Lessons from international experience in controlling pharmaceutical expenditure. II: Influencing doctors.

This is the second of three papers that review international policies to control spending on drugs and to improve the efficiency of drug use. This paper reviews policies influencing doctors'' prescribing of drugs--particularly the use of budgetary restrictions, information and feedback, and guidelines--and evaluates the impact of these policies. Studies evaluating incentive systems are limited, but evidence suggests that providing information on its own will not lead to substantial changes in practice and that more active strategies should be evaluated.     

Risk of agranulocytosis and aplastic anaemia in relation to use of antithyroid drugs. International Agranulocytosis and Aplastic Anaemia Study.

The relation of the use of antithyroid drugs to the risk of developing agranulocytosis and aplastic anaemia was evaluated in a population based case-control study with patients from Israel and seven regions in Europe. Data were obtained from cases and hospital controls by interview. Use of antithyroid drugs in the week before the onset of illness was compared in 262 patients with agranulocytosis and 1771 controls. Forty five patients (17%) and five controls (0.3%) had used antithyroid drugs. The relative risk was estimated to be 102 (95% confidence interval 38 to 275) taking into account confounding by other factors, including the use of other drugs. The excess risk for use of antithyroid drugs in any one week was estimated to be 6.3 cases of agranulocytosis per million users. Use of antithyroid drugs in a five month period ending one month before admission to hospital was compared in 135 patients with aplastic anaemia and 2145 controls. Four patients (3%) and five controls (0.2%) had taken drugs; the estimate of relative risk was 9.2 (95% confidence interval 1.8 to 47) after control for confounding. The estimate of excess risk of agranulocytosis with the use of antithyroid drugs was lower than found previously. Although the excess risk for aplastic anaemia was not calculated, these data suggest that it is very low.     

Role of drugs in traffic accidents.

Serum samples from 201 drivers who presented at emergency departments within six hours after being injured in a road accident and 325 control drivers selected randomly at petrol stations were screened for drugs by combined thin-layer and gas chromatography. Blood alcohol concentrations were also measured, and a questionnaire on the subjects'' state of health and use of drugs administered. At interview 30 patients (15%) and 44 controls (13%) said that they had taken drugs in the previous 24 hours. Four patients (2%) and six controls (2%) said that they had taken psychotropic drugs, but serum analysis detected psychotropic drugs in 10 patients (5%) and eight controls (2.5%). Diazepam was found in 16 of the 18 subjects in whom psychotropic drugs were detected. Alcohol was detected in 30 patients (15%) and three controls (1%). Drug use appeared to be somewhat lower in Finland than in other Western countries, and illness to be a more important traffic hazard than drugs in general. Interview was not a reliable method of establishing whether drivers had taken psychotropic drugs. Taking diazepam may increase the risk of being involved in a traffic accident, but alcohol was the most powerful risk factor.     

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.     

Developing drugs for the developing world: an economic,legal, moral,and political dilemma

This paper discusses the economic, legal, moral, and political difficulties in developing drugs for the developing world. It argues that large, global pharmaceutical companies have social responsibilities to the developing world, and that they may exercise these responsibilities by investing in research and development related to diseases that affect developing nations, offering discounts on drug prices, and initiating drug giveaways. However, these social responsibilities are not absolute requirements and may be balanced against other obligations and commitments in light of economic, social, legal, political, and other conditions. How a company decides to exercise its social responsibilities to the developing world depends on (1) the prospects for a reasonable profit and (2) the prospects for a productive business environment. Developing nations can either help or hinder the pharmaceutical industry's efforts to exercise social responsibility through various policies and practices. To insure that companies can make a reasonable profit, developing nations should honor pharmaceutical product patents and adhere to international intellectual property treaties, such as the Trade-Related Aspects of Intellectual Property Rights (TRIPS) agreement. To insure the companies have a good business environment, developing nations should try to promote the rule of law, ethical business practices, stable currencies, reliable banking systems, free and open markets, democracy, and other conditions conducive to business. Overall, this paper advocates for reciprocity and cooperation between pharmaceutical companies and developing nations to address the problem of developing drugs for the developing world. In pursuing this cooperative approach, developing nations may use a variety of other techniques to encourage pharmaceutical companies to act responsibly, such as subsidizing pharmaceutical research, helping to design and implement research protocols, providing a guaranteed market, and bulk buying.     

Effect of aspirin and non-steroidal anti-inflammatory drugs on colorectal adenomas: case-control study of subjects participating in the Nottingham faecal occult blood screening programme.

