence of accurate measures of the aforementioned common causes, redefining the target population or changing the study design represents a useful approach for reducing the extent of survival-related selection bias. To help researchers recognize and minimize survival-related selection bias in racial health disparities studies, we illustrate the aforementioned selection bias and how redefining the target population or changing the study design can be useful.

  1. Diabetes management in an Australian primary care population.

    PubMed

    Krass, I; Hebing, R; Mitchell, B; Hughes, J; Peterson, G; Song, Y J C; Stewart, K; Armour, C L

    2011-12-01

    Worldwide studies have shown that significant proportions of patients with type 2 diabetes (T2DM) do not meet targets for glycaemic control, blood pressure (BP) and lipids, putting them at higher risk of developing complications. However, little is known about medicines management in Australian primary care populations with T2DM. The aim of this study was to (i) describe the management of a large group of patients in primary care, (ii) identify areas for improvement in management and (iii) determine any relationship between adherence and glycaemic, BP and lipid control. This was a retrospective, epidemiological study of primary care patients with T2DM diabetes, with HbA(1c) of >7%, recruited in 90 Australian community pharmacies. Data collected included demographic details, diabetes history, current medication regimen, height, weight, BP, physical activity and smoking status. Of the 430 patients, 98% used antidiabetics, 80% antihypertensives, 73% lipid lowering drugs and 38% aspirin. BP and all lipid targets were met by only 21% and 14% of the treated patients and 21% and 12% of the untreated patients respectively. Medication adherence was related to better glycaemic control (P = 0.04). An evidence-base prescribing practice gap was seen in this Australian primary care population of T2DM patients. Patients were undertreated with antihypertensive and lipid lowering medication, and several subgroups with co-morbidities were not receiving the recommended pharmacotherapy. Interventions are required to redress the current evidence-base prescribing practice gap in disease management in primary care. © 2011 Blackwell Publishing Ltd.

  2. A novel method of estimating cost of therapy by using patient population characteristics: analysis of fluoroquinolones in various populations with different distributions of renal function.

    PubMed

    Enzweiler, Kevin A; Bosso, John A; White, Roger L

    2003-07-01

    Formulary decisions regarding a given drug class are often made in the absence of patient outcome and/or sophisticated pharmacoeconomic data. Analyses that consider factors beyond simple acquisition costs may be useful in such situations. For example, the cost implications of using manufacturers' recommendations for dosing in patients with renal dysfunction may be important, depending on the distribution of various levels of renal function within a patient population. Using four 1000-patient populations representing different renal function distributions and a fifth population of our medical center's distribution, we determined the costs of therapy for intravenous and oral levofloxacin, gatifloxacin, and moxifloxacin for a 10-day course of therapy for community-acquired pneumonia. Costs considered were average wholesale prices (AWPs), 50% of AWP, or same daily price, plus intravenous dose preparation and administration costs when applicable. Costs for each renal function distribution were examined for significant differences with an analysis-of-variance test. Also, costs of failing to adjust dosing regimens for decreased renal function were determined. Differences in fluoroquinolone costs (AWP, 50% AWP, or when matched as the same daily price) among the populations were found. When considering same daily prices, differences among populations ranged from about 35,000 dollars with intravenous gatifloxacin to more than 51,000 dollars for intravenous levofloxacin (all fluoroquinolones, p>0.05). Within a population, differences in costs among the intravenous fluoroquinolones ranged from 47,000-99,000 dollars. Rank orders of the drugs and population costs of therapy were affected by the pricing structure used and varied by the specific population and drug. Differences among the fluoroquinolones or populations were much smaller (<2100 dollars) when considering oral regimens. Costs potentially incurred by failing to adjust dosing for renal function were substantial

  3. Erectile Dysfunction in Patients with Sleep Apnea--A Nationwide Population-Based Study.

    PubMed

    Chen, Chia-Min; Tsai, Ming-Ju; Wei, Po-Ju; Su, Yu-Chung; Yang, Chih-Jen; Wu, Meng-Ni; Hsu, Chung-Yao; Hwang, Shang-Jyh; Chong, Inn-Wen; Huang, Ming-Shyan

    2015-01-01

    Increased incidence of erectile dysfunction (ED) has been reported among patients with sleep apnea (SA). However, this association has not been confirmed in a large-scale study. We therefore performed a population-based cohort study using Taiwan National Health Insurance (NHI) database to investigate the association of SA and ED. From the database of one million representative subjects randomly sampled from individuals enrolled in the NHI system in 2010, we identified adult patients having SA and excluded those having a diagnosis of ED prior to SA. From these suspected SA patients, those having SA diagnosis after polysomnography were defined as probable SA patients. The dates of their first SA diagnosis were defined as their index dates. Each SA patient was matched to 30 randomly-selected, age-matched control subjects without any SA diagnosis. The control subjects were assigned index dates as their corresponding SA patients, and were ensured having no ED diagnosis prior to their index dates. Totally, 4,835 male patients with suspected SA (including 1,946 probable SA patients) were matched to 145,050 control subjects (including 58,380 subjects matched to probable SA patients). The incidence rate of ED was significantly higher in probable SA patients as compared with the corresponding control subjects (5.7 vs. 2.3 per 1000 patient-year; adjusted incidence rate ratio = 2.0 [95% CI: 1.8-2.2], p<0.0001). The cumulative incidence was also significantly higher in the probable SA patients (p<0.0001). In multivariable Cox regression analysis, probable SA remained a significant risk factor for the development of ED after adjusting for age, residency, income level and comorbidities (hazard ratio = 2.0 [95%CI: 1.5-2.7], p<0.0001). In line with previous studies, this population-based large-scale study confirmed an increased ED incidence in SA patients in Chinese population. Physicians need to pay attention to the possible underlying SA while treating ED patients.

  4. EGFR Targeted Therapies and Radiation: Optimizing Efficacy by Appropriate Drug Scheduling and Patient Selection

    PubMed Central

    Cuneo, Kyle C.; Nyati, Mukesh K.; Ray, Dipankar; Lawrence, Theodore S.

    2015-01-01

    The epidermal growth factor receptor (EGFR) plays an important role in tumor progression and treatment resistance for many types of malignancies including head and neck, colorectal, and nonsmall cell lung cancer. Several EGFR targeted therapies are efficacious as single agents or in combination with chemotherapy. Given the toxicity associated with chemoradiation and poor outcomes seen in several types of cancers, combinations of EGFR targeted agents with or without chemotherapy have been tested in patients receiving radiation. To date, the only FDA approved use of an anti-EGFR therapy in combination with radiation therapy is for locally advanced head and neck cancer. Given the important role EGFR plays in lung and colorectal cancer and the benefit of EGFR inhibition combined with chemotherapy in these disease sites, it is perplexing why EGFR targeted therapies in combination with radiation or chemoradiation have not been more successful. In this review we summarize the clinical findings of EGFR targeted therapies combined with radiation and chemoradiation regimens. We then discuss the interaction between EGFR and radiation including radiation induced EGFR signaling, the effect of EGFR on DNA damage repair, and potential mechanisms of radiosensitization. Finally, we examine the potential pitfalls with scheduling EGFR targeted therapies with chemoradiation and the use of predictive biomarkers to improve patient selection. PMID:26205191

  5. Lower Glucose Target is Associated with Improved 30-Day Mortality in Cardiac and Cardiothoracic Patients.

    PubMed

    Hersh, Andrew M; Hirshberg, Eliotte L; Wilson, Emily L; Orme, James F; Morris, Alan H; Lanspa, Michael J

    2018-04-26

    Practice guidelines recommend against Intensive Insulin Therapy (IIT) in critically ill patients based on trials that had high rates of severe hypoglycemia. Intermountain Healthcare uses a computerized intravenous insulin protocol (eProtocol-insulin) that allows choice of blood glucose (BG) targets (80-110 mg/dl versus 90-140 mg/dl), and has low rates of severe hypoglycemia. We sought to study the effects of BG target on mortality in adult patients in cardiac intensive care units (ICUs) that have very low rates of severe hypoglycemia. Critically ill patients receiving intravenous insulin were treated with either of two BG targets (80-110 mg/dl versus 90-140 mg/dl). We created a propensity score for BG target using factors believed to have influenced clinicians' choice, and then performed a propensity-score-adjusted regression analysis for 30-day mortality. 1809 patients met inclusion criteria. Baseline patient characteristics were similar. Median glucose was lower in the 80-110 mg/dl group (104 mg/dl vs. 122 mg/dl, p<0.001). Severe hypoglycemia occurred at very low rates in both groups (1.16% vs. 0.35%, p=0.051). Unadjusted 30-day mortality was lower in the 80-110 mg/dl group (4.3% vs 9.2%, p<0.001). This remained after propensity-score-adjusted regression (OR 0.65; 95% CI, 0.43-0.98; p=0.04). Tight glucose control can be achieved with low rates of severe hypoglycemia, and is associated with decreased 30-day mortality in a cohort of largely cardiac patients. While such findings should not be used to guide clinical practice at present, the use of tight glucose control should be re-examined using a protocol that has low rates of severe hypoglycemia. Copyright © 2018. Published by Elsevier Inc.

  6. Impacts of transgenic poplar-cotton agro-ecosystems upon target pests and non-target insects under field conditions.

    PubMed

    Zhang, D J; Liu, J X; Lu, Z Y; Li, C L; Comada, E; Yang, M S

    2015-07-27

    Poplar-cotton agro-ecosystems are the main agricultural planting modes of cotton fields in China. With increasing acres devoted to transgenic insect-resistant poplar and transgenic insect-resistant cotton, studies examining the effects of transgenic plants on target and non-target insects become increasingly important. We systematically surveyed populations of both target pests and non-target insects for 4 different combinations of poplar-cotton eco-systems over 3 years. Transgenic Bt cotton strongly resisted the target insects Fall webworm moth [Hyphantria cunea (Drury)], Sylepta derogata Fabrieius, and American bollworm (Heliothis armigera), but no clear impact on non-target insect cotton aphids (Aphis gossypii). Importantly, intercrops containing transgenic Pb29 poplar significantly increased the inhibitory effects of Bt cotton on Fall webworm moth in ecosystem IV. Highly resistant Pb29 poplar reduced populations of the target pests Grnsonoma minutara Hubner and non-target insect poplar leaf aphid (Chaitophorus po-pulialbae), while Fall webworm moth populations were unaffected. We determined the effects of Bt toxin from transgenic poplar and cotton on target and non-target pests in different ecosystems of cotton-poplar intercrops and identified the synergistic effects of such combinations toward both target and non-target insects.

  7. [Prevalence of target organ damage in patients treated for primary arterial hypertension: Comparison between men and women. ESSENTIELLE study].

    PubMed

    Boivin, J-M; Koch, C; Vigié, L; Meppiel, L

    2015-06-01

    To compare the percentages of men and women treated for primary arterial hypertension presenting with at least one target organ damage; to identify factors associated with target organ damage and/or blood pressure control. Observational, transverse study carried out between March 2012 and July 2013 on a representative sample of 2666 outpatients (including 1343 men) consulting general practitioners (n=469) or cardiologists (n=250) in routine follow-up. Characteristics "men vs. women" were: mean age (62.6 ± 11.6 vs. 57.4 ± 14.7 years; P<0.0001); ≥ 60 years (61.1% vs. 43.9%; P<0.0001); waist circumference (98.9 ± 12.2 vs. 89.4 ± 14.3 cm; P<0.0001); SBP (146.5 ± 16.1 vs. 145.8 ± 17.0 mmHg; NS); DBP (85.1 ± 10.3 vs. 84.2 ± 10.4; P=0,03). Target organ damage was more frequent in men (37.6% vs. 22.9%; P<0.0001), whether it was subclinical (20.4% vs. 13.6%; P<0.0001) or documented (26.3% vs. 13.5%; P<0.0001); some patients presented with both types of damages. Men developed more often microalbuminuria (6.5% vs. 4.3%; P=0.01) and LVH (16.3% vs. 10.5%; P<0.0001); some patients presented with both types of subclinical injuries. Target organ damage was more common in men without regular physical activity than in those exercising regularly (42.1% vs. 32.5%; P=0.0004). Regular exercises had no effect in women (24.1% vs. 21.3%). For both sexes, other factors associated with target organ damage were: age ≥ 60 years, myocardial infarction/sudden death in family history, LDL-cholesterol ≥ 1.60 g/L, HDL-cholesterol ≤ 0.40 g/L. Stroke before 45 years in family history was a predictive factor in women. Hypertension was controlled in one third of patients without difference between sexes. In women, hypertension was less often controlled in case of excessive alcohol consumption compared to normal alcohol intake (17.9% vs. 36.1%; P=0.0007); this factor had no effect in men (28.1% vs. 32.6%). Other factors associated with poor blood pressure control were: BMI (P=0.002), LDL

  8. Contrast-Enhanced Computed Tomography Evaluation of Hepatic Metastases in Breast Cancer Patients Before and After Cytotoxic Chemotherapy or Targeted Therapy.

    PubMed

    He, Hongying; Cai, Chunyan; Charnsangavej, Chusilp; Theriault, Richard L; Green, Marjorie; Quraishi, Mohammad A; Yang, Wei T

    2015-11-01

    To evaluate change in size vs computed tomography (CT) density of hepatic metastases in breast cancer patients before and after cytotoxic chemotherapy or targeted therapy. A database search in a single institution identified 48 breast cancer patients who had hepatic metastases treated with either cytotoxic chemotherapy alone or targeted therapy alone, and who had contrast-enhanced CT (CECT) scans of the abdomen at baseline and within 4 months of initiation of therapy in the past 10 years. Two radiologists retrospectively evaluated CT scans and identified up to 2 index lesions in each patient. The size (centimeters) of each lesion was measured according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and CT density (Hounsfield units) was measured by drawing a region of interest around the margin of the entire lesion. The percent change in sum of lesion size and mean CT density on pre- and post-treatment scans was computed for each patient; results were compared within each treatment group. Thirty-nine patients with 68 lesions received cytotoxic chemotherapy only; 9 patients with 15 lesions received targeted therapy only. The mean percent changes in sum of lesion size and mean CT density were statistically significant within the cytotoxic chemotherapy group before and after treatment, but not significant in the targeted therapy group. The patients in the targeted therapy group tend to have better 2-year survival. The patients who survived at 2 years tend to have more decrease in tumour size in the cytotoxic chemotherapy group. Cytotoxic chemotherapy produced significant mean percent decrease in tumour size and mean CT density of hepatic metastases from breast cancer before and after treatment, whereas targeted therapy did not. Nonetheless, there is a trend that the patients in the targeted therapy group had better 2-year survival rate. This suggests that RECIST is potentially inadequate in evaluating tumour response in breast cancer liver

  9. Mortality in HIV-hepatitis C co-infected patients in Canada compared to the general Canadian population (2003-2013).

    PubMed

    Klein, Marina B; Rollet-Kurhajec, Kathleen C; Moodie, Erica E M; Yaphe, Sean; Tyndall, Mark; Walmsley, Sharon; Gill, John; Martel-Laferriere, Valerie; Cooper, Curtis

    2014-08-24

    Recent studies suggest all-cause mortality in HIV mono-infected patients approaches that of the general population. We aimed to compare participants in the Canadian Co-infection Cohort to the general population to determine if co-infected patients have had similar improvements in mortality. Prospective multicentre cohort study. Between 2003 and 2013, deaths were captured using specific case reports and through linkage to provincial vital statistics for participants lost to follow-up. Standardized mortality ratios (SMRs) were calculated using age, sex and province-specific mortality rates from the Canadian Human Mortality Database, 2009, and compared across behavioural and clinical characteristics of participants at their most recent visit. Among the 1150 patients, we observed 133 deaths over 3351 person-years (4.0 per 100 person-years, 95% confidence interval 3.3, 4.6). SMRs (95% confidence interval) were: 12.1(10.1, 14.2) overall; 9.3 (7.5, 11.1) for men and 19.4 (12.7, 26.2) for women. CD4 cell counts below 200 cells/μl [25.5 (17.7, 33.3)], active injection drug use [19.9 (13.9, 25.9)] and smoking [14.9 (12.1, 17.7)] were strongly associated with excess mortality. Lowest SMRs were seen for those who had spontaneous [4.5 (-0.6, 9.5)] or treatment-induced clearance of hepatitis C virus (HCV) infection [5.1 (1.3, 8.8)]. Conversely, high SMRs were seen with advanced liver disease [17.0 (11.7, 22.3)]. In no category did SMRs approach mortality seen in the general Canadian population. HIV-HCV co-infected persons remain at markedly increased risk for death despite antiretroviral therapy. Interventions targeting modifiable risk factors such as substance use, smoking, adherence to antiretrovirals and timely provision of HCV therapy could substantially reduce death rates.

  10. Atypical case of Wolfram syndrome revealed through targeted exome sequencing in a patient with suspected mitochondrial disease

    PubMed Central

    2012-01-01

    Background Mitochondrial diseases comprise a diverse set of clinical disorders that affect multiple organ systems with varying severity and age of onset. Due to their clinical and genetic heterogeneity, these diseases are difficult to diagnose. We have developed a targeted exome sequencing approach to improve our ability to properly diagnose mitochondrial diseases and apply it here to an individual patient. Our method targets mitochondrial DNA (mtDNA) and the exons of 1,600 nuclear genes involved in mitochondrial biology or Mendelian disorders with multi-system phenotypes, thereby allowing for simultaneous evaluation of multiple disease loci. Case Presentation Targeted exome sequencing was performed on a patient initially suspected to have a mitochondrial disorder. The patient presented with diabetes mellitus, diffuse brain atrophy, autonomic neuropathy, optic nerve atrophy, and a severe amnestic syndrome. Further work-up revealed multiple heteroplasmic mtDNA deletions as well as profound thiamine deficiency without a clear nutritional cause. Targeted exome sequencing revealed a homozygous c.1672C > T (p.R558C) missense mutation in exon 8 of WFS1 that has previously been reported in a patient with Wolfram syndrome. Conclusion This case demonstrates how clinical application of next-generation sequencing technology can enhance the diagnosis of patients suspected to have rare genetic disorders. Furthermore, the finding of unexplained thiamine deficiency in a patient with Wolfram syndrome suggests a potential link between WFS1 biology and thiamine metabolism that has implications for the clinical management of Wolfram syndrome patients. PMID:22226368

  11. Targeted Adherence Intervention to Reach Glycemic Control with Insulin Therapy for patients with Diabetes (TARGIT-Diabetes): rationale and design of a pragmatic randomised clinical trial

    PubMed Central

    Lewey, Jennifer; Wei, Wenhui; Makanji, Sagar; Chant, Alan; DiGeronimo, Jeff; Nanchanatt, Gina; Jan, Saira; Choudhry, Niteesh K

    2017-01-01

    Introduction Adherence to and persistence of medications for chronic diseases remains poor and many interventions to improve medication use have only been modestly effective. Targeting interventions to patients who are most likely to benefit should improve their efficiency and clinical impact. This study aims to test the impact of three cost-equivalent pharmacist-led interventions on insulin persistence and glycaemic control among patients with diabetes. Methods and analysis TARGIT-Diabetes (Targeted Adherence Intervention to Reach Glycemic Control with Insulin Therapy for patients with Diabetes) is a randomised controlled trial that will evaluate three different multifaceted pharmacist-outreach strategies for improving long-term insulin use among individuals with diabetes. We will randomise 6000 patients in a large insurer to one of three arms. The arms are designed to deliver an increasingly intensive intervention to a progressively targeted population, identified using predictive analytics. The central component of the intervention in all arms is a tailored telephone consultation with a pharmacist which varies across arms based on the: (A) proportion of patients offered the intervention and (B) intervention intensity, including follow-up frequency and cointerventions such as text reminders and interactions with patients’ providers. The primary outcome is insulin persistence, assessed using pharmacy claims data, and the secondary outcomes are glycaemic control as measured by glycosylated haemoglobin values, healthcare utilisation and healthcare spending. Ethics and dissemination This protocol has been approved by the Institutional Review Board of Brigham and Women’s Hospital and the Privacy Board of Horizon Blue Cross Blue Shield of New Jersey. We plan to present the results of this trial at national meetings and in manuscripts submitted to peer-reviewed journals. Trial registration number NCT 02846779. PMID:29084790

  12. Vancomycin Dosing in Obese Patients: Special Considerations and Novel Dosing Strategies.

    PubMed

    Durand, Cheryl; Bylo, Mary; Howard, Brian; Belliveau, Paul

    2018-06-01

    To review the literature regarding vancomycin pharmacokinetics in obese patients and strategies used to improve dosing in this population. PubMed, EMBASE (1974 to November 2017), and Google Scholar searches were conducted using the search terms vancomycin, obese, obesity, pharmacokinetics, strategy, and dosing. Additional articles were selected from reference lists of selected studies. Included articles were those published in English with a primary focus on vancomycin pharmacokinetic parameters in obese patients and practical vancomycin dosing strategies, clinical experiences, or challenges of dosing vancomycin in this population. Volume of distribution and clearance are the pharmacokinetic parameters that most often affect vancomycin dosing in obese patients; both are increased in this population. Challenges with dosing in obese patients include inconsistent and inadequate dosing, observations that the obese population may not be homogeneous, and reports of an increased likelihood of supratherapeutic trough concentrations. Investigators have revised and developed dosing and monitoring protocols to address these challenges. These approaches improved target trough attainment to varying degrees. Some of the vancomycin dosing approaches provided promising results in obese patients, but there were notable differences in methods used to develop these approaches, and sample sizes were small. Although some approaches can be considered for validation in individual institutions, further research is warranted. This may include validating approaches in larger populations with narrower obesity severity ranges, investigating target attainment in indication-specific target ranges, and evaluating the impact of different dosing weights and methods of creatinine clearance calculation.

  13. Light localization with low-contrast targets in a patient implanted with a suprachoroidal-transretinal stimulation retinal prosthesis.

    PubMed

    Endo, Takao; Fujikado, Takashi; Hirota, Masakazu; Kanda, Hiroyuki; Morimoto, Takeshi; Nishida, Kohji

    2018-04-20

    To evaluate the improvement in targeted reaching movements toward targets of various contrasts in a patient implanted with a suprachoroidal-transretinal stimulation (STS) retinal prosthesis. An STS retinal prosthesis was implanted in the right eye of a 42-year-old man with advanced Stargardt disease (visual acuity: right eye, light perception; left eye, hand motion). In localization tests during the 1-year follow-up period, the patient attempted to touch the center of a white square target (visual angle, 10°; contrast, 96, 85, or 74%) displayed at a random position on a monitor. The distance between the touched point and the center of the target (the absolute deviation) was averaged over 20 trials with the STS system on or off. With the left eye occluded, the absolute deviation was not consistently lower with the system on than off for high-contrast (96%) targets, but was consistently lower with the system on for low-contrast (74%) targets. With both eyes open, the absolute deviation was consistently lower with the system on than off for 85%-contrast targets. With the system on and 96%-contrast targets, we detected a shorter response time while covering the right eye, which was being implanted with the STS, compared to covering the left eye (2.41 ± 2.52 vs 8.45 ± 3.78 s, p < 0.01). Performance of a reaching movement improved in a patient with an STS retinal prosthesis implanted in an eye with residual natural vision. Patients with a retinal prosthesis may be able to improve their visual performance by using both artificial vision and their residual natural vision. Beginning date of the trial: Feb. 20, 2014 Date of registration: Jan. 4, 2014 Trial registration number: UMIN000012754 Registration site: UMIN Clinical Trials Registry (UMIN-CTR) http://www.umin.ac.jp/ctr/index.htm.

  14. Analyzing the most frequent disease loci in targeted patient categories optimizes disease gene identification and test accuracy worldwide.

    PubMed

    Lebo, Roger V; Tonk, Vijay S

    2015-01-21

    Our genomewide studies support targeted testing the most frequent genetic diseases by patient category: (1) pregnant patients, (2) at-risk conceptuses, (3) affected children, and (4) abnormal adults. This approach not only identifies most reported disease causing sequences accurately, but also minimizes incorrectly identified additional disease causing loci. Diseases were grouped in descending order of occurrence from four data sets: (1) GeneTests 534 listed population prevalences, (2) 4129 high risk prenatal karyotypes, (3) 1265 affected patient microarrays, and (4) reanalysis of 25,452 asymptomatic patient results screened prenatally for 108 genetic diseases. These most frequent diseases are categorized by transmission: (A) autosomal recessive, (B) X-linked, (C) autosomal dominant, (D) microscopic chromosome rearrangements, (E) submicroscopic copy number changes, and (F) frequent ethnic diseases. Among affected and carrier patients worldwide, most reported mutant genes would be identified correctly according to one of four patient categories from at-risk couples with <64 tested genes to affected adults with 314 tested loci. Three clinically reported patient series confirmed this approach. First, only 54 targeted chromosomal sites would have detected all 938 microscopically visible unbalanced karyotypes among 4129 karyotyped POC, CVS, and amniocentesis samples. Second, 37 of 48 reported aneuploid regions were found among our 1265 clinical microarrays confirming the locations of 8 schizophrenia loci and 20 aneuploidies altering intellectual ability, while also identifying 9 of the most frequent deletion syndromes. Third, testing 15 frequent genes would have identified 124 couples with a 1 in 4 risk of a fetus with a recessive disease compared to the 127 couples identified by testing all 108 genes, while testing all mutations in 15 genes could have identified more couples. Testing the most frequent disease causing abnormalities in 1 of 8 reported disease loci [~1 of

  15. Linked Patient-Reported Outcomes Data From Patients With Multiple Sclerosis Recruited on an Open Internet Platform to Health Care Claims Databases Identifies a Representative Population for Real-Life Data Analysis in Multiple Sclerosis.

    PubMed

    Risson, Valery; Ghodge, Bhaskar; Bonzani, Ian C; Korn, Jonathan R; Medin, Jennie; Saraykar, Tanmay; Sengupta, Souvik; Saini, Deepanshu; Olson, Melvin

    2016-09-22

    An enormous amount of information relevant to public health is being generated directly by online communities. To explore the feasibility of creating a dataset that links patient-reported outcomes data, from a Web-based survey of US patients with multiple sclerosis (MS) recruited on open Internet platforms, to health care utilization information from health care claims databases. The dataset was generated by linkage analysis to a broader MS population in the United States using both pharmacy and medical claims data sources. US Facebook users with an interest in MS were alerted to a patient-reported survey by targeted advertisements. Eligibility criteria were diagnosis of MS by a specialist (primary progressive, relapsing-remitting, or secondary progressive), ≥12-month history of disease, age 18-65 years, and commercial health insurance. Participants completed a questionnaire including data on demographic and disease characteristics, current and earlier therapies, relapses, disability, health-related quality of life, and employment status and productivity. A unique anonymous profile was generated for each survey respondent. Each anonymous profile was linked to a number of medical and pharmacy claims datasets in the United States. Linkage rates were assessed and survey respondents' representativeness was evaluated based on differences in the distribution of characteristics between the linked survey population and the general MS population in the claims databases. The advertisement was placed on 1,063,973 Facebook users' pages generating 68,674 clicks, 3719 survey attempts, and 651 successfully completed surveys, of which 440 could be linked to any of the claims databases for 2014 or 2015 (67.6% linkage rate). Overall, no significant differences were found between patients who were linked and not linked for educational status, ethnicity, current or prior disease-modifying therapy (DMT) treatment, or presence of a relapse in the last 12 months. The frequencies of the

  16. Risk and Prognosis of Bacteremia and Fungemia Among Peritoneal Dialysis Patients: A Population-Based Cohort Study.

    PubMed

    Dalgaard, Lars Skov; Nørgaard, Mette; Povlsen, Johan Vestergaard; Jespersen, Bente; Jensen-Fangel, Søren; Ellermann-Eriksen, Svend; Østergaard, Lars; Schønheyder, Henrik Carl; Søgaard, Ole Schmeltz

    ♦ BACKGROUND: The incidence of bacteremia and fungemia (BAF) is largely unknown in end-stage renal disease (ESRD) patients initiating peritoneal dialysis (PD). ♦ OBJECTIVE: The main objective was to estimate and compare incidence rates of first episodes of BAF in incident PD patients and a comparison cohort. A secondary objective was to compare causative agents and 30-day post-BAF mortality between PD patients and the comparison cohort. ♦ METHODS: Design: Observational cohort study. Central and North Denmark regions. patients who initiated PD during 1995 - 2010. For each patient we sampled up to 10 controls from the general population matched on age, sex, and municipality. ♦ MAIN OUTCOME: Data on positive blood cultures were retrieved from electronic microbiology databases covering the 2 regions. We calculated incidence rates (IRs) of first-time BAF for PD patients and population controls. Incidence-rate ratios (IRRs) were calculated to compare these rates. Thirty-day mortality was estimated by Kaplan-Meier analysis. ♦ RESULTS: Among 1,024 PD patients and 10,215 population controls, we identified 75 and 282 episodes of BAF, respectively. Incidence rates of BAF were 4.7 (95% confidence interval [CI], 3.8 - 5.9) per 100 person-years of follow-up (PYFU) in PD patients and 0.5 (95% CI, 0.4 - 0.5) per 100 PYFU in population controls (IRR = 10.4; 95% CI, 8.1 - 13.5). In PD patients, the most frequent microorganisms were Escherichia coli (18.7%) and Staphylococcus aureus (13.3%). Escherichia coli (27.3%) also ranked first among population controls. Thirty-day mortality following BAF was 20.8% (95% CI, 12.6 - 31.0) and 20.7% (95% CI, 16.3 - 25.9) among PD patients and population controls, respectively. ♦ CONCLUSIONS: Peritoneal dialysis patients are at markedly higher risk of BAF than population controls. Causative agents and the 30-day post-BAF mortality were similar in the 2 cohorts. Copyright © 2016 International Society for Peritoneal Dialysis.

  17. Who are medical marijuana patients? Population characteristics from nine California assessment clinics.

    PubMed

    Reinarman, Craig; Nunberg, Helen; Lanthier, Fran; Heddleston, Tom

    2011-01-01

    Marijuana is a currently illegal psychoactive drug that many physicians believe has substantial therapeutic uses. The medical literature contains a growing number of studies on cannabinoids as well as case studies and anecdotal reports suggesting therapeutic potential. Fifteen states have passed medical marijuana laws, but little is known about the growing population of patients who use marijuana medicinally. This article reports on a sample of 1,746 patients from a network of nine medical marijuana evaluation clinics in California. Patients completed a standardized medical history form; evaluating physicians completed standardized evaluation forms. From this data we describe patient characteristics, self-reported presenting symptoms, physician evaluations, other treatments tried, other drug use, and medical marijuana use practices. Pain, insomnia, and anxiety were the most common conditions for which evaluating physicians recommended medical marijuana. Shifts in the medical marijuana patient population over time, the need for further research, and the issue of diversion are discussed.

  18. A study of therapy targeted EGFR/ALK mutations in Indian patients with lung adenocarcinoma: A clinical and epidemiological study.

    PubMed

    Rana, Vandana; Ranjan, Praveer; Jagani, Rajat; Rathi, K R; Kumar, Dharmesh; Khera, Anurag

    2018-04-01

    Established predictive biomarkers for Non-Small Cell Lung Carcinoma (NSCLC) include sensitizing Epidermal Growth Factor Receptor (EGFR) mutations and Anaplastic Lymphoma Kinase (ALK) fusion oncogene. The primary aim of the study is to ascertain the prevalence of EGFR mutation and ALK gene rearrangement in patients of lung adenocarcinoma in Indian population and the second objective is to impress upon the importance of adequate processing of limited tissue samples. Histopathologically confirmed cases of lung adenocarcinoma, whose tumour had been tested for both EGFR and ALK gene mutations, were included in this study. The EGFR mutations were analyzed using PCR and Gene Sequencing. ALK fusion oncogene was found by Fluorescence In Situ Hybridization (FISH) technique using kit of Vysis LSI ALK Dual colour Break Apart Rearrangement probe. A total of 152 cases of lung adenocarcinoma were included. Out of which, 92 (60.5%) were male and 60 (39.5%) were female. After exclusion of 17 cases due to unsatisfactory result, EGFR mutations were found positive in 35.5% cases (48/135). ALK gene rearrangement was found in 7.6% (10/131) after excluding 21 cases with unsatisfactory result. EGFR mutations and ALK gene rearrangement was found to be mutually exclusive. Incidence of EGFR mutations (35.5%) is much higher in Indian population than in Caucasians (13%) and is close to the incidence in East Asian countries. The 7.6% incidence of ALK fusion oncogene in Indian patients establishes the importance of molecular studies to give maximum benefit of targeted therapy to the patients.

  19. Insurance problems among inflammatory bowel disease patients: results of a Dutch population based study.

    PubMed

    Russel, M G V M; Ryan, B M; Dagnelie, P C; de Rooij, M; Sijbrandij, J; Feleus, A; Hesselink, M; Muris, J W; Stockbrugger, R

    2003-03-01

    The majority of patients with inflammatory bowel disease (IBD) have a normal life expectancy and therefore should not be weighted when applying for life assurance. There is scant literature on this topic. In this study our aim was to document and compare the incidence of difficulties in application for life and medical insurance in a population based cohort of IBD patients and matched population controls. A population based case control study of 1126 IBD patients and 1723 controls. Based on a detailed questionnaire, the frequency and type of difficulties encountered when applying for life and medical insurance in matched IBD and control populations were appraised. In comparison with controls, IBD patients had an 87-fold increased risk of encountering difficulties when applying for life assurance (odds ratio (OR) 87 (95% confidence interval (CI) 31-246)), with a heavily weighted premium being the most common problem. Patients of high educational status, with continuous disease activity, and who smoked had the highest odds of encountering such problems. Medical insurance difficulties were fivefold more common in IBD patients compared with controls (OR 5.4 (95% CI 2.3-13)) although no specific disease or patient characteristics were identified as associated with such difficulties. This is the first detailed case control study that has investigated insurance difficulties among IBD patients. Acquiring life and medical insurance constituted a major problem for IBD patients in this study. These results are likely to be more widely representative given that most insurance companies use international guidelines for risk assessment. In view of the recent advances in therapy and promising survival data on IBD patients, evidence based guidelines for risk assessment of IBD patients by insurance companies should be drawn up to prevent possible discriminatory practices.

  20. Insurance problems among inflammatory bowel disease patients: results of a Dutch population based study

    PubMed Central

    Russel, M G V M; Ryan, B M; Dagnelie, P C; de Rooij, M; Sijbrandij, J; Feleus, A; Hesselink, M; Muris, J W; Stockbrugger, R

    2003-01-01

    Background and aims: The majority of patients with inflammatory bowel disease (IBD) have a normal life expectancy and therefore should not be weighted when applying for life assurance. There is scant literature on this topic. In this study our aim was to document and compare the incidence of difficulties in application for life and medical insurance in a population based cohort of IBD patients and matched population controls. Methods: A population based case control study of 1126 IBD patients and 1723 controls. Based on a detailed questionnaire, the frequency and type of difficulties encountered when applying for life and medical insurance in matched IBD and control populations were appraised. Results: In comparison with controls, IBD patients had an 87-fold increased risk of encountering difficulties when applying for life assurance (odds ratio (OR) 87 (95% confidence interval (CI) 31–246)), with a heavily weighted premium being the most common problem. Patients of high educational status, with continuous disease activity, and who smoked had the highest odds of encountering such problems. Medical insurance difficulties were fivefold more common in IBD patients compared with controls (OR 5.4 (95% CI 2.3–13)) although no specific disease or patient characteristics were identified as associated with such difficulties. Conclusions: This is the first detailed case control study that has investigated insurance difficulties among IBD patients. Acquiring life and medical insurance constituted a major problem for IBD patients in this study. These results are likely to be more widely representative given that most insurance companies use international guidelines for risk assessment. In view of the recent advances in therapy and promising survival data on IBD patients, evidence based guidelines for risk assessment of IBD patients by insurance companies should be drawn up to prevent possible discriminatory practices. PMID:12584216

  1. Attentional bias to threat in the general population is contingent on target competition, not on attentional control settings.

    PubMed

    Wirth, Benedikt Emanuel; Wentura, Dirk

    2018-04-01

    Dot-probe studies usually find an attentional bias towards threatening stimuli only in anxious participants. Here, we investigated under what conditions such a bias occurs in unselected samples. According to contingent-capture theory, an irrelevant cue only captures attention if it matches an attentional control setting. Therefore, we first tested the hypothesis that an attentional control setting tuned to threat must be activated in (non-anxious) individuals. In Experiment 1, we used a dot-probe task with a manipulation of attentional control settings ('threat' - set vs. control set). Surprisingly, we found an (anxiety-independent) attentional bias to angry faces that was not moderated by attentional control settings. Since we presented two stimuli (i.e., a target and a distractor) on the target screen in Experiment 1 (a necessity to realise the test of contingent capture), but most dot-probe studies only employ a single target, we conducted Experiment 2 to test the hypothesis that attentional bias in the general population is contingent on target competition. Participants performed a dot-probe task, involving presentation of a stand-alone target or a target competing with a distractor. We found an (anxiety-independent) attentional bias towards angry faces in the latter but not the former condition. This suggests that attentional bias towards angry faces in unselected samples is not contingent on attentional control settings but on target competition.

  2. HDL mimetic CER-001 targets atherosclerotic plaques in patients.

    PubMed

    Zheng, Kang He; van der Valk, Fleur M; Smits, Loek P; Sandberg, Mara; Dasseux, Jean-Louis; Baron, Rudi; Barbaras, Ronald; Keyserling, Constance; Coolen, Bram F; Nederveen, Aart J; Verberne, Hein J; Nell, Thijs E; Vugts, Danielle J; Duivenvoorden, Raphaël; Fayad, Zahi A; Mulder, Willem J M; van Dongen, Guus A M S; Stroes, Erik S G

    2016-08-01

    Infusion of high-density lipoprotein (HDL) mimetics aimed at reducing atherosclerotic burden has led to equivocal results, which may relate in part to the inability of HDL mimetics to adequately reach atherosclerotic lesions in humans. This study evaluated delivery of recombinant human apolipoprotein A-I (apoA-I) containing HDL mimetic CER-001 in carotid plaques in patients. CER-001 was radiolabeled with the long-lived positron emitter zirconium-89 ((89)Zr) to enable positron emission tomography with computed tomography (PET/CT) imaging. Eight patients with atherosclerotic carotid artery disease (>50% stenosis) received a single infusion of unlabeled CER-001 (3 mg/kg), co-administered with 10 mg of (89)Zr-labeled CER-001 (18 MBq). Serial PET/CT imaging and contrast enhanced-magnetic resonance imaging (CE-MRI) were performed to evaluate targeted delivery of CER-001. One hour after infusion, mean plasma apoA-I levels increased by 9.9 mg/dL (p = 0.026), with a concomitant relative increase in the plasma cholesterol efflux capacity of 13.8% (p < 0.001). Using serial PET/CT imaging, we showed that arterial uptake of CER-001 expressed as target-to-background ratio (TBRmax) increased significantly 24 h after infusion, and remained increased up to 48 h (TBRmax t = 10 min: 0.98; t = 24 h: 1.14 (p = 0.001); t = 48 h: 1.12 (p = 0.007)). TBRmax was higher in plaque compared with non-plaque segments (1.18 vs. 1.05; p < 0.001). Plaque TBRmax correlated with local plaque contrast enhancement (r = 0.56; p = 0.019) as assessed by CE-MRI. Infusion of HDL mimetic CER-001 increases plasma apoA-I concentration and plasma cholesterol efflux capacity. Our data support the concept that CER-001 targets plaque regions in patients, which correlates with plaque contrast enhancement. These clinical findings may also guide future nanomedicine development using HDL particles for drug delivery in atherosclerosis. Netherlands Trial Registry - NTR5178. http

  3. A system dynamics optimization framework to achieve population desired of average weight target

    NASA Astrophysics Data System (ADS)

    Abidin, Norhaslinda Zainal; Zulkepli, Jafri Haji; Zaibidi, Nerda Zura

    2017-11-01

    Obesity is becoming a serious problem in Malaysia as it has been rated as the highest among Asian countries. The aim of the paper is to propose a system dynamics (SD) optimization framework to achieve population desired weight target based on the changes in physical activity behavior and its association to weight and obesity. The system dynamics approach of stocks and flows diagram was used to quantitatively model the impact of both behavior on the population's weight and obesity trends. This work seems to bring this idea together and highlighting the interdependence of the various aspects of eating and physical activity behavior on the complex of human weight regulation system. The model was used as an experimentation vehicle to investigate the impacts of changes in physical activity on weight and prevalence of obesity implications. This framework paper provides evidence on the usefulness of SD optimization as a strategic decision making approach to assist in decision making related to obesity prevention. SD applied in this research is relatively new in Malaysia and has a high potential to apply to any feedback models that address the behavior cause to obesity.

  4. TargetCOPD: a pragmatic randomised controlled trial of targeted case finding for COPD versus routine practice in primary care: protocol.

    PubMed

    Jordan, Rachel E; Adab, Peymané; Jowett, Sue; Marsh, Jen L; Riley, Richard D; Enocson, Alexandra; Miller, Martin R; Cooper, Brendan G; Turner, Alice M; Ayres, Jon G; Cheng, Kar Keung; Jolly, Kate; Stockley, Robert A; Greenfield, Sheila; Siebert, Stanley; Daley, Amanda; Fitzmaurice, David A

    2014-10-04

    primary care staff views of each approach. This will be the largest RCT of its kind, and should inform how best to identify undiagnosed patients with COPD in the UK and other similar healthcare systems. Sensitivity analyses will help local policy-makers decide which sub-groups of the population to target first. Current controlled trials ISRCTN14930255.

  5. Home blood-pressure monitoring among hypertensive patients in an Asian population.

    PubMed

    Tan, N C; Khin, L W; Pagi, R

    2005-07-01

    Hypertension is a principal cause of mortality and morbidity in Singapore. The use of home blood-pressure monitoring (HBPM) to assess hypertensive control with digital devices in the local multi-racial population is unknown. The study determined the factors associated with hypertensive patients' use of HBPM in primary care in a multi-racial Asian population. Randomized cross-sectional questionnaire survey of hypertensive patients managed in a district polyclinic. A model predicting use of HBPM was constructed by univariate and multivariate logistic regression. A total of 224 eligible subjects were randomly selected from 1943 patients. Response rate was 78.1% (n = 175). In all, 61.7% of them were aware of HBPM but only 24% used HBPM. Using multivariate analysis by stepwise backward regression, the final fitted model showed that HBPM was associated with higher patients' socioeconomic status: (adjusted OR for middle-income status = 2.85, 95% CI: 1.2-6.78, P = 0.018; adjusted OR for high-income status = 3.46, 95% CI: 1.22-9.87, P = 0.020) and their documented diastolic BP (adjusted OR for diastolic BP > 80 mmHg = 2.26, 95% CI: 1.06-4.82, P = 0.034). Nonusers cited failure to recognize benefits (54.1%), lack of HBPM awareness (29.3%), understanding of device operation (18.8%) and perception of inaccuracy (10.5%) as deterrents. 76.2% of users were satisfied with HBPM but lacked knowledge in maintenance of devices. In conclusion, 61.7% of the study population were aware of HBPM but only 24% used it. Patients' failure to recognize benefits, lack of awareness, cost and perception of inaccuracy were barriers. Higher socioeconomic status and patient's documented diastolic BP correlated with HBPM usage.

  6. Glycaemic control and antidiabetic treatment trends in primary care centres in patients with type 2 diabetes mellitus during 2007–2013 in Catalonia: a population-based study

    PubMed Central

    Mata-Cases, Manel; Franch-Nadal, Josep; Real, Jordi; Mauricio, Dídac

    2016-01-01

    Objectives To assess trends in prescribing practices of antidiabetic agents and glycaemic control in patients with type 2 diabetes mellitus (T2DM). Design Cross-sectional analysis using yearly clinical data and antidiabetic treatments prescribed obtained from an electronic population database. Setting Primary healthcare centres, including the entire population attended by the Institut Català de la Salut in Catalonia, Spain, from 2007 to 2013. Participants Patients aged 31–90 years with a diagnosis of T2DM. Results The number of registered patients with T2DM in the database was 257 072 in 2007, increasing up to 343 969 in 2013. The proportion of patients not pharmacologically treated decreased by 9.7% (95% CI −9.48% to −9.92%), while there was an increase in the percentage of patients on monotherapy (4.4% increase; 95% CI 4.16% to 4.64%), combination therapy (2.8% increase; 95% CI 2.58% to 3.02%), and insulin alone or in combination (increasing 2.5%; 95% CI 2.2% to 2.8%). The use of metformin and dipeptidyl peptidase-IV inhibitors increased gradually, while sulfonylureas, glitazones and α-glucosidase inhibitors decreased. The use of glinides remained stable, and the use of glucagon-like peptide-1 receptor agonists was still marginal. Regarding glycaemic control, there were no relevant differences across years: mean glycated haemoglobin (HbA1c) value was around 7.2%; the percentage of patients reaching an HbA1c≤7% target ranged between 52.2% and 55.6%; and those attaining their individualised target from 72.8% to 75.7%. Conclusions Although the proportion of patients under pharmacological treatment increased substantially over time and there was an increase in the use of combination therapies, there have not been relevant changes in glycaemic control during the 2007–2013 period in Catalonia. PMID:27707830

  7. SeedVicious: Analysis of microRNA target and near-target sites.

    PubMed

    Marco, Antonio

    2018-01-01

    Here I describe seedVicious, a versatile microRNA target site prediction software that can be easily fitted into annotation pipelines and run over custom datasets. SeedVicious finds microRNA canonical sites plus other, less efficient, target sites. Among other novel features, seedVicious can compute evolutionary gains/losses of target sites using maximum parsimony, and also detect near-target sites, which have one nucleotide different from a canonical site. Near-target sites are important to study population variation in microRNA regulation. Some analyses suggest that near-target sites may also be functional sites, although there is no conclusive evidence for that, and they may actually be target alleles segregating in a population. SeedVicious does not aim to outperform but to complement existing microRNA prediction tools. For instance, the precision of TargetScan is almost doubled (from 11% to ~20%) when we filter predictions by the distance between target sites using this program. Interestingly, two adjacent canonical target sites are more likely to be present in bona fide target transcripts than pairs of target sites at slightly longer distances. The software is written in Perl and runs on 64-bit Unix computers (Linux and MacOS X). Users with no computing experience can also run the program in a dedicated web-server by uploading custom data, or browse pre-computed predictions. SeedVicious and its associated web-server and database (SeedBank) are distributed under the GPL/GNU license.

  8. Use of clinical simulations for patient education: targeting an untapped audience.

    PubMed

    Siwe, Karin; Berterö, Carina; Pugh, Carla; Wijma, Barbro

    2009-01-01

    In most cases, the health professional has been the target for simulation based learning curricula. We have developed a simulation based curriculum for patient education. In our curriculum lay-women learn how to perform the clinical female pelvic examination using a manikin-based trainer. Learner assessments show that prior negative expectations turned into positive expectations regarding future pelvic examinations.

  9. Patient satisfaction with community pharmacy: comparing urban and suburban chain-pharmacy populations.

    PubMed

    Malewski, David F; Ream, Aimrie; Gaither, Caroline A

    2015-01-01

    Patient satisfaction with pharmaceutical care can be a strong predictor of medication and other health-related outcomes. Less understood is the role that location of pharmacies in urban or suburban environments plays in patient satisfaction with pharmacy and pharmacist services. The purpose of this study was to serve as a pilot examining urban and suburban community pharmacy populations for similarities and differences in patient satisfaction. Community pharmacy patients were asked to self-administer a 30-question patient satisfaction survey. Fifteen questions addressed their relationship with the pharmacist, 10 questions addressed satisfaction and accessibility of the pharmacy, and five questions addressed financial concerns. Five urban and five suburban pharmacies agreed to participate. Data analysis included descriptive statistics and chi-square analysis. Most patients reported high levels of satisfaction. Satisfaction with pharmacist relationship and service was 70% or higher with no significant differences between locations. There were significant differences between the urban and suburban patients regarding accessibility of pharmacy services, customer service and some patient/pharmacist trust issues. The significant differences between patient satisfaction in the suburban and urban populations warrant a larger study with more community pharmacies in other urban, suburban and rural locations to better understand and validate study findings. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Anthropometric and Laboratory Variables Related to Weight Loss-Comparison of Heart Failure Patients with Tumor Patients and Control Population.

    PubMed

    Letilovic, Tomislav; Vrhovac, Radovan; Krznarić, Željko

    2017-01-01

    Body weight loss is an important feature of heart failure (HF) and tumors. It is related to both reduced survival and adverse reactions to therapy in both of these conditions. The mechanisms of body weight loss in patients with HF and tumors are considered to be similar. Yet, studies comparing those two populations are generally lacking. The aim of this study was to compare anthropometric and laboratory data, related to weight loss, between patients with chronic HF and patients with different tumors as well as control population. Laboratory and anthropometric data on 143 consecutive patients with chronic HF and malignant diseases as well as data for 20 controls were collected. Patients with HF had lower levels of C-reactive protein (CRP) and albumin compared to controls. Anthropometric measurements revealed lower body mass index (BMI), muscle strength, mid-arm circumference, and waist circumference in patients with HF compared to controls. Measurements of biceps, triceps, subscapular, and suprailiac skinfolds were also lower in HF group. Compared to solid tumor group, HF patients had lower levels of CRP and higher levels of hemoglobin. Solid tumor patients had lower values of BMI and subscapular skinfold thickness, as well as higher muscle strength compared to HF group. Finally, compared to patients with solid hematological tumors, HF group had lower levels of albumin, lower muscle strength, as well as lower mid-arm circumference. We found differences in anthropometric and laboratory features, related to weight loss, in patients with HF compared to control population that were expected. On the other hand, observed differences in HF group compared to patients with various tumors could imply different pathophysiological mechanisms of weight loss between those groups. Such data could serve as a cornerstone for studies with larger numbers of patients and deeper pathophysiological insight.

