Treatment patterns associated with Duloxetine and Venlafaxine use for Major Depressive Disorder

<p>Abstract</p> <p>Background</p> <p>Duloxetine and venlafaxine extended release (venlafaxine XR) are SNRIs indicated for the treatment of MDD. This study addresses whether duloxetine and venlafaxine XR are interchangeable in their patterns of use with patients who are depressed or are used more selectively based on treatment history, background characteristics, and presenting symptoms.</p> <p>Methods</p> <p>This was a retrospective analysis of an administrative insurance claims database. We studied patients in managed care with major depressive disorder (MDD) treated with duloxetine or venlafaxine XR. Predictors of treatment and cost were assessed using Chi-square and logistic regression analyses of demographics and past-year medication use and comorbidities.</p> <p>Results</p> <p>Patients with MDD treated with duloxetine (n = 9,641) versus venlafaxine XR (n = 8,514) tended to be older, slightly more likely to be female, and treated by a psychiatrist (<it>P </it>< 0.0001). In the prior year, more duloxetine patients (vs. venlafaxine XR) received ≥3 unique antidepressants (20.8% vs. 16.6%), ≥3 unique pain medications (25.5% vs. 15.6%), and had ≥8 unique diagnosed comorbid medical and psychiatric conditions (38.6% vs. 29.1%). The prior 6-month total health care costs were $1,731 higher for duloxetine than for venlafaxine XR and declined for both medications in the 6 months after treatment began. Logistic regression analysis revealed that 61% of duloxetine patients and 61% of venlafaxine XR patients were predictable from prior patient and treatment factors.</p> <p>Conclusions</p> <p>Patients with MDD treated with duloxetine tended to have a more complex and costly antecedent clinical presentation compared with venlafaxine XR patients, suggesting that physicians do not use the medications interchangeably.</p

Gender Differences in Clinical Presentation and Outcomes of Epidemic Kaposi Sarcoma in Uganda

The incidence of Kaposi sarcoma (KS) has increased dramatically among women in sub-Saharan Africa since the onset of the HIV pandemic, but data on KS disease in women are limited. To identify gender-related differences in KS presentation and outcomes, we evaluated the clinical manifestations and response in men and women with AIDS-associated KS in Uganda.HIV-infected adults with KS attending the Infectious Diseases Institute (IDI) and Uganda Cancer Institute (UCI) in Kampala, Uganda between 2004 and 2006 were included in a retrospective cohort. Evaluation of KS presentation was based on the clinical features described at the initial KS visit. Response was evaluated as the time to "improvement", as defined by any decrease in lesion size, lesion number, or edema. The cohort consisted of 197 adults with HIV and KS: 55% (108/197) were women. At presentation, the median CD4 T-cell count was significantly lower in women (58 cells/mm(3); IQR 11-156 cells/mm(3)) than men (124 cells/mm(3); IQR 22-254 cells/mm(3)) (p = 0.02). Women were more likely than men to present with lesions of the face (OR 2.8, 95% CI, 1.4, 5.7; p = 0.005) and hard palate (OR 2.0, 95% CI, 1.1, 3.7; p = 0.02), and were less likely than men to have lower extremity lesions (OR 0.54, 95% CI, 0.3, 0.99; p = 0.05). Women were less likely than men to demonstrate clinical improvement (HR = 0.52, CI 0.31, 0.88; p = 0.01) in multivariate analysis.The clinical presentation and response of KS differs between men and women in Uganda. These data suggest that gender affects the pathophysiology of KS, which may have implications for the prevention, diagnosis, and treatment of KS in both men and women. Prospective studies are needed to identify predictors of response and evaluate efficacy of treatment in women with KS, particularly in Africa where the disease burden is greatest

Dark clouds in co-creation, and their silver linings practical challenges we faced in a participatory project in a resource-constrained community in India, and how we overcame (some of) them

BACKGROUND: While any type of field-based research is challenging, building action-oriented, participatory research in resource-constrained settings can be even more so. OBJECTIVE: In this article, we aim to examine and provide insights into some of the practical challenges that were faced during the course of a participatory project based in two non-notified slums in Bangalore, India, aiming to build solutions to indoor air pollution from cooking on traditional cook stoves. METHODS: The article draws upon experiences of the authors as field researchers engaged in a community-based project that adopted an exploratory, iterative design to its planning and implementation, which involved community visits, semi-structured interviews, prioritization workshops, community forums, photo voice activities, chulha-building sessions and cooking trials. RESULTS: The main obstacles to field work were linked to fostering open, continued dialogue with the community, aimed at bridging the gap between the 'scientific' and the 'local' worlds. Language and cultural barriers led to a reliance on interpreters, which affected both the quality of the interaction as well as the relationship between the researchers and the community that was built out of that interaction. The transience in housing and location of members of the community also led to difficulties in following up on incomplete information. Furthermore, facilitating meaningful participation from the people within the context of restricted resources, differing priorities, and socio-cultural diversity was particularly challenging. These were further compounded by the constraints of time and finances brought on by the embeddedness of the project within institutional frameworks and conventional research requirements of a fixed, pre-planned and externally determined focus, timeline, activities and benchmarks for the project. CONCLUSIONS: This article calls for revisiting of scientific conventions and funding prerequisites, in order to create spaces that support flexible, emergent and adaptive field-based research projects which can respond effectively to the needs and priorities of the community

