The Canadian “National Program for hemophilia mutation testing” database: A ten‐year review

A reference genotyping laboratory was established in 2000 at Queen's University, Kingston, to provide genetic testing for Hemophilia A (HA) and B (HB) and create a Canadian mutation database. Canadian hemophilia treatment centers and genetics clinics provided DNA and clinical information from November 2000 to March 2011. The factor VIII (F8) gene was analyzed in 1,177 patients (47% of HA population) and 787 female family members and the factor IX (F9) gene in 267 patients (47% of HB population) and 123 female family members, using Southern Blot, PCR, conformation sensitive gel electrophoresis, and/or direct sequencing. The mutation detection rates for HA and HB were 91% and 94%, respectively. 380 different F8 mutations were identified: inversions of intron 22 and intron 1, 229 missense, 45 nonsense, eight deletions, 70 frameshifts, 25 splice site, and one compound mutation with a splice site and intron 1 inversion. Of these mutations, 228 were novel to the Hemophilia A Database (HADB, http://hadb.org.uk/ ). A total 125 different F9 mutations were identified: 80 missense, 12 frameshift, 12 splice site, nine nonsense and seven promoter mutations, three large deletions, and two compound mutations with both missense and nonsense changes. Of these mutations, 36 were novel to the International Haemophilia B Mutation database ( http://www.kcl.ac.uk/ip/petergreen/haemBdatabase.html ). The Canadian F8 and F9 mutation database reflects the allelic heterogeneity of HA and HB, and is similar to previously described populations. This report represents the largest and longest duration experience of a national hemophilia genotyping program documented, to date. Am. J. Hematol. 88:1030–1034, 2013. © 2013 Wiley Periodicals, Inc.     

Two New Hemoglobin Variants: Hb Tallahassee [α3(A1)Ser→Tyr; HBA2: c.11C>A] and Hb Madison-NC [β119(GH2)Gly→Ser; HBB: c.358G>A]

Of the 1570 reported hemoglobin (Hb) variants detected to date, 390 are α2-globin chain (some variants have yet to be identified by DNA analyses and are therefore presumed) and 827 are the result of mutations of the β-globin chain. Due to their location on the Hb structure, only a minority of these variants result in a clinical phenotype; most are silent and are detected during routine surveillance, are found incidentally during other disease-related investigations or following newborn screening programs. In this report we discuss phenotype/genotype and molecular characteristics of two new Hb variants, both of which were clinically silent. One is an α2-globin chain variant located at codon 3 [α3(A1)Ser→Tyr; HBA2: c.11C?>?A] named Hb Tallahassee and the other is a β-globin chain variant located at codon 119 [β119(GH2)Gly→Ser; HBB: c.358G?>?A] called Hb Madison-NC.     

Dydrogesterone treatment for menstrual-cycle regularization in routine clinical practice: a multicenter observational study

Dydrogesterone is an oral retroprogesterone widely used to treat progesterone deficiencies, including irregular menstrual cycles (MCs). This prospective, non-interventional, single-arm, post-marketing, observational study evaluated the effects of dydrogesterone on MC regularization. Women aged 18–40 years who had been prescribed dydrogesterone to treat irregular MCs due to progesterone deficiency were enrolled across 64 centers in Russia, Ukraine, Kazakhstan and Uzbekistan. Study objectives included: patients reporting ≥1 regular MC during treatment; the number of regular MCs after the end of treatment over a 6-month follow-up (FU) period. In total, 996 women were enrolled. Of those who completed treatment, 946/955 patients (99.1%) achieved ≥1 regular MC. During FU, 680/860 patients (79.1%) maintained ≥6 regular MCs. Patient grading of menstrual pain and anxiety decreased significantly during treatment (p?≤?0.0001 versus baseline); this persisted during FU. Dydrogesterone was associated with high or very high patient satisfaction (856/955; 89.6%); the clinical response was considered good or excellent in 819/955 patients (85.8%). In total, 16/986 patients (1.6%) reported an adverse event (AE); two had serious AEs (SAEs) (unrelated to treatment) and three discontinued treatment due to non-SAEs. Dydrogesterone therapy was effective in achieving MC regularization and reducing menstrual pain and anxiety, during both treatment and 6-month FU.     

“It is easier for me to shoot up”: stigma,abandonment, and why HIV-positive drug users in Russia fail to link to HIV care

Many HIV-positive people who inject drugs (PWID) globally are not receiving HIV care. This represents a major challenge among key populations to end the global HIV epidemic. This qualitative study explored the process and associated barriers of linking HIV-positive PWID who are in addiction treatment to HIV care in St. Petersburg, Russia. We conducted three focus groups and seven semi-structured interviews with participants in the LINC (“Linking Infectious and Narcology Care”) project at addiction and HIV hospitals in St. Petersburg. The sample consisted of 25 HIV-infected patients with opioid dependence and seven health-care providers, including addiction and infectious disease physicians and case managers. A variety of intertwining factors influence effective engagement of PWID with HIV treatment. Stigma, problematic patient–provider relationships, and fragmented health care were the main challenges for HIV care initiation by PWID, which were further exacerbated by injection drug use. Effective linkage of PWID to HIV care requires acknowledging and addressing stigma’s role and different perspectives of patients and providers.     

Breast cancer as photodynamic therapy target: Enhanced therapeutic efficiency by overview of tumor complexity

Photodynamic therapy is a minimally invasive and clinically approved procedure for eliminating selected malignant cells with specific light activation of a photosensitizer agent. Whereas interstitial and intra-operative approaches have been investigated for the ablation of a broad range of superficial or bulky solid tumors such as breast cancer, the majority of approved photodynamic therapy protocols are for the treatment of superficial lesions of skin and luminal organs. This review article will discuss recent progress in research focused mainly on assessing the efficacies of various photosensitizers used in photodynamic therapy, as well as the combinatory strategies of various therapeutic modalities for improving treatments of parenchymal and/or stromal tissues of breast cancer solid tumors. Cytotoxic agents are used in cancer treatments for their effect on rapidly proliferating cancer cells. However, such therapeutics often lack specificity, which can lead to toxicity and undesirable side effects. Many approaches are designed to target tumors. Selective therapies can be established by focusing on distinctive intracellular (receptors, apoptotic pathways, multidrug resistance system, nitric oxide-mediated stress) and environmental (glucose, pH) differences between tumor and healthy tissue. A rational design of effective combination regimens for breast cancer treatment involves a better understanding of the mechanisms and molecular interactions of cytotoxic agents that underlie drug resistance and sensitivity.