Risk factors of MDR-TB and impacts of COVID-19 pandemic on escalating of MDR-TB incidence in lower-middle-income countries: A scoping review.

The coronavirus disease 2019 (COVID-19) pandemic is affecting tuberculosis (TB) treatment in many ways that might lead to increasing the prevalence of multi-drugs-resistance tuberculosis (MDR-TB), especially in lower-middle-income-countries (LMICs). This scoping review aimed to identify the risk factors of MDR-TB and to determine the impacts of the COVID-19 pandemic on MDR-TB prevalence in LMICs. This study was reported according to the preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews (PRISMA-ScR) guideline. The relevant keywords were used to search studies in three databases (PubMed, ScienceDirect and SpringerLink) to identify the related articles. The English-written articles published from January 2012 to December 2022 that explored risk factors or causes of MDR-TB in LMICs were included. Out of 1,542 identified articles, 17 retrospective, prospective, case-control and cross-sectional studies from ten LMICs met were included in this scoping review. Twenty-one risk factors were discovered, with prior TB treatment (relapsed cases), diabetes, living area, living condition, smoking and low socioeconomic status were the main factors in developing MDR-TB during COVID-19 pandemic. The pandemic increased the MDR-TB prevalence through drug resistance transmission inside households, the distance between home and healthcare facilities and low socioeconomic status. This scoping review demonstrates how the COVID-19 pandemic has affected the rising incidence of MDR-TB in LMICs.

Effect of additional cytogenetic abnormalities on survival in arsenic trioxide-treated acute promyelocytic leukemia.

Frontline arsenic trioxide (ATO)-based treatment regimens achieve high rates of long-term relapse-free survival in treating acute promyelocytic leukemia (APL) and form the current standard of care. Refining prognostic estimates for newly diagnosed patients treated with ATO-containing regimens remains important in continuing to improve outcomes and identify patients who achieve suboptimal outcomes. We performed a pooled analysis of exclusively ATO-treated patients at a single academic institution and from the ALLG APML4 and Alliance C9710 studies to determine the prognostic importance of additional cytogenetic abnormalities and/or complex karyotype. We demonstrated inferior event-free survival for patients harboring complex karyotype (hazard ratio [HR], 3.74; 95% confidence interval [CI], 1.63-8.56; P = .002), but not for patients harboring additional cytogenetic abnormalities (HR, 2.13; 95% CI, 0.78-5.82; P = .142). These data support a role for full karyotypic analysis of all patients with APL and indicate a need for novel treatment strategies to overcome the adverse effect of APL harboring complex karyotype.

Domestic application of lessons learned by Canadian health care professionals working in international disaster settings: a qualitative research study.

BACKGROUND: Individuals with prior experience in international disaster response represent an essential source of expertise to support disaster response in their home countries. Our objective was to explore the experiences of personnel involved in international emergency health response regarding their perceptions of essential disaster response attributes and capacities and determine how these competencies apply to the Canadian context. METHODS: For this qualitative study, we conducted semistructured interviews with key informants in person or over the telephone from May to December 2018. Participants were delegates deployed as part of the Canadian Red Cross medical response team in a clinical or technical, or administrative role within the last 5 years. Interviews were audio-recorded and transcribed. Conventional content analysis was performed on the transcripts, and themes were developed. RESULTS: Eighteen key informants from 4 Canadian provinces provided perspectives on individual attributes acquired during international deployments, such as agility and stress management, and team capacities developed, including collaboration and conflict management. Key informants, including administrators (n = 5), technicians (n = 4), nurses (n = 4), physicians (n = 3) and psychosocial support workers (n = 2), described these experiences as highly relevant to the Canadian domestic context. INTERPRETATION: Canadian physicians and health care workers involved with international disaster response have already acquired essential capacities, and this experience can be vital to building efficient disaster response teams in Canada. These findings complement the Canadian Medical Education Directives for Specialists (CanMEDS) roles and can inform course design, competency and curriculum development for physician and professional training programs related to disaster response and preparedness.

