Search

Objective To assess sales of anti-cancer medicines in the 2017 World Health Organization's WHO Model list of essential medicines in China, Indonesia, Kazakhstan, Malaysia, Philippines and Thailand from 2007 (2008 for Kazakhstan and Malaysia) to 2017. Methods We extracted sales volume data for 39 anti-cancer medicines from the IQVIA database. We divided the total quantity sold by the reference defined daily dose to estimate the total number of defined daily doses sold, per country per year, for three types of anti-cancer therapies (traditional chemotherapy, targeted therapy and endocrine therapy). We adjusted these data by the number of new cancer cases in each country for each year. Findings We observed an increase in sales across all types of anti-cancer therapies in all countries. The largest number of defined daily doses of traditional chemotherapy per new cancer case was sold in Thailand; however, the largest relative increase per new cancer case occurred in Indonesia (9.48-fold). The largest absolute and relative increases in sales of defined daily doses of targeted therapies per new cancer case occurred in Kazakhstan. Malaysia sold the largest number of adjusted defined daily doses of endocrine therapies in 2017, while China and Indonesia more than doubled their adjusted sales volumes between 2007 and 2017. Conclusion The use of sales data can fill an important knowledge gap in the use of anti-cancer medicines, particularly during periods of insurance coverage expansion. Combined with other data, sales volume data can help to monitor efforts to improve equitable access to essential medicines. [ABSTRACT FROM AUTHOR]

We report a new polymorph of acridine, C13H9N, denoted form IX, obtained as thin needles by slow evaporation of a toluene solution. The structure was solved and refined from powder X-ray data. The structures of five unsolvated forms were previously known, but this is only the second with one molecule in the asymmetric unit. The melting point [differential scanning calorimetry (DSC) onset] and heat of fusion are 108.8 (3) °C and 19.2 (4) kJ mol−1, respectively. [ABSTRACT FROM AUTHOR]

The article discusses a study on the crystal and molecular structures of the organic compound 2-ethoxybenzamide or C9H11NO2. The ribbon-like packing motifs were instigated by additional hydrogen bonds between adjacent dimers. A T-shaped herringbone pattern characterized the ribbons. The simulated annealing global optimization algorithm was used to solve the crystal structure.

Reports on the crystal structure of beta-hematin. Use of simulated annealing techniques; Analysis of different powder diffraction data; Heme groups released from the digestion of the hemoglobin of malaria-infected red blood cells; Aggregation into an insoluble material called hemozoin; Action of antimalarial drugs.

Focuses on polymeric fullerene chains in RbC60 and KC60. Single-crystal structure determinations; Three mirror plane in icosahedral C60; Pseudo-body-centered array of rotated fullerenes; Structural parameters; Formation of a partial (pi)-bond between cages; Relationship between face-centered-cubic and body-centered orthorhombic lattices; X-ray diffraction pattern of RbC60; Bonding structures.

