Remote diagnostic imaging using artificial intelligence for diagnosing hip dysplasia in infants: Results from a mixed-methods feasibility pilot study.

Objectives: Infant hip dysplasia or Developmental Dysplasia of the Hip (DDH) occurs in 1-2% of births worldwide and leads to hip arthritis if untreated. We sought to evaluate the feasibility of implementing an artificial intelligence-enhanced portable ultrasound tool for infant hip dysplasia (DDH) screening in primary care, through determining its effectiveness in practice and evaluating patient and provider feedback. Methods: A US-FDA-cleared artificial intelligence (AI) screening device for DDH (MEDO-Hip) was added to routine well-child visits from age 6 to 10 weeks. A total of 306 infants were screened during a 1-year pilot study within three family medicine clinics in Alberta, Canada. Patient and provider satisfaction were quantified using the System Usability Survey (SUS), while provider perceptions were further investigated through semi-structured interviews. Results: Provider and user surveys commonly identified best features of the tool as immediate diagnosis, offering reassurance/knowledge and avoiding travel, and noted technical glitches most frequently as a barrier. A total of 369 scans of 306 infants were performed from Feb 1, 2021 until Mar 31, 2022. Eighty percent of hips scanned were normal on initial scans, 14% of scans required a follow-up study in the primary care clinic, and DDH cases were identified and treated at the expected 2% rate (6 infants). Conclusions: It is feasible to implement a point-of-care ultrasound AI screening tool in primary care to screen for infants with DDH. Beyond improved screening and detection, this innovation was well accepted by patients and fee-for-service providers with a culture and history of innovation.

Safety assessment for Tris(2,4-di-tert-butylphenyl) phosphite (Irgafos 168) used as an antioxidant and stabilizer in food contact applications.

During and after fabrication of polymeric food contact articles (FCA), polymers undergo oxidation by thermal decomposition processes initiated by oxygen, heat, light, shear, and catalyst residues. To reduce degradation of the polymer, a commonly used secondary antioxidant (AO), Irgafos 168 (I-168), may be included. Use of I-168 in polymeric FCAs presents a potential concern for neurotoxicity due to its phosphate-containing degradation species, I-168ate. As a result, we evaluated dietary exposure and oral toxicity data for I-168 and its degradants when used as an AO in FCAs. Our exposure assessment included extensive review of the U.S. food-contact regulatory history of I-168 resulting in a combined cumulative estimated daily intake (CEDI) of 0.09 mg/kg bw/day for I-168 and I-168ate when used as an AO in FCAs. Our comprehensive literature review of toxicological data and supporting structure activity relationship (SAR) analysis of I-168 reactivity against acetylcholinesterase diminished concern for potential neurotoxic effects of I-168 and its degradants. An acceptable daily intake (ADI) value of 1 mg/kg bw/day for I-168 was derived from a two-year rodent combined chronic toxicity/carcinogenicity study, which is higher than the CEDI and supports the safety of current authorized food contact use levels of I-168.

AI aided workflow for hip dysplasia screening using ultrasound in primary care clinics.

Developmental dysplasia of the hip (DDH) is a common cause of premature osteoarthritis. This osteoarthritis can be prevented if DDH is detected by ultrasound and treated in infancy, but universal DDH screening is generally not cost-effective due to the need for experts to perform the scans. The purpose of our study was to evaluate the feasibility of having non-expert primary care clinic staff perform DDH ultrasound using handheld ultrasound with artificial intelligence (AI) decision support. We performed an implementation study evaluating the FDA-cleared MEDO-Hip AI app interpreting cine-sweep images obtained from handheld Philips Lumify probe to detect DDH. Initial scans were done by nurses or family physicians in 3 primary care clinics, trained by video, powerpoint slides and brief in-person. When the AI app recommended follow-up (FU), we first performed internal FU by a sonographer using the AI app; cases still considered abnormal by AI were referred to pediatric orthopedic clinic for assessment. We performed 369 scans in 306 infants. Internal FU rates were initially 40% for nurses and 20% for physicians, declining steeply to 14% after ~ 60 cases/site: 4% technical failure, 8% normal at sonographer FU using AI, and 2% confirmed DDH. Of 6 infants referred to pediatric orthopedic clinic, all were treated for DDH (100% specificity); 4 had no risk factors and may not have otherwise been identified. Real-time AI decision support and a simplified portable ultrasound protocol enabled lightly trained primary care clinic staff to perform hip dysplasia screening with FU and case detection rates similar to costly formal ultrasound screening, where the US scan is performed by a sonographer and interpreted by a radiologist/orthopedic surgeon. This highlights the potential utility of AI-supported portable ultrasound in primary care.

