Mass production methods for mass vaccination: improving flow and operational performance in a COVID-19 mass vaccination centre using Lean.

The COVID-19 pandemic has infected tens of millions of people worldwide causing many deaths. Healthcare systems have been stretched caring for the most seriously ill and lockdown measures to interrupt COVID-19 transmission have had adverse economic and societal impacts. Large-scale population vaccination is seen as the solution.In the UK, a network of sites to deploy vaccines comprised National Health Service hospitals, primary care and new mass vaccination centres. Due to the pace at which mass vaccination centres were established and the scale of vaccine deployment, some sites experienced problems with queues and waiting times. To address this, one site used the Lean systematic improvement approach to make rapid operational improvements to reduce process times and improve flow.The case example identifies obstacles to flow experienced by a mass vaccination centre and how they were addressed using Lean concepts and techniques. Process cycle times were used as a proxy metric for efficiency and flow. Based on daily demand volume and open hours, takt time was calculated to give a process completion rate to achieve flow through the vaccination centre.The mass vaccination centre achieved its aim of reducing process times and improving flow. Administrative and clinical cycle times were reduced sufficiently to increase throughput and the number of queues and queueing time were reduced improving client experience.The design and operational management of vaccination centre processes contribute to client experience, efficiency and throughput. Lean provides a systematic approach that can improve operational processes and facilitate client flow through mass vaccination centres.

Oxidative Route to Indoles via Intramolecular Amino-Hydroxylation of o-Allenyl Anilines.

A new intramolecular oxidative amino-hydroxylation of o-allenyl anilines is reported. Treatment of carbamate-protected anilines with lead(IV) carboxylates in dichloromethane at room temperature results in facile tandem C-N (allene cyclization) and C-O bond formation (carboxylate trapping) to form indole products. Detailed reaction scope, mechanistic and kinetic studies suggest a reaction pathway involving an initial Wessely dearomatization step followed by cyclization and rearomatization.

Patient preferences for GI cancer surveillance and telemedical follow-up.

INTRODUCTION: Surveillance care including routine physical exams and testing following gastrointestinal (GI) cancer treatment can be fiscally and emotionally burdensome for patients. Emerging technology platforms may provide a resource-wise surveillance strategy. However, effective implementation of GI cancer surveillance is limited by a lack of patient level perspective regarding surveillance. This study aimed to describe patient attitudes toward GI cancer surveillance and which care modalities such as telemedicine and care team composition best meet the patient's needs for follow-up care. METHODS: Focused interviews were conducted with 15 GI cancer patients undergoing surveillance following curative-intent surgery. All interviews were audio recorded, transcribed verbatim, and uploaded to NVivo. Study personnel trained in qualitative methods consensus coded 10% of data inductively and iteratively developed a codebook and code descriptions. Using all transcripts, data matrices were developed to identify themes inherent in the transcripts. RESULTS: Qualitative analysis revealed three overarching themes. First, increasing ease of access to surveillance care through telemedicine follow-up services may interfere with patients' preferred follow-up routine, which is an in-office visit. Second, specialist providers were trusted by patients to deliver surveillance care more than primary care providers (PCPs). Thirdly, patients desired improved psychosocial health support during the surveillance period. CONCLUSION: These novel patient-level qualitative data demonstrate that replacing conventional in-office GI cancer surveillance care with telemedicine is not what many patients desire. These data also demonstrate that his cohort of patients prefer to see specialists for GI cancer surveillance care rather than PCPs. Future efforts to enhance surveillance should include increased psychosocial support. Telemedicine implementation should be personalized toward specific populations who may be interested in fewer in-office surveillance visits.

A Survey of the Structures of US FDA Approved Combination Drugs.

Combination drugs are an important class of US FDA approved pharmaceuticals. These drugs have been on a continuous growth trajectory since the first combination drugs were approved in the 1940s. In this Perspective, we report the first comprehensive compilation and analysis of US FDA approved combination drugs, from the first approval in 1943 through 2018. Our database contains 419 combination drugs, which are represented by 328 unique small molecule structures. Breakdown of these drugs according to disease category, structure, combination composition, and year of approval is presented as well as the top 24 most commonly used small molecule combination drug components. For frequently used small molecule components, we present "relationship diagrams" to aid in the visualization of the many drug combinations these structures are part of. The main body contains 10 disease-focused sections wherein every small molecule component utilized as part of a combination for each disease category is displayed.

From Oxiranes to Oligomers: Architectures of U.S. FDA Approved Pharmaceuticals Containing Oxygen Heterocycles.

Oxygen heterocycles are the second most common type of heterocycles that appear as structural components of U.S. Food and Drug Administration (FDA) approved pharmaceuticals. Analysis of our database of drugs approved through 2017 reveals 311 distinct pharmaceuticals containing at least one oxygen heterocycle. Most prevalent among these are pyranoses, with furanoses, macrolactones, morpholines, and dioxolanes rounding off the top five. The main body of this Perspective is organized according to ring size, commencing with three- and four-membered rings and ending with macrocycles, polymers, and unusual oxygen-containing heterocycles. For each section, all oxygen heterocycle-containing drugs are presented along with a brief discussion about structural and drug application patterns.

'The Unhealthy Other': How vaccine rejecting parents construct the vaccinating mainstream.

