搜索结果：Journal of pharmaceutical analysis

Associations between modifiable exposures and disease seen in observational epidemiology are sometimes confounded and thus misleading, despite our best efforts to improve the design and analysis of studies. Mendelian randomization—the random assortment of genes from parents to offspring that occurs during gamete formation and conception—provides one method for assessing the causal nature of some environmental exposures. The association between a disease and a polymorphism that mimics the biological link between a proposed exposure and disease is not generally susceptible to the reverse causation or confounding that may distort interpretations of conventional observational studies. Several examples where the phenotypic effects of polymorphisms are well documented provide encouraging evidence of the explanatory power of Mendelian randomization and are described. The limitations of the approach include confounding by polymorphisms in linkage disequilibrium with the polymorphism under study, that polymorphisms may have several phenotypic effects associated with disease, the lack of suitable polymorphisms for studying modifiable exposures of interest, and canalization—the buffering of the effects of genetic variation during development. Nevertheless, Mendelian randomization provides new opportunities to test causality and demonstrates how investment in the human genome project may contribute to understanding and preventing the adverse effects on human health of modifiable exposures. Genetic epidemiology—the theme of this issue of the International Journal of Epidemiology—is seen by many to be the only future for epidemiology, perhaps reflecting a growing awareness of the limitations of observational epidemiology1 (Box 1). Genetic epidemiology is concerned with understanding heritable aspects of disease risk, individual susceptibility to disease, and ultimately with contributing to a comprehensive molecular understanding of pathogenesis. The massive investment and expansion of human genetics, if it is to return value for the common good, must be integrated into public health functions. The human genome epidemiology network (HuGE Net—http://www.cdc.gov/genetics/huge.htm) has been established to promote the use of genetic knowledge—in terms of genetic tests and services—for disease prevention and health promotion.2,3 A broad taxonomy of human genome studies of public health relevance has been developed4 (Box 2). In this issue of the IJE, we publish a paper by Miguel Porta,5 who highlights the need for a more rational approach to genetic testing, given the likely low penetrance of many genes associated with cancers,6 likening the role of the genome to a jazz score that is interpreted and developed through experience and context—and is seldom predictable. Such insights may well temper enthusiasm for genetic testing in populations. However, in parallel to the approaches advocated by HuGE, genetic epidemiology can lead to a more robust understanding of environmental determinants of disease (e.g. dietary factors, occupational exposures, and health-related behaviours) relevant to whole populations (and not simply to genetically susceptible sub-populations).7–10 This approach has recently been referred to as ‘Mendelian randomization’.11–15 Here we begin by briefly reviewing reasons for current concerns about aetiological findings generated by conventional observational epidemiology and then we outline the potential contribution (and limitations) of Mendelian randomization. ‘Epidemiology set to get fast-track treatment’ ‘A consortium of leading European research centres and pharmaceutical companies will this week announce a plan to transform epidemiology by combining it with the new techniques of high-throughput biology. They plan to create a new field of study—genomic epidemiology—by using screening technologies derived from the human genome project … We think it is important to expand classical epidemiology and genetic epidemiology to take it to this high-throughput mode, says Esper Boel, vice-president of biotechnology research at Novo Nordisk. We want to use post-genomic technologies to create a new clinical science, to turn functional genomics into real clinical chemistry.’ From: Butler D. Epidemiology set to get fast-track treatment. Nature 2001;414:139. Reprinted with permission. Surveillance Population frequency of gene variants predisposing to specific diseases Population frequency of morbidity and mortality from such diseases Population frequency and effects of environmental factors known to interact with gene variants Economic costs of genetic components of diseases Coverage, access, and uptake of genetic tests and services Aetiology Magnitude of disease risk associated with gene variants in different populations Contribution of gene variants to the overall level of disease in different populations Magnitude of disease risk associated with gene–gene and gene–environment interactions in different populations Health services research Clinical validity and utility of genetic tests in different populations Determinants and impact of using genetic tests and services in different populations Adapted from Khoury MJ, Burke W, Thomson EJ (eds). Genetics and Public Health in the 21st Century. Oxford: Oxford University Press, 2000.