Co-designing person-centred quality indicator implementation for primary care in Alberta: a consensus study.

BACKGROUND: We aimed to contribute to developing practical guidance for implementing person-centred quality indicators (PC-QIs) for primary care in Alberta, Canada. As a first step in this process, we conducted stakeholder-guided prioritization of PC-QIs and implementation strategies. Stakeholder engagement is necessary to ensure PC-QI implementation is adapted to the context and local needs. METHODS: We used an adapted nominal group technique (NGT) consensus process. Panelists were presented with 26 PC-QIs, and implementation strategies. Both PC-QIs and strategies were identified from our extensive previous engagement of patients, caregivers, healthcare providers, and quality improvement leaders. The NGT objectives were to: 1. Prioritize PC-QIs and implementation strategies; and 2. Facilitate the participation of diverse primary care stakeholders in Alberta, including patients, healthcare providers, and quality improvement staff. Panelists participated in three rounds of activities. In the first, panelists individually ranked and commented on the PC-QIs and strategies. The summarized results were discussed in the second-round face-to-face group meeting. For the last round, panelists provided their final individual rankings, informed by the group discussion. Finally, we conducted an evaluation of the consensus process from the panelists' perspectives. RESULTS: Eleven primary care providers, patient partners, and quality improvement staff from across Alberta participated. The panelists prioritized the following PC-QIs: 'Patient and caregiver involvement in decisions about their care and treatment'; 'Trusting relationship with healthcare provider'; 'Health information technology to support person-centred care'; 'Co-designing care in partnership with communities'; and 'Overall experience'. Implementation strategies prioritized included: 'Develop partnerships'; 'Obtain quality improvement resources'; 'Needs assessment (stakeholders are engaged about their needs/priorities for person-centred measurement)'; 'Align measurement efforts'; and 'Engage champions'. Our evaluation suggests that panelists felt that the process was valuable for planning the implementation and obtaining feedback, that their input was valued, and that most would continue to collaborate with other stakeholders to implement the PC-QIs. CONCLUSIONS: Our study demonstrates the value of co-design and participatory approaches for engaging stakeholders in adapting PC-QI implementation for the primary care context in Alberta, Canada. Collaboration with stakeholders can promote buy-in for ongoing engagement and ensure implementation will lead to meaningful improvements that matter to patients and providers.

Person-centred care (PCC) is a model of care where patient needs and preferences are included in decisions about care and treatment. To improve PCC in primary care in Alberta, Canada, we plan to use person-centred quality indicators (PC-QIs). Using PC-QIs involves surveying patients about their care experiences and using this information to make improvements. For example, if 20% of patients do not feel they are getting enough information, the clinic may create a checklist for the providers so information is not missed. We engaged a panel of 11 people, including patients, family doctors, and staff who support quality improvement in clinics across the province to decide together which PC-QIs primary care clinics in Alberta should use. We also asked the panel to decide the most important strategies that would make using the PC-QIs more successful. The panel chose PC-QIs related to: patient and caregiver involvement in decisions about care and treatment, a trusting relationship with the healthcare provider, having health information technology to support PCC, partnering with communities in healthcare, and the patient's overall experience. The most important strategies were: developing partnerships among people working in primary care in Alberta, discussing their needs and common efforts for improving PCC, engaging "champions," and securing funding that would be needed. Finally, we asked the panelists to share their experiences with participating in this process. Panelists found the process useful and that their input was valued. Most panelists would also like to continue to work together to put the PC-QIs into practice.

Examining organization and provider challenges with the adoption of virtual domestic violence and sexual assault interventions in Alberta, Canada, during the COVID-19 pandemic.

OBJECTIVES: In Canada, calls to domestic violence and sexual assault hotlines increased during the COVID-19 pandemic as stricter public health restrictions took effect in parts of the country. Moreover, the public health measures introduced to limit the transmission of COVID-19 saw many health providers abruptly pivot to providing services virtually, with little to no opportunity to plan for this switch. We carried out a qualitative research study to understand the resulting challenges experienced by providers of domestic violence and sexual assault support services. METHODS: Twenty-four semi-structured interviews were conducted to gather in-depth information from service providers and organizational leaders in the Canadian province of Alberta about the challenges they experienced adopting virtual and remote-based domestic violence and sexual assault interventions during the COVID-19 outbreak. Interview transcripts and field notes were analysed using a thematic analysis approach. RESULTS: Our findings highlighted multiple challenges organizations, service providers and clients experienced. These included: (1) systemic (macro-level) challenges pertaining to policies, legislation and funding availability, (2) organization and provider (meso-level) challenges related to adapting services and programmes online or for remote delivery and (3) provider perceptions of client (micro-level) challenges related to accessing virtual interventions. CONCLUSIONS: Equity-focused policy and intersectional and systemic action are needed to enhance delivery and access to virtual interventions and services for domestic violence and sexual assault clients.