  11. Targeting the T-Lak cell originated protein kinase by OTS964 shrinks the size of power-law coded heterogeneous glioma stem cell populations

    PubMed Central

    Sugimori, Michiya; Hayakawa, Yumiko; Koh, Masaki; Hayashi, Tomohide; Tamura, Ryoi; Kuroda, Satoshi

    2018-01-01

    Glioblastoma resists chemoradiotherapy, then, recurs to be a fatal space-occupying lesion. The recurrence is caused by re-growing cell populations such as glioma stem cells (GSCs), suggesting that GSC populations should be targeted. This study addressed whether a novel anti-cancer drug, OTS964, an inhibitor for T-LAK cell originated protein kinase (TOPK), is effective in reducing the size of the heterogeneous GSC populations, a power-law coded heterogeneous GSC populations consisting of glioma sphere (GS) clones, by detailing quantitative growth properties. We found that OTS964 killed GS clones while suppressing the growth of surviving GS clones, thus identifying clone-eliminating and growth-disturbing efficacies of OTS964. The efficacies led to a significant size reduction in GS populations in a dose-dependent manner. The surviving GS clones reconstructed GS populations in the following generations; the recovery of GS populations fits a recurrence after the chemotherapy. The recovering GS clones resisted the clone-eliminating effect of OTS964 in sequential exposure during the growth recovery. However, surprisingly, the resistant properties of the recovered-GS clones had been plastically canceled during self-renewal, and then the GS clones had become re-sensitive to OTS964. Thus, OTS964 targets GSCs to eliminate them or suppress their growth, resulting in shrinkage of the power-law coded GSC populations. We propose a therapy focusing on long-term control in recurrence of glioblastoma via reducing the size of the GSC populations by OTS964. PMID:29423027

  12. Targeting the T-Lak cell originated protein kinase by OTS964 shrinks the size of power-law coded heterogeneous glioma stem cell populations.

    PubMed

    Sugimori, Michiya; Hayakawa, Yumiko; Koh, Masaki; Hayashi, Tomohide; Tamura, Ryoi; Kuroda, Satoshi

    2018-01-09

    Glioblastoma resists chemoradiotherapy, then, recurs to be a fatal space-occupying lesion. The recurrence is caused by re-growing cell populations such as glioma stem cells (GSCs), suggesting that GSC populations should be targeted. This study addressed whether a novel anti-cancer drug, OTS964, an inhibitor for T-LAK cell originated protein kinase (TOPK), is effective in reducing the size of the heterogeneous GSC populations, a power-law coded heterogeneous GSC populations consisting of glioma sphere (GS) clones, by detailing quantitative growth properties. We found that OTS964 killed GS clones while suppressing the growth of surviving GS clones, thus identifying clone-eliminating and growth-disturbing efficacies of OTS964. The efficacies led to a significant size reduction in GS populations in a dose-dependent manner. The surviving GS clones reconstructed GS populations in the following generations; the recovery of GS populations fits a recurrence after the chemotherapy. The recovering GS clones resisted the clone-eliminating effect of OTS964 in sequential exposure during the growth recovery. However, surprisingly, the resistant properties of the recovered-GS clones had been plastically canceled during self-renewal, and then the GS clones had become re-sensitive to OTS964. Thus, OTS964 targets GSCs to eliminate them or suppress their growth, resulting in shrinkage of the power-law coded GSC populations. We propose a therapy focusing on long-term control in recurrence of glioblastoma via reducing the size of the GSC populations by OTS964.

  13. Drug prescription patterns in patients with Addison's disease: a Swedish population-based cohort study.

    PubMed

    Björnsdottir, Sigridur; Sundström, Anders; Ludvigsson, Jonas F; Blomqvist, Paul; Kämpe, Olle; Bensing, Sophie

    2013-05-01

    There are no published data on drug prescription in patients with Addison's disease (AD). Our objective was to describe the drug prescription patterns in Swedish AD patients before and after diagnosis compared with population controls. We conducted a population-based cohort study in Sweden. Through the Swedish National Patient Register and the Swedish Prescribed Drug Register, we identified 1305 patients with both a diagnosis of AD and on combination treatment with hydrocortisone/cortisone acetate and fludrocortisone. Direct evidence of the AD diagnosis from patient charts was not available. We identified 11 996 matched controls by the Register of Population. We determined the ratio of observed to expected number of patients treated with prescribed drugs. Overall, Swedish AD patients received more prescribed drugs than controls, and 59.3% of the AD patients had medications indicating concomitant autoimmune disease. Interestingly, both before and after the diagnosis of AD, patients used more gastrointestinal medications, antianemic preparations, lipid-modifying agents, antibiotics for systemic use, hypnotics and sedatives, and drugs for obstructive airway disease (all P values < .05). Notably, an increased prescription of several antihypertensive drugs and high-ceiling diuretics was observed after the diagnosis of AD. Gastrointestinal symptoms and anemia, especially in conjunction with autoimmune disorders, should alert the physician about the possibility of AD. The higher use of drugs for cardiovascular disorders after diagnosis in patients with AD raises concerns about the replacement therapy.

  14. Population pharmacokinetics of levofloxacin in Korean patients.

    PubMed

    Kiem, Sungmin; Ryu, Sung-Mun; Lee, Yun-Mi; Schentag, Jerome J; Kim, Yang-Wook; Kim, Hyeon-Kuk; Jang, Hang-Jae; Joo, Yong-Don; Jin, Kyubok; Shin, Jae-Gook; Ghim, Jong-Lyul

    2016-08-01

    Levofloxacin (LVFX) has different effects depending on the area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC) ratio. While AUC can be expressed as dose/clearance (CL), we measured serial concentrations of LVFX in Koreans and tried to set a Korean-specific equation, estimating the CL of the antibiotic. In total, 38 patients, aged 18-87 years, received once daily intravenous LVFX doses of 500 mg or 250 mg, depending on their renal function. Four plasma samples were obtained according to a D optimal sampling design. The population pharmacokinetic (PK) parameters of LVFX were estimated using non-linear mixed-effect modeling (NONMEM, ver. 7.2). The CL of LVFX was dependent on creatinine clearance (CLCR) as a covariate. The mean population PK parameters of LVFX in Koreans were as follows: CL (l/hour) = 6.19 ×  (CLCR/75)(1.32). The CL of LVFX in Koreans is expected to be lower than that in Western people.

  15. Bi-spectral index, entropy and predicted plasma propofol concentrations with target controlled infusions in Indian patients.

    PubMed

    Puri, Goverdhan D; Mathew, Preethy J; Sethu Madhavan, J; Hegde, Harihar V; Fiehn, Andreas

    2011-10-01

    Many processed electroencephalographic signals are used now to help the anaesthesiologist titrate the depth of sedation. We investigated the relationship between target plasma propofol concentration and objective end-points of sedation- Bispectral Index (BIS), State Entropy (SE) and Response Entropy (RE)-at clinical end-points as assessed by Modified Observer Assessment of Alertness/sedation Scale (MOAAS) in Indian patients. Eighteen ASA 1 and 2 Indian adult patients scheduled to undergo elective surgery were included. The target control infusion (TCI) of propofol was administered using 'Diprifusor'. The level of sedation was assessed using MOAAS by the anaesthesiologist. BIS, SE, RE were recorded throughout. TCI was started at 0.5 μg/ml and increased by 0.5 μg/ml every 6 min till MOAAS scores reached 0 or there was sustained BIS value less than 30. The EC(50) and EC(95) of predicted plasma propofol concentration for loss of consciousness (assessed by loss of response to verbal command), were 2.3 and 2.8 μg/ml respectively and for loss of response to painful stimuli (trapezius squeeze) were 4.0 and 5.0 μg/ml respectively. The BIS and entropy values (EC(50) and EC(95)) for loss of consciousness and response to painful stimuli in Indian patients were estimated. The preliminary relation of target plasma propofol concentration with BIS was found to be BIS = 100.5-16.4 × (Target concentration). The target plasma propofol concentrations required to produce unconsciousness and loss of response to painful stimuli in Indian patients have been estimated. Also, the relations between target plasma concentration and objective measures of different levels of anaesthesia have been established.

  16. Serum uric acid and target organ damage in essential hypertension

    PubMed Central

    Ofori, Sandra N; Odia, Osaretin J

    2014-01-01

    Background Hypertension is a major risk factor for cardiovascular mortality, as it acts through its effects on target organs, such as the heart and kidneys. Hyperuricemia increases cardiovascular risk in patients with hypertension. Objective To assess the relationship between serum uric acid and target organ damage (left ventricular hypertrophy and microalbuminuria) in untreated patients with essential hypertension. Patients and methods: A cross-sectional study was carried out in 130 (85 females, 45 males) newly diagnosed, untreated patients with essential hypertension. Sixty-five healthy age- and sex-matched non-hypertensive individuals served as controls for comparison. Left ventricular hypertrophy was evaluated by cardiac ultrasound scan, and microalbuminuria was assessed in an early morning midstream urine sample by immunoturbidimetry. Blood samples were collected for assessing uric acid levels. Results Mean serum uric acid was significantly higher among the patients with hypertension (379.7±109.2 μmol/L) than in the controls (296.9±89.8 μmol/L; P<0.001), and the prevalence of hyperuricemia was 46.9% among the hypertensive patients and 16.9% among the controls (P<0.001). Among the hypertensive patients, microalbuminuria was present in 54.1% of those with hyperuricemia and in 24.6% of those with normal uric acid levels (P=0.001). Similarly, left ventricular hypertrophy was more common in the hypertensive patients with hyperuricemia (70.5% versus 42.0%, respectively; P=0.001). There was a significant linear relationship between mean uric acid levels and the number of target organ damage (none versus one versus two: P=0.012). Conclusion These results indicate that serum uric acid is associated with target organ damage in patients with hypertension, even at the time of diagnosis; thus, it is a reliable marker of cardiovascular damage in our patient population. PMID:24833906

  17. Interventional differences among Huntington's disease patients by disease progression in commercial and medicaid populations.

    PubMed

    Anderson, Karen E; Divino, Victoria; DeKoven, Mitch; Langbehn, Douglas; Warner, John H; Giuliano, Joseph; Lee, Won Chan

    2014-01-01

    Huntington's disease (HD) is a progressive neurodegenerative disease that spans distinct disease stages over 15-20 years. Various interventions are available which may allow patients to live outside of a nursing home for a longer time. However, little is known about use of these interventions by disease stage and by insurance type. We compared use of interventions among early, middle and late stages of HD in commercial (C) and Medicaid (M) health insurance populations. HD patients (ICD-9-CM 333.4) were identified from Thomson Reuters' MarketScan C and M database (2002-2009) and hierarchically grouped into disease stages based upon the presence of defining clinical markers. A total of 1,272 HD patients (752/520 C/M) were identified. While stage distribution was nearly uniform in the C database - 34.0/35.5/34.0% (early/middle/late stage) - in the M population the majority were late stage (74.0%). Overall mean age was similar between C and M populations. Among late-stage patients, more M patients resided in a nursing home (M:73.8% v. C:40.6%) and received hospice care (M:18.4% v. C:11.3%). Physical therapy (PT) and home assistance were the most frequent interventions used by middle-stage patients, however more C patients received PT (C:64.0% v. M:37.1%) while more M patients received home assistance (M:75.3% v. C:53.2%). Among late-stage patients, PT was also higher in the C population (56.3% v. 48.3%). More M patients had assistive devices at home in both middle (M:25.8% v. C:9.7%) and late stages (M:35.6% v.C:23.4%). Apparent interventional differences emerged which varied by disease stage and insurance type.

  18. Identifying clusters of falls-related hospital admissions to inform population targets for prioritising falls prevention programmes

    PubMed Central

    Finch, Caroline F; Stephan, Karen; Shee, Anna Wong; Hill, Keith; Haines, Terry P; Clemson, Lindy; Day, Lesley

    2015-01-01

    Background There has been limited research investigating the relationship between injurious falls and hospital resource use. The aims of this study were to identify clusters of community-dwelling older people in the general population who are at increased risk of being admitted to hospital following a fall and how those clusters differed in their use of hospital resources. Methods Analysis of routinely collected hospital admissions data relating to 45 374 fall-related admissions in Victorian community-dwelling older adults aged ≥65 years that occurred during 2008/2009 to 2010/2011. Fall-related admission episodes were identified based on being admitted from a private residence to hospital with a principal diagnosis of injury (International Classification of Diseases (ICD)-10-AM codes S00 to T75) and having a first external cause of a fall (ICD-10-AM codes W00 to W19). A cluster analysis was performed to identify homogeneous groups using demographic details of patients and information on the presence of comorbidities. Hospital length of stay (LOS) was compared across clusters using competing risks regression. Results Clusters based on area of residence, demographic factors (age, gender, marital status, country of birth) and the presence of comorbidities were identified. Clusters representing hospitalised fallers with comorbidities were associated with longer LOS compared with other cluster groups. Clusters delineated by demographic factors were also associated with increased LOS. Conclusions All patients with comorbidity, and older women without comorbidities, stay in hospital longer following a fall and hence consume a disproportionate share of hospital resources. These findings have important implications for the targeting of falls prevention interventions for community-dwelling older people. PMID:25618735

  19. Population Pharmacokinetics of Vancomycin in Patients Undergoing Allogeneic Hematopoietic Stem-Cell Transplantation.

    PubMed

    Okada, Akira; Kariya, Misato; Irie, Kei; Okada, Yutaka; Hiramoto, Nobuhiro; Hashimoto, Hisako; Kajioka, Ryosuke; Maruyama, Chika; Kasai, Hidefumi; Hamori, Mami; Nishimura, Asako; Shibata, Nobuhito; Fukushima, Keizo; Sugioka, Nobuyuki

    2018-05-15

    Vancomycin is a commonly used antimicrobial agent for patients undergoing allogeneic hematopoietic stem-cell transplantation (allo-HSCT). Vancomycin has large inter- and intraindividual pharmacokinetic variability, which is mainly described by renal function; various studies have indicated that vancomycin pharmacokinetics are altered in special populations. However, little is known regarding vancomycin pharmacokinetics in patients undergoing allo-HSCT. Therefore, we aimed to develop a population pharmacokinetic (PopPK) model of vancomycin in patients undergoing allo-HSCT for effective and safe antimicrobial therapy and to develop a vancomycin dosing nomogram for a vancomycin optimal-dosing strategy. In total, 285 observations from 95 patients undergoing allo-HSCT were available. The final PopPK parameter estimates were central volume of distribution (V1, L), 39.2; clearance (L/h), 4.25; peripheral volume of distribution (V2, L), 56.1; and intercompartmental clearance (L/h), 1.95. The developed vancomycin model revealed an increase in V1 and V2 compared with those in the general population that consisted of patients with methicillin-resistant Staphylococcus aureus. Moreover, serum creatinine was reduced because of an increase in the plasma fraction because of destruction of hematopoietic stem cells accompanying allo-HSCT pretreatment, suggesting that the Cockcroft-Gault equation-based creatinine clearance value was overestimated. To our knowledge, this is the first PopPK study to develop a dosing nomogram for vancomycin in patients undergoing allo-HSCT and was proven to be useful in optimizing the dosage and dosing interval of vancomycin in these patients. This strategy will provide more useful information for vancomycin therapy with an evidence-based dose adjustment. © 2018, The American College of Clinical Pharmacology.

  20. An Evaluation of Six Brief Interventions that Target Drug-Related Problems in Correctional Populations

    PubMed Central

    JOE, GEORGE W.; KNIGHT, KEVIN; SIMPSON, D. DWAYNE; FLYNN, PATRICK M.; MOREY, JANIS T.; BARTHOLOMEW, NORMA G.; TINDALL, MICHELE STATON; BURDON, WILLIAM M.; HALL, ELIZABETH A.; MARTIN, STEVE S.; O’CONNELL, DANIEL J.

    2012-01-01

    Finding brief effective treatments for criminal justice populations is a major public need. The CJ-DATS Targeted Intervention for Corrections (TIC), which consists of six brief interventions (Communication, Anger, Motivation, Criminal Thinking, Social Networks, and HIV/Sexual Health), were tested in separate federally-funded randomized control studies. In total, 1,573 criminal justice-involved individuals from 20 correction facilities participated (78% males; 54% white). Multi-level repeated measures analyses found significant gains in knowledge, attitudes, and psychosocial functioning (criteria basic to Knowledge, Attitude, and Practices (KAP) and TCU Treatment Process Models). While improvements were less consistent in criminal thinking, overall evidence supported efficacy for the TIC interventions. PMID:22547911

  1. Alterations in the Fecal Microbiota of Patients with HIV-1 Infection: An Observational Study in A Chinese Population

    PubMed Central

    Ling, Zongxin; Jin, Changzhong; Xie, Tiansheng; Cheng, Yiwen; Li, Lanjuan; Wu, Nanping

    2016-01-01

    The available evidence suggests that alterations in gut microbiota may be tightly linked to the increase in microbial translocation and systemic inflammation in patients with human immunodeficiency virus 1 (HIV-1) infection. We profiled the fecal microbiota as a proxy of gut microbiota by parallel barcoded 454-pyrosequencing in 67 HIV-1-infected patients (32 receiving highly active antiretroviral therapy [HAART] and 35 HAART naïve) and 16 healthy controls from a Chinese population. We showed that α-diversity indices did not differ significantly between the healthy control and HIV-1-infected patients. The ratio of Firmicutes/Bacteroidetes increased significantly in HIV-1-infected patients. Several key bacterial phylotypes, including Prevotella, were prevalent in HIV-1-infected patients; whereas Phascolarctobacterium, Clostridium XIVb, Dialister and Megamonas were significantly correlated with systemic inflammatory cytokines. After short-term, effective HAART, the viral loads of HIV-1 were reduced; however, the diversity and composition of the fecal microbiota were not completely restored. and the dysbiosis remained among HIV-1-infected subjects undergoing HAART. Our detailed analysis demonstrated that dysbiosis of fecal microbiota might play an active role in HIV-1 infection. Thus, new insights may be provided into therapeutics that target the microbiota to attenuate the progression of HIV disease and to reduce the risk of gut-linked disease in HIV-1-infected patients. PMID:27477587

  2. Population pharmacokinetic (PK) analysis of laromustine, an emerging alkylating agent, in cancer patients.

    PubMed

    Nassar, Ala F; Wisnewski, Adam V; King, Ivan

    2017-05-01

    1. Alkylating agents are capable of introducing an alkyl group into nucleophilic sites on DNA or RNA through covalent bond. Laromustine is an active member of a relatively new class of sulfonylhydrazine prodrugs under development as antineoplastic alkylating agents, and displays significant single-agent activity. 2. This is the first report of the population pharmacokinetic analysis of laromustine, 106 patients, 66 with hematologic malignancies and 40 with solid tumors, participated in five clinical trials worldwide. Of these, 104 patients were included in the final NONMEM analysis. 3. The population estimates for total clearance (CL) and volume of distribution of the central compartment (V 1 ) were 96.3 L/h and 45.9 L, associated with high inter-patient variability of 52.9% and 79.8% and inter-occasion variability of 26.7% and 49.3%, respectively. The population estimates for Q and V 2 were 73.2 L/h and 29.9 L, and inter-patient variability in V 2 was 63.1%, respectively. 4. The estimate of V ss (75.8 L) exceeds total body water, indicating that laromustine is distributed to tissues. The half-life is short, less than 1 h, reflecting rapid clearance. Population PK analysis showed laromustine pharmacokinetics to be independent of dose and organ function with no effect on subsequent dosing cycles.

  3. Development of a Targeted Smoking Relapse-Prevention Intervention for Cancer Patients.

    PubMed

    Meltzer, Lauren R; Meade, Cathy D; Diaz, Diana B; Carrington, Monica S; Brandon, Thomas H; Jacobsen, Paul B; McCaffrey, Judith C; Haura, Eric B; Simmons, Vani N

    2018-04-01

    We describe the series of iterative steps used to develop a smoking relapse-prevention intervention customized to the needs of cancer patients. Informed by relevant literature and a series of preliminary studies, an educational tool (DVD) was developed to target the unique smoking relapse risk factors among cancer patients. Learner verification interviews were conducted with 10 cancer patients who recently quit smoking to elicit feedback and inform the development of the DVD. The DVD was then refined using iterative processes and feedback from the learner verification interviews. Major changes focused on visual appeal, and the inclusion of additional testimonials and graphics to increase comprehension of key points and further emphasize the message that the patient is in control of their ability to maintain their smoking abstinence. Together, these steps resulted in the creation of a DVD titled Surviving Smokefree®, which represents the first smoking relapse-prevention intervention for cancer patients. If found effective, the Surviving Smokefree® DVD is an easily disseminable and low-cost portable intervention which can assist cancer patients in maintaining smoking abstinence.

  4. The Case for Diabetes Population Health Improvement: Evidence-Based Programming for Population Outcomes in Diabetes

    PubMed Central

    Maruthur, Nisa; Mathioudakis, Nestoras; Spanakis, Elias; Rubin, Daniel; Zilbermint, Mihail; Hill-Briggs, Felicia

    2017-01-01

    Purpose of Review The goal of this review is to describe diabetes within a population health improvement framework and to review the evidence for a diabetes population health continuum of intervention approaches, including diabetes prevention and chronic and acute diabetes management, to improve clinical and economic outcomes. Recent Findings Recent studies have shown that compared to usual care, lifestyle interventions in prediabetes lower diabetes risk at the population-level and that group-based programs have low incremental medial cost effectiveness ratio for health systems. Effective outpatient interventions that improve diabetes control and process outcomes are multi-level, targeting the patient, provider, and healthcare system simultaneously and integrate community health workers as a liaison between the patient and community-based healthcare resources. A multi-faceted approach to diabetes management is also effective in the inpatient setting. Interventions shown to promote safe and effective glycemic control and use of evidence-based glucose management practices include provider reminder and clinical decision support systems, automated computer order entry, provider education, and organizational change. Summary Future studies should examine the cost-effectiveness of multi-faceted outpatient and inpatient diabetes management programs to determine the best financial models for incorporating them into diabetes population health strategies. PMID:28567711

  5. Serum uric acid and target organ damage in essential hypertension.

    PubMed

    Ofori, Sandra N; Odia, Osaretin J

    2014-01-01

    Hypertension is a major risk factor for cardiovascular mortality, as it acts through its effects on target organs, such as the heart and kidneys. Hyperuricemia increases cardiovascular risk in patients with hypertension. To assess the relationship between serum uric acid and target organ damage (left ventricular hypertrophy and microalbuminuria) in untreated patients with essential hypertension. A cross-sectional study was carried out in 130 (85 females, 45 males) newly diagnosed, untreated patients with essential hypertension. Sixty-five healthy age- and sex-matched non-hypertensive individuals served as controls for comparison. Left ventricular hypertrophy was evaluated by cardiac ultrasound scan, and microalbuminuria was assessed in an early morning midstream urine sample by immunoturbidimetry. Blood samples were collected for assessing uric acid levels. Mean serum uric acid was significantly higher among the patients with hypertension (379.7±109.2 μmol/L) than in the controls (296.9±89.8 μmol/L; P<0.001), and the prevalence of hyperuricemia was 46.9% among the hypertensive patients and 16.9% among the controls (P<0.001). Among the hypertensive patients, microalbuminuria was present in 54.1% of those with hyperuricemia and in 24.6% of those with normal uric acid levels (P=0.001). Similarly, left ventricular hypertrophy was more common in the hypertensive patients with hyperuricemia (70.5% versus 42.0%, respectively; P=0.001). There was a significant linear relationship between mean uric acid levels and the number of target organ damage (none versus one versus two: P=0.012). These results indicate that serum uric acid is associated with target organ damage in patients with hypertension, even at the time of diagnosis; thus, it is a reliable marker of cardiovascular damage in our patient population.

  6. Population pharmacokinetics of the piperacillin component of piperacillin/tazobactam in pediatric oncology patients with fever and neutropenia.

    PubMed

    Cies, Jeffrey J; Jain, Jaimi; Kuti, Joseph L

    2015-03-01

    To describe the population pharmacokinetics of the piperacillin component of piperacillin/tazobactam. This pharmacokinetic study included 21 pediatric (age 3-10 years) patients receiving piperacillin/tazobactam to treat fever with neutropenia. Each patient contributed 1-3 blood samples for piperacillin concentration determination. Population pharmacokinetic analyses were conducted using Pmetrics software. A 5,000 patient Monte Carlo simulation was performed to determine the probability of target attainment (PTA) for multiple dosing regimens, using 50% of free drug time above the minimum inhibitory concentration (MIC) as the primary pharmacodynamic threshold. Mean ± SD body weight was 28.5 ± 9.7 kg. Piperacillin concentration data best fit a two-compartment model with linear clearance, using total body weight as a covariate for clearance (CLθ ) and volume of the central compartment (Vcθ ). Population estimates for CLθ , Vcθ , and intercompartment transfer constants were 0.204 ± 0.076 L/h/kg, 0.199 ± 0.107 L/kg, 0.897 ± 1.050 h(-1) , and 1.427 ± 1.609 h(-1) , respectively. R(2) , bias, and precision for the Bayesian fit were 0.998, -0.032, and 2.2 µg/ml, respectively. At the MIC breakpoint of 16 µg/ml for Pseudomonas aeruginosa, PTAs for 50 mg/kg q4h as a 0.5 hr infusion was 93.9%; for 100 mg/kg q8h as 0.5 and 4 hr infusion: 64.6% and 100%; for 100 mg/kg q6h as 0.5 and 3 hr infusion: 86.5% and 100%; and for 400 mg/kg continuous infusion: 100%, respectively. In children with fever and neutropenia, piperacillin/tazobactam dosing regimens that are administered every 4 hr or that employ prolonged or continuous infusions should be considered to optimize pharmacodynamic exposure. © 2014 Wiley Periodicals, Inc.

  7. Children and young people with diabetes in Yorkshire: a population-based clinical audit of patient data 2005/2006.

    PubMed

    McKinney, P A; Feltbower, R G; Stephenson, C R; Reynolds, C

    2008-11-01

    To provide a population-based clinical audit of children and young people with diabetes, reporting outcomes, including glycaemic control, for named individual units. Clinical audit data on care processes and glycated haemoglobin (HbA(1c)) were collected for 1742 children and young people treated in 16 paediatric units in Yorkshire, from January 2005 to March 2006. The Yorkshire Register of Diabetes in Children and Young People provided information technology support and validation that enhanced data quality. Multi-level linear regression modelling investigated factors affecting glycaemic control. An HbA(1c) measure was recorded for 91.6% of patients. The National Institute for Clinical Excellence-recommended target level for HbA(1c) of < 7.5% was achieved for 14.7% of patients. HbA(1c) was positively associated with duration of diabetes and later age at diagnosis. Patients living in deprived areas had significantly poorer control compared with those from affluent areas. Significant between-unit variation in HbA(1c) was not reflected by any association with unit size. Our population-based clinical audit of children with diabetes is the product of an effective collaboration between those who deliver care and health services researchers. High levels of recording the key care process measuring diabetes control, compared with national figures, suggests collaboration has translated into improved services. The interesting association between poor diabetes control and higher deprivation is noteworthy and requires further investigation. Future audits require recording of clinical management and clinic structures, in addition to resources to record, assemble and analyse data.

  8. c-kit mutation in a population of patients with mastocytosis.

    PubMed

    Nagata, H; Okada, T; Worobec, A S; Semere, T; Metcalfe, D D

    1997-01-01

    The c-kit Asp816Val activating mutation is found in all patients with mastocytosis with an associated hematologic disorder, and at least in a subset of patients with indolent mastocytosis. The case of an 11-month-old child is presented who was categorized as having indolent mastocytosis, and where the Asp816Val mutation was identified in lesional skin, but not in bone marrow or in peripheral blood mononuclear cell populations. The significance of these findings is discussed.

  9. Identification of alkaptonuria in the general population: a United Kingdom experience describing the challenges, possible solutions and persistent barriers.

    PubMed

    Ranganath, L; Taylor, A M; Shenkin, A; Fraser, W D; Jarvis, J; Gallagher, J A; Sireau, N

    2011-06-01

    Progress in research into rare diseases is challenging. This paper discusses strategies to identify individuals with the rare genetic disease alkaptonuria (AKU) within the general population. Strategies used included a questionnaire survey of general practitioners, a dedicated website and patient network contact, targeted family screening and medical conference targeting. Primary care physicians of the UK were targeted by a postal survey that involved mailing 11,151 UK GPs; the response rate was 18.2%. We have identified 75 patients in the UK with AKU by the following means: postal survey (23), targeted family screening (11), patient networks and the website (41). Targeting medical conferences (AKU, rare diseases, rheumatology, clinical biochemistry, orthopaedics, general practitioners) did not lead to new identification in the UK but helped identify overseas cases. We are now aware of 626 patients worldwide including newly identified non-UK people with AKU in the following areas: Slovakia (208), the rest of Europe (including Turkey) (79), North America (including USA and Canada) (110), and the rest of the world (154). A mechanism for identifying individuals with AKU in the general population-not just in the UK but worldwide-has been established. Knowledge of patients with AKU, both in the UK and outside, is often confined to establishing their location in a particular GP practice or association with a particular medical professional. Mere identification, however, does not always lead to full engagement for epidemiological research purposes or targeting treatment since further barriers exist.

  10. Lessons Learned From Trials Targeting Cytokine Pathways in Patients With Inflammatory Bowel Diseases

    PubMed Central

    Abraham, Clara; Dulai, Parambir S.; Vermeire, Séverine; Sandborn, William J.

    2016-01-01

    Insights into the pathogenesis of inflammatory bowel diseases (IBD) have provided important information for the development of therapeutics. Levels of interleukin 23 (IL23) and T-helper (Th) 17 cell pathway molecules are elevated in inflamed intestinal tissues of patients with IBD. Loss of function variants of the interleukin 23 receptor gene (IL23R) protect against IBD, and in animals, blocking IL23 reduces severity of colitis. These findings indicated that the IL23 and Th17 cell pathways might be promising targets for treatment of IBD. Clinical trials have investigated the effects of agents designed to target distinct levels of the IL23 and Th17 cell pathways, and the results are providing insights into IBD pathogenesis and additional strategies for modulating these pathways. Strategies to reduce levels of proinflammatory cytokines more broadly and increase anti-inflammatory mechanisms are also emerging for treatment of IBD. The results from trials targeting these immune system pathways have provided important lessons for future trials. Findings indicate the importance of improving approaches to integrate patient features and biomarkers of response with selection of therapeutics. PMID:27780712

  11. Are concurrent systematic cores needed at the time of targeted biopsy in patients with prior negative prostate biopsies?

    PubMed

    Albisinni, S; Aoun, F; Noel, A; El Rassy, E; Lemort, M; Paesmans, M; van Velthoven, R; Roumeguère, T; Peltier, A

    2018-01-01

    MRI-guided targeted biopsies are advised in patients who have undergone an initial series of negative systematic biopsies, in whom prostate cancer (PCa) suspicion remains elevated. The aim of the study was to evaluate whether, in men with prior negative prostate biopsies, systematic cores are also warranted at the time of an MRI-targeted repeat biopsy. We enrolled patients with prior negative biopsy undergoing real time MRI/TRUS fusion guided prostate biopsy at our institute between 2014 and 2016. Patients with at least one index lesion on multiparametric MRI were included. All eligible patients underwent both systematic random biopsies (12-14 cores) and targeted biopsies (2-4 cores). The study included 74 men with a median age of 65 years, PSA level of 9.27ng/mL, and prostatic volume of 45ml. The overall PCa detection rate and the clinically significant cancer detection rate were 56.7% and 39.2%, respectively. Targeted cores demonstrated similar clinically significant PCa detection rate compared to systematic cores (33.8% vs. 28.4%, P=0.38) with significantly less tissue sampling. Indeed, a combination approach was significantly superior to a targeted-only in overall PCa detection (+16.7% overall detection rate, P=0.007). Although differences in clinically significant PCa detection were statistically non-significant (P=0.13), a combination approach did allow detecting 7 extra clinically significant PCas (+13.8%). In patients with elevated PSA and prior negative biopsies, concurrent systematic sampling may be needed at the time of targeted biopsy in order to maximize PCa detection rate. Larger studies are needed to validate our findings. 4. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  12. Population genetic structuring of methicillin-resistant Staphylococcus aureus clone EMRSA-15 within UK reflects patient referral patterns

    PubMed Central

    Reuter, Sandra; Scriberras, James; Reynolds, Rosy; Brown, Nicholas M.; Török, M. Estée; James, Richard; Network, East of England Microbiology Research; Aanensen, David M.; Bentley, Stephen D.; Holden, Matthew T. G.; Parkhill, Julian; Spratt, Brian G.; Peacock, Sharon J.

    2017-01-01

    Antibiotic resistance forms a serious threat to the health of hospitalised patients, rendering otherwise treatable bacterial infections potentially life-threatening. A thorough understanding of the mechanisms by which resistance spreads between patients in different hospitals is required in order to design effective control strategies. We measured the differences between bacterial populations of 52 hospitals in the United Kingdom and Ireland, using whole-genome sequences from 1085 MRSA clonal complex 22 isolates collected between 1998 and 2012. The genetic differences between bacterial populations were compared with the number of patients transferred between hospitals and their regional structure. The MRSA populations within single hospitals, regions and countries were genetically distinct from the rest of the bacterial population at each of these levels. Hospitals from the same patient referral regions showed more similar MRSA populations, as did hospitals sharing many patients. Furthermore, the bacterial populations from different time-periods within the same hospital were generally more similar to each other than contemporaneous bacterial populations from different hospitals. We conclude that, while a large part of the dispersal and expansion of MRSA takes place among patients seeking care in single hospitals, inter-hospital spread of resistant bacteria is by no means a rare occurrence. Hospitals are exposed to constant introductions of MRSA on a number of levels: (1) most MRSA is received from hospitals that directly transfer large numbers of patients, while (2) fewer introductions happen between regions or (3) across national borders, reflecting lower numbers of transferred patients. A joint coordinated control effort between hospitals, is therefore paramount for the national control of MRSA, antibiotic-resistant bacteria and other hospital-associated pathogens. PMID:29026654

  13. A New Suggestion for the Radiation Target Volume After a Subtotal Gastrectomy in Patients With Stomach Cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nam, Heerim; Lim, Do Hoon; Kim, Sung

    2008-06-01

    Purpose: To compare treatment results between the use of two different radiation fields including and excluding remnant stomach and suggest new target volumes excluding remnant stomach after subtotal gastrectomy (STG) in patients with stomach cancer. Methods and Materials: We retrospectively analyzed 291 patients treated with adjuvant chemoradiotherapy after STG and D2 dissection at the Samsung Medical Center, Seoul, South Korea. Eighty-three patients registered from 1995 to 1997 underwent irradiation according to the INT 0116 protocol that recommended the inclusion of remnant stomach within the target volume (Group A). After this period, we excluded remnant stomach from the target volume formore » 208 patients (Group B). Median follow-up was 67 months. Results: Treatment failure developed in 93 patients (32.0%). Local and regional recurrence rates for Group A vs. Group B were 10.8% vs. 5.3% (p = not significant) and 9.6% vs. 6.3% (p = not significant), and recurrence rates for remnant stomach were 7.2% vs. 1.4% (p = 0.018), respectively. Overall and disease-free survival rates were not different between the two groups. Grade 3 or 4 vomiting and diarrhea developed more frequently in Group A than Group B (4.8% vs. 1.4% and 6.0% vs. 1.9%, respectively; p = 0.012; p < 0.001). Conclusion: Exclusion of remnant stomach from the radiation field had no effect on failure rates or survival, and a low complication rate occurred in patients treated excluding remnant stomach. We suggest that remnant stomach be excluded from the radiation target volume for patients with stomach cancer who undergo STG and D2 dissection.« less

  14. Most at-risk populations: contextualising HIV prevention programmes targeting marginalised groups in Zanzibar, Tanzania.

    PubMed

    Ahmed, Naheed

    2014-09-01

    According to a 2009 UNAIDS report the HIV/AIDS prevalence rate in Zanzibar, Tanzania, is low in the general population (0.6%), but high among vulnerable groups, specifically sex workers (10.8%), injecting drug users (15.1%), and men who have sex with men (12.3%). In response to this concentrated epidemic, the Government of Zanzibar, international and local non-profit organisations have focused their prevention activities on these marginal populations. Although these efforts are beneficial in terms of disseminating information about HIV/AIDS and referring clients to health clinics, they fail to address how the socio-economic status of these groups places them at a greater risk for contracting and dying from the virus. Furthermore, there is an absence of qualitative research on these populations which is needed to understand the challenges these groups face and to improve the effectiveness of interventions. Through interviews with employees of government agencies and non-profit organisations, medical professionals, vulnerable populations and HIV/AIDS patients, this paper used a political economy of health and syndemic framework to examine how local realities inform and challenge HIV/AIDS programmes in Zanzibar.

  15. Contralateral Prophylactic Mastectomy Decisions in a Population-Based Sample of Patients With Early-Stage Breast Cancer.

    PubMed

    Jagsi, Reshma; Hawley, Sarah T; Griffith, Kent A; Janz, Nancy K; Kurian, Allison W; Ward, Kevin C; Hamilton, Ann S; Morrow, Monica; Katz, Steven J

    2017-03-01

    Contralateral prophylactic mastectomy (CPM) use is increasing among women with unilateral breast cancer, but little is known about treatment decision making or physician interactions in diverse patient populations. To evaluate patient motivations, knowledge, and decisions, as well as the impact of surgeon recommendations, in a large, diverse sample of patients who underwent recent treatment for breast cancer. A survey was sent to 3631 women with newly diagnosed, unilateral stage 0, I, or II breast cancer between July 2013 and September 2014. Women were identified through the population-based Surveillance Epidemiology and End Results registries of Los Angeles County and Georgia. Data on surgical decisions, motivations for those decisions, and knowledge were included in the analysis. Logistic and multinomial logistic regression of the data were conducted to identify factors associated with (1) CPM vs all other treatments combined, (2) CPM vs unilateral mastectomy (UM), and (3) CPM vs breast-conserving surgery (BCS). Associations between CPM receipt and surgeon recommendations were also evaluated. All statistical models and summary estimates were weighted to be representative of the target population. Receipt of CPM was the primary dependent variable for analysis and was measured by a woman's self-report of her treatment. Of the 3631 women selected to receive the survey, 2578 (71.0%) responded and 2402 of these respondents who did not have bilateral disease and for whom surgery type was known constituted the final analytic sample. The mean (SD) age was 61.8 (12) years at the time of the survey. Overall, 1301 (43.9%) patients considered CPM (601 [24.8%] considered it very strongly or strongly); only 395 (38.1%) of them knew that CPM does not improve survival for all women with breast cancer. Ultimately, 1466 women (61.6%) received BCS, 508 (21.2%) underwent UM, and 428 (17.3%) received CPM. On multivariable analysis, factors associated with CPM included younger age

  16. Comparing the effect of a decision aid plus patient navigation with usual care on colorectal cancer screening completion in vulnerable populations: study protocol for a randomized controlled trial

    PubMed Central

    2014-01-01

    CRC screening. Discussion This pragmatic randomized controlled trial will test a combined decision aid and patient navigator intervention targeting CRC screening completion. Findings from this trial may inform future interventions and implementation policies designed to promote CRC screening in vulnerable patient populations and to reduce screening disparities. Clinical trial registration ClinicalTrials.gov NCT02054598. PMID:25004983

  17. Comparing the effect of a decision aid plus patient navigation with usual care on colorectal cancer screening completion in vulnerable populations: study protocol for a randomized controlled trial.

    PubMed

    Brenner, Alison T; Getrich, Christina M; Pignone, Michael; Rhyne, Robert L; Hoffman, Richard M; McWilliams, Andrew; de Hernandez, Brisa Urquieta; Weaver, Mark A; Tapp, Hazel; Harbi, Khalil; Reuland, Daniel

    2014-07-08

    pragmatic randomized controlled trial will test a combined decision aid and patient navigator intervention targeting CRC screening completion. Findings from this trial may inform future interventions and implementation policies designed to promote CRC screening in vulnerable patient populations and to reduce screening disparities. ClinicalTrials.gov NCT02054598.

  18. Patient Loyalty in a Mature IDS Market: Is Population Health Management Worth It?

    PubMed Central

    Carlin, Caroline S

    2014-01-01

    Objective To understand patient loyalty to providers over time, informing effective population health management. Study Setting Patient care-seeking patterns over a 6-year timeframe in Minnesota, where care systems have a significant portion of their revenue generated by shared-saving contracts with public and private payers. Study Design Weibull duration and probit models were used to examine patterns of patient attribution to a care system and the continuity of patient affiliation with a care system. Clustering of errors within family unit was used to account for within-family correlation in unobserved characteristics that affect patient loyalty. Data Collection The payer provided data from health plan administrative files, matched to U.S. Census-based characteristics of the patient's neighborhood. Patients were retrospectively attributed to health care systems based on patterns of primary care. Principal Findings I find significant patient loyalty, with past loyalty a very strong predictor of future relationship. Relationships were shorter when the patient's health status was complex and when the patient's care system was smaller. Conclusions Population health management can be beneficial to the care system making this investment, particularly for patients exhibiting prior continuity in care system choice. The results suggest that co-located primary and specialty services are important in maintaining primary care loyalty. PMID:24461030

  19. Patient loyalty in a mature IDS market: is population health management worth it?

    PubMed

    Carlin, Caroline S

    2014-06-01

    To understand patient loyalty to providers over time, informing effective population health management. Patient care-seeking patterns over a 6-year timeframe in Minnesota, where care systems have a significant portion of their revenue generated by shared-saving contracts with public and private payers. Weibull duration and probit models were used to examine patterns of patient attribution to a care system and the continuity of patient affiliation with a care system. Clustering of errors within family unit was used to account for within-family correlation in unobserved characteristics that affect patient loyalty. The payer provided data from health plan administrative files, matched to U.S. Census-based characteristics of the patient's neighborhood. Patients were retrospectively attributed to health care systems based on patterns of primary care. I find significant patient loyalty, with past loyalty a very strong predictor of future relationship. Relationships were shorter when the patient's health status was complex and when the patient's care system was smaller. Population health management can be beneficial to the care system making this investment, particularly for patients exhibiting prior continuity in care system choice. The results suggest that co-located primary and specialty services are important in maintaining primary care loyalty. © Health Research and Educational Trust.

  20. Population pharmacokinetics of imipenem in critically ill patients with suspected ventilator-associated pneumonia and evaluation of dosage regimens

    PubMed Central

    Couffignal, Camille; Pajot, Olivier; Laouénan, Cédric; Burdet, Charles; Foucrier, Arnaud; Wolff, Michel; Armand-Lefevre, Laurence; Mentré, France; Massias, Laurent

    2014-01-01

    Aims Significant alterations in the pharmacokinetics (PK) of antimicrobials have been reported in critically ill patients. We describe PK parameters of imipenem in intensive care unit (ICU) patients with suspected ventilator-associated pneumonia and evaluate several dosage regimens. Methods This French multicentre, prospective, open-label study was conducted in ICU patients with a presumptive diagnosis of ventilator-associated pneumonia caused by Gram-negative bacilli, who empirically received imipenem intravenously every 8 h. Plasma imipenem concentrations were measured during the fourth imipenem infusion using six samples (trough, 0.5, 1, 2, 5 and 8 h). Data were analysed with a population approach using the stochastic approximation expectation maximization algorithm in Monolix 4.2. A Monte Carlo simulation was performed to evaluate the following six dosage regimens: 500, 750 or 1000 mg with administration every 6 or 8 h. The pharmacodynamic target was defined as the probability of achieving a fractional time above the minimal inhibitory concentration (MIC) of >40%. Results Fifty-one patients were included in the PK analysis. Imipenem concentration data were best described by a two-compartment model with three covariates (creatinine clearance, total bodyweight and serum albumin). Estimated clearance (between-subject variability) was 13.2 l h−1 (38%) and estimated central volume 20.4 l (31%). At an MIC of 4 μg ml−1, the probability of achieving 40% fractional time > MIC was 91.8% for 0.5 h infusions of 750 mg every 6 h, 86.0% for 1000 mg every 8 h and 96.9% for 1000 mg every 6 h. Conclusions This population PK model accurately estimated imipenem concentrations in ICU patients. The simulation showed that for these patients, the best dosage regimen of imipenem is 750 mg every 6 h and not 1000 mg every 8 h. PMID:24903189

  1. Population pharmacokinetics of imipenem in critically ill patients with suspected ventilator-associated pneumonia and evaluation of dosage regimens.

    PubMed

    Couffignal, Camille; Pajot, Olivier; Laouénan, Cédric; Burdet, Charles; Foucrier, Arnaud; Wolff, Michel; Armand-Lefevre, Laurence; Mentré, France; Massias, Laurent

    2014-11-01

    Significant alterations in the pharmacokinetics (PK) of antimicrobials have been reported in critically ill patients. We describe PK parameters of imipenem in intensive care unit (ICU) patients with suspected ventilator-associated pneumonia and evaluate several dosage regimens. This French multicentre, prospective, open-label study was conducted in ICU patients with a presumptive diagnosis of ventilator-associated pneumonia caused by Gram-negative bacilli, who empirically received imipenem intravenously every 8 h. Plasma imipenem concentrations were measured during the fourth imipenem infusion using six samples (trough, 0.5, 1, 2, 5 and 8 h). Data were analysed with a population approach using the stochastic approximation expectation maximization algorithm in Monolix 4.2. A Monte Carlo simulation was performed to evaluate the following six dosage regimens: 500, 750 or 1000 mg with administration every 6 or 8 h. The pharmacodynamic target was defined as the probability of achieving a fractional time above the minimal inhibitory concentration (MIC) of >40%. Fifty-one patients were included in the PK analysis. Imipenem concentration data were best described by a two-compartment model with three covariates (creatinine clearance, total bodyweight and serum albumin). Estimated clearance (between-subject variability) was 13.2 l h(-1) (38%) and estimated central volume 20.4 l (31%). At an MIC of 4 μg ml(-1) , the probability of achieving 40% fractional time > MIC was 91.8% for 0.5 h infusions of 750 mg every 6 h, 86.0% for 1000 mg every 8 h and 96.9% for 1000 mg every 6 h. This population PK model accurately estimated imipenem concentrations in ICU patients. The simulation showed that for these patients, the best dosage regimen of imipenem is 750 mg every 6 h and not 1000 mg every 8 h. © 2014 The British Pharmacological Society.

  2. Population-level impact of an accelerated HIV response plan to reach the UNAIDS 90-90-90 target in Côte d’Ivoire: Insights from mathematical modeling

    PubMed Central

    Diabaté, Souleymane; Alary, Michel; Diouf, Daouda; Abo, Kouamé; Boily, Marie-Claude

    2017-01-01

    Background National responses will need to be markedly accelerated to achieve the ambitious target of the Joint United Nations Programme on HIV/AIDS (UNAIDS). This target aims for 90% of HIV-positive individuals to be aware of their status, for 90% of those aware to receive antiretroviral therapy (ART), and for 90% of those on treatment to have a suppressed viral load by 2020, with each individual target reaching 95% by 2030. We aimed to estimate the impact of various treatment-as-prevention scenarios in Côte d’Ivoire, one of the countries with the highest HIV incidence in West Africa, with unmet HIV prevention and treatment needs, and where key populations are important to the broader HIV epidemic. Methods and findings An age-stratified dynamic model was developed and calibrated to epidemiological and programmatic data using a Bayesian framework. The model represents sexual and vertical HIV transmission in the general population, female sex workers (FSW), and men who have sex with men (MSM). We estimated the impact of scaling up interventions to reach the UNAIDS targets, as well as the impact of 8 other scenarios, on HIV transmission in adults and children, compared to our baseline scenario that maintains 2015 rates of testing, ART initiation, ART discontinuation, treatment failure, and levels of condom use. In 2015, we estimated that 52% (95% credible intervals: 46%–58%) of HIV-positive individuals were aware of their status, 72% (57%–82%) of those aware were on ART, and 77% (74%–79%) of those on ART were virologically suppressed. Reaching the UNAIDS targets on time would avert 50% (42%–60%) of new HIV infections over 2015–2030 compared to 30% (25%–36%) if the 90-90-90 target is reached in 2025. Attaining the UNAIDS targets in FSW, their clients, and MSM (but not in the rest of the population) would avert a similar fraction of new infections (30%; 21%–39%). A 25-percentage-point drop in condom use from the 2015 levels among FSW and MSM would

  3. Population-level impact of an accelerated HIV response plan to reach the UNAIDS 90-90-90 target in Côte d'Ivoire: Insights from mathematical modeling.

    PubMed

    Maheu-Giroux, Mathieu; Vesga, Juan F; Diabaté, Souleymane; Alary, Michel; Baral, Stefan; Diouf, Daouda; Abo, Kouamé; Boily, Marie-Claude

    2017-06-01

    National responses will need to be markedly accelerated to achieve the ambitious target of the Joint United Nations Programme on HIV/AIDS (UNAIDS). This target aims for 90% of HIV-positive individuals to be aware of their status, for 90% of those aware to receive antiretroviral therapy (ART), and for 90% of those on treatment to have a suppressed viral load by 2020, with each individual target reaching 95% by 2030. We aimed to estimate the impact of various treatment-as-prevention scenarios in Côte d'Ivoire, one of the countries with the highest HIV incidence in West Africa, with unmet HIV prevention and treatment needs, and where key populations are important to the broader HIV epidemic. An age-stratified dynamic model was developed and calibrated to epidemiological and programmatic data using a Bayesian framework. The model represents sexual and vertical HIV transmission in the general population, female sex workers (FSW), and men who have sex with men (MSM). We estimated the impact of scaling up interventions to reach the UNAIDS targets, as well as the impact of 8 other scenarios, on HIV transmission in adults and children, compared to our baseline scenario that maintains 2015 rates of testing, ART initiation, ART discontinuation, treatment failure, and levels of condom use. In 2015, we estimated that 52% (95% credible intervals: 46%-58%) of HIV-positive individuals were aware of their status, 72% (57%-82%) of those aware were on ART, and 77% (74%-79%) of those on ART were virologically suppressed. Reaching the UNAIDS targets on time would avert 50% (42%-60%) of new HIV infections over 2015-2030 compared to 30% (25%-36%) if the 90-90-90 target is reached in 2025. Attaining the UNAIDS targets in FSW, their clients, and MSM (but not in the rest of the population) would avert a similar fraction of new infections (30%; 21%-39%). A 25-percentage-point drop in condom use from the 2015 levels among FSW and MSM would reduce the impact of reaching the UNAIDS targets

  4. Increased risk of chronic obstructive pulmonary disease in patients with bipolar disorder: A population-based study.

    PubMed

    Hsu, Jer-Hwa; Chien, I-Chia; Lin, Ching-Heng

    2017-10-01

    We conducted this nationwide study to examine the prevalence and incidence of chronic obstructive pulmonary disease (COPD) among patients with bipolar disorder in Taiwan. We used a random sample of 766,427 subjects who were aged ≥18 years in 2005. Patients with at least one primary diagnosis of bipolar disorder were identified. Study participants with one primary or secondary diagnosis of COPD for either ambulatory or inpatient care were also identified. We compared the prevalence of COPD in patients with bipolar disorder and the general population in 2005. In addition, we further investigated this cohort from 2006 to 2010 to detect incident cases of COPD in patients with bipolar disorder compared with the general population. The factors associated with COPD among patients with bipolar disorder were also analyzed. The prevalence of COPD in patients with bipolar disorder was higher than in the general population in 2005 (5.68% vs. 2.88%, odds ratio 2.03; 95% confidence interval, 1.53-2.67). The average annual incidence of COPD in patients with bipolar disorder was also higher than in the general population (2.03% vs. 1.03%, risk ratio 1.94; 95% confidence interval, 1.65-2.29) from 2006 to 2010. Some risk factors for COPD such as substance use, obesity, or lifestyle pattern were not available in this study. Patients with bipolar disorder had a higher prevalence and incidence of COPD compared with the general population. Higher prevalence of COPD among bipolar patients was associated with increased age, males, hypertension, and second-generation antidepressant use. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Population genomics of C. melanopterus using target gene capture data: demographic inferences and conservation perspectives

    PubMed Central

    Maisano Delser, Pierpaolo; Corrigan, Shannon; Hale, Matthew; Li, Chenhong; Veuille, Michel; Planes, Serge; Naylor, Gavin; Mona, Stefano

    2016-01-01

    Population genetics studies on non-model organisms typically involve sampling few markers from multiple individuals. Next-generation sequencing approaches open up the possibility of sampling many more markers from fewer individuals to address the same questions. Here, we applied a target gene capture method to deep sequence ~1000 independent autosomal regions of a non-model organism, the blacktip reef shark (Carcharhinus melanopterus). We devised a sampling scheme based on the predictions of theoretical studies of metapopulations to show that sampling few individuals, but many loci, can be extremely informative to reconstruct the evolutionary history of species. We collected data from a single deme (SID) from Northern Australia and from a scattered sampling representing various locations throughout the Indian Ocean (SCD). We explored the genealogical signature of population dynamics detected from both sampling schemes using an ABC algorithm. We then contrasted these results with those obtained by fitting the data to a non-equilibrium finite island model. Both approaches supported an Nm value ~40, consistent with philopatry in this species. Finally, we demonstrate through simulation that metapopulations exhibit greater resilience to recent changes in effective size compared to unstructured populations. We propose an empirical approach to detect recent bottlenecks based on our sampling scheme. PMID:27651217

  6. Population genomics of C. melanopterus using target gene capture data: demographic inferences and conservation perspectives.