OBJECTIVE--To examine the relation between the use of aspirin and non-steroidal anti-inflammatory drugs and the presence of asymptomatic colorectal adenomas. DESIGN--Case-control study of subjects participating in a randomised controlled trial of faecal occult blood screening for colorectal cancer. Data on analgesics and other drugs were obtained from a questionnaire which was mainly concerned with diet and was administered by an interviewer. SETTING--Nottingham. SUBJECTS--147 patients with positive results in faecal occult blood tests who were found to have colorectal adenomas (cases), 153 age and sex matched control subjects with negative results in such tests (negative controls), and 176 control subjects with positive results in the tests who were found not to have colorectal adenomas (positive controls). MAIN OUTCOME MEASURES--Relative risk of developing colorectal adenomas according to frequency and duration of use of analgesics. RESULTS--Cases reported taking less aspirin and non-steroidal anti-inflammatory drugs than the negative controls, with the estimated relative risk for any use being 0.49 (95% confidence interval 0.3 to 0.8). The inverse association was less strong when cases were compared with the positive controls (0.66 (0.4 to 1.1)). The association was specific for aspirin and non-steroidal anti-inflammatory drugs there being no association with paracetamol or other drugs. Prescribed use of non-steroidal anti-inflammatory drugs for longer than five years was associated with the lowest risk (0.21 (0.1 to 0.8)), although the numbers reporting prolonged prescribed use were small. CONCLUSIONS--These findings support the hypothesis that aspirin and non-steroidal anti-inflammatory drug use protects against the development of colorectal neoplasia.     

Multiobjective long-term planning of biopharmaceutical manufacturing facilities

Biopharmaceutical companies with large portfolios of clinical and commercial products typically need to allocate production across several multiproduct facilities, including third party contract manufacturers. This poses several capacity planning challenges which are further complicated by the need to satisfy different stakeholders often with conflicting objectives. This work addresses the question of how a biopharmaceutical manufacturer can make better long-term capacity planning decisions given multiple strategic criteria such as cost, risk, customer service level, and capacity utilization targets. A long-term planning model that allows for multiple facilities and accounts for multiple objectives via goal programming is developed. An industrial case study based on a large scale biopharmaceutical manufacturer is used to illustrate the functionality of the model. A single objective model is used to identify how best to use existing capacity so as to maximize profits for different demand scenarios. Mitigating risk due to unforeseen circumstances by including a dual facility constraint is shown to be a reasonable strategy at base case demand levels but unacceptable if demands are 150% higher than expected. The capacity analysis identifies where existing capacity fails to meet demands given the constraints. A multiobjective model is used to demonstrate how key performance measures change given different decision making policies where different weights are assigned to cost, customer service level, and utilization targets. The analysis demonstrates that a high profit can still be achieved while meeting key targets more closely. The sensitivity of the optimal solution to different limits on the targets is illustrated.     

Interactions between parasite and vector control, animal productivity and rural welfare

These fundamental economic pressures coupled with concern for the environment and for the welfare of animals and, of course, for the welfare of humans, lead us to the fundamental conclusion that the goal of livestock production must be optimisation of inputs and outputs to satisfy the market needs. Standards will have to be set for welfare, land use patterns will have to be modified for social as well as economic reasons, and these will lead to the selection of health and production policies which optimise the long term efficiency of animal use.As we have seen, arthropods and the diseases they carry have profound impact on the efficiency of production and constrain the use of land in many areas where there are deficits of food. Consequently, we have to integrate control policies for these problems into a more orderly process of livestock development. Since we have recognised and accepted that a different series of factors intervene in different regions within countries, we must also accept that control and eradication policies will differ from area to area and from time to time. Parasite control has to be slotted into the order of priorities at different points and at different levels of intensity as the development process continues. Economic and social analysis, with the help of modelling, can provide guidance on the changes that may be needed but it is imperative that they be complemented by more effective recording and monitoring schemes. These schemes must cover animal productivity, and the full mix of factors which constrain efficient animal use. Fortunately, we now understand how to do all this, at a cost which is sustainable by any and every country.     

Antibiotic abuse: the testimony of medical students.

Surveys of the use of antimicrobial drugs on students during antimicrobial drugs on students during their first 15 months in medical or dental school indicate that they have been treated with these agents at least three times as frequently as seems reasonable, and that the tetracyclines, ampicillin, penicillin G and erythromycin are the chief drugs overused. Antimicrobiol therapy is frequently instituted for probable viral respiratory tract infections and without any attempt to establish a bacteriologic diagnosis. It is likely that anitmicrobiol agents are used more widely in treating the general public in Canada than in treating medical students. Improvements in the rational use of this important group of drugs could increase the quality and probably reduced the cost of medical care.     

Transferring the costs of expensive treatments from secondary to primary care.

