Acceptability of a novel vaginal microbicide during a safety trial among low-risk women

CONTEXT: The increasing recognition that women who are unable or unwilling to discuss or use condoms with their sexual partners need female-controlled methods for preventing sexually transmitted diseases (STDs), including HIV, has led to considerable focus on the development of vaginal microbicides. While many such products are being tested for safety and effectiveness, clinical trials generally overlook another key factor in a product's impact on infection rates-its acceptability to users. METHODS: A Phase I clinical trial of a microbicidal gel included an assessment of the product's acceptability among 27 low-risk participants. Information on acceptability was gathered from structured interviews, participants' daily diaries and unstructured exit interviews. RESULTS: Participants reported only minor side effects of product use, such as itching, burning and difficulty urinating; two women developed candida infections while participating in the study. None of the side effects could be conclusively linked to use of the gel. Some women noted product discharge and messiness as drawbacks of the method, but this experience varied according to how often the women applied the gel. For example, one-third of those who used it once daily said that at least some of the time, it was too "wet or drippy," compared with two-thirds of women who inserted the gel twice a day. However, participants considered these "nuisance factors" that could be outweighed by the potential protective characteristics of the product. The majority reported that they would use the product if it were available and proven efficacious, and if they perceived that they were at risk of STD infection. CONCLUSIONS: Additional testing of this product is urgently needed. Furthermore, as other products approach Phase I testing, acceptability assessments should be a key component of clinical trials.     

Safety and tolerability of lamotrigine for bipolar disorder.

Tolerability and safety are important considerations in optimising pharmacotherapy for bipolar disorder. This paper reviews the tolerability and safety of lamotrigine, an anticonvulsant recommended in the 2002 American Psychiatric Association guidelines as a first-line treatment for acute depression in bipolar disorder and one of several options for maintenance therapy. This paper reviews the tolerability and safety of lamotrigine using data available from a large programme of eight placebo-controlled clinical trials of lamotrigine enrolling a total of nearly 1800 patients with bipolar disorder. This review is the first to collate all the safety information from these clinical trials, including data from four unpublished studies. The results these trials in which 827 patients with bipolar disorder were given lamotrigine as monotherapy or adjunctive therapy for up to 18 months for a total of 280 patient-years of exposure demonstrated that lamotrigine is well-tolerated with an adverse-event profile generally comparable with that of placebo. The most common adverse event with lamotrigine was headache. Lamotrigine did not appear to destabilise mood and was not associated with sexual adverse effects, weight gain, or withdrawal symptoms. Few patients experienced serious adverse events with lamotrigine, and the incidence of withdrawals because of adverse events was low. Serious rash occurred rarely (0.1% incidence) in the clinical development programme including both controlled and uncontrolled clinical trials. These findings - considered in the context of data showing lamotrigine to be effective for bipolar depression - establish lamotrigine as a well-tolerated addition to the psychotropic armamentarium.     

Organ slice viability extended for pathway characterization: an in vitro model to investigate fibrosis.

Liver slice viability is extended to 96 h for rat, expanding the use of this in vitro model for studying mechanisms of injury and repair, including pathways of fibrosis. The contributing factors to increased organ slice survival consist of the use of a preservation solution for liver perfusion and slice preparation, obtaining rats that are within the weight range of 250-325 g, placing a cellulose filter atop the titanium mesh roller-insert to support the slice, and maintaining the slices in an optimized culture medium which is replaced daily. The liver slices remain metabolically active, synthesizing adenosine triphosphate (ATP), glutathione, and glycogen, and exhibit preserved organelle integrity and slice morphology. Slice preparation results in 2-cut surfaces which likely triggers a repair and regenerative response. The fibrogenic pathways are evident by the activation of stellate cells, the proliferation of myofibroblast-like cells, and an increased collagen deposition by 48 h. Markers indicative of activated stellate cells, alpha-smooth muscle actin, collagen 1a1, desmin, and HSP47 are substantiated by real time-PCR. Increased staining of alpha-smooth muscle actin initially around the vessels and by 72-96 h in the tissue is accompanied by increased collagen staining. Microarray gene expression revealed extracellular matrix changes with the up-regulation of cytoskeleton, filaments, collagens, and actin genes; and the down-regulation of genes linked with lipid metabolism. The improvements in extending liver slice survival, in conjunction with its three-dimensional multi-cellular complexity, increases the application of this in vitro model for investigating pathways of injury and repair, and fibrosis.     

Contemporary Health-Related Decision Aids: Tools for Social Work Practice

The escalating complexity in health-related decisions that people face have important implications for social work interventions. This article explores the nature of these implications within the context of decisional conflict, shared decision making, and the use of decision aids. In addition, the authors present the findings of a content analysis of 29 contemporary health-related decision aids. Emergent categories from this analysis are presented as a resource for social workers as they encounter, adapt, and create decision aids in their work to help address the health-related needs of their clients.     

Interpreting DNA Evidence in Paternity Cases

The ability of jurors and juries to comprehend and utilise scientific evidence in Australian criminal trials is discussed in the context of impediments which include legislation, proce-dural law, and the inherent scientific complexity of some evidence. Existing Australian and international literature on jury performance with expert evidence is examined, and recent doctoral research utilising mock juries, real jurors and forensic scientists, is highlighted.

“Good communication with the jury is afield in which anecdote, self-assurance and self-delusion abound, within the ranks of the legal profession and the judiciary.”