Formulation and Validation of an Extended Sigmoid Emax Model in Pharmacodynamics.

PURPOSE OR OBJECTIVE: Drug concentration-response curves (DRCs) are crucial in pharmacology for assessing the drug effects on biological systems. The widely used sigmoid Emax model, which accounts for response saturation, relies heavily on the effective drug concentration ( E D 50 ). This reliance can lead to validation errors and inaccuracies in model fitting. The Emax model cannot generate multiple DRCs, raising concerns about whether the dataset is fully utilized. METHODS: This study formulates an extended Emax (eEmax) model designed to overcome these limitations. The eEmax model generates multiple DRCs from a single dataset by using various estimated α ' s ∈ 0,100 , while keeping E D α fixed, rather than estimating an E D 50 value as in the Emax model. RESULTS: This model effectively captures a broader range of concentration-response behavior, including non-sigmoidal patterns, thus providing greater flexibility and accuracy compared to the Emax model. Validation using various drug-response data and PKPD frameworks demonstrates the eEmax model's improved accuracy and versatility in handling concentration-response data. CONCLUSIONS: The eEmax model provides a robust and flexible method for drug concentration-response analysis, facilitating the generation of multiple DRCs from a single dataset and reducing the possibility of validation errors. This model is particularly valuable for its ease of use and its capability to fully utilize datasets, providing its potential in PKPD modeling and drug discovery.

Antihypertensive drug targets and breast cancer risk: a two-sample Mendelian randomization study.

Findings on the correlation between the use of antihypertensive medication and the risk of breast cancer (BC) have been inconsistent. We performed a two-sample Mendelian randomization (MR) using instrumental variables to proxy changes in gene expressions of antihypertensive medication targets to interrogate this. Genetic instruments for expression of antihypertensive drug target genes were identified with expression quantitative trait loci in blood, which should be associated with systolic blood pressure to proxy for the effect of antihypertensive drug. The association between genetic variants and BC risk were obtained from genome-wide association study summary statistics. The summary-based MR was employed to estimate the drug effects on BC risk. We further performed sensitivity analyses to confirm the discovered MR associations such as assessment of horizontal pleiotropy, colocalization, and multiple tissue enrichment analyses. The overall BC risk was only associated with SLC12A2 gene expression at a Bonferroni-corrected threshold. One standard deviation (SD) decrease of SLC12A2 gene expression in blood was associated with a decrease of 1.12 (95%CI, 0.80-1.58) mmHg of systolic blood pressure, but a 16% increased BC risk (odds ratio, 1.16, 95% confidential interval, 1.06-1.28). This signal was further observed for estrogen receptor positive (ER +) BC (1.17, 1.06-1.28). In addition, one SD decrease in expression of PDE1B in blood was associated with 7% decreased risk of ER + BC (0.93, 0.90-0.97). We detected no evidence of horizontal pleiotropy for these associations and the probability of the causal variants being shared between the gene expression and BC risk was 81.5, 40.5 and 66.8%, respectively. No significant association was observed between other target gene expressions and BC risk. Changes in expression of SLC12A2 and PDE1B mediated possibly via antihypertensive drugs may result in increased and decreased BC risk, respectively.

Methodological Approaches to Experimental Evaluation of Neuroprotective Action of Potential Drugs.

The authors propose a novel approach to a comprehensive evaluation of neuroprotective effects using both in vitro and in vivo methods. This approach allows for the initial screening of numerous newly synthesized chemical compounds and substances from plant and animal sources while saving animal life by reducing the number of animals used in research. In vitro techniques, including mitochondrial suspensions and neuronal cell cultures, enable the assessment of neuroprotective activity, which can be challenging in intact organisms. The preliminary methods help outline the neuroprotection mechanism depending on the neurodestruction agent. The authors have validated a model of acute cerebrovascular accident, which simulates key cerebrovascular phenomena such as reduced cerebral blood flow, energy deficit, glutamate-calcium excitotoxicity, oxidative stress, and early gene expression. A significant advantage of this model is its ability to reproduce the clinical picture of cerebral ischemia: impaired motor activity; signs of neurological deficits (paresis, paralysis, etc.); as well as disturbances in attention, learning, and memory. Crucial to this approach is the selection of biochemical, molecular, and cellular markers to evaluate nerve tissue damage and characterize potential neuroprotective agents. Additionally, a comprehensive set of molecular, biochemical, histological, and immunohistochemical methods is proposed for evaluating neuroprotective effects and underlying mechanisms of potential pharmaceutical compounds.

