Has the phasing out of stavudine in accordance with changes in WHO guidelines led to a decrease in single-drug substitutions in first-line antiretroviral therapy for HIV in sub-Saharan Africa?

This version is the Accepted Manuscript and is published in final edited form as: AIDS. 2017 January 02; 31(1): 147–157. doi:10.1097/QAD.0000000000001307OBJECTIVE: We assessed the relationship between phasing out stavudine in first-line antiretroviral therapy (ART) in accordance with WHO 2010 policy and single-drug substitutions (SDS) (substituting the nucleoside reverse transcriptase inhibitor in first-line ART) in sub-Saharan Africa. DESIGN: Prospective cohort analysis (International epidemiological Databases to Evaluate AIDS-Multiregional) including ART-naive, HIV-infected patients aged at least 16 years, initiating ART between January 2005 and December 2012. Before April 2010 (July 2007 in Zambia) national guidelines called for patients to initiate stavudine-based or zidovudine-based regimen, whereas thereafter tenofovir or zidovudine replaced stavudine in first-line ART. METHODS: We evaluated the frequency of stavudine use and SDS by calendar year 2004-2014. Competing risk regression was used to assess the association between nucleoside reverse transcriptase inhibitor use and SDS in the first 24 months on ART. RESULTS: In all, 33 441 (8.9%; 95% confience interval 8.7-8.9%) SDS occurred among 377 656 patients in the first 24 months on ART, close to 40% of which were amongst patients on stavudine. The decrease in SDS corresponded with the phasing out of stavudine. Competing risks regression models showed that patients on tenofovir were 20-95% less likely to require a SDS than patients on stavudine, whereas patients on zidovudine had a 75-85% decrease in the hazards of SDS when compared to stavudine. CONCLUSION: The decline in SDS in the first 24 months on treatment appears to be associated with phasing out stavudine for zidovudine or tenofovir in first-line ART in our study. Further efforts to decrease the cost of tenofovir and zidovudine for use in this setting is warranted to substitute all patients still receiving stavudine

Gender Differences in How Men and Women Referred with In Vitro Fertilization (IVF) Cope with Infertility Stress

Men and women use a variety of coping strategies to manage stress associated with infertility. While previous research has helped us understand these coping processes, questions remain about gender differences in coping and the nature of the relationship between coping and specific types of infertility stress. Methods: This study examined the coping behaviors of 1,026 (520 women, 506 men) consecutively referred patients at a Universityaffiliated teaching hospital. Participants completed the Ways of Coping Questionnaire, Fertility Problem Inventory, and the Dyadic Adjustment Scale. Results: Women used proportionately greater amounts of confrontive coping, accepting responsibility, seeking social support, and escape/avoidance when compared to men, while men used proportionately greater amounts of distancing, self-controlling, and planful problem-solving. For men and women, infertility stress was positively related to escape/avoidance and accepting responsibility, and negatively related to seeking social support, planful problem-solving, and distancing. Conclusions: By analyzing relative coping scores, this study identified key gender differences in how men and women cope with infertility. This was particularly true for men’s coping processes that had previously remained hidden because of less frequent use of coping strategies when compared to women

Feasibility and acceptability of a home-based physical activity program for postnatal women with depressive symptoms: A pilot study

Background Most postnatal women are inactive. Since new mothers, particularly those with heightened depressive symptoms experience several challenges to being active such as lack of time and childcare, home-based programs using hired exercise equipment may help overcome these barriers. This study tested the feasibility and acceptability of a home based treadmill intervention among postpartum women with heightened depressive symptoms. Methods Participants were 11 new mothers (3–9 months postpartum) who at baseline were insufficiently active and experiencing heightened depressive symptoms (based on the Edinburgh Postnatal Depression Scale). Following participation in a 12-week physical activity support program (which included free treadmill hire and access to a purposely designed smartphone web-app), semi-structured interviews were conducted with participants. Depressive symptoms were assessed at weeks 4 and 8 and change in depressive symptoms was analysed using repeated-measures analysis of variance (ANOVA). Thematic analyses were used to identify key themes in qualitative data. Results Quantitative data showed that there was a significant change over time with depressive symptoms decreasing from weeks 0–4 (mean difference = −5.9, 95% CI = −8.7, −5.5) and overall from weeks 0–8 (mean difference = −7.6, 95% CI = −9.8, −3.1). Postpartum women perceived the program to be convenient, flexible and acceptable. Women suggested that the program was useful in overcoming key barriers to physical activity and perceived that the program increased their physical activity and improved psychological health. Conclusion A home-based physical activity program involving cost-free exercise equipment hire was feasible and well accepted by postpartum women. The effectiveness of this program for increasing physical activity and improving mental health in this population should be further tested

The economic implications of HLA matching in cadaveric renal transplantation.

