Evaluation of total purchasing pilots in England and Scotland and implications for primary care groups in England: personal interviews and analysis of routine data

Objectives: To evaluate the reported achievements of the 52 first wave total purchasing pilot schemes in 1996-7 and the factors associated with these; and to consider the implications of these findings for the development of the proposed primary care groups. Design: Face to face interviews with lead general practitioners, project managers, and health authority representatives responsible for each pilot; and analysis of hospital episode statistics. Setting: England and Scotland for evaluation of pilots; England only for consideration of implications for primary care groups. Main outcome measures: The ability of total purchasers to achieve their own objectives and their ability specifically to achieve objectives in the service areas beyond fundholding included in total purchasing. Results: The level of achievement between pilots varied widely. Achievement was more likely to be reported in primary than in secondary care. Reported achievements in reducing length of stay and emergency admissions were corroborated by analysis of hospital episode statistics. Single practice and small multipractice pilots were more likely than large multipractice projects to report achieving their objectives. Achievements were also associated with higher direct management costs per head and the ability to undertake independent contracting. Large multipractice pilots required considerable organisational development before progress could be made. Conclusion: The ability to create effective commissioning organisations the size of the proposed primary care groups should not be underestimated. To be effective commissioners, these care groups will need to invest heavily in their organisational development and in the short term are likely to need an additional development budget rather than the reduction in spending on NHS management that is planned by the government.

Key messages

• The level of reported achievement between the total purchasing pilots in 1996-7 varied widely; achievement was more likely to occur in primary than in secondary care
• Single practice and small multipractice pilots were more likely than large multipractice pilots to report achieving their objectives in 1996/97; achievements were also associated with higher direct management costs per head
• Large multipractice pilots needed more time for organisational development before progress could be made
• Difficulties in creating effective commissioning organisations the size of the proposed primary care groups should not be underestimated
• Primary care groups will need to invest heavily in organisational development and are likely to need an additional development budget in the short term

     

Evolutionary transitions in parental care in cichlid fish

Cichlid fishes (Cichlidae) are well suited for testing theories of the evolution of vertebrate parental care. These freshwater teleost fish provide parental care for their offspring, display many different forms of care and have interspecific variation in which sex stays with the young. Here, we assemble the first family-wide composite phylogeny based on morphological and molecular studies, and trace two sets of character evolution: form of care (substrate guarding and mouthbrooding), and sex of care-giver (biparental, female-only, and male-only). Mouthbrooding has evolved from ancestral substrate guarding with 10 to 14 transitions and 0 to 3 reversals. The data support hypothesized transitions in the sex of care-giver, with uniparental female care having arisen from biparental care 21 to 30 times with 0 to 10 reversals. There is also evidence that male-only care evolved once from biparental care. These transitions in parental care characters are the most numerous reported for any family of vertebrates and, to our knowledge, provide the first quantitative support for models of parental care evolution in fish.     

Synthesis, characterization, and anticonvulsant activity of enaminones. Part 5: Investigations on 3-carboalkoxy-2-methyl-2,3-dihydro-1H-phenothiazin-4[10H]-one derivatives

A new series of anticonvulsant 3-carboalkoxy-2-methyl-2,3-dihydro-1H-phenothiazin-4[10H]-ones is herein reported. 2-Aminothiophenols underwent cyclocondensation with 4-carboalkoxy-5-methylcyclohexane-1,3-diones in refluxing dimethylsulfoxide (DMSO) to yield 3-carboalkoxy-2-methyl-2,3-dihydro-1H-phenothiazin-4[10H]-ones, 4a–k. In the case of the carbo-tert-butoxy derivatives (4c and 4k) prolonged reaction times led to the isolation of the respective 3-unsubstituted-2-methyl-2,3-dihydro-1H-phenothiazin-4[10H]-ones (4l and 4m) instead. Significant anticonvulsant activity was displayed by these analogues, most particularly 4k, which was active at 30 mg/kg intraperitoneally (ip) in mice in the maximal electroshock seizure (MES) evaluation, with no toxicity noted at dosages up to 300 mg/kg. Oral (po) rat evaluation of 4k in the MES evaluation provided an ED₅₀ of 17.60 mg/kg, with no toxicity noted at dosages up to 500 mg/kg, providing a protective index (PI = TD₅₀/ED₅₀) > 28.40. These compounds represent the first reported series of phenothiazines which possess anticonvulsant activity.     

