Matching Clients’ Needs With Drug Treatment Services

This paper reports results of a study that investigated whether matching drug treatment services with client needs improved outcomes for a sample of 171 clients who participated in community-based drug treatment programs. Clients were initially assessed on multiple problem areas (alcohol use, drug use, medical, psychological, family/social, legal, employment, housing) and on areas of special needs or stated preferences for services (e.g., transportation, child care, language). A 6-month follow-up interview reassessed clients’ problems/needs in all areas and collected information on the services received. The results showed that some services significantly improved client outcome for those who had expressed needs for such services. Notably, services meeting the need for vocational training, child care, transportation, and housing showed beneficial effects. A higher level of needs and services matching (defined either by the ratio of services received to services desired, or by the total level of met versus unmet needs in the eight problem areas) significantly predicted longer treatment retention.     

新药研发中的me-too, me-better, me-new

文中根据作者对我国新药研发的认识和理解,提出了新药研发过程中me-too,me-better和me-new类新药的概念,并对新药研发过程中的这3类创新活动之间的关系、新药研发的创新程度与经济效益的关系,以及目前我国新药研发的途径选择做了简要的论述。     

Analogue synthesis reveals decoupling of antibiofilm and β‐lactam potentiation activities of a lead 2‐aminoimidazole adjuvant against Mycobacterium smegmatis

Biofilm formation is one of the many mechanisms bacteria utilize to survive antibiotic treatment. It has been demonstrated that when Mycobacterium tuberculosis exists in a biofilm in vitro, it expresses phenotypic resistance to antimicrobial drugs. As the in vivo survival of M. tuberculosis following drug treatment is potentially linked to a biofilm‐like expression of drug tolerance, it is hypothesized that biofilm dispersion should increase antibiotic susceptibility and reduce the duration of the current antibiotic treatment regimen. Previously, we have identified a 2‐aminoimidazole (2‐AI) compound capable of dispersing and inhibiting M. tuberculosis and M. smegmatis biofilms in vitro. Additionally, this compound potentiated the activity of carbenicillin against M. tuberculosis and, to a lesser degree, M. smegmatis. Here, we describe a SAR study on this compound evaluating each derivative for biofilm dispersion and β‐lactam potentiation capabilities against M. smegmatis. This study identified a compound that improved upon the biofilm dispersion capabilities of the lead compound. Interestingly, a different compound was identified with an increased ability to potentiate a subset of β‐lactam antibiotics. These compounds indicate that biofilm dispersion and potentiation capabilities may not be associated.     

Deciphering the Resistance-Counteracting Functions of Ferroquine in Plasmodium falciparum-Infected Erythrocytes

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Metabolism and elimination of the catechol‐o‐methyltransferase inhibitor tolcapone in the horse

The metabolism of the masking agent tolcapone in the horse has been investigated. This substance was found to have undergone various chemical transformations that produced a large variety of phase I metabolites, as well as glucuronide and sulfate conjugation. Confirmation of the presence of tolcapone and the 3‐O‐methylated metabolite in the blood samples collected up to 240 minutes and in urine obtained up to 24 hours, was successfully conducted using both gas chromatography– and liquid chromatography–tandem mass spectrometry techniques. The 3‐O‐methyl tolcapone is the better marker to use in a screening method because, in comparison to tolcapone, we have found that this substance offers superior chromatographic performance that should potentially give a lower limit of detection.     

Searching for Dual Inhibitors of the MDM2‐p53 and MDMX‐p53 Protein–Protein Interaction by a Scaffold‐Hopping Approach

Two libraries of substituted benzimidazoles were designed using a ‘scaffold‐hopping’ approach based on reported MDM2‐p53 inhibitors. Substituents were chosen following library enumeration and docking into an MDM2 X‐ray structure. Benzimidazole libraries were prepared using an efficient solution‐phase approach and screened for inhibition of the MDM2‐p53 and MDMX‐p53 protein–protein interactions. Key examples showed inhibitory activity against both targets.     

Potential Association between Drug Shortages and High‐Cost Medications

Shortages and sudden price increases of certain drugs may both occur emergently, with little to no warning, and they can have a dramatic impact on patient care. Little data are available linking drug shortages and price increases. Many of the same characteristics that may make medications susceptible to shortages can also place them at risk for sudden price increases. These characteristics include unapproved drugs, off‐patent sole‐source medications, and infrequently used medications. We reviewed drug shortage data from the University of Utah Drug Information Service to demonstrate how frequently these characteristics occurred and resulted in higher drug prices. Clinicians can use drug shortage management principles to mitigate the impact of sudden price increases for patients and health care organizations.     

Metal‐mediated Targeting in the Body

Metal ions are important for many biological processes and are steadily available in the human body. Metal concentrations can be extremely high in diseased areas of various pathological conditions. Some synthetic and natural drugs need to be activated by metal ions as prodrugs. In this review, we provide a few examples to illustrate how metal ions activate and mediate drug targeting in the body. This knowledge may be helpful for the development of more effective drugs and pharmaceutical formulations.     

