Factors Associated With Antiretroviral Therapy Reinitiation in Medicaid Recipients With Human Immunodeficiency Virus.

BACKGROUND: This study was conducted to examine patient characteristics associated with antiretroviral therapy (ART) reinitiation in Medicaid enrollees. METHODS: This is a retrospective cohort study that uses Cox proportional hazard regression to examine the association between person-level characteristics and time from ART discontinuation to the subsequent reinitiation within 18 months. RESULTS: There were 45 409 patients who discontinued ART, and 44% failed to reinitiate. More outpatient visits (3+ vs 0 outpatient visits: adjusted hazard ratio (adjHR), 1.56; 99% confidence interval [CI], 1.45-1.67) and hospitalization (adjHR, 1.18; 99% CI,1.16-1.20) during follow-up were associated with reinitiation. CONCLUSIONS: Failure to reinitiate ART within 18 months was common in this sample. Care engagement was associated with greater ART reinitiation.

ESPACOMP Medication Adherence Reporting Guidelines (EMERGE): a reactive-Delphi study protocol.

INTRODUCTION: Medication adherence is fundamental to achieving optimal patient outcomes. Reporting research on medication adherence suffers from some issues-including conceptualisation, measurement and data analysis-that thwart its advancement. Using the ABC taxonomy for medication adherence as the conceptual basis, a steering committee of members of the European Society for Patient Adherence, COMpliance, and Persistence (ESPACOMP) launched an initiative to develop ESPACOMP Medication Adherence Reporting Guidelines (EMERGE). This paper is a protocol for a Delphi study that aims to build consensus among a group of topic experts regarding an item list that will support developing EMERGE. METHODS AND ANALYSIS: This study uses a reactive-Delphi design where a group of topic experts will be asked to rate the relevance and clarity of an initial list of items, in addition to suggesting further items and/or modifications of the initial items. The initial item list, generated by the EMERGE steering committee through a structured process, consists of 26 items distributed in 2 sections: 4 items representing the taxonomy-based minimum reporting criteria, and 22 items organised according to the common reporting sections. A purposive sample of experts will be selected from relevant disciplines and diverse geographical locations. Consensus will be achieved through predefined decision rules to keep, delete or modify the items. An iterative process of online survey rounds will be carried out until consensus is reached. ETHICS AND DISSEMINATION: An ethics approval was not required for the study according to the Swiss federal act on research involving human beings. The participating experts will be asked to give an informed consent. The results of this Delphi study will feed into EMERGE, which will be disseminated through peer-reviewed publications and presentations at conferences. Additionally, the steering committee will encourage their endorsement by registering the guidelines at the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) network and other relevant organisations.

A Comparison of Adherence Timeframes Using Missed Dose Items and Their Associations with Viral Load in Routine Clinical Care: Is Longer Better?

Questions remain regarding optimal timeframes for asking about adherence in clinical care. We compared 4-, 7-, 14-, 30-, and 60-day timeframe missed dose items with viral load levels among 1099 patients on antiretroviral therapy in routine care. We conducted logistic and linear regression analyses examining associations between different timeframes and viral load using Bayesian model averaging (BMA). We conducted sensitivity analyses with subgroups at increased risk for suboptimal adherence (e.g. patients with depression, substance use). The 14-day timeframe had the largest mean difference in adherence levels among those with detectable and undetectable viral loads. BMA estimates suggested the 14-day timeframe was strongest overall and for most subgroups although findings differed somewhat for hazardous alcohol users and those with current depression. Adherence measured by all missed dose timeframes correlated with viral load. Adherence calculated from intermediate timeframes (e.g. 14-day) appeared best able to capture adherence behavior as measured by viral load.

Characterization of an α-l-fucosidase from the periodontal pathogen Tannerella forsythia.

