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Background The increase in the adoption of electronic health records ( EHR) has contributed to physicians and nurses experiencing information overload. To address the problem of information overload, an assessment of the information needs of physicians and nurses will assist in understanding what they view as useful information to make patient care more efficient. Objective To analyse studies that assessed the information needs and information-seeking behaviour of physicians and nurses in a primary care setting to develop a better understanding of what information to present to physicians when they making clinical decisions. Method A literature review of studies was conducted with a comprehensive search in PubMed, cinahl, scopus, as well as examination of references from relevant papers and hand-searched articles to identify articles applicable to this review. Results Of the papers reviewed the most common information needs found among physicians and nurses were related to diagnoses, drug(s) and treatment/therapy. Colleagues remain a preferred information source among physicians and nurses; however, a rise in Internet usage is apparent. Conclusion Physicians and nurses need access to the Internet and job-specific resources to find practitioner-oriented information. In addition, effective usage of resources is important for improving patient care. [ABSTRACT FROM AUTHOR]

A novel method for determination of andrographolide using flow-injection chemiluminescence (FI-CL) analysis is described in this paper. The chemiluminescence intensity of the solution was enhanced proportionally while the concentration of andrographolide increased. Under the selected experimental conditions, the calibration curve of andrographolide was linear within the range of 0.2 to 35.0 µg mL−1 with a linear equation of ΔI = 23.391x (µg mL−1) + 34.191, R2 = 0.9965. The detection limit (3σ) was 7.42 × 10−2 µg mL−1. At the case of continuous determination of andrographolide, the relative standard deviation (RSD, n = 11) was less than 1.82%. The method has been successfully applied to the determination of andrographis tablets with satisfactory results. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Ang et al papers. To view these articles, visit https://doi.org/10.1111/apt.17070 and https://doi.org/10.1111/apt.17142 [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Ang et al papers. To view these articles, visit https://doi.org/10.1111/apt.17070 and https://doi.org/10.1111/apt.17167 [ABSTRACT FROM AUTHOR]

ABSTRACT Aims This paper reviews the world anthropology of drugs and alcohol use literature, identifying key issues addressed by anthropologists, methods and theoretical models in use, trends in focus over time and future directions. Methods Papers and books that comprise the literature were identified through computer search using the keywords: ethnography of drug use (and variants, e.g. drug ethnography, qualitative approaches in drug research), ethnography of drinking, anthropology and drug use, and anthropology and drinking. Search engines included Google Scholar, EBSCOHost, AnthroSource and PubMed. Identified sources were read and integrated into the review. Results and Conclusions The literature search identified a rich and growing literature on the anthropology of drinking and drug use. The research and published literature on the anthropology of drug use has grown and diversified since the 1970s, found acceptance in the wider multi-disciplinary domain of alcohol and drug studies and developed beyond the socio-cultural model to include life-style, critical medical anthropology and experiential explanatory models. Anthropological research has helped to shape the field of addiction science, e.g. ethnographic studies show that the lived worlds and self-identities of drug users have cultural order and socially constructed purpose and meaning, and experiential research shows that some addictions or aspects of addictions can be affirmative, creative and sustainable, at least at the individual level. The human immunodeficiency virus/acquired immune deficiency syndrome pandemic has significantly increased anthropological research on drug-related issues world-wide. [ABSTRACT FROM AUTHOR]

Malhi GS, Bargh DM, McIntyre R, Gitlin M, Frye MA, Bauer M, Berk M. Balanced efficacy, safety, and tolerability recommendations for the clinical management of bipolar disorder. Bipolar Disord 2012: 14 (Suppl. 2): 1-21. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objective: To provide practical and clinically meaningful treatment recommendations that amalgamate clinical experience and research findings for each phase of bipolar disorder. Methods: A comprehensive search of the literature was undertaken using electronic database search engines (Medline, PubMed, Cochrane reviews) using key words (e.g., bipolar depression, mania, treatment). All relevant randomised controlled trials were examined, along with review papers, meta-analyses, and book chapters known to the authors. In addition, the recommendations from accompanying papers in this supplement have been distilled and captured in the form of summary boxes. The findings, in conjunction with the clinical experience of international researchers and clinicians who are practiced in treating mood disorders, formed the basis of the treatment recommendations within this paper. Results: Balancing clinical experience with evidence informed and lead to the development of practical clinical recommendations that emphasise the importance of safety and tolerability alongside efficacy in the clinical management of bipolar disorder. Conclusions: The current paper summarises the treatment recommendations relating to each phase of bipolar disorder while providing additional, evidence-based, practical insights. Medication-related side effects and monitoring strategies highlight the importance of safety and tolerability considerations, which, along with efficacy information, should be given equal merit. [ABSTRACT FROM AUTHOR]

Molybdenum cofactor catabolism unravels the physiological role of the drug metabolizing enzyme thiopurine S-methyltransferase. Many drugs are inactivated by enzymes. Thus, patients who are intermediate, and, in particular, poor drug metabolizers can have higher concentrations of active drug metabolites, increasing the risk for concentration-dependent adverse events. [Extracted from the article]