Background: The steady supply of quality, affordable medicines is a pillar of a functioning health system. In addition to the public sector, the private, mission and not-for-profit sectors often serve a large part of the population in Africa. However, while there is generally systematic recording of public sector supply of medicines, detailed, systematic and reliable national market data including these non-public sectors are not commonly available in most countries in Africa. Understanding the total market is a missing part of the access puzzle: without this information, policy makers and health practitioners are not able to fully measure the impact of interventions, measure access to effective products, or fully evaluate the rational use of medicines. This article reports on a unique innovation which provides routine, national-level data on the total pharmaceuticals market, through a system which can be replicated elsewhere. It demonstrates how national-level market data contribute to the evidence base for policies on access to essential medicines, using the Zambian anti-malarial medicines market as a case study. Methods: A new, routine national database on pharmaceutical market size and structure was established through a multi-partner collaboration. Information was extracted from import authorizations and allows for information on local manufacture. Data included value and volume of products as well as pack details, manufacturer and importer. The system was continually updated: data for this analysis were extracted for 6 years: 2009–2014 inclusive. Data were analysed using Microsoft Excel and validated against other sources including donor procurement data. Analysis included public and private sector markets. The policy relevance was demonstrated through analysis of four aspects of national policies on access and rational use of malaria medicines: (i) volume of product relative to disease burden; (ii) distribution by sector relative to treatment-seeking; (iii) consistency of products with respect to national policy guidelines; (iv) market concentration as a proxy for security of supply. Results: The system developed provides the first accurate, systematic data on the breakdown of a national pharmaceutical market in an African context. The total value of the anti-malarials market in Zambia, including all sectors, was USD 5.5–6 million. This included 22 different molecules or combinations, produced by 56 different manufacturers, with 142 different permutations of molecule/manufacturer/strength. Such data provide a complementary mechanism to confirm key trends in malaria treatment and control in Zambia: (i) sufficient supply relative to disease burden, (ii) value and volume of the private/non-profit sector; 29%–2% of market value and 17%–2% of market volume (from 2009 to 2014), (iii) dominance of the 3 molecules recommended in the national treatment guidelines; and (iv) an evidence-base for national discussions on medicines quality, security of supply and rationale use. The system extracts information on all medicines and therefore could be used to analyse other therapeutic classes. Data have been used for several policy purposes, notably by ZAMRA to monitor the quality of products in Zambia, monitoring implementation of WHO Resolutions on artemisinin monotherapy as well as monitoring trends in product choice across sectors. Conclusion: Routine data are important for researchers and policy makers alike. This study shows how medicines data can be systematically gathered at national level—comprising range, volume and value in the public, private and not-for-profit sectors—to monitor more detailed trends in the market and allows triangulation of supply-side data against other sources. This systematic approach can contribute significantly to support access to medicines, monitor treatment and public health policies and create healthy markets. It can be used to monitor changes between therapeutic areas, for example the impact of improved malaria treatment on the use of antibiotics in the context of anti-microbial resistance monitoring. As data contain commercially confidential information, appropriate safeguards should be put in place to balance public health and commercial interests. [ABSTRACT FROM AUTHOR]

Objectives: New antidiabetic medications such as insulin analogues and thiazolidinediones have been introduced over the last decade. This study compares the uptake of new agents in three emerging pharmaceutical markets: Brazil, China, and Thailand. Methods: Using longitudinal IMS Health sales data, we calculated the quarterly percentage market share for types of insulins and oral hypoglycemic agents from 2002 through 2012 in each country. New oral hypoglycemic agents included: alpha-glucosidase inhibitors, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, and non-sulfonylurea secretagogues. Results: While China had the highest use of insulin cartridges and pens (85.6% in 2010), Brazil was the earliest adopter of insulin analogues and had the greatest use of these products overall (44.6% of the insulin market) in 2010, which then decreased by almost half by 2012. Together, sulfonylureas and metformin dominated the markets in Brazil and Thailand (~89% and ~96% respectively) over the 10-year period. Between 2002 and 2012, there was a shift in use from sulfonylureas to metformin; the market share of newer agents remained 10% or less in both countries. In China, however, market share of new oral agents grew rapidly from 13.1% to 44.4%. While metformin use was relatively stable in China (one-third of the market), sulfonylureas declined substantially over the 10-year period (41.5% to 20.8%). Conclusion: Given large cost differentials between newer and older insulins and among oral hypoglycemic agents, it is important to evaluate uptake of newer products over time. Uptake patterns differed in the study countries, likely due to different medicines policy approaches. Future research should evaluate how trends in use of antidiabetic products align with national clinical practice guidelines and pharmaceutical policies, as well as the impacts of different patterns of use on cost and clinical outcomes. [ABSTRACT FROM AUTHOR]

