Evidence for recency of practice standards for regulated health practitioners in Australia: a systematic review.

BACKGROUND: Health practitioner regulators throughout the world use registration standards to define the requirements health practitioners need to meet for registration. These standards commonly include recency of practice (ROP) standards designed to ensure that registrants have sufficient recent practice in the scope in which they intend to work to practise safely. As the ROP registration standards for most National Boards are currently under review, it is timely that an appraisal of current evidence be carried out. METHODS: A systematic review was conducted using databases (including MEDLINE, EMBASE, PsycInfo, and CINAHL), search engines, and a review of grey literature published between 2015 and April 2022. Publications included in the review were assessed against the relevant CASP checklist for quantitative studies and the Joanna Briggs Institute checklist for analytical cross-sectional studies. RESULTS: The search yielded 65 abstracts of which 12 full-text articles met the inclusion criteria. Factors that appear to influence skills retention include the length of time away from practice, level of previous professional experience and age, as well as the complexity of the intervention. The review was unable to find a clear consensus on the period of elapsed time after which a competency assessment should be completed. CONCLUSIONS: Factors that need to be taken into consideration in developing ROP standards include length of time away from practice, previous experience, age and the complexity of the intervention, however, there is a need for further research in this area.

Evidence for continuing professional development standards for regulated health practitioners in Australia: a systematic review.

BACKGROUND: Health practitioner regulators throughout the world use continuing professional development (CPD) standards to ensure that registrants maintain, improve and broaden their knowledge, expertise and competence. As the CPD standard for most regulated health professions in Australia are currently under review, it is timely that an appraisal of the evidence be undertaken. METHODS: A systematic review was conducted using major databases (including MEDLINE, EMBASE, PsycInfo, and CINAHL), search engines and grey literature for evidence published between 2015 and April 2022. Publications included in the review were assessed against the relevant CASP checklist for quantitative studies and the McMaster University checklist for qualitative studies. RESULTS: The search yielded 87 abstracts of which 37 full-text articles met the inclusion criteria. The evidence showed that mandatory CPD requirements are a strong motivational factor for their completion and improves practitioners' knowledge and behaviour. CPD that is more interactive is most effective and e-learning is as effective as face-to-face CPD. There is no direct evidence to suggest the optimal quantity of CPD, although there was some evidence that complex or infrequently used skills deteriorate between 4 months to a year after training, depending on the task. CONCLUSIONS: CPD is most effective when it is interactive, uses a variety of methods and is delivered in a sequence involving multiple exposures over a period of time that is focused on outcomes considered important by practitioners. Although there is no optimal quantity of CPD, there is evidence that complex skills may require more frequent CPD.

Experts' Views on FDA Regulatory Standards for Drug and High-Risk Medical Devices: Implications for Patient Care.

BACKGROUND: Drugs and high-risk medical devices are increasingly likely to receive Food and Drug Administration (FDA) approval through expedited pathways, which has implications for informed treatment consent (i.e., consent in clinical practice). OBJECTIVE: To obtain expert opinion about the clinical and ethical implications of the increasing availability of new drugs and devices approved through expedited development and regulatory review pathways. DESIGN: Qualitative study using individual semi-structured videoconference interviews. PARTICIPANTS: National leaders in medicine, ethics, and law (n=12) with expertise in medical product regulation, payor policymaking, bioethics, physician practice, patient advocacy, public health expertise/advocacy, clinical trials, the pharmaceutical and device industry, institutional review board oversight, and real-world evidence. MAIN MEASURES: Principal themes in 3 domains: expedited regulatory pathways, physician and patient understanding of and reliance on FDA approval, and informed treatment consent. KEY RESULTS: Respondents pointed out that more common use of expedited pathways translates to increased reliance on surrogate measures, some with uncertain clinical significance. While expedited development and review can have advantages, participants expressed worry that physicians were unaware when medical products were expedited and did not communicate about uncertainties in knowledge about new drug or device approvals effectively with patients. Many participants felt that informed treatment consent discussions about new drugs or devices should include some explanations of expedited pathways and use of surrogate measures. CONCLUSIONS: Experts identified advantages of expediting development and of FDA flexibility in applying its standards to new drugs and medical devices, but highlighted concerns that patients may not be adequately informed about the risks of shorter review times or about uncertainties in the evidence that result. There is a need to identify approaches to ensure effective clinical use of drugs and devices when approved through expedited pathways.