The interaction between murine double minute (MDM2) and p53 is a major target in anticancer drug design. Several potent compound series, including the nutlins and spirooxindoles, have previously been established as high-affinity antagonists of MDM2. In this paper, we describe the interaction of isoindolinone inhibitors with MDM2, as characterized by nuclear magnetic resonance spectroscopy. Isoindolinone inhibitors bind specifically to the MDM2 p53 binding site and exploit all sub-pockets used by p53, nutlins and spirooxindoles. Furthermore, isoindolinones bind with low micromolar to high nanomolar affinities, with the best compound approaching the potency of nutlin-3. The interaction between MDM2 and p53 is a major target in anti-cancer drug design. In this paper, we describe the interaction of isoindolinone inhibitors with MDM2, as characterised by NMR spectroscopy. Isoindolinone inhibitors bind specifically to the MDM2 p53 binding-site and exploit the same sub-pockets used by p53, as well as nutlin and spirooxindole inhibitors. [ABSTRACT FROM AUTHOR]

The article presents abstracts related to alcohol and drugs, which include drug-related death in recently released prisoners, the relationship between childhood trauma, mental illness, drug and alcohol use, and care for young people with substance use along with depression.

The objective of this study was to determine the level of workplace contamination with platinum-containing cytostatic drugs in a veterinary hospital. A closed chemotherapy application system was then added to the safety regimen. Workplace contamination was measured over a nine-month period by taking wipe samples from seven locations. Before the introduction of the closed system, amounts of platinum were detected at four locations. After the introduction of the closed system, there was a temporary increase in contamination at two locations, followed by an overall reduction in contamination by the end of the study period. [ABSTRACT FROM AUTHOR]

Our understanding of the causes of alcohol and other drug (AOD) use and harms has expanded in the past 20 years. In particular, aetiological theories have become substantially more complex, incorporating research on human development and social determinants of health. In this paper, factors that present challenges to the AOD sector translating this research into policy are considered. These include a) the complexity of social determinants, b) community attitudes, and c) governance and funding structures. It is concluded that the challenges are substantial, but not insurmountable. Research on social determinants of AOD use and harms is building an evidence base to inform policy. However, leadership is needed to transform funding priorities from single-issue, short-term projects focusing on individual-level changes to broader, longer-term approaches. [ABSTRACT FROM AUTHOR]

The article presents abstracts on topics related to drugs and alcohol which include the effects of drug and alcohol use on prescribed mental health drugs, research on rural and remote primary health care workers perceptions of providing drug and alcohol interventions, and a case study on the misuse of alcohol in the custody cells of Great Britain.

Objective Delirium is a very common and serious disorder with high morbidity and mortality. Despite symptomatic treatment the outcome can be poor for some especially when no underlying cause is identified. As a result, various strategies for delirium prevention have been assessed. Pharmacological agents such as antipsychotics, acetylcholinesterase inhibitors, sleep–wake cycle regulators, anti-inflammatories and others have been advocated for a potential role in delirium prevention. The aim of this paper is to review the available evidence for their use in the prevention of delirium. Methods An electronic search was carried out using Medline, EMBASE and Cochrane for randomised controlled trials (RCTs) and other studies. The words delirium, prevention, intervention, pharmacological, prophylactic, antipsychotics, acetylcholinesterase inhibitors, sleep and anti-inflammatories were used. References from selected papers were also searched. Results No multi-centre RCT has been identified. Few trials and other studies have been published so far assessing the prophylactic role of antipsychotics, acetylcholinesterase inhibitors, hypnotics, melatonin, and gabapentin. As these studies tested different drugs, regimes and protocols in diverse populations no meaningful comparison can be made. Conclusion To date there is conflicting and inconsistent data regarding the efficacy of pharmacological treatment for delirium prevention. Positive reports in few of the studies justify further assessment of the potential for some pharmacological agents in the prevention of delirium. Well designed and appropriately powered RCTs are now needed. However, based on available evidence so far, no recommendation can be made to justify the routine clinical prophylactic use of any pharmacological agent in the prevention of delirium. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Using longitudinal survey data collected over a period of two years, this paper examines the impact of antiretroviral (ARV) treatment on the time allocated to various household tasks by treated HIV-positive patients and their household members. We study outcomes such as time devoted to housework, firewood and water collection, as well as care-giving and care-seeking. As treatment improves the health and productivity of patients, we find that female patients in particular are able to increase the amount of time they devote to water and firewood collection. This increased productivity of patients coupled with large decreases in the amount of time they spend seeking medical care leads to a reduced burden on children and other household members. We find evidence that boys and girls in treated patients’ households devote less time to housework and other chores. These results suggest that the provision of ARV treatment generates a wide variety of benefits to households in resource-poor settings. [ABSTRACT FROM AUTHOR]

The article reports on the production of palm oil (PO) in Indonesia. In 2007, the total production was 17.0 million tons of crude palm oil (CPO) and 1.9 million tons of crude palm kernel oil (CPKO) in which more than 70 percent of the PO was exported and 87 percent of the domestic consumption was for food. Biomass by-products were also generated from the production of CPO and CPKO in which according to some findings can be potentially diversified into sources of energy, animal feed, chemicals, paper pulp, medicine and food ingredients. In January 2006, a presidential instruction was issued by the president of Indonesia ordering various ministries to speed up the production and use of biofuel as an alternative fuel.

