bluuebunny/crossref_metadata_2025_split huggingface dataset:
Why Are Clinicians Reluctant to Treat Smear-Negative Tuberculosis? An Inquiry about Treatment Thresholds in Rwanda
Authors: Basinga Paulin , Moreira Juan , Bisoffi Zeno , Bisig Bettina , Van den Ende Jef 
Published: January 2007

Purpose. The diagnosis of tuberculosis remains controversial between clinicians and public health officers. Public health officials fear to treat too many patients; clinicians fear that truly diseased will be denied treatment. We wondered whether an analysis of the treatment threshold could help making the often intuitive decision to treat smear-negative cases more evidence based. Methods. Eighteen clinicians and 10 public health specialists were asked for an intuitive estimate of their treatment threshold for tuberculosis and of key determinant factors for this threshold: the magnitude and subjective weight of mortality and morbidity due to both the disease and the treatment and risk and cost of the latter. With these factors, the authors calculated treatment thresholds and compared them to the intuitive thresholds of the interviewees. A prescriptive threshold was calculated based on literature data, omitting cost and subjective factors. Results. The median overall intuitive treatment threshold was 52.5%, the calculated 11.9%, and the prescriptive 2.7%. For 2 factors, public health officers provided significantly lower values than clinicians: cost of treatment (median = $20 v. $300; U = 2.5; P = 0.0002); cost of life (median = $500 v. $5000; U = 17.5; P = 0.009). Conclusion. These results suggest that clinicians and public health officers estimate wrongly the threshold even when using their own subjective estimate of influencing factors. Omitting treatment cost and subjective weight of provoked harm can result in a very low threshold. Sound training in threshold principles and providing tools to correctly assess data might help in making better decisions in tuberculosis in developing countries.
A Little Planning Goes a Long Way: Multilevel Allocation of HIV Prevention Resources
Authors: Zaric Gregory S. , Brandeau Margaret L. 
Published: January 2007

Background. HIV prevention funds are often allocated by decision makers at multiple levels. High-level decision makers may allocate funds to regions, and regional decision makers then allocate those funds to specific programs. Often, funds are allocated proportionally (e.g., in proportion to HIV incidence) rather than efficiently (i.e., to maximize HIV infections averted). The authors investigate the impact of efficient and proportional allocation methods at 2 different decision levels. Methods. The authors developed an optimization model of resource allocation at 2 levels—an aggregate upper level and multiple local levels—and considered efficient allocation and allocation proportional to HIV incidence. Using data from 40 U.S. states, they compared 4 strategies for allocating HIV prevention funds. Results. The greatest health benefit (HIV infections averted) occurred when efficient allocations were made at both levels. When funds were allocated proportionally at the higher level and efficiently at the lower level, the health benefit was about 5% less than when efficient allocations were made at both levels. When funds were allocated efficiently at the higher level and proportionally at the lower level, the health benefit was 15% less than when efficient allocations were made at both levels. The least health benefit (23% less than when efficient allocations were made at both levels) occurred with proportional allocation at both levels. Conclusions. Efficient allocation only at the higher level cannot overcome poor allocations at lower levels. Moreover, efficient allocation at the lower level is likely to yield greater gains than efficient allocation at the higher level. Thus, upper-level decision makers, such as donor organizations, should develop incentives to promote efficient allocation by lower-level decision makers.
Bedside Rationing by Health Practitioners: A Case Study in a Ugandan Hospital
Authors: Kapiriri Lydia , Martin Douglas K. 
Published: January 2007