The increase in the number of bacteria that are resistant to multiple antibiotics poses a serious clinical problem that threatens the health of humans worldwide. Nadifloxacin (1) is a highly potent antibacterial agent with broad-spectrum activity. However, its poor aqueous solubility has limited its use to topical applications. To increase its solubility, it was glycosylated herein to form a range of trans-linked (3a-e) and cis-linked (7a,b) glycosides, each of which was prepared and purified to afford single anomers. The seven glycoside derivatives (3a-e, 7a,b) were examined for potency against eight strains of S. aureus, four of which were methicillin-resistant. Although less potent than free nadifloxacin (1), the α-L-arabinofuransoside (3a) was effective against all strains that were tested (minimum inhibitory concentrations of 1–8 μg/mL compared to 0.1–0.25 μg/mL for nadifloxacin), demonstrating the potential of this glycoside as an antibacterial agent. Estimation of Log P as well as observations made during preparation of these compounds reveal that the solubilities of the glycosides were greatly improved compared with nadifloxacin (1), raising the prospect of its use in oral applications. [ABSTRACT FROM AUTHOR]

This observational study investigates the private sector, retail pharmaceutical market of 19 low and middle income countries (LMICs) in Latin America, Asia and the Middle East/South Africa analyzing the relationships between volume market share of generic and originator medicines over a time series from 2001 to 2011. Over 5000 individual pharmaceutical substances were divided into generic (unbranded generic, branded generic medicines) and originator categories for each country, including the United States as a comparator. In 9 selected LMICs, the market share of those originator substances with the largest decrease over time was compared to the market share of their counterpart generic versions. Generic medicines (branded generic plus unbranded generic) represent between 70 and 80% of market share in the private sector of these LMICs which exceeds that of most European countries. Branded generic medicine market share is higher than that of unbranded generics in all three regions and this is in contrast to the U.S. Although switching from an originator to its generic counterpart can save money, this narrative in reality is complex at the level of individual medicines. In some countries, the market behavior of some originator medicines that showed the most temporal decrease, showed switching to their generic counterpart. In other countries such as in the Middle East/South Africa and Asia, the loss of these originators was not accompanied by any change at all in market share of the equivalent generic version. For those countries with a significant increase in generic medicines market share and/or with evidence of comprehensive “switching” to generic versions, notably in Latin America, it would be worthwhile to establish cause-effect relationships between pharmaceutical policies and uptake of generic medicines. The absence of change in the generic medicines market share in other countries suggests that, at a minimum, generic medicines have not been strongly promoted. [ABSTRACT FROM AUTHOR]

Abstract: A three-layer oxynitride Ruddlesden–Popper phase Rb1+ x Ca2Nb3O10− x N x ·yH2O (, ) was synthesized by ammonialysis at 800°C from the Dion–Jacobson phase RbCa2Nb3O10 in the presence of Rb2CO3. Incorporation of nitrogen into the layer perovskite structure was confirmed by XPS, combustion analysis, and MAS NMR. The water content was determined by thermal gravimetric analysis and the rubidium content by ICP-MS. A similar layered perovskite interconversion occurred in the two-layer Dion–Jacobson oxide RbLaNb2O7 to yield Rb1+ x LaNb2O7− x N x ·yH2O (, ). Both compounds were air- and moisture-sensitive, with rapid loss of nitrogen by oxidation and hydrolysis reactions. The structure of the three-layer oxynitride Rb1.7Ca2Nb3O9.3N0.7·0.5H2O was solved in space group P4/mmm with and , by Rietveld refinement of X-ray powder diffraction data. The two-layer oxynitride structure Rb1.8LaNb2O6.3N0.7·1.0H2O was also determined in space group P4/mmm with and . GSAS refinement of synchrotron X-ray powder diffraction data showed that the water molecules were intercalated between a double layer of Rb+ ions in both the two- and three-layer Ruddlesden–Popper structures. Optical band gaps were measured by diffuse reflectance UV-vis for both materials. An indirect band gap of 2.51eV and a direct band gap of 2.99eV were found for the three-layer compound, while an indirect band gap of 2.29eV and a direct band gap of 2.84eV were measured for the two-layer compound. Photocatalytic activity tests of the three-layer compound under 380nm pass filtered light with AgNO3 as a sacrificial electron acceptor gave a quantum yield of 0.025% for oxygen evolution. [Copyright &y& Elsevier]