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Aims Regression to the mean (RTM) refers to the tendency for a group of cases that differ from the population mean to move (regress) towards the mean, on average, when re-assessed, if scores at the two points are less than perfectly correlated. This paper considers factors that affect the magnitude of RTM and how RTM may impact findings from primary studies and reviews of substance use disorder (SUD) treatment. Design and methods The paper is guided largely by A Primer on Regression Artifacts by Campbell and Kenny. It reviews potential RTM effects in three areas of SUD treatment research. One is the extent to which within-group improvement in comparative treatment trials, including ‘placebo effects’, is a function of RTM. The second is the vulnerability of treatment evaluations employing non-equivalent control group designs to RTM and biased estimates of treatment effects when matching, or statistical equating is used to adjust for pre-existing group differences. The final issue is the impact of RTM in syntheses of research findings on SUD treatments. In particular, the tendency for later studies of a particular intervention to have smaller treatment effect sizes relative to earlier studies is considered as an RTM phenomenon. Findings RTM is a pervasive, but often unrecognized phenomenon that can bias findings in SUD treatment studies and in systematic reviews of that research. Conclusion SUD treatment researchers should be aware of RTM, take any available steps to reduce it, and try to diagnose whether it is still affecting research findings. [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Sehgal et al and Sehgal and Narula papers. To view these articles, visit https://doi.org/10.1111/apt.14688 and https://doi.org/10.1111/apt.15748. [ABSTRACT FROM AUTHOR]

Noncompliance or nonadherence with medical regimens represents a major challenge to the practice of medicine including the treatment of headache. Indeed, medication use patterns are particularly relevant to headache because of the potential for headache therapies to induce medication-overuse headache. Previous research has demonstrated that adherence to long-term medication therapy for various chronic illnesses averages only about 50%. The rate of adherence among headache patients has been found to be similarly poor. Misuse or overuse of symptomatic medication has been demonstrated to contribute to treatment failure, and one-fourth to one-half of patients are noncompliant with prophylactic headache medications and at least 40% nonadherent with appointment-keeping. Adherence declines with more frequent and complex dosing regimens, side effects, and costs, and is subject to a wide range of psychosocial influences. Subjective reports of adherence are likely not only to overestimate but also to be discordant with more objective measurements. As the first of 2 articles, this paper describes the problem of noncompliance in medical practice and reviews literature addressing compliance specific to headache management. A companion paper (Behavioral Facilitation of Medical Treatment for Headache—Part II: Theoretical Models and Behavioral Strategies for Improving Adherence) summarizes social learning models proposed to characterize the multiple determinants of adherence and guide behavioral adherence-enhancing interventions, and then presents cognitive and behavioral strategies that may facilitate treatment adherence with headache patients. [ABSTRACT FROM AUTHOR]

This paper reviews the literature on the nature of innovation in the biopharmaceutical sector in the context of current approaches to the funding and provision of medicines. From this starting point the paper explores the relationship between market diffusion models, cost containment and equity of access across national populations. [ABSTRACT FROM AUTHOR]

The pharmaceutical sector is unusual amongst global regulated industries inasmuch as it is usually forbidden from advertising to the users of its products. This paper reports on research updating my 2003 review 2 of the evidence and arguments for and against the direct-to-consumer advertising (DTCA) of prescription drugs. It not only covers the two countries where significant DTCA is permitted (USA and New Zealand), but also the administrations in which there is active discussion of possibilities to ease or amend some of the current restrictions (Europe, Australia and Canada). [ABSTRACT FROM AUTHOR]

Background Little is known about the characteristics of people with intellectual disabilities (IDs) who misuse substances and how such problems impinge upon their well-being. The aim of this paper is to describe how alcohol and drugs affect the health of people with IDs. Methods A questionnaire was forwarded to all the community ID teams and mainstream addiction teams across Northern Ireland: 67 substance users with IDs and substantial substance-related problems were identified. Results Alcohol was found to be the main substance to be misused, with one-fifth of the substance users also found to be using a combination of illicit drugs and/or prescribed medication. Nearly three-quarters of the sample were found to be hazardously using alcohol for more than 5 years. Being male and young, having a borderline/mild ID, living independently and having a mental health problem were found to be risk factors for developing a ‘substance related problem’. Various problematic behaviours were identified, including aggression, erratic mood changes, sexual exploitation, difficulties in maintaining relationships and loss of daily routine. Conclusions The findings of this study suggest that greater emphasis needs to be placed upon the early identification of this hidden population by primary and secondary healthcare personnel, and also ID personnel. Such early identification may also diminish the long-established patterns of use and associated related-behaviours that have been reported within this paper. [ABSTRACT FROM AUTHOR]