Energy metabolism in Saccharomyces cerevisiae. Effect of progressive starvation on respiration and pyridine nucleotide reduction linked to ethanol oxidation in intact cells

The progressive effects of aerobic starvation on endogenous and ethanol-linked respiration and pyridine nucleotide reduction have been studied in the yeast Saccharomyces cerevisiae. Three distinct phases of pyridine nucleotide reduction were observed when ethanol was added to unstarved yeast: an initial phase of rapid reduction and accelerating respiration (A); a steady-state phase of reduction with maximal respiration (B); a final phase of rapid reduction at anaerobiosis (C).During the first 5 hr of aeration, the steady-state Phase B was replaced by a phase of slow pyridine nucleotide reduction, while Phases A and C were unaffected. During this period, both endogenous pyridine nucleotide reduction and endogenous respiration decreased sharply.Between 5 and 22 hr of aeration, the endogenous level of reduced pyridine nucleotide declined further, while endogenous respiration remained unchanged. Concurrently, the extent of the Phase A reduction doubled.The addition of ethanol to aerobic, unstarved yeast stimulated a rapid pyridine nucleotide reduction, with further reduction occurring at anaerobiosis. Under anaerobic conditions, the addition of ethanol to unstarved yeast caused little further reduction of pyridine nucleotide. Two hours of starvation decreased the extent of the endogenously supported anaerobic reduction and correspondingly increased the ethanol-induced reduction. These results suggest that, in unstarved yeast, reducing equivalents derived from ethanol under aerobic conditions and those derived from endogenous carbohydrate under anaerobic conditions have access to the same pool of pyridine nucleotide. With starvation, this pool becomes accessible to ethanol-derived (or ethanol-mobilized) reducing equivalents under anaerobic conditions.     

Stereochemistry of phytoene biosynthesis by isolated chloroplasts

The incorporation of [2-(14)C,(5R)-5-(3)H(1)]MVA* and [2-(14)C,5-(3)H(2)]MVA into geranylgeraniol and phytoene by a preparation of ;non-aqueous' bean leaf chloroplasts has been studied. In the formation of phytoene from two molecules of geranylgeranyl pyrophosphate, the loss of hydrogen is stereospecific, the hydrogen atom lost from C-1 of each molecule of geranylgeranyl pyrophosphate being that which was originally the pro-S hydrogen atom from C-5 of mevalonate. All the pro-R hydrogen atoms from C-5 of mevalonate are retained. These results with a cell-free system confirm and extend the observations made in previous work with tomato slices.     

Incorporation of [2-14C,(5R)-5-3H1]mevalonic acid into cholesterol by a rat liver homogenate and into β-sitosterol and 28-isofucosterol by Larix decidua leaves

1. Incubation of a rat liver homogenate with 3R-[2-(14)C,(5R)-5-(3)H(1)]mevalonic acid gave cholesterol with (3)H/(14)C atomic ratio 6:5. 2. Conversion of the labelled cholesterol into 3beta-acetoxy-6-nitrocholest-5-ene or cholest-4-ene-3,6-dione resulted in the loss of one tritium atom from C-6. 3. These results show that during cholesterol biosynthesis the 6alpha-hydrogen atom of a precursor sterol is eliminated during formation of the C-5-C-6 double bond. 4. Incorporation of 3R-[2-(14)C,(5R)-5-(3)H(1)]mevalonic acid into the sterols of larch (Larix decidua) leaves gave labelled cycloartenol and beta-sitosterol with (3)H/(14)C atomic ratios 6:6 and 6:5 respectively. 5. One tritium atom was lost from C-6 on conversion of the labelled beta-sitosterol into either 3beta-acetoxy-6-nitrostigmast-5-ene or stigmast-4-ene-3,6-dione, demonstrating that formation of the C-5-C-6 double bond of phytosterols also involves the elimination of the 6alpha-hydrogen atom of a precursor sterol. 6. The 3R-[2-(14)C,(5R)-5-(3)H(1)]mevalonic acid was also incorporated by larch (L. decidua) leaves into a sterol that co-chromatographed with 28-isofucosterol. Confirmation that the radioactivity was associated with 28-isofucosterol was obtained by co-crystallization with carrier 28-isofucosterol and ozonolysis of the acetate to give radioactively labelled 24-oxocholesteryl acetate. 7. The significance of these results to phytosterol biosynthesis is discussed.     

2-Nitroimipramine: A selective irreversible inhibitor of [3H] serotonin uptake and [3H] imipramine binding in platelets

The effect(s) of a new imipramine analogue, 2-nitroimipramine, on high affinity [³H] imipramine binding and [³H] serotonin uptake in human platelets were studied. 2-Nitroimipramine was found not only to be a very potent inhibitor of [³H] imipramine binding and [³H] serotonin uptake but was found to irreversibly inhibit binding and uptake simultaneously. This finding supports previous observations from our laboratory and others that high affinity imipramine binding labels serotonin uptake or transport sites. 2-Nitroimipramine should prove an important tool for subsequent studies of the molecular mechanism(s) involved in the transport of serotonin and the binding of imipramine to platelet and brain membranes.