The periodontal pathogen Tannerella forsythia expresses several glycosidases which are linked to specific growth requirements and are involved in the invasion of host tissues. α-l-Fucosyl residues are exposed on various host glycoconjugates and, thus, the α-l-fucosidases predicted in the T. forsythia ATCC 43037 genome could potentially serve roles in host-pathogen interactions. We describe the molecular cloning and characterization of the putative fucosidase TfFuc1 (encoded by the bfo_2737 = Tffuc1 gene), previously reported to be present in an outer membrane preparation. In terms of sequence, this 51-kDa protein is a member of the glycosyl hydrolase family GH29. Using an artificial substrate, p-nitrophenyl-α-fucose (KM 670 µM), the enzyme was determined to have a pH optimum of 9.0 and to be competitively inhibited by fucose and deoxyfuconojirimycin. TfFuc1 was shown here to be a unique α(1,2)-fucosidase that also possesses α(1,6) specificity on small unbranched substrates. It is active on mucin after sialidase-catalyzed removal of terminal sialic acid residues and also removes fucose from blood group H. Following knock-out of the Tffuc1 gene and analyzing biofilm formation and cell invasion/adhesion of the mutant in comparison to the wild-type, it is most likely that the enzyme does not act extracellularly. Biochemically interesting as the first fucosidase in T. forsythia to be characterized, the biological role of TfFuc1 may well be in the metabolism of short oligosaccharides in the periplasm, thereby indirectly contributing to the virulence of this organism. TfFuc1 is the first glycosyl hydrolase in the GH29 family reported to be a specific α(1,2)-fucosidase.

"If I don't use a condom I would be stressed in my heart that I've done something wrong": Routine Prevention Messages Preclude Safer Conception Counseling for HIV-Infected Men and Women in South Africa.

Intended conception likely contributes to a significant proportion of new HIV infections in South Africa. Safer conception strategies require healthcare provider-client communication about fertility intentions, periconception risks, and options to modify those risks. We conducted in-depth interviews with 35 HIV-infected men and women accessing care in South Africa to explore barriers and promoters to patient-provider communication around fertility desires and intentions. Few participants had discussed personal fertility goals with providers. Discussions about pregnancy focused on maternal and child health, not sexual HIV transmission; no participants had received tailored safer conception advice. Although participants welcomed safer conception counseling, barriers to client-initiated discussions included narrowly focused prevention messages and perceptions that periconception transmission risk is not modifiable. Supporting providers to assess clients' fertility intentions and offer appropriate advice, and public health campaigns that address sexual HIV transmission in the context of conception may improve awareness of and access to safer conception strategies.

Current management of relapsing-remitting multiple sclerosis.

Multiple sclerosis was without effective disease-modifying therapy for many years. The introduction of the injectable therapies (interferon and glatiramer acetate) some 20 years ago was considered a major advance. Recent years have heralded a revolution in treatment options with the introduction of intravenous natalizumab and, even more recently, three oral agents. We are currently in a period of determining the best use of these therapies to ensure prevention of disease progression while maintaining patient safety. Despite these new treatments, there are still many patients living with disability as a result of multiple sclerosis and significant attention must be given to symptomatic management.

Nature's necrosis factor when associated with erythrocytes may not only explain the surprises in lung cancer metastases but also suggest target therapy.

Lung cancer is so strategically situated as regards the heart and aorta that it ought to scatter its metastasizing cells far and wide. However, at careful autopsy, instead of giant opportunities, only dwarf deposition may be detected. Indeed, up to seven patterns of its metastases demonstrate surprises. What explains these surprises? Consider the thoracic duct. When this 45 cm long duct was obtained in its entirety, coiled in the Swiss-roll manner, processed in the usual way, and examined on a single microscope slide, necrosis of some transported lung cancer cells was found to be very intimately associated with the erythrocytes. Therefore, let this underlying natural mechanism be named as the "erythrocyte associated necrosis factor", i.e., EANF. It is argued that this Factor operates differently from the suspected roles of both anoikis and stem cells. Accordingly, it is hypothesized that, if intravital video microscopy is used to obtain subsets of both necrotic and lively cancer cells from the thoracic duct of consenting lung cancer patients, the underlying EANF will definitely materialize. It is predicted that the manipulative replication of this Factor in leading centers will ensure progress. In sum, EANF would not only aid in our understanding of the outlined highly inefficient metastatic processes but also effect a breakthrough in the realms of target therapy.

Evaluation of the single-item self-rating adherence scale for use in routine clinical care of people living with HIV.

The self-rating scale item (SRSI) is a single-item self-report adherence measure that uses adjectives in a 5-point Likert scale, from "very poor" to "excellent," to describe medication adherence over the past 4 weeks. This study investigated the SRSI in 2,399 HIV-infected patients in routine care at two outpatient primary HIV clinics. Correlations between the SRSI and four commonly used adherence items ranged from 0.37 to 0.64. Correlations of adherence barriers, such as depression and substance use, were comparable across all adherence items. General estimating equations suggested the SRSI is as good as or better than other adherence items (p's <0.001 vs. <0.001-0.99) at predicting adherence-related clinical outcomes, such as HIV viral load and CD4(+) cell count. These results and the SRSI's low patient burden suggest its routine use could be helpful for assessing adherence in clinical care and should be more widespread, particularly where more complex instruments may be impractical.