To address the phenomenon of vaccine hesitancy and rejection, researchers increasingly recognise the need to engage with the social context of parents' decision-making. This study examines how vaccine rejecting parents socially construct the vaccinating mainstream in opposition to themselves. We analyse qualitative data from interviews with parents in Adelaide, South Australia. Applying insights from Social Identity Theory (SIT), we show how these parents bolster their own sense of identity and self-belief by employing a discourse that casts vaccinators as an Unhealthy Other. We demonstrate how the parents identify vaccination as a marker of parental conformity to the 'toxic practices of mass industrial society', linking it to other ways in which membership of the consumerist mainstream requires individuals to 'neglect their health.' This is explored through themes of appearance, diet, (over) consumption of pharmaceuticals, inadequate parenting values and wilful or misguided ignorance. This construction of the Unhealthy Other elevates the self-concept of vaccine hesitant and rejecting parents, who see themselves as part of an enlightened, but constantly besieged, group of healthy and virtuous parents. It is common for the vaccinating mainstream to present vaccine hesitant and rejecting parents as a group subject to epistemic closure, groupthink, confirmation bias and over-confidence in their own expertise. However, vaccine hesitant and rejecting parents also see mainstream society as a group-a much larger one-subject to the same problems. We suggest the need to mitigate the 'groupness' of vaccination and non-vaccination by extending the practice of vaccination to recognisable practitioners of holistic health.

Dearomatization Approach to 2-Trifluoromethylated Benzofuran and Dihydrobenzofuran Products.

A mild dearomatization enabled ortho-selective replacement of an aromatic C-H bond with a hexafluoroacetylacetone (hfacac) substituent has been developed. This reaction is dependent on a hypervalent iodine generated phenoxonium intermediate, a critical choice of solvent, and reagent addition order. The fluorinated dihydrobenzofuran product can be transformed into dihydrobenzofuran and benzofuran products decorated with a 2-trifluoromethyl group. The 3-trifluoromethylacyl substituted benzofurans rapidly form hydrates, which can be reduced to the corresponding alcohols.

Metal-Free Synthesis of Fluorinated Indoles Enabled by Oxidative Dearomatization.

Nitrogen heterocycles are found in a majority of approved small-molecule pharmaceuticals, and the number of approved fluorinated drugs is increasing each decade. Therefore, new approaches for accessing fluorinated nitrogen heterocycles are of great significance. A novel, scalable, and metal-free method for accessing a wide range of fluorinated indoles is described. This oxidative-dearomatization-enabled approach assembles 2-trifluoromethyl NH-indole products from simple commercially available anilines with hexafluoroacetylacetone in the presence of an organic oxidant. The nature of the aniline N-capping group is critical for the success of this new reaction. Furthermore, the indole products contain a 3-trifluoroacetyl group, which can be exploited to access a plethora of useful functional groups.

Analysis of the structural diversity, substitution patterns, and frequency of nitrogen heterocycles among U.S. FDA approved pharmaceuticals.

Nitrogen heterocycles are among the most significant structural components of pharmaceuticals. Analysis of our database of U.S. FDA approved drugs reveals that 59% of unique small-molecule drugs contain a nitrogen heterocycle. In this review we report on the top 25 most commonly utilized nitrogen heterocycles found in pharmaceuticals. The main part of our analysis is divided into seven sections: (1) three- and four-membered heterocycles, (2) five-, (3) six-, and (4) seven- and eight-membered heterocycles, as well as (5) fused, (6) bridged bicyclic, and (7) macrocyclic nitrogen heterocycles. Each section reveals the top nitrogen heterocyclic structures and their relative impact for that ring type. For the most commonly used nitrogen heterocycles, we report detailed substitution patterns, highlight common architectural cores, and discuss unusual or rare structures.

A scalable rhodium-catalyzed intermolecular aziridination reaction.

The amine has landed! By employing the rhodium catalyst [Rh2 (esp)2 ] in the presence of a readily available amine source (DPH), unactivated and styrene-type olefins can now be stereospecifally transformed, in high yields at room temperature, into valuable NH aziridine products. esp=α,α,α',α'-tetramethyl-1,3-benzenedipropionic acid.

Static magnetic fields neither prevent nor diminish symptoms and signs of delayed onset muscle soreness.

OBJECTIVE: To determine whether application of a commercially available static magnetic field would alter the signs and/or symptoms of delayed onset muscle soreness (DOMS) produced by exhaustive eccentric exercise. DESIGN: A double-blinded, randomized, and placebo-controlled study, with subjects serving as their own controls. SETTING: An outpatient physical therapy and performance center. PARTICIPANTS: Twenty-three healthy volunteers (18 women; mean age, 30 y; range, 18-40 y; 5 men; mean age, 29 y; range, 19-39 y). INTERVENTION: After exhaustive eccentric exercise of both the right and left elbow flexor muscle groups, subjects received daily treatment with either a 350G magnet or a placebo device for 5 consecutive days. MAIN OUTCOME MEASURES: Outcome variables, including anthropometric measurements, perceived discomfort, and muscle force production, were compared using linear mixed models. RESULTS: Arm circumference, relaxed elbow flexion angle, and pain increased, whereas active elbow flexion angle and maximal isometric torque decreased transiently before returning to near baseline. No significant difference in outcome variables existed between the treated and control arms. Participants reported less pain in both treated and control arms after each session, suggesting a placebo effect. CONCLUSIONS: Static magnetic fields were no more effective than placebo in preventing DOMS.

Parent and professional agreement on cognitive level of children with autism.

The aim of the study was to compare the extent of agreement between parents and professional evaluators regarding the cognitive level of children with autism. We sought to determine the degree of parent and standardized test agreement about the child's cognitive level for children at different levels of cognitive functioning. Information regarding parental view of cognitive levels was collected from the questionnaires used during the initial evaluation. These levels were compared with age equivalencies obtained by professionals from standardized intellectual measures. Significant difference between parental perception and professional assessment of the child's cognitive level was found. In addition, there was significant correlation between the level of agreement and cognitive functioning; agreement increased as the level of cognitive functioning increased.