Novel Antineoplastic Inducers of Mitochondrial Apoptosis in Human Cancer Cells.

I propose a new strategy to suppress human cancer completely with two entirely new drug compounds exploiting cancer's Warburg effect characterized by a defective mitochondrial aerobic respiration, substituted by cytosolic aerobic fermentation/glycolysis of D-(+)-glucose into L-(+)-lactic acid. The two essentially new drugs, compound 1 [P(op)T(est)162] and compound 3 (PT167), represent new highly symmetric, four-bladed propeller-shaped polyammonium cations. The in vitro antineoplastic highly efficacious drug compound 3 represents a covalent combination of compound 1 and compound 2 (PT166). The intermediate drug compound 2 is an entirely new colchic(in)oid derivative synthesized from colchicine. Compound 2's structure was determined using X-ray crystallography. Compound 1 and compound 3 were active in vitro versus 60 human cancer cell lines of the National Cancer Institute (NCI) Developmental Therapeutics Program (DTP) 60-cancer cell testing. Compound 1 and compound 3 not only stop the growth of cancer cells to ±0% (cancerostatic effect) but completely kill nearly all 60 cancer cells to a level of almost -100% (tumoricidal effect). Compound 1 and compound 3 induce mitochondrial apoptosis (under cytochrome c release) in all cancer cells tested by (re)activating (in most cancers impaired) p53 function, which results in a decrease in cancer's dysregulated cyclin D1 and an induction of the cell cycle-halting cyclin-dependent kinase inhibitor p21Waf1/p21Cip1.

Novel ibuprofen prodrug: A possible promising agent for the management of complications of Alzheimer's disease.

Background: Alzheimer's disease (AD) is a severe, varied, and complex brain condition that gradually impairs memory and cognitive function. Epidemiological studies have shown that patients who have a history of long-term NSAID use have a decreased risk of developing AD. The objective of this study is to conduct the structural analysis of a novel ibuprofen prodrug and test its anti-Alzheimer's properties. Methods: Computational and docking studies were conducted using AMBER 18 package. The in-vivo studies were performed using aluminum chloride-induced experimental AD in rats. Adult Wistar rats of either sex were used and treated with aluminum chloride (32.5 mg/kg, p.o) and ibuprofen prodrug (50 mg/kg, p.o) daily for 30 days. The hole-board test and elevated plus maze were conducted on 10th, 20th and 30th day. Further, on 31st day, animals were euthanized and the brain tissue was used for histopathology. The results obtained were subjected to statistical analysis by one-way ANOVA and Dunnet's test, p < 0.05 was considered to indicate the significance. Results: The structural configuration of the novel compound indicated the presence of several structures such as aliphatic, aromatic, and asymmetry in the compound. The geometrical analysis indicated that the ibuprofen conjugate has dreiding energy of 51.22 kcal/mol with a van der waals radius of 62.56 A. The Huckel analysis confirmed the presence of aromatic rings in the compound. The molecular docking studies suggested affinity towards beta-secretase and acetylcholinesterase, besides indicating that the compound has ideal characteristics for the oral route (Log P = 2.33), cellular absorption (TPSA = 95.50), and oral bioavailability (number of rotatable bonds = 10). The toxicity profile indicated devoid of major systemic toxicity with mild possibility of cytotoxicity. The in-vivo analysis showed that the Ibu-prodrug significantly (P < 0.001) reversed the changes induced by aluminum chloride and restored histomorphological features in brain tissue. Conclusion: The findings suggested that the ibuprofen conjugate might possess the potential to manage the complications of AD. The action appears to be mediated through inhibition of beta-secretase and acetylcholinesterase activities. More studies might aid in identifying a specific therapeutic intervention that is still lacking in the treatment of AD.