Evaluating the implementation of collaborative teams in community family practice using the Primary Care Assessment Tool.

OBJECTIVE: To examine patients' perceptions of care outcomes following the introduction of collaborative teams into community family practices. DESIGN: Cross-sectional, longitudinal study comprising 4 patient telephone surveys between 2007 and 2016, using random sampling of telephone records based on postal codes. SETTING: Ten WestView Primary Care Network (WPCN) clinics in Alberta, serving a suburban-rural population of approximately 89 000 and an aggregate clinic panel of 61 611 (in 2016). PARTICIPANTS: Adults aged 18 and older with a visit to a family physician in a WPCN clinic at least once in the previous 18 months. INTERVENTIONS: In 2006, WPCN implemented a decentralized and distributed collaborative team model, integrating nonphysician health care professionals into member clinics. MAIN OUTCOME MEASURES: The Primary Care Assessment Tool (PCAT) was used to evaluate standardized primary care delivery domains. Between-year changes were compared using ANOVA (analysis of variance). Clinic-level subgroup analyses were performed. RESULTS: The number of completed surveys included 896 in 2007, 904 in 2010, 1000 in 2013, and 1800 in 2016, reaching 90% to 100% of the targeted sample size. In aggregate, the WPCN PCAT summary score and the scores of 4 core and 2 ancillary domains of primary care exceeded the quality threshold of 3.0: extent of affiliation, ongoing care, first-contact utilization, coordination of care, family-centredness, and cultural competence. The first-contact access domain significantly improved from 2007 to 2016 (P < .001). The domains extent of affiliation, first-contact utilization, and coordination of information systems were unchanged. Ongoing care, coordination of care, comprehensiveness, family-centredness, community orientation, and cultural competence decreased. Except for in 2010, the 2 highest scoring clinics were non-participating solo practices; the lowest-scoring clinic was the one with the largest number of physicians. Across survey years, the PCAT summary score increased statistically significantly for 1 solo practice, remained consistent at an above-quality threshold for another, but decreased for all multi-physician clinics. Unattached patients (ie, those without a family doctor) scored the lowest. CONCLUSION: This study found that WPCN provides high-quality primary care overall, but that patient-perceived outcomes do not indicate global improvement concurrent with team-based initiatives. Decreased standardization of the distributed model likely influenced study-observed variations in clinic performance. Future research should identify clinic and team characteristics that benefit most from team-based care and factors that explain solo practices outperforming models of team-based care.

Achievement of Accreditation by Community-Based Family Practice - Workload and Cost Analysis.

Five Alberta family practices achieved accreditation with Accreditation Canada in 2013-2015. This study conducted a workload and cost analysis of achieving accreditation. Human resources (HR) comprised 95% of the total cost. Document preparation constituted 76% of workload and 68% of total HR costs. Centralized content experts were tasked with document write-up. Clinics focused on survey preparation: 56% of staff participated, with the workload being the heaviest on managers. In CAD (2018 $ value), per capita cost was the highest for the 2-physician clinic ($65.78) and lower for the 11-physician ($19.44) clinic. Other cost determinants included culture, organizational structure, physician/staff engagement and pre-existing compliance to standards. A cost-benefit analysis shall provide insights into system-level benefits.

A review of dietary exposure and toxicological information on epoxidised soybean oil (ESBO) in food-contact applications.

