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PubMed2005

3D QSAR Markov model for drug-induced eosinophilia--theoretical prediction and preliminary experimental assay of the antimicrobial drug G1.

The application of 3D-MEDNEs as a novel alternative technique to reduce the use of animal experimentation in toxicology in the early stages of medicinal chemistry research has been extended from agranulocytosis to chemically induced eosinophilia. Firstly, a heterogeneous series of organic compounds, which are classified either as eosinophilia inductors or noninductors, was collected. A linear discriminant analysis was subsequently used to obtain a QSTR that gave rise to a very good classification of 91.82% (110 chemicals within training series). Eosinophilia inductors (88.89%) composed the first group while the other one contained only harmless compounds (97.37%). The total predictability (88.1%) was tested by means of an external validation series (42 compounds). The model correctly classifies 88.89% of harmless compounds and 87.5% of toxic ones. Finally, comparison of predicted versus experimental results for G1 [2-bromo-5-(2-bromo-2-nitroethenyl)furan, which is a promising antibacterial-antifungal compound] illustrates the practical application of the method. A dose-dependent study of G1 (9.8-185.6 mg/Kg) at 48, 72 and 96 h after oral administration in rats is reported here for the first time. The study has shown that G1 does not affect the murine eosinophils count under these conditions--a situation in total agreement with the model prediction.

Animals↗

PubMed2005

Stochastic entropy QSAR for the in silico discovery of anticancer compounds: prediction, synthesis, and in vitro assay of new purine carbanucleosides.

A Markov model based QSAR is introduced for the rational selection of anticancer compounds. The model discriminates 90.3% of 226 structurally heterogeneous anticancer/non-anticancer compounds in training series. External validation series were used to validate the model; the 91.8% containing 85 compounds, not considered to fit the model, were correctly classified. The model developed is afterwards used in a simulation of a virtual search for anticancer compounds never considered either in training or in predicting series. The 87.7% of the 213 anticancer compounds used in this simulated search were correctly classified. The model also shows high values for specificity (0.89), sensitivity (0.91), and Mathews correlation coefficient (0.79). In addition, the present model compares better-to-similar with respect to other four models elsewhere reported if one takes into consideration 26 comparison parameters. Finally, we exemplify the use of the model in practice with the design of a new series of carbanucleosides. The compounds evaluated with the model were synthesized and experimentally assayed for their antitumor effects on the proliferation of murine leukemia cells (L1210/0) and human T-lymphocyte cells (CEM/0 and Molt4/C8). The more interesting activity was detected for the compound 5a with a predicted probability of 80.2% and IC(50) = 27.0, 27.2, and 29.4 microM, respectively, against the above-mentioned cellular lines. These values are comparable to those for the control compound Ara-A.

Animals↗

PubMed2006

A comparison of socio-demographic and psychological factors between patients consenting to randomisation and those selecting treatment (the ProtecT study).

BACKGROUND: Patient preferences for treatment can pose problems for the conduct of randomised controlled trials: patients with a preference may refuse participation and thereby potentially compromise external validity. Moreover, randomising patients with a preference may affect treatment efficacy and threaten internal validity. AIMS: This study compared baseline characteristics and short-term psychological outcomes of patients who selected their treatment and those who agreed to random allocation. METHODS: Men participating in the prostate testing for cancer and treatment (ProtecT) study and who were randomised to active monitoring (n=138) were compared with those who had refused randomisation and selected this management (n=180). Socio-demographic data were collected at baseline, and anxiety and depression data were collected at baseline and six month follow-up. Socio-demographic characteristics were compared across these two groups in univariable analyses, and then linear regression was used to compare levels of anxiety and depression at follow-up with adjustments for confounders. RESULTS: Participants who selected active monitoring were more affluent (based on occupation details) and had less anxiety at baseline than those who were randomised. There were no differences with respect to age and marital status. Levels of anxiety and depression at six months follow-up were similar across the two groups of men. CONCLUSIONS: This study found some differences at baseline between the socio-demographic and psychological status of those randomised and self-selecting treatment, but no psychological differences at short-term follow-up. Further empirical evidence is required to assess whether preferences impact upon the process and outcome of randomised controlled trials.