    PubMed

    Maisano Delser, Pierpaolo; Corrigan, Shannon; Hale, Matthew; Li, Chenhong; Veuille, Michel; Planes, Serge; Naylor, Gavin; Mona, Stefano

    2016-09-21

    Population genetics studies on non-model organisms typically involve sampling few markers from multiple individuals. Next-generation sequencing approaches open up the possibility of sampling many more markers from fewer individuals to address the same questions. Here, we applied a target gene capture method to deep sequence ~1000 independent autosomal regions of a non-model organism, the blacktip reef shark (Carcharhinus melanopterus). We devised a sampling scheme based on the predictions of theoretical studies of metapopulations to show that sampling few individuals, but many loci, can be extremely informative to reconstruct the evolutionary history of species. We collected data from a single deme (SID) from Northern Australia and from a scattered sampling representing various locations throughout the Indian Ocean (SCD). We explored the genealogical signature of population dynamics detected from both sampling schemes using an ABC algorithm. We then contrasted these results with those obtained by fitting the data to a non-equilibrium finite island model. Both approaches supported an Nm value ~40, consistent with philopatry in this species. Finally, we demonstrate through simulation that metapopulations exhibit greater resilience to recent changes in effective size compared to unstructured populations. We propose an empirical approach to detect recent bottlenecks based on our sampling scheme.

  7. The relationship of quality of life and distress in prostate cancer patients compared to the general population.

    PubMed

    Zenger, Markus; Lehmann-Laue, Antje; Stolzenburg, Jens-Uwe; Schwalenberg, Thilo; Ried, Alexander; Hinz, Andreas

    2010-06-30

    The aim of this study is two-fold. The first part compares quality of life (QoL) data of prostate cancer patients with those of a representative and age-specific sample of the general population and analyzes the influence of cancer related as well as socio-demographic parameters on QoL. Secondly, differences in QoL depending on the experienced psychological distress will be shown both in prostate cancer patients and in the general population. A sample of 265 prostate cancer patients completed both the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the Hospital Anxiety and Depression Scale (HADS) during their stay in the hospital. A total HADS cut off score of 15 was used to indicate psychological distress and significant emotional concerns in patients and men of the general population. The results of the patients were compared with those of the general population (N=444). Prostate cancer patients reported significantly worse levels of social and emotional functioning as well as more symptoms like insomnia, constipation and diarrhea compared to the general population. Patients and men of the general population with a total HADS score >/=15 reported lower QoL in all sub-scales except for diarrhea in comparison to people without distress. Psychological distress is accompanied by lower QoL and therefore should be taken into consideration when QoL is assessed. Furthermore, clinicians should be trained by professionals to detect distress in their patients and to pay more attention to their emotional concerns, which are strongly associated with the patients' well-being and QoL during their stay in hospital.

  8. Increased Risk of Cerebrovascular Disease Among Patients With Neurofibromatosis Type 1: Population-Based Approach.

    PubMed

    Terry, Anna R; Jordan, Justin T; Schwamm, Lee; Plotkin, Scott R

    2016-01-01

    Although neurofibromatosis type 1 (NF1) may be associated with an incompletely understood vasculopathy, relative odds of stroke in this population is not known. Using the 1998 to 2009 US Nationwide Inpatient Sample, we performed a case-control study matching cases of NF1 to controls without such a diagnosis. We then compared the odds of stroke between the 2 groups. We used multivariable logistic regression to adjust for known or suspected confounders. NF1 was associated with younger mean age at the time of stroke (41 versus 48) and a lower prevalence of stroke risk factors among adult patients. Pediatric patients with NF1, however, were more likely to have hypertension. Patients with NF1 were significantly more likely to be diagnosed with any stroke (odds ratio, 1.2; P<0.0001) than the general population. The odds of intracerebral hemorrhage were greatest among hemorrhagic stroke types analyzed (odds ratio, 1.9; P<0.0001). In the pediatric NF1 population, the odds of intracerebral hemorrhage were more dramatically elevated (odds ratio, 8.1; P<0.0001). The odds of ischemic stroke were also increased with NF1 in the pediatric (odds ratio, 3.4; P<0.0001) but not in the adult population. When compared with the general population, the odds of any type of stroke are significantly increased for patients with NF1, both adult and pediatric. This risk is most notable for hemorrhagic strokes although it is also increased for ischemic strokes in children. Physicians should be aware of the increased risk of stroke in this population, and consider stroke as a potential cause of new neurological symptoms. © 2015 American Heart Association, Inc.

  9. Systematic Compared With Targeted Staging with Endobronchial Ultrasound in Patients with Lung Cancer.

    PubMed

    Sanz-Santos, José; Serra, Pere; Torky, Mohamed; Andreo, Felipe; Centeno, Carmen; Mendiluce, Leire; Martínez-Barenys, Carlos; López de Castro, Pedro; Ruiz-Manzano, Juan

    2018-04-06

    To evaluate the accuracy of systematic mediastinal staging by endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) (sampling of all visible nodes measuring ≥5mm from stations N3 to N1 regardless of their positron emission tomography/computed tomography (PET/CT) features) and compare this staging approach with targeted EBUS-TBNA staging (sampling only 18F-fluorodeoxyglucose (FDG)-avid nodes) in patients with N2 non-small cell lung cancer (NSCLC) on PET/CT. Retrospective study of 107 patients who underwent systematic EBUS-TBNA mediastinal staging. The results were compared with those of a hypothetical scenario where only FDG-avid nodes on PET/CT would be sampled. Systematic EBUS-TBNA sampling demonstrated N3 disease in 3 patients, N2 disease in 60 (42 single-station or N2a, 18 multiple-station or N2b) and N0/N1 disease in 44. Of these 44, seven underwent mediastinoscopy, which did not show mediastinal disease; six of the seven proceeded to lung resection, which also showed no mediastinal disease. Thirty-four N0/N1 patients after EBUS-TBNA underwent lung resection directly: N0/N1 was found in 30 and N2 in four (one N2b with a PET/CT showing N2a disease, three N2a). Sensitivity, specificity, negative predictive value, positive predictive value, and overall accuracy of systematic EBUS-TBNA were 94%, 100%, 90%, 100% and 96%, respectively. Compared to targeted EBUS-TBNA, systematic EBUS-TBNA sampling provided additional important clinical information in 14 cases (13%): three N3 cases would have passed unnoticed, and 11 N2b cases would have been staged as N2a. In clinical practice, systematic sampling of the mediastinum by EBUS-TBNA, regardless of PET/CT features, is to be recommended over targeted sampling. Copyright © 2018. Published by Elsevier Inc.

  10. Hand hygiene compliance in patients under contact precautions and in the general hospital population.

    PubMed

    Almaguer-Leyva, Martín; Mendoza-Flores, Lidia; Medina-Torres, Ana Gabriela; Salinas-Caballero, Ana Gabriela; Vidaña-Amaro, Jose Antonio; Garza-Gonzalez, Elvira; Camacho-Ortiz, Adrián

    2013-11-01

    Hand hygiene (HH) is the single most important intervention for preventing hospital-acquired infections. Contact precautions are a series of actions that infection control units take to reduce the transmission of nosocomial pathogens. We conducted an observational study of HH compliance. Observations were stratified as opportunities in patients under contact precautions and in the general hospital population. Trained infection control personnel performed all direct evaluations. A total of 3,270 opportunities were recorded. HH compliance was statistically higher in patients on contact precautions than in the overall population (70.3% vs 60.4%; P = .0001). Critical care areas had higher HH compliance when patients were isolated by contact precautions. Medical wards were statistically lower in HH when patients were under contact precautions. Respiratory technicians had the highest HH compliance in both overall performance and in patients under contact precautions. Medical students had a lower HH compliance in both evaluations (P < .001). We noted greater compliance with HH practices when patients were under contact precaution in comparison with the overall hospital population. The difference was stronger in intensive care areas and lower among medical students. Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

  11. Electronic health record use to classify patients with newly diagnosed versus preexisting type 2 diabetes: infrastructure for comparative effectiveness research and population health management.

    PubMed

    Kudyakov, Rustam; Bowen, James; Ewen, Edward; West, Suzanne L; Daoud, Yahya; Fleming, Neil; Masica, Andrew

    2012-02-01

    Use of electronic health record (EHR) content for comparative effectiveness research (CER) and population health management requires significant data configuration. A retrospective cohort study was conducted using patients with diabetes followed longitudinally (N=36,353) in the EHR deployed at outpatient practice networks of 2 health care systems. A data extraction and classification algorithm targeting identification of patients with a new diagnosis of type 2 diabetes mellitus (T2DM) was applied, with the main criterion being a minimum 30-day window between the first visit documented in the EHR and the entry of T2DM on the EHR problem list. Chart reviews (N=144) validated the performance of refining this EHR classification algorithm with external administrative data. Extraction using EHR data alone designated 3205 patients as newly diagnosed with T2DM with classification accuracy of 70.1%. Use of external administrative data on that preselected population improved classification accuracy of cases identified as new T2DM diagnosis (positive predictive value was 91.9% with that step). Laboratory and medication data did not help case classification. The final cohort using this 2-stage classification process comprised 1972 patients with a new diagnosis of T2DM. Data use from current EHR systems for CER and disease management mandates substantial tailoring. Quality between EHR clinical data generated in daily care and that required for population health research varies. As evidenced by this process for classification of newly diagnosed T2DM cases, validation of EHR data with external sources can be a valuable step.

  12. Massively Parallel Sequencing of Patients with Intellectual Disability, Congenital Anomalies and/or Autism Spectrum Disorders with a Targeted Gene Panel

    PubMed Central

    Brett, Maggie; McPherson, John; Zang, Zhi Jiang; Lai, Angeline; Tan, Ee-Shien; Ng, Ivy; Ong, Lai-Choo; Cham, Breana; Tan, Patrick; Rozen, Steve; Tan, Ene-Choo

    2014-01-01

    Developmental delay and/or intellectual disability (DD/ID) affects 1–3% of all children. At least half of these are thought to have a genetic etiology. Recent studies have shown that massively parallel sequencing (MPS) using a targeted gene panel is particularly suited for diagnostic testing for genetically heterogeneous conditions. We report on our experiences with using massively parallel sequencing of a targeted gene panel of 355 genes for investigating the genetic etiology of eight patients with a wide range of phenotypes including DD/ID, congenital anomalies and/or autism spectrum disorder. Targeted sequence enrichment was performed using the Agilent SureSelect Target Enrichment Kit and sequenced on the Illumina HiSeq2000 using paired-end reads. For all eight patients, 81–84% of the targeted regions achieved read depths of at least 20×, with average read depths overlapping targets ranging from 322× to 798×. Causative variants were successfully identified in two of the eight patients: a nonsense mutation in the ATRX gene and a canonical splice site mutation in the L1CAM gene. In a third patient, a canonical splice site variant in the USP9X gene could likely explain all or some of her clinical phenotypes. These results confirm the value of targeted MPS for investigating DD/ID in children for diagnostic purposes. However, targeted gene MPS was less likely to provide a genetic diagnosis for children whose phenotype includes autism. PMID:24690944

  13. Population targeting amid complex mental health programming: Are California's Full Service Partnerships reaching underserved children?

    PubMed

    Cordell, Katharan D; Snowden, Lonnie R

    2017-01-01

    California's Mental Health Services Act (MHSA) created Full Service Partnership programs (FSPs) targeting socially and economically vulnerable children with mental illness who are underserved by counties' public mental health treatment system. To determine whether FSPs reach a distinctive group of children, this study compares indicators of FSP-targeted underservice for FSP entrants (n = 15,598) versus everyone treated in the counties' public mental health systems (n = 282,178) and for FSP entrants versus entrants in the most intensive Medicaid delivered program in California, Therapeutic Behavioral Services (TBS, n = 11,993). Results identify that, despite first encountering mental health services systems at earlier ages, FSP clients had fewer months of treatment and were less likely to have been treated in the prior 6 months, except for crisis care, as compared to all other children served, after considering clinical severity and indicators of service need. FSP entrants also had more substance abuse and trauma-related problems. Although less seriously ill than TBS served children, FSP served children were significantly underserved. The results indicate that, amid overlapping policies and programs, carving out and reaching a distinctly underserved population can be achieved in practice, and that specialized programs, such as the FSP program, which target underserved children, have the potential to augment a system's ability to reach the underserved. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  14. Target location after deep cerebral biopsies using low-volume air injection in 75 patients. Results and technical note.

    PubMed

    Poca, Maria A; Martínez-Ricarte, Francisco-Ramon; Gándara, Dario F; Coscojuela, Pilar; Martínez-Sáez, Elena; Sahuquillo, Juan

    2017-10-01

    Stereotactic biopsy is a minimally invasive technique that allows brain tissue samples to be obtained with low risk. Classically, different techniques have been used to identify the biopsy site after surgery. To describe a technique to identify the precise location of the target in the postoperative CT scan using the injection of a low volume of air into the biopsy cannula. Seventy-five biopsies were performed in 65 adults and 10 children (40 males and 35 females, median age 51 years). Frame-based biopsy was performed in 46 patients, while frameless biopsy was performed in the remaining 29 patients. In both systems, after brain specimens had been collected and with the biopsy needle tip in the center of the target, a small volume of air (median 0.7 cm 3 ) was injected into the site. A follow-up CT scan was performed in all patients. Intracranial air in the selected target was present in 69 patients (92%). No air was observed in two patients (air volume administered in these 2 cases was below 0.7 cm 3 ), while in the remaining four patients blood content was observed in the target. The diagnostic yield in this series was 97.3%. No complications were found to be associated with intracranial air injection in any of the 75 patients who underwent this procedure. The air-injection maneuver proposed for use in stereotactic biopsies of intracranial mass lesions is a safe and reliable technique that allows the exact biopsy site to be located without any related complications.

  15. Continuous subcutaneous insulin infusion in diabetes: patient populations, safety, efficacy, and pharmacoeconomics.

    PubMed

    Pozzilli, Paolo; Battelino, Tadej; Danne, Thomas; Hovorka, Roman; Jarosz-Chobot, Przemyslawa; Renard, Eric

    2016-01-01

    The level of glycaemic control necessary to achieve optimal short-term and long-term outcomes in subjects with type 1 diabetes mellitus (T1DM) typically requires intensified insulin therapy using multiple daily injections or continuous subcutaneous insulin infusion. For continuous subcutaneous insulin infusion, the insulins of choice are the rapid-acting insulin analogues, insulin aspart, insulin lispro and insulin glulisine. The advantages of continuous subcutaneous insulin infusion over multiple daily injections in adult and paediatric populations with T1DM include superior glycaemic control, lower insulin requirements and better health-related quality of life/patient satisfaction. An association between continuous subcutaneous insulin infusion and reduced hypoglycaemic risk is more consistent in children/adolescents than in adults. The use of continuous subcutaneous insulin infusion is widely recommended in both adult and paediatric T1DM populations but is limited in pregnant patients and those with type 2 diabetes mellitus. All available rapid-acting insulin analogues are approved for use in adult, paediatric and pregnant populations. However, minimum patient age varies (insulin lispro: no minimum; insulin aspart: ≥2 years; insulin glulisine: ≥6 years) and experience in pregnancy ranges from extensive (insulin aspart, insulin lispro) to limited (insulin glulisine). Although more expensive than multiple daily injections, continuous subcutaneous insulin infusion is cost-effective in selected patient groups. This comprehensive review focuses on the European situation and summarises evidence for the efficacy and safety of continuous subcutaneous insulin infusion, particularly when used with rapid-acting insulin analogues, in adult, paediatric and pregnant populations. The review also discusses relevant European guidelines; reviews issues that surround use of this technology; summarises the effects of continuous subcutaneous insulin infusion on patients

  16. Continuous subcutaneous insulin infusion in diabetes: patient populations, safety, efficacy, and pharmacoeconomics

    PubMed Central

    Battelino, Tadej; Danne, Thomas; Hovorka, Roman; Jarosz‐Chobot, Przemyslawa; Renard, Eric

    2015-01-01

    Summary The level of glycaemic control necessary to achieve optimal short‐term and long‐term outcomes in subjects with type 1 diabetes mellitus (T1DM) typically requires intensified insulin therapy using multiple daily injections or continuous subcutaneous insulin infusion. For continuous subcutaneous insulin infusion, the insulins of choice are the rapid‐acting insulin analogues, insulin aspart, insulin lispro and insulin glulisine. The advantages of continuous subcutaneous insulin infusion over multiple daily injections in adult and paediatric populations with T1DM include superior glycaemic control, lower insulin requirements and better health‐related quality of life/patient satisfaction. An association between continuous subcutaneous insulin infusion and reduced hypoglycaemic risk is more consistent in children/adolescents than in adults. The use of continuous subcutaneous insulin infusion is widely recommended in both adult and paediatric T1DM populations but is limited in pregnant patients and those with type 2 diabetes mellitus. All available rapid‐acting insulin analogues are approved for use in adult, paediatric and pregnant populations. However, minimum patient age varies (insulin lispro: no minimum; insulin aspart: ≥2 years; insulin glulisine: ≥6 years) and experience in pregnancy ranges from extensive (insulin aspart, insulin lispro) to limited (insulin glulisine). Although more expensive than multiple daily injections, continuous subcutaneous insulin infusion is cost‐effective in selected patient groups. This comprehensive review focuses on the European situation and summarises evidence for the efficacy and safety of continuous subcutaneous insulin infusion, particularly when used with rapid‐acting insulin analogues, in adult, paediatric and pregnant populations. The review also discusses relevant European guidelines; reviews issues that surround use of this technology; summarises the effects of continuous subcutaneous insulin

  17. The ciprofloxacin target AUC : MIC ratio is not reached in hospitalized patients with the recommended dosing regimens.

    PubMed

    Haeseker, Michiel; Stolk, Leo; Nieman, Fred; Hoebe, Christian; Neef, Cees; Bruggeman, Cathrien; Verbon, Annelies

    2013-01-01

    The aim of this study was to determine the ciprofloxacin serum concentrations in hospitalized patients and to determine which percentage reached the efficacy target of AUC : MIC > 125. Additionally, the influence of demographic anthropomorphic and clinical parameters on the pharmacokinetics and pharmacodynamics of ciprofloxacin were investigated. In serum of 80 hospitalized patients ciprofloxacin concentrations were measured with reverse phase high performance liquid chromatography with fluorescence detection. The ciprofloxacin dose was 400-1200 mg day(-1) i.v. in two or three doses depending on renal function and causative bacteria. Pharmacokinetic parameters were calculated with maximum a posteriori Bayesian estimation (MW\\PHARM 3.60). A two compartment open model was used. Mean (± SD) age was 66 (± 17) years, the mean clearance corrected for bodyweight was 0.24 l h(-1) kg(-1) and the mean AUC was 49 mg l(-1) h. Ciprofloxacin clearance and thus AUC were associated with both age and serum creatinine. Of all patients, 21% and 75% of the patients, did not reach the proposed ciprofloxacin AUC : MIC > 125 target with MICs of 0.25 and 0.5 mg l(-1), respectively. A computer simulated increase in the daily dose from 800 mg to 1200 mg, decreased these percentages to 1% and 37%, respectively. A substantial proportion of the hospitalized patients did not reach the target ciprofloxacin AUC : MIC and are suboptimally dosed with recommended doses. Taking into account the increasing resistance to ciprofloxacin worldwide, a ciprofloxacin dose of 1200 mg i.v. daily in patients with normal renal function is necessary to reach the targeted AUC : MIC > 125. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

  18. Patient Populations, Clinical Associations, and System Efficiency in Healthcare Delivery System

    NASA Astrophysics Data System (ADS)

    Liu, Yazhuo

    The efforts to improve health care delivery usually involve studies and analysis of patient populations and healthcare systems. In this dissertation, I present the research conducted in the following areas: identifying patient groups, improving treatments for specific conditions by using statistical as well as data mining techniques, and developing new operation research models to increase system efficiency from the health institutes' perspective. The results provide better understanding of high risk patient groups, more accuracy in detecting disease' correlations and practical scheduling tools that consider uncertain operation durations and real-life constraints.

  19. Employment among Patients with Multiple Sclerosis-A Population Study

    PubMed Central

    Bøe Lunde, Hanne Marie; Telstad, Wenche; Grytten, Nina; Kyte, Lars; Aarseth, Jan; Myhr, Kjell-Morten; Bø, Lars

    2014-01-01

    Objective To investigate demographic and clinical factors associated with employment in MS. Methods The study included 213 (89.9%) of all MS patients in Sogn and Fjordane County, Western Norway at December 31st 2010. The patients underwent clinical evaluation, structured interviews and completed self-reported questionnaires. Demographic and clinical factors were compared between patients being employed versus patients being unemployed and according to disease course of MS. Logistic regression analysis was used to identify factors independently associated with current employment. Results After a mean disease duration of almost 19 years, 45% of the population was currently full-time or part- time employed. Patients with relapsing –remitting MS (RRMS) had higher employment rate than patients with secondary (SPMS) and primary progressive (PPMS). Higher educated MS patients with lower age at onset, shorter disease duration, less severe disability and less fatigue were most likely to be employed. Conclusions Nearly half of all MS patients were still employed after almost two decades of having MS. Lower age at onset, shorter disease duration, higher education, less fatigue and less disability were independently associated with current employment. These key clinical and demographic factors are important to understand the reasons to work ability in MS. The findings highlight the need for environmental adjustments at the workplace to accommodate individual ’s needs in order to improve working ability among MS patients. PMID:25054972

  20. Employment among patients with multiple sclerosis-a population study.

    PubMed

    Bøe Lunde, Hanne Marie; Telstad, Wenche; Grytten, Nina; Kyte, Lars; Aarseth, Jan; Myhr, Kjell-Morten; Bø, Lars

    2014-01-01

    To investigate demographic and clinical factors associated with employment in MS. The study included 213 (89.9%) of all MS patients in Sogn and Fjordane County, Western Norway at December 31st 2010. The patients underwent clinical evaluation, structured interviews and completed self-reported questionnaires. Demographic and clinical factors were compared between patients being employed versus patients being unemployed and according to disease course of MS. Logistic regression analysis was used to identify factors independently associated with current employment. After a mean disease duration of almost 19 years, 45% of the population was currently full-time or part- time employed. Patients with relapsing -remitting MS (RRMS) had higher employment rate than patients with secondary (SPMS) and primary progressive (PPMS). Higher educated MS patients with lower age at onset, shorter disease duration, less severe disability and less fatigue were most likely to be employed. Nearly half of all MS patients were still employed after almost two decades of having MS. Lower age at onset, shorter disease duration, higher education, less fatigue and less disability were independently associated with current employment. These key clinical and demographic factors are important to understand the reasons to work ability in MS. The findings highlight the need for environmental adjustments at the workplace to accommodate individual 's needs in order to improve working ability among MS patients.

  1. Comparison of Prevalence and Types of Mutations in Lung Cancers Among Black and White Populations.

    PubMed

    Campbell, Joshua D; Lathan, Christopher; Sholl, Lynette; Ducar, Matthew; Vega, Mikenah; Sunkavalli, Ashwini; Lin, Ling; Hanna, Megan; Schubert, Laura; Thorner, Aaron; Faris, Nicholas; Williams, David R; Osarogiagbon, Raymond U; van Hummelen, Paul; Meyerson, Matthew; MacConaill, Laura

    2017-06-01

    Lung cancer is the leading cause of cancer death in the United States in all ethnic and racial groups. The overall death rate from lung cancer is higher in black patients than in white patients. To compare the prevalence and types of somatic alterations between lung cancers from black patients and white patients. Differences in mutational frequencies could illuminate differences in prognosis and lead to the reduction of outcome disparities by more precisely targeting patients' treatment. Tumor specimens were collected from Baptist Cancer Center (Memphis, Tennessee) over the course of 9 years (January 2004-December 2012). Genomic analysis by massively parallel sequencing of 504 cancer genes was performed at Dana-Farber Cancer Institute (Boston, Massachusetts). Overall, 509 lung cancer tumors specimens (319 adenocarcinomas; 142 squamous cell carcinomas) were profiled from 245 black patients and 264 white patients. The frequencies of genomic alterations were compared between tumors from black and white populations. Overall, 509 lung cancers were collected and analyzed (273 women [129 black patients; 144 white patients] and 236 men [116 black patients; 120 white patients]). Using 313 adenocarcinomas and 138 squamous cell carcinomas with genetically supported ancestry, overall mutational frequencies and copy number changes were not significantly different between black and white populations in either tumor type after correcting for multiple hypothesis testing. Furthermore, specific activating alterations in members of the receptor tyrosine kinase/Ras/Raf pathway including EGFR and KRAS were not significantly different between populations in lung adenocarcinoma. These results demonstrate that lung cancers from black patients are similar to cancers from white patients with respect to clinically actionable genomic alterations and suggest that clinical trials of targeted therapies could significantly benefit patients in both groups.

  2. Targeting higher ferritin concentrations with intravenous iron dextran lowers erythropoietin requirement in hemodialysis patients.

    PubMed

    DeVita, M V; Frumkin, D; Mittal, S; Kamran, A; Fishbane, S; Michelis, M F

    2003-11-01

    Although clinical use of recombinant human erythropoietin (rHuEPO) since 1989 has improved anemia in most end-stage renal disease patients, there are still many hemodialysis patients unable to maintain an adequate hematocrit (HCT) without large doses of rHuEPO. This suggests that anemia is not solely a consequence of rHuEPO deficiency, but may be due to other factors including functional iron deficiency. Since the optimal prescription for iron replacement is not yet known, we evaluated the effect of intravenous iron dextran (IVFe) infusion on serum ferritin (SFer) concentration and rHuEPO dose. Our objective was to raise and maintain serum ferritin concentrations to 2 different levels above the National Kidney Foundation Dialysis Outcome Quality Initiative standard of 100 ng/ml to determine whether, and by what degree rHuEPO dose could be lowered. HD patients on i.v. rHuEPO with a SFer concentration > or = 70 ng/ml and an HCT of < or = 33% were enrolled. Subjects were divided as follows: Group 1: target SFer of 200 ng/ml, Group 2: target SFer of 400 ng/ml. Each subject below the target level received IVFe in up to 10 divided doses during consecutive dialysis sessions as needed to reach the target. HCT was maintained between 32.5% and 36% by adjusting rHuEPO dosage. Mean SFer concentration at the study conclusion in Group 1: 261 ng/ml; Group 2: 387 ng/ml. The mean decrease in rHuEPO dose for Group 1 was 31 U/kg body weight/week (250 - 219 U/kg bw/wk) while in Group 2 it was 154 U/kg body weight/week (312 - 158 U/kg bw/wk) (p < 0.001). There was no difference in HCT between groups. Our results suggest that higher target serum ferritin concentrations can be well tolerated and lower rHuEPO requirements.

  3. Impact of high lipoprotein(a) levels on in-stent restenosis and long-term clinical outcomes of angina pectoris patients undergoing percutaneous coronary intervention with drug-eluting stents in Asian population.

    PubMed

    Park, Sang-Ho; Rha, Seung-Woon; Choi, Byoung-Geol; Park, Ji-Young; Jeon, Ung; Seo, Hong-Seog; Kim, Eung-Ju; Na, Jin-Oh; Choi, Cheol-Ung; Kim, Jin-Won; Lim, Hong-Euy; Park, Chang-Gyu; Oh, Dong-Joo

    2015-06-01

    Lipoprotein(a) (Lp(a)) is known to be associated with cardiovascular complications and atherothrombotic properties in general populations. However, it has not been examined whether Lp(a) levels are able to predict adverse cardiovascular outcomes in patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES). A total of 595 consecutive patients with angina pectoris who underwent elective PCI with DES were enrolled from 2004 to 2010. The patients were divided into two groups according to the levels of Lp(a): Lp(a) < 50 mg/dL (n = 485 patients), and Lp(a) ≥ 50 mg/dL (n = 111 patients). The 6-9-month angiographic outcomes and 3-year cumulative major clinical outcomes were compared between the two groups. Binary restenosis occurred in 26 of 133 lesions (19.8%) in the high Lp(a) group and 43 of 550 lesions (7.9%) in the low Lp(a) group (P = 0.001). In multivariate analysis, the reference vessel diameter, low density lipoprotein cholesterol, total lesion length, and Lp(a) ≥ 50 mg/dL were predictors of binary restenosis. In the Cox proportional hazards regression analysis, Lp(a) > 50 mg/dL was significantly associated with the 3-year adverse clinical outcomes including any myocardial infarction, revascularization (target lesion revascularization (TLR) and target vessel revascularization (TVR)), TLR-major adverse cardiac events (MACEs), TVR-MACE, and All-MACEs. In our study, high Lp(a) level ≥ 50 mg/dL in angina pectoris patients undergoing elective PCI with DES was significantly associated with binary restenosis and 3-year adverse clinical outcomes in an Asian population. © 2015 Wiley Publishing Asia Pty Ltd.

  4. Changes in quality of life over time--Dutch haemodialysis patients and general population compared.

    PubMed

    Mazairac, Albert H A; de Wit, G Ardine; Penne, E Lars; van der Weerd, Neelke C; de Jong, Boudewijn; Grooteman, Muriel P C; van den Dorpel, Marinus A; Buskens, Erik; Dekker, Friedo W; Nubé, Menso J; Ter Wee, Piet M; Boeschoten, Els W; Bots, Michiel L; Blankestijn, Peter J

    2011-06-01

    Improving the health-related quality of life (HRQOL) for haemodialysis patients is a considerable challenge. The aim of the present study was to compare changes in HRQOL in haemodialysis patients with those observed in the general population over a 10-year period and explore factors that might explain possible differences. We compared 126 haemodialysis patients assessed in 1995 in the Netherlands Cooperative Study on the Adequacy of Dialysis-1 (NECOSAD-I) with 515 patients enrolled in 2006 in the ongoing Convective Transport Study (CONTRAST). Changes in HRQOL in these cohorts were compared with two representative samples from the general Dutch population, assessed in 1992 (n = 1,063) and 2001 (n = 10,600). HRQOL was measured with the SF-36 questionnaire. Differences in HRQOL were analysed with ANCOVA to adjust for demographic variables. To assess possible differences, we used multivariable regression analysis. HRQOL in haemodialysis patients in 2006 [CONTRAST, mean age 63 ± 14 years (SD), 62% male] was significantly better than in 1995 (NECOSAD-I, 59 ± 16 years, 53% male) in four domains of the SF-36: bodily pain (+ 5 points, P = 0.009), vitality (+ 7, P < 0.001), role-emotional (+ 14, P < 0.001) and mental health (+ 8, P < 0.001), after adjusting for demographic variables. This increment could partly be explained by improved haemoglobin and phosphate levels. Compared to the general population, HRQOL improvement was most outspoken in two domains: bodily pain (+ 6, P = 0.01) and role-emotional (+ 8, P = 0.007). This study showed an improvement of HRQOL in haemodialysis patients over an 11-year period of time, independent of global changes in the general population.

  5. A comparative study of symptoms and quality of life among patients with breast cancer receiving target, chemotherapy, or combined therapy.

    PubMed

    Huang, Sheng-Miauh; Tai, Chen-Jei; Lin, Kuan-Chia; Tai, Cheng-Jeng; Tseng, Ling-Ming; Chien, Li-Yin

    2013-01-01

    Studies have rarely compared health outcomes for patients with breast cancer at different treatment stages. The purpose of the study was to compare symptoms and quality of life among patients with breast carcinoma receiving target, chemotherapy, or combined therapy. A longitudinal study was carried out with 57 patients receiving chemotherapy, 30 receiving target therapy, and 34 receiving combined therapy. Data were collected before the start of treatment, at 4 weeks, and at 12 weeks following the start of treatment. Symptom severity and interference were assessed by the M. D. Anderson Symptom Inventory. The physical and mental components of quality of life (physical component score [PCS] and mental component score [MCS]) were assessed using SF-36. There were no significant differences in symptom severity and interference for patients in the 3 therapy groups. The PCSs did not differ significantly according to the therapy group but did decrease significantly after each treatment. Patients receiving target therapy had significantly higher MCSs than did patients receiving chemotherapy, but the MCSs did not differ significantly before and after the treatment. Patients with higher symptom severity and interference had worse PCS and MCS. Patients at all treatment groups had worse physical components quality of life after treatment as compared with before treatment. Patients receiving target therapy had better mental components of quality of life. The mental components of quality of life remained stable during treatment. Nurses should assess the patients' symptoms during treatment and provide timely intervention to optimize their quality of life.

  6. Characterization of the CPAP-treated patient population in Catalonia

    PubMed Central

    Gavaldá, Ricard; Teixidó, Ivan; Woehrle, Holger; Rué, Montserrat; Solsona, Francesc; Escarrabill, Joan; Colls, Cristina; García-Altés, Anna; de Batlle, Jordi; Sánchez de-la-Torre, Manuel

    2017-01-01

    There are different phenotypes of obstructive sleep apnoea (OSA), many of which have not been characterised. Identification of these different phenotypes is important in defining prognosis and guiding the therapeutic strategy. The aim of this study was to characterise the entire population of continuous positive airway pressure (CPAP)-treated patients in Catalonia and identify specific patient profiles using cluster analysis. A total of 72,217 CPAP-treated patients who contacted the Catalan Health System (CatSalut) during the years 2012 and 2013 were included. Six clusters were identified, classified as “Neoplastic patients” (Cluster 1, 10.4%), “Metabolic syndrome patients” (Cluster 2, 27.7%), “Asthmatic patients” (Cluster 3, 5.8%), “Musculoskeletal and joint disorder patients” (Cluster 4, 10.3%), “Patients with few comorbidities” (Cluster 5, 35.6%) and “Oldest and cardiac disease patients” (Cluster 6, 10.2%). Healthcare facility use and mortality were highest in patients from Cluster 1 and 6. Conversely, patients in Clusters 2 and 4 had low morbidity, mortality and healthcare resource use. Our findings highlight the heterogeneity of CPAP-treated patients, and suggest that OSA is associated with a different prognosis in the clusters identified. These results suggest the need for a comprehensive and individualised approach to CPAP treatment of OSA. PMID:28934303

  7. Imipenem in burn patients: pharmacokinetic profile and PK/PD target attainment.

    PubMed

    Gomez, David S; Sanches-Giraud, Cristina; Silva, Carlindo V; Oliveira, Amanda M Ribas Rosa; da Silva, Joao Manoel; Gemperli, Rolf; Santos, Silvia R C J

    2015-03-01

    Unpredictable pharmacokinetics (PK) in burn patients may result in plasma concentrations below concentrations that are effective against common pathogens. The present study evaluated the imipenem PK profile and pharmacokinetic/pharmacodynamics (PK/PD) correlation in burn patients. Fifty-one burn patients, 38.7 years of age (mean), 68.0 kg, 36.3% total burn surface area (TBSA), of whom 84% (43/51) exhibited thermal injury, 63% inhalation injury and 16% electrical injury (8/51), all of whom were receiving imipenem treatment were investigated. Drug plasma monitoring, PK study (120 sets of plasma levels) and PK/PD correlation were performed in a series of blood samples. Only 250 μl of plasma samples were required for drug plasma measurements using the ultra filtration technique for the purification of biological matrix and quantification using liquid chromatography. Probability of target attainment (PTA) was calculated using a PD target of 40% free drug concentrations above the minimum inhibitory concentration (40%fT>MIC). Significant differences in PK parameters (medians), such as biological half-life (2.2 vs 5.5 h), plasma clearance (16.2 vs 1.4 l h(-1)) and volume of distribution (0.86 vs 0.19 l kg(-1)), were registered in burn patients via comparisons of set periods with normal renal function against periods of renal failure. Correlations between creatinine clearance and total body plasma clearance were also obtained. In addition, the PK profile did not change according to TBSA during sets when renal function was preserved. PTA was >89% for MIC values up to 4 mg l(-1). In conclusion, imipenem efficacy for the control of hospital infection on the basis of PK/PD correlation was guaranteed for burn in patients at the recommended dose regimens for normal renal function (31.1±9.7 mg kg(-1) daily), but the daily dose must be reduced to 17.2±9.7 mg kg(-1) during renal failure to avoid neurotoxicity.

  8. Prevalence of acid-reducing agents (ARA) in cancer populations and ARA drug-drug interaction potential for molecular targeted agents in clinical development.

    PubMed

    Smelick, Gillian S; Heffron, Timothy P; Chu, Laura; Dean, Brian; West, David A; Duvall, Scott L; Lum, Bert L; Budha, Nageshwar; Holden, Scott N; Benet, Leslie Z; Frymoyer, Adam; Dresser, Mark J; Ware, Joseph A

    2013-11-04

    Acid-reducing agents (ARAs) are the most commonly prescribed medications in North America and Western Europe. There are currently no data describing the prevalence of their use among cancer patients. However, this is a paramount question due to the potential for significant drug-drug interactions (DDIs) between ARAs, most commonly proton pump inhibitors (PPIs), and orally administered cancer therapeutics that display pH-dependent solubility, which may lead to decreased drug absorption and decreased therapeutic benefit. Of recently approved orally administered cancer therapeutics, >50% are characterized as having pH-dependent solubility, but there are currently no data describing the potential for this ARA-DDI liability among targeted agents currently in clinical development. The objectives of this study were to (1) determine the prevalence of ARA use among different cancer populations and (2) investigate the prevalence of orally administered cancer therapeutics currently in development that may be liable for an ARA-DDI. To address the question of ARA use among cancer patients, a retrospective cross-sectional analysis was performed using two large healthcare databases: Thomson Reuters MarketScan (N = 1,776,443) and the U.S. Department of Veterans Affairs (VA, N = 1,171,833). Among all cancer patients, the total prevalence proportion of ARA use (no. of cancer patients receiving an ARA/total no. of cancer patients) was 20% and 33% for the MarketScan and VA databases, respectively. PPIs were the most commonly prescribed agent, comprising 79% and 65% of all cancer patients receiving a prescription for an ARA (no. of cancer patients receiving a PPI /no. of cancer patients receiving an ARA) for the MarketScan and VA databases, respectively. To estimate the ARA-DDI liability of orally administered molecular targeted cancer therapeutics currently in development, two publicly available databases, (1) Kinase SARfari and (2) canSAR, were examined. For those orally administered

  9. Population Pharmacokinetics of Ceftizoxime Administered by Continuous Infusion in Clinically Ill Adult Patients

    PubMed Central

    Facca, Bryan; Frame, Bill; Triesenberg, Steve

    1998-01-01

    Ceftizoxime is a widely used beta-lactam antimicrobial agent, but pharmacokinetic data for use with clinically ill patients are lacking. We studied the population pharmacokinetics of ceftizoxime in 72 clinically ill patients at a community-based, university-affiliated hospital. A population pharmacokinetic model for ceftizoxime was created by using a prospective observational design. Ceftizoxime was administered by continuous infusion to treat patients with proven or suspected bacterial infections. While the patients were receiving infusions of ceftizoxime, serum samples were collected for pharmacokinetic analysis with the nonlinear mixed-effect modeling program NONMEM. In addition to clearance and volume of distribution, various comorbidities were examined for their influence on the kinetics. All 72 subjects completed the study, and 114 serum samples were collected. Several demographic and comorbidity variables, namely, age, weight, serum creatinine levels, congestive heart failure, and long-term ventilator dependency, had a significant impact on the estimate for ceftizoxime clearance. A mixture model, or two populations for estimation of ceftizoxime clearance, was discovered. One population presented with an additive clearance component of 1.6 liters per h. In addition, a maximizer function for serum creatinine levels was found. In summary, two models for ceftizoxime clearance, mixture and nonmixture, were found and are presented. Clearance for ceftizoxime can be estimated with commonly available clinical information and the models presented. From the clearance estimates, the dose of ceftizoxime to maintain the desired concentration in serum can be determined. Work is needed to validate the model for drug clearance and to evaluate its predictive performance. PMID:9661021

  10. [Stigmatizing Attitudes towards Cancer Patients--Results of a Representative Population Survey].

    PubMed

    Ernst, Jochen; Brähler, Elmar; Hinz, Andreas; Friedrich, Michael; Lehmann-Laue, Antje; Mehnert, Anja; Weißflog, Gregor

    2016-03-01

    To investigate stigmatizing attitudes towards cancer patients in the general population and to examine their association with socio-structural characteristics and perceived causes of disease. We recruited a representative sample from the German general population (n=2420; mean age: 52 years; 54% women). Stigmatizing attitudes were assessed with a 9-item scale. Predictors of stigmatizing attitudes were identified using a regression analysis. Agreement with stigmatization items ranged from 3.6% (item: work together with a cancer patient) to 18.9% (item: use the same dishes as a cancer patient). Perceived causes of disease with a high levels of personal responsibility showed only weak correlations with stigmatizing attitudes (all r<0.31) and were partially statistical significant (e. g. food intake) or not significant (e. g. alcohol). The strongest predictors of stigmatizing attitudes were lack of cancer-related experiences (Beta=-0,26), age <60 years (Beta=0,1) and the assumption that one cannot protect oneself from cancer (Beta=0,11) (all p<0.001). Further predictors were male gender and living in rural area (p<0.01). The results demonstrate a need for further research and the development of valid methodological instruments to assess stigmatization towards cancer patients. © Georg Thieme Verlag KG Stuttgart · New York.

  11. Development of a scale to assess cancer stigma in the non-patient population

    PubMed Central

    2014-01-01

    Background Illness-related stigma has attracted considerable research interest, but few studies have specifically examined stigmatisation of cancer in the non-patient population. The present study developed and validated a Cancer Stigma Scale (CASS) for use in the general population. Methods An item pool was developed on the basis of previous research into illness-related stigma in the general population and patients with cancer. Two studies were carried out. The first study used Exploratory factor analysis to explore the structure of items in a sample of 462 postgraduate students recruited through a London university. The second study used Confirmatory factor analysis to confirm the structure among 238 adults recruited through an online market research panel. Internal reliability, test-retest reliability and construct validity were also assessed. Results Exploratory factor analysis suggested six subscales, representing: Awkwardness, Severity, Avoidance, Policy Opposition, Personal Responsibility and Financial Discrimination. Confirmatory factor analysis confirmed this structure with a 25-item scale. All subscales showed adequate to good internal and test-retest reliability in both samples. Construct validity was also good, with mean scores for each subscale varying in the expected directions by age, gender, experience of cancer, awareness of lifestyle risk factors for cancer, and social desirability. Means for the subscales were consistent across the two samples. Conclusions These findings highlight the complexity of cancer stigma and provide the Cancer Stigma Scale (CASS) which can be used to compare populations, types of cancer and evaluate the effects of interventions designed to reduce cancer stigma in non-patient populations. PMID:24758482

  12. Development of a scale to assess cancer stigma in the non-patient population.

    PubMed

    Marlow, Laura A V; Wardle, Jane

    2014-04-23

    Illness-related stigma has attracted considerable research interest, but few studies have specifically examined stigmatisation of cancer in the non-patient population. The present study developed and validated a Cancer Stigma Scale (CASS) for use in the general population. An item pool was developed on the basis of previous research into illness-related stigma in the general population and patients with cancer. Two studies were carried out. The first study used Exploratory factor analysis to explore the structure of items in a sample of 462 postgraduate students recruited through a London university. The second study used Confirmatory factor analysis to confirm the structure among 238 adults recruited through an online market research panel. Internal reliability, test-retest reliability and construct validity were also assessed. Exploratory factor analysis suggested six subscales, representing: Awkwardness, Severity, Avoidance, Policy Opposition, Personal Responsibility and Financial Discrimination. Confirmatory factor analysis confirmed this structure with a 25-item scale. All subscales showed adequate to good internal and test-retest reliability in both samples. Construct validity was also good, with mean scores for each subscale varying in the expected directions by age, gender, experience of cancer, awareness of lifestyle risk factors for cancer, and social desirability. Means for the subscales were consistent across the two samples. These findings highlight the complexity of cancer stigma and provide the Cancer Stigma Scale (CASS) which can be used to compare populations, types of cancer and evaluate the effects of interventions designed to reduce cancer stigma in non-patient populations.

  13. Therapeutic lipid target achievements among high and highest risk patients: results from the CEPHEUS study in the Arabian Gulf.

    PubMed

    Al-Rasadi, Khalid; Al-Zakwani, Ibrahim; Al Mahmeed, Wael; Arafah, Mohamed; Al-Hinai, Ali T; Shehab, Abdullah; Al Tamimi, Omer; Alawadhi, Mahmoud

    2014-12-01

    To determine lipid target achievements of low-density lipoprotein cholesterol (LDL-C), non-high density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (apo B) in the Centralized Pan-Middle East Survey on the undertreatment of hypercholesterolemia (CEPHEUS) in Arabian Gulf States patients with high and highest risk according to the joint Consensus Statement of the American Diabetes Association (ADA) and American College of Cardiology Foundation (ACC). CEPHEUS was conducted in patients (≥ 18 years of age) in six Middle Eastern countries between November 2009 and July 2010 on lipid lowering drugs (LLDs). Serum samples collected included total cholesterol (TC), LDL-C, HDL-C, triglycerides (TGs), apo B, and apolipoprotein A1 (apo A1). The overall mean age of the cohort (n = 5275) was 56 ± 13 years, 58% (n = 3060) were male and 69% (n = 3635) were highest risk. LDL-C target was achieved in 25%, non-HDL-C in 36% and apo B in 38% of patients in the highest risk cohort compared with LDL-C 46%, non-HDL-C 58% and apo B 51% in the high risk group. In patients with TGs ≥ 2.2 mmol/L, LDL-C target was achieved in 16% and apo B in 15% of patients in the highest risk group compared with LDL-C 32% and apo B 22% in the high risk cohort. Despite being on LLDs, a large proportion of high and highest risk patients in the Arabian Gulf are not at recommended lipid targets and remain at a substantial residual risk for cardiovascular diseases. Apo B may be used as an additional target in patients with triglycerides ≥ 2.2 mmol/L. The findings should be interpreted in light of the study's limitations.

  14. Radiation dose to the esophagus from breast cancer radiation therapy, 1943-1996: an international population-based study of 414 patients.

    PubMed

    Lamart, Stephanie; Stovall, Marilyn; Simon, Steven L; Smith, Susan A; Weathers, Rita E; Howell, Rebecca M; Curtis, Rochelle E; Aleman, Berthe M P; Travis, Lois; Kwon, Deukwoo; Morton, Lindsay M

    2013-07-15

    To provide dosimetric data for an epidemiologic study on the risk of second primary esophageal cancer among breast cancer survivors, by reconstructing the radiation dose incidentally delivered to the esophagus of 414 women treated with radiation therapy for breast cancer during 1943-1996 in North America and Europe. We abstracted the radiation therapy treatment parameters from each patient's radiation therapy record. Treatment fields included direct chest wall (37% of patients), medial and lateral tangentials (45%), supraclavicular (SCV, 64%), internal mammary (IM, 44%), SCV and IM together (16%), axillary (52%), and breast/chest wall boosts (7%). The beam types used were (60)Co (45% of fields), orthovoltage (33%), megavoltage photons (11%), and electrons (10%). The population median prescribed dose to the target volume ranged from 21 Gy to 40 Gy. We reconstructed the doses over the length of the esophagus using abstracted patient data, water phantom measurements, and a computational model of the human body. Fields that treated the SCV and/or IM lymph nodes were used for 85% of the patients and delivered the highest doses within 3 regions of the esophagus: cervical (population median 38 Gy), upper thoracic (32 Gy), and middle thoracic (25 Gy). Other fields (direct chest wall, tangential, and axillary) contributed substantially lower doses (approximately 2 Gy). The cervical to middle thoracic esophagus received the highest dose because of its close proximity to the SCV and IM fields and less overlying tissue in that part of the chest. The location of the SCV field border relative to the midline was one of the most important determinants of the dose to the esophagus. Breast cancer patients in this study received relatively high incidental radiation therapy doses to the esophagus when the SCV and/or IM lymph nodes were treated, whereas direct chest wall, tangentials, and axillary fields contributed lower doses. Published by Elsevier Inc.