BACKGROUND: Journal advertising is one of the main sources of medicines information to doctors. Despite the availability of regulations and controls of drug promotion worldwide, information on medicines provided in journal advertising has been criticized in several studies for being of poor quality. However, no attempt has been made to systematically summarise this body of research. We designed this systematic review to assess all studies that have examined the quality of pharmaceutical advertisements for prescription products in medical and pharmacy journals. METHODS AND FINDINGS: Studies were identified via searching electronic databases, web library, search engine and reviewing citations (1950 - February 2006). Only articles published in English and examined the quality of information included in pharmaceutical advertisements for prescription products in medical or pharmacy journals were included. For each eligible article, a researcher independently extracted the data on the study methodology and outcomes. The data were then reviewed by a second researcher. Any disagreements were resolved by consensus. The data were analysed descriptively. The final analysis included 24 articles. The studies reviewed advertisements from 26 countries. The number of journals surveyed in each study ranged from four to 24 journals. Several outcome measures were examined including references and claims provided in advertisements, availability of product information, adherence to codes or guidelines and presentation of risk results. The majority of studies employed a convenience-sampling method. Brand name, generic name and indications were usually provided. Journal articles were commonly cited to support pharmaceutical claims. Less than 67% of the claims were supported by a systematic review, a meta-analysis or a randomised control trial. Studies that assessed misleading claims had at least one advertisement with a misleading claim. Two studies found that less than 28% of claims were unambiguous clinical claims. Most advertisements with quantitative information provided risk results as relative risk reduction. Studies were conducted in 26 countries only and then the generalizability of the results is limited. CONCLUSIONS: Evidence from this review indicates that low quality of journal advertising is a global issue. As information provided in journal advertising has the potential to change doctors' prescribing behaviour, ongoing efforts to increase education about drug promotion are crucial. The results from our review suggest the need for a global pro-active and effective regulatory system to ensure that information provided in medical journal advertising is supporting the quality use of medicines.

BACKGROUND: Pharmaceutical companies spent $57.5 billion on pharmaceutical promotion in the United States in 2004. The industry claims that promotion provides scientific and educational information to physicians. While some evidence indicates that promotion may adversely influence prescribing, physicians hold a wide range of views about pharmaceutical promotion. The objective of this review is to examine the relationship between exposure to information from pharmaceutical companies and the quality, quantity, and cost of physicians' prescribing. METHODS AND FINDINGS: We searched for studies of physicians with prescribing rights who were exposed to information from pharmaceutical companies (promotional or otherwise). Exposures included pharmaceutical sales representative visits, journal advertisements, attendance at pharmaceutical sponsored meetings, mailed information, prescribing software, and participation in sponsored clinical trials. The outcomes measured were quality, quantity, and cost of physicians' prescribing. We searched Medline (1966 to February 2008), International Pharmaceutical Abstracts (1970 to February 2008), Embase (1997 to February 2008), Current Contents (2001 to 2008), and Central (The Cochrane Library Issue 3, 2007) using the search terms developed with an expert librarian. Additionally, we reviewed reference lists and contacted experts and pharmaceutical companies for information. Randomized and observational studies evaluating information from pharmaceutical companies and measures of physicians' prescribing were independently appraised for methodological quality by two authors. Studies were excluded where insufficient study information precluded appraisal. The full text of 255 articles was retrieved from electronic databases (7,185 studies) and other sources (138 studies). Articles were then excluded because they did not fulfil inclusion criteria (179) or quality appraisal criteria (18), leaving 58 included studies with 87 distinct analyses. Data were extracted independently by two authors and a narrative synthesis performed following the MOOSE guidelines. Of the set of studies examining prescribing quality outcomes, five found associations between exposure to pharmaceutical company information and lower quality prescribing, four did not detect an association, and one found associations with lower and higher quality prescribing. 38 included studies found associations between exposure and higher frequency of prescribing and 13 did not detect an association. Five included studies found evidence for association with higher costs, four found no association, and one found an association with lower costs. The narrative synthesis finding of variable results was supported by a meta-analysis of studies of prescribing frequency that found significant heterogeneity. The observational nature of most included studies is the main limitation of this review. CONCLUSIONS: With rare exceptions, studies of exposure to information provided directly by pharmaceutical companies have found associations with higher prescribing frequency, higher costs, or lower prescribing quality or have not found significant associations. We did not find evidence of net improvements in prescribing, but the available literature does not exclude the possibility that prescribing may sometimes be improved. Still, we recommend that practitioners follow the precautionary principle and thus avoid exposure to information from pharmaceutical companies. Please see later in the article for the Editors' Summary.

