The effect of hormonal contraception on genital tract shedding of HIV-1

OBJECTIVE: A previous cross-sectional study reported that hormonal contraception may be associated with increased infectivity in HIV-1 infected women. We conducted a prospective study to determine if cervical shedding of HIV-1 increased after initiating hormonal contraception. DESIGN: Shedding of HIV-1 DNA (a marker of HIV-1 infected cells) and HIV-1 RNA were measured before and after initiating hormonal contraception. METHODS: HIV-1 seropositive women were recruited from a Kenyan family planning clinic. At baseline, cervical secretions were collected for HIV-1 DNA and RNA assays in women initiating hormonal contraception; follow-up samples were collected a median of 64 days later. RESULTS: One-hundred and one women chose depot medroxyprogesterone (Depo), 53 chose low-dose oral contraceptives (OC), seven high-dose OC, and 52 progesterone-only OC. At follow-up, there was a significant increase in the prevalence of cervical HIV-1 DNA detection [from 42% to 52%, odds ratio (OR), 1.62; 95% confidence interval (CI), 1.03-2.63) for all hormonal contraception combined, and a trend for an increase for each individual type. Although the prevalence of cervical HIV-1 RNA increased slightly (from 82% to 86%; OR, 1.56; 95% CI, 0.83-3.03), the concentration of cervical HIV-1 RNA did not change significantly overall (from 2.81 to 2.84 log10 copies/swab; P = 0.77) or for individual contraception types. CONCLUSIONS: A modest but significant increase in shedding of HIV-1 DNA but not of HIV-1 RNA was detected after starting hormonal contraception. Our results may have important implications regarding the infectivity of women using hormonal contraception, and highlight the need for epidemiologic studies of transmission rates from women using and not using hormonal contraception.     

Evaluation of the highly sensitized transplant recipient

The immune response against alloantigens involves the production of antibodies and development of T-cell immunity. Recipients sensitized to HLA antigens may have antibodies to almost all donors and may not be able to find a suitable kidney transplant donor. Strategies available to enable these patients to obtain a transplant are to give priority to highly sensitized patients, to perform therapy for antibody reduction or to transplant with existing antibodies and to intervene as needed with post-transplant treatment. While sensitization against HLA antigens is the most important cause of immunological transplant failure, other types of alloantigens, many of them expressed selectively in endothelial cells, and autoantigens may also be involved. Molecular typing and solid-phase antibody testing have markedly changed this field in the last few years. Methods for the analysis of HLA antibodies and for the study of T-cell reactivity and sensitization will also be discussed. Virtual cross-matching can now be performed for many patients, resulting in considerable savings in time and effort. Successful application of this approach requires the intervention of highly trained personnel with a good understanding of the limitations of the procedure and with intimate knowledge of the antibody profiles of the patients on the waiting list.     

Pharmacokinetic interaction study between the new antiepileptic and CNS drug RWJ-333369 and carbamazepine in healthy adults

PURPOSE: To characterize the possible pharmacokinetic interaction between the new antiepileptic and CNS drug RWJ-333369 and carbamazepine (CBZ) following multiple dosing in healthy subjects. METHODS: In an 8-week, open-label, sequential design study, 24 healthy adults received multiple-dose RWJ-333369 alone (5 days 250 mg q12h; 5 days 500 mg q12h), then after a 4-day washout, multiple-dose CBZ alone (3 days 100 mg q12h; 3 days 200 mg q12h; 22 days 300 mg q12h), and then combination of CBZ (300 mg q12h), and RWJ-333369 (5 days 250 mg q12h; 5 days 500 mg q12h). RESULTS: At steady-state following multiple dosing, RWJ-333369 peak plasma concentration (C(max)) and area under the concentration-time-curve within the dosing interval (AUCss) increased in proportion to dose. The C(max) and AUCss of CBZ were similar when given alone or concomitantly with RWJ-333369. The 90% confidence intervals for the ratio of CBZ C(max) and AUCss with/without RWJ-333369 were: 94-104% and 95-104%, respectively (well within the equivalence range of 80-125%). When RWJ-333369 was administered with CBZ, its mean (SD) oral clearance increased from 3.2 L/h to 4.9 L/h and consequently its mean half-life was shortened from 10.4 (1.9) h to 7.4 (1.2) h, and mean AUCss and C(max) were reduced by 37% and 30%, respectively. CONCLUSIONS: There was no effect of multiple-dose RWJ-333369 on CBZ pharmacokinetics. CBZ induced RWJ-333369 clearance, resulting in shortened half-life and decreased exposure (AUCss) and C(max). Concomitant administration of RWJ-333369 with CBZ was generally safe and tolerated.     