Detailed molecular cytogenetic characterisation of the myeloid cell line U937 reveals the fate of homologous chromosomes and shows that centromere capture is a feature of genome instability.

BACKGROUND: The U937 cell line is widely employed as a research tool. It has a complex karyotype. A PICALM-MLLT10 fusion gene formed by the recurrent t(10;11) translocation is present, and the myeloid common deleted region at 20q12 has been lost from its near-triploid karyotype. We carried out a detailed investigation of U937 genome reorganisation including the chromosome 20 rearrangements and other complex rearrangements. RESULTS: SNP array, G-banding and Multicolour FISH identified chromosome segments resulting from unbalanced and balanced rearrangements. The organisation of the abnormal chromosomes containing these segments was then reconstructed with the strategic use of targeted metaphase FISH. This provided more accurate karyotype information for the evolving karyotype. Rearrangements involving the homologues of a chromosome pair could be differentiated in most instances. Centromere capture was demonstrated in an abnormal chromosome containing parts of chromosomes 16 and 20 which were stabilised by joining to a short section of chromosome containing an 11 centromere. This adds to the growing number of examples of centromere capture, which to date have a high incidence in complex karyotypes where the centromeres of the rearranged chromosomes are identified. There were two normal copies of one chromosome 20 homologue, and complex rearrangement of the other homologue including loss of the 20q12 common deleted region. This confirmed the previously reported loss of heterozygosity of this region in U937, and defined the rearrangements giving rise to this loss. CONCLUSIONS: Centromere capture, stabilising chromosomes pieced together from multiple segments, may be a common feature of complex karyotypes. However, it has only recently been recognised, as this requires deliberate identification of the centromeres of abnormal chromosomes. The approach presented here is invaluable for studying complex reorganised genomes such as those produced by chromothripsis, and provides a more complete picture than can be obtained by microarray, karyotyping or FISH studies alone. One major advantage of SNP arrays for this process is that the two homologues can usually be distinguished when there is more than one rearrangement of a chromosome pair. Tracking the fate of each homologue and of highly repetitive DNA regions such as centromeres helps build a picture of genome evolution. Centromere- and telomere-containing elements are important to deducing chromosome structure. This study confirms and highlights ongoing evolution in cultured cell lines.

Hemopoietic Cell Kinase amplification with Protein Tyrosine Phosphatase Receptor T depletion leads to polycythemia, aberrant marrow erythoid maturation, and splenomegaly.

Deletion of long arm of chromosome 20 [del(20q)] is the second most frequent recurrent chromosomal abnormality in hematological malignancies. It is detected in 10% of myeloproliferative neoplasms, 4-5% of myelodysplastic syndromes, and 1-2% of acute myeloid leukaemia. Recurrent, non-random occurrence of del(20q) indicates that it is a pathogenic driver in myeloid malignancies. Genetic mapping of patient samples has identified two regions of interest on 20q - the "Common Deleted Region" (CDR) and "Common Retained Region" (CRR), which was often amplified. We proposed that the CDR contained tumor suppressor gene(s) (TSG) and the CRR harbored oncogene(s); loss of a TSG together with over-expression of an oncogene favored development of myeloid malignancies. Protein Tyrosine Phosphatase Receptor T (PTPRT) and Hemopoietic cell kinase (HCK) were identified to be the likely candidate TSG and oncogene respectively. Retroviral transduction of HCK into PTPRT-null murine LKS+ stem and progenitor cells resulted in hyperproliferation in colony forming assays and hyperphosphorylation of intracellular STAT3. Furthermore, over half of the murine recipients of these transduced cells developed erythroid hyperplasia, polycythemia and splenomegaly at 12 months, although no leukemic phenotype was observed. The findings suggested that HCK amplification coupled with PTPRT loss in del(20q) leads to development of a myeloproliferative phenotype.