Plasticisers have a long history of use in the industrial manufacture and processing of polymers for the purpose of increasing the flexibility and strength of the material. Approximately, 80-90% of the plasticiser market is devoted to the production of PVC, a highly versatile thermoplastic used to produce both rigid and flexible articles. Many types of plasticisers, including ortho-phthalate esters (OPE), can be added to PVC to impart flexibility. Recently, alternatives to OPEs, such as epoxy esters and aliphatic adipates, are becoming more prevalent for use in PVC-based food-contact articles. Epoxidised soybean oil (ESBO) is used as a plasticiser in flexible PVC for many food-contact articles, including food packaging and food processing equipment, from which it can potentially migrate into food and become a component of an individual's daily diet. The purpose of this review is to provide an update on the US dietary exposure and toxicological information on ESBO used in PVC-based food-contact articles. The cumulative dietary concentration (CDC) and cumulative estimated daily intake (CEDI) for ESBO from its use as a plasticiser in PVC-based food-contact articles (i.e. gaskets for glass jar lids and film wraps) was calculated to be 2.6 mg/kg (i.e. ppm) and 0.13 mg/kg bw/d, respectively, for the general population. Some regulatory agencies have reported safety levels for ESBO, and the most conservative no observed adverse effect level (NOAEL) was identified to be 100 mg/kg bw/d (i.e. 2000 ppm) based on a two-year feeding study in rats. The current CEDI is well below these levels, supporting the safe use of ESBO in food-contact applications.

High-volume general practitioners in Alberta: a descriptive analysis.

BACKGROUND: Alberta is considering capping daily fee-for-service physician billings, but little is known about high-volume practice in the province and its impact on patient health outcomes. In this initial study, we conducted a descriptive analysis of general practitioners' patient volumes and billing practices in relation to associated practitioner demographic characteristics. METHODS: We conducted a retrospective descriptive analysis of the associations of practitioner characteristics, including full-time versus non-full-time practice, provider sex, years in practice, geographic location and international medical graduate status, with high-volume (> 50 visits/d) practice using general practice billing data from 2011 to 2016. Use of general practitioner service codes was described and compared by general practitioner volume status, with adjustment for physician demographic characteristics and geographic parameters. RESULTS: We included 3465 general practitioners practising fee-for-service in Alberta between 2011 and 2016, of whom 233 (6.7%) were identified as high-volume providers. Physicians who had been in practice longer (odds ratio [OR] 1.04 per year, 95% confidence interval [CI] 1.02-1.05) and international medical graduates (OR 1.89, 95% CI 1.40-2.54) were more likely to exceed 50 patient visits/day. Female physicians were less likely to exceed 50 patient visits/day (OR 0.14, 95% CI 0.07-0.28). Rural practice location was negatively associated with high-volume practice (OR 0.87, 95% CI 0.79-0.95) when we controlled for zone within the province. Zone 5 (North) was associated with high-volume practice (OR 1.95, 95% CI 1.06-3.58). Less than full-time practice was prevalent (1836 providers [53.0%]). High-volume general practitioners billed fewer service codes requiring longer visits, except for the most highly remunerated code (patients with complex health issues). INTERPRETATION: These results can inform policy-makers when considering payment system changes. Our next step is to examine the association of high-volume practice with outcomes important to patients, such as evidence of treatment failure (emergency department visits and hospital admissions) for conditions sensitive to primary care management.

Safety assessment for octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)-propionate (CAS Reg. No. 2082-79-3) from use in food contact applications.

Octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate (CAS Reg. No. 2082-79-3), currently marketed as Irganox 1076 (I-76), is a sterically hindered phenolic antioxidant used in a variety of organic substrates, including those used in the manufacture of food contact articles. In 2012, the US Food and Drug Administration (USFDA), Office of Food Additive Safety (OFAS), initiated a post-market re-evaluation of the food contact applications of I-76. This project aimed to ensure that current dietary exposures from the use of I-76 in food contact articles are accurately captured and the safety assessment considered all relevant and available toxicological information. To accomplish these aims, the USFDA reviewed the available toxicological studies and chemistry information on food contact applications of I-76. Based on this in-depth analysis, a NOAEL of 64 mg/kg-bw/d (female rats) from a chronic rat study and a cumulative estimated dietary intake (CEDI) of 4.5 mg/p/d, was used to calculate a margin of exposure (MOE) of ∼850. We concluded that the previous and current exposure levels provide an adequate margin of safety (MOS) and remain protective of human health for the regulated uses.

Defining, quantifying, and characterizing adult frequent users of a suburban Canadian emergency department.

