Grampian Health Board's joint drug formulary.

OBJECTIVE--To develop a model for creating a joint general practice-hospital formulary, using the example of ulcer healing drugs. DESIGN--A joint formulary development group produced draft guidelines based on an earlier hospital formulary, which were sent to interested local general practitioners for consultation. Revised guidelines were then drawn up and forwarded to the health board''s medicines committee for approval and distribution. SETTING--Grampian Health Board. SUBJECTS--Nine members of joint formulary development group plus local general practitioners who were invited to comment on a list of 11 ulcer healing drugs. MAIN OUTCOME MEASURE--Degree of coincidence of drugs selected by hospital doctors and general practitioners. RESULTS--The ulcer healing drugs selected by the panel of general practitioners and by hospital doctors were highly coincident. The cost of one day''s treatment with drugs varied considerably between hospital and general practice--for example, one drug cost 46p in hospital and 1 pounds in general practice and another cost 1.26 pounds in hospital and 1.01 pounds in general practice. Overall, six drugs cost more in hospital and five cost more in general practice. CONCLUSIONS--A joint formulary for use in hospitals and general practice in a health board can be devised fairly simply by consultation as virtually the same drugs are used in both types of practice. It should influence the health board''s expenditure on drugs and affect the choice of drugs when a patient is discharged from hospital or is referred to any hospital in the region.     

An empirical analysis of the cost of rearing dairy heifers from birth to first calving and the time taken to repay these costs

Rearing quality dairy heifers is essential to maintain herds by replacing culled cows. Information on the key factors influencing the cost of rearing under different management systems is, however, limited and many farmers are unaware of their true costs. This study determined the cost of rearing heifers from birth to first calving in Great Britain including the cost of mortality, investigated the main factors influencing these costs across differing farming systems and estimated how long it took heifers to repay the cost of rearing on individual farms. Primary data on heifer management from birth to calving was collected through a survey of 101 dairy farms during 2013. Univariate followed by multivariable linear regression was used to analyse the influence of farm factors and key rearing events on costs. An Excel spreadsheet model was developed to determine the time it took for heifers to repay the rearing cost. The mean±SD ages at weaning, conception and calving were 62±13, 509±60 and 784±60 days. The mean total cost of rearing was £1819±387/heifer with a mean daily cost of £2.31±0.41. This included the opportunity cost of the heifer and the mean cost of mortality, which ranged from £103.49 to £146.19/surviving heifer. The multivariable model predicted an increase in mean cost of rearing of £2.87 for each extra day of age at first calving and a decrease in mean cost of £6.06 for each percentile increase in time spent at grass. The model also predicted a decrease in the mean cost of rearing in autumn and spring calving herds of £273.20 and £288.56, respectively, compared with that in all-year-round calving herds. Farms with herd sizes⩾100 had lower mean costs of between £301.75 and £407.83 compared with farms with <100 milking cows. The mean gross margin per heifer was £441.66±304.56 (range £367.63 to £1120.08), with 11 farms experiencing negative gross margins. Most farms repaid the cost of heifer rearing in the first two lactations (range 1 to 6 lactations) with a mean time from first calving until breaking even of 530±293 days. The results of the economic analysis suggest that management decisions on key reproduction events and grazing policy significantly influence the cost of rearing and the time it takes for heifers to start making a profit for the farm.     

Cost-efficacy in measuring farmland biodiversity – lessons from the Farm Scale Evaluations of genetically modified herbicide-tolerant crops

Measuring farmland biodiversity is time‐consuming and costly. Operational data from the Farm Scale Evaluation of genetically modified crops project were collated to identify the financial and time costs of each of the 14 protocols used. A subset of 113 of the 266 experimental sites was used. The mean overall cost per site was £19 453 (£ of 2002). Laboratory time was almost 2.5 times that in the field. The most costly protocol was soil surface invertebrates because it required species level identification. The ‘bees and butterflies’ protocol at £418 per site was particularly cost‐effective. The six vegetation protocols accounted for 65% and the six arthropod protocols accounted for 29% of the total costs. The recommended reduction from 12 to 3 transects would have saved £1356 per site, 6% of total budget. A minimalist approach using the single‐season seedbank protocol would cost £3437 per site. The effect of geographical spread of sites on cost was small because of clustering of sites and the large number of protocols. Careful selection of ecological indicators can save considerable resources.     