What are the family medicine faculty development needs of partners in low- and middle-income countries?

The WHO endorses family medicine (FM) globally to improve health outcomes. The Besrour Centre (BC) brings together partners from low- and middle-income countries (LMICs) to collaborate on FM development in different contexts. Faculty development is an identified area of need, but specific needs were unknown. A qualitative study was conducted using two 1-1.5-hour focus groups at the 2015 BC conference. Ten countries and 12 universities were represented. Transcripts from semi-structured interviews were analysed for themes using a descriptive approach. There was unanimous support for the need for faculty development tools and resources, particularly in teaching skills. Most programmes lacked formal structure or funding. A consistently identified concept was how to teach specialist faculty the FM context, as was the importance of FM perspective to inform government policies. The need for faculty development of FM in LMICs is strong. FM faculty development resources can be expanded and shared through global health networks. Further expansion of faculty development workshops and toolkits is recommended. This study adds to the current knowledge because it helps to identify the gaps and priorities, specifically focused on LMICs, when developing faculty development FM programmes.

Attitudes, barriers, and enablers towards conducting primary care research in Banda Aceh, Indonesia: a qualitative research study.

BACKGROUND: Conducting university-based research is important for informing primary care, especially in lower- and middle- income countries (LMICs) such as Indonesia. Syiah Kuala University (SKU), the largest educational institution in Aceh province, Indonesia, is actively establishing itself as a leader in research innovation; however, this effort has not yet demonstrated optimum results. Understanding faculty members' perceptions of how research is conducted in this setting is crucial for the design and implementation of successful and sustainable research strategies to increase the quantity and quality of primary care research conducted at LMIC universities. The objective of this study was to identify current attitudes, barriers and enablers/facilitators towards primary care research participation and implementation in this higher education institution. METHODS: A descriptive-interpretive qualitative study was conducted. 29 participants, representing 90% of all faculty members providing primary care, were included. A mixed-methods approach was used, combining the use of a participant survey with 10 focus group discussions. Participants were encouraged to complete the survey in either English or Bahasa Indonesia. All of the focus group discussions were recorded, transcribed and translated into English. Thematic content analysis of these transcripts was carried out. RESULTS: The majority of participants agreed that SKU has set research as a priority, as it is one of the three pillars of higher education, mandatory in all Indonesian higher education institutions. This research identified many barriers in conducting research, i.e. weak research policy, lack of research funding and infrastructure, complicated research bureaucracy and administrative process, as well as time constraints for conducting research relative to other duties. Participants expressed that personal motivation was a very important enabler/facilitator for increasing research activities. In order to improve research productivity, the majority of participants suggested that having local awards and formal recognition, having the opportunity to partner with local business and communities, provision of incentives, and having access to a research help-desk would be beneficial. CONCLUSIONS: Generally, participants showed a supportive and positive attitude towards research, and provided examples of how to improve research productivity in the Asian university context.

International Emergency Medical Teams Training Workshop Special Report.

The World Health Organization's (WHO; Geneva, Switzerland) Emergency Medical Team (EMT) Initiative created guidelines which define the basic procedures to be followed by personnel and teams, as well as the critical points to discuss before deploying a field hospital. However, to date, there is no formal standardized training program established for EMTs before deployment. Recognizing that the World Association of Disaster and Emergency Medicine (WADEM; Madison, Wisconsin USA) Congress brings together a diverse group of key stakeholders, a pre-Congress workshop was organized to seek out collective expertise and to identify key EMT training competencies for the future development of training programs and protocols. The future of EMT training should include standardization of curriculum and the recognition or accreditation of selected training programs. The outputs of this pre-WADEM Congress workshop provide an initial contribution to the EMT Training Working Group, as this group works on mapping training, competencies, and curriculum. Common EMT training themes that were identified as fundamental during the pre-Congress workshop include: the ability to adapt one's professional skills to low-resource settings; context-specific training, including the ability to serve the needs of the affected population in natural disasters; training together as a multi-disciplinary EMT prior to deployment; and the value of simulation in training. AlbinaA, ArcherL, BoivinM, CranmerH, JohnsonK, KrishnarajG, ManeshiA, OddyL, Redwood-CampbellL, RussellR. International Emergency Medical Teams training workshop special report. Prehosp Disaster Med. 2018;33(3):335-338.

