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Tuberculosis treatment in complex emergencies: are risks outweighing benefits?

Tuberculosis (TB) is a major public health problem in complex emergencies. Humanitarian agencies usually postpone the decision to offer TB treatment and opportunities to treat TB patients are often missed. This paper looks at the problem of tuberculosis treatment in these emergencies and questions whether treatment guidelines could be more flexible than international recommendations. A mathematical model is used to calculate the risks and benefits of different treatment scenarios with increasing default rates. Model outcomes are compared to a situation without treatment. An economic analysis further discusses the findings in a trade-off between the extra costs of treating relapses and failures and the savings in future treatment costs. In complex emergencies, if a TB programme could offer 4-month treatment for 75% of its patients, it could still be considered beneficial in terms of public health. In addition, the proportion of patients following at least 4 months of treatment can be used as an indicator to help evaluate the public health harm and benefit of the TB programme.

Antitubercular Agents↗

[Pharmacoeconomic aspects of use of structum in osteoarthrosis].

AIM: To study cost-effect efficiency of structum in patients with knee and hip joint osteoarthrosis (OA) in a multicenter trial. MATERIAL AND METHODS: The trial enrolled 192 patients with OA. 110 patients had knee joint OA and 82 patients hip joint OA. The patients received structum for 6 months. Efficacy of the treatment was assessed before use of structum and after it by standard methods. Integral effect of therapy was estimated according to the special program complex. The cost of the drug therapy included the cost of structum and nonsteroid anti-inflammatory drugs (NSAID) on conversion to 1 mg of diclofenac plus the cost of treating side effects. The efficacy per unit cost was calculated by the formula: E1xC2/E2xC1, where E1--integral efficacy of therapy before using structum, E2--integral efficacy of therapy in administration of structum, C1--cost of drug therapy, C2--cost of drug therapy in using structum. RESULTS: E2 was equal to 94% for knee joints OA and 92% for hip joint OA, E1 and C1--21 and 19%, respectively. C2 was equal to 108.43$ for knee joint OA and 106.97 for hip joint OA, C1--29.3 and 27.44, respectively. The efficacy per unit cost for knee joint OA was 94 x 29.3/21 x 108.3 = 1.21, for hip joint OA 92 x 27.44/19 x 106.97 = 1.24. The figures evidence for much higher efficacy per unit cost of structum vs routine NSAID. CONCLUSION: The multicenter trial gave grounds not only for clinical efficacy of structum vs NSAID but also for cost-effect advantage of structum in therapy of OA.

Chondroitin Sulfates↗

Combination drug therapy for hypercholesterolemia. The trade-off between cost and simplicity.

BACKGROUND: The National Cholesterol Education Program recommends achievement of a defined target level of low-density lipoprotein cholesterol (LDL-C) for the treatment of hypercholesterolemia. They endorse the use of niacin and/or sequestrants as the first line of therapy to achieve such target LDL-C level. This recommendation has not been compared with the use of lovastatin as initial therapy if multidrug regimens are required to achieve goal LDL-C. METHODS: Prospectively collected data on tolerance and effectiveness for niacin, sequestrants, and lovastatin were obtained from a lipid clinic at a large midwestern Veterans Affairs medical center. We used a decision tree to compare the complexity and cost of three sequential drug algorithms used for the following initial LDL-C levels: 4.14, 4.91, 5.69, and 6.47 mmol/L (160, 190, 220, and 250 mg/dL). Algorithm 1 was niacin followed by a sequestrant and then lovastatin; algorithm 2, a sequestrant followed by niacin and then lovastatin; and algorithm 3, lovastatin followed by niacin and a sequestrant. Drug and laboratory costs were obtained from the pharmacy and pathology services at the same institution. Sensitivity analyses were performed on the tolerance and effectiveness of each drug as well as drug and laboratory cost estimates. RESULTS: The probability of achieving target LDL-C level (3.36 mmol/L [130 mg/dL]) decreased as initial LDL-C level increased. As a rule, algorithm 3 required fewer drugs in combination to achieve the target level for all initial LDL-C levels modeled. In addition, the use of lovastatin was high across all algorithms at all initial LDL-C levels modeled. Algorithm 1 was less expensive than algorithm 2 or 3 at a low initial LDL-C level (4.14 mmol/L [160 mg/dL]), with an average cost of $375 vs $454 vs $585, respectively. At all other initial LDL-C levels (4.91, 5.69, and 6.47 mmol/L [190, 220, and 250 mg/dL]), algorithm 2 was slightly less expensive than algorithm 1. Algorithm 3 became relatively less expensive as initial LDL-C level increased: 56% more expensive than algorithm 1 at an initial LDL-C level of 4.14 mmol/L (160 mg/dL) as compared with 7% more expensive than algorithm 1 at an initial LDL-C level of 6.47 mmol/L (250 mg/dL). CONCLUSIONS: Fulfillment of the target LDL-C approach recommended by the National Cholesterol Education Program often requires the use of multiple drugs. When lovastatin is used initially, the regimen becomes simpler, albeit more expensive. At initial LDL-C levels of 4.91 mmol/L (190 mg/dL) or higher, this difference in cost becomes progressively smaller (7% at 6.47 mmol/L [250 mg/dL]), making algorithm 3 the better alternative; at low initial LDL-C levels (4.14 mmol/L [160 mg/dL]), a niacin-first regimen is reasonably simple and substantially less expensive. At moderate and severe initial LDL-C levels (4.91 and 5.69 mmol/L [190 and 220 mg/dL]), the lovastatin-first regimen may be advantageous.