Correlation of bacterial hyperthermic survival with anaesthetic potency

We have evaluated several local anaesthetics and hypnotics for their relative ability to influence hyperthermic cell killing. Bacterial cell survival following exposure to heat and anaesthetic was used as the assay system. The E. coli bacterium used was the unsaturated fatty acid auxotroph, K1060. It was grown at 37 degrees C in medium supplemented with oleic acid and then exposed to 47 degrees C hyperthermia in the presence of an anaesthetic. The local anaesthetics tested were procaine, lidocaine, tetracaine, and benzocaine, and the general anaesthetics were barbital and pentobarbital. The dose response for each anaesthetic was determined over a five-hour heating period. The anaesthetic concentration required during heating to halve the time for cell killing found with heat alone is 5.9 mM for procaine, 0.8 mM for lidocaine, 0.12 mM for tetracaine, 2.0 mM for benzocaine, 6.7 mM for barbital and 1.2 mM for pentobarbital. There is a direct correlation between equivalent effect doses of the local anaesthetics and published data for the relative potency of the same anaesthetics as determined by respiratory arrest in mice and by myocardial contractile force in dogs. The assay we have described would be a convenient and easy test for the interaction of these drugs with hyperthermia. The use of this interaction with hyperthermia as an adjuvant in combined radiation-hyperthermia therapy should be tested.     

Anaesthesia and handling stress effects on pigmentation and monoamines in Arctic charr

Stress responsiveness differs between individuals and is often categorized into different stress coping styles. Using these stress coping styles for selection in fish farming could be beneficial, since stress is one main factor affecting welfare. In Arctic charr (Salvelinus alpinus) carotenoid pigmentation is associated with stress responsiveness and stress coping styles. Thus this could be an important tool to use for selection of stress resilient charr. However, anaesthetics seem to affect carotenoid pigmentation, and it would be better if the method for selection could be implemented during normal maintenance, which usually includes anaesthetics. Therefore, this study investigated how the use of anaesthetics affected carotenoid pigmentation, i.e. number of spots, over time compared to no-anaesthetic treatment. Additionally, the stress indicators monoamines and glucocorticoids were investigated. The results indicate that the anaesthetic MS-222 affects number of spots on the right side. This anaesthetic also increased dopaminergic activity in the telencephalon. Both brain dopaminergic and serotonergic activity was associated with spottiness. Further, behaviour during anaesthetization was associated with spots on the left side, but not the right side. Repetition of the same treatment seemed to affect spot numbers on the right side. In conclusion, this study shows that inducing stress in charr affects the carotenoid spots. Thus, it is possible to use anaesthetics when evaluating spottiness although careful planning is needed.     

Evolution of antiretroviral drug costs in Brazil in the context of free and universal access to AIDS treatment

Background

Little is known about the long-term drug costs associated with treating AIDS in developing countries. Brazil''s AIDS treatment program has been cited widely as the developing world''s largest and most successful AIDS treatment program. The program guarantees free access to highly active antiretroviral therapy (HAART) for all people living with HIV/AIDS in need of treatment. Brazil produces non-patented generic antiretroviral drugs (ARVs), procures many patented ARVs with negotiated price reductions, and recently issued a compulsory license to import one patented ARV. In this study, we investigate the drivers of recent ARV cost trends in Brazil through analysis of drug-specific prices and expenditures between 2001 and 2005.