Strengthening Primary Care Through Family Medicine Around the World Collaborating Toward Promising Practices.

BACKGROUND AND OBJECTIVES: There is a limited evidentiary base on the development of family medicine in different contexts and countries. The lack of evidence impedes our ability to compare and characterize family medicine models and identify areas of success that have led to the effective provision of care. This paper offers a comparative compilation and analysis of the development of family medicine training programs in seven countries: Brazil, Canada, Ethiopia, Haiti, Indonesia, Kenya, and Mali. METHODS: Using qualitative case studies, this paper examines the process of developing family medicine programs, including enabling strategies and barriers, and shared lessons. An appreciative inquiry framework and complex adaptive systems thinking inform our qualitative study. RESULTS: Committed partnerships, the contribution of champions, health policy, and adaptability were identified as key enablers in all seven case studies. The case studies further reveal that some enablers were more salient in certain contexts as compared to others, and that it is the interaction of enablers that is crucial for understanding how and why initiatives succeeded. The barriers that emerged across the seven case studies include: (1) resistance from other medical specialties, (2) lack of resources and capabilities, (3) difficulty in sustaining support of champions, and (4) challenges in brokering effective partnerships. CONCLUSIONS: A key insight from this study is that the implementation of family medicine is nonlinear, dynamic, and complex. The findings of this comparative analysis offer insights and strategies that can inform the design and development of family medicine programs elsewhere.

Idarubicin Dose Escalation During Consolidation Therapy for Adult Acute Myeloid Leukemia.

Purpose Higher doses of the anthracycline daunorubicin during induction therapy for acute myeloid leukemia (AML) have been shown to improve remission rates and survival. We hypothesized that improvements in outcomes in adult AML may be further achieved by increased anthracycline dose during consolidation therapy. Patients and Methods Patients with AML in complete remission after induction therapy were randomly assigned to receive two cycles of consolidation therapy with cytarabine 100 mg/m2 daily for 5 days, etoposide 75 mg/m2 daily for 5 days, and idarubicin 9 mg/m2 daily for either 2 or 3 days (standard and intensive arms, respectively). The primary end point was leukemia-free survival (LFS). Results Two hundred ninety-three patients 16 to 60 years of age, excluding those with core binding factor AML and acute promyelocytic leukemia, were randomly assigned to treatment groups (146 to the standard arm and 147 to the intensive arm). Both groups were balanced for age, karyotypic risk, and FLT3-internal tandem duplication and NPM1 gene mutations. One hundred twenty patients in the standard arm (82%) and 95 patients in the intensive arm (65%) completed planned consolidation ( P < .001). Durations of severe neutropenia and thrombocytopenia were prolonged in the intensive arm, but there were no differences in serious nonhematological toxicities. With a median follow-up of 5.3 years (range, 0.6 to 9.9 years), there was a statistically significant improvement in LFS in the intensive arm compared with the standard arm (3-year LFS, 47% [95% CI, 40% to 56%] v 35% [95% CI, 28% to 44%]; P = .045). At 5 years, the overall survival rate was 57% in the intensive arm and 47% in the standard arm ( P = .092). There was no evidence of selective benefit of intensive consolidation within the cytogenetic or FLT3-internal tandem duplication and NPM1 gene mutation subgroups. Conclusion An increased cumulative dose of idarubicin during consolidation therapy for adult AML resulted in improved LFS, without increased nonhematologic toxicity.

