Barriers of enrolment in HIV vaccine trials: a review of HIV vaccine preparedness studies

Barriers to participation in an HIV vaccine trial have been examined in many HIV vaccine preparedness studies (VPS). These barriers can be understood in terms of the locus of the barrier (personal vs. social) and the nature of the barrier (risk vs. cost). Another type of barrier is perceived misconceptions. In this systematic review, we categorize barriers, and compare these barriers between the Organization for Economic Co-operation and Development (OECD) countries and the non-OECD countries. In the OECD countries, we retrieved 25 studies reporting personal risks (PR), 9 studies reporting social risks (SR), 10 studies reporting personal costs (PC), and 16 studies reporting misconceptions. In the non-OECD countries, we retrieved 27 studies reporting PR, 19 studies reporting SR, 18 studies reporting PC, 1 study reporting social costs (SC), and 13 studies reporting misconceptions. Important PR were “adverse effects” and “vaccine-induced seropositivity”, “distrust of institutions”, and “temptation to have unsafe sex” in men who have sex with men (MSM). “Discrimination” was a common SR. “Time commitment” was an important PC, and “family commitments” were a SC in one non-OECD country. “HIV infection from the vaccine” was a common misconception. Both the OECD and the non-OECD countries have similar barriers, and people's decisions to participate in a clinical trial involve multiple barriers. However, these barriers apply to hypothetical HIV vaccine trials, and barriers for actual vaccine trials need further assessment.     

Combined photodynamic therapy with verteporfin and intravitreal bevacizumab for choroidal neovascularization in age-related macular degeneration

PURPOSE: To examine the 7-month results for patients treated with combined photodynamic therapy (PDT) with verteporfin and intravitreal bevacizumab for choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). METHODS: This is a retrospective series of 24 eyes with juxtafoveal or subfoveal CNV secondary to AMD. Patients were treated with PDT with verteporfin and 1.25 mg of intravitreal bevacizumab. All patients were naive to treatment and had either treatment within a 14-day interval. Main outcome measures were visual acuity stabilization (defined as no change or a gain in visual acuity) and retreatment rate. RESULTS: At the 7-month follow-up, 20 (83%) of 24 patients had stabilization of visual acuity. Sixteen eyes (67%) had improvement in visual acuity. Mean improvement in visual acuity (n = 24) was 2.04 Snellen lines. Fifteen eyes (63%) required only a single combined treatment for CNV resolution. There were no complications, including endophthalmitis, uveitis, and ocular hypertension. CONCLUSION: The results of this study suggest that combined treatment of PDT with verteporfin and intravitreal bevacizumab may be useful in treating neovascular AMD by reducing retreatment rates and improving visual acuity. Further investigation with large, controlled trials is warranted to outline the appropriate treatment paradigm for combination therapy.     

Alterations in Ca2+ binding by and composition of the cardiac sarcolemmal membrane in chronic diabetes.

Chronic streptozotocin-induced diabetes in rats was associated with a significant loss in the ability of isolated cardiac sarcolemmal membranes to bind Ca2+. Administration of insulin to the diabetic rats normalized the sarcolemmal Ca2+ binding capacity. The content of sialic acid residues, which are considered to represent a superficial Ca2+ pool in sarcolemma, was decreased in preparations from diabetic rats, and this change also was reversible upon insulin treatment of the diabetic rats. Treatment of sarcolemma with neuraminidase decreased Ca2+ binding by 37% in control preparations but had no effect on diabetic preparations. Diphosphatidylglycerol content was decreased but other acidic phospholipids such as phosphatidylinositol and phosphatidylserine, which also bind Ca2+, were not altered during diabetes. An increase in lysophosphatidylcholine and a decrease in phosphatidylethanolamine contents were observed in membranes isolated from diabetic rats. These results suggest that some alterations occur in Ca2+ binding and composition of heart sarcolemma in chronically diabetic rats and may provide further insight into the pathogenesis of diabetic cardiomyopathy.     

Effects of chlorpromazine and imipramine on rat heart subcellular membranes

The effects of chlorpromazine and imipramine at concentrations ranging from 25 to 120 (μm on ATPase activities, as well as calcium binding and uptake abilities of the rat heart subcellular membranes, were studied in vitro. Chlorpromazine significantly decreased calcium binding. Mg²⁺ ATPase and Na⁺?K⁺ ATPase activities of the sarcolemmal fraction, whereas imipramine decreased calcium binding, Ca²⁺ ATPase and Mg²⁺ ATPase activities. Chlorpromazine also produced significant inhibition of the calcium binding and uptake abilities of the microsomal and mitochondrial fractions, while imipramine depressed the mitochondrial calcium uptake activity only at concentrations of 80 μm or higher. The mitochondrial respiratory and oxidative phosphorylation activities were depressed at high concentrations of these drugs. Since different membrane systems have been considered to be involved in the regulation of heart function and metabolism, the observed decreases in ATPase and calcium-accumulating activities of the heart subcellular membranes may represent one of the molecular mechanisms for the cardiodepressant actions of chlorpromazine and imipramine.     