Improving screening model of pesticide risk assessment in surface soils: Considering degradation metabolites.

As pesticides can be degraded to toxic metabolites in the soil, metabolite toxicity should be considered in human health risk assessments. In this study, a screening-level modeling framework was developed to manage pesticides in surface soil, which was discussed under discrete and continuous emission scenarios. In addition, we selected glyphosate and its major metabolite (aminomethylphosphonic acid or AMPA) as examples to conduct screening-level risk management at regional, national, and global scales. The results indicated that if soil AMPA were not considered, human health risks could be significantly underestimated because of the large half-life of AMPA in the soil. For example, the added concentration factors of AMPA were simulated as 0.19 and 6.72 considering all major elimination pathways and considering the degradation pathway alone, respectively, indicating that AMPA formation could lead to severe extra health burdens. Furthermore, the evaluation of current glyphosate soil standards suggested that toxic metabolites should be considered in the regulatory process; otherwise, many standards could theoretically trigger high levels of soil AMPA, which could result in serious human health damage. Our proposed screening-level model can help to improve risk assessment and regulatory management of pesticides in surface soils.

Hazardous properties and toxicological update of mercury: From fish food to human health safety perspective.

The mercury (Hg) poisoning of Minamata Bay of Japan widely activated a global attention to Hg toxicity and its potential consequences to the aquatic ecosystem and human health. This has resulted to an increased need for a dynamic assembly, contextualization, and quantification of both the current state-of-the-art and approaches for understanding the cause-and-effect relationships of Hg exposure. Thus, the objective of this present review is to provide both hazardous toxic properties and toxicological update of Hg, focusing on how it ultimately affects the aquatic biota to potentially produce human health effects. Primarily, we discussed processes that relate to Hg exposure, including immunological aspects and risk assessment, vulnerability, toxicokinetics, and toxicodynamics, using edible fish, swordfish (Xiphias gladius), as a model. In addition, we summarized available information about Hg concentration limits set by different governmental agencies, as recognized by national and international standardization authorities.

Comparison of complement activation-related pseudoallergy in miniature and domestic pigs: foundation of a validatable immune toxicity model.

Complement activation-related pseudoallergy (CARPA) is an acute adverse immune reaction caused by many nanomedicines. There is a regulatory need for a sensitive and standardizable in vivo predictive assay. While domestic pigs are a sensitive animal model, miniature pigs are favored in toxicological studies yet their utility as a CARPA model has not yet been explored. Herein, we used liposomal doxorubicin and amphotericin B (Doxil/Caelyx and AmBisome), Cremophor EL and zymosan as CARPA triggers to induce reactions in miniature and domestic pigs, and compared the hemodynamic, hematological, biochemical, and skin alterations. The changes observed after administration of the test agents were very similar in both pig strains, suggesting that miniature pigs are a sensitive, reproducible, and, hence, validatable animal model for CARPA regulatory testing. FROM THE CLINICAL EDITOR: With the advances in nanomedicine research, many new agents are now tested for use in clinical setting. Nonetheless, complement activation-related pseudoallergy (CARPA) is a well known phenomenon which can be caused by nanoparticles. In this study, the authors looked at and compared the use of domestic pigs versus miniature pigs as experimental animals for toxicological studies. Their findings confirmed the possible use of miniature pigs for regulatory testing.

Evaluation of effluents from bench-scale treatment combinations for landfill leachate in Ibadan, Nigeria.

The removal of pollutants in landfill leachate was investigated using constructed wetlands, a trickling filter, alum flocculation and coagulation, and a sequencing batch reactor in various combinations. Thirteen combined operations were investigated involving three out of the four unit treatment methods in series. The study was conducted because unit operations, though achieved reductions in pollutants concentrations had effluent values above the national regulatory guideline values. The suspended solids of effluents were permissible in most treatment processes, while reductions in 5-day biochemical oxygen demand (BOD5), chemical oxygen demand (COD) and ammonia (NH3) of leachates ranged from 80% to 97%; 86% to 97% and 92% to 98% respectively. However, there were significant increases in nitrate (85%) and dissolved oxygen of treatment (218%). In addition, the characteristics of the recommended treatment sequence, involving constructed wetlands, alum and trickling filter produced effluents with reductions in colour (97%), alkalinity (97%), BOD (97%), COD (97%) and NH3 (98%), and in metals, except nickel (29% reduction from the influent values). The recommended treatment combination is suitable for effective leachate management at the landfill. The cost of constructing and operating the recommended treatment combination at the facility, for 5 years, would be NGN6,009,750.00 ($38,036.39). The performance should be monitored on site prior to full adoption if effluent characteristics remain consistently low over dry and wet seasons.