Methods and Findings

We compared Brazil''s ARV prices to those in other low- and middle-income countries. We analyzed trends in drug expenditures for HAART in Brazil from 2001 to 2005 on the basis of cost data disaggregated by each ARV purchased by the Brazilian program. We decomposed the overall changes in expenditures to compare the relative impacts of changes in drug prices and drug purchase quantities. We also estimated the excess costs attributable to the difference between prices for generics in Brazil and the lowest global prices for these drugs. Finally, we estimated the savings attributable to Brazil''s reduced prices for patented drugs. Negotiated drug prices in Brazil are lowest for patented ARVs for which generic competition is emerging. In recent years, the prices for efavirenz and lopinavir–ritonavir (lopinavir/r) have been lower in Brazil than in other middle-income countries. In contrast, the price of tenofovir is US$200 higher per patient per year than that reported in other middle-income countries. Despite precipitous price declines for four patented ARVs, total Brazilian drug expenditures doubled, to reach US$414 million in 2005. We find that the major driver of cost increases was increased purchase quantities of six specific drugs: patented lopinavir/r, efavirenz, tenofovir, atazanavir, enfuvirtide, and a locally produced generic, fixed-dose combination of zidovudine and lamivudine (AZT/3TC). Because prices declined for many of the patented drugs that constitute the largest share of drug costs, nearly the entire increase in overall drug expenditures between 2001 and 2005 is attributable to increases in drug quantities. Had all drug quantities been held constant from 2001 until 2005 (or for those drugs entering treatment guidelines after 2001, held constant between the year of introduction and 2005), total costs would have increased by only an estimated US$7 million. We estimate that in the absence of price declines for patented drugs, Brazil would have spent a cumulative total of US$2 billion on drugs for HAART between 2001 and 2005, implying a savings of US$1.2 billion from price declines. Finally, in comparing Brazilian prices for locally produced generic ARVs to the lowest international prices meeting global pharmaceutical quality standards, we find that current prices for Brazil''s locally produced generics are generally much higher than corresponding global prices, and note that these prices have risen in Brazil while declining globally. We estimate the excess costs of Brazil''s locally produced generics totaled US$110 million from 2001 to 2005.

Conclusions

Despite Brazil''s more costly generic ARVs, the net result of ARV price changes has been a cost savings of approximately US$1 billion since 2001. HAART costs have nevertheless risen steeply as Brazil has scaled up treatment. These trends may foreshadow future AIDS treatment cost trends in other developing countries as more people start treatment, AIDS patients live longer and move from first-line to second and third-line treatment, AIDS treatment becomes more complex, generic competition emerges, and newer patented drugs become available. The specific application of the Brazilian model to other countries will depend, however, on the strength of their health systems, intellectual property regulations, epidemiological profiles, AIDS treatment guidelines, and differing capacities to produce drugs locally.     

THE EFFECTS OF SOME NEWER ANAESTHETICS ON THE IN VITRO ACTIVITY OF GLUTAMATE DECARBOXYLASE AND GABA TRANSAMINASE IN CRUDE BRAIN EXTRACTS AND ON THE LEVELS OF AMINO ACIDS IN VIVO

—The effects of several anaesthetic and hypnotic compounds with well-defined excitatory side-effects on glutamate decarboxylase and γ-aminobutyric acid transaminase activity have been examined. The dissociative anaesthetics ketamine and γ-hydroxybutyric acid produced competitive inhibition of glutamate decarboxylase with respect to glutamate at concentrations which had no effect on GABA transaminase activity. The inhibitor constant (K_i) values were, ketamine: 13.3 mm , γ-hydroxybutyric acid; 8.8 mm . The steroid anaesthetic alphaxalone was also a potent competitive inhibitor of glutamate decarboxylase K_i= 4.1 mm ). Pentobarbitone, thiopentone and methohexitone non-competitively inhibited both glutamate decarboxylase and GABA-transaminase but only at high concentration (> 20 mm ). None of the drugs tested produced any significant change in brain GABA or glutamate levels following the injection of an hypnotic or anaesthetic dose. It is proposed that an alteration in the rate of GABA synthesis as a result of the inhibition of glutamate decarboxylase could explain the convulsive properties of the dissociative anaesthetics when given at high doses.     

Measurement and reduction of occupational exposure to inhaled anaesthetics.

The occupational exposure of hospital staff to inhaled anaesthetics was investigated using a personal sampling device that provides a measure of the average concentrations breathed by a person over a period of time, as distinct from the spot sampling in the general environment. The anaesthetist''s average exposure to nitrous oxide and halothane during complete operating sessions was twice that expected from simple dilution of the escaping gases by the operating room ventilation. The sampling technique was also used to evaluate the effect of (1) redirection of the waste gas outflow; (2) active scavenging connected to the piped vacuum system. Short-period studies under controlled conditions in the operating theatres and anaesthesia induction rooms showed that the anaesthetist''s exposure could be reduced two- or fourfold by redirecting the outflow and another four- to sixfold by active scavenging. Exposures during complete operating sessions were reduced two- to seven-fold by scavenging.     

