'The tabloid test': a qualitative interview study on the function and purpose of termination of pregnancy review committees in Victoria, Australia.

BACKGROUND: Termination of pregnancy (TOP) is not an uncommon procedure. Availability varies greatly between jurisdictions; however, additional institutional processes beyond legislation can also impact care and service delivery. This study serves to examine the role institutional processes can play in the delivery of TOP services, in a jurisdiction where TOP is lawful at all gestations (Victoria, Australia). As per the Abortion Law Reform Act 2008, TOPs post-24 weeks require the approval of two medical practitioners. However, in Victoria, hospitals that offer post-24 week TOPs generally require these cases to additionally go before a termination review committee for assessment prior to the service being provided. These committees are not stipulated in legislation. Information about these committees and how they operate is scarce and there is minimal information available to the public. METHODS: To trace the history, function, and decision-making processes of these committees, we conducted a qualitative interview study. We interviewed 27 healthcare professionals involved with these committees. We used purposive sampling to gain perspectives from a range of professions across 10 hospitals. Interviews were transcribed verbatim, identifying details removed and inductive thematic analysis was performed. RESULTS: Here, we report the three main functions of the committees as described by participants. The functions were to protect: (1) outward appearances; (2) inward functionality; and/or, (3) service users. Function (1) could mean protecting the hospital's reputation, with the "Herald Sun test"-whether the TOP would be acceptable to readers of the Herald Sun, a tabloid newspaper-used as a heuristic. Function (2) related to logistics within the hospital and protecting the psychological wellbeing and personal reputation of healthcare professionals. The final function (3) related to ensuring patients received a high standard of care. CONCLUSIONS: The primary functions of these committees appear to be about protecting hospitals and clinicians within a context where these procedures are controversial and stigmatized. The results of this study provide further clarity on the processes involved in the provision of TOPs at later gestations from the perspectives of the healthcare professionals involved. Institutional processes beyond those required by legislation are put in place by hospitals. These findings highlight the additional challenges faced by patients and their providers when seeking TOP at later gestations.

Abortion can be difficult to access. In Victoria, Australia, under the law, abortion is allowed at any time during a pregnancy­although after you have been pregnant for more than 24 weeks, the approval of two doctors is required. However, hospitals in Victoria that offer late abortions require more than the approval of two doctors. Hospitals have put in place committees that review each case and make a decision about whether the hospital will provide the abortion. There is not a lot of information about these committees­we do not know exactly why they exist, what they are for, or how they work. To find out, we interviewed doctors and other healthcare professionals (like midwives) who were involved in these committees. In this paper, we report the reasons these people gave for why the committees exist and what they are for. There were three main reasons. The first purpose of the committee is so the hospital does not get criticised in newspapers or by other people outside the hospital for performing these late abortions. The second reason is to help and protect those inside the hospital. For example, having a committee means that the doctors do not have to make the decisions themselves. People also said that the committees think about how the staff are feeling. The third reason is so that the hospitals provide the best care they can, and that they can continue to provide late abortions in the future. With this study, we found out some more important information about these committees that we did not have before. What we found shows that it is not just the law that matters­other things can also affect whether you can get an abortion.

Medical Abortion in Australia: What Are the Clinical and Legal Risks? Is Medical Abortion Over-regulated?

This article examines the clinical and legal risks of early medical abortion. After providing an overview of the history of mifepristone in Australia, the evidence concerning the efficacy and safety of medical abortion is discussed. It is argued that the negligible medical risks associated with mifepristone do not justify the restrictive regulatory measures imposed on medical practitioners. The article then turns to the legal risks and considers whether medical practitioners are vulnerable to prosecution under existing State and Territory laws. It is argued that providing early medical abortion services in a number of jurisdictions is legally ambiguous, potentially posing a threat of prosecution to medical practitioners. The need for law reform is evident by the fact that in four jurisdictions it remains in the criminal statutes, creating legal uncertainty for both medical practitioners and women. The article concludes that there is sufficient evidence to allow some "demedicalisation" of medical abortion. However, this is only possible if the legal status of abortion in State and Territory laws is addressed.

Pharmacokinetics of high-dose abetimus sodium in normal subjects with specific assessment of effect on coagulation.

Abetimus sodium is an oligonucleotide-based investigational drug designed to treat patients with lupus nephritis by specifically reducing anti-double-stranded DNA antibody levels. The safety and pharmacokinetics of abetimus were evaluated in 24 healthy volunteers at intravenous doses of 600 mg, 1200 mg, and 2400 mg. The mean half-life ranged from 0.8 to 1.5 hours. Maximum exposure assessed by maximum observed plasma concentration was dose proportional. Total exposure assessed by area under the plasma concentration-time curve was dose proportional between 1200-mg and 2400-mg doses and greater than proportionate between the 600-mg and 1200-mg doses. Abetimus was well tolerated in all dose groups, with adverse events observed in 33.3% (2/6) of placebo subjects and 16.7% (3/18) subjects receiving abetimus. No clinically significant effects were observed on laboratory values, vital signs, or electrocardiogram, with the exception of a transient, dose-dependent, prolongation in activated partial thromboplastin time. In vitro coagulation studies suggested that the effect on activated partial thromboplastin time was attributable to a nonspecific interaction rather than specific factor depletion. Exposure to abetimus at intravenous doses of 600 mg, 1200 mg, and 2400 mg was well tolerated. Total exposure assessed by area under the plasma concentration-time curve was greater than dose proportional across the dose range of 600 mg to 2400 mg.

