Table Table1 Research Articles

Retention in Care and Health Outcomes of Transgender Persons Living With HIV

To the Editor—Little is known about the health outcomes of transgender persons living with human immunodeficiency virus (HIV), or PLWH [1]. Discrimination and social isolation may decrease engagement in care, while concerns about adverse interactions between antiretroviral therapy (ART) and hormone therapy may reduce ART receipt and medication adherence in this population [2–4]. We examined whether retention in care, use of ART, and HIV suppression differed between transgender and nontransgender PLWH. We performed a retrospective cohort study of HIV-infected adults (≥18 years) initiating care at 13 HIV clinics in the HIV Research Network (HIVRN) between 2001 and 2011. Clinics are located in the Northeastern (n = 6), Midwestern (n = 1), Southern (n = 3), and Western (n = 3) regions of the United States. Data from patients’ medical records were abstracted, quality assured, and assembled into a uniform database [5]. All clinics had institutional review board approval. Gender was self-identified and categorized as nontransgender men, nontransgender women, and transgender. Dichotomous outcomes were retention in care (≥2 primary HIV visits ≥90 days apart), use of ART, and HIV suppression (median HIV RNA <400 copies/mL) in each calendar year. Multivariate logistic regression, adjusted for age, race/ethnicity, HIV risk, insurance, CD4 count, calendar year, and site of care, examined associations between gender and each outcome. Because patients contributed data in multiple years, we used generalized estimating equations, clustered on patient, with exchangeable working correlation and robust standard errors to deal with the correlation across years for individual patients. Two-sided testing was used, with a P value of <.05 considered significant. A total of 36 845 PLWH, of whom 285 self-identified as transgender, received care at HIVRN clinics between 2001 and 2011 (Table ​(Table1).1). Transgender patients were more likely to be young and Hispanic, and to be men who have sex with men as their HIV risk behavior compared to nontransgender PLWH. Transgender persons were retained in care, received ART, and achieved HIV suppression in 80%, 76%, and 68% of patient-years, respectively. Corresponding results were 81%, 77%, and 69% for nontransgender men, and 81%, 73%, and 63% for nontransgender women. Table 1. Demographics and Outcomes of Study Sample by Gender Identity In multivariate analyses, retention in care was similar for nontransgender men compared with transgender PLWH (adjusted odds ratio [AOR], 1.15; 95% confidence interval [CI], .94–1.42), but was higher for nontransgender women (AOR, 1.32; 95% CI, 1.08–1.64). Use of ART was similar for nontransgender men (AOR, 0.98; 95% CI, .78–1.23) and nontransgender women (AOR, 0.81; 95% CI, .64–1.02) compared to transgender PLWH. Likewise, nontransgender men (AOR, 1.11; 95% CI, .89–1.39) and nontransgender women (AOR, 1.13; 95% CI, .90–1.42) had similar rates of HIV suppression as transgender PLWH. Compared to prior studies, which document low ART coverage and suboptimal adherence to HIV treatment in transgender PLWH, these results reflect improvements in health equity for HIV-infected transgender individuals [3, 6]. Advances in HIV therapy, including new antiretroviral drugs with simplified dosing and greater tolerability, and treatment guidelines may explain these findings [7, 8]. This study is limited by its retrospective nature, small sample of transgender individuals, and focus on patients engaged in care. While our findings may not generalize to all transgender PLWH, they suggest that when engaged in care transgender PLWH have similar outcomes as nontransgender men and women.

Methylene‐Bridged Bis(imidazoline)‐Derived 2‐Oxopyrimidinium Salts as Catalysts for Asymmetric Michael Reactions

Methylene‐Bridged Bis(imidazoline)‐Derived 2‐Oxopyrimidinium Salts as Catalysts for Asymmetric Michael Reactions

Implementing health system change: What are the lessons from the African Health Initiative?

Implementing health system change: What are the lessons from the African Health Initiative?

