A real-world observational cohort of patients with primary biliary cholangitis: TARGET-primary biliary cholangitis study design and rationale.

Primary biliary cholangitis (PBC) is a rare chronic cholestatic liver disease that may progress to biliary cirrhosis if left untreated. The first-line therapy for PBC is ursodeoxycholic acid (UDCA). Unfortunately, 1 of 3 patients does not respond to UDCA. These patients are at risk for developing clinical events, including cirrhosis, complications of portal hypertension, hepatocellular carcinoma, liver transplant, or death. Recently, the U.S. Food and Drug Administration approved obeticholic acid to be used in certain patients with PBC. Off-label therapies are also used, and several other therapies are currently under evaluation. Real-world effectiveness of newly approved and off-label therapies remains unknown. TARGET-PBC is a 5-year, longitudinal, observational study of patients with PBC that will evaluate the effectiveness of clinical practice interventions and provide practical information unobtainable in registration trials. Enrollment will take place at both academic and community sites. In addition to consenting to medical records review, participants will be asked to provide an annual blood sample and complete patient reported outcome surveys at predetermined intervals. Any available liver biopsies will be digitally preserved. Conclusion: Key study outcomes will be the evaluation of the safety and effectiveness of PBC interventions and the assessment of disease progression under real-world conditions. (Hepatology Communications 2018;2:484-491).

Chlorpheniramine Analogues Reverse Chloroquine Resistance in Plasmodium falciparum by Inhibiting PfCRT.

The emergence and spread of malaria parasites that are resistant to chloroquine (CQ) has been a disaster for world health. The antihistamine chlorpheniramine (CP) partially resensitizes CQ-resistant (CQR) parasites to CQ but possesses little intrinsic antiplasmodial activity. Mutations in the parasite's CQ resistance transporter (PfCRT) confer resistance to CQ by enabling the protein to transport the drug away from its site of action, and it is thought that resistance-reversers such as CP exert their effect by blocking this CQ transport activity. Here, a series of new structural analogues and homologues of CP have been synthesized. We show that these compounds (along with other in vitro CQ resistance-reversers) inhibit the transport of CQ via a resistance-conferring form of PfCRT expressed in Xenopus laevis oocytes. Furthermore, the level of PfCRT-inhibition was found to correlate well with both the restoration of CQ accumulation and the level of CQ resensitization in CQR parasites.

Chiral Birch reduced tertiary phosphines: precursors to asymmetric 1,2-cyclohexenebis(tertiary phosphines).

The first examples of an optically active Birch reduced tertiary phosphine, viz. (R(P))-(cyclohexa-2,5-dienyl)(3-pentyl)phenylphosphine, and successful hydrophosphination of the related racemic ligand (±)-(cyclohexa-2,5-dienyl)(2-propyl)phenylphosphine with PHPh(2) in the presence of KOBu(t) in thf to give a 1,2-cyclohexenebis(tertiary phosphine), viz. (±)-1,2-C(6)H(8)(PPh(2))(PPhPr(i)), are described; as confirmed by crystal structure determinations of [SP-4-4-(S(P),S)]-chloro[(cyclohexa-2,5-dienyl)(3-pentyl)phenylphosphine][2-{1-(dimethylamino)ethyl}phenyl-C,N]palladium(II) and [SP-4-3-(±)]-dimethyl[(1-diphenylphosphino)(2-isopropylphenylphosphino)cyclohexene]platinum(II).

Cancer peer support programs-do they work?

Cancer can be a devastating diagnosis, creating social, emotional, financial and psychological problems. Peer support programs are based on the premise that support from others who have been through a similar experience can help reduce the negative impacts of this disease. While there is strong theoretical rationale for this, empirical evidence that would guide program planning is scarce. We conducted a systematic literature review of evaluation studies published over the last 20 years. Seventeen volunteers delivered peer support programs were reviewed, ranging from needs assessments to randomized controlled trials. The scientific quality was moderate--most lacked a theoretical framework, adequate program descriptions, data on non-participants and validated instruments. Despite these methodological shortcomings, consistent informational, emotional and instrumental benefits were identified. We provide recommendations for practitioners to improve evaluation studies and suggest a research agenda to develop better methods for assessing the contribution of peer support to quality of life.

Living with ovarian cancer: women's perspectives on treatment and treatment decision-making.

In the year 2002, 2,500 women will have been diagnosed with ovarian cancer. Treatment for ovarian cancer is arduous, involving invasive surgery, chemotherapy, and/or radiation therapy. Studies have described the side effects of ovarian cancer treatment, but little has been written about women's perspectives on receiving that treatment. This work was undertaken to describe women's perceptions of living with ovarian cancer and their experiences with treatment. Eighteen women who had been diagnosed with ovarian cancer were interviewed in depth and theme analysis was undertaken with their transcripts. Three prominent themes emerged during the analysis: 1) initial treatment plans were overwhelming, 2) involvement in treatment decision-making was minimal, and 3) treatment had many side effects and complications.

Impact of ovarian cancer perceived by women.

Ovarian cancer may be particularly challenging for women, both physically and psychologically, because of the advanced nature of the disease at the time of diagnosis, the side effects of the disease, the repetitive cycles of aggressive therapy, and the perceived loss of femininity from the removal of reproductive organs. In addition, women with this disease rarely have an opportunity for cure. Most will face the very real possibility of dying. This qualitative study examined the perspectives of women living with ovarian cancer. Eighteen women participated in interviews, in which they described their experiences living with the disease. Women reported the myriad day-to-day changes in their lives, the major challenges they had to face, and the sources to which they turned for support. Implications for the practice of oncology nurses involve assessment, an understanding of the profound impact that this illness has on both the woman and her family, and the need to access a variety of supportive care programs.

Women's experiences with recurrent ovarian cancer.

Most women with a diagnosis of ovarian cancer, because of the advanced nature of the disease at the time of diagnosis, will face the very real possibility of an early death. Thus the disease can have a significant impact on women who play a central role in the day-to-day management of family life, the nurture of children, and the care of extended family. This article reports the perspectives of women living with ovarian cancer regarding their experiences confronting recurrent disease. For this qualitative study 18 women were interviewed. Four primary themes emerged from the analysis of the verbatim interview transcripts: waiting for recurrence, facing the diagnosis of recurrence, managing treatment-related concerns, and attempting to regain control. The practice implications for oncology nurses involve understanding the significant meaning associated with monitoring tumor markers and recurrent disease, assisting women in accessing information and support, and engaging in sensitive communication.

Women's experiences with ovarian cancer: reflections on being diagnosed.

The purpose of this qualitative study was to describe the perspectives of women living with ovarian cancer about their experiences with diagnosis, treatment, and follow-up care. A convenience sample of 18 women was interviewed using an open-ended interview guide. This paper will focus on their perspectives during the peri-diagnostic period. Most of the women in this study experienced changes in their bodies--bloating, weight gain around their middles, indigestion, bowel changes, and abdominal pain. The vagueness of the symptoms and lack of awareness by the women and, in the women's opinion, health care professionals caused delays in diagnosis and initial investigations of other body systems. The symptoms were often dismissed by the women as being related to normal body changes such as childbirth, menopause, or stress responses. It was often not until the women's symptoms became severe or included pain that referrals were made to relevant specialists. At this point, many of the women were physically and emotionally spent, leaving them vulnerable and in a weakened state for confronting the diagnosis and coping with the difficult course of treatment. Clearly, the subtle, nebulous nature of the symptoms confounded the diagnosis of ovarian cancer for these women, resulting in patient delays and physician delays.