Purpose. The purpose of this study was to describe bedside rationing by health practitioners in a teaching hospital in Uganda. Methods. This was a case study involving in-depth interviews. A modified thematic approach was used in data analysis. Types of decisions, the decision-making process, key players, and hospital-, medical-, and patient-related considerations in the process were identified. Klein’s 6 forms of rationing were used to identify the forms of rationing used. The setting was a tertiary hospital in Uganda. Theoretical sampling was used to identify 40 doctors and 16 nurses from the Departments of Medicine, Surgery, Paediatrics, and Obstetric and Gynaecology. Results. Four types of bedside rationing decisions were identified: 1) which patients are seen first, 2) which treatment the patients receive, 3) which patients are admitted, and 4) which patients are taken to the operating theatre first. Hospital-related considerations regarding bedside rationing included the hospital budget and number of beds; medical-related considerations included the patient’s diagnosis and effectiveness of treatment; and patient-related considerations included poverty, social status, and age. All forms of rationing (denial, dilution, deflection, deterrence, delay, and termination) were practiced. Conclusion. Although bedside rationing decisions in the study hospital seem somewhat similar to that in developed countries, the rationing of 1st-line drugs by health practitioners in Uganda is complex, difficult, and different from what has been described in industrialized countries. The complexity and severity of the consequences of the bedside decisions necessitate the development of resource-sensitive clinical guidelines and transparent decision-making processes to foster patients’ understanding of the reasons and the procedures and to ensure fair decision-making processes.
Assessing the Accuracy of Hospital Clinical Performance Measures
Authors: Normand Sharon-Lise T. , Wolf Robert E. , Ayanian John Z. , McNeil Barbara J. 
Published: January 2007

Objective. To control costs and improve quality, payers are designing new hospital reimbursement policies that link payment to quality. The authors determine the extent to which quality measures discriminate hospitals into tiers in 2 geographic areas. Data Sources. Administrative and medical record data for patients discharged with acute myocardial infarction (AMI) in 368 California and 81 Massachusetts hospitals. Methods. Through simulation, the minimum numbers of patients per hospital needed to identify highquality hospitals with sensitivity ranging from 75% to 95% under a variety of clinical scenarios are determined. Results. Massachusetts hospitals had twice the number of eligible patients per hospital than California hospitals. Regardless of state, few hospitals had sufficient sample size needed to achieve >85% sensitivity for high-variation quality measures. Clinical Implications. Reliability of quality-based reimbursement systems relies on the distribution of the hospital sample sizes within geographic areas and the size of practice differences. Selection of conformance thresholds and sensitivity levels depends on the user of the information. To assess the usefulness of performance measures to tier hospitals, information regarding between-hospital variation in quality for specific clinical measures needs to be collected and reported.
Temperature Dependence of Erythromelalgia Mutation L858F in Sodium Channel Nav1.7
Authors: Han Chongyang , Lampert Angelika , Rush Anthony M , Dib-Hajj Sulayman D , Wang Xiaoliang , Yang Yong , Waxman Stephen G 
Published: January 2007

Background: The disabling chronic pain syndrome erythromelalgia (also termed erythermalgia) is characterized by attacks of burning pain in the extremities induced by warmth. Pharmacological treatment is often ineffective, but the pain can be alleviated by cooling of the limbs. Inherited erythromelalgia has recently been linked to mutations in the gene SCN9A, which encodes the voltage-gated sodium channel Nav1.7. Nav1.7 is preferentially expressed in most nociceptive DRG neurons and in sympathetic ganglion neurons. It has recently been shown that several disease-causing erythromelalgia mutations alter channel-gating behavior in a manner that increases DRG neuron excitability. Results: Here we tested the effects of temperature on gating properties of wild type Nav1.7 and mutant L858F channels. Whole-cell voltage-clamp measurements on wild type or L858F channels expressed in HEK293 cells revealed that cooling decreases current density, slows deactivation and increases ramp currents for both mutant and wild type channels. However, cooling differentially shifts the midpoint of steady-state activation in a depolarizing direction for L858F but not for wild type channels. Conclusion: The cooling-dependent shift of the activation midpoint of L858F to more positive potentials brings the threshold of activation of the mutant channels closer to that of wild type Nav1.7 at lower temperatures, and is likely to contribute to the alleviation of painful symptoms upon cooling in affected limbs in patients with this erythromelalgia mutation.
POU-domain factor Brn3a regulates both distinct and common programs of gene expression in the spinal and trigeminal sensory ganglia
Authors: Eng S Raisa , Dykes Iain M , Lanier Jason , Fedtsova Natalia , Turner Eric E 
Published: January 2007

Abstract
Background
General somatic sensation is conveyed to the central nervous system at cranial levels by the trigeminal ganglion (TG), and at spinal levels by the dorsal root ganglia (DRG). Although these ganglia have similar functions, they have distinct embryological origins, in that both contain neurons originating from the neural crest, while only the TG includes cells derived from the placodal ectoderm.