INTRODUCTION: Frequent emergency department (ED) users are inconsistently defined and poorly studied in Canada. The purpose of this study was to develop uniform definitions, quantify ED burden, and characterize adult frequent users of a suburban community ED. METHODS: We retrospectively reviewed the administrative database of the WestView ED in Alberta for patients ≥ 18 years of age presenting during the fiscal year of 2010. Adult frequent users and extreme frequent users were defined as patients with yearly visit numbers greater than the 95th and 99th percentiles, respectively. Demographic information including age, sex, ED length of stay, diagnoses, Canadian Triage and Acuity Scale (CTAS) level, and disposition were collected and stratified by ED frequency of use categories. RESULTS: The study included 22,333 ED visits by 14,223 patients. Frequent users represented 3.1% of patients and 13.8% of visits. Extreme frequent users represented 0.8% of patients, 5.4% of visits, and 568,879 cumulative ED minutes (395 days). Nonfrequent users had one to four, frequent users had five or more, and extreme frequent users had eight or more visits over a 12-month period. Frequent users and extreme frequent users had a significantly longer ED length of stay overall and in most age categories. Alcohol-related behavioural disorders, anxiety, nausea/vomiting, and chronic obstructive pulmonary disease were prominent diagnoses, suggesting that psychiatric, somatic, and chronic illnesses may underlie recurrent visits. Admission rates were significantly higher for frequent compared to nonfrequent users. CONCLUSIONS: We propose reproducible definitions for adult frequent and extreme frequent ED users and provide information on the characteristics and burden of care of these groups at a community Canadian suburban ED. Adoption of these definitions would allow comparison across centres in future research and facilitate targeted interventions for frequent and extreme frequent ED users.

An interprofessional collaborative practice model: primary-care clinical associates at the family practice setting.

A persistent physician shortage challenges the ability of our healthcare system to meet the growing health needs of our aging population. Health system redesign must maximize the efficient use of available human resources. The Alberta Westview Primary Care Network (WPCN) introduced the Primary Care Clinical Associate (CA) program in 2005. This interprofessional collaborative practice model recruits nonphysician health professionals from various disciplines as autonomous, independent practitioners. They are associates of the family physician and use their full scope of practice to jointly care for a panel of patients in family practice settings. Three years after its inception, the CA program has grown steadily from two initial participating family practices to its current implementation in six of seven WPCN clinics. The present direction of Canadian primary healthcare reform is towards team approaches. Accordingly, the CA program has wide applicability provincially across Canada. The objective of this article is to describe in detail the design of the WPCN CA program including its conceptual framework and operational strategies and to share program implementation learning. This knowledge transfer will enable replication of the WPCN CA model, where appropriate, in other jurisdictions.

Tolerability outcomes of a multicenter, observational, open-label, drug-surveillance study in patients with type 2 diabetes mellitus treated with pioglitazone for 2 years.

OBJECTIVE: Pioglitazone (PIO), a thiazolidinedione (TZD), is reported to be highly effective in the treatment of type 2 diabetes mellitus, but is associated with edema, heart failure, and weight gain. This study documented long-term tolerability outcomes of patients taking pioglitazone and assessed how troublesome these adverse events were for the patients. METHODS: This was a prospective, multicenter, observational, open-label, drug-surveillance study that followed patients for 2 years. Patients were already taking or received prescriptions for PIO (PIO group) or a non-TZD (comparator group). Data on glycosylated hemoglobin, fasting plasma glucose, and physician-assessed hypoglycemia were gathered every 4 to 6 months. Patients answered a questionnaire about edema, shortness of breath, and weight gain and were asked to self-assess how troublesome these events were. Peripheral edema and weight gain were selected for post hoc analysis. The Edema Severity scale (ranging from no edema to very deep edema causing gross distortion to amputation) was used to evaluate peripheral edema. Physicians determined the relationship between treatment and serious adverse events. RESULTS: Investigators at 176 sites across Canada enrolled 1871 patients (53 patients in the comparator group were later excluded for receiving PIO). Data from 1527 PIO patients and 291 comparator patients were analyzed (mean age: 59.5 years PIO, 61.6 years comparator; males: 58.0% PIO, 59.8% comparator; white: 77.9% PIO, 81.4% comparator; mean weight: 87.2 kg PIO, 86.1 kg comparator). Median dose of PIO was 30 mg/d. Edema and weight gain were the only adverse events for which statistical models were fitted. Results at 2 years were as follows: peripheral edema-p25.1% (383/1527) of patients in the PIO group, 16.5% (48/291) in the comparator group (adjusted odds ratio [OR]: 1.92 [95% CI, 1.32-2.79]); pulmonary edema-1.3% (20/1527) PIO, 0.7% (2/291) comparator; heart failure-2.4% (37/1527) PIO, 1.4% (4/291) comparator; weight gain-49.6% (757/1527) PIO, 36.8% (107/291) comparator; mean weight gain-2.19 kg PIO (n = 1344), 0.34 kg comparator (n = 251) (adjusted OR: 1.70 [95% CI, 1.29-2.22]). Patient self-assessment at 2 years revealed: edema-rated very or extremely troublesome by 11.2% (29/258) PIO, 13.8% (5/36) comparator; shortness of breath on exertion-15.1% (174/1153) PIO, 16.2% (32/198) comparator (rated very or extremely troublesome by 8.6% [15/174] PIO, 21.9% [7/32] comparator); shortness of breath lying down and at night occurred less frequently (1.8%-4.5% in both groups) than shortness of breath on exertion; and weight gain-rated very or extremely troublesome by 4.8% (22/455) PIO, 2.9% (2/70) comparator. Deaths occurred in approximately 2% of patients in each group (37/1527 PIO, 6/344 comparator); none of the deaths in the PIO group were judged by the investigators to be related to the study drug. CONCLUSIONS: After 2 years of treatment, the incidences of heart failure (2.4%) and pulmonary edema (1.3%) in the patients who received PIO in this observational study were low and consistent with published literature. In this study, patients in the PIO group experienced more peripheral edema (adjusted OR, 1.92) and greater weight gain (adjusted OR, 1.70) than did patients in the non-TZD (comparator) group. The subjective assessment of the troublesome nature of these adverse events on these patients taking PIO was low.

