Design, delivery and effectiveness of health practitioner regulation systems: an integrative review.

BACKGROUND: Health practitioner regulation (HPR) systems are increasingly recognized as playing an important role in supporting health workforce availability, accessibility, quality, and sustainability, while promoting patient safety. This review aimed to identify evidence on the design, delivery and effectiveness of HPR to inform policy decisions. METHODS: We conducted an integrative analysis of literature published between 2010 and 2021. Fourteen databases were systematically searched, with data extracted and synthesized based on a modified Donabedian framework. FINDINGS: This large-scale review synthesized evidence from a range of academic (n = 410) and grey literature (n = 426) relevant to HPR. We identified key themes and findings for a series of HPR topics organized according to our structures-processes-outcomes conceptual framework. Governance reforms in HPR are shifting towards multi-profession regulators, enhanced accountability, and risk-based approaches; however, comparisons between HPR models were complicated by a lack of a standardized HPR typology. HPR can support government workforce strategies, despite persisting challenges in cross-border recognition of qualifications and portability of registration. Scope of practice reform adapted to modern health systems can improve access and quality. Alternatives to statutory registration for lower-risk health occupations can improve services and protect the public, while standardized evaluation frameworks can aid regulatory strengthening. Knowledge gaps remain around the outcomes and effectiveness of HPR processes, including continuing professional development models, national licensing examinations, accreditation of health practitioner education programs, mandatory reporting obligations, remediation programs, and statutory registration of traditional and complementary medicine practitioners. CONCLUSION: We identified key themes, issues, and evidence gaps valuable for governments, regulators, and health system leaders. We also identified evidence base limitations that warrant caution when interpreting and generalizing the results across jurisdictions and professions. Themes and findings reflect interests and concerns in high-income Anglophone countries where most literature originated. Most studies were descriptive, resulting in a low certainty of evidence. To inform regulatory design and reform, research funders and governments should prioritize evidence on regulatory outcomes, including innovative approaches we identified in our review. Additionally, a systematic approach is needed to track and evaluate the impact of regulatory interventions and innovations on achieving health workforce and health systems goals.

Exploring Criteria for the Translation of Traditional Knowledge Within Contemporary Clinical Practice, Research, Policy, and Education: A Stakeholder Forum.

Background: The 2018 Declaration of Astana identifies traditional knowledge (TK) as one of the drivers for strengthening primary health care systems through the use of technology (traditional medicines) and knowledge and capacity building (traditional practitioners). While TK underpins both traditional practice and the use of traditional medicines, facilitating the use of TK in contemporary health care systems has been difficult to achieve. The aim of this study was to identify key factors related to the translation of TK into contemporary settings to help establish tools to support the knowledge translation process. Methods: This study used World Café methodology to collect the observations, ideas, and perspectives of experts who use TK in their practice. These experts (n = 9) were from a variety of contexts, including clinical practice, research, education, policy, and consumer advocacy, participated in the 1-day event. Data were collected into NVivo 12 software and analyzed using inductive-deductive thematic analysis. Results: Thematic analysis identified five themes: the need to define the elements required for critical evaluation of sources of TK as evidence, the importance of applying a tradition-centric lens when translating TK for contemporary use, the need to bridge gaps between TK and its contemporary applications, the value of critically evaluating the TK translation process itself, and the recognition of traditions as living systems. Taken together, the themes showed holistic interpretation of the translation process that incorporates critical analysis of the TK itself and accountable, transparent, and ethical processes of translation that consider safety, socioeconomical and intellectual property impacts of TK in contemporary use. Conclusions: Stakeholders identified TK as a valid and important source of evidence that should guide practice in a range of contemporary settings (e.g., policy and clinical practice), and outlined important consideration for critiquing, evaluating, communicating, and using TK within these settings.

Small molecule inhibition of the CBFß/RUNX interaction decreases ovarian cancer growth and migration through alterations in genes related to epithelial-to-mesenchymal transition.