Quality Assurance for Hepatitis C Virus Point-of-Care Diagnostics in Sub-Saharan Africa.

As part of a multinational study to evaluate the Bioline Hepatitis C virus (HCV) point-of-care (POC) testing in sub-Saharan Africa (SSA), this narrative review summarises regulatory standards and quality indicators for validating and approving HCV clinical diagnostics. In addition, this review also provides a summary of their diagnostic evaluations using the REASSURED criteria as the benchmark and its implications on the WHO HCV elimination goals 2030.

Importance of Sanitation for Stored-Product Pest Management.

Sanitation is essential for the cost-effective pest management of stored-product insects. The Food, Drug and Cosmetic Act of 1938 led to the Food and Drug Administration (FDA) tightening regulatory standards, and many local surveys, courses and conferences were organized to prepare the industry for these new regulations. Sanitation removes insects and residual food, which may also provide shelter for insects, with heat treatments and insecticide applications. The number of insects removed by cleaning may be reduced as the number of available hiding places increases. Decreased sanitation negatively affects the efficacy of most other pest management practices, with means of 1.3- to 17-fold decreases in efficacy. The majority of studies quantifying the efficacy of sanitation have been performed on the farm storage of grain, but some studies have been conducted for grain elevators, food processing, and the marketing system. Results ranged from no effect of sanitation alone to very effective alone or with other methods. Sanitation can also reduce insect infestation prior to harvest. Some cost-benefit analyses have been conducted for sanitation.

Estimation of the mortality rate of workers in Japan.

BACKGROUND: Risk-based decision-making is used to identify risk factors for which threshold points have not been identified. The occupational mortality rate was referred to as a reference risk. This study aimed to analyze recent trends in worker mortality using three data sources. METHODS: The Reports of Worker Casualties (RWC), the Annual Statistics Report of the Industrial Accident Compensation Insurance Council (ASR), and the Annual Business Report of the Industrial Accident Compensation Insurance Council (ABR) were used. Mortality rates were estimated by age group and industry category (overall, and manufacturing and construction industries) from 1991 to 2019. The mortality rates were compared with those estimated in Western countries. RESULTS: The mortality rates for the three industry categories in the RWC and ASR decreased, whereas those for the manufacturing and construction industries in the ABR did not. In 2019, the mortality rates in the ABR were 3.1, 4.8, and 3.1 times higher than those in the RWC overall and in the manufacturing and construction industries, respectively. The differences decreased when deaths after long-term medical treatment were considered. The mortality rate trends in Japan were similar to those in Western countries. The upper mortality rate among Japan and Western countries was at least five to 15 times higher than the lowest. CONCLUSION: When occupational mortality rates are used as a reference risk, it is important to consider any changes with time, the data sources used, and the differences between countries.

Aflatoxin M1 in milk does not contribute substantially to global liver cancer incidence.