Results
Here we use microarray analysis of E13.5 embryos to demonstrate that the developing DRG and TG have very similar overall patterns of gene expression. In mice lacking the POU-domain transcription factor Brn3a, the DRG and TG exhibit many common changes in gene expression, but a subset of Brn3a target genes show increased expression only in the TG. In the wild-type TG these Brn3a-repressed genes are silent, yet their promoter regions exhibit histone H3-acetylation levels similar to constitutively transcribed gene loci. This increased H3-acetylation is not observed in the DRG, suggesting that chromatin modifications play a role in cell-specific target gene regulation by Brn3a.

Conclusion
These results demonstrate that one developmental role of Brn3a is to repress potential differences in gene expression between sensory neurons generated at different axial levels, and to regulate a convergent program of developmental gene expression, in which functionally similar populations of neurons are generated from different embryological substrates.
Near infrared spectroscopy in the development of solid dosage forms
Authors: Räsänen Eetu , Sandler Niklas 
Published: January 2007

Abstract
The use of near infrared (NIR) spectroscopy has rapidly grown partly due to demands of process analytical applications in the pharmaceutical industry. Furthermore, newest regulatory guidelines have advanced the increase of the use of NIR technologies. The non-destructive and non-invasive nature of measurements makes NIR a powerful tool in characterization of pharmaceutical solids. These benefits among others often make NIR advantageous over traditional analytical methods. However, in addition to NIR, a wide variety of other tools are naturally also available for analysis in pharmaceutical development and manufacturing, and those can often be more suitable for a given application. The versatility and rapidness of NIR will ensure its contribution to increased process understanding, better process control and improved quality of drug products. This review concentrates on the use of NIR spectroscopy from a process research perspective and highlights recent applications in the field.
Determination of amorphous content in the pharmaceutical process environment
Authors: Savolainen Marja , Jouppila Kirsi , Pajamo Outi , Christiansen Leena , Strachan Clare , Karjalainen Milja , Rantanen Jukka 
Published: January 2007

Abstract
The amorphous state has different chemical and physical properties compared with a crystalline one. Amorphous regions in an otherwise crystalline material can affect the bioavailability and the processability. On the other hand, crystalline material can function as nuclei and decrease the stability of an amorphous system. The aim of this study was to determine amorphous content in a pharmaceutical process environment using near infrared (NIR) and Raman spectroscopic techniques together with multivariate modelling tools. Milling was used as a model system for process-induced amorphization of a crystalline starting material, α-lactose monohydrate. In addition, the crystallization of amorphous material was studied by storing amorphous material, either amorphous lactose or trehalose, at high relative humidity conditions. The results show that both of the spectroscopic techniques combined with multivariate methods could be applied for quantitation. Preprocessing, as well as the sampling area, was found to affect the performance of the models. Standard normal variate (SNV) transformation was the best preprocessing approach and increasing the sampling area was found to improve the models. The root mean square error of prediction (RMSEP) for quantitation of amorphous lactose using NIR spectroscopy was 2.7%, when a measuring setup with a larger sampling area was used. When the sampling area was smaller, the RMSEPs for lactose and trehalose were 4.3% and 4.2%, respectively. For Raman spectroscopy, the RMSEPs were 2.3% and 2.5% for lactose and trehalose, respectively. However, for the optimal performance of a multivariate model, all the physical forms present, as well as the process environment itself, have to be taken into consideration.
Process analytical applications of Raman spectroscopy
Authors: Rantanen Jukka 
Published: January 2007

