The interaction between N-methyl 8-hydroxy quinoline methyl sulfate, a drug that absorbs erymathogenic near-ultraviolet radiation, and smectite was studied by X-ray powder diffraction (XRD) and adsorption and desorption techniques. From the adsorption studies, (1) the amount of the drug adsorbed by Na-smectite increased with the pH of the solution to pH 6.5 and then decreased as the pH was further increased; (2) the maximum amount adsorbed at pH 6.5 was 102 meq/100 g of clay; and (3) the maximum amount of drug adsorbed, according to the adsorption isotherms at pH 4, was close to the cation-exchange capacity of the smectite (80 meq/100 g). The XRD studies showed that the drug molecules were adsorbed in the interlayer space of smectite and that cation exchange was the chief mechanism responsible for these interactions. The results of the adsorption-desorption cycles of the drug by smectite showed that this clay is a good support for this compound. In addition, an alternative method was developed to obtain the intercalation compound to avoid the standard method of exchange by impregnation. The method consisted of grinding a mixture of the drug with the clay. The characteristics of the complex thus formed were similar to those of the complex formed by exchange at pH 4 to 7.

To gain insight into the pharmacological properties of the intercalation compound studied, its capacity for absorption of visible and near-ultraviolet light was investigated. The diffuse reflectance spectrum of the complex showed intense absorption bands, absent or weak in the spectra of the pure drug or the untreated clay, at 250, 290, and ~390 nm.

This RCD analyzes the Alabama Supreme Court’s recent answer to two certified questions sent to the court from the Eleventh Circuit. The questions involved whether a pharmaceutical company’s duty to warn included a duty to provide instructions about how to properly mitigate for warned of risks, and if the pharmaceutical company had such a duty could a plaintiff recover if their physician would have prescribed the same drug but just changed their monitoring scheme. The Alabama Supreme Court answered both questions in the affirmative, expanding the causation standard in failure to warn claims.

The work Πϵρὶ ἁπλῶν φαρμάκων or De simplicibus (Simp., also known as Πϵρὶ ϵὐποριστῶν) is ascribed in the MSS to Dioscorides. This ascription, first found in Oribasius (fourth century AD), was accepted by the most recent editor of the work, Max Wellmann, and is enshrined in LSJ, but has often been questioned. This article aims to disprove Dioscoridean authorship on the grounds of two characteristics of Simp.: first, its use of alphabetical organization; second, its unsatisfactory treatment of material that is better handled in Dioscorides’ De materia medica (MM). The use of alphabetical ordering in Simp. is inconsistent and frequently disrupted; furthermore, in the preface to MM, Dioscorides explicitly rejected alphabetization as a means of organizing lists of medications. Internal evidence shows that the author of Simp. made ineffectual attempts to conceal the alphabetical ordering of his material, possibly in response to Dioscorides’ criticism of that method. In its treatment of material that is paralleled in MM, Simp. sometimes lacks clarity or omits important details or makes errors, failings that would be highly unlikely if Dioscorides himself were its author.

Enhancing research and development and ensuring equitable pricing and access to cutting-edge treatments are both vital to a biopharmaceutical innovation system that works in the public interest. However, despite delivering numerous therapeutic advances, the existing system suffers from major problems: a lack of directionality to meet key needs, inefficient collaboration, high prices that fail to reflect the public contribution, and an overly-financialized business model.

A collection of 65 formulated tablets and capsules were analyzed for phase composition by full pattern matching powder diffraction methods. The collection contained 32 of the top 200 prescription drugs sold in 2016 as well as many high-volume prescriptions and over the counter drugs from prior years. The study was used to evaluate new methods of analysis as well as the efficacy of programs designed to collect references on high volume excipients and pharmaceuticals for inclusion in the Powder Diffraction File™. The use of full pattern matching methods as well as reference pattern additions of many common excipients enabled major phase excipient identification in all formulations. This included identification of crystalline, nanocrystalline, and amorphous ingredients because full pattern matching involved the use of characteristic coherent and incoherent scatter. Oftentimes identification of the major excipients significantly aided the clean identification of the active pharmaceutical ingredients (APIs) and their polymorphic form, even at low concentrations (1–10 wt. %). Overall 93% of the APIs were identified, most through a PDF® material reference, but also through patent cross-referencing and similarity analysis comparisons.