Orthodontic marketing through social media networks: The patient and practitioner's perspective

Objective:To (1) assess orthodontic patient and practitioner use of and preferences for social media and (2) investigate the potential benefit of social media in marketing and communication strategies in orthodontic practices.Materials and Methods:A survey was developed and randomly distributed to orthodontists via the American Association of Orthodontists and to patients/parents via private practices throughout the United States. Participants were asked to answer questions related to their use of social media and their perceptions of the use of social media in the orthodontic practice.Results:Of the participants, 76% of orthodontists and 89% of patients/parents use social media. Furthermore, Facebook was the social media platform that was most preferred. Social media use was more common in female and younger adult participants. Orthodontists posted information more often in the morning (40%) and afternoon (56%), and patients/parents used social media mainly in the evening (76%). The most commonly used marketing strategies in the orthodontic practices were social media (76%) and a practice website (59%). Social media and practice websites were positively related with new patient starts (P  =  .0376, P  =  .0035, respectively).Conclusions:Most orthodontists and patients/parents used social media. Social media may be an effective marketing and communication tool in an orthodontic practice.     

Understanding the cumulative impacts of inequalities in environmental health: implications for policy

Racial or ethnic minority groups and low-income communities have poorer health outcomes than others. They are more frequently exposed to multiple environmental hazards and social stressors, including poverty, poor housing quality, and social inequality. Researchers are grappling with how best to characterize the cumulative effects of these hazards and stressors in order to help regulators and decision makers craft more-effective policies to address health and environmental disparities. In this article we synthesize the existing scientific evidence regarding the cumulative health implications of higher rates of exposure to environmental hazards, along with individual biological susceptibility and social vulnerability. We conclude that current environmental policy, which is focused narrowly on pollutants and their sources, should be broadened to take into account the cumulative impact of exposures and vulnerabilities encountered by people who live in neighborhoods consisting largely of racial or ethnic minorities or people of low socioeconomic status.     

Evaluation of a word recognition instrument to test health literacy in dentistry: the REALD-99

OBJECTIVE: This study aims to evaluate a dental health literacy word recognition instrument. METHODS: Based on a reading recognition test used in medicine, the Rapid Estimate of Adult Literacy in Medicine (REALM), we developed the Rapid Estimate of Adult Literacy in Dentistry (REALD-99). Parents of pediatric dental patients were recruited from local dental clinics and asked to read aloud words in both REALM and REALD-99. REALD-99 scores had a possible range of 0 (low literacy) to 99 (high literacy); REALM scores ranged from 0 to 66. Outcome measures included parents' perceived oral health for themselves and of their children, and oral health-related quality of life of the parent as measured by the short-form Oral Health Impact Profile (OHIP-14). To determine the validity, we tested bivariate correlations between REALM and REALD-99, REALM and perceived dental outcomes, and REALD-99 and perceived dental outcomes. We used ordinary least squares regression and logit models to further examine the relationship between REALD-99 and dental outcomes. We determined internal reliability using Cronbach's alpha. RESULTS: One hundred two parents of children were interviewed. The average REALD-99 and REALM-66 scores were high (84 and 62, respectively). REALD-99 was positively correlated with REALM (PCC = 0.80). REALM was not related to dental outcomes. REALD-99 was associated with parents' OHIP-14 score in multivariate analysis. REALD-99 had good reliability (Cronbach's alpha = 0.86). CONCLUSIONS: REALD-99 has promise for measuring dental health literacy because it demonstrated good reliability and is quick and easy to administer. Additional studies are needed to examine the validity of REALD-99 using objective clinical oral health measures and more proximal outcomes such as behavior and compliance to specific health instructions.     