  15. The relationship of quality of life and distress in prostate cancer patients compared to the general population

    PubMed Central

    Zenger, Markus; Lehmann-Laue, Antje; Stolzenburg, Jens-Uwe; Schwalenberg, Thilo; Ried, Alexander; Hinz, Andreas

    2010-01-01

    Background: The aim of this study is two-fold. The first part compares quality of life (QoL) data of prostate cancer patients with those of a representative and age-specific sample of the general population and analyzes the influence of cancer related as well as socio-demographic parameters on QoL. Secondly, differences in QoL depending on the experienced psychological distress will be shown both in prostate cancer patients and in the general population. Material and Methods: A sample of 265 prostate cancer patients completed both the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the Hospital Anxiety and Depression Scale (HADS) during their stay in the hospital. A total HADS cut off score of 15 was used to indicate psychological distress and significant emotional concerns in patients and men of the general population. The results of the patients were compared with those of the general population (N=444). Results: Prostate cancer patients reported significantly worse levels of social and emotional functioning as well as more symptoms like insomnia, constipation and diarrhea compared to the general population. Patients and men of the general population with a total HADS score ≥15 reported lower QoL in all sub-scales except for diarrhea in comparison to people without distress. Discussion: Psychological distress is accompanied by lower QoL and therefore should be taken into consideration when QoL is assessed. Furthermore, clinicians should be trained by professionals to detect distress in their patients and to pay more attention to their emotional concerns, which are strongly associated with the patients’ well-being and QoL during their stay in hospital. PMID:20628652

  16. Broad Resistance to ACCase Inhibiting Herbicides in a Ryegrass Population Is Due Only to a Cysteine to Arginine Mutation in the Target Enzyme

    PubMed Central

    Kaundun, Shiv Shankhar; Hutchings, Sarah-Jane; Dale, Richard Paul; McIndoe, Eddie

    2012-01-01

    Background The design of sustainable weed management strategies requires a good understanding of the mechanisms by which weeds evolve resistance to herbicides. Here we have conducted a study on the mechanism of resistance to ACCase inhibiting herbicides in a Lolium multiflorum population (RG3) from the UK. Methodology/Principal Findings Analysis of plant phenotypes and genotypes showed that all the RG3 plants (72%) that contained the cysteine to arginine mutation at ACCase codon position 2088 were resistant to ACCase inhibiting herbicides. Whole plant dose response tests on predetermined wild and mutant 2088 genotypes from RG3 and a standard sensitive population indicated that the C2088R mutation is the only factor conferring resistance to all ten ACCase herbicides tested. The associated resistance indices ranged from 13 for clethodim to over 358 for diclofop-methyl. Clethodim, the most potent herbicide was significantly affected even when applied on small mutant plants at the peri-emergence and one leaf stages. Conclusion/Significance This study establishes the clear and unambiguous importance of the C2088R target site mutation in conferring broad resistance to ten commonly used ACCase inhibiting herbicides. It also demonstrates that low levels “creeping”, multigenic, non target site resistance, is not always selected before single gene target site resistance appears in grass weed populations subjected to herbicide selection pressure. PMID:22768118

  17. Contralateral Prophylactic Mastectomy Decisions in a Population-Based Sample of Patients with Early-Stage Breast Cancer

    PubMed Central

    Jagsi, Reshma; Hawley, Sarah T.; Griffith, Kent A.; Janz, Nancy K.; Kurian, Allison W.; Ward, Kevin C.; Hamilton, Ann S.; Morrow, Monica; Katz, Steven J.

    2017-01-01

    Importance Contralateral prophylactic mastectomy (CPM) use is increasing among women with unilateral breast cancer, but little is known about treatment decision making or physician interactions in diverse patient populations. Objective To evaluate patient motivations, knowledge, and decisions, as well as the impact of surgeon recommendations, in a large, diverse sample of patients who underwent recent treatment for breast cancer. Design/Setting/Participants A survey was sent to 3631 women with newly diagnosed, unilateral stage 0, I, or II breast cancer between July 2013 and September 2014. Women were identified through the population-based Surveillance Epidemiology and End Results registries of Los Angeles County and Georgia. Data on surgical decisions, motivations for those decisions, and knowledge were included in the analysis. Logistic and multinomial logistic regression of the data were conducted to identify factors associated with (1) CPM vs all other treatments combined, 2) CPM vs unilateral mastectomy (UM), and (3) CPM vs breast-conserving surgery (BCS). Associations between CPM receipt and surgeon recommendations were also evaluated. All statistical models and summary estimates were weighted to be representative of the target population. Main Outcome and Measures Receipt of CPM was the primary dependent variable for analysis and was measured by a woman’s self-report of her treatment. Results Of the 3631 women selected to receive the survey, 2578 (71.0%) responded and 2402 of these respondents who did not have bilateral disease and for whom surgery type was known constituted the final analytic sample. The mean (SD) age was 61.8 (12) years at the time of the survey. Overall, 1301 (43.9%) patients considered CPM (601[24.8%] considered it very strongly or strongly; only 395 (38.1%) of them knew that CPM does not improve survival for all women with breast cancer. Ultimately, 1466 women (61.6%) received BCS, 508 (21.2%) underwent UM, and 428 (17.3%) received

  18. Dose-escalation study for the targeting of CD44v+ cancer stem cells by sulfasalazine in patients with advanced gastric cancer (EPOC1205).

    PubMed

    Shitara, Kohei; Doi, Toshihiko; Nagano, Osamu; Imamura, Chiyo K; Ozeki, Takeshi; Ishii, Yuya; Tsuchihashi, Kenji; Takahashi, Shunji; Nakajima, Takako E; Hironaka, Shuichi; Fukutani, Miki; Hasegawa, Hiromi; Nomura, Shogo; Sato, Akihiro; Einaga, Yasuaki; Kuwata, Takeshi; Saya, Hideyuki; Ohtsu, Atsushi

    2017-03-01

    Cancer stem cells (CSCs) have enhanced mechanisms of protection from oxidative stress. A variant form of CD44 (CD44v), a major CSC marker, was shown to interact with xCT, a subunit of cystine-glutamate transporter, which maintains high levels of intracellular reduced glutathione (GSH) which defend the cell against oxidative stress. Sulfasalazine (SSZ) is an inhibitor of xCT and was shown to suppress the survival of CD44v-positive stem-like cancer cells both in vitro and in vivo. To find the dose of SSZ which can safely reduce the population of CD44v-positive cells in tumors, a dose-escalation study in patients with advanced gastric cancer was conducted. SSZ was given four times daily by oral administration with 2 weeks as one cycle. Tumor biopsies were obtained before and after 14 days of administration of SSZ to evaluate expression of CD44v and the intratumoral level of GSH. Eleven patients were enrolled and received a dosage from 8 to 12 g/day. Safety was confirmed up to a dosage of 12 g/day, which was considered the maximum tolerated dose. Among the eight patients with CD44v-positive cells in their pretreatment biopsy samples, the CD44v-positive cancer cell population appeared to be reduced in the posttreatment biopsy tissues of four patients. Intratumoral GSH levels were also decreased in two patients, suggesting biological effectiveness of SSZ at 8 g/day or greater. This is the first study of SSZ as an xCT inhibitor for targeting CSCs. Reduction of the levels of CD44v-positive cells and GSH was observed in some patients, consistent with the mode of action of SSZ in CSCs.

  19. Target specific oral anticoagulants in the management of thromboembolic disease in the elderly.

    PubMed

    Maddula, Surekha; Ansell, Jack

    2013-08-01

    The elderly population represents a population at highest risk of thromboembolism, but also the most vulnerable to hemorrhage. In the community setting there is a general tendency to under- treat this patient group. Specific consideration must be taken with elderly patients because they have reduced renal function, co-morbidities and risk of falls, altered pharmacodynamics, and challenges with adherence. Vitamin K antagonists, most often warfarin, have been the first line choice of therapy for long-term anticoagulation and enjoyed an unopposed position in the market for the last 70 years. Recently several new oral anticoagulants have been developed and found to be equally effective as warfarin in phase III studies and may provide an optimal treatment option in the elderly population. In this review we explore the target-specific oral anticoagulants and the pharmacological differences between them with a focus on the elderly population in whom these new drugs would constitute a possible alternative to warfarin therapy.

  20. Optimisation of the dosage of tranexamic acid in trauma patients with population pharmacokinetic analysis.

    PubMed

    Grassin-Delyle, S; Theusinger, O M; Albrecht, R; Mueller, S; Spahn, D R; Urien, S; Stein, P

    2018-06-01

    Tranexamic acid is used both pre-hospital and in-hospital as an antifibrinolytic drug to treat or prevent hyperfibrinolysis in trauma patients; dosing, however, remains empirical. We aimed to measure plasma levels of tranexamic acid in patients receiving pre-hospital anti-hyperfibrinolytic therapy and to build a population pharmacokinetic model to propose an optimised dosing regimen. Seventy-three trauma patients were enrolled and each received tranexamic acid 1 g intravenously pre-hospital. A blood sample was drawn after arrival in the emergency department, and we measured the plasma tranexamic acid concentration using liquid chromatography-mass spectrometry, and modelled the data using non-linear mixed effect modelling. Tranexamic acid was administered at a median (IQR [range]) time of 43 (30-55 [5-135]) min after trauma. Plasma tranexamic acid levels were determined on arrival at hospital, 57 (43-70 [20-148]) min after pre-hospital administration of the drug. The measured concentration was 28.7 (21.5-38.5 [8.7-89.0]) μg.ml -1 . Our subjects had sustained severe trauma; injury severity score 20 (16-29 [5-75]), including penetrating injury in 2.8% and isolated traumatic brain injury in 19.7%. The pharmacokinetics were ascribed a two-compartment open model with body-weight as the main covariate. As tranexamic acid concentrations may fall below therapeutic levels during initial hospital treatment, we propose additional dosing schemes to maintain a specific target blood concentration for as long as required. This is the first study to investigate plasma level and pharmacokinetics of tranexamic acid after pre-hospital administration in trauma patients. Our proposed dosing regimen could be used in subsequent clinical trials to better study efficacy and tolerance profiles with controlled blood concentrations. © 2018 The Association of Anaesthetists of Great Britain and Ireland.

  1. Detecting population recovery using gametic disequilibrium-based effective population size estimates

    Treesearch

    David A. Tallmon; Robin S. Waples; Dave Gregovich; Michael K. Schwartz

    2012-01-01

    Recovering populations often must meet specific growth rate or abundance targets before their legal status can be changed from endangered or threatened. While the efficacy, power, and performance of population metrics to infer trends in declining populations has received considerable attention, how these same metrics perform when populations are increasing is less...

  2. Patient engagement with research: European population register study.

    PubMed

    McKevitt, Christopher; Fudge, Nina; Crichton, Siobhan; Bejot, Yannick; Daubail, Benoît; Di Carlo, Antonio; Fearon, Patricia; Kolominsky-Rabas, Peter; Sheldenkar, Anita; Newbound, Sophie; Wolfe, Charles D A

    2015-12-01

    Lay involvement in implementation of research evidence into practice may include using research findings to guide individual care, as well as involvement in research processes and policy development. Little is known about the conditions required for such involvement. To assess stroke survivors' research awareness, use of research evidence in their own care and readiness to be involved in research processes. Cross sectional survey of stroke survivors participating in population-based stroke registers in six European centres. The response rate was 74% (481/647). Reasons for participation in register research included responding to clinician request (56%) and to 'give something back' (19%); however, 20% were unaware that they were participating in a stroke register. Research awareness was generally low: 57% did not know the purpose of the register they had been recruited to; 73% reported not having received results from the register they took part in; 60% did not know about any research on stroke care. Few participants (7.6%) used research evidence during their consultations with a doctor. The 34% of participants who were interested in being involved in research were younger, more highly educated and already research aware. Across Europe, stroke survivors already participating in research appear ill informed about stroke research. Researchers, healthcare professionals and patient associations need to improve how research results are communicated to patient populations and research participants, and to raise awareness of the relationship between research evidence and increased quality of care. © 2014 John Wiley & Sons Ltd.

  3. Treatment Patterns and Burden of Illness in Patients Initiating Targeted Therapy or Chemotherapy for Pancreatic Neuroendocrine Tumors.

    PubMed

    Broder, Michael S; Chang, Eunice; Reddy, Sheila R; Neary, Maureen P

    2017-08-01

    The aim of this study was to characterize treatment patterns and burden of pancreatic neuroendocrine tumors (PNET). Using 2 claims databases, we identified patients with PNET initiating targeted therapy (everolimus, sunitinib) or chemotherapy from 2009 to 2012. The first targeted/cytotoxic therapy was considered index treatment. Treatment patterns were graphically evaluated from index treatment initiation until enrollment or study end, whichever occurred first. Disease burden was examined by index group for first follow-up year. In treatment pattern analyses (582 newly treated patients with PNET), 72.2% received chemotherapy index treatment, 16.2% everolimus, and 11.7% received sunitinib. Median index treatment duration was 242, 146, and 126 days for everolimus, sunitinib, and cytotoxics (P < 0.01). Sunitinib initiators switched most often followed by everolimus and cytotoxic initiators. In disease burden analyses, 338 patients met inclusion criteria, with mean age of 54.5 (standard deviation, 9.9) years, 45.6% were female, and there were no significant between-group differences. Targeted therapy initiators had more prior somatostatin analog use versus cytotoxics (53.4% vs 25.1%, P < 0.001); 72.5% had comorbidities after treatment initiation; 42.9% had 1 or more inpatient hospitalization; and 47.9% had 1 or more emergency department visit. Pancreatic neuroendocrine tumor treatment patterns varied; cytotoxics were more often used as early therapy than targeted agents, but for less time. Patients had high health care utilization, irrespective of treatment, potentially from burdensome symptoms and comorbidities.

  4. EGFR, HER2 and VEGF pathways: validated targets for cancer treatment.

    PubMed

    Press, Michael F; Lenz, Heinz-Josef

    2007-01-01

    Targeted therapies are rationally designed to interfere with specific molecular events that are important in tumour growth, progression or survival. Several targeted therapies with anti-tumour activity in human cancer cell lines and xenograft models have now been shown to produce objective responses, delay disease progression and, in some cases, improve survival of patients with advanced malignancies. These targeted therapies include cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody; gefitinib and erlotinib, EGFR-specific tyrosine kinase inhibitors; trastuzumab, an anti-human EGFR type 2 (HER2)-related monoclonal antibody; lapatinib, a dual inhibitor of both EGFR- and HER2-associated tyrosine kinases; and bevacizumab, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody. On the basis of preclinical and clinical evidence, EGFR, HER2 and VEGF represent validated targets for cancer therapy and remain the subject of intensive investigation. Both EGFR and HER2 are targets found on cancer cells, whereas VEGF is a target that acts in the tumour microenvironment. Clinical studies are focusing on how to best incorporate targeted therapy into current treatment regimens and other studies are exploring whether different strategies for inhibiting these targets will offer greater benefit. It is clear that optimal use of targeted therapy will depend on understanding how these drugs work mechanistically, and recognising that their activities may differ across patient populations, tumour types and disease stages, as well as when and how they are used in cancer treatment. The results achieved with targeted therapies to date are promising, although they illustrate the need for additional preclinical and clinical study.

  5. Quality of life domains important and relevant to family caregivers of advanced cancer patients in an Asian population: a qualitative study.

    PubMed

    Lee, Geok Ling; Ow, Mandy Yen Ling; Akhileswaran, Ramaswamy; Pang, Grace Su Yin; Fan, Gilbert Kam Tong; Goh, Brandon Huat Heng; Wong, Cai Fong; Cheung, Yin Bun; Wee, Hwee Lin

    2015-04-01

    This study aims to identify domains of quality of life (QoL) that are culturally relevant to Chinese caregivers of advanced cancer patients in Singapore and to evaluate content adequacy of currently available instruments for use in the target population. English- and Chinese-speaking caregivers of advanced cancer patients receiving care under a tertiary cancer center and/or a community hospice home care/day care provider were recruited for in-depth interviews. The interviews were analyzed using thematic analysis. The identified domains, themes and sub-themes were compared to concepts addressed by items from five existing cancer-specific caregiver QoL instruments. Eighteen female and eight male caregivers aged 28-74 years participated in the study. Twenty-nine QoL themes and 59 sub-themes were identified in six domains, namely physical health, mental health, social health, spiritual health, financial health and daily life. Collectively, but not individually, the content of the five existing instruments adequately cover the physical health domain, social health domain and some themes on mental health domain for the study population. Content gaps were identified in the domains of mental health, spiritual health, daily life and financial health. The present study found culturally and contextually specific themes and sub-themes about positive emotional health, spiritual health and financial health.

  6. Venous Thromboembolism and Cerebrovascular Events in Patients with Giant Cell Arteritis: A Population-Based Retrospective Cohort Study

    PubMed Central

    Crowson, Cynthia S.; Makol, Ashima; Ytterberg, Steven R.; Saitta, Antonino; Salvarani, Carlo; Matteson, Eric L.; Warrington, Kenneth J.

    2016-01-01

    Objective To investigate the incidence of venous thromboembolism (VTE) and cerebrovascular events in a community-based incidence cohort of patients with giant cell arteritis (GCA) compared to the general population. Methods A population-based inception cohort of patients with incident GCA between January 1, 1950 and December 31, 2009 in Olmsted County, Minnesota and a cohort of non-GCA subjects from the same population were assembled and followed until December 31, 2013. Confirmed VTE and cerebrovascular events were identified through direct medical record review. Results The study population included 244 patients with GCA with a mean ± SD age at diagnosis of 76.2 ± 8.2 years (79% women) and an average length of follow-up of 10.2 ± 6.8 years. Compared to non-GCA subjects of similar age and sex, patients diagnosed with GCA had a higher incidence (%) of amaurosis fugax (cumulative incidence ± SE: 2.1 ± 0.9 versus 0, respectively; p = 0.014) but similar rates of stroke, transient ischemic attack (TIA), and VTE. Among patients with GCA, neither baseline characteristics nor laboratory parameters at diagnosis reliably predicted risk of VTE or cerebrovascular events. Conclusion In this population-based study, the incidence of VTE, stroke and TIA was similar in patients with GCA compared to non-GCA subjects. PMID:26901431

  7. Use of Targeted Therapeutics in Epithelial Ovarian Cancer: A Review of Current Literature and Future Directions.

    PubMed

    Vetter, Monica Hagan; Hays, John L

    2018-03-01

    Epithelial ovarian cancer (EOC) is the leading cause of gynecologic cancer death in the United States. Most patients will ultimately fail platinum-based chemotherapy and have the disease recur. Interest is increasing in the use of targeted therapies in the treatment of EOC. This review focuses on the current use of targeted therapeutics in EOC as well as future directions. A literature search of Medline and PubMed was conducted (January 2000-October 2017) to identify recent reports of targeted drugs in EOC. A wide range of targeted therapeutics is currently being used as both monotherapy and in combination in the treatment of EOC. Clinically, the most commonly used classes of drugs currently are antiangiogenics and poly (ADP-ribose) polymerase inhibitors. However, a number of drugs in varying stages in development target a wide range of biochemical pathways. Activity and response rates of these drugs vary greatly. Questions continue about combination drug therapy and appropriate patient selection. The use of targeted therapeutics in the treatment of EOC, both as monotherapy and in combination, will continue to expand as more mechanisms of tumorigenesis are identified. Multiple clinical trials of a wide range of targeted therapeutics are currently ongoing. Evidence-based selection of drug targets and appropriate patient populations will allow strategic application of targeted therapeutics. Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved.

  8. Social comparisons in adults with type 2 diabetes: Patients' reasons for target selection.

    PubMed

    Arigo, Danielle; Cornell, Max; Smyth, Joshua M

    2018-07-01

    To examine reasons for selecting a social comparison target (i.e. a specific other for relative self-evaluation), and their influence on affect and motivation for self-care, in type 2 diabetes (T2DM). Adults with T2DM (n = 180, M A1c  = 7.6%) chose to read about one of four targets. Participants rated five reasons for their choice (strongly disagree - strongly agree), and rated affect and self-care motivation before and after reading. To boost confidence in my ability to manage diabetes was rated highest overall (ps < 0.01), though choosing worse-off (vs. better-off) targets was associated with to gain useful information about how to improve (p = 0.04, [Formula: see text] = 0.05). Selection in order to feel better worked for those who chose better-off targets; choosing worse-off targets for this purpose worsened mood and stress (ps < 0.04, [Formula: see text]s = 0.02). Choosing worse-off targets to learn about similar others reduced self-care motivation (p < 0.01, [Formula: see text] = 0.05). Selection in order to boost confidence showed increased motivation only among those who chose better-off targets (p = 0.01). Patients' reasons for a particular comparison are associated with short-term changes in affect and self-care motivation, and warrant greater empirical and clinical attention.

  9. Transgene expression in target-defined neuron populations mediated by retrograde infection with adeno-associated viral vectors.

    PubMed

    Rothermel, Markus; Brunert, Daniela; Zabawa, Christine; Díaz-Quesada, Marta; Wachowiak, Matt

    2013-09-18

    Tools enabling the manipulation of well defined neuronal subpopulations are critical for probing complex neuronal networks. Cre recombinase (Cre) mouse driver lines in combination with the Cre-dependent expression of proteins using viral vectors--in particular, recombinant adeno-associated viral vectors (rAAVs)--have emerged as a widely used platform for achieving transgene expression in specified neural populations. However, the ability of rAAVs to further specify neuronal subsets on the basis of their anatomical connectivity has been reported as limited or inconsistent. Here, we systematically tested a variety of widely used neurotropic rAAVs for their ability to mediate retrograde gene transduction in the mouse brain. We tested pseudotyped rAAVs of several common serotypes (rAAV 2/1, 2/5, and 2/9) as well as constructs both with and without Cre-dependent expression switches. Many of the rAAVs tested--in particular, though not exclusively, Cre-dependent vectors--showed a robust capacity for retrograde infection and transgene expression. Retrograde expression was successful over distances as large as 6 mm and in multiple neuron types, including olfactory projection neurons, neocortical pyramidal cells projecting to distinct targets, and corticofugal and modulatory projection neurons. Retrograde infection using transgenes such as ChR2 allowed for optical control or optically assisted electrophysiological identification of neurons defined genetically as well as by their projection target. These results establish a widely accessible tool for achieving combinatorial specificity and stable, long-term transgene expression to isolate precisely defined neuron populations in the intact animal.

  10. Transgene Expression in Target-Defined Neuron Populations Mediated by Retrograde Infection with Adeno-Associated Viral Vectors

    PubMed Central

    Rothermel, Markus; Brunert, Daniela; Zabawa, Christine; Díaz-Quesada, Marta

    2013-01-01

    Tools enabling the manipulation of well defined neuronal subpopulations are critical for probing complex neuronal networks. Cre recombinase (Cre) mouse driver lines in combination with the Cre-dependent expression of proteins using viral vectors—in particular, recombinant adeno-associated viral vectors (rAAVs)—have emerged as a widely used platform for achieving transgene expression in specified neural populations. However, the ability of rAAVs to further specify neuronal subsets on the basis of their anatomical connectivity has been reported as limited or inconsistent. Here, we systematically tested a variety of widely used neurotropic rAAVs for their ability to mediate retrograde gene transduction in the mouse brain. We tested pseudotyped rAAVs of several common serotypes (rAAV 2/1, 2/5, and 2/9) as well as constructs both with and without Cre-dependent expression switches. Many of the rAAVs tested—in particular, though not exclusively, Cre-dependent vectors—showed a robust capacity for retrograde infection and transgene expression. Retrograde expression was successful over distances as large as 6 mm and in multiple neuron types, including olfactory projection neurons, neocortical pyramidal cells projecting to distinct targets, and corticofugal and modulatory projection neurons. Retrograde infection using transgenes such as ChR2 allowed for optical control or optically assisted electrophysiological identification of neurons defined genetically as well as by their projection target. These results establish a widely accessible tool for achieving combinatorial specificity and stable, long-term transgene expression to isolate precisely defined neuron populations in the intact animal. PMID:24048849

  11. A Primer on Population Health Management and Its Perioperative Application.

    PubMed

    Boudreaux, Arthur M; Vetter, Thomas R

    2016-07-01

    The movement toward value-based payment models, driven by governmental policies, federal statutes, and market forces, is propelling the importance of effectively managing the health of populations to the forefront in the United States and other developed countries. However, for many anesthesiologists, population health management is a new or even foreign concept. A primer on population health management and its potential perioperative application is thus presented here. Although it certainly continues to evolve, population health management can be broadly defined as the specific policies, programs, and interventions directed at optimizing population health. The Population Health Alliance has created a particularly cogent conceptual framework and interconnected and very useful population health process model, which together identify the key components of population health and its management. Population health management provides a useful rationale for patients, providers, payers, and policymakers to move collectively away from the traditional system of individual, siloed providers to a more integrated, coordinated, team-based approach, thus creating a holistic view of the patient population. The goal of population health management is to keep the targeted patient population as healthy as possible, thus minimizing the need for costly interventions such as emergency department visits, acute hospitalizations, laboratory testing and imaging, and diagnostic and therapeutic procedures. Population health management strategies are increasingly more important to leaders of health care systems as the health of populations for which they care, especially in a strong cost risk-sharing environment, must be optimized. Most population health management efforts rely on a patient-centric team approach, coordination of care, effective communication, robust outcomes data analysis, and continuous quality improvement. Anesthesiologists have an opportunity to help lead these efforts in

  12. Serving some and serving all: how providers navigate the challenges of providing racially targeted health services.

    PubMed

    Zhou, Amy

    2017-10-01

    Racially targeted healthcare provides racial minorities with culturally and linguistically appropriate health services. This mandate, however, can conflict with the professional obligation of healthcare providers to serve patients based on their health needs. The dilemma between serving a particular population and serving all is heightened when the patients seeking care are racially diverse. This study examines how providers in a multi-racial context decide whom to include or exclude from health programs. This study draws on 12 months of ethnographic fieldwork at an Asian-specific HIV organization. Fieldwork included participant observation of HIV support groups, community outreach programs, and substance abuse recovery groups, as well as interviews with providers and clients. Providers managed the dilemma in different ways. While some programs in the organization focused on an Asian clientele, others de-emphasized race and served a predominantly Latino and African American clientele. Organizational structures shaped whether services were delivered according to racial categories. When funders examined client documents, providers prioritized finding Asian clients so that their documents reflected program goals to serve the Asian population. In contrast, when funders used qualitative methods, providers could construct an image of a program that targets Asians during evaluations while they included other racial minorities in their everyday practice. Program services were organized more broadly by health needs. Even within racially targeted programs, the meaning of race fluctuates and is contested. Patients' health needs cross cut racial boundaries, and in some circumstances, the boundaries of inclusion can expand beyond specific racial categories to include racial minorities and underserved populations more generally.

  13. Quality of life in elderly patients with an ostomy - a study from the population-based PROFILES registry.

    PubMed

    Verweij, N M; Bonhof, C S; Schiphorst, A H W; Maas, H A; Mols, F; Pronk, A; Hamaker, M E

    2018-04-01

    Ostomies are being placed frequently in surgically treated elderly patients with colorectal cancer (CRC). An insight into the (potential) impact of ostomies on quality of life (QoL) could be useful in patient counselling as well as in the challenging shared treatment decision-making. Patients with CRC diagnosed between 2000 and 2009 and registered in the population-based Eindhoven Cancer Registry received a QoL questionnaire (EORTC QLQ-C30) in 2010. In addition, QoL was compared with an age- and sex-matched normative population. The study included 2299 CRC patients, of whom 494 had an ostomy. No differences were found in reported ostomy-related problems between patients aged ≤65, 66-75 and ≥76 years. Ostomy patients aged 66-75 and ≥76 years reported significantly lower physical functioning compared with those without an ostomy. In the elderly (those aged ≥76 years) ostomates reported a worse physical and social functioning compared with the normative population. All these differences were of small clinical relevance. The impact of an ostomy seems to be more prominent in younger (≤75 years old) ostomates, as they experience more functional limitations and a decrease in global health status compared with younger nonostomy patients and the normative population. Although elderly (≥76 years old) patients with an ostomy report significantly more limitations in functioning compared with a normative population and elderly CRC patients without an ostomy, the clinical relevance of this finding is limited. In contrast, the impact of an ostomy is more prominent in younger patients. Thus, age itself is not a reason for withholding an ostomy. Colorectal Disease © 2017 The Association of Coloproctology of Great Britain and Ireland.

  14. Some Chronic Rhinosinusitis Patients Have Significantly Elevated Populations of Seven Fungi in their Sinuses

    EPA Science Inventory

    Abstract: Objectives/Hypothesis: To measure the populations of 36 fungi in the homes and sinuses of chronic rhinosinusitis (CRS) and non-CRS patients. Study Design: Single-blind cross-sectional study. Methods: Populations of 36 fungi were measured in sinus samples and in the home...

  15. Continuous monitoring and intrafraction target position correction during treatment improves target coverage for patients undergoing SBRT prostate therapy.

    PubMed

    Lovelock, D Michael; Messineo, Alessandra P; Cox, Brett W; Kollmeier, Marisa A; Zelefsky, Michael J

    2015-03-01

    To compare the potential benefits of continuous monitoring of prostate position and intervention (CMI) using 2-mm displacement thresholds during stereotactic body radiation therapy (SBRT) treatment to those of a conventional image-guided procedure involving single localization prior to treatment. Eighty-nine patients accrued to a prostate SBRT dose escalation protocol were implanted with radiofrequency transponder beacons. The planning target volume (PTV) margin was 5 mm in all directions, except for 3 mm in the posterior direction. The prostate was kept within 2 mm of its planned position by the therapists halting dose delivery and, if necessary, correcting the couch position. We computed the number, type, and time required for interventions and where the prostate would have been during dose delivery had there been, instead, a single image-guided setup procedure prior to each treatment. Distributions of prostate displacements were computed as a function of time. After the initial setup, 1.7 interventions per fraction were required, with a concomitant increase in time for dose delivery of approximately 65 seconds. Small systematic drifts in prostate position in the posterior and inferior directions were observed in the study patients. Without CMI, intrafractional motion would have resulted in approximately 10% of patients having a delivered dose that did not meet our clinical coverage requirement, that is, a PTV D95 of >90%. The posterior PTV margin required for 95% of the dose to be delivered with the target positioned within the PTV was computed as a function of time. The margin necessary was found to increase by 2 mm every 5 minutes, starting from the time of the imaging procedure. CMI using a tight 2-mm displacement threshold was not only feasible but was found to deliver superior PTV coverage compared with the conventional image-guided procedure in the SBRT setting. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Continuous Monitoring and Intrafraction Target Position Correction During Treatment Improves Target Coverage for Patients Undergoing SBRT Prostate Therapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lovelock, D. Michael, E-mail: lovelocm@mskcc.org; Messineo, Alessandra P.; Cox, Brett W.

    2015-03-01

    Purpose: To compare the potential benefits of continuous monitoring of prostate position and intervention (CMI) using 2-mm displacement thresholds during stereotactic body radiation therapy (SBRT) treatment to those of a conventional image-guided procedure involving single localization prior to treatment. Methods and Materials: Eighty-nine patients accrued to a prostate SBRT dose escalation protocol were implanted with radiofrequency transponder beacons. The planning target volume (PTV) margin was 5 mm in all directions, except for 3 mm in the posterior direction. The prostate was kept within 2 mm of its planned position by the therapists halting dose delivery and, if necessary, correcting themore » couch position. We computed the number, type, and time required for interventions and where the prostate would have been during dose delivery had there been, instead, a single image-guided setup procedure prior to each treatment. Distributions of prostate displacements were computed as a function of time. Results: After the initial setup, 1.7 interventions per fraction were required, with a concomitant increase in time for dose delivery of approximately 65 seconds. Small systematic drifts in prostate position in the posterior and inferior directions were observed in the study patients. Without CMI, intrafractional motion would have resulted in approximately 10% of patients having a delivered dose that did not meet our clinical coverage requirement, that is, a PTV D95 of >90%. The posterior PTV margin required for 95% of the dose to be delivered with the target positioned within the PTV was computed as a function of time. The margin necessary was found to increase by 2 mm every 5 minutes, starting from the time of the imaging procedure. Conclusions: CMI using a tight 2-mm displacement threshold was not only feasible but was found to deliver superior PTV coverage compared with the conventional image-guided procedure in the SBRT setting.« less

  17. Population pharmacokinetic modeling of furosemide in patients with hypertension and fluid overload conditions.

    PubMed

    Kodati, Devender; Yellu, Narsimhareddy

    2017-06-01

    Furosemide is a loop diuretic drug frequently indicated in hypertension and fluid overload conditions such as congestive heart failure and hepatic cirrhosis. The purpose of the study was to establish a population pharmacokinetic model for furosemide in Indian hypertensive and fluid overload patients, and to evaluate effects of covariates on the volume of distribution (V/F) and oral clearance (CL/F) of furosemide. A total of 188 furosemide plasma sample concentrations from 63 patients with hypertension or fluid overload conditions were collected in this study. The population pharmacokinetic model for furosemide was built using Phoenix NLME 1.3 software. The covariates included age, sex, body surface area, bodyweight, height and creatinine clearance (CRCL). The pharmacokinetic data of furosemide was adequately explained by a two-compartment linear pharmacokinetic model with first-order absorption and an absorption lag-time. The mean values of CL/F and Vd/F of furosemide in the patients were 15.054Lh -1 and 4.419L, respectively. Analysis of covariates showed that CRCL was significantly influencing the clearance of furosemide. The final population pharmacokinetic model was demonstrated to be appropriate and effective and it can be used to assess the pharmacokinetic parameters of furosemide in Indian patients with hypertension and fluid overload conditions. Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.

  18. Targeted marketing and public health.

    PubMed

    Grier, Sonya A; Kumanyika, Shiriki

    2010-01-01

    Targeted marketing techniques, which identify consumers who share common needs or characteristics and position products or services to appeal to and reach these consumers, are now the core of all marketing and facilitate its effectiveness. However, targeted marketing, particularly of products with proven or potential adverse effects (e.g., tobacco, alcohol, entertainment violence, or unhealthful foods) to consumer segments defined as vulnerable raises complex concerns for public health. It is critical that practitioners, academics, and policy makers in marketing, public health, and other fields recognize and understand targeted marketing as a specific contextual influence on the health of children and adolescents and, for different reasons, ethnic minority populations and other populations who may benefit from public health protections. For beneficial products, such understanding can foster more socially productive targeting. For potentially harmful products, understanding the nature and scope of targeted marketing influences will support identification and implementation of corrective policies.

  19. Targeted Therapy Database (TTD): A Model to Match Patient's Molecular Profile with Current Knowledge on Cancer Biology

    PubMed Central

    Mocellin, Simone; Shrager, Jeff; Scolyer, Richard; Pasquali, Sandro; Verdi, Daunia; Marincola, Francesco M.; Briarava, Marta; Gobbel, Randy; Rossi, Carlo; Nitti, Donato

    2010-01-01

    Background The efficacy of current anticancer treatments is far from satisfactory and many patients still die of their disease. A general agreement exists on the urgency of developing molecularly targeted therapies, although their implementation in the clinical setting is in its infancy. In fact, despite the wealth of preclinical studies addressing these issues, the difficulty of testing each targeted therapy hypothesis in the clinical arena represents an intrinsic obstacle. As a consequence, we are witnessing a paradoxical situation where most hypotheses about the molecular and cellular biology of cancer remain clinically untested and therefore do not translate into a therapeutic benefit for patients. Objective To present a computational method aimed to comprehensively exploit the scientific knowledge in order to foster the development of personalized cancer treatment by matching the patient's molecular profile with the available evidence on targeted therapy. Methods To this aim we focused on melanoma, an increasingly diagnosed malignancy for which the need for novel therapeutic approaches is paradigmatic since no effective treatment is available in the advanced setting. Relevant data were manually extracted from peer-reviewed full-text original articles describing any type of anti-melanoma targeted therapy tested in any type of experimental or clinical model. To this purpose, Medline, Embase, Cancerlit and the Cochrane databases were searched. Results and Conclusions We created a manually annotated database (Targeted Therapy Database, TTD) where the relevant data are gathered in a formal representation that can be computationally analyzed. Dedicated algorithms were set up for the identification of the prevalent therapeutic hypotheses based on the available evidence and for ranking treatments based on the molecular profile of individual patients. In this essay we describe the principles and computational algorithms of an original method developed to fully exploit

  20. Targeted Therapy Database (TTD): a model to match patient's molecular profile with current knowledge on cancer biology.

    PubMed

    Mocellin, Simone; Shrager, Jeff; Scolyer, Richard; Pasquali, Sandro; Verdi, Daunia; Marincola, Francesco M; Briarava, Marta; Gobbel, Randy; Rossi, Carlo; Nitti, Donato

    2010-08-10

    The efficacy of current anticancer treatments is far from satisfactory and many patients still die of their disease. A general agreement exists on the urgency of developing molecularly targeted therapies, although their implementation in the clinical setting is in its infancy. In fact, despite the wealth of preclinical studies addressing these issues, the difficulty of testing each targeted therapy hypothesis in the clinical arena represents an intrinsic obstacle. As a consequence, we are witnessing a paradoxical situation where most hypotheses about the molecular and cellular biology of cancer remain clinically untested and therefore do not translate into a therapeutic benefit for patients. To present a computational method aimed to comprehensively exploit the scientific knowledge in order to foster the development of personalized cancer treatment by matching the patient's molecular profile with the available evidence on targeted therapy. To this aim we focused on melanoma, an increasingly diagnosed malignancy for which the need for novel therapeutic approaches is paradigmatic since no effective treatment is available in the advanced setting. Relevant data were manually extracted from peer-reviewed full-text original articles describing any type of anti-melanoma targeted therapy tested in any type of experimental or clinical model. To this purpose, Medline, Embase, Cancerlit and the Cochrane databases were searched. We created a manually annotated database (Targeted Therapy Database, TTD) where the relevant data are gathered in a formal representation that can be computationally analyzed. Dedicated algorithms were set up for the identification of the prevalent therapeutic hypotheses based on the available evidence and for ranking treatments based on the molecular profile of individual patients. In this essay we describe the principles and computational algorithms of an original method developed to fully exploit the available knowledge on cancer biology with the

  1. Tissues from population-based cancer registries: a novel approach to increasing research potential.

    PubMed

    Goodman, Marc T; Hernandez, Brenda Y; Hewitt, Stephen; Lynch, Charles F; Coté, Timothy R; Frierson, Henry F; Moskaluk, Christopher A; Killeen, Jeffrey L; Cozen, Wendy; Key, Charles R; Clegg, Limin; Reichman, Marsha; Hankey, Benjamin F; Edwards, Brenda

    2005-07-01

    Population-based cancer registries, such as those included in the Surveillance, Epidemiology, and End-Results (SEER) Program, offer tremendous research potential beyond traditional surveillance activities. We describe the expansion of SEER registries to gather formalin-fixed, paraffin-embedded tissue from cancer patients on a population basis. Population-based tissue banks have the advantage of providing an unbiased sampling frame for evaluating the public health impact of genes or protein targets that may be used for therapeutic or diagnostic purposes in defined communities. Such repositories provide a unique resource for testing new molecular classification schemes for cancer, validating new biologic markers of malignancy, prognosis and progression, assessing therapeutic targets, and measuring allele frequencies of cancer-associated genetic polymorphisms or germline mutations in representative samples. The assembly of tissue microarrays will allow for the use of rapid, large-scale protein-expression profiling of tumor samples while limiting depletion of this valuable resource. Access to biologic specimens through SEER registries will provide researchers with demographic, clinical, and risk factor information on cancer patients with assured data quality and completeness. Clinical outcome data, such as disease-free survival, can be correlated with previously validated prognostic markers. Furthermore, the anonymity of the study subject can be protected through rigorous standards of confidentiality. SEER-based tissue resources represent a step forward in true, population-based tissue repositories of tumors from US patients and may serve as a foundation for molecular epidemiology studies of cancer in this country.

  2. A Randomized Trial Adapting Contingency Management Targets Based on Initial Abstinence Status of Cocaine-Dependent Patients

    ERIC Educational Resources Information Center

    Petry, Nancy M.; Barry, Danielle; Alessi, Sheila M.; Rounsaville, Bruce J.; Carroll, Kathleen M.

    2012-01-01

    Objective: Contingency management (CM) reduces drug use, but questions remain regarding optimal targets and magnitudes of reinforcement. We evaluated the efficacy of CM reinforcing attendance in patients who initiated treatment with cocaine-negative samples, and of higher magnitude abstinence-based CM in patients who began treatment positive.…

  3. Patient centric drug product design in modern drug delivery as an opportunity to increase safety and effectiveness.

    PubMed

    Stegemann, Sven

    2018-06-01

    The advances in drug delivery technologies have enabled pharmaceutical scientists to deliver a drug through various administration routes and optimize the drug release and absorption. The wide range of drug delivery systems and dosage forms represent a toolbox of technology for the development of pharmaceutical drug products but might also be a source of medication errors and nonadherence. Patient centric drug product development is being suggested as an important factor to increase therapeutic outcomes. Areas covered: Patients have impaired health and potentially disabilities and they are not medical or pharmaceutical experts but are requested to manage complex therapeutic regimens. As such the application of technology should also serve to reduce complexity, build on patients' intuition and ease of use. Patients form distinct populations based on the targeted disease, disease cluster or age group with specific characteristics or therapeutic contexts. Expert opinion: Establishing a target product and patient profile is essential to guide drug product design development. Including the targeted patient populations in the process is a prerequisite to achieve patient-centric pharmaceutical drug product design. Addressing the needs early on in the product design process, will create more universal design, avoiding the necessity for multiple product presentations to cover the different patient populations.

  4. The collaborative edge: patient empowerment for vulnerable populations.

    PubMed

    Safran, Charles

    2003-03-01

    The problems with access to care and the special needs for educational outreach for disadvantage or vulnerable populations of patients require innovation. This paper describes Baby CareLink use of information technology to support communication, consultation, and collaboration among colleagues as well as with patients, their families, and community resources. In response to the educational, emotional and communication needs of parents of premature infants and the clinicians who care for the infants and support the families, we developed Baby CareLink, a secure collaborative environment. Baby CareLink provides a nurturing environment where parents, even though remote from the Neonatal Intensive Care Unit, can actively participate in decisions surrounding their baby's care. In a southeastern hospital serving a mostly Medicaid population in a rural setting, more than 300 parents have used Baby CareLink more than 11000 times during the past year. Despite the common wisdom that Medicaid families do not have access to the Internet, approximately 85% of the parents access Baby CareLink from home, at work, from the library or other public access point. The median use of Baby CareLinks from outside the hospital by parents is 17 separate sessions. In a city hospital in the midwestern US which exclusively serves a Medicaid population, experience has been equally encouraging. More than 70 parents have initiated more than 600 secure sessions with Baby CareLink. In contrast to the rural hospital, only 35% of sessions have been initiated outside the hospital. Experience with Baby CareLink suggests that families from all walks of life will use and benefit from collaborative tools that keep them informed and involved in the care of their children. The most significant barrier to wider deployment is bandwidth limitations into the homes of most families. The care of premature infants is a great example of an area where medical knowledge and ability has grown dramatically, and where

  5. Management of rheumatoid arthritis in clinical practice using treat-to-target strategy: Where do we stand in the multi-ethnic Malaysia population?

    PubMed

    Tan, Bee Eng; Lim, Ai Lee; Kan, Sow Lai; Lim, Chong Hong; Ng, Ying Fun; Tng, Serene Li Ching; Hassin, Nur Syakirah; Chandran, Losshenee; Hamid, Norshahida Abdul; Lee, Yvonne Yin Leng

    2017-06-01

    To evaluate the achievement of treat-to-target (T2T) strategy in rheumatoid arthritis (RA) and identify factors associated with failed treatment target in a public rheumatology center. A cross-sectional study was conducted from June 2015 to February 2016. RA patients with disease duration greater than 2 years and under T2T for over a year were invited to the study. Demographic, clinical data, disease activity score of 28 joints (DAS28), and clinical disease activity index (CDAI) were collected in a single routine clinic visit. Treatment target was defined as DAS28 <3.2 or CDAI ≤10. Retrospective chart review was performed to determine reasons of failed treatment target. A total of 371 patients were recruited and 87.1% were female. Mean age and duration of RA were 53.5 years (SD 10.3) and 9.1 years (SD 6.6), respectively. Ethnic distribution was 49% Chinese, 27% Malay, and 24% Indian. T2T was achieved in 81.7% of the cohort. Non-Chinese ethnicity, positive rheumatoid factor, and treatment with three disease modifying anti-rheumatic drugs (DMARDs) were associated with failed treatment target. After controlling for covariates, Malay ethnicity (OR 2.96; 95% CI 1.47-5.96) and treatment with three DMARDs (OR 2.14; 95% CI 1.06-4.35) were associated with failed treatment target. There was no association between age, gender, duration of RA, BMI, smoking status, anti-citrulinated cyclic peptide, and achievement of T2T. The most common reasons of failed treatment target were inability to escalate DMARDs due to side effects (18.8%), lack of biologics fund (15.6%), and persistent disease despite optimum treatment (14.1%). T2T was successfully implemented. Malay patients need aggressive treatment adaptation to achieve optimal outcome.

  6. Economic Evaluation of Companion Diagnostic Testing for EGFR Mutations and First-Line Targeted Therapy in Advanced Non-Small Cell Lung Cancer Patients in South Korea.

    PubMed

    Lim, Eun-A; Lee, Haeyoung; Bae, Eunmi; Lim, Jaeok; Shin, Young Kee; Choi, Sang-Eun

    2016-01-01

    As targeted therapy becomes increasingly important, diagnostic techniques for identifying targeted biomarkers have also become an emerging issue. The study aims to evaluate the cost-effectiveness of treating patients as guided by epidermal growth factor receptor (EGFR) mutation status compared with a no-testing strategy that is the current clinical practice in South Korea. A cost-utility analysis was conducted to compare an EGFR mutation testing strategy with a no-testing strategy from the Korean healthcare payer's perspective. The study population consisted of patients with stage 3b and 4 lung adenocarcinoma. A decision tree model was employed to select the appropriate treatment regimen according to the results of EGFR mutation testing and a Markov model was constructed to simulate disease progression of advanced non-small cell lung cancer. The length of a Markov cycle was one month, and the time horizon was five years (60 cycles). In the base case analysis, the testing strategy was a dominant option. Quality-adjusted life-years gained (QALYs) were 0.556 and 0.635, and total costs were $23,952 USD and $23,334 USD in the no-testing and testing strategy respectively. The sensitivity analyses showed overall robust results. The incremental cost-effectiveness ratios (ICERs) increased when the number of patients to be treated with erlotinib increased, due to the high cost of erlotinib. Treating advanced adenocarcinoma based on EGFR mutation status has beneficial effects and saves the cost compared to no testing strategy in South Korea. However, the cost-effectiveness of EGFR mutation testing was heavily affected by the cost-effectiveness of the targeted therapy.

  7. Measuring populations to improve vaccination coverage

    NASA Astrophysics Data System (ADS)

    Bharti, Nita; Djibo, Ali; Tatem, Andrew J.; Grenfell, Bryan T.; Ferrari, Matthew J.

    2016-10-01

    In low-income settings, vaccination campaigns supplement routine immunization but often fail to achieve coverage goals due to uncertainty about target population size and distribution. Accurate, updated estimates of target populations are rare but critical; short-term fluctuations can greatly impact population size and susceptibility. We use satellite imagery to quantify population fluctuations and the coverage achieved by a measles outbreak response vaccination campaign in urban Niger and compare campaign estimates to measurements from a post-campaign survey. Vaccine coverage was overestimated because the campaign underestimated resident numbers and seasonal migration further increased the target population. We combine satellite-derived measurements of fluctuations in population distribution with high-resolution measles case reports to develop a dynamic model that illustrates the potential improvement in vaccination campaign coverage if planners account for predictable population fluctuations. Satellite imagery can improve retrospective estimates of vaccination campaign impact and future campaign planning by synchronizing interventions with predictable population fluxes.

  8. Measuring populations to improve vaccination coverage

    PubMed Central

    Bharti, Nita; Djibo, Ali; Tatem, Andrew J.; Grenfell, Bryan T.; Ferrari, Matthew J.

    2016-01-01

    In low-income settings, vaccination campaigns supplement routine immunization but often fail to achieve coverage goals due to uncertainty about target population size and distribution. Accurate, updated estimates of target populations are rare but critical; short-term fluctuations can greatly impact population size and susceptibility. We use satellite imagery to quantify population fluctuations and the coverage achieved by a measles outbreak response vaccination campaign in urban Niger and compare campaign estimates to measurements from a post-campaign survey. Vaccine coverage was overestimated because the campaign underestimated resident numbers and seasonal migration further increased the target population. We combine satellite-derived measurements of fluctuations in population distribution with high-resolution measles case reports to develop a dynamic model that illustrates the potential improvement in vaccination campaign coverage if planners account for predictable population fluctuations. Satellite imagery can improve retrospective estimates of vaccination campaign impact and future campaign planning by synchronizing interventions with predictable population fluxes. PMID:27703191

  9. Using a Treat-to-Target Management Strategy to Improve the Doctor-Patient Relationship in Inflammatory Bowel Disease.

    PubMed

    Rubin, David T; Krugliak Cleveland, Noa

    2015-09-01

    The doctor-patient relationship (DPR) in inflammatory bowel disease (IBD) has been facing new challenges, in part due to the substantial progress in medical and surgical management and also due to the rapid expansion of patient access to medical information. Not surprisingly, the complexity of IBD care and heterogeneity of the disease types may lead to conflict between a physician's therapeutic recommendations and the patient's wishes. In this commentary, we propose that the so-called "treat-to-target" approach of objective targets of disease control and serial adjustments to therapies can also strengthen the DPR in IBD by enabling defined trials of alternative approaches, followed by a more objective assessment and reconsideration of treatments. We contend that such respect for patient autonomy and the use of objective markers of disease activity improves the DPR by fostering trust and both engaging and empowering patients and physicians with the information necessary to make shared decisions about therapies.

  10. Health related quality of life in patients with neuroendocrine tumors compared with the general Norwegian population.

    PubMed

    Haugland, Trude; Vatn, Morten H; Veenstra, Marijke; Wahl, Astrid Klopstad; Natvig, Gerd Karin

    2009-08-01

    Health related quality of life (HRQoL) was characterized among patients with neuroendocrine tumor (NET) and compared with the general Norwegian population. A cross sectional, comparative design was chosen, and the samples comprised 196 NET patients and 5,258 individuals from the general Norwegian population. We used Chi-square cross tab calculations to evaluate sociodemographic characteristics, T-tests for independent samples and Analysis of Variance (ANOVA) in order to compare HRQoL (SF-36) scores across a range of background variables. Furthermore, T-tests were used to analyze differences in HRQoL scores between the samples. NET patients demonstrated significantly lower on all HRQoL subscales when compared with the general population with the lowest values on general health, physical limitation and vitality. Individuals above 70 years reported lower scores on physical functioning and physical limitations compared with those who were younger. Individuals with higher levels of education reported increased physical functioning compared with those with less education and full-time or part-time workers described higher physical functioning and less physical limitations compared with those who were retired. All SF-36 HRQoL scores were significantly lower among the NET patients when compared with the general population. Assistance from health personnel to NET patients should focus on those domains.