Aged↗

PubMed2005

A method for assessing accurate application of the Partin Tables in the pre-therapy evaluation of patients with prostate cancer.

AIMS: The treatment of prostate cancer is frequently influenced by the Partin Tables. This predictive model has been internally and externally validated since it was conceived, and has proved to be remarkably reliable and consistent. This paper proposes that, by using the statistical programme for the social sciences (SPSS) and receiver-operator characteristic curves, it is possible to detect institutions that apply this model sub-optimally. MATERIALS AND METHODS: This theory was supported by a PUBMED search using relevant search words. RESULTS: This is a novel technique with the potential to allow retrospective and prospective accrual of results. CONCLUSIONS: A systematic institutional review of how accurately a hospital assesses the clinical stage, Gleason score and PSA has the potential to increase an institution's predictive accuracy when it uses the Partin Tables. The proposed method allows for quantitation of the level of error and comparison of predictive accuracy between institutions. It also may be used as an internal outcome measure to assess improvement in a hospital's investigative procedures over time.

Humans↗

PubMed2026

In silico screening of anti-atherosclerotic compounds from Morus alba leaves by machine learning and network pharmacology.

OBJECTIVE: This study integrates machine learning with network pharmacology, molecular docking, and molecular dynamics simulations to screen bioactive compounds from Mulberry leaves and elucidate their potential mechanisms against atherosclerosis (AS). METHODS: A training dataset of anti-AS active compounds was compiled and encoded as Morgan fingerprints. Three machine learning classifiers, specifically Random Forest (RF), Support Vector Machine (SVM), and Extreme Gradient Boosting (XG-Boost), were constructed and evaluated using multiple performance metrics. Potential active components from Mulberry leaves and AS-related targets were retrieved, followed by protein-protein interaction network construction and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking was then performed to evaluate binding affinities between core targets and candidate compounds, and the most stable complex was subjected to molecular dynamics simulations using GROMACS (2025). RESULTS: The RF model achieved superior performance (accuracy= 0.8354, F1 = 0.8408, AUC = 0.9119) with 100% external validation accuracy. Thirteen anti-AS candidates were prioritized from mulberry leaves, four of which have been previously documented. Network pharmacology revealed AKT1 and IL6 as core targets, enriched in pathways such as endocrine resistance. Molecular docking and dynamics simulations confirmed strong binding between oxysanguinarine and AKT1, with the complex exhibiting high stability. CONCLUSION: The RF model provides a reliable computational tool for prioritizing anti-AS compounds from Mulberry leaves. The integrated analysis reveals that Mulberry leaves exert anti-atherosclerotic effects through multi-target (e.g., AKT1, IL6) and multi-pathway (e.g., PI3K-Akt) mechanisms, offering a framework for further experimental validation.

Morus↗

PubMedDate not supplied

The Positive and Negative Symptoms Questionnaire: a self-report scale in schizophrenia.