Evaluation of Anticonvulsant-Induced Leukocytosis: A Review of Evidence for Carbamazepine, Lamotrigine, and Phenobarbital.

Objective: The objective was to determine the incidence of leukocytosis associated with carbamazepine, lamotrigine, and phenobarbital. Data sources: A comprehensive literature review was conducted with the assistance of a medical reference librarian on PubMed, MEDLINE, Embase, and Google Scholar through June 2023 using the following search terminology: "leukocytosis/chemically induced"[MeSH Terms] AND ("Anticonvulsants"[MeSH Terms] OR ("Anticonvulsants"[Pharmacological Action] OR "Anticonvulsants"[MeSH Terms] OR "Anticonvulsants"[All Fields] OR "anticonvulsant"[All Fields] OR "anticonvulsion"[All Fields] OR "anticonvulsive"[All Fields] OR "anticonvulsives"[All Fields]) OR ("Anticonvulsants"[Pharmacological Action] OR "Anticonvulsants"[MeSH Terms] OR "Anticonvulsants"[All Fields] OR "antiepileptic"[All Fields] OR "antiepileptics"[All Fields])). Study selection and data extraction: Thirteen reports were included from 64 potential results of our literature review following the application of inclusion and exclusion criteria: 7 of the reports involved carbamazepine, 4 of the reports involved lamotrigine, and 2 of the reports involved phenobarbital. Data synthesis: Drug-induced leukocytosis is commonly a diagnosis of exclusion and is a phenomenon that has numerous ramifications to patients and clinicians at the bedside, including mandating a full infectious evaluation, the identification of confounding variables, and the eventual discontinuation of the offending agent. Despite several medications and medication classes possessing this adverse drug effect, an evaluation of the specific clinical presentation and management strategies for drug-induced leukocytosis associated with anticonvulsant medications has not been elucidated in the literature. Conclusions: Clinicians should be judicious when evaluating leukocytosis in patients on potentially precipitating medications, including carbamazepine, lamotrigine, and phenobarbital.

[Drug induced gastro-intestinal tract lesions: A pathologist point of view]. / Lésions iatrogènes du tube digestif vues par le pathologiste.

The number of drugs available to clinicians, especially targeted therapies, grows continuously. Some drugs are known to cause frequent digestive adverse effects, which may affect the gastro-intestinal tract in a diffuse or localized manner. Some treatments may leave relatively pathognomonic deposits, but histological lesions of iatrogenic origin are mostly non-specific. The diagnostic and etiological approach is often complex because of these non-specific aspects and also because (1) a single type of drug may cause different histological lesions, (2) different drugs may cause identical histological lesions, (3) the patient may receive different drugs, and (4) drug-induced lesions may mimic other pathological entities such as inflammatory bowel disease, celiac disease, or graft versus host disease. The diagnosis of iatrogenic gastrointestinal tract injury therefore requires close anatomic-clinical correlation. The iatrogenic origin can only be formally established if the symptomatology improves when the incriminating drug is stopped. This review aims to present the different histological patterns of gastrointestinal tract iatrogenic lesions, the potentially incriminate drugs, as well as the histological signs to look for in order to help the pathologist to distinguish an iatrogenic injury from another pathology of the gastrointestinal tract.

The relationship between chronic disease and drugs/toxins-how important is negative disease-drug synergy?