BACKGROUND: For 60 y, it has been known that aflatoxin B1 (AFB1), a mycotoxin produced by Aspergillus fungi in certain food and feed crops, causes hepatocellular carcinoma (liver cancer; HCC) in humans. The annual global burden of AFB1-related HCC has been estimated. However, much less is known about the potential carcinogenic impact of a metabolite of AFB1 called aflatoxin M1 (AFM1), which is secreted in milk when dairy animals consume AFB1-contaminated feed. The cancer risk of AFM1 to humans from milk consumption has not yet been evaluated. OBJECTIVES: We sought to estimate the global risk of AFM1-related liver cancer through liquid milk consumption, accounting for possible synergies between AFM1 and chronic infection with hepatitis B virus (HBV) in increasing cancer risk. METHODS: We conducted a quantitative cancer risk assessment by analyzing extensive datasets of national population sizes, dairy consumption patterns, AFM1 concentrations in milk in 40 nations, and chronic HBV prevalence. Two separate cancer risk assessments were conducted: assuming a possible synergy between AFM1 and HBV in increasing cancer risk in a manner similar to that of AFB1 and HBV, and assuming no such synergy. RESULTS: If there is no synergy between AFM1 and HBV, AFM1 may contribute ∼0.001% of total annual HCC cases globally. If there is synergy between AFM1 and HBV infection, AFM1 may contribute ∼0.003% of all HCC cases worldwide. In each case, the total expected AFM1-attributable cancer cases are ∼13-32 worldwide. CONCLUSION: AFM1 exposure through liquid milk consumption does not substantially increase liver cancer risk in humans. Policymakers should consider this low risk against the nutritional benefits of milk consumption, particularly to children, in a current global situation of milk being discarded because of AFM1 concentrations exceeding regulatory standards.

Evidence for Continuing Professional Development and Recency of Practice Standards for Regulated Health Professionals in Australia: Protocol for a Systematic Review.

BACKGROUND: Continuing professional development (CPD) and recency of practice (ROP) standards are components of health practitioner regulation in Australia. The CPD and ROP standards are currently under review, and an evidence base to assist the development of consistent standards is required. Preliminary searching was unable to find a recent systematic review of the literature to provide an evidence base to underpin the standards review. OBJECTIVE: This paper presents the protocol for a systematic review that aims to develop a current evidence base that will support the National Boards to develop more consistent, evidence-based, effective standards that are clear and easy to understand and operationalize. METHODS: Research questions were developed to support the planned review of CPD and ROP registration standards. Major databases and relevant journals were searched for articles published in English between 2015 and 2021, using key search terms based on previous unpublished reviews of the CPD and ROP registration standards. The quality of the articles retrieved will be assessed using an instrument suitable for use in the development of public policy. The findings will be published in a peer-reviewed journal. RESULTS: In September 2021, our search strategy identified 18,002 studies for the CPD-related research questions after removal of duplicates. Of these, 509 records were screened based on their title, and 66 full-text articles were assessed for eligibility based on their abstract, of which 31 met the inclusion criteria. A further 291 articles were identified as relevant to the ROP research questions. Of these, 87 records were screened based on their title, and 46 full-text articles were assessed for eligibility based on their abstract, of which 8 studies met our inclusion criteria. CONCLUSIONS: This protocol outlines the scope and methodology that will be used to conduct a systematic review of evidence for CPD and ROP and inform a review of the standards for regulated health professionals in Australia. Previous research has shown that while CPD improves practitioner knowledge, the link to public safety is unclear. While there has been a greater focus on maintenance of certification and other quality assurance activities over the past 10 years, there remains great variability in CPD requirements across both professions and jurisdictions. ROP was found to be a poorly researched area with most research concentrating on medical practitioners, nurses, and midwives and no clear consensus about the optimal time period after which retraining or an assessment of competence should be introduced. As the CPD and ROP standards are currently under review, it is timely that a review of current evidence be undertaken. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/28625.

Redefining and Validating Digital Biomarkers as Fluid, Dynamic Multi-Dimensional Digital Signal Patterns.

"Digital biomarker" is a term broadly and indiscriminately applied and often limited in its conceptualization to mimic well-established biomarkers as defined and approved by regulatory agencies such as the United States Food and Drug Administration (FDA). There is a practical urgency to revisit the definition of a digital biomarker and expand it beyond current methods of identification and validation. Restricting the promise of digital technologies within the realm of currently defined biomarkers creates a missed opportunity. A whole new field of prognostic and early diagnostic digital biomarkers driven by data science and artificial intelligence can break the current cycle of high healthcare costs and low health quality that is being driven by today's chronic disease detection and treatment approaches. This new class of digital biomarkers will be dynamic and require developing new FDA approval pathways and next-generation gold standards.

The Global Bioequivalence Harmonisation Initiative (GBHI): Report of EUFEPS/AAPS fourth conference.