The assessment of various symptoms in schizophrenia has received much interest, although few studies have compared evaluations by clinicians to those of their patients. Self-report tools may improve service delivery, data collection, and possibly also treatment adherence. We constructed the Positive and Negative Symptoms Questionnaire (PNS-Q), a self-report measure, after items from the Scale for Assessment of Positive Symptoms (SAPS) and the Scale for Assessment of Negative Symptoms (SANS). The PNS-Q contained 68 items and was administered to 61 schizophrenic inpatients. We examined its psychometric properties and utility as a self-report tool in schizophrenia. The PNS-Q exhibited high internal consistency for both its positive and negative subscales. External validity with the SAPS and SANS was low. The positive symptoms subscale correlated significantly with the SAPS ( r = .341, P < .01), whereas the negative symptoms subscale did not correlate at all with the SANS ( r = -0.086, P > .1). The correlation between patients' insight and scores of the PNS-Q was mixed. A partial correlation analysis failed to confirm a relationship between the rating of the patients' level of insight (measured by the Amador Scale to Assess Unawareness of Mental Disorders [SUMD]) and the disparity between the PNS-Q and the SAPS and SANS. However, the PNS-Q correlated highly with McEvoy's Vignettes, a measure of self-perception of symptoms. The results of this study are discussed in light of current research and methodologic issues. The PNS-Q reflects schizophrenics' self-perception, an important, yet neglected, aspect of schizophrenia. Using this new measure, we believe that clinicians and researchers will be able to gain insight to the inner world of these patients and improve their condition, as well as enhance patients' involvement in treatment planning.

Adult↗

PubMed2026

Artificial intelligence-derived myocardial fibrosis on cardiac magnetic resonance for prognosis in cardiomyopathy: A systematic review of a sparse evidence base.

BACKGROUND: Myocardial fibrosis on cardiovascular magnetic resonance (CMR), assessed by late gadolinium enhancement (LGE) and parametric mapping, is an established predictor of adverse events in cardiomyopathy. We assessed whether artificial intelligence (AI) quantification of fibrosis adds independent prognostic value. METHODS: We searched six databases, a clinical-trials register, and a preprint server from inception to 13 June 2026. Eligible studies used AI to generate a fibrosis marker in adults with ischemic or nonischemic cardiomyopathy, with covariate-adjusted outcomes over ≥12 months. Risk of bias was assessed using PROBAST, PROBAST+AI, and QUIPS. Fewer than three comparable studies precluded meta-analysis; certainty was rated using GRADE. RESULTS: Of 448 records (381 after de-duplication), 18 full texts were reviewed and two included, one peer-reviewed and one preprint. In an ischemic-cardiomyopathy registry (Ghanbari et al.; n = 216 analytic, 26 events), AI-derived dense LGE scar predicted arrhythmic events (univariable hazard ratio [HR] 2.35, 95% CI 1.33-4.15), and AI-derived but not manual scar improved discrimination beyond guideline criteria (area under the curve 0.63 to 0.68; p = 0.02). In a nonischemic dilated-cardiomyopathy preprint (Kim et al.; n = 347, 119 events), automated extracellular volume ≥30% predicted cardiovascular death or heart-failure hospitalization (adjusted HR 2.00, 95% CI 1.32-3.03). Both were at high risk of bias, with data-derived thresholds and no external validation. CONCLUSIONS: Across only two studies, AI-derived fibrosis was independently associated with adverse cardiovascular events, but its added value over manual quantification remains unproven. Certainty was very low. The evidence base is sparse and not yet ready for clinical use.

Humans↗

PubMed2006

Redefining the randomized controlled trial in the context of acupuncture research.

BACKGROUND: The randomized controlled trial (RCT) is considered the 'gold standard' methodology for evaluating efficacy of an intervention. It has been argued that RCTs cannot be used to examine the effectiveness of acupuncture. PURPOSE: The purpose of this paper is to examine the applicability of an RCT study design for acupuncture research. FINDINGS: RCTs would be more effective in studying acupuncture if study participants were randomized to groups based on the acupuncture diagnosis and not solely on the Western diagnostic criteria. Treatments must also be standardized somewhat to ensure replicability of the study and the information it provides. Blinding is not absolutely necessary for a good-quality RCT; however, if used, control groups need to be standardized and sham techniques evaluated to ensure accurate interpretation of results. CONCLUSIONS: With these factors combined, it is possible to greatly increase internal and external validity in acupuncture RCTs.

Acupuncture Therapy↗

PubMed2004

Choosing a behavioral therapy platform for pharmacotherapy of substance users.