Efficiency of antisense oligonucleotide drug discovery

The costs for discovering and developing new drugs continue to escalate, with current estimates that the average cost is more than $800 million for each new drug brought to the market. Pharmaceutical companies are under enormous pressure to increase their efficiency for bringing new drugs to the market by third-party payers, shareholders, and their patients, and at the same time regulators are placing increased demands on the industry. To be successful in the future, pharmaceutical companies must change how they discover and develop new drugs. So far, new technologies have done little to increase overall efficiency of the industry and have added additional costs. Platform technologies such as monoclonal antibodies and antisense oligonucleotides have the potential of reducing costs for discovery of new drugs, in that many of the steps required for traditional small molecules can be skipped or streamlined. Additionally the success of identifying a drug candidate is much higher with platform technologies compared to small molecule drugs. This review will highlight some of the efficiencies of antisense oligonucleotide drug discovery compared to traditional drugs and will point out some of the current limitations of the technology.     

一次性氧气湿化瓶与重复使用湿化瓶应用的对比观察

目的：检测一次性氧气湿化瓶与重复使用湿化瓶用后细菌污染的程度和患者对噪音感受的舒适程度,对比两者的成本效益。方法：随机选出心内科病房内持续吸氧时间超过10天的患者100名,以随机分组的方法分出A组50名、B组50名。A组使用一次性氧气湿化瓶,B组使用重复使用的氧气湿化瓶。按照《医疗卫生机构消毒技术规范》进行采样后送微生物检验室进行病原学检验;同时对两组患者进行噪音感受舒适度的调查;根据使用的氧气湿化瓶成本费用、氧气湿化用灭菌注射用水的价格、含氯消毒剂健之素的费用计算成本。结果：50只一次性氧气湿化瓶使用时间120小时（5天）,微生物学检测未发现致病菌,成本费用9-3元／日,患者噪音感受舒适度满意度调查结果为100％;重复使用氧气湿化瓶使用24小时染茵率28％,成本费用9．6元／日,患者噪音感受舒适度满意度调查结果为60％。结论：使用合格的一次性氧气湿化瓶,在患者费用不会增加的前提下,减少了医院感染机会,增加了患者的舒适度,值得推广使用。     

Economic consequences for UK farmers of growing GM herbicide tolerant sugar beet

Weed control is important and one of the more expensive inputs to sugar beet production. The introduction of genetically modified herbicide tolerant (GMHT) sugar beet would result in a major saving in weed control costs in the crop for growers, including control of problem weeds such as perennial weeds and weed beet. However, there would be other economic consequences of growing GMHT beet, some of which would manifest themselves in other parts of the rotation, such as the previous crop, the cereal stubbles that proceed most beet crops, soil tillage and spray application. The average national saving for UK sugar beet growers if they could use the technology would be in excess of £150 ha^?1 yr^?1 or £23 million yr^?1, which includes reductions in agrochemical use of c. £80 ha,^?1 yr^?1 or £12 million yr^?1. However, for some growers, the gains would be much larger and for a few, less than these figures. The possible cost savings are sufficiently large that they could ensure that sugar beet production, with its regionally important environmental benefits as a spring crop, remains economically viable in the UK post reform of the EU sugar regime.     

Specific effects of drugs at pressure: animal investigations

The interactions of anaesthetics and other drugs with high pressure suggest that protection against the high pressure neurological syndrome (h.p.n.s.) can no longer be considered in terms of generalized non-specific mechanisms. The evidence from our work shows that anaesthetics may either protect, have no effect, or potentiate h.p.n.s. Structural analogues of the steroid anaesthetic Althesin have a protective effect against high pressure tremors in spite of the fact that they have no anaesthetic effects. Low doses of flurazepam are effective against tremor but can be antagonized by Ro 15-1788, which implies in this case a role for the benzodiazepine receptor complex. Pressure interactions with other drugs have included the classic anticonvulsants--which, in general, were relatively ineffective--and various agents perturbing the balance of specific neurotransmitter systems. Representative examples from different studies include 6-hydroxydopamine, muscimol, and sodium valproate. Finally, the potent protection against h.p.n.s. by 2-amino-phosphonoheptanoic acid, an antagonist with preferential action against excitation produced by aspartate and N-methyl-D-aspartate, provides the first evidence that enhanced excitatory amino acid neurotransmission may have an important role in the h.p.n.s.     