BACKGROUND: Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide in adults. Pharmacological and non-pharmacological treatments are available; however, because of inadequate resources, antidepressants are used more frequently than psychological interventions. Prescription of these agents should be informed by the best available evidence. Therefore, we aimed to update and expand our previous work to compare and rank antidepressants for the acute treatment of adults with unipolar major depressive disorder. METHODS: We did a systematic review and network meta-analysis. We searched Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS database, MEDLINE, MEDLINE In-Process, PsycINFO, the websites of regulatory agencies, and international registers for published and unpublished, double-blind, randomised controlled trials from their inception to Jan 8, 2016. We included placebo-controlled and head-to-head trials of 21 antidepressants used for the acute treatment of adults (≥18 years old and of both sexes) with major depressive disorder diagnosed according to standard operationalised criteria. We excluded quasi-randomised trials and trials that were incomplete or included 20% or more of participants with bipolar disorder, psychotic depression, or treatment-resistant depression; or patients with a serious concomitant medical illness. We extracted data following a predefined hierarchy. In network meta-analysis, we used group-level data. We assessed the studies' risk of bias in accordance to the Cochrane Handbook for Systematic Reviews of Interventions, and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. Primary outcomes were efficacy (response rate) and acceptability (treatment discontinuations due to any cause). We estimated summary odds ratios (ORs) using pairwise and network meta-analysis with random effects. This study is registered with PROSPERO, number CRD42012002291. FINDINGS: We identified 28 552 citations and of these included 522 trials comprising 116 477 participants. In terms of efficacy, all antidepressants were more effective than placebo, with ORs ranging between 2·13 (95% credible interval [CrI] 1·89-2·41) for amitriptyline and 1·37 (1·16-1·63) for reboxetine. For acceptability, only agomelatine (OR 0·84, 95% CrI 0·72-0·97) and fluoxetine (0·88, 0·80-0·96) were associated with fewer dropouts than placebo, whereas clomipramine was worse than placebo (1·30, 1·01-1·68). When all trials were considered, differences in ORs between antidepressants ranged from 1·15 to 1·55 for efficacy and from 0·64 to 0·83 for acceptability, with wide CrIs on most of the comparative analyses. In head-to-head studies, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants (range of ORs 1·19-1·96), whereas fluoxetine, fluvoxamine, reboxetine, and trazodone were the least efficacious drugs (0·51-0·84). For acceptability, agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine were more tolerable than other antidepressants (range of ORs 0·43-0·77), whereas amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine had the highest dropout rates (1·30-2·32). 46 (9%) of 522 trials were rated as high risk of bias, 380 (73%) trials as moderate, and 96 (18%) as low; and the certainty of evidence was moderate to very low. INTERPRETATION: All antidepressants were more efficacious than placebo in adults with major depressive disorder. Smaller differences between active drugs were found when placebo-controlled trials were included in the analysis, whereas there was more variability in efficacy and acceptability in head-to-head trials. These results should serve evidence-based practice and inform patients, physicians, guideline developers, and policy makers on the relative merits of the different antidepressants. FUNDING: National Institute for Health Research Oxford Health Biomedical Research Centre and the Japan Society for the Promotion of Science.