Objective: In 2003 the New South Wales (NSW) Centre for Rural and Remote Mental Health (CRRMH) conducted an analysis of co-morbid drug and alcohol (D&A) and mental health issues for service providers and consumers in a rural NSW Area Health Service. This paper will discuss concerns raised by rural service providers and consumers regarding the care of people with co-morbid D&A and mental health disorders. Design: Current literature on co-morbidity was reviewed, and local area clinical data were examined to estimate the prevalence of D&A disorders within the mental health service. Focus groups were held with service providers and consumer support groups regarding strengths and gaps in service provision. Setting: A rural Area Health Service in NSW. Participants: Rural health and welfare service providers, consumers with co-morbid D&A and mental health disorders. Results: Data for the rural area showed that 43% of inpatient and 20% of ambulatory mental health admissions had problem drinking or drug-taking. Information gathered from the focus groups indicated a reasonable level of awareness of co-morbidity, and change underway to better meet client needs; however, the results indicated a lack of formalised care coordination, unclear treatment pathways, and a lack of specialist care and resources. Discussion: Significant gaps in the provision of appropriate care for people with co-morbid D&A and mental health disorders were identified. Allocation of service responsibly for these clients was unclear. It is recommended that D&A, mental health and primary care services collaborate to address the needs of clients so that a coordinated and systematic approach to co-morbid care can be provided. [ABSTRACT FROM AUTHOR]

For the treatment of secondary hyperparathyroidism (HPTH-II) in dialysis patients and hypercalcemia in patients with parathyroid carcinoma. Calcimimetics are a new class of drugs approved in the European Community and the United States by the Food and Drug Administration that were designed to suppress parathyroid hormone (PTH) levels with a simultaneous reduction in serum calcium and phosphorus levels, and calcium phosphorus product (Ca × P). Hypocalcemia is a frequent finding during the correction phase of the HPTH-II with calcimimetics. By contrast, the appearance of a hypercalcemia has yet to be described. In this paper, we report a case of severe hypercalcemia of immobilization in a 40-year-old hemodialyzed woman treated by cinacalcet HCl for a severe HPTH-II (PTH>1,000 pg/mL). A kidney transplantation recipient 1983 to 1995, she was diagnosed with Charcot-Marie Tooth disease in 1991. She had multiple orthopedic interventions for kidney-related osteoarticular problems probably favored by the kidney graft and the immunosuppressive treatment. While she was receiving the maximum dose of 180 mg/day of cinacalcet HCl and PTH at 443 pg/mL, she needed to be hospitalized for a right hip prothesis. Two weeks after the intervention she developed a symptomatic hypercalcemia of 3.57 mmol/L which was resistant to several measures including lowering the calcium concentration in the dialysate, withdrawing all vitamin D and calcium supplementation and the administration of calcitonin. Her serum calcium level was finally stabilized in the 2.37–2.95 mmol/L by administration of a single intravenous dose of pamidronate. This observation illustrates that the pharmacological activation of the parathyroid CaR and other putative CaR on bone cells by calcimimetics did not protect against the occurrence of hypercalcemia of immobilization favored by a severe HPTH-II in a hemodialysis patient. [ABSTRACT FROM AUTHOR]

Medicines that are vital for the saving and preserving of life in conditions of public health emergency or endemic serious disease are known as essential medicines. In many developing world settings such medicines may be unavailable, or unaffordably expensive for the majority of those in need of them. Furthermore, for many serious diseases (such as HIV/AIDS and tuberculosis) these essential medicines are protected by patents that permit the patent-holder to operate a monopoly on their manufacture and supply, and to price these medicines well above marginal cost. Recent international legal doctrine has placed great stress on the need to globalise intellectual property rights protections, and on the rights of intellectual property rights holders to have their property rights enforced. Although international intellectual property rights law does permit compulsory licensing of protected inventions in the interests of public health, the use of this right by sovereign states has proved highly controversial. In this paper I give an argument in support of states’ sovereign right to expropriate private intellectual property in conditions of public health emergency. This argument turns on a social contract argument for the legitimacy of states. The argument shows, further, that under some circumstances states are not merely permitted compulsory to license inventions, but are actually obliged to do so, on pain of failure of their legitimacy as sovereign states. The argument draws freely on a loose interpretation of Thomas Hobbes's arguments in hisLeviathan, and on an analogy between his state of War and the situation of public health disasters. [ABSTRACT FROM AUTHOR]

The research literature on the social determinants of health focuses on socio-economic inequalities and disadvantage. ‘Culture’ is usually seen as part of this picture of difference—associated with minority status, ethnicity or race; but we also need to address the role of dominant or mainstream cultures in health and well-being. Cultures provide the underlying assumptions of an entire way of life, allowing us to make sense of the world and our lives. This paper argues that aspects of modern western culture are a potent and under-estimated social factor behind drug use and abuse. It draws on a wide range of evidence from different disciplines to suggest that Western culture's emphasis on the material and the individual, in particular, amounts to ‘cultural fraud’: the promotion of images and ideals of life that do not meet human needs or reflect social realities. This failure is conducive to diminished well-being, including addiction to drug use or other behaviours. [Eckersley RM. ‘Cultural fraud’: the role of culture in drug abuse. Drug Alcohol Rev 2005;24:157 – 163] [ABSTRACT FROM AUTHOR]