Report of the Journal Editor

This report is a compilation of activity and statistics for the American Journal of Pharmaceutical Education for 2006 (Volume 70). The Journal was published in electronic format at www.ajpe.org. A print edition of the full volume was also produced and sent to all AACP member institutions and paid subscribers. Six issues were published in 2006 plus supplementary material. Two supplements were published, one on Community Pharmacy and one on Nonprescription Medications and Self-Care. One of the objectives for these supplements is to serve as useful materials for practice-based faculty and for adjunct clinical faculty and preceptors. Community pharmacy continues to be the primary employment of our graduates and the Journal has an obligation to support instruction in this area. In a typical month, there are approximately 20,000 visitors to the Journal web site at www.ajpe.org. The Journal began submission of content to PubMed This year, and Journal content is now available on Medline. Open access availability and coverage by Medline has led to an increased number of international submissions. Five new Editorial Board members were appointed in 2006, Bradley Boucher (Tennessee-Memphis), Sudip Das (Butler), Wendy Duncan-Hewitt (St. Louis), Jeffrey Delafuente (Virginia Commonwealth), and JoLaine Draugalis (Oklahoma). Patrick Davis (Texas) and Gary DeLander (Oregon) were reappointed to the Board. Eighty-seven peer-reviewed manuscripts were published in Volume 70 along with a large number of Viewpoints, Addresses, Reports, Statements, Book Reviews, and other material (Table ​(Table1).1). One hundred and sixty-six manuscripts were submitted to the Journal in 2006, an increase of 18% from the previous year. Of these, 53% were accepted for publication. Almost 200 individuals served as manuscript and book reviewers in 2006. Table 1 Journal activity in 2006 Each year the best paper published in the Journal is recognized with the Rufus A. Lyman Award. Rufus A. Lyman was the first Editor of the American Journal of Pharmaceutical Education. Papers are selected based on utility and significance to pharmacy education, originality, research methodology, and writing style. The Lyman Award Committee, which is appointed by the President and chaired by the Editor, selected the top paper. From volume 70, 16 papers were nominated for the Lyman Award and the paper selected was “Development of an Instrument to Measure Professionalism” by Marie A. Chisholm, Henry Cobb, Lori Duke, Charles McDuffie and William K. Kennedy, from the University of Georgia. The Editor is indebted to the Associate Editors Gayle Brazeau and Jack Fincham and Assistant Editor Karen Shipp, Editorial Board Members, the manuscript and book reviewers, and the AACP Board of Directors and staff for their continued efforts and support. The success of the Journal is dependent on the diligent and dedicated efforts of these individuals.

Can we decipher indications and outcomes of the PHILOS plate for fractures of the proximal humerus?

Sir, I read with interest the recent article by Zhou et al. [1] describing the outcome of the proximal humeral internal locking system (PHILOS) plate in 74 patients. However, I am still unsure of the exact indications for the plate. Despite the escalation in the use and publications regarding the outcome of the PHILOS plate, the evidence as to whether this device is beneficial to patients it was designed for remains difficult to decipher. There have been 27 studies of the 63 cited on PubMed that have used the Constant score as their outcome assessment tool (Table 1). There is, however, marked heterogeneity between these studies, with mean age ranging from 42 to 78 years and reported cohort size ranging from nine to 294 fractures. It is interesting to note the epidemiology of proximal humeral fractures where the mean age is 65 years [2], with three- and four-part fractures occurring in older patients [3]. Mean patient age in those studies reporting the outcome of the PHILOS is 62 years old, which may suggest that there is an inclusion bias for some studies, which may reserve such an intervention for younger patients. However, this does seem to be at odds with the design and intention of the PHILOS plate. Table 1 Twenty-seven studies identified on PubMed (search term “PHILOS plate”) that report the outcome of the proximal humeral internal locking system (PHILOS) plate using the Constant score as their measure Furthermore the Constant score has been demonstrated to diminish with patient age in a normal population [4]. The variation in the reported Constant score after PHILOS plating ranges from 58 to 95 (Table ​(Table1).1). In part, this probably reflects the differing mean age between study cohorts. However, even if these scores are adjusted for patient age, the variation in score ranges from 24 points less than predicted to 21 points greater than predicted for their age (Fig. 1). This variation may also be due to inclusion criteria of the studies, which may reflect that only higher functioning patients were offered surgery. However, it is hard to believe that most patients will regain their prior functional status or even improve relative to their predicted score. Fig. 1 Difference in the reported Constant score relative to patient age-matched score for the 27 identified studies reporting the outcome of the proximal humeral internal locking system (PHILOS) plate The only randomised controlled trial comparing the outcome of the PHILOS plate with conservative management for proximal humeral fractures in elderly patients concluded that there was no statistical difference in any of the outcome measures assessed [5]. The authors also demonstrated a reoperation rate of 17%. The cost and complication risk of operative intervention with a PHILOS plate would seem, on current evidence, to be of no significant benefit to the elderly patients for which this plate was designed. Hence, it would seem the PHILOS plate is not for the masses, and its insertion should be performed by the few.

On the Unique Reactivity of Pd(OAc)2 with Organic Azides: Expedient Synthesis of Nitriles and Imines

On the Unique Reactivity of Pd(OAc)₂ with Organic Azides: Expedient Synthesis of Nitriles and Imines

Transparency or Proper Study Valuation Procedures Missed?