Dandelion or Taraxacum officinale is a well-known medicinal plant that grows naturally in Europe, North and South America and Asia. Dandelion is a source of various nutrients and biologically active substances and its root and leaves contain vitamins (A, K, C and B-complex), minerals (calcium, magnesium, potassium, zinc and iron), micronutrients, fibre, lecithin and choline. The various parts of the plant have a long history of use as an herbal remedy; roots of this herb are firstly considered for enhancing digestion. Also, the roots are generally used for as liver tonic by stimulating bile production and removing toxins and re-establishing hydration and electrolyte balance. Dandelion leaves could be used successfully as digestive stimulant and diuretic. Moreover, dandelion leaves were reported to improve growth and productive performance of poultry. Several beneficial effects have been reported on intestinal mucosa regarding architecture of villi, villus height/ crypt depth ratio as well as cellular infiltration. Dandelion has many properties like immunomodulator, digestive stimulant, prebiotic, insulin stimulant, anti-inflammation, antiangiogenic, antineoplastic and demulcent. Furthermore, dandelion treats indigestion and hepatitis B infection as well as enhances metabolise androgenic hormones. Because of the scarcity of in vivo studies on dandelion, further investigations are needed to confirm its benefits and efficacy.

For many years, virtually all pharmaceutical companies had an agrochemical division. This was partly to maximize the benefits of expensive chemical synthesis efforts by searching for many types of useful biological activities. Leads for pharmaceuticals and pesticides often overlap, in some cases leading to similar compounds used for human health and weed management purposes. This review will focus on herbicides and herbicide classes that have potential pharmaceutical properties, both as therapeutic agents that act through human molecular target sites and those that act on infectious agents. An example of the first case is compounds that target plant acetyl coenzyme A carboxylases, inhibiting fatty acid synthesis, and similar compounds used in humans as anti-inflammatory agents. Another such example is the triketone class of compounds that can act both as herbicides and as treatments for the genetic disease tyrosinemia, targeting the same enzyme in both cases. Examples of the second case are the relatively large number of herbicides that have activity against the malaria protozoan (Plasmodium spp.). It turns out that Plasmodium spp. and related disease organisms have an organelle that is apparently analogous to the plant plastid, the apicoplast. Herbicides such as dinitroanilines are active against several protozoan parasites by the same mechanism by which they kill plants, interaction with tubulin to halt cell division and other tubulin-dependent processes. These and other multiple activities of various herbicides and herbicide classes provide perspective on the broad biological activity of herbicides and related compounds.

Objectives: The aim of this study was to investigate originator pharmaceutical companies’ practices in relation to health technology assessment (HTA) and the views and perceptions of their executives on the importance of HTA in pricing and reimbursement of medicines in Greece.

Methods: A qualitative study was performed, using individual semi-structured interviews based on an interview schedule with open-ended questions. The target population was market access departments’ executives of originator pharmaceutical companies. Our target sample consisted of sixteen executives, of whom ten agreed to participate. Saturation point was reached after eight interviews. Data were audio recorded, transcribed verbatim, and analyzed using content analysis.

Results: Participants considered HTA as a very important complementary tool for decision making in health policy, particularly in the field of pharmaceuticals and medical devices. They believed that, in Greece, HTA could be institutionalized for the reimbursement mechanism of medicines under certain conditions relating to current health policy-making attitudes and conditions pertaining in the country. They considered that there are many constraints which must be overcome as well as opportunities to be exploited.

Conclusions: Decisions in pharmaceutical policy should be scientifically substantiated and HTA should be institutionalized primarily for reimbursement decisions. Development of guidelines for conducting pharmaco-economic evaluation, change in health policy goals, recording of cost and epidemiological data, and broader participation of all stakeholders in HTA decision-making processes are suggested as prerequisites for a successful implementation of HTA in Greece.