Tet2 disruption leads to enhanced self-renewal and altered differentiation of fetal liver hematopoietic stem cells

Somatic mutation of ten-eleven translocation 2 (TET2) gene is frequently found in human myeloid malignancies. Recent reports showed that loss of Tet2 led to pleiotropic hematopoietic abnormalities including increased competitive repopulating capacity of bone marrow (BM) HSCs and myeloid transformation. However, precise impact of Tet2 loss on the function of fetal liver (FL) HSCs has not been examined. Here we show that disruption of Tet2 results in the expansion of Lin−Sca-1+c-Kit+ (LSK) cells in FL. Furthermore, Tet2 loss led to enhanced self-renewal and long-term repopulating capacity of FL-HSCs in in vivo serial transplantation assay. Disruption of Tet2 in FL also led to altered differentiation of mature blood cells, expansion of common myeloid progenitors and increased resistance for hematopoietic progenitor cells (HPCs) to differentiation stimuli in vitro. These results demonstrate that Tet2 plays a critical role in homeostasis of HSCs and HPCs not only in the BM, but also in FL

Selective Serotonin Reuptake Inhibitor Use Is Associated with Right Ventricular Structure and Function: The MESA-Right Ventricle Study

PURPOSE:Serotonin and the serotonin transporter have been implicated in the development of pulmonary hypertension (PH). Selective serotonin reuptake inhibitors (SSRIs) may have a role in PH treatment, but the effects of SSRI use on right ventricular (RV) structure and function are unknown. We hypothesized that SSRI use would be associated with RV morphology in a large cohort without cardiovascular disease (N = 4114). METHODS:SSRI use was determined by medication inventory during the Multi-Ethnic Study of Atherosclerosis baseline examination. RV measures were assessed via cardiac magnetic resonance imaging. The cross-sectional relationship between SSRI use and each RV measure was assessed using multivariable linear regression; analyses for RV mass and end-diastolic volume (RVEDV) were stratified by sex. RESULTS:After adjustment for multiple covariates including depression and left ventricular measures, SSRI use was associated with larger RV stroke volume (RVSV) (2.75 mL, 95% confidence interval [CI] 0.48-5.02 mL, p = 0.02). Among men only, SSRI use was associated with greater RV mass (1.08 g, 95% CI 0.19-1.97 g, p = 0.02) and larger RVEDV (7.71 mL, 95% 3.02-12.40 mL, p = 0.001). SSRI use may have been associated with larger RVEDV among women and larger RV end-systolic volume in both sexes. CONCLUSIONS:SSRI use was associated with higher RVSV in cardiovascular disease-free individuals and, among men, greater RV mass and larger RVEDV. The effects of SSRI use in patients with (or at risk for) RV dysfunction and the role of sex in modifying this relationship warrant further study

Marine Actinomycetes: A New Source of Compounds against the Human Malaria Parasite

Background Malaria continues to be a devastating parasitic disease that causes the death of 2 million individuals annually. The increase in multi-drug resistance together with the absence of an efficient vaccine hastens the need for speedy and comprehensive antimalarial drug discovery and development. Throughout history, traditional herbal remedies or natural products have been a reliable source of antimalarial agents, e.g. quinine and artemisinin. Today, one emerging source of small molecule drug leads is the world's oceans. Included among the source of marine natural products are marine microorganisms such as the recently described actinomycete. Members of the genus Salinispora have yielded a wealth of new secondary metabolites including salinosporamide A, a molecule currently advancing through clinical trials as an anticancer agent. Because of the biological activity of metabolites being isolated from marine microorganisms, our group became interested in exploring the potential efficacy of these compounds against the malaria parasite.[br/] Methods We screened 80 bacterial crude extracts for their activity against malaria growth. We established that the pure compound, salinosporamide A, produced by the marine actinomycete, Salinispora tropica, shows strong inhibitory activity against the erythrocytic stages of the parasite cycle. Biochemical experiments support the likely inhibition of the parasite 20S proteasome. Crystal structure modeling of salinosporamide A and the parasite catalytic 20S subunit further confirm this hypothesis. Ultimately we showed that salinosporamide A protected mice against deadly malaria infection when administered at an extremely low dosage.[br/] Conclusion These findings underline the potential of secondary metabolites, derived from marine microorganisms, to inhibit Plasmodium growth. More specifically, we highlight the effect of proteasome inhibitors such as salinosporamide A on in vitro and in vivo parasite development. Salinosporamide A (NPI-0052) now being advanced to phase I trials for the treatment of refractory multiple myeloma will need to be further explored to evaluate the safety profile for its use against malaria

Relatively Low HIV Infection Rates in Rural Uganda, but with High Potential for a Rise: A Cohort Study in Kayunga District, Uganda