Effect of Metal Ions on Melanin – Local Anaesthetic Drug Complexes

The affinity of melanin biopolymers for metal ions, drugs and other organic compounds is an important factor in the etiology of toxic retinopathy, hiperpigmentation, otic lesions and irreversible extrapyramidal disorders. The aim of the presented work was to examine the interaction of local anaesthetic drugs used in ophthalmology with model DOPA-melanin in the presence of metal ions. It has been demonstrated that the analyzed drugs form complexes with melanin biopolymer. Based on the .values of association constants,, the following order of drugs affinity to melanin was found: tetracaine > procaine >> bupivacaine > lidocaine. It has also been shown that Cu²⁺ and Zn²⁺ ions administered to DOPA-melanin before complexing with drugs decrease the total amount of local anaesthetics bound to melanin. The blocking of some active centers in melanin molecules by metal ions, which potentially exist in living systems, may change the clinical therapeutic efficiency of the analyzed local anaesthetic drugs.     

A Male Sterilization Clinic

In the Cardiff Family Planning Association Clinic 330 men have been sterilized during the past 20 months. Selection for operation was made after a detailed discussion between husband, wife, and a Family Planning Association doctor, and with the general practitioner''s agreement. The outpatient operation was performed under local anaesthetic by a surgeon. It was regarded as being successful or complete when two semen analyses showed azoospermia at an interval of one month.     

Impact Assessment of an Independent Agency for Animal Health in England

The applicability of a stochastic model was explored to assess the impact of a new independent agency for animal health in England in terms of the cost of animal disease outbreaks. The new agency was proposed to take responsibility for animal disease management in England. The stochastic model estimates the likelihood that the proposed new agency would face animal disease outbreaks of major and minor magnitude; and how many outbreaks of each magnitude, within its first 30 years of operation. Large variability in the potential total cost of the new agency was attributable to the possibility of an outbreak of an unknown major disease, although Bluetongue, Foot and Mouth Disease, and Avian Influenza were also influential. The results show that if the new agency reduces disease costs by even 0.5%, this could benefit society by an estimated £21 million per year. The stochastic approach offers a method for dealing with uncertainties in any continuing deliberations regarding the proposed new agency, resulting in a potential annual gain of £73 million ranging to an annual loss of £144 million.     

Cost of urology: financial audit in a clinical department.

OBJECTIVES--To cost a clinical unit over one month in 1991, to cost treatment of individual patients from audit data, and to compare this costing method with the hospital charging system. DESIGN--A financial breakdown was obtained for one month''s work. Ward stay, operating time, investigations, and outpatient visits were costed and a formula (episode = days on ward+hours of operating+investigations+outpatient visits) was used to cost patient episodes from audit data. SETTING--The adult urology unit in a teaching hospital. MAIN OUTCOME MEASURES--Costs for each part of patients'' treatment. RESULTS--Total cost was 147,796 pounds for 159 admissions, 738 inpatient days, 131 operations in 29 operating lists, and 615 outpatient visits. An uncomplicated transurethral prostatectomy cost 1140 pounds but complications increased this to 1500 pounds in another patient. The costs of diagnostic cystoscopy were 130 pounds in outpatients, 240 pounds in day surgery, and 430 pounds in inpatients. Hospital charges do not reflect the individual costs of treatment, charges being greater than costs for some patients and lower than costs for others. CONCLUSIONS--Clinicians can produce a financial analysis of their work and cost their patients'' treatment. Audit is strongly advocated as a resource planning tool.     

Benefits and costs of the schools' BCG vaccination programme.

By the mid-1980s the schools'' BCG vaccination programme will be uneconomic. It is estimated that it will cost about pounds5500 to prevent one case of tuberculosis, the average total cost of which would be between pounds400 and pounds1300 depending on medical policy about the degree of illness for which hospital admission is necessary. In December 1975 the costs of the BCG programme were greater than its monetary benefits, probably by a factor of about 2.