Adenosine A₁ receptors do not play a major role in the regulation of lipogenic gene expression in hepatocytes

Activation of adenosine A? receptors was reported to promote fatty acid synthesis in AML-12 cells, by increasing the expression of SREBP-(1c) (sterol regulatory binding protein 1c) and FAS (fatty acid synthase). Since these findings have important therapeutic implications for the discovery of adenosine A? receptor agonists, further studies were undertaken to determine the expression and functional relevance of adenosine A? receptor in the liver. To that end, we used two classes of distinct adenosine A? receptor agonists: CPA (N?-cyclopentyl-adenosine), a full agonist and GS-9667 (2-{6-[((1R,2R)-2-hydroxycyclopentyl)-amino]purin-9-yl}(4S,5S,2R,3R)-5-[(2-fluorophenylthio)methyl]-oxolane-3,4-diol), a partial agonist. Treatment of AML-12 cells, HepG2 cells and primary human hepatocytes with either CPA or GS-9667 did not increase the gene expression of SREBP-(1c) or FAS. Furthermore, in AML-12 and HepG2 cells, CPA did not antagonize forskolin-stimulated cAMP production, a characteristic of adenosine A? receptor activation, indicating that these cells lack adenosine A? receptor function. Consistent with this finding, adenosine A? receptor gene expression was found to be very low and adenosine A? receptor protein levels were hardly detectable by radioligand binding assays in hepatic cell lines such as AML-12 and HepG2 as well as in both mouse and human liver tissues. Finally, acute treatment with adenosine A? receptor agonist GS-9667 had no significant effect on gene expression of both SREBP-(1c) and FAS in livers of Sprague Dawley rats. Taken together, our data suggest that the expression of adenosine A? receptor is too low to play a major role in the regulation of lipogenic gene expression in hepatocytes.     

Outcomes and reasons for dacryocystorhinostomy (DCR) at KCMC, a Tanzanian referral hospital, 2001-2006

Background

External dacryocystorhinostomy (DCR) is a surgical intervention aimed to treat blocked nasolacrimal ducts of almost all causes. To date there is only limited data available from the Sub Saharan African setting.

Objectives

This study aimed to provide further information of the outcomes of DCR in Africa.

Methods

Records of all patients undergoing external DCR operations from January 2001 to April 2006 were systematically searched. 55 patients were identified and notes were available for 45 patients.

Results

Discharge and epiphora were resolved in 90.9% (30/33) and 84.4% (27/32) of patients respectively. Over half the cases (51.1%) were children. The commonest reason for operation was chronic dacryocystitis (51.1%). Outcomes for DCR were not significantly different for either children or adults and a clear improvement of symptoms was found in the vast majority of cases.

Conclusion

This study provides information on the outcomes of DCR in the African population. An 84.4% cure rate of epiphora and 90.9% cure rate of discharge is comparable with findings in other developing countries. This study supports the continued use of this intervention in skilled hands for treatment of blocked nasolacrimal duct.     

HIV vaccine preparedness studies in the non-organization for economic co-operation and development (non-OECD) countries

HIV vaccine development remains an urgent priority. Vaccine preparedness studies to assess feasibility are an important precursor to HIV vaccine trials. Studies such as these have taken place in many non-Organization for Economic Co-operation and Development (non-OECD) countries using diverse cohorts. This article is a systematic review of retention rates and willingness to participate (WTP) in HIV vaccine trials. Studies took place in Brazil, the Democratic Republic of Congo, Haiti, India, Russia, Thailand, and several sub-Saharan African countries. Studies generally reported recruitment of high-risk individuals. Of 33 studies we identified, retention was assessed in 16 studies, and the 12-month retention ranged from 77 to 85%. Willingness to participate was assessed in 21 studies. Willingness to participate ranged from 23 to 100%, and increased knowledge was associated with an increased WTP. Vaccine preparedness studies have taken place using diverse cohorts in the non-OECD countries. In general, retention rates and WTP have been adequate to conduct HIV vaccine trials. Educational programs to improve knowledge about HIV vaccines may contribute to better follow-up and an increased WTP in these countries.