OBJECTIVE: Ovarian cancer survival and treatment have improved minimally in the past 20years. Novel treatment strategies are needed to combat this disease. This study investigates the effects of chemical inhibition of the CBFß/RUNX protein-protein interaction on ovarian cancer cell lines. METHODS: Ovarian cancer cell lines were treated with CBFß/RUNX inhibitors, and the effects on proliferation, DNA replication, wound healing, and anchorage-independent growth were measured. RNA-Seq was performed on compound-treated cells to identify differentially expressed genes. Genes altered by compound treatment were targeted with siRNAs, and effects on DNA replication and wound healing were measured. RESULTS: Chemical inhibition of the CBFß/RUNX interaction decreases ovarian cancer cell proliferation. Inhibitor treatment leads to an S-phase cell cycle delay, as indicated by an increased percentage of cells in S-phase, and a decreased DNA replication rate. Inhibitor treatment also reduces wound healing and anchorage-independent growth. RNA-Seq on compound-treated cells revealed changes in a small number of genes related to proliferation and epithelial-to-mesenchymal transition. siRNA-mediated knockdown of INHBA and MMP1 - two genes whose expression decreases with compound treatment - slowed DNA replication and impaired wound healing. CONCLUSIONS: Chemical inhibition of the CBFß/RUNX interaction is a viable strategy for the treatment of ovarian cancer.

Genetic and Molecular Analyses indicate independent effects of TGIFs on Nodal and Gli3 in neural tube patterning.

Holoprosencephaly (HPE) is a prevalent craniofacial developmental disorder that has both genetic and environmental causes. The gene encoding TG-interacting factor 1 (TGIF1) is among those that are routinely screened in HPE patients. However, the mechanisms by which TGIF1 variants cause HPE are not fully understood. TGIF1 is a transcriptional repressor that limits the output of the Transforming Growth Factor ß (TGFß)/Nodal signaling pathway, and HPE in patients with TGIF1 variants has been suggested to be due to increased Nodal signaling. Mice lacking both Tgif1 and its paralog, Tgif2, have HPE, and embryos lacking Tgif function do not survive past mid-gestation. Here, we show that in the presence of a Nodal heterozygous mutation, proliferation defects are rescued and a proportion of embryos lacking all Tgif function survive to late gestation. However, these embryos have a classic HPE phenotype, suggesting that this is a Nodal-independent effect of Tgif loss of function. Further, we show that the Gli3 gene is a direct target for repression by Tgifs, independent of TGFß/Nodal signaling, consistent with Tgif mutations causing HPE via Nodal-independent effects on the Sonic Hedgehog (Shh) pathway. Based on this work, we propose a model for distinct functions of Tgifs in the Nodal and Shh/Gli3 pathways during forebrain development.

High-throughput tyrosine kinase activity profiling identifies FAK as a candidate therapeutic target in Ewing sarcoma.

Limited progress has been made in the treatment of advanced-stage pediatric solid tumors despite the accelerated pace of cancer discovery over the last decade. Tyrosine kinase inhibition is one tractable therapeutic modality for treating human malignancy. However, little is known about the kinases critical to the development or maintenance of many pediatric solid tumors such as Ewing sarcoma. Using a fluorescent, bead-based technology to profile activated tyrosine kinases, we identified focal adhesion kinase (FAK, PTK2) as a candidate target in Ewing sarcoma. FAK is a tyrosine kinase critical for cellular adhesion, growth, and survival. As such, it is a compelling target for cancer-based therapy. In this study, we have shown that FAK is highly phosphorylated in primary Ewing sarcoma tumor samples and that downregulation of FAK by short hairpin RNA and treatment with a FAK-selective kinase inhibitor, PF-562271, impaired growth and colony formation in Ewing sarcoma cell lines. Moreover, treatment of Ewing sarcoma cell lines with PF-562271 induced apoptosis and led to downregulation of AKT/mTOR and CAS activity. Finally, we showed that small-molecule inhibition of FAK attenuated Ewing sarcoma tumor growth in vivo. With FAK inhibitors currently in early-phase clinical trials for adult malignancies, these findings may bear immediate relevance to patients with Ewing sarcoma.