Lessons learned in global family medicine education from a Besrour Centre capacity-building workshop.

At a global level, institutions and governments with remarkably different cultures and contexts are rapidly developing family medicine centred health and training programmes. Institutions with established family medicine programmes are willing to lend expertise to these global partners but run the risk of imposing a postcolonial, directive approach when providing consultancy and educational assistance. Reflecting upon a series of capacity building workshops in family medicine developed by the Besrour Centre Faculty Development Working Group, this paper outlines approaches to the inevitable challenges that arise between healthcare professionals and educators of differing contexts when attempting to share experience and expertise. Lessons learned from the developers of these workshops are presented in the desire to help others offer truly collaborative, context-centred faculty development activities that help emerging programmes develop their own clinical and educational family medicine frameworks. Established partner relationships, adequate preparation and consultation, and adaptability and sensitivity to partner context appear to be particularly significant determinants for success.

The Dicentric Chromosome dic(20;22) Is a Recurrent Abnormality in Myelodysplastic Syndromes and Is a Product of Telomere Fusion.

We describe a recurrent dicentric chromosome formed by telomere fusion between chromosome 20 and chromosome 22 in 4 cases of myelodysplastic syndromes (MDS) or acute myeloid leukaemia (AML). In particular, the presence of residual telomere sequences at the site of translocation in 3 of the 4 cases makes a compelling case for telomere fusion. This is the first description of a recurrent telomere fusion event in any malignant condition. The 20q subtelomeric region was retained in all 4 examples despite deletion of the 20q12 region closer to the centromere. The original dicentric chromosome in all 4 cases contained nucleolus organiser region material from the short arm of chromosome 22 and had also undergone secondary rearrangements that produced amplification of the common gained region on 20q. We propose that the sequence of events producing this chromosome abnormality is: degradation of the telomeres, formation of an unstable dicentric chromosome by 20q and 22p telomere fusion, breakage-fusion-bridge cycles causing copy number aberration between the centromeres, selection of cells with 20q12 deletion, and further selection of cells with 20q11.2 gain. The last 2 steps are driver events responsible for the abnormal chromosomes found in the malignant cells. Finding recurrent patterns in the complex genome reorganisation events that characterise poor-prognosis, complex-karyotype AML and MDS will help us understand the mechanisms and oncogenic driver mutations in these poorly understood malignancies.

Use of arsenic trioxide in remission induction and consolidation therapy for acute promyelocytic leukaemia in the Australasian Leukaemia and Lymphoma Group (ALLG) APML4 study: a non-randomised phase 2 trial.