The interaction of diseases with drugs and toxins may result in significantly worse outcomes in a forensic context when i) chronic diseases cause toxicity by increasing drug levels due to reduced renal clearance or slowed hepatic breakdown, and ii) drugs exacerbate underlying lethal mechanisms. In other words, 'negative disease-drug synergy' may result in increased drug toxicity and/or greater organ dysfunction despite the use of standard dosages. This is yet another confounding factor to be considered in the interpretation of postmortem toxicological results, as underlying illness and disease states may significantly alter drug availability and physiological responses.

How do they add up? The interaction between the placebo and treatment effect: A systematic review.

AIM: The placebo effect and the specific effect are often thought to add up (additive model). Whether additivity holds can dramatically influence the external validity of a trial. This assumption of additivity was tested by Kleijnen et al in 1994 but the data produced since then have not been synthetized. In this review, we aimed to systematically review the literature to determine whether additivity held. METHODS: We searched Medline and PsychInfo up to 10 January 2019. Studies using the balanced placebo design (BPD), testing two different strengths of placebos, were included. The presence of interaction was evaluated by comparing each group in the BPD with analysis of variance or covariance. RESULTS: Thirty studies were included and the overall risk of bias was high: four found evidence of additivity and 16 studies found evidence of interaction (seven had evidence of positive additivity). CONCLUSION: Evidence of additivity between placebo and specific features of treatments was rare in included studies. We suggest interventions for placebo-sensitive ailments should be tested in trials designed to take interactions seriously once an exploratory RCTs has proven their efficacy with sufficient internal validity.

Levamisole and ANCA positivity in childhood nephrotic syndrome.

BACKGROUND: This study aimed to determine the prevalence of ANCA positivity in children managed with levamisole as a steroid-sparing agent for nephrotic syndrome (NS). METHODS: Medical records of children with steroid-sensitive NS managed with levamisole therapy at Sydney Children's Hospital between 1/1/2000 and 31/12/2018 were retrospectively reviewed. Main outcome measure was side effects of levamisole therapy including ANCA positivity. RESULTS: Seventy-one children, median age 3 years and 1 month (IQR 29-68 months) at first presentation, were subsequently managed with levamisole. 60.6% were male and 65% Caucasian. 47.9% had frequently relapsing (FR)NS and 52.1% steroid-dependent (SD)NS. Overall, there was a median reduction in relapses from 3 (IQR 1-5) to 0.4 relapses (IQR 0-1) per year after levamisole was commenced. Levamisole was successful in preventing relapse in 19 (29%) patients and was used for median 24 (22 to 25) months. Levamisole was discontinued due to relapse in 25 patients (38%) after median 12 (5-28) months. Side effects occurred in 28 patients (42.4%); the most common side effect was ANCA positivity in 12 patients. In eleven of these patients, levamisole was discontinued; in one patient, low-level titres were documented and spontaneously resolved without cessation of levamisole. Two patients developed ANCA-associated vasculitis. CONCLUSION: ANCA positivity is a common side effect of levamisole and was seen in 18.2% of our patients. Monitoring is required to determine side effects including ANCA positivity and treatment modified accordingly.

Hemoptysis in a cannabis user.

A healthy young man presented to the emergency department with mild hemoptysis associated with cannabis abuse. He was on no medications and cocaine abuse was ruled out by both history and negative toxicology screens. There were neither signs of an infection, nor of a systemic or cardiac disease. Imaging studies were consistent with diffuse alveolar hemorrhage, a reported, albeit rare adverse drug reaction of tetrahydrocannabinol (Naranjo score 6). The patient improved spontaneously within a few days, hemoptysis stopped and repeat imaging was entirely normal. With the increase in cannabis abuse and enhanced cannabis potency worldwide clinicians may increasingly encounter even unusual cannabis-associated adverse drug reactions, including associated diffuse alveolar hemorrhage.

Hydroxyurea-induced genital ulcers and erosions: Two case reports.