An iron sulfate of nominal composition Fe2(SO4)3(H2O)5 has been synthesized and its structure determined and refined by high resolution powder diffraction using synchrotron radiation. The structure consists of corrugated slabs in which iron octahedra are linked by sulfate tetrahedra in the monoclinic space group P21/m with lattice parameters a = 10.711(1), b = 11.085(1), and c = 5.5747(5) Å, β = 98.853(3)°. We compare these results with the type specimen of lausenite from Jerome, Arizona, which has monoclinic lattice parameters a = 10.679(2), b = 11.053(3), and c = 5.567(1) Å, β = 98.89(1)°. Weight loss experiments show that it is currently a pentahydrate, despite earlier reports that lausenite is a hexahydrate. We argue that our synthetic material provides a structure determination for the type specimen of lausenite. [ABSTRACT FROM AUTHOR]

β-Hematin, the crystalline heme detoxification product of red blood cell digestion by the malaria parasite, can reversibly absorb up to 14% of its mass in water. Heating hydrated β-hematin to temperatures greater than 150 °C results in loss of the hydrated water, which is readily reabsorbed on standing in air at room temperature. The amount of water absorbed is source dependent with highly crystalline samples produced by the anhydrous-base-mediated dehydrohalogenation being twice as absorptive as more amorphous samples produced by the aqueous acid precipitation method. Infrared spectroscopy and thermal gravimetric analysis have been used to measure the amount of water lost and gained during these experiments. X-ray powder diffraction has been used to characterize the effect of hydration state on the lattice parameters. Taken together these experiments resolve literature discrepancies concerning the elemental composition of synthetic and extracted natural β-hematin. [ABSTRACT FROM AUTHOR]

Background: This phase 1 study examined the safety, maximum-tolerated dose (MTD) and antitumour activity of E7449, a novel PARP 1/2 and tankyrase 1/2 inhibitor.Methods: E7449 was orally administered once daily in 28-day cycles to patients with advanced solid tumours (50-800-mg doses). Archival tumour samples from consenting patients were evaluated for the expression of 414 genes in a biomarker panel (2X-121 drug-response predictor [DRP]) found to be predictive of the response to E7449 in cell lines.Results: Forty-one patients were enrolled (13 pancreatic, 5 ovarian, 4 each with breast, lung or colorectal cancer and 11 with other tumour types). The most common grade ≥3 treatment-related adverse event was fatigue (n = 7, 17.1%). Five patients experienced a dose-limiting toxicity (fatigue, n = 4, 800 mg; anaphylaxis, n = 1, 600 mg) for an MTD of 600 mg. E7449 exhibited antitumour activity in solid tumours, including 2 partial responses (PRs), and stable disease (SD) in 13 patients, which was durable (>23 weeks) for 8 patients. In 13 patients, the 2X-121 DRP identified those achieving PR and durable SD. E7449 showed good tolerability, promising antitumour activity and significant concentration-dependent PARP inhibition following 50-800-mg oral dosing.Conclusion: The results support further clinical investigation of E7449 and its associated biomarker 2X-121 DRP.Clinical Trial Registration: www.ClinicalTrials.gov code: NCT01618136. [ABSTRACT FROM AUTHOR]

The crystal structure, redox electrochemical stability, and reaction chemistry of 1,4-dicyanotetrazine (DCNT) has been experimentally characterized. These experimental results were rationalized by the results of theoretical calculations of the electronic structure, spin and charge distributions, electronic absorption spectra, and electron affinity and compared with the results for related the tetracyano electron acceptors tetracyanoethylene (TCNE), 7,7,8,8-tetracyano-p-quinodimethane (TCNQ), and 2,3,5,6-tetracyanopyrazine (TCNP). DCNT is made from the dehydration of 1,2,4,5-tetrazine-3,6-dicarboxamide, and because of the unusual deep-magenta color of the dicarboxamide in the solid state, its hydrogen-bonded layered structure, electronic structure, and electronic absorption spectra were determined. The magenta color is attributed to its absorptions at 532 nm (18 800 cm-1), and this corresponds to normalized chromaticity coordinates of x = 0.42 and y = 0.31 in the pink/red/orange part of the 1931 CIE chromaticity diagram. In contrast with previous reports, DCNT exhibits an irreversible one-electron reduction at -0.09 V vs SCE (MeCN), and reduced forms of DCNT have yet to be isolated and characterized. In addition, the reactions of DCNT with V(CO)6, FeII(C5Me5)2, and I- are discussed. [ABSTRACT FROM AUTHOR]