Aged↗

Health coverage in Italy.

Italy, as other developed European countries, has a national health service (NHS) that, in principle, offers universal health care and coverage to Italians and other legal (non-Italian) residents who have full access to health care. Although Italy has always spent less for health care than other European countries (Italy, in 2002, spent about 8% of its gross national product for health care, which is approximately half the level of spending in the U.S.), the government's lack of control over spending remained the most relevant problem. To enhance the capability to control and monitor the system, mainly in terms of expenditures and costs, from the late 1990s to the present, new health reforms were introduced. These reforms were in the context of a wider change involving other politics and administrative aspects, with a strong push to decentralize the decisions and the accountability at the regional level. Now, each region has an individual Health Regional Fund allocated for health care, along with the subsequent need to implement regional and individualized strategies to assure the governance of the cost and quality of care. The National Department of Health now is solely responsible to control and monitor the delivery of the essential level of care at the regional level, and they have maintained the governance of the drug policy. Although the changes synthesized above will require a long period to be fully implemented, a few negative effects have already occurred. Nevertheless, all citizens in Italy will have full access to any level of care, without any restrictions, for complex and costly procedures (as no explicit selection/adverse criteria were implemented), and the current policy on drugs does not imply any barriers for people (as essential drugs are directly and fully reimbursed by the NHS, with a small copayment being the only intervention that may be occasionally implemented when considered necessary).

Female↗

Clinical use of the new beta-lactam antimicrobial drugs. Practical considerations for physicians, microbiology laboratories, pharmacists, and formulary committees.

New beta-lactam antimicrobial agents with extended antibacterial activity for gram-negative bacilli are being developed and marketed. These drugs provide major advances, especially for treatment of serious infections caused by multiresistant organisms. Several of the drugs have been marketed and many more will be available. Some of these drugs are considerably more costly than the older beta-lactams. The large number of new antimicrobial drugs coupled with their high costs pose complex problems for physicians, microbiology laboratories, and pharmacists. Community hospitals, large general hospitals, and tertiary care hospitals have different needs for patient care and will need different formats for unbiased education, susceptibility testing, pharmacy stocking, and controlling or monitoring for inappropriate use.

Anti-Bacterial Agents↗

[Analysis of parameters used for the evaluation of the Relative Complexity Index beta].

The Relative Complexity Index beta (RCI beta) has been devised as an indicator of the relative complexity and cost of anaesthesia. It takes into account the type of anaesthesia, the duration, the type of surgery and the patients' ASA status. This study analyses the relative weight of each component of RCI by a multiple regression analysis. The results show the pre-eminence of the surgical procedure in the formula. The weight of surgical procedure is responsible of 80 p. cent of the model's variance. In these conditions, the RCI beta cannot be accepted as an accurate complexity index of anaesthesia.

Anesthesia, General↗

Experiences with dose finding in patients in early drug development: the use of biomarkers in early decision making.