Behavioral therapy platforms have become virtual requirements in pharmacotherapy trials due to their utility in reducing noise variability, preventing differential medication adherence and protocol attrition, enhancing statistical power and addressing ethical issues in placebo-controlled trials. Selecting an appropriate behavioral platform for a particular trial requires study-specific tailoring, taking into account both the stage of development of the medication being evaluated, as well as the specific strengths and weaknesses of a broad array of available empirically supported behavioral therapies and the range of their possible targets (e.g., enhancing medication adherence, preventing attrition, addressing co-morbid problems, fostering abstinence, and targeting specific weaknesses of the pharmacologic agent). Choosing a suitable behavioral platform also requires consideration of the characteristics of the population to be treated, stage of scientific knowledge regarding the medication's effects, appropriate balance of internal and external validity, and consideration of potential ceiling effects. Available manualized behavioral treatments are reviewed, noting their strengths and limitations as behavioral therapy platforms for pharmacotherapy trials and as potential concomitant therapies in clinical practice.

Behavior Therapy↗

PubMed2003

Are the Framingham and PROCAM coronary heart disease risk functions applicable to different European populations? The PRIME Study.

AIMS: To assess whether the Framingham and PROCAM risk functions were applicable to men in Belfast and France. METHODS AND RESULTS: We performed an external validation study within the PRIME (Prospective Epidemiological Study of Myocardial Infarction) cohort study. It comprised men recruited in Belfast (2399) and France (7359) who were aged 50 to 59 years, free of CHD at baseline (1991 to 1993) and followed over 5 years for CHD events (coronary death, myocardial infarction, angina pectoris). We compared the relative risks of CHD associated with the classic risk factors in PRIME with those in Framingham and PROCAM cohorts. We then compared the number of predicted and observed 5-year CHD events (calibration). Finally, we estimated the ability of the risk functions to separate high risk from low risk subjects (discrimination). The relative risk of CHD calculated for the various factors in the PRIME population were not statistically different from those published in the Framingham and PROCAM risk functions. The number of CHD events predicted by these risk functions however clearly overestimated those observed in Belfast and France. The two risk functions had a similar ability to separate high risk from low risk subjects in Belfast and France (c-statistic range: 0.61-0.68). CONCLUSION: The Framingham and PROCAM risk functions should not be used to estimate the absolute CHD risk of middle-aged men in Belfast and France without any CHD history because of a clear overestimation. Specific population risk functions are needed.

Adult↗

PubMed2004

How real are patients in placebo-controlled studies of acute manic episode?

OBJECTIVE: To determine whether the results from placebo-controlled studies conducted in patients with manic episode can be generalised to a routine population of hospitalised acute manic patients. METHODS: A list of four most prevalent inclusion and the nine most prevalent exclusion criteria was constructed for participation in previous randomised-controlled trials (RCTs). On the basis of this list, a consecutive series of 68 patients with 74 episodes of acute mania who had been referred for routine treatment were retrospectively assessed to determine their eligibility for a hypothetical but representative randomised controlled trial. RESULTS: Only 16% of the manic episodes would qualify for the hypothetical trial (male episodes 28%, female episodes 10%), whereas 37%, 20% and 27% of the manic episodes would have to be excluded because they did no fulfil one, two or at least three of the inclusion or exclusion criteria. The most common exclusion criterion was "no use of contraceptives". If this criterion was not taken into account, 28% of the male episodes and 33% of the female episodes would qualify for inclusion in the hypothetical study. Apart from the use of contraceptives, no significant differences between male and female episodes were observed in the reasons for exclusion: 11% suicidal ideation, 29% prior mood stabilising medication, 1% depot medication, 22% other axis I diagnosis, 27% internal disease somatic disease, 5% neurological disorder, 15% alcohol use disorder and 10% drug use disorder. CONCLUSION: Only a small percentage acute manic episodes in a routine mental hospital seem to qualify for a standard placebo-controlled RCT. It could be argued, however, that certain exclusion criteria (e.g. no use of contraceptives) are not very likely to reduce the external validity of a standard RCT. In contrast, some other exclusion criteria (e.g. comorbid alcohol and drug use disorders) may have resulted in an overestimation of the efficacy of anti-manic medications. These notions should be taken into account when evaluating the results of RCTs in bipolar patients with an acute manic episode.