BACKGROUND: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. METHODS: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. FINDINGS: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990-2010 time period, with the greatest annualised rate of decline occurring in the 0-9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10-24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10-24 years were also in the top ten in the 25-49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50-74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. INTERPRETATION: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and development investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. FUNDING: Bill & Melinda Gates Foundation.

Importance: While guidance on statistical principles for clinical trials exists, there is an absence of guidance covering the required content of statistical analysis plans (SAPs) to support transparency and reproducibility. Objective: To develop recommendations for a minimum set of items that should be addressed in SAPs for clinical trials, developed with input from statisticians, previous guideline authors, journal editors, regulators, and funders. Design: Funders and regulators (n = 39) of randomized trials were contacted and the literature was searched to identify existing guidance; a survey of current practice was conducted across the network of UK Clinical Research Collaboration-registered trial units (n = 46, 1 unit had 2 responders) and a Delphi survey (n = 73 invited participants) was conducted to establish consensus on SAPs. The Delphi survey was sent to statisticians in trial units who completed the survey of current practice (n = 46), CONSORT (Consolidated Standards of Reporting Trials) and SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guideline authors (n = 16), pharmaceutical industry statisticians (n = 3), journal editors (n = 9), and regulators (n = 2) (3 participants were included in 2 groups each), culminating in a consensus meeting attended by experts (N = 12) with representatives from each group. The guidance subsequently underwent critical review by statisticians from the surveyed trial units and members of the expert panel of the consensus meeting (N = 51), followed by piloting of the guidance document in the SAPs of 5 trials. Findings: No existing guidance was identified. The registered trials unit survey (46 responses) highlighted diversity in current practice and confirmed support for developing guidance. The Delphi survey (54 of 73, 74% participants completing both rounds) reached consensus on 42% (n = 46) of 110 items. The expert panel (N = 12) agreed that 63 items should be included in the guidance, with an additional 17 items identified as important but may be referenced elsewhere. Following critical review and piloting, some overlapping items were combined, leaving 55 items. Conclusions and Relevance: Recommendations are provided for a minimum set of items that should be addressed and included in SAPs for clinical trials. Trial registration, protocols, and statistical analysis plans are critically important in ensuring appropriate reporting of clinical trials.

International Journal of Pharmaceutical Sciences and Research (IJPSR) is an official publication of Society of Pharmaceutical Sciences & Research. It is an open access online and print International Journal published monthly. Website: www.ijpsr.com Projected Impact Factor (2012): 2.44, ICV 2012: 5.50, 2011: 5.07, 2010: 4.57 DOI: 10.13040/IJPSR.0975-8232 SJ Impact Factor (2012): 3.226 Global Impact Factor (2013): 0.533, (2012): 0.452 Indexing - EMBASE- Elsevier's