When the influenza A ( H1 N1) pandemic spread across the globe from April 2009 to August 2010, many WHO Member States used antiviral drugs, specifically neuraminidase inhibitors ( NAIs) oseltamivir and zanamivir, to treat influenza patients in critical condition. Antivirals have been found to be effective in reducing severity and duration of influenza illness, and likely reduce morbidity; however, it is unclear whether NAIs used during the pandemic reduced H1 N1 mortality. To assess the association between antivirals and influenza mortality, at an ecologic level, country-level data on supply of oseltamivir and zanamivir were compared to laboratory-confirmed H1 N1 deaths (per 100 000 people) from July 2009 to August 2010 in 42 WHO Member States. From this analysis, it was found that each 10% increase in kilograms of oseltamivir, per 100 000 people, was associated with a 1·6% reduction in H1 N1 mortality over the pandemic period [relative rate ( RR) = 0·84 per log increase in oseltamivir supply]. Each 10% increase in kilogram of active zanamivir, per 100 000, was associated with a 0·3% reduction in H1 N1 mortality ( RR = 0·97 per log increase). While limitations exist in the inference that can be drawn from an ecologic evaluation, this analysis offers evidence of a protective relationship between antiviral drug supply and influenza mortality and supports a role for influenza antiviral use in future pandemics. This article summarises the original study described previously, which can be accessed through the following citation: Miller PE, Rambachan A, Hubbard RJ, Li J, Meyer AE, et al. (2012) Supply of Neuraminidase Inhibitors Related to Reduced Influenza A (H1N1) Mortality during the 2009-2010 H1N1 Pandemic: An Ecological Study. PLoS ONE 7(9): e43491. [ABSTRACT FROM AUTHOR]

Background: The influenza A (H1N1) pandemic swept across the globe from April 2009 to August 2010 affecting millions. Many WHO Member States relied on antiviral drugs, specifically neuraminidase inhibitors (NAIs) oseltamivir and zanamivir, to treat influenza patients in critical condition. Such drugs have been found to be effective in reducing severity and duration of influenza illness, and likely reduced morbidity during the pandemic. However, it is less clear whether NAIs used during the pandemic reduced H1N1 mortality. Methods: Country-level data on supply of oseltamivir and zanamivir were used to predict H1N1 mortality (per 100,000 people) from July 2009 to August 2010 in forty-two WHO Member States. Poisson regression was used to model the association between NAI supply and H1N1 mortality, with adjustment for economic, demographic, and health-related confounders. Results: After adjustment for potential confounders, each 10% increase in kilograms of oseltamivir, per 100,000 people, was associated with a 1.6% reduction in H1N1 mortality over the pandemic period (relative rate (RR) = 0.84 per log increase in oseltamivir supply). While the supply of zanamivir was considerably less than that of oseltamivir in each Member State, each 10% increase in kilogram of active zanamivir, per 100,000, was associated with a 0.3% reduction in H1N1 mortality (RR = 0.97 per log increase). Conclusion: While there are limitations to the ecologic nature of these data, this analysis offers evidence of a protective relationship between antiviral drug supply and influenza mortality and supports a role for influenza antiviral use in future pandemics. [ABSTRACT FROM AUTHOR]