Anti-inflammatory effects of LJP 1586 [Z-3-fluoro-2-(4-methoxybenzyl)allylamine hydrochloride], an amine-based inhibitor of semicarbazide-sensitive amine oxidase activity.

Semicarbazide-sensitive amine oxidase (SSAO, amine oxidase, copper-containing 3, and vascular adhesion protein-1) is a copper-containing enzyme that catalyzes the oxidative deamination of primary amines to an aldehyde, ammonia, and hydrogen peroxide. SSAO is also involved in leukocyte migration to sites of inflammation, and the enzymatic activity of SSAO is essential to this role. Thus, inhibition of SSAO enzyme activity represents a target for the development of small molecule anti-inflammatory compounds. Here, we have characterized the novel SSAO inhibitor, Z-3-fluoro-2-(4-methoxybenzyl)allylamine hydrochloride (LJP 1586), and assessed its anti-inflammatory activity. LJP 1586 is a potent inhibitor of rodent and human SSAO activity, with IC(50) values between 4 and 43 nM. The selectivity of LJP 1586 was confirmed with a broad panel of receptors and enzymes that included the monoamine oxidases A and B. Oral administration of LJP 1586 resulted in complete inhibition of rat lung SSAO, with an ED(50) between 0.1 and 1 mg/kg, and a pharmacodynamic half-life of greater than 24 h. In a mouse model of inflammatory leukocyte trafficking oral dosing with LJP 1586 resulted in significant dose-dependent inhibition of neutrophil accumulation, with an effect comparable to that of anti-leukocyte function-associated antigen-1 antibody. In a rat model of LPS-induced lung inflammation, administration of 10 mg/kg LJP 1586 resulted in a 55% significant reduction in transmigrated cells recovered by bronchoalveolar lavage. The results demonstrate that a selective, orally active small molecule inhibitor of SSAO is an effective anti-inflammatory compound in vivo and provide further support for SSAO as a therapeutic anti-inflammatory target.

Design, synthesis, and biological evaluation of semicarbazide-sensitive amine oxidase (SSAO) inhibitors with anti-inflammatory activity.

In an attempt to examine the effect of inhibition of semicarbazide-sensitive amine oxidase (SSAO; EC 1.4.3.6, also known as VAP-1) as a novel anti-inflammatory target, the structure/mechanism based design and synthesis of a series of novel hydrazino-containing small molecules are described. The in vitro biological results show that compounds 4a,c are highly potent SSAO inhibitors with notable selectivity toward SSAO over monoamine oxidases A and B (MAO-A and MAO-B). SAR studies based on compound 4c were performed, and the results are discussed. The most potent and selective compound, 4a (IC(50) = 2 nM), is an orally active, competitive, and apparently irreversible inhibitor of SSAO that is effective at reducing disease incidence and severity in an in vivo animal disease model of multiple sclerosis.

Anti-inflammatory effects of inhibiting the amine oxidase activity of semicarbazide-sensitive amine oxidase.

Human semicarbazide-sensitive amine oxidase (SSAO) or vascular adhesion protein-1 (VAP-1) is a copper-containing amine oxidase (AOC3, EC 1.4.3.6) that has both enzymatic and adhesive function. SSAO catalyzes the oxidative deamination of primary amines, resulting in the formation of the corresponding aldehyde and release of hydrogen peroxide and ammonia. Membrane-bound SSAO is an inflammation-inducible endothelial cell adhesion molecule that mediates the interaction between leukocytes and activated endothelial cells in inflamed vessels. Both the direct adhesive and enzymatic functions seem to be involved in the adhesion cascade. LJP 1207 [N'-(2-phenyl-allyl)-hydrazine hydrochloride] is a potent (human SSAO IC(50) = 17 nM), selective, and orally available SSAO inhibitor that blocks both the enzymatic and adhesion functions of SSAO/VAP-1. In a mouse model of ulcerative colitis, LJP 1207 significantly reduces mortality, loss of body weight, and colonic cytokine levels. Quantitative histopathological assessment of colitis activity in this model showed a highly significant suppression of inflammation, injury, and ulceration scores in the animals treated with the SSAO/VAP-1 inhibitor. LJP 1207 also reduced serum levels of tumor necrosis factor-alpha and interleukin 6 in lipopolysaccharide (LPS)-challenged mice and prolonged survival post-LPS-induced endotoxemia. Therapeutic and prophylactic administration of LJP 1207 in the rat carrageenan footpad model also markedly inhibited swelling and inflammation. Overall, the data suggest that small molecule SSAO/VAP-1 inhibitors may provide clinical benefit in the treatment of acute and chronic inflammatory diseases.