Induction Type and Outcomes in HLA-DR Mismatch Kidney Transplantation

BackgroundIn kidney transplantation, donor recipient human leukocyte antigen (HLA)-DR mismatch signals high immunologic risk and portends inferior outcomes. We compared the impacts of depleting vs non-depleting antibody induction on the outcomes in kidney transplant recipients (KTRs) at different levels of HLA-DR mismatches.MethodsUsing the Organ Procurement and Transplantation Network/United Network for Organ Sharing database, we identified adult KTRs from 2001 to 2015 who received induction therapy with either depleting (thymoglobulin/alemtuzumab) or non-depleting (basiliximab/daclizumab) antibody and were discharged on calcineurin inhibitor/mycophenolic acid maintenance. Patients were then stratified by the number of donor-recipient HLA-DR mismatches (0, 1, 2) in both living donor (LD) and deceased donor (DD) KTRs. Under each HLA-DR mismatch category, long-term outcomes were compared for depleting vs non-depleting induction using a Cox model.ResultsA total of 63,821 LD (HLA-DR mismatches: 0, n = 6945 [depleting = 4409, non-depleting = 2536]; 1, n = 19,557 [depleting = 13,558, non-depleting = 6019]; and 2, n = 10,727 [depleting = 7694, non-depleting = 3033]) and 64,922 DD (HLA-DR mismatches: 0, n = 13,915 [depleting = 10,124, non-depleting = 3791]; 1, n = 27,994 [depleting = 20,454, non-depleting = 7540]; and 2, n = 23,013 [depleting = 16,908, non-depleting = 6105]) KTRs were included in the analysis. Adjusted patient death risk was significantly lower in the depleting vs non-depleting antibody induction group among DD kidney recipients (hazard ratio 0.90, 95% CI 0.85–0.96, P = .001) and trended lower among LD kidney recipients (HR 0.88, 95% 0.79–1.01, P = .05) with 2 HLA-DR mismatches.DiscussionOur study found a patient survival benefit associated with the use of perioperative induction with depleting when compared to non-depleting antibody in KTRs with 2 HLA-DR mismatches and maintained on a calcineurin inhibitor/mycophenolic acid regimen.     

Primary and secondary hyperoxaluria: Understanding the enigma

Hyperoxaluria is characterized by an increased urinary excretion of oxalate. Primary and secondary hyperoxaluria are two distinct clinical expressions of hyperoxaluria. Primary hyperoxaluria is an inherited error of metabolism due to defective enzyme activity. In contrast, secondary hyperoxaluria is caused by increased dietary ingestion of oxalate, precursors of oxalate or alteration in intestinal microflora. The disease spectrum extends from recurrent kidney stones, nephrocalcinosis and urinary tract infections to chronic kidney disease and end stage renal disease. When calcium oxalate burden exceeds the renal excretory ability, calcium oxalate starts to deposit in various organ systems in a process called systemic oxalosis. Increased urinary oxalate levels help to make the diagnosis while plasma oxalate levels are likely to be more accurate when patients develop chronic kidney disease. Definitive diagnosis of primary hyperoxaluria is achieved by genetic studies and if genetic studies prove inconclusive, liver biopsy is undertaken to establish diagnosis. Diagnostic clues pointing towards secondary hyperoxaluria are a supportive dietary history and tests to detect increased intestinal absorption of oxalate. Conservative treatment for both types of hyperoxaluria includes vigorous hydration and crystallization inhibitors to decrease calcium oxalate precipitation. Pyridoxine is also found to be helpful in approximately 30% patients with primary hyperoxaluria type 1. Liver-kidney and isolated kidney transplantation are the treatment of choice in primary hyperoxaluria type 1 and type 2 respectively. Data is scarce on role of transplantation in primary hyperoxaluria type 3 where there are no reports of end stage renal disease so far. There are ongoing investigations into newer modalities of diagnosis and treatment of hyperoxaluria. Clinical differentiation between primary and secondary hyperoxaluria and further between the types of primary hyperoxaluria is very important because of implications in treatment and diagnosis. Hyperoxaluria continues to be a challenging disease and a high index of clinical suspicion is often the first step on the path to accurate diagnosis and management.