OBJECTIVE: To determine the effects of antiplatelet therapy among patients at high risk of occlusive vascular events. DESIGN: Collaborative meta-analyses (systematic overviews). INCLUSION CRITERIA: Randomised trials of an antiplatelet regimen versus control or of one antiplatelet regimen versus another in high risk patients (with acute or previous vascular disease or some other predisposing condition) from which results were available before September 1997. Trials had to use a method of randomisation that precluded prior knowledge of the next treatment to be allocated and comparisons had to be unconfounded-that is, have study groups that differed only in terms of antiplatelet regimen. STUDIES REVIEWED: 287 studies involving 135 000 patients in comparisons of antiplatelet therapy versus control and 77 000 in comparisons of different antiplatelet regimens. MAIN OUTCOME MEASURE: "Serious vascular event": non-fatal myocardial infarction, non-fatal stroke, or vascular death. RESULTS: Overall, among these high risk patients, allocation to antiplatelet therapy reduced the combined outcome of any serious vascular event by about one quarter; non-fatal myocardial infarction was reduced by one third, non-fatal stroke by one quarter, and vascular mortality by one sixth (with no apparent adverse effect on other deaths). Absolute reductions in the risk of having a serious vascular event were 36 (SE 5) per 1000 treated for two years among patients with previous myocardial infarction; 38 (5) per 1000 patients treated for one month among patients with acute myocardial infarction; 36 (6) per 1000 treated for two years among those with previous stroke or transient ischaemic attack; 9 (3) per 1000 treated for three weeks among those with acute stroke; and 22 (3) per 1000 treated for two years among other high risk patients (with separately significant results for those with stable angina (P=0.0005), peripheral arterial disease (P=0.004), and atrial fibrillation (P=0.01)). In each of these high risk categories, the absolute benefits substantially outweighed the absolute risks of major extracranial bleeding. Aspirin was the most widely studied antiplatelet drug, with doses of 75-150 mg daily at least as effective as higher daily doses. The effects of doses lower than 75 mg daily were less certain. Clopidogrel reduced serious vascular events by 10% (4%) compared with aspirin, which was similar to the 12% (7%) reduction observed with its analogue ticlopidine. Addition of dipyridamole to aspirin produced no significant further reduction in vascular events compared with aspirin alone. Among patients at high risk of immediate coronary occlusion, short term addition of an intravenous glycoprotein IIb/IIIa antagonist to aspirin prevented a further 20 (4) vascular events per 1000 (P<0.0001) but caused 23 major (but rarely fatal) extracranial bleeds per 1000. CONCLUSIONS: Aspirin (or another oral antiplatelet drug) is protective in most types of patient at increased risk of occlusive vascular events, including those with an acute myocardial infarction or ischaemic stroke, unstable or stable angina, previous myocardial infarction, stroke or cerebral ischaemia, peripheral arterial disease, or atrial fibrillation. Low dose aspirin (75-150 mg daily) is an effective antiplatelet regimen for long term use, but in acute settings an initial loading dose of at least 150 mg aspirin may be required. Adding a second antiplatelet drug to aspirin may produce additional benefits in some clinical circumstances, but more research into this strategy is needed.

IMPORTANCE: The association between industry payments to physicians and prescribing rates of the brand-name medications that are being promoted is controversial. In the United States, industry payment data and Medicare prescribing records recently became publicly available. OBJECTIVE: To study the association between physicians' receipt of industry-sponsored meals, which account for roughly 80% of the total number of industry payments, and rates of prescribing the promoted drug to Medicare beneficiaries. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional analysis of industry payment data from the federal Open Payments Program for August 1 through December 31, 2013, and prescribing data for individual physicians from Medicare Part D, for all of 2013. Participants were physicians who wrote Medicare prescriptions in any of 4 drug classes: statins, cardioselective β-blockers, angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers (ACE inhibitors and ARBs), and selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRIs and SNRIs). We identified physicians who received industry-sponsored meals promoting the most-prescribed brand-name drug in each class (rosuvastatin, nebivolol, olmesartan, and desvenlafaxine, respectively). Data analysis was performed from August 20, 2015, to December 15, 2015. EXPOSURES: Receipt of an industry-sponsored meal promoting the drug of interest. MAIN OUTCOMES AND MEASURES: Prescribing rates of promoted drugs compared with alternatives in the same class, after adjustment for physician prescribing volume, demographic characteristics, specialty, and practice setting. RESULTS: A total of 279 669 physicians received 63 524 payments associated with the 4 target drugs. Ninety-five percent of payments were meals, with a mean value of less than $20. Rosuvastatin represented 8.8% (SD, 9.9%) of statin prescriptions; nebivolol represented 3.3% (7.4%) of cardioselective β-blocker prescriptions; olmesartan represented 1.6% (3.9%) of ACE inhibitor and ARB prescriptions; and desvenlafaxine represented 0.6% (2.6%) of SSRI and SNRI prescriptions. Physicians who received a single meal promoting the drug of interest had higher rates of prescribing rosuvastatin over other statins (odds ratio [OR], 1.18; 95% CI, 1.17-1.18), nebivolol over other β-blockers (OR, 1.70; 95% CI, 1.69-1.72), olmesartan over other ACE inhibitors and ARBs (OR, 1.52; 95% CI, 1.51-1.53), and desvenlafaxine over other SSRIs and SNRIs (OR, 2.18; 95% CI, 2.13-2.23). Receipt of additional meals and receipt of meals costing more than $20 were associated with higher relative prescribing rates. CONCLUSIONS AND RELEVANCE: Receipt of industry-sponsored meals was associated with an increased rate of prescribing the brand-name medication that was being promoted. The findings represent an association, not a cause-and-effect relationship.