Transparency or Proper Study Valuation Procedures Missed?

Comparative oncology – the North American experience

Comparative oncology can be used to describe a discipline that integrates the study of naturally occurring cancers in animals into studies of human cancer biology and therapy. The term is most often used when referring to the study of cancers seen in companion (pet) animals. Cancers in companion species are well suited to uniquely inform investigations of cancer biology and drug development. Clinical trials in veterinary oncology have gained interest and focus over the last decade, with both veterinary and comparative oncology drug development leading the effort. There have also been a growing number of consortia and cooperative groups that have functioned successfully by uniting multiinstitutional efforts, advocating for veterinary clinical trials, and emphasizing the synergy between basic science and clinical progress. With support from clients who are motivated to seek advanced care for their pets and to enroll them in investigational trials that offer new therapies, clinical research in veterinary oncology is growing in scope and importance. Oncology clinical trials attempt to answer questions and find better ways to prevent, diagnose, or treat cancer. Their model is different from trials involving infectious or even chronic diseases because the risks involved have greater morbidity and mortality. Traditional drug development follows a strict, step-wise paradigm that begins with a phase I dose-finding trial, followed by a phase II efficacy/activity trial, and concludes with a phase III pivotal trial that pits a novel agent against or with the current standard of care (Table ​(Table1).1). Although veterinary oncology trials sometimes combine these concepts, their individual descriptions serve as the framework for new drug development. Clinical designs, pertinent endpoints and analyses, the process for drug approval, and clinical trial ethics will be explored in the following sections. Table 1 Goals of Phase I–III Clinical Trials

Comments on the use of expiratory time constant for determinations of plateau pressure, respiratory system compliance, and total resistance

In the previous issue of Critical Care, Al-Rawas and colleagues [1] presented a method for assessing elastic and resistive properties of the respiratory system in patients with respiratory failure. The method assumes a first-order resistance-compliance (RC) model of breathing mechanics. Although the procedure for estimating expiratory time constant (τE) is correct and efficient, some clarifications need to be made about the use of equations 3 to 5 in mechanically ventilated patients, in whom an intrinsic positive end-expiratory pressure (PEEPi) can be present [2,3]. Equations 3 to 5 are correct only if the term indicated with the acronym PEEP accounts not only for external PEEP but also for PEEPi. Neglecting PEEPi can lead to significant errors, as demonstrated by the following model-to-model analysis, in which data were generated by using a first-order RC model. Table ​Table11 shows the true model values and their corresponding estimates, which were obtained with the method of Al-Rawas and colleagues and which neglect PEEPi. Table 1 True model values and corresponding estimates The estimate of τE is correct for both patients because, in the first-order RC model, the relationship between lung volume changes and expiratory flow does not depend on PEEP (intrinsic or external or both). The estimates of total resistance (Rtot), respiratory system compliance (Crs), and plateau pressure (Pplt) for patient A (in whom PEEPi is 0) are identical to the true values. For patient B (in whom PEEPi is equal to about 3 cm H2O), the percentages of error of the estimations of Rtot, Crs, and Pplt are 17%, −14.5%, and −18.2%, respectively. This confirms that these estimates necessitate the measurement of PEEPi and this requires, for example, the end-expiratory occlusion technique [4,5].

Predicting the protein localization sites using artificial neural networks

Chemoinformatics, the brain child of Frank Brown [1], has now evolved into a new branch of science, which has high correlations with computer science, bioinformatics, and chemistry. The major functionalities of Chemoinformatics include, but not limited to, chemical structure/property prediction, molecular similarity/diversity analysis, virtual screening, qualitative/quantitative structural/activity/property relationship, design of combinatorial libraries, statistical models, descriptors, drug discovery, representation of chemical compounds/reactions, classification/search/storage methods, management of compound databases, high-throughput docking, data analysis methods, etc. This paper deals with the prediction of localization sites of protein using neural network. Neural Network [2] provides learning capability and it is one of the important components of softcomputing. A neural network will consist of one input layer, one or more number of hidden layers and an output layer. Number of neurons in the input layer will be equal to the number of features passed to the neural network. Number of neurons in the output layer will be equal to the number of classes for classification purpose. Hidden neurons are usually fixed by experts depending on the problem. There are various types of neural network available like feedforward neural networks, feedback networks, reccurrent networks, self organizing maps, anfis, etc. In this paper E.coli protein dataset [3] is used for prediction. The data set with 336 instances is having 7 attributes with 8 classes (localization sites). The dataset can be obtained from UCI machine repository. Neural network with 500 hidden neurons and scaled conjugate gradient algorithm are used in this work. The classification result shown in the table ​table11 for our method, is the average of 4 cross validation and the results are promising. Table 1 Classification rates.