BACKGROUND: Initial treatment of acute promyelocytic leukaemia traditionally involves tretinoin (all-trans retinoic acid) combined with anthracycline-based risk-adapted chemotherapy, with arsenic trioxide being the treatment of choice at relapse. To try to reduce the relapse rate, we combined arsenic trioxide with tretinoin and idarubicin in induction therapy, and used arsenic trioxide with tretinoin as consolidation therapy. METHODS: Patients with previously untreated genetically confirmed acute promyelocytic leukaemia were eligible for this study. Eligibilty also required Eastern Cooperative Oncology Group performance status 0-3, age older than 1 year, normal left ventricular ejection fraction, Q-Tc interval less than 500 ms, absence of serious comorbidity, and written informed consent. Patients with genetic variants of acute promyelocytic leukaemia (fusion of genes other than PML with RARA) were ineligible. Induction comprised 45 mg/m(2) oral tretinoin in four divided doses daily on days 1-36, 6-12 mg/m(2) intravenous idarubicin on days 2, 4, 6, and 8, adjusted for age, and 0·15 mg/kg intravenous arsenic trioxide once daily on days 9-36. Supportive therapy included blood products for protocol-specified haemostatic targets, and 1 mg/kg prednisone daily as prophylaxis against differentiation syndrome. Two consolidation cycles with tretinoin and arsenic trioxide were followed by maintenance therapy with oral tretinoin, 6-mercaptopurine, and methotrexate for 2 years. The primary endpoints of the study were freedom from relapse and early death (within 36 days of treatment start) and we assessed improvement compared with the 2 year interim results. To assess durability of remission we compared the primary endpoints and disease-free and overall survival at 5 years in APML4 with the 2 year interim APML4 data and the APML3 treatment protocol that excluded arsenic trioxide. This study is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12605000070639. FINDINGS: 124 patients were enrolled between Nov 10, 2004, and Sept 23, 2009, with data cutoff of March 15, 2012. Four (3%) patients died early. After a median follow-up of 4·2 years (IQR, 3·2-5·2), the 5 year freedom from relapse was 95% (95% CI 89-98), disease-free survival was 95% (89-98), event-free survival was 90% (83-94), and overall survival was 94% (89-97). The comparison with APML3 data showed that hazard ratios were 0·23 (95% CI 0·08-0·64, p=0·002) for freedom from relapse, 0·21 (0·07-0·59, p=0·001) for disease-free survival, 0·34 (0·16-0·69, p=0·002) for event-free survival, and 0·35 (0·14-0·91, p=0·02) for overall survival. INTERPRETATION: Incorporation of arsenic trioxide in initial therapy induction and consolidation for acute promyelocytic leukaemia reduced the risk of relapse when compared with historical controls. This improvement, together with a non-significant reduction in early deaths and absence of deaths in remission, translated into better event-free and overall survival. FUNDING: Phebra.

Developing the evidentiary basis for family medicine in the global context: The Besrour Papers: a series on the state of family medicine in the world.

OBJECTIVE: To provide an overview of the main methodologic challenges to finding definitive evidence of the positive effects of family medicine and family medicine training on a global scale. COMPOSITION OF THE COMMITTEE: In 2012, 2013, and 2014, the College of Family Physicians of Canada hosted the Besrour Conferences to reflect on its role in advancing the discipline of family medicine globally. The Besrour Papers Working Group, which was struck at the 2013 conference, was tasked with developing a series of papers to highlight the key issues, lessons learned, and outcomes emerging from the various activities of the Besrour collaboration. The working group comprised members of various academic departments of family medicine in Canada and abroad who attended the conferences. METHODS: We performed a scoping review to determine the methodologic obstacles to understanding the positive effects of family medicine globally. REPORT: The main obstacle to evaluating family medicine globally is that one of its core dimensions and assets is its local adaptability. Family medicine takes on very different roles in different health systems, making aggregation of data difficult. In many countries family medicine competes with other disciplines rather than performing a gatekeeping role. Further, most research that has been conducted thus far comes from industrialized contexts, and patient continuity and its benefits might not be achievable in the short term in developing countries when clinical demands are great. We must find frameworks to permit strengthening the evidentiary basis of the discipline across different contexts without sacrificing its beneficial adaptability. CONCLUSION: We believe that developing family medicine and its attributes is one of the keys to achieving global health. These attributes­including its comprehensiveness, adaptability, and attention to both local and patient needs­are key to advancing global health priorities, but make common evaluative frameworks for the discipline a challenge. The spread of family medicine over the past decades is indirect evidence of its utility, but we need to generate more evidence. We present some of the initial challenges to a broader and more rigorous evaluative framework.

Monosomal karyotype predicts inferior survival independently of a complex karyotype in patients with myelodysplastic syndromes.