Complementary genomic screens identify SERCA as a therapeutic target in NOTCH1 mutated cancer.

Notch1 is a rational therapeutic target in several human cancers, but as a transcriptional regulator, it poses a drug discovery challenge. To identify Notch1 modulators, we performed two cell-based, high-throughput screens for small-molecule inhibitors and cDNA enhancers of a NOTCH1 allele bearing a leukemia-associated mutation. Sarco/endoplasmic reticulum calcium ATPase (SERCA) channels emerged at the intersection of these complementary screens. SERCA inhibition preferentially impairs the maturation and activity of mutated Notch1 receptors and induces a G0/G1 arrest in NOTCH1-mutated human leukemia cells. A small-molecule SERCA inhibitor has on-target activity in two mouse models of human leukemia and interferes with Notch signaling in Drosophila. These studies "credential" SERCA as a therapeutic target in cancers associated with NOTCH1 mutations.

The Victorian experience of transitional registration for Chinese Medicine practitioners and its implications for national registration.

BACKGROUND: Statutory registration of Chinese Medicine (CM) practitioners was introduced in Victoria in 2000. The application assessment process for those who were granted registration during the transitional period (2002-04) was resource intensive, as little was known about their age, education, practice and language proficiency. This study offers insights that may be useful for the planning of national registration to commence in 2012. METHODS: Data were extracted from registration application forms submitted to the Chinese Medicine Registration Board of Victoria (CMRB) between 2002 and 2004, using pre-defined data collection forms. RESULTS: In 2006, 639 'grandparented' Victorian CM practitioners had been registered, with a median age of 44 years old (range 23-86). There was a higher proportion of younger female, English-speaking, acupuncturists v. a higher proportion of older male, non-English-speaking, Chinese herbalists. There were few CM practitioners in rural areas, particularly herbalists. More than one-third of practitioners had obtained qualifications overseas and almost half of these practitioners provided no evidence of past study in professional issues and medical ethics. CONCLUSIONS: Ageing, diversity in qualifications and training, English proficiency, and level of study in professional issues and medical ethics represent major challenges for the implementation of CM national registration in 2012.

Development in and challenge for traditional Chinese medicine in Australia.

BACKGROUND: Demand for and use of Traditional Chinese Medicine (TCM) has been growing steadily in Australia. This article outlines the growth of TCM in usage, research capacity, and availability of tertiary training. However, there are continuing challenges, institutional recognition of TCM is lagging behind consumer demand, and there is little TCM practiced in the Australian public health system. This article suggests some possible reasons. The tools of evidence-based medicine (EBM) have the potential to provide a bridge between, and a common language for, TCM and Western biomedicine (WB) researchers and practitioners. CONCLUSIONS: While there is no sign of a slowing in consumer demand for TCM services, EBM has the potential to increase the legitimacy and institutional recognition of TCM, thereby encouraging the integration of TCM into the Australian health care system.

Attitudes toward using condoms and condom use: difference between sexually abused and nonabused African American female adolescents.

Rates of many sexually transmitted diseases remain higher among adolescents than among any other age group. The associations between abuse experiences and risky sexual behaviors suggest that exploring the relationships between adolescents' abuse history and condom use beliefs and behaviors is warranted. Females (N = 725) attending an adolescent clinic reported demographic characteristics, beliefs about condom use, sexual behaviors, and sexual abuse or molestation history. Those reporting sexual abuse or molestation (23%) were more likely to think condoms interfered with sexual pleasure and less likely to think condoms were important to partners. They also reported more unprotected vaginal sex and more lifetime sex partners. Beliefs were correlated with condom use consistency, number of lifetime partners, and number of unprotected sex experiences. The greater levels of behavioral risk among those reporting abuse suggest greater risk for acquisition and transmission in abused female adolescents. The authors discuss hypotheses to inform future research and intervention.