The article presents a study that evaluates the use of powder diffraction on crystalline mixtures. It shows that the disparities in the data among the three sets of diffraction measurements described are non-statistical in nature. It suggests that the extinction effect should be considered with regard to all quantitative phase analysis experiments on highly crystalline materials.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Cyclooxygenase-2 (COX-2) inhibitors are selective nonsteroidal anti-inflammatory drugs (NSAIDs), purported to demonstrate lower gastrointestinal toxicity than nonselective NSAIDs. • Prescriptions of selective COX-2 inhibitors declined internationally after 2004 following voluntary withdrawal and regulatory intervention because of possible cardiovascular side-effects. • A study in Canada indicated that rates of gastrointestinal haemorrhage actually increased during the period of increasing COX-2 inhibitor prescriptions, due to the increased number of people receiving NSAIDs. WHAT THIS STUDY ADDS • The reduction in availability of COX-2 inhibitors in the UK was temporally associated with a favourable reversal of the trend in emergency hospital admissions for acute myocardial infarction among people aged ≥65 years, but there were no related changes in myocardial infarction mortality trends. • There was some indication that hospital admissions for gastrointestinal haemorrhage among people aged 55–64 years started to increase following a previously declining trend, but this change predated withdrawal/regulation of COX-2 inhibitors by up to 2 years. • The withdrawal/regulation of coxibs did not appear to have any adverse impact on population health and may have been beneficial. AIMS To investigate impacts of withdrawal and regulatory advice regarding cyclooxygenase-2 (COX-2) inhibitors on UK population rates of gastrointestinal haemorrhage and acute myocardial infarction (MI). METHODS Ecological time series study of prescribing, mortality and hospital admission trends in people aged ≥55 years. RESULTS Withdrawal and regulatory advice limiting COX-2 inhibitor availability from 2004 were temporally associated with reversal of previously unfavourable trends in emergency MI admissions among people aged ≥65 years. Annual admission rate trends changed from +4.6% to −3.1% ( P < 0.001) among women and from +2.1% to −3.8% ( P= 0.003) among men. Absolute changes in average annual trend in the number of individuals aged ≥65 years admitted following MI were from +981 (1999–2004) to −819 (2004–2006) per year for women and from +713 to −995 for men. No change in trend was apparent among people aged 55–64 years, or in MI mortality trends. There was some suggestion of an unfavourable change in admission trends for gastrointestinal haemorrhage among 55−64-year-olds, although this appeared to occur prior to COX-2 inhibitor withdrawal/regulation by up to 2 years. These trends were not apparent in older people, or in gastrointestinal haemorrhage mortality rates. CONCLUSIONS Withdrawal/regulation of COX-2 inhibitors was temporally associated with a favourable reversal of population-level hospital admission trends in MI among people aged ≥65 years. Unfavourable reversal of previous declines in gastrointestinal haemorrhage admissions probably occurred before changes in COX-2 inhibitor availability. Withdrawal/ regulation of COX-2 inhibitors did not appear to have any adverse impact on population health and may have been beneficial. [ABSTRACT FROM AUTHOR]

The European Surveillance of Antimicrobial Consumption (ESAC) project collects data on antibacterial use in Europe, applying the Anatomic Therapeutic Chemical classification system and defined daily dose methodology, as recommended by the World Health Organization. Comparable data for the United States have been collected from IMS Health. The IMS Health sales data, processed according to ESAC methodology, suggest that outpatient antibacterial use in the United States is high (only 3 of 27 European countries used more) and is mainly characterized by a shift towards newer antibiotics. [ABSTRACT FROM AUTHOR]

Abstract: A series of powdered cobalt ferrites, Co x Fe3− x O4 with 0.66⩽x<1.00 containing different amounts of FeII, were synthesized by a mild procedure, and their Fe and Co site occupancies and structural characteristics were explored using X-ray anomalous scattering and the Rietveld refinement method. The dissolution kinetics, measured in 0.1M oxalic acid aqueous solution at 70°C, indicate in all cases the operation of a contracting volume rate law. The specific rates increased with the FeII content following approximately a second-order polynomial expression. This result suggests that the transfer of FeIII controls the dissolution rate, and that the leaching of a first layer of ions CoII and FeII leaves exposed a surface enriched in slower dissolving octahedral FeIII ions. Within this model, inner vicinal lattice FeII accelerates the rate of FeIII transfer via internal electron hopping. A chain mechanism, involving successive electron transfers, fits the data very well. [Copyright &y& Elsevier]