The analysis of 87 peer-reviewed journal articles reveals that sampling for pharmaceuticals and personal care products (PPCPs) and illicit drugs in sewers and sewage treatment plant influents is mostly carried out according to existing tradition or standard laboratory protocols. Less than 5% of all studies explicitly consider internationally acknowledged guidelines or methods for the experimental design of monitoring campaigns. In the absence of a proper analysis of the system under investigation, the importance of short-term pollutant variations was typically not addressed. Therefore, due to relatively long sampling intervals, potentially inadequate sampling modes, or insufficient documentation, it remains unclear for the majority of reviewed studies whether observed variations can be attributed to "real" variations or if they simply reflect sampling artifacts. Based on results from previous and current work, the present paper demonstrates that sampling errors can lead to overinterpretation of measured data and ultimately, wrong conclusions. Depending on catchment size, sewer type, sampling setup, substance of interest, and accuracy of analytical method, avoidable sampling artifacts can range from "not significant" to "100% or more" for different compounds even within the same study. However, in most situations sampling errors can be reduced greatly, and sampling biases can be eliminated completely, by choosing an appropriate sampling mode and frequency. This is crucial, because proper sampling will help to maximize the value of measured data for the experimental assessment of the fate of PPCPs as well as for the formulation and validation of mathematical models. The trend from reporting presence or absence of a compound in "clean" water samples toward the quantification of PPCPs in raw wastewater requires not only sophisticated analytical methods but also adapted sampling methods. With increasing accuracy of chemical analyses, inappropriate sampling increasingly represents the major source of inaccuracy. A condensed step-by-step Sampling Guide is proposed as a starting point for future studies.

Liquid chromatography (LC) based techniques in combination with mass spectrometry (MS) detection have had a large impact on the development of new pharmaceuticals in the past decades. Continuous improvements in mass spectrometry and interface technologies, combined with advanced liquid chromatographic techniques for high-throughput qualitative and quantitative analysis, have resulted in a wider scope of applications in the pharmaceutical field. LC-MS tools are increasingly used to analyze pharmaceuticals across a variety of stages in their discovery and development. These stages include drug discovery, product characterization, metabolism studies (in vitro and in vivo) and the identification of impurities and degradation products. The increase in LC-MS applications has been enormous, with retention times and molecular weights (and related fragmentation patterns) emerging as crucial analytical features in the drug development process. The goal of this review is to give an overview of the main developments in LC-MS based techniques for the analysis of small pharmaceutical molecules in the last decade and give a perspective on future trends in LC-MS in the pharmaceutical field.

The entire pharmaceutical sector is in an urgent need of both innovative technological solutions and fundamental scientific work, enabling the production of highly engineered drug products. Commercial-scale manufacturing of complex drug delivery systems (DDSs) using the existing technologies is challenging. This review covers important elements of manufacturing sciences, beginning with risk management strategies and design of experiments (DoE) techniques. Experimental techniques should, where possible, be supported by computational approaches. With that regard, state-of-art mechanistic process modeling techniques are described in detail. Implementation of materials science tools paves the way to molecular-based processing of future DDSs. A snapshot of some of the existing tools is presented. Additionally, general engineering principles are discussed covering process measurement and process control solutions. Last part of the review addresses future manufacturing solutions, covering continuous processing and, specifically, hot-melt processing and printing-based technologies. Finally, challenges related to implementing these technologies as a part of future health care systems are discussed.