General practitioners, especially fundholders, are becoming increasingly concerned about being asked to prescribe treatments for their patients that are outside their therapeutic experience. They are concerned about the clinical responsibility for such prescribing and the effects on their budgets. In some specialties transferring the costs of expensive treatments from secondary to primary care (cost shifting) has become partly institutionalised because of the separate sources of funding for drugs prescribed in the two sectors. With increased efforts to control the rising costs of the drugs budget and the emergence of new expensive treatments, cost shifting will be a challenge to clinicians and purchasers as they strive for rational, cost effective prescribing. A review of the funding mechanisms for drugs prescribing and of the relation between the licensing process and the decision to support the use of a treatment in primary or secondary care is needed.     

西北半干旱区深旋松耕作对马铃薯水分利用和产量的影响

探明深旋松耕作技术(VRT)对西北黄土高原半干旱区马铃薯阶段性耗水、个体和群体生长状况、产量、水分利用效率和经济收益的影响,可为寻求抗旱增产、资源高效利用的耕作方法提供依据.本研究采用随机区组设计,于2016和2017年设置旋耕15 cm (TT)、深松40 cm (DLT)、深旋松耕40 cm (VRT) 3种耕作方式,测定马铃薯不同生育时期0～200 cm土层土壤贮水量、叶片SPAD值、叶面积指数、植株干物质量和产量等指标,计算阶段耗水量、水分利用效率(WUE)、商品率、商品产量、纯收益和新增收益等指标,探究深旋松耕作对马铃薯生产效率和经济效益的影响.结果表明: 与TT和DLT相比,VRT能显著促进马铃薯在盛花期和块茎膨大期的耗水,2016和2017年分别较DLT、TT增加了46.7、35.7和27.2、47.3 mm.由于VRT促进马铃薯耗水,叶片SPAD值、干物质量和叶面积指数均显著提高,证明它能促进马铃薯个体和群体发育.基于较高的个体和群体生长量,VRT的马铃薯块茎产量显著提高,分别在2016和2017年较DLT和TT增加了156.8%、47.8%和24.8%、41.0%,WUE相应地提高了92.3%、19.2%和18.9%、26.6%.深旋松耕作使马铃薯商品薯产量显著增加,纯收益和新增纯收益显著提高,在2016和2017年分别达到 12631.9、11019.1和29498.3、18245.5元·hm^-2.深旋松耕作促进马铃薯花期和块茎膨大期耗水,使马铃薯叶片SPAD值、干物质量和叶面积指数显著提高,导致块茎产量和水分利用效率明显升高,并提高了商品薯产量和纯收益,是适宜于西北黄土高原半干旱区马铃薯种植的耕作技术.     

A comparative study on resource allocation and energy efficient job scheduling strategies in large-scale parallel computing systems

In the large-scale parallel computing environment, resource allocation and energy efficient techniques are required to deliver the quality of services (QoS) and to reduce the operational cost of the system. Because the cost of the energy consumption in the environment is a dominant part of the owner’s and user’s budget. However, when considering energy efficiency, resource allocation strategies become more difficult, and QoS (i.e., queue time and response time) may violate. This paper therefore is a comparative study on job scheduling in large-scale parallel systems to: (a) minimize the queue time, response time, and energy consumption and (b) maximize the overall system utilization. We compare thirteen job scheduling policies to analyze their behavior. A set of job scheduling policies includes (a) priority-based, (b) first fit, (c) backfilling, and (d) window-based policies. All of the policies are extensively simulated and compared. For the simulation, a real data center workload comprised of 22385 jobs is used. Based on results of their performance, we incorporate energy efficiency in three policies i.e., (1) best result producer, (2) average result producer, and (3) worst result producer. We analyze the (a) queue time, (b) response time, (c) slowdown ratio, and (d) energy consumption to evaluate the policies. Moreover, we present a comprehensive workload characterization for optimizing system’s performance and for scheduler design. Major workload characteristics including (a) Narrow, (b) Wide, (c) Short, and (d) Long jobs are characterized for detailed analysis of the schedulers’ performance. This study highlights the strengths and weakness of various job scheduling polices and helps to choose an appropriate job scheduling policy in a given scenario.     

Global Climate Change: Benefit-Cost Analysis vs. the Precautionary Principle

The precautionary principle appears to be directly applicable to the prospect that human activities will cause substantial changes to global climate. The magnitude and characteristics of the change in climate and its effects on human activities and unmanaged ecosystems are highly uncertain, potentially catastrophic, and nearly irreversible on human time scales. Nevertheless, the precautionary principle adds little to benefit cost analysis for evaluating climate policies. Benefit cost analysis can incorporate aversion to uncertainty about future outcomes, and also provides a method for balancing this concern against concern for uncertain near term policy costs. The policies favored by setting constraints on future outcomes, such as atmospheric stabilization and tolerable windows, may be less precautionary than the policies favored by benefit cost analysis, as benefit cost analysis can more readily accommodate concerns for moderate as well as severe harms. Concerns about possible climate catastrophes can also be incorporated in benefit cost analysis and, in any event, may have limited implications for policy choice.     