Hydroxyurea is a chemotherapeutic agent used for myeloproliferative disorders and sickle cell anemia that is well known to cause painful mucocutaneous ulcers, typically involving the legs or mouth. However, genital ulcerations due to hydroxyurea therapy are a rare, and likely underrecognized, adverse effect with only a few cases reported in the literature to date. Ulcers of the lower legs caused by hydroxyurea are associated with a diagnostic delay, and this is likely exacerbated in cases of genital ulceration due to a lack of awareness. Herein we present two cases of painful genital ulceration in patients on hydroxyurea therapy. In the first Case, an 87 year-old male with polycythemia vera developed an ulcer on the scrotum, which was assessed initially through virtual visits during the COVID-19 pandemic, and was refractory to topical and oral antibiotic treatments. The second case was a 79 year-old male with essential thrombocythemia and a history of persistent leg ulcers who developed erosions of the glans penis. Both patients experienced complete resolution within weeks of discontinuing hydroxyurea therapy. In conclusion, genital ulcers and erosions induced by hydroxyrea may be underrecognized in clinical practice, but if identified, withdrawal of hydroxyurea leads to quick resolution of these lesions and the associated pain.

Class 1C antiarrhythmic drugs in atrial fibrillation and coronary artery disease.

BACKGROUND: Class 1C antiarrhythmic drugs (AADs) are effective first-line agents for atrial fibrillation (AF) treatment. However, these agents commonly are avoided in patients with known coronary artery disease (CAD), due to known increased risk in the postmyocardial infarction population. Whether 1C AADs are safe in patients with CAD but without clinical ischemia or infarct is unknown. Reduced coronary flow capacity (CFC) on positron emission tomography (PET) reliably identifies myocardial regions supplied by vessels with CAD causing flow limitation. OBJECTIVE: To assess whether treatment with 1C AADs increases mortality in patients without known CAD but with CFC indicating significantly reduced coronary blood flow. METHODS: In this pilot study, we compared patients with AF and left ventricular ejection fraction ≥50% who were treated with 1C AADs to age-matched AF patients without 1C AAD treatment. No patient had clinically evident CAD (ie, reversible perfusion defect, known ≥70% epicardial lesion, percutaneous coronary intervention, coronary artery bypass grafting, or myocardial infarction). All patients had PET-based quantification of stress myocardial blood flow and CFC. Death was assessed by clinical follow-up and social security death index search. RESULTS: A total of 78 patients with 1C AAD exposure were matched to 78 controls. Over a mean follow-up of 2.0 years, the groups had similar survival (P = .54). Among patients with CFC indicating the presence of occult CAD (ie, reduced CFC involving ≥50% of myocardium), 1C-treated patients had survival similar to (P = .44) those not treated with 1C agents. CONCLUSIONS: In a limited population of AF patients with preserved left ventricle function and PET-CFC indicating occult CAD, treatment with 1C AADs appears not to increase mortality. A larger study would be required to confidently assess the safety of these drugs in this context.

Bolus pharmacokinetics: moving beyond mass-based dosing to guide drug administration.

Despite the common approach of bolus drug dosing using a patient's mass, a more tailored approach would be to use empirically derived pharmacokinetic models. Previously, this could only be possible though the use of computer simulation using programs which are rarely available in clinical practice. Through mathematical manipulations and approximations, a simplified set of equations is demonstrated that can identify a bolus dose required to achieve a specified target effect site concentration. The proposed solution is compared against simulations of a wide variety of pharmacokinetic models. This set of equations provides a near-identical solution to the simulation approach. A boundary condition is established to ensure the derived equations have an acceptable error. This approach may allow for more precise administration of medications with the use of point of care technology and potentially allows for pharmacokinetic dosing in artificial intelligence problems.

A Camera Sensors-Based System to Study Drug Effects On In Vitro Motility: The Case of PC-3 Prostate Cancer Cells.