Expression, purification and preliminary crystallographic analysis of Drosophila melanogaster lysosomal α-mannosidase.

The lysosomal α-mannosidases are class II mannosidases that belong to glycoside hydrolase family 38 and play an important role in the degradation of asparagine-linked carbohydrates of glycoproteins. Based on peptide similarity to human and bovine lysosomal mannosidase (LM), recombinant α-mannosidase from Drosophila melanogaster (dLM408) was cloned and heterologously expressed in Pichia pastoris. The recombinant form of dLM408 designed for structural analysis lacks the transmembrane domain and was crystallized using standard vapour-diffusion and counter-diffusion techniques. The crystals grew as flat plates and as tetragonal bipyramids, respectively. The plate-shaped crystals exhibited the symmetry of space group P2(1)2(1)2(1) and diffracted to a minimum d-spacing of 3.5 Å.

Spontaneous regression of breast carcinoma: review of English publications from 1753 to 1897.

Regression is an important phenomenon in oncology. Two reviews in 2011 dealt at length with what in modern parlance may be called its permutations and combinations. Specifically, in both 1982 and 1987, when its occurrence in breast cancer was presented from two centers, the oldest accounts of it were dated back to 1900. Therefore, a search for much older English literature was undertaken in order to widen current knowledge of this important problem. Consequently, a published long case dating back to 1897 is abridged and a short 1846 case is also noted. Furthermore, general etiological concepts are exemplified as far back as 1753. It is concluded that the history of cancer regression is like fishing in an ocean of this illness. However, the findings are deemed to complement what modern historical accounts lack.

Lymphangiogenesis may explain adrenal selectivity in lung cancer metastases.

The 'seed and soil' hypothesis of organ selectivity in cancer metastasis dated back to the 1870s. A century later, a review of significant selectivity data revealed that the adrenals featured in 11 of 12 classes of it, thus promoting these two organs for research. Fortunately, two discoveries have also occurred, namely, (a) that cancer stimulates lymph vessel formation, i.e., lymphangiogenesis, and (b) that lymph and blood vessels are differentially stainable. Accordingly, these interesting ideas should be exploited with a hypothesis. Therefore, it is proposed that, at autopsy in lung cancer cases, the tissues between the primary lung tumor and the adrenal secondary should be meticulously serially sectioned and disjunctively stained because they must reveal what naturally occurs in this zone during life. It is predicted that this maneuver will identify lymphangiogenesis as the phenomenon responsible for the age-old puzzle of adrenal selectivity. Indeed, it may explain other puzzles such as intracranial lymphatic connectivity.

The quality of care received by HIV patients without a primary provider.

The goal of this study was to compare the quality of care received by HIV patients who report that their primary HIV care provider is a physician, a nurse practitioner (NP) or a physician assistant (PA) to that of patients who cannot identify a primary HIV provider. We used data from patients who participated in the HIV Cost and Services Utilization Study (HCSUS), a study of a probability sample of non-institutionalized HIV-infected individuals in care in the US. We compared patients who did and did not name a primary HIV care provider in terms of patient and care site characteristics, and level of clinician HIV expertise. Care quality measures included receipt of highly active antiretroviral therapy (HAART), reported problems with care, satisfaction with care, unmet needs and perceived access to care. Patients in care who did not report having a primary HIV care provider received HAART at significantly lower rates (p<0.05) and were less satisfied with their care (p<0.05) than patients with a primary HIV care provider, after adjusting for illness severity and other patient characteristics. There were similar but non-significant trends for reported problems, unmet needs and perceived access to care. Patients who had lower income or were drug users were more likely not to have a primary provider. We conclude that having a primary HIV care provider who is knowledgeable about a patient's care is related to the quality of medical care received by persons with HIV infection.

Epidemiology of skin cancer arisen from the burn scars in Nigerian Ibos.

During the period 20 February 1970-19 February 2000, burns resulting in squamous cell carcinoma of the skin were documented by using a histopathology data pool of surgical specimens kept by the author as regards his Ibos ethnic group in Nigeria, West Africa. There were 21 cases. The males outnumbered the females in the ratio of 3:1. The youngest patient was aged 8 years and the oldest 75 years (mean age 39 years). Most of the antecedent injuries occurred during childhood. The two etiologic agents of albinism and burns were combined in one patient while another rarity was the presentation of the cancer within keloids. In conclusion, in dark skinned races, research should be directed on the comparative role of burns in predisposing to squamous cell carcinoma in individuals whose skin is compromised by either albinism or keloids.