Abstract Background: The potential economic effects of the allocation of cadaveric kidneys on the basis of tissue-matching criteria are controversial. We analyzed the economic costs associated with the transplantation of cadaveric kidneys with various numbers of HLA mismatches and examined the potential economic benefits of a local, as compared with a national, system designed to minimize HLA mismatches between donor and recipient in first cadaveric renal transplantations. Methods: All data were supplied by the U.S. Renal Data System. Data on all payments made by Medicare from 1991 through 1997 for the care of recipients of a first cadaveric renal transplant were analyzed according to the number of HLA-A, B, and DR mismatches between donor and recipient and the duration of cold ischemia before transplantation. Results: Average Medicare payments for renal-transplant recipients in the three years after transplantation increased from $60,436 per patient for fully HLA-matched kidneys (those with no HLA-A, B, or DR mismatches) to$80,807 for kidneys with six HLA mismatches between donor and recipient, a difference of 34 percent (P\u3c0.001). By three years after transplantation, the average Medicare payments were $64,119 for transplantations of kidneys with less than 12 hours of cold-ischemia time and$74,997 for those with more than 36 hours (P\u3c0.001). In simulations, the assignment of cadaveric kidneys to recipients by a method that minimized HLA mismatching within a local geographic area (i.e., within one of the approximately 50 organ-procurement organizations, which cover widely varying geographic areas) produced the largest cost savings ($4,290 per patient over a period of three years) and the largest improvements in the graft-survival rate (2.3 percent) when the potential costs of longer cold-ischemia time were considered. Conclusions: Transplantation of better-matched cadaveric kidneys could have substantial economic advantages. In our simulations, HLA-based allocation of kidneys at the local level produced the largest estimated cost savings, when the duration of cold ischemia was taken into account. No additional savings were estimated to result from a national allocation program, because the additional costs of longer cold-ischemia time were greater than the advantages of optimizing HLA matching

Metal nanofilm in strong ultrafast optical fields

We predict that a metal nanofilm subjected to an ultrashort (single oscillation) optical pulse of a high field amplitude $\sim 3 \mathrm{V/\AA}$ at normal incidence undergoes an ultrafast (at subcycle times $\lesssim 1 \mathrm{fs}$) transition to a state resembling semimetal. Its reflectivity is greatly reduced, while the transmissivity and the optical field inside the metal are greatly increased. The temporal profiles of the optical fields are predicted to exhibit pronounced subcycle oscillations, which are attributed to the Bloch oscillations and formation of the Wannier-Stark ladder of electronic states. The reflected, transmitted, and inside-the-metal pulses have non-zero areas approaching half-cycle pulses. The effects predicted are promising for applications to nanoplasmonic modulators and field-effect transistors with petahertz bandwidth

Clinical effectiveness of baclofen for the treatment of alcohol dependence: A review

Baclofen, an agonist at the B subunit of gaba-aminobutyric acid receptor, possesses pharmacologic properties that may confer utility for the treatment of alcohol dependence. Research suggests that not only can it be useful in promoting maintenance of alcohol abstinence but also it may play a key role in decreasing alcohol cravings and anxiety often associated with alcohol dependence. To assess the benefit of baclofen for alcohol dependence, a review of the literature was conducted to identify published data investigating this off-label treatment. Four randomized controlled trials to date have been published and were included in this review. Although primary outcomes differ between studies, patients randomized to baclofen experience higher rates of abstinence from alcohol than those taking placebo in two of the trials. Secondary analyses indicate that baclofen is safe in patients with alcohol dependence, including those with moderate to severe liver cirrhosis, and may provide beneficial anxiolytic effects. Despite some positive data, the largest available randomized controlled trial failed to find any differences between baclofen and placebo. In all studies, individuals with severe medical comorbidities, seizure disorders, and psychiatric disorders were excluded from trials, which may limit external validity. In summary, there may be beneficial effects from using baclofen for the treatment of alcohol dependence; however, limited conclusions can be drawn from the small number of studies currently available for review. Larger well-designed trials are needed to further define baclofen’s role for the treatment of alcohol dependence

Voting and the Cardinal Aggregation of Judgments

The paper elaborates the idea that voting is an instance of the aggregation of judgments, this being a more general concept than the aggregation of preferences. To aggregate judgments one must first measure them. I show that such aggregation has been unproblematic whenever it has been based on an independent and unrestricted scale. The scales analyzed in voting theory are either context dependent or subject to unreasonable restrictions. This is the real source of the diverse 'paradoxes of voting' that would better be termed 'voting pathologies'. The theory leads me to advocate what I term evaluative voting. It can also be called utilitarian voting as it is based on having voters express their cardinal preferences. The alternative that maximizes the sum wins. This proposal operationalizes, in an election context, the abstract cardinal theories of collective choice due to Fleming and Harsanyi. On pragmatic grounds, I argue for a three valued scale for general elections