  11. New drugs and patient-centred end-points in old age: setting the wheels in motion.

    PubMed

    Mangoni, Arduino A; Pilotto, Alberto

    2016-01-01

    Older patients with various degrees of frailty and disability, a key population target of pharmacological interventions in acute and chronic disease states, are virtually neglected in pre-marketing studies assessing the efficacy and safety of investigational drugs. Moreover, aggressively pursuing established therapeutic targets in old age, e.g. blood pressure, serum glucose or cholesterol concentrations, is not necessarily associated with the beneficial effects, and the acceptable safety, reported in younger patient cohorts. Measures of self-reported health and functional status might represent additional, more meaningful, therapeutic end-points in the older population, particularly in patients with significant frailty and relatively short life expectancy, e.g. in the presence of cancer and/or neurodegenerative disease conditions. Strategies enhancing early knowledge about key pharmacological characteristics of investigational drugs targeting older adults are discussed, together with the rationale for incorporating non-traditional, patient-centred, end-points in this ever-increasing group.

  12. Contralesional arm preference depends on hemisphere of damage and target location in unilateral stroke patients

    PubMed Central

    Mani, Saandeep; Przybyla, Andrzej; Good, David C.; Haaland, Kathleen Y.; Sainburg, Robert L.

    2014-01-01

    Background Previous research has shown that during simulated activities of daily living right handed stroke patients use their contralesional arm more after left than right hemisphere stroke. These findings were attributed to a hand preference effect. However, these decisions about when to use the contralesional arm may be modulated by where in the work space the task is performed, a factor that could be used in physical rehabilitation to influence recovery by decreasing learned non-use. Objective To examine how target location and side of stroke influences arm selection choices for simple reaching movements. Methods Fourteen right-handed stroke patients (7 with left hemisphere damage, 7 with right hemisphere damage) with similar degree of hemiparesis (Fugl-Meyer motor score), and 16 right-handed control subjects participated in this experiment. Thirty-two targets were presented throughout the reachable horizontal plane workspace in a pseudo-random fashion, and the subjects were asked to select one hand to reach the target on each trial. Results The left hemisphere damaged group chose their contralesional arm significantly more often than the right hemisphere damaged group. Patients with right hemisphere damage also chose their left (contralesional) arm significantly less than the control group. However, these patterns of choice were most pronounced in the center of the workspace. Conclusion Both the side of hemisphere damage and workspace location played a significant role in the choice of whether to use the contralesional arm for reaching. These findings have implications for structuring rehabilitation for unilateral stroke patients. PMID:24523143

  13. Both Patient and Facility Contribute to Achieving the Centers for Medicare and Medicaid Services' Pay-for-Performance Target for Dialysis Adequacy

    PubMed Central

    Tighiouart, Hocine; Meyer, Klemens B.; Miskulin, Dana C.

    2011-01-01

    The Centers for Medicare and Medicaid Services (CMS) designated the achieved urea reduction ratio (URR) as a pay-for-performance measure, but to what extent this measure reflects patient characteristics and adherence instead of its intent to reflect facility performance is unknown. Here, we quantified the contributions of patient case-mix and adherence to the variability in achieving URR targets across dialysis facilities. We found that 92% of 10,069 hemodialysis patients treated at 173 facilities during the last quarter of 2004 achieved the target URR ≥65%. Mixed-effect models with random intercept for dialysis facility revealed a significant facility effect: 11.5% of the variation in achievement of target URR was attributable to the facility level. Adjusting for patient case-mix reduced the proportion of variation attributable to the facility level to 6.7%. Patient gender, body surface area, dialysis access, and adherence with treatment strongly associated with achievement of the URR target. We could not identify specific facility characteristics that explained the remaining variation between facilities. These data suggest that if adherence is not a modifiable patient characteristic, providers could be unfairly penalized for caring for these patients under current CMS policy. These penalties may have unintended consequences. PMID:22025629

  14. Impact of Clinical Factors on the Achievement of Target Blood Pressure in Hypertensive Patients from Ivanovo Region of Russia: Data of 2015.

    PubMed

    Kiselev, A R; Posnenkova, O M; Belova, O A; Romanchuk, S V; Popova, Y V; Prokhorov, M D; Gridnev, V I

    2017-12-01

    In Russia, blood pressure (BP) control is below the optimal. The little is known about regional features and barriers to adequate BP control in Russian primary care. To evaluate the impact of clinical factors on achieving the target BP in hypertensive patients in one region of Russia. Retrospective medical data of 2015 on 11,129 patients (31.4% male) with hypertension (Htn) from Ivanovo region of Russia were examined. Achievement of target BP was assessed in all patients. We study association between BP control and clinical factors. 45.9% of studied patients with Htn had controlled BP. The frequency of achieving the target BP in subsets of hypertensive patients was 37.8% in patients with diabetes, 39.5% in patients with coronary artery disease, and 29.9% in patients with chronic heart failure. The main clinical factors associated with achieving the target BP in studied hypertensive patients were the advice on alcohol consumption, advice on smoking cessation, and advice on weight reduction. Therapy with main antihypertensive drugs (in particular, beta-blockers and thiazide diuretics) were also factors of optimal BP control in these patients. Comorbidities (chronic heart failure and cardiovascular diseases requiring the prescription of aspirin and statins) and family history of coronary artery disease were associated with inadequate BP control. A negative effect of some antihypertensive drugs (potassium sparing diuretics, ARBs, ACE-Is, and dihydropyridine CCBs) on BP control that was found out in our study requires further investigation. Other studied factors had no influence on BP control in patients with Htn from Ivanovo region. We identified regional factors of BP control in hypertensive patients from Ivanovo region of Russia. It is shown that individual medical education (in particular, medical advices) is the most important factor of optimal BP control. The intervention with antihypertensive therapy (beta-blockers and thiazide diuretics) facilitates the

  15. Epidermal growth factor receptor mutations in non- small cell lung cancers in a multiethnic malaysian patient population.

    PubMed

    Liam, Chong-Kin; Leow, Hwong-Ruey; How, Soon-Hin; Pang, Yong-Kek; Chua, Keong-Tiong; Lim, Boon-Khaw; Lai, Nai-Lang; Kuan, Yeh-Chunn; Pailoor, Jayalakshmi; Rajadurai, Pathmanathan

    2014-01-01

    Mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) in non- small cell lung cancer (NSCLC) are predictive of response to EGFR-targeted therapy in advanced stages of disease. This study aimed to determine the frequency of EGFR mutations in NSCLCs and to correlate their presence with clinical characteristics in multiethnic Malaysian patients. In this prospective study, EGFR mutations in exons 18, 19, 20 and 21 in formalin-fixed paraffin-embedded biopsy specimens of consecutive NSCLC patients were asessed by real-time polymerase chain reaction. EGFR mutations were detected in NSCLCs from 55 (36.4%) of a total of 151 patients, being significantly more common in females (62.5%) than in males (17.2%) [odds ratio (OR), 8.00; 95% confidence interval (CI), 3.77-16.98; p<0.001] and in never smokers (62.5%) than in ever smokers (12.7%) (OR, 11.50; 95%CI, 5.08-26.03; p<0.001). Mutations were more common in adenocarcinoma (39.4%) compared to non-adenocarcinoma NSCLCs (15.8%) (p=0.072). The mutation rates in patients of different ethnicities were not significantly different (p=0.08). Never smoking status was the only clinical feature that independently predicted the presence of EGFR mutations (adjusted OR, 5.94; 95%CI, 1.94- 18.17; p=0.002). In Malaysian patients with NSCLC, the EGFR mutation rate was similar to that in other Asian populations. EGFR mutations were significantly more common in female patients and in never smokers. Never smoking status was the only independent predictor for the presence of EGFR mutations.

  16. Comparison of Prevalence and Types of Mutations in Lung Cancers Among Black and White Populations

    PubMed Central

    Campbell, Joshua D.; Lathan, Christopher; Sholl, Lynette; Ducar, Matthew; Vega, Mikenah; Sunkavalli, Ashwini; Lin, Ling; Hanna, Megan; Schubert, Laura; Thorner, Aaron; Faris, Nicholas; Williams, David R.; Osarogiagbon, Raymond U.; van Hummelen, Paul; Meyerson, Matthew; MacConaill, Laura

    2017-01-01

    IMPORTANCE Lung cancer is the leading cause of cancer death in the United States in all ethnic and racial groups. The overall death rate from lung cancer is higher in black patients than in white patients. OBJECTIVE To compare the prevalence and types of somatic alterations between lung cancers from black patients and white patients. Differences in mutational frequencies could illuminate differences in prognosis and lead to the reduction of outcome disparities by more precisely targeting patients’ treatment. DESIGN, SETTING, AND PARTICIPANTS Tumor specimens were collected from Baptist Cancer Center (Memphis, Tennessee) over the course of 9 years (January 2004-December 2012). Genomic analysis by massively parallel sequencing of 504 cancer genes was performed at Dana-Farber Cancer Institute (Boston, Massachusetts). Overall, 509 lung cancer tumors specimens (319 adenocarcinomas; 142 squamous cell carcinomas) were profiled from 245 black patients and 264 white patients. MAIN OUTCOMES AND MEASURES The frequencies of genomic alterations were compared between tumors from black and white populations. RESULTS Overall, 509 lung cancers were collected and analyzed (273 women [129 black patients; 144 white patients] and 236 men [116 black patients; 120 white patients]). Using 313 adenocarcinomas and 138 squamous cell carcinomas with genetically supported ancestry, overall mutational frequencies and copy number changes were not significantly different between black and white populations in either tumor type after correcting for multiple hypothesis testing. Furthermore, specific activating alterations in members of the receptor tyrosine kinase/Ras/Raf pathway including EGFR and KRAS were not significantly different between populations in lung adenocarcinoma. CONCLUSIONS AND RELEVANCE These results demonstrate that lung cancers from black patients are similar to cancers from white patients with respect to clinically actionable genomic alterations and suggest that clinical

  17. Patient Navigation for Comprehensive Cancer Screening in High-Risk Patients Using a Population-Based Health Information Technology System: A Randomized Clinical Trial.

    PubMed

    Percac-Lima, Sanja; Ashburner, Jeffrey M; Zai, Adrian H; Chang, Yuchiao; Oo, Sarah A; Guimaraes, Erica; Atlas, Steven J

    2016-07-01

    Patient navigation (PN) to improve cancer screening in low-income and racial/ethnic minority populations usually focuses on navigating for single cancers in community health center settings. We evaluated PN for breast, cervical, and colorectal cancer screening using a population-based information technology (IT) system within a primary care network. Randomized clinical trial conducted from April 2014 to December 2014 in 18 practices in an academic primary care network. All patients eligible and overdue for cancer screening were identified and managed using a population-based IT system. Those at high risk for nonadherence with completing screening were identified using an electronic algorithm (language spoken, number of overdue tests, no-show visit history), and randomized to a PN intervention (n = 792) or usual care (n = 820). Navigators used the IT system to track patients, contact them, and provide intense outreach to help them complete cancer screening. Mean cancer screening test completion rate over 8-month trial for each eligible patient, with all overdue cancer screening tests combined using linear regression models. Secondary outcomes included the proportion of patients completing any and each overdue cancer screening test. Among 1612 patients (673 men and 975 women; median age, 57 years), baseline patient characteristics were similar among randomized groups. Of 792 intervention patients, patient navigators were unable to reach 151 (19%), deferred 246 (38%) (eg, patient declined, competing comorbidity), and navigated 202 (32%). The mean proportion of patients who were up to date with screening among all overdue screening examinations was higher in the intervention vs the control group for all cancers combined (10.2% vs 6.8%; 95% CI [for the difference], 1.5%-5.2%; P < .001), and for breast (14.7% vs 11.0%; 95% CI, 0.2%-7.3%; P = .04), cervical (11.1% vs 5.7%; 95% CI, 0.8%-5.2%; P = .002), and colon (7.6% vs 4.6%; 95% CI, 0.8%-5.2%; P

  18. CLL2-BXX Phase II trials: sequential, targeted treatment for eradication of minimal residual disease in chronic lymphocytic leukemia.

    PubMed

    Cramer, Paula; von Tresckow, Julia; Bahlo, Jasmin; Engelke, Anja; Langerbeins, Petra; Fink, Anna-Maria; Fischer, Kirsten; Wendtner, Clemens-Martin; Kreuzer, Karl-Anton; Stilgenbauer, Stephan; Böttcher, Sebastian; Eichhorst, Barbara; Hallek, Michael

    2018-03-01

    Four Phase II trials (clinical trials numbers: NCT02345863, NCT02401503, NCT02445131 and NCT02689141) evaluate a different combination of targeted agents in an all-comer population of approximately 60 patients with chronic lymphocytic leukemia irrespective of prior treatment, physical fitness and genetic risk factors. Patients with a higher tumor load start with a debulking treatment with bendamustine. The subsequent induction and maintenance treatment with an anti-CD20 antibody (obinutuzumab or ofatumumab) and a targeted oral agent (ibrutinib, idelalisib or venetoclax) are continued until achievement of a complete response and minimal residual disease negativity. This strategy represents a new era of chronic lymphocytic leukemia therapy where chemotherapy is increasingly replaced by targeted agents and treatment duration is tailored to the patient's individual tumor load and response.

  19. Policies and Programs to Facilitate Access to Targeted Cancer Therapies in Thailand

    PubMed Central

    Sruamsiri, Rosarin; Ross-Degnan, Dennis; Lu, Christine Y.; Chaiyakunapruk, Nathorn; Wagner, Anita K.

    2015-01-01

    Background Increasing access to clinically beneficial targeted cancer medicines is a challenge in every country due to their high cost. We describe the interplay of innovative policies and programs involving multiple stakeholders to facilitate access to these medicines in Thailand, as well as the utilization of selected targeted therapies over time. Methods We selected two medicines on the 2013 Thai national list of essential medicines (NLEM) [letrozole and imatinib] and three unlisted medicines for the same indications [trastuzumab, nilotinib and dasatinib]. We created timelines of access policies and programs for these products based on scientific and grey literature. Using IMS Health sales data, we described the trajectories of sales volumes of the study medicines between January 2001 and December 2012. We compared estimated average numbers of patients treated before and after the implementation of policies and programs for each product. Results Different stakeholders implemented multiple interventions to increase access to the study medicines for different patient populations. During 2007–2009, the Thai Government created a special NLEM category with different coverage requirements for payers and issued compulsory licenses; payers negotiated prices with manufacturers and engaged in pooled procurement; pharmaceutical companies expanded patient assistance programs and lowered prices in different ways. Compared to before the interventions, estimated numbers of patients treated with each medicine increased significantly afterwards: for letrozole from 645 (95% CI 366–923) to 3683 (95% CI 2,748–4,618); for imatinib from 103 (95% CI 72–174) to 350 (95% CI 307–398); and for trastuzumab from 68 (95% CI 45–118) to 412 (95% CI 344–563). Conclusions Government, payers, and manufacturers implemented multi-pronged approaches to facilitate access to targeted cancer therapies for the Thai population, which differed by medicine. Routine monitoring is needed to

  20. Controversies in targeted therapy of adult T cell leukemia/lymphoma: ON target or OFF target effects?

    PubMed

    Nasr, Rihab; El Hajj, Hiba; Kfoury, Youmna; de Thé, Hugues; Hermine, Olivier; Bazarbachi, Ali

    2011-06-01

    Adult T cell leukemia/lymphoma (ATL) represents an ideal model for targeted therapy because of intrinsic chemo-resistance of ATL cells and the presence of two well identified targets: the HTLV-I retrovirus and the viral oncoprotein Tax. The combination of zidovudine (AZT) and interferon-alpha (IFN) has a dramatic impact on survival of ATL patients. Although the mechanism of action remains unclear, arguments in favor or against a direct antiviral effect will be discussed. Yet, most patients relapse and alternative therapies are mandatory. IFN and arsenic trioxide induce Tax proteolysis, synergize to induce apoptosis in ATL cells and cure Tax-driven ATL in mice through specific targeting of leukemia initiating cell activity. These results provide a biological basis for the clinical success of arsenic/IFN/AZT therapy in ATL patients and suggest that both extinction of viral replication (AZT) and Tax degradation (arsenic/IFN) are needed to cure ATL.

  1. Patient navigation improves cancer diagnostic resolution: an individually randomized clinical trial in an underserved population.

    PubMed

    Raich, Peter C; Whitley, Elizabeth M; Thorland, William; Valverde, Patricia; Fairclough, Diane

    2012-10-01

    Barriers to timely resolution of abnormal cancer screening tests add to cancer health disparities among low-income, uninsured, and minority populations. We conducted a randomized trial to evaluate the impact of lay patient navigators on time to resolution and completion of follow-up testing among patients with abnormal screening tests in a medically underserved patient population. Denver Health, the safety-net health care system serving Denver, is one of 10 performance sites participating in the Patient Navigation Research Program. Of 993 eligible subjects with abnormal screening tests randomized to navigation and no-navigation (control) arms and analyzed, 628 had abnormal breast screens (66 abnormal clinical breast examinations, 304 BIRADS 0, 200 BIRADS 3, 58 BIRADS 4 or 5) whereas 235 had abnormal colorectal and 130 had abnormal prostate screens. Time to resolution was significantly shorter in the navigated group (stratified log rank test, P < 0.001). Patient navigation improved diagnostic resolution for patients presenting with mammographic BIRADS 3 (P = 0.0003) and BIRADS 0 (P = 0.09), but not BIRADS 4/5 or abnormal breast examinations. Navigation shortened the time for both colorectal (P = 0.0017) and prostate screening resolution (P = 0.06). Participant demographics included 72% minority, 49% with annual household income less than $10,000, and 36% uninsured. Patient navigation positively impacts time to resolution of abnormal screening tests for breast, colorectal, and prostate cancers in a medically underserved population. By shortening the time to and increasing the proportion of patients with diagnostic resolution patient navigation could reduce disparities in stage at diagnosis and improve cancer outcomes. 2012 AACR

  2. Statistical inference on censored data for targeted clinical trials under enrichment design.

    PubMed

    Chen, Chen-Fang; Lin, Jr-Rung; Liu, Jen-Pei

    2013-01-01

    For the traditional clinical trials, inclusion and exclusion criteria are usually based on some clinical endpoints; the genetic or genomic variability of the trial participants are not totally utilized in the criteria. After completion of the human genome project, the disease targets at the molecular level can be identified and can be utilized for the treatment of diseases. However, the accuracy of diagnostic devices for identification of such molecular targets is usually not perfect. Some of the patients enrolled in targeted clinical trials with a positive result for the molecular target might not have the specific molecular targets. As a result, the treatment effect may be underestimated in the patient population truly with the molecular target. To resolve this issue, under the exponential distribution, we develop inferential procedures for the treatment effects of the targeted drug based on the censored endpoints in the patients truly with the molecular targets. Under an enrichment design, we propose using the expectation-maximization algorithm in conjunction with the bootstrap technique to incorporate the inaccuracy of the diagnostic device for detection of the molecular targets on the inference of the treatment effects. A simulation study was conducted to empirically investigate the performance of the proposed methods. Simulation results demonstrate that under the exponential distribution, the proposed estimator is nearly unbiased with adequate precision, and the confidence interval can provide adequate coverage probability. In addition, the proposed testing procedure can adequately control the size with sufficient power. On the other hand, when the proportional hazard assumption is violated, additional simulation studies show that the type I error rate is not controlled at the nominal level and is an increasing function of the positive predictive value. A numerical example illustrates the proposed procedures. Copyright © 2013 John Wiley & Sons, Ltd.

  3. Rehospitalization in a national population of home health care patients with heart failure.

    PubMed

    Madigan, Elizabeth A; Gordon, Nahida H; Fortinsky, Richard H; Koroukian, Siran M; Piña, Ileana; Riggs, Jennifer S

    2012-12-01

    Patients with heart failure (HF) have high rates of rehospitalization. Home health care (HHC) patients with HF are not well studied in this regard. The objectives of this study were to determine patient, HHC agency, and geographic (i.e., area variation) factors related to 30-day rehospitalization in a national population of HHC patients with HF, and to describe the extent to which rehospitalizations were potentially avoidable. Chronic Condition Warehouse data from the Centers for Medicare & Medicaid Services. Retrospective cohort design. The 2005 national population of HHC patients was matched with hospital and HHC claims, the Provider of Service file, and the Area Resource File. The 30-day rehospitalization rate was 26 percent with 42 percent of patients having cardiac-related diagnoses for the rehospitalization. Factors with the strongest association with rehospitalization were consistent between the multilevel model and Cox proportional hazard models: number of prior hospital stays, higher HHC visit intensity category, and dyspnea severity at HHC admission. Substantial numbers of rehospitalizations were judged to be potentially avoidable. The persistently high rates of rehospitalization have been difficult to address. There are health care-specific actions and policy implications that are worth examining to improve rehospitalization rates. © Health Research and Educational Trust.

  4. Geolocalization of Influenza Outbreak Within an Acute Care Population: A Layered-Surveillance Approach.

    PubMed

    Kannan, Vijay Christopher; Hodgson, Nicole; Lau, Andrew; Goodin, Kate; Dugas, Andrea Freyer; LoVecchio, Frank

    2016-11-01

    We seek to use a novel layered-surveillance approach to localize influenza clusters within an acute care population. The first layer of this system is a syndromic surveillance screen to guide rapid polymerase chain reaction testing. The second layer is geolocalization and cluster analysis of these patients. We posit that any identified clusters could represent at-risk populations who could serve as high-yield targets for preventive medical interventions. This was a prospective observational surveillance study. Patients were screened with a previously derived clinical decision guideline that has a 90% sensitivity and 30% specificity for influenza. Patients received points for the following signs and symptoms within the past 7 days: cough (2 points), headache (1 point), subjective fever (1 point), and documented fever at triage (temperature >38°C [100.4°F]) (1 point). Patients scoring 3 points or higher were indicated for influenza testing. Patients were tested with Xpert Flu (Cepheid, Sunnyvale, CA), a rapid polymerase chain reaction test. Positive results were mapped with ArcGIS (ESRI, Redlands, CA) and analyzed with kernel density estimation to create heat maps. There were 1,360 patients tested with Xpert Flu with retrievable addresses within the greater Phoenix metro area. One hundred sixty-seven (12%) of them tested positive for influenza A and 23 (2%) tested positive for influenza B. The influenza A virus exhibited a clear cluster pattern within this patient population. The densest cluster was located in an approximately 1-square-mile region southeast of our hospital. Our layered-surveillance approach was effective in localizing a cluster of influenza A outbreak. This region may house a high-yield target population for public health intervention. Further collaborative efforts will be made between our hospital and the Maricopa County Department of Public Health to perform a series of community vaccination events before the next influenza season. We hope these

  5. The Effects of In-Hospital Intravenous Cold Saline in Postcardiac Arrest Patients Treated with Targeted Temperature Management.

    PubMed

    Suppogu, Nissi; Panza, Gregory A; Kilic, Sena; Gowdar, Shreyas; Kallur, Kamala R; Jayaraman, Ramya; Lundbye, Justin; Fernandez, Antonio B

    2018-03-01

    Recent data suggest that rapid infusion of intravenous (IV) cold saline for Targeted Temperature Management (TTM) after cardiac arrest is associated with higher rates of rearrest, pulmonary edema, and hypoxia, with no difference in neurologic outcomes or survival when administered by Emergency Medical Services. We sought to determine the effects of IV cold saline administration in the hospital setting in postcardiac arrest patients to achieve TTM and its effect on clinical parameters and neurologic outcomes. A cohort of 132 patients who completed TTM after cardiac arrest in a single institution was retrospectively studied. Patients who did not receive cold saline were matched by age, gender, Glasgow coma scale, downtime, and presenting rhythm to patients who received cold saline. Demographics, cardiac rearrest, diuretic use, time to target temperature, and Cerebral Performance Category (CPC) scores were recorded among other variables. Patients who received cold saline achieved target temperature sooner (280 vs. 345 minutes, p = 0.05), had lower lactate levels on day 1 (4.2 ± 3.5 mM vs. 6.0 ± 4.9 mM, p = 0.019) and day 2 (1.3 ± 2.2 mM vs. 2.2 ± 3.2 mM, p = 0.046), increased incidence of pulmonary edema (51.5% vs. 31.8%, p = 0.006), and increased diuretic utilization (63.6% vs. 42.4%, p = 0.014). There was no significant difference in cardiac rearrest, arterial oxygenation, and CPC scores (ps > 0.05). Infusion of IV cold saline is associated with shorter time to target temperature, increased incidence of pulmonary edema, and diuretic use, with no difference in cardiac rearrest, survival, and neurologic outcomes.

  6. Does estrogen play a role in response to adjuvant bone-targeted therapies?

    PubMed Central

    Russell, Kent; Amir, Eitan; Paterson, Alexander; Josse, Robert; Addison, Christina; Kuchuk, Iryna; Clemons, Mark

    2013-01-01

    Bone remains the most common site of breast cancer recurrence. The results of population studies, pre-clinical research and clinical studies in patients with metastatic disease provided a rationale for testing bone-targeted agents in the adjuvant setting. Despite the initial optimism, results from eight prospectively designed, randomized control studies powered to assess the value of adjuvant bone-targeted therapy in early breast cancer are conflicting. Data have shown that, where benefit exists, it tends to be in women with a “low estrogen environment”, either through menopause or suppression of ovarian function. In this manuscript, we review clinical data supporting the hypothesis that estrogen levels may play a part in explaining the response of patients to bone-targeted agents in the adjuvant setting. The results presented to date suggest that there may be data supporting a unifying role for estrogen in adjuvant trials. However, in the absence of any prospective randomized trials in which estrogen data has been systematically collected we cannot specifically answer this question. We await the results of the Oxford overview analysis of individual patient data with interest. PMID:26909288

  7. Targeted Therapies in Hematology and Their Impact on Patient Care: Chronic and Acute Myeloid Leukemia

    PubMed Central

    Cortes, Elias Jabbour Jorge; Ravandi, Farhad; O’Brien, Susan; Kantarjian, Hagop

    2014-01-01

    Advances in the genetic and molecular characterizations of leukemias have enhanced our capabilities to develop targeted therapies. The most dramatic examples of targeted therapy in cancer to date are the use of targeted BCR-ABL protein tyrosine kinase inhibitors (TKI) which has revolutionized the treatment of chronic myeloid leukemia (CML). Inhibition of the signaling activity of this kinase has proved to be a highly successful treatment target, transforming the prognosis of patients with CML. In contrast, acute myeloid leukemia (AML) is an extremely heterogeneous disease with outcomes that vary widely according to subtype of the disease. Targeted therapy with monoclonal antibodies and small molecule kinase inhibitors are promising strategies to help improve the cure rates in AML. In this review, we will highlight the results of recent clinical trials in which outcomes of CML and AML have been influenced significantly. Also, novel approaches to sequencing and combining available therapies will be covered. PMID:24246694

  8. The effect of targeted and tailored patient depression engagement interventions on patient-physician discussion of suicidal thoughts: a randomized control trial.

    PubMed

    Shah, Ruby; Franks, Peter; Jerant, Anthony; Feldman, Mitchell; Duberstein, Paul; Fernandez y Garcia, Erik; Hinton, Ladson; Strohecker, Lorrie; Kravitz, Richard L

    2014-08-01

    Despite improvements in the diagnosis and treatment of depression, primary care provider (PCP) discussion regarding suicidal thoughts among patients with depressive symptoms remains low. To determine whether a targeted depression public service announcement (PSA) video or an individually tailored interactive multimedia computer program (IMCP) leads to increased primary care provider (PCP) discussion of suicidal thoughts in patients with elevated risk for clinical depression when compared to an attention control. Randomized control trial at five different healthcare systems in Northern California; two academic, two Veterans Affairs (VA), and one group-model health maintenance organization (HMO). Eight-hundred sixty-seven participants, with mean age 51.7; 43.9% women, 43.4% from a racial/ethnic minority group. The PSA was targeted to gender and socio-economic status, and designed to encourage patients to seek depression care or request information regarding depression. The IMCP was an individually tailored interactive health message designed to activate patients to discuss possible depressive symptoms. The attention control was a sleep hygiene video. Clinician reported discussion of suicidal thoughts. Analyses were stratified by depressive symptom level (Patient Health Questionnaire [PHQ-9] score < 9 [mild or lower] versus ≥ 10 [at least moderate]). Among patients with a PHQ-9 score ≥ 10, PCP discussion of suicidal thoughts was significantly higher in the IMCP group than in the control group (adjusted odds ratio = 2.33, 95% confidence interval = 1.5, 5.10, p = 0.03). There were no significant effects of either intervention on PCP discussion of suicidal thoughts among patients with a PHQ-9 score < 9. Exposure of patients with at least moderate depressive symptoms to an individually tailored intervention designed to increase patient engagement in depression care led to increased PCP discussion of suicidal thoughts.

  9. The timing of general population and patient suicide in England, 1997-2012.

    PubMed

    Cavanagh, Brendan; Ibrahim, Saied; Roscoe, Alison; Bickley, Harriet; While, David; Windfuhr, Kirsten; Appleby, Louis; Kapur, Nav

    2016-06-01

    There have been conflicting findings on temporal variation in suicide risk and few have examined the phenomenon in clinical populations. The study investigated seasonal and other temporal patterns using national data. Data on 73,591 general population and 19,318 patient suicide deaths in England between 1997 and 2012 were collected through the National Confidential Inquiry into Suicide examining suicide rates in relation to month of the year, day of the week, and individual days of national or religious significance. Suicide incidence fell over successive months of the year and there was evidence of an overall spring peak. Monday was associated with the highest suicide rates and in the patient population this effect appeared to be more pronounced in those aged over 50 or those who lived alone. Suicide risk was significantly lower during Christmas, particularly for women. There was a peak in suicide on New Year's Day in the general population. Other 'special days' were not associated with a change in suicide incidence. We were limited to identifying associations between the variables investigated and were unable to explore causal mechanisms. We did not carry out comprehensive multi-variable adjustment in our regression models. There is substantial seasonal and temporal variation in suicide deaths, and there appears to be some evidence in the clinical as well as the general population in England. Clinical services should be aware of the risk of suicide just after the weekend, especially in people who live alone, and the potential need for closer supervision during this period. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Exploring the concept of medication discrepancy within the context of patient safety to improve population health.

    PubMed

    Murphy, Catherine R; Corbett, Cynthia L; Setter, Stephen M; Dupler, Alice

    2009-01-01

    Medication discrepancy is a concept often used in discussions about medication safety but has neither been fully explained nor clearly defined in the literature. This article explores medication discrepancy as it relates to patient safety and population health in the management of medications. Literature review reveals 2 main aspects of discrepancies in medication management; prescribing issues and patient adherence to regimens. Further development of the concept of medication discrepancy can be beneficial to the theorist, researcher, or clinician. Conceptual clarity about the various aspects of medication discrepancy in the context of patient safety has the potential to enhance quality improvement efforts and patient outcomes to improve population health.

  11. Molecular characterization of oral squamous cell carcinoma using targeted next-generation sequencing.

    PubMed

    Er, Tze-Kiong; Wang, Yen-Yun; Chen, Chih-Chieh; Herreros-Villanueva, Marta; Liu, Ta-Chih; Yuan, Shyng-Shiou F

    2015-10-01

    Many genetic factors play an important role in the development of oral squamous cell carcinoma. The aim of this study was to assess the mutational profile in oral squamous cell carcinoma using formalin-fixed, paraffin-embedded tumors from a Taiwanese population by performing targeted sequencing of 26 cancer-associated genes that are frequently mutated in solid tumors. Next-generation sequencing was performed in 50 formalin-fixed, paraffin-embedded tumor specimens obtained from patients with oral squamous cell carcinoma. Genetic alterations in the 26 cancer-associated genes were detected using a deep sequencing (>1000X) approach. TP53, PIK3CA, MET, APC, CDH1, and FBXW7 were most frequently mutated genes. Most remarkably, TP53 mutations and PIK3CA mutations, which accounted for 68% and 18% of tumors, respectively, were more prevalent in a Taiwanese population. Other genes including MET (4%), APC (4%), CDH1 (2%), and FBXW7 (2%) were identified in our population. In summary, our study shows the feasibility of performing targeted sequencing using formalin-fixed, paraffin-embedded samples. Additionally, this study also reports the mutational landscape of oral squamous cell carcinoma in the Taiwanese population. We believe that this study will shed new light on fundamental aspects in understanding the molecular pathogenesis of oral squamous cell carcinoma and may aid in the development of new targeted therapies. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. A method to combine target volume data from 3D and 4D planned thoracic radiotherapy patient cohorts for machine learning applications.

    PubMed

    Johnson, Corinne; Price, Gareth; Khalifa, Jonathan; Faivre-Finn, Corinne; Dekker, Andre; Moore, Christopher; van Herk, Marcel

    2018-02-01

    The gross tumour volume (GTV) is predictive of clinical outcome and consequently features in many machine-learned models. 4D-planning, however, has prompted substitution of the GTV with the internal gross target volume (iGTV). We present and validate a method to synthesise GTV data from the iGTV, allowing the combination of 3D and 4D planned patient cohorts for modelling. Expert delineations in 40 non-small cell lung cancer patients were used to develop linear fit and erosion methods to synthesise the GTV volume and shape. Quality was assessed using Dice Similarity Coefficients (DSC) and closest point measurements; by calculating dosimetric features; and by assessing the quality of random forest models built on patient populations with and without synthetic GTVs. Volume estimates were within the magnitudes of inter-observer delineation variability. Shape comparisons produced mean DSCs of 0.8817 and 0.8584 for upper and lower lobe cases, respectively. A model trained on combined true and synthetic data performed significantly better than models trained on GTV alone, or combined GTV and iGTV data. Accurate synthesis of GTV size from the iGTV permits the combination of lung cancer patient cohorts, facilitating machine learning applications in thoracic radiotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. A population-specific Mini-Nutritional Assessment can effectively grade the nutritional status of stroke rehabilitation patients in Taiwan.

    PubMed

    Tsai, Alan C; Shih, Chi-Ling

    2009-01-01

    To determine whether a modified version of the Mini-Nutritional Assessment without body mass index could effectively assess the nutritional risk status of stroke rehabilitation patients in Taiwan. The Mini-Nutritional Assessment was developed on the basis of clinical data of Western populations. Although widely used, its application to assess stroke rehabilitation patients has been limited. Further, to get best results, population-specific modifications to address anthropometric and lifestyle differences have been suggested, especially for non-Caucasian populations. The study assessed the nutritional status of stroke rehabilitation patients who enrolled in the Long-Term Care Service of Taipei. Strokes who were >40 years old, in the program for >1 month and cognitively able to answer the questions were recruited to participate in the study. An on-site in-person interview with structured questionnaire elicited information on personal data, disease history and healthcare use and answers to the Mini-Mental State Examination, the Activities of Daily Living and the Mini-Nutritional Assessment. Patient's nutritional status was assessed with the Mini-Nutritional Assessment in three versions: the original, population-specific (MNA-TI) and population-specific, without body mass index (MNA-TII). The original Mini-Nutritional Assessment rated 24% of patients malnourished and 57% at risk of malnutrition. Similar results, 14 and 64%, respectively, for MNA-TI; and 19 and 57%, respectively, for MNA-TII were observed. Both the original and the modified versions of the Mini-Nutritional Assessment can effectively rate the nutritional risk status of stroke rehabilitation patients in Taiwan. Version MNA-TII that adopted population-specific anthropometric cut-values but without body mass index can effectively predict the nutritional status of stroke patients. The modified scale (MNA-TII) can enhance the application of the tool and timely detection and intervention of undernutrition

  14. Targeting LKB1 in cancer – exposing and exploiting vulnerabilities

    PubMed Central

    Momcilovic, M; Shackelford, D B

    2015-01-01

    The LKB1 tumour suppressor is a serine/threonine kinase that functions as master regulator of cell growth, metabolism, survival and polarity. LKB1 is frequently mutated in human cancers and research spanning the last two decades have begun decoding the cellular pathways deregulated following LKB1 inactivation. This work has led to the identification of vulnerabilities present in LKB1-deficient tumour cells. Pre-clinical studies have now identified therapeutic strategies targeting this subset of tumours that promise to benefit this large patient population harbouring LKB1 mutations. Here, we review the current efforts that are underway to translate pre-clinical discovery of therapeutic strategies targeting LKB1 mutant cancers into clinical practice. PMID:26196184

  15. Increased Heat Generation in Postcardiac Arrest Patients During Targeted Temperature Management Is Associated With Better Outcomes.

    PubMed

    Uber, Amy J; Perman, Sarah M; Cocchi, Michael N; Patel, Parth V; Ganley, Sarah E; Portmann, Jocelyn M; Donnino, Michael W; Grossestreuer, Anne V

    2018-04-03

    Assess if amount of heat generated by postcardiac arrest patients to reach target temperature (Ttarget) during targeted temperature management is associated with outcomes by serving as a proxy for thermoregulatory ability, and whether it modifies the relationship between time to Ttarget and outcomes. Retrospective cohort study. Urban tertiary-care hospital. Successfully resuscitated targeted temperature management-treated adult postarrest patients between 2008 and 2015 with serial temperature data and Ttarget less than or equal to 34°C. None. Time to Ttarget was defined as time from targeted temperature management initiation to first recorded patient temperature less than or equal to 34°C. Patient heat generation ("heat units") was calculated as inverse of average water temperature × hours between initiation and Ttarget × 100. Primary outcome was neurologic status measured by Cerebral Performance Category score; secondary outcome was survival, both at hospital discharge. Univariate analyses were performed using Wilcoxon rank-sum tests; multivariate analyses used logistic regression. Of 203 patients included, those with Cerebral Performance Category score 3-5 generated less heat before reaching Ttarget (median, 8.1 heat units [interquartile range, 3.6-21.6 heat units] vs median, 20.0 heat units [interquartile range, 9.0-33.5 heat units]; p = 0.001) and reached Ttarget quicker (median, 2.3 hr [interquartile range, 1.5-4.0 hr] vs median, 3.6 hr [interquartile range, 2.0-5.0 hr]; p = 0.01) than patients with Cerebral Performance Category score 1-2. Nonsurvivors generated less heat than survivors (median, 8.1 heat units [interquartile range, 3.6-20.8 heat units] vs median, 19.0 heat units [interquartile range, 6.5-33.5 heat units]; p = 0.001) and reached Ttarget quicker (median, 2.2 hr [interquartile range, 1.5-3.8 hr] vs median, 3.6 hr [interquartile range, 2.0-5.0 hr]; p = 0.01). Controlling for average water temperature between initiation and Ttarget, the

  16. Who Should We Target? The Impact of Individual and Family Characteristics on the Expressed Need for Community-Based Treatment Support in HIV Patients in South Africa.

    PubMed

    Wouters, Edwin; Booysen, Frederik le Roux; Masquillier, Caroline

    2016-01-01

    Reviews of impact evaluations of community-based health workers and peer support groups highlight the considerable variability in the effectiveness of such support in improving antiretroviral treatment (ART) outcomes. Evidence indicates that community-based support interventions targeting patients known to be at risk will probably display better results than generic interventions aimed at the entire population of people living with HIV. It is however difficult to identify these at-risk populations, rendering knowledge on the characteristics of patients groups who are in need of community-based support a clear research priority. The current study aims to address the knowledge gap by exploring the predictors of the willingness to (1) receive the support from a community-based health worker or (2) to participate in a support group in public sector ART programme of the Free State Province of South Africa. Based on the Individual-Family-Community framework for HIV research, the study employs a comprehensive approach by not only testing classical individual-level but also family-level predictors of the willingness to receive community-based support. In addition to individual-level predictors-such as age, health status and coping styles-our analysis demonstrated the importance of family characteristics. The results indicated that discrepancies in the family's changeability level were an important predictor of the demand for community-based support services. Conversely, the findings indicated that patients living in a family more flexible than deemed ideal are more likely to require the support of a community health worker. The current study expands theory by indicating the need to acknowledge all social ecological levels in the study of chronic HIV care. The detection of both individual level and family level determinants of the expressed need for community-based support can inform health policy to devise strategies to target scarce resources to those vulnerable patients

  17. Who Should We Target? The Impact of Individual and Family Characteristics on the Expressed Need for Community-Based Treatment Support in HIV Patients in South Africa

    PubMed Central

    Wouters, Edwin; Booysen, Frederik le Roux; Masquillier, Caroline

    2016-01-01

    Reviews of impact evaluations of community-based health workers and peer support groups highlight the considerable variability in the effectiveness of such support in improving antiretroviral treatment (ART) outcomes. Evidence indicates that community-based support interventions targeting patients known to be at risk will probably display better results than generic interventions aimed at the entire population of people living with HIV. It is however difficult to identify these at-risk populations, rendering knowledge on the characteristics of patients groups who are in need of community-based support a clear research priority. The current study aims to address the knowledge gap by exploring the predictors of the willingness to (1) receive the support from a community-based health worker or (2) to participate in a support group in public sector ART programme of the Free State Province of South Africa. Based on the Individual-Family-Community framework for HIV research, the study employs a comprehensive approach by not only testing classical individual-level but also family-level predictors of the willingness to receive community-based support. In addition to individual-level predictors—such as age, health status and coping styles—our analysis demonstrated the importance of family characteristics. The results indicated that discrepancies in the family’s changeability level were an important predictor of the demand for community-based support services. Conversely, the findings indicated that patients living in a family more flexible than deemed ideal are more likely to require the support of a community health worker. The current study expands theory by indicating the need to acknowledge all social ecological levels in the study of chronic HIV care. The detection of both individual level and family level determinants of the expressed need for community-based support can inform health policy to devise strategies to target scarce resources to those vulnerable

  18. Heart failure in patients with kidney disease.

    PubMed

    Tuegel, Courtney; Bansal, Nisha

    2017-12-01

    Heart failure (HF) is a leading cause of morbidity and mortality in patients with chronic kidney disease (CKD), and the population of CKD patients with concurrent HF continues to grow. The accurate diagnosis of HF is challenging in patients with CKD in part due to a lack of validated imaging and biomarkers specifically in this population. The pathophysiology between the heart and the kidneys is complex and bidirectional. Patients with CKD have greater prevalence of traditional HF risk factors as well as unique kidney-specific risk factors including malnutrition, acid-base alterations, uraemic toxins, bone mineral changes, anemia and myocardial stunning. These risk factors also contribute to the decline of kidney function seen in patients with subclinical and clinical HF. More targeted HF therapies may improve outcomes in patients with kidney disease as current HF therapies are underutilised in this population. Further work is also needed to develop novel HF therapies for the CKD population. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  19. Small D-type asteroids in the NEO population: new targets for space missions

    NASA Astrophysics Data System (ADS)

    Barucci, Maria Antonietta; Perna, D.; Popescu, M.; Fornasier, S.; Doressoundiram, A.; Lantz, C.; Merlin, F.; Fulchignoni, M.; Dotto, E.; Kanuchova, S.

    2018-06-01

    In the framework of the Near Earth Objects (NEOs) observational campaign carried out within the NEOShield-2 project, we identify nine new small D-type asteroids with estimated diameter less than 600 m. The link with meteorites for this class of asteroids is weak and the best fit obtained is with the Tagish Lake meteorite for seven of them. D-type asteroids are believed to contain the most pristine material of the Solar system and could have delivered the pre-biotic material to the Earth. Our results double the known sample of the D-types in the NEO population and triple the candidates of this class for a sample-return mission (at very low ΔV). Our finding increases considerably the number of targets for sample-return mission. A sample-return mission to a D-type asteroid will provide a major progress in understanding the early history of the Solar system and to investigate the origin of life on the Earth.

  20. OVERCOMING BARRIERS To DIVERSITY IN CHIROPRACTIC PATIENT AND PRACTITIONER POPULATIONS: A COMMENTARY.

    PubMed

    Young, Kenneth J

    2015-01-01

    Increasing the diversity of practitioner and patient populations has been identified as a worthy goal in the chiropractic profession, which has predominantly white male practitioners and white female patients in the USA. Toward that end, 'diversity' has been the topic of several papers and was the theme of a 2012 conference of chiropractic educators. However, generally just the microcosm of the interactions of practitioners with patients or teachers with students has been discussed. The macrocosm of larger societal issues and government policies has not been broached. Examples of issues and policies that affect diversity within a profession include portrayals of, and value judgements on diversity by the media and politicians, as well as public funding for healthcare and education. Diversity was defined in this paper to mean differences in race, sex, sexual orientation, economic status, ethnicity, religion and other life circumstances in a population. The purpose of this paper is to raise awareness of evidence that social issues and government policy affect the diversity of practitioners and patients, and to suggest that the barriers to diversity present in these realms be addressed with a cogent, profession-wide effort in order to help increase the diversity of people involved with chiropractic.

  1. Real world heart failure epidemiology and outcome: A population-based analysis of 88,195 patients

    PubMed Central

    Vela, Emili; Clèries, Montse; Bustins, Montse; Cainzos-Achirica, Miguel; Enjuanes, Cristina; Moliner, Pedro; Ruiz, Sonia; Verdú-Rotellar, José María; Comín-Colet, Josep

    2017-01-01

    Background Heart failure (HF) is frequent and its prevalence is increasing. We aimed to evaluate the epidemiologic features of HF patients, the 1-year follow-up outcomes and the independent predictors of those outcomes at a population level. Methods and results Population-based longitudinal study including all prevalent HF cases in Catalonia (Spain) on December 31st, 2012. Patients were divided in 3 groups: patients without a previous HF hospitalization, patients with a remote (>1 year) HF hospitalization and patients with a recent (<1 year) HF admission. We analyzed 1year all-cause and HF hospitalizations, and all-cause mortality. Logistic regression was used to identify the independent predictors of each of those outcomes. A total of 88,195 patients were included. Mean age was 77 years, 55% were women. Comorbidities were frequent. Fourteen percent of patients had never been hospitalized, 71% had a remote HF hospitalization and 15% a recent hospitalization. At 1-year follow-up, all-cause and HF hospitalization were 53% and 8.8%, respectively. One-year all-cause mortality rate was 14%, and was higher in patients with a recent HF hospitalization (24%). The presence of diabetes mellitus, atrial fibrillation or chronic kidney disease was independently associated with all-cause and HF hospitalization and all-cause mortality. Hospital admissions and emergency department visits the previous year were also found to be independently associated with the three study outcomes. Conclusions Outcomes are different depending on the HF population studied. Some comorbidity, an all-cause hospitalization or emergency department visit the previous year were associated with a worse outcome. PMID:28235067

  2. Real world heart failure epidemiology and outcome: A population-based analysis of 88,195 patients.

    PubMed

    Farré, Núria; Vela, Emili; Clèries, Montse; Bustins, Montse; Cainzos-Achirica, Miguel; Enjuanes, Cristina; Moliner, Pedro; Ruiz, Sonia; Verdú-Rotellar, José María; Comín-Colet, Josep

    2017-01-01

    Heart failure (HF) is frequent and its prevalence is increasing. We aimed to evaluate the epidemiologic features of HF patients, the 1-year follow-up outcomes and the independent predictors of those outcomes at a population level. Population-based longitudinal study including all prevalent HF cases in Catalonia (Spain) on December 31st, 2012. Patients were divided in 3 groups: patients without a previous HF hospitalization, patients with a remote (>1 year) HF hospitalization and patients with a recent (<1 year) HF admission. We analyzed 1year all-cause and HF hospitalizations, and all-cause mortality. Logistic regression was used to identify the independent predictors of each of those outcomes. A total of 88,195 patients were included. Mean age was 77 years, 55% were women. Comorbidities were frequent. Fourteen percent of patients had never been hospitalized, 71% had a remote HF hospitalization and 15% a recent hospitalization. At 1-year follow-up, all-cause and HF hospitalization were 53% and 8.8%, respectively. One-year all-cause mortality rate was 14%, and was higher in patients with a recent HF hospitalization (24%). The presence of diabetes mellitus, atrial fibrillation or chronic kidney disease was independently associated with all-cause and HF hospitalization and all-cause mortality. Hospital admissions and emergency department visits the previous year were also found to be independently associated with the three study outcomes. Outcomes are different depending on the HF population studied. Some comorbidity, an all-cause hospitalization or emergency department visit the previous year were associated with a worse outcome.

  3. Assessing the impact of heart failure specialist services on patient populations.

    PubMed

    Lyratzopoulos, Georgios; Cook, Gary A; McElduff, Patrick; Havely, Daniel; Edwards, Richard; Heller, Richard F

    2004-05-24

    The assessment of the impact of healthcare interventions may help commissioners of healthcare services to make optimal decisions. This can be particularly the case if the impact assessment relates to specific patient populations and uses timely local data. We examined the potential impact on readmissions and mortality of specialist heart failure services capable of delivering treatments such as b-blockers and Nurse-Led Educational Intervention (N-LEI). Statistical modelling of prevented or postponed events among previously hospitalised patients, using estimates of: treatment uptake and contraindications (based on local audit data); treatment effectiveness and intolerance (based on literature); and annual number of hospitalization per patient and annual risk of death (based on routine data). Optimal treatment uptake among eligible but untreated patients would over one year prevent or postpone 11% of all expected readmissions and 18% of all expected deaths for spironolactone, 13% of all expected readmisisons and 22% of all expected deaths for b-blockers (carvedilol) and 20% of all expected readmissions and an uncertain number of deaths for N-LEI. Optimal combined treatment uptake for all three interventions during one year among all eligible but untreated patients would prevent or postpone 37% of all expected readmissions and a minimum of 36% of all expected deaths. In a population of previously hospitalised patients with low previous uptake of b-blockers and no uptake of N-LEI, optimal combined uptake of interventions through specialist heart failure services can potentially help prevent or postpone approximately four times as many readmissions and a minimum of twice as many deaths compared with simply optimising uptake of spironolactone (not necessarily requiring specialist services). Examination of the impact of different heart failure interventions can inform rational planning of relevant healthcare services.