BACKGROUND: Conflicting data exist about the impact of a monosomal karyotype (MK) on overall survival (OS) for patients with myelodysplastic syndromes (MDSs) and particularly for those with a complex karyotype (CK). This study was aimed at determining whether an MK is associated with OS independently of the number of cytogenetic abnormalities (CAs) in a population-based MDS cohort. METHODS: Cancer registry data on incident MDS cases were linked with cytogenetic data and hospital administrative data from 2000 to 2010 for the Australian state of Victoria. RESULTS: Between 2000 and 2010, 1404 incident MDS cases with cytogenetic results were identified. A CK, defined as 3 or more abnormalities, was present in 126 (9%). A very complex karyotype (vCK), defined as 5 or more abnormalities, was present in 95 (7%). An MK was associated with worse OS in the whole cohort (median 6 vs 39 months, P < 0.001) including those with a coexisting CK (6 vs 17 months, P < 0.001) or vCK (6 vs 9 months, P = 0.02). After adjustments for the number of CAs, an MK remained independently associated with OS, although its effect size decreased with increasing cytogenetic complexity (hazard ratio for an MK, 4.81; 95% confidence interval, 3.08-7.52; hazard ratio for the number of CAs, 1.22; 95% confidence interval, 1.15-1.30; and hazard ratio for the interaction between an MK and CAs, 0.83; 95% confidence interval, 0.77-0.89). CONCLUSIONS: These results support the clinical utility of an MK as an independent predictor of adverse outcomes for MDS patients, even among CK and vCK groups, although its prognostic effect decreases with increasing cytogenetic complexity.

Understanding attitudes, barriers and challenges in a small island nation to disease and partner notification for HIV and other sexually transmitted infections: a qualitative study.

BACKGROUND: In Barbados sexually transmitted infections (STIs) including HIV are not notifiable diseases and there is not a formal partner notification (PN) programme. Objectives were to understand likely attitudes, barriers, and challenges to introducing mandatory disease notification (DN) and partner notification (PN) for HIV and other STIs in a small island state. METHODS: Six key informants identified study participants. Interviews were conducted, recorded, transcribed and analysed for content using standard methods. RESULTS: Participants (16 males, 13 females, median age 59 years) included physicians, nurses, and representatives from governmental, youth, HIV, men's, women's, church, and private sector organisations. The median estimated acceptability by society of HIV/STI DN on a scale of 1 (unacceptable) to 5 (completely acceptable) was 3. Challenges included; maintaining confidentiality in a small island; public perception that confidentiality was poorly maintained; fear and stigma; testing might be deterred; reporting may not occur; enacting legislation would be difficult; and opposition by some opinion leaders. For PN, contract referral was the most acceptable method and provider referral the least. Contract referral unlike provider referral was not "a total suspension of rights" while taking into account that "people need a little gentle pressure sometimes". Extra counselling would be needed to elicit contacts or to get patients to notify partners. Shame, stigma and discrimination in a small society may make PN unacceptable and deter testing. With patient referral procrastination may occur, and partners may react violently and not come in for care. With provider referral patients may have concerns about confidentiality including neighbours becoming suspicious if a home visit is used as the contact method. Successful contact tracing required time and effort. With contract referral people may neither inform contacts nor say that they did not. Strategies to overcome barriers to DN and PN included public education, enacting appropriate legislation to allow DN and PN, good patient counselling and maintaining confidentiality. CONCLUSIONS: There was both concern that mandatory DN and PN would deter testing and recognition of the benefits. Public and practitioner education and enabling legislation would be necessary, and the public needed to be convinced that confidentiality would be maintained.

Src family kinases and their role in hematological malignancies.

The Src family protein tyrosine kinases (SFKs) are non-receptor intracellular kinases that have important roles in both hematopoiesis and leukemogenesis. The derangement of their expression or activation has been demonstrated to contribute to hematological malignancies. This review first examines the mechanisms of SFK overexpression and hyperactivation, emphasizing the dysregulation of the upstream modulators. Subsequently, the role of SFK up-regulation in the initiation, progression and therapy resistance of many hematological malignancies is also analyzed. The presented evidence endeavors to highlight the influence of SFK up-regulation on an extensive number of hematological malignancies and the need to consider them as candidates in targeted anticancer therapy.