This report provides a summary of the 4th International Conference on Global Bioequivalence Harmonisation Initiative (GBHI) that was co-organised by the European Federation of Pharmaceutical Sciences (EUFEPS) and the American Association of Pharmaceutical Scientists (AAPS). The goal of the GBHI conference is to offer the most informative and up to date science and regulatory thinking of bioequivalence (BE) in global drug development to support the intended process of a scientific global harmonisation. The workshop provided an open forum for pharmaceutical scientists from academia, industry and regulatory agencies to discuss three BE topics of interest, (a) BE assessment for long-acting injectables and implants, (b) necessity of fed BE studies for immediate-release products and (c) procedures to demonstrate equivalence of orally inhaled products. Moreover, in keynote lectures, a potential road map to an international BE reference product was discussed, and visions and perspectives for future global BE harmonisation activities have been presented. The meeting delivered a cutting-edge insight into the topics in an interactive and at the same time focused way.

The global bioequivalence harmonisation initiative: Report of EUFEPS/AAPS third conference.

The European Federation of Pharmaceutical Sciences (EUFEPS) and American Association of Pharmaceutical Scientists (AAPS) have collaborated since 2015 to organize international conferences to support global harmonization of regulatory requirements for bioequivalence (BE) assessment. This collaboration has resulted in three Global Bioequivalence Harmonization Initiative (GBHI) workshops which provided a unique opportunity for scientists from academia, industry, and regulatory agencies to discuss current, complex BE issues. The 3rd GBHI workshop was held in April 2018 in Amsterdam/The Netherlands and covered the following topics: (a) the necessity of multiple-dose studies in BE testing; (b) BE of transdermal delivery systems, and (c) liposomal parenteral preparations. This report summarizes the extensive discussions that led to better understanding of the similarities and differences across the major regulatory agencies on these topics and paved the way for future international harmonization.

Summary report of second EUFEPS/AAPS conference on global harmonization in bioequivalence.

The Global Bioequivalence Harmonization Initiative (GBHI) was launched by the Network on Bioavailability and Biopharmaceutics (BABP) under the auspices of European Federation for Pharmaceutical Sciences (EUFEPS) several years ago. Since 2015, EUFEPS in collaboration with the American Association of Pharmaceutical Scientists (AAPS) has organized three international conferences to support global harmonization of regulatory requirements for bioequivalence (BE) assessment. These conferences provided an open forum for pharmaceutical scientists from academia, industry and regulatory agencies to discuss various BE topics at issue. The current report summarizes the discussion of BE issues at the 2nd GBHI conference held in 2016, Rockville, USA. Three important BE topics were discussed at the meeting: (a) prodrugs and compounds with pre-systemic extraction, (b) scaling procedures and two-stage designs, and (c) exclusion of pharmacokinetic data in BE assessment. The presentations and discussions of these issues have enhanced the mutual understanding of scientific background for BE evaluation and further facilitated harmonization of regulatory approaches for establishing BE of multisource drug products.

The Global Bioequivalence Harmonization Initiative: Summary report for EUFEPS international conference.

Bioequivalence (BE) is considered one of the key questions in new and generic drug product development and registration worldwide. However, the regulations and jurisdiction vary from country to country and continent to continent. Harmonization of regulatory requirements and criteria for BE determination may avoid unnecessary repetition of BE studies and minimize drug exposure to humans. Harmonization around the globe may be achieved by a better understanding of scientific principles and expectations from different regulatory authorities. To facilitate global harmonization, the Network on Bioavailability and Biopharmaceutics (BABP) under the European Federation for Pharmaceutical Sciences (EUFEPS) launched a Global Bioequivalence Harmonization Initiative (GBHI) several years ago. This international conference was the first in a series of workshops organized by EUFEPS/BABP under GBHI. The workshop provided a forum for pharmaceutical scientists from academia, industry and regulatory agencies to have open discussions on selected BE issues in the hope of identifying common ground and arriving at a harmonized view on these topics.

Limited output transcranial electrical stimulation (LOTES-2017): Engineering principles, regulatory statutes, and industry standards for wellness, over-the-counter, or prescription devices with low risk.