Abstract
There is an increasing demand for new approaches to understand the chemical and physical phenomena that occur during pharmaceutical unit operations. Obtaining real-time information from processes opens new perspectives for safer and more efficient manufacture of pharmaceuticals. Raman spectroscopy provides a molecular level insight into processing, and therefore it is a future process analytical tool. In this review, different applications of Raman spectroscopy in the field of process analysis of pharmaceutical solid dosage forms are summarized. In addition, pitfalls associated with interfacing to the process environment and challenges within data management are discussed.
Raman spectroscopy for quantitative analysis of pharmaceutical solids
Authors: Strachan Clare J , Rades Thomas , Gordon Keith C , Rantanen Jukka 
Published: January 2007

Abstract
Raman spectroscopy is experiencing a surge in interest in solid-state pharmaceutical applications. It is rapid, non-destructive, no sample preparation is required and measurements can be made in aqueous environments. It can be used for not only qualitative, but also quantitative, analysis. In this paper, the use of Raman spectroscopy for quantitative analysis of pharmaceutical solids is reviewed. The technique has been used for chemical and physical form analysis. Physical form analysis has involved quantification of polymorphism, hydrates, the amorphous form and, recently, protein conformation. Initially, simple powder systems were quantified, although this has since extended to complex pharmaceutical formulations, including tablets, capsules, microspheres and suspensions. Formulations have also been analysed through packaging. The characteristics of the technique make it ideal for process monitoring and it has been used to quantify changes in-situ during processes such as wet granulation and batch crystallisation. The theoretical basis of quantitative Raman spectroscopy, common data analysis approaches, including multivariate analysis, and sources of error in quantitative analysis are also discussed.
The influence of various excipients on the conversion kinetics of carbamazepine polymorphs in aqueous suspension
Authors: Tian Fang , Saville Dorothy J , Gordon Keith C , Strachan Clare J , Zeitler J Axel , Sandler Niklas , Rades Thomas 
Published: January 2007

Abstract
The influence of various excipients on the conversion of carbamazepine polymorphs to the dihydrate in aqueous suspension has been investigated. Ten excipients having functional groups which were potentially able to form hydrogen bonds with carbamazepine (group 1: methylcellulose, hypromellose (hydroxypropyl methylcellulose), hydroxypropylcellulose (HPC), 2-hydroxyethylcellulose (HEC), carmellose sodium (sodium carboxymethylcellulose), cellobiose; group 2: povidone (polyvinylpyrrolidone), povidone-vinyl acetate copolymer (povidone/VA) and N-methyl-2-pyrrolidone; group 3: macrogol (polyethylene glycol) and polyethylene oxide-polypropylene oxide copolymer (PEO/PPO)) were selected. Carbamazepine polymorphic forms III and I were dispersed separately into each aqueous excipient solution (0.1%, w/v) for 30 min at room temperature. The inhibition effect of each excipient was quantified using Raman spectroscopy combined with multivariate analyses. The solubility parameter of each excipient was calculated and used for categorizing excipients. Excipients in groups 1 and 2, which had both low solubility parameters (&lt; 27.0 MPa½) and strong hydrogen bonding groups, inhibited the conversion completely. With increasing solubility parameter, the inhibition effect decreased for group 1 excipients, especially for carbamazepine form I, which had a higher specific surface area. Also, the excipients of group 3, lacking strong hydrogen bonding groups, showed poor inhibition although they had low solubility parameters (&lt; 21.0 MPa½). This study indicated the importance of both hydrogen bonding interaction and a suitable hydrophobicity (expressed by the solubility parameter) in the inhibition of the conversion of carbamazepine to the dihydrate.
Characterization of silicone elastomer vaginal rings containing HIV microbicide TMC120 by Raman spectroscopy
Authors: Bell Steven E J , Dennis Andrew C , Fido Louise A , Malcolm R Karl , Sirimuthu Narayana M S , Toner Clare F , Woolfson A David 
Published: January 2007