  4. Prevalence of upper gastrointestinal bleeding risk factors among the general population and osteoarthritis patients.

    PubMed

    Kim, Sang Hyuck; Yun, Jae Moon; Chang, Chong Bum; Piao, Heng; Yu, Su Jong; Shin, Dong Wook

    2016-12-28

    To assess the prevalence of possible risk factors of upper gastrointestinal bleeding (UGIB) and their age-group specific trend among the general population and osteoarthritis patients. We utilized data from the National Health Insurance Service that included claims data and results of the national health check-up program. Comorbid conditions (peptic ulcer, diabetes, liver disease, chronic renal failure, and gastroesophageal reflux disease), concomitant drugs (aspirin, clopidogrel, cilostazol, non-steroidal anti-inflammatory drugs, steroid, anticoagulants, and SSRI), personal habits (smoking, and alcohol consumption) were considered as possible UGIB risk factors. We randomly imputed the prevalence of infection in the data considering the age-specific prevalence of Helicobacter pylori ( H. pylori ) infection in Korea. The prevalence of various UGIB risk factors and the age-group specific trend of the prevalence were identified. Prevalence was compared between osteoarthritis patients and others. A total of 801926 subjects (93855 osteoarthritis patients) aged 20 and above were included. The prevalence of individual and concurrent multiple risk factors became higher as the age increased. The prevalence of each comorbid condition and concomitant drug were higher in osteoarthritis patients. Thirty-five point zero two percent of the overall population and 68.50% of osteoarthritis patients had at least one or more risk factors of UGIB. The prevalence of individual and concurrent multiple risk factors in younger age groups were also substantial. Furthermore, when personal habits (smoking, and alcohol consumption) and H. pylori infection were included, the prevalence of concurrent multiple risk factors increased greatly even in younger age groups. Prevalence of UGIB risk factors was high in elderly population, but was also considerable in younger population. Patient with osteoarthritis was at higher UGIB risk than those without osteoarthritis. Physicians should consider

  5. Controversies in Targeted Therapy of Adult T Cell Leukemia/Lymphoma: ON Target or OFF Target Effects?

    PubMed Central

    Nasr, Rihab; Hajj, Hiba El; Kfoury, Youmna; de Thé, Hugues; Hermine, Olivier; Bazarbachi, Ali

    2011-01-01

    Adult T cell leukemia/lymphoma (ATL) represents an ideal model for targeted therapy because of intrinsic chemo-resistance of ATL cells and the presence of two well identified targets: the HTLV-I retrovirus and the viral oncoprotein Tax. The combination of zidovudine (AZT) and interferon-alpha (IFN) has a dramatic impact on survival of ATL patients. Although the mechanism of action remains unclear, arguments in favor or against a direct antiviral effect will be discussed. Yet, most patients relapse and alternative therapies are mandatory. IFN and arsenic trioxide induce Tax proteolysis, synergize to induce apoptosis in ATL cells and cure Tax-driven ATL in mice through specific targeting of leukemia initiating cell activity. These results provide a biological basis for the clinical success of arsenic/IFN/AZT therapy in ATL patients and suggest that both extinction of viral replication (AZT) and Tax degradation (arsenic/IFN) are needed to cure ATL. PMID:21994752

  6. Mapping Patterns of Ipsilateral Supraclavicular Nodal Metastases in Breast Cancer: Rethinking the Clinical Target Volume for High-risk Patients

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jing, Hao; Wang, Shu-Lian, E-mail: wsl20040118@yahoo.com; Li, Jing

    2015-10-01

    Purpose: To map the location of metastatic supraclavicular (SCV) lymph nodes (LNMs) in breast cancer patients with SCV node involvement and determine whether and where the radiation therapy clinical target volume (CTV) of this region could be modified in high-risk subsets. Methods and Materials: Fifty-five patients with metastatic SCV LNMs were eligible for geographic mapping and atlas coverage analysis. All LNMs and their epicenters were registered proportionally by referencing the surrounding landmarks onto simulation computed tomography images of a standard patient. CTVs based on selected SCV atlases, including the one by the Radiation Therapy Oncology Group (RTOG) were contoured. Amore » modified SCV CTV was tried and shown to have better involved-node coverage and thus theoretically improved prophylaxis in this setting. Results: A total of 50 (91%) and 45 (81.8%) patients had LNMs in the medial and lateral SCV subregions, respectively. Also, 36 patients (65.5%) had LNMs located at the junction of the jugular-subclavian veins. All nodes were covered in only 25.5% to 41.8% of patients by different atlases. The RTOG atlas covered all nodes in 25.5% of patients. Stratified by the nodes in all the patients as a whole, 49.2% to 81.3% were covered, and the RTOG atlas covered 62.6%. The lateral and posterior borders were the most overlooked locations. Modification by extending the borders to natural anatomic barriers allowed the new CTV to cover all the nodes in 81.8% of patients and encompass 96.1% of all the nodes. Conclusions: According to the distribution of SCV LNMs, the extent of existing atlases might not be adequate for potential metastatic sites in certain groups of patients. The extension of the lateral and posterior CTV borders in high-risk or recurrent patients might be a reasonable approach for increasing coverage. However, additional data in more homogeneous populations with localized disease are needed before routine application.« less

  7. Reaching lost-to-care populations.

    PubMed

    Jordan, Wilbert C

    2007-12-15

    Identification of patients who are at high risk for human immunodeficiency virus (HIV) infection can lead to reduced frequencies of high-risk behaviors, provision of timely care for infected individuals, and decreased transmission of HIV. The HIV-associated outreach programs at the OASIS Clinic of the King-Harbor/Drew University complex (Los Angeles, CA) has 3 components: a traditional partner-notification (i.e., contact-tracing) component, a focused-intervention component through which clients are given incentives to bring in persons they feel are at high risk for HIV infection, and an outreach component targeting hard-to-reach populations. These interventions are highly effective in identifying individuals early during the course of their disease, when initiation of antiretroviral therapy is most effective. The partner-services program at the OASIS Clinic has been particularly useful in identifying partners of HIV-positive women, whereas the focused-intervention program is most useful for identifying gay men who are unaware of their positive HIV serostatus. Successful targeted outreach programs can identify many individuals who would not otherwise be aware of their HIV infection, but the programs also require more clinicians to manage these patients.

  8. Incremental healthcare resource utilization and costs in US patients with Cushing's disease compared with diabetes mellitus and population controls.

    PubMed

    Broder, Michael S; Neary, Maureen P; Chang, Eunice; Ludlam, William H

    2015-12-01

    Resource utilization and costs in Cushing's disease (CD) patients have not been studied extensively. We compared CD patients with diabetes mellitus (DM) patients and population-based controls to characterize differences in utilization and costs. Using 2008-2012 MarketScan® database, we identified three patient groups: (1) CD patients; (2) DM patients; and (3) population-based control patients without CD. DM and control patients were matched to CD patients by age, gender, region, and review year in a 2:1 ratio. Outcomes included annual healthcare resource utilization and costs. There were 1852 CD patients, 3704 DM patients and 3704 controls. Mean age was 42.9 years; 78.2 % were female. CD patients were hospitalized more frequently (19.3 %) than DM patients (11.0 %, p < .001) or controls (5.6 %, p < .001). CD patients visited the ED more frequently (25.4 %) than DM patients (21.1 %, p < .001) or controls (14.3 %, p < .001). CD patients had more office visits than DM patients (19.1 vs. 10.7, p < .001) or controls (7.1, p < .001). CD patients on average filled more prescriptions than DM patients (51.7 vs. 42.7, p < .001) or controls (20.5, p < .001). Mean total healthcare costs for CD patients were $26,269 versus $12,282 for DM patients (p < .001) and $5869 for controls (p < .001). CD patients had significantly higher annual rates of healthcare resource utilization compared to matched DM patients and population controls without CD. CD patient costs were double DM costs and quadruple control costs. This study puts into context the additional burdens of CD over DM, a common, chronic endocrine condition affecting multiple organ systems, and population controls.

  9. Using injectable hydrogel markers to assess resimulation for boost target volume definition in a patient undergoing whole-breast radiotherapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Patel, Henal; Goyal, Sharad; Kim, Leonard, E-mail: kimlh@rutgers.edu

    Several publications have recommended that patients undergoing whole-breast radiotherapy be resimulated for boost planning. The rationale for this is that the seroma may be smaller when compared with the initial simulation. However, the decision remains whether to use the earlier or later images to define an appropriate boost target volume. A patient undergoing whole-breast radiotherapy had new, injectable, temporary hydrogel fiducial markers placed 1 to 3 cm from the seroma at the time of initial simulation. The patient was resimulated 4.5 weeks later for conformal photon boost planning. Computed tomography (CT) scans acquired at the beginning and the end ofmore » whole-breast radiotherapy showed that shrinkage of the lumpectomy cavity was not matched by a corresponding reduction in the surrounding tissue volume, as demarcated by hydrogel markers. This observation called into question the usual interpretation of cavity shrinkage for boost target definition. For this patient, it was decided to define the boost target volume on the initial planning CT instead of the new CT.« less

  10. Comparison of the low-density lipoprotein cholesterol target value and the preventive effect of statins in elderly patients and younger patients.

    PubMed

    Endo, Akihiro; Okada, Taiji; Pak, Misun; Kagawa, Yuzo; Ito, Shimpei; Sato, Hirotomo; Kageshima, Kenji; Yoshida, Yasuyuki; Tanabe, Kazuaki

    2017-06-01

    To assess whether the low-density lipoprotein cholesterol (LDL-C) target value and preventive effect of statins are different between elderly and younger patients. We investigated 304 patients with previous percutaneous coronary intervention who underwent coronary angiography from January 2007 to December 2016 for examination of recurrent ischemia beyond the early restenosis. Patients were classified into two groups: age ≥ 75 years (elderly group: n = 140) and < 75 years (younger group: n = 164). Relationships between the achieved LDL-C level, incidence of late coronary events, and the effectiveness of statins were evaluated. During follow-up, 179 patients underwent late coronary revascularization. Recurrent ischemia presenting as acute coronary syndrome (ACS) occurred in 83 cases. Kaplan-Meier curve analysis revealed that in the younger group, recurrent ACS was significantly lower in patients with LDL-C < 70 mg/dL than in those with LDL-C ranging from 70 to < 100 mg/dL ( P = 0.035); however, there was no difference between these in the elderly group ( P = 0.863). Instead, recurrent ACS was less frequent in patients with LDL-C ranging from 70 mg/dL to < 100 mg/dL than in those with LDL-C ≥ 100 mg/dL in the elderly group ( P = 0.033). Statin use was associated with decreased recurrent ACS ( P = 0.005); moreover, only using statins was an independent predictor in the elderly group (HR: 0.375; P = 0.007). Strict control of LDL-C to < 70 mg/dL was effective for reducing the incidence of recurrent ACS in younger patients. However, LDL-C < 100 mg/dL might be sufficient as the target value of LDL-C-lowering therapy for secondary prevention of ischemic events in Japanese elderly patients.

  11. MicroRNA-320a suppresses in GBM patients and modulates glioma cell functions by targeting IGF-1R.

    PubMed

    Guo, Tianzhu; Feng, Ying; Liu, Qingyang; Yang, Xue; Jiang, Tao; Chen, Yan; Zhang, Quangeng

    2014-11-01

    Glioblastoma (GBM) is the most aggressive and malignant glioma. Currently, a few modern surgical and medical therapeutic strategies are applied for GBM, but the prognosis of GBM patients remains poor, and the average median survival time is only 14.6 months. In this study, we for the first time found that the levels of miR-320a were decreased in both GBM patients and glioma cells. In GBM patients, elevated miR-320a expression was associated with better prognosis. In addition, insulin-like growth factor-1 receptor (IGF-1R) was identified as a key direct target of miR-320a. Overexpression of miR-320a led to the inhibition of cell proliferation, migration, invasion, as well as tumorigenesis by targeting IGF-1R, and thus regulated the signaling pathways downstream, including PI3K/AKT and MAPK/ERK. In tumor orthotopic xenograft experiment, the tumor growth was depressed and survival time of mice model was prolonged when miR-320a was overexpressed. Therefore, our results suggested that miR-320a could suppress tumor development and growth by targeting IGF-1R, and miR-320a might serve as a new effective target for anti-cancer therapy strategies.

  12. Targeted agents for patients with advanced/metastatic pancreatic cancer: A protocol for systematic review and network meta-analysis.

    PubMed

    Di, Baoshan; Pan, Bei; Ge, Long; Ma, Jichun; Wu, Yiting; Guo, Tiankang

    2018-03-01

    Pancreatic cancer (PC) is a devastating malignant tumor. Although surgical resection may offer a good prognosis and prolong survival, approximately 80% patients with PC are always diagnosed as unresectable tumor. National Comprehensive Cancer Network's (NCCN) recommended gemcitabine-based chemotherapy as efficient treatment. While, according to recent studies, targeted agents might be a better available option for advanced or metastatic pancreatic cancer patients. The aim of this systematic review and network meta-analysis will be to examine the differences of different targeted interventions for advanced/metastatic PC patients. We will conduct this systematic review and network meta-analysis using Bayesian method and according to Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) statement. To identify relevant studies, 6 electronic databases including PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of science, CNKI (Chinese National Knowledge Infrastructure), and CBM (Chinese Biological Medical Database) will be searched. The risk of bias in included randomized controlled trials (RCTs) will be assessed using the Cochrane Handbook version 5.1.0. And we will use GRADE approach to assess the quality of evidence from network meta-analysis. Data will be analyzed using R 3.4.1 software. To the best of our knowledge, this systematic review and network meta-analysis will firstly use both direct and indirect evidence to compare the differences of different targeted agents and targeted agents plus chemotherapy for advanced/metastatic pancreatic cancer patients. This is a protocol of systematic review and meta-analysis, so the ethical approval and patient consent are not required. We will disseminate the results of this review by submitting to a peer-reviewed journal.

  13. Understanding and treating hypertension in diabetic populations.

    PubMed

    Volpe, Massimo; Battistoni, Allegra; Savoia, Carmine; Tocci, Giuliano

    2015-10-01

    Hypertension and diabetes frequently occurs in the same individuals in clinical practice. Moreover, the presence of hypertension does increase the risk of new-onset diabetes, as well as diabetes does promote development of hypertension. Whatever the case, the concomitant presence of these conditions confers a high risk of major cardiovascular complications and promotes the use integrated pharmacological interventions, aimed at achieving the recommended therapeutic targets. While the benefits of lowering abnormal fasting glucose levels in patients with hypertension and diabetes have been consistently demonstrated, the blood pressure (BP) targets to be achieved to get a benefit in patients with diabetes have been recently reconsidered. In the past, randomized clinical trials have, indeed, demonstrated that lowering BP levels to less than 140/90 mmHg was associated to a substantial reduction of the risk of developing macrovascular and microvascular complications in hypertensive patients with diabetes. In addition, epidemiological and clinical reports suggested that "the lower, the better" for BP in diabetes, so that levels of BP even lower than 130/80 mmHg have been recommended. Recent randomized clinical trials, however, designed to evaluate the potential benefits obtained with an intensive antihypertensive therapy, aimed at achieving a target systolic BP level below 120 mmHg as compared to those obtained with less stringent therapy, have challenged the previous recommendations from international guidelines. In fact, detailed analyses of these trials showed a paradoxically increased risk of coronary events, mostly myocardial infarction, in those patients who achieved the lowest BP levels, particularly in the high-risk subsets of hypertensive populations with diabetes. In the light of these considerations, the present article will briefly review the common pathophysiological mechanisms, the potential sites of therapeutic interactions and the currently recommended BP

  14. Population Pharmacokinetics and Pharmacodynamics Modeling To Optimize Dosage Regimens of Sulbactam in Critically Ill Patients with Severe Sepsis Caused by Acinetobacter baumannii

    PubMed Central

    Wongpoowarak, Wibul; Wattanavijitkul, Thitima; Sukarnjanaset, Waroonrat; Samaeng, Maseetoh; Nawakitrangsan, Monchana; Ingviya, Natnicha

    2016-01-01

    Sulbactam is being considered as an alternative concomitant medication with other effective antibiotics for the treatment of multidrug-resistant (MDR) Acinetobacter baumannii infections. Pathophysiological changes in critically ill patients with severe sepsis, resulting in altered pharmacokinetic (PK) patterns for antibiotics, are important factors in determining therapeutic success. The aims of this study were (i) to examine the population PK parameters and (ii) to assess the probability of target attainment (PTA) for sulbactam in patients with severe sepsis caused by A. baumannii. PK studies were carried out following administration of 2 g of sulbactam every 12 h on the 4th day of drug administration in 27 patients, and a Monte Carlo simulation was performed to determine the PTA of achieving 40% exposure time during which the plasma drug concentration remained above the MIC (T>MIC) and 60% T>MIC. The central and peripheral volumes of distribution were 14.56 and 9.55 liters, respectively, and total clearances of sulbactam were 2.26 liters/h and 7.64 liters/h in patients aged >65 years and ≤65 years, respectively. The high PTAs (≥90%) for targets of 40% T>MIC and 60% T>MIC with a MIC of 4 μg/ml were observed when sulbactam was administered by a 4-h infusion of 1 g every 12 h and 1 g every 8 h, respectively. Sulbactam would be an alternative antibiotic option to coadminister with colistin for the treatment of infections caused by MDR A. baumannii. However, for pathogens with MICs of >4 μg/ml, higher dosage regimens of sulbactam are required. PMID:27671056

  15. Alcohol and Sexuality Research in the AIDS Era: Trends in Publication Activity, Target Populations and Research Design

    PubMed Central

    George, William H.

    2009-01-01

    Research addressing relationships between alcohol and human sexuality has proliferated, due in part to efforts to characterize alcohol's role in HIV risk behavior. This study provides a descriptive review of the alcohol–sexuality literature, using abstracts from 264 identified studies to estimate changes in publication activity, target populations, and the prevalence of HIV-related studies over time. We also examine methodological trends by estimating the prevalence of experimental vs. non-experimental studies. Findings show considerable increases in research activity and diversity of populations studied since the mid-1980's and highlight the emergence of HIV-related studies as a focal point of alcohol–sexuality research efforts. Results also demonstrate a substantial decline in the proportion of studies utilizing experimental methods, in part because of frequent use of non-experimental approaches in studies of alcohol and HIV risk behavior. We discuss implications and review the role of experiments in evaluating causal relationships between alcohol and sexual risk behavior. PMID:16897352

  16. Alcohol and sexuality research in the AIDS era: trends in publication activity, target populations and research design.

    PubMed

    Hendershot, Christian S; George, William H

    2007-03-01

    Research addressing relationships between alcohol and human sexuality has proliferated, due in part to efforts to characterize alcohol's role in HIV risk behavior. This study provides a descriptive review of the alcohol-sexuality literature, using abstracts from 264 identified studies to estimate changes in publication activity, target populations, and the prevalence of HIV-related studies over time. We also examine methodological trends by estimating the prevalence of experimental vs. non-experimental studies. Findings show considerable increases in research activity and diversity of populations studied since the mid-1980's and highlight the emergence of HIV-related studies as a focal point of alcohol-sexuality research efforts. Results also demonstrate a substantial decline in the proportion of studies utilizing experimental methods, in part because of frequent use of non-experimental approaches in studies of alcohol and HIV risk behavior. We discuss implications and review the role of experiments in evaluating causal relationships between alcohol and sexual risk behavior.

  17. Rationale and efficacy of CD52 targeting in HTLV-1-associated myositis.

    PubMed

    Cochereau, Delphine; Georgin-Lavialle, Sophie; Maisonobe, Thierry; Dubourg, Odile; Melboucy-Belkhir, Sara; Hermine, Olivier; Aouba, Achille

    2014-07-01

    We retrospectively analysed two selected patients, referred to our Haematology Department for refractory HTLV-1 associated myositis with circulating pathologic T-cell population with ATL phenotype. They respectively presented also HTLV-1 associated Crohn-like disease and myelopathy. Muscle biopsy of both patients was analysed to determine the pathologic infiltrate. Alemtuzumab was proposed as salvage therapy. Targeting CD52 with alemtuzumab showed good efficacy on myopathy of both patients for respectively 11 and 10 months. Interestingly, this treatment showed also efficacy on circulating pathologic T-cell population and on concomitant digestive and neurological diseases. The double infected cells ablation and immunosuppressive propriety of alemtuzumab probably explains its interest in this infectious and dysimmunitary disorder. Even though alemtuzumab probably remains a suspensive treatment, its place should be assessed in controlled trial in this difficult to treat rare disease. Copyright © 2014 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  18. Population pharmacokinetics of rituximab in patients with diffuse large B-cell lymphoma and association with clinical outcome.

    PubMed

    Rozman, Samo; Grabnar, Iztok; Novaković, Srdjan; Mrhar, Ales; Jezeršek Novaković, Barbara

    2017-08-01

    Pharmacokinetic (PK) studies suggest that there is a room for improvement in clinical use of rituximab through more individualized treatment. The objective of this study was to characterize rituximab PK in 29 newly diagnosed patients with diffuse large B-cell lymphoma treated with rituximab in combination with cyclophosphamide, doxorubicin, vincristine and methylprednisolone every 3 weeks. We also evaluated the association of rituximab PK with clinical outcome. Rituximab serum levels were determined by enzyme-linked immunosorbent assay and evaluated by a population PK analysis applying nonlinear mixed effects modelling. The data were best described by a two-compartment model comprising linear nonspecific clearance of 0.252 [95% confidence interval (CI): 0.227-0.279] l day -1 and time-varying specific clearance of 0.278 (95% CI: 0.181-0.390) l day -1 , corresponding to target-mediated drug disposition of rituximab. Nonspecific clearance was lower in older patients and those with lower body weight. Additionally, volume of the central compartment was higher in males. A clear association of clinical response with rituximab PK has been observed. Rate constant of specific clearance decay was 0.143 day -1 (95% CI: 0.0478-0.418) in patients with no disease progression, while in patients with disease progression it was 82.2% lower (95% CI: 33.4-95.0). This finding indicates that time-changes in clearance could serve as a predictive marker of response to rituximab. Our report demonstrates the rationale for studies evaluating higher doses of rituximab in selected patients. © 2017 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

  19. Patients with multiple sclerosis do not necessarily consume more alcohol or tobacco than the general population.

    PubMed

    Fragoso, Yara Dadalti; Gomes, Sidney; Goncalves, Marcus Vinicius M; Machado, Suzana C Nunes; Morales, Rogerio de Rizo; Oliveira, Francisco Tomas M de; Oliveira, João Filipe de; Olmo, Neide R Simoes; Parolin, Monica K Fiuza; Siquineli, Fabio; Stoney, Patrick N

    2015-10-01

    Purpose Recent papers suggest that patients with multiple sclerosis (MS) are prone to alcohol misuse. This may be due to the combination of a lifelong and disabling disease with a psychiatric profile typical of MS. The objective of the present study was to assess these findings in a culturally different population of patients with MS.Method The present case-control transversal study assessed 168 patients with MS and 168 control subjects from Brazil.Results There were no evidence that patients with MS drank more alcohol or, smoked more than did controls. In fact, control subjects had a significantly higher alcohol consumption. The only trait associated to higher alcohol consumption was anxiety, both for patients and controls.Conclusion Unlike previous reports in the literature, patients with MS in our study did not drink or smoked more than a control population.

  20. Inter- and Intrafraction Target Motion in Highly Focused Single Vocal Cord Irradiation of T1a Larynx Cancer Patients

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kwa, Stefan L.S., E-mail: s.kwa@erasmusmc.nl; Al-Mamgani, Abrahim; Osman, Sarah O.S.

    2015-09-01

    Purpose: The purpose of this study was to verify clinical target volume–planning target volume (CTV-PTV) margins in single vocal cord irradiation (SVCI) of T1a larynx tumors and characterize inter- and intrafraction target motion. Methods and Materials: For 42 patients, a single vocal cord was irradiated using intensity modulated radiation therapy at a total dose of 58.1 Gy (16 fractions × 3.63 Gy). A daily cone beam computed tomography (CBCT) scan was performed to online correct the setup of the thyroid cartilage after patient positioning with in-room lasers (interfraction motion correction). To monitor intrafraction motion, CBCT scans were also acquired just after patient repositioning and aftermore » dose delivery. A mixed online-offline setup correction protocol (“O2 protocol”) was designed to compensate for both inter- and intrafraction motion. Results: Observed interfraction, systematic (Σ), and random (σ) setup errors in left-right (LR), craniocaudal (CC), and anteroposterior (AP) directions were 0.9, 2.0, and 1.1 mm and 1.0, 1.6, and 1.0 mm, respectively. After correction of these errors, the following intrafraction movements derived from the CBCT acquired after dose delivery were: Σ = 0.4, 1.3, and 0.7 mm, and σ = 0.8, 1.4, and 0.8 mm. More than half of the patients showed a systematic non-zero intrafraction shift in target position, (ie, the mean intrafraction displacement over the treatment fractions was statistically significantly different from zero; P<.05). With the applied CTV-PTV margins (for most patients 3, 5, and 3 mm in LR, CC, and AP directions, respectively), the minimum CTV dose, estimated from the target displacements observed in the last CBCT, was at least 94% of the prescribed dose for all patients and more than 98% for most patients (37 of 42). The proposed O2 protocol could effectively reduce the systematic intrafraction errors observed after dose delivery to almost zero (Σ = 0.1, 0.2, 0.2 mm). Conclusions

  1. A population-based analysis of incentive payments to primary care physicians for the care of patients with complex disease

    PubMed Central

    Lavergne, M. Ruth; Law, Michael R.; Peterson, Sandra; Garrison, Scott; Hurley, Jeremiah; Cheng, Lucy; McGrail, Kimberlyn

    2016-01-01

    Background: In 2007, the province of British Columbia implemented incentive payments to primary care physicians for the provision of comprehensive, continuous, guideline-informed care for patients with 2 or more chronic conditions. We examined the impact of this program on primary care access and continuity, rates of hospital admission and costs. Methods: We analyzed all BC patients who qualified for the incentive based on their diagnostic profile. We tracked primary care contacts and continuity, hospital admissions (total, via the emergency department and for targeted conditions), and cost of physician services, hospital care and pharmaceuticals, for 24 months before and 24 months after the intervention. Results: Of 155 754 eligible patients, 63.7% had at least 1 incentive payment billed. Incentive payments had no impact on primary care contacts (change in contacts per patient per month: 0.016, 95% confidence interval [CI] −0.047 to 0.078) or continuity of care (mean monthly change: 0.012, 95% CI −0.001 to 0.024) and were associated with increased total rates of hospital admission (change in hospital admissions per 1000 patients per month: 1.46, 95% CI 0.04 to 2.89), relative to preintervention trends. Annual costs per patient did not decline (mean change: $455.81, 95% CI −$2.44 to $914.08). Interpretation: British Columbia’s $240-million investment in this program improved compensation for physicians doing the important work of caring for complex patients, but did not appear to improve primary care access or continuity, or constrain resource use elsewhere in the health care system. Policymakers should consider other strategies to improve care for this patient population. PMID:27527484

  2. Seroepidemiological study of Toxoplasma gondii infection in a population of Iranian epileptic patients.

    PubMed

    Babaie, Jalal; Sayyah, Mohammad; Gharagozli, Kourosh; Mostafavi, Ehsan; Golkar, Majid

    2017-01-01

    Epilepsy is one of the most common neurologic disorders. Underlying cause of epilepsy is unknown in 60 % of the patients. Toxoplasma gondii is an intracellular parasite which is capable of forming tissue cysts in brain of chronically infected hosts including humans. Some epidemiological studies suggested an association between toxoplasmosis and acquisition of epilepsy. In this study we determined seroprevalence of latent Toxoplasma infection in a population of Iranian epileptic patients. Participants were classified in three groups as Iranian epileptic patients (IEP, n = 414), non-epileptic patients who had other neurologic disorders (NEP, n = 150), and healthy people without any neurologic disorders (HP, n = 63). The presence of anti- Toxoplasma IgG antibodies and IgG titer in the sera were determined by ELISA method. Anti- T. gondii IgG seroprevalence obtained 35.3 %, 34.7 % and 38.1 % in IEP, NEP and HP, respectively. The seroprevalence rate was not significantly different among the three groups (P = 0.88). Anti- T. gondii IgG titer was 55.7 ± 78, 52.4 ± 74 and 69.7 ± 92 IU/ml in IEP, NEP and HP, respectively. There was not any statistically significant difference in the antibody titer between the study groups (P = 0.32). The rate of T. gondii infection in epileptic patients was not higher than non-epileptic patients and healthy people in the Iranian population.

  3. Target Population of Non-deferrable Surgery and Uncontrolled Severe Bleeding Related to Dabigatran.

    PubMed

    Calabria, Silvia; Forcesi, Emanuele; Dondi, Letizia; Pedrini, Antonella; Maggioni, Aldo Pietro; Martini, Nello

    2018-06-04

    This observational study was aimed to identify patients who experienced non-deferrable surgery and/or uncontrolled severe bleeding following dabigatran administration and then are potentially eligible to the use of the specific antidote idarucizumab in a real-world setting. From the big Italian real-world database ARCO, a cohort of adult patients treated with dabigatran and hospitalized due to diagnoses attributable to urgent interventions and/or major bleeding was selected in 2014. Baseline characteristics and all-cause hospitalizations, specialist/diagnostic outpatient services, and healthcare costs over the 1-year follow-up were described. Out of 16,756,843 Italian citizens, 271,540 (1.9%) were prescribed with oral anticoagulants, and specifically, 17,450 with dabigatran. Patients identified to be hospitalized for non-deferrable surgery (n = 106) and/or uncontrolled severe bleeding (n = 190) following dabigatran use were 289 (1.7%) [mean age (± SD) 79 ± 7, 50% of female sex]. On average, patients stayed in hospital 13.7 and 17.0 days, respectively. The per patient and per year cost to the Italian National Health System was on average 19,708€ (specifically 1487€ for drugs, of which 311€ for dabigatran, 17,353€ for all-cause hospitalizations, and 869€ for outpatient care), about four times more than the mean healthcare integrated cost of a single patient treated with dabigatran (4775€). This analysis of the ARCO database reliably describes the population potentially eligible to the dabigatran reversal agent, idarucizumab. These data may be useful for Healthcare Decision Makers to organize, define, and improve present and future emergency healthcare, mainly as starting point for cost-effectiveness analyses of new reversal agents.

  4. Risk of fragility fracture among patients with sarcoidosis: a population-based study 1976-2013.

    PubMed

    Ungprasert, P; Crowson, C S; Matteson, E L

    2017-06-01

    Incidence of fragility fracture of a population-based cohort of 345 patients with sarcoidosis was compared with age and sex-matched comparators. The incidence of fragility fracture was higher among patients with sarcoidosis with hazard ratio (HR) of 2.18. Several chronic inflammatory disorders increase the risk of fragility fracture. However, little is known about the risk of fragility fracture in patients with sarcoidosis. This study was conducted using a previously identified population-based cohort of 345 patients with incident sarcoidosis from Olmsted County, Minnesota. Diagnosis of sarcoidosis required physician diagnosis supported by biopsy showing non-caseating granuloma, radiographic evidence of intrathoracic sarcoidosis, and compatible clinical presentations without evidence of other granulomatous diseases. Sex and age-matched subjects randomly selected from the same underlying population were used as comparators. Medical records of cases and comparators were reviewed for baseline characteristics and incident fragility fracture. Fragility fractures were observed in 34 patients with sarcoidosis, corresponding to a cumulative incidence of 5.6% at 10 years, while 18 fragility fractures were observed among comparators for a cumulative incidence of 2.4% at 10 years. The HR of fragility fractures among cases compared with comparators was 2.18 (95% confidence interval [CI], 1.23-3.88). The risk of fragility fracture by site was significantly higher among patients with sarcoidosis, and was due to a higher rate of distal forearm fracture (HR 3.58; 95% CI 1.53-8.40). Statistically non-significant increased risk was also observed in proximal femur (HR 1.66; 95% CI 0.45-6.06) and proximal humerus (HR 3.27; 95% CI 0.66-16.21). Risk of vertebral fracture was not increased (HR 1.00; 95% CI 0.32-3.11). Patients with sarcoidosis have an increased risk of fragility fracture which is primarily driven by the higher incidence of distal forearm fracture.

  5. SEGMENTING CT PROSTATE IMAGES USING POPULATION AND PATIENT-SPECIFIC STATISTICS FOR RADIOTHERAPY.

    PubMed

    Feng, Qianjin; Foskey, Mark; Tang, Songyuan; Chen, Wufan; Shen, Dinggang

    2009-08-07

    This paper presents a new deformable model using both population and patient-specific statistics to segment the prostate from CT images. There are two novelties in the proposed method. First, a modified scale invariant feature transform (SIFT) local descriptor, which is more distinctive than general intensity and gradient features, is used to characterize the image features. Second, an online training approach is used to build the shape statistics for accurately capturing intra-patient variation, which is more important than inter-patient variation for prostate segmentation in clinical radiotherapy. Experimental results show that the proposed method is robust and accurate, suitable for clinical application.

  6. [Vitamin B12 levels in the patient population attending an urban health centre in Madrid].

    PubMed

    Camarero-Shelly, M

    2018-04-01

    Vitamin B 12 levels are usually measured in Primary Care when the patients have symptoms or risk factors associated with its deficiency, mostly in the elderly. However, no evidence has been found to support the recommendation of screening in the general population. The aim of this study is to assess the relevance of having extended the screening of vitamin B 12 deficiency to a younger population, after observing an increase in the prescription of this injected vitamin in a population under 65 years, by analysing the vitamin B 12 values obtained. A descriptive, retrospective, observational study was conducted on a sample consisting of 5,531 patients from Barajas Health Primary Centre, Madrid, between 2008 and 2012, and on whom a blood test was performed for any reason, with values of vitamin B 12 . A deficiency was found in 9.1% (SD 2.3) of the patients, of whom 49.4% were less than 65 years. The deficiencies were associated (P<.001, 95% CI) with age, dementia, changes in blood red cell counts, memory, and with the taking of metformin and proton pump inhibitors (P=.007). The prevalence of vitamin B 12 deficiency in our served population is similar in patients older and younger than 65 years. The extended screening was relevant. Copyright © 2017 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  7. Targeting interventions for ethnic minority and low-income populations.

    PubMed

    Kumanyika, Shiriki; Grier, Sonya

    2006-01-01

    Although rates of childhood obesity among the general population are alarmingly high, they are higher still in ethnic minority and low-income communities. The disparities pose a major challenge for policymakers and practitioners planning strategies for obesity prevention. In this article Shiriki Kumanyika and Sonya Grier summarize differences in childhood obesity prevalence by race and ethnicity and by socioeconomic status. They show how various environmental factors can have larger effects on disadvantaged and minority children than on their advantaged white peers-and thus contribute to disparities in obesity rates. The authors show, for example, that low-income and minority children watch more television than white, non-poor children and are potentially exposed to more commercials advertising high-calorie, low-nutrient food during an average hour of TV programming. They note that neighborhoods where low-income and minority children live typically have more fast-food restaurants and fewer vendors of healthful foods than do wealthier or predominantly white neighborhoods. They cite such obstacles to physical activity as unsafe streets, dilapidated parks, and lack of facilities. In the schools that low-income and minority children attend, however, they see opportunities to lead the way to effective obesity prevention. Finally, the authors examine several aspects of the home environment-breast-feeding, television viewing, and parental behaviors-that may contribute to childhood obesity but be amenable to change through targeted intervention. Kumanyika and Grier point out that policymakers aiming to prevent obesity can use many existing policy levers to reach ethnic minority and low-income children and families: Medicaid, the State Child Health Insurance Program, and federal nutrition "safety net" programs. Ultimately, winning the fight against childhood obesity in minority and low-income communities will depend on the nation's will to change the social and physical

  8. Fidaxomicin versus Vancomycin as a First-Line Treatment for Clostridium difficile-Associated Diarrhea in Specific Patient Populations: A Pharmacoeconomic Evaluation.

    PubMed

    Reveles, Kelly R; Backo, Jennifer L; Corvino, Frank A; Zivkovic, Marko; Broderick, Kelly C

    2017-12-01

    The reduction in recurrent Clostridium difficile-associated diarrhea (CDAD) with fidaxomicin therapy may reduce hospital readmissions and lead to lower overall CDAD costs. However, studies assessing the cost-effectiveness of fidaxomicin as first-line therapy from the U.S. hospital perspective are lacking. This study evaluated the costs associated with utilizing fidaxomicin or vancomycin as a first-line therapy for CDAD in specific patient populations from a U.S. hospital perspective. A decision-analytic model was developed to estimate total costs (hospitalization and drug costs) associated with using fidaxomicin or vancomycin as first-line therapy for a first episode and up to two recurrences of CDAD in five patient populations: general population, elderly, patients receiving concomitant antibiotics, and patients with renal impairment or cancer. The total cost of CDAD treatment using fidaxomicin first line in the general population was $14,442 per patient versus $14,179 per patient with vancomycin first line. In subgroup analyses, fidaxomicin use resulted in total hospital cost savings of $616 per patient in patients with cancer and $312 in patients with concomitant antibiotic use; vancomycin use was associated with total hospital cost savings of $243 per patient in the elderly and $371 in patients with renal impairment. Fidaxomicin as first-line CDAD therapy is associated with similar total costs as compounded vancomycin oral solution in the general population. In elderly and renally impaired patients, slight increases in hospital cost were observed with fidaxomicin therapy, and in patients with cancer or concomitant antibiotic use, hospital cost savings were observed. © 2017 Pharmacotherapy Publications, Inc.

  9. Comparison of various risk indicators among patients with chronic and aggressive periodontitis in davangere population

    PubMed Central

    Vandana, Kharidhi Laxman; Nadkarni, Rahul Dilip; Guddada, Kaveri

    2015-01-01

    Background: The aim of the present study was to compare various risk indicators of chronic periodontitis (CP) and aggressive periodontitis (AP) among patients of Davangere population. Materials and Methods: Totally, 89 CP and 90 AP patients were selected from outpatient Department of Periodontics, College of Dental Sciences, Davangere. Various clinical parameters proven to be risk indicators were determined for each patient such as age, gender, occupation, oral hygiene habits, personal habits, income, level of education, place of residence, frequency of dental visits, various oral hygiene indices, gingival status, wasting diseases, malocclusion, laboratory investigations, and the results were subjected to statistical analysis. Results: This study demonstrated that AP is manifested early in life in susceptible individuals. Proven risk indicators for AP and CP in the present study population included young age, place of residence, income and education levels, frequency of dental visits. Patients with AP had better oral hygiene habits and oral hygiene index results than patients with CP. Paan chewing and smoking could be considered as risk factors, both in CP and AP cases. The similar association of plaque scores but higher bleeding tendency in AP patients supported the fact of higher susceptibility of AP patients to periodontal breakdown. Malocclusion being present in the majority of cases could also be put forth as a risk factor for AP and CP. Conclusion: This study identifies the different risk indicators for CP and AP and demonstrates the need for constructing nationwide oral health promotion programs to improve the level of oral health awareness and standards in Indian population. PMID:26392693

  10. Long-Term Health-Related Quality of Life in German Patients with Juvenile Idiopathic Arthritis in Comparison to German General Population.

    PubMed

    Barth, Swaantje; Haas, Johannes-Peter; Schlichtiger, Jenny; Molz, Johannes; Bisdorff, Betty; Michels, Hartmut; Hügle, Boris; Radon, Katja

    2016-01-01

    Aims of the study were to investigate health-related quality of life (HRQOL) in adult patients with former diagnosis of Juvenile Idiopathic Arthritis (JIA), to compare their HRQOL with the general population and to identify factors related to a poor outcome. In 2012, a cross-sectional survey was performed by mailing a questionnaire to a large cohort of former and current patients of the German Centre for Rheumatology in Children and Adolescents. Only adult patients (≥18 years) with a diagnosis compatible with JIA were included (n = 2592; response 66%). The questionnaire included information about HRQOL (EQ5D), disease-related questions and socio-demographics. Prevalence and 95% confidence intervals (CI) of problems with mobility, self-care, usual activities, pain and anxiety/depression were standardized to the German general population. Factors associated with low HRQOL in JIA patients were identified using logistic regression models. Sixty-two percent of the study population was female; age range was 18-73 years. In all dimensions, JIA patients reported statistically significantly more problems than the general population with largest differences in the pain dimension (JIA patients 56%; 95%CI 55-58%; general population 28%; 26-29%) and the anxiety/depression dimension (28%; 27-29% vs. 4%; 4-5%). Lower HRQOL in JIA patients was associated with female sex, older age, lower level of education, still being under rheumatic treatment and disability. HRQOL in adult JIA patients is considerably lower than in the general population. As this cohort includes historic patients the new therapeutic schemes available today are expected to improve HRQOL in future.

  11. Blood pressure targets for vasopressor therapy: a systematic review.

    PubMed

    D'Aragon, Frederick; Belley-Cote, Emilie P; Meade, Maureen O; Lauzier, François; Adhikari, Neill K J; Briel, Matthias; Lalu, Manoj; Kanji, Salmaan; Asfar, Pierre; Turgeon, Alexis F; Fox-Robichaud, Alison; Marshall, John C; Lamontagne, François

    2015-06-01

    Physicians often prescribe vasopressors to correct pathological vasodilation and improve tissue perfusion in patients with septic shock, but the evidence to inform practice on vasopressor dosing is weak. We undertook a systematic review of clinical studies evaluating different blood pressure targets for the dosing of vasopressors in septic shock. We searched MEDLINE, EMBASE, CENTRAL (to November 2013), reference lists from included articles, and trial registries for randomized controlled trials (RCTs) and observational and crossover intervention studies comparing different blood pressure targets for vasopressor therapy in septic shock. Two reviewers independently selected eligible studies and extracted data on standardized forms. We identified 2 RCTs and 10 crossover trials but no observational studies meeting our criteria. Only one RCT measured clinical outcomes after comparing mean arterial pressure targets of 80 to 85 mmHg versus 65 to 70 mmHg. There was no effect on 28-day mortality, but confidence intervals were wide (hazard ratio, 95% confidence interval [95% CI] 0.84 - 1.38). In contrast, this intervention was associated with a greater risk of atrial fibrillation (relative risk, 2.36; 95% CI, 1.18 - 4.72) and a lower risk of renal replacement therapy in hypertensive patients (relative risk, 0.75; 95% CI, 0.57 - 1.0). Crossover trials suggest that achieving higher blood pressure targets by increasing vasopressor doses increases heart rate and cardiac index with no effect on serum lactate. Our findings underscore the paucity of clinical evidence to guide the administration of vasopressors in critically ill patients with septic shock. Further rigorous research is needed to establish an evidence base for vasopressor administration in this population.

  12. RNA therapeutics targeting osteoclast-mediated excessive bone resorption

    PubMed Central

    Wang, Yuwei; Grainger, David W

    2011-01-01

    RNA interference (RNAi) is a sequence-specific post-transcriptional gene silencing technique developed with dramatically increasing utility for both scientific and therapeutic purposes. Short interfering RNA (siRNA) is currently exploited to regulate protein expression relevant to many therapeutic applications, and commonly used as a tool for elucidating disease-associated genes. Osteoporosis and their associated osteoporotic fragility fractures in both men and women are rapidly becoming a global healthcare crisis as average life expectancy increases worldwide. New therapeutics are needed for this increasing patient population. This review describes the diversity of molecular targets suitable for RNAi-based gene knock-down in osteoclasts to control osteoclast-mediated excessive bone resorption. We identify strategies for developing targeted siRNA delivery and efficient gene silencing, and describe opportunities and challenges of introducing siRNA as a therapeutic approach to hard and connective tissue disorders. PMID:21945356

  13. Targeted therapies: a nursing perspective.

    PubMed

    Kay, Polly

    2006-02-01

    To review the development of targeted therapies and the biology of relevant therapeutic targets. To analyze the relevance of targeted agents as part of current clinical practice. Research articles. Several targeted agents are now available for clinical use. Their mechanisms of action are more specific against tumor cells than traditional cytotoxics. Monotherapy regimens based on targeted agents tend to be better tolerated than chemotherapy, and most combination regimens with targeted agents have proven feasible. Their availability has greatly expanded cancer treatment options, especially for chemorefractory patients. Nurses involved in the care of patients with cancer can benefit from an increased understanding of targeted therapies, including their mechanisms of action, their efficacy profile, as well as prophylaxis and management of adverse events and administration procedures.

  14. Population pharmacokinetics of intravenous acetaminophen in Japanese patients undergoing elective surgery.

    PubMed

    Imaizumi, Tsuyoshi; Obara, Shinju; Mogami, Midori; Iseki, Yuzo; Hasegawa, Makiko; Murakawa, Masahiro

    2017-06-01

    Intravenous (i.v.) acetaminophen is administered during surgery for postoperative analgesia. However, little information is available on the pharmacokinetics of i.v. acetaminophen in Japanese patients undergoing surgery under general anesthesia. The study was approved by the Institutional Review Board and registered at UMIN-CTR (UMIN000013418). Patients scheduled to undergo elective surgery under general anesthesia were enrolled after obtaining written informed consent. During surgery, 1 g of i.v. acetaminophen was administered over 15, 60, or 120 min. Acetaminophen concentrations (15 or 16 samples per case) were measured at time points from 0-480 min after the start of administration (liquid chromatography-mass spectrometry/tandem mass spectrometry; limit of quantitation 0.1 μg/mL). The predictive performance of three published pharmacokinetic models was evaluated. Population pharmacokinetics were also analyzed using a nonlinear mixed-effect model based on the NONMEM program. Data from 12 patients who underwent endoscopic or lower limb procedures were analyzed (male/female = 7/5, median age 55 years, weight 63 kg). Anesthesia was maintained with remifentanil and propofol or sevoflurane. The pharmacokinetic model of i.v. acetaminophen reported by Würthwein et al. worked well. Using 185 datapoints, the pharmacokinetics of i.v. acetaminophen were described by a two-compartment model with weight as a covariate but not age, sex, or creatinine clearance. The median prediction error and median absolute prediction error of the final model were -1 and 10%, respectively. A population pharmacokinetic model of i.v. acetaminophen in Japanese patients was constructed, with performance within acceptable ranges.

  15. Analysis of SOX10 mutations identified in Waardenburg-Hirschsprung patients: Differential effects on target gene regulation.

    PubMed

    Chan, Kwok Keung; Wong, Corinne Kung Yen; Lui, Vincent Chi Hang; Tam, Paul Kwong Hang; Sham, Mai Har

    2003-10-15

    SOX10 is a member of the SOX gene family related by homology to the high-mobility group (HMG) box region of the testis-determining gene SRY. Mutations of the transcription factor gene SOX10 lead to Waardenburg-Hirschsprung syndrome (Waardenburg-Shah syndrome, WS4) in humans. A number of SOX10 mutations have been identified in WS4 patients who suffer from different extents of intestinal aganglionosis, pigmentation, and hearing abnormalities. Some patients also exhibit signs of myelination deficiency in the central and peripheral nervous systems. Although the molecular bases for the wide range of symptoms displayed by the patients are still not clearly understood, a few target genes for SOX10 have been identified. We have analyzed the impact of six different SOX10 mutations on the activation of SOX10 target genes by yeast one-hybrid and mammalian cell transfection assays. To investigate the transactivation activities of the mutant proteins, three different SOX target binding sites were introduced into luciferase reporter gene constructs and examined in our series of transfection assays: consensus HMG domain protein binding sites; SOX10 binding sites identified in the RET promoter; and Sox10 binding sites identified in the P0 promoter. We found that the same mutation could have different transactivation activities when tested with different target binding sites and in different cell lines. The differential transactivation activities of the SOX10 mutants appeared to correlate with the intestinal and/or neurological symptoms presented in the patients. Among the six mutant SOX10 proteins tested, much reduced transactivation activities were observed when tested on the SOX10 binding sites from the RET promoter. Of the two similar mutations X467K and 1400del12, only the 1400del12 mutant protein exhibited an increase of transactivation through the P0 promoter. While the lack of normal SOX10 mediated activation of RET transcription may lead to intestinal aganglionosis

  16. Methods of Suicide among Cancer Patients: A Nationwide Population-Based Study

    ERIC Educational Resources Information Center

    Chung, Kuo-Hsuan; Lin, Herng-Ching

    2010-01-01

    A 3-year nationwide population-based data set was used to explore methods of suicide (violent vs. nonviolent) and possible contributing factors among cancer patients in Taiwan. A total of 1,065 cancer inpatients who committed suicide were included as our study sample. The regression shows that those who had genitourinary cancer were 0.55 times (p…

  17. Effect of nutritional status on clinical outcome in a population of geriatric rehabilitation patients.

    PubMed

    Donini, Lorenzo M; De Bernardini, Laura; De Felice, Maria Rosaria; Savina, Claudia; Coletti, Cecilia; Cannella, Carlo

    2004-04-01

    In a geriatric patient, nutritional status (NS), particularly in the case of malnutrition (M), may influence not only clinical results but also achievement of targets expected by geriatric rehabilitation. The aim of this study was to evaluate the effect of nutritional status (NS) on the occurrence of Adverse Clinical Events (ACE) and on mortality in geriatric rehabilitation patients. We retrospectively examined the clinical records of 278 elderly subjects (154 women, 124 men), admitted to a geriatric hospital between September 2000 and December 2001 and evaluated for clinical, functional, cognitive and NS within the first 48 hours of admission. Clinical outcomes (ACE, mortality) were recorded during follow-up. Logistic regression analysis estimated models having mortality or the occurrence of ACE as outcome variables. Malnutrition was detected upon admission in 56.1% of the sample population. Incidence of ACE in malnourished subjects was higher than that in well-nourished patients (28.2 vs 13.1%). Equally, mortality among malnourished subjects was higher than among those whose NS was normal (23.1 vs 9.8%). The logistic regression models were able to predict: 1) mortality from comorbidity (OR 1.43; 95% CI 1.16-1.78; p=0.001) and NS (OR 2.64; 95% CI 1.29-5.4; p=0.008), and 2) occurrence of ACE from comorbidity (OR 1.69; 95% CI 1.36-2.1; p=0.000), cognitive (OR 1.22; 95% CI 1.11-1.35; p=0.000) and nutritional status (OR 2.38; 95% CI 1.19-4.8; p=0.015). NS emerged as the main independent predictor of both mortality and occurrence of ACE. Although most patients fell into the category of mild/moderate (energy) malnutrition (148/156), a mild deterioration of NS, for instance, reduction in triceps skinfold thickness (TSF) seemed to be sufficient to cause an increase in the incidence of ACE and in mortality.

  18. Factors associated with reaching or not reaching target HbA1c after initiation of basal or premixed insulin in patients with type 2 diabetes.