With the increasing cost and complexity of drug development, biomarkers will play an increasing role in the early phases. Biomarkers can be classified into target, mechanistic, or outcome with varying degrees of linkage to disease or treatment effect. They can be used to determine proof of concept by characterising the efficacy or safety profiles, or determining differentiation from any competitor drugs. PK/PD modelling of biomarker data for novel and marketed compounds can be used to predict outpatient dose response. Subsequent simulations may replace or reduce the size and cost of larger phase 2b outpatient studies. Two examples of biomarkers and PK/PD modelling used to characterise dose response are presented. Penile plethysmography (RigiScan Plus) in male erectile dysfunction and phenylephrine challenge urethral pressure in benign prostatic hyperplasia are used to reduce time and cost to reach major exploratory development decision points in these indications.

Biomarkers↗

Fluorescence staining and flow cytometry for monitoring microbial cells.

Large numbers of microbiological samples are analysed annually using traditional culture-based techniques. These techniques take hours to days to yield a result, are tedious and are not suitable for non-culturable microorganisms. Further, culture-based techniques do not provide real-time information on the physiological status of the organism in situ which is important in the industrial manufacture of many microbial products. Flow cytometry offers the prospect of real-time microbial analysis of individual microorganisms, without dependency on microbial culture. However, flow cytometry has not been extensively used as a tool for routine microbial analysis. This has been mainly due to the high cost and complexity of instrumentation, the need for trained flow cytometrists and the lack of assay kits with appropriate biological reagents for specific applications. Many modern instruments are now relatively simple to operate, due to improvements in the user-interface, and no longer need a specialist operator. However, most cytometers are still reliant on analogue technology first developed 20-30 years ago. The incorporation of modern, solid state opto-electronics combined with micro-fabrication and digital signal processing technology offers the prospect of simple to use, low cost and robust instruments suitable for microbial analyses. Advances are being made in the development of a range of biological reagents and these are now being formulated into simple to use kits for microbiological applications. Currently, these kits are largely restricted to simple analyses, for example to assay for total or viable numbers of microorganisms present. However, technologies are available to selectively label specific types of microorganisms. For example, fluorescent antibodies can be used to label microorganisms according to expression of particular antigens, fluorescent in situ hybridisation to label according to phylogeny and fluorogenic enzymatic substrates to label according to expression of specific enzyme activities. Reagents are also available that stain viruses sufficiently brightly to enable their direct detection in environments such as sea water. Microorganisms need to be detected in a variety of different matrices (e.g., water, mud, food, and beverages) and these matrices may be highly variable in nature (e.g., tap water compared to river water). Many matrices have high background autofluorescence (e.g., algae and minerals in water samples) or may bind non-specifically to the fluorescent biological reagents used (e.g., protein micelles in milk). Formulation of biological reagents and sample pre-treatments are critical to the development of suitable microbiological assays. Here, developments in instrumentation and biological reagents for microbiological applications are reviewed with specific examples from environmental or industrial microbiology. The broader considerations for the development of microbial assays for flow cytometry are also considered.

Animals↗

Managing medical workforces: from relative stability to disequilibrium in the UK NHS.

The management of the medical workforce, in particular the market for physicians, is costly and complex. For decades this process has been dominated by largely mechanistic forecasting (e.g., fixed doctor-population ratios), which ignored economic determinants. Internationally, and specifically in the UK, such practices achieved some success in producing modest cyclical shortages and surpluses in the past. However with large increases in UK health care funding, together with the international recognition of significant practice, activity and outcome variations in health care, this approach is now inadequate. With physician shortages emerging internationally, the impact of incentives (both financial and non-financial) on skill-mix (are nurses cost effective substitutes or complements for physicians?), activity (can distribution means be shifted and variation reduced?) and outcomes (can survival duration and quality of life of survival be improved?) is now central to policy development. Such issues create nice challenges for researchers and policy makers.

Budgets↗

Challenges to the funding of prevention research.