Cell motility is the brilliant result of cell status and its interaction with close environments. Its detection is now possible, thanks to the synergy of high-resolution camera sensors, time-lapse microscopy devices, and dedicated software tools for video and data analysis. In this scenario, we formulated a novel paradigm in which we considered the individual cells as a sort of sensitive element of a sensor, which exploits the camera as a transducer returning the movement of the cell as an output signal. In this way, cell movement allows us to retrieve information about the chemical composition of the close environment. To optimally exploit this information, in this work, we introduce a new setting, in which a cell trajectory is divided into sub-tracks, each one characterized by a specific motion kind. Hence, we considered all the sub-tracks of the single-cell trajectory as the signals of a virtual array of cell motility-based sensors. The kinematics of each sub-track is quantified and used for a classification task. To investigate the potential of the proposed approach, we have compared the achieved performances with those obtained by using a single-trajectory paradigm with the scope to evaluate the chemotherapy treatment effects on prostate cancer cells. Novel pattern recognition algorithms have been applied to the descriptors extracted at a sub-track level by implementing features, as well as samples selection (a good teacher learning approach) for model construction. The experimental results have put in evidence that the performances are higher when a further cluster majority role has been considered, by emulating a sort of sensor fusion procedure. All of these results highlighted the high strength of the proposed approach, and straightforwardly prefigure its use in lab-on-chip or organ-on-chip applications, where the cell motility analysis can be massively applied using time-lapse microscopy images.

Use of Contemporary Protease Inhibitors and Risk of Incident Chronic Kidney Disease in Persons With Human Immunodeficiency Virus: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study.

BACKGROUND: It is unclear whether use of contemporary protease inhibitors pose a similar risk of chronic kidney disease (CKD) as use of older protease inhibitors. METHODS: Participants in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study were followed up until the earliest occurrence of CKD, the last visit plus 6 months, or 1 February 2016. Adjusted Poisson regression was used to assess associations between CKD and the use of ritonavir-boosted atazanavir (ATV/r) or ritonavir-boosted darunavir (DRV/r). RESULTS: The incidence of CKD (10.0/1000 person-years of follow-up; 95% confidence interval, 9.5-10.4/1000 person-years of follow-up) increased gradually with increasing exposure to ATV/r, but the relation was less clear for DRV/r. After adjustment, only exposure to ATV/r (adjusted incidence rate ratio, 1.4; 95% confidence interval, 1.2-1.6), but not exposure to DRV/r (1.0; .8-1.3), remained significantly associated with CKD. CONCLUSION: While DRV/r use was not significantly associated with CKD an increasing incidence with longer ATV/r use was confirmed.

Placebos and the Placebo Effect in Drug Trials.

In this review, we explored different ways of controlling the placebo effects in clinical trials and described various factors that may increase/decrease the placebo effect in randomized placebo-controlled trials. These factors can be subdivided into four groups, and while not all factors are effective in every study and under all clinical conditions, they show on the whole that - even under the ideal condition of drug therapy, where blinded placebo provision is much easier and warranted than in, e.g., psychotherapy - many factors need to be controlled to ascertain that the goal of the clinical trials, fair assessment of superiority of the drug over placebo in placebo-controlled trials and fair assessment of non-inferiority of the drug compared to another drug in comparator trials, is reached. Ignorance towards the placebo effect, which was common in the past, is no longer acceptable; instead, it should be the goal of all therapeutic trials to minimize the placebo effect in clinical trials, while utilizing and maximizing it in clinical routine.

[Research and development thought on biopharmaceutics classification system of Chinese materia medica].