This paper considers the current performance and future prospects of the UK biotech industry, particularly the biomedical sector. The central argument is that the performance of the UK biotech industry cannot be understood in isolation from the European system of regulation and, increasingly, the international regulatory environment, and from what is happening elsewhere in the regulation of science– particularly in the U.S. To develop this argument, it adopts as its conceptual framework Kim and von Tunzelmann's network alignment approach following Radosevic. It explores the link between regulatory policies and the biotechnology production system– networks between academic research, biotech firms, and large pharmaceutical companies. [ABSTRACT FROM AUTHOR]

An important factor that has thus far limited the effectiveness of pharmacotherapies for patients with alcohol and opioid dependence is poor adherence to medication regimens. This paper presents a review of issues related to medication adherence in patients with these substance use disorders.A literature review was conducted of English language publications relating to medication adherence among patients with alcohol or opioid dependence.The paper places the topic in the context of adherence difficulties among patients with a variety of chronic medical and psychiatric illnesses. Difficulties measuring adherence are discussed, and strategies to improve medication adherence are reviewed. These include specific interventions that prescribing clinicians can implement in their individual meetings with patients; the use of external reinforcers, such as positive and negative contingencies, and involvement of family members or significant others; and specific prescribing and dosing practices that may improve adherence.As the use of pharmacotherapy for substance-dependent patients increases, rigorous and innovative approaches to encourage medication adherence should be sought. [ABSTRACT FROM AUTHOR]

This paper deals with the use of 180 animal species as medicinal resources in the state of Bahia, Northeastern Brazil. Data, which come from field works carried out in different indigenous, traditional, rural and urban communities within Bahia State, were gathered through the compilation of information available in scientific articles, monographs, theses, reports and presented papers. The animal-based folk medicines come from millipedes (0.5%), annelids (1.0%), amphibians (1.0%), arachnids (1.0%), echinoderms (1.5%), crustaceans (4.0%), molluscs (6.0%), reptiles (12.0%), birds (13.0%), fishes (17.0%), mammals (20.0%) and insects (23.0%). These bioresources provide about 300 raw materials, which are turned into medicines and prescribed to treat a wide range of locally diagnosed ailments. The result shows how important this ethnozoological phenomenon is, and indicates that traditional knowledge on zootherapy is to be seriously studied in order to lead to the discovery of new sources of drugs. Copyright © 2004 John Wiley & Sons, Ltd and ERP Environment. [ABSTRACT FROM AUTHOR]

More than a third of the world's population has no access to essential drugs. More than half of this group of people live in the poorest regions of Africa and Asia. Several factors determine the accessibility of drugs in developing countries. Hardly any medicines for tropical diseases are being developed, but even existing drugs are often not available to the patients who need them. One of the important determinants of access to drugs is the working of the patent system. This paper first maps out some facts about the global patent regime that has emerged as a consequence of the conclusion of the WTO-TRIPs Agreement in 1994. Attempts to construct a moral justification of the patent system have been based on three grounds: natural rights, distributive justice, and utilitarian arguments. This paper examines to what extent and on which grounds drug patents can be justified. The final section looks at the so-called ‘Doha Declaration on the TRIPs Agreement and Public Health’, which was adopted by the WTO Ministerial Conference two years ago, recognising the primacy of public health over the interests of patent proprietors. [ABSTRACT FROM AUTHOR]

This paper critically reviews the major drug types that are currently used in the management of acute cardiogenic pulmonary oedema. As decompensated heart failure becomes an increasingly common problem in emergency departments in the developed world, optimization of emergency drug therapy for these critically ill patients is essential. The evidence base for ‘routine therapy’ in the ED is considered. The review also briefly considers emerging pharmacological therapies that may have an impact on future management of cardiogenic pulmonary oedema. [ABSTRACT FROM AUTHOR]

Glutathione S‐transferases (EC 2.5.1.18, GSTs), consisting of at least seven subfamilies, such as alpha, kappa, mu, pi, theta, zeta, and omega, are the family of cytosolic proteins with many known functions and also are abundant in cells. Moreover, they play significant roles in influencing the efficacy and bioavailability of pharmaceutical agents in humans. It is also known that multiple types of cancer tissue frequently have high levels of GSTs compared to the corresponding healthy tissue. Herein, firstly, the GST was purified from human erythrocytes by rapid and straightforward chromatographic techniques. Subsequently, the active infection medications, the antimycotics (amphotericin B, anidulafungin, and caspofungin), antibacterials (daptomycin, ertapenem, and tigecycline), and antiviral (ganciclovir) were assessed for their inhibitory actions versus GST. All drugs demonstrated micromolar levels of potent inhibitory activity towards GST. Antifungal drugs had KI constants ranging between 20.60±0.05 μM and 50.43±0.12 μM, whilst antibacterial drugs exhibited KIs in the range of 20.92±0.09–114.80±0.41 μM. Daptomycin and ertapenem exhibited competitive inhibition, while other drugs in noncompetitive inhibition. Moreover, amphotericin B exhibited the most potent inhibitory activity (KI=20.60±0.05 μM), and in contrast, antiviral drug ganciclovir had the highest inhibition constant (KI=463.10±1.28 μM). Studying both in‐vitro inhibitory activity and molecular docking interactions in silico activities of these infection medications in complex with the GST, an enzyme biologically important, demonstrates was caused significant associations between these drugs and GST were detected. The results here might provide structural guidance to design more potent GST inhibitors. [ABSTRACT FROM AUTHOR]