Abstract: The perovskite-structured compound methylammonium lead chloride orders into a low-temperature phase of space group Pnma, in which at 80K each of the orthorhombic axes , and is doubled with respect to the room temperature disordered cubic phase (). The structure was solved by ab initio methods using the programs EXPO and FOX. This unusual cell basis for space group is not that of a standard tilt system. This phase, in which the methylammonium ions, are ordered shows distorted octahedra. The octahedra possess a bond angle variance of 60.663°2 and a quadratic elongation of 1.018, and are more distorted than those in the ordered phase of methylammonium lead bromide. There is also an alternating long and short Pb–Cl bond along a, due to an off-center displacement of Pb within the octahedron. This suggests that the most rigid unit is actually the methylammonium cation, rather than the PbCl6 octahedra, in agreement with existing spectroscopic data. [Copyright &y& Elsevier]

Provides information on a study that ascertained resistance trends to ciprofloxacin, the most widely used fluoroquinolone in Great Britain, in the prevalent Enterobacteriaceae species from bacteremias in England and Wales during the 1990s. Methodology of the study; Results and discussion on the study.

CHCl[sub 3] and CHBr[sub 3] intercalated C[sub 60] have attracted particular interest after a superconductivity transition temperature (T[sub c]) of up to 117 K was discovered. We have determined the structure using synchrotron x-ray powder-diffraction and found that the expansion of the lattice mainly takes place in one dimension (triclinic b axis), Leaving planes of C[sub 60] molecules on an approximarely hexagonal, slightly expanded lattice. We have performed tight-binding band structure calculations for the surface layer. In spite of the slight expansion of the layers, for the range of dopings where a large T[sub c] has been observed, the density of states at the Fermi energy is smaller for C[sub 60] ·2CHCl[sub 3] and C[sub 60]·2CHBr[sub 3] than for C[sub 60]. This suggests that the lattice expansion alone cannot explain the increase of T[sub c]. [ABSTRACT FROM AUTHOR]

A further example of using a covalent-bond-forming reaction to alter supramolecular assembly by modification of hydrogen-bonding possibilities is presented. This concept was introduced by Lemmerer, Bernstein & Kahlenberg [ CrystEngComm (2011), 13, 55-59]. The title structure, C9H11N3O·C7H6O4, which consists of a reacted niazid molecule, viz. N′-(propan-2-ylidene)nicotinohydrazide, and 2,4-dihydroxybenzoic acid, was solved from powder diffraction data using simulated annealing. The results further demonstrate the relevance and utility of powder diffraction as an analytical tool in the study of cocrystals and their hydrogen-bond interactions. [ABSTRACT FROM AUTHOR]

Objectives: To describe changes in the private market for selected originators, branded generics ('similares'), and generic products during the 10 years following passage of the Brazilian Generics Law. Methods: We analyzed longitudinal data collected by IQVIA® on quarterly sales by wholesalers to retail pharmacies in Brazil from 1998 through 2010, grouped by originators, branded generics, and generic products in three therapeutic classes (antibiotics, antidiabetics, and antihypertensives). Outcomes included market share (proportion of the total private market volume), sales volume per capita, prices and number of manufacturers by group. Results: In the private market share, generics became dominant in each therapeutic class but the speed of uptake varied. Originators consistently lost most market share while branded generics varied over time. By the end of the study period, generics were the most sold product type in all classes, followed by branded generics. The number of generic manufacturers increased in all classes, while branded generics increased just after the policy but then decreased slowly through the end of 2010. For approximately 50% of the antibiotics analyzed, branded generics and generics had lower prices than originators. For antidiabetics, branded generic and generic prices were quite similar during the period analyzed. Price trends for the various subclasses of antihypertensive exhibited very different patterns over time. Conclusion: Sales of branded generics and originators decreased substantially in the three therapeutic classes analysed following the introduction of the generics policy in Brazil, but the time to market dominance of generics varied by class. [ABSTRACT FROM AUTHOR]