Adolescent↗

PubMed2005

Assessing health-related quality of life in patients suffering from schizophrenia: a comparison of instruments.

OBJECTIVE: To compare three different kinds of health-related quality of life (HRQL) questionnaires available for use in patients suffering from schizophrenia: the SF-36 (a generic instrument), the QoLI (an instrument designed to a broad range of mental illnesses), the S-QoL (a questionnaire specific to schizophrenic patients), in terms of external validity and sensitivity to change. METHODS: Two hundred and five patients were included at D0 and one-third retested at D30. Socio-demographic data and clinical history were recorded, clinical evaluation comprised psychotic symptoms (PANSS), depression (Calgary depression scale for schizophrenia), global functioning (GAF), clinical severity (CGI), and extrapyramidal symptoms (ESRS). HRQL was assessed using the SF-36, the QoLI and the S-QoL. RESULTS: A better agreement is observed between the SF-36 and the S-QoL than between the QoLI and the two other instruments. S-QoL and SF-36 are more strongly correlated with clinical status than QoLI. Compared to the SF-36 and the QoLI, the S-QoL better discriminates patients with comorbidity from others. The S-QoL shows better responsiveness than the QoLI and the SF-36. CONCLUSION: For descriptive purpose, either generic tools like SF-36 or specific ones should be used, whereas when aiming at evaluating health treatment and care for schizophrenic patients, specific instruments like the S-QoL should be favoured.

Adolescent↗

PubMed2005

Evaluating preference trials of oral phosphodiesterase 5 inhibitors for erectile dysfunction.

More treatment options are available now for the treatment of erectile dysfunction (ED) than ever. Treatments include oral phosphodiesterase 5 (PDE5) inhibitors, intracavernosal injections, vacuum constriction devices, and penile implants. Clinicians, researchers, and patients are interested in making direct comparisons between the response of newer treatments and that of established and more developed therapies. Of the currently available treatment options for ED, the most commonly prescribed therapies are oral PDE5 inhibitors, which include sildenafil citrate (Viagra, Pfizer Inc), tadalafil (Cialis, Lilly ICOS), and vardenafil (Levitra, Bayer). However, most patient preference studies of these drugs conducted to date have serious design flaws that hinder interpretation of the data, and thus limit the utility of the results. To make an informed decision on the most appropriate treatment option available, physicians and their patients require a thorough understanding of the methodology of these studies. Clinical comparison or preference trials must establish internal and external validity if the data are to be used in a generalized patient population. We review preference studies that compared sildenafil, tadalafil, and vardenafil, and highlight study designs that can introduce bias. We propose that, like safety and efficacy trials, randomized controlled trials (RCTs) should be the gold standard for evaluating patient preference treatments for ED. We do not wish to discourage individual investigators from performing preference studies, but rather to highlight the features of current preference trials to help patients and clinicians alike become aware of potential biases from independent or industry-sponsored patient preference trials so that they can interpret the results accordingly. Key components of patient preference RCTs are reviewed: period and carryover effects, preference assessments, eligibility criteria, and data analysis. We discuss why these components of patient-preference RCTs are important for evaluating the validity and relevance of patient preference studies. The preference studies discussed in this brief review are summarized in , and the methodological problems with each study are indicated. We provide a recommendation for the design of such trials that can minimize bias and provide better data for physicians and their patients.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2026

Multi-omics analysis reveals coordinated epigenetic dysregulation in atrazine-induced dopaminergic neurotoxicity.