With the dramatic increases in cost and complexity of medical treatment over the past few decades, the public has emphasized the need to increase efforts aimed at the primary prevention of major causes of illness and death. Screening, early detection, and preventive measures have become attractive alternatives to heroic treatment efforts that exhaust huge resources on the late stages of disease. A large number of research projects have demonstrated substantial public health benefits from preventive measures. While much more prevention research is needed, it is important to bear in mind that the answers to promising research questions are limited by a shortage of funding. The costly nature of prevention research in particular is a roadblock to funding. Due to the current organization of the National Institutes of Health, research in prevention often receives low priority. It is also increasingly apparent that coordination of the national research agenda for disease prevention needs to be better structured. This paper highlights a number of issues that need to be addressed in order to strengthen the prevention research program.

Humans↗

Inconsistencies in the drug use process.

Rational drug therapy has historically been viewed as the right drug, in the right dose, at the right time, for the right patient. Today, the emphasis on cost containment has added an extra dimension: cost-effective therapeutic regimens. Most stages of the DUP have not been extensively studied. Evidence presented to date reflects duplication of efforts and suboptimal decisions, with little concerted effort to identify means for improvements that may have a favorable impact on cost and patient outcome. The increasing use of drugs as the primary mode to treat diseases, the reduction in the number of hospital employees at a time increased severity of patient illness, the nursing shortage, and the increasing cost and complexity of drugs, along with the inconsistencies that exist in drug use, demonstrate a need for a complete review of the DUP. The DUP, as it currently operates, is not conducive to the provision of a systematic approach to therapy. The stages in this process are often independent of each other and poorly performed by a variety of health professionals. The subsequent development of strategies for improving the chance for optimal drug therapy through the use of pharmacists as drug therapy experts is needed. The pharmacy profession is in a prime position where expanded patient care services and supervision of the entire DUP may actually decrease the total cost of health care. This expansion represents the key to increasing acceptance of pharmacists' clinical role and for ensuring long-term survival of the profession.

Cost-Benefit Analysis↗

Current limitations into the application of virtual reality to mental health research.

Virtual Reality (VR) environments have significant potential as a tool in mental health research, but are limited by technical factors and by mental health research factors. Technical difficulties include cost and complexity of virtual environment creation. Mental health research difficulties include current inadequacy of standards to specify needed details for virtual environment design. Technical difficulties are disappearing with technological advances, but the mental health research difficulties will take a concerted effort to overcome. Some of this effort will need to be directed at the formation of collaborative projects and standards for how such collaborations should proceed.

Computer Simulation↗

Surface acoustic wave (SAW) microsensor array for measuring VOCs in drinking water.

Exposure to volatile organic chemicals (VOCs) in drinking water has been linked to a number of adverse health effects including cancer, liver, and kidney damage. However, the large number of potential contaminants and the cost and complexity of existing analytical methods limits the extent to which water quality is routinely characterized. This project focused on the laboratory development and evaluation of an instrument for field analysis of VOCs in drinking water. The instrument is based on an array of six polymer-coated surface-acoustic-wave microsensors. A test-set consisting of dichloromethane, chloroform, 1,1,1-trichloroethane, perchloroethylene, and m-xylene was used in a series of experiments designed to optimize the purge-trap preconcentration system, calibrate the instrument over the concentration range of 0.2-2 times the USEPA maximum contaminant levels (MCLs), and compare results to those of a reference laboratory. The primary goal was to develop a cost-effective alternative for on-site evaluation of VOCs in water. Calibration and evaluation test results for spiked water samples demonstrate adequate sensitivity for 19 of the 21 regulated VOCs considered using a ten minute sampling and analysis cycle. Monte Carlo simulations characterized the performance of trained artificial neural networks (ANNs) which had correct classification rates of 99%, 90%, and 80% for the five individual test-set vapors and their binary and ternary mixtures, respectively. These results demonstrate the excellent potential of this technology for addressing the need for improved VOC field-screening methods for water supplies.

Acoustics↗

SPECT instrumentation.