We present device standards for low-power non-invasive electrical brain stimulation devices classified as limited output transcranial electrical stimulation (tES). Emerging applications of limited output tES to modulate brain function span techniques to stimulate brain or nerve structures, including transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and transcranial pulsed current stimulation (tPCS), have engendered discussion on how access to technology should be regulated. In regards to legal regulations and manufacturing standards for comparable technologies, a comprehensive framework already exists, including quality systems (QS), risk management, and (inter)national electrotechnical standards (IEC). In Part 1, relevant statutes are described for medical and wellness application. While agencies overseeing medical devices have broad jurisdiction, enforcement typically focuses on those devices with medical claims or posing significant risk. Consumer protections regarding responsible marketing and manufacture apply regardless. In Part 2 of this paper, we classify the electrical output performance of devices cleared by the United States Food and Drug Administration (FDA) including over-the-counter (OTC) and prescription electrostimulation devices, devices available for therapeutic or cosmetic purposes, and devices indicated for stimulation of the body or head. Examples include iontophoresis devices, powered muscle stimulators (PMS), cranial electrotherapy stimulation (CES), and transcutaneous electrical nerve stimulation (TENS) devices. Spanning over 13 FDA product codes, more than 1200 electrical stimulators have been cleared for marketing since 1977. The output characteristics of conventional tDCS, tACS, and tPCS techniques are well below those of most FDA cleared devices, including devices that are available OTC and those intended for stimulation on the head. This engineering analysis demonstrates that with regard to output performance and standing regulation, the availability of tDCS, tACS, or tPCS to the public would not introduce risk, provided such devices are responsibly manufactured and legally marketed. In Part 3, we develop voluntary manufacturer guidance for limited output tES that is aligned with current regulatory standards. Based on established medical engineering and scientific principles, we outline a robust and transparent technical framework for ensuring limited output tES devices are designed to minimize risks, while also supporting access and innovation. Alongside applicable medical and government activities, this voluntary industry standard (LOTES-2017) further serves an important role in supporting informed decisions by the public.

Normas ocupacionais do benzeno: uma abordagem sobre o risco e exposição nos postos de revenda de combustíveis / Occupational regulation for benzene: an approach on risk and exposure in gas stations

Resumo Introdução: trabalhadores estão sujeitos a riscos decorrentes da exposição ambiental e ocupacional ao benzeno, situação ainda mais crítica quando associada a fatores como desigualdade social, múltipla exposição, suscetibilidade individual, degradação ambiental e às possíveis interações entre os contaminantes ambientais. Além disso, nem sempre as regulamentações são estabelecidas e/ou atualizadas apenas a partir de achados científicos, pois são processos permeados por conflitos de interesses. Objetivo: realizar análise crítica sobre a identificação de risco e avaliação da exposição ao benzeno. Métodos: revisão bibliográfica e documental do marco normativo brasileiro e internacional sobre exposição ao benzeno, com relação aos aspectos toxicológicos, de exposição ocupacional e ambiental e de avaliação de risco. Discussão: o controle da exposição ao benzeno permeia o campo da disputa técnico-política de saúde e segurança, constituindo-se em marco regulatório resultante de consenso de entendimentos. Esses entendimentos são marcados pela disputa entre a proteção à saúde e a gestão empresarial das condições de trabalho, em detrimento das evidencias científicas. Em tal contexto, os Limites de Exposição Ocupacional podem variar significativamente entre os países e agências, apesar do reconhecimento universal de que não há limites seguros para exposição ao benzeno, por ser um composto carcinogênico.

Abstract Introduction: workers are subject to risks from environmental and occupational exposure to benzene. This situation is even more critical when combined with social inequality, multiple exposure, individual susceptibility, environmental degradation, and possible interactions between environmental contaminants. In addition, regulations are not always established and/or updated only from scientific evidences, because they are processes permeated by conflicts of interest. Objective: to produce a critical analysis on risk identification and benzene exposure evaluation. Methods: literature and documentary review of the Brazilian and international regulatory standards on benzene exposure, toxicological aspects, occupational and environmental exposure, and risk evaluation. Discussion: benzene exposure control permeates the technical-political dispute of health and safety, resulting in a regulatory standard from consensus of understandings. These understandings are shaped by the dispute between health protection and business management of working conditions, to the detriment of scientific evidence. In this context, the Occupational Exposure Limits can vary significantly between countries and agencies, despite the universal recognition that there are no safe limits for benzene exposure, because it is a carcinogenic compound.