BACKGROUND: Few studies have been conducted in Uganda to identify and quantify the determinants of HIV-1 infection. We report results from a community-based cohort study, whose primary objectives were to determine HIV-1 prevalence, incidence, and determinants of these infections, among other objectives. METHODOLOGY: Consenting volunteers from the rural district of Kayunga in Uganda aged 15-49 years were enrolled between March and July 2006. Participants were evaluated every six months. A questionnaire that collected information on behavioral and other HIV-1 risk factors was administered, and a blood sample obtained for laboratory analysis at each study visit. PRINCIPAL FINDINGS: HIV-1 prevalence among the 2025 participants was 9.9% (95% CI = 8.6%-11.2%). By the end of 12 months of follow-up, 1689.7 person-years had been accumulated, with a median follow-up time of 11.97 months. Thirteen HIV-1 incident cases were detected giving an annual HIV-1 incidence of 0.77% (95% CI = 0.35-1.19). Prevalence of HSV-2 infection was 57% and was strongly associated with prevalent HIV-1 infection (adjusted Odds Ratio = 3.9, 95% CI = 2.50-6.17); as well as incident HIV-1 infection (adjusted Rate Ratio (RR) = 8.7, 95% CI = 1.11-67.2). The single most important behavioral characteristic associated with incident HIV infection was the number of times in the past 6 months, a participant had sex with person(s) they suspected/knew were having sex with others; attaining statistical significance at 10 times and higher (adjusted RR = 6.3, 95% CI = 1.73-23.1). By the end of 12 months of follow-up, 259 participants (13%) were lost to follow-up, 13 (0.6%) had died, and 2 (0.1%) had withdrawn consent. CONCLUSIONS: Despite relatively low HIV-1 incidence observed in this community, prevalence remains relatively high. In the presence of high prevalence of HSV-2 infection and the behavioral characteristic of having sex with more than one partner, there is potential for increase in HIV-1 incidence

Total synthesis of Escherichia coli with a recoded genome

Nature uses 64 codons to encode the synthesis of proteins from the genome, and chooses 1 sense codon—out of up to 6 synonyms—to encode each amino acid. Synonymous codon choice has diverse and important roles, and many synonymous substitutions are detrimental. Here we demonstrate that the number of codons used to encode the canonical amino acids can be reduced, through the genome-wide substitution of target codons by defined synonyms. We create a variant of Escherichia coli with a four-megabase synthetic genome through a high-fidelity convergent total synthesis. Our synthetic genome implements a defined recoding and refactoring scheme—with simple corrections at just seven positions—to replace every known occurrence of two sense codons and a stop codon in the genome. Thus, we recode 18,214 codons to create an organism with a 61-codon genome; this organism uses 59 codons to encode the 20 amino acids, and enables the deletion of a previously essential transfer RNA

Seroprevalence of HHV-8, CMV, and EBV among the general population in Ghana, West Africa

<p>Abstract</p> <p>Background</p> <p>Human herpesvirus 8 (HHV-8), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are prevalent in Africa, but less common elsewhere and the modes of transmission are still subject to debate. Generally, they rarely cause disease in the immunocompetent host but are highly oncogenic when associated with immunosuppression. Although the high prevalence of HHV-8, CMV and EBV has been well documented in Africa, such data are sparse from Ghana.</p> <p>Methods</p> <p>Serum samples from 3275 HIV-seronegative healthy blood donors and 250 HIV-AIDS patients were tested for antibodies specific for HHV-8, CMV and EBV by IgG ELISA assays. Differences in seropositivity rates by gender and age were evaluated using the Chi-square test with Yates correction.</p> <p>Results</p> <p>Of the 3275 HIV-seronegative healthy blood donors tested, 2573 (78.6%) were males and 702 (21.4%) were females, with ages ranging from 18 to 65 years (median 32.6; mean 31.2; mode 30). Of the 250 HIV-AIDS patients tested, 140 (56%) were males and 110 (44%) were females, with ages ranging from 17 to 64 years (median 30.8; mean 30.3; mode 28). Among the HIV-seronegative healthy blood donors, overall seroprevalence of HHV-8, CMV and EBV was 23.7%, 77.6% and 20.0%, respectively. Among the HIV-AIDS patients, overall seroprevalence of HHV-8, CMV and EBV was 65.6%, 59.2% and 87.2%, respectively. The seroprevalence of HHV-8 (p < 0.005) and EBV (p < 0.001) was statistically significantly higher in HIV-AIDS patients compared to HIV-seronegative healthy blood donors. There was no statistically significant difference (p = 0.24) between CMV seroprevalence in HIV-AIDS patients and HIV-seronegative healthy blood donors. Age and gender were not independent determinants (p > 0.05) for all three infections among HIV-seronegative healthy blood donors and HIV-AIDS patients in Ghana.</p> <p>Conclusion</p> <p>The results presented herein indicate that HHV-8, CMV and EBV infections are hyperendemic in both HIV-seronegative and HIV-seropositive Ghanaians, and suggest primarily a horizontal route of transmission of these three viral infections in Ghana.</p