A new generative model, in which the Variational Autoencoder network is combined with the Transformer architecture, is developed. The proposed model, the Variational Autoencoding Transformer (VAT), is applied to the task of generating molecules, showing that, with proper training, the VAT model can not only produce similar molecules to input ones with high accuracy but also generate new molecules from a predefined prior almost perfectly. A desirable aspect of our VAT is that no heuristic setting is necessary for optimal performance, which suggests that the model can readily be available to a variety of datasets. As practical directions toward materials/drug discovery, two strategies: a fine‐tuning method for directed molecular generation and a method of mixing molecules in the latent space, are demonstrated. [ABSTRACT FROM AUTHOR]

The authors from Ferrara show that a NSAID has a role in patients who have oligoasthenospermia associated with a left-sided varicocele, although not in every case. Peyronie's disease is discussed in two papers; in the first of these, the authors make the case for histopathological diagnosis by drawing the reader's attention to the possible presence of penile epithelioid sarcoma. In the second paper, attention is drawn to the possibility of using a combination of vitamin E and colchicine in the early stages of the condition. Objective To ascertain whether a nonsteroidal anti-inflammatory drug (cinnoxicam) or surgical varicocelectomy are suitable therapies for oligoasthenospermia associated with varicocele. Patients and methods Patients who were oligoasthenospermic and had a varicocele were blindly randomized into three groups and the varicocele graded using echo-colour Doppler ultrasonography. In group 1, seven men had grade V, four grade IV and 30 grade III varicoceles; in group 2 eight had grade V, 10 grade IV and 43 grade III; in group 3 six had grade V, eight grade IV and 40 grade III. Group 1 underwent surgery, group 2 received cinnoxicam (one 30 mg suppository every 4 days for 12 months) and group 3 received a placebo (one glycerine suppository every 4 days for 12 months). Sperm was analysed at intervals to follow the response in the three groups, and any side-effects considered. Results Surgery significantly increased sperm values in men with grade III–V varicocele within 4 months, the highest values being obtained at 8 and 12 months. Cinnoxicam significantly improved sperm quality after 2 months in men with grade III varicocele, but the results were best at 4 months and stable at 12 months; stopping therapy caused a decline to the baseline values. Cinnoxicam did not change the sperm quality of men with grade IV or V varicocele. The placebo was inactive, and there were no side-effects of active treatment. Conclusions Cinnoxicam is a safe and... [ABSTRACT FROM AUTHOR]

Over the past decade, the prediction of drug-drug interactions from in vitro studies has become a rapidly expanding field of research. Numerous papers and excellent review articles (Bertz & Granneman 1997; Ito et al. 1998a & b: Lin 2000; Bachmann & Ghosh 2001; Ekins & Wrighton 2001; Weaver 2001) have been published in this area. Yet like any new and fast-growing subject, this one has been developing with some confusion and without any real. efficient organisation. Depending on the drug tested, the models and extrapolation parameters used, etc., results and conclusions may vary widely from study to study (yon Moltke et al. 1998; Weaver 2001). Several authors have called for validation of these procedures (Rodrigues et al. 2001: Kummar & Surapaneni 2001; Pelkonen et al. 2001a & b: Kremers 2002), and regulatory authorities intend to require better traceability and reliability (FDA & EMEA guidelines). A systematic and reliable approach is needed also to allow such protocols to be incorporated into early screening for potential drugs and new chemical entities. There is certainly a great need to standardise these studies and to verify their conclusions, but is true validation possible in this field? The main purpose of the present paper is to discuss this issue and to examine what is possible and what is needed to improve the quality of predictions made from in vitro experiments. [ABSTRACT FROM AUTHOR]

This paper explores young homeless drug users' ways of coping with harassment. Discussions of coping and harassment are based on the cognitive appraisal model. Coping accounts were essentially problem-focused and action-oriented. Results indicate the need for more policy developments to prevent homelessness and for specific interventions around homelessness and harassment. Copyright © 2000 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Everhov et al paper. To view this article, visit https://doi.org/10.1111/apt.17675 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Roblin et al papers. To view these articles, visit https://doi.org/10.1111/apt.16852 and https://doi.org/10.1111/apt.16893 [ABSTRACT FROM AUTHOR]

ABSTRACT Over the last 20 years, there has been increasing interest in the occurrence, fate, effects, and risk of pharmaceuticals in the natural environment. However, we still have only limited or no data on ecotoxicological risks of many of the active pharmaceutical ingredients (APIs) currently in use. This is partly due to the fact that the environmental assessment of an API is an expensive, time-consuming, and complicated process. Prioritization methodologies, which aim to identify APIs of most concern in a particular situation, could therefore be invaluable in focusing experimental work on APIs that really matter. The majority of approaches for prioritizing APIs require annual pharmaceutical usage data. These methods cannot therefore be applied to countries, such as Kazakhstan, that have very limited data on API usage. The present paper therefore offers an approach for prioritizing APIs in surface waters in information-poor regions such as Kazakhstan. Initially data were collected on the number of products and active ingredients for different therapeutic classes in use in Kazakhstan and on the typical doses. These data were then used alongside simple exposure modeling approaches to estimate exposure indices for active ingredients (about 240 APIs) in surface waters in the country. Ecotoxicological effects data were obtained from the literature or predicted. Risk quotients were then calculated for each pharmaceutical based on the exposure and the substances were ranked in order of risk quotient. Highest exposure indices were obtained for benzylpenicillin, metronidazole, sulbactam, ceftriaxone, and sulfamethoxazole. The highest risk was estimated for amoxicillin, clarithromycin, azithromycin, ketoconazole, and benzylpenicillin. In the future, the approach could be employed in other regions where usage information is limited. Integr Environ Assess Manag 2017;13:832-839. © 2017 SETAC [ABSTRACT FROM AUTHOR]