    PubMed

    Scheen, A J; Schmitt, H; Jiang, H H; Ivanyi, T

    2017-02-01

    To evaluate factors associated with reaching or not reaching target glycated haemoglobin (HbA 1c ) levels by analysing the respective contributions of fasting hyperglycaemia (FHG), also referred to as basal hyperglycaemia, vs postprandial hyperglycaemia (PHG) before and after initiation of a basal or premixed insulin regimen in patients with type 2 diabetes. This post-hoc analysis of insulin-naïve patients in the DURABLE study randomised to receive either insulin glargine or insulin lispro mix 25 evaluated the percentages of patients achieving a target HbA 1c of <7.0% (<53mmol/mol) per baseline HbA 1c quartiles, and the effect of each insulin regimen on the relative contributions of PHG and FHG to overall hyperglycaemia. Patients had comparable demographic characteristics and similar HbA 1c and FHG values at baseline in each HbA 1c quartile regardless of whether they reached the target HbA 1c . The higher the HbA 1c quartile, the greater was the decrease in HbA 1c , but also the smaller the percentage of patients achieving the target HbA 1c . HbA 1c and FHG decreased more in patients reaching the target, resulting in significantly lower values at endpoint in all baseline HbA 1c quartiles with either insulin treatment. Patients not achieving the target HbA 1c had slightly higher insulin doses, but lower total hypoglycaemia rates. Smaller decreases in FHG were associated with not reaching the target HbA 1c , suggesting a need to increase basal or premixed insulin doses to achieve targeted fasting plasma glucose and improve patient response before introducing more intensive prandial insulin regimens. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  19. Analysis of FET-PET imaging for target volume definition in patients with gliomas treated with conformal radiotherapy.

    PubMed

    Rieken, Stefan; Habermehl, Daniel; Giesel, Frederik L; Hoffmann, Christoph; Burger, Ute; Rief, Harald; Welzel, Thomas; Haberkorn, Uwe; Debus, Jürgen; Combs, Stephanie E

    2013-12-01

    Modern radiotherapy (RT) techniques such as stereotactic RT, intensity-modulated RT, or particle irradiation allow local dose escalation with simultaneous sparing of critical organs. Several trials are currently investigating their benefit in glioma reirradiation and boost irradiation. Target volume definition is of critical importance especially when steep dose gradient techniques are employed. In this manuscript we investigate the impact of O-(2-(F-18)fluoroethyl)-l-tyrosine-positron emission tomography/computer tomography (FET-PET/CT) on target volume definition in low and high grade glioma patients undergoing either first or re-irradiation with particles. We investigated volumetric size and uniformity of magnetic resonance imaging (MRI)- vs. FET-PET/CT-derived gross tumor volumes (GTVs) and planning target volumes (PTVs) of 41 glioma patients. Clinical cases are presented to demonstrate potential benefits of integrating FET-PET/CT-planning into daily routine. Integrating FET-uptake into the delineation of GTVs yields larger volumes. Combined modality-derived PTVs are significantly enlarged in high grade glioma patients and in case of primary RT. The congruence of MRI and FET signals for the identification of glioma GTVs is poor with mean uniformity indices of 0.39. MRI-based PTVs miss 17% of FET-PET/CT-based GTVs. Non significant alterations were detected in low grade glioma patients and in those undergoing reirradiation. Target volume definition for malignant gliomas during initial RT may yield significantly differing results depending upon the imaging modality, which the contouring process is based upon. The integration of both MRI and FET-PET/CT may help to improve GTV coverage by avoiding larger incongruences between physical and biological imaging techniques. In low grade gliomas and in cases of reirradiation, more studies are needed in order to investigate a potential benefit of FET-PET/CT for planning of RT. Copyright © 2013 Elsevier Ireland Ltd. All

  20. Targeting RET in Patients With RET-Rearranged Lung Cancers: Results From the Global, Multicenter RET Registry

    PubMed Central

    Milia, Julie; Filleron, Thomas; Wolf, Juergen; Carbone, David P.; Owen, Dwight; Camidge, Ross; Narayanan, Vignhesh; Doebele, Robert C.; Besse, Benjamin; Remon-Masip, Jordi; Janne, Pasi A.; Awad, Mark M.; Peled, Nir; Byoung, Chul-Cho; Karp, Daniel D.; Van Den Heuvel, Michael; Wakelee, Heather A.; Neal, Joel W.; Mok, Tony S.K.; Yang, James C.H.; Ou, Sai-Hong Ignatius; Pall, Georg; Froesch, Patrizia; Zalcman, Gérard; Gandara, David R.; Riess, Jonathan W.; Velcheti, Vamsidhar; Zeidler, Kristin; Diebold, Joachim; Früh, Martin; Michels, Sebastian; Monnet, Isabelle; Popat, Sanjay; Rosell, Rafael; Karachaliou, Niki; Rothschild, Sacha I.; Shih, Jin-Yuan; Warth, Arne; Muley, Thomas; Cabillic, Florian; Mazières, Julien; Drilon, Alexander

    2017-01-01

    Purpose In addition to prospective trials for non–small-cell lung cancers (NSCLCs) that are driven by less common genomic alterations, registries provide complementary information on patient response to targeted therapies. Here, we present the results of an international registry of patients with RET-rearranged NSCLCs, providing the largest data set, to our knowledge, on outcomes of RET-directed therapy thus far. Methods A global, multicenter network of thoracic oncologists identified patients with pathologically confirmed NSCLC that harbored a RET rearrangement. Molecular profiling was performed locally by reverse transcriptase polymerase chain reaction, fluorescence in situ hybridization, or next-generation sequencing. Anonymized data—clinical, pathologic, and molecular features—were collected centrally and analyzed by an independent statistician. Best response to RET tyrosine kinase inhibition administered outside of a clinical trial was determined by RECIST v1.1. Results By April 2016, 165 patients with RET-rearranged NSCLC from 29 centers across Europe, Asia, and the United States were accrued. Median age was 61 years (range, 29 to 89 years). The majority of patients were never smokers (63%) with lung adenocarcinomas (98%) and advanced disease (91%). The most frequent rearrangement was KIF5B-RET (72%). Of those patients, 53 received one or more RET tyrosine kinase inhibitors in sequence: cabozantinib (21 patients), vandetanib (11 patients), sunitinib (10 patients), sorafenib (two patients), alectinib (two patients), lenvatinib (two patients), nintedanib (two patients), ponatinib (two patients), and regorafenib (one patient). The rate of any complete or partial response to cabozantinib, vandetanib, and sunitinib was 37%, 18%, and 22%, respectively. Further responses were observed with lenvantinib and nintedanib. Median progression-free survival was 2.3 months (95% CI, 1.6 to 5.0 months), and median overall survival was 6.8 months (95% CI, 3.9 to 14

  1. Targeted ethnography as a critical step to inform cultural adaptations of HIV prevention interventions for adults with severe mental illness.

    PubMed

    Wainberg, Milton L; Alfredo González, M; McKinnon, Karen; Elkington, Katherine S; Pinto, Diana; Gruber Mann, Claudio; Mattos, Paulo E

    2007-07-01

    As in other countries worldwide, adults with severe mental illness (SMI) in Brazil are disproportionately infected with HIV relative to the general population. Brazilian psychiatric facilities lack tested HIV prevention interventions. To adapt existing interventions, developed only in the US, we conducted targeted ethnography with adults with SMI and staff from two psychiatric institutions in Brazil. We sought to characterize individual, institutional, and interpersonal factors that may affect HIV risk behavior in this population. We conducted 350 hours of ethnographic field observations in two mental health service settings in Rio de Janeiro, and 9 focus groups (n=72) and 16 key-informant interviews with patients and staff in these settings. Data comprised field notes and audiotapes of all exchanges, which were transcribed, coded, and systematically analyzed. The ethnography identified and/or characterized the institutional culture: (1) patients' risk behaviors; (2) the institutional setting; (3) intervention content; and (4) intervention format and delivery strategies. Targeted ethnography also illuminated broader contextual issues for development and implementation of HIV prevention interventions for adults with SMI in Brazil, including an institutional culture that did not systematically address patients' sexual behavior, sexual health, or HIV sexual risk, yet strongly impacted the structure of patients' sexual networks. Further, ethnography identified the Brazilian concept of "social responsibility" as important to prevention work with psychiatric patients. Targeted ethnography with adults with SMI and institutional staff provided information critical to the adaptation of tested US HIV prevention interventions for Brazilians with SMI.

  2. Smoking paradox in the development of psoriatic arthritis among patients with psoriasis: a population-based study.

    PubMed

    Nguyen, Uyen-Sa D T; Zhang, Yuqing; Lu, Na; Louie-Gao, Qiong; Niu, Jingbo; Ogdie, Alexis; Gelfand, Joel M; LaValley, Michael P; Dubreuil, Maureen; Sparks, Jeffrey A; Karlson, Elizabeth W; Choi, Hyon K

    2018-01-01

    Smoking is associated with an increased risk of psoriatic arthritis (PsA) in the general population, but not among patients with psoriasis. We sought to clarify the possible methodological mechanisms behind this paradox. Using 1995-2015 data from The Health Improvement Network, we performed survival analysis to examine the association between smoking and incident PsA in the general population and among patients with psoriasis. We clarified the paradox using mediation analysis and conducted bias sensitivity analyses to evaluate the potential impact of index event bias and quantify its magnitude from uncontrolled/unmeasured confounders. Of 6.65 million subjects without PsA at baseline, 225 213 participants had psoriasis and 7057 developed incident PsA. Smoking was associated with an increased risk of PsA in the general population (HR 1.27; 95% CI 1.19 to 1.36), but with a decreased risk among patients with psoriasis (HR 0.91; 95% CI 0.84 to 0.99). Mediation analysis showed that the effect of smoking on the risk of PsA was mediated almost entirely through its effect on psoriasis. Bias-sensitivity analyses indicated that even when the relation of uncontrolled confounders to either smoking or PsA was modest (both HRs=~1.5), it could reverse the biased effect of smoking among patients with psoriasis (HR=0.9). In this large cohort representative of the UK general population, smoking was positively associated with PsA risk in the general population, but negatively associated among patients with psoriasis. Conditioning on a causal intermediate variable (psoriasis) may even reverse the association between smoking and PsA, potentially explaining the smoking paradox for the risk of PsA among patients with psoriasis. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  3. Clinical and molecular characterization of Diastrophic Dysplasia in the Portuguese population.

    PubMed

    Barbosa, M; Sousa, A B; Medeira, A; Lourenço, T; Saraiva, J; Pinto-Basto, J; Soares, G; Fortuna, A M; Superti-Furga, A; Mittaz, L; Reis-Lima, M; Bonafé, L

    2011-12-01

    SLC26A2-related dysplasias encompass a spectrum of diseases: from lethal achondrogenesis type 1B (ACG1B; MIM #600972) and atelosteogenesis type 2 (AO2; MIM #256050) to classical diastrophic dysplasia (cDTD; MIM #222600) and recessive multiple epiphyseal dysplasia (rMED; MIM #226900). This study aimed at characterizing clinically, radiologically and molecularly 14 patients affected by non-lethal SLC26A2-related dysplasias and at evaluating genotype-phenotype correlation. Phenotypically, eight patients were classified as cDTD, four patients as rMED and two patients had an intermediate phenotype (mild DTD - mDTD, previously 'DTD variant'). The Arg279Trp mutation was present in all patients, either in homozygosity (resulting in rMED) or in compound heterozygosity with the known severe alleles Arg178Ter or Asn425Asp (resulting in DTD) or with the mutation c.727-1G>C (causing mDTD). The 'Finnish mutation', c.-26+2T>C, and the p.Cys653Ser, both frequent mutations in non-Portuguese populations, were not identified in any of the patients of our cohort and are probably very rare in the Portuguese population. A targeted mutation analysis for p.Arg279Trp and p.Arg178Ter in the Portuguese population allows the identification of approximately 90% of the pathogenic alleles. © 2010 John Wiley & Sons A/S.

  4. Long-Term Health-Related Quality of Life in German Patients with Juvenile Idiopathic Arthritis in Comparison to German General Population

    PubMed Central

    Barth, Swaantje; Haas, Johannes-Peter; Schlichtiger, Jenny; Molz, Johannes; Bisdorff, Betty; Michels, Hartmut; Hügle, Boris; Radon, Katja

    2016-01-01

    Objective Aims of the study were to investigate health-related quality of life (HRQOL) in adult patients with former diagnosis of Juvenile Idiopathic Arthritis (JIA), to compare their HRQOL with the general population and to identify factors related to a poor outcome. Methods In 2012, a cross-sectional survey was performed by mailing a questionnaire to a large cohort of former and current patients of the German Centre for Rheumatology in Children and Adolescents. Only adult patients (≥18 years) with a diagnosis compatible with JIA were included (n = 2592; response 66%). The questionnaire included information about HRQOL (EQ5D), disease-related questions and socio-demographics. Prevalence and 95% confidence intervals (CI) of problems with mobility, self-care, usual activities, pain and anxiety/depression were standardized to the German general population. Factors associated with low HRQOL in JIA patients were identified using logistic regression models. Results Sixty-two percent of the study population was female; age range was 18–73 years. In all dimensions, JIA patients reported statistically significantly more problems than the general population with largest differences in the pain dimension (JIA patients 56%; 95%CI 55–58%; general population 28%; 26–29%) and the anxiety/depression dimension (28%; 27–29% vs. 4%; 4–5%). Lower HRQOL in JIA patients was associated with female sex, older age, lower level of education, still being under rheumatic treatment and disability. Conclusions HRQOL in adult JIA patients is considerably lower than in the general population. As this cohort includes historic patients the new therapeutic schemes available today are expected to improve HRQOL in future. PMID:27115139

  5. CFTR mutation distribution among U.S. Hispanic and African American individuals: evaluation in cystic fibrosis patient and carrier screening populations.

    PubMed

    Sugarman, Elaine A; Rohlfs, Elizabeth M; Silverman, Lawrence M; Allitto, Bernice A

    2004-01-01

    We reviewed CFTR mutation distribution among Hispanic and African American individuals referred for CF carrier screening and compared mutation frequencies to those derived from CF patient samples. Results from CFTR mutation analyses received from January 2001 through September 2003, were analyzed for four populations: Hispanic individuals with a CF diagnosis (n = 159) or carrier screening indication (n = 15,333) and African American individuals with a CF diagnosis (n = 108) or carrier screening indication (n = 8,973). All samples were tested for the same 87 mutation panel. In the Hispanic population, 42 mutations were identified: 30 in the patient population (77.5% detection rate) and 33 among carrier screening referrals. Five mutations not included in the ACMG/ACOG carrier screening panel (3876delA, W1089X, R1066C, S549N, 1949del84) accounted for 7.55% detection in patients and 5.58% among carriers. Among African American referrals, 33 different mutations were identified: 21 in the patient population (74.4% detection) and 23 in the carrier screening population. Together, A559T and 711+5G>A were observed at a detection rate of 3.71% in CF patients and 6.38% in carriers. The mutation distribution seen in both the carrier screening populations reflected an increased frequency of mutations with variable expression such as D1152H, R117H, and L206W. A detailed analysis of CFTR mutation distribution in the Hispanic and African American patient and carrier screening populations demonstrates that a diverse group of mutations is most appropriate for diagnostic and carrier screening in these populations. To best serve the increasingly diverse U.S. population, ethnic-specific mutations should be included in mutation panels.

  6. SEGMENTING CT PROSTATE IMAGES USING POPULATION AND PATIENT-SPECIFIC STATISTICS FOR RADIOTHERAPY

    PubMed Central

    Feng, Qianjin; Foskey, Mark; Tang, Songyuan; Chen, Wufan; Shen, Dinggang

    2010-01-01

    This paper presents a new deformable model using both population and patient-specific statistics to segment the prostate from CT images. There are two novelties in the proposed method. First, a modified scale invariant feature transform (SIFT) local descriptor, which is more distinctive than general intensity and gradient features, is used to characterize the image features. Second, an online training approach is used to build the shape statistics for accurately capturing intra-patient variation, which is more important than inter-patient variation for prostate segmentation in clinical radiotherapy. Experimental results show that the proposed method is robust and accurate, suitable for clinical application. PMID:21197416

  7. Determining the Number of Ischemic Strokes Potentially Eligible for Endovascular Thrombectomy: A Population-Based Study.

    PubMed

    Chia, Nicholas H; Leyden, James M; Newbury, Jonathan; Jannes, Jim; Kleinig, Timothy J

    2016-05-01

    Endovascular thrombectomy (ET) is standard-of-care for ischemic stroke patients with large vessel occlusion, but estimates of potentially eligible patients from population-based studies have not been published. Such data are urgently needed to rationally plan hyperacute services. Retrospective analysis determined the incidence of ET-eligible ischemic strokes in a comprehensive population-based stroke study (Adelaide, Australia 2009-2010). Stroke patients were stratified via a prespecified eligibility algorithm derived from recent ET trials comprising stroke subtype, pathogenesis, severity, premorbid modified Rankin Score, presentation delay, large vessel occlusion, and target mismatch penumbra. Recognizing centers may interpret recent ET trials either loosely or rigidly; 2 eligibility algorithms were applied: restrictive (key criteria modified Rankin Scale score 0-1, presentation delay <3.5 hours, and target mismatch penumbra) and permissive (modified Rankin Scale score 0-3 and presentation delay <5 hours). In a population of 148 027 people, 318 strokes occurred in the 1-year study period (crude attack rate 215 [192-240] per 100 000 person-years). The number of ischemic strokes eligible by restrictive criteria was 17/258 (7%; 95% confidence intervals 4%-10%) and by permissive criteria, an additional 16 were identified, total 33/258 (13%; 95% confidence intervals 9%-18%). Two of 17 patients (and 6/33 permissive patients) had thrombolysis contraindications. Using the restrictive algorithm, there were 11 (95% confidence intervals 4-18) potential ET cases per 100 000 person-years or 22 (95% confidence intervals 13-31) using the permissive algorithm. In this cohort, ≈7% of ischemic strokes were potentially eligible for ET (13% with permissive criteria). In similar populations, the permissive criteria predict that ≤22 strokes per 100 000 person-years may be eligible for ET. © 2016 American Heart Association, Inc.

  8. Population Pharmacokinetic Model for Vancomycin Used in Open Heart Surgery: Model-Based Evaluation of Standard Dosing Regimens.

    PubMed

    Alqahtani, Saeed A; Alsultan, Abdullah S; Alqattan, Hussain M; Eldemerdash, Ahmed; Albacker, Turki B

    2018-04-23

    The purpose of this study was to investigate the population pharmacokinetics of vancomycin in patients undergoing open heart surgery. In this observational pharmacokinetic study, multiple blood samples were drawn over a 48-h period of intravenous vancomycin in patients who were undergoing open heart surgery. Blood samples were analysed using the Architect i4000SR Immunoassay Analyzer. Population pharmacokinetic models were developed using Monolix 4.4 software. Pharmacokinetic-pharmacodynamic (PK-PD) simulations were performed to explore the ability of different dosage regimens to achieve the pharmacodynamic targets. One-hundred and sixty-eight blood samples were analysed from 28 patients. The pharmacokinetics of vancomycin was best described by a two-compartment model with between-subject variability in CL, V of the central compartment, and V of the peripheral compartment. CL and central compartment V of vancomycin were related to CL CR , body weight, and albumin concentration. Dosing simulations showed that standard dosing regimens of 1 and 1.5 g failed to achieve the PK-PD target of AUC 0--24 /MIC > 400 for an MIC of 1 mg/L, while high weight-based dosing regimens were able to achieve the PK-PD target. In summary, administration of standard doses of 1 and 1.5 g of vancomycin two times daily provided inadequate antibiotic prophylaxis in patients undergoing open heart surgery. The same findings were obtained when 15 mg/kg and 20 mg/kg doses of vancomycin were administered. Achieving the PK-PD target required higher doses (25 mg/kg and 30 mg/kg) of vancomycin. Copyright © 2018 American Society for Microbiology.

  9. Population Pharmacokinetic Model-Based Evaluation of Standard Dosing Regimens for Cefuroxime Used in Coronary Artery Bypass Graft Surgery with Cardiopulmonary Bypass.

    PubMed

    Alqahtani, Saeed A; Alsultan, Abdullah S; Alqattan, Hussain M; Eldemerdash, Ahmed; Albacker, Turki B

    2018-04-01

    The purpose of this study was to investigate the population pharmacokinetics (PK) of cefuroxime in patients undergoing coronary artery bypass graft (CABG) surgery. In this observational pharmacokinetic study, multiple blood samples were collected over a 48-h interval of intravenous cefuroxime administration. The samples were analyzed by using a validated high-performance liquid chromatography (HPLC) method. Population pharmacokinetic models were developed using Monolix (version 4.4) software. Pharmacokinetic-pharmacodynamic (PD) simulations were performed to explore the ability of different dosage regimens to achieve the pharmacodynamic targets. A total of 468 blood samples from 78 patients were analyzed. The PK for cefuroxime were best described by a two-compartment model with between-subject variability on clearance, the volume of distribution of the central compartment, and the volume of distribution of the peripheral compartment. The clearance of cefuroxime was related to creatinine clearance (CL CR ). Dosing simulations showed that standard dosing regimens of 1.5 g could achieve the PK-PD target of the percentage of the time that the free concentration is maintained above the MIC during a dosing interval ( fT MIC ) of 65% for an MIC of 8 mg/liter in patients with a CL CR of 30, 60, or 90 ml/min, whereas this dosing regimen failed to achieve the PK-PD target in patients with a CL CR of ≥125 ml/min. In conclusion, administration of standard doses of 1.5 g three times daily provided adequate antibiotic prophylaxis in patients undergoing CABG surgery. Lower doses failed to achieve the PK-PD target. Patients with high CL CR values required either higher doses or shorter intervals of cefuroxime dosing. On the other hand, lower doses (1 g three times daily) produced adequate target attainment for patients with low CL CR values (≤30 ml/min). Copyright © 2018 American Society for Microbiology.

  10. Population Pharmacokinetic Modeling of Olmesartan, the Active Metabolite of Olmesartan Medoxomil, in Patients with Hypertension.

    PubMed

    Kodati, Devender; Kotakonda, Harish Kaushik; Yellu, Narsimhareddy

    2017-08-01

    Olmesartan medoxomil is an orally given angiotensin II receptor antagonist indicated for the treatment of hypertension. The aim of the study was to establish a population pharmacokinetic model for olmesartan, the active metabolite of olmesartan medoxomil, in Indian hypertensive patients, and to evaluate effects of covariates on the volume of distribution (V/F) and oral clearance (CL/F) of olmesartan. The population pharmacokinetic model for olmesartan was developed using Phoenix NLME 1.3 with a non-linear mixed-effect model. Bootstrap and visual predictive check were used simultaneously to validate the final population pharmacokinetic models. The covariates included age, sex, body surface area (BSA), bodyweight, height, creatinine clearance (CL CR ) as an index of renal function and liver parameters as indices of hepatic function. A total of 205 olmesartan plasma sample concentrations from 69 patients with hypertension were collected in this study. The pharmacokinetic data of olmesartan was well described by a two-compartment linear pharmacokinetic model with first-order absorption and an absorption lag-time. The mean values of CL/F and V/F of olmesartan in the patients were 0.31565 L/h and 44.5162 L, respectively. Analysis of covariates showed that age and CL CR were factors influencing the clearance of olmesartan and the volume of distribution of olmesartan was dependent on age and BSA. The final population pharmacokinetic model was demonstrated to be appropriate and effective and it can be used to assess the pharmacokinetic parameters of olmesartan in Indian patients with hypertension.

  11. Why patients visit their doctors: assessing the most prevalent conditions in a defined American population.

    PubMed

    St Sauver, Jennifer L; Warner, David O; Yawn, Barbara P; Jacobson, Debra J; McGree, Michaela E; Pankratz, Joshua J; Melton, L Joseph; Roger, Véronique L; Ebbert, Jon O; Rocca, Walter A

    2013-01-01

    To describe the prevalence of nonacute conditions among patients seeking health care in a defined US population, emphasizing age, sex, and ethnic differences. The Rochester Epidemiology Project (REP) medical records linkage system was used to identify all residents of Olmsted County, Minnesota, on April 1, 2009, who had consented to review of their medical records for research (142,377 patients). We then electronically extracted all International Classification of Diseases, Ninth Revision codes noted in the records of these patients by any health care institution between January 1, 2005, and December 31, 2009. We grouped International Classification of Diseases, Ninth Revision codes into clinical classification codes and then into 47 broader disease groups associated with health-related quality of life. Age- and sex-specific prevalence was estimated by dividing the number of individuals within each group by the corresponding age- and sex-specific population. Patients within a group who had multiple codes were counted only once. We included a total of 142,377 patients, 75,512 (53%) of whom were female. Skin disorders (42.7%), osteoarthritis and joint disorders (33.6%), back problems (23.9%), disorders of lipid metabolism (22.4%), and upper respiratory tract disease (22.1%, excluding asthma) were the most prevalent disease groups in this population. Ten of the 15 most prevalent disease groups were more common in women in almost all age groups, whereas disorders of lipid metabolism, hypertension, and diabetes were more common in men. Additionally, the prevalence of 7 of the 10 most common groups increased with advancing age. Prevalence also varied across ethnic groups (whites, blacks, and Asians). Our findings suggest areas for focused research that may lead to better health care delivery and improved population health. Copyright © 2013 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  12. The patient perspective: utilizing focus groups to inform care coordination for high-risk medicaid populations.

    PubMed

    Sheff, Alex; Park, Elyse R; Neagle, Mary; Oreskovic, Nicolas M

    2017-07-25

    Care coordination programs for high-risk, high-cost patients are a critical component of population health management. These programs aim to improve outcomes and reduce costs and have proliferated over the last decade. Some programs, originally designed for Medicare patients, are now transitioning to also serve Medicaid populations. However, there are still gaps in the understanding of what barriers to care Medicaid patients experience, and what supports will be most effective for providing them care coordination. We conducted two focus groups (n = 13) and thematic analyses to assess the outcomes drivers and programmatic preferences of Medicaid patients enrolled in a high-risk care coordination program at a major academic medical center in Boston, MA. Two focus groups identified areas where care coordination efforts were having a positive impact, as well as areas of unmet needs among the Medicaid population. Six themes emerged from the focus groups that clustered in three groupings: In the first group (1) enrollment in an existing medical care coordination programs, and (2) provider communication largely presented as positive accounts of assistance, and good relationships with providers, though participants also pointed to areas where these efforts fell short. In the second group (3) trauma histories, (4) mental health challenges, and (5) executive function difficulties all presented challenges faced by high-risk Medicaid patients that would likely require redress through additional programmatic supports. Finally, in the third group, (6) peer-to-peer support tendencies among patients suggested an untapped resource for care coordination programs. Programs aimed at high-risk Medicaid patients will want to consider programmatic adjustments to attend to patient needs in five areas: (1) provider connection/care coordination, (2) trauma, (3) mental health, (4) executive function/paperwork and coaching support, and (5) peer-to-peer support.

  13. Increasing global burden of cardiovascular disease in general populations and patients with schizophrenia.

    PubMed

    Hennekens, Charles H

    2007-01-01

    Cardiovascular disease (CVD), which includes coronary heart, cerebrovascular, and peripheral vascular disease, is the leading cause of death in the United States and most developed countries, accounting for about 50% of all deaths. The major risk factors include obesity and its consequences, dyslipidemia, hypertension, insulin resistance leading to diabetes, and cigarette smoking. In developing countries, CVD will become the leading cause of death due to alarming increases in obesity, sedentary lifestyles, cigarette smoking, and improvements in prevention and treatment of malnutrition and infection. Compared with nonschizophrenics, patients with schizophrenia have a 20% shorter life expectancy (i.e., from 76 to 61 years). In general populations, about 1% die from suicide compared with about 10% among patients with schizophrenia (relative risk = 10). For CVD, the corresponding figures are 50% and about 75% (relative risk = 1.5). In patients with schizophrenia, however, CVD occurs more frequently and accounts for more premature deaths than suicide. Patients with schizophrenia have alarmingly higher rates of obesity, dyslipidemia, hypertension, diabetes, and cigarette smoking than nonschizophrenic individuals in the general population. Compounding these data, patients with schizophrenia have less access to medical care, consume less medical care, and are less compliant. Primary prevention strategies should include the choice of antipsychotic drug regimens that do not adversely affect the major risk factors for CVD.

  14. Segmenting lung fields in serial chest radiographs using both population-based and patient-specific shape statistics.

    PubMed

    Shi, Y; Qi, F; Xue, Z; Chen, L; Ito, K; Matsuo, H; Shen, D

    2008-04-01

    This paper presents a new deformable model using both population-based and patient-specific shape statistics to segment lung fields from serial chest radiographs. There are two novelties in the proposed deformable model. First, a modified scale invariant feature transform (SIFT) local descriptor, which is more distinctive than the general intensity and gradient features, is used to characterize the image features in the vicinity of each pixel. Second, the deformable contour is constrained by both population-based and patient-specific shape statistics, and it yields more robust and accurate segmentation of lung fields for serial chest radiographs. In particular, for segmenting the initial time-point images, the population-based shape statistics is used to constrain the deformable contour; as more subsequent images of the same patient are acquired, the patient-specific shape statistics online collected from the previous segmentation results gradually takes more roles. Thus, this patient-specific shape statistics is updated each time when a new segmentation result is obtained, and it is further used to refine the segmentation results of all the available time-point images. Experimental results show that the proposed method is more robust and accurate than other active shape models in segmenting the lung fields from serial chest radiographs.

  15. Population pharmacokinetics of phenytoin after intravenous administration of fosphenytoin sodium in pediatric patients, adult patients, and healthy volunteers.

    PubMed

    Tanaka, Jun; Kasai, Hidefumi; Shimizu, Kenji; Shimasaki, Shigeki; Kumagai, Yuji

    2013-03-01

    We performed a population pharmacokinetic analysis of phenytoin after intravenous administration of fosphenytoin sodium in healthy, neurosurgical, and epileptic subjects, including pediatric patients, and determined the optimal dose and infusion rate for achieving the therapeutic range. We used pooled data obtained from two phase I studies and one phase III study performed in Japan. The population pharmacokinetic analysis was performed using NONMEM software. The optimal dose and infusion rate were determined using simulation results obtained using the final model. The therapeutic range for total plasma phenytoin concentration is 10-20 μg/mL. We used a linear two-compartment model with conversion of fosphenytoin to phenytoin. Pharmacokinetic parameters of phenytoin, such as total clearance and central and peripheral volume of distribution were influenced by body weight. The dose simulations are as follows. In adult patients, the optimal dose and infusion rate of phenytoin for achieving the therapeutic range was 22.5 mg/kg and 3 mg/kg/min respectively. In pediatric patients, the total plasma concentration of phenytoin was within the therapeutic range for a shorter duration than that in adult patients at 22.5 mg/kg (3 mg/kg/min). However, many pediatric patients showed phenytoin concentration within the toxic range after administration of a dose of 30 mg/kg. The pharmacokinetics of phenytoin after intravenous administration of fosphenytoin sodium could be described using a linear two-compartment model. The administration of fosphenytoin sodium 22.5 mg/kg at an infusion rate of 3 mg/kg/min was optimal for achieving the desired plasma phenytoin concentration.

  16. High need patients receiving targeted entitlements: what responsibilities do they have in primary health care?

    PubMed

    Buetow, S

    2005-05-01

    Patient responsibilities in primary health care are controversial and, by comparison, the responsibilities of high need patients are less clear. This paper aims to suggest why high need patients receiving targeted entitlements in primary health care are free to have prima facie special responsibilities; why, given this freedom, these patients morally have special responsibilities; what these responsibilities are, and how publicly funded health systems ought to be able to respond when these remain unmet. It is suggested that the special responsibilities and their place in public policy acquire moral significance as a means to discharge a moral debt, share special knowledge, and produce desirable consequences in regard to personal and collective interests. Special responsibilities magnify ordinary patient responsibilities and require patients not to hesitate regarding attendance for primary health care. Persistent patient disregard of special responsibilities may necessitate limiting the scope of these responsibilities, removing system barriers, or respecifying special rights.

  17. [Folic acid fortified foods available in Spain: types of products, level of fortification and target population groups].

    PubMed

    Samaniego Vaesken, M L; Alonso-Aperte, E; Varela-Moreiras, G

    2009-01-01

    Folic acid is a potentially relevant factor in the prevention of a number of pathologies (congenital abnormalities, cardiovascular disease, colorectal cancer and neurocognitive decline). This has led to the introduction of different strategies in order to increase folate intake: nutritional education, pharmacological supplementation and mandatory or voluntary fortification of staple foods with folic acid. In Spain there is a growing number of folic acid fortified products on a voluntary basis, but there is also a lack of reliable data to assess their impact on the population's dietary folate intakes. To gather a better knowledge of folic acid food fortification practices in Spain. A Food Composition Database was developed using data from a market study. Also, previously published data of unfortified staple foods from Food Composition Tables was reviewed. The Database included 260 folic acid fortified food items and it was periodically updated. Food groups included were primarily "Cereals and derivatives" (52%) followed by "Dairy products". Most of these foodstuffs lacked a target population for their consumption (37%) or were aimed at "Weight control" (28%) and "Children" (23%), but only 2% targeted women at a reproductive age. Number of unfortified foods included was 690. Fortification levels declared by manufacturers ranged between 15 and 430% of the Recommended Dietary Allowances (RDA) for folic acid per 100 g/ml, and simultaneous addition of B6 and B12 vitamins was observed in 75% of the products. Currently, Spain market offers a significant number of folic acid fortified products on a voluntary basis and at a level > or = 15% of the RDA per 100 g/ml or serving declared by manufacturers.

  18. Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy

    PubMed Central

    Lohr, Jens G.; Stojanov, Petar; Carter, Scott L.; Cruz-Gordillo, Peter; Lawrence, Michael S.; Auclair, Daniel; Sougnez, Carrie; Knoechel, Birgit; Gould, Joshua; Saksena, Gordon; Cibulskis, Kristian; McKenna, Aaron; Chapman, Michael A.; Straussman, Ravid; Levy, Joan; Perkins, Louise M.; Keats, Jonathan J.; Schumacher, Steven E.; Rosenberg, Mara; Getz, Gad

    2014-01-01

    SUMMARY We performed massively parallel sequencing of paired tumor/normal samples from 203 multiple myeloma (MM) patients and identified significantly mutated genes and copy number alterations, and discovered putative tumor suppressor genes by determining homozygous deletions and loss-of-heterozygosity. We observed frequent mutations in KRAS (particularly in previously treated patients), NRAS, BRAF, FAM46C, TP53 and DIS3 (particularly in non-hyperdiploid MM). Mutations were often present in subclonal populations, and multiple mutations within the same pathway (e.g. KRAS, NRAS and BRAF) were observed in the same patient. In vitro modeling predicts only partial treatment efficacy of targeting subclonal mutations, and even growth promotion of non-mutated subclones in some cases. These results emphasize the importance of heterogeneity analysis for treatment decisions. PMID:24434212

  19. Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy.

    PubMed

    Lohr, Jens G; Stojanov, Petar; Carter, Scott L; Cruz-Gordillo, Peter; Lawrence, Michael S; Auclair, Daniel; Sougnez, Carrie; Knoechel, Birgit; Gould, Joshua; Saksena, Gordon; Cibulskis, Kristian; McKenna, Aaron; Chapman, Michael A; Straussman, Ravid; Levy, Joan; Perkins, Louise M; Keats, Jonathan J; Schumacher, Steven E; Rosenberg, Mara; Getz, Gad; Golub, Todd R

    2014-01-13

    We performed massively parallel sequencing of paired tumor/normal samples from 203 multiple myeloma (MM) patients and identified significantly mutated genes and copy number alterations and discovered putative tumor suppressor genes by determining homozygous deletions and loss of heterozygosity. We observed frequent mutations in KRAS (particularly in previously treated patients), NRAS, BRAF, FAM46C, TP53, and DIS3 (particularly in nonhyperdiploid MM). Mutations were often present in subclonal populations, and multiple mutations within the same pathway (e.g., KRAS, NRAS, and BRAF) were observed in the same patient. In vitro modeling predicts only partial treatment efficacy of targeting subclonal mutations, and even growth promotion of nonmutated subclones in some cases. These results emphasize the importance of heterogeneity analysis for treatment decisions. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Health services utilization for people with HIV infection: comparison of a population targeted for outreach with the U.S. population in care.

    PubMed

    Cunningham, William E; Sohler, Nancy L; Tobias, Carol; Drainoni, Mari-lynn; Bradford, Judith; Davis, Cynthia; Cabral, Howard J; Cunningham, Chinazo O; Eldred, Lois; Wong, Mitchell D

    2006-11-01

    Many persons with HIV infection do not receive consistent ambulatory medical care and are excluded from studies of patients in medical care. However, these hard-to-reach groups are important to study because they may be in greatest need of services. This study compared the sociodemographic, clinical, and health care utilization characteristics of a multisite sample of HIV-positive persons who were hard to reach with a nationally representative cohort of persons with HIV infection who were receiving care from known HIV providers in the United States and examined whether the independent correlates of low ambulatory utilization differed between the 2 samples. We compared sociodemographic, clinical, and health care utilization characteristics in 2 samples of adults with HIV infection: 1286 persons from 16 sites across the United States interviewed in 2001-2002 for the Targeted HIV Outreach and Intervention Initiative (Outreach), a study of underserved persons targeted for supportive outreach services; and 2267 persons from the HIV Costs and Services Utilization Study (HCSUS), a probability sample of persons receiving care who were interviewed in 1998. We conducted logistic regression analyses to identify differences between the 2 samples in sociodemographic and clinical associations with ambulatory medical visits. Compared with the HCSUS sample, the Outreach sample had notably greater proportions of black respondents (59% vs. 32%, P = 0.0001), Hispanics (20% vs. 16%), Spanish-speakers (9% vs. 2%, P = 0.02), those with low socioeconomic status (annual income < Dollars 10,000 75% vs. 45%, P = 0.0001), the unemployed, and persons with homelessness, no insurance, and heroin or cocaine use (58% vs. 47%, P = 0.05). They also were more likely to have fewer than 2 ambulatory visits (26% vs. 16%, P = 0.0001), more likely to have emergency room visits or hospitalizations in the prior 6 months, and less likely to be on antiretroviral treatment (82% vs. 58%, P = 0.0001). Nearly

  1. Effectiveness of influenza vaccine against laboratory-confirmed influenza, in the late 2011–2012 season in Spain, among population targeted for vaccination

    PubMed Central

    2013-01-01

    Background In Spain, the influenza vaccine effectiveness (VE) was estimated in the last three seasons using the observational study cycEVA conducted in the frame of the existing Spanish Influenza Sentinel Surveillance System. The objective of the study was to estimate influenza vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza-like illness (ILI) among the target groups for vaccination in Spain in the 2011–2012 season. We also studied influenza VE in the early (weeks 52/2011-7/2012) and late (weeks 8-14/2012) phases of the epidemic and according to time since vaccination. Methods Medically attended patients with ILI were systematically swabbed to collect information on exposure, laboratory outcome and confounding factors. Patients belonging to target groups for vaccination and who were swabbed <8 days after symptom onset were included. Cases tested positive for influenza and controls tested negative for any influenza virus. To examine the effect of a late season, analyses were performed according to the phase of the season and according to the time between vaccination and symptoms onset. Results The overall adjusted influenza VE against A(H3N2) was 45% (95% CI, 0–69). The estimated influenza VE was 52% (95% CI, -3 to 78), 40% (95% CI, -40 to 74) and 22% (95% CI, -135 to 74) at 3.5 months, 3.5-4 months, and >4 months, respectively, since vaccination. A decrease in VE with time since vaccination was only observed in individuals aged ≥ 65 years. Regarding the phase of the season, decreasing point estimates were only observed in the early phase, whereas very low or null estimates were obtained in the late phase for the shortest time interval. Conclusions The 2011–2012 influenza vaccine showed a low-to-moderate protective effect against medically attended, laboratory-confirmed influenza in the target groups for vaccination, in a late season and with a limited match between the vaccine and circulating strains. The

  2. Population Pharmacokinetics and Pharmacodynamics of Levofloxacin in Acutely Hospitalized Older Patients with Various Degrees of Renal Function

    PubMed Central

    Cojutti, Pier Giorgio; Ramos-Martin, Virginia; Schiavon, Isabella; Rossi, Paolo; Baraldo, Massimo; Hope, William

    2016-01-01

    ABSTRACT A retrospective study was conducted in a large sample of acutely hospitalized older patients who underwent therapeutic drug monitoring during levofloxacin treatment. The aim was to assess the population pharmacokinetics (popPK) and pharmacodynamics of levofloxacin among older patients. PopPK and Monte Carlo simulation were performed to define the permissible doses in older patients according to various degrees of renal function. Classification and regression tree (CART) analysis was used to detect the cutoff 24-hour area under the concentration-time curve (AUC24)/MIC ratio that best correlated with the clinical outcome. The probability of target attainment (PTA) of this value was calculated against different pathogens. A total of 168 patients were included, and 330 trough and 239 peak concentrations were used for the popPK analysis. Creatinine clearance (CrCL) was the only covariate that improved the model fit (levofloxacin CL = 0.399 + 0.051 × CrCLCKD-EPI [creatinine clearance estimated by means of the chronic kidney disease epidemiology]). Drug doses ranged between 500 mg every 48 h and 500 mg every 12 h in relation to different renal functions. The identified cutoff AUC24/MIC ratio (≥95.7) was the only covariate that correlated with a favorable clinical outcome in multivariate regression analysis (odds ratio [OR], 20.85; 95% confidence interval [CI], 1.56 to 186.73). PTAs were optimal (>80%) against Escherichia coli and Haemophilus influenzae, borderline against Staphylococcus aureus, and suboptimal against Pseudomonas aeruginosa. The levofloxacin doses defined in our study may be effective for the treatment of infections due to bacterial pathogens, with an MIC of ≤0.5 mg/liter in older patients with various degrees of renal function, while minimizing the toxicity risk. Conversely, the addition of another active antimicrobial should be considered whenever treating infections caused by less susceptible pathogens. PMID:28031199

  3. Known and putative mechanisms of resistance to EGFR targeted therapies in NSCLC patients with EGFR mutations—a review

    PubMed Central

    Stewart, Erin L.; Tan, Samuel Zhixing; Liu, Geoffrey

    2015-01-01

    Lung cancer is the leading cause of cancer related deaths in Canada with non-small cell lung cancer (NSCLC) being the predominant form of the disease. Tumor characterization can identify cancer-driving mutations as treatment targets. One of the most successful examples of cancer targeted therapy is inhibition of mutated epidermal growth factor receptor (EGFR), which occurs in ~10-30% of NSCLC patients. While this treatment has benefited many patients with activating EGFR mutations, almost all who initially benefited will eventually acquire resistance. Approximately 50% of cases of acquired resistance (AR) are due to a secondary T790M mutation in exon 20 of the EGFR gene; however, many of the remaining mechanisms of resistance are still unknown. Much work has been done to elucidate the remaining mechanisms of resistance. This review aims to highlight both the mechanisms of resistance that have already been identified in patients and potential novel mechanisms identified in preclinical models which have yet to be validated in the patient settings. PMID:25806347

  4. Osteoporosis in adult patients with atopic dermatitis: A nationwide population-based study

    PubMed Central

    Lu, Chun-Ching; Su, Yu-Feng; Tsai, Tai-Hsin; Wu, Chieh-Hsin

    2017-01-01

    The aim of this study was to investigate osteoporosis risk in atopic dermatitis (AD) patients. This study included patients in the Taiwan National Health Insurance Research dataset. The population-based study included all patients aged 20–49 years who had been diagnosed with AD during 1996–2010. In total, 35,229 age and gender-matched patients without AD in a 1:1 ratio were randomly selected as the non-AD group. Cox proportional-hazards regression and Kaplan–Meier analyses were used to measure the hazard ratios and the cumulative incidences of osteoporosis, respectively. During the follow-up period, 360(1.02%) AD patients and 127(0.36%) non-AD patients developed osteoporosis. The overall incidence of osteoporosis was4.72-fold greater in the AD patients compared to the non-AD patients (1.82 vs. 0.24 per 1,000 person-years, respectively) after adjusting for potential confounding factors. Osteoporosis risk factors included female gender, age, advanced Charlson Comorbidity Index, depression and use of corticosteroids. The dataset analysis showed that AD was significantly associated with subsequent risk of osteoporosis. PMID:28207767

  5. On the Problem of Patient-Specific Endogenous Glucose Production in Neonates on Stochastic Targeted Glycemic Control

    PubMed Central

    Dickson, Jennifer L.; Hewett, James N.; Gunn, Cameron A.; Lynn, Adrienne; Shaw, Geoffrey M.; Chase, Geoffrey

    2013-01-01

    Background: Both stress and prematurity can induce hyperglycemia in the neonatal intensive care unit, which, in turn, is associated with worsened outcomes. Endogenous glucose production (EGP) is the formation of glucose by the body from substrates and contributes to blood glucose (BG) levels. Due to the inherent fragility of the extremely low birth weight (ELBW) neonates, true fasting EGP cannot be explicitly determined, introducing uncertainty into glycemic models that rely on quantifying glucose sources. Stochastic targeting, or STAR, is one such glycemic control framework. Methods: A literature review was carried out to gather metabolic and EGP values on preterm infants with a gestational age (GA) <32 weeks and a birth weight (BW) <2 kg. The data were analyzed for EGP trends with BW, GA, BG, plasma insulin, and glucose infusion (GI) rates. Trends were modeled and compared with a literature-derived range of population constant EGP models using clinically validated virtual trials on retrospective clinical data. Results: No clear relationship was found for EGP and BW, GA, or plasma insulin. Some evidence of suppression of EGP with increasing GI or BG was seen. Virtual trial results showed that population-constant EGP models fit clinical data best and gave tighter control performance to a target band in virtual trials. Conclusions: Variation in EGP cannot easily be quantified, and EGP is sufficiently modeled as a population constant in the neonatal intensive care insulin–nutrition–glucose model. Analysis of the clinical data and fitting error suggests that ELBW hyperglycemic preterm neonates have unsuppressed EGP in the higher range than that seen in literature. PMID:23911173

  6. Targeting inflammation in the prevention of cardiovascular disease in patients with inflammatory arthritis.

    PubMed

    Shen, Jiayun; Shang, Qing; Tam, Lai-Shan

    2016-01-01

    Patients with inflammatory arthritis have increased risk of cardiovascular diseases (CVDs) compared with the general population. Subclinical carotid atherosclerosis and increased arterial stiffness are also common in these patients, which may serve as surrogate end points for cardiovascular (CV) events in clinical trials. Although exact mechanisms are still unclear, persistent systemic inflammation in patients with inflammatory arthritis may contribute to the development of CVD. Dysregulated innate immunity pathways in these patients may also play a role in accelerating atherosclerosis. During the last decade, effective suppression of inflammation by biological disease-modifying antirheumatic drugs has improved the disease outcome dramatically in patients with inflammatory arthritis. Growing evidence suggests that antitumor necrosis factor (TNF) therapy may prevent CVD in patients with rheumatoid arthritis. Nonetheless, data on non-TNF biologics are limited. Whether anti-TNF therapy may prevent CVD in patients with spondyloarthritis also remained unclear. In this review, we summarized the effect of both anti-TNF and non-TNF biologics on the CV system, including traditional CVD risk factors, endothelial function, arterial stiffness, subclinical atherosclerosis, and clinical CVD in patients with inflammatory arthritis. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Population pharmacokinetics of intravenous Erwinia asparaginase in pediatric acute lymphoblastic leukemia patients.

    PubMed

    Sassen, Sebastiaan D T; Mathôt, Ron A A; Pieters, Rob; Kloos, Robin Q H; de Haas, Valérie; Kaspers, Gertjan J L; van den Bos, Cor; Tissing, Wim J E; Te Loo, Maroeska; Bierings, Marc B; Kollen, Wouter J W; Zwaan, Christian M; van der Sluis, Inge M

    2017-03-01

    Erwinia asparaginase is an important component in the treatment of pediatric acute lymphoblastic leukemia. A large variability in serum concentrations has been observed after intravenous Erwinia asparaginase. Currently, Dutch Childhood Oncology Group protocols dose alterations are based on trough concentrations to ensure adequate asparaginase activity (≥100 IU/L). The aim of this study was to describe the population pharmacokinetics of intravenous Erwinia asparaginase to quantify and gather insight into inter-individual and inter-occasion variability. The starting dose was evaluated on the basis of the derived population pharmacokinetic parameters. In a multicenter prospective observational study, a total of 714 blood samples were collected from 51 children (age 1-17 years) with acute lymphoblastic leukemia. The starting dose was 20,000 IU/m 2 three times a week and adjusted according to trough levels from week three onwards. A population pharmacokinetic model was developed using NONMEM ® A 2-compartment linear model with allometric scaling best described the data. Inter-individual and inter-occasion variability of clearance were 33% and 13%, respectively. Clearance in the first month of treatment was 14% higher ( P <0.01). Monte Carlo simulations with our pharmacokinetic model demonstrated that patients with a low weight might require higher doses to achieve similar concentrations compared to patients with high weight. The current starting dose of 20,000 IU/m 2 might result in inadequate concentrations, especially for smaller, lower weight patients, hence dose adjustments based on individual clearance are recommended. The protocols were approved by the institutional review boards. (Registered at NTR 3379 Dutch Trial Register; www.trialregister.nl). Copyright© Ferrata Storti Foundation.

  8. Systemic hyperfibrinolysis after trauma: a pilot study of targeted proteomic analysis of superposed mechanisms in patient plasma.

    PubMed

    Banerjee, Anirban; Silliman, Christopher C; Moore, Ernest E; Dzieciatkowska, Monika; Kelher, Marguerite; Sauaia, Angela; Jones, Kenneth; Chapman, Michael P; Gonzalez, Eduardo; Moore, Hunter B; D'Alessandro, Angelo; Peltz, Erik; Huebner, Benjamin E; Einerson, Peter; Chandler, James; Ghasabayan, Arsen; Hansen, Kirk

    2018-06-01

    Viscoelastic measurements of hemostasis indicate that 20% of seriously injured patients exhibit systemic hyperfibrinolysis, with increased early mortality. These patients have normal clot formation with rapid clot lysis. Targeted proteomics was applied to quantify plasma proteins from hyperfibrinolytic (HF) patients to elucidate potential pathophysiology. Blood samples were collected in the field or at emergency department arrival and thrombelastography (TEG) was used to characterize in vitro clot formation under native and tissue plasminogen activator (tPA)-stimulated conditions. Ten samples were taken from injured patients exhibiting normal lysis time at 30 min (Ly30), "eufibrinolytic" (EF), 10 from HF patients, defined as tPA-stimulated TEG Ly30 >50%, and 10 from healthy controls. Trauma patient samples were analyzed by targeted proteomics and ELISA assays for specific coagulation proteins. HF patients exhibited increased plasminogen activation. Thirty-three proteins from the HF patients were significantly decreased compared with healthy controls and EF patients; 17 were coagulation proteins with anti-protease consumption (p < 0.005). The other 16 decreased proteins indicate activation of the alternate complement pathway, depletion of carrier proteins, and four glycoproteins. CXC7 was elevated in all injured patients versus healthy controls (p < 0.005), and 35 proteins were unchanged across all groups (p > 0.1 and fold change of concentrations of 0.75-1.3). HF patients had significant decreases in specific proteins and support mechanisms known in trauma-induced hyperfibrinolysis and also unexpected decreases in coagulation factors, factors II, X, and XIII, without changes in clot formation (SP, R times, or angle). Decreased clot stability in HF patients was corroborated with tPA-stimulated TEGs. Prognostic, level III.