Implementation and evaluation of a community-based medication reconciliation (CMR) system at the hospital-community interface of care.

The WestView community-based medication reconciliation (CMR) aims to decrease medication error risk. A clinical pharmacist visits patients' homes within 72 hours of hospital discharge and compares medications in discharge orders, family physicians' charts, community pharmacy profiles and in the home. Discrepancies are discussed and reconciled with the dispenser, hospital prescriber and follow-up care provider. The CMR demonstrates successful integration that is patient-centred and standardized, bridging the hospital-community interface and improving information flow and communication channels across a family-physician-led multi-disciplinary team. A concurrent research study will evaluate the impact of CMR on health services utilization and to develop a risk prediction model.

The WestView Primary Care Network in the first six months: defragmenting the system.

The objective of this article is to describe the integration of local primary care services through the development of a primary care network in Alberta. WestView Primary Care Network (WPCN) has the vision of integrating primary care teams into the health system. As a result, WPCN has incorporated integrative primary care teams into its clinical programs. Through its strategy of "defragmentation," WPCN is accomplishing the beginnings of service integration in the local health care context.

The use of structure-activity relationship analysis in the food contact notification program.

Food contact substances (FCS) include polymers, paper and paperboard, and substances used in their manufacture, that do not impart a technical effect on food. Moreover, FCSs are industrial chemicals generally consumed at dietary concentrations (DC) of less than 1mg/kg food (ppm), and more commonly at less than 0.05 ppm (50 ppb), in the daily diet. As such, many industrial chemicals have been analyzed for toxicological concern, some of which may share structural similarity with FCSs or their constituents, and the majority of these studies are available in the public domain. The DCs of these compounds lend themselves to using structure-activity relationship (SAR) analysis, as the available "expert systems" and use of analogs allows for prediction and management of potential carcinogens. This paper describes the newly implemented food contact notification (FCN) program, the program by which FDA reviews FCSs for safe use, the administrative review of FCSs, the SAR tools available to FDA, and qualitative and quantitative risk assessments using SAR analysis within the regulatory framework of reviewing the safety of FCSs.

Optimizing the Synthesis of Tetratellurafulvalene.

A systematic synthetic study of the pi-donor tetratellurafulvalene (TTeF, 6) has resulted in an optimized preparation producing repeatable yields of over 20%. The use of a "one-step" Li/Sn metal exchange/Te(0) insertion procedure and freshly prepared microcrystalline Te(0) serve to drive toward products, the equilibria converting (Z)-1,2-bis(trimethylstannyl)ethylene (1) to its corresponding metal-exchanged vinyllithium species and subsequently to lithium ditellurolate 5. Furthermore, the use of LiCl as an additive to enhance the reactivity of n-BuLi in these metal exchange reactions also increases yields and reproducibility. The slow addition of 1 equiv of tetrahaloethylene during the final cyclization step favors intramolecular reactions which produce TTeF vs intermolecular reactions that lead to oligomeric byproducts. The use of tetrabromoethylene in place of tetrachloroethylene in this step also reduces byproduct formation.