One-pot deracemization of sec-alcohols: enantioconvergent enzymatic hydrolysis of alkyl sulfates using stereocomplementary sulfatases.

One-pot deracemization of sec-alcohols: enantioconvergent enzymatic hydrolysis of alkyl sulfates using stereocomplementary sulfatases.

Racial/Ethnic Disparities in Engagement in Care and Viral Suppression in a Large Urban HIV Clinic

To the Editor—We read with great interest the study by Moore et al [1], which showed that among human immunodeficiency virus (HIV)–infected adults followed at Moore Clinic during 1996–2012, there were no significant differences in virologic, immunologic, or HIV clinical outcomes by race/ethnicity. The study was of particular interest because the Moore clinic population is analogous to ours. We report findings from the CORE Center, Chicago, that describe differences in the rate of engagement in care and virologic suppression by demographic characteristics. The CORE Center is the largest HIV care center in the Midwest and provides care to a large number of ethnic minorities, many uninsured. The CORE Center provides comprehensive primary care including extensive psychosocial support. Access to visits and antiretrovirals are available regardless of insurance status or ability to pay. We performed a cross-sectional electronic medical record review of patients ≥13 years of age who had ≥1 clinic visit at the CORE Center in 2010. Engagement in care was defined as having ≥2 HIV RNA measurements in 2010 and viral suppression as having ≥2 undetectable HIV RNA measurements (<75 copies/mL) in 2010. Factors associated with nonengagement and viral nonsuppression (VNS) were assessed by multivariable logistic regression controlling for age, race/ethnicity, and sex. Engagement in Care A total of 4810 HIV-infected patients had ≥1 clinic visit at the CORE center in 2010; 3572 (74%) were male, 65% non-Hispanic black, 20% Hispanic, and 12% non-Hispanic white. The median age was 45 years, the median CD4 count was 401 cells/mm3, and 71% had undetectable HIV RNA; 1286 (27%) were not actively engaged in care. Nonengaged patients were younger and more likely to be black (Table ​(Table1).1). They also had lower rates of virologic suppression (50% vs 78%; P < .0001), and lower CD4 counts (335 vs 412 cells/mm3; P < .0001). Table 1. Multivariable Logistic Regression: Factors Associated With Not Being Actively Engaged in Care Among HIV-Infected Patients at CORE in 2010 (n = 4577) Virologic Suppression Of the 3524 patients engaged in care, 2499 (71%) were suppressed. Patients who had VNS were more likely to be young, female, and black compared to suppressed patients (Table ​(Table2).2). Patients with VNS had lower median CD4 counts (300 vs 456 cells/mm3; P < .0001). Table 2. Multivariable Logistic Regression: Factors Associated With Viral Nonsuppression Among Patients in Care at CORE in 2010 (n = 3342) While overall rates of viral suppression were relatively high at 71%, we found significant differences in rates of engagement in care and viral suppression by demographic characteristics. The lower rate of active engagement among young, non-Hispanic black patients contributes to the documented racial disparities in HIV prevalence in Chicago and other communities across the United States. Among patients engaged in care, non-Hispanic black race, younger age, and being female were independently associated with viral nonsuppression. In both analyses, age 13–24 years was independently associated with poor outcomes, highlighting the need for new and innovative methods for engaging and retaining HIV-infected young adults in care. This initial study allows us to define subgroups within the larger CORE population who require targeted interventions. Our clinic model and diverse population, similar to the Moore clinic, allows us to actively study and address these disparities. Interventions to improve engagement in care and viral suppression are necessary to reduce health-related disparities and achieve the full salutary effect of treatment as prevention in Chicago.

Are tetraplegic handbikers going to disappear from team relay in para-cycling?

Are tetraplegic handbikers going to disappear from team relay in para-cycling?

Grand Challenge: Computational Models Validated Against Critical Experiments.

Grand Challenge: Computational Models Validated Against Critical Experiments.