Aspirin and bleeding peptic ulcers in the elderly.

A case-control study was performed to determine whether aspirin confers a similar risk of bleeding from gastric or duodenal ulcers in the elderly as non-aspirin, non-steroidal anti-inflammatory drugs. The intake of analgesics in 230 patients with bleeding ulcers aged 60 and over and in hospital and community controls matched for age and sex was examined. Those who had taken aspirin were between two and three times more likely to be admitted to hospital with bleeding ulcers. This increased risk was not accounted for by aspirin taken for indigestion or by concurrent use of non-aspirin, non-steroidal anti-inflammatory drugs. A similar effect was not seen for paracetamol. When aspirin and other non-steroidal anti-inflammatory drugs were considered together the overall risk attributed to the drugs suggested that these drugs may be responsible for over a third of admissions for bleeding peptic ulcers in the elderly.     

Carrier-mediated delivery of peptidic drugs for cancer therapy

Protein and peptide drugs are used for treatment of a variety of ailments. However, their wider use has been hindered by issues such as poor bioavailability in vivo and the cost involved in producing these drugs. This review discusses the various carrier-mediated methods used for delivery of peptide and protein drugs, with emphasis on liposomal and microspherical drug delivery systems. A brief look at the types of peptidic drugs currently in use clinically, and a brief discourse on several novel ideas for better protein delivery systems for cancer therapy is included.     

Identification of cultured cells expressing ligand-gated cationic channels.

We have identified cultured cells that express ligand-gated cation channels using a simple method which may also be applied to the screening of chemical agents for their use as agonists or antagonists. This assay is based upon the observation that many ligand-gated cation channels are permeable to lithium and agonists induce the flux of lithium into the cells which contain them. Since the accumulation of intracellular lithium can alter the cell cycle, the measurement of [3H]thymidine ([3H]thy) incorporation should reflect this occurrence. This expectation was realized using the PC12 cell line which expresses neuronal-like nicotinic acetylcholine receptor (nAChR). When cholinergic agonists are applied to PC12 cells in the presence of lithium-containing buffer and cells are subsequently pulsed with [3H]thy, the radiolabel incorporation into these cells relative to controls is reduced. If cholinergic antagonists are included or if the concentration of agonist either rapidly desensitizes receptors or is insufficient to induce channel opening, the reduction in [3H]thy incorporation is not observed. This method also provides a rapid way to screen cultured cell lines for those that express ligand-gated cation channels. This assay offers the potential to be automated for the low cost screening of drugs which act upon ligand-gated ion channels.     

Seventeen years' experience of a voluntarily based drug rationalisation programme in hospital.

A study was carried out analysing the operation of a drug rationalisation programme in a central London teaching district that had evolved from experience over 17 years. Creation of a limited list of about 700 drugs had been achieved by local consensus. Drug selection was based on appraisal of efficacy, safety, and cost and was undertaken by means of collaborative participation of most consultant specialists in the district. Educative and other non-restrictive strategies for reinforcing the rationalisation policy had achieved a consistently high rate of compliance in prescribing recommended drugs. The concept of selectivity in drug use and its continuous local reappraisal had a beneficial impact on the prescribing habits of doctors at all levels of seniority as well as on the training of medical undergraduates and nurses in the therapeutic use of medicines. Peer review and self audit were encouraged by use of an extensive monitoring system which incorporated continuous "facilitative" dialogue between ward pharmacists and prescribers. Two models of drug rationalisation programme were studied, the second of which together with other local initiatives had been associated with substantial and sustained reductions in drug spending each year over nine years since 1978. It is concluded that the second drug rationalisation programme model substantially improves the cost effective use of drugs in hospital and furthermore has the potential of being extended to general practice, especially in types of prescribing that are common to both forms of patient care.     

Improved fruiting of the straw mushroom (Volvariella volvacea) on cotton waste supplemented with sodium acetate

Compared with controls, treatment of the cultivation substrate for Volvariella volvacea with 0.02% NaAc at the “spraying water” stage increased the number of fruiting body primordia by 280, the mushroom yield by 16.25%, the number of fruiting bodies by 35.57%, and the biological efficiency by 16.28%. The average single mushroom weight increased by 19.33%, but there was no significant difference between treatments and controls. A correlation analysis revealed a significant (p < 0.05) positive correlation between the total yield and the number of fruiting bodies. Comparisons of the cost and profit values for the sodium acetate-treated and untreated groups revealed that the former generated a higher income for the grower. Our data indicate that sodium acetate treatment is a promising new method for increasing V. volvacea yields. A possible mechanism whereby sodium acetate increased the mushroom yield is discussed.