Care for homeless people in general and homeless substance abusers in particular has been well explored as a research topic (Fisher and Collins ; Seal ; Desjarlais ; Pleace and Quilgars ; Bevan ; Briggs ). Historically, academics have been interested in care in settings as diverse as families, hospitals, asylums, poorhouses, the criminal justice system and more recently what has been called the 'community'. In this paper, I want to look at two different dimensions of care in a particular social world of substance using homeless people in London where the people are not always the likely recipients but active providers of care. I understand care in Mol's and Winance's sense as a process of tinkering (Mol ; Winance ). The most dominant form of care is produced by many homeless substance users themselves: they care for drugs. The relationship to 'their' substance is often highly intimate and characterized by physical and emotional closeness, commitment and accord. Drugs develop person-like characteristics and 'demand' care, promising intimacy and a sense of self. Dominated by the need to care for drugs in this way, other (human-to-human) relationships can become increasingly fragmented and the social net can become hollowed out, instrumental and even violent. Geographies split apart with different logics between public and intimate; sub-cities emerge. But at the same time as the drug develops into the object of care demanding attention, the responsibility to care can develop a shared dimension. Friendships and love relationships grow based on intimate care which still centre on drugs but go far beyond it in their carefulness and interconnection. This is where geographies merge, connections are made and futures are built. [ABSTRACT FROM AUTHOR]

Patient-centered drug development (PCDD) is a shift in the way that drugs are developed, systematically incorporating patient participation in all stages of medicines development. The more the research sector understands the needs and values of patients, the more effective and efficient it can be in bringing meaningful drugs and evidence to patients and providers. In this paper, we describe PCDD, provide examples of PCDD work across the phases of drug development, and discuss the challenges to making PCDD systematic. We describe how the developing Learning Health System will enable PCCD: we believe that the Learning Health System will address PCDD barriers by connecting stakeholders, enabling the more efficient flow of data, information, and evidence in the health ecosystem, and by providing governance for the connected ecosystem. [ABSTRACT FROM AUTHOR]

Background and aims Treatment for opioid use disorders (OUD) reduces the risk of mortality and infectious disease transmission; however, opportunities to quantify the potential economic benefits of associated decreases in drug-related crime are scarce. This paper aimed to estimate the costs of crime during and after periods of engagement in publicly funded treatment for OUD to compare total costs of crime during a hypothetical 6-month period following initiation of opioid agonist treatment (OAT) versus detoxification. Design Retrospective, administrative data-based cohort study with comprehensive information on drug treatment and criminal justice systems interactions. Setting Publicly funded drug treatment facilities in California, USA (2006-10). Participants A total of 31 659 individuals admitted for the first time to treatment for OUD, and who were linked with criminal justice and mortality data, were followed during a median 2.3 years. Median age at first treatment admission was 32, 35.8% were women and 37.1% primarily used prescription opioids. Measurements Daily costs of crime (US$2014) were calculated from a societal perspective and were composed of the costs of policing, court, corrections and criminal victimization. We estimated the average marginal effect of treatment engagement in OAT or detoxification adjusting for potential fixed and time-varying confounders, including drug use and criminal justice system involvement prior to treatment initiation. Findings Daily costs of crime during treatment compared with after treatment were $126 lower for OAT [95% confidence interval (CI) = $116, $136] and $144 lower for detoxification (95% CI = $135, $154). Summing the costs of crime during and after treatment over a hypothetical 6-month period using the observed median durations of OAT (161 days) and detoxification (19 days), we estimated that enrolling an individual in OAT as opposed to detoxification would save $17 550 ($16 840, $18 383). Conclusions In publicly funded drug treatment facilities in California, USA, engagement in treatment for opioid use disorders is associated with lower costs of crime in the 6 months following initiation of treatment, and the economic benefits were far greater for individuals receiving time-unlimited treatment. [ABSTRACT FROM AUTHOR]