The sensitivity of conventionally collimated SPECT systems is essentially fixed by the number of resolution elements desired. A variety of collimation methods are proposed or in use that distribute sensitivity and resolution differently among the various projection elements, but the effects on image quality have not really been documented. Of the many existing systems, the camera-based systems, which are useful for both head and body imaging, will be most useful in a clinical environment. For brain imaging, it is clear that fan beam collimation offers a large performance advantage over parallel collimation. However, comparison of the various instruments based on specifications alone is difficult if not impossible, and careful 3-dimensional imaging studies are an absolute necessity. In view of the fairly healthy price of dedicated brain instruments, it is interesting to speculate on their role in nuclear imaging. Their cost is from $50,000 to $200,000 less than a multi-headed general purpose system, and they have excellent resolution and sensitivity for brain imaging. They cost from $175,000 to $300,000 more than a single head camera-computer system yet offer 3 to 4 times the resolution-adjusted sensitivity. This suggests that a special purpose instrument would need to be heavily utilized or located (physically or politically) where the body imaging capability of a two or three-headed system would not be used. A good case might be made for locating a dedicated instrument in a neurological ICU in order to avoid transporting critically ill patients out of the unit. The various non-conventional imaging methods show promise for exceeding the sensitivity limit of regular collimators. At present it is speculative as to how much can be gained and whether it will be worth the added complexity and/or cost. Nevertheless, they are very interesting and certainly justify additional research.

Brain↗

Analysis of a swimmer's hand and arm in steady flow conditions using computational fluid dynamics.

Propulsive forces generated by swimmers' hands and arms have, to date, been determined strictly through experimental testing. As an alternative to these complex and costly experiments, the present research has applied the numerical technique of computational fluid dynamics (CFD) to calculate the steady flow around a swimmer's hand and arm at various angles of attack. Force coefficients computed for the hand and arm compared well with steady-state coefficients determined experimentally. The simulations showed significant boundary layer separation from the arm and hand, suggesting that Bernoulli's equation should not be used to mathematically describe the lift generated by a swimmer. Additionally, "2D" lift was shown to be inaccurate for the arm at all angles of attack and for the hand near angles of attack of 90 degrees. Such simulations serve to validate the chosen CFD techniques, and are an important first step towards the use of CFD methods for determining swimming hydrodynamic forces in more complex unsteady flow conditions.

Adult↗

Exploiting sequence and structure homologs to identify protein-protein binding sites.

A rapid increase in the number of experimentally derived three-dimensional structures provides an opportunity to better understand and subsequently predict protein-protein interactions. In this study, structurally conserved residues were derived from multiple structure alignments of the individual components of known complexes and the assigned conservation score was weighted based on the crystallographic B factor to account for the structural flexibility that will result in a poor alignment. Sequence profile and accessible surface area information was then combined with the conservation score to predict protein-protein binding sites using a Support Vector Machine (SVM). The incorporation of the conservation score significantly improved the performance of the SVM. About 52% of the binding sites were precisely predicted (greater than 70% of the residues in the site were identified); 77% of the binding sites were correctly predicted (greater than 50% of the residues in the site were identified), and 21% of the binding sites were partially covered by the predicted residues (some residues were identified). The results support the hypothesis that in many cases protein interfaces require some residues to provide rigidity to minimize the entropic cost upon complex formation.

Adrenodoxin↗

A dynamic focusing technique for delta-sigma-based beamformers.

Beamformation using oversampling delta-sigma (deltasigma) modulators has been proposed for diagnostic ultrasound. Such a beamformer can reduce the size, complexity and cost of an imaging system while providing adequate signal-to-quantization noise ratio (SQNR). High quality images can also be generated if dynamic receive delays are applied correctly. Several dynamic focusing techniques were previously proposed. Generally, an additional bit or extra compensation circuit is required to preserve the power and frequency distribution of the signal. Without preserving the power and frequency distribution, the image background noise is increased. In this paper, an alternative technique is presented. The new technique exploits the symmetry of focusing delays relative to the center of a transducer array. By properly synchronizing the delays and selecting the inserted values, no noise is added to the beam sum signal and the image background level is not increased. Using real ultrasound data, it is shown that the proposed technique provides the same imaging performance as the previous approaches with reduced system complexity by using only a single bit to encode the output of the deltasigma modulator.

Electronics, Medical↗

Technology in France.

The author describes how France has attempted to reconcile its ethos of optimum health care for all with a belief in free enterprise, with increasing medical costs and complex technological innovations, and with a traditional distrust of widespread regulation. Effective oversight of the diffusion of technology is further hampered by the shared responsibilities of several government agencies. Although France has enacted a fee schedule for physicians, created national procedures for evaluating equipment, and exercised some control over hospitals, the general sentiment is anti-bureaucratic and third-party insurers will most likely play an important role in limiting the diffusion of technology in the future.

Communication↗