Differences in patient and clinic characteristics at CARE Act funded versus non-CARE Act funded HIV clinics.

The Ryan White CARE Act supports comprehensive care to persons with HIV infection. With an annual budget of over $1 billion, it is the largest federally funded programme for HIV care in the USA. We analysed data from the HIV Costs and Services Utilization Study, a nationally representative sample of HIV patients. Patient data were collected in 1996-97 and clinic data were collected in 1998-99. We examined whether CARE Act funded clinics differed from other HIV clinics in (1) the characteristics of their patients, and (2) their organization, staffing, and services. We found that patients at CARE Act clinics were younger, less educated, poorer, and more likely to be female, non-white, unemployed, uninsured, and have heterosexual contact as an HIV risk factor, compared to patients at other HIV clinics. CARE Act clinics tended to specialize in HIV care, had more infectious disease specialists, had fewer total patients, and provided more support services (e.g. mental health, nutrition, case management, child care). These results are consistent with findings of other studies that were limited by non-probability samples or restricted geographical areas.

The never-ending story of peptide O-xylosyltransferase.

In a journey lasting 40 years from the first reports on its activity in the 1960s to its purification and the cloning of relevant complementary DNAs, peptide O-xylosyltransferase has finally arrived at the same point as many other enzymes. This enzyme, whose systematic name is UDP-alpha-D-xylose:proteoglycan core protein beta-D-xylosyltransferase (EC 2.4.2.26), catalyses the first step in the biosynthesis of chondroitin, dermatan and heparan sulphates in the endoplasmic reticulum and/or the cis-Golgi cisternae. Analyses of their primary structure show that peptide O-xylosyltransferases are members of glycosyltransferase family 14 and so are homologous to beta1,6- N-acetylglucosaminyltransferases involved in O-glycan and poly- N-acetyllactosamine branching. Furthermore, vertebrates appear to have two rather similar genes encoding xylosyltransferase I and xylosyltransferase II, but enzymatic activity was only detected for a recombinant form of the first isoform. On the other hand, Caenorhabditis and Drosophila have each only one peptide O-xylosyltransferase gene. In the worm sqv-6 mutant, a mutation of the xylosyltransferase gene is associated with defective vulval morphogenesis, indicative of the importance of the glycosaminoglycan chains of proteoglycans in animal development. There remain, however, open questions, for instance, on the enzyme's intracellular localisation and structure-function relationships.

Changes in lean body mass and total body weight are weakly associated with physical functioning in patients with HIV infection.

CONTEXT: For clinicians managing weight loss in patients with HIV, it would be useful to understand how changes in lean body mass (LBM) effect physical functioning, and whether LBM is more strongly related to physical functioning than total body weight (TBW). OBJECTIVE: To determine the relationship of changes in LBM and changes in total body weight (TBW) to changes in self-reported physical functioning in men and women with HIV infection. METHODS: Study design was longitudinal analysis of 1474 patient-intervals (each interval was approximately 6 months long) in 486 persons. Patients were participants in Nutrition for Healthy Living, a cohort study of HIV positive persons in Massachusetts and Rhode Island. The main outcome measure was change in self-reported physical functioning. RESULTS: Of the 1,474 intervals, 1,165 were contributed by men and 309 by women. The mean CD4 count for the 1,474 intervals was 383 cells/ micro L. In men, 5 kg changes in LBM and TBW were associated with 2.2 (95% confidence interval, 0.9, 3.4, P= 0.001) and 2.6 (95% confidence interval, 1.3, 3.9, P= 0.0002) point changes in physical functioning (on a 100-point scale), respectively, after adjusting for covariates. The relationships of changes in LBM and TBW to changes in physical functioning were linear. In women, there were no significant relationships between changes in LBM or TBW to changes in physical functioning. CONCLUSIONS: In this longitudinal analysis of relatively healthy persons with HIV infection, changes in LBM and TBW were significantly related to changes in physical functioning in men, but the magnitude of the relationship was small. In women, changes in LBM and TBW were not related to changes in physical functioning. Our data suggest that it is not necessary to measure body composition (lean and fat compartments) to understand the impact of changes in weight on physical functioning - it is sufficient to follow total body weight.