Using the Severity of Dependence Scale to screen for DSM‐5 khat use disorder

Objective

This study aimed to determine the efficacy of the Severity of Dependence Scale (SDS) as a screening tool for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition‐defined khat use disorder.

Methods

Cross‐sectional, purposive sample of past‐year khat consumers aged 16 and above were recruited from khat markets and cafes from university and general community in Adama, Ethiopia. Participants self‐completed a survey comprising current substance use disorder.

Results

The SDS formed a unifactorial structure, consistent with the dependence construct. Almost three quarters (73%) of the sample were identified as experiencing Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition khat use disorder. The SDS demonstrated excellent discrimination (area under the curve = 0.92) and an optimal cut‐off as a score of 3 or greater, with sensitivity of 81% and specificity of 96%. This classification validly identified a group with more frequent and higher dose khat use than participants that did not screen positive.

Conclusion

Although khat is a mild stimulant, there is clear evidence that some consumers are both concerned with their use and experience problems associated with their use. Consistent with its application for other drugs, the SDS is a brief and simple screening tool that appears to validly identify individuals experiencing a khat use disorder syndrome and experiencing high rates of adverse consequences in association with use.     

Optimization and Application of In Vitro and Ex Vivo Models for Vaginal Semisolids Safety Evaluation

Preclinical safety assessment of vaginal products includes cytotoxicity assays upon cell lines. Furthermore, tissue explants have been considered for application on ex vivo models. In this study, traditional and renewed methods were studied for toxicity assessment of vaginal semisolids upon products currently used in clinical practice as antimicrobials (Gino-Canesten^®, Sertopic^®, Dermofix^®, Gyno-Pevaryl^®, Lomexin^®, Gino Travogen^®, Dalacin V^®), containing estrogens (Ovestin^®, Blissel^®, Colpotrophine^®), and reference formulations (Replens^®, Universal Placebo). Two in vitro cytotoxicity tests were performed: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutral red uptake upon uterine (HEC-1A), cervical (HeLa) and vaginal (VK2 E6/E7) cells, according to ISO/EN 10993-5 (in vitro evaluation of medical devices). Similarly, a strategy to determine tissue viability on ex vivo porcine vaginal model (through MTT reduction assay and histological analysis) was developed and optimized. The vaginal cell line VK2 E6/E7 conducted to the most accurate calculation of half-maximal toxic concentration among all cells on the MTT assay. However, it was shown not be sensitive to the neutral red uptake assay. Tissues from the porcine model were collected with approx. 15% variability in thickness and variation coefficients lower than 25% when testing negative and positive controls were achieved. These models can improve cost-efficiency in early steps of product development.     

Correlation between drug–drug interaction-induced Stevens–Johnson syndrome and related deaths in Taiwan

Concomitant use of some drugs can lead to interactions between them resulting in severe adverse effects. To date, there are few reports of incidences of Stevens-Johnson syndrome (SJS) associated with combination drug administration. Therefore, we studied the relationship between drug combinations and SJS-related mortality, with the hope that a retrospective study of this nature would provide information crucial for the prevention of future drug-drug interaction related deaths attributable to SJS. This retrospective longitudinal study used mortality cases from 1999 to 2008 that were diagnosed as erythema multiforme (International Classification of Diseases, Ninth Revision, Clinical Modification 695.1) from the National Health Insurance database in Taiwan. Statistical comparisons of the results were performed using analysis of variance (ANOVA), independent sample t-tests, and odds ratio (OR). In this way, the relationship between combinations of SJS-inducing drugs and mortality could be determined. A total of 111 patients who had died, including 63 males and 48 females (66.0 ± 20 and 70.0 ± 17.7 years, respectively), were suspected of having experienced drug-drug interaction-related adverse effects. The associated drug combinations included allopurinol and ampicillin (p = 0.049), carbamazepine and sulfamethoxazole/trimethoprim (TMP) (p < 0.0001), carbamazepine and phenytoin (p < 0.0001), sulfamethoxazole/TMP and phenytoin (p = 0.015), sulfadoxine and piroxicam (p = 0.045), phenobarbital and cephalexin (p < 0.0001), ampicillin and erythromycin (p < 0.0001), erythromycin and minocycline (p < 0.0001), and vancomycin and ethambutol (p < 0.0001) administered 1 month before the patients’ deaths. Caution should be exercised when administering any drugs that may possibly induce SJS. In addition, attention should be paid to ensure prompt identification of possible drug-drug interactions, and patients should be closely monitored. Furthermore, medications should be immediately discontinued at the first sign or symptom suggesting the occurrence of drug-related SJS, and then prompt, adequate supportive care should be provided.