Atrazine (ATR), a widely used triazine herbicide, has been linked to neurotoxicity, yet the epigenetic mechanisms underlying its dopaminergic effects remain unclear. This study investigated whether coordinated miRNA dysregulation and DNA methylation alterations contribute to ATR-induced Parkinson's disease (PD)-like neurotoxicity. Male Sprague-Dawley rats were administered ATR (50 mg/kg/day) for 90 days, resulting in motor and cognitive deficits with dopaminergic dysfunction, including increased α-synuclein and reduced tyrosine hydroxylase expression. Small RNA sequencing identified 72 differentially expressed miRNAs in the substantia nigra, enriched in PI3K-Akt, MAPK, and Ras signaling pathways. In a cohort of six PD patients and six matched controls, genome-wide DNA methylation profiling revealed 4694 differentially methylated positions, predominantly hypomethylated, with overlapping enrichment in neuronal signaling pathways. Weighted gene co-expression network analysis identified a PD-associated module strongly correlated with disease status (r = -0.95, P < 0.001). Multi-omics integration identified CASP3 as a central hub gene. External validation supported CASP3 relevance in PD (AUC = 0.833), and molecular docking suggested potential ATR-CASP3 interaction. Further analysis predicted upregulated miR-3552 as a potential upstream regulator of CASP3. These findings indicate that ATR-induced neurotoxicity may be mediated through the miR-3552/CASP3 signaling axis, ultimately regulating apoptosis and contributing to neurodegeneration.

Animals↗

PubMed2006

Novel 2D maps and coupling numbers for protein sequences. The first QSAR study of polygalacturonases; isolation and prediction of a novel sequence from Psidium guajava L.

The development of 2D graph-theoretic representations for DNA sequences was very important for qualitative and quantitative comparison of sequences. Calculation of numeric features for these representations is useful for DNA-QSAR studies. Most of all graph-theoretic representations identify each one of the four bases with a unitary walk in one axe direction in the 2D space. In the case of proteins, twenty amino acids instead of four bases have to be considered. This fact has limited the introduction of useful 2D Cartesian representations and the corresponding sequences descriptors to encode protein sequence information. In this study, we overcome this problem grouping amino acids into four groups: acid, basic, polar and non-polar amino acids. The identification of each group with one of the four axis directions determines a novel 2D representation and numeric descriptors for proteins sequences. Afterwards, a Markov model has been used to calculate new numeric descriptors of the protein sequence. These descriptors are called herein the sequence 2D coupling numbers (zeta(k)). In this work, we calculated the zeta(k) values for 108 sequences of different polygalacturonases (PGs) and for 100 sequences of other proteins. A Linear Discriminant Analysis model derived here (PG=5.36.zeta1-3.98.zeta3-42.21) successfully discriminates between PGs and other proteins. The model correctly classified 100% of a subset of 81 PGs and 75 non-PG proteins sequences used to train the model. The model also correctly classified 51 out of 52 (98.07%) of proteins sequences used as external validation series. The uses of different group of amino acids and/or axes orientation give different results, so it is suggested to be explored for other databases. Finally, to illustrates the use of the model we report the isolation and prediction of the PG action for a novel sequence (AY908988) isolated by our group from Psidium guajava L. This prediction coincides very well with sequence alignment results found by the BLAST methodology. These findings illustrate the possibilities of the sequence descriptors derived for this novel 2D sequence representation in proteins sequence QSAR studies.

Algorithms↗

PubMed2004

Prediction of an ongoing pregnancy after intrauterine insemination.