The biopharmaceutics classification system( BCS) is a scientific framework or method for classifying drugs based on drug solubility and permeability,which can be used to provide drug bioavailability-absorption correlation analysis. Based on the characteristics of multi-component and multi-target of traditional Chinese medicine( TCM) as well as the concept,method and technology of BCS,the research group proposed biopharmaceutics classification system of Chinese materia medica( CMMBCS) and carried out research and data accumulation of classical prescriptions. Based on the previous research results,further development ideas under the CMMBCS concept and framework were further proposed in this study. In the course of research,the influence of the intermediate links of the complex interactions of the multi-component environment was omitted,and the component absorption studies on the main clinical effects of prescription ingredients were directly concerned,or the components and data were reversely extracted from the aspects of metabolism,pharmacodynamic pathways and absorption principles. Studies were conducted from two aspects( single component and compound prescription) to comprehensively evaluate the absorption properties of TCM compound. In the research path,the different ways in which Chinese medicine could exert its efficacy were fully considered,and CMMBCS classification and establishment rules were clarified mainly by focusing on the absorption pathway into the blood. Specifically,the network pharmacology and molecular docking technology were used to screen the compound index components of TCM; the absorption rules were studied by the physiologically based pharmacokinetic models and the absorption parameters of CMMBCS were calculated by reverse reasoning. Then the CMMBCS classification of TCM prescription was corrected by studying the efficacy or absorption pathway. In this paper,the theoretical framework and research methodology of CMMBCS were systematically improved based on the establishment of CMMBCS basic theory,the supplementary of drug-oriented research ideas and the application of modern mature Chinese medicine methodology.

The pharmacological treatment of chronic comorbidities in COPD: mind the gap!

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is commonly associated with other chronic diseases, which poses several diagnostic and therapeutic problems. Indeed, important comorbidities frequently remain unrecognized and, then, untreated, whereas respiratory drugs may have non respiratory side effects, and selected non respiratory drugs may variably affect the respiratory function. OBJECTIVE: to describe: how COPD affects the presentation and contributes to the diagnostic challenges of its most common comorbidities; how coexisting COPD impacts the therapeutic approach to selected comorbidities and viceversa. METHODS: we distinguish comorbidities of COPD depending upon whether they are complications of COPD or share risk factors, mainly smoke, with it or, finally, aggravate COPD. We describe atypical presentations of and diagnostic clues to comorbidities and suggest screening procedures. Finally, the main therapeutic problems, as resulting from the risk of untoward effects of therapies of COPD and its comorbidity, with special attention to drug-drug interactions and possible overdosages, are described. RESULTS: selected complications of COPD, such as osteoporosis, sarcopenia and dysphagia, are rarely recognized and treated, likely due to the poor awareness of them. Important comorbidities, such as coronary artery disease, chronic heart failure, obstructive sleep apnoea syndrome and chronic renal failure, also should be systematically searched for because of their commonly variant presentation. Disease-related symptoms should be distinguished from drug effects or drug-drug interaction effects. CONCLUSIONS: a truly comprehensive view of the complex COPD patient, hopefully capitalizing on multidimensional geriatric assessment, is needed to dissect the many components of health status impairment and to provide the optimal care. Selected screening procedures are highly desirable to identify frequently missed comorbidities. Pharmacosurveillance is an essential part of the approach to COPD and its comorbidities.

[Drug-target protein interaction prediction based on AdaBoost algorithm].

The drug-target protein interaction prediction can be used for the discovery of new drug effects. Recent studies often focus on the prediction of an independent matrix filling algorithm, which apply a single algorithm to predict the drug-target protein interaction. The single-model matrix-filling algorithms have low accuracy, so it is difficult to obtain satisfactory results in the prediction of drug-target protein interaction. AdaBoost algorithm is a strong multiple classifier combination framework, which is proved by the past researches in classification applications. The drug-target interaction prediction is a matrix filling problem. Therefore, we need to adjust the matrix filling problem to a classification problem before predicting the interaction among drug-target protein. We make full use of the AdaBoost algorithm framework to integrate several weak classifiers to improve performance and make accurate prediction of drug-target protein interaction. Experimental results based on the metric datasets show that our algorithm outperforms the other state-of-the-art approaches and classical methods in accuracy. Our algorithm can overcome the limitations of the single algorithm based on machine learning method, exploit the hidden factors better and improve the accuracy of prediction effectively.