Spectroscopy is widely used to characterize pharmaceutical products or processes, especially due to its desirable characteristics of being rapid, cheap, non-invasive/non-destructive and applicable both off-line and in-/at-/on-line. Spectroscopic techniques produce profiles containing a high amount of information, which can profitably be exploited through the use of multivariate mathematic and statistic (chemometric) techniques. The present paper aims at providing a brief overview of the different chemometric approaches applicable in the context of spectroscopy-based pharmaceutical analysis, discussing both the unsupervised exploration of the collected data and the possibility of building predictive models for both quantitative (calibration) and qualitative (classification) responses.

OBJECTIVE: The authors sought to determine the efficacy and acceptability of lithium for relapse prevention in bipolar disorder. METHOD: A systematic review and meta-analysis of randomized controlled trials comparing lithium with placebo in the long-term treatment of bipolar disorders was conducted. Data were obtained from searching the registers of the Cochrane Collaboration; reviewing reference lists, journals, and conference abstracts; and contacting authors, experts, and pharmaceutical companies. Outcomes investigated included risk of relapse (manic, depressive, and total) as well as risk of specific adverse effects and total withdrawal rates. RESULTS: Five randomized controlled trials (770 participants) were included. Lithium was more effective than placebo in preventing all relapses (random effects relative risk=0.65, 95% CI=0.50 to 0.84) and manic relapses (relative risk=0.62, 95% CI=0.40 to 0.95). The protective effect of lithium on depressive relapses was smaller and was less robust (relative risk=0.72, 95% CI=0.49 to 1.07). CONCLUSIONS: Lithium treatment reduces the risk of relapse in bipolar disorder. The preventive effect is clear for manic episodes, although it is equivocal for depressive episodes.

The Pharmaceutical and Chemical Journal is an open access, peer-reviewed and online journal that will encompass all aspects of Chemical Sciences like  Cluster Chemistry, Astrochemistry, Soil Chemistry, Agricultural Chemistry, Biochemistry, Electrochemistry, Photochemistry, Forensic Chemistry, Green Chemistry, Macromolecular Chemistry, Nanochemistry, Analytical Chemistry, Environmental Chemistry, Petroleum Chemistry, Food Chemistry, Computational Chemistry, Thermochemistry, Phytochemistry, Industrial Chemistry, Inorganic Chemistry,  Organic Chemistry, Physical Chemistry, Polymer Chemistry, Quantum Chemistry,  Surface chemistry and Chemical Engineering etc. The Pharmaceutical and Chemical Journal  also promotes research in all fields of Pharmaceutical Sciences like Pharmaceutical Technology, Pharmaceutics, Clinical and Hospital Pharmacy, Pharmaceutical Microbiology, Biopharmaceutics, Pharmacokinetics, Medicinal Chemistry, Molecular Drug Design, Pharmacognosy, Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Genomics and Proteomics, Pharmacogenomics, Biotechnology, Bioinformatics  and Chemoinformatics etc.

This article outlines a framework for the analysis of economic integration and its relation to the asymmetries of economic and social development. Consciously breaking with state-centric forms of social science, it argues for a research agenda that is more adequate to the exigencies and consequences of globalization than has traditionally been the case in 'development studies'. Drawing on earlier attempts to analyse the cross-border activities of rms, their spatial con gurations and developmental consequences, the article moves beyond these by proposing the framework of the 'global production network' (GPN). It explores the conceptual elements involved in this framework in some detail and then turns to sketch a stylized example of a GPN. The article concludes with a brief indication of the bene ts that could be delivered by research informed by GPN analysis.