Verification of materials is an increasingly important need in pharmaceutical distribution. XStream Systems, Inc. has developed an energy dispersive X-ray diffraction (EDXRD) system which can quickly verify crystalline pharmaceuticals in the distribution cycle. Materials may be in solid or powder form and the technique is nondestructive. Unlike angular X-ray diffraction (AXRD), a “white” X-ray beam between 20 and 80 keV is used. This energetic beam can penetrate through relatively thick materials, diffracting from crystallites within the samples. Materials can be observed even when they are located within opaque, sealed containers. That is, for most cases the drugs can be examined in their sealed, packaged vials without any sample preparation. The tabletop unit uses a confocal geometry to maximize the X-ray intensity from a relatively low-powered, air-cooled X-ray source. The beam is collimated by a circular slit assembly before the sample. A similar slit assembly after the sample collimates the diffracted beam. A single, state-of-the-art, CdTe solid-state detector with a multichannel analyzer is used to process the diffracted signal. This collimation system interrogates a doughnut-shaped volume within the sample under test. One of the design goals was to develop a unit that is capable of performing quick verification or detection of complex materials and mixtures at a number of points along the distribution paths yet can be operated by personnel with minimal scientific knowledge. Rapid identification of unknowns is possible using neural network search algorithms or pattern matching techniques. The Material Recognition Software Engine (MRSE) utilizes a localized SQL database to store and process the raw spectra data. The MRSE takes the sample data and determines if it matches any known patterns within its database. This engine has demonstrated that it can verify a number of drugs within 30 s with better than 97% accuracy.

Objectives: To develop and evaluate strategies for estimating hospitalization costs in multinational clinical trials.

Methods: Hospital cost estimates for eleven diagnoses were collected from twelve countries participating in a trial of therapies for congestive heart failure. Estimates were combined with U.S.-based diagnosis-related group weights to compute country-specific unit cost estimates for all reasons for hospitalization. Variations of hospital costing methods were developed. The unit cost method assigns a country-specific unit cost estimate to each hospitalization. The other methods adjust for length of stay using a daily cost (DC) estimate for each diagnosis, based on either the mean length of stay (DC-mean method) or the median length of stay (DC-median method) for each diagnosis in each country. Additional modifications were explored through adjustment of the distribution of daily costs incurred during a hospital stay.

Results: The mean cost for all hospitalizations was $10,242 (SD, 10,042) using the unit cost method, $10,242 (SD, 12,760) using the standard DC-mean method, and $13,967 (SD, 18,762) using the standard DC-median method. In comparisons of costs for all 5,486 hospitalizations incurred by a subset of 2,352 patients in the trial, the unit cost method provided 92% power to detect a $1,000 cost difference. The standard DC-mean method provided 76% power, and the standard DC-median method provided 44% power.

Conclusions: Hospital costing methods that adjust for differences in length of stay require a significantly larger sample to attain comparable statistical power as methods that assign unadjusted unit cost estimates to hospitalization events.

Objective: A United Kingdom Department of Health directive (EL[94]72) asked Health Authorities to manage the entry of new drugs into practice. There seem to be costs associated with the decision-making process of managed entry, but no clear evidence of benefit to patient populations. The objective of this study was to assess the potential costs and outcomes of different models of managed entry, using the example of donepezil in the North West Health Region of the U.K. National Health Service. This is a preliminary study designed to identify the key pieces of information required to evaluate the value of managed entry.

Methods: Decision analytic models of three Health Authorities' approaches to manage the entry of donepezil were used to estimate the expected costs and effectiveness of the process. Resource use data were obtained from published sources and the relevant Health Authority. Probabilistic sensitivity analysis was used to determine the robustness of the results.

Results: The process of managed entry of donepezil was associated with higher expected costs and higher expected outcome than no managed entry. The 95% confidence intervals for the net expected costs and net expected outcomes were relatively narrow and did not cross zero, which suggests a statistical difference between managed entry and no managed entry for donepezil. The incremental cost-effectiveness ratios for managed entry of donepezil indicate that, compared with no managed entry, there were substantial differences between the different models used in the three study sites. The expected cost per unit of cognitive function gained was between £18,000 in study site 001 to £28,000 in study site 010. The expected cost per person with a clinically significant improvement was between £140,000 and £230,000. The expected cost per QALY ranged from £470,000 to £19.3 million.

Conclusions: Managed entry does not appear to be a worthwhile mechanism to introduce drugs into practice. However, poor accessibility and availability of data means that the results are highly uncertain. The lack of data presents serious obstacles for both researchers and policy makers wishing to develop evidence-based policy and practice.

Background and objective: The study was designed to compare the costs of propofol versus sevoflurane for the maintenance of the hypnotic component of anaesthesia during general anaesthesia, guided by the bispectral index, for gynaecological laparoscopic surgery.