  9. Patient opinions regarding 'pay for performance for patients'.

    PubMed

    Long, Judith A; Helweg-Larsen, Marie; Volpp, Kevin G

    2008-10-01

    Pay for performance (P4P) programs have shown only modest improvements in outcomes and do not target patient behaviors. Many large employers and payers are turning to pay for performance for patients (P4P4P) to reduce health costs and improve the health of their covered populations. How these programs may be perceived by patients is unknown. To assess patients' opinion of the acceptability of P4P4P. Cross-sectional self-administered survey. Patients in waiting rooms in two university-based primary care clinics. Participants were asked their opinions about paying people to quit smoking, lose weight, control their blood pressure, or control their diabetes. Respondents were split on whether P4P4P is desirable. Thirty-six to 42% thought it was a good/excellent idea to pay smokers to quit smoking, obese people to lose weight, people with hypertension to control their blood pressure, or people with diabetes to control their blood sugar, while 41-44% of the sample thought it was a bad/very bad idea. Smokers and patients who were obese endorsed P4P4P more favorably as a means to achieving tobacco cessation and weight loss than their non-smoking and non-obese counterparts. Acceptance of paying patients for performance by the general population is equivocal. Establishing the efficacy of paying patients for performance may help it gain wider acceptance.

  10. SU-E-J-44: A Novel Approach to Quantify Patient Setup and Target Motion for Real-Time Image-Guided Radiotherapy (IGRT)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, S; Charpentier, P; Sayler, E

    2015-06-15

    Purpose Isocenter shifts and rotations to correct patient setup errors and organ motion cannot remedy some shape changes of large targets. We are investigating new methods in quantification of target deformation for realtime IGRT of breast and chest wall cancer. Methods Ninety-five patients of breast or chest wall cancer were accrued in an IRB-approved clinical trial of IGRT using 3D surface images acquired at daily setup and beam-on time via an in-room camera. Shifts and rotations relating to the planned reference surface were determined using iterative-closest-point alignment. Local surface displacements and target deformation are measured via a ray-surface intersection andmore » principal component analysis (PCA) of external surface, respectively. Isocenter shift, upper-abdominal displacement, and vectors of the surface projected onto the two principal components, PC1 and PC2, were evaluated for sensitivity and accuracy in detection of target deformation. Setup errors for some deformed targets were estimated by superlatively registering target volume, inner surface, or external surface in weekly CBCT or these outlines on weekly EPI. Results Setup difference according to the inner-surface, external surface, or target volume could be 1.5 cm. Video surface-guided setup agreed with EPI results to within < 0.5 cm while CBCT results were sometimes (∼20%) different from that of EPI (>0.5 cm) due to target deformation for some large breasts and some chest walls undergoing deep-breath-hold irradiation. Square root of PC1 and PC2 is very sensitive to external surface deformation and irregular breathing. Conclusion PCA of external surfaces is quick and simple way to detect target deformation in IGRT of breast and chest wall cancer. Setup corrections based on the target volume, inner surface, and external surface could be significant different. Thus, checking of target shape changes is essential for accurate image-guided patient setup and motion tracking of large

  11. Patient navigation and financial incentives to promote smoking cessation in an underserved primary care population: A randomized controlled trial protocol.

    PubMed

    Quintiliani, Lisa M; Russinova, Zlatka L; Bloch, Philippe P; Truong, Ve; Xuan, Ziming; Pbert, Lori; Lasser, Karen E

    2015-11-01

    Despite the high risk of tobacco-related morbidity and mortality among low-income persons, few studies have connected low-income smokers to evidence-based treatments. We will examine a smoking cessation intervention integrated into primary care. To begin, we completed qualitative formative research to refine an intervention utilizing the services of a patient navigator trained to promote smoking cessation. Next, we will conduct a randomized controlled trial combining two interventions: patient navigation and financial incentives. The goal of the intervention is to promote smoking cessation among patients who receive primary care in a large urban safety-net hospital. Our intervention will encourage patients to utilize existing smoking cessation resources (e.g., quit lines, smoking cessation groups, discussing smoking cessation with their primary care providers). To test our intervention, we will conduct a randomized controlled trial, randomizing 352 patients to the intervention condition (patient navigation and financial incentives) or an enhanced traditional care control condition. We will perform follow-up at 6, 12, and 18 months following the start of the intervention. Evaluation of the intervention will target several implementation variables: reach (participation rate and representativeness), effectiveness (smoking cessation at 12 months [primary outcome]), unintended consequences (e.g., purchase of illicit substances with incentive money), adoption (use of intervention across primary care suites), implementation (delivery of intervention), and maintenance (smoking cessation after conclusion of intervention). Improving the implementation of smoking cessation interventions in primary care settings serving large underserved populations could have substantial public health impact, reducing cancer-related morbidity/mortality and associated health disparities. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Bradycardia During Targeted Temperature Management: An Early Marker of Lower Mortality and Favorable Neurologic Outcome in Comatose Out-of-Hospital Cardiac Arrest Patients.

    PubMed

    Thomsen, Jakob Hartvig; Nielsen, Niklas; Hassager, Christian; Wanscher, Michael; Pehrson, Steen; Køber, Lars; Bro-Jeppesen, John; Søholm, Helle; Winther-Jensen, Matilde; Pellis, Tommaso; Kuiper, Michael; Erlinge, David; Friberg, Hans; Kjaergaard, Jesper

    2016-02-01

    Bradycardia is common during targeted temperature management, likely being a physiologic response to lower body temperature, and has recently been associated with favorable outcome following out-of-hospital cardiac arrest in smaller observational studies. The present study sought to confirm this finding in a large multicenter cohort of patients treated with targeted temperature management at 33°C and explore the response to targeted temperature management targeting 36°C. Post hoc analysis of a prospective randomized study. Thirty-six ICUs in 10 countries. We studied 447 (targeted temperature management = 33°C) and 430 (targeted temperature management = 36°C) comatose out-of-hospital cardiac arrest patients with available heart rate data, randomly assigned in the targeted temperature management trial from 2010 to 2013. Targeted temperature management at 33°C and 36°C. Endpoints were 180-day mortality and unfavorable neurologic function (cerebral performance category 3-5). Patients were stratified by target temperature and minimum heart rate during targeted temperature management (< 50, 50-59, and ≥ 60 beats/min [reference]) at 12, 20, and 28 hours after randomization. Heart rates less than 50 beats/min and 50-59 beats/min were recorded in 132 (30%) and 131 (29%) of the 33°C group, respectively. Crude 180-day mortality increased with increasing minimum heart rate (< 50 beats/min = 32%, 50-59 beats/min = 43%, and ≥ 60 beats/min = 60%; p(log-rank) < 0.0001). Bradycardia less than 50 beats/min was independently associated with lower 180-day mortality (hazard ratio(adjusted) = 0.50 [0.34-0.74; p < 0.001]) and lower odds of unfavorable neurologic outcome (odds ratio(adjusted) = 0.38 [ 0.21-0.68; p < 0.01]) in models adjusting for potential confounders including age, initial rhythm, time to return of spontaneous circulation, and lactate at admission. Similar, albeit less strong, independent associations of lower heart rates and favorable outcome were found in

  13. Acute myeloid leukemia in the real world: why population-based registries are needed

    PubMed Central

    Lazarevic, Vladimir; Hörstedt, Ann-Sofi; Hagberg, Oskar; Höglund, Martin

    2012-01-01

    Population-based registries may provide data complementary to that from basic science and clinical intervention studies, all of which are essential for establishing recommendations for the management of patients in the real world. The same quality criteria apply for the evidence-based label, and both high representation and good data quality are crucial in registry studies. Registries with high coverage of the target population reduce the impact of selection on outcome and the subsequent problem with extrapolating data to nonstudied populations. Thus, data useful for clinical decision in situations not well covered by clinical studies can be provided. The potential clinical impact of data from population-based studies is exemplified with analyses from the Swedish Acute Leukemia Registry containing more than 3300 acute myeloid leukemia (AML) patients diagnosed between 1997 and 2006 with a median follow-up of 6.2 years on (1) the role of intensive combination chemotherapy for older patients with AML, (2) the impact of allogeneic stem cell transplantation on survival of younger patients with AML, and (3) the continuing problem with early deaths in acute promyelocytic leukemia. We also present the first Web-based dynamic graph showing the complex interaction between age, performance status, the proportion of patients given intensive treatment, early death rate, complete remission rate, use of allogeneic transplants, and overall survival in AML (non-AML). PMID:22383796

  14. Acute myeloid leukemia in the real world: why population-based registries are needed.

    PubMed

    Juliusson, Gunnar; Lazarevic, Vladimir; Hörstedt, Ann-Sofi; Hagberg, Oskar; Höglund, Martin

    2012-04-26

    Population-based registries may provide data complementary to that from basic science and clinical intervention studies, all of which are essential for establishing recommendations for the management of patients in the real world. The same quality criteria apply for the evidence-based label, and both high representation and good data quality are crucial in registry studies. Registries with high coverage of the target population reduce the impact of selection on outcome and the subsequent problem with extrapolating data to nonstudied populations. Thus, data useful for clinical decision in situations not well covered by clinical studies can be provided. The potential clinical impact of data from population-based studies is exemplified with analyses from the Swedish Acute Leukemia Registry containing more than 3300 acute myeloid leukemia (AML) patients diagnosed between 1997 and 2006 with a median follow-up of 6.2 years on (1) the role of intensive combination chemotherapy for older patients with AML, (2) the impact of allogeneic stem cell transplantation on survival of younger patients with AML, and (3) the continuing problem with early deaths in acute promyelocytic leukemia. We also present the first Web-based dynamic graph showing the complex interaction between age, performance status, the proportion of patients given intensive treatment, early death rate, complete remission rate, use of allogeneic transplants, and overall survival in AML (non-AML).

  15. Beyond Monoamines-Novel Targets for Treatment-Resistant Depression: A Comprehensive Review

    PubMed Central

    Rosenblat, Christian; McIntyre, Roger S.; Alves, Gilberto S.; Fountoulakis, Konstantinos N.; Carvalho, André F.

    2015-01-01

    Major depressive disorder (MDD) is a leading cause of disability worldwide. Current first line therapies target modulation of the monoamine system. A large variety of agents are currently available that effectively alter monoamine levels; however, approximately one third of MDD patients remain treatment refractory after adequate trials of multiple monoamine based therapies. Therefore, patients with treatment-resistant depression (TRD) may require modulation of pathways outside of the classic monoamine system. The purpose of this review was thus to discuss novel targets for TRD, to describe their potential mechanisms of action, the available clinical evidence for these targets, the limitations of available evidence as well as future research directions. Several alternate pathways involved in the patho-etiology of TRD have been uncovered including the following: inflammatory pathways, the oxidative stress pathway, the hypothalamic-pituitary-adrenal (HPA) axis, the metabolic and bioenergetics system, neurotrophic pathways, the glutamate system, the opioid system and the cholinergic system. For each of these systems, several targets have been assessed in preclinical and clinical models. Preclinical models strongly implicate these pathways in the patho-etiology of MDD. Clinical trials for TRD have been conducted for several novel targets; however, most of the trials discussed are small and several are uncontrolled. Therefore, further clinical trials are required to assess the true efficacy of these targets for TRD. As well, several promising novel agents have been clinically tested in MDD populations, but have yet to be assessed specifically for TRD. Thus, their applicability to TRD remains unknown. PMID:26467412

  16. Use of volume-targeted non-invasive bilevel positive airway pressure ventilation in a patient with amyotrophic lateral sclerosis*,**

    PubMed Central

    Diaz-Abad, Montserrat; Brown, John Edward

    2014-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease in which most patients die of respiratory failure. Although volume-targeted non-invasive bilevel positive airway pressure (BPAP) ventilation has been studied in patients with chronic respiratory failure of various etiologies, its use in ALS has not been reported. We present the case of a 66-year-old woman with ALS and respiratory failure treated with volume-targeted BPAP ventilation for 15 weeks. Weekly data downloads showed that disease progression was associated with increased respiratory muscle weakness, decreased spontaneous breathing, and increased use of non-invasive positive pressure ventilation, whereas tidal volume and minute ventilation remained relatively constant. PMID:25210968

  17. Differences Between Patients that Made an Impulsive or Premeditated Suicide Attempt in a Mexican Population.

    PubMed

    Reyes-Tovilla, Jorge E; Hernández Yánez, Homero Daniel; Peralta-Jiménez, Yesenia; Ramón-Frías, Teresa; Juárez-Rojop, Isela; Pool-García, Sherezada; Velázquez-Sánchez, Martha Patricia; López-Narvóez, Lilia; Fresán, Ana; Tovilla-Zárate, Carlos Alfonso

    2015-01-01

    We performed a study to identify differences between patients with impulsive suicide attempt and those with premeditated suicide attempt in a Mexican population. We studied 144 patients who recently attempted suicide. Impulsive and premeditated suicide attempts were evaluated with the Suicide Intent Scale. These data were divided according to the type of attempt. Subsequently, the characteristics between the two groups were compared. The rate of patients that made an impulsive attempt was 61.8% and only 9.7% of the patients carried out a premeditated suicide attempt. More years of schooling/education and less severity of the attempt were observed in patients that carried out an impulsive suicide attempt (p < 0.001). Alcohol consumption (0.003) and use of cannabis (0.002) were present in patients who premeditated a suicide attempt. Our findings demonstrate that there are clinical differences among the individuals who carried out an impulsive suicide attempt from those who premeditated an attempt in a Mexican population. As a result, when planning interventions and prevention efforts it may be helpful to consider these clinical differences and demographic characteristics. © 2015 The Author(s).

  18. Risk of cancer in patients with scleroderma: a population based cohort study

    PubMed Central

    Hill, C; Nguyen, A; Roder, D; Roberts-Thomson, P

    2003-01-01

    Background: Previous studies have suggested an increased risk of cancer among patients with scleroderma. Objective: To study a population based cohort of patients with scleroderma in South Australia. Methods: Subjects with scleroderma were identified from the South Australian Scleroderma Registry established in 1993. All subjects on the scleroderma registry were linked to the South Australian Cancer Registry to identify all cases of cancer until 31 December 2000. Standardised incidence ratios (SIRs) for cancer for subjects with scleroderma were determined using the age- and sex-specific rates for South Australia. Results: In 441 patients with scleroderma, 90 cases of cancer were identified, 47 of which developed after inclusion on the scleroderma registry. The SIRs for all cancers among these patients were significantly increased (SIR=1.99; 95% confidence interval (95% CI) 1.46 to 2.65) compared with the cancer incidence rates for South Australia. The SIRs for lung cancer (SIR=5.9; 95% CI 3.05 to 10.31) were also significantly increased. The SIRs for all cancers among the subgroups with diffuse scleroderma (SIR=2.73; 95% CI 1.31 to 5.02) and limited scleroderma (SIR=1.85; 95% CI 1.23 to 2.68) were significantly increased. Conclusions: This population based cohort study provides evidence that scleroderma is associated with cancer, and in particular, lung cancer. In addition, both diffuse and limited forms of scleroderma are associated with a similarly increased risk of cancer. PMID:12860727

  19. Organizational strategies for promoting patient and provider uptake of personal health records

    PubMed Central

    Wells, Susan; Rozenblum, Ronen; Park, Andrea; Dunn, Marie; Bates, David W

    2015-01-01

    Objective To investigate organizational strategies to promote personal health records (PHRs) adoption with a focus on patients with chronic disease. Methods Using semi-structured interviews and a web-based survey, we sampled US health delivery organizations which had implemented PHRs for at least 12 months, were recognized as PHR innovators, and had scored highly in national patient satisfaction surveys. Respondents had lead positions for clinical information systems or high-risk population management. Using grounded theory approach, thematic categories were derived from interviews and coupled with data from the survey. Results Interviews were conducted with 30 informants from 16 identified organizations. Organizational strategies were directed towards raising patient awareness via multimedia communications, and provider acceptance and uptake. Strategies for providers were grouped into six main themes: organizational vision, governance and policies, work process redesign, staff training, information technology (IT) support, and monitoring and incentives. Successful organizations actively communicated their vision, engaged leaders at all levels, had clear governance, planning, and protocols, set targets, and celebrated achievement. The most effective strategy for patient uptake was through health professional encouragement. No specific outreach efforts targeted patients with chronic disease. Registration and PHR activity was routinely measured but without reference to a denominator population or high risk subpopulations. Discussion and conclusion Successful PHR implementation represents a social change and operational project catalyzed by a technical solution. The key to clinician acceptance is making their work easier. However, organizations will likely not achieve the value they want from PHRs unless they target specific populations and monitor their uptake. PMID:25326601

  20. The acid pocket: a target for treatment in reflux disease?

    PubMed

    Kahrilas, Peter J; McColl, Kenneth; Fox, Mark; O'Rourke, Lisa; Sifrim, Daniel; Smout, Andre J P M; Boeckxstaens, Guy

    2013-07-01

    The nadir esophageal pH of reflux observed during pH monitoring in the postprandial period is often more acidic than the concomitant intragastric pH. This paradox prompted the discovery of the "acid pocket", an area of unbuffered gastric acid that accumulates in the proximal stomach after meals and serves as the reservoir for acid reflux in healthy individuals and gastroesophageal reflux disease (GERD) patients. However, there are differentiating features between these populations in the size and position of the acid pocket, with GERD patients predisposed to upward migration of the proximal margin onto the esophageal mucosa, particularly when supine. This upward migration of acid, sometimes referred to as an "acid film", likely contributes to mucosal pathology in the region of the squamocolumnar junction. Furthermore, movement of the acid pocket itself to a supradiaphragmatic location with hiatus hernia increases the propensity for acid reflux by all conventional mechanisms. Consequently, the acid pocket is an attractive target for GERD therapy. It may be targeted in a global way with proton pump inhibitors that attenuate acid pocket development, or with alginate/antacid combinations that colocalize with the acid pocket and displace it distally, thereby demonstrating the potential for selective targeting of the acid pocket in GERD.

  1. Trehalose pathway as an antifungal target.

    PubMed

    Perfect, John R; Tenor, Jennifer L; Miao, Yi; Brennan, Richard G

    2017-02-17

    With an increasing immunocompromised population which is linked to invasive fungal infections, it is clear that our present 3 classes of antifungal agents may not be sufficient to provide optimal management to these fragile patients. Furthermore, with widespread use of antifungal agents, drug-resistant fungal infections are on the rise. Therefore, there is some urgency to develop the antifungal pipeline with the goal of new antifungal agent discovery. In this review, a simple metabolic pathway, which forms the disaccharide, trehalose, will be characterized and its potential as a focus for antifungal target(s) explained. It possesses several important features for development of antifungal agents. First, it appears to have fungicidal characteristics and second, it is broad spectrum with importance across both ascomycete and basidiomycete species. Finally, this pathway is not found in mammals so theoretically specific inhibitors of the trehalose pathway and its enzymes in fungi should be relatively non-toxic for mammals. The trehalose pathway and its critical enzymes are now in a position to have directed antifungal discovery initiated in order to find a new class of antifungal drugs.

  2. Does contemporary vancomycin dosing achieve therapeutic targets in a heterogeneous clinical cohort of critically ill patients? Data from the multinational DALI study

    PubMed Central

    2014-01-01

    Introduction The objective of this study was to describe the pharmacokinetics of vancomycin in ICU patients and to examine whether contemporary antibiotic dosing results in concentrations that have been associated with favourable response. Methods The Defining Antibiotic Levels in Intensive Care (DALI) study was a prospective, multicentre pharmacokinetic point-prevalence study. Antibiotic dosing was as per the treating clinician either by intermittent bolus or continuous infusion. Target trough concentration was defined as ≥15 mg/L and target pharmacodynamic index was defined as an area under the concentration-time curve over a 24-hour period divided by the minimum inhibitory concentration of the suspected bacteria (AUC0–24/MIC ratio) >400 (assuming MIC ≤1 mg/L). Results Data of 42 patients from 26 ICUs were eligible for analysis. A total of 24 patients received vancomycin by continuous infusion (57%). Daily dosage of vancomycin was 27 mg/kg (interquartile range (IQR) 18 to 32), and not different between patients receiving intermittent or continuous infusion. Trough concentrations were highly variable (median 27, IQR 8 to 23 mg/L). Target trough concentrations were achieved in 57% of patients, but more frequently in patients receiving continuous infusion (71% versus 39%; P = 0.038). Also the target AUC0–24/MIC ratio was reached more frequently in patients receiving continuous infusion (88% versus 50%; P = 0.008). Multivariable logistic regression analysis with adjustment by the propensity score could not confirm continuous infusion as an independent predictor of an AUC0–24/MIC >400 (odds ratio (OR) 1.65, 95% confidence interval (CI) 0.2 to 12.0) or a Cmin ≥15 mg/L (OR 1.8, 95% CI 0.4 to 8.5). Conclusions This study demonstrated large interindividual variability in vancomycin pharmacokinetic and pharmacodynamic target attainment in ICU patients. These data suggests that a re-evaluation of current vancomycin dosing recommendations in

  3. Population Pharmacokinetics and Optimal Sampling Strategy for Model-Based Precision Dosing of Melphalan in Patients Undergoing Hematopoietic Stem Cell Transplantation.

    PubMed

    Mizuno, Kana; Dong, Min; Fukuda, Tsuyoshi; Chandra, Sharat; Mehta, Parinda A; McConnell, Scott; Anaissie, Elias J; Vinks, Alexander A

    2018-05-01

    High-dose melphalan is an important component of conditioning regimens for patients undergoing hematopoietic stem cell transplantation. The current dosing strategy based on body surface area results in a high incidence of oral mucositis and gastrointestinal and liver toxicity. Pharmacokinetically guided dosing will individualize exposure and help minimize overexposure-related toxicity. The purpose of this study was to develop a population pharmacokinetic model and optimal sampling strategy. A population pharmacokinetic model was developed with NONMEM using 98 observations collected from 15 adult patients given the standard dose of 140 or 200 mg/m 2 by intravenous infusion. The determinant-optimal sampling strategy was explored with PopED software. Individual area under the curve estimates were generated by Bayesian estimation using full and the proposed sparse sampling data. The predictive performance of the optimal sampling strategy was evaluated based on bias and precision estimates. The feasibility of the optimal sampling strategy was tested using pharmacokinetic data from five pediatric patients. A two-compartment model best described the data. The final model included body weight and creatinine clearance as predictors of clearance. The determinant-optimal sampling strategies (and windows) were identified at 0.08 (0.08-0.19), 0.61 (0.33-0.90), 2.0 (1.3-2.7), and 4.0 (3.6-4.0) h post-infusion. An excellent correlation was observed between area under the curve estimates obtained with the full and the proposed four-sample strategy (R 2  = 0.98; p < 0.01) with a mean bias of -2.2% and precision of 9.4%. A similar relationship was observed in children (R 2  = 0.99; p < 0.01). The developed pharmacokinetic model-based sparse sampling strategy promises to achieve the target area under the curve as part of precision dosing.

  4. Evaluation of a practical expert defined approach to patient population segmentation: a case study in Singapore.

    PubMed

    Low, Lian Leng; Kwan, Yu Heng; Liu, Nan; Jing, Xuan; Low, Edwin Cheng Tee; Thumboo, Julian

    2017-11-23

    Segmenting the population into groups that are relatively homogeneous in healthcare characteristics or needs is crucial to facilitate integrated care and resource planning. We aimed to evaluate the feasibility of segmenting the population into discrete, non-overlapping groups using a practical expert and literature driven approach. We hypothesized that this approach is feasible utilizing the electronic health record (EHR) in SingHealth. In addition to well-defined segments of "Mostly healthy", "Serious acute illness but curable" and "End of life" segments that are also present in the Ministry of Health Singapore framework, patients with chronic diseases were segmented into "Stable chronic disease", "Complex chronic diseases without frequent hospital admissions", and "Complex chronic diseases with frequent hospital admissions". Using the electronic health record (EHR), we applied this framework to all adult patients who had a healthcare encounter in the Singapore Health Services Regional Health System in 2012. ICD-9, 10 and polyclinic codes were used to define chronic diseases with a comprehensive look-back period of 5 years. Outcomes (hospital admissions, emergency attendances, specialist outpatient clinic attendances and mortality) were analyzed for years 2012 to 2015. Eight hundred twenty five thousand eight hundred seventy four patients were included in this study with the majority being healthy without chronic diseases. The most common chronic disease was hypertension. Patients with "complex chronic disease" with frequent hospital admissions segment represented 0.6% of the eligible population, but accounted for the highest hospital admissions (4.33 ± 2.12 admissions; p < 0.001) and emergency attendances (ED) (3.21 ± 3.16 ED visits; p < 0.001) per patient, and a high mortality rate (16%). Patients with metastatic disease accounted for the highest specialist outpatient clinic attendances (27.48 ± 23.68 visits; p < 0.001) per patient

  5. Persistence of Antipsychotic Treatment in Elderly Dementia Patients: A Retrospective, Population-Based Cohort Study.

    PubMed

    Mast, Gavin; Fernandes, Kimberly; Tadrous, Mina; Martins, Diana; Herrmann, Nathan; Gomes, Tara

    2016-06-01

    Antipsychotics are commonly used to manage behavioral and psychological symptoms of dementia. Concerns over their safety and efficacy in this role have resulted in antipsychotics typically being recommended for short-term usage only when used among dementia patients. However, there is little work examining the duration of antipsychotic treatment in the elderly dementia patient population. To determine the persistence of use of antipsychotics in elderly dementia patients and the role of dose on therapy duration. A retrospective, population-based cohort study using administrative data, including dispensing records from a provincial public drug program, from Ontario, Canada between 2009 and 2012. Elderly dementia patients newly initiated onto antipsychotics were followed until drug discontinuation, death, 2-year follow-up, or end of study. Competing risk analysis was performed to determine time to discontinuation, stratified by categories of initial dose. After 2 years 49.1 % of the cohort ( N  = 22,927 of 46,695) had discontinued treatment. When stratified by dose, the high-dose group (51.1 % discontinued) discontinued more frequently than the medium- (48.7 % discontinued) and low- (47.5 % discontinued) dose groups ( p  < 0.0001). Approximately half of elderly dementia patients treated with antipsychotics discontinue within 2 years, with those on higher doses more likely to discontinue. However, the number of patients remaining on therapy represents a serious public health concern.

  6. Epidemiology and cardiovascular comorbidities in patients with psoriasis: A Korean nationwide population-based cohort study.

    PubMed

    Oh, Eui Hyun; Ro, Young Suck; Kim, Jeong Eun

    2017-06-01

    There is a lack of nationwide studies examining the epidemiology and comorbidities of psoriasis vulgaris (PsV) and psoriatic arthritis (PsA) in Asian populations. The purpose of this study is to determine the demographics of psoriasis in Korea along with the incidence of cerebro-cardiovascular (CV) comorbidities and to compare these risks between populations with PsA and with PsV. This cohort study identified 15 484 patients with psoriasis among 855 003 subjects in the Korean National Health Insurance Database from 2002 through 2010. The cases were further classified into PsA and PsV. We used hazard ratios (HR) and 95% confidence intervals (CI) from the univariate and age-sex adjusted logistic regression model to assess the risk of comorbidities in patients with PsA and PsV. The annual prevalence of psoriasis increased from 313.2 to 453.5/100 000 people from 2002 through 2010; however, the overall incidence rate for psoriasis slightly decreased (252.7-212.6/100 000 population). Of psoriatic patients, 10.8% had PsA, and after adjusting for age and sex, PsA patients had a significantly higher risk of dyslipidemia than PsV patients (adjusted HR, 1.185; 95% CI, 1.049-1.338). When stratified by age group, subjects aged 20-39 years had a higher risk of stroke and many CV risk factors. In conclusion, the prevalence of psoriasis, while within the range of previous reports, tended to increase over time. Patients with PsA had higher burdens of specific comorbid diseases than those with PsV, especially at a comparatively early age. © 2017 Japanese Dermatological Association.

  7. Impact of target area selection in 125 Iodine seed brachytherapy on locoregional recurrence in patients with non-small cell lung cancer.

    PubMed

    Yan, Wei-Liang; Lv, Jin-Shuang; Guan, Zhi-Yu; Wang, Li-Yang; Yang, Jing-Kui; Liang, Ji-Xiang

    2017-05-01

    Computed tomography (CT)-guided percutaneous implantation of 125 Iodine radioactive seeds requires the precise arrangement of seeds by tumor shape. We tested whether selecting target areas, including subclinical areas around tumors, can influence locoregional recurrence in patients with non-small cell lung cancer (NSCLC). We divided 82 patients with NSCLC into two groups. Target areas in group 1 (n = 40) were defined along tumor margins based on lung-window CT. Target areas in group 2 (n = 42) were extended by 0.5 cm in all dimensions outside tumor margins. Preoperative plans for both groups were based on a treatment plan system, which guided 125 I seed implantation. Six months later, patients underwent chest CT to evaluate treatment efficacy (per Response Evaluation Criteria in Solid Tumors version 1). We compared locoregional recurrences between the groups after a year of follow-up. We then used the treatment plan system to extend target areas for group 1 patients by 0.5 cm (defined as group 3 data) and compared these hypothetical group 3 planned seeds with the actual seed numbers used in group 1 patients. All patients successfully underwent implantation; none died during the follow-up period. Recurrence was significantly lower in group 2 than in group 1 ( P  < 0.05). Group 1 patients and group 3 data significantly differed in seed numbers ( P  < 0.01). Our results imply that extending the implantation area for 125 I seeds can decrease recurrence risk by eradicating cancerous lymph-duct blockades within the extended areas. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

  8. Population pharmacokinetics-pharmacodynamics of vedolizumab in patients with ulcerative colitis and Crohn's disease.

    PubMed

    Rosario, M; Dirks, N L; Gastonguay, M R; Fasanmade, A A; Wyant, T; Parikh, A; Sandborn, W J; Feagan, B G; Reinisch, W; Fox, I

    2015-07-01

    Vedolizumab, an anti-α(4)β(7) integrin monoclonal antibody (mAb), is indicated for treating patients with moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD). As higher therapeutic mAb concentrations have been associated with greater efficacy in inflammatory bowel disease, understanding determinants of vedolizumab clearance may help to optimise dosing. To characterise vedolizumab pharmacokinetics in patients with UC and CD, to identify clinically relevant determinants of vedolizumab clearance, and to describe the pharmacokinetic-pharmacodynamic relationship using population modelling. Data from a phase 1 healthy volunteer study, a phase 2 UC study, and 3 phase 3 UC/CD studies were included. Population pharmacokinetic analysis for repeated measures was conducted using nonlinear mixed effects modelling. Results from the base model, developed using extensive phase 1 and 2 data, were used to develop the full covariate model, which was fit to sparse phase 3 data. Vedolizumab pharmacokinetics was described by a 2-compartment model with parallel linear and nonlinear elimination. Using reference covariate values, linear elimination half-life of vedolizumab was 25.5 days; linear clearance (CL(L)) was 0.159 L/day for UC and 0.155 L/day for CD; central compartment volume of distribution (V(c)) was 3.19 L; and peripheral compartment volume of distribution was 1.66 L. Interindividual variabilities (%CV) were 35% for CLL and 19% for V(c); residual variance was 24%. Only extreme albumin and body weight values were identified as potential clinically important predictors of CL(L). Population pharmacokinetic parameters were similar in patients with moderately to severely active UC and CD. This analysis supports use of vedolizumab fixed dosing in these patients. Clinicaltrials.gov Identifiers: NCT01177228; NCT00783718 (GEMINI 1); NCT00783692 (GEMINI 2); NCT01224171 (GEMINI 3). © 2015 Takeda Pharmaceuticals International Co published by John Wiley & Sons

  9. Smoking, cessation, and cessation counseling in patients with cancer: A population-based analysis.

    PubMed

    Ramaswamy, Apoorva T; Toll, Benjamin A; Chagpar, Anees B; Judson, Benjamin L

    2016-04-15

    Smoking is known to be carcinogenic and an important factor in the outcome of cancer treatment. However, to the authors' knowledge, smoking habits and smoking cessation counseling in patients with cancer have been poorly studied. The authors sought to analyze smoking habits among Americans diagnosed with cancer in a nationally representative dataset. The cancer supplement of the National Health Interview Survey (NHIS) in 2010 was used to obtain information regarding self-reported smoking behavior in a representative sample of the US population. Cancer history, smoking history, quitting behavior, cessation counseling, cessation approaches, and sociodemographic variables were analyzed. A total of 27,157 individuals were interviewed for the NHIS in 2010, representing 216,052,891 individuals, 7,058,135 of whom had ever smoked and 13,188,875 of whom had been told that they had cancer. Approximately 51.7% of individuals diagnosed with cancer and who were active smokers reported being counseled to quit smoking by a health professional within the previous 12 months. Cancer survivors were no more likely to quit smoking than individuals in the general population. Those diagnosed with a tobacco-related cancer were found to be no more likely to report quitting smoking than those with other types of cancers. Rates of quitting did not appear to vary based on the type of smoking cessation method used (P = .50). Patients with cancer, including those diagnosed with a tobacco-related cancer, do not appear to be more likely to quit smoking than the general population. Only approximately one-half of patients with cancer who smoke are counseled to quit. Smoking cessation in patients with cancer is an important area for intervention and investigation. © 2016 American Cancer Society.

  10. Target Acquired: Progress and Promise of Targeted Therapeutics in the Treatment of Prostate Cancer.

    PubMed

    Stuchbery, Ryan; Kurganovs, Natalie J; McCoy, Patrick J; Nelson, Colleen C; Hayes, Vanessa M; Corcoran, Niall M; Hovens, Christopher M

    2015-01-01

    Cancer is fundamentally a genomic disease caused by mutations or rearrangements in the DNA or epigenetic machinery of a patient. An emerging field in cancer treatment targets key aberrations arising from the mutational landscape of an individual patient's disease rather than employing a cancer-wide cytotoxic therapy approach. In prostate cancer in particular, where there is an observed variation in response to standard treatments between patients with disease of a similar pathological stage and grade, mutationdirected treatment may grow to be a viable tool for clinicians to tailor more effective treatments. This review will describe a number of mutations across multiple forms of cancer that have been successfully antagonised by targeted therapeutics including their identification, the development of targeted compounds to combat them and the development of resistance to these therapies. This review will continue to examine these same mutations in the treatment and management of prostate cancer; the prevalence of targetable mutations in prostate cancer, recent clinical trials of targeted-agents and the potential or limitations for their use.

  11. Demographic and genetic status of an isolated population of bog turtles (Glyptemys muhlenbergii): Implications for managing small populations of long-lived animals

    USGS Publications Warehouse

    Pittman, Shannon E.; King, T.L.; Faurby, S.; Dorcas, M.E.

    2011-01-01

    In this study, we sought to determine the population stability and genetic diversity of one isolated population of the federally-threatened bog turtle (Glyptemys muhlenbergii) in North Carolina. Using capture-recapture data, we estimated adult survival and population growth rate from 1992 to 2007. We found that the population decreased from an estimated 36 adult turtles in 1994 to approximately 11 adult turtles in 2007. We found a constant adult survival of 0. 893 (SE = 0. 018, 95% confidence interval, 0. 853-0. 924) between 1992 and 2007. Using 18 microsatellite markers, we compared the genetic status of this population with five other bog turtle populations. The target population displayed allelic richness (4. 8 ?? 0. 5) and observed heterozygosity (0. 619 ?? 0. 064) within the range of the other bog turtle populations. Coalescent analysis of population growth rate, effective population size, and timing of population structuring event also indicated the genetics of the target population were comparable to the other populations studied. Estimates of effective population size were a proportion of the census size in all populations except the target population, in which the effective population size was larger than the census size (30 turtles vs. 11 turtles). We attribute the high genetic diversity in the target population to the presence of multiple generations of old turtles. This study illustrates that the demographic status of populations of long-lived species may not be reflected genetically if a decline occurred recently. Consequently, the genetic integrity of populations of long-lived animals experiencing rapid demographic bottlenecks may be preserved through conservation efforts effective in addressing demographic problems. ?? 2011 Springer Science+Business Media B.V.

  12. Evaluating targeted interventions via meta-population models with multi-level mixing.

    PubMed

    Feng, Zhilan; Hill, Andrew N; Curns, Aaron T; Glasser, John W

    2017-05-01

    Among the several means by which heterogeneity can be modeled, Levins' (1969) meta-population approach preserves the most analytical tractability, a virtue to the extent that generality is desirable. When model populations are stratified, contacts among their respective sub-populations must be described. Using a simple meta-population model, Feng et al. (2015) showed that mixing among sub-populations, as well as heterogeneity in characteristics affecting sub-population reproduction numbers, must be considered when evaluating public health interventions to prevent or control infectious disease outbreaks. They employed the convex combination of preferential within- and proportional among-group contacts first described by Nold (1980) and subsequently generalized by Jacquez et al. (1988). As the utility of meta-population modeling depends on more realistic mixing functions, the authors added preferential contacts between parents and children and among co-workers (Glasser et al., 2012). Here they further generalize this function by including preferential contacts between grandparents and grandchildren, but omit workplace contacts. They also describe a general multi-level mixing scheme, provide three two-level examples, and apply two of them. In their first application, the authors describe age- and gender-specific patterns in face-to-face conversations (Mossong et al., 2008), proxies for contacts by which respiratory pathogens might be transmitted, that are consistent with everyday experience. This suggests that meta-population models with inter-generational mixing could be employed to evaluate prolonged school-closures, a proposed pandemic mitigation measure that could expose grandparents, and other elderly surrogate caregivers for working parents, to infectious children. In their second application, the authors use a meta-population SEIR model stratified by 7 age groups and 50 states plus the District of Columbia, to compare actual with optimal vaccination during the

  13. BMI-1 targeting interferes with patient-derived tumor-initiating cell survival and tumor growth in prostate cancer

    PubMed Central

    Yusuff, Shamila; Davis, Stephani; Flaherty, Kathleen; Huselid, Eric; Patrizii, Michele; Jones, Daniel; Cao, Liangxian; Sydorenko, Nadiya; Moon, Young-Choon; Zhong, Hua; Medina, Daniel J.; Kerrigan, John; Stein, Mark N.; Kim, Isaac Y.; Davis, Thomas W.; DiPaola, Robert S.; Bertino, Joseph R.; Sabaawy, Hatem E.

    2016-01-01

    Purpose Current prostate cancer (PCa) management calls for identifying novel and more effective therapies. Self-renewing tumor-initiating cells (TICs) hold intrinsic therapy-resistance and account for tumor relapse and progression. As BMI-1 regulates stem cell self-renewal, impairing BMI-1 function for TICs-tailored therapies appears to be a promising approach. Experimental design We have previously developed a combined immunophenotypic and time-of-adherence assay to identify CD49bhiCD29hiCD44hi cells as human prostate TICs. We utilized this assay with patient derived prostate cancer cells and xenograft models to characterize the effects of pharmacological inhibitors of BMI-1. Results We demonstrate that in cell lines and patient-derived TICs, BMI-1 expression is upregulated and associated with stem cell-like traits. From a screened library, we identified a number of post-transcriptional small molecules that target BMI-1 in prostate TICs. Pharmacological inhibition of BMI-1 in patient-derived cells significantly decreased colony formation in vitro and attenuated tumor initiation in vivo, thereby functionally diminishing the frequency of TICs, particularly in cells resistant to proliferation- and androgen receptor (AR)-directed therapies, without toxic effects on normal tissues. Conclusions Our data offer a paradigm for targeting TICs and support the development of BMI-1-targeting therapy for a more effective PCa treatment. PMID:27307599

  14. Exclusion of patients with concomitant chronic conditions in ongoing randomised controlled trials targeting 10 common chronic conditions and registered at ClinicalTrials.gov: a systematic review of registration details.

    PubMed

    Buffel du Vaure, Céline; Dechartres, Agnès; Battin, Constance; Ravaud, Philippe; Boutron, Isabelle

    2016-09-27

    To systematically assess registration details of ongoing randomised controlled trials (RCTs) targeting 10 common chronic conditions and registered at ClinicalTrials.gov and to determine the prevalence of (1) trial records excluding patients with concomitant chronic condition(s) and (2) those specifically targeting patients with concomitant chronic conditions. Systematic review of trial registration records. ClinicalTrials.gov register. All ongoing RCTs registered from 1 January 2014 to 31 January 2015 that assessed an intervention targeting adults with coronary heart disease (CHD), hypertension, heart failure, stroke/transient ischaemic attack, atrial fibrillation, type 2 diabetes, chronic obstructive pulmonary disease, painful condition, depression and dementia with a target sample size ≥100. From the trial registration records, 2 researchers independently recorded the trial characteristics and the number of exclusion criteria and determined whether patients with concomitant chronic conditions were excluded or specifically targeted. Among 319 ongoing RCTs, despite the high prevalence of the concomitant chronic conditions, patients with these conditions were excluded in 251 trials (79%). For example, although 91% of patients with CHD had a concomitant chronic condition, 69% of trials targeting such patients excluded patients with concomitant chronic condition(s). When considering the co-occurrence of 2 chronic conditions, 31% of patients with chronic pain also had depression, but 58% of the trials targeting patients with chronic pain excluded patients with depression. Only 37 trials (12%) assessed interventions specifically targeting patients with concomitant chronic conditions; 31 (84%) excluded patients with concomitant chronic condition(s). Despite widespread multimorbidity, more than three-quarters of ongoing trials assessing interventions for patients with chronic conditions excluded patients with concomitant chronic conditions. Published by the BMJ

  15. Radiation Dose to the Esophagus From Breast Cancer Radiation Therapy, 1943-1996: An International Population-Based Study of 414 Patients

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lamart, Stephanie, E-mail: stephanie.lamart@nih.gov; Stovall, Marilyn; Simon, Steven L.

    2013-07-15

    Purpose: To provide dosimetric data for an epidemiologic study on the risk of second primary esophageal cancer among breast cancer survivors, by reconstructing the radiation dose incidentally delivered to the esophagus of 414 women treated with radiation therapy for breast cancer during 1943-1996 in North America and Europe. Methods and Materials: We abstracted the radiation therapy treatment parameters from each patient’s radiation therapy record. Treatment fields included direct chest wall (37% of patients), medial and lateral tangentials (45%), supraclavicular (SCV, 64%), internal mammary (IM, 44%), SCV and IM together (16%), axillary (52%), and breast/chest wall boosts (7%). The beam typesmore » used were {sup 60}Co (45% of fields), orthovoltage (33%), megavoltage photons (11%), and electrons (10%). The population median prescribed dose to the target volume ranged from 21 Gy to 40 Gy. We reconstructed the doses over the length of the esophagus using abstracted patient data, water phantom measurements, and a computational model of the human body. Results: Fields that treated the SCV and/or IM lymph nodes were used for 85% of the patients and delivered the highest doses within 3 regions of the esophagus: cervical (population median 38 Gy), upper thoracic (32 Gy), and middle thoracic (25 Gy). Other fields (direct chest wall, tangential, and axillary) contributed substantially lower doses (approximately 2 Gy). The cervical to middle thoracic esophagus received the highest dose because of its close proximity to the SCV and IM fields and less overlying tissue in that part of the chest. The location of the SCV field border relative to the midline was one of the most important determinants of the dose to the esophagus. Conclusions: Breast cancer patients in this study received relatively high incidental radiation therapy doses to the esophagus when the SCV and/or IM lymph nodes were treated, whereas direct chest wall, tangentials, and axillary fields contributed

  16. Poster - Thur Eve - 55: Monte Carlo simulations of variations in planned dose distributions in a prostate patient population.

    PubMed

    Balderson, M J; Brown, D W; Quirk, S; Ghasroddashti, E; Kirkby, C

    2012-07-01

    Clinical outcome studies with clear and objective endpoints are necessary to make informed radiotherapy treatment decisions. Commonly, clinical outcomes are established after lengthy and costly clinical trials are performed and the data are analyzed and published. One the challenges with obtaining meaningful data from clinical trials is that by the time the information gets to the medical profession the results may be less clinically relevant than when the trial began, An alternative approach is to estimate clinical outcomes through patient population modeling. We are developing a mathematical tool that uses Monte Carlo techniques to simulate variations in planned and delivered dose distributions of prostate patients receiving radiotherapy. Ultimately, our simulation will calculate a distribution of Tumor Control Probabilities (TCPs) for a population of patients treated under a given protocol. Such distributions can serve as a metric for comparing different treatment modalities, planning and setup approaches, and machine parameter settings or tolerances with respect to outcomes on broad patient populations. It may also help researchers understand differences one might expect to find before actually doing the clinical trial. As a first step and for the focus of this abstract we wanted to see if we could answer the question: "Can a population of dose distributions of prostate patients be accurately modeled by a set of randomly generated Gaussian functions?" Our results have demonstrated that using a set of randomly generated Gaussian functions can simulate a distribution of prostate patients. © 2012 American Association of Physicists in Medicine.

  17. Bringing state-of-the-art diagnostics to vulnerable populations: The use of a mobile screening unit in active case finding for tuberculosis in Palawan, the Philippines.

    PubMed

    Morishita, Fukushi; Garfin, Anna Marie Celina Gonzales; Lew, Woojin; Oh, Kyung Hyun; Yadav, Rajendra-Prasad; Reston, Janeth Cuencaho; Infante, Lenie Lucio; Acala, Maria Rebethia Crueldad; Palanca, Dean Lim; Kim, Hee Jin; Nishikiori, Nobuyuki

    2017-01-01

    Globally, case detection of tuberculosis (TB) has stabilized in recent years. Active case finding (ACF) has regained an increased attention as a complementary strategy to fill the case detection gap. In the Philippines, the DetecTB project implemented an innovative ACF strategy that offered a one-stop diagnostic service with a mobile unit equipped with enhanced diagnostic tools including chest X-ray (CXR) and Xpert®MTB/RIF (Xpert). The project targeted the rural poor, the urban poor, prison inmates, indigenous population and high school students. This is a retrospective review of TB screening data from 25,103 individuals. A descriptive analysis was carried out to compare screening and treatment outcomes across target populations. Univariate and multivariate analyses were performed to identify predictors of TB for each population. The composition of bacteriologically-confirmed cases by smear and symptom status was further investigated. The highest yield with lowest number needed to screen (NNS) was found in prison (6.2%, NNS: 16), followed by indigenous population (2.9%, NNS: 34), the rural poor (2.2%, NNS: 45), the urban poor (2.1%, NNS: 48), and high school (0.2%, NNS: 495). The treatment success rate for all populations was high with 89.5% in rifampicin-susceptible patients and 83.3% in rifampicin-resistant patients. A relatively higher loss to follow-up rate was observed in indigenous population (7.5%) and the rural poor (6.4%). Only cough more than two weeks showed a significant association with TB diagnosis in all target populations (Adjusted Odds Ratio ranging from 1.71 to 6.73) while other symptoms and demographic factors varied in their strength of association. The urban poor had the highest proportion of smear-positive patients with cough more than two weeks (72.0%). The proportion of smear-negative (Xpert-positive) patients without cough more than two weeks was the highest in indigenous population (39.3%), followed by prison inmates (27.7%), and the

  18. Risk of fragility fracture among patients with sarcoidosis: a population-based study 1976-2013-supplementary presentation.

    PubMed

    Ungprasert, P; Crowson, C S; Matteson, E L

    2018-05-01

    Incidence of fragility fracture of a population-based cohort of 345 patients with sarcoidosis was compared with age- and sex-matched comparators. The incidence of fragility fracture was higher among patients with sarcoidosis with a hazard ratio (HR) of 2.18.

  19. Corruption, inequality and population perception of healthcare quality in Europe.

    PubMed

    Nikoloski, Zlatko; Mossialos, Elias

    2013-11-11

    Evaluating the quality of healthcare and patient safety using general population questionnaires is important from research and policy perspective. Using a special wave of the Eurobarometer survey, we analysed the general population's perception of health care quality and patient safety in a cross-country setting. We used ordered probit, ordinary least squares and probit analysis to estimate the determinants of health care quality, and ordered logit analysis to analyse the likelihood of being harmed by a specific medical procedure. The models used population weights as well as country-clustered standard errors. We found robust evidence for the impact of socio-demographic variables on the perception of quality of health care. More specifically, we found a non-linear impact of age on the perception of quality of health care and patient safety, as well as a negative impact of poverty on both perception of quality and patient safety. We also found robust evidence that countries with higher corruption levels were associated with worse perceptions of quality of health care. Finally, we found evidence that income inequality affects patients' perception vis-à-vis safety, thus feeding into the poverty/health care quality nexus. Socio-demographic factors and two macro variables (corruption and income inequality) explain the perception of quality of health care and likelihood of being harmed by adverse events. The results carry significant policy weight and could explain why targeting only the health care sector (without an overall reform of the public sector) could potentially be challenging.

  20. Comorbid subjective health complaints in patients with sciatica: a prospective study including comparison with the general population.

    PubMed

    Grøvle, Lars; Haugen, Anne J; Ihlebaek, Camilla M; Keller, Anne; Natvig, Bård; Brox, Jens I; Grotle, Margreth

    2011-06-01

    Chronic nonspecific low back pain is accompanied by high rates of comorbid mental and physical conditions. The aims of this study were to investigate if patients with specific back pain, that is, sciatica caused by lumbar herniation, report higher rates of subjective health complaints (SHCs) than the general population and if there is an association between change in sciatica symptoms and change in SHCs over a 12-month period. A multicenter cohort study of 466 sciatica patients was conducted with follow-up at 3 months and 1 year. Comorbid SHCs were measured by 27 items of the SHC inventory. Odds ratios (ORs) for each SHC were calculated with comparison to a general population sample (n=928) by logistic regression. The SHC number was calculated by summing all complaints present. At baseline, the ORs for reporting SHCs for the sciatica patients were significantly elevated in 15 of the 27 items with a mean (S.D.) SHC number of 7.5 (4.4), compared to 5.2 (4.4) in the general population (P<.01). Among those who during the 1-year follow-up period fully recovered from their sciatica, the SHC number was reduced to normal levels. Among those with persisting or worsening sciatica, the number increased to a level almost double that of the general population. Compared to the general population, the prevalence of subjective health complaints in sciatica is increased. During follow-up, the number of health complaints increased in patients with persisting or worsening sciatica. Copyright © 2010 Elsevier Inc. All rights reserved.