OBJECTIVE: To develop a prognostic model for the outcome of IUI. DESIGN: Retrospective cohort study. SETTING: Four fertility centers in The Netherlands. PATIENT(S): Couples of whom the female partners had a regular cycle and who had been treated with IUI. INTERVENTION(S): Intrauterine insemination with and without ovarian hyperstimulation. MAIN OUTCOME MEASURE(S): Ongoing pregnancy. RESULT(S): Overall, 3371 couples were included who underwent 14968 cycles. There were 1229 (8.2%) pregnancies, of which 1000 (6.7%) pregnancies were ongoing. Logistic regression analysis demonstrated that increasing maternal age, longer duration of subfertility, presence of male factor subfertility, one-sided tubal pathology, endometriosis, uterine anomalies, and an increasing number of cycles were unfavorable predictors for an ongoing pregnancy. Cervical factor and the use of ovarian hyperstimulation were favorable predictors. The area under the receiver operating characteristic curve was 0.59. When couples were divided into four categories based on prognosis, the difference between the predicted and observed chance, that is, the calibration, was less than 0.5% in each of the four groups. CONCLUSION(S): Although our model had a relatively poor discriminative capacity, data on calibration showed that the selected prognostic factors allow distinction between couples with a poor prognosis and couples with a good prognosis. After external validation, this model could be of use in patient counseling and clinical decision making.

Adult↗

PubMed2005

Adaptations to normal human gait on potentially slippery surfaces: the effects of awareness and prior slip experience.

Prior knowledge of potentially slippery conditions has been shown to alter normal human gait in slip and fall experiments. Here we quantify the effects of two aspects of prior knowledge - awareness of a possible slip and prior slip experience - on normal gait. Sixty-eight subjects (40F, 28M) each walked over 48 high-friction surfaces (control trials) and 12 low-friction surfaces. Within- and between-subject changes in lower limb muscle activation, gait kinematics and ground reaction forces were analyzed in three non-slip control trials: one before and one after the first unexpected slip exposure, and a third after repeated slip exposures. Subjects knew they might slip in the latter two trials but not the first trial. Twenty subjects slipped during their first low-friction exposure (early slip group), 32 in later low-friction exposures (late slip group), and 16 subjects did not slip at all. Simultaneous changes in awareness and experience between the first two analyzed trials of the early slip group altered the muscle activity in both limbs, reduced the foot and knee angles at heel strike in the slip limb and reduced the ground reaction forces, impulses and utilized friction after heel strike in the slip limb. A change in only awareness between the first two analyzed trials of the late slip group produced the same kinematic changes seen in the early slip group, but only small muscle activity change and no kinetic changes. Subsequent slip experience in the late slip group produced the muscle activation and kinetic changes observed in the early slip group, but no further kinematic changes. These results showed that awareness of a potential slip primarily alters how the slip-limb approaches the floor, whereas prior slip experience primarily alters the anticipatory muscle activation and how the foot interacts with the floor. These muscle, kinematic and kinetic changes were consistent with a more cautious "normal" gait, and can reduce the external validity of slip and fall experiments.

Adolescent↗

PubMedDate not supplied

Patients' preferences in the treatment of depressive disorder in primary care.

Patients' preferences in the treatment of depression are important in clinical practice and in research. Antidepressant medication is often prescribed, but adherence is low. This may be caused by patients preferring psychotherapy, which is often not available in primary care. In randomized clinical trials, patients' preferences may affect the external validity. The aim of this article is to study patients' preferences regarding psychotherapy and antidepressant medication and the impact of these preferences on treatment outcome. A systematic review of the literature was performed. The majority of patients preferred psychotherapy in all available studies. Antidepressants were often regarded as addictive and psychotherapy was assumed to solve the cause of depression. Discussing and supporting preferences as part of a quality improvement program of depression care, resulted in more patients receiving the treatment that was most suitable to them. In two patient-preference trials, preferences did not influence treatment outcome. It can be concluded that a substantial percentage of well-informed patients prefer psychotherapy. Patients with strong preferences, mostly for psychotherapy, are likely not to enter antidepressant treatment or randomized clinical trials if their preferences are not supported.

Antidepressive Agents↗