Extrapolating from information available on one patient group to support conclusions about another is common in clinical research. For example, the findings of clinical trials, often conducted in highly selective patient cohorts, are routinely extrapolated to wider populations by policy makers. Meanwhile, the results of adult trials may be used to support conclusions about the effects of a medicine in children. For example, if the effective concentration of a drug can be assumed to be similar in adults and children, an appropriate paediatric dosing rule may be found by 'bridging', that is, by matching the adult effective concentration. However, this strategy may result in children receiving an ineffective or hazardous dose if, in fact, effective concentrations differ between adults and children. When there is uncertainty about the equality of effective concentrations, some pharmacokinetic-pharmacodynamic data may be needed in children to verify that differences are small. In this paper, we derive optimal group sequential tests that can be used to verify this assumption efficiently. Asymmetric inner wedge tests are constructed that permit early stopping to accept or reject an assumption of similar effective drug concentrations in adults and children. Asymmetry arises because the consequences of under- and over-dosing may differ. We show how confidence intervals can be obtained on termination of these tests and illustrate the small sample operating characteristics of designs using simulation. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aims This paper describes the major findings and public health implications of a cross-site evaluation of a national Screening, Brief Intervention and Referral to Treatment (SBIRT) demonstration program funded by the US Substance Abuse and Mental Health Services Administration (SAMHSA). Methods Eleven multi-site programs in two cohorts of SAMHSA grant recipients were each funded for 5 years to promote the adoption and sustained implementation of SBIRT. The SBIRT cross-site evaluation used a multi-method evaluation design to provide comprehensive information on the processes, outcomes and costs of SBIRT as implemented in a variety of medical and community settings. Findings SBIRT programs in the two evaluated SAMHSA cohorts screened more than 1 million patients/clients. SBIRT implementation was facilitated by committed leadership and the use of substance use specialists, rather than medical generalists, to deliver services. Although the quasi-experimental nature of the outcome evaluation does not permit causal inferences, pre-post differences were clinically meaningful and statistically significant for almost every measure of substance use. Greater intervention intensity was associated with larger decreases in substance use. Both brief intervention and brief treatment were associated with positive outcomes, but brief intervention was more cost-effective for most substances. Sixty-nine (67%) of the original performance sites adapted and redesigned SBIRT service delivery after initial grant funding ended. Four factors influenced SBIRT sustainability: presence of program champions, availability of funding, systemic change and effective management of SBIRT provider challenges. Conclusions The US Substance Abuse and Mental Health Services Administration's Screening, Brief Intervention and Referral to Treatment (SBIRT) demonstration program was adapted successfully to the needs of early identification efforts for hazardous use of alcohol and illicit drugs. SBIRT is an innovative way to integrate the management of substance use disorders into primary care and general medicine. Screening, Brief Intervention and Referral to Treatment implementation was associated with improvements in treatment system equity, efficiency and economy. [ABSTRACT FROM AUTHOR]

Over the past seven decades, randomised controlled trials (RCTs) have revolutionised clinical research and achieved a gold standard status. However, extending their use to evaluate complex interventions is problematic. In this paper we will demonstrate that complex intervention RCTs violate the necessary premises that govern the RCTs logic and underpin their rigour. The lack of blinding, heterogeneity of participants, as well as poor treatment standardisation and difficulty of controlling for confounders, which characterise complex intervention RCTs, can potentially be profoundly detrimental to their integrity. Proponents of this approach argue that matching 'real world' circumstances, while maintaining the randomised design, enhances external validity. We counter this argument by pointing out that an inverted U relation exists between internal and external validity, and thus relaxing the experimental conditions beyond a certain threshold can potentially paradoxically render the RCT externally invalid, i.e. its results cannot be used anywhere. We shall illustrate the inappropriate use of RCTs to evaluate community treatment orders and propose an alternative epistemic model that is based on mechanistic reasoning and Cartwright's capacity concept. [ABSTRACT FROM AUTHOR]

The authors examine the human immunodeficiency virus (HIV) eradication in this study using a mathematical model and analyse the occurrence of virus eradication during the early stage of infection. To this end they use a deterministic HIV‐infection model, modify it to describe the pharmacological dynamics of antiretroviral HIV drugs, and consider the clinical experimental results of preexposure prophylaxis HIV treatment. They also use numerical simulation to model the experimental scenario, thereby supporting the clinical results with a model‐based explanation. The study results indicate that the protocol employed in the experiment can eradicate HIV in infected patients at the early stage of the infection. [ABSTRACT FROM AUTHOR]

A mathematical model to simulate drug delivery from a viscoelastic erodible matrix is presented in this paper. The drug is initially distributed in the matrix that is in contact with water. The entrance of water in the material changes the molecular weight, and bulk erosion can be developed depending on how fast this entrance is and how fast degradation occurs. The viscoelastic properties of the matrix also change in the presence of water as the molecular weight changes. The model is represented by a system of quasi-linear partial differential equations that take into account different phenomena: the uptake of water, the decreasing of the molecular weight, the viscoelastic behavior, the dissolution of the solid drug, and the delivery of the dissolved drug. Numerical simulations illustrating the behavior of the model are included. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Wong and Coenen et al and Hooymans papers. To view these articles visit https://doi.org/10.1111/apt.13879 and https://doi.org/10.1111/apt.13955. [ABSTRACT FROM AUTHOR]

In this issue of Allergy, the review focuses on "old" but still controversial problem of whether immunotherapy (IT) is effective in asthma. On the basis of several controlled studies, the authors conclude that IT should be considered an effective treatment of allergic asthma. However, after the review was in press a paper was published which might discourage the use of IT in asthmatic children. In fact, these authors found on benefit in the group receiving IT in comparison with the group on appropriate medication only.