Alzheimer's disease (AD) as a disorder of the plasma membrane

GENERAL COMMENTARY article Front. Physiol., 15 February 2013Sec. Membrane Physiology and Membrane Biophysics https://doi.org/10.3389/fphys.2013.00024

Working memory capacity: the need for process task-analysis

Working memory capacity: the need for process task-analysis

Conjoint measurement of disorder prevalence, test sensitivity, and test specificity: notes on Botella, Huang, and Suero's multinomial model

Conjoint measurement of disorder prevalence, test sensitivity, and test specificity: notes on Botella, Huang, and Suero's multinomial model

The assessment of side effects of tyrosine kinase inhibitors (TKI) applied in patients with advanced thyroid cancer (TC) - one centre experience

TKI constitute a new group of drugs evaluated in TC patients. The efficacy of some of them in prolongation of progression free survival has been recently documented. However, possible side effects may affect the quality of life as well as limit their clinical use. Only drugs which were known to inhibit VEGFR were considered. In the study adverse effects were evaluated in patients treated in our centre within the prospective clinical trials phase II and III. The aim of the study was to analyze the frequency and severity of side effects related to TKI in TC patients. Thus, we retrospectively re-evaluated side effects on the basis of Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The comparison of the drugs was not aimed. 37 therapies with TKI due to advanced TC were assessed. 19 subjects were given vandetanib, 15 - lenvatinib, 3 - axitinib. Median treatment duration was 26.7 months (range: 4.0 - 62.2). The drug was discontinued due to TC progression in 9 subjects, adverse events in 5 and for other reasons in 4. Adverse events leading to treatment withdrawal were: weight loss (1), lymphopenia (1), QTC prolongation (1), tracheo-esophageal fistula (1) and purulent meningitis (1). The results are given in table ​table11. Table 1 Frequency and severity of the most common treatment-related side effects.

Erratum: The promise of neuroprotective agents in Parkinson's disease

After our article was published online, it was brought to our attention that in Table ​Table11 we incorrectly stated the findings from a study testing the safety of Isradipine (Simuni et al., 2010). We have thus changed the text in the table to reflect the results that Isradipine has been shown to be safe and well-tolerated in PD patients. Table 1 Neuroprotective Agents in PD models.

Potential long non-coding RNAs to be considered as biomarkers or therapeutic targets in gastric cancer

Long non-coding RNAs are attracting the attention of researchers in many fields. These RNAs are longer than 200 nucleotides and do not encode any protein. A subset of them is reported to be strongly correlated with poor patient prognosis, suggesting a potential role in cancer progression (Esteller, 2011). Gastric cancer is one of the most common malignant tumors worldwide. Therefore, there is an urgent need to find genes which are helpful in the diagnosis, prognosis, and understanding of the molecular pathways of this cancer (Hajjari et al., 2013a). Finding novel molecular biomarkers of malignancy has been always important for clinical management. Like proteins, mRNAs, and miRNAs, lncRNAs show potentials as novel biomarkers and therapeutic targets in different cancer types (Zhang et al., 2013). However, there are a few reports on studying the relationship between gastric cancer progression and lncRNAs. Some useful clues for further researches seem necessary for deciphering the potential role of lncRNAs in gastric cancer. In this report, we present and highlight some evidences about the potential role of lncRNAs in gastric cancer based on the data indicated in Microarray databases. The results may give novel perspectives for further researches on the role of lncRNAs in gastric carcinogenesis. We used different databases including Oncomine, Gene Expression Atlas, Gene Expression Omnibus (GEO), and Array Express Databases to analyze the expression level of most recent cited and noted lncRNAs in studies on cancer progression (Niland et al., 2012; Zhang et al., 2013). The selected lncRNAs have been regarded as the most potential biomarkers in the studies on different cancer types (Zhang et al., 2013). The RNAs include H19, MALAT-1, HOTAIR, ANRIL, CRNDE, and MEG3. Some descriptions of these lncRNAs are presented below. Oncomine cancer microarray database was used to mine the lncRNA expression profile data according to the established methodology (Rhodes et al., 2007). Four publicly available datasets [Chen Gastric (Chen et al., 2003), DErrico Gastric (D'Errico et al., 2009), Wang Gastric (Wang et al., 2012), and Cho Gastric (Cho et al., 2011)] were inquired for our analysis. By using Oncomine and other microarray expression data accessible from GEO, Gene expression Atlas, and Array Express database, we found some significant differences of expression level for the lncRNAs. The datasets and clinopathological data of each study are presented in Table ​Table11. Table 1 Different datasets and their clinicopathological data used in the current study. Student's t-test was used for the differential expression analyses. Those which have significant differences (Fold change > 1.5, P-value < 0.01) between gastric cancer and normal tissues are brought in Table ​Table22. Table 2 Significant difference (Fold change > 1.5, P-value < 0.01) of the expression level of lncRNAs between gastric cancer types and normal tissues.