Methods: Forty ASA Grade I—II female patients scheduled for gynaecological laparoscopy were randomly allocated to two groups. All patients received a continuous infusion of remifentanil (0.25 µg kg−1 min−1) for 2 min. Then anaesthesia was induced with propofol 1% at 300 mL h−1 until loss of consciousness. To guide the bispectral index between 40 and 60, Group 1 patients received propofol 10 mg kg−1 h−1 initially, which was increased or decreased by 2 mg kg−1 h−1 steps; Group 2 patients received sevoflurane, initially set at 2 vol.% and adjusted with steps of 0.2–0.4%. The time and quality of anaesthesia and recovery were assessed in two postoperative standardized interviews.

Results: Patient characteristics, the propofol induction dose, the bispectral index and the haemodynamic profiles during induction of anaesthesia, and its duration, were similar between the groups. In Group 1, 7.55 ± 1.75 mg kg−1 h−1 propofol and in Group 2, 0.20 ± 0.09 mL kg−1 h−1 liquid sevoflurane were used for maintenance. The cost for maintenance, including wasted drugs, was higher when using propofol (€25.14 ± 10.69) than sevoflurane (€12.80 ± 2.67). Postoperatively, recovery profiles tended to be better with propofol; however, the day after discharge no differences were found.

Conclusions: When applying the bispectral index to guide the administration of hypnotic anaesthetic drugs, propofol-based maintenance of anaesthesia was associated with the highest cost. A trend towards a better recovery profile was obtained with propofol. However, on the day after discharge, no differences in quality were observed.

Background and objective: To evaluate preparation and discharge times as well as the anaesthesia-related costs of out-patient knee arthroscopy performed with a combined sciatic-femoral nerve block, or a propofol-remifentanil general anaesthetic.

Methods: With Ethics Committee approval and written informed consent, 40 healthy patients were premedicated with intravenous midazolam (0.05 mg kg−1) and ketoprofen (50 mg). They were then randomly allocated to receive either a combined sciatic-femoral nerve block with 25 mL mepivacaine 2% (15 mL for the femoral nerve, 10 mL for the sciatic nerve) (PNB group, n = 20), or a general anaesthetic with a continuous intravenous infusion of remifentanil (0.1–0.3 μg kg−1min−1) and propofol (target plasma concentration 2–4 μg mL−1) with a laryngeal mask airway (GA group, n = 20).

Results: The median (range) preparation time was 16 (10–28) min in the PNB group and 13 (8–22) min in the GA group (P = 0.015). Ten PNB patients were directly discharged to the day-surgery unit after the procedure as compared with one GA patient (P = 0.003). Discharge from the postanaesthesia care unit (PACU) required 5 (5–20) min in the PNB group and 23 (7–95) min in the GA group (P = 0.001). Home discharge criteria were fulfilled after 277 (150–485) min in the PNB group and 170 (100–400)min in the GA group (P = 0.005). Costs related to the time spent in the PACU were lower for the PNB group (€1.10, range 0–22) compared with the GA group (€30, range €0–176) (P = 0.0005). There were no differences in total costs: PNB group €158 (range €105–194) versus GA group €160 (range €101–238) (P = 0.61).

Conclusions: In patients undergoing out-patient knee arthroscopy, the length of stay in the PACU can be shorter after a sciatic-femoral nerve block with a small volume of mepivacaine 2% compared with a propofol-remifentanil anaesthetic, and there is an increased likelihood that they will bypass the first phase of the postoperative recovery.

Newer anaesthetic agents provide a faster onset, easier titration and a more rapid recovery than the older agents, but are more expensive. In assessing the financial consequences associated with their use, it is important to examine the total costs (including personnel costs) and not just the acquisition costs of new drugs. Claims of cost savings from new drugs should be subjected to close scrutiny, with studies designed to demonstrate that the preferential use of the newer drug is associated with actual decreased payments for personnel, an earlier return to normal activities by the patient and/or their caretakers, or the completion of an additional case in the same operating session. It may be necessary to alter work patterns to obtain the full benefits of the new drugs (e.g. bypass of the labour-intensive [phase I] postanaesthetic care unit). Finally, greater cost savings in the operating room can be achieved by increasing efficiency in resource utilization. A delay in starting a case, or a prolonged turnover time between cases, can negate any cost savings related to the anaesthetist's choice of drugs.