Abstract
Silicone elastomer vaginal rings are currently being pursued as a controlled-release strategy for delivering microbicidal substances for the prevention of heterosexual transmission of HIV. Although it is well established that the distribution of drugs in delivery systems influences the release characteristics, in practice the distribution is often difficult to quantify in-situ. Therefore, the aim of this work was to determine whether Raman spectroscopy might provide a rapid, non-contact means of measuring the concentrations of the lead candidate HIV microbicide TMC120 in a silicone elastomer reservoir-type vaginal ring. Vaginal rings loaded with TMC120 were manufactured and sectioned before either Raman mapping an entire ring cross-section (100 μm resolution) or running line scans at appropriate time intervals up to 30 h after manufacture. The results demonstrated that detectable amounts of TMC120, above the silicone elastomer saturation concentration, could be detected up to 1 mm into the sheath, presumably as a consequence of permeation and subsequent reprecipitation. The extent of permeation was found to be similar in rings manufactured at 25 and 80°C.
Terahertz pulsed spectroscopy and imaging in the pharmaceutical setting - a review
Authors: Zeitler J Axel , Taday Philip F , Newnham David A , Pepper Michael , Gordon Keith C , Rades Thomas 
Published: January 2007

Abstract
Terahertz pulsed spectroscopy (TPS) and terahertz pulsed imaging (TPI) are two novel techniques for the physical characterization of pharmaceutical drug materials and final solid dosage forms, utilizing spectral information in the far infrared region of the electromagnetic spectrum. This review focuses on the development and performance of pharmaceutical applications of terahertz technology compared with other tools for physical characterization. TPS can be used to characterize crystalline properties of drugs and excipients. Different polymorphic forms of a drug can be readily distinguished and quantified. Recent developments towards a better understanding of the fundamental theory behind spectroscopy in the far infrared have been discussed. Applications for TPI include the measurement of coating thickness and uniformity in coated pharmaceutical tablets, structural imaging and 3D chemical imaging of solid dosage forms.
Applications of solid-state NMR to pharmaceutical polymorphism and related matters
Authors: Harris Robin K 
Published: January 2007

Abstract
Magic-angle spinning NMR is now making a significant contribution to our understanding of the structure of polymorphs and solvates of pharmaceutical significance. This personal review article discusses a range of applications, with particular emphasis on information about crystallography, for which NMR can address problems that cannot be readily solved by diffraction techniques (such as dynamic disorder and non-stoichiometric hydration). Unlike diffractograms, NMR spectra yield immediate chemical information. Moreover, heterogeneous samples can be investigated and amorphous content provides no significant barrier to studies. Furthermore, NMR can be an effective technique for quantitation (down to the level of ca. 1%). Additional strength is being derived from computation of chemical shifts in solids, using a code that takes account of the spatial repetition inherent in crystalline materials.
Characterization of the bulk properties of pharmaceutical solids using nonlinear optics - a review
Authors: Lee Chris J , Strachan Clare J , Manson Peter J , Rades Thomas 
Published: January 2007

Abstract
With the development of stable, compact and reliable pulsed laser sources the field of characterizing materials through their nonlinear optical response has bloomed. Second harmonic generation by non-centrosymmetric crystal structures has provided a new spectroscopic tool of potentially great utility in the pharmaceutical field. The nonlinear optical response of various materials provides a very sensitive technique for the characterization of pharmaceutically interesting bulk compounds and dispersions, and determining their concentrations. This work has potential application for in-line monitoring and quality control of pharmaceutical manufacturing. In this article we have presented an extensive review of the spectroscopic techniques that make use of the nonlinear optical response of solid media. Also, we have presented the results of our own work in this field.
Time-of-flight secondary-ion mass spectrometry for the surface characterization of solid-state pharmaceuticals
Authors: Prestidge Clive A , Barnes Timothy J , Skinner William 
Published: January 2007

AbstractTime-of-flight secondary-ion mass spectrometry (ToF-SIMS) is a highly surface sensitive analytical method for surface chemical identification and surface chemical distribution analysis (mapping). Here we have explored the application of ToF-SIMS for the characterization of solid-state pharmaceuticals and highlight specific case studies concerning the distribution and stability of pharmaceutical actives within solid matrices (pellets and polymeric carriers) and the face-specific properties of pharmaceutical crystals.