Economic cost-benefit analysis of person-centred medicines reviews by general practice pharmacists.

BACKGROUND: Medicines reviews by general practice pharmacists improve patient outcomes, but little is known about the associated economic outcomes, particularly in patients at higher risk of medicines-related harm. AIM: To conduct an economic cost-benefit analysis of pharmacists providing person-centred medicines reviews to patients with hyperpolypharmacy (prescribed ≥ 10 regular medicines) and/or at high risk of medicines-related harm across multiple general practice settings. METHOD: Service delivery costs were calculated based on the pharmacist's salary, recorded timings, and a general practitioner fee. Direct cost savings were calculated from the cost change of patients' medicines post review, projected over 1 year. Indirect savings were calculated using two models, a population-based model for avoidance of hospital admissions due to adverse drug reactions and an intervention-based model applying a probability of adverse drug reaction avoidance. Sensitivity analyses were performed using varying workday scenarios. RESULTS: Based on 1471 patients (88.4% with hyperpolypharmacy), the cost of service delivery was €153 per review. Using the population-based model, net cost savings ranging from €198 to €288 per patient review and from €73,317 to €177,696 per annum per pharmacist were calculated. Using the intervention-based model, net cost savings of €651-€741 per review, with corresponding annual savings of €240,870-€457,197 per annum per pharmacist, were calculated. Savings ratios ranged from 181 to 584% across all models and inputs. CONCLUSION: Person-centred medicines reviews by general practice pharmacists for patients at high risk of medicines-related harm result in substantial cost savings. Wider investment in general practice pharmacists will be beneficial to minimise both patient harm and healthcare system expenditure.

Evidence-based practice guidelines for prescribing home modifications for clients with bariatric care needs.

BACKGROUND/AIM: Home modifications maintain people's functional independence and safety. No literature exists to guide the prescription of home modifications for clients with bariatric care needs. With Australia's increasing obesity rate, more evidence is needed to support home modification prescribers. This study aimed to map Australian home modification prescribing practices for clients with bariatric care needs and to establish and evaluate a clinical resource for this prescription process. METHODS: The study included two phases. Phase 1 conducted a cross-sectional survey of therapists practicing in Australia, and Australian industry partners who prescribe or install home modifications for clients with bariatric care needs. Phase 2 included design, implementation and evaluation of a clinical resource. Data were analysed with means and frequencies; multivariable regression analysis was used to explore prescribing habits. RESULTS: Therapists surveyed (n = 347) reported 11 different bariatric weight definitions. Less than 3% constantly or regularly prescribed home modifications for these clients; rails were most commonly prescribed. Many therapists (n = 171, 58%) 'never' or 'rarely' knew rail load capacity. Therapists' knowledge of rail load capacity was associated with previous experience prescribing home modifications (P = 0.009); rail manufacturer's advice (P = 0.016) and not using advice from builders (P = 0.001). Clinical resources were used by 11% (n = 26) of therapists to support their prescription, and industry sporadically relied on therapists to specify modification design requirements (n = 5, 45%). Post-implementation of a clinical resource increased consensus regarding understanding of the term bariatric and increased consultation with builders and manufacturers. CONCLUSION: There was a lack of consistency in bariatric terminology, uncertainty of rail load capacities and minimal use of clinical practice guidelines. Additional resources will assist with consistency in prescribing practices to maximise occupational performance for clients with bariatric care needs.

Catalytic wittig reactions of semi- and nonstabilized ylides enabled by ylide tuning.

The first examples of catalytic Wittig reactions with semistabilized and nonstabilized ylides are reported. These reactions were enabled by utilization of a masked base, sodium tert-butyl carbonate, and/or ylide tuning. The acidity of the ylide-forming proton was tuned by varying the electron density at the phosphorus center in the precatalyst, thus facilitating the use of relatively mild bases. Steric modification of the precatalyst structure resulted in significant enhancement of E selectivity up to >95:5, E/Z.

Part I: the development of the catalytic Wittig reaction.

We have developed the first catalytic (in phosphane) Wittig reaction (CWR). The utilization of an organosilane was pivotal for success as it allowed for the chemoselective reduction of a phosphane oxide. Protocol optimization evaluated the phosphane oxide precatalyst structure, loading, organosilane, temperature, solvent, and base. These studies demonstrated that to maintain viable catalytic performance it was necessary to employ cyclic phosphane oxide precatalysts of type 1. Initial substrate studies utilized sodium carbonate as a base, and further experimentation identified N,N-diisopropylethylamine (DIPEA) as a soluble alternative. The use of DIPEA improved the ease of use, broadened the substrate scope, and decreased the precatalyst loading. The optimized protocols were compatible with alkyl, aryl, and heterocyclic (furyl, indolyl, pyridyl, pyrrolyl, and thienyl) aldehydes to produce both di- and trisubstituted olefins in moderate-to-high yields (60-96%) by using a precatalyst loading of 4-10 mol%. Kinetic E/Z selectivity was generally 66:34; complete E selectivity for disubstituted α,ß-unsaturated products was achieved through a phosphane-mediated isomerization event. The CWR was applied to the synthesis of 54, a known precursor to the anti-Alzheimer drug donepezil hydrochloride, on a multigram scale (12.2 g, 74% yield). In addition, to our knowledge, the described CWR is the only transition-/heavy-metal-free catalytic olefination process, excluding proton-catalyzed elimination reactions.

Breaking the ring through a room temperature catalytic Wittig reaction.

One ring no longer rules them all: Employment of 2.5-10 mol % of 4-nitrobenzoic acid with phenylsilane led to the development of a room temperature catalytic Wittig reaction (see scheme). Moreover, these enhanced reduction conditions also facilitated the use of acyclic phosphine oxides as catalysts for the first time. A series of alkenes were produced in moderate to high yield and selectivity.

Transformation of 5-ene steroids by the fungus Aspergillus tamarii KITA: mixed molecular fate in lactonization and hydroxylation pathways with identification of a putative 3beta-hydroxy-steroid dehydrogenase/Delta5-Delta4 isomerase pathway.

The fungus Aspergillus tamarii metabolizes progesterone to testololactone in high yield through a sequential four step enzymatic pathway which, has demonstrated flexibility in handling a range of steroidal probes. These substrates have revealed that subtle changes in the molecular structure of the steroid lead to significant changes in route of metabolism. It was therefore of interest to determine the metabolism of a range of 5-ene containing steroidal substrates. Remarkably the primary route of 5-ene steroid metabolism involved a 3beta-hydroxy-steroid dehydrogenase/Delta(5)-Delta(4) isomerase (3beta-HSD/isomerase) enzyme(s), generating 3-one-4-ene functionality and identified for the first time in a fungus with the ability to handle both dehydroepiansdrosterone (DHEA) as well as C-17 side-chain containing compounds such as pregnenolone and 3beta-hydroxy-16alpha,17alpha-epoxypregn-5-en-20-one. Uniquely in all the steroids tested, 3beta-HSD/isomerase activity only occurred following lactonization of the steroidal ring-D. Presence of C-7 allylic hydroxylation, in either epimeric form, inhibited 3beta-HSD/isomerase activity and of the substrates tested, was only observed with DHEA and its 13alpha-methyl analogue. In contrast to previous studies of fungi with 3beta-HSD/isomerase activity DHEA could also enter a minor hydroxylation pathway. Pregnenolone and 3beta-hydroxy-16alpha,17alpha-epoxypregn-5-en-20-one were metabolized solely through the putative 3beta-HSD/isomerase pathway, indicating that a 17beta-methyl ketone functionality inhibits allylic oxidation at C-7. The presence of the 3beta-HSD/isomerase in A. tamarii and the transformation results obtained in this study highlight an important potential role that fungi may have in the generation of environmental androgens.

Micro-photochemistry: photochemistry in microstructured reactors. The new photochemistry of the future?

The use of a confined space in which to carry out reactions has proven popular in recent years, as demonstrated by the large volume of work published on 'molecular microreactors' such as zeolites, micelles and nanoparticles. This article looks at reactions in microstructured reactors, also known as microchannelled reactors or microreactors. In general, these consist of a 'chip' with narrow channels etched into it. Microstructured reactors have been the subject of several review articles to date, focusing on preparation, types of reactions that may be carried out and on the potential for 'green' applications. However, the use of microstructured reactor technology in photochemistry has, until now, not been subject to review. This perspective aims to outline the work done to date in this area and in particular to demonstrate the advantages and future prospectives of this technology in photochemical processes. Photochemistry in microstructured reactors is an emerging area of interest and to date has demonstrated significant potential as a viable alternative to traditional photochemical synthesis.